Low dose depot oral vitamin D3v. daily oral vitamin D3 for treating nutritional rickets: a randomised clinical trial.

We aimed to compare the efficacy of daily v. low dose depot oral vitamin D3 for treating nutritional rickets. We conducted a randomised controlled trial in the department of paediatrics of a tertiary care hospital catering to semi-urban and rural population in Delhi, India. We randomised sixty-six children aged 3 months to 5 years with nutritional rickets to receive either daily oral vitamin D3 drops (3-12 months: 2000 IU; > 12 months to 5 years: 4000 IU; n 33) for 12 weeks duration or a single oral depot dose of vitamin D3 granules (3-12 months: 60 000 IU; > 12 months to 5 years: 150 000 IU; n 33). Participants in both groups had comparable demographic characteristics, laboratory features and radiological severity of rickets. Thirty-three participants in each group received the assigned intervention and all were followed up till 12 weeks. At 12 weeks follow-up, children in both groups showed a significant improvement in all biochemical parameters (serum Ca, P, alkaline phosphatase (ALP), parathormone and 25(OH) vitamin D levels) as well as radiological healing. At 12 weeks, the mean serum 25(OH) vitamin D levels (nmol/l) were statistically comparable in both groups (daily: 120·2 (sd 83·2), depot: 108 (sd 74), P = 0·43) and 31 (93·9 %) children in each group had radiological healing (Thacher score < 1·5). Two children in each group persisted to have raised ALP, and one child each in the daily group continued to have hypocalcaemia and hypophosphataemia at 12 weeks. Low dose oral depot vitamin D3 is an effective alternative to daily oral vitamin D3 for nutritional rickets.

Demographic and clinical profile of youth onset diabetes patients in India-Results from the baseline data of a clinic based registry of people with diabetes in India with young age at onset-[YDR-02].

BACKGROUND: We here report the demographic and clinical profile of the patients enrolled in the Indian Council of Medical Research funded Registry of people with diabetes in India with young age at onset (YDR) from 1 January 2000 to 31 July 2011. METHODS: The YDR registry recruits all diabetes cases (newly diagnosed or treated) reporting on or after 1 January 2000 with age of diagnosis ≤25 years, and residing within the assigned geographical area of the reporting centres. A baseline proforma was used to obtain information on demographic and clinical details at registration. RESULTS: The registry has enrolled 5546 patients (49.5% male; 50.5% female) with youth onset diabetes from 205 reporting centres linked to 8 regional collaborating centres (RCC) across India. T1DM (63.9%; n = 3545) and T2DM (25.3%; n = 1401) were the commonest variants of youth onset diabetes, though their relative proportion varied across RCCs. The mean (SD) age at diagnosis for T1DM was 12.9 (6.5) years, while that for T2DM was 21.7 (3.7) years. Nearly half the T1DM patients were registered within 6 months of the onset of disease. Most cases of T2DM (47.3%) were registered after 3 years from their date of diagnosis. 56.1% of patients had at least one episode of hospitalization at registration. CONCLUSION: The observations from YDR registry indicate the need to establish a surveillance system in India to monitor diabetes in youth, not only to understand its complex etiology and natural history but also due to its detrimental socio economic impact.

Diabetic ketoacidosis at diagnosis among youth with type 1 and type 2 diabetes: Results from SEARCH (United States) and YDR (India) registries.

BACKGROUND: There is significant global variation in the prevalence of diabetic ketoacidosis (DKA) at diagnosis among youth with type 1 diabetes (T1D). However, data for youth with type 2 diabetes (T2D) are limited, even in developed countries. We compared the prevalence of DKA at diagnosis among individuals with T1D and T2D from the SEARCH for Diabetes in Youth (SEARCH) and the Registry of Youth Onset Diabetes in India (YDR) registries. METHODS: We harmonized the SEARCH and YDR registries to the structure and terminology in the Observational Medical Outcome Partnership Common Data Model. Data used were from youth with T1D and T2D diagnosed before 20 years and newly diagnosed between 2006 and 2012 in YDR and 2009 and 2012 in SEARCH. RESULTS: There were 5366 US youth (4078 with T1D, 1288 with T2D) and 2335 Indian youth (2108 with T1D, 227 with T2D). More than one third of T1D youth enrolled in SEARCH had DKA at diagnosis which was significantly higher than in YDR (35.3% vs 28.7%, P < .0001). The burden of DKA in youth with T1D was significantly higher among younger age groups; this relationship was similar across registries (P = .4). The prevalence of DKA among T2D in SEARCH and YDR were 5.5% and 6.6% respectively (P = .4). CONCLUSIONS: There is significant burden of DKA at diagnosis with T1D among youth from United States and India, especially among the younger age groups. The reasons for this high prevalence are largely unknown but are critical to developing interventions to prevent DKA at diagnosis.

Association of Copeptin With Sense of Coherence in Individuals With Varying Degrees of Glucose Intolerance.

OBJECTIVE: This study aimed to examine the association of serum copeptin levels, a surrogate marker of arginine-vasopressin secretion with sense of coherence (SOC) among individuals with varying degrees of glucose intolerance. METHODS: The study was conducted in 120 age- and sex-matched individuals who were divided equally into three groups. Group A included individuals with normal glucose tolerance; group B, individuals with prediabetes (impaired glucose tolerance and/or impaired fasting glucose); and group C, individuals with newly detected diabetes mellitus (NDDM). SOC, perceived stress scale (PSS), copeptin, anthropometry, glycated hemoglobin, insulin, and salivary cortisol were measured in all study participants. RESULTS: The SOC score was found to be significantly lower in group C compared with group A (p < .001) and group B (p = .006). The PSS score was found to be significantly higher in group C compared with group A (p = .002). No significant difference was found between PSS scores of groups B and C (p = .25). Copeptin levels were found to be significantly higher in group C compared with group A (p = .016). Copeptin levels in group C did not differ significantly from those in group B (p = .056). There was a significant negative correlation between serum copeptin levels and SOC in the NDDM group C (r = 0.31, p = .048) and overall (r = 0.19, p = .037). In multiple regression analysis, SOC emerged as the variable with the strongest association with 2-hour postprandial plasma glucose and glycated hemoglobin. CONCLUSION: Individuals with NDDM displayed significantly higher serum copeptin levels that inversely correlated with SOC, a global measure of stress coping ability.

Association of postprandial triglyceride responses with insulin resistance among rotational night shift healthcare workers.

NEW FINDINGS: What is the central question of this study? Does long-term rotational night shift work among healthcare workers alter postprandial triglyceride metabolism, and are the postprandial triglyceride responses associated with insulin resistance? What is the main finding and its importance? Rotational night shift duties in healthcare workers might have a negative impact on postprandial triglyceride responses and insulin sensitivity. This is the first study in which postprandial triglyceride responses among shift workers exposed to long-term night shifts have been studied. ABSTRACT: Studies on the postprandial period demonstrate that in experimental conditions, abrupt or acute changes in sleep timing and work are followed by significantly altered postprandial glucose, insulin secretion and lipid tolerance. Whether shift work results in altered postprandial triglyceride (PPTG) metabolism in the long term is not known. In the present study, we aimed to ascertain the association between PPTG and shift work in relationship to cardiometabolic risks and to compare the PPTG response among healthcare workers with and without night shift duties. Twenty healthcare workers with rotational night shifts (group 2) and 20 age- and sex-matched healthcare workers who had not done night shift duty in the past 1 year or ever (group 1) were recruited. Only subjects with normal glucose tolerance were recruited. A standardized fat challenge test was done in all study subjects. The postprandial triglyceride area under the curve (PPTG AUC) showed overall (n = 40) a significant positive correlation with fasting insulin and homeostatic model assessment of insulin resistance (HOMA-IR) (r = 0.40, P = 0.01 and r = 0.37, P = 0.01, respectively) and in group 2 (r = 0.49, P = 0.02 and r = 0.44, P = 0.042, respectively). The PPTG peak also showed a significant positive correlation with fasting insulin and HOMA-IR in group 2 (r = 0.52, P = 0.01 and r = 0.47, P = 0.03, respectively). No significant correlation was found in group 1. The PPTG AUC and PPTG peak were, however, comparable between both groups. The findings of this pilot study suggest that rotational night shift duties in healthcare workers might have a negative impact on metabolic parameters, including postprandial triglyceride responses and insulin sensitivity.

Glucose Homeostasis and Effect of Chelation on ß Cell Function in Children With ß-Thalassemia Major.

OBJECTIVE: To assess the prevalence of impaired glucose tolerance in ß-thalassemia major and correlate it with chelation therapy. MATERIALS AND METHODS: Sixty-seven subjects with ß-thalassemia major, aged 1 to 20 years, were enrolled in our prospective cohort. Clinical details were recorded. Baseline oral glucose tolerance test, serum insulin, C peptide, and insulin resistance were measured. The biochemical profile was repeated after 6 months. RESULTS: The mean age of subjects was 7.43±4.48 years. Eight (11.9%) subjects had impaired fasting glucose, 7 (10.4%) had impaired glucose tolerance, and 1 (1.4%) subject had diabetes at baseline. Subjects with abnormal glucose profile had longer disease duration (95% confidence interval [CI] of difference=-6.64 to -0.68; P=0.019) and higher fasting blood glucose (95% CI of difference=-32.1 to -10.5; P=0.001) and serum ferritin (95% CI of difference=-219.8 to -3.4; P=0.001) than normoglycemic subjects. Insulin resistance and serum ferritin showed significant increase at 6 months (P<0.001 and P=0.001, respectively). Patients on deferiprone alone significantly improved glucose homeostasis on follow-up than those on desferrioxamine or combination therapy of desferrioxamine and deferiprone (P<0.05). CONCLUSIONS: Prolonged disease duration and higher serum ferritin adversely affects glucose homeostasis in thalassemic children. Deferiprone was the most effective chelator to improve glucose homeostasis in chronically transfused thalassemics.

Prevalence of generalized & abdominal obesity in urban & rural India--the ICMR-INDIAB Study (Phase-I) [ICMR- NDIAB-3].

BACKGROUND & OBJECTIVES: Overweight and obesity are rapidly increasing in countries like India. This study was aimed at determining the prevalence of generalized, abdominal and combined obesity in urban and rural India. METHODS: Phase I of the ICMR-INDIAB study was conducted in a representative population of three States [Tamil Nadu (TN), Maharashtra (MH) and Jharkhand (JH)] and one Union Territory (UT)[Chandigarh (CH)] of India. A stratified multi-stage sampling design was adopted and individuals ≥ 20 yr of age were included. WHO Asia Pacific guidelines were used to define overweight [body mass index (BMI) ≥ 23 kg/m [2] but < 25 kg/m [2]], generalized obesity (GO, BMI ≥ 25 kg/m [2], abdominal obesity (AO, waist circumference ≥ 90 cm for men and ≥ 80 cm for women) and combined obesity (CO, GO plus AO). Of the 14,277 participants, 13,800 subjects (response rate, 96.7%) were included for the analysis (urban: n = 4,063; rural: n = 9737). RESULTS: The prevalence of GO was 24.6, 16.6, 11.8 and 31.3 per cent among residents of TN, MH, JH and CH, while the prevalence of AO was 26.6, 18.7, 16.9 and 36.1 per cent, respectively. CO was present in 19.3, 13.0, 9.8 and 26.6 per cent of the TN, MH, JH and CH population. The prevalence of GO, AO and CO were significantly higher among urban residents compared to rural residents in all the four regions studied. The prevalence of overweight was 15.2, 11.3, 7.8 and 15.9 per cent among residents of TN, MH, JH and CH, respectively. Multiple logistic regression analysis showed that female gender, hypertension, diabetes, higher socio-economic status, physical inactivity and urban residence were significantly associated with GO, AO and CO in all the four regions studied. Age was significantly associated with AO and CO, but not with GO. INTERPRETATION & CONCLUSIONS: Prevalence of AO as well as of GO were high in India. Extrapolated to the whole country, 135, 153 and 107 million individuals will have GO, AO and CO, respectively. However, these figures have been estimated from three States and one UT of India and the results may be viewed in this light.

Role of advanced glycation end product (AGE)-induced receptor (RAGE) expression in diabetic vascular complications.

AIMS: Vascular complications are the major causes of morbidity and mortality in diabetic subjects. Interaction of advanced glycation end products (AGEs) with their receptor (RAGE) induces signal transduction that culminates in vascular complications. Therefore, in the present study we investigated the dependence of RAGE expression on circulating AGEs and evaluated the outcome of AGE-RAGE interaction by the oxidative stress and nature of vascular complications in type 2 diabetes mellitus (T2DM) patients. METHODS: RAGE expression was determined by quantitative real-time PCR and western blotting, serum AGEs were estimated by ELISA and spectrofluorometry and oxidative stress markers namely protein carbonyl (PCO), advanced oxidation protein products (AOPP) and lipid peroxidation (MDA) were assayed spectrophotometerically in 75 T2DM patients (DM without vascular complication n=25; DM with microvascular complications n=25; DM with macrovascular complications n=25) and 25 healthy controls. RESULTS: Serum AGE level was significantly higher in diabetic patients having vascular complications as compared to T2DM without complications (p<0.01). RAGE m-RNA expression level in PBMCs assayed by quantitative real time PCR was four times higher in diabetic subjects without vascular complications while DM patients having microvascular and macrovascular complications showed 12 fold and 8 fold higher RAGE m-RNA expression respectively compared to healthy controls. Circulating AGE level showed significant positive correlation with RAGE m-RNA expression and oxidative stress markers. CONCLUSION: AGE-mediated exacerbation of RAGE expression may contribute to oxidative stress generation that plays a key role in pathogenesis of vascular complications in diabetes.

High level of psychological stress in COVID-19 recovered individuals: role of copeptin as a potential biomarker.

Background: Study aimed to assess stress in COVID-19 recovered individuals using a validated questionnaire PSS-10 score and stress biomarkers - salivary cortisol and serum copeptin. Methods: A total of 83 subjects of which 54 subjects (66.3%) who were hospitalized were recruited 8-20 weeks following recovery from COVID-19. Stress was assessed by PSS-10 stress-scale after a mean duration of 14.5 weeks after recovery. Sixty-eight subjects (81.9%) had new or persistent symptoms after recovery. Subjects were divided into two groups on the basis of PSS score; mild stress (PSS:0-13) and moderate to severe stress (PSS:>14) and levels of biomarkers (serum copeptin, DHEAS and salivary cortisol) were compared in the two groups. Results: Forty-four subjects (53%) had moderate to severe stress and 39 subjects (47%) had mild stress. Subjects with post COVID symptoms had significantly higher stress levels as compared to subjects who were asymptomatic [15 vs. 9; p = 0.003]. Serum copeptin levels were significantly higher among subjects with moderate to severe stress as compared to those with mild stress [0.41 vs. 0.67 ng/mL; p = 0.031]. Subjects with moderate to severe stress had higher median salivary cortisol compared to subjects with mild stress [1.03 vs. 1.44 nmol/L; p = 0.448]. Conclusion: Our study demonstrated moderate to severe stress in over half and some level of stress in nearly all COVID recovered individuals even after 3 months. Serum copeptin was found to be a useful biomarker to objectively measure stress in these subjects.

Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17).

BACKGROUND: Non-communicable disease (NCD) rates are rapidly increasing in India with wide regional variations. We aimed to quantify the prevalence of metabolic NCDs in India and analyse interstate and inter-regional variations. METHODS: The Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study, a cross-sectional population-based survey, assessed a representative sample of individuals aged 20 years and older drawn from urban and rural areas of 31 states, union territories, and the National Capital Territory of India. We conducted the survey in multiple phases with a stratified multistage sampling design, using three-level stratification based on geography, population size, and socioeconomic status of each state. Diabetes and prediabetes were diagnosed using the WHO criteria, hypertension using the Eighth Joint National Committee guidelines, obesity (generalised and abdominal) using the WHO Asia Pacific guidelines, and dyslipidaemia using the National Cholesterol Education Program-Adult Treatment Panel III guidelines. FINDINGS: A total of 113 043 individuals (79 506 from rural areas and 33 537 from urban areas) participated in the ICMR-INDIAB study between Oct 18, 2008 and Dec 17, 2020. The overall weighted prevalence of diabetes was 11·4% (95% CI 10·2-12·5; 10 151 of 107 119 individuals), prediabetes 15·3% (13·9-16·6; 15 496 of 107 119 individuals), hypertension 35·5% (33·8-37·3; 35 172 of 111 439 individuals), generalised obesity 28·6% (26·9-30·3; 29 861 of 110 368 individuals), abdominal obesity 39·5% (37·7-41·4; 40 121 of 108 665 individuals), and dyslipidaemia 81·2% (77·9-84·5; 14 895 of 18 492 of 25 647). All metabolic NCDs except prediabetes were more frequent in urban than rural areas. In many states with a lower human development index, the ratio of diabetes to prediabetes was less than 1. INTERPRETATION: The prevalence of diabetes and other metabolic NCDs in India is considerably higher than previously estimated. While the diabetes epidemic is stabilising in the more developed states of the country, it is still increasing in most other states. Thus, there are serious implications for the nation, warranting urgent state-specific policies and interventions to arrest the rapidly rising epidemic of metabolic NCDs in India. FUNDING: Indian Council of Medical Research and Department of Health Research, Ministry of Health and Family Welfare, Government of India.

Association of Organochlorine Pesticides With Genetic Markers of Endoplasmic Reticulum Stress in Type 2 Diabetes Mellitus: A Case-Control Study Among the North-Indian Population.

Background: Organochlorine pesticides (OCPs) have been long linked to type 2 diabetes mellitus (T2DM); however, this relation at the molecular level has not been explored yet. Endoplasmic reticulum (ER) stress and pro-inflammatory pathways are considered vital ones in the pathogenesis of T2DM. We aimed to investigate the existence of any association between OCPs, ER stress, and pro-inflammatory pathways in subjects with known T2DM. Methods: Seventy subjects each with T2DM and normal glucose tolerance were recruited from the surgery department. Their visceral adipose tissue was collected intraoperatively. OCP concentration, ER stress, and pro-inflammatory markers were analyzed and compared between two study groups. Results: We found 18 OCPs and their metabolites in visceral adipose tissue samples of study participants. The levels of δ-HCH, heptachlor, endrin, and p,p'DDT were significantly higher in the T2DM group and were also positively correlated with fasting and postprandial plasma glucose levels (p < 0.01). We observed a positive association of δ-HCH (p < 0.01), heptachlor (p < 0.05), and endrin (p < 0.05) with central adiposity and ER stress markers. However, we failed to establish the correlation of OCPs with any of the pro-inflammatory markers. Conclusion: The existence and simultaneous complex correlation of OCPs with ER stress may explain their role in the pathogenesis of T2DM, revealing the persistence of the gene-environment interaction in the etiology of T2DM.

TCF7L2 gene associated postprandial triglyceride dysmetabolism- a novel mechanism for diabetes risk among Asian Indians.

Aim: TCF7L2 gene is believed to increase the risk of T2DM by its effects on insulin secretion. However, the exact mechanism of this enhanced risk is not clearly known. While TCF7L2 gene has been shown to affect lipid metabolism, these effects have remained largely unexplored in the context of diabetes risk. Methods: Postprandial lipid responses to a standardized fat challenge test were performed in 620 Asian Indian subjects (310 with NGT and 310 with T2DM/prediabetes) and compared between the risk and wild genotypes of the rs7903146 TCF7L2 gene. In 30 subjects scheduled to undergo abdominal surgery (10 each with NGT, Prediabetes and T2DM), adipocyte TCF7L2 gene expression was also performed by real time qPCR and confirmed by protein expression in western blot. Results: T allele of rs7903146 TCF7L2 gene was confirmed as the risk allele for T2DM (OR=1.8(1.2-2.74), p=0.005). TT+CT genotypes of rs7903146 TCF7L2 gene showed significantly higher 4hrTg (p<0.01), TgAUC (p<0.01), peakTg (p<0.01) as well as higher postprandial plasma glucose (p=.006) levels and HOMA-IR (p=0.03) and significantly lower adiponectin levels (p=0.02) as compared to CC genotype. The expression of TCF7L2 gene in VAT was 11-fold higher in prediabetes group as compared to NGT (P<0.01) and 5.7-fold higher in T2DM group as compared to NGT group(P=0.003) and was significantly associated with PPTg and glucose levels. Conclusion: There is significant PPTg dysmetabolism associated with the risk allele of rs7903146 polymorphism as well as adipocyte expression of TCF7L2 gene. Significant upregulation of TCF7L2 gene expression in VAT that correlates with PPTg and glycaemia is also seen in Asian Indians with glucose intolerance. Modulation of PPTg metabolism by TCF7L2 gene and the resultant PPHTg may be a novel mechanism that contributes to its diabetes risk in them.

Variations in glycated haemoglobin with age among individuals with normal glucose tolerance: Implications for diagnosis and treatment-Results from the ICMR-INDIAB population-based study (INDIAB-12).

AIM: To report on glycated haemoglobin (HbA1c) values among individuals with normal glucose tolerance (NGT) at different age groups, using data acquired from a large national survey in India. MATERIALS AND METHODS: Data on glycaemic parameters at different age groups were obtained from the Indian Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study, in adults aged ≥ 20 years representing all parts of India. Age-wise distribution of HbA1c was assessed among individuals with NGT (n = 14,222) confirmed by an oral glucose tolerance test using the World Health Organization (WHO) criteria. Results were validated in another large epidemiological study (n = 1077) conducted in Chennai, India. RESULTS: Among NGT individuals, HbA1c increased gradually with age from 5.16 ± 0.71% (33 mmol/mol) in the age group of 20-29 years to 5.49 ± 0.69% (37 mmol/mol) in those aged 70 + years. In the validation study, conducted in another study population, HbA1c was 5.35 ± 0.43% (35 mmol/mol) in age group of 20-29 years and 5.74 ± 0.50% (39 mmol/mol) in those aged 70 and above. In the INDIAB study, for every decadal increase in age, there is a 0.08% increase in HbA1c and this increase was more significant in females (females: 0.10% vs. males: 0.06%) and in urban (urban: 0.10% vs. rural: 0.08%) population. CONCLUSIONS: HbA1c levels increase steadily with age. This suggests that age-specific cutoffs be used while utilizing HbA1c to diagnose diabetes and prediabetes, so as to minimize the risk of overdiagnosis and unnecessary initiation of treatment in elderly people who could have physiological increase in HbA1c levels.

Achievement of guideline recommended diabetes treatment targets and health habits in people with self-reported diabetes in India (ICMR-INDIAB-13): a national cross-sectional study.

BACKGROUND: There is little information on comprehensive diabetes care comprising glycaemic, lipid, and blood pressure control in India; therefore, we aimed to assess the achievement of treatment targets among adults with self-reported diabetes. METHODS: The Indian Council of Medical Research (ICMR)-India Diabetes (INDIAB) study is a cross-sectional, population-based survey of adults aged 20 years or older in all 30 states and union territories of India. We used a stratified multistage sampling design, sampling states in a phased manner, and selected villages in rural areas and census enumeration blocks in urban areas. We used a three-level stratification method on the basis of geography, population size, and socioeconomic status for each state. For the outcome assessment, good glycaemic control was defined as HbA1c of less than 7·0% (A), blood pressure control was defined as less than 140/90 mm Hg (B), and the LDL cholesterol target was defined as less than 100 mg/dL (C). ABC control was defined as the proportion of individuals meeting glycaemic, blood pressure, and LDL cholesterol targets together. We also performed multiple logistic regression to assess the factors influencing achievement of diabetes treatment targets. FINDINGS: Between Oct 18, 2008, and Dec 17, 2020, 113 043 individuals (33 537 from urban areas and 79 506 from rural areas) participated in the ICMR-INDIAB study. For this analysis, 5789 adults (2633 in urban areas and 3156 in rural areas) with self-reported diabetes were included in the study population. The median age was 56·1 years (IQR 55·7-56·5). Overall, 1748 (weighted proportion 36·3%, 95% CI 34·7-37·9) of 4834 people with diabetes achieved good glycaemic control, 2819 (weighted proportion 48·8%, 47·2-50·3) of 5698 achieved blood pressure control, and 2043 (weighted proportion 41·5%, 39·9-43·1) of 4886 achieved good LDL cholesterol control. Only 419 (weighted proportion 7·7%) of 5297 individuals with self-reported diabetes achieved all three ABC targets, with significant heterogeneity between regions and states. Higher education, male sex, rural residence, and shorter duration of diabetes (<10 years) were associated with better achievement of combined ABC targets. Only 951 (weighted proportion 16·7%) of the study population and 227 (weighted proportion 36·9%) of those on insulin reported using self-monitoring of blood glucose. INTERPRETATION: Achievement of treatment targets and adoption of healthy behaviours remains suboptimal in India. Our results can help governments to adopt policies that prioritise improvement of diabetes care delivery and surveillance in India. FUNDING: Indian Council of Medical Research and Department of Health Research, Ministry of Health and Family Welfare.

Macronutrient Recommendations for Remission and Prevention of Diabetes in Asian Indians Based on a Data-Driven Optimization Model: The ICMR-INDIAB National Study.

OBJECTIVE: To derive macronutrient recommendations for remission and prevention of type 2 diabetes (T2D) in Asian Indians using a data-driven optimization approach. RESEARCH DESIGN AND METHODS: Dietary, behavioral, and demographic assessments were performed on 18,090 adults participating in the nationally representative, population-based Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study. Fasting and 2-h postglucose challenge capillary blood glucose and glycosylated hemoglobin (HbA1c) were estimated. With HbA1c as the outcome, a linear regression model was first obtained for various glycemic categories: newly diagnosed diabetes (NDD), prediabetes (PD), and normal glucose tolerance (NGT). Macronutrient recommendations were formulated as a constrained quadratic programming problem (QPP) to compute optimal macronutrient compositions that would reduce the sum of the difference between the estimated HbA1c from the linear regression model and the targets for remission (6.4% for NDD and 5.6% for PD) and prevention of progression in T2D in PD and NGT groups. RESULTS: Four macronutrient recommendations (%E- Energy) emerged for 1) diabetes remission in NDD: carbohydrate, 49-54%; protein, 19-20%; and fat, 21-26%; 2) PD remission to NGT: carbohydrate, 50-56%; protein,18-20%; fat, 21-27%; 3 and 4) prevention of progression to T2D in PD and NGT: carbohydrate, 54-57% and 56-60%; protein, 16-20% and 14-17%, respectively; and fat 20-24% for PD and NGT. CONCLUSIONS: We recommend reduction in carbohydrates (%E) and an increase in protein (%E) for both T2D remission and for prevention of progression to T2D in PD and NGT groups. Our results underline the need for new dietary guidelines that recommend appropriate changes in macronutrient composition for reducing the burden due to diabetes in South Asia.

Common variants of FTO and the risk of obesity and type 2 diabetes in Indians.

Common variants of fat mass and obesity-associated gene (FTO, fat mass- and obesity-associated gene) have been shown to be associated with obesity and type 2 diabetes in population of European and non-European ethnicity. However, studies in Indian population have provided inconsistent results. Here, we examined association of eight FTO variants (rs1421085, rs8050136, rs9939609, rs9930506, rs1861867, rs9926180, rs2540769 and rs708277) with obesity and type 2 diabetes in 5364 North Indians (2474 type 2 diabetes patients and 2890 non-diabetic controls) in two stages. None of the variants including previously reported intron 1 variants (rs1421085, rs8050136, rs9939609 and rs9930506) showed body mass index (BMI)-dependent/independent association with type 2 diabetes. However, rs1421085, rs8050136 and rs9939609 were associated with obesity status and measures of obesity (BMI, waist circumference and waist-to-hip ratio) in stage 2 and combined study population. Meta-analysis of the two study population results also revealed that rs1421085, rs8050136 and rs9939609 were significantly associated with BMI both under the random- and fixed-effect models (P (random/fixed)=0.02/0.0001, 0.004/0.0006 and 0.01/0.01, respectively). In conclusion, common variants of FTO were associated with obesity, but not with type 2 diabetes in North Indian population.

Family history of diabetes determines the association of HOMA-IR with fasting and postprandial triglycerides in individuals with normal glucose tolerance.

BACKGROUND: Individuals with family history of diabetes carry nearly double the risk of diabetes than those without. However, the mechanism for this increased risk of diabetes in them is not fully understood. OBJECTIVE: To study fasting and postprandial triglyceride levels in individuals with normal glucose tolerance (NGT) who had family history of diabetes and to ascertain their association with insulin resistance. METHODS: Fasting triglyceride levels and HOMA-IR were compared in 671 NGT individuals with and without a family history of diabetes. A standardized fat challenge test was also done in one tenth of individuals of each group and postprandial triglyceride responses were compared between them. Association of HOMA-IR with fasting and postprandial triglyceride levels was ascertained through pearson's coefficient of correlation. RESULTS: Individuals with family history of diabetes had significantly higher HOMA-IR (P < 0.001) and significantly higher postprandial triglyceride AUC (P = 0.04) after standardized fat meal despite having similar fasting triglyceride levels (P = 0.51) as those without family history of diabetes. Fasting as well as postprandial triglyceride levels significantly correlated with HOMA-IR (r = 0.35, P < 0.001 and r = 0.39, P = 0.04) only in those with a positive family history of diabetes but not in those without. Triglyceride levels mediated the associations of BMI (Δ ß = -0.053) and waist circumference (Δ ß = -0.075) with HOMA-IR. CONCLUSION: Triglyceride levels, both in the fasting and the postprandial state are associated with insulin resistance in NGT individuals with a family history of diabetes but not in those without.

Level of Organochlorine Pesticide in Prediabetic and Newly Diagnosed Diabetes Mellitus Patients with Varying Degree of Glucose Intolerance and Insulin Resistance among North Indian Population.

BACKGROUND: Organochlorine pesticides (OCPs) exposure may induce an endocrine disruption which may lead to the risk of developing diabetes through alteration and disturbance of glucose metabolism, insulin resistance, and destruction of ß-cells. The present study determines the recent trend of OCPs residue in blood samples and their association with the known risk factors responsible for developing the risk of diabetes among the North Indian population. METHODS: Blood sample of 300 patients (100 each of normal glucose tolerance [NGT], prediabetes and newly detected diabetes mellitus [DM]) between the age group of 30 to 70 years were collected. OCPs residue in whole blood samples was analyzed by using gas chromatography equipped with a 63Ni selective electron capture detector. RESULTS: Significantly higher levels of ß-hexachlorocyclohexane (HCH), dieldrin, and p,p'-dichloro-diphenyl-dichloroethylene (DDE) were found in the prediabetes and newly detected DM groups as compared to NGT group. Insulin resistance showed to be significantly positive correlation with ß-HCH and dieldrin. Also, fasting and postprandial glucose levels were significantly positively correlated with levels of ß-HCH, dieldrin, and p,p'-DDE. Further, when OCPs level was adjusted for age and body mass index (BMI), it was found that ß-HCH, dieldrin, and p,p'-DDE levels in blood increases the risk of diabetes by 2.70, 2.83, and 2.55 times respectively. Moreover, when we adjust OCPs level based on BMI categories (BMI <23, ≥23, and ≤25, and >25 kg/m2); ß-HCH and p,p'-DDE showed a significant risk of developing newly detected DM with BMI >25 and ≥23 and ≤25 kg/m2. CONCLUSION: The OCPs level present in the environment may be responsible for biological, metabolic, and endocrine disruptions within the human body which may increase the risk of developing newly detected DM. Hence, OCPs exposure can play a crucial role in the etiology of diabetes.

Adipose Tissue Levels of DDT as Risk Factor for Obesity and Type 2 Diabetes Mellitus.

BACKGROUND: Exposure to dichlorodiphenyltrichloroethane (DDT), a potent lipophilic organochlorine pesticide, has long been linked as a risk factor for type 2 diabetes mellitus (T2DM). However, its presence in the adipose tissues of the T2DM subjects has not been explored in the Indian population, where this long-banned pesticide is still in use. The present study was conducted to evaluate the possible association of DDT and its metabolites in obese and non-obese T2DM subjects. METHODS: Subjects with normal glucose tolerance (n = 50) and T2DM (n = 50) were divided into equal numbers in obese and non-obese groups. Their plasma glucose levels, HbA1c, and lipid profile were measured. The adipose tissues were collected intraoperatively, and DDT and its metabolites were measured using a gas chromatograph equipped with an electron capture detector. RESULTS: Obese subjects, irrespective of their glycemic status, and T2DM subjects had higher concentrations of DDT. p, p' DDT was found to increase the odds for diabetes, and o, p' DDT for central obesity. p, p' DDD was also strongly correlated with central obesity, glycemic parameters, and triglycerides. CONCLUSION: The excess deposition of p, p' DDD, o, p' DDT, and p, p' DDT in obese subjects may proceed to T2DM by disrupting triglycerides and glycemic parameters.