Thigh fat and muscle each contribute to excess cardiometabolic risk in South Asians, independent of visceral adipose tissue.

OBJECTIVE: To compare fat distribution and associations between fat depots and cardiometabolic traits in South Asians and Europeans. METHODS: Five hundred and fourteen South Asians and 669 Europeans, aged 56-86. Questionnaires, record review, blood testing, and coronary artery calcification scores provided diabetes and clinical plus subclinical coronary heart disease (CHD) diagnoses. Abdominal visceral (VAT) and subcutaneous adipose tissue, thigh subcutaneous adipose tissue (TSAT), intermuscular and intramuscular thigh fat and thigh muscle were measured by CT. RESULTS: Accounting for body size, South Asians had greater VAT and TSAT than Europeans, but less thigh muscle. Associations between depots and disease were stronger in South Asians than Europeans. In multivariable analyses in South Asians, VAT was positively associated with diabetes and CHD, while TSAT and thigh muscle were protective for diabetes, and thigh muscle for CHD. Differences in VAT and thigh muscle only partially explained the excess diabetes and CHD in South Asians versus Europeans. Insulin resistance did not account for the effects of TSAT or thigh muscle. CONCLUSIONS: Greater VAT and TSAT and lesser thigh muscle in South Asians contributed to ethnic differences in cardiometabolic disease. Effects of TSAT and thigh muscle were independent of insulin resistance

A game for all shapes and sizes? Changes in anthropometric and performance measures of elite professional rugby union players 1999-2018

Background: Rugby union player size has increased since the game turned professional in 1995. Changes in physical and performance capability over this period have yet to be fully described. Hypothesis: Increases in player momentum would result from changes in body mass. Methods: Within-player rates of change in anthropometric and kinetic variables with season played were sampled in three successively studied professional rugby union club cohorts playing at the highest level of European competition between 1999-2019. Data comprised 910 seasons of observation for 291 elite male players. Most players had 2, 3 or 4 seasons of observation. Mixed-effects modelling distinguished changes independent of position played, club and international status. Results: With each season played, player body mass, fat-free mass, and maximum speed increased significantly, while percent fat decreased. The mean maximal velocity of a rugby player in 1999 was 8.2 (±0.18) m/s, which in 2019 had risen to 9.1 (±0.10) m/s. Player’s momentum in 2019 was 14% more than those playing in 1999. In the Front Five, momentum increased in this period by more than 25%, mainly driven by greater running speed, disproving our hypothesis. Conclusions: The momentum of players, particularly forwards, increased markedly over 20 seasons of professional rugby. The resulting forces generated in collisions are thus significantly greater, although these may be mitigated by better player conditioning. Proactive regulation to address player safety may be required to address the changing nature of anthropometric measures and physical performance, minimising injury rates and potential long-term sequelae

Identifying crop variants with high resistant starch content to maintain healthy glucose homeostasis

Identifying dietary tools that prevent disordered insulin secretion from pancreatic β‐cells is an attractive strategy to combat the increasing prevalence of type 2 diabetes. Dietary resistant starch has been linked to improvements in the function of β‐cells, possibly via increased colonic fermentation and production of short‐chain fatty acids (SCFAs). Increasing the resistant starch content of commonly consumed foods could therefore maintain glucose homeostasis at the population level. As part of Biotechnology and Biological Sciences Research Council (BBSRC) Diet and Health Research Industry Club (DRINC) initiative, variants of Pisum sativum L. (pea) are being investigated to identify the features of pea starch that make it resistant to digestion and available for colonic fermentation and SCFA production. Parallel in vitro and in vivo studies are being conducted using both whole pea seeds and pea flour to facilitate a better understanding of how cells in the pea cotyledons are affected by processing and, in turn, how this influences starch digestibility. Trials in human volunteers are being used to monitor a full spectrum of short‐ and long‐term physiological responses relevant to pancreatic β‐cell function and glucose homeostasis. This project is providing new insights into variants of crops that are associated with the specific types of resistant starch that provide the best protection against defects in insulin secretion and function

Ethnicity and prediction of cardiovascular disease: performance of QRISK2 and Framingham scores in a U.K. tri-ethnic prospective cohort study (SABRE--Southall And Brent REvisited).

OBJECTIVE: To evaluate QRISK2 and Framingham cardiovascular disease (CVD) risk scores in a tri-ethnic U.K. population. DESIGN: Cohort study. SETTING: West London. PARTICIPANTS: Randomly selected from primary care lists. Follow-up data were available for 87% of traced participants, comprising 1866 white Europeans, 1377 South Asians, and 578 African Caribbeans, aged 40-69 years at baseline (1998-1991). MAIN OUTCOME MEASURES: First CVD events: myocardial infarction, coronary revascularisation, angina, transient ischaemic attack or stroke reported by participant, primary care or hospital records or death certificate. RESULTS: During follow-up, 387 CVD events occurred in men (14%) and 78 in women (8%). Both scores underestimated risk in European and South Asian women (ratio of predicted to observed risk: European women: QRISK2: 0.73, Framingham: 0.73; South Asian women: QRISK2: 0.52, Framingham: 0.43). In African Caribbeans, Framingham over-predicted in men and women and QRISK2 over-predicted in women. Framingham classified 28% of participants as high risk, predicting 54% of all such events. QRISK2 classified 19% as high risk, predicting 42% of all such events. Both scores performed poorly in identifying high risk African Caribbeans; QRISK2 and Framingham identified as high risk only 10% and 24% of those who experienced events. CONCLUSIONS: Neither score performed consistently well in all ethnic groups. Further validation of QRISK2 in other multi-ethnic datasets, and better methods for identifying high risk African Caribbeans and South Asian women, are required

Semaglutide improves postprandial glucose and lipid metabolism, and delays first‐hour gastric emptying in subjects with obesity

Aim: To investigate the effects of semaglutide on fasting and postprandial glucose and lipid responses, and on gastric emptying. Materials and Methods: This was a randomised, double-blind, placebo-controlled, two-period, crossover trial. Subjects with obesity (N = 30) received once-weekly subcutaneous semaglutide, dose-escalated to 1.0 mg, or placebo. After each 12-week treatment period, glucose and lipid metabolism were assessed before and after standardised meals. Gastric emptying (paracetamol absorption test) and peptide YY (PYY) response were also assessed. Results: Semaglutide treatment significantly lowered fasting concentrations of glucose and glucagon, and increased insulin versus placebo (estimated treatment ratio: 0.95 [95% confidence interval: 0.91, 0.98]; 0.86 [0.75, 0.98]; 1.45 [1.20, 1.75], respectively). Postprandial glucose metabolism significantly improved with semaglutide versus placebo (incremental area under the curve 0–5 hours [iAUC0-5h]; estimated treatment difference: glucose −1.34 mmol*h/L [−2.42, −0.27]; insulin −921 pmol*h/L [−1461, −381]; C-peptide −1.42 nmol*h/L [−2.33, −0.51]). Fasting and postprandial lipid metabolism improved with semaglutide versus placebo. First-hour gastric emptying after the meal was delayed versus placebo (AUC0-1h; estimated treatment ratio: 0.73 [0.61, 0.87]); this may have contributed to the lower postprandial glucose increase in semaglutide-treated subjects. Overall gastric emptying (AUC0-5h) was not statistically different between treatments. Fasting and postprandial PYY responses were significantly lower with semaglutide versus placebo (p=0.0397 and p=0.0097, respectively). Conclusion: Semaglutide improved fasting and postprandial glucose and lipid metabolism. Overall gastric emptying was similar to placebo; however, the observed first-hour delay with semaglutide may contribute to a slower entry of glucose into the circulation

Loss-of-Function Mutations in the Cell-Cycle Control Gene CDKN2A Impact on Glucose Homeostasis in Humans.

At the CDKN2A/B locus, three independent signals for type 2 diabetes risk are located in a non-coding region near CDKN2A. The disease-associated alleles have been implicated in reduced β-cell function, but the underlying mechanism remains elusive. In mice, β-cell specific loss of Cdkn2a causes hyperplasia whilst overexpression leads to diabetes, highlighting CDKN2A as a candidate effector transcript. Rare CDKN2A loss-of-function mutations are a cause of familial melanoma and offer the opportunity to determine the impact of CDKN2A haploinsufficiency on glucose homeostasis in humans. To test the hypothesis that such individuals have improved β-cell function, we performed oral and intravenous glucose tolerance tests on mutation carriers and matched controls. Compared with controls, carriers displayed increased insulin secretion, impaired insulin sensitivity and reduced hepatic insulin clearance. These results are consistent with a model whereby CDKN2A-loss affects a range of different tissues, including pancreatic β-cells and liver. To test for direct effects of CDKN2A-loss on β-cell function, we performed knockdown in a human β-cell line, EndoC-bH1. This revealed increased insulin secretion independent of proliferation. Overall, we demonstrate that CDKN2A is an important regulator of glucose homeostasis in humans, thus supporting its candidacy as an effector transcript for type 2 diabetes-associated alleles in the region