Shobhit Bhansali

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.

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.

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.

Evaluation of the ability of clinical research participants to comprehend informed consent form

BACKGROUND The comprehension of informed consent is an integral part of clinical trials. Though India is rapidly becoming a hub of clinical trials very few studies have dealt with the issue of comprehension of informed consent by the patients participating in these trials. METHODS Patients who were invited to participate in a phase 3 multicentric trial of a novel lipid lowering agent were evaluated for comprehension score. The participants were explained about the structured consent form which included the question on background details for the study, design of the study, rights of the patients and miscellaneous aspects pertinent to the clinical trial. The questionnaire comprised of 24 items and each correct answer was assigned a score of 1. Total comprehension score (CS) was obtained by summing all the scores. RESULTS Participants were from diverse socio economic and educational backgrounds. The mean +/- SD CS achieved by the participants was 13.4 +/- 2.9; median 14(6 to 20). The highest correct responses were obtained for questions on background details (38%). For most of the categories the mean CS was more than 50%. Aspects related to design were mostly difficult to comprehend. No significant difference in the CS was noted between participants from different educational and socioeconomic groups. 8 patients refused to give consent, fear of adverse drug reactions (n = 3) and inability to follow up (n = 5) were the reasons cited by the patients. CONCLUSION In conclusion, CS of patients in trials conducted in developing countries can be reasonably good if the investigators explain the consent form in simple language to the participants and CS is not related to the educational status of the participants. Moreover, though a larger majority of patients agree to participate after knowing study details, some patients exercise their right to refuse.

Prevalence and risk factors of diabetes in a community-based study in North India: The Chandigarh Urban Diabetes Study (CUDS)

AIMS As there have been few studies in North India of the prevalence of diabetes within the past decade, this study aimed to assess the prevalence and risk factors associated with diabetes in the North Indian city of Chandigarh. METHODS This cross-sectional survey of 2227 subjects (response rate: 94%), aged ≥20 years and representative of the urban Chandigarh population, was conducted from April 2008 to June 2009. Fasting plasma glucose (FPG) and 2-h plasma glucose (2hPG) following ingestion of 75 g of an anhydrous glucose equivalent were estimated by glucometer in all subjects except those with known diabetes, in whom only FPG was measured. Diagnosis of diabetes was based on 1999 WHO criteria. The collected prevalence data was age-standardized for the Chandigarh population, and multivariate logistic-regression analysis was used to correlate risk factors with the presence of diabetes. RESULTS A total of 349 subjects (15.7%, 95% CI: 13.9-16.9) were diabetic, comprising 210 (9.4%) with known diabetes and 139 (6.2%) with newly diagnosed diabetes, and 344 (15.4%, 95% CI: 14.3-17.1) subjects were prediabetic. The age-standardized prevalence of diabetes and prediabetes were 11.1% (95% CI: 9.7-12.4) and 13.2% (95% CI: 11.8-14.6), respectively. Age ≥50 years, a family history of diabetes, BMI ≥23 kg/m(2), abdominal obesity and hypertension were significantly and positively associated with the presence of diabetes, whereas educational status was negatively associated with diabetes (P<0.001 for all). CONCLUSION The age-standardized prevalence of diabetes and prediabetes were 11.1% and 13.2%, respectively. Older age, family history of diabetes, obesity and hypertension were positively related, while educational status was negatively related, to the presence of diabetes.

Effects of three different doses of a fruit extract of Terminalia chebula on metabolic components of metabolic syndrome, in a rat model

There is documented evidence of the use of Terminalia chebula for various ailments in the Ayurvedic literature. The extract has been shown to possess glucose lowering activity and to improve insulin sensitivity in animal models of type 2 diabetes mellitus. The present study was carried out to study the dose response relationship of this extract in a rat model of metabolic syndrome. Six groups of rats were fed a high fructose diet (HFD) for a period of 20 days to induce metabolic syndrome. Three doses of fruit extract of T. chebula 50, 100 and 200 mg/kg were administered orally and pioglitazone 2.7 mg/kg was used as a positive control. Blood samples were collected at days 0, 20 and 40 from the tail vein. Systolic blood pressure (SBP) was measured using the tail cuff method and an oral glucose tolerance test (OGTT) was done on the day of blood collection. Administration of HFD for 20 days significantly increased fasting blood glucose (FBG), SBP and the area under the curve of OGTT. On day 40 the FBG in the 50, 100 and 200 mg/kg group was 97.33 ± 5.82 (NS), 86.83 ± 5.08 (p = 0.038) and 85.67 ± 6.74 (p = 0.15), respectively. These results show that the fruit extract of T. chebula exerts a significant and dose‐dependent glucose lowering effect in the rat model of metabolic syndrome. Copyright

Effect of mesenchymal stem cells transplantation on glycaemic profile & their localization in streptozotocin induced diabetic Wistar rats.

Background & objectives: Bone marrow is a rich source of adult stem cells that can differentiate into various cell types. Administration of mesenchymal stem cells (MSCs) in irradiated diabetic rat model has transiently shown to decrease blood glucose level. This study examines the effect of high dose and multiple injections of MSCs on glycemic profile, their localization and regeneration of islet in diabetic Wistar rat. Methods: The study was carried out in male Wistar rats categorized into three groups (n=6, in each group): Group 1 as control, group 2 streptozotocin (STZ) (50 mg/kg) induced diabetic group and group 3 experimental group; 5-bromo-2-deoxyuridine (BrdU) labelled allogenic MSCs were injected in the non-irradiated diabetic rat of the experimental group through tail vein. The blood glucose profile was subsequently monitored at regular intervals. Rats were sacrificed on day 45 and pancreas was examined for localization of BrdU labelled stem cells by immunofluorescence and islet-neogenesis by immunohistochemistry. Results: There was a significant reduction in blood glucose level after administration of MSCs in the experimental group (P<0.001). The presence of BrdU labelled MSCs in islet suggested their localization in the pancreas. Co-expression of anti-BrdU and anti-insulin antibody indicated trans-differentiation/fusion into insulin producing cells evidenced by significant increase in total number of islet (P=0.004) and insulin positive cells (P<0.0001) in experimental group. Interpretation & conclusions: Our results showed that the MSCs administration in non-irradiated diabetic Wistar rat reduced hyperglycaemia and was accompanied by increased islet-neogengesis, possibly through trans- differentiation/fusion.

Efficacy and safety of autologous bone marrow derived hematopoietic stem cell transplantation in patients with type 2 DM: A 15 months follow-up study.

Background: there are dearths of studies describing the effect of autologous bone marrow derived stem cell transplantation (ABMSCT) through targeted approach in Type 2 Diabetes Mellitus. This study reports the efficacy and safety of super-selective injection of ABMSCT in T2DM. Materials and Methods: Ten patients (8 men and 2 women) with T2DM, with duration of disease >5 years and with documented triple drug failure receiving insulin (0.7 U/Kg/day), metformin and pioglitazone underwent super-selective injection of stem cells into superior pancreaticoduodenal artery under fluoroscopic guidance. The primary outcome measure was decrease in insulin requirement by ≥50% (defined as responders), while secondary endpoints were improvement in glucagon stimulated C-peptide levels, changes in weight, HbA1c, lipid profile and quality of life (QOL) at the end of 15 months. Results: Six patients (60%) were ‘responders’ at 15 months of follow-up showing a reduction in mean insulin requirement by 74% as compared to baseline and one patient was off-insulin till the end of the study. Mean HbA1c reduction in ‘responders’ was 1.1% (8.1 ± 0.5% to 7.0 ± 0.6%, P = 0.03), accompanied with a significant improvement in glucagon stimulated C-peptide levels (P = 0.03), Homeostasis Model Assessment -β (P = 0.03) and QOL scores. However, ‘non-responders’ did not show any significant alterations in these parameters. No serious adverse events were noted. Conclusion: Our observations indicate that ABMSCT is effective in management of T2DM and its efficacy is maintained over a period of 15 months without any adverse events. However, more number of patients and longer duration of follow-up are required to substantiate these observations.