Sadishkumar Kamalanathan

Predictors for antenatal insulin requirement in gestational diabetes

Abstract The purpose of this study was to identify pre-gestational and gestational factors predicting subsequent insulin requirement in patients with gestational diabetes mellitus (GDM). Maternal parameters were compared between mothers achieving glycemic control with or without the addition of antenatal insulin therapy (AIT). Insulin was required only in 8/83 (10%) patients for glycemic control. Those who needed insulin had a stronger family history of diabetes and higher first hour plasma glucose along with multiple (>1) abnormal values during oral glucose tolerance test (OGTT) in univariate analysis (p < 0.05). The first hour plasma glucose value of ≥9.72 mmol/l predicted requirement of AIT in GDM mothers with a sensitivity of 100% and specificity of 73%. However, only positive family history of diabetes mellitus among first degree relatives and multiple abnormal values in OGTT were independent predictors for antenatal insulin requirement in regression analysis. Chinese abstract 本研究的目的是探讨妊娠期糖尿病（gestational diabetes mellitus ，GDM）患者孕期是否需要使用胰岛素治疗的孕前及孕期的预测因素。比较了除饮食控制和适当运动外，需要和不需要用胰岛素治疗(antenatal insulin therapy,AIT)来控制血糖的两组孕妇的各项参数。在83例妊娠期糖尿病患者中，只有8例需要用胰岛素来控制血糖。这些孕妇有更明显的糖尿病家族史；口服葡萄糖耐量试验（oral glucosetolerance test，OGTT）多项值（大于1项）高出正常范围且1小时血糖值明显高于不需要使用胰岛素的孕妇（p<0.05）。1小时血糖值≥9.72 mmol/l对于预测GDM的孕妇是否应用AIT的敏感性为100%，特异性为73%。然而，回归分析显示：只有一级亲属有糖尿病家族史和OGTT多项值异常是预测孕期需使用胰岛素治疗的独立预测因素。

Pregnancy in polycystic ovary syndrome

Polycystic ovary syndrome affects 6 to 15% of reproductive age women worldwide. It is associated with increased risk of miscarriage, gestational diabetes mellitus, hypertensive disorders of pregnancy, preterm delivery, and birth of small for gestational age infant. Many studies on issues relating to pathophysiology and management of these complications have been published recently. These issues are being reviewed here using relevant articles retrieved from Pubmed database, especially from those published in recent past.

Comparison of different criteria for diagnosis of gestational diabetes mellitus.

Introduction: The International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria for gestational diabetes mellitus (GDM) has been adopted by most associations across the world including the American Diabetes Association and World Health Organization (WHO). We conducted a study comparing the IADPSG and previous WHO criteria and their effects on neonatal birth weight. Methods: The study was carried out in Obstetrics and Gynaecology Department of a tertiary care institute in South India in collaboration with Endocrinology Department. Thousand two hundred and thirty-one antenatal cases with at least one risk factor for GDM and gestational age of more than 24 weeks were included in the study. Both criteria were compared on the basis of 75 g oral glucose tolerance test results. Results: The prevalence of GDM using IADPSG and previous WHO criteria were 12.6% and 12.4%, respectively. The prevalence of GDM was 9.9% when both criteria had to be satisfied. Both GDM criteria groups did not differ in neonatal birth weight and macrosomia rate. However, there was a significant increase in lower segment cesarean section in IADPSG criteria group. Elevated fasting plasma glucose alone picked up only one GDM in the previous WHO criteria group. Conclusions: A single 2 h plasma glucose is both easy to perform and economical. A revised WHO criterion using a 2 h threshold of ≥140 mg % can be adopted as a one-step screening and diagnostic procedure for GDM in our country.

Improper sharp disposal practices among diabetes patients in home care settings: Need for concern?

In the recent years, outbreaks of blood-borne infections have been reported from assisted living facilities, which were traced back to improper blood glucose monitoring practices. Needle-stick injuries have been implicated in many such cases. This directly raises concerns over sharp disposal practices of diabetic patients self-managing their condition in home care settings. With India being home to a huge diabetic population, this issue, if neglected, can cause substantial damage to the health of the population and a marked economic loss. This article discusses the sharp disposal practices prevalent among diabetes patients, the importance of proper sharp disposal, barriers to safe disposal of sharps, and the options available for doing the same. For adopting an environmentally safe wholesome approach, disposal of plastics generated as a result of diabetes self-care at home is important as well. The article also looks at the possible long-term solutions to these issues that are sustainable in an Indian context.

Effect of metformin on exercise capacity in metabolic syndrome

OBJECTIVE Metabolic syndrome is a constellation of risk factors with increased predilection towards occurrence of cardiovascular diseases. Currently physical exercise and management with metformin are the prevailing treatment modalities for metabolic syndrome. Patients with metabolic syndrome have been found to have reduced exercise capacity over a period of time. Likewise metformin has been shown to decrease exercise capacity among healthy volunteers. Hence this study aims to evaluate the effect of metformin on the exercise capacity of patients with metabolic syndrome. DESIGN Prospective study with 6 weeks follow up. METHODS Newly diagnosed patients with metabolic syndrome and to be started on Table Metformin 500mg twice a day were recruited for the study after obtaining written informed consent. Cardiopulmonary Exercise Testing (CPET) was done at baseline before the subjects were started on metformin and after 6 weeks of treatment using cardiopulmonary exercise testing apparatus (ZAN600). RESULTS Fifteen treatment naïve patients with metabolic syndrome completed six weeks of therapy with metformin. In these patients oxygen uptake [VO2] showed statistically significant decrease from 1.10±0.44 at baseline to 0.9±0.39 (l/min) after six weeks of treatment with metformin [mean difference of -0.20 (-0.31 to -0.09); P=0.001]. Similarly oxygen uptake/kg body weight [VO2/Kg] showed a significant decrease from 14.10±4.73 to 11.44±3.81 (mlkg-1min-1) at the end of six weeks of treatment [mean difference of -2.66 (-4.06 to -1.26); P=0.001]. CONCLUSION Six weeks of treatment with metformin significantly decreases exercise capacity in newly diagnosed patients with metabolic syndrome.

Assessment of insulin injection techniques among diabetes patients in a tertiary care centre.

AIMS The efficacy of insulin therapy in diabetes depends on proper storage and injection technique. The purpose of this study was to assess the practice of insulin administration among diabetes patients in a tertiary care center. MATERIALS AND METHODS This observational study was done in Endocrinology department of a tertiary care center during April-June 2015. The consecutive patients using insulin for at least three months by either syringe or pen were recruited. All of them underwent a survey by the questionnaire which focused on key insulin injection parameters. RESULTS One hundred and sixty eight (74.67%) patients were storing insulin vials properly. The thigh was the most common site of insulin injection and 209(92.89%) study participants were rotating at the injection sites. Only 48.57% (34/70) subjects were mixing insulin properly before injection. The practice of hand washing and the cleaning of the injection site was practiced by 158(70%) & 171(76.44%) subjects respectively. One hundred and fifty six (69%) patients were injecting with the proper skin fold and 123(55%) subjects were injecting insulin at 90° angle. The majority of patients (91%) were throwing the needle and syringes directly into the garbage and public drainage system. CONCLUSIONS There was a significant gap between the insulin administration guidelines and current insulin injection practice. The diabetic education and counseling about proper insulin injection techniques should be provided to all diabetic subjects.

Evidence for current diagnostic criteria of diabetes mellitus

Diabetes mellitus is a non-communicable metabolic derangement afflicting several millions of individuals globally. It is associated with several micro and macrovascular complications and is also a leading cause of mortality. The unresolved issue is that of definition of the diagnostic threshold for diabetes. The World Health Organization and the American Diabetes Association (ADA) have laid down several diagnostic criteria for diagnosing diabetes and prediabetes based on the accumulating body of evidence.This review has attempted to analyse the scientific evidence supporting the justification of these differing criteria. The evidence for diagnosing diabetes is strong, and there is a concordance between the two professional bodies. The controversy arises when describing the normal lower limit of fasting plasma glucose (FPG) with little evidence favouring the reduction of the FPG by the ADA. Several studies have also shown the development of complications specific for diabetes in patients with prediabetes as defined by the current criteria though there is a significant overlap of such prevalence in individuals with normoglycemia. Large multinational longitudinal prospective studies involving subjects without diabetes and retinopathy at baseline will ideally help identify the threshold of glycemic measurements for future development of diabetes and its complications.

Germline mutations and genotype–phenotype correlation in Asian Indian patients with pheochromocytoma and paraganglioma

BACKGROUND Genetic aetiology of pheochromocytoma (PCC) and paraganglioma (PGL) is increasingly being studied; however, Asian Indian data on this aspect are scarce. OBJECTIVE To study the prevalence of germline mutations and genotype-phenotype correlation in Asian Indian PCC/PGL patients. DESIGN In this study, 150 index patients (M:F, 73:77) with PCC/PGL were evaluated. Phenotypic data were collected. Germline mutations in five susceptibility genes (RET, VHL, SDHB, SDHD and SDHC) were tested by sequencing and NF1 was diagnosed according to phenotype. RESULT Of the total population, 49 (32.7%) PCC/PGL patients had germline mutations (VHL: 23 (15.3%), RET: 13 (8.7%), SDHB: 9 (6%), SDHD: 2 (1.3%) and NF1: 2 (1.3%)). Amongst the 30 patients with familial and/or syndromic presentation, all had germline mutations (VHL: 14 (46.7%), RET: 13 (43.3%), SDHB: 1 (3.3%) and NF1: 2 (6.7%)). Out of 120 patients with apparently sporadic presentation, 19 (15.8%) had a germline mutation (VHL: 9 (7.5%), SDHB: 8 (6.7%) and SDHD: 2 (1.7%)). Mutation carriers were younger (29.9 ± 14.5 years vs 36.8 ± 14.9; P = 0.01) and had a higher prevalence of bilateral PCC (26.5% vs 2.9%, P < 0.001) and multifocal tumours (12.2% vs 0.96%, P = 0.06). Based on syndromic features, metastasis, location and number of tumours, around 96% mutations in our cohort could be detected by appropriately selected single gene testing. CONCLUSION Asian Indians with PCC/PGL differ from Western cohorts in having preponderance of VHL mutations in multifocal tumours and apparently sporadic unilateral PCC. Syndromic presentation, metastasis, location and number of PCC/PGL can be effectively used for guiding genetic prioritisation.

Tumor(s) induced osteomalacia--a curious case of double trouble.

CONTEXT We report a case of tumor-induced osteomalacia with evidence of synchronous multifocal fibroblast growth factor 23 (FGF23) production. OBJECTIVE The aim is to present a case of tumor-induced osteomalacia and to highlight the fact that incomplete removal of multifocal FGF23-producing tumors, which are not entirely picked up by functional imaging, could be the cause of treatment failure. SETTING The patient was treated in the Department of Endocrinology of a tertiary care center in India. PATIENT We report the case of a 42-year-old male with tumor-induced osteomalacia. INTERVENTION We treated the tumor-induced osteomalacia with staged surgery of the two tumors. The 18F-fluorodeoxyglucose (FDG)-avid lesion (considered the sole culprit lesion after functional imaging) was resected first, followed by the non-FDG-avid lesion. The sequential removal of both tumors resulted in complete cure. RESULTS The patient had hypophosphatemia and hyperphosphaturia. C-Terminal FGF23 level was elevated. Positron emission tomography-computed tomography showed two lesions-an FDG-avid lesion in the right leg, and a non-avid lesion in the left thigh. After removal of the FDG-avid lesion, the hypophosphatemia persisted, and the FGF23 level showed only modest reduction. The patient had complete clinical and biochemical resolution only after removal of the second non-FDG-avid tumor. CONCLUSIONS We present the case of a tumor-induced osteomalacia whose biochemical parameters did not improve after removal of the FDG-avid tumor initially. The possibility of multifocal FGF23 production was considered, and the second, non-FDG-avid lesion was resected, which resulted in complete cure. Thorough clinical examination and meticulous follow-up with documentation of the biochemical resolution are necessary for management of all patients with this rare disorder.

The serological and biochemical markers of adrenal cortex and endocrine pancreas dysfunction in patients with Hashimoto's thyroiditis: A hospital-based pilot study

Background: The prevalence of both islet cell and adrenal autoimmunity among Asian Indian hypothyroidism patients with Hashimotos thyroiditis (HT) is lacking in literature. Objectives: The objective of this study was to assess the proportion of Addisons disease (AD) and type 1 diabetes mellitus (T1DM) in patients with HT. Materials and Methods: The patients with hypothyroidism due to HT were included in this study over 2 years. Primary hypothyroidism was defined as high serum thyroid-stimulating hormone (>5.5 mIU/L) with or without low thyroxine level. HT was defined by the presence of high thyroid peroxidase antibody (Ab) titer (>35 IU/ml). Autoimmune markers of AD and T1DM, i.e., adrenal (21-hydroxylase) Ab, glutamic acid decarboxylase (GAD) Ab, and insulinoma-associated antigen-2 (IA-2) Ab were measured among them. In addition, 250 μg adrenocorticotropic hormone (ACTH) stimulation test was done in patients with adrenal Ab. Similarly, beta cell function was assessed in patients with GAD and/or IA-2 Ab. Results: Out of 150 patients screened, 136 patients were included in this study. Seven patients had adrenal Ab while 15 had IA-2 Ab. The GAD Ab was not present in any of the patients in the study. ACTH stimulation test was done in four of seven patients with adrenal Ab and beta cell function was assessed in 8 of 15 patients with islet cell Ab. All patients with adrenal Ab had normal adrenal function and 1 out of 15 with IA-2 Ab developed diabetes mellitus during follow-up. Conclusions: Either adrenal or islet cell Ab was found in 16% Asian Indian hypothyroidism patients with HT.