Endocrinology and Metabolism

Zinc and Glycemic Control Mala Dharmalingam, Justin Easow Sam Indian Journal of Endocrinology and Metabolism 2019 23(2):173-174

SAVOR-TIMI to DECLARE-TIMI: A review on cardiovascular outcome trials of incretin-modulators and gliflozins Awadhesh K Singh, Ritu Singh Indian Journal of Endocrinology and Metabolism 2019 23(2):175-183 Introduction: Since 2008 United State (US) food drug administration mandate, several newer anti-diabetic drugs (ADD) have undergone a mandatory cardiovascular (CV) outcome trial (CVOT) in type diabetes (T2DM) patients with high CV risk. These includes CVOT done with dipeptidyl-peptidase-4 inhibitors, sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonist (GLP-1RAs). Several double-blind, randomized, placebo-controlled CVOT have been presented and published in the last decade (2008-2018). Aims and Objectives: We systematically searched the database of PubMed and ClinicalTrials.gov from January 1, 2008 to December 31, 2018 using specific key words. Subsequently, we pooled the data of different cardiovascular endpoints and made a comparative forest plot using GraphPad software Inc. Prism Version 8, US. Results and Conclusion: Saxagliptin, alogliptin, sitagliptin and linagliptin are CV neutral drugs. Saxagliptin showed a significantly higher hospitalization due to heart failure (HHF). Empagliflozin and canagliflozin have shown a significant reduction in composite of 3-point major cardiac adverse events (3P-MACE). Additionally, empagliflozin, canagliflozin and dapagliflozin significantly reduced the HHF and the composite of CV death or HHF. Moreover, empagliflozin showed significant reduction in CV- and all-cause death in patients with T2DM with established CV disease. While both exendin-backbone-based GLP-1RAs such as lixisenatide and extended-release exenatide were CV neutral; GLP-1-backbone-based GLP-1RAs such as liraglutide, semaglutide and albiglutide shown a significant reduction in the composite of 3-P MACE. Additionally, liraglutide shown a significant reduction in CV- and all-cause death. Moreover, semaglutide reduced non-fatal stroke and albiglutide reduced myocardial infarction, while extended-release exenatide reduced all-cause death; however, P value of significance for these outcomes should be considered nominal.

Relationship between Salivary Alpha-2 Macroglobulin and HbA1c among Patients with Type-2 Diabetes Mellitus: A Cross-sectional Study Vanshika Rastogi, Pramila Kalra, MN Vanitha Gowda Indian Journal of Endocrinology and Metabolism 2019 23(2):184-187 Context: Type-2 diabetes mellitus (DM2) requires an adequate glycemic control to avoid diabetic complications. The best parameter available is glycosylated hemoglobin (HbA1c), as it gives us an overview of an individuals' glycemic control of the previous 4 months. Salivary biomarkers used as a diagnostic tool can indicate the control or degree of progression of diseases. Studies indicate that salivary alpha-2-macroglobulin (A2MG) levels are elevated in diabetes patients. Aims: To study the relationship of salivary A2MG with glycosylated Hba1c among patients with DM2. Settings and Design: A total of 87 patients of DM2, age 35–65 years were recruited. Materials and Methods: The routine oral cavity examination and dental check-up was done to rule out any dental disease. The patients with hepatic diseases and inflammatory diseases of oral cavity and body were excluded. The values of HbA1c were collected from the records of patients. Salivary A2MG levels were estimated by enzyme-linked immunosorbent assay. Levels of fasting and postprandial blood sugar, serum creatinine, and A2MG were compared with the HbA1c groups (<7 and ≥ 7). Statistical Analysis Used: Descriptive statistics (Software SPSS version 20.0). Nonparametric Pearson correlation test was used to assess the correlation between HbA1c and A2MG. Results: A positive correlation between salivary levels of A2MG and blood levels of HbA1c in blood was observed in this study. Results showed that there was also a significant correlation in mean values of fasting and postprandial blood sugar, serum creatinine, and salivary A2MG in diabetic subjects. Conclusion: Measurement of A2MG in saliva represents a promising noninvasive alternative method to evaluate glycemic index and consequently avoiding comorbidities.

A medley correlation of serum zinc with glycemic parameters in T2DM patients Santosh K Naik, Sunita J Ramanand, Jaiprakash B Ramanand Indian Journal of Endocrinology and Metabolism 2019 23(2):188-192 Background: Studies in diabetic have reported zinc deficiency due to zincuria. Effective treatment of oral antidiabetic drugs should improve glycemic status correcting serum zinc levels. This study evaluated serum zinc level and its correlation with glycemic parameters in type 2 Diabetes Mellitus (T2DM) patients receiving oral antidiabetics. Aim: To study correlation of serum zinc and glycemic parameters in patients receiving oral antidiabetics. Materials and Methods: It was a prospective cross sectional pilot study, conducted for 1 year, with the approval of IEC. Patients of T2DM satisfying inclusion/exclusion criteria were enrolled. Serum zinc and glycemic parameters were estimated. The data was stratified into- Group A: Metformin (n = 20), Group B: Metformin and glimiperide (n = 13). Correlation analysis of serum zinc and glycemic parameters was carried. Result: The mean age and duration of 33 patients was 57 ± 9.1 and 6.30 ± 6.52 years respectively. The mean FBG, PPBG, HbA1c and zinc were 164 ± 35, 257 ± 63 mg/dL, 9.3 ± 2.2% and 58 ± 23 ug/dL respectively. Thirty patients had HbA1c >6.5%. The percentage of zinc deficiency was 76.92 and 90 in group A and B, respectively. Correlation of serum zinc and glycemic parameters was insignificant in overall group. It varied at different HbA1c levels and in different groups. A positive correlation existed between serum zinc level and HbA1c at ≥9.5%. Conclusion: Zinc deficiency was common in T2DM and to a greater extent in combination group. Correlation of serum zinc levels with glycemic parameters varied at different HbA1c and treatment groups.

Outcomes of Bilateral Adrenalectomy in Cushing's Syndrome Lakshmi Nagendra, Nisha Bhavani, Praveen V Pavithran, Ginil P Kumar, Usha V Menon, Arun S Menon, Lakshmi Kumar, Harish Kumar, Vasantha Nair, Nithya Abraham, Prem Narayanan Indian Journal of Endocrinology and Metabolism 2019 23(2):193-197 Context: The literature on outcomes of bilateral adrenalectomy (BADx) in Cushing's syndrome (CS) is scant. Aims: The aim of this study is to analyze the short- and long-term outcomes of patients who underwent BADx and to compare the outcomes among different etiologies of CS. Settings and Design: This is a retrospective analysis of patients who underwent BADx for CS at our center between 2005 and 2018. Materials and Methods: In all, 33 patients were studied for clinical outcomes, survival rates, and long-term complications. Statistical Analysis: All analyses were performed with SPSS software (version 21.0). Results: The mean age at surgery was 39.33 ± 15.67 years. The primary etiology for CS was Cushing's disease (CD) in 42.42%, ectopic source in 36.36%, primary pigmented nodular adrenocortical disease (PPNAD) in 12.12%, and adrenocorticotrophin hormone–independent macronodular adrenal hyperplasia (AIMAH) in 9.09% of patients. The median follow-up time was 72.77 months. Improvement in hypertension and diabetes status after surgery was seen in 78% and 76.19% of patients, respectively. Proximal myopathy improved in 68% of patients. Nelson's syndrome and adrenal crisis were seen in 21.4% of patients each on long-term follow-up. Total mortality after BADx was 33.3%. Mortality in the first 30 days after surgery was seen in five patients (15.15%). Higher cortisol levels at presentation and age more than 40 years were predictors of mortality. Among the Cushing's subtypes, PPNAD had the best prognosis followed by CD. Perioperative Infections were a major cause of mortality. Conclusion: BADx is an effective treatment for CS especially in patients with PPNAD and CD but carries a significant mortality rate too.

Bone mass in newborns assessed by DXA – A systematic review and meta-analysis Rekha Ramot, Garima Kachhawa, Vidushi Kulshreshtha, Shweta Varshney, M Jeeva Sankar, K Devasenathipathy, V Sreenivas, Rajesh Khadgawat Indian Journal of Endocrinology and Metabolism 2019 23(2):198-205 Purpose: Peak bone mass - a key determinant of osteoporotic fractures result from bone accretion starting form intrauterine life to early adulthood. Optimal skeletal growth in-utero and infancy may offer protection against osteoporosis in adult life. We attempted to pool the data from available literature to get a consensus on average bone mass among healthy newborns (age ≤30 days after birth). Methods: Systematic review was conducted (PRISMA guidelines) to generate pooled estimates of bone mass parameters at whole body (WB) and lumbar spine (LS), based on both fixed and random effect models of meta-analyses. Two investigators independently carried out a comprehensive literature search using PubMed, Google Scholar and Embase. Meta-regression was applied to further explore causes of heterogeneity. Results: Out of a total 2703 studies, 2682 was excluded leaving 21 studies for final analysis. Thirteen studies reported bone mass by Hologic® and eight by Lunar®. The pooled WBBMC was 66.2g (95% CI 65.4 to 67.05 by fixed effect model, while the corresponding parameter for LS was 2.3g (95% CI 2.2 to 2.4). The subgroup and meta-regression analyses done for controlling potential confounders did not significantly affect heterogeneity. Conclusion: We generated the pooled estimate of bone mass (WBBMC) among healthy newborn subjects. There was high degree of heterogeneity among studies.

Platelet Indices as a Predictor of Microvascular Complications in Type 2 Diabetes Rajas S Walinjkar, Satish Khadse, Sunil Kumar, Shilpa Bawankule, Sourya Acharya Indian Journal of Endocrinology and Metabolism 2019 23(2):206-210 Background: Type 2 diabetes mellitus (T2DM) patients have a higher risk of developing micro- and macrovascular complications, which lead to decrease in the quality of life and increase in morbidity. Platelet indices have been available in the laboratory routine using blood cell counters for several years. These indices could alert us regarding endothelial dysfunction and in turn regarding the microvascular complications. Hence, this study was done to prove the correlation between platelet indices and microvascular complications in T2DM. Materials and Methods: In total, 125 diabetic patients attending diabetes OPD and admitted in medicine department along with age and sex-matched non-diabetic controls were studied. A detailed history was taken regarding duration of diabetes, medication, past history of stroke, IHD, and hypertension. Patients with T2DM were specially evaluated for microvascular complications. Platelet indices, fasting blood glucose, Post prandial blood glucose, HbA1C, and Sr. Creatinine were obtained from venous blood samples. All parameters were then subjected to statistical analysis using SPSS 17.0. Results: Platelet indices, namely MPV, PCT, PDW, and P/LCR were significantly higher in diabetic individuals than those in age and gender-matched controls. Moreover, the increase in MPV, PDW, and P/LCR was more significant in diabetic subjects with microvascular complications when compared with those without microvascular complications. Platelet dysfunction also showed a positive association with HbA1C, retinopathy, nephropathy, and neuropathy individually. Conclusions: Changes in platelet indices were found to be statistically associated with diabetes and its complications.

Vitamin B12 deficiency is endemic in Indian population: A perspective from North India Rajiv Singla, Arpan Garg, Vineet Surana, Sameer Aggarwal, Geetu Gupta, Sweta Singla Indian Journal of Endocrinology and Metabolism 2019 23(2):211-214 Background: Vitamin B12 deficiency is believed to be widespread in Indian population. However, more data is needed to fuel a meaningful debate on preventive and therapeutic strategies. Aims and Objectives: Objective of the current study is to evaluate status of vitamin B12 levels in people from a tier 3 city and among people living in an urban area with or without diabetes. Settings and Design: Retrospective, cross-sectional study. Methodology: Data captured in electronic medical records (EMR) of an endocrine practice and from a diagnostic laboratory was analysed. Statistical Analysis Used: Statistical analysis was done using open source software “Jamovi”. Results: Prevalence of vitamin B12 deficiency (Vitamin B12 levels <200 pg/ml) in tier 3 city was 47.19% (n = 267). From an urban endocrine practice, database of 11913 patients was searched for reports of vitamin B12 levels. Prevalence of vitamin B12 deficiency was 37.76% in people with pre-diabetes (n = 92), 31.23% in people with endocrine problems other than diabetes and pre-diabetes (n = 285) and 18.25% in people with diabetes (n = 378). Tier 3 city population had significantly lower vitamin B12 levels than people living in an urban area and attending an endocrine clinic. Vitamin B12 levels were significantly higher in people with diabetes as compared to people with other endocrine problems. Conclusion: Prevalence of vitamin B12 deficiency is 47% in north Indian population. People with diabetes have higher vitamin B12 levels than general population though still have high prevalence of deficiency. This data shows that Vitamin B12 deficiency is widespread in Indian population.

Pandemic of Vitamin D deficiency: Cardiometabolic concern or skeletal biochemical abnormality? Pradip Mukhopadhyay, Sujoy Ghosh, Kaushik Pandit, Purushottam Chatterjee, Partha Sarathi Mukherjee, Subhankar Chowdhury Indian Journal of Endocrinology and Metabolism 2019 23(2):215-221 Context: Biochemical Vitamin D deficiency is said to be present universally in recent times. However, its effect is more profound in modulation of anthropometric and biochemical risk factors of various chronic metabolic disorders rather than its influence on bone mineral abnormalities. The present study was undertaken to compare various anthropometric and biochemical parameters including basic bone mineral biochemistry in various strata of Vitamin D status. Materials and Methods: A population based study was done in the rural area of West Bengal comprising 405 people (initially targeted 400) to look for various anthropometric and biochemical parameters. Results: Anthropometric metabolic markers like BMI, WC, waist to height ratio and biochemical parameters like total cholesterol, LDL, TG, insulin, ALT, FPG were statistically significantly higher in vitamin D deficient (<20 ng/ml) (n = 228) subjects compared to Vitamin D non-deficient subjects (≥20 ng/ml) (n = 177) which persisted even after adjustment for BMI except for FPG. The difference was similarly present when severely Vitamin D deficient (<10 ng/ml) (n = 39) subjects were compared to Vitamin D sufficient subjects (≥30 ng/ml) (n = 38) and persisted after adjustment for BMI except for FPG. However, WHR, blood pressure (both systolic and diastolic), HbA1c, HDL, AST, Uric acid, freeT4, TSH, HOMA-IR were not different in both the above-mentioned comparisons. Metabolic syndrome was statistically significantly lower in vitamin D non-deficient subjects. Though iPTH was statistically significantly higher in the low vitamin D cohorts in both the comparisons, bone mineral markers like serum calcium, phosphorus and alkaline phosphatase were not different even when severely vitamin D deficient subjects were compared to vitamin D sufficient subjects. Conclusion: Pandemic of vitamin D deficiency is more likely to be associated with cardio-metabolic risk factors than biochemical bone mineral abnormality.

Body mass composition among underweight type 2 diabetes mellitus patients—A cross-sectional comparative study Deepak Kumar Garg, Manoj Kumar Dutta Indian Journal of Endocrinology and Metabolism 2019 23(2):222-226 Background: Over the past decades, various epidemiological data have shown that the pattern and profile of diabetes mellitus in India are different. The present study was carried out with an aim to study body mass composition in underweight type 2 diabetics and to compare with the normal population. Materials and Methods: The cross-sectional comparative study was conducted between January 2015 and December 2016 and included 60 participants who were selected using the convenient sampling technique. Newly diagnosed patients with type 2 diabetes mellitus and BMI less than 18.5 kg/m2 were considered for the study. Chi square test and Independent student t test were used for finding the statistically significant difference in proportions and between means, respectively; Pearson correlation coefficient was estimated for finding the linear association between two continuous variables. Results: No statistically significant difference was observed between the two groups in terms of age, waist-hip ratio, and BMI. Higher amount of fat mass and percentage were observed among the patients with diabetes as compared to that of the control group (P value < 0.05). However, there was no statistically significant difference between the underweight and the control group patients (P value > 0.05). A significant positive correlation was observed between HbA1c values and body fat mass values (P value < 0.05). Conclusion: Underweight type 2 diabetic patients were found to have high body fat mass as compared to healthy controls and the HbA1C values of the study participants were found to be positively correlated with fat mass.

 

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