Pinaki Dutta

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.

Heterogeneous Genetic Background of the Association of Pheochromocytoma/Paraganglioma and Pituitary Adenoma: Results From a Large Patient Cohort

Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence. Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL. Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples. Setting: The study was conducted at university hospitals. Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. Outcome: Outcomes included genetic screening and clinical characteristics. Results: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context. Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma.

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.

Predictors of outcome in myxoedema coma: a study from a tertiary care centre.

BackgroundWith the easy availability of thyroid hormone assays, thyroid disorders are now recognised even in a subclinical state. However, patients are still seen with advanced manifestations of the disease, particularly in developing countries. This observational study analysed the predictors of outcome in patients with myxoedema coma and tested the validity of different modules to define morbidity and mortality in these patients.MethodsTwenty-three consecutive patients with myxoedema coma who presented from January 1999 to August 2006 were studied. The thyroid function test and random serum cortisol were measured in all patients at the time of admission. Patients were given oral or intravenous (IV) thyroxine with intention to treat with the latter according to availability. Various modules that predict outcome, including Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Sequential Organ Failure Assessment (SOFA) score, were analysed. SOFA score was repeated every 2 days until the time of discharge or demise.ResultsTwenty-three patients (20 women; 87%) of 59.5 ± 14.4 years of age (range, 30 to 89 years) were seen during the study period. Nine (39%) patients were diagnosed with hypothyroidism for the first time at the time of presentation of myxoedema coma, whereas 14 (70%) were diagnosed with hypothyroidism previously. However, the treatment defaulters presented early to the hospital and had more severe manifestations than de novo subjects. Nineteen (82%) had thyroprivic (primary) and 4 (17%) had trophoprivic (secondary) hypothyroidism. Fifteen (65%) patients presented in the winter and in 17 (74%) sepsis was the major accompanying comorbidity. Twelve (52%) had a history of diuretic use, thereby delaying the initial diagnosis. Patients who received oral L-thyroxine had no difference in outcome from those receiving IV thyroxine. Twelve (52%) subjects died and sepsis was the predominant cause of death. Various predictors of mortality included hypotension (p = 0.01) and bradycardia (p = 0.03) at presentation, need for mechanical ventilation (p = 0.00), hypothermia unresponsive to treatment (p = 0.01), sepsis (p = 0.01), intake of sedative drugs (p = 0.02), lower GCS (p = 0.03), high APACHE II score (p = 0.04), and high SOFA score (p = 0.00). However, SOFA score was more effective than other predictive models as baseline and day 3 SOFA scores of more than 6 were highly predictive of poor outcome.ConclusionL-Thyroxine treatment defaulters had more severe manifestations compared with de novo subjects. Outcome was not influenced by either aetiology or route of administration of L-thyroxine, and SOFA score was the best outcome predictor model.

Pituitary abscess: report of four cases and review of literature.

Pituitary abscess is a rare disorder and its presenting manfestations are non-specific therefore, the diagnosis is usually made either postoperatively or at postmortem. We describe four such cases seen over a period of 10 years. All the patients presented with fever, systemic signs of toxaemia and endocrine dysfunctions. Two of them had pre-existing pituitary pathology. A preoperative diagnosis of pituitary abscess was considered in all in view of characteristic MR findings. Three patients underwent transsphenoidal drainage of abscess, whereas the remaining one succumbed to sepsis and was diagnosed at necropsy. Offending organisms including Pseudomonas, Acinetobacter and Staphylococcus were isolated in three cases respectively. During follow-up for 4 years, 2 patients are doing well, one had a recurrent abscess after 1 year and required redo-surgery.

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.

A Comparative Evaluation of Amitriptyline and Duloxetine in Painful Diabetic Neuropathy: A randomized, double-blind, cross-over clinical trial

OBJECTIVE To compare the efficacy and safety of duloxetine and amitriptyline in painful diabetic neuropathy (PDN). RESEARCH DESIGN AND METHODS In this randomized, double-blind, cross-over, active-control trial, 58 patients received amitriptyline and duloxetine orally once daily at bedtime, each for 6 weeks with optional dose uptitration fortnightly. Single-blinded placebo washout was given for 2 weeks between the two treatments and a single-blinded placebo run-out phase of 4 weeks was given at the end of the treatment period. Pain relief was measured by the patient’s global assessment of efficacy, using a visual analog scale (0–100) as a primary end point, and overall improvement and adverse events were assessed as secondary outcome measures. Median pain score reductions of >50%, 25–50%, and <25% were considered good, moderate, and mild responses, respectively. RESULTS There was a significant improvement in pain with both treatments compared with their baseline values (P < 0.001 for both). Good, moderate, and mild pain relief was achieved in 55, 24, and 15% of patients, respectively, on amitriptyline and 59, 21, and 9% of patients, respectively, on duloxetine. There were no significant differences in various other outcome measures between the groups. Of the reported adverse events, dry mouth was significantly more common with amitriptyline than duloxetine (55 vs. 24%; P < 0.01). Although, numerically, more patients preferred duloxetine, overall this was not statistically significant (48 vs. 36%; P = 0.18). CONCLUSIONS Both duloxetine and amitriptyline demonstrated similar efficacy in PDN. A large, multicentric clinical trial in other populations could possibly demonstrate the superiority of either drug.

Fine needle aspiration cytology of primary thyroid lymphoma: a report of ten cases

Primary lymphoma is an uncommon malignancy of the thyroid, comprising of 0.6 to 5 per cent of thyroid cancers in most series. Primary thyroid lymphomas (PTL) occur most commonly in elderly women and are commonly of B- cell origin. These frequently present in clinical stage IE and IIE. We report here ten cases of PTL diagnosed over a period of about 7 years in our institute. Out of these ten cases, nine were diagnosed on fine needle aspiration cytology (FNAC) and one case was misdiagnosed as lymphocytic thyroiditis. This case was diagnosed as Non- Hodgkins lymphoma on surgical specimen. Five patients are disease free and doing well, while two died of disease and the other two were lost to follow-up. One patient is currently on chemotherapy. The salient clinical, biochemical, radiological features, FNA findings along with diagnostic difficulties are discussed.

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.

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.