The Shape of the Plasma Glucose Curve During an Oral Glucose Tolerance Test as an Indicator of Beta Cell Function and Insulin Sensitivity in End-Pubertal Obese Girls

Abstract

It is hypothesized that the shape of the glucose curve during an oral glucose tolerance test is an early indicator of the risk for developing type 2 diabetes mellitus. In this study, we aimed to examine the shape of plasma glucose response curves and study their relationship with insulin sensitivity, insulin secretion and components of the metabolic syndrome in end-pubertal obese girls. Eighty-one end-pubertal obese girls [median (range) age: 14.4 (11.2–18.0) years; BMI: 34.6 (25.4–50.8) kg/m²] who underwent a 2-h oral glucose tolerance test were classified according to the shape of the glucose curve. Four shape types of the plasma glucose response curve were observed: 28 (34.6%) monophasic, 30 (37.0%) biphasic, 14 (17.3%) triphasic, and 9 (11.1%) unclassified. Patients with a monophasic shape had a higher area under the curve for glucose (p=0.008), a lower early-phase insulin secretion (p=0.005), and a poorer beta cell function relative to insulin sensitivity as reflected by the oral disposition index (p=0.022) compared to the bi- and triphasic shape types. In addition, the triglyceride level and TG/HDL-C ratio was higher in patients with a monophasic shape compared to those with a biphasic shape (p=0.040 and p=0.048, respectively). In conclusion, end-pubertal obese girls with a monophasic plasma glucose curve are at increased risk for insulin resistance, which can contribute to the development of type 2 diabetes mellitus and cardiovascular diseases.

Key words

insulin secretion - metabolic syndrome - type 2 diabetes mellitus - adolescence - obesity

• References

• 1 Wiegand S, Maikowski U, Blankenstein O, Biebermann H, Tarnow P, Gruters A. Type 2 diabetes and impaired glucose tolerance in European children and adolescents with obesity – a problem that is no longer restricted to minority groups. Eur J Endocrinol 2004; 151: 199-206
• 2 Sen Y, Kandemir N, Alikasifoglu A, Gonc N, Ozon A. Prevalence and risk factors of metabolic syndrome in obese children and adolescents: the role of the severity of obesity. Eur J Pediatr 2008; 167: 1183-1189
• 3 Franks PW, Hanson RL, Knowler WC, Sievers ML, Bennett PH, Looker HC. Childhood obesity, other cardiovascular risk factors, and premature death. N Engl J Med 2010; 362: 485-493
• 4 Makkes S, Renders CM, Bosmans JE, van der Baan-Slootweg OH, Seidell JC. Cardiometabolic risk factors and quality of life in severely obese children and adolescents in the Netherlands. BMC Pediatr 2013; 13: 1-9
• 5 Dietz WH. Childhood weight affects adult morbidity and mortality. J Nutr 1998; 128: 411S-414S
• 6 Reilly JJ, Kelly J. Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: systematic review. Int J Obes 2011; 35: 891-898
• 7 Roemmich JN, Clark PA, Lusk M, Friel A, Weltman A, Epstein LH, Rogol AD. Pubertal alterations in growth and body composition. VI. Pubertal insulin resistance: relation to adiposity, body fat distribution and hormone release. Int J Obes 2002; 26: 701-709
• 8 Brufani C, Tozzi A, Fintini D, Ciampalini P, Grossi A, Fiori R, Kiepe D, Manco M, Schiaffini R, Porzio O. Sexual dimorphism of body composition and insulin sensitivity across pubertal development in obese Caucasian subjects. Eur J Endocrinol 2009; 160: 769-775
• 9 Pilia S, Casini MR, Foschini ML, Minerba L, Musiu MC, Marras V, Civolani P, Loche S. The effect of puberty on insulin resistance in obese children. J Endocrinol Invest 2009; 32: 401-405
• 10 Chiarelli F, Marcovecchio ML. Insulin resistance and obesity in childhood. Eur J Endocrinol 2008; 159: S67-S74
• 11 Weiss R, Kaufman FR. Metabolic Complications of Childhood Obesity Identifying and mitigating the risk. Diabetes Care 2008; 31: S310-S316
• 12 DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol Endocrinol Metab 1979; 237: 214-223
• 13 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RF. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
• 14 Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999; 22: 1462-1470
• 15 Stumvoll M, Mitrakou A, Pimenta W, Jenssen T, Yki-Järvinen 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
• 16 Tschritter O, Fritsche A, Shirkavand F, Machicao F, Häring H, Stumvoll M. Assessing the shape of the glucose curve during an oral glucose tolerance test. Diabetes Care 2003; 26: 1026-1033
• 17 Abdul-Ghani MA, Lyssenko V, Tuomi T, Defronzo RA, Groop L. The shape of plasma glucose concentration curve during OGTT predicts future risk of type 2 diabetes. Diabetes Metab Res Rev 2010; 26: 280-286
• 18 Kanauchi M, Kimura K, Kanauchi K, Saito Y. Beta-cell function and insulin sensitivity contribute to the shape of plasma glucose curve during an oral glucose tolerance test in non-diabetic individuals. Int J Clin Pract 2005; 59: 427-432
• 19 Tura A, Morbiducci U, Sbrignadello S, Winhofer Y, Pacini G, Kautzy-Willer A. Shape of glucose, insulin, C-peptide curves during a 3-h oral glucose tolerance test: any relationship with the degree of glucose tolerance?. Am J Physiol Regul Integr Comp Physiol 2011; 300: 941-948
• 20 Nolfe G, Spreghini MR, Sforza RW, Morino G, Manco M. Beyond the morphology of the glucose curve following an oral glucose tolerance test in obese youth. Eur J Endocrinol 2012; 166: 107114
• 21 Sorensen K, Aksglaede L, Petersen JH, Andersson AM, Juul A. Serum IGF1 and insulin levels in girls with normal and precocious puberty. Eur J Endocrinol 2012; 166: 903-910
• 22 Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969; 44: 291-303
• 23 Cole T, Lobstein T. Extended international (IOTF) body mass index cut-offs for thinness, overweight and obesity. Pediatr Obes 2012; 7: 284-294
• 24 Bervoets L, Massa G. Defining morbid obesity in children based on BMI 40 at age 18 using the extended international (IOTF) cut-offs. Pediatr Obes 2014; 9: e94-e98
• 25 American Diabetes Association . Diagnosis and classification of diabetes mellitus. Diabetes Care 2014; 37: S81-S90
• 26 Zimmet P, Alberti K, George MM, Kaufman F, Tajima N, Silink M, Arslanian S, Wong G, Bennett P, Shaw J, Caprio S. The metabolic sydrome in children and adolescents – an IDF consensus report. Pediatr Diabetes 2007; 8: 299-306
• 27 Trujillo-Arriaga HM, Roman-Ramos R. Fitting and evaluating the glucose curve during a quasi continuous sampled oral glucose tolerance test. Comput Biol Med 2008; 38: 185-195
• 28 Matthews JN, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. BMJ 1990; 300: 230-235
• 29 Yeckel CW, Weiss R, Dziura J, Taksali SE, Dufour S, Burgert TS, Tamborlane WV, Caprio S. Validation of insulin sensitivity indices from oral glucose tolerance test parameters in obese children and adolescents. J Clin Endocrinol Metab 2004; 89: 1096-1101
• 30 Sjaarda LG, Bacha F, Lee S, Tfayli H, Andreatta E, Arslanian S. Oral disposition index in obese youth from normal to prediabetes to diabetes: relationship to clamp disposition index. J Pediatr 2012; 161: 51-57
• 31 Giannini C, Santoro N, Caprio S, Kim G, Lartaud D, Shaw M, Pierpont B, Weiss R. The Triglyceride-to-HDL Cholesterol Ratio Association with insulin resistance in obese youths of different ethnic backgrounds. Diabetes Care 2011; 34: 1869-1874
• 32 Fuchigami M, Nakano H, Oba K, Metori S. Oral glucose tolerance test using a continuous blood sampling technique for analysis of the blood glucose curve. Nihon Ronen Igakkai Zasshi 1994; 31: 518-524
• 33 Zhou W, Gu Y, Li H, Luo M. Assessing 1-h plasma glucose and shape of the glucose curve during oral glucose tolerance test. Eur J Endocrinol 2006; 155: 191-197
• 34 Kim JY, Coletta DK, Mandarino LJ, Shaibi GQ. Glucose response curve and type 2 diabetes risk in Latino adolescents. Diabetes Care 2012; 35: 1925-1930
• 35 Weiss R, Taksali SE, Tamborlane WV, Burgert TS, Savoye M, Caprio S. Predictors of changes in glucose tolerance status in obese youth. Diabetes Care 2005; 28: 902-909
• 36 Tfayli H, Lee SJ, Bacha F, Arslanian S. One-hour plasma glucose concentration during the OGTT: what does it tell about beta-cell function relative to insulin sensitivity in overweight/obese children?. Pediatr Diabetes 2011; 12: 572-579
• 37 Manco M, Del Giudice EM, Spreghini MR, Cappa M, Perrone L, Brufani C, Rustico C, Morino G, Caprio S. 1-Hour plasma glucose in obese youth. Acta Diabetol 2012; 49: 435-443
• 38 Giannini C, Weiss R, Cali A, Bonadonna R, Santoro N, Pierpont B, Shaw M, Caprio S. Evidence for early defects in insulin sensitivity and secretion before the onset of glucose dysregulation in obese youths: a longitudinal study. Diabetes 2012; 61: 606-614
• 39 Lyssenko V, Almgren P, Anevski D, Perfekt R, Lahti K, Nissen M, Isomaa B, Forsen B, Homstrom N, Saloranta C, Taskinen MR, Groop L, Tuomi T. Botnia study g. Predictors of and longitudinal changes in insulin sensitivity and secretion preceding onset of type 2 diabetes. Diabetes 2005; 54: 166-174
• 40 Abdul-Ghani MA, Williams K, DeFronzo RA, Stern M. What is the best predictor of future type 2 diabetes?. Diabetes Care 2007; 30: 1544-1548
• 41 Wabitsch M, Hauner H, Hertrampf M, Muche R, Hay B, Mayer H, Kratzer W, Debatin K, Heinze E. Type II diabetes mellitus and impaired glucose regulation in Caucasian children and adolescents with obesity living in Germany. Int J Obes 2004; 28: 307-313
• 42 Quijada Z, Paoli M, Zerpa Y, Camacho N, Cichetti R, Villarroel V, Arata-Bellabarba G, Lanes R. The triglyceride/HDL-cholesterol ratio as a marker of cardiovascular risk in obese children; association with traditional and emergent risk factors. Pediatr Diabetes 2008; 9: 464-471
• 43 Weiss R, Otvos JD, Sinnreich R, Miserez AR, Kark JD. The Triglyceride to High-Density Lipoprotein-Cholesterol Ratio in Adolescence and Subsequent Weight Gain Predict Nuclear Magnetic Resonance-Measured Lipoprotein Subclasses in Adulthood. J Pediatr 2011; 158: 44-50
• 44 Urbina EM, Khoury PR, McCoy CE, Dolan LM, Daniels SR, Kimball TR. Triglyceride to HDL-C ratio and increased arterial stiffness in children, adolescents, and young adults. Pediatrics 2013; 131: e1082-e1090
• 45 Reinehr T, Wabitsch M, Kleber M, De Sousa G, Denzer C, Toschke AM. Parental diabetes, pubertal stage, and extreme obesity are the main risk factors for prediabetes in children and adolescents: a simple risk score to identify children at risk for prediabetes. Pediatr Diabetes 2009; 10: 395-400
• 46 Kramer CK, Vuksan V, Choi H, Zinman B, Retnakaran R. Emerging parameters of the insulin and glucose response on the oral glucose tolerance test: reproducibility and implications for glucose homeostasis in individuals with and without diabetes. Diabetes Res Clin Pract 2014; 105: 88-95
• 47 Dedik L, Durisova M, Penesova A, Miklovicova D, Tvrdonova M. Estimation of influence of gastric emptying on shape of glucose concentration-time profile measured in oral glucose tolerance test. Diabetes Res Clin Pract 2007; 77: 377-384
• 48 Salehi M, Aulinger B, D’Alessio DA. Effect of glycemia on plasma incretins and the incretin effect during oral glucose tolerance test. Diabetes 2012; 61: 2728-2733
• 49 Libman I, Barinas-Mitchell E, Bartucci A, Robertson R, Arslanian S. Reproducibility of the oral glucose tolerance test in overweight children. J Clin Endocr Metab 2008; 93: 4231-4237