Naresh Sachdeva

Utility of Glycated Hemoglobin in Diagnosing Type 2 Diabetes Mellitus: A Community-Based Study

CONTEXT Although glycated hemoglobin (HbA1c) has recently been incorporated as a diagnostic test by the American Diabetes Association, its validity needs to be established in Asian Indians in a community setting. OBJECTIVE The objective of the study was to assess the validity of HbA1c as a screening and diagnostic test in individuals with newly detected diabetes mellitus. DESIGN AND SETTING Community based randomized cross sectional study in urban Chandigarh, a city in north India, from April 2008 to August 2009. SUBJECTS Subjects included 1972 subjects aged 20 yr or older. INTERVENTION Intervention included an oral glucose tolerance test and glycated hemoglobin in all the subjects. MAIN OUTCOME MEASURES Utility of HbA1c as a diagnostic method in newly detected diabetes mellitus subjects was evaluated. RESULTS Using World Health Organization criteria for diagnosis of diabetes mellitus, 134 (6.7%) had newly detected diabetes mellitus, 192 (9.7%) known diabetes mellitus, 329 (16.6%) prediabetes, and 1317 (69.4%) were normal of 1972 people screened. Using only the ADA criteria, 38% people were underdiagnosed. An HbA1c level of 6.1% had an optimal sensitivity and specificity of 81% for diagnosing diabetes. A HbA1c level of 6.5% (+/-2 SD) and 7% (+/-2.7 SD) had sensitivity and specificity of 65 and 88% and 42 and 92%, respectively, with corresponding positive predictive value and negative predictive value of 75.2 and 96.5% and 90.4 and 94.4%, respectively, for diagnosis of newly detected diabetes mellitus. CONCLUSION A HbA1c cut point of 6.1% has an optimal sensitivity and specificity of 81% and can be used as a screening test, and a cut point of 6.5% has optimal specificity of 88% for diagnosis of diabetes.

Efficacy of Autologous Bone Marrow–Derived Stem Cell Transplantation in Patients With Type 2 Diabetes Mellitus

Progressive and inexorable beta-cell dysfunction is the hallmark of type 2 diabetes mellitus (T2DM) and beta-cell regeneration using stem cell therapy may prove to be an effective modality. A total of 10 patients (8 men) with T2DM for >5 years, failure of triple oral antidiabetic drugs, currently on insulin (> or = 0.7 U/kg/day) at least for 1 year, and glutamic acid decarboxylase antibody negative were included. Patients on stable doses of medications for past 3 months were recruited. Primary end points were reduction in insulin requirement by > or = 50% and improvement in glucagon-stimulated C-peptide levels at the end of 6 months of autologous bone marrow-derived stem cell transplantation (SCT), while secondary end points were a change in weight and HbA1c and lipid levels as compared to baseline. Seven patients were responders and showed a reduction in insulin requirement by 75% as compared to baseline. Mean duration to achieve the primary objective was 48 days. Three patients were able to discontinue insulin completely, although it was short-lived in one. Mean HbA1c reduction was 1% and 3 of the 7 responders had HbA1c value <7%. A significant weight loss of 5.5 kg was noted in the responders, whereas, nonresponders gained 2.2 kg of weight. However, weight loss did not correlate with reduction in insulin requirement (r = 0.68, P = 0.06). There was a significant improvement in both fasting and glucagon-stimulated C-peptide level in the group (P = 0.03) and responders (P = 0.03). HOMA-B increased significantly in the whole group (P = 0.02) and responders (P = 0.04) whereas, HOMA-IR did not change significantly (P = 0.74). Reduction in insulin doses correlated with stimulated C-peptide response at the baseline (r = 0.83, P = 0.047) and mononuclear cell count of infused stem cells (r = 0.57, P = 0.04). No serious adverse effects were noted. Our observations indicate that SCT is a safe and effective modality of treatment to improve beta-cell function in patients with T2DM. However, further large-scale studies are needed to substantiate these observations.

Prevalence and risk factors of metabolic syndrome among Asian Indians: A community survey

AIM To determine the prevalence of and risk factors for metabolic syndrome (MS) among urban Asian Indian adults. METHODS 2225 subjects aged > or =20 years were studied in a population based cross-sectional survey in Chandigarh, a city in north India. Anthropometric measurements, estimation of capillary plasma glucose, HDL cholesterol and triglycerides were done. Metabolic syndrome prevalence was estimated using National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP III), modified NCEP ATP III and International Diabetes Federation (IDF) criteria. Multiple logistic regression analysis was done to find out risk factors for metabolic syndrome. RESULTS The prevalence rates of metabolic syndrome were 35.8% (NCEP ATP III), 45.3% (modified NCEP ATP III) and 39.5% (IDF criteria). As per modified NCEP ATP III criteria, central obesity was the commonest abnormality among females and elevated blood pressure among males. Risk factors for MS were increasing age, female gender, sedentary lifestyle and diabetes in parents. CONCLUSIONS Our study showed a high prevalence of metabolic syndrome and its individual components. Independent risk factors for metabolic syndrome included increasing age, female gender, sedentary lifestyle and diabetes mellitus in parents.

Successful Management of Tubercular Subretinal Granulomas

Purpose: To report the successful management of 12 eyes of 11 patients with tubercular subretinal granulomas. Methods: Eleven consecutive patients with a presumed or confirmed diagnosis of tubercular subretinal granulomas were treated with four-drug anti-tuberculosis chemotherapy with concomitant oral corticosteroids. Two patients underwent pars plana vitrectomy. Results: The study included seven males and four women with a median age of 30.5 years. Ten eyes responded well to medical management and a final visual acuity of 20/80 or better was achieved in eight of them. The eyes subjected to pars plana vitrectomy had a relatively worse outcome. Conclusions: Tubercular subretinal granulomas are amenable to medical management provided an early diagnosis is made and treatment is initiated promptly. Once the diagnosis of presumed or confirmed tuberculosis is established, surgical intervention should be avoided.

Growth failure in children with chronic myeloid leukemia receiving imatinib is due to disruption of GH/IGF‐1 axis

The frontline treatment for chronic myeloid leukemia (CML) is tyrosine kinase inhibitor therapy. There is increasing evidence that imatinib results in growth failure in children; etiology is unclear.

Pantoprazole Improves Glycemic Control in Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVE Proton pump inhibitors, by elevating plasma gastrin, can influence glucose-insulin homeostasis. Because there are no controlled clinical trials, the present study was planned to evaluate the effect of pantoprazole, a proton pump inhibitor, on glucose-insulin homeostasis in patients with type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS IN this 12-wk, randomized, double-blind, placebo-controlled study, patients with T2DM were allocated to either the pantoprazole or placebo treatment in an equal ratio. Alterations in glycosylated hemoglobin (HbA1c), fasting plasma glucose, insulin, and gastrin were measured at baseline and at 12 wk. RESULTS Thirty-one eligible patients were randomized to receive either the pantoprazole (n = 16) or placebo (n = 15). Twelve weeks of pantoprazole therapy significantly increased plasma gastrin and insulin levels and improved β-cell function (P < 0.05 for all parameters), along with a significant decrease in HbA1c (7.6 ± 1.17 to 6.8 ± 1.16; P < 0.001). The decrease in HbA1c correlated with an increase in gastrin and insulin (r = 0.54, P =0.010; and r = 0.67, P =0.01, respectively). CONCLUSIONS Pantoprazole therapy increases plasma gastrin and insulin levels, thereby improving the glycemic control in T2DM. The effect of pantoprazole on glucose-insulin homeostasis requires further study.

Efficacy and Safety of Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients with Type 2 Diabetes Mellitus: A Randomized Placebo-Controlled Study

There is a growing interest in cell-based therapies in T2DM as β-cell failure is progressive and inexorable with the advancing duration of disease. This prospective, randomized, single-blinded placebo-controlled study evaluates the efficacy and safety of autologous bone marrow-derived stem cell transplantation (ABMSCT) in T2DM. Twenty-one patients with triple oral antidiabetic drug failure and requiring insulin ≥0.4 IU per kg per day with HbA1c <7.5% were randomly assigned to an intervention (n = 11) and control group (n = 10) and followed for 12 months. Patients in the intervention group received ABMSCT through a targeted approach, and after 12 weeks, a second dose of stem cells was administered through the antecubital vein after mobilization with G-CSF, while the control group underwent a sham procedure. The primary end point was a reduction in insulin requirement by ≥50% from baseline while maintaining HbA1c <7%. Nine out of the 11 (82%) patients in the intervention group achieved the primary end point, whereas none of the patients in the control group did over the study period (p = 0.002). The insulin requirement decreased by 66.7% in the intervention group from 42.0 (31.0-64.0) IU per day to 14.0 (0.0-30.0) IU per day (p = 0.011), while in controls it decreased by 32.1% from 40.5 (31.8-44.3) IU per day to 27.5 (23.5-33.3) IU per day (p = 0.008) at 12 months. The reduction in insulin requirement was significantly more in the intervention group compared to controls at both 6 (p = 0.001) and 12 months (p = 0.004). There was a modest but nonsignificant increase in HbA1c (%) in cases from 6.9% (6.4-7.2%) to 7.1% (6.6-7.5%) as well as in controls from 6.9% (6.2-7.0%) to 7.0% (6.9-7.5%). Ten out of 11 (91%) patients could maintain HbA1c <7% in the intervention group, whereas 6 out of 10 did (60%) in the control group (p = 0.167). The glucagon-stimulated C-peptide significantly increased in treated cases compared to controls (p = 0.036). The decrease in insulin requirement positively correlated with stimulated C-peptide (r = 0.8, p = 0.001). In conclusion, ABMSCT results in a significant decrease in the insulin dose requirement along with an improvement in the stimulated C-peptide levels in T2DM. However, a greater number of patients with a longer duration of follow-up are required to substantiate these observations.

Methylation status of the CpG islands in vitamin d and calcium-sensing receptor gene promoters does not explain the reduced gene expressions in parathyroid adenomas

AIM The exact mechanism causing decreased expression of the vitamin D receptor (VDR) and calcium-sensing receptor (CASR) genes in parathyroid adenoma is not known, but methylation of promoter regions is often detected during epigenetic downregulation of gene expression. We investigated whether epigenetic silencing is involved in the decreased expression of VDR and CASR. EXPERIMENTAL DESIGN Real-time PCR and immunohistochemistry confirmed the downregulation of the VDR and CASR genes at transcriptional and translational levels. Bisulfite-converted DNA samples from parathyroid adenomas with control samples were analyzed for methylation in the promoter region of VDR and CASR genes. RESULTS There was no significant methylation in the promoter regions of VDR and CASR genes in parathyroid adenomatous tissues. CONCLUSIONS Methylation-mediated silencing of VDR and CASR promoter does not appear to be associated with reduced expression, indicating the involvement of other factors in specific suppression of VDR and CASR in parathyroid adenomas.

Effect of pioglitazone on testosterone in eugonadal men with type 2 diabetes mellitus: a randomized double-blind placebo-controlled study.

Pioglitazone is an insulin sensitizer used for the management of type 2 diabetes mellitus (T2DM). It has been shown to reduce testosterone level in patients with polycystic ovarian syndrome. However, its effect on testosterone in men has not been studied.

CdTe nanobioprobe based optoelectrochemical immunodetection of diabetic marker HbA1c.

Highly luminescent water soluble CdTe quantum dots (QDs) were synthesized and conjugated with anti-HbA1c antibody to generate specific nanobioprobe. A sandwich immunoassay model was employed using capture HbA1c antibody as a specific receptor molecule and the QD-labeled secondary antibody as a dual (fluorescence cum electrochemical) tracer to quantify the concentration of HbA1c. A linear increase in current was observed for HbA1c analytical standards with a R(2) value of 0.990 and coefficient of variance ~5%. A comparison between HPLC and dual immunoassay for clinical samples showed a correlation coefficient of 89% and 96% for fluorescence and electrochemical detection methods respectively. The QD-based immunoassay shows great promise for rapid reproducible and cost effective analysis of HbA1c in clinical samples.