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Background: Although the exact role of mitophagy in the pathogenesis of diabetic cardiomyopathy (DCM) caused by type 2 diabetes mellitus (T2DM) remains controversial, recent studies revealed inhibition of mitophagy exacerbates cardiac injury in DCM. The zinc transporter ZIP7 has been reported to be upregulated by high glucose in cardiomyocytes and ZIP7 upregulation leads to inhibition of mitophagy in mouse hearts in the setting of ischemia/reperfusion. Nevertheless, little is known about the role of ZIP7 and its relationship with mitophagy in DCM caused by T2DM. Methods: T2DM was induced with high-fat diet (HFD) and streptozotocin. The cardiac-specific ZIP7 conditional knockout (ZIP7 cKO) mice were generated by adopting CRISPR/Cas9 system. Cardiac function was evaluated with echocardiography. Mitophagy was assessed by detecting mito-LC3II, mitoKeima, and mitoQC. Reactive oxygen species (ROS) were detected with DHE and mitoB. Results: ZIP7 was upregulated by T2DM in mouse hearts and ZIP7 cKO reduced mitochondrial ROS generation in mouse hearts with T2DM. Mitophagy was suppressed by T2DM in mouse hearts, which was prevented by ZIP7 cKO. T2DM inhibited PINK1 and Parkin accumulation in cardiac mitochondria, an effect that was prevented by ZIP7 cKO, pointing to that ZIP7 upregulation mediates T2DM-induced suppression of mitophagy by inhibiting the PINK1/Parkin pathway. T2DM induced mitochondrial hyperpolarization and decrease of mitochondrial Zn2+ and this was blocked by ZIP7 cKO, indicating that upregulation of ZIP7 leads to mitochondrial hyperpolarization by reducing Zn2+ within mitochondria. Finally, ZIP7 cKO prevented cardiac dysfunction and fibrosis caused by T2DM. Conclusions: ZIP7 upregulation mediates the inhibition of mitophagy by T2DM in mouse hearts by suppressing the PINK1/Parkin pathway. Reduction of mitochondrial Zn2+ due to upregulation of ZIP7 accounts for the inhibition of the PINK1/Parkin pathway. Prevention of ZIP7 upregulation is essential for the treatment of T2DM-induced cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori) is a known gastro-intestinal pathogen but implicated in extra-gastric diseases. The relationship between H. pylori infection and type 2 diabetes (T2DM) remains insufficiently elucidated, particularly in terms of molecular mediators such as microRNAs (miRNAs) and messenger RNAs (mRNAs). Objective: We aimed to characterize expression pattern of insulin signalling mRNAs and targeted miRNAs in T2DM patients exposed to H. pylori infection. Methods: We conducted a cross-sectional study among patients diagnosed with type 2 diabetes mellitus and were aged 18 to 60 years. Overnight fasting blood samples were collected and processed for plasma and serum. The plasma samples were used for glucose estimation and the serum used for H. pylori IgG screening. Total RNA was extracted from the serum with commercial kit, and mRNAs and miRNAs quantified by RT-qPCR with specific primers and under predetermined amplification conditions. Clinical data were obtained from medical records of patients. Results: Among 351 patients enrolled, 267 (76.1%) were females, 224 (63.8%) were married, and 79 (22.5%) had tertiary education. Expression level of insulin receptor mRNA was significantly lower in H. pylori positive T2DM patients compared to H. pylori negative (P <.05). There was no evidence of a difference in insulin receptor substrate 1 mRNA level (P >.05). Although not statistically significant, the expression levels of miRNA-222 and miRNA-155 in the patients exposed to H. pylori were higher than that of the unexposed group (P >.05). Conclusions: We found a significantly reduced serum insulin receptor messenger RNA level and higher levels of miRNA-222 and miRNA-155 in H. pylori exposed T2DM patients. The findings suggest a possible role of the infection in insulin signalling alteration in the patients. [ABSTRACT FROM AUTHOR]

This paper aims to clarify the effect of Undercarboxylated osteocalcin (ucOC) on cognitive function in rats with type 2 diabetes mellitus (T2DM). This research reviewed the cognitive function of 35 diabetic patients, 33 non-diabetic patients and the serum levels of Undercarboxylated osteocalcin (ucOC) in patients. What's more, we analyzed the correlation between serum ucOC levels and cognitive function. Diabetic rats were treated with high (30 μg·kg−1·d−1) and low (10 μg·kg−1·d−1) doses of ucOC to investigate its effects in regulating ucOC on blood lipid, blood glucose and cognitive function. We systematically detected the phosphorylation levels of cognitive level-related proteins (PI3K, AKT, and GSK/3β) in the hippocampus by Western Blot. Finally, PI3K-Akt pathway involved in regulating cognitive function in diabetic rats by ucOC was verified with AKT pathway inhibitor LY294002. MoCA score and serum ucOC levels were significantly reduced in patients with diabetes mellitus. ucOC could concentration-dose-dependently decrease the blood glucose and lipid levels, and improve glucose metabolism and weaken insulin resistance in diabetic rats (P < 0.001). In addition, escape latency in diabetic rats was significantly higher than that of normal rats in the Morris maze test, and ucOC dose-dependently shortened the escape latency in diabetic rats (all with P < 0.05). After using AKT pathway inhibitor, ucOC failed to shorten the escape latency in diabetic rats. In conclusion, this study explored the relevant mechanisms in inducing cognitive dysfunction of T2DM, suggesting the potential value of ucOC as a drug to improve cognitive dysfunction in patients with T2DM in clinical. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to assess mortality and years of life lost from diabetes mellitus in Poland between 2000 and 2022. Methods: The database was created from death cards made available for the purposes of this study by Statistics Poland. The study used data on deaths caused by type 1 diabetes mellitus, T1DM (N = 33,328), and type 2 diabetes mellitus, T2DM (N = 113,706). Standardized death rates (SDRs) and standard expected years of life lost per person (SEYLLp) and per death (SEYLLd) were calculated. A time trend analysis was performed using joinpoint models. The annual percentage change (APC) and the average annual percentage change (AAPC) were estimated. Results: Between 2000 and 2022, 33,328 people died from T1DM in Poland. The SDR rate increased from 6.0 to 8.8 per 100,000 population in the analyzed period. The APC was 1.3% (p < 0.05). SEYLLp rates per 100,000 population were 79.3 in 2000 and 109.2 in 2022. SEYLLd rates were 22.9 and 17.9 years, respectively (APC = −1.0%, p < 0.05). The mean age of those who died from T1DM increased from 66.1 in 2000 to 72.5 in 2022. Between 2000 and 2022, 113,706 people died from T2DM. The SDR increased from 12.5 to 37.7 per 100,00 (APC = 5.5%, p < 0.05). SEYLLp rates were 88.8 and 296.0 per 100,000 population (APC = 6.4%, p < 0.05). SEYLLd rates decreased from 16.9 in 2000 to 13.4 in 2022 (AAPC = −1.0%, p < 0.05). The mean age of those who died from T2DM increased from 73.1 to 78.1 years. Conclusions: The study showed a growing problem of diabetes as a cause of death and years of life lost. [ABSTRACT FROM AUTHOR]

Prolonged hyperglycemic conditions in type 2 diabetes mellitus (T2DM) cause pathological and functional damage to many organs and tissues, including the kidneys, retina, skin, and neuronal tissues, resulting in the development of microvascular diabetic complications. The altered renin angiotensin aldosterone system (RAAS) pathway has been reported to play an important role in the development of insulin resistance in T2DM and associated complications. The current study was carried out to evaluate the association of risk factors and altered expression of RAAS genes in T2DM patients without complications and T2DM patients with complications (retinopathy, nephropathy, and neuropathy). Four hundred and twenty subjects including 140 healthy controls, 140 T2DM patients with diabetic complications, and 140 T2DM patients without diabetic complications were included in the study. Risk factors associated with the development of T2DM and diabetic complications were evaluated. Further, expression analysis of RAAS genes (AGT, ACE, ACE2, and AGT1R) was carried out using qRTPCR in healthy controls, T2DM patients with complications, and T2DM patients without complications. Various risk factors like urban background, higher BMI, alcoholism, smoking, and family history of diabetes among others were found to be associated with the development of T2DM as well as diabetic complications. The expression level of AGT, ACE, and AGT1R was found to be upregulated whereas ACE2 was found to be downregulated in T2DM patients with complications and T2DM patients without complications as compared to controls. Altered expression of the studied genes of RAAS pathway is associated with the development of microvascular diabetic complications. [ABSTRACT FROM AUTHOR]

Nicotinamide adenine dinucleotide (NAD+) is crucial for cellular energy production, serving as a coenzyme in oxidation-reduction reactions. It also supports enzymes involved in processes such as DNA repair, aging, and immune responses. Lower NAD+ levels have been associated with various diseases, highlighting the importance of replenishing NAD+. Nicotinamide phosphoribosyltransferase (NAMPT) plays a critical role in the NAD+ salvage pathway, which helps sustain NAD+ levels, particularly in high-energy tissues like skeletal muscle.This review explores how the NAMPT-driven NAD+ salvage pathway influences skeletal muscle health and functionality in aging, type 2 diabetes mellitus (T2DM), and skeletal muscle injury. The review offers insights into enhancing the salvage pathway through exercise and NAD+ boosters as strategies to improve muscle performance. The findings suggest significant potential for using this pathway in the diagnosis, monitoring, and treatment of skeletal muscle conditions. [ABSTRACT FROM AUTHOR]

Nicotinamide adenine dinucleotide (NAD+) is crucial for cellular energy production, serving as a coenzyme in oxidation-reduction reactions. It also supports enzymes involved in processes such as DNA repair, aging, and immune responses. Lower NAD+ levels have been associated with various diseases, highlighting the importance of replenishing NAD+. Nicotinamide phosphoribosyltransferase (NAMPT) plays a critical role in the NAD+ salvage pathway, which helps sustain NAD+ levels, particularly in high-energy tissues like skeletal muscle.This review explores how the NAMPT-driven NAD+ salvage pathway influences skeletal muscle health and functionality in aging, type 2 diabetes mellitus (T2DM), and skeletal muscle injury. The review offers insights into enhancing the salvage pathway through exercise and NAD+ boosters as strategies to improve muscle performance. The findings suggest significant potential for using this pathway in the diagnosis, monitoring, and treatment of skeletal muscle conditions. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is linked to a heightened likelihood of experiencing fractures. It is crucial to ascertain whether medications used to lower blood sugar levels can elevate the risk of fractures. We aimed to investigate and compare the effects of glucagon-like peptide 1 receptor agonists (GLP-1RA), Dipeptidyl Peptidase-4 Inhibitors (DPP-4i), and Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) on the fracture risk in patients with T2D in the real world. Methods: A network meta-analysis conducted an inclusive literature search in PubMed, Scopus, Web of Science, and Cochrane Library to select appropriate population-based cohort studies that investigated the risk of bone fractures of (GLP-1RA), (DPP-4i) or (SGLT-2i) in the real world. A network meta-analysis (NMA) was performed using R software to investigate the risk of total fractures as a primary outcome among patients who used (GLP-1RAs), (SGLT-2i) or (DPP-4i) versus each other or other glucose-lowering medications (GLMs). The odds ratio (OR) and 95% confidence interval (CI)were summarized overall network and for each pairwise direct and indirect comparison. The surface under the cumulative ranking curve (SUCRA) with the P-scores was calculated for each treatment in the network meta-analysis to detect their cumulative ranking probabilities in lowering the risk of total fractures. Results: In our NMA, we identified a set of 13 population-based cohort studies comprising a total of 1,064,952 patients. The risk of fracture was identified with the follow-up duration for each class. We found a significant decrease in the fracture risk by about 87% associated with patients who used SGLT2 inhibitors in combination with other glucose-lowering medications, followed by SGLT2 inhibitors alone by about 67%, then GLP-1 receptor agonists by about 60%, and at last DPP-4 inhibitors by about 55%. Conclusion: Our study's collective findings suggest a significant association of the low risk of fracture with the use of SGLT2i with other GLMs combination, SGLT2i alone, GLP-1RA, and DPP-4i, respectively. This population-based analysis offers the best available evidence and might be helpful for clinicians in the decision of the most suitable T2DM treatment strategies, especially for elderly type 2 diabetic patients, as they may be safe in terms of fracture.3 [ABSTRACT FROM AUTHOR]

Background: Psychological Insulin Resistance (PIR) and negative perceptions regarding insulin treatment are noteworthy challenges in T2DM management, which hinder the timely initiation of insulin treatment. To get past these obstacles a reliable tool is required to evaluate patients' perspectives on insulin administration. Our study aims to conduct a comprehensive systematic review to evaluate the validity and reliability of different validation tests used in the psychometric validation of the ITAS in T2DM patients. Methods: A literature search was carried out, using PubMed, Google Scholar, EMBASE, Cochrane Library and Science Direct. Only those studies assessing content validity, construct validity, concurrent validity, discriminant validity, internal consistency reliability (Cronbach' α), and items-total correlation were retrieved. Results: A total of 14 studies illustrated the validity and reliability of ITAS in T2DM patients. Content validity results of S-CVI was 0.97, and I-CVI was 0.8–1.00. Construct validity with factor loading was greater than the threshold value of 0.3. The concurrent validity of ITAS vs. PAID, WHO-5, and SPI was 0.35 (P < 0.05), −0.14 (P < 0.05), and 0.80 (P < 0.001) respectively. The mean difference between insulin and non-insulin group was significant (P < 0.001) showing reliable discriminant validity. Reported results of Cronbach's α for the main scale (0.79–0.89), subscale-1 (0.72–0.9), and subscale-2 (0.61–0.89) showed "good to excellent" internal consistency reliability of ITAS. Item-total correlation results for the main scale, subscale-1, and subscale-2 were (0.40–0.82), (0.31–0.74) and (0.34–0.58) respectively. Test-retest reliability of ITAS was 0.571–0.87. Conclusions: Study findings confirm the robustness of various validation tests utilized in the psychometric validation of ITAS in T2DM patients. ITAS is a well-validated and reliable tool for determining the perspectives, PIR, and changes in patients' perception over time and it can be used to overcome hurdles in the timely initiation of insulin treatment in T2DM patients. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the circulating levels of asprosin, clusterin, zinc-alpha-2-glycoprotein (ZAG), nuclear factor-kappa B (NF-κB), and peroxisome proliferator-activated receptor-gamma (PPAR-γ) in patients with T2DM in relation to microvascular and macrovascular complications. Measuring these biomarkers may provide insight into the pathophysiology of T2DM and indicate novel targets for the therapy of diabetes-related complications. Methods: A total of 260 subjects consisting of four groups: healthy controls (Group-1), T2DM patients without complications (Group-2), T2DM patients with microvascular complications (Group-3), and T2DM patients with macrovascular complications (Group-4). Results: The mean age of all subjects was 52.96 ± 6.4, 127 of whom were male. Asprosin, clusterin, and NF-κB levels were significantly higher, while ZAG and PPAR-γ levels were significantly lower in diabetic patients than healthy subjects (p < 0.01, for all). Asprosin (p < 0.01), clusterin (p < 0.01), and NF-κB (p: 0.002) levels were significantly higher and PPAR-γ (p < 0.01) level was significantly lower (p < 0.001) in Group-3 than Group-2. Asprosin (p < 0.01) and NF-κB (p: 0.011) levels were significantly higher while ZAG (p < 0.01) level was significantly lower in Group-4 than Group-2. Serum ZAG level was found lower in Group-4 than in Group-3 (p = 0.037). Further, the biomarkers presented significant correlation with biomarkers like HbA1c and HOMA-IR. It was observed that increasing serum asprosin, clusterin, and NF-κB levels and decreasing serum PPAR-γ levels were effective in the development of microvascular complications while the increased asprosin levels and decreased ZAG levels had a significant effect on the development of macrovascular complications in the binary logistic regression analysis. Conclusions: This study confirms that altered levels of asprosin, clusterin, ZAG, NF-κB, and PPAR-γ are associated with T2DM and its complications. These biomarkers reflect the pathophysiological processes of metabolic disturbance and inflammation in T2DM and, therefore, have the potential for use in targeted interventions to prevent and manage diabetes-related complications. [ABSTRACT FROM AUTHOR]

Aim: To explore the topological organization alterations of functional connectomes in type 2 diabetes (T2DM) patients with and without mild cognitive impairment (MCI), and compare these with structural connectomes changes. Methods: Twenty-six T2DM patients with MCI (DM-MCI), 26 without cognitive impairment (DM-NC), and 28 healthy controls were included. Diffusion tensor imaging (DTI) and resting-state functional MRI images were acquired. Networks were constructed and graph-theory based network measurements were calculated. The global network parameters and nodal efficiencies were compared across the three groups using one-way ANOVA and a false-discovery rate correction was applied for multiple comparisons. Partial correlation analyses were performed to investigate relationships between network parameters, cognitive performance and clinical variables. Results: In the structural connectome, the DM-MCI group exhibited significantly decreased global efficiency (Eglob) and local efficiency (Eloc) compared to the DM-NC and control groups. In the functional connectome, the DM-MCI group exhibited increased Eloc and clustering coefficient (Cp) compared to the controls. No significant differences were found in Eglob, Eloc, or Cp between the DM-NC and the control group, both in structural and functional connectomes. Nodal efficiencies decreased in some brain regions of structural and functional networks in the DM-MCI and DM-NC groups, but increased in five regions in functional network, some of which were involved in the default-mode network. Conclusion: Unlike the consistently decreased global properties and nodal efficiencies in the structural connectome of T2DM patients, increases in Eloc, Cp, and nodal efficiencies in the functional connectome may be viewed as a compensatory mechanism due to functional plasticity and reorganization. Altered nodal efficiency can hint at cognitive decrements at an early stage in T2DM patients. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus is a growing public health problem in many countries. Poor Adherence to drugs, especially among patients with type 2 diabetes mellitus (T2DM) is often a challenging issue Objectives: The aim of the current study was to evaluate the demographic profile and serum insulin level in T2DM and patients taking oral hypoglycemic agents Methods: This comparative cross-sectional study was enrolled 120 patients of newly diagnosed T2DM and patients taking oral hypoglycemic agents. Patients demographic profile (age, gender, body mass index and waist circumference) were recorded. Investigations like; Serum insulin levels, Fasting blood sugar, Post lunch blood sugar and lipid profile were done in all the patients. Results: Most of the patients were 41-60 years age group, mean age was 52.2 + 10.5 years. Majority of the patients were male (70% in Metformin/Glimepiride group & 63% in both). Body mass index (BMI) were significantly higher among patients taking both Metformin and Glimepiride as compared to patients taking Metformin or Glimepiride alone (p<0.05). Serum insulin levels were significantly higher among patients taking oral Antidiabetics as compared to newly diagnosed T2DM patients (p<0.05). Lipid profile also significantly de-arranged among newly diagnosed diabetes mellitus patients (p<0.05). Conclusion: Serum insulin levels were significantly higher in patients taking oral Antidiabetic therapy and also significantly altered metabolic lipid profile among T2DM patients. [ABSTRACT FROM AUTHOR]

Immune cell–mediated chronic inflammation is one of the causes of type 2 diabetes mellitus (T2DM). Therefore, identifying inflammatory markers in circulating immune cells is highly important for predicting insulin resistance (IR) and the occurrence of T2DM. In this study, we discovered that differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) from T2DM patients were associated with innate immunity and chronic inflammatory responses through bulk transcriptome sequencing (bulk RNA-seq). Gene integration analysis revealed that nine DEGs were upregulated, and receiver operating characteristic (ROC) curve analysis revealed that V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), a candidate biomarker, has a certain predictive value for T2DM. In population-based cohort studies, we found that MAFB expression was significantly upregulated in the PBMCs of T2DM patients and was significantly correlated with homeostasis model assessment of IR (HOMA-IR), tumor necrosis factor-α (TNF-α), adiponectin (Adipoq), etc. We further evaluated the sensitivity and specificity of MAFB and other clinical parameters for predicting and diagnosing T2DM and found that MAFB expression in PBMCs had a positive effect on the prediction and diagnosis of T2DM. Finally, single-cell RNA sequencing (scRNA-seq) analysis revealed that the increase in MAFB expression was mainly in nonclassical monocytes. Our results suggest that increased MAFB expression in circulating monocytes may mediate chronic inflammatory status in patients with T2DM. Therefore, MAFB gene expression in circulating monocytes has certain clinical significance for predicting and assisting in the diagnosis of T2DM. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is not just a local health issue but a significant global health burden, affecting patient outcomes and clinical management worldwide. Despite the wealth of studies reporting T2DM biomarkers, there is an urgent need for a comparative review. This review aims to provide a comprehensive analysis based on the reported T2DM biomarkers and how these are linked with other conditions, such as inflammation and wound healing. A comparative review was conducted on 24 001 study participants, including 10 024 T2DM patients and 13 977 controls (CTL; age 30–90 years). Four main profiles were extracted and analysed from the clinical reports over the past 11 years: haematological (1084 cases vs. 1458 CTL), protein (6753 cases vs. 9613 CTL), cytokine (975 cases vs. 1350 CTL) and lipid (1212 cases vs. 1556 CTL). This review provides a detailed analysis of the haematological profile in T2DM patients, highlighting fundamental changes such as increased white blood cells and platelet counts, accompanied by decreases in red blood cell counts and iron absorption. In the serum protein profile, a reduction in albumin and anti‐inflammatory cytokines was noted along with an increase in globulin levels and pro‐inflammatory cytokines. Furthermore, changes in lipid profiles were discussed, specifically the decreases in high‐density lipoprotein (HDL) and the increases in low‐density lipoprotein (LDL) and triglycerides. Understanding the changes in these four biomarker profiles is essential for developing innovative strategies to create diagnostic and prognostic tools for diabetes management. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is an important public health issue owing to its rising global prevalence. Phthalates cause various health problems and are currently regulated in developed countries. However, studies on the impacts of low-level phthalate exposure under these regulations on T2DM are limited. This study investigated the impacts of combined and single exposures to phthalates and their alternatives on the prevalence of T2DM in 3,005 adults in the United States. The results indicated a positive joint effect of phthalate mixtures on the prevalence of T2DM. The joint effect was primarily attributed to Di-2-ethylhexyl phthalate (DEHP) metabolites, whereas the contributions of others were limited. This study suggests that, despite the stringent regulations on phthalates, low levels of phthalates, including DEHP, still have joint effects on T2DM. The findings highlight the importance of regulating hazardous phthalates and the need for safer alternatives to reduce public health risks. [ABSTRACT FROM AUTHOR]

Obesity has increased dramatically worldwide. Being overweight or obese can lead to various conditions, including dyslipidaemia, hypertension, glucose intolerance and metabolic syndrome (MetS), which may further lead to type 2 diabetes mellitus (T2DM). Previous studies have identified a link between β‐cell dysfunction and the severity of MetS, with multiple organs and tissues affected. Identifying the associations between pancreatic β‐cell dysfunction and organs is critical. Research has focused on the interaction between the liver, gut and pancreatic β‐cells. However, the mechanisms and related core targets are still not perfectly elucidated. The aims of this review were to summarize the mechanisms of β‐cell dysfunction and to explore the potential pathogenic pathways and targets that connect the liver, gut, adipose tissue, muscle, and brain to pancreatic β‐cell dysfunction. [ABSTRACT FROM AUTHOR]

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Purpose: Meteorin-like (Metrnl) is a novel adipokine which is highly expressed in adipose tissue and has a beneficial effect on glucose and lipid metabolism. High density lipoprotein cholesterol (HDL-C) is well recognized to be inversely associated with cardiovascular events. However, the relationship between serum Metrnl levels and HDL-C in the type 2 diabetes mellitus (T2DM) remains unclear. Therefore, the present study aimed to evaluate the association of serum Metrnl with HDL-C levels in T2DM. Materials and Methods: Eighty participants with T2DM were included in this cross-sectional study. They were divided into two groups according to HDL-C levels: Group1 (lower HDL-C group): HDL-C < 1.04 mmol/L; Group2 (higher HDL-C group): HDL-C ≥ 1.04 mmol/L. Serum Metrnl levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: As compared with lower HDL-C levels groups, serum Metrnl levels were significantly higher in the group with higher HDL-C. Binary logistic regression analysis showed serum Metrnl levels were positively associated with HDL-C group after adjustment with sex, age, body mass index (BMI), mean arterial pressure (MAP), fasting blood glucose (FPG), triglyceride (TG). Furthermore, serum Metrnl levels were inversely correlated with insulin resistance index (HOMA-IR). HDL-C levels were lowest in the group with the lowest Metrnl levels group and remained positively associated with Metrnl after adjustment for sex, age, BMI, TG, and HOMA-IR by using multivariate logistic regression analysis. Conclusion: Serum Metrnl levels were positively associated with HDL-C levels in patients with T2DM.This suggests that increasing serum Metrnl levels maybe a candidate for improving lipid metabolism and preventing cardiovascular events in T2DM. Registry and the Registration No. of the Study/Trial: The study was registered in the Chinese clinical trial registry (ChiCTR- 2100047148). [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) remains a significant global health issue, marked by insulin resistance and disrupted glucose metabolism. AMP-activated protein kinase (AMPK) serves as a key regulator of cellular energy balance, playing a crucial role in enhancing insulin sensitivity, promoting glucose uptake, and reducing glucose production in the liver. Recently, there has been growing interest in plant-derived flavonoids as natural activators of AMPK, offering a promising complementary approach to conventional diabetes treatments. This review delves into ten flavonoids identified as AMPK activators, including baicalein, dihydromyricetin, bavachin, 7-O-MA, derrone, and alpinumisoflavone. Their activation mechanisms are explored, which include both direct binding to the AMPK complex and indirect pathways involving upstream signaling. Through molecular docking studies, the binding affinities and interaction profiles of these flavonoids with AMPK are assessed, revealing varying levels of activation potential. Notably, baicalein and dihydromyricetin showed strong binding to the α1 subunit of AMPK, indicating high potential for robust activation. Additionally, this review provides a thorough analysis of the pharmacokinetic properties and drug-likeness of these flavonoids using the SwissADME tool, focusing on aspects such as ADME (Absorption, Distribution, Metabolism, and Excretion). While the overall profiles of these compounds are promising, issues like solubility and possible drug–drug interactions are areas that need further refinement. In summary, plant-derived flavonoids emerge as a promising avenue for developing new natural therapies for T2DM. Moving forward, research should aim at optimizing these compounds for clinical application, elucidating their specific mechanisms of AMPK activation, and confirming their efficacy in T2DM treatment. This review highlights the potential of flavonoids as safer and more holistic alternatives or adjuncts to current diabetes therapies. [ABSTRACT FROM AUTHOR]

Background: Depression in type 2 diabetes mellitus (T2DM) impacts glycemic control and complications. This study examines the influence of depression on compliance with recommended annual diabetes assessments in patients within the Local Healthcare Authority of Romagna. From a clinical health psychology perspective, understanding how depression influences patients' engagement in managing their conditions is crucial. This insight can help improve healthcare services by ensuring they address mental health needs and thereby enhance treatment effectiveness and overall patient outcomes. Methods: This retrospective cohort study included residents of Romagna with incident T2DM from 2015 to 2017, followed from 1 January 2018 to 31 December 2022. Depression was identified via hospital discharge records or antidepressant prescriptions. Adherence to diabetes care guidelines was measured using the Guideline Composite Indicator (GCI). Results: The study included 13,285 patients, with a mean age of 61.1 years. Prevalence of post-diabetes depression increased from 3.0% in 2018 to 8.9% in 2022. Initial analyses showed higher GCI rates among patients with depression. However, propensity-score adjustment revealed that by 2021–2022, patients with pre-diabetes depression had 5% lower compliance rates (p-value ≤ 0.05). Older adults with depression had reduced adherence, while younger adults with post-diabetes depression had higher adherence rates. Conclusions: Depression significantly affects adherence to diabetes care guidelines in T2DM patients, particularly among older adults. Integrated care models addressing both diabetes and depression are crucial for improving health outcomes. [ABSTRACT FROM AUTHOR]

Objectives: The metabolic syndrome in patients with schizophrenia has consistently been a challenge for clinicians. Previous studies indicate that individuals with schizophrenia are highly prone to developing type 2 diabetes mellitus (T2DM). In recent years, a continuous stream of new observational studies has been reported, emphasizing the pressing need for clinicians to gain a more precise understanding of the association between schizophrenia and T2DM. The objective of this meta-analysis is to integrate new observational studies and further explore the potential link between schizophrenia and the risk of T2DM. Methods: We conducted a comprehensive search of PubMed, Cochrane Library, Embase, and Web of Science using medical subject headings (MeSH) and relevant keywords. The risk of bias in cohort studies and case-control studies was assessed using the Newcastle-Ottawa Scale (NOS), while cross-sectional studies were evaluated using the Agency for Healthcare Research and Quality scale (AHRQ), scoring was based on the content of the original studies. A fixedeffects model was employed if P > 0.1 and I2 ≤ 50%, indicating low heterogeneity. Conversely, a random-effects model was utilized if I2 > 50%, indicating substantial heterogeneity. Publication bias was assessed using funnel plots and Egger's test. Statistical analyses were carried out using Stata statistical software version 14.0. Results: This meta-analysis comprised 32 observational studies, involving a total of 2,007,168 patients with schizophrenia and 35,883,980 without schizophrenia, published from 2004 to 2023. The pooled analysis revealed a significant association between a history of schizophrenia and an increased risk of T2DM (Odds Ratio [OR] = 2.15; 95% Confidence Interval [CI]: 1.83--2.52; I2 = 98.9%, P < 0.001). Stratified by gender, females with schizophrenia (OR = 2.12; 95% CI: 1.70- 2.64; I2 = 90.7%, P < 0.001) had a significantly higher risk of T2DM than males (OR = 1.68; 95% CI: 1.39-2.04; I2 = 91.3%, P < 0.001). Regarding WHO regions, EURO (OR = 2.73; 95% CI: 2.23-3.35; I2 = 97.5%, P < 0.001) exhibited a significantly higher risk of T2DM compared to WPRO (OR = 1.72; 95% CI: 1.32-2.23; I2 = 95.2%, P < 0.001) and AMRO (OR = 1.82; 95% CI: 1.40-2.37; I2 = 99.1%, P < 0.001). In terms of follow-up years, the >20 years subgroup (OR = 3.17; 95% CI: 1.24- 8.11; I2 = 99.4%, P < 0.001) showed a significantly higher risk of T2DM than the 10-20 years group (OR = 2.26; 95% CI: 1.76-2.90; I2 = 98.6%, P < 0.001) and <10 years group (OR = 1.68; 95% CI: 1.30-2.19; I2 = 95.4%, P < 0.001). Conclusions: This meta-analysis indicates a strong association between schizophrenia and an elevated risk of developing diabetes, suggesting that schizophrenia may function as an independent risk factor for T2DM. [ABSTRACT FROM AUTHOR]

People with type 2 diabetes mellitus (T2DM) show a high prevalence of steatotic liver disease (SLD), and especially metabolic dysfunction-associated steatotic liver disease (MASLD), with liver fibrosis. Their health-related quality of life (HRQL) is affected by multiple in part overlapping factors and aggravated by metabolic and liver-related comorbidities, including liver fibrosis stage. The aim of this study was to investigate the effect size of advanced fibrosis (AF) on the HRQL in people with T2DM. A total of 149 individuals with T2DM treated at a primary care provider within the German disease management program (DMP) were included in the final analysis. Vibration-controlled transient elastography (VCTE) was used to non-invasively detect steatosis and AF. The EQ-5D-3L questionnaire was used to assess the HRQL. Uni- and multivariable linear regression models were used to identify independent predictors of impaired HRQL. The majority was male (63.1%), and the median age was 67 years (IQR 59; 71). In the entire cohort, the prevalence of MASLD and AF was 70.7% and 19.5%, respectively. People with T2DM and AF had an overall lower HRQL in comparison to those without AF (p < 0.001). Obesity (β: − 0.247; 95% CI − 0.419, − 0.077) and AF (β: − 0.222; 95% CI − 0.383, − 0.051) remained independent predictors of a poor HRQL. In turn, T2DM-related comorbidities were not predictive of an impaired HRQL. Obesity and AF negatively affect the HRQL in patients with SLD and T2DM in primary care. Awareness of liver health and specific interventions may improve patient-reported and liver-related outcomes in people with T2DM. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder affecting people worldwide. It is characterized by several key features, including hyperinsulinemia, hyperglycemia, hyperlipidemia, and dysbiosis. Epidemiologic studies have shown that T2DM is closely associated with the development and progression of cancer. T2DM-related hyperinsulinemia, hyperglycemia, and hyperlipidemia contribute to cancer progression through complex signaling pathways. These factors increase drug resistance, apoptosis resistance, and the migration, invasion, and proliferation of cancer cells. Here, we will focus on the role of hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with T2DM in cancer development. Additionally, we will elucidate the potential molecular mechanisms underlying their effects on cancer progression. We aim to identify potential therapeutic targets for T2DM-related malignancies and explore relevant directions for future investigation. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease represents a significant risk factor for mortality in individuals with type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) is believed to play a crucial role in maintaining cardiovascular health through its multifaceted atheroprotective effects and its capacity to enhance glycemic control. The impact of dietary interventions and intermittent fasting (IF) on HDL functionality remains uncertain. The objective of this study was to assess the effects of dietary interventions and IF as a strategy to safely improve glycemic control and reduce body weight on functional parameters of HDL in individuals with T2DM. Methods: Before the 12-week intervention, all participants (n = 41) of the INTERFAST-2 study were standardized to a uniform basal insulin regimen and randomized to an IF or non-IF group. Additionally, all participants were advised to adhere to dietary recommendations that promoted healthy eating patterns. The IF group (n = 19) followed an alternate-day fasting routine, reducing their calorie intake by 75% on fasting days. The participants' glucose levels were continuously monitored. Other parameters were measured following the intervention: Lipoprotein composition and subclass distribution were measured by nuclear magnetic resonance spectroscopy. HDL cholesterol efflux capacity, paraoxonase 1 (PON1) activity, lecithin cholesterol acyltransferase (LCAT) activity, and cholesterol ester transfer protein (CETP) activity were assessed using cell-based assays and commercially available kits. Apolipoprotein M (apoM) levels were determined by ELISA. Results: Following the 12-week intervention, the IF regimen significantly elevated serum apoM levels (p = 0.0144), whereas no increase was observed in the non-IF group (p = 0.9801). ApoM levels correlated with weight loss and fasting glucose levels in the IF group. Both groups exhibited a robust enhancement in HDL cholesterol efflux capacity (p < 0.0001, p = 0.0006) after 12 weeks. Notably, only the non-IF group exhibited significantly elevated activity of PON1 (p = 0.0455) and LCAT (p = 0.0117) following the 12-week intervention. In contrast, the changes observed in the IF group did not reach statistical significance. Conclusions: A balanced diet combined with meticulous insulin management improves multiple metrics of HDL function. While additional IF increases apoM levels, it does not further enhance other aspects of HDL functionality. Trial registration: The study was registered at the German Clinical Trial Register (DRKS) on 3 September 2019 under the number DRKS00018070. [ABSTRACT FROM AUTHOR]

Objective: Type 2 diabetes mellitus (T2DM) incidence is increasing around the world as a progressive metabolic condition. The miRNA expression profile changes in the early stages of diabetes in body fluids. It can help in early diagnosis of diabetes, which reduces diabetes-related mortality. In this study, miR-194-5p gene expression levels in diabetic and pre-diabetic patients will be examined and compared to the healthy controls. Materials and Methods: The expression levels of miR-194-5p were evaluated in 90 participants, referred to Yazd diabetes centers (Iran) in 2022, including 30 T2DM, 30 prediabetics, and 30 healthy subjects by real-time PCR. The potential pathways affected by microRNA were fitted to the Enrichr web server by applying target genes predicted to miR-194-5p in the Target Scan Human 7.2 database. Results: The results of these studies indicate a gradual decrease in miR-194-5p expression levels in prediabetic and T2DM patients compared to healthy controls (P< 0.001). The role of the miR-194-5p target genes in T2DM-related signaling pathways such as the Wnt and TGF-beta pathways was also determined. Conclusion: The results indicate that miR-194-5p is a potential biomarker for the early diagnosis of T2DM due to its down-regulation in the serum of prediabetics and diabetics compared to healthy subjects. [ABSTRACT FROM AUTHOR]

Objectives: HbA1c is the most widely used test as an indicator of glucoregulation in patients with type 2 diabetes mellitus (T2DM). Asprosin and oxidative stress levels can be reduced with good glycemic control (GC) and thus prevented or delayed micro/macro complications in patients with T2DM. The relationship between asprosin, which is thought to affect GC, and oxidative stress parameters such as lipid hydroperoxides (LOOHs), glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (Cu,Zn-SOD), and total antioxidant capacity (TAC) was evaluated in T2DM patients. Materials and Methods: The study was conducted prospectively in 75 healthy people admitted to the hospital for a general health check-up and 150 T2DM patients treated in the diabetes outpatient clinic. The patient's glycemic status measurements were categorized as good glycemic control group (GGC) is defined as HbA1c < 7 and poor glycemic control (PGC) group is defined as HbA1c ≥ 7. Results: The study found a consistent increase in LOOH and MDA levels across the control, GGC, and PGC groups, while GSH, Cu/Zn-SOD, and TAC levels decreased in these respective groups. Additionally, asprosin levels showed a gradual rise in all groups. Positive correlations were observed between asprosin levels and various metabolic and oxidative stress markers, including BMI, WC, FBG, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), DM duration, LOOH, and MDA, while negative correlations were noted with GSH, Cu/Zn-SOD, and TAC specifically in the PGC group. Furthermore, multivariate regression analysis identified HOMA-IR as the primary influencing factor on asprosin levels in PGC patients. Conclusions: Current glycemic dysregulation may lead to increased circulating asprosin and oxidative stress, which cause complications. Since asprosin levels may be an important hormonal factor in determining GC in T2DM, the use of this hormone may be recommended in the future to accelerate therapeutic approaches in T2DM. Early diagnosis and appropriate treatment may delay the development and progression of diabetic complications. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to determine the effects of Taraxacum officinale extracts on mitochondrial unfolded protein response (UPRmt) and mitophagy in the hippocampi of type 2 diabetes mellitus (T2DM) rats. Materials and Methods: The T2DM model was established by a high-fat high-sucrose diet (HFSD) for 6 weeks and streptozotocin (STZ) administration. The rats were randomly divided into control, model, metformin (100 mg/kg/day), and T. officinale extracts (1,500 mg/kg/day) treatment groups. Fasting plasma glucose (FPG) levels, 2-h postprandial plasma glucose (2hPPG) levels, and sucrose preference rates (SPR) were ascertained. Enzyme-linked immunosorbent assay (ELISA) was used to quantify the levels of superoxide dismutase (SOD) and malonaldehyde (MDA) in the serum. Finally, the expression levels of UPRmt and mitophagy-related proteins were determined via Western blot analysis. Results: Rats in the model group exhibited significantly higher levels of FPG and 2hPPG but lower SPR than those in the control group. Rats in the Taraxacum group had lower FPG and 2hPPG levels and higher SPR than those of the model group. Moreover, clpP, HSP60, PINK-1, Parkin, P62, Beclin-1, and LC3-II/I proteins were significantly upregulated in the rats of the model group, relative to the control group. UPRmt and mitophagy-related proteins were markedly downregulated in rats of the Taraxacum group, relative to the model group. Conclusion: T2DM rats exhibited certain levels of anhedonia and depression, which were effectively alleviated by T. officinale extracts through the downregulation of UPRmt and mitophagy, and also by conferring protection to mitochondrial function. [ABSTRACT FROM AUTHOR]

Background: Although observational studies have reported a correlation between vitamin D deficiency and type 2 diabetes mellitus (T2DM), epidemiological evidence on the risk of obese subjects suffering T2DM due to a vitamin D deficiency is limited. Therefore, we investigated the correlation between T2DM and serum vitamin D, lipids, blood pressure, insulin indexes in an obese population. Methods: A total of 1440 participants including 450 healthy controls and 990 obese subjects, 470 without T2DM and 520 with T2DM. Serum vitamin D levels were measured, and the association between low levels and T2DM in obese subjects was examined using multinomial and linear regression analyses. Results: Of the participants, 35% had deficient or insufficient vitamin D levels (ie, < 20 ng/mL). Compared with healthy controls, obese subjects, particularly those with T2DM had lower vitamin D levels. Multinomial logistic regression analysis showed that obese subjects with T2DM had a gradually increasing risk for desirable (RO = 1.41, 95% CI 1.06– 1.93, P = 0.027), insufficient (RO = 1.83, 95% CI 1.27– 2.84, P < 0.001), or deficient ((RO = 2.14, 95% CI 1.15– 3.75, P = 0.014) vitamin D levels. In obese subjects with T2DM, vitamin D levels correlated inversely with the risk indicators for diabetes, such as the levels of HbA1c (β = − 0.16, P = 0.002), fasting insulin (Fins; β = − 0.31, P = 0.008), and HOMA-IR (β = − 0.19, P < 0.001). In obese subjects without T2DM, vitamin D was associated negatively with the risk of having T2DM at five-year follow-up (relative risk = 0.93, 95% CI 0.79– 0.97, P = 0.037). Conclusion: This study demonstrates that low vitamin D levels correlate with the presence of T2DM in the obese population. This finding indicates that hypovitaminosis D may be a potential biological vulnerability factor for the development of T2DM in obese subjects. [ABSTRACT FROM AUTHOR]

Introduction: The long-acting insulin analogue insulin degludec (IDeg) is increasingly recommended for type two diabetes (T2DM), yet clinical experience in China remains limited. This retrospective study aimed to delineate the initiation strategy for IDeg in Chinese hospitalized patients with T2DM. Methods: We retrospectively analyzed 217 Chinese hospitalized patients with T2DM who initiated IDeg from December 2018 to June 2020, calculating the initial dose and examining correlations between clinical characteristics and glucose profiles. Results: The initial IDeg doses ranged from 0.15 to 0.18 IU/kg·d, showing no association with clinical characteristics. During titration, mean blood glucose levels (MEAN) correlated positively with diabetes duration, age, and Glycosylated Hemoglobin (HbA1c), and negatively with body mass index (BMI), triglycerides (TG), and low-density lipoprotein (LDL). The coefficient of variation (CV) in glucose levels correlated positively with HbA1c and negatively with BMI and TG. The mean amplitude of glycemic excursions (MAGE) mirrored these trends, with additional negative correlations to estimated glomerular filtration rate (eGFR) and serum albumin (ALB). Notably, glycemic variability parameters did not correlate with the presence of diabetic ketoacidosis (DKA) at admission. Hypoglycemia was observed in 21 patients, with differences in MEAN and CV during titration being the only significant findings. Conclusion: The initial IDeg dosing was inadequate and not tailored to clinical features, and there were weak correlations between diabetes duration, age, BMI, eGFR, LDL, and ALB levels and glucose profile post-initiation. [ABSTRACT FROM AUTHOR]

Background and Aim: Endothelial dysfunction is a crucial precursor to atherosclerosis and cardiovascular complications, particularly prevalent in individuals with type 2 diabetes mellitus (T2DM). This study aimed to assess endothelial impairment in T2DM using flow-mediated dilatation (FMD) and to determine its correlation with body mass index (BMI), duration of diabetes, C-reactive protein (CRP) levels, and glycemic control. Materials and Methods: A total of 100 T2DM patients aged thirty to sixty participated. Doppler ultrasonography was used to measure brachial artery FMD, while blood samples were used to assess glycosylated hemoglobin A1c (HbA1c) and CRP levels. Correlations were evaluated using the Pearson correlation coefficient. Result: The duration of diabetes r value is negative 0.866, p-value less than 0.001, CRP levels as "r value" is negative 0.724, "P-value" less than 0.001, and HbA1c levels "r value" is negative 0.722, "P-value" less than 0.001 were observed to have negative relationships with FMD. Additionally, there was a significant association r value was negative 0.342, "P-value" less than 0.001 between BMI and FMD. These results were corroborated by subgroup analyses, which highlighted the intricacy of "endothelial dysfunction" in T2DM and the significance of comprehensively addressing several risk variables. This study elucidates the intricate interplay of metabolic, inflammatory, and vascular factors contributing to "endothelial dysfunction" in T2DM patients. Elevated HbA1c and CRP levels, prolonged diabetes duration, and high BMI were linked to impaired endothelial function, underscoring the importance of holistic risk factor management. Conclusion: For patients with T2DM, maintaining endothelial function and reducing cardiovascular risk require comprehensive treatment plans that target inflammation, obesity, and glycaemic management. Timely intervention and vigilant monitoring of risk factors are crucial to prevent vascular complications in high-risk populations. [ABSTRACT FROM AUTHOR]

The adzuki bean is a mature seed of the red bean leguminous plant, and people like to eat it because of its nutritious properties and moderate proportion of amino acids. Adzuki bean germination and the enrichment of GABA greatly improve the health effects of the adzuki bean. The effects of the GABA-rich adzuki bean on the expression of insulin-pathway-related genes and proteins in the liver of T2DM mice were studied via Western blotting and qPCR. The results showed that a GABA-rich adzuki bean diet could promote glycogen synthesis in the liver of T2DM mice, inhibit the activities of PEPCK and G-6-Pase, and significantly down-regulate the gene expression levels of PEPCK, G6PC and FOXO1 (p < 0.05) and the phosphorylation levels of FOXO1 and GSK3β. In addition, it can also up-regulate the expression of the AMPKα gene and down-regulate the expression of the SREBP1c gene to inhibit the synthesis of triglycerides and cholesterol in T2DM mice. Lipid accumulation in mice can alleviate glucose and lipid metabolism disorders and play an effective role in regulating blood glucose at liver tissue targets. This study suggested that the GABA-rich adzuki bean can improve hyperglycemia in type 2 diabetic mice by activating the IRS/PI3K/AKT signaling pathway in the liver. [ABSTRACT FROM AUTHOR]

Purpose: Rising obesity and type 2 diabetes mellitus (T2DM) rates can be mitigated by various strategies, with a 10% total body weight loss (TBWL) threshold often required for T2DM remission. T2DM remission rates after bariatric surgery like Roux-en-Y gastric bypass (RYGB) are well established; endoscopic sleeve gastroplasty (ESG) is a less invasive option that averages 15% TBWL and allows for T2DM remission. This study explores the DiaRem (Diabetes Remission post-RYGB) score's ability to predict T2DM remission 1-year post-ESG. Materials and Methods: We conducted a retrospective cohort study on 39 individuals with T2DM who underwent ESG. Age, utilization of diabetes medications, insulin administration, and hemoglobin A1c levels were used to calculate the DiaRem score. The area under the receiver operating characteristic curve (AUC) was employed to evaluate the discriminative ability of DiaRem in distinguishing diabetes remission. Results: Among the 39 patients with a median hemoglobin A1c of 6.7, 12.8% required insulin, and 43.6% used diabetes medication. At 1-year post-ESG, 69.2% of patients experienced diabetes remission with a median %TWBL of 12.7. The DiaRem score's ability to detect diabetes resolution for ESG patients had a sensitivity of 100% and a specificity of 58.3%, at the optimal cutoff value of 10. The AUC was 0.779 (95% CI 0.546–0.959). Conclusion: Our study demonstrated the DiaRem score's predictive value for T2DM remission post-ESG, highlighting its utility in clinical decision-making for ESG-related outcomes. Further investigation is needed to identify alternative indicators that may enhance predictive accuracy, thus refining personalized decision-making for this patient group. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes mellitus is the most common type of diabetes, characterized by varying degrees of insulin resistance and diminishing beta-cell function, which increases the risk of macrovascular and microvascular complications. Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist that is administered once weekly and approved for treating adults with type 2 diabetes mellitus. It can be used as a monotherapy or in addition to oral hypoglycemic or insulin therapy. Aim: This study aims to provide information contributing to assessing the efficacy and safety of weekly 1.5 mg dulaglutide therapy in Saudi adult patients with type 2 diabetes mellitus. Methods: A retrospective single-arm cohort study using a purposive sample to recruit type 2 diabetes mellitus patients on dulaglutide from endocrine and diabetic outpatient clinics in King Saud Medical City (N = 205). Data were collected from participants' medical profiles and through the phone using interview questionnaires. Results: Most participants were female and married; approximately 33% had had diabetes for more than 20 years, 41.4% of the sample had third-class obesity, and more than half had used dulaglutide for the last 1–2 years. With therapy, weight, body mass index, hemoglobin A1c, and fasting blood sugar were significantly improved after 6 and 12 months from baseline. The main side effects reported were nausea (52%) and fatigue (28%). Conclusion: Dulaglutide is a safe and effective therapy that demonstrated favorable glycemic control and weight reduction in obese type 2 diabetes patients of Saudi origin. [ABSTRACT FROM AUTHOR]

Kang-Xin Li,1,&ast; Hui Yuan,1,&ast; Jing Zhang,2,3 Xiao-bin Peng,1 Wei-Fen Zhuang,1 Wen-Tao Huang,1 Hui-Xin Liang,1 Ying Lin,1 Ying-Zhen Huang,1 Shu-Lan Qin1 1Department of Endocrinology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, People’s Republic of China; 3China Resources Jiangzhong Pharmaceutical Group Co., Ltd., Nanchang, Jiangxi, 330004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shu-Lan Qin, Email qinshulan@smu.edu.cnIntroduction: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterised by insulin resistance, hyperglycaemia, and inflammation, with oxidative stress contributing to its progression. Curcumin (CUR), known for its anti-inflammatory, antioxidant, and insulin sensitising effects, has shown potential for the treatment of T2DM but is limited by low solubility and bioavailability. This study investigated long-circulating curcumin-loaded liposomes (CUR-LPs) to improve curcumin stability, solubility, and circulation and assessed their effect on insulin resistance in a murine model of T2DM.Methods: CUR-LPs were prepared using the ethanol injection method and characterized for morphology, particle size, zeta potential, encapsulation efficiency, drug-loading capacity, and in vitro release. Cell viability was tested on murine L929 cells. In a T2DM murine model, after four weeks of CUR-LP treatment, inflammatory markers TNF-α and IL-6 were measured by real-time polymerase chain reaction, and liver tissues were analyzed for glutathione (GSH) and superoxide dismutase (SOD) via colorimetry.Results: CUR-LPs were spherical, with an average diameter of (249 ± 2.3) nm and a zeta potential of (− 33.5 ± 0.8) mV. They exhibited an encapsulation efficiency of (99.2 ± 0.5) %and a drug-loading capacity of (1.63 ± 0.02) %. CUR embedding in liposomes significantly maintained CUR release. In L929 cells, over 80% viability was maintained at 12 uM CUR concentration after 24 h. In HFD/STZ-induced T2DM mice, CUR-LPs improved blood glucose and insulin levels more efficiently than free CUR, and CUR-LPs also reduced hepatic inflammation (TNF-α, IL-6), enhanced hepatic GSH and SOD, and attenuated liver injury.Conclusion: CUR-LPs improved glucose metabolism and insulin resistance in HFD/STZ-induced T2DM mice, which may be associated with a decrease in liver inflammation and oxidative stress.Keyworks: T2DM, curcumin, liposomes, insulin resistance, glucose metabolism, oxidative stress

Abstract Background Although the exact role of mitophagy in the pathogenesis of diabetic cardiomyopathy (DCM) caused by type 2 diabetes mellitus (T2DM) remains controversial, recent studies revealed inhibition of mitophagy exacerbates cardiac injury in DCM. The zinc transporter ZIP7 has been reported to be upregulated by high glucose in cardiomyocytes and ZIP7 upregulation leads to inhibition of mitophagy in mouse hearts in the setting of ischemia/reperfusion. Nevertheless, little is known about the role of ZIP7 and its relationship with mitophagy in DCM caused by T2DM. Methods T2DM was induced with high-fat diet (HFD) and streptozotocin. The cardiac-specific ZIP7 conditional knockout (ZIP7 cKO) mice were generated by adopting CRISPR/Cas9 system. Cardiac function was evaluated with echocardiography. Mitophagy was assessed by detecting mito-LC3II, mitoKeima, and mitoQC. Reactive oxygen species (ROS) were detected with DHE and mitoB. Results ZIP7 was upregulated by T2DM in mouse hearts and ZIP7 cKO reduced mitochondrial ROS generation in mouse hearts with T2DM. Mitophagy was suppressed by T2DM in mouse hearts, which was prevented by ZIP7 cKO. T2DM inhibited PINK1 and Parkin accumulation in cardiac mitochondria, an effect that was prevented by ZIP7 cKO, pointing to that ZIP7 upregulation mediates T2DM-induced suppression of mitophagy by inhibiting the PINK1/Parkin pathway. T2DM induced mitochondrial hyperpolarization and decrease of mitochondrial Zn2+ and this was blocked by ZIP7 cKO, indicating that upregulation of ZIP7 leads to mitochondrial hyperpolarization by reducing Zn2+ within mitochondria. Finally, ZIP7 cKO prevented cardiac dysfunction and fibrosis caused by T2DM. Conclusions ZIP7 upregulation mediates the inhibition of mitophagy by T2DM in mouse hearts by suppressing the PINK1/Parkin pathway. Reduction of mitochondrial Zn2+ due to upregulation of ZIP7 accounts for the inhibition of the PINK1/Parkin pathway. Prevention of ZIP7 upregulation is essential for the treatment of T2DM-induced cardiomyopathy.

Jingjing Li,1 Yu Zhang,2 Rui Wu,1 Guodong Ma,1 Li Sheng,1 Yun Feng,1 Yang Han,1 Lina Zhang,1 Janfeng Guo,1 Rongbo Li1 1Department of Infectious Diseases, Hohhot First Hospital, Hohhot, Inner Mongolia Autonomous Region, 010000, People’s Republic of China; 2Department of Dermatology and Venereology, Hohhot, Inner Mongolia Autonomous Region People’s Hospital, 010000, People’s Republic of ChinaCorrespondence: Jingjing Li, Department of Infectious Diseases, Hohhot First Hospital, No. 148, South Second Ring Road, Zhaojun Road, Yuquan District, Hohhot, Inner Mongolia Autonomous Region, 010000, Tel +86-18047422188, Email 1151664990@qq.comPurpose: To explore the value of different inflammatory markers in predicting the severity of coronavirus disease 2019 (COVID-19) in patients with type 2 diabetes mellitus (T2DM).Patients and Methods: A total of 116 patients with COVID-19 in patients with T2DM were collected from December 2022 to March 2023 and were divided into a mild case group (77 cases) and a severe case group (39 cases). The ratio of neutrophil to lymphocyte (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil to lymphocyte × platelet ratio (NLPR), lymphocyte ratio to monocyte (LMR), systemic inflammatory response index (SIRI), systemic inflammatory index (SII), systemic inflammatory composite index (AISI), procalcitonin (PCT), C-reactive protein (CRP) and lactate dehydrogenase (LDH) were compared between the two groups. The screening effect of each variable on the progression of the disease was analyzed using receiver operating characteristic (ROC) curves.Results: NLR, PLR, NLPR, MLR, SIRI, SII, AISI, LDH, CRP and PCT in severe case group were higher than those in mild case group (P< 0.05), and LMR was lower than those in mild case group (P< 0.05). ROC curve analysis further demonstrated the diagnostic performance of these biomarkers, with PCT having the largest area under the ROC curve (AUCROC) of 0.83.Conclusion: NLR, PLR, NLPR, SIRI, SII, LDH, CRP and PCT demonstrate greater reliability in diagnostic value and clinical utility for predicting the severity of COVID-19 in patients with T2DM.Keywords: COVID-19, T2DM, inflammatory index, LDH, CRP, PCT

Abstract Background Psychological Insulin Resistance (PIR) and negative perceptions regarding insulin treatment are noteworthy challenges in T2DM management, which hinder the timely initiation of insulin treatment. To get past these obstacles a reliable tool is required to evaluate patients’ perspectives on insulin administration. Our study aims to conduct a comprehensive systematic review to evaluate the validity and reliability of different validation tests used in the psychometric validation of the ITAS in T2DM patients. Methods A literature search was carried out, using PubMed, Google Scholar, EMBASE, Cochrane Library and Science Direct. Only those studies assessing content validity, construct validity, concurrent validity, discriminant validity, internal consistency reliability (Cronbach’ α), and items-total correlation were retrieved. Results A total of 14 studies illustrated the validity and reliability of ITAS in T2DM patients. Content validity results of S-CVI was 0.97, and I-CVI was 0.8–1.00. Construct validity with factor loading was greater than the threshold value of 0.3. The concurrent validity of ITAS vs. PAID, WHO-5, and SPI was 0.35 (P

Abstract Aim To explore the topological organization alterations of functional connectomes in type 2 diabetes (T2DM) patients with and without mild cognitive impairment (MCI), and compare these with structural connectomes changes. Methods Twenty-six T2DM patients with MCI (DM-MCI), 26 without cognitive impairment (DM-NC), and 28 healthy controls were included. Diffusion tensor imaging (DTI) and resting-state functional MRI images were acquired. Networks were constructed and graph-theory based network measurements were calculated. The global network parameters and nodal efficiencies were compared across the three groups using one-way ANOVA and a false-discovery rate correction was applied for multiple comparisons. Partial correlation analyses were performed to investigate relationships between network parameters, cognitive performance and clinical variables. Results In the structural connectome, the DM-MCI group exhibited significantly decreased global efficiency (Eglob) and local efficiency (Eloc) compared to the DM-NC and control groups. In the functional connectome, the DM-MCI group exhibited increased Eloc and clustering coefficient (Cp) compared to the controls. No significant differences were found in Eglob, Eloc, or Cp between the DM-NC and the control group, both in structural and functional connectomes. Nodal efficiencies decreased in some brain regions of structural and functional networks in the DM-MCI and DM-NC groups, but increased in five regions in functional network, some of which were involved in the default-mode network. Conclusion Unlike the consistently decreased global properties and nodal efficiencies in the structural connectome of T2DM patients, increases in Eloc, Cp, and nodal efficiencies in the functional connectome may be viewed as a compensatory mechanism due to functional plasticity and reorganization. Altered nodal efficiency can hint at cognitive decrements at an early stage in T2DM patients.

Abstract People with type 2 diabetes mellitus (T2DM) show a high prevalence of steatotic liver disease (SLD), and especially metabolic dysfunction-associated steatotic liver disease (MASLD), with liver fibrosis. Their health-related quality of life (HRQL) is affected by multiple in part overlapping factors and aggravated by metabolic and liver-related comorbidities, including liver fibrosis stage. The aim of this study was to investigate the effect size of advanced fibrosis (AF) on the HRQL in people with T2DM. A total of 149 individuals with T2DM treated at a primary care provider within the German disease management program (DMP) were included in the final analysis. Vibration-controlled transient elastography (VCTE) was used to non-invasively detect steatosis and AF. The EQ-5D-3L questionnaire was used to assess the HRQL. Uni- and multivariable linear regression models were used to identify independent predictors of impaired HRQL. The majority was male (63.1%), and the median age was 67 years (IQR 59; 71). In the entire cohort, the prevalence of MASLD and AF was 70.7% and 19.5%, respectively. People with T2DM and AF had an overall lower HRQL in comparison to those without AF (p

Mohammad Abu Shaphe,1 Mohammed M Alshehri,1 Ramzi Abdu Alajam,1 Bushra Alfaifi,1 Ali Hakamy,2 Monira I Aldhahi,3 Ausaf Ahmad,4 Ashfaque Khan,5 Aafreen,5 Abdur Raheem Khan5 1Department of Physical Therapy, College of Nursing and Health Sciences, Jazan University, Jazan, Saudi Arabia; 2Respiratory Therapy Department, College of Nursing and Health Sciences, Jazan University, Jazan, Saudi Arabia; 3Department of Rehabilitation Sciences, College of Health and Rehabilitation Sciences, Princess Nourah bint Abdulrahman University (PNU), Riyadh, Saudi Arabia; 4Department of Community Medicine, Kalyan Singh Government Medical College Bulandshahr, Uttar Pradesh, India; 5Department of Physiotherapy, Integral University, Lucknow, IndiaCorrespondence: Abdur Raheem Khan, Department of Physiotherapy, Integral University, Lucknow, India, Email abdul.fortis@gmail.comBackground: Hypertension (HTN) is prevalent in individuals with type 2 Diabetes Mellitus (T2DM), doubling the risk of developing chronic complications. Despite normal routine checks, many patients with diabetes exhibit abnormal blood pressure (BP) profiles identified by 24-hour ambulatory Blood Pressure monitoring (ABPM). This study aimed to analyse blood pressure variability in patients with diabetes to enhance current knowledge and improve clinical practice.Methods: This cross-sectional study obtained ethical approval from Jazan University and involved 58 patients with type 2 Diabetes Mellitus (T2DM) who adhered to the strict inclusion and exclusion criteria. Comprehensive clinical and laboratory data, including demographic, clinical, and essential laboratory parameters, were collected using a standardized form. Blood Pressure (BP) was meticulously monitored using the Sun Tech Oscar 2 ABPMR device, with measurements commencing between 8 am and 10 am, extending over 24 hours. The study calculated averages and evaluated systolic and diastolic percentage dipping during 24-hour, daytime, and night-time intervals. Participants classified as “dippers” experienced a BP reductions of at least 10%.Results: Fifty-eight normotensive T2DM patients, with a mean age of 45.51 ± 6.7 years, were monitored over 24 months. Among the 58 individuals assessed using ABPM, a non-dipping pattern was observed in 45 participants (77.58%), whereas 13 (22.41%) exhibited a dipping pattern. Postprandial and fasting blood sugar levels were distinct; the dipper group demonstrated better post-meal glucose control (p=0.02), whereas the non-dipper group had superior fasting glucose control (p=0.04). The dipper group showed a higher 24-hour average systolic BP (p=0.00) and increased dipping percentages for systolic and diastolic BP during sleep.Conclusion: Over 77% of ABPM-evaluated individuals showed non-dipping patterns, with a higher BMI being strongly associated. Laboratory findings revealed distinct variations in the postprandial and fasting blood sugar levels, suggesting a potential genetic predisposition.Keywords: hypertension, T2DM, ABPM, cardiovascular, haemodynamic

Background and Aim: Endothelial dysfunction is a crucial precursor to atherosclerosis and cardiovascular complications, particularly prevalent in individuals with type 2 diabetes mellitus (T2DM). This study aimed to assess endothelial impairment in T2DM using flow-mediated dilatation (FMD) and to determine its correlation with body mass index (BMI), duration of diabetes, C-reactive protein (CRP) levels, and glycemic control. Materials and Methods: A total of 100 T2DM patients aged thirty to sixty participated. Doppler ultrasonography was used to measure brachial artery FMD, while blood samples were used to assess glycosylated hemoglobin A1c (HbA1c) and CRP levels. Correlations were evaluated using the Pearson correlation coefficient. Result: The duration of diabetes r value is negative 0.866, p-value less than 0.001, CRP levels as “r value” is negative 0.724, “P-value” less than 0.001, and HbA1c levels “r value” is negative 0.722, “P-value” less than 0.001 were observed to have negative relationships with FMD. Additionally, there was a significant association r value was negative 0.342, “P-value” less than 0.001 between BMI and FMD. These results were corroborated by subgroup analyses, which highlighted the intricacy of “endothelial dysfunction” in T2DM and the significance of comprehensively addressing several risk variables. This study elucidates the intricate interplay of metabolic, inflammatory, and vascular factors contributing to “endothelial dysfunction” in T2DM patients. Elevated HbA1c and CRP levels, prolonged diabetes duration, and high BMI were linked to impaired endothelial function, underscoring the importance of holistic risk factor management. Conclusion: For patients with T2DM, maintaining endothelial function and reducing cardiovascular risk require comprehensive treatment plans that target inflammation, obesity, and glycaemic management. Timely intervention and vigilant monitoring of risk factors are crucial to prevent vascular complications in high-risk populations.

Abstract Background Cardiovascular disease represents a significant risk factor for mortality in individuals with type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) is believed to play a crucial role in maintaining cardiovascular health through its multifaceted atheroprotective effects and its capacity to enhance glycemic control. The impact of dietary interventions and intermittent fasting (IF) on HDL functionality remains uncertain. The objective of this study was to assess the effects of dietary interventions and IF as a strategy to safely improve glycemic control and reduce body weight on functional parameters of HDL in individuals with T2DM. Methods Before the 12-week intervention, all participants (n = 41) of the INTERFAST-2 study were standardized to a uniform basal insulin regimen and randomized to an IF or non-IF group. Additionally, all participants were advised to adhere to dietary recommendations that promoted healthy eating patterns. The IF group (n = 19) followed an alternate-day fasting routine, reducing their calorie intake by 75% on fasting days. The participants’ glucose levels were continuously monitored. Other parameters were measured following the intervention: Lipoprotein composition and subclass distribution were measured by nuclear magnetic resonance spectroscopy. HDL cholesterol efflux capacity, paraoxonase 1 (PON1) activity, lecithin cholesterol acyltransferase (LCAT) activity, and cholesterol ester transfer protein (CETP) activity were assessed using cell-based assays and commercially available kits. Apolipoprotein M (apoM) levels were determined by ELISA. Results Following the 12-week intervention, the IF regimen significantly elevated serum apoM levels (p = 0.0144), whereas no increase was observed in the non-IF group (p = 0.9801). ApoM levels correlated with weight loss and fasting glucose levels in the IF group. Both groups exhibited a robust enhancement in HDL cholesterol efflux capacity (p

In Ayurveda, every individual is believed to possess a unique entity known as Prakriti, which distinguishes them from others physically, physiologically, and psychologically. This entity also determines an individual's response to a particular stimulus, and it is believed that such responses are not solely determined by genetics. The present research aims to validate the Ayurvedic concept of Prakriti from a modern molecular perspective to strengthen the personalized and precise treatment approach. A study was conducted to investigate the role of the KCNJ11gene in the susceptibility of individuals to type 2 diabetes mellitus (T2DM) with their metabolic status. The research involved allele mining on three major Prakriti groups - Vata, Pitta, and Kapha - in 112 patients with T2DM and 112 healthy individuals. The KCNJ11 gene, responsible for insulin secretion membrane pore formation, was analyzed to determine the susceptibility of different Prakriti types to T2DM. The MutPred tool predicted the molecular cause of disease-related amino acid substitution. According to the study, only Pitta and Kapha Prakriti were diagnosed with diabetes, while all three Prakriti types were present in the control group of healthy individuals. A protein model was prepared, and the changes resulting from mutations were observed for each group in their protein sequence, both as synonymous and non-synonymous mutations. Ultimately, these changes contributed to the manifestation of T2DM. Based on the findings, it appears that Prakriti groups may experience changes in protein function due to nonsynonymous mutations and differences in amino acids at the protein level.

Jie Zhang, Xuelin Yao, Yijing Chen, Qing Feng, Yi Zhang, Tian Jiang, Songtao Tang, Nan Zhang, Fang Dai, Honglin Hu, Qiu Zhang Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Qiu Zhang; Honglin Hu, Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Shushan District, 230032, People’s Republic of China, Email zhangqiu@ahmu.edu.cn; huhonglin@ahmu.edu.cnBackground: Diabetes mellitus and hypertension often coexist and share common risk factors. This study investigated the correlation between glycemic management and the prevalence of hypertension among Chinese adults diagnosed with type 2 diabetes mellitus (T2DM).Methods: This study included 1715 patients with T2DM from four cities in Anhui Province, China. Sociodemographic characteristics of the sample participants were collected via questionnaires. A univariate analysis of variance (ANOVA) was utilized for continuous variables, and chi-square testing was used for categorical variables. Binary logistic regression was utilized to examine the relationship between blood pressure and variables including fasting plasma glucose (FPG), glycosylated haemoglobin (HbA1c), body mass index (BMI), waist circumference (WC), physical activity, dyslipidemia, and family history of hypertension.Results: FPG levels did not increase the risk of hypertension, while HbA1c was significantly and negatively associated with hypertension risk. HbA1c levels ranged from 7.2 to 8.6%, with odds ratios (OR) of 0.68 and 95% confidence intervals (CI) of 0.48 to 0.97 and a significant p value of less than 0.05. For the HbA1c levels above 8.6%, the OR was 0.58 with a 95% CI of 0.39 to 0.87 and a significant p value of less than 0.01. Furthermore, advanced age, higher BMI, greater waist circumference, presence of dyslipidemia, and positive family history of hypertension were all found to be significantly and independently linked to a heightened risk of developing hypertension. These associations remain significant after further adjustment.Conclusion: There was a negative association between HbA1c and the risk of hypertension, and the association remained significant after adjustment for antihypertensive drug use.Keywords: FPG, HbA1c, T2DM, hypertension

Caiyun Guo, Yang Lu Department of Endocrinology, YuYao People’s Hospital, Ningbo, Zhejiang Province, People’s Republic of ChinaCorrespondence: Caiyun Guo, Department of Endocrinology, YuYao People’s Hospital, 800 Chengdong Road, Ningbo, Zhejiang Province, 315400, People’s Republic of China, Email guocaiyun9112@163.comBackground: A short-term insulin intensive therapy is an important method used in clinical practice to control blood glucose, and a scientific post-treatment plan is key to long-term blood glucose stability control. This study aimed to investigate efficacy and safety of early conversion of intensive insulin therapy to IDegLira in T2DM patients.Methods: This study was a prospective study, involving 80 T2DM patients finally. Patients were firstly treated with insulin for intensified therapy (Pre-IDegLira group), then switched to insulin degludec and liraglutide (IDegLira) for 3 months (IDegLira-3 months group). Data including HbA1c, fasting blood glucose, fasting C-peptide, weight, insulin dosage, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were analyzed. Correlations between fasting blood glucose and other parameters were evaluated with Pearson correlation analysis.Results: IDegLira early conversion significantly reduced fasting blood glucose (p< 0.001), weight (p=0.015), and insulin dosage (p=0.001) of T2DM patients compared to those of Pre-IDegLira group. HbA1c level was remarkably lower in T2DM patients underwent IDegLira early conversion compared to that in Pre-IDegLira group (p< 0.001), with HbA1c < 7% proportion of 73.75% (59/80). IDegLira early conversion significantly downregulated levels of TC (p< 0.001), TG (p< 0.001), LDL-C (p< 0.001), and upregulated HDL-C level (p=0.017) of T2DM patients, compared to those in Pre-IDegLira group. IDegLira early conversion markedly reduced ALT (p< 0.001) and AST (p=0.002) levels of T2DM patients compared to those in Pre-IDegLira group. IDegLira early conversion demonstrated a positive correlation between fasting blood glucose and HbA1c (r=0.531, p< 0.001) or TG level (r=0.336, p=0.002) in T2DM patients.Conclusion: Early conversion of intensive insulin therapy to IDegLira effectively reduced fasting blood glucose and HbA1c in T2DM patients with higher safety.Keywords: insulin intensive therapy, IDegLira, T2DM, early conversion, safety

Objective: Type 2 diabetes mellitus (T2DM) incidence is increasing around the world as a progressive metabolic condition. The miRNA expression profile changes in the early stages of diabetes in body fluids. It can help in early diagnosis of diabetes, which reduces diabetes-related mortality. In this study, miR-194-5p gene expression levels in diabetic and pre-diabetic patients will be examined and compared to the healthy controls. Materials and Methods: The expression levels of miR-194-5p were evaluated in 90 participants, referred to Yazd diabetes centers (Iran) in 2022, including 30 T2DM, 30 prediabetics, and 30 healthy subjects by real-time PCR. The potential pathways affected by microRNA were fitted to the Enrichr web server by applying target genes predicted to miR-194-5p in the Target Scan Human 7.2 database. Results: The results of these studies indicate a gradual decrease in miR-194-5p expression levels in prediabetic and T2DM patients compared to healthy controls (P< 0.001). The role of the miR-194-5p target genes in T2DM-related signaling pathways such as the Wnt and TGF-beta pathways was also determined. Conclusion: The results indicate that miR-194-5p is a potential biomarker for the early diagnosis of T2DM due to its down-regulation in the serum of prediabetics and diabetics compared to healthy subjects.

Abstract Background Uncontrolled type 2 diabetes mellitus (UT2DM) and its associated consequences nowadays have been a global health crisis, especially for adults. Iron has the property to oxidize and reduce reversibly, which is necessary for metabolic processes and excess accumulation of iron indicated by serum ferritin levels could have a significant impact on the pathophysiology of T2DM via generation of reactive oxygen species (ROS). However, no conclusive evidence existed about the association of serum ferritin with the state of glycemic control status. Therefore, this study aimed to evaluate serum ferritin levels and associated factors in uncontrolled T2DM patients and compare them with those of controlled T2DM and non-diabetic control groups. Methods A hospital-based comparative cross-sectional study was conducted among conveniently selected 156 study participants, who were categorized into three equal groups of uncontrolled T2DM, controlled T2DM, and non-diabetic control groups from October 2 to December 29, 2023 at St. Paul’s Hospital Millennium Medical College. A pre-tested structured questionnaire was used to collect socio-demographic and diabetes-related information. The laboratory tests were done using an automated chemistry analyzer and IBM-SPSS statistical software (version-27) was utilized for data entry and analysis with a significance level of p

Purpose: To assess cytological conjunctival changes in patients with type 2 diabetes mellitus (T2DM)-associated dry eye disease in the presence of treatment with a combination of trehalose and sodium hyaluronate. Material and Methods: This study was conducted at the Pirogov Vinnytsia Regional Clinical Hospital, the clinical site of the National Pirogov Memorial Medical University, from April to December 2023. We used prospective data of 46 patients (92 eyes; mean age, 62.47 ± 6.24 years). Results: Most patients (67%) showed abnormal conjunctival impression cytology (CIC) changes (Nelson’s grade 2 and 3) before treatment. Among these, grade 3 squamous metaplasia was twice as common as grade 2 squamous metaplasia; this demonstrated apparent CIC changes in the group of patients, and a substantial prevalence of squamous metaplasia in type 2 diabetics. After treatment with a combination of trehalose 3% plus sodium hyaluronate 0.15%, neutrophil infiltration was observed only in 5 (11%) patients (р = 0.0375), which may indicate an anti-inflammatory effect of the combination. Conclusion: We found a significant effect of a combination of trehalose 3% plus sodium hyaluronate 0.15% on the state of the ocular surface, with the resolution of inflammatory conjunctival infiltration, in patients with T2DM (p = 0.0375). Because stabilization or slowing of damage to epithelial cells is important for patients with T2DM and was observed in the presence of treatment with the combination eye drop, these patients require long-term treatment with the medication.

Abstract Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion and/or insulin action. Increasing evidence suggests that inflammation played an important role in the pathogenesis of T2DM. Prospective studies on the link between immunoglobulins concentrations and the risk of T2DM in adults are limited. We developed a cohort study including 7,093 adults without T2DM history. The incidence of T2DM was 16.45 per 1,000 person-years. Compared with the lowest quartiles, the hazard ratios (95% confidence intervals) of T2DM for the highest quartiles of IgG, IgE, IgM and IgA were 0.64 (0.48–0.85), 0.94 (0.72–1.23), 0.68 (0.50–0.92) and 1.62 (1.24–2.11) (P for trend was