Inflammation, Insulin Resistance, and Adiposity

Abstract

OBJECTIVE -Inflammatory markers such as C-reactive protein (CRP) are associated with insulin resistance, adiposity, and type 2 diabetes. Whether inflammation causes insulin resistance or is an epiphenomenon of obesity remains unresolved. We aimed to determine whether first-degree relatives of type 2 diabetic subjects differ in insulin sensitivity from control subjects without a family history of diabetes, whether first-degree relatives of type 2 diabetic subjects and control subjects differ in CRP, adiponectin, and complement levels, and whether CRP is related to insulin sensitivity independently of adiposity.RESEARCH DESIGN AND METHODS -We studied 19 young normoglycemic nonobese first-degree relatives of type 2 diabetic subjects and 22 control subjects who were similar for age, sex, and BMI. Insulin sensitivity (glucose infusion rate [GIR]) was measured by the euglycemic-hyperinsulinemic clamp. Dual-energy X-ray absorptiometry determined total and abdominal adiposity. Magnetic resonance imaging measured abdominal adipose tissue volumes.RESULTS -First-degree relatives of type 2 diabetic subjects had a 20% lower GIR than the control group (51.8 Ϯ 3.9 vs. 64.9 Ϯ 4.6 mol ⅐ min Ϫ1 ⅐ kg fat-free mass Ϫ1 , P ϭ 0.04). However, first-degree relatives of subjects with type 2 diabetes and those without a family history of diabetes had normal and comparable levels of CRP, adiponectin, and complement proteins. When the cohort was examined as a whole, CRP was inversely related to GIR (r ϭ Ϫ0.33, P ϭ 0.04) and adiponectin (r ϭ Ϫ0.34, P ϭ 0.03) and positively related to adiposity (P Ͻ 0.04). However, CRP was not related to GIR independently of fat mass. In contrast to C3 (r ϭ 0.41, P ϭ 0.009) and factor B (r ϭ 0.43, P ϭ 0.005), CRP was unrelated to factor D.CONCLUSIONS -The insulin-resistant state is not associated with changes in inflammatory markers or complement proteins in subjects at high risk of type 2 diabetes. Our study confirms a strong relationship between CRP and fat mass. Increasing adiposity and insulin resistance may interact to raise CRP levels. Diabetes Care 27:2033-2040, 2004I nsulin resistance is fundamental to the pathogenesis of the metabolic syndrome and type 2 diabetes (1) and is a heritable trait (2). Type 2 diabetes is also strongly genetically determined (3). Consequently, first-degree relatives of subjects with type 2 diabetes demonstrate the metabolic accompaniments of insulin resistance before they develop overt diabetes (4). Because hyperglycemia further impairs both insulin action and insulin secretion (5), the study of primary metabolic defects leading to insulin resistance is best undertaken before insulin secretion begins to fail and blood glucose rises (6). In addition to genetic factors, excess body fat, particularly visceral fat, has been linked to the pathogenesis of insulin resistance and type 2 diabetes. We have reported that increased central adiposity is strongly related to reduced insulin sensitivity in subjects with and without firstdegree relatives with type 2 diabetes (7). Furthermo...

Impaired Fat Oxidation After a Single High-Fat Meal in Insulin-Sensitive Nondiabetic Individuals With a Family History of Type 2 Diabetes

“…In contrast to our previous studies, insulin sensitivity, as measured by the euglycemichyperinsulinemic clamp, was not significantly different between groups (Fig. 1) and may reflect that relatives presented and were studied at an earlier time point in the evolution of the disease process compared with previous volunteers (21). Serum factors.…”

“…On the first visit, subjects fasted for 10 h overnight, and body weight was measured in a hospital gown and height measured by a stadiometer. Insulin sensitivity was then measured by 2-h hyperinsulinemic-euglycemic clamp (50 mU/m 2 per min), according to previously described methods (21). Briefly, two intravenous cannula were inserted, one for infusion of regular insulin (Novo Nordisk, Baulkham Hills, NSW, Australia) and glucose (Baxter, Old Toongabbie, NSW, Australia), and the other was placed in the contralateral hand for blood withdrawal with the hand placed in a heating pad.…”

Selenium intake reduces serum C3, an early marker of metabolic syndrome manifestations, in healthy young adults

“…The correlations found between circulating concentrations of C3 and tricipital ST, sum of STs, BMI and body fat mass as well as the associations between serum C3 and BMI, waist circumference, waist-to-height ratio and body fat (Table 3) reveal that C3 is in some way related with several adiposity markers. These findings are in accordance with previous studies reporting the association between C3 and several adiposity measurements in healthy adolescents (Warnberg et al, 2006), obese adults (Gabrielsson et al, 2003) and type 2 diabetic subjects (Kriketos et al, 2004). Anthropometrical measurements, such as BMI (Halkes et al, 2001;Ylitalo et al, 2001;Onat et al, 2005), waist circumference (Halkes et al, 2001;Onat et al, 2005) and waist-to-hip ratio (Ylitalo et al, 2001), have been considered predictors of high C3 concentrations and have been related with higher expression in visceral than in subcutaneous white adipose tissue (Gabrielsson et al, 2003).…”

“…As C3 is associated with smoking status (Engstrom et al, 2005a), risk factors of obesity (Engstrom et al, 2005a), type 2 diabetes (Engstrom et al, 2005b), cardiovascular diseases (Onat et al, 2005) and several complications associated with inflammation (Kriketos et al, 2004) and inflammatory biomarkers (Halkes et al, 2001;Sampietro et al, 2004), C3 should be a good candidate as a marker of inflammation. However, we could not directly correlate smoking status neither physical activity with C3 concentrations although an effect of those variables was evident in our trial.…”

Brothers of women with polycystic ovary syndrome are characterised by impaired glucose tolerance, reduced insulin sensitivity and related metabolic defects

“…Our results are also comparable with the findings of reduced insulin sensitivity without evidence of inflammation (normal levels of hsCRP) in non-obese participants with two relatives with type 2 diabetes or one relative plus a personal history of gestational diabetes, compared with control individuals [41]. It has been estimated that 51% of participants with one first-degree relative affected with type 2 diabetes [42], and 76% of those with two affected firstdegree relatives [43], will ultimately develop type 2 diabetes.…”