Associations of Adiponectin Levels With Incident Impaired Glucose Metabolism and Type 2 Diabetes in Older Men and Women

Abstract

OBJECTIVE -Adiponectin is an adipose tissue-derived protein. Low levels are associated with obesity, insulin resistance, and type 2 diabetes. Our objective was to investigate the prospective association between adiponectin levels and the 6.4-year risk of type 2 diabetes and of impaired glucose metabolism (IGM). RESEARCH DESIGN AND METHODS -The Hoorn Study is a cohort study amongCaucasians, aged 50 -75 years. BMI, waist-to-hip ratio (WHR), fasting glucose, 2-h glucose, triglycerides, HDL cholesterol, LDL cholesterol, alanine aminotransferase, leptin, and adiponectin were measured at baseline. Lifestyle (alcohol intake, smoking, and physical activity) was assessed by questionnaires. After a mean follow-up of 6.4 years, glucose tolerance was assessed by a 75-g oral glucose tolerance test. Analyses were performed in 1,264 subjects (584 men and 680 women) without type 2 diabetes at baseline. For analyses of incident IGM, 239 subjects with IGM at baseline and/or type 2 diabetes at follow-up were excluded. RESULTS CONCLUSIONS-A high adiponectin level was strongly associated with a lower risk of IGM and type 2 diabetes, particularly in women. These results suggest that adiponectin is involved in the pathophysiology linking obesity to type 2 diabetes. Diabetes Care 29:2498 -2503, 2006T he pathophysiology linking obesity to type 2 diabetes is not completely understood, but adipokines are thought to be involved (1). Adiponectin is a recently discovered protein that seems to be exclusively secreted by adipocytes and is the most abundant adipose tissuederived protein (2,3). In contrast to other adipokines (such as leptin and interleukin-6) that are often elevated in obese subjects, adiponectin is reduced (3-6).In animal studies, adiponectin has been shown to have insulin-sensitizing properties. Adiponectin knockout mice are insulin resistant in a gene-dose fashion (7,8). Overexpression of adiponectin prevented diabetes in transgenic mice (9), and administration of adiponectin reversed insulin resistance in various mouse models of obesity and diabetes (10). Adiponectin increased insulin action via effects on hepatic glucose production and by increasing fat oxidation and lowering circulating free fatty acids (10 -13).In humans, several cross-sectional studies showed that adiponectin correlates negatively with measures of insulin resistance and type 2 diabetes, but cause or consequence cannot be distinguished. Results from a few prospective studies suggest that a low adiponectin level is predictive of insulin resistance or diabetes in Pima Indians (14), Asian Indians (15), and Japanese subjects (16,17). Some of these studies are rather small (14,15) or had a short follow-up period (15,17). To our knowledge, the only prospective study in Caucasians was a nested casecontrol study based on self-reported diabetes after a follow-up of 2-3 years (18). All of these previous prospective studies were performed in relatively young subjects.The objective of the present study was to investigate the association between adiponectin and subs...

Sex differences during the course of diet-induced obesity in mice: adipose tissue expandability and glycemic control

“…34,53,54 In fact, female mice consistently showed much higher levels of adiponectin in plasma compared with males, including the biologically active HMW form, 47 and this feature was independent of the type of diet, expression of inflammatory markers in adipose tissue and duration of HF feeding. These results are in accordance with other animal 36,55,56 as well as human 57,58 studies showing higher adiponectin levels in females and suggesting involvement of adipose tissue expandability in the beneficial metabolic effects of adiponectin. 36 .…”

Variations in Adiponectin Receptor Genes and Susceptibility to Type 2 Diabetes in Women

“…It has also been documented that adiponectin concentrations were higher in women than in men (34). A recent study suggests that the associations between circulating adiponectin levels and diabetes risk may be different in men and women (35). In addition, body fat may affect the expression of adiponectin and ADIPORs (29,36).…”

Effects of the traditional Mediterranean diet on adiponectin and leptin concentrations in men and premenopausal women: do sex differences exist?

“…Moreover, the fullycontrolled nature of the nutritional phase permitted to document sex differences in adipocytokine responses to the MedDiet with a maximum of control over confounding variables. In addition, since previous studies have suggested that associations between these adipocytokines and cardiovascular risk factors may be sex-specific 5,6,12,13 , the inclusion of both men and premenopausal women allowed us to document for the first time sex-related differences in these associations in response to the MedDiet. On the other hand, one limitation of the present study is the absence of a control diet, which limits the conclusions on true treatment effects.…”

“…Moreover, some previous studies have found sex-related differences in the link between these adipose tissuederived hormones and the development of type 2 diabetes. In fact, the association between leptin concentrations and type 2 diabetes has been shown to be stronger in men than in women 5,6 while adiponectin concentrations would be more closely associated with type 2 diabetes in women than in men 12 . Sex-related differences have also been found in the relationship between blood concentrations of these adipocytokines and markers of cardiovascular risk 11,13 .…”