The Adiponectin Paradox for All-Cause and Cardiovascular Mortality (original) (raw)
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Cardiovascular Diabetology, 2016
Background: Despite its beneficial role on insulin resistance and atherosclerosis, adiponectin has been repeatedly reported as an independent positive predictor of cardiovascular mortality. Methods: A Mendelian randomization approach was used, in order to evaluate whether such counterintuitive association recognizes a cause-effect relationship. To this purpose, single nucleotide polymorphism rs822354 in the ADIPOQ locus which has been previously associated with serum adiponectin at genome-wide level, was used as an instrument variable. Our investigation was carried out in the Gargano Heart Study-prospective design, comprising 356 patients with type 2 diabetes, in whom both total and high molecular weight (HMW) adiponectin were measured and cardiovascular mortality was recorded (mean follow-up = 5.4 ± 2.5 years; 58 events/1922 person-year). Results: The A allele of rs822354 was associated with both total and HMW adiponectin [β (SE) = 0.10 (0.042), p = 0.014 and 0.17 (0.06), p = 0.003; respectively]. In a Poisson model comprising age, sex, smoking habits, BMI, HbA1c, total cholesterol, HDL-cholesterol, triglycerides, insulin therapy and hypertension, both rs822354 (IRR = 1.94, 95 % CI 1.23-3.07; p = 0.005), as well as the genetic equivalent of total adiponectin change (IRR = 1.07, 95 % CI 1.02-1.12; p = 0.003) were significantly associated with cardiovascular mortality. The observed genetic effect was significantly greater than that exerted by the genetic equivalent change of serum adiponectin (p for IRR heterogeneity = 0.012). In the above-mentioned adjusted model, very similar results were obtained when HMW, rather than total, adiponectin was used as the exposure variable of interest. Conclusions: Our data suggest that the paradoxical association between high serum adiponectin levels and increased cardiovascular mortality rate is based on a cause-effect relationship, thus pointing to an unexpected deleterious role of adiponectin action/metabolism on atherosclerotic processes.
Adiponectin and All-Cause Mortality in Elderly People With Type 2 Diabetes
Diabetes Care, 2012
OBJECTIVEdTo assess the association between serum adiponectin level and all-cause mortality in people with type 2 diabetes. Because of the insulin-sensitizing, anti-inflammatory, and antiatherogenic effects of adiponectin, we hypothesized that higher adiponectin level would be associated with lower all-cause mortality.
European Journal of Endocrinology, 2006
Objectives: Adiponectin has insulin-sensitizing properties, and high adiponectin levels have been shown to be associated with reduced risk of developing diabetes. Patients with coronary artery disease (CAD) have relatively low adiponectin levels and high prevalence of glucose intolerance. The role of adiponectin in predicting the development of diabetes in this high-risk group has not been determined. The study aimed to determine whether baseline adiponectin levels predict the development of diabetes in a group of patients with CAD and impaired fasting glucose (IFG). Methods: A total of 588 patients who participated in the Bezafibrate Infarction Prevention (BIP) study and who had at baseline fasting glucose of 100 -125 mg/dl were included and followed for 6.2^1.3 years. Adiponectin was determined in frozen plasma samples taken at baseline. Results: Of the patients with IFG at baseline, 256 (44%) developed diabetes during follow-up. The patients who developed diabetes had at baseline higher body-mass index, fasting glucose, C-reactive protein, triglycerides, homeostatic assessment of insulin resistance (HOMA-IR) and diastolic blood pressure than patients who did not develop diabetes. Adiponectin levels at baseline were significantly lower in patients who developed diabetes than in patients who did not develop diabetes (P ¼ 0.009, nonparametric Kruskall -Wallis test). An increase of 1 unit of natural logarithm of adiponectin level was associated with a hazard ratio of 0.77 (95% CI, 0.61-0.96) for diabetes development. Conclusion: Patients with CAD and IFG have a very high rate of conversion to type 2 diabetes. Even in this high-risk group, high adiponectin levels are associated with reduced risk of developing diabetes.
Journal of Internal Medicine, 2011
Forsblom C, Thomas MC, Moran J, Saraheimo M, Thorn L, Wadén J, Gordin D, Frystyk J, Flyvbjerg A, Groop P-H, on behalf of the FinnDiane Study
British Journal of Pharmacology, 2016
Adipose tissue (AT) has recently been identified as a dynamic endocrine organ secreting a wide range of adipokines. Adiponectin is one such hormone, exerting endocrine and paracrine effects on the cardiovascular system. At a cellular and molecular level, adiponectin has anti-inflammatory, anti-oxidant and anti-apoptotic roles, thereby mitigating key mechanisms underlying cardiovascular disease (CVD) pathogenesis. However, adiponectin expression in the human AT as well as its circulating levels are increased in advanced CVD states, and it is actually considered by many as a "rescue hormone". Due to the complex mechanisms regulating adiponectin's biosynthesis in the human AT, measurement of its levels as a biomarker in CVD is highly controversial, given that it exerts protective effects on the cardiovascular system but at the same time its increased levels flag advanced CVD. In this review article we present the role of adiponectin in CVD pathogenesis and we discuss its role as a clinical biomarker.
Adiponectin and Cardiovascular Disease
Circulation Journal, 2009
Adiponectin is a protein secreted specifically by adipose cells that may couple regulation of insulin sensitivity with energy metabolism and serve to link obesity with insulin resistance. Obesity-related disorders including the metabolic syndrome, diabetes, atherosclerosis, hypertension, and coronary artery disease are associated with decreased plasma levels of adiponectin, insulin resistance, and endothelial dysfunction. Adiponectin has insulinsensitizing effects as well as antiatherogenic properties. Lifestyle modifications and some drug therapies to treat atherosclerosis, hypertension, and coronary heart disease have important effects to simultaneously increase adiponectin levels, decrease insulin resistance, and improve endothelial dysfunction. In this review, we discuss insights into the relationships between adiponectin levels, insulin resistance, and endothelial dysfunction that are derived from various therapeutic interventions. The effects of lifestyle modifications and cardiovascular drugs on adiponectin levels and insulin resistance suggest plausible mechanisms that may be important for treating atherosclerosis and coronary heart disease. (J Am Coll Cardiol 2007;49:531-8)
Association of Adiponectin with Coronary Heart Disease and Mortality: The Rancho Bernardo Study
American Journal of Epidemiology, 2006
Hypoadiponectinemia has been implicated in the development of obesity-related conditions, including dyslipidemia and coronary heart disease (CHD). In this study, the authors examined the association of adiponectin with CHD prevalence, incidence, and mortality among 1,513 community-dwelling men and women aged 50-91 years who were followed from 1984-1987 through 2004. In cross-sectional analyses, adiponectin concentrations were positively related to female sex, age, and high density lipoprotein cholesterol level and inversely related to waist girth, triglyceride level, and fasting plasma glucose level (all p's < 0.001). Adiponectin levels in the highest sex-specific quintile, as compared with the lowest, were associated with 44% decreased odds of prevalent CHD (p for trend ¼ 0.03); adjustment for high density lipoprotein cholesterol and/or triglycerides eliminated this association. In 20-year prospective analyses, higher adiponectin concentrations predicted reduced risk of nonfatal myocardial infarction in men only; adiponectin was not associated with fatal incident CHD events or 20-year CHD mortality (n ¼ 215 deaths) in either sex. Adiponectin levels in the highest sex-specific quintile, as compared with lower levels, were associated with almost 40% increased risks of cardiovascular disease death (n ¼ 441) and death from all causes (n ¼ 925), independent of age, sex, waist girth, lipid levels, and glucose level (both p's < 0.001). These results suggest that use of adiponectin for cardiovascular disease risk stratification is premature. adiponectin; cardiovascular diseases; coronary disease; mortality Abbreviations: CHD, coronary heart disease; HDL, high density lipoprotein.
Insights Into the Controversial Aspects of Adiponectin in Cardiometabolic Disorders
Hormone and Metabolic Research
In 2016, the World Health Organization estimated that more than 1.9 billion adults were overweight or obese. This impressive number shows that weight excess is pandemic. Overweight and obesity are closely associated with a high risk of comorbidities, such as insulin resistance and its most important outcomes, including metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Adiponectin has emerged as a salutary adipocytokine, with insulin-sensitizing, anti-inflammatory, and cardiovascular protective properties. However, under metabolically unfavorable conditions, visceral adipose tissue-derived inflammatory cytokines might reduce the transcription of the adiponectin gene and consequently its circulating levels. Low circulating levels of adiponectin are negatively associated with various conditions, such as insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. In contrast, several recent clinical trials and meta-analyses have ...
Adiponectin and the Development of Type 2 Diabetes: The Atherosclerosis Risk in Communities Study
Diabetes, 2004
Adipocyte-derived secretory proteins have been increasingly linked to diabetes. To investigate whether adiponectin, a major adipocyte secretory protein, predicts diabetes, we conducted a case-cohort study representing the ϳ9-year experience of the 10,275 middle-aged, U.S. African-American and white participants of the Atherosclerosis Risk in Communities (ARIC) study. Adiponectin was measured on stored plasma of 581 incident diabetes case subjects and 572 noncase subjects. Overall hazard ratios (95% CIs) for developing diabetes, for those in the second, third, and fourth (versus the first) quartile of adiponectin were 0.57 (0.41-0.78), 0.39 (0.27-0.56), and 0.18 (0.11-0.27), respectively, after adjustment for age, sex, ethnicity, study center, parental history of diabetes, and hypertension and 0.72 , respectively, after additional adjustment for BMI, waist-to-hip ratio, fasting glucose, insulin, and a score composed of six inflammation markers. The association was of similar magnitude in men and women and in whites and African Americans, but was absent in smokers and in those with a greater inflammation score (interaction P < 0.01 for each). In conclusion, in this community-based sample of U.S. adults, higher adiponectin levels were associated with a lower incidence of diabetes.