Krishna G Seshadri

Role of vitamin D on the expression of glucose transporters in L6 myotubes

Altered expression of glucose transporters is a major characteristic of diabetes. Vitamin D has evolved widespread interest in the pathogenesis and prevention of diabetes. The present study was designed to investigate the effect of vitamin D in the overall regulation of muscle cell glucose transporter expression. L6 cells were exposed to type 1 and type 2 diabetic conditions and the effect of calcitriol (1,25, dihydroxy cholicalciferol) on the expression of glucose transporters was studied by real time polymerase chain reaction (RT-PCR). There was a significant decrease in glucose transporter type 1 (GLUT1), GLUT4, vitamin D receptor (VDR), and IR expression in type 1 and 2 diabetic model compared to control group. Treatment of myoblasts with 10-7 M calcitriol for 24 h showed a significant increase in GLUT1, GLUT4, VDR, and insulin receptor (IR) expression. The results indicate a potential antidiabetic function of vitamin D on GLUT1, GLUT4, VDR, and IR by improving receptor gene expression suggesting a role for vitamin D in regulation of expression of the glucose transporters in muscle cells.

An observational, cross-sectional study to assess the prevalence of chronic kidney disease in type 2 diabetes patients in India (START -India).

Objective: The primary objective of this study is to estimate the prevalence of chronic kidney disease (CKD) among type 2 diabetes mellitus (T2DM) patients in India. Materials and Methods: This cross-sectional, observational, epidemiological, multi-center, study is enrolling T2DM patients of either gender aged 30 years or above. This study aimed to enroll a total of 3000 T2DM patients at 30 participating hospitals/clinics across India and the data from a planned interim analysis of 1500 patients are presented here. The primary endpoint of the study is to estimate proportion of T2DM patients with CKD (glomerular filtration rate [GFR] <60 ml/min/1.73 m2 or albumin creatinine ratio [ACR] ≥30 mg/g or ≥3 mg/mmol or both). Routine treatment, as administered by the treating physician, was continued without any study specific intervention. Patients’ data pertaining to demographic characteristics, medical history, current medication and physical examination were recorded. The blood/plasma and urine samples, were collected for estimation of hemoglobin A1c, microalbuminuria, serum creatinine, urine creatinine, and routine urine analysis. ACR was calculated from urine creatinine and albumin while GFR was estimated by using a modification of diet in the renal disease equation. Results: Study recruited 1500 patients from 18 centers across India. The study population included 840 (56.05%) males. Mean age, body mass index and systolic blood pressure were 55.1 years, 27.4 kg/m2 and 134.5 mmHg respectively. The mean duration of diabetes was 102.2 months. History of co-morbid diseases such as dyslipidemia, hypertension, microvascular complications and macrovascular complications was present in 657 (43.8%), 655 (43.7%), 268 (17.9%) and 104 (6.93%), respectively. This interim analysis revealed that about 46% of the T2DM patients had CKD (urinary albumin creatinine ratio (UACR) ≥30 mg/g and/or estimated GFR [eGFR] <60 mL/min/1.73 m2). The renal dysfunction as per eGFR criteria (<60 mL/min/1.73 m2) was reported in about 23% while as per UACR criteria (≥30 mg/g) it was reported in about 35% patients. Conclusion: This interim analysis results suggests that over 40% of T2DM patients have CKD. Despite this high number of T2DM patients with CKD, eGFR analysis shows there are almost 80% of T2DM patients still have reasonably good renal function (eGFR above 60 ml/min), which ensures less restrictions in selecting oral anti-diabetic drugs. Full study results from Start-India study will provide detail insights into the occurrence of CKD in patients with T2DM in India.

Knowledge of hypoglycemia and its associated factors among type 2 diabetes mellitus patients in a Tertiary Care Hospital in South India

Introduction: Hypoglycemia being the rate limiting complication in the attainment of strict glycemic control in diabetes management, in this study, we intended to study the knowledge of its symptoms, target blood levels during treatment and ways of prevention among type 2 diabetes patients attending Outpatient Department (OPD) of a medical college hospital. Materials and Methods: Every fifth patient attending the OPD during the 4 months between March and June 2013 was interviewed using a questionnaire. Results: The study included 366 type 2 diabetic patients, of which 76.5% were females. The target fasting and postprandial blood glucose levels while on treatment was known to 135 (36.9%) and 126 (34.4%) patients, respectively. The common symptoms of hypoglycemia known to the study subjects were dizziness (81.4%), weakness (73.8%), and drowsiness (72.1%). Overall, 242 (66.1%) diabetic patients had good knowledge on hypoglycemia (knowledge of at least three symptoms of hypoglycemia together with at least one precipitating factor and at least one remedial measure). Higher age, illiteracy, low socioeconomic status were associated with poor knowledge whereas treatment with insulin along with oral hypoglycemic agents was associated with good knowledge on hypoglycemia. Sex and duration of disease were not associated with knowledge on hypoglycemia. Conclusion: Although the knowledge on symptoms of hypoglycemia, precipitating factors, remedial measures are high in this study, the target blood levels, complications were known to just a third of them. There is a knowledge gap on important aspects of hypoglycemia among type 2 diabetic patients.

Circulating adiponectin levels in Indian patients with psoriasis and its relation to metabolic syndrome.

Background: Adiponectin is a cytokine mainly secreted from the adipose tissue, which has insulin-sensitizing effects, antiatherosclerotic actions, and antiinflammatory properties. There are a few studies that have demonstrated that adiponectin is reduced in patients with psoriasis suggesting that this adipocytokine may have a role in the pathogenesis of psoriasis. There have been no studies so far on adiponectin in relation to psoriasis and metabolic syndrome (MetS). Objectives: This study was performed to analyze serum adiponectin and insulin levels in psoriasis patients with and without MetS and in controls with and without MetS. Materials and Methods: We performed a case control study on 60 psoriasis patients, 29 with MetS and 31 without MetS and 40 controls, 20 with and 20 without MetS, matched for age, sex, and body mass index (BMI). Fasting serum insulin and adiponectin levels were measured in all groups. Results: The overall serum adiponectin levels were significantly reduced in psoriasis patients when compared with controls (P = 0.000). A significant reduction was also observed in psoriasis patients with MetS than those without MetS in the same group (P = 0.000). Similar decrease was observed between those with MetS in the psoriasis and control groups (P = 0.001). The lowest mean value of serum adiponectin (6387.9 ng/ml) was observed in psoriasis with MetS group and highest value (12146.3 ng/ml) in controls without MetS. Conclusion: Adiponectin levels are decreased in psoriasis patients irrespective of MetS thus indicating a role in its pathogenesis. This study prompts future trials on drugs increasing adiponectin levels in patients with psoriasis.

Subclinical hypothyroidism in children

The prevalence of SH in the pediatric population is < 2%, the caveat being the limited number of studies addressing SCH in the pediatric population. congenital deveolopental anamolies. Mutations in the several proteins are important causes of this condition. Despite the limited data available, SCH in children and adolescents appears to be a benign and remitting disease with a low risk of evolution to OH. It appears that thyroid hormones appear to be functioning well despite elevated TSH. Predictors of progression include, goiter, celiac disease, and positive anti TPO.

Effect of mild physical activity in obese and elderly women with type 2 diabetes

Background: Elderly, obese women with diabetes who have limitations in mobility often are unable to walk for a sustained period of time. We need to find a way to increase physical activity in these subjects. Aim: To evaluate the effect of low-intensity, repetitive, home-based walking regimen on glycemic control in elderly, obese women with diabetes. Research Design: A 24-week open, 2 arms, and prospective study. Materials and Methods: A total of 18 elderly people with type 2 diabetes were recruited. Nine subjects were instructed to walk for 5 minutes per hour for most waking hours for 24 weeks. The rest were given standard advice regarding diet and exercise. Glycemic control, HbA1c, weight, BMI, subjects’ physical fitness, QOL, and distance walked in 6 minutes were determined before and after the intervention. Intervention: A mild physical activity of 5 minutes walking/hour everyday and antidiabetic medications prescribed as per clinic procedure. Results: There was a significant reduction in HbA1c within the study group (8.76% to 7.43%) (P = 0.08) vs rise in the control group (8.34% to 9.34%) (P = 0.07). There was a significant weight loss within the group which exercised (P = 0.01), but there was no significant difference between the groups. Conclusion: Repetitive low-intensity activity is effective in improving glycemic control and weight management in elderly obese women.

Gut Microbiota in Type 2 Diabetes Individuals and Correlation with Monocyte Chemoattractant Protein1 and Interferon Gamma from Patients Attending a Tertiary Care Centre in Chennai, India

Background: Type 2 diabetes mellitus (T2DM) and obesity are associated with changes in gut microbiota and characterized by chronic low-grade inflammation. Monocyte chemoattractant protein-1 (MCP-1) and interferon gamma (IFNγ) are proinflammatory cytokines which play an important role in the development of T2DM. We undertook this study to analyze the gut microbiota of T2DM and nondiabetic subjects and to determine the profile of MCP 1 and IFNγ in the same subjects attending a tertiary care center in Chennai, Tamil Nadu, India. Methods: The study included 30 subjects with clinical details. Stool and blood samples were collected from all the subjects. DNA was extracted from fecal samples and polymerase chain reaction was done using fusion primers. Metagenomic analysis was performed using ion torrent sequencing. The reads obtained were in FASTA format and reported as operational taxonomic units. Human MCP 1 and IFNγ enzyme linked immunosorbent assay (ELISA) were performed for 23 serum samples. Results: The study consisted of 30 subjects; 17 were T2DM and 13 were nondiabetics. The gut microbiota among T2DM consisted predominantly of Gram negative bacteria; Escherichia and Prevotella, when compared with the nondiabetic group with predominantly Gram positive organisms suchas Faecalibacterium, Eubacterium, and Bifidobacterium. The mean MCP-1 values in the diabetic group were 232.8 pg/ml and in the nondiabetic group 170.84 pg/ml. IFNγ (mean 385.5 pg/ml) was raised in glycated hemoglobin (HbA1c) group of 6.5–7.5% which was statistically significant. Association of Escherichia with T2DM and association of Bifidobacteria in the nondiabetics were also statistically significant. Conclusion: Escherichia counts were elevated in T2DM with HbA1c of 6.5–8.5% which was statistically significant suggesting that lipopolysaccharides present in the cell wall of Gram-negative bacteria may be responsible for low-grade inflammation as evidenced by elevated MCP-1 and IFNγ levels in T2DM with the same HbA1c levels.

Hunches on hunchbacks.

The hunchback has long been a symbol of revilement in art and literature. This write up tries to find the cause of the deformity into two iconic hunchbacks in literature, Manthara and Quasimodo.

Obesity: A Venusian story of Paleolithic proportions.

Art through the ages has been a marker of societal trends and fashion. Obesity is proscribed by physicians and almost reviled by todays society. While Venus (Aphrodite) continues to be the role model for those to aspire to free themselves from the clutches of obesity, Paleolithic humans had a different view of the perfect female form. Whether the Venus of Willendorf was a fashion symbol will be never answered, but the fact is that she remains testimony to the fact that obesity has been with us for several millennia.

Prevalence of Chronic Kidney Disease (CKD) in Type 2 Diabetes Mellitus Patients: START-India Study

Objective: Despite rising incidence of diabetes in India, we currently lack country wide data on the prevalence of CKD in T2DM patients. Hence this nationwide study was planned. Methods: This was a nationwide, cross-sectional, observational, multi-centric study to assess prevalence of CKD among T2DM patients. The primary endpoint of the study was to estimate proportion of T2DM patients with CKD (glomerular filtration rate [GFR] <60 ml/min/1.73 m2or albumin creatinine ratio [ACR] ≥ 30 mg/g or ≥ 3 mg/mmol or both). The blood/plasma and urine samples, were collected for estimation of hemoglobin A1c, microalbuminuria, serum creatinine, urine creatinine, and routine urine analysis. Results: Of the 3043 screened subjects, 3000 eligible subjects were enrolled, out of which 46% were females. The mean age was 53.4 (± 11.9) years, with a mean body mass index of 27.3 (± 4.8) kg/m2. Both micro and macro vascular complications were reported. In the studied population with T2DM, 47.8% had mildly decreased, 15.1% had mild to moderately decreased, and 1.8% had severely decreased GFR respectively. As per ACR categorization, 61.3% had normal to mildly increased ACR, 25.6% with moderately increased and 7.2% with severely increased ACR were seen. We observed a significant (p<0.0001) weak negative correlation (-0.23069) between eGFR< 60 mL/ min/1.73 m² and urinary ACR in over six hundred patients. We found 48.4% prevalence of CKD in T2DM patients. The results on analysis of HbA1c goal achievement showed that the patients without CKD had a better success rate to achieve the target <7% goal of HbA1c compared to those who had CKD (29.6% vs. 23.4%). Conclusion: Study reported higher prevalence of CKD which was driven by the ACR levels and majority of the patients had reasonable eGFR. This can be a guide to select drug and dosage of diabetes drug as it depends on kidney function.