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Aberration of the "gut-liver axis" contributes to the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we use multi-omics to analyze the gut microbiota composition and metabolic profile of patients with type-2 diabetes mellitus (T2DM). T2DM patients were screened for liver disease by blood tests, ultrasound, and liver stiffness measurements. Stool microbiota was analyzed by 16S rRNA gene sequencing; metabolomic profiling by Nuclear Magnetic Resonance spectroscopy and Ultra-High Performance-Mass Spectrometry. Microbiome and metabolic signatures were analyzed in the whole cohort and in matched subsets to identify signatures specific for steatosis (MASLD±) or fibrosis (Fibrosis±). Gut permeability was assessed in-vitro using monolayers of MDCK cells and trans-epithelial electric resistance (TEER). Cytokine profile was assessed in serum and stools.Overall, 285 patients were enrolled: 255 serum, 252 urine and 97 stool samples were analyzed. Anaeroplasma and Escherichia/Shigella ASVs were higher, while Butyricicoccus ASVs were lower in those with normal liver. In MASLD±, Butyricicoccus ASV was significantly higher in those with steatosis. In the Fibrosis±, Butyricicoccus ASV was significantly lower in those with fibrosis. Glycochenodeoxycholic acid-3-sulfate (G-UDCA-3S) appeared to be higher in MASLD with fibrosis. Fecal water from patients with MASLD and fibrosis caused the greatest drop in the TEER vs those with normal liver; this was reversed with protease inhibitors. Finally, fecal IL-13 was lower in MASLD with fibrosis. We identified microbiome signatures which were specific for steatosis and fibrosis and independent of other metabolic risk factors. Moreover, we conclude that protease-related gut permeability plays a role in those MASLD patients with fibrosis, and that disease progression is linked to a gut-liver axis which is at least partially independent of T2DM.

We studied the regulation dynamics of cerebral blood velocity (CBv) at middle cerebral arteries (MCA) in response to spontaneous changes of arterial blood pressure (ABP), termed dynamic cerebral autoregulation (dCA), and end-tidal CO2 as proxy for blood CO2 tension, termed dynamic vasomotor reactivity (DVR), by analyzing time-series data collected at supine rest from 36 patients with Type-2 Diabetes Mellitus (T2DM) and 22 age/sex-matched non-diabetic controls without arterial hypertension. Our analysis employed a robust dynamic modeling methodology that utilizes Principal Dynamic Modes (PDM) to estimate subject-specific dynamic transformations of spontaneous changes in ABP and end-tidal CO2 (viewed as two "inputs") into changes of CBv at MCA measured via Transcranial Doppler ultrasound (viewed as the "output"). The quantitative results of PDM analysis indicate significant alterations in T2DM of both DVR and dCA in terms of two specific PDM contributions that rise to significance (p < 0.05). Our results further suggest that the observed DVR and dCA alterations may be due to reduction of cholinergic activity (based on previously published results from cholinergic blockade data) that may disturb the sympatho-vagal balance in T2DM. Combination of these two model-based "physio-markers" differentiated T2DM patients from controls (p = 0.0007), indicating diabetes-related alteration of cerebrovascular regulation, with possible diagnostic implications. [ABSTRACT FROM AUTHOR]

Fruits and vegetables are laden with antioxidants and have been used to quench reactive oxygen species. The combination of two or more fruits and vegetables to produce smoothies is expected to yield a synergistic effect that could further improve functionality. This study investigated the antioxidative and blood glucose-lowering potentials of smoothies made from selected fruits and vegetables as well as their effect on the expression of pro-inflammatory genes in streptozotocin-induced diabetic Wistar rats. Standard procedures were used for the in vitro antioxidant determination while pancreas tissue was excised for molecular study. The inclusion of beetroot increased the total phenolic contents by 30-50% while the flavonoid content was increased by more than 3-fold. Similarly, smoothies with beetroot and bitter gourd exhibited stronger free radical scavenging abilities as shown by DPPH (1, 1- diphenyl-2-picrylhydrazyl), ABTS (2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid), Nitric oxide (NO) scavenging ability, metal chelation (Fe2+) and ferric reducing antioxidant properties (FRAP) compared to the sample devoid of the duo. The blood glucose levels of the rats fed the smoothie were significantly lowered with a similar trend in the animals that were administered metformin. The smoothies significantly (p<0.05) reduced the malondialdehyde (MDA) content thus reducing lipid peroxidation in the animals. The endogenous antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) in the pancreas were all significantly (p<0.05) increased when the animals were fed smoothies. The expression of pro-inflammatory genes, IL-1β, IL-6 and TNF-α, was down-regulated in the animals fed with smoothies. The findings showed that the smoothies made from the combination have the potential for managing type-2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Curcumin is a natural polyphenol, with a different name diferuloylmethane, found in Curcuma longa (turmeric) with remarkable antioxidant, antimicrobial, anti-inflammatory, antiangiogenic, and antiplatelet aggregation properties. In recent years, several studies have verified that curcumin may benefit glucolipid metabolic disorders due to its various properties. Glucolipid metabolic disorders, major health threats to human life, is a series of diseases with the metabolic disturbance of glucose and lipid which are influenced by genetic, environmental, psychiatric, dietary, and other factors, including diabetes, hyperlipidemia, hypertension, obesity, metabolic dysfunction-associated fatty liver disease, and atherosclerosis. Here, we discusses the effects and underlying mechanisms on how curcumin alleviate the glucolipid metabolic disorders. [ABSTRACT FROM AUTHOR]

Background & Objective: Type-2 Diabetes Mellitus (T2DM) is one of the most common chronic non-communicable diseases and a serious health issue worldwide because of its rising prevalence amongst the young adults. Dietary diversity, rapid economic development and sedentary lifestyle are amongst the common factors contributing for the rapid rise of diabetes. Our objective was to assess the average carbohydrate (CHO) and caloric consumption and its association with obesity and disease status in patients with Type-2 diabetic patients in an outpatient setting. Methods: This study was performed at an outpatient department (OPD), of Hayatabad Medical Complex, Peshawar. Patients with T2DM were interviewed who completed dietary assessment using 24 hours dietary recall method. Results: A total of 150 patients with Type-2 diabetes were interviewed. The mean carbohydrate intake was 400.3±106 mg/day, out of which 43.3 % participant’s had carbohydrate intake above recommendations. The mean energy intake for all participants was 2504.5±587.4 Kcal/day. Majority of the participants were overweight and obese with mean BMI of 28kg/m² ± 4.4. There was no significant difference in energy and carbohydrate intake between male and female participants. Conclusions: Majority of Pakistani patients with Type-2 diabetes consume foods rich in carbohydrate as well as have high caloric value. These finding were more in patients with no formal education compared to those who were well educated with a degree. [ABSTRACT FROM AUTHOR]

In this paper, we measured B cell function in elderly healthy individuals (EH) and in elderly patients with Type-2 Diabetes Mellitus (T2DM, ET2DM), which are treatment-naive, as compared to healthy young (YH) individuals. Results show a higher serum inflammatory status of elderly versus young individuals, and especially of ET2DM versus EH. This status is associated with a reduced response to the seasonal influenza vaccine and with increased frequencies of the circulating pro-inflammatory B cell subset called Double Negative (DN) B cells. B cells from ET2DM patients are not only more inflammatory but also hyper-metabolic as compared to those from EH controls. The results herein are to our knowledge the first to show that T2DM superimposed on aging further increases systemic and B cell intrinsic inflammation, as well as dysfunctional humoral immunity. Our findings confirm and extend our previously published findings showing that inflammatory B cells are metabolically supported. [ABSTRACT FROM AUTHOR]

Amylin promoter and transcriptional factors are well-established, inducible factors in the production of the main amyloidogenic pancreatic hormone, human islet amyloid peptide (hIAPP) or amylin. However, posttranscriptional mechanisms driving hIAPP expression in pancreas remain enigmatic, and hence were explored here. The translational assay revealed that both 5′ and 3′ untranslated regions (UTRs) of hIAPP restricted expression of the luciferase constructs only in constructs driven by the hIAPP promoter. Bioinformatics analysis revealed several putative seed sequences for a dozen micro RNAs (miRNAs) in hIAPP's 3′ UTR. miR-182, miR-335, and miR-495 were the most downregulated miRNAs in stressed human islets exposed to endoplasmic reticulum (ER) or metabolic stressors, thapsigargin (TG) or high glucose (HG). Correspondingly, miR-335 mimics alone or in combination with miR-495 and miR-182 mimics significantly and potently (>3-fold) reduced hIAPP protein expression in HG-treated cultured human islets. siRNA-mediated silencing of Ago2 but not Ago1 significantly stimulated hIAPP expression and secretion from transfected, HG-treated human islets. Conversely, ectopic expression of Ago2 in hIAPP-expressing RIN-m5F cell line driven by CMV promoter reduced hIAPP intracellular protein levels. Collectively, the results point to a novel and synergistic role for hIAPP promoter, 5/3′ UTRs and Ago-2/miR-335 complex in post-transcriptional regulation of hIAPP gene expression in normal and metabolically active β-cells. [ABSTRACT FROM AUTHOR]

Abstract Background Type-2 diabetes mellitus (T2DM) is considered one of the chronic diseases that can have a relationship with age of menopause onset. Several studies have revealed that early menopause or late menopause can have a correlation with type-2 diabetes. This systematic review and meta-analysis aimed to investigate the association between the age of menopause onset and type-2 diabetes. Methods and materials PubMed, Web of Science, Scopus, Science Direct, Google Scholar, and Cochrane were searched for studies that have evaluated the relationship between T2DM and age of menopause onset. We pooled the effect sizes of the included studies using both adjusted odds ratios (OR) and hazard ratios (HR) of interest outcomes with their 95% confidence interval (CI). Results Nineteen papers were included in this study, 8 studies were cohorts, and 11 were cross sectional. Studies revealed a statistically significant association between early menopause age and increased odds of T2DM (OR = 1.24, 95% CI: 1.09–1.40; I2 = 67%; p = 0.001). Late menopause age was also associated with an increased odds of T2DM (OR = 1.14, 95% CI: 1.03–1.26; I2 = 56%; p = 0.01) compared to the reference group with normal menopausal age. As our secondary outcome, the hazard of developing T2DM in individuals with early or late menopausal age was assessed. Pooled analysis demonstrated a significantly higher hazard of T2DM among women with early menopause age (HR = 1.31, 95% CI: 1.05–1.64; I2 = 72%; p = 0.02). Late menopause age did not show a significant association (HR = 0.96, 95% CI: 0.84–1.10; I2 = 68%; p = 0.56). Conclusion Early and late menopause can both increase the risk of T2DM. Future research is needed to warrant the certainty of our findings.

Abstract Fruits and vegetables are laden with antioxidants and have been used to quench reactive oxygen species. The combination of two or more fruits and vegetables to produce smoothies is expected to yield a synergistic effect that could further improve functionality. This study investigated the antioxidative and blood glucose-lowering potentials of smoothies made from selected fruits and vegetables as well as their effect on the expression of pro-inflammatory genes in streptozotocin-induced diabetic Wistar rats. Standard procedures were used for the in vitro antioxidant determination while pancreas tissue was excised for molecular study. The inclusion of beetroot increased the total phenolic contents by 30-50% while the flavonoid content was increased by more than 3-fold. Similarly, smoothies with beetroot and bitter gourd exhibited stronger free radical scavenging abilities as shown by DPPH (1, 1- diphenyl-2-picrylhydrazyl), ABTS (2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid), Nitric oxide (NO) scavenging ability, metal chelation (Fe2+) and ferric reducing antioxidant properties (FRAP) compared to the sample devoid of the duo. The blood glucose levels of the rats fed the smoothie were significantly lowered with a similar trend in the animals that were administered metformin. The smoothies significantly (p

Abstract Diabetes is a metabolic condition defined by abnormal blood sugar levels. Targeting starch-hydrolyzing enzymes and Dipeptidyl Peptidase 4 (DPP-4) expressed on the surface of numerous cells is one of the key strategies to lower the risk of Type-2 diabetes mellitus (T2DM). Dalbergia sissoo Roxb. bark (DSB) extracts have been reported to have anti-diabetic properties. This study intended to scientifically validate use of alcoholic and hydro-alcoholic extracts of DSB for T2DM by conducting preliminary phytochemical investigations, characterising potential phytochemicals using Fourier transform infrared (FT-IR) spectroscopy and Gas chromatography-mass spectrometry (GC–MS) analysis followed by comprehensive in-silico analysis. A qualitative phytochemical evaluation indicated the presence of alkaloids, phenolics, glycosides, conjugated acids and flavonoids. Ethanolic extracts showed highest total phenolic content (TPC) (127.072 ± 14.08031 μg GAE/g dry extract) and total flavonoid content (106.911 ± 5.84516 μg QE /g dry extract). Further FT-IR spectroscopy also revealed typical band values associated with phenol, alcohol, alkene, alkane and conjugated acid functional groups. The GC–MS analysis identified 139 compounds, 18 of which had anti-diabetic potential. In-silico ADMET analysis of potential compounds revealed 15 compounds that followed Lipinski’s rule and demonstrated drug-like properties, as well as good oral bioavailability. Molecular docking was utilised to analyse their potential to interact with three targets: α-amylase, α-glucosidase, and DPP-4, which are crucial in managing diabetes-related problems. Molecular Docking analysis and membrane permeability test utilising the PerMM platform revealed that compounds in the extracts, such as Soyasapogenol B and Corydine, had better interactions and permeability across the plasma membrane than standard drugs in use. Molecular dynamics simulations also showed that selected compounds remained stable upon interaction with α-amylase. Overall, using the in-silico approaches it was predicted that DSB extracts contain potential phytochemicals with diverse anti-diabetic properties. It further needs to be investigated for possible development as formulation or drug of choice for treating T2DM.

ABSTRACT Aims/Introduction Research has suggested that vitamin D deficiency is associated with diabetic retinopathy (DR). Our study aimed to determine whether vitamin D deficiency is the cause of diabetic retinopathy or if diabetic retinopathy reduces vitamin D levels. Materials and Methods Participants with type‐2 diabetes were recruited for this prospective observational clinical study and were divided into a diabetic group without retinopathy and a diabetic group with retinopathy, with additional healthy volunteers serving as a control group. The differences in clinical characteristics among the three groups were also compared. Patients without retinopathy were then followed for 1 year to monitor the incidence of diabetic retinopathy. After follow‐up, participants were divided into subgroups based on whether diabetic retinopathy occurred. The baseline data of the subgroups were compared, and the independent risk factors were analyzed. Results Vitamin D levels were generally low. Participants with diabetic retinopathy had significantly lower vitamin D levels than did those without retinopathy (P

Aims. Retinoids participate in multiple key processes in the human body e.g., vision, cell differentiation and embryonic development. There is growing evidence of the relationship between retinol, its active metabolite- all-trans retinoic acid (ATRA) - and several pancreatic disorders. Although low levels of ATRA in pancreatic ductal adenocarcinoma (PDAC) tissue have been reported, data on serum levels of ATRA in PDAC is still limited. The aim of our work was to determine serum concentrations of retinol and ATRA in patients with PDAC, type-2 diabetes mellitus (T2DM), chronic pancreatitis (CHP) and healthy controls. Methods. High performance liquid chromatography with UV detection (HPLC) was used to measure serum levels of retinol and ATRA in 246 patients with different stages of PDAC, T2DM, CHP and healthy controls. Results. We found a significant decrease in the retinol concentration in PDAC (0.44+/-0.18 mg/L) compared to T2DM (0.65+/-0.19 mg/L, P

Type 2 diabetes mellitus (T2DM) is common and increasing in prevalence worldwide, with devastating public health consequences. While peripheral insulin resistance is a key feature of most forms of T2DM and has been investigated for over a century, research on brain insulin resistance (BIR) has more recently been developed, including in the context of T2DM and non-diabetes states. Recent data support the presence of BIR in the aging brain, even in non-diabetes states, and found that BIR may be a feature in Alzheimer’s disease (AD) and contributes to cognitive impairment. Further, therapies used to treat T2DM are now being investigated in the context of AD treatment and prevention, including insulin. In this review, we offer a definition of BIR, and present evidence for BIR in AD; we discuss the expression, function, and activation of the insulin receptor (INSR) in the brain; how BIR could develop; tools to study BIR; how BIR correlates with current AD hallmarks; and regional/cellular involvement of BIR. We close with a discussion on resilience to both BIR and AD, how current tools can be improved to better understand BIR, and future avenues for research. Overall, this review and position paper highlights BIR as a plausible therapeutic target for the prevention of cognitive decline and dementia due to AD. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of Gegen Qinlian Decoction (GQD) combined with dietary management in the treatment of patients with Type-2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) (T2DM MetS). Methods: This is a retrospective analysis of 102 cases of T2DM in the Brain Hospital of Hunan Province, China from April 2020 to February 2023. Of them, 49 patients received conventional drug treatment (control group), and 53 patients received GQD combined with dietary management on the basis of conventional drugs (observation group). Treatment efficacy was calculated, and blood glucose levels before and after the treatment, blood lipid-related indicators, tumor necrosis factor-α (TNF-α) and adiponectin (ADP) levels, and incidence of adverse reactions were compared between the two groups. Results: The total efficacy of the observation group (92.45%) was significantly higher than that of the control group (75.51%) (P<0.05). After the treatment, blood glucose and lipid indicators in both groups were significantly improved compared to pretreatment levels, and were significantly better in the observation group than in the control group (P<0.05). After the treatment, TNF-α levels in both groups decreased compared to before the treatment, and were significantly lower in the observation group compared to the control group. Levels of ADP after the treatment increased, and were significantly higher in the observation group compared to the control group (P<0.05). Conclusions: When taken as an adjunct to the conventional drug regimen, GQD combined with dietary management can effectively regulate blood glucose and lipid metabolism in patients with T2DM and MetS (T2DM MetS), improve TNF-α and ADP levels, and enhance disease treatment effectiveness. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Research has suggested that vitamin D deficiency is associated with diabetic retinopathy (DR). Our study aimed to determine whether vitamin D deficiency is the cause of diabetic retinopathy or if diabetic retinopathy reduces vitamin D levels. Materials and Methods: Participants with type‐2 diabetes were recruited for this prospective observational clinical study and were divided into a diabetic group without retinopathy and a diabetic group with retinopathy, with additional healthy volunteers serving as a control group. The differences in clinical characteristics among the three groups were also compared. Patients without retinopathy were then followed for 1 year to monitor the incidence of diabetic retinopathy. After follow‐up, participants were divided into subgroups based on whether diabetic retinopathy occurred. The baseline data of the subgroups were compared, and the independent risk factors were analyzed. Results: Vitamin D levels were generally low. Participants with diabetic retinopathy had significantly lower vitamin D levels than did those without retinopathy (P < 0.01). A comparison of the two subgroups revealed lower baseline vitamin D concentrations in the new‐DR subgroup than in the non‐DR subgroup (P < 0.01). Vitamin D deficiency and elevated HbA1c levels were found to be independent risk factors for diabetic retinopathy (OR = 0.935, 95% CI: 0.867–0.981, P = 0.006; OR = 2.208, 95% CI: 1.764–2.764, P < 0.01). The limit of vitamin D intake according to the receiver‐operating characteristic (ROC) curve was 26.01 ng/mL, and the area under the ROC curve was 0.603 (95% CI: 0.559–0.706, P = 0.002). Conclusions: Vitamin D levels were significantly lower in patients diagnosed with diabetic retinopathy. More importantly, vitamin D deficiency may accelerate the onset of diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Here we have shown for the first time altered expression of the vascular smooth muscle (VSM) KATP channel subunits in segments of the human internal mammary artery (HIMA) in patients with type-2 diabetes mellitus (T2DM). Functional properties of vascular KATP channels in the presence of T2DM, and the interaction between its subunits and endogenous ligands known to relax this vessel, were tested using the potassium (K) channels opener, pinacidil. HIMA is the most commonly used vascular graft in cardiac surgery. Previously it was shown that pinacidil relaxes HIMA segments through interaction with KATP (SUR2B/Kir6.1) vascular channels, but it is unknown whether pinacidil sensitivity is changed in the presence of T2DM, considering diabetes-induced vascular complications commonly seen in patients undergoing coronary artery bypass graft surgery (CABG). KATP subunits were detected in HIMA segments using Western blot and immunohistochemistry analyses. An organ bath system was used to interrogate endothelium-independent vasorelaxation caused by pinacidil. In pharmacological experiments, pinacidil was able to relax HIMA from patients with T2DM, with sensitivity comparable to our previous results. All three KATP subunits (SUR2B, Kir6.1 and Kir6.2) were observed in HIMA from patients with and without T2DM. There were no differences in the expression of the SUR2B subunit. The expression of the Kir6.1 subunit was lower in HIMA from T2DM patients. In the same group, the expression of the Kir6.2 subunit was higher. Therefore, KATP channels might not be the only method of pinacidil-induced dilatation of T2DM HIMA. T2DM may decrease the level of Kir6.1, a dominant subunit in VSM of HIMA, altering the interaction between pinacidil and those channels. [ABSTRACT FROM AUTHOR]

Aims. Retinoids participate in multiple key processes in the human body e.g., vision, cell differentiation and embryonic development. There is growing evidence of the relationship between retinol, its active metabolite- all-trans retinoic acid (ATRA) -- and several pancreatic disorders. Although low levels of ATRA in pancreatic ductal adenocarcinoma (PDAC) tissue have been reported, data on serum levels of ATRA in PDAC is still limited. The aim of our work was to determine serum concentrations of retinol and ATRA in patients with PDAC, type-2 diabetes mellitus (T2DM), chronic pancreatitis (CHP) and healthy controls. Methods. High performance liquid chromatography with UV detection (HPLC) was used to measure serum levels of retinol and ATRA in 246 patients with different stages of PDAC, T2DM, CHP and healthy controls. Results. We found a significant decrease in the retinol concentration in PDAC (0.44+/-0.18 mg/L) compared to T2DM (0.65+/-0.19 mg/L, P<0.001), CHP (0.60+/-0.18 mg/L, P< 0.001) and healthy controls (0.61+/-0.15 mg/L, P<0.001), significant decrease of ATRA levels in PDAC (1.14+/-0.49 ug/L) compared to T2DM (1.37+/-0.56 ug/L, P<0.001) and healthy controls(1.43+/-0.55 ug/L, P<0.001). Differences between early stages (I+II) of PDAC and non-carcinoma groups were not significant. We describe correlations between retinol, prealbumin and transferrin, and correlation of ATRA and IGFBP-2. Conclusion. Significant decrease in retinol and ATRA levels in PDAC compared to T2DM, healthy individuals and/or CHP supports existing evidence of the role of retinoids in PDAC. However, neither ATRA nor retinol are suitable for detection of early PDAC. Correlation of ATRA levels and IGFBP-2 provides new information about a possible IGF and retinol relationship. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) represents an increasing public health problem in Peru. This study aims to estimate the national economic burden of this disease for the public funder, the social security, and private sector insurers. Direct healthcare costs were estimated for a cohort of 45-to-75-year-old adults diagnosed with T2DM in 2019, over a 20-year period. Disease progression was modeled using PROSIT Models and literature, including acute and chronic microvascular and macrovascular complications. Three scenarios of glycemic control were considered: current levels of 35.8% of the population controlled (HbA1c < 7%) (S1); 100% controlled (S2) and; 100% uncontrolled (S3). The impact of diabetes prevalence on overall costs was evaluated in sensitivity analysis. Total national economic burden was estimated at $15,405,448,731; an annual average per patient of $2,158. Total costs would decrease to $12,853,113,596 (−16.6%) in S2 and increase to $16,828,713,495 (+9.2%) in S3. Treating patients with complications and risk factors could cost 6.5 times more, being stroke the complication with the highest impact. Up to a 67.6% increase in total costs was found when increasing T2DM prevalence. T2DM places a heavy burden on the Peruvian healthcare budget that will be even greater if poor glycemic control is maintained. [ABSTRACT FROM AUTHOR]

Background and objective: Since it has been demonstrated that inflammation and oxidative stress (OS) are important in the etiology and complexity of type 2 diabetes mellitus (T2DM), antioxidant treatment is recognized as an effective approach for managing the progression of the disease. The current study was conducted to assess the effects of crocin administration on metabolic and genetic indices in T2DM patients who were receiving metformin. Materials and methods: Sixty T2DM patients, receiving metformin, were included in our randomized double-blind placebo-controlled clinical trial. Patients were divided into two groups (n = 30) and received either 15 mg/day crocin supplementation or a placebo twice a day for 12 weeks. Fasting blood was obtained at the beginning and end of the intervention to assess glycemic index, lipid content, indicators of inflammation, and OS. Patients’ peripheral blood mononuclear cells (PBMC) were analyzed for gene expression associated with OS and inflammation using real-time polymerase chain reaction (real-time PCR). Results: Crocin intake significantly decreased fasting plasma glucose (P < 0.001), HbA1c (P = 0.002), serum insulin levels (P = 0.03), and insulin resistance (P < 0.001), while significantly enhanced insulin sensitivity (P

Introduction: Type 2 Diabetes Mellitus (DM) is a significant global health concern. In Type 2 DM, hyperglycemia results from inadequate insulin production and the body’s reduced ability to respond to insulin, a condition known as insulin resistance. Diabetes Mellitus is often associated with cognitive decline, as observed in many patients with Type 2 DM. This study aims to analyze factors influencing cognitive status in Type 2 Diabetes Mellitus patients at Royal Prima General Hospital Medan. Methods: This descriptive quantitative study used a cross-sectional design. The study population consisted of 754 patients with Type 2 DM, with a sample of 150 selected. A mini-mental state exam was used to check the cognitive status. Data were analyzed using univariate, bivariate, and multivariate methods. Results: The findings indicate that gender, education level, blood glucose status, and duration of DM significantly influenced cognitive status in Type 2 DM patients at Royal Prima General Hospital Medan, with a p-value < 0.05 for each variable. In contrast, occupational status did not show a significant influence (p-value > 0.05). Collectively, gender, education level, occupational status, blood glucose status, and DM duration impacted cognitive status in these patients (p-value < 0.05). Conclusion: Among the variables studied, the duration of Type 2 DM was the most influential factor affecting cognitive status in patients at Royal Prima General Hospital Medan.

Abstract Background Observational studies have suggested an association between birth weight and type 2 diabetes mellitus, but the causality between them has not been established. We aimed to obtain the causal relationship between birth weight with T2DM and quantify the mediating effects of potential modifiable risk factors. Methods Two-step, two-sample Mendelian randomization (MR) techniques were applied using SNPs as genetic instruments for exposure and mediators. Summary data from genome-wide association studies (GWAS) for birth weight, T2DM, and a series of fatty acids traits and their ratios were leveraged. The inverse variance weighted (IVW) method was the main analysis approach. In addition, the heterogeneity test, horizontal pleiotropy test, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test, and leave-one-out analysis were carried out to assess the robustness. Results The IVW method showed that lower birth weight raised the risk of T2DM (β: −1.113, 95% CI: −1.573 ∼ −0.652). Two-step MR identified 4 of 17 candidate mediators partially mediating the effect of lower birth weight on T2DM, including ratio of polyunsaturated fatty acids to monounsaturated fatty acids (proportion mediated: 7.9%), ratio of polyunsaturated fatty acids to total fatty acids (7.2%), ratio of omega-6 fatty acids to total fatty acids (8.1%) and ratio of linoleic acid to total fatty acids ratio (6.0%). Conclusions Our findings supported a potentially causal effect of birth weight against T2DM with considerable mediation by modifiable risk factors. Interventions that target these factors have the potential to reduce the burden of T2DM attributable to low birth weight.

Abstract Background At present, the relationship between serum uric acid and blood glucose is controversial, and even opposite conclusions have been reached. We aimed to investigate the relationship between time in range and serum uric acid and estimate the influence of serum uric acid on blood glucose fluctuations in Chinese patients with type-2 diabetes mellitus (T2DM). Methods A total of 458 hospitalized patients with T2DM were selected. According to the SUA level, patients were divided into four groups by quartile: Q1 (≤ 254.5 µmol/L), Q2 (254.5–306.0 µmol/L), Q3 (306.0–385.5 µmol/L) and Q4 (> 385.5 µmol/L). The differences in general data, TIR and other clinical indicators between the four groups were assessed. Multifactor regression was used to analyze the relationship between subgroups of SUA and TIR, TBR, TAR, MAGE, SD, ADRR, MODD and M value. Curve fitting was used to analyze the association between TIR and SUA and to identify the inflection point. Results TIR showed an overall increasing trend with increasing SUA, while HbA1c, TAR, MAGE, SD, ADRR, MODD and M value showed an overall decreasing trend with increasing SUA. Multivariate regression analysis showed that, compared with Q1, there was no correlation between SUA and TIR, TAR, ADRR, SD, or MODD in all models of Q2. In the Q3 and Q4 groups, SUA was correlated with SD, MODD, and MAGE in all models. In the Q4 group, SUA was correlated with TIR, TAR, ADRR, and the M value in all models. When SUA > 306 µmol/L (Q3 and Q4), TIR and SUA have a curve-like relationship, and the inflection point of the fitted curve was SUA = 460 mmol/L. Before the inflection point, β was 0.1, indicating that when SUA increases by 10 mmol/L, the corresponding TIR increases by 1%. After the inflection point, there was no significant difference in the correlation between TIR and SUA (P > 0.05). Conclusions There is a close relationship between TIR and SUA in T2DM patients, it is speculated that SUA in a certain range had a positive protective effect on blood glucose control.

ABSTRACTAberration of the “gut-liver axis” contributes to the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we use multi-omics to analyze the gut microbiota composition and metabolic profile of patients with type-2 diabetes mellitus (T2DM). T2DM patients were screened for liver disease by blood tests, ultrasound, and liver stiffness measurements. Stool microbiota was analyzed by 16S rRNA gene sequencing; metabolomic profiling by Nuclear Magnetic Resonance spectroscopy and Ultra-High Performance-Mass Spectrometry. Microbiome and metabolic signatures were analyzed in the whole cohort and in matched subsets to identify signatures specific for steatosis (MASLD±) or fibrosis (Fibrosis±). Gut permeability was assessed in-vitro using monolayers of MDCK cells and trans-epithelial electric resistance (TEER). Cytokine profile was assessed in serum and stools.Overall, 285 patients were enrolled: 255 serum, 252 urine and 97 stool samples were analyzed. Anaeroplasma and Escherichia/Shigella ASVs were higher, while Butyricicoccus ASVs were lower in those with normal liver. In MASLD±, Butyricicoccus ASV was significantly higher in those with steatosis. In the Fibrosis±, Butyricicoccus ASV was significantly lower in those with fibrosis. Glycochenodeoxycholic acid-3-sulfate (G-UDCA-3S) appeared to be higher in MASLD with fibrosis. Fecal water from patients with MASLD and fibrosis caused the greatest drop in the TEER vs those with normal liver; this was reversed with protease inhibitors. Finally, fecal IL-13 was lower in MASLD with fibrosis. We identified microbiome signatures which were specific for steatosis and fibrosis and independent of other metabolic risk factors. Moreover, we conclude that protease-related gut permeability plays a role in those MASLD patients with fibrosis, and that disease progression is linked to a gut-liver axis which is at least partially independent of T2DM.

Background: Observational studies have suggested an association between birth weight and type 2 diabetes mellitus, but the causality between them has not been established. We aimed to obtain the causal relationship between birth weight with T2DM and quantify the mediating effects of potential modifiable risk factors. Methods: Two-step, two-sample Mendelian randomization (MR) techniques were applied using SNPs as genetic instruments for exposure and mediators. Summary data from genome-wide association studies (GWAS) for birth weight, T2DM, and a series of fatty acids traits and their ratios were leveraged. The inverse variance weighted (IVW) method was the main analysis approach. In addition, the heterogeneity test, horizontal pleiotropy test, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test, and leave-one-out analysis were carried out to assess the robustness. Results: The IVW method showed that lower birth weight raised the risk of T2DM (β: −1.113, 95% CI: −1.573 ∼ −0.652). Two-step MR identified 4 of 17 candidate mediators partially mediating the effect of lower birth weight on T2DM, including ratio of polyunsaturated fatty acids to monounsaturated fatty acids (proportion mediated: 7.9%), ratio of polyunsaturated fatty acids to total fatty acids (7.2%), ratio of omega-6 fatty acids to total fatty acids (8.1%) and ratio of linoleic acid to total fatty acids ratio (6.0%). Conclusions: Our findings supported a potentially causal effect of birth weight against T2DM with considerable mediation by modifiable risk factors. Interventions that target these factors have the potential to reduce the burden of T2DM attributable to low birth weight. [ABSTRACT FROM AUTHOR]

Background: At present, the relationship between serum uric acid and blood glucose is controversial, and even opposite conclusions have been reached. We aimed to investigate the relationship between time in range and serum uric acid and estimate the influence of serum uric acid on blood glucose fluctuations in Chinese patients with type-2 diabetes mellitus (T2DM). Methods: A total of 458 hospitalized patients with T2DM were selected. According to the SUA level, patients were divided into four groups by quartile: Q1 (≤ 254.5 µmol/L), Q2 (254.5–306.0 µmol/L), Q3 (306.0–385.5 µmol/L) and Q4 (> 385.5 µmol/L). The differences in general data, TIR and other clinical indicators between the four groups were assessed. Multifactor regression was used to analyze the relationship between subgroups of SUA and TIR, TBR, TAR, MAGE, SD, ADRR, MODD and M value. Curve fitting was used to analyze the association between TIR and SUA and to identify the inflection point. Results: TIR showed an overall increasing trend with increasing SUA, while HbA1c, TAR, MAGE, SD, ADRR, MODD and M value showed an overall decreasing trend with increasing SUA. Multivariate regression analysis showed that, compared with Q1, there was no correlation between SUA and TIR, TAR, ADRR, SD, or MODD in all models of Q2. In the Q3 and Q4 groups, SUA was correlated with SD, MODD, and MAGE in all models. In the Q4 group, SUA was correlated with TIR, TAR, ADRR, and the M value in all models. When SUA > 306 µmol/L (Q3 and Q4), TIR and SUA have a curve-like relationship, and the inflection point of the fitted curve was SUA = 460 mmol/L. Before the inflection point, β was 0.1, indicating that when SUA increases by 10 mmol/L, the corresponding TIR increases by 1%. After the inflection point, there was no significant difference in the correlation between TIR and SUA (P > 0.05). Conclusions: There is a close relationship between TIR and SUA in T2DM patients, it is speculated that SUA in a certain range had a positive protective effect on blood glucose control. [ABSTRACT FROM AUTHOR]

Introduction: Despite the importance of postpartum type-2 diabetes mellitus (T2DM) screening to ensure early detection and effective management of T2DM among women previously diagnosed with gestational diabetes mellitus, low uptake has been reported. In view of the proven effectiveness of theory-based interventions, this study aimed to evaluate the effectiveness of Information Motivation Behavioural Skills (IMB)-based intervention to improve postpartum T2DM screening uptake among pregnant women with GDM in Negeri Sembilan, Malaysia. Methods: A prospective quasi-experimental study was carried out among comparable respondents in the intervention and control groups, involving 61 and 55 respondents respectively. Validated and reliable self-administered questionnaire was used to measure pre- and post-intervention of knowledge, attitude and self-efficacy, based on the constructs of the IMB model, with postpartum T2DM screening uptake measured at 6-week postpartum. Results: The IMB-based intervention was effectively improved knowledge on gestational diabetes mellitus (GDM), and attitude as well as self-efficacy related to the screening, with significant difference in the 6-week postpartum T2DM screening uptake between the intervention and control groups. Between groups comparison revealed significantly higher mean scores for knowledge (?p 2=0.11), attitude (?p 2=0.031) and self-efficacy (?p 2=0.52) in the intervention group compared to the control group, with self-efficacy is showing the largest size effect. Conclusion: The IMB-based health intervention had effectively improved the 6-week postpartum T2DM screening among women with GDM in the intervention group, through the significant improvement of knowledge on GDM and attitude as well as self-efficacy related to the screening. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relevant risk factors of proliferative diabetic retinopathy (PDR) in patients with Type-2 diabetes mellitus (T2DM) and their correlations with the central macular thickness (CMT). Methods: This is a retrospective study. The clinical data of 300 patients with T2DM were collected and divided into a PDR group (observation group) and non-PDR group (control group) according to the occurrence of PDR in Aier Eye Hospital (Taiyuan) from February 2019 to February 2022. The relevant risk factors were screened out through the t test and the χ2 test, and analyzed by logistic regression. Results: Logistic regression analysis showed that systolic blood pressure, diastolic blood pressure, course of diabetes, fasting blood glucose (FBG), two hours postprandial blood glucose (two hours PBG) and urinary albumin were independent risk factors for T2DM complicated with PDR. ROC curve revealed that systolic blood pressure, course of diabetes and urinary albumin had the highest diagnostic efficiency. Correlation analysis demonstrated that CMT was positively correlated with systolic blood pressure, course of diabetes, HbA1c level and urinary albumin level. Conclusion: For patients with T2DM, blood pressure, course of diabetes, FBG, 2hPBG and urinary albumin are independent risk factors for PDR, and increased systolic blood pressure, course of diabetes, HbA1c level and urinary albumin level will increase CMT. Combining the above indexes to predict the occurrence of PDR has a synergistic effect, and the increase in systolic blood pressure, course of diabetes, HbA1c level and urinary albumin level will increase the CMT of the patients. [ABSTRACT FROM AUTHOR]

Hyperglycaemia-induced inflammation plays a vital role in the development of diabetic peripheral neuropathy (DPN). Recent evidences had reported the involvement of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) in diabetic experimental models. So, this pilot study aimed to evaluate serum NF-κB levels in DPN patients. We recruited 50 T2DM patients, of which 25 were T2DM with neuropathy and 25 were T2DM without neuropathy. In all the participants peripheral neuropathy was diagnosed based on Total neuropathy score (TNS). Serum NF-κB levels were measured by ELISA. We observed that the serum NF-κB levels were higher in DPN patients in comparison to T2DM patients without neuropathy. On spearman correlation, a positive correlation was found between serum NF-κB levels and TNS in the DPN group (r=0.741, p<0.001). The regression model shows the TNS to be an independent determinant of serum NF-κB levels after adjustment for potential confounders like age, duration of diabetes, and HbA1C (B=81.34; p<0.001). NF-κB activation plays a key role in promoting inflammation which is associated with the progression of DPN. In this respect, the study of NF-κB levels in serum may be an additional diagnostic marker for DPN. [ABSTRACT FROM AUTHOR]

Background To investigate the efficacy of "dapagliflozin" in the treatment of type 2 diabetes mellitus when combined with insulin &/or other OHAs Methods At this investigation, 130 subjetcs with uncontrolled T-2 DM combined with various OHAs &/or insulin were studied at the department of medicine. Pre-made questionnaires were used to record specifics regarding each patient's family history, medical history, clinical examination, & course of therapy. In this study, dapagliflozin was administered as an adjuvant medication to all patients who have received standard treatment for their diabetes. After three months of Dapagliflozin medication, differences in HbA1c & FBS levels were assessed. Results At baseline, the study subjects' mean HbA1C was 8.31%, mean FBS was 184.7 mg/dl, & mean PPBS was 279.25 mg/dl. These were the diabetic values. Following the intervention, the study participants' mean HbA1C was 7.05%, mean FBS was 131.73 mg/dl, & mean PPBS was 204.98 mg/dl. These were the diabetic parameters. Therefore, both FBS & PPBS significantly decreased. Conclusion In ordinary clinical practice, this research offers compelling real-world proof supporting the untimely use of "dapagliflozin" in Indian subjects with type 2 diabetes to improve glucose control & gain additional benefits including weight loss. [ABSTRACT FROM AUTHOR]

In people over 60 years, the most common diseases are those of the cardiovascular system and geriatric syndromes. Dyslipidemia and hyperglycemia are traditional cardiovascular risk factors. However, their impact on the development of major geriatric syndromes among people over 60 years remains unclear. The relationship between the presence of type-2 diabetes mellitus and the development of frailty, sarcopenia, and cognitive impairment depends on age. The influence of chronic hyperglycemia on geriatric syndromes decreases with increasing age and acquires a neutral role in long-living people. Recent studies have shown that low high-density lipoprotein (HDL) levels in people over 60 years old are associated with the development of frailty, sarcopenia, and cognitive impairment. [ABSTRACT FROM AUTHOR]

In this paper, we measured B cell function in elderly healthy individuals (EH) and in elderly patients with Type-2 Diabetes Mellitus (T2DM, ET2DM), which are treatment-naive, as compared to healthy young (YH) individuals. Results show a higher serum inflammatory status of elderly versus young individuals, and especially of ET2DM versus EH. This status is associated with a reduced response to the seasonal influenza vaccine and with increased frequencies of the circulating pro-inflammatory B cell subset called Double Negative (DN) B cells. B cells from ET2DM patients are not only more inflammatory but also hyper-metabolic as compared to those from EH controls. The results herein are to our knowledge the first to show that T2DM superimposed on aging further increases systemic and B cell intrinsic inflammation, as well as dysfunctional humoral immunity. Our findings confirm and extend our previously published findings showing that inflammatory B cells are metabolically supported.

This study addresses global concerns about diabetes mellitus by exploring a novel approach to manage hyperglycemia through pulses-supplemented designer biscuits. Control and designer biscuits were prepared with varying proportions of wheat flour and pulses (chickpea, mungbean). The pulses-supplemented biscuits exhibited increased protein content and reduced readily available carbohydrates. Selected designer biscuits, with 12.5 % incorporation of chickpea and mungbean pulse flour, demonstrated significantly lower glycemic index (69.17 ± 5.01) and higher satiety index (122.19 ± 8.85) compared to control biscuits. These showed 13 % less glycemic index and 9 % higher satiety index as compared to control biscuits. A four-week bio-efficacy trial involving diabetic subjects consuming these biscuits as a routine snack resulted in an 11.45 % decrease in fasting blood glucose and a 19.15 % reduction in random blood glucose levels. Insulin and HDL levels also significantly improved. The study concludes that these designer biscuits possess a hypoglycemic effect, offering a potential dietary intervention for managing diabetes.

Introduction: The prevalence of type 2 diabetes mellitus (T2DM) has increased in Saudi Arabia over recent decades, with current estimates showing that 19% of adults have T2DM. There is a need to confirm the clinical outcomes and safety of iGlarLixi in the routine clinical practice setting. Methods: A multicenter retrospective non-comparative study was conducted on 224 people with T2DM on Oral anti-diabetics (OADs) or in combination with basal insulin who initiated treatment with iGlarLixi in Saudi Arabia. Data of at least 180 days (± 30 days) before and after initiating iGlarLixi were retrieved. Results: Mean HbA1c significantly decreased after iGlarLixi start, with a mean reduction of 1.6% at six months. The mean reduction in the FPG was −38.8 (95% CI -46.5 to −31.1, p

Abstract Background It is hypothesized that whole salivary prostaglandin E2 (PgE2) levels are higher in patients with type-2 diabetes mellitus (type-2 DM) than non-diabetic individuals with periodontal inflammation; and that whole salivary expression of PgE2 is correlated with hemoglobin A1C (HbA1c) levels. The aim of the present study was to compare whole salivary PgE2 levels among patients with type-2 DM and non-diabetic individuals with periodontal inflammation. Methods Sociodemographic data, duration since the diagnosis and management of type-2 DM, most recent hemoglobin A1C (HbA1c level), and any familial history of DM was retrieved from patient’s healthcare records. Participants were divided into four groups: Group-1: type-2 diabetics with periodontal inflammation; Group-2: type-2 diabetics without periodontal inflammation; Group-3: non-diabetics with periodontal inflammation; and Group-4: non-diabetics without periodontal inflammation. Plaque and gingival indices (PI and GI), probing depth (PD), clinical attachment loss (CAL) and marginal bone loss (MBL) were measured. Unstimulated whole saliva samples were collected and PgE2 levels were measured. Group-comparisons were done and P

Amylin promoter and transcriptional factors are well-established, inducible factors in the production of the main amyloidogenic pancreatic hormone, human islet amyloid peptide (hIAPP) or amylin. However, posttranscriptional mechanisms driving hIAPP expression in pancreas remain enigmatic, and hence were explored here. The translational assay revealed that both 5′ and 3′ untranslated regions (UTRs) of hIAPP restricted expression of the luciferase constructs only in constructs driven by the hIAPP promoter. Bioinformatics analysis revealed several putative seed sequences for a dozen micro RNAs (miRNAs) in hIAPP’s 3′ UTR. miR-182, miR-335, and miR-495 were the most downregulated miRNAs in stressed human islets exposed to endoplasmic reticulum (ER) or metabolic stressors, thapsigargin (TG) or high glucose (HG). Correspondingly, miR-335 mimics alone or in combination with miR-495 and miR-182 mimics significantly and potently (>3-fold) reduced hIAPP protein expression in HG-treated cultured human islets. siRNA-mediated silencing of Ago2 but not Ago1 significantly stimulated hIAPP expression and secretion from transfected, HG-treated human islets. Conversely, ectopic expression of Ago2 in hIAPP-expressing RIN-m5F cell line driven by CMV promoter reduced hIAPP intracellular protein levels. Collectively, the results point to a novel and synergistic role for hIAPP promoter, 5/3′ UTRs and Ago-2/miR-335 complex in post-transcriptional regulation of hIAPP gene expression in normal and metabolically active β-cells.

Background: It is hypothesized that whole salivary prostaglandin E2 (PgE2) levels are higher in patients with type-2 diabetes mellitus (type-2 DM) than non-diabetic individuals with periodontal inflammation; and that whole salivary expression of PgE2 is correlated with hemoglobin A1C (HbA1c) levels. The aim of the present study was to compare whole salivary PgE2 levels among patients with type-2 DM and non-diabetic individuals with periodontal inflammation. Methods: Sociodemographic data, duration since the diagnosis and management of type-2 DM, most recent hemoglobin A1C (HbA1c level), and any familial history of DM was retrieved from patient's healthcare records. Participants were divided into four groups: Group-1: type-2 diabetics with periodontal inflammation; Group-2: type-2 diabetics without periodontal inflammation; Group-3: non-diabetics with periodontal inflammation; and Group-4: non-diabetics without periodontal inflammation. Plaque and gingival indices (PI and GI), probing depth (PD), clinical attachment loss (CAL) and marginal bone loss (MBL) were measured. Unstimulated whole saliva samples were collected and PgE2 levels were measured. Group-comparisons were done and P < 0.05 were considered statistically significant. Results: One-hundred-sixty individuals were included. Mean HbA1c levels were higher in Group-1 than groups 2 (P < 0.05), 3 (P < 0.05) and 4 (P < 0.05). The PI (P < 0.05), GI (P < 0.05) and PD (P < 0.05) were higher in Group-1 than groups 2 and 4. The CAL was higher in Group-1 than groups 2 (P < 0.05) and 3 (P < 0.05). The PD (P < 0.05), PI (P < 0.05) and GI (P < 0.05) were higher in Group-3 than Group-4. The MBL was higher in Group-1 than groups 2 (P < 0.05), 3 (P < 0.05) and 4 (P < 0.05). The PgE2 levels were higher in Group-1 than groups 2 (P < 0.05), 3 (P < 0.05) and 4 (P < 0.05). Conclusion: Hyperglycemia in patients with type-2 DM is associated with increased expression of whole salivary PgE2 levels and worsened periodontal inflammation compared with individuals with well-controlled type-2 DM and non-diabetic individuals. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the association between controlling nutritional status (CONUT) score and chronic kidney disease (CKD) in type-2 diabetes mellitus (T2DM) patients. Methods: This was a cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES). The data on demographic characteristics, physical examination, lifestyle behaviors, comorbidities, medicine use, laboratory values, and energy were extracted. Nutritional status was assessed using CONUT score, and patients were divided into normal nutrition group and malnutrition group. Association between CONUT score and CKD in T2DM patients was assessed using logistic regression analysis, and odds ratio (OR) and 95% confidence intervals (CIs) were reported. Subgroup analysis based on age, body mass index (BMI), cardiovascular disease (CVD), diabetic retinopathy, and hyperlipidemia was performed. Results: A total of 4581 patients were finally included for analysis. In the adjusted model, high CONUT score was found to be associated with the high odds of CKD (OR = 1.28, 95% CI 1.05–1.56). Also, high CONUT score was associated with the high odds of CKD in T2DM patients with age ≥ 65 years, with BMI < 25 kg/m2, with BMI ≥ 25 kg/m2, without CVD, without diabetic retinopathy, with hyperlipidemia, or without hyperlipidemia (all P < 0.05). Conclusions: Malnutrition was associated with the high odds of CKD in T2DM patients, indicating that actively monitoring the nutritional status is important for the management of CKD in T2DM patients. [ABSTRACT FROM AUTHOR]

Aims: To investigate the renal, cardiovascular, and safety outcomes when sodium–glucose cotransporter-2 inhibitors (SGLT2is) were added to insulin therapy in patients with type-2 diabetes mellitus (T2DM). Materials and methods: We searched Embase, PubMed, and Cochrane libraries for reports published up to Feb 2023. Randomized controlled trials (RCTs) comparing SGLT2is and insulin combination therapy (SGLT2is + INS group) with insulin therapy alone (INS group) in T2DM were included. Results: Fourteen RCTs involving six thousand one hundred twenty subjects with durations of 12–104 weeks were included. Compared with the insulin group, the SGLT2is + INS group showed decreased glycosylated hemoglobin values and insulin dosages (P < 0.00001). Meanwhile, the SGLT2is + INS group had a reduced urinary albumin/creatinine ratio (UACR) by 25.42 mg/g and uric acid concentration (P = 0.030; P = 0.001, respectively) but the estimated glomerular filtration rate (eGFR) and renal-related adverse events were unaffected (P = 0.070; P = 0.880, respectively). Blood pressure and body weight were lower in the SGLT2is + INS group (P < 0.01). However, the risk of genital infection was bigger when SGLT2is were added to insulin therapy (P < 0.00001), but the risks of severe hypoglycemia or urinary tract infection were equal between the two groups (P > 0.05). Conclusion: Adding SGLT2is to insulin therapy in T2DM patients showed better glucose control and decreased albuminuria, uric acid, blood pressure, and body weight without a reduction in the eGFR. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the association of the GHRd3 polymorphism with height and type-2 diabetes mellitus (T2DM) in Saudi Arabia. Methods: This case-control study included a total of 284 participants, divided into healthy controls (n = 142) and patients with T2DM (n = 142), recruited from Jazan University Hospital, southwest of Saudi Arabia in the period between January to September 2022. The GHRd3 polymorphism was genotyped using multiplex PCR. The correlation between height and genotypes was analyzed using one-way analysis of variance. The association between GHRd3 polymorphism and T2DM was assessed using logistic regression analysis. Results: The data showed a significant difference between the means of heights associated with each GHRd3 genotype, flfl, fld3, and d3d3. Logistic regression analysis showed no association between GHRd3 variants and T2DM. Conclusion: Homozygous GHRd3 polymorphism carriers, d3d3 genotype, were taller than fld3 or flfl carriers in our population. None of the GHRd3 variants were associated with T2DM. Thus, the GHRd3 polymorphism has growth-related actions with a minor contribution to T2DM. However, more studies with a larger sample size are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Background & Objective: Diabetes is considered a condition that is characterized by an increase in oxidative stress and inflammation. Transforming growth factor-beta (TGF-β) belongs to the TGF-β subfamily of the TGF-β superfamily. Numerous biological processes, such as cell growth, differentiation, adhesion, proliferation, tissue repair, morphogenesis, and apoptosis, are regulated by the TGF-β subfamily. Five TGF-β isoforms in this subfamily have been found in vertebrates; however, only TGF-β 1-3 has been demonstrated to be expressed in mammals. Methodology: The current research comprised of a total of 130 individuals, all of whom were placed into one of three primary groups; 50 (25 males and 25 females) diabetic patients without nephropathy; 50 (25 males and 25 females) diabetic patients with nephropathy as cases, and 30 (15 males and 15 females) persons in good health, who were of the same age as the patients being studied. In order to measure the concentrations of the parameters, the standard procedures and techniques were used. Results: The mean value of serum TGF-β1was significantly higher in diabetic patients without nephropathy and diabetic patients with nephropathy (40.19 ± 3.56 ng/ml),(51.21 ± 5.20 ng/ml) respectively as compared to controls (24.80 ± 3.51 ng/ml) with a high significant difference (P < 0.01). The level of TGF β1 showed a positive correlation in the study population with fasting blood sugar (r = 0.273, P = 0.006), creatinine (r = 0.546, P = 0.004), and cystatin C (r = 0.597, P = 0.005). The main finding of the present study was that the mean value of serum TGF-β1 in diabetic patients without nephropathy was 40.19 ± 3.56, and for diabetic patients with nephropathy 51.21 ± 5.20, while for controls was 24.80 ± 3.51, a significant difference (P < 0.05). In addition, there was a statistically significant and positive link between the blood TGF 1 levels and the serum creatinine levels of the individuals who participated in the study (r = 0.611, P = 0.003). In addition, patients who had diabetes for a longer period of time (more than five years) had higher levels of TGF β1 than those who had just been diagnosed with the condition. This difference, however, was not statistically significant (P > 0.05), which may be due to the fact that the level of TGF 1 rises with increasing duration of the participant's cases. Conclusion: There is no significant correlation between cystatin-C with fasting blood sugar. There was a statistically significant and positive link between the blood TGF-β1 levels and the serum creatinine and cystatin-C levels. [ABSTRACT FROM AUTHOR]

Introduction: Increasingly, SGLT2 inhibitors save patients with heart failure and comorbidities such as type-2 diabetes mellitus (T2DM) and chronic kidney disease (CKD); the inhibition of sodium-glucose cotransporter 2 (SGLT2) was first studied in patients with diabetes as a solution to lower glucose levels by preventing glucose reabsorption and facilitating its elimination; in the process, researchers took notice of how SGLT2 inhibitors also seemed to have beneficial cardiovascular effects in patients with both diabetes and cardiovascular disease. Aim: Our single-center prospective study assesses outcomes of post-coronary artery bypass grafting (CABG) rehabilitation and SLGT2 inhibition in CABG patients with/without T2DM and with/without CKD. Materials and Methods: One hundred twenty consecutive patients undergoing CABG were included in the analysis. Patients were divided into four subgroups: diabetes patients with chronic kidney disease (T2DM + CKD), diabetes patients without chronic kidney disease (T2DM−CKD), prediabetes patients with chronic kidney disease (PreD+CKD), and prediabetes patients without chronic kidney disease (PreD−CKD). Echocardiographic and laboratory investigations post-surgery (phase I) and 6 months later (phase II) included markers for cardiac ischemia, glycemic status, and renal function, and metabolic equivalents were investigated. Results: One hundred twenty patients participated, mostly men, overweight/obese, hypertensive, smokers; 65 had T2DM (18 with CKD), and 55 were prediabetic (17 with CKD). The mean ejection fraction increased by 8.43% overall but significantly more in the prediabetes group compared to the T2DM group (10.14% vs. 6.98%, p < 0.05). Overall, mean heart-type fatty-acid-binding protein (H-FABP) levels returned to normal levels, dropping from 68.40 ng/mL to 4.82 ng/mL (p = 0.000), and troponin data were more nuanced relative to an overall, strongly significant decrease of 44,458 ng/L (p = 0.000). Troponin levels in patients with CKD dropped more, both in the presence of T2DM (by 82,500 ng/L, p = 0.000) and in patients without T2DM (by 73,294 ng/L, p = 0.047). As expected, the overall glycated hemoglobin (HbA1c) levels improved significantly in those with prediabetes (from 6.54% to 5.55%, p = 0.000); on the other hand, the mean HbA1c changed from 7.06% to 6.06% (p = 0.000) in T2DM, and the presence or absence of CKD did not seem to make any difference: T2DM+CKD 7.01–6.08% (p = 0.000), T2DM−CKD 7.08–6.04% (p = 0.000), PreD+CKD 5.66–4.98% (p = 0.014), and PreD−CKD 6.03–4.94% (p = 0.00). Compared to an overall gain of 11.51, the GFRs of patients with CKD improved by 18.93 (68.15–87.07%, p = 0.000) in the presence of established diabetes and 14.89 (64.75–79.64%, p = 0.000) in the prediabetes group. Conclusions: Regarding the patients' cardiac statuses, the results from our single-center analysis revealed a significant decrease in ischemic risk (H-FABP and hs-cTnI levels) with improvements in mean ejection fraction, glycemic status, and renal function in patients post-CABG with/without T2DM, with/without CKD, and with SGLT2 inhibitor dapagliflozin treatment while undergoing cardiac rehabilitation. [ABSTRACT FROM AUTHOR]

Aim: Vitamin D deficiency is linked with type 2 diabetes mellitus (T2DM) and the occurrence of complications in patients with type 2 diabetes mellitus. None of the studies have focused on the association between vitamin D levels in patients with type 2 diabetes mellitus and diabetic nephropathy (DN) in the Makkah region, Saudi Arabia. Hence, the purpose of this study is to investigate the relationship of vitamin D with kidney disease in patients with T2DM in the Makkah region, of Saudi Arabia.Materials and Methods: This descriptive cross-sectional study was conducted at different hospitals in the Makkah region on T2DM patients from 2021 to 2022. In total, 328 patients with confirmed diabetes were enrolled in this study. T2DM patients over the aged> 18 to 92 years were included in the study. General laboratory characteristics of the study population were measured, including fasting blood sugar, HbA1C (Glycated hemoglobin), vitamin D, kidney function (BUN-Blood urea nitrogen and creatinine), and lipid profiles (cholesterol, triglycerides, LDL-Low density lipoprotein, and HDL-High density lipoprotein).Results: 46.6% (n=153) of participants had normal serum vitamin D levels. Insufficient and deficient serum vitamin D level were observed in 43.9% (n=144) and 9.5% (n=31) of participants, respectively. Of the participants, 25.9% (n=85) had good glycemic control (< 7.0%). Moderate and poor glycemic control were observed in 39.9% (n=131) and 34.1% (n=112) of the participants, respectively. A significant negative correlation (p< 0.5) was found between vitamin D levels and kidney function test results (blood urea nitrogen and serum creatinine levels). An inverse relationship was observed between HbA1c levels and vitamin D deficiency.Conclusion: Nephropathy is more likely to develop in people with type 2 diabetes mellitus and vitamin D deficiency. [ABSTRACT FROM AUTHOR]

The basic pathology that relates complications of Diabetes with blood sugar levels is atherosclerosis. The basic mechanism that is responsible for atherosclerosis in Diabetics is non-enzymatic reaction between glucose and proteins or lipoproteins in arterial walls. This ultimately leads to the formation of form Advanced Glycosylation End products (AGEs). Once formed, AGE-protein adducts are stable and virtually irreversible. This single centre, prospective, observational study was carried out in Diabetes unit of tertiary care hospital in patients of type 2 Diabetes Mellitus (T2DM). After the approval of institutional ethics committee, Diabetic patients attending the Diabetology unit of a tertiary care centre were recruited into the study. Overall increased CIMT was similar in males and females (36% vs. 35%). Mean BMI was not significantly different in two groups (26.56 ± 2.25 vs. 25.80 ± 1.65, p=0.105) as was the waist: hip ratio (0.87 ± 0.05 vs. 0.85 ± 0.05, p=0.225) respectively. More number of smokers had increased CIMT (25% vs. 8%, p=0.462). Systolic (138.08 ± 10.41 vs. 133.79 ± 11.81, 0.075) as well as diastolic BP (82.45 ± 11.49 vs. 79.59 ± 7.82, p=0.222) were not significantly different in increased and normal CIMT patients respectively. Among Diabetes parameters, fasting blood sugar (131.75 ± 26.35 vs. 119.59 ± 23.83, p=0.034), HbA1c (8.48 ± 0.91 vs. 8.05 ± 0.84, p=0.030) and duration of Diabetes (12.61 ± 5.23 vs. 7.62 ± 5.03, 0.0001) were significantly higher in increased CIMT patients compared to normal CIMT group whereas no significant difference was observed for post-prandial blood sugar (177.10 ± 34.31 vs. 162.34 ± 41.53, p=0.070) in two groups respectively. [ABSTRACT FROM AUTHOR]

Based on epidemiological data, the prevelance of Erectile Dysfunction (ED) and Benign prostate hyperplasia (BPH) increases with the same risk factors, such as age, metabolic disease, and others. This study aimed to determine the prevalence of ED and its relationship to age and the presence of hypertension (HT) and type-2 diabetes mellitus (T2DM) comorbid in BPH patients. This is a cross-sectional study conducted at RSUD Dr. Saiful Anwar and Hermina Hospital Tangku-banprahu Malang utilizes two questionnaires, including the translated version of The International Index of Erectile Function (IIEF-5) and Erectile Hardness Score (EHS) in Indonesian. There were 44 research subjects with only 21 respondents to the IIEF-5 questionnaire, while the EHS questionnaire was given to all subjects. The prevalence of ED was found to reach 100.0% at the age of 70-79 years through the IIEF-5 questionnaire and aged ≥ 80 years through the EHS questionnaire. The prevalence of ED in BPH patients with HT was found to be higher than non-HT patients through both questionnaires. The prevalence of ED in BPH patients with T2DM was found to be higher through the IIEF-5 questionnaire and slightly lower through the EHS questionnaire than non-T2DM patients. Age had a significant relationship with ED through the EHS questionnaire (p = 0.006), while no significant relationship was found through the IIEF-5 questionnaire (p = 1.000). HT and T2DM did not have a significant relationship with ED (IIEF-5: p = 0.229 and 0.526; EHS: p = 0.518 and 1.000). The prevalence of ED in BPH patients increases with age and the presence of comorbid HT and T2DM. Even so, there was no significant relationship between HT and T2DM with ED in BPH patients. A significant relationship between age and ED was only found in the EHS questionnaire but not in the IIEF-5 questionnaire. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the prevalence of depression, anxiety, and stress among in-patients diagnosed with various endocrine disorders. Quality of life (QoL) was also evaluated using the WHOQoL-BREF questionnaire. Material and Methods: The study included 110 patients. Participants were assessed for depression using the Hamilton Depression Rating Scale (HDRS), for anxiety using the Hamilton Anxiety Scale (HAM-A), and for stress using the Perceived Stress Scale (PSS). Results: The majority of patients had Type-2 Diabetes Mellitus (46.4%) or hypothyroidism (33.6%). The study showed that 22% of endocrine patients exhibited signs of depression, with the highest depression rate found among PCOD patients (58.3%). Anxiety was prevalent across all endocrine disorders, with the most severe cases found among hyperthyroid patients (66%). Regarding stress levels, most patients with Type-2 Diabetes and hypothyroidism reported moderate stress (70% and 86% respectively), while PCOD patients reported moderate (66%) and high stress (33.3%). Quality of life varied, with physical health ranging from 17.86 to 85.7 (mean 48.5), psychological health ranging from 20.83 to 70.8 (mean 50.9), social health ranging from 8.33 to 91.6 (mean 56.4), and environmental health ranging from 15.63 to 87.5 (mean 56.5). Conclusion: In conclusion, endocrine disorders can have far-reaching effects on mental health, causing depression, anxiety, and stress. Understanding these connections and integrating mental health care into treatment plans is crucial to improving patient outcomes. [ABSTRACT FROM AUTHOR]

Researches are gradually drifting towards adoption of food as therapies for the management of diseases that result from metabolic derangement, in extension genetical diseases can as well be managed by functional and nutritional diet that will maintain health of an individual through life. Diabetes mellitus is not an exception, there are several functional meals designed for the management of diabetes, many of these have unripe plantain as the base, with emphasis on just glycemic response limiting the antioxidant and anti-inflammatory influence. The aim of this study is to formulate a functional and optimized diet of unripe plantain base containing soycake and rice bran and compare the antidiabetic potentials of the well known cerolina and unripe plantain with the formulated optimized blend which will be in both flour and dough forms. Determine the effects that cooking of the flour samples could have on the antioxidant and overall antidiabetic potentials, through the comparison of the dough and flour. The uripe mature plantain, rice bran and soybean cake were obtained, response surface methodology (RSM) was used to establish the combination of the flour samples, and the runs generated were screened by proximate analysis and sensory evaluation to select the best blend regarded as the optimized flour blend. Dough meal (PSRD) was prepared from the optimized flour blend (PSRF) and the antidiabetic (α-amylase and α-glucosidase) and antioxidant (DPPH and hydroxyl scavenging, metal chelating activities and ferric reducing antioxidant power) effects were evaluated (in vitro). Male Wistar rats were obtained and subjected to 4-week high fat diet and low dose of streptozotocin (35 mg/kg i.p.), the animals were screened for manifestation of hyperglycemic signs and divided into eight (8) groups which included the positive control, and groups treated with PSRD, PSRF, PLTF, PLTD, CERF, CERD and glybenclamide, the ninth group is the negative control. The doughs and flours, and glybenclamide were administered orally for twenty-eight (28) days. The pancreas and liver were excised from anesthetized rats and subjected to histological and biochemical evaluations. The biochemical evaluations could be divided into antioxidant (activities of GST, GPx, catalase and superoxide dismutase and concentrations of NP-SH, GSH and MDA) and anti-inflammation (MPO, XO, TNF-α, IL-1β and IL-6). The results confirmed the relationship between diabetes mellitus, oxidative stress, inflammation and pro-inflammatory cytokines. The optimized dough sample had higher inhibition of α-amylase and α-glucosidase activities than the flour blend. The optimized dough sample further demonstrated antioxidant and anti-inflammatory protection against pancreatic and hepatic dysfunctions that could ensue as a result of type-2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Objective: To compare differences in CA-19.9 levels among participants with and without Type 2 diabetes mellitus and to correlate increasing glycemia levels and HbA1c with CA-19.9 Study Design: Comparative cross-sectional study Place and Duration of Study: Department of Chemical Pathology, Combined Military Hospital, Multan Pakistan, from Feb to Aug 2022. Methodology: One hundred thirty-one patients with diabetes and without diabetes were enrolled. CA-19.9, fasting plasma glucose, HbA1c, amylase, lipase, and anthropometric parameters were assessed. Patients with diabetes were divided into three groups based on FPG and HbA1c levels to investigate the relationship between CA-19.9 and glycemic status. Results: There was no significant difference among CA-19.9 of Controls and patients with diabetes (19.45±14.89 versus 15.83±13.98, p=0.155). FPG and HbA1c showed a moderate positive correlation to CA-19.9 (r = 0.283, p= 0.001 and r= = 0.305, p7.0% (p=0.020), HbA1c 7.0%(p=0.037) and with increasing FPG in groups with FPG 5.6-7.0 mmol/L Vs >7.0 mmol/L (p=0.005). Conclusion: The glycemic status of patients with diabetes can influence their serum CA-19.9 levels, and glycemic control should be considered while interpreting these levels in such patients. T2DM patients with poor glycemic control have a higher CA of 19.9 than those with better control.

ABSTRACT: Type-2 diabetes mellitus (T2DM) is characterized by defects in insulin secretion and combined peripheral resistance to the hormone. Several non-human primates (NHP) species develop T2DM, mainly captive animals with reduced physical activity and incorrect feeding. This case report describes the T2DM treatment of a black-eared marmoset (Callithrix penicillata) by diet reformulation and metformin oral administration. An adult female was diagnosed with T2DM after hyperglycemia and high serum fructosamine associated with glycosuria and obesity. Metformin hydrochloride (125mg/animal, orally, q24h) associated with feeding intervention was started. After 26 days, a significant reduction in weight, glycemia, and serum fructosamine could be observed, showing satisfactory results for the adopted therapy. Metformin is considered a safe drug for T2DM treatment due to its low hypoglycemia risk. The new diet consisted of sweet potato, squash, and varied fruits offered twice daily. In addition, thawed-mice newborns, egg whites, and small portions of pelleted primate food. In the present report, metformin use, associated with a low glycemic index diet, was effective in treating this particular marmoset and may present a potential for T2DM treatment in other NHPs.

Diabetes self-management behavior is important for patients to lessen disease-related complications, obtain optimum glycemic control and achieve a better quality of life. The study aimed to determine the relationship between dietary intake, nutrition knowledge, and self-management behaviors in Bangladeshi patients with type 2 diabetes mellitus (T2DM), with a focus on achieving optimal glycemic control, improving their quality of life. A cross-sectional study was conducted among T2DM patients from seven districts throughout Bangladesh. Data were collected using a validated semi-structured questionnaire for evaluating diabetes-related self-management behavior and existing nutrition knowledge. Dietary intakes were obtained using 24 h 3-days diet recall. Logistic regression analysis, Pearson's correlation and independent t-test were used to observe correlation and association among variables. A total of 411 patients with T2DM participated in the study, 59.4 % of patients achieved good dietary control, while 14.4 % were physically active, 49.4 % adhered well to medication, 44.0 % practiced effective self-monitoring, and 27.0 % possessed good diabetic nutrition knowledge. In fully adjusted multivariate logistic regression analysis, patients with a better glycemic control showed 14 times more control in their dietary intake [AOR: 14.21; 95 % CI: 5.62–35.94], and performing a good physical exercise 5 times more than the patients with high blood glucose level [AOR: 5.671; 95 % CI: 1.55–20.686]. Adherence toward medication prescription was also significantly higher among these patients. Glucose level was significantly higher among patients who had moderate [AOR: 3.367; 95 % CI: 1.29–8.73] and poor [AOR: 9.87; 95 % CI: 3.19–30.57] diabetes related nutritional knowledge. Patients with poor glycemic control consumed significantly more carbohydrates (251 ± 62 g vs 213 ± 47 g) and less dietary fiber (16.7 ± 4.5 g vs 20.5 ± 6.1 g) compared to the patients with optimum glycemic control. Our study findings suggest that, an improved level of nutrition knowledge may be beneficial to ensure optimum dietary intake, thus aid in an effective diabetes self-management behavior among Bangladeshi T2DM patients. Efforts should be made to help patient achieve optimum glycemic control, thus reduce their health-related complications and contribute to overall well-being.

Here we have shown for the first time altered expression of the vascular smooth muscle (VSM) KATP channel subunits in segments of the human internal mammary artery (HIMA) in patients with type-2 diabetes mellitus (T2DM). Functional properties of vascular KATP channels in the presence of T2DM, and the interaction between its subunits and endogenous ligands known to relax this vessel, were tested using the potassium (K) channels opener, pinacidil. HIMA is the most commonly used vascular graft in cardiac surgery. Previously it was shown that pinacidil relaxes HIMA segments through interaction with KATP (SUR2B/Kir6.1) vascular channels, but it is unknown whether pinacidil sensitivity is changed in the presence of T2DM, considering diabetes-induced vascular complications commonly seen in patients undergoing coronary artery bypass graft surgery (CABG). KATP subunits were detected in HIMA segments using Western blot and immunohistochemistry analyses. An organ bath system was used to interrogate endothelium-independent vasorelaxation caused by pinacidil. In pharmacological experiments, pinacidil was able to relax HIMA from patients with T2DM, with sensitivity comparable to our previous results. All three KATP subunits (SUR2B, Kir6.1 and Kir6.2) were observed in HIMA from patients with and without T2DM. There were no differences in the expression of the SUR2B subunit. The expression of the Kir6.1 subunit was lower in HIMA from T2DM patients. In the same group, the expression of the Kir6.2 subunit was higher. Therefore, KATP channels might not be the only method of pinacidil-induced dilatation of T2DM HIMA. T2DM may decrease the level of Kir6.1, a dominant subunit in VSM of HIMA, altering the interaction between pinacidil and those channels.