Obese Type 2 Diabetes Mellitus Research Articles

Correlation between obesity and serum 25-hydroxyvitamin D levels in patients with type 2 diabetes

[Objective] The paper analyzes the correlation of vitamin D level with obesity degree and serum 25-hydroxyvitamin D level in patients with type 2 diabetes mellitus (T2DM) through clinical case studies, which can provide clinical guidance for obese T2DM patients' weight control to lower their risk of developing metabolic illnesses. [Methods] A total of 249 patients with T2DM were chosen from among those hospitalized at Lanzhou University's First Hospital between April and September of 2023. The serum 25-hydroxyvitamin D level, body fat rate, fasting blood glucose, and fasting insulin of the subjects were detected, and 198 T2DM patients with low serum 25-hydroxyvitamin D levels were selected as the observation group. 51 T2DM patients with normal serum 25-hydroxyvitamin D levels were selected as the control group, and the correlation between type 2 diabetes mellitus and vitamin D levels and obesity was analyzed. [Results] Obesity and serum vitamin D insufficiency are associated with type 2 diabetes. Both vitamin D deficiency and obesity eventually lead to T2D, endocrine disorders, and other common diseases. [Conclusions] Low plasma 25-hydroxyvitamin D (25[OH]D) concentration and high BMI are correlated with an increased risk of diabetes.

Preoperative contributing factors and the remission of diabetes after metabolic surgery: the mediating role of preoperative triglyceride

Background and objectiveLimited understanding exists regarding the factors affecting the prognosis of surgical treatment for type 2 diabetes mellitus (T2DM), particularly in Chinese patients. In this study, we examined a cohort of early and intermediate obese T2DM patients to explore the potential impact of preoperative lipid metabolism in metabolic surgery on the postoperative remission of T2DM.MethodsParticipants with T2DM and obesity underwent metabolic surgery. Clinical data, including baseline body mass index, percentage of excess weight loss, and preoperative biochemical indicators, were collected and analyzed. A multidisciplinary team conducted patient follow-up. Remission was defined as sub-diabetic hyperglycemia (HbA1c < 48 mmol/mol, fasting glucose 100–125 mg/dl) without pharmacological intervention for at least 12 months.ResultsOver a median follow-up of 27 months, 96 T2DM patients with metabolic surgery were studied, with no laparotomies required. Among these patients, 61 (63.5%) achieved complete remission, and 85 (88.5%) experienced remission. In multivariable analysis models, preoperative fasting blood glucose (FBG) significantly correlated with all postoperative outcomes. Furthermore, mediation analysis indicated that preoperative triglycerides (TG) mediated 26.31% of the association between preoperative FBG and postoperative remission. Both preoperative FBG and TG were negatively associated with the postoperative remission of T2DM.ConclusionIn summary, our findings suggest that lower preoperative fasting glucose levels enhance the likelihood of postoperative T2DM remission. Moreover, preoperative TG could potentially play a mediating role in the postoperative remission of T2DM. Therefore, evaluating and managing fasting glucose and lipids before the procedure may aid in assessing the prognosis of metabolic surgery.Level of evidence Level III, designed cohort.

CD36 gene variant rs1761667(G/A) as a biomarker in obese type 2 diabetes mellitus cases

BackgroundSeveral reports discussed a connection between CD36 genotypes associated with obesity, influencing the development of Type 2 diabetes mellitus (T2DM). Therefore, this study examines the prognostic value of CD36 polymorphism rs1761667 (G/A) in individuals with obese T2DM. The investigation also explores the correlation between this genetic variation and the clinical/biochemical parameters of the subjects.MethodsBlood samples of a total of 475 subjects from north India were collected from the outpatient unit (OPD), Department of Medicine, KGMU, Lucknow as per inclusion/exclusion criteria. Anthropometric details of study subjects were recorded and biochemical parameters were estimated in 250 T2DM cases, 75 obese T2DM cases, and 150 controls. The CD36 gene variant rs1761667 (G/A) was subject to genotypic analysis using the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method, utilizing specific primers and HhaI enzyme. All statistical analysis was done using SPSS (ver. 21.0) and Prism (5.01) software.ResultsFasting plasma glucose (FPG), systolic blood pressure (SBP), post-prandial glucose (PPG) were significant in T2DM subjects. Lipid profile such as Total Cholesterol (TC), Low-Density Lipoprotein (LDL) and Very Low-Density Lipoprotein (VLDL) were also found significantly associated with obese T2DM cases. GA and AA genotypes of rs1761667 (G/A) showed significant associations in obese T2DM cases. The GA genotype demonstrated a considerable association (P < 0.001) with a 2.77-fold increased susceptibility to the high risk of T2DM. The AA genotype was found to be significantly associated (P = 0.008) with 2.94-fold higher risk of T2DM in obesity while 9.33 folds significant risk of developing obesity in T2DM cases.ConclusionsThe risk of obesity in T2DM cases can be assessed by genotyping the CD36 genetic variant rs1761667 (G/A). However, raised FPG, PPG, TC, LDL, and VLDL showed poor prognosis in obese T2DM cases. CD36 gene variant can be proposed as a prognostic biomarker for risk prediction of T2DM and obesity, while anthro-biochemical risk factors as preventive biomarker.

Heterogeneously elevated branched-chain/aromatic amino acids among new-onset type-2 diabetes mellitus patients are potentially skewed diabetes predictors.

The lack of specific predictors for type-2 diabetes mellitus (T2DM) severely impacts early intervention/prevention efforts. Elevated branched-chain amino acids (BCAAs: Isoleucine, leucine, valine) and aromatic amino acids (AAAs: Tyrosine, tryptophan, phenylalanine)) show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies. However, improvement is needed to support its clinical utility. To evaluate the effects of body mass index (BMI) and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight. Ninety-seven new-onset T2DM patients (< 12 mo) differing in BMI [normal weight (NW), n = 33, BMI = 22.23 ± 1.60; overweight, n = 42, BMI = 25.9 ± 1.07; obesity (OB), n = 22, BMI = 31.23 ± 2.31] from the First People's Hospital of Yunnan Province, Kunming, China, were studied. One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs. Fasting serum AAAs, BCAAs, glutamate, and alanine were greater and high-density lipoprotein (HDL) was lower (P < 0.05, each) in OB-T2DM patients than in NW-T2DM patients, especially in male OB-T2DM patients. Arginine, histidine, leucine, methionine, and lysine were greater in male patients than in female patients. Moreover, histidine, alanine, glutamate, lysine, valine, methionine, leucine, isoleucine, tyrosine, phenylalanine, and tryptophan were significantly correlated with abdominal adiposity, body weight and BMI, whereas isoleucine, leucine and phenylalanine were negatively correlated with HDL. Heterogeneously elevated amino acids, especially BCAAs/AAAs, across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development. The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals, whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals. This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.

Roux-en-Y Gastric Bypass Improves Insulin Sensitivity in Obese Rats with Type 2 Diabetes Mellitus by Regulating the Grin3a/AMPK Signal Axis in Hypothalamic Arcuate Nucleus.

The objective of this study was to explore the effects and related mechanisms of Roux-en-Y gastric bypass (RYGB) on insulin sensitivity in obese rats with type 2 diabetes mellitus (T2DM). The obese T2DM rat model was constructed by feeding a high-fat diet and injecting streptozotocin (STZ), and treated with RYGB. Grin3a shRNA was injected into the bilateral hypothalamic arcuate nucleus (ARC) to knockdown the Grin3a expression on T2DM rats. Eight weeks after operation, the body weight, fasting blood glucose (FBG), fasting serum insulin (FSI), homeostatic model assessment of insulin resistance (HOMA-IR), and plasma triglyceride (TG) levels were assessed. Hematoxylin & eosin (H&E) staining was adopted to observe the white adipose tissue (WAT) of rats. Western blot and qRT-PCR were used to detect the expression of Grin3a, adenosine 5' monophosphate-activated protein kinase (AMPK) and p-AMPK in ARC of rats. Later, the plasmid over-expressing or knocking down Grin3a was transfected into differentiated 3T3-L1 adipocytes, and the TG level and the formation of lipid droplets in adipocyte were assessed by TG kit and oil red O staining. The expression of lipogenic transcription factors in cells was detected by qRT-PCR. RYGB reduced FBG, FSI, HOMA-IR and plasma TG levels in T2DM rats while increasing Grin3a expression and p-AMPK/AMPK ratio in ARC. Knockdown of Grin3a not only reversed the decrease of FBG, FSI, HOMA-IR and plasma TG levels in T2DM rats induced by RYGB, but also reversed the up-regulation of p-AMPK/AMPK ratio in ARC affected by RYGB. Moreover, knocking down Grin3a significantly increased the TG level, promoted the formation of lipid droplets and up-regulated the expressions of lipogenic transcription factors in adipocytes. RYGB improved the insulin sensitivity, reduced the plasma TG level and lessens the fat accumulation in obese T2DM rats by regulating the Grin3a/AMPK signal in ARC.

A Mediterranean-Style Diet Improves the Parameters for the Management and Prevention of Type 2 Diabetes Mellitus.

Background and Objectives: Type 2 diabetes mellitus (T2DM) is a chronic condition recognized as the inability to maintain glucose homeostasis, typically presenting with insulin resistance and systemic inflammation. With the prevalence of T2DM and major risk factors, such as prediabetes and obesity, increasing each year, the need to address risk factor reduction strategies is crucial. Materials and Methods: Twenty-two men and women, overweight-to-obese adults (BMI mean: 26.1-31.6) (age range mean: 44.6-51.8) with T2DM, indicators of prediabetes, or who were metabolically healthy, participated in Cal Poly's Nutrition and Exercise in Type 2 Diabetes (CPNET) study. There were no significant differences in terms of age, BMI, or sex distribution among the groups at the baseline. This study's protocol included following a Mediterranean-style diet, the daily consumption of a high-quality whey protein supplement, and physical activity recommendations for 16 weeks. Body composition data, via dual-energy X-ray absorptiometry (DXA), and fasting blood samples were collected at the baseline and following the intervention. Due to restrictions associated with the outbreak of the COVID-19 pandemic, only 13 of the 22 participants who started this study were able to return for the second data collection to complete this study following the 16-week intervention. Results: The prediabetic and T2DM groups exhibited reductions in their fasting plasma glucose (12.0 mg/dL reduction in the prediabetic group; 19.6 mg/dL reduction in the T2DM group) to that of normal and prediabetic levels, respectively, while the T2DM group also demonstrated improvement in their hemoglobin A1c (reduced from 6.8% to 6.0%) to prediabetic levels. Additionally, the metabolically healthy, overweight group exhibited significant improvements in adiposity, while the obese prediabetic and T2DM groups showed non-significant improvements in all the measured metrics of body composition. No significant changes were observed in the inflammatory biomarkers (p-values ranged from 0.395 to 0.877). Conclusions: Collectively, our results suggest that adherence to a well-balanced, nutritious diet and activity may improve the parameters of glycemic control and provide benefits to body composition that help to manage and prevent the development of T2DM. Our study was able to yield significant findings signifying that the effects of a Mediterranean-style diet are observed even for a more conservative sample size.

Endothelial dysfunction in patients with obesity and type 2 diabetes mellitus or normoglycemia: assessment of specific markers

BACKGROUND: One of the function of the endothelium is the maintenance of body's homeostasis. Endothelial dysfunction is known to be profoundly implicated in the pathogenesis of cardiovascular diseases (CVD). The presence of diabetes mellitus significantly increases the risks of CVD. Type 2 diabetes mellitus (T2DM) is often observed in obesity, however, there is a population of people with obesity, who do not develop T2DM for a long time.AIM: To compare the level of markers of endothelial dysfunction in two groups of individuals (without T2DM and with T2DM), as well as to evaluate the impact of cardioprotective medication (GPP-1 and SGLT-2) on these markers.MATERIALS AND METHODS: We recruited 2 groups of patients with obesity into this study: the 1st group with no carbohydrate metabolism disorders, the 2nd with T2DM. Several markers of endothelial dysfunction were evaluated: human von Willebrand factor (VWF), vascular endothelial growth factor A (VEGF-A), soluble form E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM1).RESULTS: A significant increase in sE-Selectin was seen in the group of patients with obesity and T2DM compared with those without carbohydrate metabolism disorders (46.65 [36.23; 66.66] vs 33.05 [22.1;53.31] ng/ml). There were no differences in the level of markers of endothelial dysfunction in the subgroups of patients with T2DM with HbA1c &lt; 8% and &gt;8%. There was also no effect of cardioprotective drugs (SGLT-2 and / or GPP-1) on any of endothelial dysfunction markers in individuals with T2DM.CONCLUSION: We suggest that an increase in sE-selectin may be an early marker of endothelial dysfunction in obese individuals and T2DM.

Prevalence of GCKR rs1260326 Variant in Subjects with Obesity Associated NAFLD and T2DM: A Case-Control Study in South Punjab, Pakistan.

The glucokinase regulatory protein (GCKR) regulates glycogen metabolism and insulin secretion, and the GCKR rs1260326 is a putative single nucleotide polymorphism (SNP) associated with metabolic disorders including nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). This study was conducted to investigate the genetic association of the GCKR rs1260326 in NAFLD and T2DM in our population. NAFLD (n = 103), T2DM (n = 100), and control (n = 100) samples were collected and genotyped for GCKR rs1260326 by tetra-arm PCR. The genetic variant GCKR rs1260326 was significantly linked with NAFLD and T2DM, while the GCKR rs1260326 was significantly associated with the progression of obesity only in NAFLD subjects. The frequency of the C allele (mutant) was higher in both NAFLD (f = 0.69) and T2DM (f = 0.66) subjects as compared to healthy controls of NAFLD (0.52) and T2DM (f = 0.32). The frequency of the C allele was also positively linked with the progression of obesity in both diseases. The frequency of the C allele was 0.66, 0.67, and 0.74 in NAFLD normal weight, overweight, and obese subjects, respectively, while the frequency of the C allele was 0.60, 0.60, and 0.74 in T2DM in normal weight, overweight, and obese subjects, respectively. Homozygous mutant (CC) was 53% in both NAFLD and T2DM subjects, while heterozygous mutant (CT) was 15.53% in NAFLD and 22% in T2DM subjects. Wild-type allele (TT) was 31.06% in NAFLD and 25% in T2DM subjects. In conclusion, the GCKR rs1260326 is a highly prevalent SNP in NAFLD and T2DM subjects, which possibly contributed to obesity, insulin resistance, and metabolic disorders in our population.

Garcinia Mangostana Pericarp Extract Protection on Reproductive Function of Obese-Diabetic Rats Model

Background: Type 2 diabetes mellitus (T2DM) in obese has been considered a risk factor for male infertility. Garcinia mangostana pericarp extract (GMPE) is known to have anti-hyperglycemic, anti-diabetic, and anti-inflammatory effects. This study aimed to evaluate the effect of GMPE therapy on reproductive function in obese T2DM rats by examining testosterone level, testicular histopathological features, and hs-CRP level.Methods: Thirty-six male Wistar rats, aged 2-3 months, were randomly divided into 6 groups and treated with a standard diet (NC), high-fat diet (HFD) with GMPE 200 mg/kgBW (obese GMPE control/OGC200), HFD with 45 mg/kgBW STZ-NA (obese-diabetic control/ODC), obese-diabetic rats with GMPE 100 (DG100); 200 (DG200); and 400 mg/kgBW (DG400). STZ-NA was administered after 8 weeks of HFD treatment and followed by GMPE for 8 weeks after T2DM was confirmed. The level of hs-CRP and testosterone were measured in the serum using an enzyme-linked immunosorbent assay. Testicular histopathological examination was measured after 8 weeks of treatment by using Modified Jonhson Score (MJS) with HE staining.Results: ODC rats significantly showed increased hs-CRP level compared to NC (8.76±0.27 vs 0.30±0.07 ng/mL, P&lt;0.001) and reduced testosterone level and MJS compared to NC (73.69±2.22 vs170.14±1.34 ng/dL, 4.57±0.93 vs 9.87±0.16 MJS, respectively, P&lt;0.001). Testosterone and hs-CRP levels showed a negative and significant correlation (r=-0.974 and P&lt;0.001). On the treatment group, GMPE significantly reduced hs-CRP and increased testosterone levels in a dose-dependent manner.Conclusion: GMPE effectively protects reproductive function in obese DM rats by increasing testosterone levels and advanced spermatogenesis, as well as decreasing hs-CRP level.

Effect of laparoscopic mini-gastric bypass versus laparoscopic sleeve gastrectomy on hypertension and dyslipidemia in obese type 2 diabetes mellitus patients.

The aim of the research was to compare the effect of the laparoscopic mini-gastric bypass (LMGB) technique with the laparoscopic sleeve gastrectomy (LSG) technique in bariatric surgery on type 2 diabetes mellitus (T2DM), hypertension (HTN), and dyslipidemia in obese T2DM patients. A prospective, cross-sectional study, conducted in Surgery Department at Al-Mouwasat and Al-Assad University Hospitals in Damascus, and included T2DM obese patients who would undergo bariatric surgery using the LMGB or LSG technique. The research included two groups: the LSG group (92 patients, 60.9% female, age 44.6 year, BMI 41.85kg/m2) and the LMGB group (137 patients, 59.1% female, age 47.1 year, BMI 43kg/m2). Before surgery, the prevalence of HTN and dyslipidemia were similar in the two groups. After one year: T2DM improvement and remission rate in the LMGB group (13.9, 80.3%) were greater than in the LSG group (13, 62%), the difference was statistically significant. The HTN improvement and remission rate in the LMGB group (52.9, 41.4%) were greater than in the LSG group (47.5, 39%), the difference was not statistically significant. The dyslipidemia improvement rate was greater in LSG group (47.2 vs. 32.7%), while the dyslipidemia remission rate was greater in LMGB group (67.3 vs. 52.8%), the difference was statistically significant. The authors found that the LMGB technique was more effective than the LSG technique in controlling cardiovascular risk factors of obesity, T2DM, HTN, and dyslipidemia.

CORRELATION BETWEEN THYROID FUNCTION AND OBESITY IN TYPE 2 DIABETES INDIVIDUALS

Objectives: In the present study, it is aimed to investigate the prevalence of thyroid dysfunction and blood glucose parameters and their correlation in Type 2 diabetes mellitus (T2DM) obese patients. Methods: The present study was a cross-sectional and observational study conducted for a period of 1 year January 2020–January 2022. The patient demographic data, age, and gender were collected from the medical records. After an overnight fast, venous blood samples were collected in the morning for laboratory tests. Electrochemiluminescence immunoassays were used to assess serum free T3 (FT3), FT4, and thyroid stimulating hormone (TSH). Fasting blood glucose, postprandial blood glucose, and random sugar levels were measured using enzymatic method. Body mass index (BMI) was calculated as weight (kg) divided by squared height (m). Results: In the present study, the mean values of thyroid harmones T3, T4 between the obese and non-obese individuals showed that no much significant variations might be due to low sample size. However, the mean values of TSH values were significantly higher 8.7ng/dl for obese individuals than non-obese individuals. There was a significant positive correlation that was identified for thyroid parameters TSH between obese and non-obese T2DM patients. On the other hand, there was a significant influence of postprandial blood sugar, random blood sugar, hemoglobin A1C, and BMI in obese and non-obese T2DM patients and insignificant influence for thyroid parameters T3 and T4. However, the results also showed that there was a highly significant influence of THS levels in obese T2DM patients. Conclusion: The findings of the present investigation showed a high correlation between thyroid function, mainly TSH levels, and Type 2 diabetes, particularly in obese persons.

Association of Serum Leptin and Adiponectin Concentrations with Type 2 Diabetes Biomarkers and Complications Among Saudi Women.

Hyperglycemia and insulin resistance (IR) put obese women with Type 2 diabetes mellitus (T2DM)at risk for cardiovascular disease (CVD). 150 T2DM women aged 30-45 were studied cross-sectionally at Madinah Hospital lab to find T2DM risk factors and their association with adiponectin/leptin levels. Women with T2DM showed greater fasting blood glucose (FBG), hemoglobin A1c (HbA1c), triglycerides (TG), body mass index (BMI), waist circumference (WC), insulin resistance (IR), high-sensitivity C-reactive protein (hs-CRP), and CVD risk (high atherogenic index of plasma (AIP) and leptin), but decreased high-density lipoprotein (HDL-cholesterol) and poor insulin sensitivity with low adiponectin. Obese women with T2DM had increased leptin and reduced adiponectin. Leptin levels were significantly related to IR, BMI, and AIP (B= 3.97, P= 0.02) but not WC. Leptin levels were negatively correlated with insulin sensitivity (IS) and HDL-c (P<0.05). In linear regression analysis, adiponectin levels had a significant association with IS and HDL-c (P= 0.03, P= 0.04) but an inverse relationship with IR, BMI, WC (B=-2.91, P= 0.04), and AIP (P<0.05). Increased leptin levels are related to high IR, AIP, and BMI among T2DM female patients. Similarly, adiponectin levels decrease IS and HDL-c. Therefore, obese T2DM women with high leptin and low adiponectin levels should be periodically checked to avoid or decrease consequences like CVD.

Serum Isthmin-1 Was Increased in Type 2 Diabetic Patients but Not in Diabetic Sensorimotor Peripheral Neuropathy.

This study aimed to investigate the relationship between serum isthmin-1 (ISM1) and type 2 diabetes mellitus (T2DM), and the alteration of serum ISM1 level in both diabetic sensorimotor peripheral neuropathy (DSPN) and diabetic adults with obesity. We recruited 180 participants (120 T2DM and 60 controls) in the cross-sectional study. First, we compared the serum ISM1 concentration in diabetic patients and non-diabetic controls. Secondly, according to DSPN, patients were divided into DSPN and non-DSPN groups. Last, patients were categorized as lean T2DM (15 males, 15 females), overweight T2DM (35 males, 19 females), and obese T2DM groups (23 males, 13 females) according to gender and body mass index (BMI). All participants were collected with clinical characteristics and biochemical profiles. Serum ISM1 was detected in all subjects by ELISA. Higher serum ISM1 [7.78 ng/mL (IQR: 6.33-9.06) vs 5.22 (3.86-6.04), P <0.001] was observed in diabetic patients compared to non-diabetic controls. Binary logistic regression analysis showed that serum ISM1 was a risk factor for type 2 diabetes after adjustment (OR=4.218, 95% CI: 1.843-9.653, P=0.001). Compared to the non-DSPN group, serum ISM1 level was not changed significantly in patients who suffered from DSPN. Diabetic females with obesity had lower level of serum ISM1 (7.10±1.29 ng/mL) when compared to the lean T2DM (8.42±1.36 ng/mL, P <0.05) and the overweight T2DM (8.33±1.27 ng/mL, P <0.05). However, serum ISM1 was not changed significantly in male groups or all patients together. Serum ISM1 was a risk factor for type 2 diabetes, and it was associated with diabetic adults with obesity while there was sexual dimorphism. However, serum ISM1 levels were not correlated with DSPN.

THE EFFICACY OF COMBITATION OF EMPAGLIFLOZIN AND METFORMIN IN PATIENTS WITH ARTERIAL HYPERTENSION AND TYPE 2 DIABETES MELLITUS

Objective: To determine the efficacy of combination of empagliflozin and metformin in patients with arterial hypertension (AH) and type 2 diabetes mellitus (T2DM). Design and method: A total of 52 patients with AH, stage II; obesity, stage I and concomitant T2DM were examined (28 women and 24 men, mean age 58.4 ± 2.9, fasting plasma glucose &lt; 9 mmol/L, glycosylated hemoglobin (HbA1c) - 7.54 ± 1.2%, mean blood pressure (BP) 167/104 ± 15.5/3.6 mm Hg, BMI 32.2 ± 2.1 kg/m2, disease duration 5.4 ± 1.6 years,). Two groups of patients were formed: the comparison group included 25 patients who received metformin 1000 mg 2/day, amlodipine 10 mg 1/day and lisinopril 10 mg 1/day. Patients of the main group (n = 27) received empagliflozin 10 mg in addition to standard therapy. The follow-up period lasted 6 months. Results: The following results were obtained by the end of the study period: HbA1C in the main group was 6.23±0.7%, while in the comparison group – 6.58±0.5% (p &lt; 0.05). 46.6% of patients in the main group had achieved the target HgA1c&lt;7.0% compared to 24.5% in the control group (p&lt;0.01). There was no significant increase in the frequency and severity of hypoglycemic episodes. The patients of the main group were characterized by greater weight loss (3.4±0.4 kg) than those of comparison group (0.9±0.3 kg), p&lt;0.01. The mean systolic BP in the main group was 133 ± 6.12 mm Hg., while in the comparison group - 147.2 ± 8.13 mm Hg., p &lt; 0.05. The diastolic blood pressure (DBP) was 84.6 ± 3.7 mm Hg and 89,8 ± 5.1 mm Hg, respectively. Conclusions: The obtained data suggest that inclusion of empagliflozin into a standard therapy of hypertension and type 2 diabetes provides multiple benefits, namely: improves glycemic control, ensures better regulation of blood pressure and promotes weight loss.

Role of obesity related inflammation in pathogenesis of peripheral artery disease in patients of type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) has emerged as one of the greatest global health challenges of twenty-first century. Visceral obesity is one of the most important determinant of insulin resistance (IR) as well as T2DM complications. Therefore this review focuses on the molecular mechanism of obesity induced inflammation, signaling pathways contributing to diabetes, as well as role of lifestyle interventionsand medical therapies in the prevention and management of T2DM. Articles were searched on digital data base PubMed, Cochrane Library, and Web of Science. The key words used for search included Type 2 diabetes mellitus, obesity, insulin resistance, vascular inflammation and peripheral arterial disease. Visceral obesity is associated with chronic low grade inflammation and activation of immune systems which are involved in pathogenesis of obesity related IR and T2DM. Metabolic dysregulation of adipose tissue leads to local hypoxia, misfolded/unfolded protein response and increased circulating free fatty acids, which in turn initiate inflammatory signaling cascades in the population of infiltrating cells. Mechanism that relates the role of adipocytokines with insulin sensitivity and glucose homeostasis might throw a light on the development of therapeutic interventions and subsequently might result in the reduction of vascular complications.

Comparison of Plasma Exosome Proteomes Between Obese and Non-Obese Patients with Type 2 Diabetes Mellitus.

Obesity is considered a promoter of type 2 diabetes mellitus (T2DM). However, the underlying mechanism remains unclear. This study aimed to identify plasma exosome differentially expressed proteins (DEPs) that are potentially involved in the development of obesity-related T2DM. Exosomes were isolated from the plasma of obese and non-obese T2DM patients (n = 10 for each group). A label-free quantitative mass spectrometry analysis was applied to identify plasma exosome DEPs in obese patients compared with non-obese patients, followed by bioinformatics analysis including GO annotation, KEGG analysis, subcellular localization prediction, transcription factor analysis, and protein-protein interaction (PPI) prediction. We identified 2 significantly upregulated proteins (C9 and PON1) and 5 significantly downregulated proteins (HPX, A1BG, CFHR1, ANG, and CALM) in obese patients compared with those in non-obese patients. KEGG analysis demonstrated that the insulin signaling pathway was one of the pathways that significantly correlated with the DEPs. The DEPs were primarily localized in the extracellular space (5 out of 7). HMG-box and NF-Y beta might regulate the transcription of the DEPs. C9, PON1, HPX, and CFHR1 were present in the PPI network. The plasma exosome DEPs are potentially responsible for the development of obesity-related T2DM possibly through the insulin signaling pathway and the interaction with other proteins. Our study may guide future research direction toward the pathogenesis of obesity-related T2DM.

Sphingolipidomic profile and HDL subfractions in obese dyslipidemic type 2 diabetic patients

PurposeThe aim of the study was to investigate changes in serum sphingolipid levels and high density lipoprotein (HDL) subtypes with relation to low-density lipoprotein cholesterol (LDL-C), non-HDL-C and triglyceride (TG) levels in type 2 diabetes mellitus (T2DM) patients. MethodsBlood was obtained from 60 patients with T2DM. Levels of sphingosine-1-phosphate (S1P), C16-C24 sphingomyelins (SMs), C16-C24 ceramides (CERs), and C16 CER-1 P were determined by LC-MS/MS. Serum concentrations of cholesterol ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT) and apolipoprotein A-1 (apoA-I) were analyzed by enzyme-linked immunosorbent assay (ELISA). HDL subfraction analysis was performed by Disc polyacrylamide gel electrophoresis. ResultsC16 SM, C24 SM, C24-C16 CER and C16 CER-1 P levels were significantly increased in T2DM patients with LDL-C above 160 mg/dL, compared to those with LDL-C below 100 mg/dL. A significant correlation was observed between C24:C16 SM, C24:C16 CER ratios and LDL-C, non HDL-C levels. Higher serum levels of C24 SM, C24-C18 CER and C24:C16 SM ratio was seen in obese T2DM patients (BMI>30) compared to those with BMI 27–30. Patients with fasting TG levels below 150 mg/dL had significantly increased HDL-large and significantly decreased HDL-small fractions compared to those with fasting TG levels above 150 mg/dL. ConclusionObese dyslipidemic T2DM patients had increased levels of serum sphingomyelins, ceramides and HDL-small fractions. The ratio of serum C24:C16 SM, C24:C16 CER and long chain CER levels may be used as diagnostic and prognostic indicators of dyslipidemia in T2DM.

Comparison of novel markers of metabolic complications and cardiovascular risk factors between obese non-diabetic and obese type 1 diabetic children and young adults.

For the past years, the prevalence of obesity is growing in the general population of children, as well as among diabetic patients, resulting in increased risk of cardiovascular complications. Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in children and young adults, leading to decreased life quality and lifespan, with obesity being recognized recently as a major contributing factor to these health problems. The objective of this study was to analyze and compare the selected novel markers for metabolic complications of obesity and vascular risk factors between obese non-diabetic and obese T1DM children and young adults. One hundred four subjects, aged between 10 and 24 years (31 with T1DM and excessive body weight, 41 with obesity without diabetes, and 32 with T1DM and normal weight), and 32 matched lean controls were included in the study. Clinical characteristics, blood pressure measurements, daily requirement for insulin, HbA1c%, plasma lipids, fetuin-A, E-selectin, and osteoprotegerin levels were compared with respect to body mass index (BMI), body mass index standard deviation score (BMI-SDS), and carotid intima-media thickness (cIMT) of common carotid arteries. Patients with T1DM and excessive body weight compared to non-diabetic obese subjects had similar values of systolic blood pressure (125.6 ± 8.2 vs. 127.3 ± 12.9 mmHg, p = 0.515), diastolic blood pressure (78.19 ± 7.03 vs. 78.02 ± 8.01 mmHg, p = 0.918), cholesterol (175.26 ± 34.1 vs. 163.51 ± 26.08 mg/dl, p = 0.102), LDL (108.03 ± 32.55 vs. 112.22 ± 26.36 mg/dl, p = 0.548), and triglyceride levels (118.19 ± 71.20 vs. 117 ± 55.80 mg/dl, p = 0.937); all values were found to be higher compared to non-obese T1DM and healthy controls. HbA1c level and insulin resistance indices were significantly worse in T1DM obese vs. T1DM non-obese patients. Fetuin-A levels were higher among obese non-diabetic patients (p = 0.01), and E-selectin and osteoprotegerin levels were similar in both groups with obesity, but higher than in the reference group. There were no statistical differences in cIMT with T1DM with normal weight, excessive weight, and non-diabetic obese children; however, the cIMT value was higher compared to the reference group. Novel markers of metabolic complications of obesity are similar between obese T1DM and non-diabetic subjects. Obesity in patients with T1DM results in worse metabolic control, insulin resistance, and increased risk for vascular complications.

Evaluation of miRNA-143 and miRNA-145 Expression and Their Association with Vitamin-D Status Among Obese and Non-Obese Type-2 Diabetic Patients.

Growing epidemics of type-2 diabetes mellitus (T2DM) and obesity have become a serious health concern. Since miRNAs and vitamin levels affect the development and progression of numerous pathogenic diseases, including diabetes, the present study aimed to evaluate miRNA-143 and miRNA-145 expression and vitamin-D status among obese and non-obese T2DM patients. The study included 100 clinically confirmed newly diagnosed obese and non-obese T2DM cases and 100 healthy subjects. Total RNA was extracted from collected blood samples and 100 ng of RNA was used for cDNA synthesis, then TaqMan assay was performed to evaluate the miRNA-143 and miRNA-145 relative expression. T2DM cases with hypertension (4.08 fold, p=0.01; 5.36 fold, p=0.009), fatigue (5.07 fold, p=0.04; 5.32 fold, p=0.03) and blurred vision (5.15 fold, p=0.01) showed higher miRNA-143 and miRNA-145 relative expression compared with their counterparts, respectively. A positive correlation was observed between miRNA-143 and miRNA-145 expression and decreased vitamin-D status in T2DM had significant association with impaired blood glucose fasting (p=0.001) and HDL level (p<0.0001). Obese T2DM cases showed higher miRNA-143 and miRNA-145 expression compared with their counterparts. Vitamin-D deficient T2DM cases had higher miRNA-143 and miRNA-145 expression (5.69 fold, 5.91 fold) compared with insufficient (4.27 fold, p=0.03; 4.61 fold, p=0.03) and sufficient (4.08 fold, p=0.002; 4.29 fold, p=0.003). ROC curve for miRNA-143 and miRNA-145 between obese T2DM vs non-obese T2DM cases, at best possible cutoff value of 4.39 fold, 4.0 fold showed increased miRNA-143 and miRNA-145 expression, the sensitivity and specificity were 85%, 88% and 61%, 53% respectively (AUC=0.83, p<0.0001; AUC=0.81, p<0.0001). Higher miRNA-143 and miRNA-145 expression could be a predictive indicator for obese T2DM cases, decreased status of vitamin-D was also significantly associated with impaired fasting blood sugar and HDL level, therefore it is important to evaluate the vitamin-D status among T2DM cases for better clinical outcome during the intervention.

The Correlation of Nrf2 rs6721961 Variants with the Risk of Type 2 Diabetes Mellitus and Obesity in Kurdistan of Iraq

Background: Type 2 diabetes mellitus (T2DM) is an endocrine and metabolic disease that the interaction of genetic background with environmental factors could enhance its risk. The nuclear erythroid-2-related factor 2 (Nrf2) protects cells against oxidative damage and toxicity. Objectives: This study aimed to determine the possible correlation between the Nrf2 gene variants with the risk of T2DM and obesity in the Kurdistan of Iraq. Methods: This study was conducted on 250 individuals categorized into 4 groups: 67 obese T2DM patients (body mass index (BMI) ≥ 30 kg/m2), 65 normal BMI diabetic patients (BMI &lt; 25 kg/m2), 62 obese non-diabetics, and 56 normal BMI non-diabetic individuals. The Nrf2 rs6721961 variants were identified by polymerase chain reaction (PCR) technique followed by digestion with the restriction enzyme of NgoMIV. Results: In the obese T2DM group, the levels of waist, and wrist circumference were significantly more than those of obese non-diabetic controls. Total antioxidant capacity level was not significantly different comparing patients with their controls. The Nrf2 T allele significantly decreased the risk of T2DM in normal BMI patients. In addition, carrying the T allele significantly reduced the risk of obesity. Conclusions: According to the results, significantly higher levels of anthropometric parameters was detected in obese T2DM compared with obese non-diabetic controls. The T allele of Nrf2 decreased T2DM risk among patients with normal BMI and obesity risk among Kurdish residents of Iraq. The findings of our research can be used in the prevention and management of T2DM by improving lifestyle habits.