Circulating adiponectin levels are associated with better glycemic control, more favorable lipid profile, and reduced inflammation in women with type 2 diabetes.

CONTEXT Low adiponectin levels, by regulating insulin resistance and metabolic profile, may contribute to the markedly increased risk of atherosclerosis in diabetic subjects. OBJECTIVE The complex interrelationships between adiponectin and metabolic abnormalities have not yet been fully assessed in diabetic women. DESIGN/SETTING/PATIENTS We performed a cross-sectional evaluation of the association between circulating adiponectin and glycemia, lipid-lipoprotein levels, and inflammatory markers in 925 women with type 2 diabetes enrolled in the Nurses' Health Study. RESULTS Circulating adiponectin levels were significantly and positively associated with high-density lipoprotein (HDL) cholesterol and physical activity levels, and inversely with body mass index and plasma concentrations of hemoglobin A1c (HgbA1c), triglycerides, non-HDL cholesterol, apolipoprotein B-100, C-reactive protein, fibrinogen, soluble E-selectin, and soluble intercellular adhesion molecule-1. The above associations were not appreciably altered after adjusting for lifestyle factors, existing medical conditions, obesity, and body fat distribution, with the exception of HgbA1c and soluble intercellular adhesion molecule-1 (which became nonsignificant). Associations between adiponectin and inflammatory markers persisted after control for the potential confounding effects of HgbA1C and HDL cholesterol, suggesting that the antiinflammatory properties of adiponectin are not mediated by its effect on glycemia and lipidemia. With the exception of the associations with triglycerides and apolipoprotein B100, which were significant only in subjects with body mass index less than 30, all other associations observed herein were consistent among obese and nonobese diabetic women. CONCLUSIONS In summary, higher adiponectin levels are associated with better glycemic control, more favorable lipid profile, and reduced inflammation in diabetic women.

[1]  J. Manson,et al.  Adiposity as compared with physical activity in predicting mortality among women. , 2005, The New England journal of medicine.

[2]  R. Eckel,et al.  The metabolic syndrome and inflammation. , 2004, Metabolic syndrome and related disorders.

[3]  C. Mantzoros,et al.  Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes. , 2004, Diabetes care.

[4]  J. Manson,et al.  Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction. , 2004, The American journal of clinical nutrition.

[5]  E. Rimm,et al.  Relationship between adiponectin and glycemic control, blood lipids, and inflammatory markers in men with type 2 diabetes. , 2004, Diabetes care.

[6]  T. Funahashi,et al.  Plasma adiponectin, insulin sensitivity, and subclinical inflammation in women with prior gestational diabetes mellitus. , 2004, Diabetes care.

[7]  J. Chan,et al.  Serum adiponectin levels are inversely associated with overall and central fat distribution but are not directly regulated by acute fasting or leptin administration in humans: cross-sectional and interventional studies. , 2003, The Journal of clinical endocrinology and metabolism.

[8]  P. Elder,et al.  Plasma adiponectin in overweight, nondiabetic individuals with or without insulin resistance , 2003, Diabetes, obesity & metabolism.

[9]  R. Henry,et al.  Adiponectin: more than just another fat cell hormone? , 2003, Diabetes care.

[10]  M. Igarashi,et al.  Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese Population: the Funagata study. , 2003, Diabetes care.

[11]  U. Müller-Ladner,et al.  Adiponectin represents an independent cardiovascular risk factor predicting serum HDL‐cholesterol levels in type 2 diabetes , 2003, FEBS letters.

[12]  T. Funahashi,et al.  Inflammatory markers, adiponectin, and risk of type 2 diabetes in the Pima Indian. , 2003, Diabetes care.

[13]  J. Fernández-Real,et al.  Novel interactions of adiponectin with the endocrine system and inflammatory parameters. , 2003, The Journal of clinical endocrinology and metabolism.

[14]  M. Cnop,et al.  Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex , 2003, Diabetologia.

[15]  N. Al-Daghri,et al.  Fasting serum adiponectin concentration is reduced in Indo‐Asian subjects and is related to HDL cholesterol , 2003, Diabetes, obesity & metabolism.

[16]  NoriyukiOuchi,et al.  Reciprocal Association of C-Reactive Protein With Adiponectin in Blood Stream and Adipose Tissue , 2003 .

[17]  M. Stumvoll,et al.  Plasma adiponectin concentrations predict insulin sensitivity of both glucose and lipid metabolism. , 2003, Diabetes.

[18]  C. Mantzoros,et al.  Hypoadiponectinemia is associated with insulin resistance, hypertriglyceridemia, and fat redistribution in human immunodeficiency virus-infected patients treated with highly active antiretroviral therapy. , 2003, The Journal of clinical endocrinology and metabolism.

[19]  H. Boeing,et al.  Adiponectin and protection against type 2 diabetes mellitus , 2003, The Lancet.

[20]  S. Kihara,et al.  Adiponectin Reduces Atherosclerosis in Apolipoprotein E-Deficient Mice , 2002, Circulation.

[21]  R. Marfella,et al.  Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans: Role of Oxidative Stress , 2002, Circulation.

[22]  M. Matsuda,et al.  Role of Adiponectin in Preventing Vascular Stenosis , 2002, The Journal of Biological Chemistry.

[23]  E. Rimm,et al.  The impact of diabetes mellitus and prior myocardial infarction on mortality from all causes and from coronary heart disease in men. , 2002, Journal of the American College of Cardiology.

[24]  S. Maruoka,et al.  Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. , 2002, European journal of endocrinology.

[25]  T. Saruta,et al.  Correlation of the adipocyte-derived protein adiponectin with insulin resistance index and serum high-density lipoprotein-cholesterol, independent of body mass index, in the Japanese population. , 2002, Clinical science.

[26]  Philippe Froguel,et al.  Disruption of Adiponectin Causes Insulin Resistance and Neointimal Formation* , 2002, The Journal of Biological Chemistry.

[27]  Jonathan Krakoff,et al.  Adiponectin and development of type 2 diabetes in the Pima Indian population , 2002, The Lancet.

[28]  C. Kahn,et al.  Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance. , 2002, Developmental cell.

[29]  M. Matsuda,et al.  Diet-induced insulin resistance in mice lacking adiponectin/ACRP30 , 2002, Nature Medicine.

[30]  C. Bogardus,et al.  Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. , 2002, Diabetes.

[31]  H. Lodish,et al.  ACRP30, a new hormone controlling fat and glucose metabolism. , 2002, European journal of pharmacology.

[32]  P. Scherer,et al.  The adipocyte-secreted protein Acrp30 enhances hepatic insulin action , 2001, Nature Medicine.

[33]  Y. Terauchi,et al.  The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity , 2001, Nature Medicine.

[34]  T. Funahashi,et al.  Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. , 2001, Diabetes.

[35]  NoriyukiOuchi,et al.  Adiponectin, an Adipocyte-Derived Plasma Protein, Inhibits Endothelial NF-&kgr;B Signaling Through a cAMP-Dependent Pathway , 2000, Circulation.

[36]  S. Kihara,et al.  Adiponectin, an Adipocyte-Derived Plasma Protein, Inhibits Endothelial NF-&kgr;B Signaling Through a cAMP-Dependent Pathway , 2000, Circulation.

[37]  S. Kihara,et al.  Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. , 2000, Blood.

[38]  NoriyukiOuchi,et al.  Novel Modulator for Endothelial Adhesion Molecules , 1999 .

[39]  G. Assmann,et al.  HDL3-mediated inhibition of thrombin-induced platelet aggregation and fibrinogen binding occurs via decreased production of phosphoinositide-derived second messengers 1,2-diacylglycerol and inositol 1,4,5-tris-phosphate. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[40]  M. Raftery,et al.  Oxidation of High Density Lipoproteins , 1998, The Journal of Biological Chemistry.

[41]  Y. Nakano,et al.  Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. , 1996, Journal of biochemistry.

[42]  F. Numano,et al.  Glucose-Dependent Interleukin 6 and Tumor Necrosis Factor Production by Human Peripheral Blood Monocytes In Vitro , 1996, Diabetes.

[43]  J. Manson,et al.  A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. , 1991, Archives of internal medicine.

[44]  H. White.  A Heteroskedasticity-Consistent Covariance Matrix Estimator and a Direct Test for Heteroskedasticity , 1980 .

[45]  J. Manson,et al.  Genetic variation at the adiponectin locus and risk of type 2 diabetes in women. , 2004, Diabetes.

[46]  A. Kappes,et al.  DECREASED PLASMA ADIPONECTIN CONCENTRATIONS IN WOMEN WITH DYSLIPIDEMIA , 2002 .

[47]  Teven,et al.  MORTALITY FROM CORONARY HEART DISEASE IN SUBJECTS WITH TYPE 2 DIABETES AND IN NONDIABETIC SUBJECTS WITH AND WITHOUT PRIOR MYOCARDIAL INFARCTION , 2000 .