Senthil K. Vasan

Structural and Functional Properties of Deep Abdominal Subcutaneous Adipose Tissue Explain Its Association With Insulin Resistance and Cardiovascular Risk in Men

OBJECTIVE Fat distribution is an important variable explaining metabolic heterogeneity of obesity. Abdominal subcutaneous adipose tissue (SAT) is divided by the Scarpa’s fascia into a deep subcutaneous adipose tissue (dSAT) and a superficial subcutaneous adipose tissue (sSAT) layer. This study sought to characterize functional differences between the two SAT layers to explore their relative contribution to metabolic traits and cardiovascular risk (CVR) profile. RESEARCH DESIGN AND METHODS We recruited 371 Caucasians consecutively from a local random, population-based screening project in Oxford and 25 Asian Indians from the local community. The depth of the SAT layers was determined by ultrasound (US), and adipose tissue (AT) biopsies were performed under US guidance in a subgroup of 43 Caucasians. Visceral adipose tissue (VAT) mass was quantified by dual-energy X-ray absorptiometry scan. RESULTS Male adiposity in both ethnic groups was characterized by a disproportionate expansion of dSAT, which was strongly correlated with VAT mass. dSAT depth was a strong predictor of global insulin resistance (IR; homeostatic model assessment of IR), liver-specific IR (insulin-like growth factor binding protein-1), and Framingham risk score independently of other measures of adiposity in men. Moreover, dSAT had higher expression of proinflammatory, lipogenic, and lipolytic genes and contained higher proportions of saturated fatty acids. There was increased proportion of small adipocytes in dSAT. CONCLUSIONS SAT is heterogeneous; dSAT expands disproportionally more than sSAT with increasing obesity in Caucasian males (confirmed also in Asian Indians). Its expansion is related to increased CVR independent of other adiposity measures, and it has biological properties suggestive of higher metabolic activity contributing to global IR.

Associations of variants in FTO and Near MC4R with obesity traits in South Asian Indians

Recent genome‐wide association studies show that loci in FTO and melanocortin 4 receptor (MC4R) associate with obesity‐related traits. Outside Western populations the associations between these variants have not always been consistent and in Indians it has been suggested that FTO relates to diabetes without an obvious intermediary obesity phenotype. We investigated the association between genetic variants in FTO (rs9939609) and near MC4R (rs17782313) with obesity‐ and type 2 diabetes (T2DM)‐related traits in a longitudinal birth cohort of 2,151 healthy individuals from the Vellore birth cohort in South India. The FTO locus displayed significant associations with several conventional obesity‐related anthropometric traits. The per allele increase is about 1% for BMI, waist circumference (WC), hip circumference (HC), and waist—hip ratio. Consistent associations were observed for adipose tissue‐specific measurements such as skinfold thickness reinforcing the association with obesity‐related traits. Obesity associations for the MC4R locus were weak or nonsignificant but a signal for height (P < 0.001) was observed. The effect on obesity‐related traits for FTO was seen in adulthood, but not at younger ages. The loci also showed nominal associations with increased blood glucose but these associations were lost on BMI adjustment. The effect of FTO on obesity‐related traits was driven by an urban environmental influence. We conclude that rs9939609 variant in the FTO locus is associated with measures of adiposity and metabolic consequences in South Indians with an enhanced effect associated with urban living. The detection of these associations in Indians is challenging because conventional anthropometric obesity measures work poorly in the Indian “thin‐fat” phenotype.

The new Scandinavian Donations and Transfusions database (SCANDAT2): a blood safety resource with added versatility

Risks of transfusion‐transmitted disease are currently at a record low in the developed world. Still, available methods for blood surveillance might not be sufficient to detect transmission of diseases with unknown etiologies or with very long incubation periods.

Maturity onset diabetes of the young in India - a distinctive mutation pattern identified through targeted next-generation sequencing

To establish and utilize a Next‐Generation Sequencing (NGS)‐based strategy to screen for maturity onset diabetes of the young (MODY) gene mutations in subjects with early‐onset diabetes.

FTO genetic variants and risk of obesity and type 2 diabetes: A meta-analysis of 28,394 Indians

To investigate the magnitude of association of FTO variants with obesity, type 2 diabetes (T2DM), and related traits among Asian Indians.

Epidemiology of Massive Transfusion: A Binational Study From Sweden and Denmark*

Objective:There is an increasing focus on massive transfusion, but there is a paucity of comprehensive descriptions of the massively transfused patients and their outcomes. The objective of this study is to describe the incidence rate of massive transfusion, patient characteristics, and the mortality of massively transfused patients. Design:Descriptive cohort study. Setting:Nationwide study with data from Sweden and Denmark. Patients:The study was based on the Scandinavian Donations and Transfusions database, including all patients receiving 10 or more red cell concentrate transfusions in Sweden from 1987 and in Denmark from 1996. A total of 92,057 patients were included. Patients were followed until the end of 2012. Measurements and Main Results:Descriptive statistics were used to characterize the patients and indications. Post transfusion mortality was expressed as crude 30-day mortality and as long-term mortality using the Kaplan-Meier method and using standardized mortality ratios. The incidence of massive transfusion was higher in Denmark (4.5 per 10,000) than in Sweden (2.5 per 10,000). The most common indication for massive transfusion was major surgery (61.2%) followed by trauma (15.4%). Massive transfusion due to obstetrical bleeding constituted only 1.8%. The overall 5-year mortality was very high (54.6%), however with large differences between indication groups, ranging from 91.1% among those transfused for a malignant disease without surgery to 1.7% among patients transfused for obstetrical bleeding. The early standardized mortality ratios were high and decreased thereafter, but remained elevated throughout the time period. Conclusions:This large-scale study based on nationwide data from Sweden and Denmark describes the complete range of massive transfusion. We report a nonnegligible incidence and both a high absolute mortality and high standardized mortality ratio. The general pattern was similar for Sweden and Denmark, and we believe that similar patterns may be found in other high-resource countries. The study provides a relevant background for clinicians and researchers for designing future studies in this field.

ABO Blood Group and Risk of Thromboembolic and Arterial Disease A Study of 1.5 Million Blood Donors

Background— ABO blood groups have been shown to be associated with increased risks of venous thromboembolic and arterial disease. However, the reported magnitude of this association is inconsistent and is based on evidence from small-scale studies. Methods and Results— We used the SCANDAT2 (Scandinavian Donations and Transfusions) database of blood donors linked with other nationwide health data registers to investigate the association between ABO blood groups and the incidence of first and recurrent venous thromboembolic and arterial events. Blood donors in Denmark and Sweden between 1987 and 2012 were followed up for diagnosis of thromboembolism and arterial events. Poisson regression models were used to estimate incidence rate ratios as measures of relative risk. A total of 9170 venous and 24 653 arterial events occurred in 1 112 072 individuals during 13.6 million person-years of follow-up. Compared with blood group O, non-O blood groups were associated with higher incidence of both venous and arterial thromboembolic events. The highest rate ratios were observed for pregnancy-related venous thromboembolism (incidence rate ratio, 2.22; 95% confidence interval, 1.77–2.79), deep vein thrombosis (incidence rate ratio, 1.92; 95% confidence interval, 1.80–2.05), and pulmonary embolism (incidence rate ratio, 1.80; 95% confidence interval, 1.71–1.88). Conclusions— In this healthy population of blood donors, non-O blood groups explain >30% of venous thromboembolic events. Although ABO blood groups may potentially be used with available prediction systems for identifying at-risk individuals, its clinical utility requires further comparison with other risk markers. # CLINICAL PERSPECTIVE {#article-title-45}Background— ABO blood groups have been shown to be associated with increased risks of venous thromboembolic and arterial disease. However, the reported magnitude of this association is inconsistent and is based on evidence from small-scale studies. Methods and Results— We used the SCANDAT2 (Scandinavian Donations and Transfusions) database of blood donors linked with other nationwide health data registers to investigate the association between ABO blood groups and the incidence of first and recurrent venous thromboembolic and arterial events. Blood donors in Denmark and Sweden between 1987 and 2012 were followed up for diagnosis of thromboembolism and arterial events. Poisson regression models were used to estimate incidence rate ratios as measures of relative risk. A total of 9170 venous and 24 653 arterial events occurred in 1 112 072 individuals during 13.6 million person-years of follow-up. Compared with blood group O, non-O blood groups were associated with higher incidence of both venous and arterial thromboembolic events. The highest rate ratios were observed for pregnancy-related venous thromboembolism (incidence rate ratio, 2.22; 95% confidence interval, 1.77–2.79), deep vein thrombosis (incidence rate ratio, 1.92; 95% confidence interval, 1.80–2.05), and pulmonary embolism (incidence rate ratio, 1.80; 95% confidence interval, 1.71–1.88). Conclusions— In this healthy population of blood donors, non-O blood groups explain >30% of venous thromboembolic events. Although ABO blood groups may potentially be used with available prediction systems for identifying at-risk individuals, its clinical utility requires further comparison with other risk markers.

A double-blind, randomized, multicenter study evaluating the effects of pioglitazone in fasting Muslim subjects during Ramadan

AIM: Hypoglycemia in fasting subjects with diabetes pioglitazone arm were a mean weight gain of 3.02 kg during Ramadan is a problem that demands attention. (P=0.001) and ankle edema in 16 subjects (P=0.0002). We aimed to assess the efficacy and cost-effectiveness Direct cost per month per subject in the pioglitazone of pioglitazone on subjects fasting during the Ramadan group was INR 780.62 (US

Absence of birth-weight lowering effect of ADCY5 and near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians.

17.36) vs INR 1232.50 period and to determine its role in improving the (US

Lack of association between blood donor age and survival of transfused patients

27.41) in the placebo group (P=0.02). glycemic control and reducing hypoglycemic episodes CONCLUSION: Pioglitazone is safe and efficacious when used as an adjunctive form of therapy for subj cts in lowering blood glucose in fasting subjects during with type 2 diabetes mellitus. Ramadan in combination with other OHAs. There is METHODOLOGY: This multicenter, double-blind no reduction in the number of hypoglycemic events randomized controlled trial included 86 fasting Muslim when compared with conventional therapy without subjects with type 2 diabetes mellitus. The study was pioglitazone. There is a significant cost benefit when initiated 74 days prior to Ramadan to optimize pioglitazone is added to other OHAs in this study. glycemic control. The subjects were randomized to 30 mg of pioglitazone once daily and placebo in