Jayaprakash Sahoo

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。

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.

Hemophagocytic lymphohistiocytosis: An unusual complication in disseminated Mycobacterium tuberculosis.

Background: Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially fatal, hyperinflammatory syndrome that may rarely complicate the clinical course of disseminated Mycobacterium tuberculosis (MTB). The clinical course of tuberculosis-associated HLH (TB-HLH) has been reported to be unpredictable. Materials and Methods: Here we describe the clinicopathological features, laboratory parameters, management, and outcome data of a patient who satisfied the 2004 diagnostic criteria for HLH secondary to disseminated MTB; we also do a systematic review of the international literature on TB-HLH. The literature review (January 1975–March 2014) found that HLH complicated the clinical course of 63 tuberculosis patients (41 males, 22 females, mean age = 45 ± 23.5 years) with a high mortality rate of 49% (31/63 died). The mean serum ferritin level (n = 44/63) was 5963 ng/mL (range 500–38,539 ng/mL); and a higher proportion (54.2%) of patients had pancytopenia at presentation. On univariate analysis (n = 53/63), age >30 years [hazard ratio (HR): 2.79, 95% confidence interval (CI):1.03–7.56, P = 0.03], presence of comorbidities (HR 4.59, CI: 1.08–19.52, P = 0.04), marked hemophagocytosis in bone marrow (HR: 2.65, CI: 1.16–6.05, P = 0.02), and nonusage/delayed usage of antitubercular therapy (ATT) (HR: 3.44, CI: 1.51–7.87, P = 0.003) were associated with decreased survival, though none of these parameters attained statistical significance (P > 0.05) in multivariate analysis. Usage of corticosteroids and/or immunomodulator drugs (HR 1.00, CI: 0.66–3.22, P = 0.35) did not alter the outcome in these patients. Conclusion: HLH should be considered as a differential diagnosis in patients with tuberculosis who present with cytopenias, organomegaly, and coagulopathy. Strong clinical suspicion and early usage of ATT might be useful in reducing the morbidity and mortality. The utility of immunosuppressive/immunomodulator therapy lacks general concensus among treating physicians, and warrants further studies.

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.

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.

Phenytoin Induced Osteopathy -Too Common to be Neglected

Anticonvulsants have the broad spectrum of side effects on the bone that are collectively known as osteopathy. Anticonvulsant induced osteopathy can have detrimental consequences. We present an unusual case that uniquely highlights both adverse effects of phenytoin on bone metabolism and side effects of its overtreatment. A 29-year-old lady came for evaluation of metabolic bone disease. Since last one year, she had severe bilateral hip pain resulting in restriction of movements. She was taking phenytoin 300 mg daily for last ten years for a seizure disorder. During evaluation at another center, she was diagnosed to have vitamin D deficiency, osteomalacia and secondary hyperparathyroidism. She received recombinant parathormone, high doses of vitamin D along with phenytoin. She presented at our centre with persistent pain and hypervitaminosis D. We stopped recombinant PTH, vitamin D and changed phenytoin to levetiracetam. Her condition improved over next six months with normalization of vitamin D. Thus, patients on phenytoin should be actively screened for side effects and the appropriate preventive and correctional measures should be undertaken. While managing these side effects overtreatment should be avoided.

Correction of metabolic acidosis improves muscle mass and renal function in chronic kidney disease stages 3 and 4: a randomized controlled trial

Background Metabolic acidosis (MA) is associated with a loss of muscle mass and faster deterioration of kidney function in patients with chronic kidney disease (CKD). A few single-centre randomized trials have reported favourable outcomes following correction of MA. Additional good quality evidence on the safety and efficacy of alkali supplementation is required in epidemiologically different patient subsets with CKD. Methods A single-centre, open-label, randomized, prospective parallel-group study was conducted to assess the effect of correction of MA on body composition and kidney function. A total of 188 patients with CKD stages 3 and 4, with venous bicarbonate levels <22 mEq/L were randomized. The intervention arm received standard care as per Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines along with oral sodium bicarbonate supplementation to maintain venous bicarbonate levels at 24-26 mEq/L, whereas the control group received standard care alone. The mid-arm muscle circumference (MAMC), lean body mass (LBM) and estimated glomerular filtration rate (eGFR) were compared between the groups at the end of 6 months. Results The intervention arm showed a higher LBM {36.8 kg [95% confidence interval (CI) 36.5-37.1] versus 36 [35.7-36.4]; P = 0.002} and MAMC [22.9 cm (95% CI 22.8-23) versus 22.6 (22.5-22.7); P = 0.001] when compared with the control group. The GFR in the intervention arm was higher [32.74 mL/1.73 m2 (95% CI 31.5-33.9) versus 28.2 (27-29.4); P ≤ 0.001]. A rapid decline in GFR was documented in 39 (41.5%) patients in the control arm and 19 (20.2%) patients in the intervention arm (P = 0.001). Conclusions Alkali supplementation to increase venous bicarbonate levels to 24-26 mEq/L is associated with preservation of LBM and kidney function in patients with CKD stages 3 and 4.