Ectopic fat and aerobic fitness are key determinants of glucose homeostasis in nonobese Asians

Abstract

Background The importance of ectopic fat deposition and physical fitness in the pathogenesis of insulin resistance and beta cell dysfunction in subjects from the nonobese Asians is not known. Materials and methods We conducted a cross‐sectional study and measured insulin sensitivity (M value; 4‐hour hyperinsulinaemic‐euglycaemic clamp), insulin secretion rate (3‐hour mixed meal tolerance test with oral minimal modelling), percent body fat, visceral adipose tissue, intramyocellular and intrahepatic lipid contents (magnetic resonance imaging and spectroscopy), cardiorespiratory fitness (VO2max; graded exercise test) and habitual physical activity (short International Physical Activity Questionnaire) in 60 healthy nonobese Asian subjects (BMI = 21.9 ± 1.7 kg/m2, age = 41.8 ± 13.4 years). Results M was inversely associated with percent body fat (r = −0.460, P < 0.001), visceral fat (r = −0.623, P < 0.001) and liver fat (r = −0.601, P < 0.001), whereas insulin secretion correlated positively with these adiposity indices (percent body fat: r = 0.303, P = 0.018; visceral fat: r = 0.409, P = 0.010; hepatic fat: r = 0.393, P = 0.002). VO2max correlated negatively with insulin secretion rate (r = −0.420, P < 0.001) and positively with M (r = 0.658, P < 0.001). The amount of vigorous physical activity was positively associated with VO2max (r = 0.682, P < 0.001). Multiple stepwise linear regression analyses indicated that VO2max, age, and IHTG or VAT were independent determinants of insulin sensitivity and secretion (adjusted R2 = 69% and 33%, respectively, P < 0.001). Conclusions Increased ectopic fat deposition is associated with reduced insulin sensitivity and increased insulin secretion in healthy nonobese Asians. Poor cardiorespiratory fitness, likely due to inadequate participation in vigorous exercise, is strongly related to suboptimal metabolic function. Interventions to encourage engagement in physical activity may thus be important for improving metabolic health in nonobese Asians.

Obesity indicators that best predict type 2 diabetes in an Indian population: insights from the Kerala Diabetes Prevention Program

“…This is mainly brought about by reduction in the pancreatic and hepatic fat content (37) . Presence of fat at ectopic sites is now considered as a key driver connecting adiposity with T2DM and other cardiometabolic disorders (38,39) .…”

Visceral fat and cardiorespiratory fitness with prevalence of pre-diabetes/diabetes mellitus among middle-aged and elderly Japanese people: WASEDA’S Health Study

“…Furthermore, the IMAT volume was inversely proportional to aerobic physical fitness quantified based on total treadmill duration [34]. A previous study of non-obese Asians revealed that VF and intrahepatic triglycerides (IHTGs), which were measured using magnetic resonance spectroscopy, were inversely correlated to insulin sensitivity [35] and that VF and IHTGs were inversely proportional to CRF (VO 2 max/BW). These results suggest that the deposition of ectopic fat might be suppressed in individuals with high CRF and high VF levels.…”

The importance of cardiorespiratory fitness in obesity-related disease: a cross sectional-analysis

“…While the mechanistic interplay between low CRF, MAFLD, and T2D remains unclear, it is purported that the incomplete oxidation of fatty acids in the mitochondria may contribute to the build-up of fatty acid by-products, such as ceramides and diacylglycerol intracellularly, which impair insulin signalling pathways and mitochondrial function and may contribute to, or be the result of, low CRF [38,39]. Importantly, T2D-related exercise intolerance appears to be reversed by structured exercise and is made evident by the amelioration of mitochondrial impairments, increased mitochondrial content, improved insulin sensitivity, decreased IHL and increased CRF [15,16,40,41].…”