Assessing the shape of the glucose curve during an oral glucose tolerance test.

OBJECTIVE The oral glucose tolerance test (OGTT) is used to define the status of glucose tolerance based on the plasma glucose level at 120 min. The purpose of the present study was to identify parameters that determine the shape of the plasma glucose course measured at 0, 30, 60, 90, and 120 min during an OGTT. RESEARCH DESIGN AND METHODS OGTT data from 551 subjects (485 with normal glucose tolerance [NGT] and 66 with impaired glucose tolerance [IGT]) were analyzed. We distinguished between "monophasic," "biphasic," and unclassified glucose shapes. A "shape" index based on the extent and the direction of the plasma glucose change in the second hour allowed us to treat shape as a continuous variable. RESULTS In the biphasic group, the NGT-to-IGT ratio was slightly higher (173/20 vs. 209/40, P = 0.08) and the male-to-female ratio was lower (60/133 vs. 120/129, P = 0.0003). Subjects with a biphasic shape had significantly lower age, BMI, waist-to-hip ratio (WHR), HbA(1c), plasma glucose, and area under the insulin curve (insulin(AUC)) and a better estimated insulin sensitivity and secretion (using validated indexes) than monophasic subjects (all P < 0.05). By adjusting this shape index for glucose(AUC) (as continuous measure of glucose tolerance), correlations with age, BMI, WHR, HbA(1c), and insulin(AUC) were completely abolished. The adjusted shape index was still higher in female than in male subjects but lower in IGT than in NGT subjects (both P = 0.0003). Finally, we tested common polymorphisms in insulin receptor substrate (IRS)-1, IRS-2, calpain-10, hepatic lipase, and peroxisome proliferator-activated receptor-gamma for association with the shape index. CONCLUSIONS We conclude that the plasma glucose shape during an OGTT depends on glucose tolerance and sex. In addition, genetic factors seem to play a role. The shape index may be a useful metabolic screening parameter in epidemiological and genetic association studies.

[1]  堀川 幸男 Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus , 2003 .

[2]  M. Stumvoll,et al.  Effect of experimental elevation of free fatty acids on insulin secretion and insulin sensitivity in healthy carriers of the Pro12Ala polymorphism of the peroxisome proliferator--activated receptor-gamma2 gene. , 2001, Diabetes.

[3]  U. Boggi,et al.  Insulin secretory function is impaired in isolated human islets carrying the Gly(972)-->Arg IRS-1 polymorphism. , 2002, Diabetes.

[4]  F. Sharbrough,et al.  Oral glucose tolerance test compared with a mixed meal in the diagnosis of reactive hypoglycemia. A caveat on stimulation. , 1983, Mayo Clinic proceedings.

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

[6]  Tom H. Lindner,et al.  Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus , 2000, Nature Genetics.

[7]  James P. Parker Reactive hypoglycemia. , 1971, Postgraduate medicine.

[8]  W. Reitsma,et al.  [WHO Expert Committee on diabetes mellitus]. , 1981, Nederlands tijdschrift voor geneeskunde.

[9]  M. Stumvoll,et al.  The prevalent Gly1057Asp polymorphism in the insulin receptor substrate-2 gene is not associated with impaired insulin secretion. , 2001, The Journal of clinical endocrinology and metabolism.

[10]  M. Laakso,et al.  Association of the Pro12Ala polymorphism in the PPAR-gamma2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study. , 2002, Diabetes.

[11]  M. Stumvoll,et al.  The Peroxisome Proliferator-Activated Receptor-γ2 Pro12Ala Polymorphism , 2002 .

[12]  P. Talmud,et al.  Genotypic associations of the hepatic secretion of VLDL apolipoprotein B-100 in obesity. , 2000, Journal of lipid research.

[13]  H. Nakano,et al.  [Oral glucose tolerance test using a continuous blood sampling technique for analysis of the blood glucose curve]. , 1994, Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics.

[14]  R. DeFronzo,et al.  The disposal of an oral glucose load in patients with non-insulin-dependent diabetes. , 1988, Metabolism: clinical and experimental.

[15]  C. Lindgren,et al.  Variants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels. , 2002, Diabetes.

[16]  K J Rothman,et al.  No Adjustments Are Needed for Multiple Comparisons , 1990, Epidemiology.

[17]  Debra D. Johnson Reactive Hypoglycemia , 1981, JAMA.

[18]  M. Kasuga,et al.  The Pro12 -->Ala substitution in PPAR-gamma is associated with resistance to development of diabetes in the general population: possible involvement in impairment of insulin secretion in individuals with type 2 diabetes. , 2001, Diabetes.

[19]  M. McCarthy,et al.  Studies of association between the gene for calpain-10 and type 2 diabetes mellitus in the United Kingdom. , 2001, American journal of human genetics.

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

[21]  H. Häring,et al.  The PPARγ2 amino acid polymorphism Pro 12 Ala is prevalent in offspring of Type II diabetic patients and is associated to increased insulin sensitivity in a subgroup of obese subjects , 1999, Diabetologia.

[22]  M. Stumvoll,et al.  Functional significance of the UCSNP-43 polymorphism in the CAPN10 gene for proinsulin processing and insulin secretion in nondiabetic Germans. , 2001, Diabetes.

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

[24]  M. Stumvoll,et al.  The Gly972Arg polymorphism in the insulin receptor substrate-1 gene contributes to the variation in insulin secretion in normal glucose-tolerant humans. , 2001, Diabetes.

[25]  M. Stumvoll,et al.  The OGTT as test for beta cell function? , 2001, European journal of clinical investigation.

[26]  E. Hardt,et al.  A novel hyperglycaemic clamp for characterization of islet function in humans: assessment of three different secretagogues, maximal insulin response and reproducibility , 2000, European journal of clinical investigation.

[27]  D. Kelley,et al.  Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance. , 1992, The New England journal of medicine.

[28]  C. Bogardus,et al.  A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance. , 2000, The Journal of clinical investigation.

[29]  M. Stumvoll,et al.  Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes. , 2002, Diabetes.

[30]  Eric S. Lander,et al.  The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes , 2000, Nature Genetics.

[31]  G. Nijpels,et al.  Variations in insulin secretion in carriers of gene variants in IRS-1 and -2. , 2002, Diabetes.

[32]  Andrea Mari,et al.  A Model-Based Method for Assessing Insulin Sensitivity From the Oral Glucose Tolerance Test , 2001 .