Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR).

Abstract

Insulin resistance and insulin hypersecretion are established features of obesity. Their prevalence, however, has only been inferred from plasma insulin concentrations. We measured insulin sensitivity (as the whole-body insulin-mediated glucose uptake) and fasting posthepatic insulin delivery rate (IDR) with the use of the euglycemic insulin clamp technique in a large group of obese subjects in the database of the European Group for the Study of Insulin Resistance (1,146 nondiabetic, normotensive Caucasian men and women aged 18-85 yr, with a body mass index (BMI) ranging from 15 to 55 kg·m Ϫ 2 ). Insulin resistance, defined as the lowest decile of insulin sensitivity in the lean subgroup (608 subjects with BMI Յ 25 kg·m Ϫ 2 ), was present in 26% of the obese subgroup (538 subjects with a mean BMI of 29 kg·m Ϫ 2 ). Insulin sensitivity declined linearly with BMI at an age-and sex-adjusted rate of 1.2 mol·min Ϫ 1 ·kg FFM Ϫ 1 per BMI unit (95% confidence intervals ϭ 1.0-1.4). Insulin hypersecretion, defined as the upper decile of IDR, was significantly ( P Ͻ 0.0001) more prevalent (38%) than insulin resistance in the obese group. In the whole dataset, IDR rose as a function of both BMI and insulin resistance in a nonlinear fashion. Neither the waist circumference nor the waistto-hip ratio, indices of body fat distribution, was related to insulin sensitivity after adjustment for age, gender, and BMI; both, however, were positively associated ( P Ͻ 0.001) with insulin hypersecretion, particularly in women.In nondiabetic, normotensive obese subjects, the prevalence of insulin resistance is relatively low, and is exceeded by the prevalence of insulin hypersecretion, particularly in women with central obesity. In the obese with preserved insulin sensitivity, risk for diabetes, cardiovascular risk, and response to treatment may be different than in insulin resistant obesity. ( J. Clin. Invest. 1997. 100:1166-1173.)

CYP7A1 genotypes and haplotypes associated with hypertension in an obese Han Chinese population

“…Visceral obesity and insulin resistance have a key role in the etiology of hypertension. 22 Excessive body fat might be detrimental not only because of the metabolic implications but also because adipose tissue seems to be active in the synthesis and release of cytokine-like molecules that may influence insulin action, endothelial function and inflammatory responses. 23 Our results show that the CYP7A1 À204A/C SNP was associated with hypertension in obese men, and that the CYP7A1 À204AA SNP could be an independent risk factor for hypertension in the presence of increased TG in obese subjects.…”

Trends in Cardiovascular Health Metrics in Obese Adults: National Health and Nutrition Examination Survey (NHANES), 1988–2014

“…Obese persons who are free from cardiovascular disease (CVD) risk factors, such as hypertension, dyslipidemia, and hyperglycemia, are relatively insulin sensitive 4, 5, 6, 7, 8, 9. Epidemiological data indicate low risk of progression to diabetes mellitus and CVD outcomes among such people compared with obese persons with risk factors10, 11, 12, 13, 14 but increased risk of diabetes mellitus compared with healthy lean persons.…”

Dissociation between albuminuria and insulinaemia in hypertensive and atherosclerotic men

“…Moreover, our negative conclusions cannot exclude that, as both in diabetic 23 and non-diabetic subjects, 16,19 renal excretion of albumin might be elevated in the presence of a greater degree of insulin resistance, perhaps because of its association with higher BP levels. 10 In fact, an exaggerated insulin response and lower tolerance to glucose load, somewhat increased body weight and hypertriglyceridaemia-in itself suggestive of insulin resistance 24 -characterised our patients. However, insulin sensitivity cannot be predicted easily from circulating levels because of the presence of a decreased insulin metabolic clearance in some essential hypertensives.…”

“…8 vs 9 To better understand how circulating insulin levels relate to albuminuria, plasma insulinaemic responses to oral glucose and UAE were measured in a group of carefully screened essential hypertensive and age-matched normal males. To allow any direct albuminuric effect of insulin to emerge more clearly independent of confounding pressormediated influences, 10 we also looked for a clinical condition in which hyperinsulinaemia may coexist with normal BP. For this reason, those same parameters were also evaluated in normotensive patients with atherosclerotic peripheral vascular disease (PVD) in whom hyperinsulinaemia could be anticipated on the basis of previous reports.…”