The role of structural racism and geographical inequity in diabetes outcomes.

Diabetes is pervasive, exponentially growing in prevalence, and outpacing most diseases globally. In this Series paper, we use new theoretical frameworks and a narrative review of existing literature to show how structural inequity (structural racism and geographical inequity) has accelerated rates of diabetes disease, morbidity, and mortality globally. We discuss how structural inequity leads to large, fixed differences in key, upstream social determinants of health, which influence downstream social determinants of health and resultant diabetes outcomes in a cascade of widening inequity. We review categories of social determinants of health with known effects on diabetes outcomes, including public awareness and policy, economic development, access to high-quality care, innovations in diabetes management, and sociocultural norms. We also provide regional perspectives, grounded in our theoretical framework, to highlight prominent, real-world challenges.

Interventions to address global inequity in diabetes: international progress.

Diabetes is a serious chronic disease with high associated burden and disproportionate costs to communities based on socioeconomic, gender, racial, and ethnic status. Addressing the complex challenges of global inequity in diabetes will require intentional efforts to focus on broader social contexts and systems that supersede individual-level interventions. We codify and highlight best practice approaches to achieve equity in diabetes care and outcomes on a global scale. We outline action plans to target diabetes equity on the basis of the recommendations established by The Lancet Commission on Diabetes, organising interventions by their effect on changing the ecosystem, building capacity, or improving the clinical practice environment. We present international examples of how to address diabetes inequity in the real world to show that approaches addressing the individual within a larger social context, in addition to addressing structural inequity, hold the greatest promise for creating sustainable and equitable change that curbs the global diabetes crisis.

Risk factors for incident cardiovascular events and their population attributable fractions in rural India: The Rishi Valley Prospective Cohort Study.

OBJECTIVE: We prospectively determined incident cardiovascular events and their association with risk factors in rural India. METHODS: We followed up with 7935 adults from the Rishi Valley Prospective Cohort Study to identify incident cardiovascular events. Using Cox proportional hazards regression, we estimated hazard ratios (HRs) with 95% confidence intervals (95% CI) for associations between potential risk factors and cardiovascular events. Population attributable fractions (PAFs) for risk factors were estimated using R ('averisk' package). RESULTS: Of the 4809 participants without prior cardiovascular disease, 57.7% were women and baseline mean age was 45.3 years. At follow-up (median of 4.9 years, 23,180 person-years [PYs]), 202 participants developed cardiovascular events, equating to an incidence of 8.7 cardiovascular events/1000 PYs. Incidence was greater in those with hypertension (hazard ratio [HR] [95% CI] 1.73 [1.21-2.49], adjusted PAF 18%), diabetes (1.96 [1.15-3.36], 4%) or central obesity (1.77 [1.23, 2.54], 9%) which together accounted for 31% of the PAF. Non-traditional risk factors such as night sleeping hours and number of children accounted for 16% of the PAF. CONCLUSIONS: Both traditional and non-traditional cardiovascular risk factors are important contributors to incident cardiovascular events in rural India. Interventions targeted to these factors could assist in reducing the incidence of cardiovascular events.

A Novel Large Deletion in the EVER1 Gene in a Family With Epidermodysplasia Verruciformis From India.

ABSTRACT: Epidermodysplasia verruciformis (EV) is a rare autosomal recessive genodermatosis due to mutations in EVER1 and EVER2 genes. The genetic profile of Indian patients with EV has not been previously studied. This report describes the clinical presentation and molecular analysis of a family with EV. Using genomic DNA from two affected probands and healthy controls (two other siblings), conventional polymerase chain reaction (PCR) was conducted with novel primer sets designed to amplify the coding and splice-site regions in the genes EVER1 and EVER 2. This revealed no amplification with a primer set for exons 16 to 18 in the EVER1 gene of both the probands. Subsequently, long-range PCR spanning the length of exon 15-20 and next-generation sequencing demonstrated a homozygous deletion of 2078 bp in the EVER1 gene (EVER1:c.2072_2278del). Screening the family revealed the same homozygous deletion (similar to index cases) in two other affected siblings. The parents and two asymptomatic siblings were heterozygous carriers for the deletion while one healthy sibling was negative. These results were validated with Sanger sequencing. This deletion in exons 17 and 18 of the EVER1 gene results in a frameshift, followed by a premature termination resulting in a severe phenotype. The identification and validation of this large deletion was detected using stepwise amplicon-based target enrichment and long-range PCR, respectively. In this family, this simple strategy greatly enhanced genetic counseling as well as early genetic diagnosis and screening. However, functional assays and larger studies are required to characterize and validate the genetic diversity among Indians with EV.

Predictors of Delayed Hyponatraemia After Surgery for Pituitary Tumour.

Delayed hyponatraemia(DH) is a common complication following trans-sphenoidal surgery(TSS) for pituitary tumour. We evaluated the prevalence of DH following TSS, and assessed the factors associated with DH, including early post-operative diabetes insipidus(EPDI). This retrospective study included 100 TSS for pituitary tumours in 98 patients, over a period of 26 months. Subjects were divided into two groups: those who developed hyponatraemia and those who did not develop hyponatraemia, during post-operative days 4 to 14. The clinical characteristics and peri-operative parameters were compared between the two groups, to identify factors predicting DH. The mean age of the patients was 42.0±13.6 years, 58 (59%) were females and 61 (61%) had functional tumours. Thirty-six patients(36%) developed DH following TSS of whom majority(58%) were diagnosed on post-operative days 7 and 8; only 8/36 (22%) were symptomatic. Syndrome of inappropriate antidiuretic hormone secretion(SIADH) was found to be the most common aetiology of DH. On logistic regression analysis, intra-operative cerebrospinal fluid(CSF) leak (OR 5.0; 95% CI 1.9-13.8; p=0.002), EPDI (OR 3.4; 95% CI 1.3-9.2; p=0.015) and peri-operative steroid use (OR 3.6; 95% CI 1.3-9.8; p=0.014) were found to be significantly associated with DH. In conclusion, EPDI, intra-operative CSF leak and peri-operative steroid use were significant predictors of DH. EPDI predicts moderate to severe hyponatraemia with 80% specificity but has low sensitivity(47%). As most patients have asymptomatic hyponatraemia, serum sodium measurement on POD 7 to 10 would be helpful to identify DH in patients at increased risk.

The prevalence of vertebral fractures among Indian perimenopausal women and its association with ovarian biomarkers.

INTRODUCTION: There is dearth of data on prevalent vertebral fractures in perimenopausal women in India and limited literature on the utility of FSH, AMH and estradiol in evaluating bone health them. The objective was to study the prevalence of vertebral fractures (VF) and to assess the utility of FSH, estradiol and AMH in predicting them in Indian perimenopausal women MATERIALS AND METHODS: It was a cross-sectional study. Perimenopausal women aged 40-49 years underwent assessment for prevalent vertebral fractures, bone mineral density (BMD) and trabecular bone score (TBS). Utility of serum FSH, estradiol and AMH in predicting prevalent vertebral fractures was also assessed. RESULTS: A total of 300 perimenopausal women with mean (SD) age of 43.2 (2.8) years was recruited and 18% had moderate-severe VF. Mean (SD) serum AMH was lower in perimenopausal women with VF as compared to those without fractures [0.752 (0.594) vs 1.023 (0.704) P = 0.006]. AMH showed significant positive correlation with TBS (r = 0.3; P < 0.001) and BMD at the femoral neck (r = 0.2; P < 0.001) and lumbar spine (r = 0.3; P < 0.001).On ROC analysis, AMH demonstrated good performance in predicting prevalent VF with an AUC of 0.800 (95% CI 0.705-0.880) and a sensitivity of 85% and specificity of 60% at a cut-off of 1.12 ng/mL. On an exploratory multivariate logistic regression analysis, AMH significantly predicted prevalent fractures with an adjusted OR (OR) of 1.85 (95% CI: 1.03-3.00; P = 0.04). The performance of FSH and estradiol in predicting prevalent fractures was sub-optimal. CONCLUSION: About one-fifth of the study subjects had prevalent vertebral fractures. AMH may be a menstrual cycle independent biomarker and may reflect bone loss in perimenopausal women. Further prospective studies are needed to validate these findings.

Proximal Hip Geometry, Trabecular Bone Score, Bone Mineral Density and Bone Mineral Parameters in Patients With Cryptogenic and Hepatitis B Related Cirrhosis- A Study From the Indian Subcontinent.

The impact of cryptogenic cirrhosis on skeleton has not been studied in Indian context. So this study investigated bone health in male patients with early cryptogenic cirrhosis as defined by Child-Turcot-Pugh A (CTP-A) categorization and compared it with patients diagnosed to have hepatitis B related chronic liver disease (CLD) on treatment and age, sex-matched healthy controls. It was a cross-sectional study, in which thirty male subjects were recruited in each group. Bone mineral density (BMD), trabecular bone score (TBS), hip structural analysis (HSA) and bone mineral parameters were assessed. The mean ±SD age of the study subjects was 39.3 ± 9.2 years. The mean 25-hydroxy vitamin D was significantly lower in subjects with cryptogenic cirrhosis as compared to controls (p = 0.001). Subjects with cryptogenic cirrhosis had significantly lower (1.297 ± 0.099) TBS as compared to hepatitis-B related CLD (1.350 ± 0.094) control subjects (1.351 ± 0.088) (p = 0.04). BMD at the hip and lumbar spine was also significantly lower in subjects with cryptogenic cirrhosis as compared to hepatitis-B related CLD and healthy age matched controls (p < 0.05). Most components of HSA were significantly affected in subjects with cryptogenic cirrhosis as compared to control subjects (p < 0.05). Patients with cryptogenic cirrhosis had significantly low TBS and BMD lumbar spine and hip as well as poor proximal hip geometry which may be good predictor of future fragility fractures.

Distinct opposing associations of upper and lower body fat depots with metabolic and cardiovascular disease risk markers.

BACKGROUND: To examine the associations of total and regional adiposity with metabolic and cardiovascular disease (CVD) risk markers. METHODS: This cross-sectional study included 1080 (53.8% men, aged 39-44 years) individuals from South India. Anthropometry (height, weight, waist and hip circumference), body composition assessment using dual-energy X-ray absorptiometry (DXA), blood pressure (BP), and plasma glucose, insulin and lipids were measured. Regression analysis was used to examine associations of standardized fat measurements with type 2 diabetes (T2D), insulin resistance (IR), hypertension and hypertriglyceridemia and continuous measurements of BP, glucose, insulin, HOMA-IR and lipids. Contour plots were constructed to visualize the differential effect of upper and lower fat depots. RESULTS: DXA-measured fat depots were positively associated with metabolic and CVD risk markers. After adjusting for fat mass index, upper body fat remained positively, while lower body fat was negatively associated with risk markers. A one standard deviation (SD) increase in android fat showed higher odds ratios (ORs) for T2D (6.59; 95% CI 3.17, 13.70), IR (4.68; 95% CI 2.31, 9.50), hypertension (2.57; 95% CI 1.56, 4.25) and hypertriglyceridemia (6.39; 95% CI 3.46, 11.90) in men. A 1 SD increase in leg fat showed a protective effect with ORs for T2D (0.42; 95% CI 0.24, 0.74), IR (0.31; 95% CI 0.17, 0.57) and hypertriglyceridemia (0.61; 95% CI 0.38, 0.98). The magnitude of the effect was greater with DXA-measured fat compared with anthropometry. CONCLUSION: At any level of total body fat, upper and lower body fat depots demonstrate opposite risk associations with metabolic and CVD risk markers in Asian Indians.

Clinical Profile and Mutations Associated with Multiple Endocrine Neoplasia-Type1 (MEN1) and Their First-Degree Relatives at Risk of Developing MEN1: A Prospective Study.

Multiple Endocrine Neoplasia type-1 (MEN1) is an autosomal dominant disorder with a combined occurrence of tumours of parathyroid glands, pancreatic islets, and anterior pituitary. About 90% of these patients carry mutations in the MEN1 gene, though the spectrum is not well defined in India. Forty clinically suspected cases of MEN1 were enrolled prospectively over six years; 32 patients (23 index-cases and nine affected relatives) with≥2 classical endocrine tumours of MEN1 were considered definite, and eight were categorised as 'MEN1-like'. Details of their clinical presentation, treatment and mutational analysis including MEN1 gene, 3' and 5' untranslated regions (UTR) of MEN1, CDKN1B, and CaSR genes were collated. Asymptomatic first-degree relatives were also screened. Among the 32 definite MEN1 patients, all had primary hyperparathyroidism, 22 (68.7%) had gastroentero-pancreatic neuroendocrine tumours, and 21 (66%) had pituitary adenoma. Of the 23 definite index-cases, 13 (56.5%) carried mutations in the MEN1 gene. Five of nine affected first-degree relatives (55.5%), and four of 10 asymptomatic relatives (40%) also had MEN1 mutations. Seven of 10 MEN1 mutation-negative definite index-cases harboured p.V109G polymorphism in the CDKN1B gene. All eight MEN1-like cases were negative for mutations and large deletions in MEN1, mutations in 3' and 5' UTR of MEN1, CaSR and CDKN1B genes. The study has helped to clearly document the pattern of mutations among Indian MEN1 patients. However, the absence of MEN1 mutation in ~44% of cases and the presence of p.V109G polymorphism in CDKN1B gene raise the question whether such polymorphisms could independently contribute to pathogenesis.

DXA Measured Visceral Adipose Tissue, Total Fat, Anthropometric Indices and its Association With Cardiometabolic Risk Factors in Mother-Daughter Pairs From India.

Visceral fat is the pathogenic fat depot associated with diabetes, dyslipidemia, and cardiovascular diseases. Estimation of visceral adipose tissue (VAT) by dual energy-X-ray absorptiometry (DXA) is a newer technique with less radiation exposure, shorter scanning time, and lower cost. In this study, we attempted to look at relationship between cardiometabolic risk factors and VAT, total body fat percent (TBF%) and anthropometry. We also studied the changes in body composition and metabolic parameters with menopause. The familial resemblance of VAT and TBF% in mother-daughter pair was also compared. This was a cross sectional community study of 300 women (150 postmenopausal mothers and 150 premenopausal daughters). Body composition indices by DXA and metabolic parameters were assessed. The association between DXA-VAT, TBF%, anthropometric measures, and cardiometabolic risk factors were studied by correlation, receiver operating characteristics curves, and logistic regression analysis. VAT indices were significantly higher and lean indices lower in postmenopausal women as compared to premenopausal women. One fourth of postmenopausal women were categorized as metabolically obese normal weight. DXA-VAT was a better predictor of cardiometabolic risk factors as compared to waist circumference, body mass index, and TF% in postmenopausal women (AUC:0.68 vs 0.62, 0.60 & 0.5, respectively), whereas body mass index had a better prediction in premenopausal women(AUC:0.68). VAT area >100 cm² had a significant association with the presence of ≥2 cardiometabolic risk factors (p = 0.04, OR: 2.2, CI:1.0-4.7) in the postmenopausal women. Daughters of the mothers with higher TBF% were found to have a higher TBF% compared to daughters of mothers with normal TBF% (36.2 ± 4.2 vs 32.2 ± 4.4, p = 0.03), similar resemblance was not seen for VAT. The study showed that the VAT increases and lean mass decreases with age and menopause. DXA measured VAT is a better predictor of cardiometabolic risk in postmenopausal women but not in premenopausal women. Total body fat may have a familial resemblance, but not the VAT which is determined by age, menopause, and probable life style factors.

Effectiveness of a scalable group-based education and monitoring program, delivered by health workers, to improve control of hypertension in rural India: A cluster randomised controlled trial.

BACKGROUND: New methods are required to manage hypertension in resource-poor settings. We hypothesised that a community health worker (CHW)-led group-based education and monitoring intervention would improve control of blood pressure (BP). METHODS AND FINDINGS: We conducted a baseline community-based survey followed by a cluster randomised controlled trial of people with hypertension in 3 rural regions of South India, each at differing stages of epidemiological transition. Participants with hypertension, defined as BP ≥ 140/90 mm Hg or taking antihypertensive medication, were advised to visit a doctor. In each region, villages were randomly assigned to intervention or usual care (UC) in a 1:2 ratio. In intervention clusters, trained CHWs delivered a group-based intervention to people with hypertension. The program, conducted fortnightly for 3 months, included monitoring of BP, education about hypertension, and support for healthy lifestyle change. Outcomes were assessed approximately 2 months after completion of the intervention. The primary outcome was control of BP (BP < 140/90 mm Hg), analysed using mixed effects regression, clustered by village within region and adjusted for baseline control of hypertension (using intention-to-treat principles). Of 2,382 potentially eligible people, 637 from 5 intervention clusters and 1,097 from 10 UC clusters were recruited between November 2015 and April 2016, with follow-up occurring in 459 in the intervention group and 1,012 in UC. Mean age was 56.9 years (SD 13.7). Baseline BP was similar between groups. Control of BP improved from baseline to follow-up more in the intervention group (from 227 [49.5%] to 320 [69.7%] individuals) than in the UC group (from 528 [52.2%] to 624 [61.7%] individuals) (odds ratio [OR] 1.6, 95% CI 1.2-2.1; P = 0.001). In secondary outcome analyses, there was a greater decline in systolic BP in the intervention than UC group (-5.0 mm Hg, 95% CI -7.1 to -3.0; P < 0.001) and a greater decline in diastolic BP (-2.1 mm Hg, 95% CI -3.6 to -0.6; P < 0.006), but no detectable difference in the use of BP-lowering medications between groups (OR 1.2, 95% CI 0.8-1.9; P = 0.34). Similar results were found when using imputation analyses that included those lost to follow-up. Limitations include a relatively short follow-up period and use of outcome assessors who were not blinded to the group allocation. CONCLUSIONS: While the durability of the effect is uncertain, this trial provides evidence that a low-cost program using CHWs to deliver an education and monitoring intervention is effective in controlling BP and is potentially scalable in resource-poor settings globally. TRIAL REGISTRATION: The trial was registered with the Clinical Trials Registry-India (CTRI/2016/02/006678).

Do Bone Density, Bone Microarchitecture, and Body Composition Differ in Recipients of Allogeneic Hematopoietic Stem Cell Transplant? A Cross-Sectional Study from Southern India.

The significant advancements made in the field of allogeneic hematopoietic stem cell transplantation (allo-HSCT) have ensured increased longevity in transplant recipients. However, they do have late effects that may adversely affect the endocrine system, bone health, and body composition. This study was undertaken to evaluate bone mineral density (BMD), trabecular bone score, and body composition in recipients of allo-HSCT and compare them with age, sex, and body mass index (BMI) matched controls. This was a cross-sectional study done in 63 cases and 65 matched controls. The mean femoral neck BMD was found to be lower in cases than in controls (0.777 [0.119] versus 0.846 [0.122] g/cm2, P =  .002). Among cases, the mean BMD at the neck of femur was lower in patients who had received myeloablative conditioning compared with those who had received the nonmyeloablative regimen (0.731 [0.090] versus 0.802 [0.126] g/cm2, P = .014]. The mean (SD) bone density at the lumbar spine was significantly lower in the group that had received total body irradiation compared with the group that did not (0.930 [0.111] versus 0.993 [0.127], P = .044). Trabecular bone score did not differ between cases and controls (1.383 [0.877] versus 1.389 [0.750], P = .670). The lean mass was significantly lower (15.9 [2.4] versus 18.6 [4.8] kg/m2, P < .001) and the prevalence of sarcopenia (42% versus 11%, P < .001) significantly higher in cases than in controls. Normal-weight obesity was also noted to be higher among those with sarcopenia than in those without (12/26 versus 5/36; P = .009). The procedure of allo-HSCT may thus cause an impairment of bone health and alterations in body composition well after the cure of the primary disease.

Platelet-Lymphocyte Ratio as a Novel Surrogate Marker to Differentiate Thyrotoxic Patients with Graves Disease from Subacute Thyroiditis: a Cross-Sectional Study from South India.

OBJECTIVE: Graves disease (GD) and the toxic phase of subacute thyroiditis (SAT) have similar clinical and biochemical presentations, and differentiating them requires sophisticated investigations. Since thyroid hormones have been noted to affect all hematologic cell lines, we have used the platelet lymphocyte ratio (PLR)-an index usually utilized in inflammatory or malignant disorders-to compare patients with and without thyrotoxicosis and to analyze its use in distinguishing between patients with GD and SAT prior to therapy. METHODS: This was a cross-sectional study conducted in the Department of Endocrinology, Christian Medical College, Vellore, India. During the study period, 800 patients with features of thyrotoxicosis visited the outpatient clinic. Those who had thyroid radioiodine (131I) uptake (RAIU) study and complete blood count (CBC) at diagnosis were included (N = 500). Based on the RAIU values, these were divided as GD (n = 354) and SAT (n = 146). Baseline characteristics, thyroid function tests, and components of the CBC and PLR were obtained. The data were compared with a group of 250 matched euthyroid controls. Analyses were performed using SPSS version 21.0 software. RESULTS: PLR showed significant reductions in both GD and SAT patients when compared to euthyroid controls (P = .01), with greater reductions seen in GD than SAT (74.5 ± 19 vs. 84.4 ± 26; P = .01). Using receiver operating characteristic analysis of PLR, an optimal PLR cut-off of 70.4 was found to differentiate GD from SAT with a sensitivity of 86% and specificity of 74%. CONCLUSION: PLR can be used as a novel surrogate marker to differentiate between patients with GD and SAT prior to therapy, especially in resource-limited settings.

Does Baseline PTH Influence Recovery of Bone Mineral Density, Trabecular Bone Score and Bone Turnover Markers? A Prospective Study Following Curative PArathyroidectomy in Primary Hyperparathyroidism.

OBJECTIVE: This prospective study was carried out to assess trabecular bone score, bone mineral density (BMD), and bone biochemistry in Indian subjects with symptomatic primary hyperparathyroidism (PHPT), and to study the influence of baseline parathyroid hormone (PTH) on recovery of these parameters following curative surgery. METHODS: This was a 2-year prospective study conducted at a tertiary care centre in southern India. Baseline assessment included demographic details, mode of presentation, bone mineral biochemistry, BMD, trabecular bone score (TBS), and bone turnover markers (BTMs). These parameters were reassessed at the end of the first and second years following curative parathyroid surgery. RESULTS: Fifty-one subjects (32 men and 19 women) with PHPT who had undergone curative parathyroidectomy were included in this study. The mean (SD) age was 44.6 (13.7) years. The TBS, BTMs, and BMD at lumbar spine and forearm were significantly worse at baseline in subjects with higher baseline PTH (≥250 pg/mL) when compared to the group with lower baseline PTH (<250 pg/mL). At the end of 2 years, the difference between high versus low PTH groups (mean ± SD) persisted only for forearm BMD (0.638±0.093 versus 0.698±0.041 g/cm2; P =.01). However, on follow-up visits in the first and second year after curative parathyroidectomy, there was no significant difference in BTMs, BMD at the femoral neck, lumbar spine, and TBS between the 2 groups stratified by baseline PTH. CONCLUSION: The BMD at the forearm remained significantly worse in individuals with high baseline PTH even at 2 years after surgery, while other parameters including TBS improved significantly from baseline. ABBREVIATIONS: 25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; BMI = body mass index; BTMs = Bone turnover markers; CTX = C-terminal telopeptide of type 1 collagen; DXA = dual energy X-ray absorptiometry; P1NP = N-terminal propeptide of type 1 procollagen; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; TBS = trabecular bone score.

Renal Tubular Function, Bone Health and Body Composition in Wilson's Disease: A Cross-Sectional Study from India.

There is limited literature from India with regard to the prevalence and magnitude of renal tubular and bone manifestations in Wilson's disease (WD). Thus, we studied the prevalence of renal tubular acidosis among Indian patients with WD and also evaluated bone health and body composition in them. It was a cross-sectional study conducted at a south Indian tertiary care center. Twenty-five consecutive patients with WD aged more than 12 years attending the hepatology and neurology departments and 50 age, sex and BMI-matched controls were recruited. After clinical assessment, they underwent biochemical testing to assess renal tubular dysfunction. Bone mineral density (BMD) and body composition were assessed using a dual energy X-ray absorptiometry (DXA) scanner. Fifty-six percent (14/25) of patients with WD had renal tubular acidosis (RTA). Of them, 24% were diagnosed to have distal RTA. RTA was more common in hepatic WD patients who had prolonged duration of illness. Patients with WD had significantly lower BMD as compared to control subjects (p < 0.05). Low BMI, low IGF-1 and a shorter duration of therapy were key determinants of low bone mass in them (p < 0.05). Patients with WD had significantly more body fat (p = 0.01) and lower lean muscle mass (p = 0.03) when compared to age, sex and BMI-matched controls. In conclusion, renal tubular acidosis was common in patients with Wilson's disease. These patients had a lower bone mineral density, higher body fat percentage and lower lean muscle mass as compared to controls.

Heterogeneity in the aetiology of diabetes mellitus in young adults: A prospective study from north India.

Background & objectives: In contrast to Caucasians of European origin, the aetiology of diabetes mellitus (DM) in young adults in other ethnic groups, including Indians is likely to be heterogeneous and difficult to determine. This study was undertaken to determine the aetiology of diabetes in young Indian adults using a protocol-based set of simple clinical and investigation tools. Methods: In this prospective study, 105 Indian young adults with diabetes (age at onset 18-35 yr; duration <2 yr) were studied for a period of 1-3 years. Pancreatic imaging, fasting C-peptide, islet antibodies (against glutamic acid decarboxylase, tyrosine phosphatase and zinc transporter-8) and mitochondrial A3243G mutational analysis were performed in all patients. Four patients were screened for maturity-onset diabetes of the young (MODY) using next-generation sequencing. Results: Type 1 and type 2 diabetes mellitus (T1DM and T2DM) were equally frequent (40% each), followed by fibrocalculous pancreatic diabetes (FCPD, 15%). Less common aetiologies included MODY (2%), mitochondrial diabetes (1%) and Flatbush diabetes (2%). There was considerable phenotypic overlap between the main aetiological subtypes. Elevated islet antibodies were noted in 62 per cent of T1DM patients [positive predictive value (PPV) 84%; negative predictive value (NPV) 78%] while low plasma C-peptide (<250 pmol/l) was present in 56 per cent of T1DM patients [PPV 96% (after excluding FCPD), NPV 72%]. Using these tests and observing the clinical course over one year, a final diagnosis was made in 103 (99%) patients, while the diagnosis at recruitment changed in 23 per cent of patients. Interpretation & conclusions: The aetiology of diabetes in young adults was heterogeneous, with T1DM and T2DM being equally common. FCPD was also frequent, warranting its screening in Indian patients. Testing for islet antibodies and C-peptide in this age group had good PPV for diagnosis of T1DM.

Ethnicity-specific cut-offs that predict co-morbidities: the way forward for optimal utility of obesity indicators.

Obesity indicators are useful clinical tools in the measurement of obesity, but it is important for clinicians to appropriately interpret their values in individuals with different ethnicities. Future research is needed to identify optimal cut-offs that can predict the occurrence of cardio-metabolic comorbidities in individuals of different ethnic descent. Assessment of more recently developed indicators like the Edmonton Obesity Staging System and visceral adipose tissue are able to appropriately identify metabolically at-risk individuals.

The BMI-adiposity conundrum in South Asian populations: need for further research.

High body fat in apparently lean individuals is a commonly described phenotype in individuals of Asian descent, but very limited consolidated scientific literature is available on this topic. This phenotype is known as 'normal-weight obesity' and may explain the large disparity between the prevalence of obesity (as measured by BMI) and diabetes that occurs in these individuals. Routine use of obesity indicators that best predict body fat content would help to identify these individuals in clinical practice. In this debate, we would like to highlight that even though fat and BMI have a good correlation, as suggested by Kryst et al. (2019), clinicians, public health researchers and policymakers should consider the use of these indicators in conjunction with each other rather than individually. Future research is needed on pathogenic mechanisms, diagnostic modalities and therapeutic options in these individuals which will help to further characterize and manage these patients appropriately.

An Open-label Randomized Controlled Trial to Compare Weight Gain of Very Low Birth Weight Babies with or without Addition of Coconut Oil to Breast Milk.

Background: Nutritional guidelines involving the feeding of very low birth weight babies (VLBW) recommend addition of Human Milk Fortifiers to breast milk. Owing to financial constraints, it is a practice in low- and middle-income countries (LMIC) to add coconut oil to aid better weight gain. There are inadequate data on improvement of growth parameters with oral coconut oil supplementation of breast milk. Methods: In this randomized controlled trial, we measured growth parameters and body composition of 60 babies who received either breast milk with coconut oil or breast milk alone. Randomization was stratified according to intrauterine growth appropriate for gestational age (n = 30) and small for gestational age (n = 30). Results: There was no difference in weight gain between the two groups. The weight gain velocity was 15 ± 3.6 and 14.4 ± 3.4 g/kg/day (p value = 0.49) in the breast milk alone and in the breast milk with coconut oil group, respectively. There was no difference in increase in head circumference and length. Triceps skinfold thickness (n = 56) was similar in both groups, but subscapular skinfold thickness was significantly more in the coconut oil group. Total body fat percentage did not differ between the groups (25.2 ± 4.3 vs. 25.5 ± 4.3%, p = 0.79). Conclusion: Oral supplementation of coconut oil along with breast milk did not increase growth parameters or result in change in body composition in very low birth weight (VLBW) babies.

Evaluation of Different Screening Tools for Predicting Femoral Neck Osteoporosis in Rural South Indian Postmenopausal Women.

The measurement of bone mineral density by dual-energy X-ray absorptiometry scan is the "gold standard" for the diagnosis of osteoporosis, which has limited availability in many parts of India. This study was done to assess the diagnostic performance of 6 internationally validated tools (Simple Calculated Osteoporosis Risk Estimation [SCORE], age, bulk, one or never estrogen [ABONE], Osteoporosis Risk Assessment Instrument [ORAI] and Osteoporosis Self-Assessment Tool for Asians [OSTA], Fracture Risk Assessment Tool [FRAX®], and calcaneal quantitative ultrasound [QUS]) for the diagnosis of osteoporosis at the femoral neck (FN). This was a cross-sectional study conducted in 2108 ambulatory South Indian rural postmenopausal women who were assessed with SCORE, ABONE, ORAI, OSTA, and FRAX® tools. QUS was performed in 850 subjects. Bone mineral density was estimated by dual-energy X-ray absorptiometry scan at the FN, and sensitivity and specificity were calculated for all tools for predicting FN osteoporosis. The receiver operating characteristic curve was constructed for each tool and the area under the curve (AUC) was calculated. FN osteoporosis was seen in 27%. The sensitivities of SCORE, ABONE, OSTA, ORAI, FRAX®, and QUS were 91.3%, 91.0%, 88.5%, 81.0%, 72.7%, and 81.9%, and the specificities were 36.0%, 33.5%, 41.7%, 52.0%, 60.5%, and 50.3%, respectively, for the FN osteoporosis. When the receiver operating characteristics were constructed, the AUC was good only for SCORE (0.806), and the performance of the rest was under fair category (0.713-0.766). In our large cohort of rural postmenopausal women, the SCORE screening tool was found to be useful with good sensitivity and good AUC for predicting FN osteoporosis. Thus, this tool may be used in resource-limited countries to screen the population at risk and to enable treating physicians to make appropriate management decisions.