Soluble CD36 and Risk Markers of Insulin Resistance and Atherosclerosis Are Elevated in Polycystic Ovary Syndrome and Significantly Reduced During Pioglitazone Treatment

Abstract

OBJECTIVE -We investigated the relation between soluble CD36 (sCD36), risk markers of atherosclerosis and body composition, and glucose and lipid metabolism in polycystic ovary syndrome (PCOS).RESEARCH DESIGN AND METHODS -Thirty PCOS patients were randomized to 30 mg/day pioglitazone or placebo for 16 weeks. Fourteen weight-matched healthy female subjects were included as control subjects. sCD36, oxidized LDL (oxLDL), high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, euglycemic-hyperinsulinemic clamps, and whole-body dual-energy X-ray absorptiometry scans were performed. were significantly increased in PCOS patients versus control subjects (geometric mean Ϯ 2 SD). In PCOS, positive correlations were found between central fat mass and sCD36 (r ϭ 0.43), hsCRP (r ϭ 0.43), and IL-6 (r ϭ 0.42) (all P Ͻ 0.05). After adjusting for fat mass, sCD36 and oxLDL correlated inversely with measures of insulinstimulated glucose metabolism and positively with lipid oxidation during insulin stimulation in PCOS patients and control subjects (n ϭ 44). sCD36 and oxLDL were significant independent predictors of glucose and lipid metabolism, whereas hsCRP and IL-6 showed no significant contribution. RESULTSFollowing pioglitazone treatment, insulin sensitivity increased, whereas sCD36 (3.21 relative units [0.76 -13.6] vs. 2.33 relative units [0.84 -6.46]) and hsCRP decreased (P Ͻ 0.05). No significant changes were measured in body composition.CONCLUSIONS -sCD36 and oxLDL correlated with measures of insulin sensitivity independent of central fat mass. Pioglitazone treatment reduced sCD36 while improving insulinstimulated glucose metabolism, further supporting the association between sCD36 and insulin resistance in PCOS. Diabetes Care 31:328-334, 2008P olycystic ovary syndrome (PCOS) is characterized by anovulation, hyperandrogenemia, and/or polycystic ovaries. About 50% of PCOS patients fulfill the criteria of the metabolic syndrome. A five-to eightfold increased risk for type 2 diabetes in PCOS patients compared with weight-matched female control subjects makes the syndrome of high socioeconomic importance (1). Previous studies found significantly increased risk of hypertension and coronary heart disease in women with irregular cycles, suggesting a 4-to 11-fold increased risk for coronary heart disease (2). Increased risk factors for coronary heart disease in PCOS patients were documented in several previous studies, including atherogenic lipid profiles, increased coronary artery calcification, and echocardiographic abnormalities (3).Abdominal obesity is seen in overweight and in most normal-weight PCOS patients. Abdominal obesity, especially visceral adiposity, is associated with insulin resistance and increased levels of inflammatory markers including highsensitive C-reactive protein (hsCRP) and cytokines. Previous studies (4,5) reported higher levels of inflammatory markers in PCOS patients compared with weightmatched control subjects.CD36 is expressed on the surface of monoytes and macrophages (6). CD36 may initiate ...

Circulating soluble CD36 is associated with glucose metabolism and interleukin-6 in glucose-intolerant men

“…15 Elevated monocyte CD36 in ob/ob diabetic mice was proposed to result from a compromised insulin signal. 16 We have previously reported negative associations between circulating sCD36 and insulin sensitivity in type 2 diabetic patients, and in obese subjects 13 and women with polycystic ovary syndrome (PCOS), 17 both groups having normal glucose tolerance. Our present finding that sCD36 is negatively associated with insulin sensitivity in glucose-intolerant subjects only indicates that when insulin sensitivity decreases it is reflected by higher sCD36 levels.…”

“…13,17 Macrophage infiltration of the subendothelial space as a result of accumulation of oxidised cholesterol, among other factors, 15,26,27 may create a systemic low-grade inflammatory state that promotes atherogenesis. Elevated sCD36 in insulin-resistant states might thus represent a marker of the accelerated fat accumulation in the vessel wall.…”

MANAGEMENT OF ENDOCRINE DISEASE: Morbidity in polycystic ovary syndrome

“…Whether HbA1c is superior to OGTT regarding long-term metabolic and cardiovascular risk in PCOS must be established in prospective studies. It was estimated that 70% newly diagnosed women with PCOS had borderline or high lipid levels (33), including increased total cholesterol, TG, LDL or decreased HDL levels (34,35). In a Danish study population with median BMI 27 kg/m 2 , 41% patients with PCOS had HDL <1.29 mmol/L and 21% patients had TG >1.68 mmol/L (36).…”

Is plasma-soluble CD36 associated with density of atheromatous plaque and ankle–brachial index in early-onset coronary artery disease patients?

“…Tontonoz et al [9] hypothesised that decreased sCD36 level is a result of lower activity of endogenous peroxisome proliferator-activated receptor gamma (PPARg). Plasma CD36 is released into circulation during cell apoptosis, such as that taking place after cholesterol accumulation in foam cells [10,11]. Positive association of plasma sCD36 concentration with insulin resistance has been reported, and it has been proposed that sCD36 might represent a marker of macrophage activation and inflammation leading to atherosclerosis [12,13].…”