447 results on '"Kahn S"'
Search Results
2. FTO predicts weight regain in the Look AHEAD clinical trial.
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McCaffery, J M, Papandonatos, G D, Huggins, G S, Peter, I, Kahn, S E, Knowler, W C, Hudnall, G E, Lipkin, E W, Kitabchi, A E, Wagenknecht, L E, and Wing, R R
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OBESITY ,WEIGHT loss ,WEIGHT gain ,ALLELES ,TYPE 2 diabetes ,GENETIC polymorphism research - Abstract
Background:Genome-wide association studies have provided new insights into the genetic factors that contribute to the development of obesity. We hypothesized that these genetic markers would also predict magnitude of weight loss and weight regain after initial weight loss.Methods:Established obesity risk alleles available on the Illumina CARe iSelect (IBC) chip were characterized in 3899 overweight or obese participants with type 2 diabetes from the Look AHEAD (Action for Health in Diabetes), a randomized trial to determine the effects of intensive lifestyle intervention (ILI) and diabetes support and education (DSE) on cardiovascular morbidity and mortality. Primary analyses examined the interaction between 13 obesity risk polymorphisms in eight genes and randomized treatment arm in predicting weight change at year 1, and weight regain at year 4 among individuals who lost 3% or more of their baseline weight by year 1.Results:No single-nucleotide polymorphisms (SNPs) were significantly associated with magnitude of weight loss or interacted with treatment arm at year 1. However, fat mass and obesity associated gene (FTO) rs3751812 predicted weight regain within DSE (1.56 kg per risk allele, P=0.005), but not ILI (P=0.761), resulting in SNP × treatment arm interaction (P=0.009). In a partial replication of prior research, the obesity risk (G) allele at BDNF rs6265 was associated with greater weight regain across treatment arms (0.773 kg per risk allele), although results were of borderline statistical significance (P=0.051).Conclusions:Variations in the FTO and BDNF loci may contribute risk of weight regain after weight loss. [ABSTRACT FROM AUTHOR]
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- 2013
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3. Interactions between genetic background, insulin resistance and β-cell function.
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Kahn, S. E., Suvag, S., Wright, L. A., and Utzschneider, K. M.
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INSULIN resistance , *PANCREATIC beta cells , *HYPERGLYCEMIA , *TYPE 2 diabetes , *GLUCOKINASE , *PROINSULIN - Abstract
An interaction between genes and the environment is a critical component underlying the pathogenesis of the hyperglycaemia of type 2 diabetes. The development of more sophisticated techniques for studying gene variants and for analysing genetic data has led to the discovery of some 40 genes associated with type 2 diabetes. Most of these genes are related to changes in β-cell function, with a few associated with decreased insulin sensitivity and obesity. Interestingly, using quantitative traits based on continuous measures rather than dichotomous ones, it has become evident that not all genes associated with changes in fasting or post-prandial glucose are also associated with a diagnosis of type 2 diabetes. Identification of these gene variants has provided novel insights into the physiology and pathophysiology of the β-cell, including the identification of molecules involved in β-cell function that were not previously recognized as playing a role in this critical cell. [ABSTRACT FROM AUTHOR]
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- 2012
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4. A Diabetes Outcome Progression Trial (ADOPT): baseline characteristics of Type 2 diabetic patients in North America and Europe.
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Viberti, G., Lachin, J., Holman, R., Zinman, B., Haffner, S., Kravitz, B., Heise, M. A., Jones, N. P., O&'Neill, M. C., Freed, M. I., Kahn, S. E., and Herman, W. H.
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TYPE 2 diabetes ,DISEASE relapse ,HEMOGLOBINS ,PHENOTYPES ,PEOPLE with diabetes - Abstract
Aims To examine baseline characteristics of patients recruited into ADOPT, a multinational trial comparing three oral glucose-lowering monotherapies. Methods Between April 2000 and June 2002, 4360 patients aged 30–75 years with Type 2 diabetes diagnosed for < 3 years and remaining on diet therapy alone with fasting plasma glucose levels (FPG) between 7.0 and 10.0 mmol/l were enrolled by 488 North American and European centres. Medical histories, anthropometric data and laboratory measurements were determined using common methodologies. Results The mean (sd) age of the patients was 57 (10) years, body mass index 32.2 (6.4) kg/m
2 , HbA1c 7.4 (0.9)%; 58% were male, 88% Caucasian and 15% smoked. North American Caucasians (NAC) were younger, more obese, and more insulin resistant than European Caucasians (EUC), but had better pancreatic B-cell function. NAC had lower total, low-density lipoprotein- and high-density liporpotein-cholesterol concentrations with higher triglyceride concentrations and were more often on lipid-lowering treatment. They had lower blood pressure levels but were equally likely to be on antihypertensive treatment. Metabolic syndrome was more frequent and microalbuminuria less frequent in NAC. Within North America, NAC had lower HbA1c concentrations than Blacks, Hispanics and Asians despite similar or higher FPG and 30-min postchallenge glucose concentrations. Conclusions Caucasian North American and European ADOPT patients differ with respect to adiposity, insulin resistance and metabolic syndrome prevalence. North American Blacks, Hispanics and Asians had lower HbA1c concentrations than NAC despite similar or higher glucose concentrations. These phenotypic differences may influence the progression of Type 2 diabetes and the response to initial oral glucose-lowering monotherapy. [ABSTRACT FROM AUTHOR]- Published
- 2006
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5. Truncated (des-[27–31]) C-peptide is not a major secretory product of human islets Paoletta et al.: Truncated C-peptide in human islets.
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Paoletta, M., Kahn, S. E, and Halban, P. A.
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C-peptide ,TYPE 2 diabetes ,BLOOD plasma ,ISLANDS of Langerhans ,ENDOCRINE diseases ,DIABETES - Abstract
Aims/hypothesis. It has been suggested that C-peptide is bioactive and that such bioactivity is lost when the last five amino acids are removed. In rats, C-peptide is truncated in beta-cell granules leading to the loss of these last five residues and secretion of des-[27–31]-C-peptide. The aim of this study was to determine whether this truncated form of C-peptide was also a secretory product of human islets. Methods. Plasma from healthy subjects, patients with Type II (non-insulin-dependent) diabetes mellitus or insulinoma and cord blood was analysed by HPLC and ELISA. This method allows for separation and quantification of intact C-peptide and des-[27–31]-C-peptide. Human islets were pulse-chased and secretion stimulated by a mixture of secretagogues. Radioactive products secreted to the medium were analysed by HPLC and the relative amount of intact and truncated C-peptide measured. Results. The proportion of total C-peptide immunoreactivity comprised of des-[27–31]-C-peptide was 1.5% or less in all plasma samples, except for that from one patient with insulinoma where it was 4.2%. The proportion of radiolabelled des-[27–31]-C-peptide released from isolated islets was less than 1%. Conclusion/interpretation. In contrast to the situation in rats, des-[27–31]-C-peptide is not a major secretory product of human islets and its contribution to total circulating C-peptide is not increased in Type II diabetes or in patients with insulinoma. [ABSTRACT FROM AUTHOR]
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- 2002
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6. beta-cell dysfunction and failure in type 2 diabetes: potential mechanisms.
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Porte Jr., Daniel, Porte, D Jr, and Kahn, S E
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PANCREATIC beta cells ,TYPE 2 diabetes ,INSULIN ,SECRETION ,PROTEIN metabolism ,ANIMAL experimentation ,COMPARATIVE studies ,HYPERINSULINISM ,ISLANDS of Langerhans ,RESEARCH methodology ,MEDICAL cooperation ,MICE ,PROTEINS ,RESEARCH ,CYTOMETRY ,EVALUATION research ,PANCREATIC hormones - Abstract
Type 2 diabetes is characterized by a progressive loss of beta-cell function throughout the course of the disease. The pattern of loss is an initial defect in early or first-phase insulin secretion, followed by a decreasing maximal capacity of glucose to potentiate all nonglucose signals. Last, a defective steady-state and basal insulin secretion develops, leading to complete beta-cell failure requiring insulin treatment. This functional loss exceeds the expected impact of a 20-50% loss of beta-cells reported at autopsy, which has been associated with amyloid deposits. This review summarizes the nature of the amyloid deposition process and its association with disproportionate hyperproinsulinemia. It reviews recent studies in IAPP (islet-amyloid polypeptide, or amylin) transgenic mice developing islet amyloid deposits and hyperglycemia to suggest that the process of amyloid fibril formation impairs function early and leads to beta-cell failure and eventual death. Based on the known association of amyloid deposits and relative hyperproinsulinemia, it is hypothesized that fibril formation begins during impaired glucose tolerance after other factors cause the initial defects in early insulin secretion and insulin action. Thus, the process that leads to beta-cell loss is implicated in the deposition of amyloid and the late unrelenting progressive hyperglycemia now found in all patients despite current therapies. [ABSTRACT FROM AUTHOR]
- Published
- 2001
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7. beta-cell glucokinase deficiency and hyperglycemia are associated with reduced islet amyloid deposition in a mouse model of type 2 diabetes.
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Andrikopoulos, Sofianos, Verchere, C. Bruce, Andrikopoulos, S, Verchere, C B, Terauchi, Y, Kadowaki, T, and Kahn, S E
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PANCREATIC beta cells ,GLUCOKINASE ,HYPERGLYCEMIA ,TYPE 2 diabetes ,LABORATORY mice - Abstract
Type 2 diabetes is characterized by impaired beta-cell function, hyperglycemia, and islet amyloid deposition. The primary constituent of islet amyloid is the 37-amino acid beta-cell product called islet amyloid polypeptide (IAPP) or amylin. To study mechanisms of islet amyloid formation, we developed a transgenic mouse model that produces and secretes the amyloidogenic human IAPP (hIAPP) molecule and have shown that 81% of male transgenic mice develop islet amyloid after 14 months on a high-fat diet. To test whether impaired beta-cell function and hyperglycemia could enhance islet amyloid formation, we cross-bred our hIAPP transgenic mice with beta-cell glucokinase-knockout mice (GKKO) that have impaired glucose-mediated insulin secretion and fasting hyperglycemia. The resulting new (hIAPPxGKKO) line of mice had higher basal plasma glucose concentrations than the hIAPP transgenic mice at 3, 6, and 12 months of age (P < 0.05), as did GKKO mice compared with hIAPP transgenic mice at 6 and 12 months of age (P < 0.05). Basal plasma immunoreactive insulin (IRI) levels were lower in hIAPP x GKKO mice than in hIAPP transgenic mice at 6 months of age (P < 0.05). The area under the glucose curve in response to an intraperitoneal glucose challenge (1 g/kg body weight) was larger in hIAPPxGKKO mice than in hIAPP transgenic mice at 3, 6, and 12 months of age (P < 0.005) and in GKKO mice compared with hIAPP transgenic mice at 6 and 12 months of age (P < 0.005). The area under the IRI curve was lower in hIAPPxGKKO mice at 6 and 12 months of age (P < 0.05) than in hIAPP transgenic mice and in GKKO mice compared with hIAPP transgenic mice at 12 months of age (P < 0.05). Despite the presence of hyperglycemia, hIAPPxGKKO mice had a lower incidence (4 of 17 vs. 12 of 19, P < 0.05) and amount (0.40 +/- 0.24 vs. 1.2 +/- 0.3 arbitrary units, P < 0.05) of islet amyloid than hIAPP transgenic mice had. As expected, no islet amyloid was observed in GKKO mice lacking the hIAPP transgene (0 of 13). There was no difference in pancreatic content of IRI and hIAPP among the three groups of mice. Thus, despite the presence of impaired islet function and hyperglycemia, hIAPPxGKKO mice had a decreased incidence and quantity of islet amyloid. Therefore, our data suggest that impaired beta-cell glucose metabolism or hyperglycemia are not likely to contribute to islet amyloid formation in diabetes. Furthermore, this finding may explain the lack of progression of glycemia in patients with maturity-onset diabetes of the young. [ABSTRACT FROM AUTHOR]
- Published
- 2000
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8. Oophorectomy promotes islet amyloid formation in a transgenic mouse model of Type II diabetes.
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Kahn, S. E., Andrikopoulos, S., Verchere, C. B., Wang, F., Hull, R. L., and Vidal, J.
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TYPE 2 diabetes ,AMYLOID ,GLYCOPROTEINS ,OVARIECTOMY ,OVARIAN surgery ,TRANSGENIC mice ,TRANSGENIC animals ,DIABETES - Abstract
Aims/hypothesis. In Type II (non-insulin-dependent) diabetes mellitus, amyloid depletes islet mass. We previously found that 81 % of male human islet amyloid polypeptide (IAPP) transgenic mice but only 11 % of female mice developed islet amyloid, suggesting that either testosterone promotes or ovarian products protect against amyloid deposition.¶Methods. We did a bilateral oophorectomy or sham procedure in female human IAPP transgenic mice (n = 11 and n = 8, respectively) and in female non-transgenic mice (n = 7 and n = 9, respectively) at 6–8 weeks of age. Animals were followed for 1 year on a 9 % fat (w/w) diet. Before we killed them we measured, fasting plasma human IAPP and did an intraperitoneal glucose tolerance test. Pancreatic content of IAPP and immunoreactive insulin (IRI) were estimated and pancreata were analysed for islet amyloid.¶Results. No amyloid was detected in either the sham-operated transgenic mice or, as expected, in both groups of non-transgenic mice. In strong contrast, 7 of 11 (64 %) oophorectomized mice developed islet amyloid (p < 0.05). Amyloid deposition in the oophorectomized transgenic mice was not associated with any differences in incremental body weight, fasting human IAPP concentrations or glucose tolerance between the groups. Furthermore, pancreatic content of mouse IAPP, human IAPP and immunoreactive insulin did not differ between groups.¶Conclusion/interpretation. Oophorectomy is associated with an enhancement of islet amyloid formation in the absence of changes in glucose tolerance, circulating IAPP or pancreatic content of IRI, mouse or human IAPP. Thus, the early stages of islet amyloidogenesis seem to be independent of glucose tolerance, with ovarian products having a protective role. [Diabetologia (2000) 43: 1309–1312] [ABSTRACT FROM AUTHOR]
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- 2000
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9. Efficacy and Safety of SGLT2 Inhibitors in Pediatric Patients and Young Adults: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials.
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dos Santos Borges, Rafael, Conegundes, Ana Flávia, Haikal de Paula, Luiza, Lara Santos, Rodrigo, Alves, Samuel Norberto, Machado, Raquel Amaral, Bussolaro Viana, Isadora, Simões e Silva, Ana Cristina, and Al Khalifah, Reem
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MEDICAL information storage & retrieval systems ,PATIENT compliance ,PATIENT safety ,GLYCOSYLATED hemoglobin ,GLYCEMIC control ,META-analysis ,DESCRIPTIVE statistics ,SYSTEMATIC reviews ,MEDLINE ,SODIUM-glucose cotransporter 2 inhibitors ,DRUG efficacy ,TYPE 2 diabetes ,MEDICAL databases ,INFERENTIAL statistics ,ONLINE information services ,DATA analysis software ,CONFIDENCE intervals ,DRUGS ,ADOLESCENCE ,CHILDREN ,ADULTS - Abstract
Introduction: In recent decades, an increase in the incidence of type 2 diabetes mellitus (T2DM) in children and adolescents has been observed. Pediatric‐onset T2DM differs from the adult‐onset form, particularly regarding the durability of glycemic control and earlier appearance of complications. However, the scarcity of approved treatments and comprehensive studies on T2DM management in youth persists. Ongoing clinical trials seek to ascertain the efficacy and safety of sodium‐glucose cotransporter 2 inhibitors (SGLT2i) in patients aged between 10 and 24 years with T2DM. Therefore, we aimed to perform a meta‐analysis exploring the efficacy and safety of SGLT2i in pediatric patients and young adults with T2DM. Methods: We searched PubMed, Embase, Cochrane, and Web of Science for randomized controlled clinical trials on the efficacy and safety of SGLT2i in children, adolescents, and young adults with T2DM compared with placebo. Statistical analysis was performed using RevMan 5.4 and R statistical software 4.2.1. Heterogeneity was assessed with I2 statistics. Results: We included three studies totaling 334 patients followed for 37.79 weeks. Reduction in HbA1C (MD = −0.93; 95% CI = −1.36 to −0.49; p < 0.0001; I2 = 0%) was significantly higher in SGLT2i group compared with placebo. The proportion of patients requiring rescue or discontinuation of study medication due to lack of efficacy was statistically lower in SGLT2i group compared with placebo (RR = 0.64; 95% CI = 0.43–0.94; p = 0.02; I2 = 0%). SGLT2i and placebo were similar in terms of any adverse event (RR = 1.10; 95% CI = 0.96–1.27; p = 0.17; I2 = 0%), serious side effects (RR = 1.06; 95% CI = 0.44–2.57; p = 0.90; I2 = 0%), and individual adverse effects. Conclusion: In children, adolescents, and young adults with T2DM, SGLT2i appears to be effective and safe for glycemic control. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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10. Empagliflozin Use Is Associated With Lower Risk of All‐Cause Mortality, Hospitalization for Heart Failure, and End‐Stage Renal Disease Compared to DPP‐4i in Nordic Type 2 Diabetes Patients: Results From the EMPRISE (Empagliflozin Comparative Effectiveness and Safety) Study
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Langslet, Gisle, Nyström, Thomas, Vistisen, Dorte, Carstensen, Bendix, Grip, Emilie Toresson, Casajust, Paula, Tskhvarashvili, Giorgi, Hoti, Fabian, Klement, Riho, Karlsdotter, Kristina, Tuovinen, Mikko, Ofstad, Anne Pernille, Lajer, Maria, Shay, Christina, Koeneman, Lisette, Farsani, Soulmaz Fazeli, Niskanen, Leo, Halvorsen, Sigrun, and Infante, Marco
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TYPE 2 diabetes ,CONGESTIVE heart failure ,PROPORTIONAL hazards models ,CD26 antigen ,CHRONIC kidney failure ,HEART failure ,MYOCARDIAL infarction - Abstract
Objective: To evaluate the effectiveness of empagliflozin in reducing all‐cause mortality (ACM), hospitalization for heart failure (HHF), myocardial infarction (MI), stroke, cardiovascular mortality (CVM), and end‐stage renal disease (ESRD) in routine clinical practice in the Nordic countries of the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) study. Methods: This noninterventional, multicountry cohort study used secondary data from four Nordic countries (Denmark, Sweden, Finland, and Norway). Propensity score (PS) matched (1:1) adults with type 2 diabetes (T2D) initiating empagliflozin (a sodium‐glucose cotransporter‐2 inhibitor) during 2014–2018 who were compared to those initiating a dipeptidyl peptidase‐4 inhibitor (DPP‐4i). Cox proportional hazards regression modelling was used to assess the risk for ACM, HHF, MI, stroke, CVM, and ESRD. Meta‐analyses were conducted and hazard ratios (HRs) with 95% confidence intervals (CIs) from random‐effects models were calculated. Results: A total of 43,695 pairs of PS‐matched patients were identified. Patients initiating empagliflozin exhibited a 49% significantly lower risk of ACM (HR: 0.51, 95% CI 0.40–0.64) compared to DPP‐4i. Additionally, empagliflozin was associated with a 36% significantly lower risk of HHF (HR: 0.64, 95% CI 0.46–0.89), a 52% significantly lower risk of CVM (HR: 0.48, 95% CI 0.37–0.63), and a 66% significantly lower risk of ESRD (HR: 0.34, 95% CI 0.15–0.77) compared to DPP‐4i. No significant differences were observed in the risk of stroke and MI between patients initiating empagliflozin compared with those initiating a DPP‐4i. Results were generally consistent for subgroups (with/without pre‐existing CV disease or congestive heart failure) and in sensitivity analyses. Conclusion: Empagliflozin initiation was associated with a significantly reduced risk of ACM, HHF, CVM, and ESRD compared with initiation of DPP‐4i in patients with T2D when examining routine clinical practice data from Nordic countries. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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11. Tirzepatide's innovative applications in the management of type 2 diabetes and its future prospects in cardiovascular health.
- Author
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Jingqi Yang, Yuncheng Gu, Huaigang Chen, Hong Wang, Lang Hong, Bin Li, and Liu Yang
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TYPE 2 diabetes ,REGULATION of body weight ,BLOOD sugar ,CLINICAL trials ,CLINICAL medicine ,DIABETES complications - Abstract
Tirzepatide, a novel GLP-1/GIP dual receptor agonist, shows significant advantages in glycemic management and weight control. By summarizing the results of the SURMOUNT and SURPASS clinical trials, we evaluate the efficacy and safety of tirzepatide in reducing blood glucose and weight. These trials indicate that tirzepatide significantly lowers HbA1c levels (with a maximum reduction of 2.24%) and promotes weight loss (up to 11.2 kg) with good tolerability. However, there are still some challenges in its clinical application, including high treatment costs and gastrointestinal discomfort. Additionally, the safety and efficacy of tirzepatide in special populations, such as patients with renal impairment, require further investigation. Future large-scale clinical trials, such as SURPASS-CVOT and SUMMIT, are expected to further verify the long-term benefits of tirzepatide in cardiovascular health management, providing stronger evidence for its comprehensive treatment of diabetes and its complications. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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12. Two novel immortal pancreatic beta-cell lines expressing and secreting human islet amyloid polypeptide do not spontaneously develop islet amyloid.
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Andrikopoulos, Sofianos, Verchere, C. Bruce, Teague, Jeanette C., Howell, William M., Fujimoto, Wilfred Y., Wight, Thomas N., Kahn, Steven E., Andrikopoulos, S, Verchere, C B, Teague, J C, Howell, W M, Fujimoto, W Y, Wight, T N, and Kahn, S E
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PANCREATIC beta cells ,AMYLOID ,TYPE 2 diabetes - Abstract
Type 2 diabetes is characterized by islet amyloid deposits, which are primarily composed of the amyloidogenic human form of islet amyloid polypeptide (IAPP, amylin). The mechanism of islet amyloido-genesis is not known, but other products (e.g., apolipoprotein E and perlecan) contained within islet amyloid may be necessary. Because rodent IAPP does not form islet amyloid, the currently available beta-cell lines are not useful for studying processes involved in amyloid formation. To develop a suitable in vitro cell system for the study of islet amyloid formation, we generated two new beta-cell lines that express the amyloidogenic human IAPP. We did this by crossbreeding human IAPP transgenic mice with RIP-Tag mice that develop islet tumors and then culturing one of these islet tumors from two separate offspring of this cross. The resultant 2350-2C0 and 2511 cell lines produce human as well as mouse IAPP-like immunoreactivity (IAPP-LI) and immunoreactive insulin (IRI). Incubation of both these cell lines with 16.7 mmol/l glucose resulted in a two- to fourfold increase in human IAPP-LI, mouse IAPP-LI, and IRI secretion compared with 1.67 mmol/l glucose and the combination of 16.7 mmol/l glucose and 10 mmol/l arginine, 0.1 mmol/l 3-isobutyl-1-methylxanthine (IBMX), and 5 micromol/l carbachol induced a >50-fold increase in the release of these peptides. The omission of calcium from the above secretagogue cocktail reduced secretion of all three peptides to only two- to sixfold higher than the 16.7 mmol/l glucose condition. Perifusion with 16.7 mmol/l glucose plus 0.1 mmol/l IBMX caused a biphasic secretion of human IAPP-LI and mouse IAPP-LI, as well as IRI, in both cell lines, with the peak of the first phase being five- to sixfold higher than the prestimulated 1.67 mmol/l glucose condition. Immunoelectron microscopic inspection of both 2350-2C0 and 2511 cells after 7 days of culture did not reveal the presence of amyloid fibrils, suggesting the need for other critical components. We conclude that we have established two novel beta-cell lines that produce and secrete human IAPP in a regulated manner. These cell lines will be a useful tool to investigate the secretion of human IAPP as well as the necessity of other components for islet amyloid formation. [ABSTRACT FROM AUTHOR]
- Published
- 1999
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13. Autonomic modulation by SGLT2i or DPP4i in patients with diabetes favors cardiovascular outcomes as revealed by skin sympathetic nerve activity.
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Jien-Jiun Chen, Chen Lin, Men-Tzung Lo, Lian-Yu Lin, Hsiang-Chih Chang, and Geng-Chi Liu
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SODIUM-glucose cotransporters ,SODIUM-glucose cotransporter 2 inhibitors ,TYPE 2 diabetes ,AUTONOMIC nervous system ,CD26 antigen ,HEART beat - Abstract
Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i) are important second-line treatments for patients with type 2 diabetes mellitus (T2DM). Patients taking SGLT2i have favorable cardiovascular outcomes via various mechanisms, including autonomic nervous system (ANS) modulation. This study aimed to use neuroelectrocardiography (neuECG) to test the effects of SGLT2i or DPP4i on the ANS. Methods: Patients with T2DM, who did not reach target hemoglobin (Hb)A1C levels despite metformin treatment, were enrolled. SGLT2i or DPP4i were prescribed randomly unless a compelling indication was present. NeuECG and heart rate were recorded for 10 min before and after a 3-month treatment. The patients were treated according to standard practice and the obtained data for skin sympathetic nerve activity (SKNA) and ANS entropy were analyzed offline. Results: We enrolled 96 patients, of which 49 received SGLT2i and 47 received DPP4i. The baseline parameters were similar between the groups. No adverse event was seen during the study period. In the burst analysis of SKNA at baseline, all parameters were similar. After the 3-month treatment, the firing frequency was higher in SGLT2i group (0.104 ± 0.045 vs 0.083 ± 0.033 burst/min, p < 0.05), with increased long firing duration (7.34 ± 3.66 vs 5.906 ± 2.921, p < 0.05) in 3-s aSKNA scale; the other parameters did not show any significant change. By symbolic entropy, the most complex patterns (Rank 3) were found to be significantly higher in SGLT2i-treated patients than in DDP4i-treated group (0.084 ± 0.028 vs 0.07 ± 0.024, p = 0.01) and the direction of change in Rank 3, after SGLT2i treatment, was opposite to that observed in the DDP4i group (0.012 ± 0.036 vs. -0.005 ± 0.037, p = 0.024). Our findings demonstrated the favorable autonomic modulation by SGLTi and the detrimental effects of DPP4i on ANS. Conclusion: We demonstrated the autonomic modulation by SGLTi and DPP4i using SKNA in patients with DM, which might provide insights into the favorable outcomes of SGLT2i. Furthermore, we refined the analytical methods of neuECG, which uses SKNA to evaluate autonomic function. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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14. Advancements in glucagon-like peptide-1 receptor agonist therapy for type 2 diabetes.
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Yaping Peng and Ying Fu
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GLUCAGON-like peptide-1 receptor ,PEPTIDE receptors ,GLUCAGON-like peptide-1 agonists ,TYPE 2 diabetes ,MEDICAL personnel ,GLYCEMIC control - Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are novel hypoglycemic agents that have garnered widespread acceptance in the treatment of type 2 diabetes, largely attributed to their safety profile, potent hypoglycemic effects, and metabolic advantages. Their primary mechanisms of action encompass promoting insulin release, inhibiting glucagon secretion, bolstering pancreatic islet cell function, curbing appetite, and slowing gastric emptying. This article delves into the clinical evidence underscoring the efficacy of various GLP-1RAs. Notably, these agents have demonstrated marked improvements in glycemic control, significant weight reduction, and substantial cardiovascular and renal protection. Nonetheless, certain adverse effects of GLP-1RAs, such as pancreatitis and intestinal obstruction, have been reported, warranting vigilant monitoring by healthcare professionals. In sum, GLP-1RAs hold significant promise in the management of type 2 diabetes, offering notable cardiovascular and renal advantages. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Insulin Resistance, a Risk Factor for Alzheimer's Disease: Pathological Mechanisms and a New Proposal for a Preventive Therapeutic Approach.
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Affuso, Flora, Micillo, Filomena, and Fazio, Serafino
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DISEASE risk factors ,TYPE 2 diabetes ,INSULIN resistance ,ALZHEIMER'S disease ,SCIENTIFIC literature - Abstract
Peripheral insulin resistance (IR) is a well-documented, independent risk factor for the development of type 2 diabetes, cardiovascular disease, cancer and cellular senescence. Recently, the brain has also been identified as an insulin-responsive region, where insulin acts as regulator of the brain metabolism. Despite the clear link between IR and the brain, the exact mechanisms underlying this relationship remain unclear. Therapeutic intervention in patients showing symptoms of neurodegenerative diseases has produced little or no results. It has been demonstrated that insulin resistance plays a significant role in the pathogenesis of neurodegenerative diseases, particularly cognitive decline. Peripheral and brain IR may represent a modifiable state that could be used to prevent major brain disorders. In this review, we will analyse the scientific literature supporting IR as a risk factor for Alzheimer's disease and suggest some therapeutic strategies to provide a new proposal for the prevention of brain IR and its consequences. [ABSTRACT FROM AUTHOR]
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- 2024
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16. The Role of Fecal Microbiota Transplantation (FMT) in the Management of Metabolic Diseases in Humans: A Narrative Review.
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Zikou, Eva, Koliaki, Chrysi, and Makrilakis, Konstantinos
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GUT microbiome ,METABOLIC syndrome ,FECAL microbiota transplantation ,TYPE 2 diabetes ,WEIGHT loss ,METABOLIC disorders - Abstract
The gut microbiota represents a complex ecosystem of trillions of microorganisms residing in the human gastrointestinal tract, which is known to interact with the host physiology and regulate multiple functions. Alterations in gut microbial composition, diversity, and function are referred to as dysbiosis. Dysbiosis has been associated with a variety of chronic diseases, including Clostridioides difficile infections, but also cardiometabolic diseases, including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). The implication of gut microbiota dysbiosis in the pathogenesis of both obesity and T2DM has paved the way to implementing novel therapeutic approaches for metabolic diseases through gut microbial reconfiguration. These interventions include probiotics, prebiotics, and synbiotics, while a more innovative approach has been fecal microbiota transplantation (FMT). FMT is a procedure that delivers healthy human donor stool to another individual through the gastrointestinal tract, aiming to restore gut microbiota balance. Several studies have investigated this approach as a potential tool to mitigate the adverse metabolic effects of gut microbiota aberrations associated with obesity and T2DM. The aim of the present review was to critically summarize the existing evidence regarding the clinical applications of FMT in the management of obesity and T2DM and provide an update on the potential of this method to remodel the entire host microbiota, leading thus to weight loss and sustained metabolic benefits. Safety issues, long-term efficacy, limitations, and pitfalls associated with FMT studies are further discussed, emphasizing the need for further research and standardization in certain methodological aspects in order to optimize metabolic outcomes. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Growth differentiation factor 15 is not modified after weight loss induced by liraglutide in South Asians and Europids with type 2 diabetes mellitus.
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Hoekx, Carlijn A., Straat, Maaike E., Bizino, Maurice B., van Eyk, Huub J., Lamb, Hildebrandus J., Smit, Johannes W. A., Jazet, Ingrid M., de Jager, Saskia C. A., Boon, Mariëtte R., and Martinez‐Tellez, Borja
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GROWTH differentiation factors ,TYPE 2 diabetes ,SOUTH Asians ,WEIGHT loss ,METABOLIC disorders - Abstract
Glucagon‐like peptide‐1 receptor (GLP‐1R) agonists induce weight loss in patients with type 2 diabetes mellitus (T2DM), but the underlying mechanism is unclear. Recently, the mechanism by which metformin induces weight loss could be explained by an increase in growth differentiation factor 15 (GDF15), which suppresses appetite. Therefore, we aimed to investigate whether the GLP‐1R agonist liraglutide modifies plasma GDF15 levels in patients with T2DM. GDF15 levels were measured in plasma samples obtained from Dutch Europids and Dutch South Asians with T2DM before and after 26 weeks of treatment with daily liraglutide (n = 44) or placebo (n = 50) added to standard care. At baseline, circulating GDF15 levels did not differ between South Asians and Europids with T2DM. Treatment with liraglutide, compared to placebo, decreased body weight, but did not modify plasma GDF15 levels in all patients, or when data were split by ethnicity. Also, the change in plasma GDF15 levels after treatment with liraglutide did not correlate with changes in body weight or HbA1c levels. In addition, the dose of metformin used did not correlate with baseline plasma GDF15 levels. Compared to placebo, liraglutide treatment for 26 weeks does not modify plasma GDF15 levels in Dutch Europid or South Asian patients with T2DM. Thus, the weight loss induced by liraglutide is likely explained by other mechanisms beyond the GDF15 pathway. Highlights: What is the central question of this study?Growth differentiation factor 15 (GDF15) suppresses appetite and is increased by metformin: does the GLP‐1R agonist liraglutide modify plasma GDF15 levels in patients with type 2 diabetes mellitus (T2DM)?What is the main finding and its importance?Plasma GDF15 levels did not differ between South Asians and Europids with T2DM and were not modified by 26 weeks of liraglutide in either ethnicity. Moreover, there was no correlation between the changes in plasma GDF15 levels and dosage of metformin administered, changes in body weight or HbA1c levels. The appetite‐suppressing effect of liraglutide is likely exerted via pathways other than GDF15. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Association of dipeptidyl peptidase-4 inhibitor and recurrent pancreatitis risk among patients with type 2 diabetes: A retrospective cohort study.
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Yi-Sun Yang, Kornelius, Edy, Yu-Hsun Wang, Shih-Chan Lo, and Chien-Ning Huang
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PROPORTIONAL hazards models ,WARNINGS ,CD26 antigen ,TYPE 2 diabetes ,PANCREATITIS ,NATIONAL health insurance ,COHORT analysis - Abstract
Introduction: Following the introduction of incretin-based drugs to the market, instances of acute pancreatitis have been reported, leading the FDA to mandate a warning label. Incretin-based therapy has been linked to a rare yet significant adverse event known as acute pancreatitis. However, these concerns of use of incretin therapy remained an ongoing debate. Methods: This retrospective cohort study was extracted data from the National Health Insurance (NHI) program in Taiwan focused on those having prior hospitalization history of acute pancreatitis. We identified adult patients with type 2 diabetes, all patients who received new prescriptions one year after the diagnosis of hospitalization for acute pancreatitis for DPP-4 inhibitors (index date). Study participants were divided into two groups: those taking DPP-4 inhibitors (the DPP-4 inhibitors group, n=331) and those not taking DPP-4 inhibitors (the non-DPP-4 inhibitors group, n=918). The outcome of interest is the recurrence of hospitalization of acute pancreatitis. Results: The incidence density (per 1000 person-years) of acute pancreatitis was 23.16 for DPP-4 inhibitors group and 19.88 for non-DPP-4 inhibitor group. The relative risk is 0.86 (95% confidence interval (CI) 0.53-1.38). Results from the Cox proportional hazard model (HR) analysis, the DPP-4 inhibitor was associated with a neutral risk of acute pancreatitis HR 0.68; 95% CI: 0.42-1.09. Conclusions: In this extensive nationwide cohort study conducted in Taiwan, involving a substantial number of newly diagnosed cases, the utilization of DPP-4 inhibitors appears to show no significant correlation with an elevated risk of acute pancreatitis, even among diabetic patients deemed to be at a high risk. These results extend the safety reassurance of incretin-based therapy to individuals considered high-risk for such complications. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Insufficient Plasma Melatonin and Its Association With Neuropsychiatric Impairments in Patients With T2DM.
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He, Shuai, Yu, Yue, Chen, Peng-quan, Sun, Hui-min, Gao, Xin-ran, Sun, Huai-zhi, Ge, Jin-fang, and Yamagata, Kazuya
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TYPE 2 diabetes ,GLYCOSYLATED hemoglobin ,PEARSON correlation (Statistics) ,RECEIVER operating characteristic curves ,EXECUTIVE function - Abstract
Purpose: Type 2 diabetes mellitus (T2DM) is associated with multiple neuropsychiatric impairments, including cognitive dysfunction, and melatonin (MLT) plays a crucial role in maintaining normal neuropsychiatric functions. This study is aimed at investigating the change in plasma MLT levels and its association with neuropsychiatric impairments in T2DM patients. Methods: One hundred twenty‐six T2DM patients were recruited, and their demographics and clinical data were collected. Apart from the plasma glycated hemoglobin (HbA1c) levels and other routine metabolic indicators, the plasma concentrations of MLT, C‐reactive protein (CRP), Interleukin 6 (IL‐6), soluble myeloid triggered receptor 1 (sTREM 1), and receptor 2 (sTREM 2) were measured. Moreover, the executive function and depressive tendency were evaluated via the Behavior Rating Inventory of Executive Function‐Adult Version (BRIEF‐A) and the Epidemiological Research Center Depression Scale (CES‐D), respectively. Result: Compared with the low HbA1c group, the T2DM patients in the high HbA1c group presented lower plasma MLT levels but higher plasma concentrations of inflammatory biomarker levels, together with higher scores in the BRIEF‐A and CES‐D scales. Moreover, results of the Pearson correlation test showed that the plasma MLT levels were negatively correlated with the BRIEF‐A and CES‐D scores, as well as plasma concentrations of HbA1c and inflammatory indications, indicating that MLT may mediate their neuroinflammation and neuropsychiatric impairments. Furthermore, the ROC curve results indicated that plasma MLT levels have a predictive effect on executive impairment and depressive status in T2DM patients. Conclusion: MLT levels decreased in patients with T2DM and were associated with neuropsychiatric impairments and inflammatory status, and MLT might be developed as a therapeutic agent and predictive indicator for T2DM‐associated executive impairment and depression status. [ABSTRACT FROM AUTHOR]
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- 2024
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20. High-Intensity Interval Versus Moderate-Intensity Continuous Exercise Training on Glycemic Control, Beta Cell Function, and Aerobic Fitness in Women with Type 2 Diabetes.
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Niyazi, Arghavan, Yasrebi, Seyed Mohammad Ali, Yazdanian, Mohtaram, and Mohammad Rahimi, Gholam Rasul
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LIPID analysis ,ANALYSIS of triglycerides ,BLOOD sugar analysis ,EXERCISE physiology ,CARDIOPULMONARY fitness ,HIGH density lipoproteins ,REPEATED measures design ,GLYCOSYLATED hemoglobin ,ADIPOSE tissues ,BODY mass index ,COMPUTER software ,FOOD consumption ,T-test (Statistics) ,DATA analysis ,HIGH-intensity interval training ,PANCREATIC beta cells ,GLYCEMIC control ,EXERCISE therapy ,SEDENTARY lifestyles ,BODY composition ,BLOOD collection ,ENZYME-linked immunosorbent assay ,INSULIN ,RANDOMIZED controlled trials ,INSULIN resistance ,WAIST circumference ,LOW density lipoproteins ,PRE-tests & post-tests ,TYPE 2 diabetes ,CHOLESTEROL ,ONE-way analysis of variance ,STATISTICS ,WOMEN'S health ,OXYGEN consumption ,FOOD diaries ,DATA analysis software - Abstract
Objective: This study aimed to compare the effects of High-Intensity Interval Training (HIIT) and Moderate-Intensity Continuous Training (MICT) on glycemic control, beta-cell function, and aerobic fitness in women with Type 2 Diabetes Mellitus (T2DM). Methods: Thirty-six women with T2DM were assigned equally to HIIT, MICT, and control (CON) groups. Participants in the exercise cohorts underwent a 12-week training regimen (three sessions per week), while the CON group maintained an inactive lifestyle. Glycaemia variables, beta-cell function, maximal oxygen uptake (VO
2max ), lipid profiles, and body composition were assessed at baseline and post-intervention. Results: Both HIIT and MICT interventions led to significant improvements in glucose, insulin, HbA1c, and insulin resistance index. Moreover, visceral adiposity index (VAI), lipid accumulation product (LAP), total cholesterol (TC), and low-density lipoprotein (LDL) levels significantly decreased in the HIIT and MICT groups after 12 weeks. Triglyceride (TG) levels decreased only after MICT, while high-density lipoprotein (HDL) levels increased after both interventions. Maximal oxygen uptake (VO2max ), body mass, body mass index (BMI), and waist circumference (WC) significantly improved in all exercise groups. Notably, the HIIT group showed greater reductions in body mass compared to MICT. Nevertheless, beta-cell function remained unaltered after these two exercise regimens. Conclusion: Both HIIT and MICT interventions effectively managed T2DM in women, regardless of exercise intensity. The HIIT regimen can be considered for time-efficient lifestyle interventions in people with T2DM. [ABSTRACT FROM AUTHOR]- Published
- 2024
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21. Evaluation of the auditory brainstem response test in patients with type 2 diabetes mellitus.
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Sheikhzadeh, Mahbubeh, Bagheri, Fereshteh, Bayani, Mohammad Ali, Kami, Milad, and Monadi, Mohsen
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TYPE 2 diabetes ,WORD deafness ,BRAIN stem ,DIABETES complications ,PEOPLE with diabetes - Abstract
Background: Hearing loss is an unknown complication of diabetes mellitus (DM). The aim of this study was to evaluate hearing function using auditory brainstem response (ABR) in diabetic patients. Methods: The present case-control study was performed on thirty diabetic patients as a case group and thirty healthy individuals as a control group. Baseline demographic information, HbA1c level, and duration of diabetes were obtained from all diabetic patients. In all subjects, the ABR and pure-tone audiometry (PTA) tests were performed and the results were analyzed using the t-test and logistic regression. Results: The absolute latency of I was significantly lower in diabetes patients. The absolute latency of III and the interpeak latencies (IPL) I-III were significantly higher in diabetic patients. No significant relationship was noticed in the absolute latency of V and the IPL I-V among diabetic patients in the right and left ears (P>0.05). Conclusion: The results of this study suggested that diabetes may cause central auditory dysfunction manifested on the absolute latency of III, the IPL I-III and III-V. [ABSTRACT FROM AUTHOR]
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- 2024
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22. Therapy of Type 2 Diabetes.
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Landgraf, Rüdiger, Aberle, Jens, Birkenfeld, Andreas L., Gallwitz, Baptist, Kellerer, Monika, Klein, Harald H., Müller-Wieland, Dirk, Nauck, Michael A., Wiesner, Tobias, and Siegel, Erhard
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DIABETIC nephropathies ,HEART failure ,TYPE 2 diabetes ,TYPE 1 diabetes ,MEDICAL personnel ,SODIUM-glucose cotransporter 2 inhibitors ,MEDICAL societies - Abstract
GLP-1 receptor agonists and SGLT-2 inhibitors has shown positive effects on HbA1c, body weight, and blood pressure in patients with type 2 diabetes. Insulin therapy can be delayed in many cases and can be combined with other antidiabetic medications when necessary. Basal insulin analogues, such as insulin degludec and insulin glargine 300, have been effective in controlling blood glucose levels with lower rates of hypoglycemia. Biosimilar insulin glargine 100 has similar pharmacokinetics and dynamics to the original insulin glargine 100. Insulin icodec, a weekly injection insulin analogue, has shown comparable safety and efficacy to insulin glargine U 100. [Extracted from the article]
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- 2024
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23. Intermuscular adipose tissue accumulation is associated with higher tissue sodium in healthy individuals.
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Ertuglu, Lale A., Sahinoz, Melis, Alsouqi, Aseel, Deger, Serpil Muge, Guide, Andrew, Pike, Mindy, Robinson‐Cohen, Cassianne, Akwo, Elvis, Pridmore, Michael, Crescenzi, Rachelle, Madhur, Meena S., Kirabo, Annet, Harrison, David G., Luft, Friedrich C., Titze, Jens, Ikizler, T. Alp, and Gamboa, Jorge L.
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ADIPOSE tissues ,SODIUM ,TYPE 2 diabetes ,INSULIN sensitivity ,CHRONIC kidney failure - Abstract
Background and Aims: High tissue sodium accumulation and intermuscular adipose tissue (IMAT) are associated with aging, type 2 diabetes, and chronic kidney disease. In this study, we aim to investigate whether high lower‐extremity tissue sodium accumulation relates to IMAT quantity and whether systemic inflammatory mediators and adipocytokines contribute to such association. Methods: Tissue sodium content and IMAT accumulation (percentage of IMAT area to muscle area) were measured in 83 healthy individuals using sodium imaging (23Na‐MRI) and proton (1H‐MRI) imaging of the calf. Insulin sensitivity was assessed by glucose disposal rate (GDR) measured with the hyperinsulinemic‐euglycemic clamp. Results: Median (interquartile range) muscle and skin sodium contents were 16.6 (14.9, 19.0) and 12.6 (10.9, 16.7) mmol/L, respectively. Median IMAT was 3.69 (2.80, 5.37) %. In models adjusted for age, sex, BMI, GDR, adiponectin, and high‐sensitivity C‐reactive protein, increasing tissue sodium content was significantly associated with higher IMAT quantity (p = 0.018 and 0.032 for muscle and skin tissue sodium, respectively). In subgroup analysis stratified by sex, skin sodium was significantly associated with IMAT only among men. In interaction analysis, the association between skin sodium and IMAT was greater with increasing levels of high‐sensitivity C‐reactive protein and interleukin‐6 (p for interaction = 0.022 and 0.006, respectively). Conclusions: Leg muscle and skin sodium are associated with IMAT quantity among healthy individuals. The relationship between skin sodium and IMAT may be mediated by systemic inflammation. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, anti-diabetic drugs in heart failure and cognitive impairment: potential mechanisms of the protective effects.
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Riemma, Maria Antonietta, Mele, Elena, Donniacuo, Maria, Telesca, Marialucia, Bellocchio, Gabriella, Castaldo, Giuseppe, Rossi, Francesco, De Angelis, Antonella, Cappetta, Donato, Urbanek, Konrad, and Berrino, Liberato
- Subjects
GLUCAGON-like peptide-1 receptor ,SODIUM-glucose cotransporters ,SODIUM-glucose cotransporter 2 inhibitors ,GLUCAGON-like peptide-1 agonists ,HEART failure ,COGNITION disorders ,EXCITATORY amino acids - Abstract
Heart failure and cognitive impairment emerge as public health problems that need to be addressed due to the aging global population. The conditions that often coexist are strongly related to advancing age and multimorbidity. Epidemiological evidence indicates that cardiovascular disease and neurodegenerative processes shares similar aspects, in term of prevalence, age distribution, and mortality. Type 2 diabetes increasingly represents a risk factor associated not only to cardiometabolic pathologies but also to neurological conditions. The pathophysiological features of type 2 diabetes and its metabolic complications (hyperglycemia, hyperinsulinemia, and insulin resistance) play a crucial role in the development and progression of both heart failure and cognitive dysfunction. This connection has opened to a potential new strategy, in which new classes of anti-diabetic medications, such as glucagon-like peptide-1 receptor (GLP-1R) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, are able to reduce the overall risk of cardiovascular events and neuronal damage, showing additional protective effects beyond glycemic control. The pleiotropic effects of GLP-1R agonists and SGLT2 inhibitors have been extensively investigated. They exert direct and indirect cardioprotective and neuroprotective actions, by reducing inflammation, oxidative stress, ions overload, and restoring insulin signaling. Nonetheless, the specificity of pathways and their contribution has not been fully elucidated, and this underlines the urgency for more comprehensive research. [ABSTRACT FROM AUTHOR]
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- 2024
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25. Improving glycemic control: transitioning from dulaglutide to tirzepatide in patients with type 2 diabetes undergoing hemodialysis.
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Emiko Otsuka, Mineaki Kitamura, Satoshi Funakoshi, Hiroshi Mukae, and Tomoya Nishino
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GLYCEMIC control ,TYPE 2 diabetes ,GLUCAGON-like peptide-1 receptor ,INSULIN ,GASTRIC inhibitory polypeptide ,CONTINUOUS glucose monitoring ,PEPTIDE receptors - Abstract
Background: Tirzepatide--a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist--is used to treat type 2 diabetes. However, the efficacy and safety of tirzepatide in patients undergoing hemodialysis remain unclear. Methods: We conducted a single-center retrospective study of patients with type 2 diabetes undergoing hemodialysis who were transitioned from dulaglutide to tirzepatide. We continuously monitored glucose levels in patients undergoing hemodialysis before and after switching from dulaglutide to tirzepatide. Results: Fourteen patients (mean age: 61.9 ± 9.9 years, male: female = 11:3) were included in this study. After switching to tirzepatide, time in range increased to 50.8% from 42.7% (p = 0.02), time above range decreased to 37.8% from 48.4% (p = 0.02), and mean glucose levels decreased to 137.4 mg/dL from 156.6 mg/dL (p = 0.006). In contrast, there was no significant difference in time below range before and after tirzepatide administration (11.3% and 8.9%) (p = 0.75). Three patients experienced dyspepsia (21.4%), and one patient experienced nausea (7.1%); however, no critical adverse events were reported. Conclusion: Transitioning from dulaglutide to tirzepatide improved glycemic control without increasing hypoglycemia in patients undergoing hemodialysis for type 2 diabetes. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Identification of common genes and pathways between type 2 diabetes and COVID-19.
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Ya Wang, Kai Li, Shuangyang Mo, Peishan Yao, Jiaxing Zeng, Shunyu Lu, and Shanyu Qin
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TYPE 2 diabetes ,GENE regulatory networks ,COVID-19 ,GENE expression ,RECEIVER operating characteristic curves ,GENES - Abstract
Background: Numerous studies have reported a high incidence and risk of severe illness due to coronavirus disease 2019 (COVID-19) in patients with type 2 diabetes (T2DM). COVID-19 patients may experience elevated or decreased blood sugar levels and may even develop diabetes. However, the molecular mechanisms linking these two diseases remain unclear. This study aimed to identify the common genes and pathways between T2DM and COVID-19. Methods: Two public datasets from the Gene Expression Omnibus (GEO) database (GSE95849 and GSE164805) were analyzed to identify differentially expressed genes (DEGs) in blood between people with and without T2DM and COVID-19. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the common DEGs. A proteinprotein interaction (PPI) network was constructed to identify common genes, and their diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analysis. Validation was performed on the GSE213313 and GSE15932 datasets. A gene co-expression network was constructed using the GeneMANIA database to explore interactions among core DEGs and their coexpressed genes. Finally, a microRNA (miRNA)-transcription factor (TF)-messenger RNA (mRNA) regulatory network was constructed based on the common feature genes. Results: In the GSE95849 and GSE164805 datasets, 81 upregulated genes and 140 downregulated genes were identified. GO and KEGG enrichment analyses revealed that these DEGs were closely related to the negative regulation of phosphate metabolic processes, the positive regulation of mitotic nuclear division, T-cell co-stimulation, and lymphocyte co-stimulation. Four upregulated common genes (DHX15, USP14, COPS3, TYK2) and one downregulated common feature gene (RIOK2) were identified and showed good diagnostic accuracy for T2DM and COVID-19. The AUC values of DHX15, USP14, COPS3, TYK2, and RIOK2 in T2DM diagnosis were 0.931, 0.917, 0.986, 0.903, and 0.917, respectively. In COVID-19 diagnosis, the AUC values were 0.960, 0.860, 1.0, 0.9, and 0.90, respectively. Validation in the GSE213313 and GSE15932 datasets confirmed these results. The miRNA-TFmRNA regulatory network showed that TYH2 was targeted by PITX1, PITX2, CRX, NFYA, SREBF1, RELB, NR1L2, and CEBP, whereas miR-124-3p regulates THK2, RIOK2, and USP14. Conclusion: We identified five common feature genes (DHX15, USP14, COPS3, TYK2, and RIOK2) and their co-regulatory pathways between T2DM and COVID-19, which may provide new insights for further molecular mechanism studies. [ABSTRACT FROM AUTHOR]
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- 2024
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27. Ziabetus (Prediabetes): A Harbinger of Critical Stage in the Continuum of Glucose Metabolism Disorder: A Review.
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Afzal, Rafat, Sultana, Asia, Shoaib, Mohammad, and Ashraf, Hamid
- Subjects
GLUCOSE metabolism disorders ,TYPE 2 diabetes ,PREDIABETIC state ,MUSCLE cramps ,DRUG toxicity ,INSULIN resistance ,DISEASE complications - Abstract
Background: Prediabetes is a metabolic condition characterized by blood glucose levels higher than normal but below the threshold for diabetes mellitus. It represents a critical stage in the progression towards type 2 diabetes mellitus (T2DM) and is associated with an increased risk of cardiovascular disease and other complications. The two major pathophysiologic defects responsible for losing glucose tolerance are insulin resistance and β-cell glucose insensitivity, both appearing in subjects of Intermediate Hyperglycaemia. In classical literature, Unani physicians have described the initial symptoms and factors leading to the pathology, the risk factors are described in terms of ‘Su-e-mizaj’ as per the concept of Tibb. So, it is considered in the context of Ziabetus which is described as a disease that develops due to Sue-mizaj haar (abnormal hot temperament). The symptoms mentioned in Unani medicine are increased frequency of micturition (ants and flies are attracted to urine), increased thirst, nocturia, dryness of mouth and whole body, fatigue, loss of weight, malaise, and cramps in lower extremities. The modern drug-based approach for the management of Intermediate Hyperglycaemia is associated with inherent drawbacks, including toxicity, tolerability, cost, and efficacy.Objective: The purpose of this review is to provide an in-depth understanding of prediabetes concerning the classical literature of Greek medicine based on the analysis of certain parameters like etiopathophysiology, current diagnostic criteria, risk factors, and evidence-based management strategies. By synthesizing findings from epidemiological studies, and clinical trials, this paper aims to enhance understanding of prediabetes and facilitate effective preventive measures and interventions [ABSTRACT FROM AUTHOR]
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- 2024
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28. The role of thrombolytic protein therapy in the prevention of microvascular complications in non-insulin-dependent diabetes mellitus: an integrative approach.
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Alnahdi, Haifa Munif and Issa Mohammed, Yasser Hussein
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TYPE 2 diabetes ,THROMBOLYTIC therapy ,NEOVASCULARIZATION ,BIOINFORMATICS ,SINGLE nucleotide polymorphisms - Abstract
Non-Insulin-Dependent Diabetes Mellitus (NIDDM) is associated with an increased risk of microvascular complications. Thrombolytic protein therapy may help prevent these complications, but its efficacy remains unclear. We aimed to comprehensively evaluate the role of thrombolytic protein therapy in preventing microvascular complications in NIDDM patients through an integrated analysis of bioinformatics and clinical data. A retrospective cohort study design was utilized. Bioinformatics analysis included transcriptomic profiling, single-nucleotide polymorphism identification, and predictive modeling. Clinical parameters involving patient demographics, medical history, and lab results were collected and analyzed. Transcriptomic analysis identified differentially expressed genes related to microvascular complications, including ABCA1, MMP9, VEGFA, and FN1. Pathway enrichment analysis revealed associations with blood vessel development, extracellular matrix organization, inflammation, and angiogenesis pathways. Single-nucleotide polymorphism analysis identified genetic variants associated with complications. Predictive models achieved high accuracy, sensitivity, and specificity in forecasting individual thrombolytic therapy responses. Clinical data provided insights into population characteristics and comorbidities. The results provide evidence that thrombolytic protein therapy may help prevent microvascular complications in NIDDM patients by modulating molecular pathways and genetic risks. Bioinformatics-guided predictive modeling shows promise for personalized treatment. Further research is needed to validate these findings and optimize thrombolytic protein therapy approaches. [ABSTRACT FROM AUTHOR]
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- 2024
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29. Evaluating the effectiveness of a novel somatostatin receptor 2 antagonist, ZT-01, for hypoglycemia prevention in a rodent model of type 2 diabetes.
- Author
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D’Souza, Ninoschka C., Aiken, Julian A., Hoffman, Emily G., Atherley, Sara C., Champsi, Sabrina, Aleali, Nadia, Shakeri, Dorsa, El-Zahed, Maya, Akbarian, Nicky, Nejad-Mansouri, Mehran, Bavani, Parinaz Z., Liggins, Richard L., Chan, Owen, and Riddell, Michael C.
- Subjects
TYPE 2 diabetes ,INSULIN aspart ,SOMATOSTATIN receptors ,INSULIN ,HYPOGLYCEMIA ,TYPE 1 diabetes ,INSULIN resistance ,GLUCOSE tolerance tests - Abstract
Background: Elevated levels of somatostatin blunt glucagon counterregulation during hypoglycemia in type 1 diabetes (T1D) and this can be improved using somatostatin receptor 2 (SSTR2) antagonists. Hypoglycemia also occurs in latestage type 2 diabetes (T2D), particularly when insulin therapy is initiated, but the utility of SSTR2 antagonists in ameliorating hypoglycemia in this disease state is unknown. We examined the efficacy of a single-dose of SSTR2 antagonists in a rodent model of T2D. Methods: High-fat fed (HFF), low dose streptozotocin (STZ, 35 mg/kg)-induced T2D and HFF only, nondiabetic (controls-no STZ) rats were treated with the SSTR2 antagonists ZT-01/PRL-2903 or vehicle (n = 9–11/group) 60 min before an insulin tolerance test (ITT; 2–12 U/kg insulin aspart) or an oral glucose tolerance test (OGTT; 2 g/kg glucose via oral gavage) on separate days. Results: This rodent model of T2D is characterized by higher baseline glucose and HbA1c levels relative to HFF controls. T2D rats also had lower c-peptide levels at baseline and a blunted glucagon counterregulatory response to hypoglycemia when subjected to the ITT. SSTR2 antagonists increased the glucagon response and reduced incidence of hypoglycemia, which was more pronounced with ZT01 than PRL-2903. ZT-01 treatment in the T2D rats increased glucagon levels above the control response within 60 min of dosing, and values remained elevated during the ITT (glucagon Cmax: 156 ± 50 vs. 77 ± 46 pg/mL, p < 0.01). Hypoglycemia incidence was attenuated with ZT-01 vs. controls (63% vs. 100%) and average time to hypoglycemia onset was also delayed (103.1 ± 24.6 vs. 66.1 ± 23.6 min, p < 0.05). ZT-01 administration at the OGTT onset increased the glucagon response without exacerbating hyperglycemia (2877 ± 806 vs. 2982 ± 781), potentially due to the corresponding increase in c-peptide levels (6251 ± 5463 vs. 14008 ± 5495, p = 0.013). Conclusion: Treatment with SSTR2 antagonists increases glucagon responses in a rat model of T2D and results in less hypoglycemia exposure. Future studies are required to determine the best dosing periods for chronic SSTR2 antagonism treatment in T2D. [ABSTRACT FROM AUTHOR]
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- 2024
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30. Lab-on-chip technologies for exploring the gut–immune axis in metabolic disease.
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Wheeler, Alexandra E., Stoeger, Verena, and Owens, Róisín M.
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METABOLIC disorders ,TYPE 2 diabetes ,CELLULAR inclusions - Abstract
The continued rise in metabolic diseases such as obesity and type 2 diabetes mellitus poses a global health burden, necessitating further research into factors implicated in the onset and progression of these diseases. Recently, the gut–immune axis, with diet as a main regulator, has been identified as a possible role player in their development. Translation of conventional 2D in vitro and animal models is however limited, while human studies are expensive and preclude individual mechanisms from being investigated. Lab-on-chip technology therefore offers an attractive new avenue to study gut–immune interactions. This review provides an overview of the influence of diet on gut–immune interactions in metabolic diseases and a critical analysis of the current state of lab-on-chip technology to study this axis. While there has been progress in the development of "immuno-competent" intestinal lab-on-chip models, with studies showing the ability of the technology to provide mechanical cues, support longer-term co-culture of microbiota and maintain in vivo-like oxygen gradients, platforms which combine all three and include intestinal and immune cells are still lacking. Further, immune cell types and inclusion of microenvironment conditions which enable in vivo-like immune cell dynamics as well as host-microbiome interactions are limited. Future model development should focus on combining these conditions to create an environment capable of hosting more complex microbiota and immune cells to allow further study into the effects of diet and related metabolites on the gut–immune ecosystem and their role in the prevention and development of metabolic diseases in humans. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Distinguishing islet amyloid polypeptide fibril structures with infrared isotope-label spectroscopy.
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Saxena, Vishesh, Steendam, Ruben, and Jansen, Thomas L. C.
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AMYLIN ,INFRARED spectroscopy ,INFRARED spectra ,TYPE 2 diabetes ,INFRARED absorption ,VIBRATIONAL spectra - Abstract
Here, we performed spectral simulations of the amide-I vibrational spectra for three proposed fibril structures of the human islet amyloid polypeptide, which is involved in type II diabetes. We modeled both the overall absorption and two-dimensional infrared spectra for these structures. We further analyzed the isotope-labeled spectra, including the variation between structures. The analysis suggests that the infrared spectra of the cryo-electron microscopy structure provide the best match with experimental data. We further simulated isotope-labeled dilution spectroscopy investigating the correlation between the predicted spectral peak shift and the coupling between the amide units. While this correlation works in most cases, failures were observed when the isotope-labeled spectra were broad compared to the coupling or exhibited structure. These findings will be useful in the quest for potential toxic fibril formation intermediates. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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32. Exosomes as Emerging Regulators of Immune Responses in Type 2 Diabetes Mellitus.
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Zheng, Wei, Ji, Xin, Yin, Qiao qiao, Wu, Chensi, Xu, Chengan, Pan, Hongying, and Wu, Chun
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TYPE 2 diabetes ,METABOLIC disorders ,EXOSOMES ,IMMUNE response ,EXTRACELLULAR vesicles ,CELL communication - Abstract
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood glucose levels resulting from insulin resistance and impaired insulin secretion. Immune dysregulation-mediated chronic low-grade inflammation is a critical factor that poses a significant risk to the metabolic disorders of T2DM and its related complications. Exosomes, as small extracellular vesicles secreted by various cells, have emerged as essential regulators of intercellular communication and immune regulation. In this review, we summarize the current understanding of the role of exosomes derived from immune and nonimmune cells in modulating immune responses in T2DM by regulating immune cell functions and cytokine production. More importantly, we suggest potential strategies for the clinical applications of exosomes in T2DM management, including biomarkers for disease diagnosis and monitoring, exosome-based therapies for drug delivery vehicles, and targeted therapy for exosomes. [ABSTRACT FROM AUTHOR]
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- 2024
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33. Fecal Microbiota Transplantation: A Prospective Treatment for Type 2 Diabetes Mellitus.
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Zhou, Xiaolan, Chen, Rumeng, Cai, Yichen, and Chen, Qiu
- Subjects
TYPE 2 diabetes ,FECAL microbiota transplantation ,SHORT-chain fatty acids ,INSULIN ,MACROPHAGE colony-stimulating factor ,TRIMETHYLAMINE oxide ,METABOLIC disorders ,BILE acids - Abstract
Purpose of Review: The aim of this review is to summarize the role of gastrointestinal microbiome (GM) in the development of type 2 diabetes mellitus (T2DM). Besides, we discuss the feasibility of applying FMT in the treatment of T2DM and propose a series of processes to refine the use of FMT in the treatment of T2DM. Recent Findings: T2DM is a metabolic disease which is connected with the GM. According to many researches, GM can produce a variety of metabolites such as bile acid, short chain fatty acids, lipopolysaccharides and trimethylamine oxide which play an important role in metabolism. FMT is a method to regulate GM and has been observed to be effective in the treatment of metabolic diseases such as T2DM in some mouse models and people. However, there is still a lack of direct evidence for the use of FMT in the treatment of T2DM, and the process of FMT is not standardized. Summary: Dysregulation of GM is closely related to the development of T2DM. Promoting the conversion of GM in T2DM patients to normal population through FMT can reduce insulin resistance and lower their blood glucose level, which is an optional treatment for T2DM patients in the future. At present, the feasibility and limitations of applying FMT to the treatment of T2DM need to be further studied. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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34. Racial/ethnic and socioeconomic disparities in achievement of treatment goals within a clinical trial: a secondary analysis of the ACCORD trial.
- Author
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Cromer, Sara J., Thaweethai, Tanayott, and Wexler, Deborah J.
- Abstract
Aims/hypothesis: Clinical trial participation should theoretically reduce barriers to care by ensuring medication and healthcare access. We aimed to evaluate disparities in achieving diabetes treatment targets by race/ethnicity and educational attainment within the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (ClinicalTrials.gov NCT00000620). Methods: The ACCORD trial included three interventions of varying participant burden: glycaemic (high burden), blood pressure (medium burden) and triglyceride-lowering (low burden). We examined adjusted odds ratios (aORs) for achievement of glycaemic targets, blood pressure targets and a ≥25% reduction in triglyceride levels (a proxy for adherence to fenofibrate therapy) in the first year, and for hypoglycaemia requiring medical assistance at any time, by treatment arm, race/ethnicity and educational attainment using multivariable models adjusted for demographics and clinical characteristics. We explored whether disparities in glycaemic goal achievement were mediated by hypoglycaemia, medication use, change in BMI or number of study visits attended. Results: Compared with White participants, participants who identified as Black, Hispanic and Other race/ethnicity were less likely to achieve glycaemic targets (aOR [95% CI]) 0.63 [0.55,0.71], 0.73 [0.61, 0.88], 0.82 [0.71, 0.96], respectively); Black participants but not Hispanic and Other race/ethnicity participants were less likely to achieve blood pressure targets (aOR [95% CI] 0.77 [0.65, 0.90], 1.01 [0.78, 1.32], 1.01 [0.81, 1.26], respectively); and Black, Hispanic and Other race/ethnicity participants were equally or more likely to achieve triglyceride reduction (aOR [95% CI] 1.77 [1.38, 2.28], 1.34 [0.98, 1.84], 1.43 [1.10, 1.85], respectively). Differences in goal achievement by educational attainment were generally not significant after adjusting for baseline characteristics. Rates of hypoglycaemia requiring medical assistance were highest among Black individuals and those with lower educational attainment. Associations between race/ethnicity and glycaemic control were partially mediated by differences in insulin dosing and oral medication use. Conclusions/interpretation: Racially/ethnically minoritised participants in the ACCORD trial were less likely to achieve high-burden (glycaemic) treatment goals but were generally similarly likely to achieve goals of less intensive interventions. Differences in glycaemic treatment goal achievement were partially mediated by differences in medication use but not mediated by hypoglycaemia, change in BMI or study visit attendance. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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35. Incidence Trends of Type 2 Diabetes Mellitus, Medication-Induced Diabetes, and Monogenic Diabetes in Canadian Children, Then (2006–2008) and Now (2017–2019).
- Author
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Patel, Trisha J., Ayub, Aysha, Bone, Jeffrey N., Hadjiyannakis, Stasia, Henderson, Mélanie, Nour, Munier A., Pinto, Teresa E., Wicklow, Brandy, Hamilton, Jill K., Sellers, Elizabeth A. C., and Amed, Shazhan
- Subjects
GENETICS of diabetes ,DIABETES ,TYPE 2 diabetes ,COMPARATIVE studies ,SYMPTOMS ,QUESTIONNAIRES ,DESCRIPTIVE statistics ,LONGITUDINAL method ,CHILDREN - Abstract
Introduction. The landscape of childhood diabetes has evolved and addressing the knowledge gaps in non-Type 1 diabetes mellitus are key to accurate diagnosis. Objectives. A national surveillance study was completed between 2006 and 2008 and then repeated between 2017 and 2019 to describe Canadian incidence trends and clinical characteristics of non-Type 1 diabetes mellitus. Methods. We prospectively tracked new cases of non-Type 1 diabetes mellitus in children <18 years of age between June 1, 2017 and May 31, 2019. For each reported new case, a detailed questionnaire was completed, and cases were classified as Type 2 diabetes mellitus, medication-induced diabetes (MID), monogenic diabetes, or "indeterminate." Minimum incidence rates and 10-year incidence trends of non-Type 1 diabetes mellitus and its subtypes were calculated. Results. 441 cases of non-Type 1 diabetes mellitus were included (Type 2 diabetes mellitus = 332; MID = 52; monogenic diabetes = 30; indeterminate = 27). Compared to 10 years ago, the incidence of MID and monogenic diabetes remained stable, while Type 2 diabetes mellitus increased by 60% (p < 0.001) overall and by 37% (p = 0.005) and 50% (p = 0.001) in females and males, respectively. Type 2 diabetes mellitus incidence increased by 1.5 times in Indigenous (p < 0.001) and doubled in Asian (p = 0.003) children. Conclusions. Canadian incidence rates of childhood-onset Type 2 diabetes mellitus have significantly increased. Further research, policy, and prevention efforts are needed to curb rising rates of youth onset Type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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36. Lonicera caerulea L. polyphenols improve short-chain fatty acid levels by reshaping the microbial structure of fermented feces in vitro.
- Author
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Xinbo Cao, Xuemeng Wang, Yanxin Ren, Yangcun Sun, Zhichao Yang, Jingping Ge, and Wenxiang Ping
- Subjects
SHORT-chain fatty acids ,BACTEROIDES fragilis ,POLYPHENOLS ,HONEYSUCKLES ,TYPE 2 diabetes ,GUT microbiome ,FECES - Abstract
Increasing evidence suggests that the pathogenesis of type 2 diabetes mellitus (T2DM) is closely related to the gut microbiota. Polyphenols have been shown to alleviate T2DM, but the effects of L. caerulea L. polyphenols (LPs) on the gut microbiota and metabolites remain elusive. In this study, the inhibitory effects of fermented L. caerulea L. polyphenols (FLPs) and unfermented L. caerulea L. polyphenols (ULPs) on α-amylase and α-glucosidase and the impact of LP on the gut microbiota and metabolites were investigated. Furthermore, the relationship between the two was revealed through correlation analysis. The results showed that ULP and FLP had the highest inhibitory rates against α-amylase and α-glucosidase at 4 mg ml
-1 , indicating a strong inhibitory ability. In addition, LP plays a regulatory role in the concentration of short-chain fatty acids (SCFAs) and tends to restore them to their normal levels. LP reversed the dysbiosis of the gut microbiota caused by T2DM, as evidenced by an increase in the abundance of bacterial genera such as Lactobacillus, Blautia, and Bacteroides and a decrease in the abundance of bacterial genera such as Escherichia-Shigella and Streptococcus. Similarly, after LP intervention, the relationships among microbial species became more complex and interconnected. In addition, the correlation between the gut microbiota and metabolites was established through correlation analysis. These further findings clarify the mechanism of action of LP against T2DM and provide a new target for T2DM interventions. [ABSTRACT FROM AUTHOR]- Published
- 2023
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- View/download PDF
37. Increased Insulin Secretion and Glucose Effectiveness in Obese Patients with Type 2 Diabetes following Bariatric Surgery.
- Author
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Visentin, Roberto, Brodersen, Katrine, Richelsen, Bjørn, Møller, Niels, Dalla Man, Chiara, Pedersen, Andreas Kristian, Abrahamsen, Jan, Holst, Jens Juul, and Nielsen, Michael Festersen
- Subjects
GASTRIC bypass ,TYPE 2 diabetes ,BARIATRIC surgery ,GLUCOSE ,BLOOD sugar ,INSULIN - Abstract
Background. β-cell dysfunction and insulin resistance are the main mechanisms causing glucose intolerance in type 2 diabetes (T2D). Bariatric surgeries, i.e., sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), are procedures both known to induce weight loss, increase insulin action, and enhance β-cell function, but hepatic insulin extraction and glucose effectiveness may also play a role. Methods. To determine the contribution of these regulators on glucose tolerance after bariatric surgery, an oral glucose tolerance test (OGTT) was performed before and 2 months after surgery in 9 RYGB and 7 SG subjects. Eight healthy subjects served as metabolic controls. Plasma glucose, insulin, C-peptide, GLP-1, and GIP were measured during each OGTT. Insulin sensitivity and secretion, glucose effectiveness, and glucose rate of appearance were determined via oral minimal models. Results. RYGB and SG resulted in similar weight reductions (13%, RYGB (p < 0.01); 14%, SG (p < 0.05)). Two months after surgery, insulin secretion (p < 0.05) and glucose effectiveness both improved equally in the two groups (11%, RYGB (p < 0.01); 8%, SG (p > 0.05)), whereas insulin sensitivity remained virtually unaltered. Bariatric surgery resulted in a comparable increase in the GLP-1 response during the OGTT, whereas GIP concentrations remained unaltered. Following surgery, oral glucose intake resulted in a comparable increase in hepatic insulin extraction, the response in both RYGB and SG patients significantly exceeding the response observed in the control subjects. Conclusions. These results demonstrate that the early improvement in glucose tolerance in obese T2D after RYGB and SG surgeries is attributable mainly to increased insulin secretion and glucose effectiveness, while insulin sensitivity seems to play only a minor role. This trial is registered with NCT02713555. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
38. Examining the associations between testosterone and biomarkers as men age.
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Smith, Stephen J., Bekele, Daniel, Lopresti, Adrian L., and Fairchild, Timothy J.
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INSULIN ,HEALTH & Nutrition Examination Survey ,BODY mass index ,OLDER men ,TYPE 2 diabetes ,GLUCOSE tolerance tests ,AGE ,TESTOSTERONE - Abstract
Objectives: Testosterone concentrations in men decline with advancing age. However, the cause of the decline is yet to be fully elucidated. Therefore, the aims of this study were to examine the associations between chronic diseases such as obesity and type 2 diabetes mellitus (T2DM) with total testosterone (TT) and sex hormone‐binding globulin (SHBG), using a large nationally‐representative data set (National Health and Nutrition Examination Survey; NHANES). Methods: NHANES is a cross‐sectional survey, physical examination, and laboratory evaluation of a nationally‐representative sample of a non‐institutionalized United States population. Male participants aged ≥18 years during the NHANES 2013–2014 and NHANES 2015–2016 survey periods were selected for this analysis. The analysis included the following data: body mass index (BMI), oral glucose tolerance test (OGTT), homeostatic model assessment of insulin resistance (HOMA‐IR), insulin, glucose, and age. Results: An overweight or obese condition was significantly inversely associated with TT and SHBG, even after adjusting for other variables. Several variables associated with T2DM (OGTT, HOMA‐IR, insulin, and glucose) were also inversely associated with TT; however, only the associations between OGTT and insulin with TT remained significant after adjusting for the other variables. Insulin and HOMA‐IR levels were significantly inversely associated with SHBG; however, only the association between SHBG and pre‐diabetic HOMA‐IR levels remained significant after adjusting for the other variables. OGTT became significantly associated with SHBG after adjusting for the other variables. Age was significantly inversely associated with TT, but positively associated with SHBG, even after adjusting for other variables. Conclusion: The results of the present study, which is the largest to date, indicate that a marker of obesity, BMI, and some markers of T2DM are both independently and significantly inversely associated with TT and SHBG. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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- View/download PDF
39. Association of poor sleep and HbA1c in metformin‐treated patients with type 2 diabetes: Findings from the UK Biobank cohort study.
- Author
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Xue, Pei, Tan, Xiao, and Benedict, Christian
- Abstract
Summary: The American Diabetes Association recommends a glycated haemoglobin target of less than 7% for treating type 2 diabetes mellitus. However, it is still being determined if poor sleep affects this therapeutic goal, despite being treated with the blood‐glucose‐lowering medication metformin. Thus, we used data from 5703 patients on metformin monotherapy participating in the UK Biobank baseline investigation between 2006 and 2010. We combined self‐reported chronotype, daily sleep duration, insomnia, daytime sleepiness and snoring into a multidimensional poor sleep score ranging from 0 to 5, with higher scores indicating a less healthy sleep pattern. With each point increase on the poor sleep score scale, the odds of patients having an glycated haemoglobin of ≥ 7% increased by 6% (odds ratio [95% confidence interval], 1.06 [1.01, 1.11], p = 0.021). When examining the components of the poor sleep score separately, snoring was specifically associated with a glycated haemoglobin of ≥ 7% (1.12 [1.01, 1.25] versus no snoring, p = 0.038). However, adjusting for health and lifestyle conditions, such as body mass index, weekly physical activity level and hypertension status, eliminated the significant associations between the poor sleep score and snoring with glycated haemoglobin of ≥ 7%. Our findings suggest that poor sleep, specifically snoring, a symptom of obstructive sleep apnea, may interfere with the therapeutic goal of achieving a glycated haemoglobin below 7%. However, other factors known to be promoted by poor sleep, such as high body mass index, low physical activity and hypertension, may also contribute to the link between poor sleep and higher glycated haemoglobin levels. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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- View/download PDF
40. A Mediterranean-Style Diet Improves the Parameters for the Management and Prevention of Type 2 Diabetes Mellitus.
- Author
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Derrick, Stefani A., Nguyen, Sarah T., Marthens, Jordan R., Dambacher, Leah L., Sikalidis, Angelos K., and Reaves, Scott K.
- Subjects
TYPE 2 diabetes ,MEDITERRANEAN diet ,HYPERGLYCEMIA ,DUAL-energy X-ray absorptiometry ,BODY composition ,GLYCEMIC control - Abstract
Background and Objectives: Type 2 diabetes mellitus (T2DM) is a chronic condition recognized as the inability to maintain glucose homeostasis, typically presenting with insulin resistance and systemic inflammation. With the prevalence of T2DM and major risk factors, such as prediabetes and obesity, increasing each year, the need to address risk factor reduction strategies is crucial. Materials and Methods: Twenty-two men and women, overweight-to-obese adults (BMI mean: 26.1–31.6) (age range mean: 44.6–51.8) with T2DM, indicators of prediabetes, or who were metabolically healthy, participated in Cal Poly's Nutrition and Exercise in Type 2 Diabetes (CPNET) study. There were no significant differences in terms of age, BMI, or sex distribution among the groups at the baseline. This study's protocol included following a Mediterranean-style diet, the daily consumption of a high-quality whey protein supplement, and physical activity recommendations for 16 weeks. Body composition data, via dual-energy X-ray absorptiometry (DXA), and fasting blood samples were collected at the baseline and following the intervention. Due to restrictions associated with the outbreak of the COVID-19 pandemic, only 13 of the 22 participants who started this study were able to return for the second data collection to complete this study following the 16-week intervention. Results: The prediabetic and T2DM groups exhibited reductions in their fasting plasma glucose (12.0 mg/dL reduction in the prediabetic group; 19.6 mg/dL reduction in the T2DM group) to that of normal and prediabetic levels, respectively, while the T2DM group also demonstrated improvement in their hemoglobin A1c (reduced from 6.8% to 6.0%) to prediabetic levels. Additionally, the metabolically healthy, overweight group exhibited significant improvements in adiposity, while the obese prediabetic and T2DM groups showed non-significant improvements in all the measured metrics of body composition. No significant changes were observed in the inflammatory biomarkers (p-values ranged from 0.395 to 0.877). Conclusions: Collectively, our results suggest that adherence to a well-balanced, nutritious diet and activity may improve the parameters of glycemic control and provide benefits to body composition that help to manage and prevent the development of T2DM. Our study was able to yield significant findings signifying that the effects of a Mediterranean-style diet are observed even for a more conservative sample size. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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41. PEGylated exenatide injection (PB-119) improves beta-cell function and insulin resistance in treatment-naïve type 2 diabetes mellitus patients.
- Author
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Xu Liu, Ling Song, Yuanhui Zhang, Haiyan Li, Cheng Cui, and Dongyang Liu
- Subjects
PANCREATIC beta cells ,INSULIN ,TYPE 2 diabetes ,INSULIN resistance ,PEOPLE with diabetes ,EXENATIDE ,INSULIN sensitivity - Abstract
Objective: PB-119, a PEGylated exenatide injection, is a once-weekly glucagonlike peptide-1 receptor agonist. In the present study, we aimed to evaluate the effects of PB-119 on insulin resistance and beta-cell function in Chinese patients with type 2 diabetes mellitus (T2DM) to uncover its antidiabetic characteristics. Methods: A total of 36 Chinese T2DM patients were randomized to receive 25 μg and 50 μg PB-119 once weekly and exenatide (5--10 μg injected under the skin 2 times a day adjusted by the doctor) for 12 weeks. Oral mixed meal tolerance tests were conducted before the study and on Day 79. The data were fitted to estimate beta-cell function and insulin sensitivity parameters using the SAAM II package integrating the oral minimal model (OMM), which was compared with Homeostatic Model Assessment (HOMA) analysis results. Results: Exenatide or PB-119 treatment, compared with their baseline, was associated with higher beta-cell function parameters (φb, φs and φtot), disposition index, insulin secretion rates, and a lower glucose area under the curve. High-dose PB-119 also has a higher insulin resistance parameter (SI) than the baseline, but HOMA-IR did not. For the homeostatic model assessment parameters, HOMA-IR showed no statistically significant changes within or between treatments. Only high-dose PB-119 improved HOMA-β after 12 weeks of treatment. Conclusion: After 12 weeks of treatment, PB-119 decreased glycemic levels by improving beta-cell function and insulin resistance. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
42. Exosomes as biomarkers and therapy in type 2 diabetes mellitus and associated complications.
- Author
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Satyadev, Nihal, Rivera, Milagros I., Nikolov, Nicole K., and Fakoya, Adegbenro O. J.
- Subjects
TYPE 2 diabetes ,DIABETIC retinopathy ,EXOSOMES ,EXTRACELLULAR vesicles ,DIABETIC cardiomyopathy ,DIABETIC neuropathies - Abstract
Type 2 diabetes mellitus (T2DM) is one of the most prevalent metabolic disorders worldwide. However, T2DM still remains underdiagnosed and undertreated resulting in poor quality of life and increased morbidity and mortality. Given this ongoing burden, researchers have attempted to locate newtherapeutic targets aswell asmethodologies to identify the disease and its associated complications at an earlier stage. Several studies over the last few decades have identified exosomes, small extracellular vesicles that are released by cells, as pivotal contributors to the pathogenesis of T2DM and its complications. These discoveries suggest the possibility of novel detection and treatment methods. This review provides a comprehensive presentation of exosomes that hold potential as novel biomarkers and therapeutic targets. Additional focus is given to characterizing the role of exosomes in T2DM complications, including diabetic angiopathy, diabetic cardiomyopathy, diabetic nephropathy, diabetic peripheral neuropathy, diabetic retinopathy, and diabetic wound healing. This study reveals that the utilization of exosomes as diagnostic markers and therapies is a realistic possibility for both T2DM and its complications. However, the majority of the current research is limited to animal models, warranting further investigation of exosomes in clinical trials. This review represents the most extensive and up-to-date exploration of exosomes in relation to T2DM and its complications. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
43. Experiences and perceptions of self‐management in people with prediabetes: A qualitative meta‐synthesis.
- Author
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Wang, Zixin, Shi, Qifang, Zeng, Yue, and Li, Yuzhe
- Subjects
META-synthesis ,ONLINE information services ,OCCUPATIONAL roles ,MEDICAL information storage & retrieval systems ,SELF-management (Psychology) ,SYSTEMATIC reviews ,PATIENTS' attitudes ,TYPE 2 diabetes ,FINANCIAL stress ,DESCRIPTIVE statistics ,MEDLINE ,THEMATIC analysis ,PSYCHOLOGICAL adaptation ,PREDIABETIC state - Abstract
Background: Diabetes has become a global public health problem. Strengthening the self‐management ability of people with prediabetes plays an important role in preventing the occurrence and development of type 2 diabetes. The aim of this study is to synthesise the self‐management experiences and perceptions of people with prediabetes, which can contribute to the development of self‐management programs. Methods: This review adheres to the ENTREQ Guide. Evidence‐based medicine database (JBI and Cochrane) and original literature database (PubMed, Medline, EMbase, Web of Science, Wanfang, CNKI and VIP) were searched up to 31 May 2022. Both Chinese and English literature of qualitative research on self‐management experiences and perceptions of prediabetic patients were included. The quality of the included studies was evaluated, and the data were synthesised and analysed by thematic synthesis method. Results: A total of 23 primary studies containing 504 participants were included. After repeated reading and coding of the literature, three analytical themes were finally identified: coping with role management, success and failure in medical management, seeking and perceiving support. Conclusion: Role management for people with prediabetes needs more attention. Healthcare providers should identify problems from patients' self‐management experiences and improve professional skills to assist program modifications. Integrating the self‐management program into community activities under the guidance of medical staff and inviting family members and peers to participate can increase involvement and improve the self‐management ability. Relevance to Clinical Practice: These findings describe the different stages and issues in the self‐management process of prediabetic patients. The practice of prediabetes self‐management should incorporate the psychosocial, physical, and financial issues of the patients. As the main provider of health services, nurses should make patients aware of the susceptibility and severity of prediabetes and help them improve their self‐management skills. No Patient or Public Contribution: This is a meta‐synthesis without direct participation of patients. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
44. Targeting metabolic pathways: a novel therapeutic direction for type 2 diabetes.
- Author
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Zhihui Song, An Yan, Zehui Guo, Yuhang Zhang, Tao Wen, Zhenzhen Li, Zhihua Yang, Rui Chen, and Yi Wang
- Subjects
TYPE 2 diabetes ,GUT microbiome ,DOPAMINE ,ARACHIDONIC acid ,METABOLIC disorders ,MICROBIAL metabolites - Abstract
Background: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease that causes multi-organ complications, seriously affecting patients' quality of life and survival. Understanding its pathogenesis remains challenging, with current clinical treatment regimens often proving ineffective. Methods: In this study, we established a mouse model of T2DM and employed 16s rDNA sequencing to detect changes in the species and structure of gut flora. Additionally, we used UPLC-Q-TOF-MS to identify changes in urinary metabolites of T2DM mice, analyzed differential metabolites and constructed differential metabolic pathways. Finally, we used Pearman correlation analysis to investigate the relationship between intestinal flora and differential metabolites in T2DM mice, aiming to elucidate the pathogenesis of T2DM and provide an experimental basis for its clinical treatment. Results: Our findings revealed a reduction in both the species diversity and abundance of intestinal flora in T2DM mice, with significantly decreased levels of beneficial bacteria such as Lactobacillus and significantly increased levels of harmful bacteria such as Helicobacter pylori. Urinary metabolomics results identified 31 differential metabolites between T2DM and control mice, including Phosphatidylcholine, CDP-ethanolamine and Leukotriene A4, which may be closely associated with the glycerophospholipid and arachidonic acid pathways. Pearman correlation analysis showed a strong correlation between dopamine and gonadal, estradiol and gut microbiota, may be a novel direction underlying T2DM. Conclusion: In conclusion, our study suggests that alterations in gut microbiota and urinary metabolites are characteristic features of T2DM in mice. Furthermore, a strong correlation between dopamine, estradiol and gut microbiota, may be a novel direction underlying T2DM, the aim is to provide new ideas for clinical treatment and basic research. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
45. Differentially Expressed Genes Regulating Glutathione Metabolism, Protein-Folding, and Unfolded Protein Response in Pancreatic β-Cells in Type 2 Diabetes Mellitus.
- Author
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Klyosova, Elena, Azarova, Iuliia, Buikin, Stepan, and Polonikov, Alexey
- Subjects
UNFOLDED protein response ,GENE expression ,TYPE 2 diabetes ,HOMEOSTASIS ,PROTEIN folding ,METABOLIC regulation ,MOLECULAR chaperones - Abstract
Impaired redox homeostasis in the endoplasmic reticulum (ER) may contribute to proinsulin misfolding and thus to activate the unfolded protein response (UPR) and apoptotic pathways, culminating in pancreatic β-cell loss and type 2 diabetes (T2D). The present study was designed to identify differentially expressed genes (DEGs) encoding enzymes for glutathione metabolism and their impact on the expression levels of genes regulating protein folding and UPR in β-cells of T2D patients. The GEO transcriptome datasets of β-cells of diabetics and non-diabetics, GSE20966 and GSE81608, were analyzed for 142 genes of interest using limma and GREIN software, respectively. Diabetic β-cells showed dataset-specific patterns of DEGs (FDR ≤ 0.05) implicated in the regulation of glutathione metabolism (ANPEP, PGD, IDH2, and CTH), protein-folding (HSP90AB1, HSP90AA1, HSPA1B, HSPA8, BAG3, NDC1, NUP160, RLN1, and RPS19BP1), and unfolded protein response (CREB3L4, ERP27, and BID). The GCLC gene, encoding the catalytic subunit of glutamate–cysteine ligase, the first rate-limiting enzyme of glutathione biosynthesis, was moderately down-regulated in diabetic β-cells from both datasets (p ≤ 0.05). Regression analysis established that genes involved in the de novo synthesis of glutathione, GCLC, GCLM, and GSS affect the expression levels of genes encoding molecular chaperones and those involved in the UPR pathway. This study showed for the first time that diabetic β-cells exhibit alterations in the expression of genes regulating glutathione metabolism, protein-folding, and UPR and provided evidence for the molecular crosstalk between impaired redox homeostasis and abnormal protein folding, underlying ER stress in type 2 diabetes. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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- View/download PDF
46. β-Cell function during a high-fat meal in young versus old adults: role of exercise.
- Author
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Malin, Steven K., Frick, Hannah, Wisseman, William S., Edwards, Elizabeth S., Edwards, David A., Emerson, Sam R., and Kurti, Stephanie P.
- Subjects
INSULIN ,INSULIN sensitivity ,DUAL-energy X-ray absorptiometry ,BODY composition ,BLOOD lipids ,FREE fatty acids ,OXYGEN consumption ,ARTIFICIAL pancreases - Abstract
The acute effect of exercise on β-cell function during a high-fat meal (HFM) in young adults (YA) versus old adults (OA) is unclear. In this randomized crossover trial, YA (n = 5 M/7 F, 23.3 ± 3.9 yr) and OA (n = 8 M/4 F, 67.7 ± 6.0 yr) underwent a 180-min HFM (12 kcal/kg body wt; 57% fat, 37% CHO) after a rest or exercise [~65% heart rate peak (HR
peak )] condition ~12 h earlier. After an overnight fast, plasma lipids, glucose, insulin, and free fatty acid (FFA) were determined to estimate peripheral, or skeletal muscle, insulin sensitivity (Matsuda index) as well as hepatic [homeostatic model assessment of insulin resistance (HOMA-IR)] and adipose insulin resistance (adipose-IR). β-Cell function was derived from C-peptide and defined as early-phase (0-30 min) and total-phase (0-180 min) disposition index [DI, glucose-stimulated insulin secretion (GSIS) adjusted for insulin sensitivity/resistance]. Hepatic insulin extraction (HIE), body composition [dual-energy X-ray absorptiometry (DXA)], and peak oxygen consumption (VO2peak ) were also assessed. OA had higher total cholesterol (TC), LDL, HIE, and DI across organs as well as lower adipose-IR (all, P < 0.05) and VO2peak (P = 0.056) despite similar body composition and glucose tolerance. Exercise lowered early-phase TC and LDL in OA versus YA (P < 0.05). However, C-peptide area under the curve (AUC), total phase GSIS, and adipose-IR were reduced postexercise in YA versus OA (P < 0.05). Skeletal muscle DI increased in YA and OA after exercise (P < 0.05), whereas adipose DI tended to decline in OA (P = 0.06 and P = 0.08). Exercise-induced skeletal muscle insulin sensitivity (r = -0.44, P = 0.02) and total-phase DI (r = -0.65, P = 0.005) correlated with reduced glucose AUC180min . Together, exercise improved skeletal muscle insulin sensitivity/DI in relation to glucose tolerance in YA and OA, but only raised adipose-IR and reduced adipose-DI in OA. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
47. A flavonoid-rich fraction of Euphorbia peplus attenuates hyperglycemia, insulin resistance, and oxidative stress in a type 2 diabetes rat model.
- Author
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Alruhaimi, Reem S., Mostafa-Hedeab, Gomaa, Abduh, Maisa Siddiq, Bin-Ammar, Albandari, Hassanein, Emad H. M., Kamel, Emadeldin M., and Mahmoud, Ayman M.
- Subjects
TYPE 2 diabetes ,INSULIN resistance ,OXIDATIVE stress ,EUPHORBIA ,GLYCOGEN phosphorylase ,PHOSPHORYLASES ,HYPERGLYCEMIA - Abstract
Background: Type 2 diabetes (T2D) is a metabolic disorder characterized by insulin resistance (IR) and hyperglycemia. Plants are valuable sources of therapeutic agents for the management of T2D. Euphorbia peplus has been widely used as a traditional medicine for the treatment of various diseases, but its beneficial role in T2D has not been fully explored. Methods: The anti-diabetic efficacy of E. peplus extract (EPE) was studied using rats with T2D induced by high-fat diet (HFD) and streptozotocin (STZ). The diabetic rats received 100, 200, and 400 mg/kg EPE for 4 weeks. Results: Phytochemical fractionation of the aerial parts of E. peplus led to the isolation of seven known flavonoids. Rats with T2D exhibited IR, impaired glucose tolerance, decreased liver hexokinase and glycogen, and upregulated glycogen phosphorylase, glucose-6-phosphatase (G-6-Pase), and fructose-1,6-bisphosphatase (F-1,6-BPase). Treatment with 100, 200, and 400 mg/kg EPE for 4 weeks ameliorated hyperglycemia, IR, liver glycogen, and the activities of carbohydrate-metabolizing enzymes. EPE attenuated dyslipidemia, serum transaminases, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and liver lipid accumulation, nuclear factor (NF)-κB p65, and lipid peroxidation, nitric oxide and enhanced antioxidants. All EPE doses upregulated serum adiponectin and liver peroxisome proliferator-activated receptor γ (PPARγ) in HFD/STZ-induced rats. The isolated flavonoids showed in silico binding affinity toward hexokinase, NF-κB, and PPARγ. Conclusion: E. peplus is rich in flavonoids, and its extract ameliorated IR, hyperglycemia, dyslipidemia, inflammation and redox imbalance, and upregulated adiponectin and PPARγ in rats with T2D. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
48. Geroprotective interventions in the 3xTg mouse model of Alzheimer's disease.
- Author
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Sonsalla, Michelle M. and Lamming, Dudley W.
- Subjects
ALZHEIMER'S disease ,POPULATION aging ,LABORATORY mice ,DRIVERS' licenses ,HIGH-protein diet ,ANIMAL disease models ,LOW-calorie diet ,TYPE 2 diabetes - Abstract
Alzheimer's disease (AD) is an age-associated neurodegenerative disease. As the population ages, the increasing prevalence of AD threatens massive healthcare costs in the coming decades. Unfortunately, traditional drug development efforts for AD have proven largely unsuccessful. A geroscience approach to AD suggests that since aging is the main driver of AD, targeting aging itself may be an effective way to prevent or treat AD. Here, we discuss the effectiveness of geroprotective interventions on AD pathology and cognition in the widely utilized triple-transgenic mouse model of AD (3xTg-AD) which develops both β-amyloid and tau pathologies characteristic of human AD, as well as cognitive deficits. We discuss the beneficial impacts of calorie restriction (CR), the gold standard for geroprotective interventions, and the effects of other dietary interventions including protein restriction. We also discuss the promising preclinical results of geroprotective pharmaceuticals, including rapamycin and medications for type 2 diabetes. Though these interventions and treatments have beneficial effects in the 3xTg-AD model, there is no guarantee that they will be as effective in humans, and we discuss the need to examine these interventions in additional animal models as well as the urgent need to test if some of these approaches can be translated from the lab to the bedside for the treatment of humans with AD. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
49. Initial Insights into the Genetic Variation Associated with Metformin Treatment Failure in Youth with Type 2 Diabetes.
- Author
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Srinivasan, Shylaja, Chen, Ling, Udler, Miriam, Todd, Jennifer, Kelsey, Megan M., Haymond, Morey W., Arslanian, Silva, Zeitler, Philip, Gubitosi-Klug, Rose, Nadeau, Kristen J., Kutney, Katherine, White, Neil H., Li, Josephine H., Perry, James A., Kaur, Varinderpal, Brenner, Laura, Mercader, Josep M., Dawed, Adem, Pearson, Ewan R., and Yee, Sook-Wah
- Subjects
STATISTICS ,GLYCEMIC control ,GENETIC variation ,TYPE 2 diabetes ,TREATMENT failure ,INSULIN ,DESCRIPTIVE statistics ,GENOMES ,RESEARCH funding ,METFORMIN ,DATA analysis ,SECONDARY analysis ,PANCREATIC beta cells ,C-peptide ,INSULIN resistance - Abstract
Metformin is the first-line treatment for type 2 diabetes (T2D) in youth but with limited sustained glycemic response. To identify common variants associated with metformin response, we used a genome-wide approach in 506 youth from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study and examined the relationship between T2D partitioned polygenic scores (pPS), glycemic traits, and metformin response in these youth. Several variants met a suggestive threshold (P < 1 × 10 − 6 ), though none including published adult variants reached genome-wide significance. We pursued replication of top nine variants in three cohorts, and rs76195229 in ATRNL1 was associated with worse metformin response in the Metformin Genetics Consortium (n = 7,812), though statistically not being significant after Bonferroni correction (P = 0.06). A higher β-cell pPS was associated with a lower insulinogenic index (P = 0.02) and C-peptide (P = 0.047) at baseline and higher pPS related to two insulin resistance processes were associated with increased C-peptide at baseline (P = 0.04 , 0.02). Although pPS were not associated with changes in glycemic traits or metformin response, our results indicate a trend in the association of the β-cell pPS with reduced β-cell function over time. Our data show initial evidence for genetic variation associated with metformin response in youth with T2D. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
50. Renoprotective Effect of Thai Patients with Type 2 Diabetes Mellitus Treated with SGLT-2 Inhibitors versus DPP-4 Inhibitors: A Real-World Observational Study.
- Author
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Chanawong, Apichaya, Uitrakul, Suriyon, Incomenoy, Supatcha, and Poonchuay, Natnicha
- Subjects
THAI people ,TYPE 2 diabetes ,SODIUM-glucose cotransporters ,BLOOD sugar ,GLYCOSYLATED hemoglobin ,WILCOXON signed-rank test ,CD26 antigen ,MANN Whitney U Test - Abstract
Background. Recently, there is a lack of studies comparing the renoprotective effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. This study therefore aimed to investigate the renoprotective effects of SGLT-2 inhibitors and DPP-4 inhibitors on Thai patients with type 2 diabetes mellitus. Methods. Patient medication records of all patients who used those two antidiabetic classes at Fort Wachirawut Hospital were reviewed. Renal function tests, blood glucose levels, and other baseline characteristics were collected. Continuous variables were compared within the group using the Wilcoxon signed-rank test and between groups using the Mann–Whitney U test. Results. There were 388 and 691 patients with SGLT-2 inhibitors and DPP-4 inhibitors, respectively. The mean estimated glomerular filtration rate (eGFR) of the SGLT-2 inhibitor group was significantly lower from baseline at 18 months of treatment, as well as the DPP-4 inhibitor group. However, the trend of eGFR reduction in patients with baseline eGFR <60 mL/min/1.73 m
2 was smaller than those with baseline eGFR ≥60 mL/min/1.73 m2 . In addition, the fasting blood sugar and haemoglobin A1c levels significantly decreased from baseline in both the groups. Conclusions. Both SGLT-2 inhibitors and DPP-4 inhibitors showed the same trends of eGFR reductions from baseline in Thai patients with type 2 diabetes mellitus. However, SGLT-2 inhibitors should be considered in patients with impaired renal function rather than in all T2DM patients. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
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