Type 2 Diabetes Mellitus Subjects Research Articles

Force Generation and Muscle Activation of Knee Extensor and Flexor Muscles in Type 2 Diabetes Mellitus Patients.

Type 2 diabetes mellitus (T2DM) is associated with decreased muscle force generation. The disturbed force generation process in T2DM could be attributed to either or both agonist and antagonist muscles activation. The present study aims to assess the effects of T2DM on the interaction of antagonist and agonist muscles in the knee joint. The peak torque, root mean square (RMS) of the SEMG signals, the ratio of torque/RMS, and the interaction of antagonists and agonist muscles were compared between healthy and T2DM patients. Surface ElectroMyoGraphy (SEMG) of knee flexor and extensor muscles were recorded during concentric contraction with an isokinetic dynamometer at 60°/s in 13 T2DM and 12 healthy subjects. The independent sample t-tests were used to compare diabetic and healthy subjects. The significance level was set at 0.05. The antagonist/agonist interaction during maximal extension (P = 0.010) and flexion (P = 0.022) torques of the knee joint showed significantly lower activation of antagonist muscles in T2DM patients than in healthy subjects. Lower knee flexion (41.3%) and extension torques (49.1%) and RMS of agonist and antagonist muscles were observed in T2DM. The torque/RMS ratio (P > 0.05) showed no significant differences in T2DM and healthy subjects. The reduced maximal knee flexor and extensor torques in T2DM are accompanied with the decreased myoelectric activity of corresponding muscles. The related mechanism could be attributed to lower values of antagonist/agonist interaction, which may point out some neural compensatory processes to preserve the functional capacity of the neuromuscular system in T2DM.

Higher systolic blood pressure is specifically associated with better islet beta-cell function in T2DM patients with high glycemic level

BackgroundPatients with type 2 diabetes mellitus (T2DM) usually have higher blood viscosity attributed to high blood glucose that can decrease blood supply to the pancreas. A mild increase in blood pressure (BP) has been reported as a potential compensatory response that can maintain blood perfusion in the islet. However, how BP influences beta-cell function in T2DM subjects remains inconsistent. This study aimed to examine the relationship between BP and beta-cell function in patients with T2DM under different HbA1c levels.MethodsThis is a cross-sectional study of 615 T2DM patients, whose clinical data were extracted from hospital medical records. Beta-cell function was assessed by insulin secretion-sensitivity index-2 (ISSI2). Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between systolic BP (SBP) and ISSI2. Mediation analysis was performed to determine whether higher SBP could reduce blood glucose by enhancing beta-cell function.ResultsAfter adjustment of potential confounders, in participants with HbA1c ≥ 10%, the SBP between 140 to150 mmHg had the highest log ISSI2 (b = 0.227, 95% CI 0.053–0.402), an association specific to participants with < 1 year duration of diabetes. RCS analyses demonstrated an inverted U-shaped association between SBP and ISSI2 with the SBP at 144 mmHg corresponding to the best beta-cell function. This higher SBP was “paradoxically” associated with lower 2 h postprandial blood glucose (PBG) when SBP < 150 mmHg that was almost exclusively mediated by ISSI2 (mediating effect = − 0.043, 95%CI − 0.067 to − 0.018; mediating effect percentage = 94.7%, P < 0.01). SBP was however not associated with improvement in ISSI2 or 2 h PBG in participants with HbA1c < 10%.ConclusionsIn early stage of diabetes, a slightly elevated SBP (140–150 mmHg) was transiently associated with better beta-cell function in T2DM patients with HbA1c ≥ 10% but not in those with HbA1c < 10%.

Elevated Glucagon-like Peptide-1 Receptor Level in the Paraventricular Hypothalamic Nucleus of Type 2 Diabetes Mellitus Patients.

Glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists have been approved for the treatment of type 2 diabetes mellitus (T2DM); however, the brain actions of these drugs are not properly established. We used post mortem microdissected human hypothalamic samples for RT-qPCR and Western blotting. For in situ hybridization histochemistry and immunolabelling, parallel cryosections were prepared from the hypothalamus. We developed in situ hybridization probes for human GLP-1R and oxytocin. In addition, GLP-1 and oxytocin were visualized by immunohistochemistry. Radioactive in situ hybridization histochemistry revealed abundant GLP-1R labelling in the human paraventricular hypothalamic nucleus (PVN), particularly in its magnocellular subdivision (PVNmc). Quantitative analysis of the mRNA signal demonstrated increased GLP-1R expression in the PVNmc in post mortem hypothalamic samples from T2DM subjects as compared to controls, while there was no difference in the expression level of GLP-1R in the other subdivisions of the PVN, the hypothalamic dorsomedial and infundibular nuclei. Our results in the PVN were confirmed by RT-qPCR. Furthermore, we demonstrated by Western blot technique that the GLP-1R protein level was also elevated in the PVN of T2DM patients. GLP-1 fibre terminals were also observed in the PVNmc closely apposing oxytocin neurons using immunohistochemistry. The data suggest that GLP-1 activates GLP-1Rs in the PVNmc and that GLP-1R is elevated in T2DM patients, which may be related to the dysregulation of feeding behaviour and glucose homeostasis 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.

The novel inflammatory biomarker GlycA and triglyceride-rich lipoproteins are associated with the presence of subclinical myocardial dysfunction in subjects with type 1 diabetes mellitus

BackgroundSubjects with Type 1 diabetes mellitus (T1DM) have an increased incidence of heart failure (HF). Several pathophysiological mechanisms have been involved in its development. The aim of this study was to analyze the potential contribution of the advanced lipoprotein profile and plasma glycosylation (GlycA) to the presence of subclinical myocardial dysfunction in subjects with T1DM.MethodsWe included subjects from a Danish cohort of T1DM subjects (Thousand & 1 study) with either diastolic and/or systolic subclinical myocardial dysfunction, and a control group without myocardial dysfunction, matched by age, sex and HbA1c. All underwent a transthoracic echocardiogram and an advanced lipoprotein profile obtained by using the NMR-based Liposcale® test. GlycA NMR signal was also analyzed. Systolic dysfunction was defined as left ventricular ejection fraction ≤ 45% and diastolic dysfunction was considered as E/e′≥12 or E/e′ 8–12 + volume of the left atrium > 34 ml/m2. To identify a metabolic profile associated with the presence of subclinical myocardial dysfunction, a multivariate supervised model of classification based on least squares regression (PLS-DA regression) was performed.ResultsOne-hundred forty-six subjects had diastolic dysfunction and 18 systolic dysfunction. Compared to the control group, patients with myocardial dysfunction had longer duration of diabetes (p = 0.005), and higher BMI (p = 0.013), serum NTproBNP concentration (p = 0.001), systolic blood pressure (p < 0.001), albuminuria (p < 0.001), and incidence of advanced retinopathy (p < 0.001). The supervised classification model identified a specific pattern associated with myocardial dysfunction, with a capacity to discriminate patients with myocardial dysfunction from controls. PLS-DA showed that triglyceride-rich lipoproteins (TGRLs), such as VLDL (total VLDL particles, large VLDL subclass and VLDL-TG content) and IDL (IDL cholesterol content), as well as the plasma concentration of GlycA, were associated with the presence of subclinical myocardial dysfunction.ConclusionProatherogenic TGRLs and the proinflammatory biomarker Glyc A are strongly associated to myocardial dysfunction in T1DM. These findings suggest a pivotal role of TGRLs and systemic inflammation in the development of subclinical myocardial dysfunction in T1DM.

GA/HbA1c ratio is a simple and practical indicator to evaluate the risk of metabolic dysfunction-associated fatty liver disease in type 2 diabetes: an observational study

BackgroundIt is still debatable whether glycated albumin/glycated hemoglobin A1C (GA/HbA1C) ratio is associated with metabolic dysfunction-associated fatty liver disease (MAFLD), and few studies have been conducted in type 2 diabetes mellitus (T2DM). Therefore, we aimed to investigate the association between GA/HbA1C ratio and MAFLD and to evaluate whether GA/HbA1C ratio can be used an indicator of MAFLD in Chinese patients with T2DM.MethodsThis cross-sectional study consisted of 7117 T2DM patients including 3296 men and 3821 women from real-world settings. Abdominal ultrasonography was performed to diagnose MAFLD. In addition to comparing the clinical characteristics among the GA/HbA1C ratio quartile groups, we also investigated the associations of GA/HbA1C ratio and quartiles with MAFLD in T2DM subjects.ResultsThere was a significantly decreased trend in the MAFLD prevalence across the GA/HbA1C ratio quartiles (56.3%, 47.4%, 37.8%, and 35.6% for the first, second, third, and fourth quartile, respectively, P < 0.001 for trend) after adjusting for gender, age, and diabetes duration. Fully adjusted Binary logistic regression indicated that both GA/HbA1C ratio (OR: 0.575, 95% CI: 0.471 to 0.702, P < 0.001) and quartiles (P < 0.001 for trend) were inversely associated with the presence of MAFLD among T2DM patients. Additionally, HOMA2-IR values were clearly increased in the T2DM subjects with MAFLD compared with those without MAFLD (P < 0.001), and markedly increased from the highest to the lowest GA/HbA1C ratio quartile (P < 0.001 for trend).ConclusionsGA/HbA1C ratio is closely and negatively associated with MAFLD in T2DM subjects, which may attribute to that GA/HbA1C ratio reflects the degree of insulin resistance. GA/HbA1C ratio may act as a simple and practical indicator to evaluate the risk of MAFLD in T2DM.

The correlation of vitamin D with HOMA-IR and glycated hemoglobin in type 2 diabetes mellitus patients

Background and objective: Diabetes mellitus, the most common endocrine condition, is characterised by an elevated level of plasma glucose. Vitamin D's primary functions are homeostasis of calcium and metabolism of bone, but it also has a significant role in homeostasis of plasma glucose. This study sought to examine the relationship between vitamin D and glycated haemoglobin and insulin resistance in type 2 diabetes mellitus (T2DM) subjects by analysing vitamin D, homeostasis model assessment of insulin resistance (HOMA-IR), and haemoglobin A1c (HbA1c) levels. Methods: 150 patients with newly diagnosed T2DM participated in this case-control research. Additionally, 150 controls of the same age and gender were also recruited. Serum vitamin D and fasting insulin levels were estimated by the electrochemiluminescence immunoassay (ECLIA) method. High-performance liquid chromatography (HPLC) was used to analyse HbA1c. Pearson's correlation coefficient was used to determine the relationship of vitamin D with HbA1c and HOMA-IR. Results: Around 70.7% of diabetes subjects had low vitamin D levels, compared to 31.3% in the control group. Vitamin D-deficient T2DM subjects had significantly higher HOMA-IR and HbA1c levels. Both vitamin D and HOMA-IR (r = -0.75) and vitamin D and HbA1c (r = -0.73) showed a strong inverse connection in T2DM patients. Conclusions: Vitamin D deficiency is correlated with ineffective glycemic control, and the reason might be its potential role in the secretion and sensitivity of insulin. Therefore, vitamin D screening must be incorporated as a routine check-up for T2DM patients.

Correlation Between Skin Advanced Glycation End Products and Cardiac Autonomic Neuropathy Among Subjects with Type 2 Diabetes Mellitus.

Advanced glycation end products (AGEs) are frequently increased in the skin of subjects with type 2 diabetes mellitus (T2DM). This study aimed to examine the correlation of AGEs with cardiac autonomic neuropathy (CAN) in T2DM. To this aim, 132 participants (88 men) with a mean age of 64.57 years and a median T2DM duration of 14.5 years were included. Skin AGEs were measured with AGE reader mu connect (Diagnoptics) on the dominant arm (both single and automated triplicate measurements). Diagnosis of CAN, sympathetic and parasympathetic nervous system impairment was based on the four standardised cardiovascular reflex tests (CARTs). On a single measurement, AGEs were increased in subjects with vs. those without CAN (3.20±0.74 vs. 2.66±0.66, p<0.001). As compared with normal results, AGEs were increased for each one of the 4 abnormal CARTs: Valsalva Ratio (3.36±0.67 vs. 2.66±0.72, p=0.004), E/I ratio (3.01±0.72 vs. 2.53±0.68, p=0.001), 30:15 ratio (3.08±0.76 vs. 2.75±0.69, p=0.011), postural hypotension (3.30±0.72 vs. 2.75±0.66, p<0.001). Similar results were obtained for triplicate measurements. Among T2DM subjects, skin AGEs appear to increase in the presence of CAN. This holds true both for sympathetic and parasympathetic nervous system impairment.

Low-normal serum unconjugated bilirubin levels are associated with late but not early carotid atherosclerotic lesions in T2DM subjects.

We aimed to examine the association of serum unconjugated bilirubin (UCB) within normal limits with carotid atherosclerosis in Chinese patients with type 2 diabetes mellitus (T2DM). This cross-sectional, real-world study was performed in 8,006 hospitalized T2DM patients including 4,153 men and 3,853 women with normal UCB. The subjects were stratified into quintiles based on serum UCB levels (<6.2, 6.2-7.9, 8.0-8.9, 9.0-10.9, and >10.9 μmol/l, respectively). Carotid atherosclerotic lesions detected by ultrasonography, including carotid intima-media thickness (CIMT), carotid plaque, and stenosis, were compared among the five groups. The associations of serum UCB levels and quintiles with carotid atherosclerotic lesions were also determined by multiple logistic regression. The prevalence of carotid plaque (55.3%, 49.5%, 47.4%, 43.8%, and 37.5%, respectively; p < 0.001 for trend) and stenosis (15.2%, 12.2%, 9.1%, 7.7%, and 5.4%, respectively; p < 0.001 for trend) was progressively lower across the UCB quintiles even after adjusting for age, sex, and duration of diabetes. Results of a fully adjusted multiple logistic regression analysis revealed that serum UCB levels and quintiles were significantly associated with carotid plaque and stenosis. Compared with the subjects in the lowest UCB quintile, the risk of carotid plaque decreased by 25.5%, 28.7%, 33.5%, and 42.8%, and that of carotid stenosis by 24.6%, 37.4%, 44.9%, and 47.3%, respectively, in those from the second to highest UCB quintiles. High serum UCB within the normal range was a protective factor against carotid plaque [odds ratio (OR) 0.810, 95% confidence interval (CI) 0.747-0.878; p < 0.001] and stenosis [OR 0.722, 95% CI 0.647-0.805; p < 0.001]. However, no significant association was observed between serum UCB and CIMT in T2DM patients. Furthermore, C-reactive protein (CRP) levels were significantly higher in the subjects with carotid atherosclerosis than in those without carotid atherosclerosis and clearly decreased across the UCB quintiles. Serum UCB within normal limits is inversely associated with late carotid atherosclerotic lesions including carotid plaque and stenosis but not CIMT, an early carotid atherosclerotic lesion in T2DM patients. High-normal UCB may be protective against carotid atherosclerosis by its anti-inflammation effect, which was indicated by significantly decreased CRP levels from the lowest to highest UCB quintiles.

Diabetes incidence in subjects with PREDIABetes from ReUNion Island: the PREDIABRUN observational cohort study protocol

IntroductionImproved knowledge of prediabetic subjects’ profile and their risk of developing type 2 diabetes mellitus (T2DM) would enhance secondary prevention. The primary objective is to describe factors associated with incident...

PSUN200 Effect of carbohydrate counting education in children and adolescents with type I diabetes

Abstract Background The achievement and maintenance of normoglycemia is one of the most important goals to prevent both short and long-term complications in type 1 diabetes mellitus (T1DM). As carbohydrate acts as the primary macronutrient affecting postprandial glycemic response, carbohydrate counting is crucial in adjusting prandial insulin doses to preserve postprandial blood glucose within normal limits. The purpose of this study is to evaluate the effect of carbohydrate counting education in children and adolescents with T1DM. Method: A retrospective chart review of 128 diagnosed T1DM patients who underwent carbohydrate counting education was conducted. All subjects were diagnosed with T1DM before December 2019, and were educated carbohydrate counting before December 2020 in pediatric endocrinology, Severance Children's Hospital, Seoul, Korea. We analyzed the data including clinical characteristics, education on carbohydrate counting, and glycated hemoglobin A1c (HbA1c) levels. Results In 128 T1DM subjects educated, 48 (38%) were male. Their mean age at diagnosis was 8.6 ± 4.0 (years) and mean age at the time of education was 22.6 ± 7.8 (years). Overall, HbA1c levels at 3, 6, and 12 months after education showed a significant decrease compared to the baseline. The mean ±SD(standard deviation) HbA1c level, which was 8.8 ±1.9 (%) at the baseline, decreased to 8.3 ±1.7 at 3 months, 8.3 ±1.7 at 6 months, and 8.3 ±1.7 at 12 months after education. In multivariate linear regression analyses, only the value of baseline HbA1c (P&amp;lt;0.001) as an indicator of DM management was significantly correlated with decrease in HbA1c. Conclusions In our study, carbohydrate counting education seems effective in glycemic control in patients with type 1 diabetes mellitus, but the decrease in HbA1c seems not enough. The effect of education differs according to the degree of glycemic management. For patients with poor management, providing proper education of carbohydrate counting can make improvement in glycemic control. For well-managed patients, more advanced approach beyond traditional education appears to be required. With proper education, better blood glucose control can be expected to reduce complications and improve quality of life in T1DM patients. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Serum uric acid level among type-2 diabetes subjects attending in a tertiary hospital of Bangladesh

Introduction: Type 2 Diabetes mellitus (T2DM) is a heterogeneous disease which is characterized by variable degrees of insulin resistance, impaired insulin secretion and increased glucose production. Serum uric acid, an end product of purine metabolism, has been shown to be associated with an increased risk of insulin resistance and components of the metabolic syndrome in previous epidemiological studies. However, the putative association of serum uric acid levels with type 2 diabetes mellitus is not clear. Therefore, the present study has been undertaken to determine the levels of explore the association of serum uric acid among male and female type 2 diabetic subjects. Materials and Method: Under an observational analytical design a total of 104 T2DM (M/F, 40/64; age in years, 45±9; M±SD) were recruited. Among laboratory investigations, serum glucose was measured by glucose-oxidase method, lipid profile and serum uric acid by enzymatic colorimetric method. Results: In male T2DM subjects, mean±SD fasting serum glucose (mmol/l) and 2hr after breakfast serum glucose were 7.99±1.45 and 10.93±2.24 respectively. In female T2DM subjects, mean±SD fasting serum glucose (mmol/l) and 2hr after breakfast serum glucose were 58.44±14.63 and 9.65±4.16 respectively. The 2hr after breakfast serum glucose was significantly higher in male T2DM subjects compared to female counteracts (p=0.026). In male T2DM subjects, mean±SD total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c) and very low-density lipoprotein cholesterol (VLDL-c) levels were 07.57±48.96, 144.30±72.20, 36.71±8.30, 137.80±34.14 and 28.86±14.44 respectively. In female T2DM subjects, these values were 186.21±47.946, 207.81±158.12, 39.43±13.12, 108.31±37.11 and 41.56±31.62 respectively. Among these lipidemic variables serum LDL-c was significantly higher in male T2DM subjects compared to female counterparts (p=0.050). Serum uric acid levels was significantly higher in male T2DM subjects compared to female counteracts (4.38±1.96 vs. 5.73±1.34, p=0.013). Conclusion: From the above result it can be concluded that elevated level of serum uric acid is common in female T2DM subjects compared to male counterparts. Further studies with large sample size are warranted to explore the causal effects of this elevation. Therefore, uric acid serves as a potential biomarker of the glucose metabolism.

Association of glutathione S-transferase M1 and T1 polymorphisms on the susceptibility of diabetic retinopathy in the Bangladeshi population.

This study investigated the role of glutathione-S-transferase gene (GSTM1 and GSTT1) polymorphisms in the predisposition of type 2 diabetes mellitus (T2DM) with or without diabetic retinopathy (DR). Thecase-control study included188 subjects: 50 T2DMwith DR, 63T2DM without DR, and 75 healthy individuals' presenting no clinical signs or evidence of diabetes mellitus. Zinc and magnesium levels were measured using a flame atomic absorption spectrophotometer, and the lipid profile was evaluated using standard methods. The gene polymorphism of GSTs was performed by the multiplex-PCR method. Compared to the control, DR and T2DM had considerably greater total cholesterol, LDL-C, and decreased HDL-C levels. Magnesium levels were significantly lower in DR and T2DM than in control. Total cholesterol, LDL, TG, and magnesium levels didn't differ significantly between DR and T2DM groups. In DR, the GSTT1-null genotype was more prevalent than in T2DM subjects and controls (26.0%, 12.7%, and 10.7%, respectively). GSTT1-null genotype was considerably more common in DR than in controls and associated with 2.94-folds enhancing the chance of developing DR (OR = 2.94; 95% CI = 1.12-7.75;p = 0.02). However, the recurrence of GSTM1-null genotype was not clearly distinguishable among these three populations (28.0%, 38.1% and 29.3%, respectively) and not particularly prone to the risk of DR compared to T2DM subjects and controls (OR = 0.63; 95% CI = 0.28-1.41; p = 0.26; OR = 0.94; 95% CI = 0.42-2.07; p = 0.87, respectively). Taken together, these findings suggest the potential role of GSTT1 deletion mutation as a risk factor for the vulnerability of DR among T2DM patients in the Bangladeshi population.

Impaired rate-dependent depression of the H-reflex in type-2 diabetes, prediabetes, overweight and obesity: A cross-sectional study.

Type-2 diabetes is a chronic metabolic disorder characterized by hyperglycemia, resulting from deficits in insulin secretion or insulin resistance. According to the International Diabetes Federation, approximately 463 million people suffered from this condition in 2019, with a rapidly increasing impact in low-and middle-income countries. Obesity is a well-known risk factor for diabetes, and current data project a continuous increase in diabetes prevalence worldwide in obese individuals. Among the common complications, diabetic peripheral neuropathy (DPN) causes sensory symptoms, including pain that contributes to foot ulceration, and if not controlled, limb amputation may occur. The diagnosis of DPN is a clinical problem. Rate-dependent depression (RDD) of the Hoffmann reflex in the lower limbs has been proposed as a test to determine the presence of neuropathic pain in subjects with type-1 and type-2 diabetes. Recently, impaired RDD has been described in obese and diabetic rodent models. In this study, we characterized the RDD by evaluating the H-reflex at 0.2, 1, 2, 5, and 10 Hz in 39 patients with type-2 Diabetes mellitus (T2DM) and 42 controls without diabetes, subsequently classified as overweight/obese and prediabetic. A significant decrease in the RDD of the H-reflex was found in T2DM subjects at 1, 2, 5, and 10 Hz (P < .001) stimulation frequencies compared to controls, but not at 0.2 Hz (P = .48). A major finding of this study is that impaired RDD was also found in 11/25 overweight and obese subjects in at least 2 stimulation frequencies, being 10 of those classified in prediabetic levels according to their HbA1C values. The RDD of the H-reflex could be used as a quantitative and sensitive tool to study T2DM subpopulations with peripheral neuropathy. RDD could be used as a screening tool in combination with clinical tests to diagnose DPN and evaluate the progression of this condition.

Taste dyfunction in obese type 2 diabetic individuals

Obesity is a well-known risk factor for many diseases. It is also known to enhance complications of many diseases eg. Type 2 Diabetes mellitus (T2DM). This study was done to assess the gustatory functions in obese T2DM individuals. This study was done to assess the gustatory functions in obese T2DM subjects and compare the same with lean T2DM individuals. A comparative study with a sample size of 40 was conducted. Patients aged 25 to 50 years with T2DM &amp;#60; 5 years duration and HBA1C ≤ 7 were divided into 2 groups, Group I- with normal weight (BMI of 18.5 to &amp;#60;25) and Group II with grade 1 obesity (BMI of 30 to &amp;#60; 35). Triple Drop Test was done to evaluate gustatory functions. Scoring from “5” to “1” was done on the identification of different concentrations of tastants. Taste scores for sweet, salty, sour, and bitter tastants were lesser in obese diabetics as compared to the lean T2DM subjects. This was statistically significant (p &amp;#60; 0.05) Conclusion: Taste impairment is observed in obese diabetic subjects. This could be an indication of early central diabetic neuropathy. Hypogeusia may cause an increased preference for sweet-tasting or salty foods thus imposing greater health risks, increasing obesity, and negatively affecting the quality of life.

Analysis of two intestinal bacterial metabolites (trimethylamine N-oxide and phenylacetylglutamine) in human serum samples of patients with T2DM and AMI using a liquid chromatography tandem mass spectrometry method

BackgroundTrimethylamine N-oxide (TMAO) and phenylacetylglutamine (PAGln) are associated with acute myocardial infarction (AMI) and type 2 diabetes mellitus (T2DM). This study developed and validated a simple method firstly for simultaneously quantifying serum TMAO and PAGln using liquid chromatography-tandem mass spectrometry (LC–MS/MS). MethodsSerum samples from patients with T2DM, AMI, and healthy subjects were analyzed using a new LC–MS/MS method to evaluate TMAO and PAGln levels. Statistical analyses were performed to evaluate TMAO and PAGln distributions among different groups. ResultsRetention and separation of the two metabolites were achieved within 5 min. For both analytes, the assay was linear in a 0.02–10 µg/mL range, with >0.99 average linear correlation coefficients, and quantification limit values of approximately 0.010 µg/mL. The average recoveries of TMAO and PAGln were 96.3 % and 96.4 %, respectively. The intra-run and total coefficient variations were 3.5–4.8 % and 3.9–5.7 % respectively for TMAO; and 4.0–5.1 % and 4.6–6.3 % respectively for PAGln. TMAO and PAGln showed a moderate correlation (P < 0.001) and their levels in patients with T2DM were significantly higher than those in healthy individuals (P < 0.001). TMAO levels were higher in patients with T2DM than in patients with AMI (P < 0.01). Patients with AMI had higher PAGln levels than healthy individuals (P < 0.05). After adjusting for sex and age, the top tertile of PAGln was positively correlated with T2DM and AMI while that of TMAO was positively correlated with T2DM. ConclusionsOverall, a robust isotope dilution LC–MS/MS method was established, which may be beneficial for assessing the association between two metabolites with AMI and T2DM.

Association of cluster determinant 36, scavenger receptor class B type 1, and major facilitator superfamily domain containing the 2a genetic polymorphism with serum lipid profile in aging population with type 2 diabetes mellitus.

BackgroundLipid metabolism disorder commonly happens in subjects with Type 2 diabetes mellitus (T2DM) which may be linked to genetic variants of lipid metabolism-related genes. However, few studies have explored the relationship between lipid metabolism-related gene polymorphism and serum lipid profile in aging subjects with T2DM. The present study was designed to explore the impact of genetic polymorphism of cluster determinant 36 (CD36) (rs1049673, rs1054516, rs2151916), scavenger receptor class B type 1 (SCARB1) (rs5888), and major facilitator superfamily domain containing the 2a (MFSD2A) (rs12083239, rs4233508, rs12072037) on the relationship between circulating lipids in aging subjects with T2DM.Methods205 T2DM patients and 205 age and gender matched control subjects were recruited. Information on demographic characteristics was collected by using a self-administered questionnaire. Fasting venous blood samples were taken for lipid-related gene genotyping and serum lipid profile measurement. The Chi-square test was used to compare percentage differences and to calculate P-value for Hardy-Weinberg equilibrium. Logistic regression and multiple linear regression were used to explore the risk or correlation between variables, and general linear model (GLM) was used to compare the means of serum lipids between the groups.ResultsIn T2DM group, CD36 rs1054516 and MFSD2A rs12072037 were correlated with serum TC level. In control group, CD36 rs1049673 was correlated with serum HDL-C level. Meanwhile, T2DM subjects with MFSD2A rs12083239 (CG), MFSD2A rs4233508 (TT), and MFSD2A rs12072037 (AA) had higher TG level than control subjects. T2DM subjects with CD36 rs1049673 (CG, GG), CD36 rs1054516 (CT), CD36 rs2151916 (TT, CT), SCARB1 rs5888 (GG), MFSD2A rs12083239 (GG, CG), MFSD2A rs4233508 (TT), and MFSD2A rs12072037 (CA, AA) had lower HDL-C level than control subjects. T2DM subjects with MFSD2A rs12072037 (AA) had lower LDL-C level than control subjects. In dominant model, major genotype (GG) of SCARB1 gene was associated with the risk of T2DM (OR = 0.636, P = 0.032).ConclusionThe genetic polymorphism of CD36 (rs1049673, rs1054516, rs2151916), SCARB1 (rs5888), and MFSD2A (rs12083239, rs4233508, rs12072037) were associated with serum lipids in T2DM subjects. The SCARB1 rs5888 major genotype (GG) was a protective factor for T2DM. Large scale cohort study is required to determine the relationship between lipid metabolism-related gene polymorphism, serum lipid profile and T2DM in aging subjects.

Assessment of dyslipidemia and its association with Type 2 Diabetes Mellitus in Bangladeshi subjects

Background : Globally incidence of Type 2 Diabetes Mellitus (T2DM) shows an upward trend which a challenge for physicians and public health specialists. Patients with T2DM have 2- 4-fold increased risk of coronary artery disease (CAD), the leading cause of death among people with T2DM. Dyslipidemia considered an important factor for cardiovascular complication of T2DM. Objective : Assessment of dyslipidemia and its association with T2DM in Bangladeshi subjects. Methods : A case control study was conducted in CARe Medical College Hospital, Dhaka, during the period of July 2018 to June 2019. A total 153 subjects were included in study of which 90 belonged to Group-I were T2DM and 63 subjects were healthy Controls in Group-II. The Fasting glucose, postprandial glucose. Serum Lipid Profile were assayed in patients and controls, using standardized assay methods. Data were analyzed by using SPSS version 21. Results : Fasting plasma glucose levels [mmol/l, (Mean± SD)] of the study group were Control (4.96 ± 0.76) and T2DM (8.27±2.19) difference was statistically significant (p &lt;0.001), 2 hours post prandial plasma glucose level [mmol/l, (Mean± SD)] of the study groups were Control (5.81±0.87) and T2DM (11.79 ± 2.69). A significant difference found between Control vs T2DM (p &lt;0.001). Fasting Triglyceride [mg/dl, (Mean± SD) was higher in T2DM (189±82.06), compared to Control (142±80.14) and statistically significant p=0.001. Total Cholesterol [mg/dl, (Mean± SD), Control (172±45) and T2DM (189±50.76) p=0.029] was significantly higher in T2DM than healthy subjects. HDL cholesterol [mg/dl, (Mean± SD); Control (30.6±8.10) and T2DM (26±9.94), p&lt;0.001] significantly increased in healthy Controls compared to T2DM subjects. LDL cholesterol [kg/m,2 (Mean± SD); Control (114±43.54) and T2DM (118±49.66), p=0.572] which was not significantly different among the study subjects. Conclusion : The present study concludes that important parameter of dyslipidemia, Fasting Triglyceride, total Cholesterol, were higher in T2DM patients and statistically significant. LDL cholesterol higher and not significant on the other hand HDL cholesterol was lower but significant difference between T2DM and healthy control found. Therefore, T2DM is associated with higher incidence of dyslipidemia Northern International Medical College Journal Vol. 12 No.1 July 2020, Page 507-510

Effects of Physical Exercise on Mitochondrial Biogenesis of Skeletal Muscle Modulated by Histones Modifications in Type 2 Diabetes

Epigenetic modification in skeletal muscle induced by environmental factors seems to modulate several metabolic pathways that underlie Type 2 Diabetes Mellitus (T2DM) development. Mitochondrial biogenesis is an important process for maintaining lipid metabolism homeostasis, as well as epigenetic modifications in proteins that regulate this pathway have been observed in the skeletal muscle of T2DM subjects. Moreover, physical exercise affects several metabolic pathways attenuating metabolic deregulation observed in T2DM. The pathways that regulate mitochondrial homeostasis are one of the key components for understanding such physical exercise beneficial effects. Thus, in this study, we investigate the epigenetic mechanisms underlying mitochondrial biogenesis in the skeletal muscle in T2DM, focusing on histone modifications and the possible mechanisms by which physical exercise delay or inhibit T2DM onset. The results indicate that exercise promotes improvements in cellular metabolism through increasing enzymes of the antioxidant system, AMPK and ATP-citrate lyase activity, Acetyl-CoA concentration, and enhancing the acetylation of histones. A key mediator of mitochondrial biogenesis such as peroxisome proliferator-activated receptor γ coactivator-1α (PGC1) seems to be upregulated by exercise in T2DM and such factor positively regulates the skeletal muscle mitochondrial biogenesis, which improves energy metabolism and glucose homeostasis inhibiting or delaying insulin resistance and further T2DM.

LEP G2548A polymorphism is associated with increased serum leptin and insulin resistance among T2DM Malaysian patients.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic syndrome that is rapidly increasing across the world, especially in Malaysia. Leptin plays a vital role in the regulation of metabolism through its effect on peripheral tissues. G2548A polymorphism in the LEP gene promoter has been associated with insulin resistance, leptin, and type 2 diabetes mellitus across different population, but has not been inclusively reported within the Malaysian population. Thus, our study aimed to investigate the impact of G2548A polymorphism on serum leptin levels and insulin resistance among Malaysian T2DM patients. This case-control study involved 150 T2DM patients and 150 non-diabetic volunteers from ethnic Malays, Chinese and Indians. Genotyping of G2548A polymorphism was carried out using PCR-RFLP. Serum leptin and insulin levels were determined via ELISA. ANOVA and Chi-square tests were used to determine the distribution of genotypes and allelic frequencies based on serum leptin and insulin levels. Frequency of AA genotype and A allele of G2548A variant were significantly (P < 0.05) higher in T2DM patients of Malay and Indian ethnicities (4%, 35%, and 36%, 57%, respectively) as compared to the control groups (0%, 22%, and 18%, 35%, respectively). Fasting serum leptin levels were significantly (P < 0.001) higher in T2DM patients compared to non-diabetic subjects (166.78 pg/ml, 101.94 pg/ml, respectively). Additionally, elevated serum leptin, insulin levels, and BMI in diabetic patients were found to be associated with the AA genotype of this variant, compared to GG, and GA genotypes (P < 0.05). Our findings suggest a significant association between G2548A polymorphism among Malaysian T2DM subjects, particularly among Malay and Indian ethnic groups. Moreover, the A allele frequency of the G2548A variant significantly increased the risk of T2DM and is significantly associated with increased serum leptin, insulin levels, and elevated BMI.