Rama Walia

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.

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.

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.

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.

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.

Vitamin D status and its seasonal variability in healthy young adults in an Asian Indian urban population.

OBJECTIVE To assess the vitamin D status and its seasonal variability in healthy young adults in Chandigarh, a city in northern India. METHODS The history was elicited and examination was performed pertaining to metabolic bone disease in 329 young adults (18 to 25 years of age) at the end of summer and 237 subjects from the same cohort at the end of winter. The calcium profile, 25-hydroxyvitamin D [25(OH)D], and intact parathyroid hormone were measured during both the seasons. RESULTS Among the young adults in this study cohort, 25(OH)D sufficiency (≥ 30 ng/mL) was found in 72.5% in summer and in 50.7% in winter. A significantly higher number of men were 25(OH)D sufficient in comparison with women in summer (P = .001). The mean (standard deviation) serum 25(OH)D levels were significantly higher at the end of summer-52.9 (33.7) ng/mL-in comparison with that at the end of winter-31.8 (21.1) ng/mL; P<.001. The intact parathyroid hormone levels were significantly lower in the 25(OH)D-sufficient group (P = .001) and began to increase at 25(OH)D levels below 25 ng/mL. The serum 25(OH)D levels correlated positively with the duration of exposure to sunlight during summer (r = 0.111; P = .05) and also the calcium intake during summer (r = 0.129; P = .03). CONCLUSION Vitamin D sufficiency may be a reality with a combination of young skin, optimal and effective exposure to sunlight, and adequate calcium intake.

Large but benign adrenal mass: Adrenal oncocytoma.

Adrenal incidentalomas of more than 4 cm size are usually malignant. We describe a 28-year-old woman with a 7-cm, non-functioning, well-demarcated adrenal mass, which was identified as an oncocytoma on histopathological examination. Therefore, a large, non-functioning, unilateral adrenal mass with preserved tumor outline should invoke the suspicion of oncocytoma, which is invariably a benign tumor.

Can Ascending Infection from Bladder Serve as the Portal of Entry for Primary Renal Zygomycosis

Mucormycosis is an uncommon opportunistic infection by filamentous fungi that usually develops in immmunocompromised patients. Most individuals have an underlying systemic disease, such as diabetes mellitus, malignancy, uraemia, burns, renal transplant recipients and those on corticosteroid and immunosuppressive therapy. Many cases of primary renal zygomycosis with lungs serving as the portal of entry have been reported from this region. We describe two autopsy cases of renal zygomycosis where bladder appeared to be the portal of entry for the fungus.