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      Adiponectin is Associated with Impaired Fasting Glucose in the Non-Diabetic Population

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          Abstract

          OBJECTIVES

          Adiponectin is strongly associated with diabetes in the Western population. However, whether adiponectin is independently associated with impaired fasting glucose (IFG) in the non-obese population is unknown.

          METHODS

          The serum adiponectin, insulin resistance (IR), and waist circumference (WC) of 27,549 healthy Koreans were measured. Individuals were then classified into tertile groups by gender. IFG was defined as a fasting serum glucose of 100-125 mg/dL without diabetes. IR was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). The association of adiponectin and IFG was determined using logistic regression analysis.

          RESULTS

          WC and adiponectin were associated with IFG in both men and women. However, the association of WC with IFG was attenuated in both men and women after adjustment for the HOMA-IR. Adiponectin was still associated with IFG after adjustment for and stratification by HOMA-IR in men and women. Strong combined associations of IR and adiponectin with IFG were observed in men and women. Multivariate adjusted odds ratios (ORs) (95% confidence interval [CI]) among those in the highest tertile of IR and the lowest tertile of adiponectin were 9.8 (7.96 to 12.07) for men and 24.1 (13.86 to 41.94) for women.

          CONCLUSION

          These results suggest that adiponectin is strongly associated with IFG, and point to adiponectin as an additional diagnostic biomarker of IFG in the non-diabetic population.

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          Most cited references28

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          Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.

          C Weyer, T. Funahashi, S. Tanaka … (2001)
          Plasma concentrations of adiponectin, a novel adipose-specific protein with putative antiatherogenic and antiinflammatory effects, were found to be decreased in Japanese individuals with obesity, type 2 diabetes, and cardiovascular disease, conditions commonly associated with insulin resistance and hyperinsulinemia. To further characterize the relationship between adiponectinemia and adiposity, insulin sensitivity, insulinemia, and glucose tolerance, we measured plasma adiponectin concentrations, body composition (dual-energy x-ray absorptiometry), insulin sensitivity (M, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) in 23 Caucasians and 121 Pima Indians, a population with a high propensity for obesity and type 2 diabetes. Plasma adiponectin concentration was negatively correlated with percent body fat (r = -0.43), waist-to-thigh ratio (r = -0.46), fasting plasma insulin concentration (r = -0.63), and 2-h glucose concentration (r = -0.38), and positively correlated with M (r = 0.59) (all P < 0.001); all relations were evident in both ethnic groups. In a multivariate analysis, fasting plasma insulin concentration, M, and waist-to-thigh ratio, but not percent body fat or 2-h glucose concentration, were significant independent determinates of adiponectinemia, explaining 47% of the variance (r(2) = 0.47). Differences in adiponectinemia between Pima Indians and Caucasians (7.2 +/- 2.6 vs. 10.2 +/- 4.3 microg/ml, P < 0.0001) and between Pima Indians with normal, impaired, and diabetic glucose tolerance (7.5 +/- 2.7, 6.1 +/- 2.0, 5.5 +/- 1.6 microg/ml, P < 0.0001) remained significant after adjustment for adiposity, but not after additional adjustment for M or fasting insulin concentration. These results confirm that obesity and type 2 diabetes are associated with low plasma adiponectin concentrations in different ethnic groups and indicate that the degree of hypoadiponectinemia is more closely related to the degree of insulin resistance and hyperinsulinemia than to the degree of adiposity and glucose intolerance.
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            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.

            K. Hotta, T. Funahashi, N L Bodkin … (2001)
            Adiponectin is an adipose-specific plasma protein whose plasma concentrations are decreased in obese subjects and type 2 diabetic patients. This protein possesses putative antiatherogenic and anti-inflammatory properties. In the current study, we have analyzed the relationship between adiponectin and insulin resistance in rhesus monkeys (Macaca mulatta), which spontaneously develop obesity and which subsequently frequently progress to overt type 2 diabetes. The plasma levels of adiponectin were decreased in obese and diabetic monkeys as in humans. Prospective longitudinal studies revealed that the plasma levels of adiponectin declined at an early phase of obesity and remained decreased after the development of type 2 diabetes. Hyperinsulinemic-euglycemic clamp studies revealed that the obese monkeys with lower plasma adiponectin showed significantly lower insulin-stimulated peripheral glucose uptake (M rate). The plasma levels of adiponectin were significantly correlated to M rate (r = 0.66, P < 0.001). Longitudinally, the plasma adiponectin decreased in parallel to the progression of insulin resistance. No clear association was found between the plasma levels of adiponectin and its mRNA levels in adipose tissue. These results suggest that reduction in circulating adiponectin may be related to the development of insulin resistance.
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              The natural history of progression from normal glucose tolerance to type 2 diabetes in the Baltimore Longitudinal Study of Aging.

              Kelly D Blake, , Frank-Michael Müller … (2003)
              The natural history of progression from normal glucose tolerance (NGT) to impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes is not well defined. We studied this progression using biennial oral glucose tolerance tests performed in the Baltimore Longitudinal Study of Aging and survival analysis to assess progression from NGT to abnormal fasting plasma glucose (FPG; > or =6.1 mmol/l), abnormal 2-h plasma glucose (2hPG; > or =7.8 mmol/l), IFG (FPG 6.1-6.9 mmol/l, 2hPG or =7.0 mmol/l or 2hPG > or =11.1 mmol/l). At baseline, the 815 subjects had a mean age of 57 years, 35% were women, and 60% had NGT. Of the 488 subjects with NGT, over half were followed for at least 10 years. By 10 years, 14% had progressed to abnormal FPG and 48% to abnormal 2hPG. Of the 267 subjects who progressed to IFG-IGT, 216 had additional follow-up. By 10 years, 8% of these progressed to diabetes by FPG whereas 27% progressed by 2hPG. In subsidiary analyses, we defined "abnormal" FPG as > or =5.55 mmol/l and "diabetic" FPG as > or =6.1 mmol/l, making the baseline prevalence of IFG similar to that of IGT. By these criteria, 43% progressed to abnormal FPG and 43% to abnormal 2hPG by 10 years of follow-up; among subjects developing impaired FPG or 2hPG, 22% progressed to diabetes by FPG whereas 17% progressed by 2hPG at 10 years. Nonetheless, 42% of subjects developing abnormal FPG did not develop abnormal 2hPG, and vice versa. We conclude that, although phenotypic differences in rates of progression are partly a function of diagnostic thresholds, fasting and postchallenge hyperglycemia may represent phenotypes with distinct natural histories in the evolution of type 2 diabetes.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Epidemiol Health
                Journal ID (publisher-id): EPIH
                Title: Epidemiology and Health
                Publisher: Korean Society of Epidemiology
                ISSN (Electronic): 2092-7193
                Publication date Collection: 2011
                Publication date (Electronic): 20 August 2011
                Volume: 33
                Electronic Location Identifier: e2011007
                Affiliations
                [1 ]Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea.
                [2 ]Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea.
                [3 ]Department of Food and Nutrition and Research Institute of Obesity Sciences, Sungshin Women's University, Seoul, Korea.
                [4 ]Division of Cardiology, Department of Internal Medicine, Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
                Author notes
                Correspondence: Sun Ha Jee, MPH, PhD. Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, 250 Seongsan-ro, Seodaemun-gu, Seoul 120-752, Korea. Tel: +82-2-2228-1523, Fax: +82-2-365-5118, jsunha@ 123456yuhs.ac
                Article
                DOI: 10.4178/epih/e2011007
                PMC ID: 3163270
                PubMed ID: 21909476
                SO-VID: 014c2480-ed76-4877-8cff-08981c1e50a6
                Copyright © © 2011, Korean Society of Epidemiology
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 22 March 2011
                Date accepted : 08 July 2011
                Categories
                Subject: Original Article

                ScienceOpen disciplines: Public health
                Keywords: diabetes,impaired fasting glucose,adiponectin,insulin resistance
                Data availability:
                ScienceOpen disciplines: Public health
                Keywords: diabetes, impaired fasting glucose, adiponectin, insulin resistance

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