What is a normal glucose value? Differences in indexes of plasma glucose homeostasis in subjects with normal fasting glucose.

OBJECTIVE To evaluate differences in indexes of plasma glucose/insulin homeostasis and cardiovascular disease risk factors among subjects with normal fasting glucose (NFG), impaired fasting glucose, or glucose intolerance. Although individuals with fasting plasma glucose (FPG) concentrations > 5.4 mmol/l but < 6.1 mmol/l have been shown to have an increased risk of developing type 2 diabetes over 5 years, little is known about glucose metabolism abnormalities in this population. RESEARCH DESIGN AND METHODS We compared insulin secretion and insulin sensitivity using several indexes derived from an oral glucose tolerance test (OGTT) in 668 subjects from the Quebec Family Study who had varying degrees of FPG. RESULTS There was a progressive decline in indexes of beta-cell function and insulin sensitivity when moving from NFG to type 2 diabetes. Compared with subjects with low NFG (FPG < 4.9 mmol/l), subjects with high NFG (FPG 5.3-6.1 mmol/l) were more insulin resistant (P < 0.01), had higher insulin and C-peptide responses during an OGTT (P < 0.05), and had reduced insulin secretion (corrected for insulin resistance). Subjects with high NFG were also characterized by higher plasma triglyceride levels and reduced HDL cholesterol concentrations and by a smaller LDL particle size. All these differences remained significant, even after adjustment for age, sex, BMI, and waist circumference. In addition, subjects with mid NFG (FPG 4.9-5.3 mmol/l) were characterized by impaired insulin secretion, decreased insulin sensitivity, higher triglyceride concentrations, and lower HDL cholesterol concentrations compared with subjects with low NFG. CONCLUSIONS Independent of age, sex, and adiposity, there are differences in indexes of plasma glucose/insulin homeostasis and in cardiovascular risk factors among subjects with low, mid, and high NFG, suggesting the presence, in the upper normal glucose range, of abnormalities in glucose homeostasis, which may predispose to type 2 diabetes.

[1]  Moon-Kyu Lee,et al.  The cutoff value of fasting plasma glucose to differentiate frequencies of cardiovascular risk factors in a Korean population. , 2003, Diabetes care.

[2]  G. Reaven The insulin resistance syndrome , 2003, Current atherosclerosis reports.

[3]  J. Shaw,et al.  Impaired glucose tolerance and impaired fasting glycaemia: the current status on definition and intervention , 2002, Diabetic medicine : a journal of the British Diabetic Association.

[4]  R. Pratley,et al.  The role of impaired early insulin secretion in the pathogenesis of Type II diabetes mellitus , 2001, Diabetologia.

[5]  C. Bouchard,et al.  Effects of Endurance Exercise Training on Plasma HDL Cholesterol Levels Depend on Levels of Triglycerides: Evidence From Men of the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[6]  J. Després,et al.  Contribution of visceral obesity to the deterioration of the metabolic risk profile in men with impaired glucose tolerance , 2000, Diabetologia.

[7]  M. Stumvoll,et al.  Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. , 2000, Diabetes care.

[8]  T. Harris,et al.  American Diabetes Association diabetes diagnostic criteria, advancing age, and cardiovascular disease risk profiles: results from the Third National Health and Nutrition Examination Survey. , 2000, Diabetes care.

[9]  C. Bogardus,et al.  Evaluation of simple indices of insulin sensitivity and insulin secretion for use in epidemiologic studies. , 2000, American journal of epidemiology.

[10]  E. Feskens,et al.  Glucose tolerance and mortality: comparison of WHO and American Diabetic Association diagnostic criteria , 1999, The Lancet.

[11]  M. Matsuda,et al.  Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. , 1999, Diabetes care.

[12]  S. Yusuf,et al.  The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. , 1999, Diabetes care.

[13]  P. Raskin,et al.  Report of the expert committee on the diagnosis and classification of diabetes mellitus. , 1999, Diabetes care.

[14]  M. Fantone,et al.  Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus , 1997, Diabetes Care.

[15]  K. Polonsky,et al.  Alterations in the glucose-stimulated insulin secretory dose-response curve and in insulin clearance in nondiabetic insulin-resistant individuals. , 1997, The Journal of clinical endocrinology and metabolism.

[16]  M. Hammami Diabetes Mellitus: A Fundamental and Clinical Text , 1997 .

[17]  J. Després,et al.  The Dense LDL Phenotype: Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men , 1996, Diabetes Care.

[18]  R. Bergman,et al.  Quantification of the Relationship Between Insulin Sensitivity and β-Cell Function in Human Subjects: Evidence for a Hyperbolic Function , 1993, Diabetes.

[19]  A. Fontbonne,et al.  Risk Factors for NIDDM in White Population: Paris Prospective Study , 1991, Diabetes.

[20]  P. Wahl,et al.  Association of fasting glucose levels with a delayed secretion of insulin after oral glucose in subjects with glucose intolerance. , 1990, The Journal of clinical endocrinology and metabolism.

[21]  J. Cederholm,et al.  Insulin release and peripheral sensitivity at the oral glucose tolerance test. , 1990, Diabetes research and clinical practice.

[22]  C. Bouchard,et al.  Assessment of adipose tissue distribution by computed axial tomography in obese women: association with body density and anthropometric measurements , 1989, British Journal of Nutrition.

[23]  A Cederblad,et al.  Determination of total adipose tissue and body fat in women by computed tomography, 40K, and tritium. , 1986, The American journal of physiology.

[24]  L. Wilhelmsen,et al.  Fasting Blood Glucose and Risk of Coronary Heart Disease, Stroke, and All‐cause Mortality: A 17‐year Follow‐up Study of Men Born in 1913 , 1986, Diabetic medicine : a journal of the British Diabetic Association.

[25]  R. Turner,et al.  Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man , 1985, Diabetologia.

[26]  Jerrold M. Olefsky,et al.  Diabetes mellitus : a fundamental and clinical text , 2004 .

[27]  J. Shaw,et al.  Impaired fasting glucose: how low should it go? , 2000, Diabetes care.

[28]  S. Nitter‐Hauge,et al.  Fasting blood glucose: an underestimated risk factor for cardiovascular death. Results from a 22-year follow-up of healthy nondiabetic men. , 1999, Diabetes care.

[29]  S. Haffner,et al.  Waist circumference as the best predictor of noninsulin dependent diabetes mellitus (NIDDM) compared to body mass index, waist/hip ratio and other anthropometric measurements in Mexican Americans--a 7-year prospective study. , 1997, Obesity research.

[30]  C. Bouchard Genetic epidemiology, association, and sib-pair linkage: results from the Quebec Family Study , 1996 .

[31]  G. Bray,et al.  Molecular and genetic aspects of obesity , 1996 .

[32]  S. Punsar,et al.  Glucose tolerance and coronary heart disease: Helsinki policemen study. , 1979, Journal of chronic diseases.