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   Table of Contents - Current issue
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September-October 2017
Volume 21 | Issue 5
Page Nos. 647-789

Online since Friday, September 15, 2017

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EDITORIALS  

Choices and challenges of antibiotics therapy in diabetic foot infection p. 647
SK Singh, Balram Gupta
DOI:10.4103/ijem.IJEM_481_17  
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Medical nutrition therapy in type 1 diabetes mellitus p. 649
K Sandhya Rani, Sanjay Kumar Bhadada
DOI:10.4103/ijem.IJEM_539_17  
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Glucocorticoid-induced osteoporosis p. 652
Kripa Elizabeth Cherian, Nitin Kapoor, Thomas Vizhalil Paul
DOI:10.4103/ijem.IJEM_187_17  
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ORIGINAL ARTICLES Top

“Riding high on low fuel” - Our experience with endogenous hyperinsulinemic hypoglycemia p. 655
PR Manjunath, Belinda George, Vivek Mathew, Ganapathi Bantwal, Vageesh Ayyar
DOI:10.4103/ijem.IJEM_174_17  
Introduction: Endogenous hyperinsulinemic hypoglycemia (EHH) is a condition in which the insulin levels are inappropriately high in the presence of low plasma glucose. Materials and Methods: We did a retrospective analysis of case records of those patients admitted and evaluated for EHH from June 2004 to June 2016 in our center, excluding those that were diagnosed with reactive hypoglycemia. We collected data regarding demographics, clinical presentation, laboratory results, localization techniques, and treatment administered. Results: Sixteen patients who were admitted for evaluation based on history suggestive of repeated hypoglycemic episodes were included in the study. All but one pregnant patient was subjected to a supervised fast in the hospital. All patients developed hypoglycemia (defined using Whipple's triad) within the first 24 h. Three patients had autoimmune hypoglycemia which differed significantly from insulinoma-mediated hypoglycemia in certain clinical and laboratory parameters. They were older in age with marked fluctuations in the 24 h glucose profile ranging from frank hypoglycemia to frank hyperglycemia. The insulin levels were markedly elevated in this group of patients along with a significantly elevated insulin C peptide molar ratio (ICMR) when compared with patients with insulinoma-mediated hypoglycemia. Conclusions: Although insulinoma is the most common cause of EHH, autoimmune hypoglycemia should be considered as a differential diagnosis, particularly in older individuals with plasma glucose values increasing to the hyperglycemic range. Degree of elevation of insulin levels and ICMR may provide additional clues. Overall, the survival and prognosis of patients with EHH are excellent.
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Prepregnancy hypothyroidism versus gestational hypothyroidism: A comparative study p. 660
Prashant Ulhas Kaduskar, Mala Dharmalingam, Pramila Kalra
DOI:10.4103/ijem.IJEM_158_17  
Introduction: Hypothyroidism managed inadequately in pregnancy may have grave outcomes for both mother and baby. Understanding pregnancy outcomes in our country with low awareness about thyroid diseases is important. Objectives: The objectives of the study were to evaluate demographic features and biochemical parameters in patients with prepregnancy hypothyroidism versus patients diagnosed to have primary hypothyroidism during pregnancy and to assess pregnancy outcomes. Study Design: Prospective design Materials and Methods: The study was conducted in a tertiary care center in Bengaluru for 2 years. The patients were divided into two groups - Group I: Prepregnancy hypothyroidism and Group II: Hypothyroid during pregnancy. They were further staged according to ESI guidelines as subclinical or overt hypothyroidism. Statistical Analysis: Chi-square and Mann–Whitney test. Results: A total of 452 pregnant women with hypothyroidism were analyzed. The data of 371 delivered pregnancies were available. Group I and II had 196 (43.36%) and 256 (56.64%) patients, respectively. Age at presentation (years) was 27.09 ± 4.19 in Group I versus 25.74 ± 4.29 in Group II (P = 0.003); gestational age (weeks) was 9.04 ± 5.41 in Group I versus 13.81 ± 9.12 in Group II (P = 0.000). There was one case of congenital hypothyroidism in baby in each group. Mean birth weight was 2.90 ± 0.39 kg in Group I versus 2.88 ± 0.36 kg in Group II; P = 0.608. There were four abortions in Group I versus ten in Group II (P = 0.231), 104 cesarean sections in Group I compared to 133 in Group II; (P = 0.382). There was no difference in number of cesarean sections, abortions and low birth weight babies between overt and subclinical hypothyroidism subgroups. Conclusions: Group I patients presented earlier for testing suggesting awareness was good in this group. There was no difference in pregnancy outcome between the two groups. Overt versus subclinical status did not have any different effects on pregnancy outcomes in any group.
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Prevalence and risk factors for peripheral neuropathy among type 2 diabetes mellitus patients at a tertiary care hospital in coastal Karnataka p. 665
Sonalika Gogia, Chythra R Rao
DOI:10.4103/ijem.IJEM_43_17  
Context and Objective: In view of the growing burden of type 2 diabetes mellitus (T2DM) globally and associated microvascular and macrovascular complications, the study was done to assess the prevalence and risk factors for diabetic neuropathy among T2DM patients attending a tertiary care hospital. Subjects and Methods: T2DM patients' ≥30 years of both gender, presenting to the Medicine Department at a tertiary care hospital were included in the study. Diabetic Neuropathy Symptom (DNS) questionnaire to assess symptoms and Diabetic Neuropathy Examination (DNE) scoring to assess clinical signs were used. Results: A total of 273 patients were included. The mean age was 57.8 ± 11.5 years. The male to female distribution was 75% (202) and 25% (71), respectively. According to DNS instrument, 41.4% patients scored positive for the presence of neuropathy while only 24.5% had neuropathy according to DNE score. The proportion of males affected by neuropathy was more than females. 43.1% males had a positive DNS score while only 27.2% of them had a positive DNE score. Duration of the disease was positively correlated with neuropathy. Neuropathy was more prevalent among people who had higher systolic and diastolic blood pressure as per DNS and DNE instruments. Conclusions: The present study identified a higher proportion of males to be affected by neuropathy. Hence, more detailed evaluation must be accorded to elderly male diabetic patients with longer duration of the disease. Lifestyle modifications and watchful screening need to be incorporated as part of routine patient health education during follow-up clinic visits.
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Current indicators of nutritional care in children with type 1 diabetes in India: Do we need a national nutritional guideline? p. 670
Sanjay Kalra, Ashok Kumar Das, P Raghupathy, Subhankar Chowdhury, Banshi D Saboo, P Dinakaran, Shuchy Chugh
DOI:10.4103/ijem.IJEM_183_17  
Background: Nutrition is an important pillar of management in children with type 1 diabetes. Indian food is heavily influenced by region, religion, traditions, seasons, and cultural choices. This survey was done to assess current practices and the need for India specific nutritional guidelines for children with type 1 diabetes. Materials and Methods: Two 12-item questionnaires were administered to forty health-care professionals across India. The first questionnaire evaluated current clinical practice indicators for nutrition in these children and second assessed practices for counseling a child on dietary habits. Results: There is great heterogeneity across the country with regard to dietary advice offered to children with type 1 diabetes. 97.5% of the respondents feel there is a need for an Indian dietary guideline for children with type 1 diabetes. Conclusion: There is need of India specific nutritional guidelines that should be made considering key variants such as age, region, cultural preference, economic burden and psychosocial beliefs, to offer guidance to diabetes care professionals.
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Effect of metformin-sustained release therapy on low-density lipoprotein size and adiponectin in the South Indian women with polycystic ovary syndrome p. 679
D Rama Nagendra Kumar, Krishna G Seshadri, Monna Pandurangi
DOI:10.4103/ijem.IJEM_154_17  
Objectives: The aim of the study is to compare surrogate markers of cardiovascular disease (CVD) risk, such as adiponectin (APN) levels and low-density lipoprotein (LDL) size, before and after sustained release metformin (Met-SR) therapy in women with polycystic ovarian syndrome (PCOS). Methods: Sixty women with PCOS and sixty age-matched controls in the age group 18–45 years were recruited after obtaining informed consent. Women with PCOS were initiated on Met-SR 1 g orally, which was increased to 1.5 g after 2 weeks and continued up to 24 weeks. Demographic data along with family history of type 2 diabetes mellitus, PCOS, and CVD were collected. Lipid profile plasma APN levels and LDL size were measured before and after therapy in the PCOS group. Data analysis was performed using the GraphPad Prism-5 software. Results: Women with PCOS had greater dyslipidemia, lower APN level and LDL size, and increased lipid accumulating product index as compared to controls. After 6 months of Met-SR therapy, women with PCOS demonstrated significant increase in plasma APN levels and LDL size and significant decrease in weight, waist-hip ratio (WHR), waist circumference (WC), and blood pressure (BP). A significant decrease was observed in body mass index (BMI) in the overweight and obese PCOS subgroups. Conclusion: Met-SR increases LDL size, APN concentration and decreases weight, WC, WHR, and BP in patients with PCOS. Met-SR may have salutary effects on LDL particle size through effects on APN levels in women with PCOS.
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Metabolic status and hypogonadism in human immunodeficiency virus-infected males p. 684
Sarita Bajaj, Yashaswi Pathak, Sharad Varma, Sujit Verma
DOI:10.4103/ijem.IJEM_127_17  
Aims and Objectives: The aim of this study is to determine the prevalence of hypogonadism in human immunodeficiency virus (HIV)-infected males and to study its relation to age, CD4 count, body mass index (BMI), duration of highly active antiretroviral therapy (HAART), and metabolic status. Methodology: Eighty-one HIV positive cases and 82 healthy controls were included in this case–control study. Each case underwent a complete physical examination and serum fasting plasma glucose, A1c, lipid profile, total testosterone (TT), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were estimated. Serum TT level <300 ng/dl, or TT >300 ng/dl with high LH and FSH (compensatory hypogonadism) were taken as markers for hypogonadism, and it was correlated with age, CD4 count, duration of HAART, and metabolic status of the patient. Results: Out of 81 cases, 21 (25.9%) were found to have hypogonadism as compared to 4 (4.9%) out of 82 controls. Of these 21, 14 cases had secondary hypogonadism, five had primary, and the remaining two had compensatory hypogonadism. The mean serum TT value among cases (371.7 ± 102.9 ng/dl) was significantly lower than that among controls (419.7 ± 71.5 ng/dl) (P = 0.007). Hypogonadism was found to be significantly associated with the age of the patient (P = 0.007), CD4 count (P = 0.002), and duration of HAART (P = 0.04) and was independent of the BMI (P = 0.9) and the waist circumference (P = 0.8). Dyslipidemia and dysglycemia were significantly more common among cases as compared to controls (P < 0.05) but were not associated with hypogonadism. Conclusion: The prevalence of hypogonadism is higher among HIV-infected males as compared to healthy individuals. Hypogonadism was significantly associated with age, CD4 count, and duration of HAART and was independent of BMI, glycemic status, and dyslipidemia.
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Bacteriological profile of diabetic foot ulcer with special reference to drug-resistant strains in a tertiary care center in North-East India p. 688
Sudhir K Jain, Rashmisnata Barman
DOI:10.4103/ijem.IJEM_546_16  
Aim: This study was carried out to determine the bacteriological profile of infected diabetic foot ulcers (DFUs) and the antibiotic resistance pattern from the isolates. An attempt was made to suggest an empiric antibiotic regimen to treat such patients. Materials and Methods: Tissue samples were collected from 150 patients between February 2015 and January 2016 with DFUs under aseptic precautions and they were processed as per the Clinical and Laboratory Standards Institute guidelines. Results: A total of 185 bacterial isolates were obtained from 150 persons with diabetic and with foot ulcers. The age group of these persons ranged from 35 to 80 years and the maximum number of persons with DFUs was in the age group of 60–65 years. Among the isolates, Gram-negative bacilli were isolated in 112/185 (61%) and Gram-positive cocci in 73/185 (39%) cases. The most common isolate was Staphylococcus spp. 46 (25%), followed by Escherichia coli (20%) and Enterococcus spp. (15%). The antibiotic sensitivity profile of the bacteria was also studied. Among the isolates, 59/112 (53%) of the Gram-negative bacilli were extended spectrum beta-lactamase producers, 19/46 (41%) were methicillin-resistant Staphylococcus aureus, and 5/27 (19%) were vancomycin-resistant Enterococcus. Conclusions: This study showed a preponderance of multidrug-resistant strains among the isolates from the DFUs. Knowledge on the antibiotic sensitivity pattern of the isolates will be helpful in determining the drugs for the empirical treatment of diabetic ulcers. Thus, indiscriminate use of antibiotics and chances of subsequent development of antibiotic resistance can also be reduced.
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Metabolic derangement in acute and chronic liver disorders p. 695
Sarita Bajaj, Richi Kashyap, Anubha Srivastava, Smriti Singh
DOI:10.4103/ijem.IJEM_146_17  
Aims: This study aims to assess glycemic and lipid derangement in acute and chronic liver disorders. Materials and Methods: A cross-sectional study was conducted on 104 patients diagnosed with acute or chronic liver disorder. Acute liver disease (ALD) patients were 40 and chronic liver disease (CLD) patients were 64. Results: The mean value of fasting plasma glucose (FPG) in patients with ALD was 91.8 ± 5.4 mg/dl and in CLD was 115.7 ± 17.9 mg/dl, the difference was significant. The mean value of A1c was 4.3 ± 0.6 in ALD and 6.1 ± 0.8 in CLD, the difference was significant. In patients with CLD mean cholesterol was higher 177.4 ± 28.8 mg/dl when compared to ALD 140 ± 35.1 mg/dl, but the difference was not significant. ALD patients' high-density lipoprotein (HDL) was 50.4 ± 5.1 mg/dl, and in CLD patients, HDL was 44.4 ± 6.1 mg/dl. In CLD mean triglyceride (T) was 148.9 ± 6.4 mg/dl while in ALD T was 134.8 ± 14.2 mg/dl, the difference was significant. Conclusions: CLD is associated with glycemic derangement demonstrated by deranged FPG and A1c. In patients of ALD, no metabolic derangement was observed.
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Postpartum follow-up in women diagnosed with subclinical hypothyroidism during pregnancy p. 699
K Neelaveni, K. V. S. Hari Kumar, Rakesh Sahay, Jayanthy Ramesh
DOI:10.4103/ijem.IJEM_452_16  
Background: Management guidelines about the thyroid disease in pregnancy are silent about the postpartum course of new onset subclinical hypothyroidism (SCH). Hence, we analyzed the 2 years outcome of SCH diagnosed during pregnancy. Materials and Methods: We conducted this retrospective study using the medical records of patients with new onset SCH during pregnancy between 2010 and 2013 (n = 718). Patients who stopped their levothyroxine after delivery with a 2-year follow-up record were included. We excluded patients with known thyroid disorders and continuous use of drugs that affect the thyroid results. The patients were divided into two groups (Group 1 – euthyroid and Group 2 – hypothyroid) based on the final outcome after 2 years. The data were analyzed using appropriate statistical methods and a P < 0.05 was considered statically significant. Results: A total of 559 (77.8%) women stopped levothyroxine after delivery, and the final follow-up data were available for 467 patients only. At the end of 2 years, 384 (82.2%) remained euthyroid, and the remaining 83 (17.8%) developed hypothyroidism. SCH and overt hypothyroidism were seen in 22 and 61 patients, respectively. Group 2 patients had higher mean age (25.5 vs. 23.6 years), goiter (51 vs. 2%), initial thyroid stimulating hormone (7.9 vs. 5.1 μIU/mL), and thyroid antibody positivity (76 vs. 13%) (P < 0.001). Conclusion: The majority of patients with SCH during pregnancy remain euthyroid after delivery. Advanced age, goiter, positive family history, and thyroid autoimmunity increase the future risk of hypothyroidism in patients with SCH diagnosed during pregnancy.
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Prevalence of metabolic syndrome markers among women at 1-year postpartum as per prepregnancy body mass index status: A longitudinal study p. 703
Neha A Kajale, Vaman Khadilkar, Shashi A Chiplonkar, Raja Padidela, Anuradha V Khadilkar
DOI:10.4103/ijem.IJEM_145_17  
Introduction: Maternal body composition (BC) changes during lactation. Increased prepregnancy obesity is associated with poor obstetric outcomes. The aim was to study changes in maternal BC postpartum (PP) to 1-year PP with reference to their prepregnancy body mass index (BMI) status. Methods: The study design was a 1-year follow-up study. Sixty-five apparently healthy primiparous women (28.6 ± 3.4 years delivered full-term infants) were randomly selected from December 2010 to June 2013 and postclassified on the basis of their prepregnancy BMI status. Anthropometry, sociodemographic status, physical activity, diet, clinical examination, biochemical tests, and BC at total body (dual energy X-ray absorptiometry, GE, Lunar DPX) were collected using standardized protocols. Results: Forty-one women were classified in Group A with normal prepregnancy BMI (20.4 ± 2.0 kg/m2) and 24 women in Group B with overweight/obese (OW/OB) prepregnancy BMI (26.1 ± 1.9 kg/m2). At 1 year, 75% of women returned to normal BMI in Group A, whereas all 100% of women from Group B remained in OW category at 1-year PP. Nearly 43% of Group B women showed the presence of at least two metabolic syndrome risk factors as compared to 36% in Group A at 1 year. Conclusion: Women with OW/OB prepregnancy BMI accumulated higher visceral fat with a higher prevalence of metabolic risk factors at 1-year PP. Our study underlines the importance of maintaining BMI status in reference range in reproductive years.
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Root cause analysis of diabetic ketoacidosis admissions at a tertiary referral pediatric emergency department in North India p. 710
Muralidharan Jayashree, Rohit Sasidharan, Sunit Singhi, Karthi Nallasamy, Mullai Baalaaji
DOI:10.4103/ijem.IJEM_178_17  
Objectives: To identify system-based factors contributing to Emergency Department (ED) admissions of children with diabetic ketoacidosis (DKA) and related complications with emphasis on parental and physician awareness and prereferral management. Materials and Methods: A prospective observational root cause analysis study of all consecutive admissions of children with DKA to pediatric ED of a tertiary care referral hospital in northern India over a period of 1 year (July 2010–June 2011). Prehospital, health-care system, referral, follow-up, and continuum of care related details were obtained through direct interview of parents and physicians and/or field observations for all enrolled children. Results: Of the 30 children enrolled, 26 (86.6%) were referrals; 16 (61.5%) from first, 7 (26.9%) from second, and 3 (11.5%) from third health-care facility. More than half (n [%], 18 [60%]) had new onset diabetes and belonged to lower socioeconomic strata. Twenty-two (73.3%) were complicated DKA; shock (n [%], 19 [63%]), hypokalemia (n [%], 11 [36%]), and CE (n [%], 3 [10%]) were the most common complications. Most parents were ignorant of diabetes, its symptoms or complicating DKA. Nearly, half of the cases remained undiagnosed (n = 11) at first contact health-care facility; more so for new onset as compared to known diabetes (9/18 vs. 2/8; P = 0.022). The referring hospitals had limited facilities for rapid blood glucose estimation (n [%], 12 [40%]), blood gas analysis (n [%], 6 [20%]) and insulin infusion. On univariate analysis, patients with missed/delayed diagnosis more often had severe and complicated DKA. Conclusion: Parental ignorance, lower socioeconomic status, lack of clinical experience, and limited primary health-care facilities were root causes for severe and complicated DKA.
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Arrhythmias in type 2 diabetes mellitus p. 715
Gaurav Agarwal, Satish Kumar Singh
DOI:10.4103/ijem.IJEM_448_16  
Chronic hyperglycaemia of Type 2 diabetes mellitus causes long term damage to heart resulting in coronary artery disease (CAD), myocardial infarction (MI), congestive heart failure (CHF), and sudden death from arrhythmias. AIMS: To study the prevalence of different types of arrhythmias in T2DM, particularly in association with Cardiac Autonomic Neuropathy (CAN). METHODS: A cross-sectional study including 100 patients of Type 2 Diabetes Mellitus (T2DM) presenting with cardiac arrhythmias, was done at our hospital over 2 years. Detailed history along with physical examination and tests for CAN were done. Routine investigations along with echocardiography, stress test, Holter monitoring were done. RESULTS: Sinus Tachycardia (ST) was the commonest arrhythmia, found in 32% of patients. 20% had Complete Heart Block (CHB), 15% had Sinus Bradycardia (SB), and 15% had Atrial Fibrillation (AF). Ventricular Premature Complex (VPC) was found in 10% and 3% had Atrial Premature Complex (APC). 3% had first degree AV block, whereas 1% had Paroxysmal Supra Ventricular Tachycardia (PSVT), and another 1% had Ventricular Tachycardia (VT). Poorly controlled diabetes and co-morbidities was associated with higher incidence of arrhythmias. 62% of patients had prolonged QTc, majority of which had CAN. Most of the patients responded to standard therapy.
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Iodine status among subclinical and overt hypothyroid patients by urinary iodine assay: A case–control study p. 719
Uma Shrestha, Narayan Gautam, Krishna Kumar Agrawal, Amit Chandra Jha, Archana Jayan
DOI:10.4103/ijem.IJEM_413_16  
Objectives: The objective of the study was to assess the differences of iodine status as measured by urinary iodine excretion (UIE) between cases of hypothyroidism and healthy controls. Materials and Methods: The study was conducted in cases with subclinical hypothyroidism (n = 58) and overt hypothyroidism (n = 41) and compared with age- and sex-matched healthy euthyroid controls (n = 52) attending Universal College of Medical Sciences Teaching Hospital, Bhairahawa, Nepal. Serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) were estimated by competitive ELISA and sandwich ELISA, respectively (Diametra, Italy). The urinary iodine concentration (UIC) in urine samples was estimated by ammonium persulfate digestion method recommended by the WHO. Results: A significantly higher median UIC was observed among cases of subclinical hypothyroidism (224.90 μg/l) and overt hypothyroidism (281.0 μg/l) as compared to the controls (189.90 μg/l) (P = 0.0001, P = 0.001). Serum TSH in the cases of subclinical hypothyroid was higher, whereas fT3 was lower as compared to controls (P = 0.028, P = 0.0001), respectively. Similarly, serum TSH in the cases of overt hypothyroid was higher and fT3 and fT4 were lower as compared to controls (P = 0.0001, P = 0.0001, P = 0.015), respectively. There was positive correlation of UIC with TSH (r = 0.269, P = 0.0001), whereas negative correlation was seen with fT3 (r = −0.328, P = 0.0001) and fT4 (r = −0.145, P = 0.076). The test of multiple regression has shown that fT3(β = −0.262, P = 0.012) as an independent predictor in association with UIE in cases. Conclusion: Excessive iodine intake was found in hypothyroid patients as assessed by UIE concluding that it may trigger the thyroid hypofunction. Cohort studies to generate further evidence should be done to explore potential mechanism of hypothyroidism in excess iodine intake.
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Effect of short-term erythropoietin therapy on insulin resistance and serum levels of leptin and neuropeptide Y in hemodialysis patients p. 724
Hamed M Osman, Osama A Khamis, Mohamed S Elfeky, Amani M El Amin Ali, Mostafa Y Abdelwahed
DOI:10.4103/ijem.IJEM_462_16  
Introduction: Insulin resistance (IR) is a known complication of end-stage kidney disease (ESKD). It may be an important therapeutic target in stages of chronic kidney disease. Aim: The study was conducted to evaluate the effect of short-term treatment with recombinant human erythropoietin (rHuEpo) therapy on IR, serum leptin, and neuropeptide Y in ESKD patients on hemodialysis. Materials and Methods: Thirty ESKD patients were enrolled in the study and were randomly assigned into two groups. Erythropoietin (rHuEpo) group consisted of 15 patients (7 females, 8 males, mean age 47.8 ± 9.3 years) treated with rHuEpo therapy after each session of dialysis. No-rHuEpo group consisted of 15 patients (7 females, 8 males, mean age 45.5 ± 8.6 years) not treated with rHuEpo. In addition to, control group consisted of 15 healthy controls (6 females, 9 males, mean age 48.8 ± 11 years). Results: The mean fasting insulin (11 ± 4.2 mU/L) and homeostatic model assessment of IR (HOMA-IR) test (2.6 ± 1.1) were significantly higher in ESKD patients than control group (6.6 ± 1.4 mU/L and 1.5 ± 0.3, respectively). There were significant decreases in glycated hemoglobin (HbA1c) (5.6 ± 1%), fasting insulin level (9.3 ± 3.1 μU/mL), HOMA-IR (2.2 ± 0.7), and serum leptin levels (17.4 ± 8.7 ng/mL) also significant increase in neuropeptide Y levels (113 ± 9.9 pg/mL) after 3 months of rHuEpo therapy, in addition to further significantly decrease fasting insulin levels (7.1 ± 2.1 μU/mL) and HOMA-IR (1.7 ± 6) after 6 months in rHuEpo group. In contrast, there were significantly increases in HbA1c% (5.9 ± 0.5%) and leptin levels (42.3 ± 25.3 ng/mL) in No-rHuEpo group throughout the study. Conclusion: IR and hyperleptinemia are improved by recombinant human erythropoietin therapy.
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Status of serum vitamin D and calcium levels in women of reproductive age in national capital territory of India p. 731
Nighat Yaseen Sofi, Monika Jain, Umesh Kapil, Vuthaluru Seenu, Lakshmy Ramakrishnan, Chander Prakash Yadav, Ravindra Mohan Pandey
DOI:10.4103/ijem.IJEM_134_17  
Context: In India, Vitamin D deficiency is a major public health problem, associated with lack of sunlight exposure in spite of abundant sunshine usually accompanied by reduced dietary intake. In women of reproductive age, Vitamin D deficiency in pregnancy has been associated with an increased risk of gestational diabetes mellitus, preeclampsia, maternal and perinatal morbidity and mortality. Aims: The aim of the present cross-sectional study was to evaluate the levels of serum Vitamin D 25(OH) D and calcium in women of reproductive age from India. Settings and Design: A cross-sectional study was carried on a total of 224 healthy nonpregnant and nonlactating women in the reproductive age group of 20–49 years. Materials and Methods: Demographic, socioeconomic class, and biochemical parameters for the estimation of serum 25(OH)D and calcium levels in women of reproductive age were studied. Statistical Analysis: Statistical Package for Social Sciences version 20.0 was utilized for conducting the statistical analysis of the data. Results: Vitamin D deficiency (<20 ng/ml) was present in 88% of women. Women from middle socioeconomic class had the lowest mean serum 25(OH) D levels (9.6 ± 6 ng/ml) as compared to women from upper middle (11.4 ± 8 ng/ml), lower (11.2 ± 8 ng/ml), and upper (10 ± 8.6 ng/ml) socioeconomic class. Serum calcium levels were found in the normal range of 8.5–10.5 mg/dl for all the study subjects. Conclusions: There is a high prevalence of hypovitaminosis D among women of reproductive age. These women may possibly have a higher risk of development of osteoporosis and pregnancy-related complications in future life.
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Diagnosis of adrenocortical tumors by reticulin algorithm p. 734
Daphne Fonseca, Sudha S Murthy, K Ravindranath Tagore, B Vishal Rao, Subramanyeshwar Rao Thamminedi, K. V. V. N. Raju, Rakesh Sharma, Sundaram Challa
DOI:10.4103/ijem.IJEM_573_16  
Aims: To apply reticulin algorithm (RA) to the diagnosis of adrenocortical tumors on adrenalectomy specimens and compare its efficacy to the modified Weiss criteria or Lin–Weiss–Bisceglia (LWB) criteria for oncocytic variant. Materials and Methods: Adrenocortical tumors (ACTs) diagnosed on resected specimens including the variants during January 2010–June 2016 were retrieved from the pathology records. The demographic and clinical data were obtained from medical records. The functional status of the tumor was noted based on clinical and biochemical evaluation. The location, size, and gross appearance of the tumor were noted. The corresponding hematoxylin and eosin-stained slides were independently assessed by two pathologists applying modified Weiss criteria and LWB criteria for the oncocytic variant as applicable. Reticulin stain was performed on representative sections in all cases. All the tumors were classified according to RA, and the diagnoses made by each system were correlated. Results: There were 15 ACTs in the study period. There were two adenomas including one oncocytoma which showed Weiss score (WS) of 2 and intact reticulin framework. There were 13 adrenal cortical carcinomas including two oncocytic variants with WS ranging from 4 to 7. There was disruption of reticulin and thick, irregular reticulin fibers in all tumors, irrespective of the histology. It correlated with modified Weiss and LWB criteria. Conclusions: The RA was simple, easy to apply, and correlated well with modified Weiss criteria in the diagnosis of ACTs including the oncocytic variant.
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Impact of severity of illness on the function of the hypothalamo-pituitary-gonadal axis in postmenopausal women with acute severe illness: Implications for predicting disease outcome p. 738
Suresh Vaikkakara, Marella Neelima Raj, Alok Sachan, Alladi Mohan, Bhuma Vengamma, P. V. L. N. Srinivas Rao, Arun Mukka, Chiruvella Sravani, Amaresh P Reddy
DOI:10.4103/ijem.IJEM_398_16  
Background: While elevated levels of estradiol were predictive of mortality in critically ill surgical and trauma patients, their ability to predict outcome in nonsurgical patients has not been studied. We aimed to study the determinants of gonadotropin levels in acutely ill postmenopausal women with nonsurgical disease and the impact of changes in the gonadal axis on the outcome of these patients. Methods: Thirty-five postmenopausal women admitted to medical intensive care with acute severe illness and having a Simplified Acute Physiology Score (SAPS II score) ≥30 (in-hospital mortality rate ≥ 10%) were recruited. On the 5th day of hospitalization, fasting samples were collected at 8.00 am and tested for luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, free triiodothyronine, free thyroxine, thyrotropin, cortisol, prolactin, dehydroepiandrosterone, androstenedione, and sex hormone-binding globulin. Multiple linear regression analysis was performed to identify independent determinants if any of LH and FSH. Receiver operating characteristic (ROC) curves were drawn for different cutoffs of LH, FSH, and estradiol to diagnose mortality and prolonged hospitalization. Results: There was an independent negative association between the FSH and the SAPS II score (beta = −0.435; P = 0.014), but not with any of the other tested parameters (estradiol, prolactin, or cortisol). Among components of the SAPS II score, the total leukocyte count (TLC) was negatively associated with serum FSH (beta coefficient = −0.635, P = 0.013). None of these parameters were determinants of LH. On ROC analysis, neither estradiol nor gonadotropins were diagnostic for in-hospital mortality. However, among survivors, low estradiol was diagnostic for prolonged hospital stay (area under the curve = 0.785; P = 0.015). Conclusion: FSH, but not LH, is negatively associated with the severity of illness, particularly to its inflammatory component (TLC). Low estradiol in survivors was a predictor of prolonged hospital stay.
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Comparative evaluation of safety and efficacy of glimepiride and sitagliptin in combination with metformin in patients with type 2 diabetes mellitus: Indian multicentric randomized trial - START Study Highly accessed article p. 745
TV Devarajan, S Venkataraman, Narayanan Kandasamy, Abraham Oomman, Hari Kishan Boorugu, S. K. P. Karuppiah, Dushyant Balat
DOI:10.4103/ijem.IJEM_176_17  
Background and Objective: Modern sulfonylureas like glimepiride offer effective glycemic control with extrapancreatic benefits and good tolerability. The objective of the present study was to evaluate and compare safety and efficacy of glimepiride and sitagliptin in combination with metformin in patients with type 2 diabetes mellitus (T2DM). Methods: In this open-label, randomized, comparative, multicenter study, a total of 305 T2DM patients who were either drug naïve or uncontrolled on metformin were randomized to glimepiride 1 or 2 mg/sustained-release metformin 1000 mg once daily (glimepiride group, n = 202) or sitagliptin 50 mg/metformin 500 mg twice daily (sitagliptin group, n = 103) for 12 weeks. Primary endpoint was change in glycosylated hemoglobin (HbA1c). Secondary endpoints were change in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), body mass index (BMI) and to assess overall safety profile. Results: At 12 weeks, there was a statistically significant difference in the mean HbA1c reduction in glimepiride group (0.42%) as compared to sitagliptin group (0.30%) (P = 0.001). Mean reduction in FPG and PPG was also statistically significant in the glimepiride group as compared to the sitagliptin group (P = 0.008). There was no significant difference in terms of change in BMI (0.07 ± 0.39 kg/m2 vs. 0.08 ± 0.31 kg/m2) in glimepiride and sitagliptin groups, respectively, (P = 0.644) between both the groups. The incidences of hypoglycemic events were also comparable among both the groups. Conclusion: In T2DM patients, glimepiride/metformin combination exhibited significant reduction in glycemic parameters as compared to sitagliptin/metformin combination. Moreover, there was no significant difference between both the groups in terms of change in BMI and incidence of hypoglycemia.
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REVIEW ARTICLES Top

A pragmatic approach to the indeterminate thyroid nodule p. 751
Krishna G Seshadri
DOI:10.4103/ijem.IJEM_143_17  
Thyroid nodules are prevalent in upto 68% of randomly selected individuals in whom high resolution ultrasound is performed . The majority of nodules are benign. The use of ultrasound coupled with FNAC has dramatically reduced the number of patients who undergo surgery for nodules. The six tier Bethesda scoring system has reduced variability and increased the ability to clinicians to guide patients with thyroid nodules. There is good correlation between cytology and histopathologic outcomes. A significant proportion of patients will however fall into an indeterminate category. The availability of molecular markers enhanced with next generation sequencing technology and the expression classifier are added diagnostic aids that can help in management. However these are not available in many countries and in resource limited settings. A pragmatic approach to the diagnosis of indeterminate nodules includes utilising pre and post test probability, clinical acumen, correlation of ultrasound findings and expert opinion in some settings. Using this approach high risk patients can be appropriately chosen for surgery while relegating patients with lower risk to watchful followup.
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Sleep disorders in type 2 diabetes Highly accessed article p. 758
Deepak Khandelwal, Deep Dutta, Sachin Chittawar, Sanjay Kalra
DOI:10.4103/ijem.IJEM_156_17  
Type 2 diabetes mellitus (T2DM) has shown to be associated with higher incidence of sleep disorders, which may be due to disease itself or because of secondary complications or associated comorbidities associated with diabetes. On the other hand, shorter sleep duration and erratic sleep behavior itself have been linked with higher incidence of obesity, metabolic syndrome, and T2DM. Assessment of sleep quality and sleep disorders as a part of the comprehensive medical evaluation is recommended based on emerging evidence suggesting a relationship between sleep quality and glycemic control in persons with T2DM. In this review, we attempt to summarize common sleep disorders associated with T2DM, their impacts on glycemic and other metabolic control, and various preventive and therapeutic strategies to tackle these problems.
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Sodium-glucose cotransporter 2 inhibitor use: A pharmaco-ergonomic qualification tool p. 762
Sanjay Kalra, AG Unnikrishnan, Manash Baruah, Pallavi Kawatra, Jignesh Ved
DOI:10.4103/ijem.IJEM_184_17  
Pharmaco-ergonomics implies tailoring the drug therapy to an individual patient's requirement(s). The development of sodium-glucose cotransporter 2 inhibitor (SGLT2-i) agents has impelled multiple clinical considerations, in the management of type-2 diabetes. This paper attempts to summarize the pharmaco-ergonomic considerations for these agents, in the form of an SGLT2-i qualification tool, based on a clinical score. This tool may serve as a simple and inexpensive practical guide, to optimize the risk-benefit considerations for SGLT2-i agents.
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SYSTEMATIC REVIEW Top

Systematic review on vitamin D level in apparently healthy Indian population and analysis of its associated factors p. 765
Sandhiya Selvarajan, Vikneswaran Gunaseelan, Nishanthi Anandabaskar, Alphienes Stanley Xavier, Sureshkumar Srinivasamurthy, Sadish Kumar Kamalanathan, Jaya Prakash Sahoo
DOI:10.4103/ijem.IJEM_168_17  
Background: Vitamin D which is involved in the maintenance of bone mineral homeostasis has been found to portray various pleiotropic effects. Although it has been widely accepted that serum 25-hydroxy Vitamin D level above 30 ng/ml is considered optimal for the biological actions of Vitamin D, there is a need to explore the levels of Vitamin D reported among Indians from various regions of the country. Hence, this systematic review aims to appraise the status of Vitamin D levels reported from apparently healthy Indians across various parts of India. Methodology: A comprehensive literature search was carried out to identify the range of Vitamin D levels among apparently healthy individuals from various parts of India, with the search term “Vitamin D and India” in the search portals of PubMed, Google Scholar, Indmed, and ScienceDirect. A total of 2998 articles were retrieved by the above search strategy, of which only forty studies fulfilled the criteria to be included in the systematic review. Studies done in various states were compiled under the respective zones based on the classification of Indian zones as specified in Zonal maps of India. Results: The level of Vitamin D from all the forty included studies ranged from 3.15 ± 1.4 to 52.9 ± 33.7 ng/ml. The effect size of Vitamin D level was higher in the South Zone compared to other zones. Conclusion: The present study shows that Vitamin D deficiency is prevalent among apparently healthy Indians living in different regions of India, irrespective of their exposure to sunlight.
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BRIEF COMMUNICATIONS Top

Effect of a low-calorie diet on restoration of normoglycemia in obese subjects with type 2 diabetes p. 776
Anjali Amit Bhatt, Priya K Choudhari, Rutuja R Mahajan, Mehmood G Sayyad, Devi D Pratyush, Imtiaz Hasan, Rajesh S Javherani, Manish M Bothale, Vedavati B Purandare, Ambika Gopalakrishnan Unnikrishnan
DOI:10.4103/ijem.IJEM_206_17  
Introduction: Type 2 diabetes mellitus (T2DM) is considered to be an inevitably progressive disease. Complex therapies add to the financial and psychological burden. Very low-calorie diets (LCDs) are emerging as an option in the management of type 2 diabetes. Methods: We performed a clinical audit of patients with T2DM who received 12 weeks of LCD. Results: This case series documents that 6 out of 12 participants (median baseline HbA1c 9%) achieved HbA1c level in nondiabetes range with LCD despite stopping all antidiabetes medications. There was an improvement in serum triglycerides, HDL cholesterol, total cholesterol, C-Reactive protein, urine microalbumin, liver transaminases, liver fat and the indices of insulin resistance, beta cell secretory capacity, and insulin sensitivity. Conclusion: If long-term follow-up proves sustained benefits, such dietary restriction may be an alternative to more drastic options for reversal of type 2 diabetes. This may also help in changing the treatment perspective of a newly detected T2DM from an incurable and inevitably progressive disease to a potentially reversible disease.
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Management of primary adrenal insufficiency: Review of current clinical practice in a developed and a developing country p. 781
Uzma Khan, Om J Lakhani
DOI:10.4103/ijem.IJEM_193_17  
Treatment of primary adrenal insufficiency (PAI) requires lifelong hormone replacement with glucocorticoids (GCs) and mineralocorticoids. Impaired quality of life and increased standardized mortality ratio in these patients emphasize the importance of tailoring therapy to individual needs. Role of education is paramount in improving patient compliance and in anticipating and preventing adrenal crises. Although discovery of synthetic GCs was a major breakthrough in treatment of patients with this life-threatening condition, management of PAI continues to be challenging. The obstacles for clinicians appear to vary widely across the globe. While optimization and individualization of therapy after diagnosis of PAI remain the main challenges for clinicians in the developed world, doctors in a developing country face problems at almost every stage from the diagnosis to the treatment and follow-up of these patients; cost of therapy, lack of resources, and funding are the main hindrances. Adherence to therapy and patient education are found to be common issues in most parts of the world. This commentary highlights the challenges from both developed and developing country's perspective in treating PAI; it also provides an update on current management scenario and future treatment options.
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CASE REPORT Top

An intriguing family with type 2 diabetes mellitus and complete heart block p. 784
Gaurav Agarwal, Satish Kumar Singh
DOI:10.4103/ijem.IJEM_449_16  
Chronic hyperglycaemia of Type 2 Diabetes Mellitus (T2DM) causes long term damage to heart resulting in coronary artery disease (CAD), myocardial infarction (MI), congestive heart failure (CHF), and sudden death from arrhythmias. A 62 year old male presented to our emergency with complaint of sudden onset giddiness from last 2 hours. This was followed by loss of consciousness. Patient was a known case of T2DM since last 1 year. Family history- patient has two brothers who also have T2DM and both of them also developed Complete Heart Block (CHB) spontaneously. The patient's mother also had T2DM and she also developed CHB. On examination of the cardiovascular system, pulse rate was 36 per minute and a variable intensity of first heart sound was present. Rest of the cardiovascular examination and other system examination was within normal limits. Routine investigations were within normal limits and ECG showed CHB. Echocardiography revealed normal ventricular function with no evidence of ischemic heart disease. This was a case of Type 2 DM and spontaneous onset CHB with a strong family history. This case underscores the fact that CHB can occur spontaneously in Type 2 diabetics without ischemic heart disease. The cause of CHB was most likely Cardiac Autonomic Neuropathy (CAN), which is determined not only by poor glycaemic control, metabolic derangements and duration of diabetes but also by genetic factors (likely maternal).
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LETTERS TO THE EDITOR Top

Endocrine covfefe p. 787
Sanjay Kalra
DOI:10.4103/ijem.IJEM_235_17  
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Verapamil in diabetes p. 788
Resham Raj Poudel, Nisha Kusum Kafle
DOI:10.4103/ijem.IJEM_190_17  
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