Beta Cell Function, Insulin Resistance and Plasma Adiponectin Concentrations are Predictors for the Change of Postprandial Glucose in Non-diabetic Subjects at Risk for Type 2 Diabetes

Abstract

Insulin resistance, impaired insulin secretion, and low adiponectin levels have been shown to be predictors for type 2 diabetes. However, it is not yet clear whether these associations (1) are independent of changes in body weight, or (2) are valid for changes in glucose tolerance in the prediabetic state. Sixty-two non-diabetics (50 with normal glucose tolerance) aged 41 ± 11 years, BMI 30.5 ± 5.3 kg/m² (mean ± SD) were studied twice with a standard oral glucose tolerance test (oGTT, mean follow-up time 3.0 ± 1.8 years (mean ± SD) [range 0.5 - 6.5 years]). Insulin sensitivity and insulin secretion were estimated from oGTT using validated indices. Two-hour blood glucose during oGTT deteriorated over time (baseline 2 h glucose 6.32 ± 0.21 vs. follow-up 2 h glucose 7.14 ± 0.22 mM, p < 0.001) while the percentage body fat did not change (32.7 ± 1.2 vs. 32.6 ± 1.2 %, p = 0.46). Follow-up 2 h blood glucose was predicted by adiponectin (p = 0.01), baseline insulin sensitivity (p = 0.02) and baseline insulin secretion relative to insulin sensitivity (p = 0.03) independent of sex, age, baseline 2 h blood glucose or change in percentage body fat. Our results suggest that low adiponectin levels, insulin resistance and low beta cell function predict the continuous deterioration of glucose tolerance in early prediabetic states, independent of changes in adiposity. Therefore, the early influence of these parameters should be the subject of future prevention programs to prevent deterioration of glucose tolerance.

Key words

Glucose tolerance - body composition - insulin sensitivity - insulin secretion - adiponectin

References

• 1 Gerich J E. The genetic basis of type 2 diabetes mellitus: impaired insulin secretion versus impaired insulin sensitivity.  Endocr Rev. 1998;  19 491-503
• 2 Ferrannini E. Insulin resistance versus insulin deficiency in non-insulin-dependent diabetes mellitus: problems and prospects.  Endocr Rev. 1998;  19 477-490
• 3 Weyer C, Bogardus C, Mott D M, Pratley R E. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus.  J Clin Invest. 1999;  104 787-794
• 4 Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley R E, Tataranni P A. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.  J Clin Endocrinol Metab. 2001;  86 1930-1935
• 5 Larsson H, Ahren B. Glucose intolerance is predicted by low insulin secretion and high glucagon secretion: outcome of a prospective study in postmenopausal Caucasian women.  Diabetologia. 2000;  43 194-202
• 6 Martin B C, Warram J H, Krolewski A S, Bergman R N, Soeldner J S, Kahn C R. Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study.  Lancet. 1992;  340 925-929
• 7 Lindsay R S, Funahashi T, Hanson R L, Matsuzawa Y, Tanaka S, Tataranni P A, Knowler W C, Krakoff J. Adiponectin and development of type 2 diabetes in the Pima Indian population.  Lancet. 2002;  360 57-58
• 8 Spranger J, Kroke A, Mohlig M, Bergmann M M, Ristow M, Boeing H, Pfeiffer A F. Adiponectin and protection against type 2 diabetes mellitus.  Lancet. 2003;  361 226-228
• 9 Lillioja S, Mott D M, Spraul M, Ferraro R, Foley J E, Ravussin E, Knowler W C, Bennett P H, Bogardus C. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians.  N Engl J Med. 1993;  329 1988-1992
• 10 Snehalatha C, Mukesh B, Simon M, Viswanathan V, Haffner S M, Ramachandran A. Plasma adiponectin is an independent predictor of type 2 diabetes in Asian indians.  Diabetes Care. 2003;  26 3226-3229
• 11 Daimon M, Oizumi T, Saitoh T, Kameda W, Hirata A, Yamaguchi H, Ohnuma H, Igarashi M, Tominaga M, Kato T. Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese Population: the Funagata study.  Diabetes Care. 2003;  26 2015-2020
• 12 Matsuda M, De Fronzo R A. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp.  Diabetes Care. 1999;  22 1462-1470
• 13 Stumvoll M, Mitrakou A, Pimenta W, Jenssen T, Yki-Jarvinen H, van Haeften T, Renn W, Gerich J. Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity.  Diabetes Care. 2000;  23 295-301
• 14 Ahren B, Pacini G. Importance of quantifying insulin secretion in relation to insulin sensitivity to accurately assess beta cell function in clinical studies.  Eur J Endocrinol. 2004;  150 97-104
• 15 Baecke J A, Burema J, Frijters J E. A short questionnaire for the measurement of habitual physical activity in epidemiological studies.  Am J Clin Nutr. 1982;  36 936-942
• 16 Swinburn B A, Nyomba B L, Saad M F, Zurlo F, Raz I, Knowler W C, Lillioja S, Bogardus C, Ravussin E. Insulin resistance associated with lower rates of weight gain in Pima Indians.  J Clin Invest. 1991;  88 168-173
• 17 Ravussin E, Gautier J F. Metabolic predictors of weight gain.  Int J Obes Relat Metab Disord. 1999;  23 (Suppl 1) 37-41
• 18 Vozarova B, Stefan N, Lindsay R S, Krakoff J, Knowler W C, Funahashi T, Matsuzawa Y, Stumvoll M, Weyer C, Tataranni P A. Low plasma adiponectin concentrations do not predict weight gain in humans.  Diabetes. 2002;  51 2964-2967
• 19 Yamamoto Y, Hirose H, Saito I, Nishikai K, Saruta T. Adiponectin, an adipocyte-derived protein, predicts future insulin resistance: two-year follow-up study in Japanese population.  J Clin Endocrinol Metab. 2004;  89 87-90
• 20 Stefan N, Vozarova B, Funahashi T, Matsuzawa Y, Weyer C, Lindsay R S, Youngren J F, Havel P J, Pratley R E, Bogardus C, Tataranni P A. 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.  Diabetes. 2002;  51 1884-1888
• 21 Stefan N, Stumvoll M, Vozarova B, Weyer C, Funahashi T, Matsuzawa Y, Bogardus C, Tataranni P A. Plasma adiponectin and endogenous glucose production in humans.  Diabetes Care. 2003;  26 3315-3319
• 22 Tiikkainen M, Hakkinen A M, Korsheninnikova E, Nyman T, Makimattila S, Yki-Jarvinen H. Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes.  Diabetes. 2004;  53 2169-2176
• 23 Bajaj M, Suraamornkul S, Piper P, Hardies L J, Glass L, Cersosimo E, Pratipanawatr T, Miyazaki Y, De Fronzo R A. Decreased plasma adiponectin concentrations are closely related to hepatic fat content and hepatic insulin resistance in pioglitazone-treated type 2 diabetic patients.  J Clin Endocrinol Metab. 2004;  89 200-206
• 24 Mitrakou A, Kelley D, Veneman T, Jenssen T, Pangburn T, Reilly J, Gerich J. Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM.  Diabetes. 1990;  39 1381-1390
• 25 Bavenholm P N, Pigon J, Ostenson C G, Efendic S. Insulin sensitivity of suppression of endogenous glucose production is the single most important determinant of glucose tolerance.  Diabetes. 2001;  50 1449-1454