Type 2 Diabetes Mellitus Subjects Research Articles

Influence of Bifidobacterium breve on the Glycaemic Control, Lipid Profile and Microbiome of Type 2 Diabetic Subjects: A Preliminary Randomized Clinical Trial.

Type 2 diabetes mellitus (T2DM) is one of the most highly prevalent metabolic disorders worldwide. Uncontrolled T2DM can lead to other health threats such as cardiac arrest, lower-limb amputation, blindness, stroke, impaired kidney function, and microvascular and macrovascular complications. Many studies have demonstrated the association between gut microbiota and diabetes development and probiotic supplementation in improving glycemic properties in T2DM. The study aimed to evaluate the influence of Bifidobacterium breve supplementation on glycemic control, lipid profile, and microbiome of T2DM subjects. Forty participants were randomly divided into two groups, and they received probiotics (50 × 109 CFU/day) or placebo interventions (corn starch; 10 mg/day) for 12 weeks. The changes in the blood-urea nitrogen (BUN), aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), fasting blood sugar (FBS), glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine levels, and other factors such as body-mass index, visceral fat, body fat, and body weight were assessed at baseline and after 12 weeks. B. breve supplementation significantly reduced BUN, creatinine, LDL, TG, and HbA1c levels compared to the placebo group. Significant changes were observed in the microbiome of the probiotic-treated group compared to the placebo group. Firmicutes and proteobacteria were predominant in the placebo and probiotic-treated groups. Genera Streptococcus, Butyricicoccus, and species Eubacterium hallii were significantly reduced in the probiotic-treated group compared to the placebo. Overall results suggested that B. breve supplementation could prevent worsening of representative clinical parameters in T2DM subjects. The current study has limitations, including fewer subjects, a single probiotic strain, and fewer metagenomic samples for microbiome analysis. Therefore, the results of the current study require further validation using more experimental subjects.

STUDY ON PLASMA LEPTIN LEVELS IN TYPE 2 DIABETES MELLITUS PATIENTS WITH OVERWEIGHT OR OBESITY

Objectives: To investigate plasma leptin level and its association with some risk factors in type 2 diabetes mellitus (T2DM) patients with overweight or obesity. Subjects and methods: A cross-sectional descriptive and comparable study was conducted on 266 patients assigned into three groups, including T2DM patients with overweight or obesity (study group, n = 104), non-overweight/non-obese atients with T2DM (disease-control, n = 109) and healthy control subjects (n = 53). Plasma leptin levels were quantified with ELISA Kit at the Department of Pathophysiology, Vietnam Military Medical University. Results: For type 2 diabetic patients with obesity/overweight, we found no significant difference in plasma leptin levels between the study group and the disease-control and healthy subjects (0.43; 0.35-0.53 ng/mL vs 0.42; 0.34-0.52 ng/mL and 0.46; 0.36-0.60 ng/mL, respectively) with p > 0.05. In the overweight or obese diabetic patients, there was a positive correlation of leptin levels with age (r = 0.228; p = 0.02), waist circumference (WC) (r = 0.638; p < 0.001), hip circumference (HC) (r = 0.473; p < 0.001), W/H (r = 0.471; p < 0.001) and serum creatinine levels (r = 0.508; p < 0.001). Additionally, plasma leptin levels were higher in overweight/obese patients who were diabetic for more than 5 years (0.47 ± 0.16 ng/mL) than in those with diabetes less than 5 years (0.38 ± 0.15 ng/mL) (p < 0.05). Significantly higher blood leptin levels were noted in the group with hypertension than in normotensive individuals (p < 0.05).

Evidence from genetic studies among rs2107538 variant in the CCL5 gene and Saudi patients diagnosed with type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a chronic and metabolic disorder that affects the adult population. Chemokines are proinflammatory cytokines that play a role in the development of chronic diseases such as obesity, gestational diabetes, and T2DM. The C-C Motif Chemokine Ligand 5 (CCL5) gene plays a role in antiviral immunity, tumor development, obesity, impaired glucose tolerance, and T2DM. This study aimed to investigate the genetic role of the rs2107538 variant in the CCL5 gene in Saudi patients with T2DM. Sixty subjects with T2DM patients and 60 healthy controls participated in this prospective case-control study. Prior to Sanger sequencing, genomic DNA was extracted and amplified with Polymerase chain reaction (PCR), after which the PCR products were purified. The collected data were used to conduct various statistical analyses to determine the relationship between T2DM and control subjects. The findings of the current study revealed a positive association for most parameters between T2DM and control subjects (p < 0.05). The frequency of genotypes (p = 0.002, AA vs.GG: p = 0.008, GA + AA vs. GG: p = 0.0002) and alleles (A vs. G: p = 0.0007) revealed a strong risk association. Multiple logistic regression with individual effects revealed a link between SBP and HDLc levels (p = 0.03). In patients with T2DM, waist (p = 0.001), TG (p = 0.0007), and LDLc (p = 0.0004) levels were all associated with the ANOVA. Finally, the rs2107538 variant was linked to an increased risk of T2DM in the Saudi Population. The GA and AA genotypes were strongly connected to the T2DM subjects. In order to rule out disease-causing variants in the global population, future research should use a large sample size.

Metabolic Overlap between Alzheimer's Disease and Metabolic Syndrome Identifies the PVRL2 Gene as a New Modulator of Diabetic Dyslipidemia.

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) share metabolic alterations such as abnormal insulin and lipid metabolism and have some common genetic factors such as APOE genotype. Taking this into account, we hypothesized that we could identify common genetic factors involved in the development of diabetes and cardiovascular diseases. We first genotyped 48 single nucleotide polymorphisms (SNPs) previously associated with AD in a cohort composed of 330 patients with cognitive impairment (CI) to assess their association with plasma lipids. Second, we conducted pleiotropy-informed conjunctional false discovery rate (FDR) analysis designed to identify shared variants between AD and plasma lipid levels. Finally, we used the SNPs to be found associated with lipid parameters and AD to search for associations with lipoprotein parameters in 281 patients with cardiometabolic risk. Five SNPs were significantly associated with lower levels of cholesterol transported in remnant lipoprotein particles (RLPc) in subjects with CI; among these SNPs was the rs73572039 variant in PVRL2. Stratified QQ-plots were conducted on GWAS designed for AD and triglycerides (TG). The cross-trait analysis resulted in a total of 22 independent genomic loci associated with both AD and TG levels with a conjFDR < 0.05. Among these loci, two pleiotropic variants were located in PVRL2 (rs12978931 and rs11667640). The three SNPs in PVRL2 were significantly associated with RLPc, TG, and number of circulating VLDL and HDL particles in subjects with cardiometabolic risk. We have identified three variants in PVRL2 that predispose individuals to AD that also influence the lipid profile that confers cardiovascular risk in T2DM subjects. PVRL2 is a potential new modulating factor of atherogenic dyslipidemia.

Connecting islet-specific hub genes and pathways in type 2 diabetes mellitus through the bioinformatics lens

Type 2 diabetes mellitus (T2DM) is a non-communicable, metabolic disorder in which the loss of function and/or mass of pancreatic β-cells occurs. The incidence of T2DM is increasing worldwide and needs more efficient biomarkers for diagnosis along with better therapeutic interventions with fewer side effects. Transcriptomics analysis provides a complete overview of the molecular mechanisms involved at the system level to identify the set of genes that have stayed unnoticed so far for complex diseases, like T2DM. This study has been conducted to identify novel hub gene candidates for T2DM. Five human GEO datasets from pancreatic islets of normal healthy volunteers and T2DM subjects, namely, GSE118139, GSE20966, GSE25724, GSE38642 and GSE41762 were chosen and the differentially expressed genes were shortlisted. The overlapping hub genes between these datasets were identified, which included ERBB2, HGF, MET, MMP1, PDGFRA and PLAU as downregulated genes; and ABCC8, G6PC2, IAPP, PCSK1 and SLC2A2 as up-regulated genes in the pancreatic islets from T2DM subjects. These hub genes could be developed as a panel for diagnosis/prognosis of T2DM in the population and can be targeted for drug development for more effective management of T2DM in the future.

Low physical activity among middle-aged type-2 diabetic outpatients of two peripheral hospitals in Bangladesh.

Physical activity (PA) is an important lifestyle recommendation for managing type-2 diabetes mellitus (T2DM). However, low PA among them is a global public health concern, including Bangladesh. We aimed to investigate the prevalence of low PA levels and its associated sociodemographic factors particularly among middle-aged T2DM subjects, which is quite limited globally and unknown in Bangladesh. In this cross-sectional study, we conveniently recruited 356 T2DM subjects (aged 40-60 years) from outpatient departments of the corresponding diabetic hospitals from Pirojpur and Dinajpur, the southern and northern districts, respectively. The primary outcome was low PA (via metabolic equivalents <600), using the Global Physical Activity Questionnaire. Univariable and multivariable binary logistic regression analyses were used to identify the factors associated with low PA. Among the participants (mean age 51.0±6.9 years), men and women were with almost equal proportions (48.9% and 51.1%, respectively). The prevalence (95% Confidence Intervals [CI]) of low PA was 34.8% (29.9-39.7). The median sitting or reclining time was 6 hours on a typical day. The odds (OR [95% CI]; P) of low PA was found to be significantly higher in respondents with primary or no education compared to the above-primary level, in unadjusted (1.6 [1.1-2.6]; 0.029) and adjusted (2.0 [1.1-3.7]; 0.028) associations both. In conclusion, over one-third of the middle-aged study subjects had a low PA level, which was associated with education. There is a high demand for designing and implementing PA enhancing interventions among them.

Acute bouts of aerobic and resistance exercise similarly alter inhibitory control and response time while inversely modifying plasma BDNF concentrations in middle-aged and older adults with type 2 diabetes.

Impairments in several domains of cognitive functions are observed in people with Type 2 Diabetes Mellitus (T2DM), often accompanied by low Brain-derived neurotrophic factor (BDNF) concentrations. Although aerobic and resistance exercise enhances cognitive functions and raises BDNF concentrations in several populations, it remained uncertain in T2DM subjects. This study compared the effects of a single bout of aerobic (AER, 40min of treadmill walk at 90-95% of the maximum walk speed) or resistance (RES, 3 × 10 repetitions in eight exercises at 70% of 10-RM) exercise on specific cognitive domain performance and plasma BDNF concentrations of physically active T2DM subjects. Eleven T2DM subjects (9 women/2 men; 63 ± 7years) performed two counterbalanced trials on non-consecutive days. Stroop Color and Word (SCW) task [assessing the attention (congruent condition) and inhibitory control (incongruent condition)], Visual response time (assessing the response time), and blood collection (for plasma BDNF concentrations) were performed pre and post-exercise sessions. With distinct magnitude, both AER and RES improved the incongruent-SCW (d = -0.26 vs. -0.43 in AER and RES, respectively; p < 0.05), RT(best) (d = -0.31 vs. -0.52, p < 0.05), and RT(1-5) (d = -0.64 vs. -0.21, p < 0.05). The congruent-SCW and RT(6-10) were not statistically different. Plasma BDNF concentrations were elevated 11% in AER (d = 0.30) but decreased by 15% in RES (d = -0.43). A single session of aerobic or resistance exercise similarly improved the inhibitory control and response time of physically active T2DM subjects. Nevertheless, aerobic and resistance exercise sessions induced an opposite clinical effect in plasma BDNF concentrations.

U-shaped association between serum IGF2BP3 and T2DM: A cross-sectional study in Chinese population.

To clarify the expression of N6-methyladenosine (m6 A) modulators involved in the pathogenesis of type 2 diabetes mellitus (T2DM). We further explored the association of serum insulin-like growth factor 2 mRNA-binding proteins 3 (IGF2BP3) levels and odds of T2DM in a high-risk population. The gene expression data set GSE25724 was obtained from the Gene Expression Omnibus, and a cluster heatmap was generated by using the R package ComplexHeatmap. Differential expression analysis for 13 m6 A RNA methylation regulators between nondiabetic controls and T2DM subjects was performed using an unpaired t test. A cross-sectional design, including 393 subjects (131 patients with newly diagnosed T2DM, 131 age- and sex-matched subjects with prediabetes, and 131 healthy controls), was carried out. The associations between serum IGF2BP3 concentrations and T2DM were modeled by restricted cubic spline and logistic regression models. Two upregulated (IGF2BP2 and IGF2BP3) and 5 downregulated (methyltransferase-like 3 [METTL3], alkylation repair homolog protein 1 [ALKBH1], YTH domain family 2 [YTHDF2], YTHDF3, and heterogeneous nuclear ribonucleoprotein [HNRNPC]) m6 A-related genes were found in islet samples of T2DM patients. A U-shaped association existed between serum IGF2BP3 levels and odds of T2DM according to cubic natural spline analysis models, after adjustment for body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyeride. Multivariate logistic regression showed that progressively higher odds of T2DM were observed when serum IGF2BP3 levels were below 0.62 ng/mL (odds ratio 3.03 [95% confidence interval 1.23-7.47]) in model 4. Seven significantly altered m6 A RNA methylation genes were identified in T2DM. There was a U-shaped association between serum IGF2BP3 levels and odds of T2DM in the general Chinese adult population. This study provides important evidence for further examination of the role of m6 A RNA methylation, especially serum IGF2BP3 in T2DM risk assessment.

Changes in the Microbiota and their Roles in Patients with Type 2 Diabetes Mellitus

An association between type 2 diabetes mellitus (T2DM) and gut microbiota is well established, but the results of related studies are inconsistent. The purpose of this investigation is to elucidate the characteristics of the gut microbiota in T2DM and non-diabetic subjects. Forty-five subjects were recruited for this study, including 29 T2DM patients and 16 non-diabeticsubjects. Biochemical parameters, including body mass index (BMI), fasting plasma glucose (FPG), serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and hemoglobin A1c (HbA1c), were analyzed and correlated with the gut microbiota. Bacterial community composition and diversity were detected in fecal samples using direct smear, sequencing, and real-time polymerase chain reaction (PCR). In this study, it was observed that indicators such as BMI, FPG, HbA1c, TC, and TG in T2DM patients were on the rise, concurrent with dysbiosis of the microbiota. We observed an increase in Enterococci and a decrease in Bacteroides, Bifidobacteria, and Lactobacilli in patients with T2DM. Meanwhile, total short-chain fatty acids (SCFAs) and D-lactate concentrations were decreased in the T2DM group. In addition, FPG was positively correlated with Enterococcus and negatively correlated with Bifidobacteria, Bacteroides, and Lactobacilli. This study reveals that microbiota dysbiosis is associated with disease severity in patients with T2DM. The limitation of this study is that only common bacteria were noted in this study, and more in-depth related studies are urgently needed.

High serum Bhlhe40 levels are associated with subclinical atherosclerosis in patients with type 2 diabetes mellitus: A cross-sectional study.

Our previous studies have shown that the basic helix-loop-helix family member e40 (Bhlhe40) plays a critical role in regulating calcification and senescence of vascular smooth muscle cells induced by high glucose. In this study, we determined the association between serum Bhlhe40 levels and subclinical atherosclerosis in patients with type 2 diabetes mellitus (T2DM). 247 patients with T2DM were included in this cross-sectional study between June 2021 and July 2022. The presence of subclinical atherosclerosis was evaluated by carotid ultrasonography. Serum Bhlhe40 concentrations were measured with an ELISA kit. Serum Bhlhe40 levels were remarkably higher in the subclinical atherosclerosis group than in the subjects without subclinical atherosclerosis (p < 0.001). Correlation analysis showed a positive correlation between serum Bhlhe40 and carotid intima-media thickness (C-IMT) (r = 0.155, p = 0.015). The optimal threshold of serum Bhlhe40 > 5.67ng/mL had an area under the ROC curve (AUC) was 0.709 (p < 0.001). In addition, serum Bhlhe40 levels were associated with the prevalence of subclinical atherosclerosis (OR: 1.790, 95% CI: 1.414-2.266, p < 0.001). Serum Bhlhe40 levels were significantly higher in T2DM subjects with subclinical atherosclerosis and positively associated with C-IMT.

Th1 bias of liver mucosal-associated invariant T cells promotes hepatic gluconeogenesis in type 2 diabetes mellitus.

It is acknowledged that aberrant liver immunity contributes to the development of type 2 diabetes mellitus (T2DM). Mucosal-associated invariant T (MAIT) cells, an innate-like T-cell subset, are enriched in the human liver. Nevertheless, the characterisation and potential role of hepatic MAIT cells in T2DM remain unclear. Fourteen newly diagnosed T2DM subjects and 15 controls received liver biopsy. The frequency and cytokine production of MAIT cells were analysed by flow cytometry. The expression of genes involved in glucose metabolism was determined in HepG2 cells co-cultured with hepatic MAIT cells. Compared with controls, hepatic MAIT cell frequency was significantly increased in T2DM patients (24.66% vs. 14.61%, p=0.001). There were more MAIT cells producing interferon-γ (IFN-γ, 60.49% vs. 33.33%, p=0.021) and tumour necrosis factor-α (TNF-α, 46.84% vs. 5.91%, p=0.021) in T2DM than in controls, whereas their production of interleukin 17 (IL-17) was comparable (15.25% vs. 4.55%, p=0.054). Notably, an IFN-γ+ TNF-α+ IL-17+/- producing MAIT cell subset was focussed, which showed an elevated proportion in T2DM (42.66% vs. 5.85%, p=0.021) and positively correlated with plasma glucose levels. A co-culture experiment further indicated that hepatic MAIT cells from T2DM upregulated the gene expression of pyruvate carboxylase, a key molecule involved in gluconeogenesis, in HepG2 cells, and this response was blocked with neutralising antibodies against IFN-γ and TNF-α. Our data implicate an increased Th1-like MAIT cell subset in the liver of newly diagnosed T2DM subjects, which induces hyperglycaemia by promoting hepatic gluconeogenesis. It provides novel insights into the immune regulation of metabolic homoeostasis. NCT03296605 (registered at www. gov on 12 October 2018).

The prevalence of left ventricular hypertrophy associated with type-2 diabetes in Shiraz, Iran: a cross-sectional study

BackgroundLeft ventricular hypertrophy (LVH) is a common diagnosis in patients with cardiovascular disease (CVD). The prevalence of LVH among patients with Type-2 Diabetes Mellitus (T2DM), high blood pressure and aging is higher than the healthy population and has been independently associated with an increased risk for future cardiac event, including stroke. The aim of this study is to identify the prevalence of LVH among T2DM subjects and evaluate its association with related risk factors of CVD patients in the metropolis of Shiraz, Iran. The novelty of this study is that there has been no known published epidemiological study related to the relationship of LVH and T2DM on this unique population.Materials and methodThis cross-sectional study was designed based on collected data of 7715 free dwelling subjects in the community-based Shiraz Cohort Heart Study (SCHS) from 2015 to 2021, ages 40–70 years. Overall, 1118 subjects with T2DM were identified in the SCHS and after exclusion criteria, 595 subjects remained eligible for study. Subjects with electrocardiography (ECG) results, which are appropriate and diagnostics tools, were evaluated for the presence of LVH. Thus, the variables related to LVH and non-LVH in subjects with diabetes were analyzed using version-22 statistical package for social sciences software program to ensure consistency, accuracy, reliability, and validity for final analysis. Based upon related variables and identifying LVH and non-LVH subjects, the relevant statistical analysis was implemented to ensure its consistency, accuracy, reliability, and validity for final analysis.ResultsOverall, the prevalence of diabetic subjects was 14.5% in the SCHS study. Furthermore, the prevalence of hypertension in the study subjects aged 40–70 years was 37.8%. The prevalence of hypertension history in T2DM study subjects for LVH compared to non-LVH was (53.7% vs. 33.7%). The prevalence of LVH among patients with T2DM as the primary target of this study was 20.7%. Analytical findings comparing both LVH and non-LVH subjects who have T2DM identified significance for variables in the older (≥ 60) mean and categorical age group (P < 0.0001), history of hypertension (P < 0.0001), mean and categorical duration of hypertension in years (P < 0.0160), status of controlled versus uncontrolled hypertension level (P < 0.0120), the mean systolic blood pressure (P < 0.0001) as well as mean duration years of T2DM and categorical duration of diabetes in years (< 0.0001 and P < 0.0060), mean fasting blood sugar (< 0.0307) and categorical status of FBS Level (mg/dl): controlled and uncontrolled FBS status of controlled vs. uncontrolled FBS levels P < 0.0020). However, there were no significant findings for gender (P = 0.3112), diastolic blood pressure mean (P = 0.7722) and body mass index (BMI) mean and categorical BMI (P = 0.2888 and P = 0.4080, respectively).ConclusionThe prevalence of LVH in the study increases significantly among T2DM patients with hypertension, older age, years of hypertension, years of diabetes, and higher FBS. Thus, given the significant risk of diabetes and CVD, evaluation of LVH through reasonable diagnostic testing with ECG can help reduce the risk of future complications through the development of risk factor modifications and treatments guidelines.

Association of High sensitivity C-reactive protein (Hs-CRP) with poor Glycaemic control and Coronary Heart Disease in Type 2 Diabetes Mellitus

High sensitivity C-reactive protein (Hs-CRP) is a sensitive marker of subclinical inflammation associated with atherosclerosis. Uncontrolled diabetes mellitus (DM) is one of the important risk factors of coronary heart disease (CHD). The aim of this study was to evaluate the association between Hs-CRP levels and both glycaemic control and CHD in Syrian type 2 diabetes mellitus (T2DM) patients. A random sample of 108 subjects was selected from T2DM and/or CHD patients seen in the National Centre for Diabetes, and the outpatient clinic of cardiology department at Tishreen University Hospital in Latakia. Four groups were formed: Group 1 [T2DM (+) CHD (-), N=29], Group 2 [T2DM (-) CHD (+), N=25], Group 3 [T2DM (+) CHD (+), N=29], and Group 4 (T2DM (-) CHD (-), N=25). Serum Hs-CRP and glycated haemoglobin (HBA1C) were determined. The SPSS 25.0 program was used for the statistical analysis. Probability (P) value less than 0.05 was considered statistically significant. Mean Hs-CRP level was higher in T2DM subjects with (5.23±1.56mg/l) or without (2.29±0.78mg/l) CHD compared to T2DM (-) CHD (-) patients (0.16±0.04mg/l), (p&lt;0.0001 for both). Mean Hs-CRP level in T2DM with CHD was not only higher than T2DM patients without CHD (p&lt;0.0001), but also than non-diabetic subjects with CHD (2.56±0.45mg/l) (p&lt;0.0001). There was a positive correlation between serum Hs-CRP and HBA1C in T2DM patients with CHD (r=0.781, P&lt;0.0001), Similarly, Hs-CRP levels were positively and significantly correlated with HBA1C in T2DM patients without CHD (r=0.800, p&lt;0.0001). We also noticed that for every 1.0% increase in HbA1c there was an 77% increase in the likelihood of having an elevated Hs-CRP. We concluded that Hs-CRP was strongly correlated with glycaemic control in T2DM patients. The highest Hs-CRP level was observed in T2DM with CHD patients. Hs-CRP could predict the incidence of coronary heart disease in T2DM patients.

Altered dynamic functional architecture in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) can accelerate cognitive decline and even dementia so that the underlying mechanism deserves further exploration. In the resting state, brain function is still changing dynamically. At present, it is still unknown whether the dynamic functional connectivity (dFC) between various brain regions is in a stable state. It is necessary to interpret brain changes from a new perspective, that is, the stability of brain architecture. In this study, we used a fixed dynamic time scale to explore the stability of dynamic functional architecture in T2DM, then the dynamic effective connectivity (dEC) was used to further explain how information flows through dynamically fluctuating brain architecture in T2DM. Two brain regions with decreased stability were found including the right supra-marginal gyrus (SMG) and the right median cingulate gyrus (MCG) in T2DM subjects. The dEC variation has increased between the left inferior frontal gyrus (IFG) and the right MCG. The direction of causal flow is from the right MCG to the left IFG. The combination of stability and dEC can not only show the stability of dynamic functional architecture in brain but also reflect the fluidity of brain information, which is an innovative and interesting attempt in the field of neuroimaging. The changes of dynamic architecture in T2DM patients may present an innovative perspective and explanation for their cognitive decline.

Evaluation of the Pharmacokinetics of Dapagliflozin in Patients With Chronic Kidney Disease With or Without Type 2 Diabetes Mellitus.

Evidence shows that sodium-glucose cotransporter 2 inhibitors, such as dapagliflozin, can delay the progressive decline of kidney function in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). We used a population pharmacokinetics (popPK) model to characterize the pharmacokinetics of dapagliflozin in patients with CKD and compare dapagliflozin systemic exposure in different populations, such as CKD with or without T2DM and T2DM without CKD. A 2-compartmental popPK model was developed from a previous popPK model. The final popPK model was based on 9715 dapagliflozin plasma concentrations from 3055 patients included in clinical studies involving adults with CKD with or without T2DM, adults with T2DM, healthy subjects, and pediatric patients with T2DM. Overall, the apparent clearance for patients treated with dapagliflozin was 21.6L/h, similar to previous estimates in adults with T2DM and healthy subjects (22.9L/h). Model-derived area under the plasma concentration-time curve (AUC) was not meaningfully different between patients with CKD with and without T2DM. Median AUC was 1.6-fold higher in adult patients with CKD with T2DM compared with adult patients with T2DM without CKD. Compared with patients with normal kidney function (estimated glomerular filtration rate ≥90mL/min/1.73m2 ), median AUC was 2.4-fold higher in patients with CKD (with/without T2DM) with estimated glomerular filtration rate 15-29mL/min/1.73m2 owing to decreased renal clearance of dapagliflozin. A higher AUC was observed in patients with a higher age or lower body weight but was not considered clinically relevant. This popPK model adequately described dapagliflozin pharmacokinetics and found that systemic exposure in patients with CKD was consistent, irrespective of T2DM status.

Association between METS-IR and Prediabetes or Type 2 Diabetes Mellitus among Elderly Subjects in China: A Large-Scale Population-Based Study.

The metabolic score for insulin resistance (METS-IR) was recently proposed as a non-insulin-based, novel index for assessing insulin resistance (IR) in the Western population. However, evidence for the link between METS-IR and prediabetes or type 2 diabetes mellitus (T2DM) among the elderly Chinese population was still limited. We aimed to investigate the associations between METS-IR and prediabetes or T2DM based on large-scale, cross-sectional, routine physical examination data. In a total of 18,112 primary care service users, an increased METS-IR was independently associated with a higher prevalence of prediabetes (adjusted odds ratio [aOR] = 1.457, 95% confidence interval [CI]: 1.343 to 1.581, p < 0.001) and T2DM (aOR = 1.804, 95%CI: 1.720 to 1.891, p < 0.001), respectively. The aOR for prediabetes in subjects with the highest quartile of METS-IR was 3.060-fold higher than that in those with the lowest quartile of METS-IR. The aOR for T2DM in subjects with the highest quartile of METS-IR was 6.226-fold higher than that in those with the lowest quartile of METS-IR. Consistent results were obtained in subgroup analyses. Our results suggested that METS-IR was significantly associated with both prediabetes and T2DM. The monitoring of METS-IR may add value to early identification of individuals at risk for glucose metabolism disorders in primary care.

PANCREATIC FAT CONTENT PLAYS AN IMPORTANT ROLE IN THE DEVELOPMENT OF TYPE 2 DIABETES MELLITUS SIMILAR TO THAT OF LIVER FAT CONTENT.

Type 2 diabetes mellitus (T2DM) is a major health problem worldwide. Earlier studies have reported that pancreatic fat content (PFC) and liver fat content (LFC) are risk factors for T2DM. The aim of the present study was to demonstrate the relationship between PFC, LFC and T2DM. A total of 70 T2DM subjects and 30 non-diabetic volunteers who underwent Dixon-based magnetic resonance imaging (MRI) method at Yixing People's Hospital between December 2018 to December 2020 were included in the study. The three-point Dixon (3p-Dixon) method was used to measure the fat content in the pancreas and liver. Clinical indices including gender, age, body mass index (BMI), total cholesterol, triglyceride, glucose and C peptide levels were collected. The association between PFC, LFC, and OGTT-derived parameters was examined by Pearson and Spearman correlation analyses. T2DM subjects had higher PFC and LFC than those measured in the non-diabetic subjects (p <0.05). PFC and LFC were associated positively with OGTT-derived parameters such as insulin secretion, insulin resistance, and early- and late-phase insulin secretion in the male T2DM subjects(p <0.05), but not in the non-diabetic and female T2DM subjects. The relationship between PFC and OGTT-derived parameters was also more obvious than that for LFC in overweight and obese male patients with T2DM whose BMI was >24 kg/m2. PFC and LFC were both associated with β-cell dysfunction and insulin resistance in males with T2DM. The relationship between PFC and β-cell dysfunction and insulin resistance was more obvious than that observed for LFC in overweight and obese male T2DM patients. More attention should therefore be paid to PFC in clinical settings.

Association of Adiponectin-Leptin Ratio and HOMA-IR in Obese Patients with and without Type 2 Diabetes Mellitus: A Cross-sectional Study

Introduction: Obesity is one of the leading causes of morbidity and mortality due to associated risk factors, including Type 2 Diabetes Mellitus (T2DM). Obese and diabetic patients have lower amounts of adiponectin. Leptin, a hormone released by adipocytes that controls hunger, is crucial in the emergence of obesity. Furthermore, it has been claimed that the Adiponectin/ Leptin Ratio (ALR) correlates with Insulin Resistance (IR) better than adiponectin or leptin alone. Aim: To evaluate adiponectin, leptin, and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) in obese subjects with and without T2DM and compare the variations, if any, from the normal subjects. Materials and Methods: This hospital-based, cross-sectional study was carried out at Sri Guru Ram Das (SGRD) University of Health Sciences, Amritsar, and Punjab Institute of Medical Sciences (PIMS), Jalandhar from January 2020 to December 2022. A total of 125 subjects of either gender aged above 18 years, visiting the medicine Outpatient Department (OPD) of PIMS, Jalandhar, were included in the study. Among them, 25 healthy volunteers served as controls. Serum levels of Adiponectin, Leptin, and Insulin were estimated using the Enzyme-Linked Immunosorbent Assay (ELISA) method. The data obtained were statistically analysed using one-way Analysis of Variance (ANOVA) test (with Bonferroni post-hoc). Results: A total of 125 participants were analysed in the present study, with 50 being obese with T2DM (mean age: 50.22±8.6 years), 50 being obese without T2DM (mean age: 46.9±9.8 years), and 25 being non obese non diabetic individuals (controls) (mean age: 42.8±9.09 years). A higher number of females 78 (62.4%) reported to the OPD compared to males 47 (37.6%). Although no statistical significance was found, there was a considerable decrease in adiponectin levels in obese and obese with T2DM subjects. Moreover, the leptin levels and HOMA-IR were increased in obese and obese with T2DM subjects compared to the control subjects. Conclusion: ALR may be used as a clinical marker for assessing the morbidity due to obesity and in T2DM subjects. Moreover, lifestyle modifications can be targeted to prevent IR.

Insulin Resistance and Hypertension among Type 2 Diabetes Subjects in a Tertiary Institution in South East Nigeria

Background: Type 2 diabetes mellitus (T2DM) is frequently associated with hypertension (HTN), adding significantly to its overall morbidity and mortality. Aim: This study aimed to investigate the relationship between insulin resistance (IR) and blood pressure and other factors associated with both conditions. Patients, Materials and Methods: A case–control study of 180 subjects consisting of 60 with T2DM and HTN, 60 with T2DM and normal blood pressure, and 60 without T2DM or HTN (control). Sociodemographic, anthropometric, and clinical parameters were obtained from each subject and control. IR was derived from homeostasis model assessment (HOMA)-IR index calculated from fasting blood glucose and insulin. Results: The mean age of subjects with T2DM and HTN was 49.58 ± 10.50 years, that of subjects with T2DM and normotension was 48.50 ± 10.44 years, while that of controls was 48.85 ± 10.15 years. IR (HOMA-IR ≥2) was found in 96.7% of subjects with T2DM and HTN, 88.3% of those with T2DM and normotension, and 1.7% of subjects with neither of both conditions. Central obesity (Waist circumference “WC”), overweight, and obesity (BMI) significantly related to IR in subjects with T2DM and HTN (p = 0.020, 0.021 and 0.016 respectively) while only WC and obesity (BMI) significantly related to IR in subjects with T2DM and normotension (p = 0.001 and 0.036 respectively). Conclusions: There is a high prevalence of IR in T2DM subjects which is heightened by the presence of HTN.

Association of GCK (rs1799884), GCKR (rs780094), and G6PC2 (rs560887) Gene Polymorphisms with Type 2 Diabetes among Malay Ethnics.

Background Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder, and the underlying causes remain unknown and have not been fully elucidated. Several candidate genes have been associated with T2DM in various populations with conflicting results. The variations found in glucokinase ( GCK ), glucokinase regulatory protein ( GCKR ), and glucose-6-phosphatase 2 ( G6PC2 ) genes were not well studied, particularly among Asians. Aims The main objective of this study was to determine the candidate genetic polymorphisms of GCK (rs1799884), GCKR (rs780094), and G6PC2 (rs560887) genes in T2DM among Malay ethnics. Methods In this candidate gene association study, a total of 180 T2DM subjects and 180 control subjects were recruited to determine the genotypes using polymerase chain reaction-restriction fragment length polymorphism and Taqman probe assay methods. Genotype and allele frequencies in case and control samples were compared using the chi-squared test to determine a significant difference. Results The body mass index, fasting blood glucose, hemoglobin A1c, systolic and diastolic blood pressure, and total cholesterol were significantly different ( p < 0.05) between T2DM and control subjects. The genotypic and allelic frequencies of GCK (rs1799884), GCKR (rs780094), and G6PC2 (rs560887) gene polymorphisms were significantly different between T2DM and controls ( p < 0.05). Conclusion Hence, rs1799884 of GCK gene and rs780094 of GCKR gene and rs560887 of the G6PC2 gene are possible genetic biomarkers in T2DM development among Malay ethnics in Malaysia.