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01-11-2014 | Article

A low disposition index in adolescent offspring of mothers with gestational diabetes: a risk marker for the development of impaired glucose tolerance in youth

Authors: Tara Holder, Cosimo Giannini, Nicola Santoro, Bridget Pierpont, Melissa Shaw, Elvira Duran, Sonia Caprio, Ram Weiss

Published in: Diabetologia | Issue 11/2014

Abstract

Aims/hypothesis

With the increase in gestational diabetes mellitus (GDM), there is a growing need to understand the effects of intrauterine glucose exposure on the newborn at birth and later in life. The risk of developing impaired glucose tolerance (IGT) in individuals exposed to diabetes in utero has not been adequately investigated.

Methods

We studied 255 obese adolescents with normal glucose tolerance. All of them were investigated for in utero exposure to GDM and underwent an OGTT, which was repeated after approximately 2.8 years.

Results

210 (82.3%) participants were not exposed to GDM (NGDM group), and 45 (17.7%) were exposed to GDM (EGDM group). In the NGDM group, only 8.6% (n = 18) developed either IGT or type 2 diabetes compared with 31.1% (n = 14) of the EGDM group who developed either IGT or type 2 diabetes (p < 0.001). Exposure to GDM was the most significant predictor of developing IGT or type 2 diabetes (OR 5.75, 95% CI 2.19, 15.07, p < 0.001). At baseline and at follow-up, the EGDM group showed a reduction in beta cell function determined by the oral disposition index (p = 0.03 and p = 0.01, respectively), and, at follow-up, they also displayed a reduction in insulin sensitivity compared with the NGDM group (p = 0.05).

Conclusions/interpretation

Obese youth exposed in utero to GDM show early inability of the beta cell to compensate adequately in response to decreasing levels of insulin sensitivity.

Zimmet P, Alberti KG, Shaw J (2001) Global and societal implications of the diabetes epidemic. Nature 414:782–787PubMedCrossRef

Arslanian S (2002) Type 2 diabetes in children: clinical aspects and risk factors. Horm Res 57(Suppl 1):19–28PubMedCrossRef

Fagot-Campagna A, Pettitt DJ, Engelgau MM et al (2000) Type 2 diabetes among North American children and adolescents: an epidemiologic review and a public health perspective. J Pediatr 136:664–672PubMedCrossRef

Dabelea D, Mayer-Davis EJ, Saydah S et al (2014) Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009. JAMA 311:1778–1786

Sobngwi E, Boudou P, Mauvais-Jarvis F et al (2003) Effect of a diabetic environment in utero on predisposition to type 2 diabetes. Lancet 361:1861–1865PubMedCrossRef

Pettitt DJ, Aleck KA, Baird HR, Carraher MJ, Bennett PH, Knowler WC (1988) Congenital susceptibility to NIDDM. Role of intrauterine environment. Diabetes 37:622–628PubMedCrossRef

Silverman BL, Metzger BE, Cho NH, Loeb CA (1995) Impaired glucose tolerance in adolescent offspring of diabetic mothers. Relationship to fetal hyperinsulinism. Diabetes Care 18:611–617PubMedCrossRef

Dabelea D, Hanson RL, Lindsay RS et al (2000) Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes 49:2208–2211PubMedCrossRef

HAPO Study Cooperative Research Group, Metzger BE, Lowe LP et al (2008) Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 358:1991–2002PubMedCrossRef

10.

Petitt DJ, Bennett PH, Knowler WC, Baird HR, Aleck KA (1985) Gestational diabetes mellitus and impaired glucose tolerance during pregnancy. Long-term effects on obesity and glucose tolerance in the offspring. Diabetes 34(Suppl 2):119–122PubMedCrossRef

11.

Tam WH, Ma RC, Yang X et al (2008) Glucose intolerance and cardiometabolic risk in children exposed to maternal gestational diabetes mellitus in utero. Pediatrics 122:1229–1234PubMedCrossRef

12.

Bush NC, Chandler-Laney PC, Rouse DJ, Granger WM, Oster RA, Gower BA (2011) Higher maternal gestational glucose concentration is associated with lower offspring insulin sensitivity and altered beta-cell function. J Clin Endocrinol Metab 96:E803–E809PubMedCrossRefPubMedCentral

13.

Yeckel CW, Taksali SE, Dziura J et al (2005) The normal glucose tolerance continuum in obese youth: evidence for impairment in beta-cell function independent of insulin resistance. J Clin Endocrinol Metab 90:747–754PubMedCrossRef

14.

Kuczmarski RJ, Ogden CL, Grummer-Strawn LM et al (2000) CDC growth charts: United States. Adv Data 314:1–27PubMed

15.

Gunderson EP, Lewis CE, Tsai AL et al (2007) A 20-year prospective study of childbearing and incidence of diabetes in young women, controlling for glycemia before conception: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Diabetes 56:2990–2996PubMedCrossRefPubMedCentral

16.

Zeitler P, Hirst K, Pyle L et al (2012) A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med 366:2247–2256PubMedCrossRef

17.

Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (2003) Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 26(Suppl 1):S5–S20

18.

American Diabetes Association (2004) Diagnosis and classification of diabetes mellitus. Diabetes Care 27(Suppl 1):S5–S10

19.

Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22:1462–1470PubMedCrossRef

20.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRef

21.

Phillips DI, Clark PM, Hales CN, Osmond C (1994) Understanding oral glucose tolerance: comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion. Diabet Med J 11:286–292CrossRef

22.

Weiss R, Cali AM, Dziura J, Burgert TS, Tamborlane WV, Caprio S (2007) Degree of obesity and glucose allostasis are major effectors of glucose tolerance dynamics in obese youth. Diabetes Care 30:1845–1850PubMedCrossRef

23.

Nelder JA, Wedderburn RWM (1972) Generalized linear models. JR Statist Soc A 135:370–384

24.

Metzger BE, Gabbe SG, Persson B et al (2010) International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 33:676–682PubMedCrossRef

25.

International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger BE, Gabbe SG et al (2010) International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 33:676–682PubMedCrossRef

26.

Retnakaran R, Qi Y, Goran MI, Hamilton JK (2009) Evaluation of proposed oral disposition index measures in relation to the actual disposition index. Diabet Med 26:1198–1203PubMedCrossRef

27.

Sjaarda LG, Bacha F, Lee S, Tfayli H, Andreatta E, Arslanian S (2012) Oral disposition index in obese youth from normal to prediabetes to diabetes: relationship to clamp disposition index. J Pediatr 161:51–57PubMedCrossRefPubMedCentral

28.

Lorenzo C, Wagenknecht LE, Rewers MJ et al (2010) Disposition index, glucose effectiveness, and conversion to type 2 diabetes: the Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Care 33:2098–2103PubMedCrossRefPubMedCentral

29.

Giannini C, Weiss R, Cali A et al (2012) Evidence for early defects in insulin sensitivity and secretion before the onset of glucose dysregulation in obese youths: a longitudinal study. Diabetes 61:606–614PubMedCrossRefPubMedCentral

30.

Kelstrup L, Damm P, Mathiesen ER et al (2013) Insulin resistance and impaired pancreatic beta-cell function in adult offspring of women with diabetes in pregnancy. J Clin Endocrinol Metab 98:3793–3801PubMedCrossRefPubMedCentral

31.

Malcolm JC, Lawson ML, Gaboury I, Lough G, Keely E (2006) Glucose tolerance of offspring of mother with gestational diabetes mellitus in a low-risk population. Diabet Med 23:565–570PubMedCrossRef

32.

DeFronzo RA, Abdul-Ghani MA (2009) Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels: response to Utzschneider et al. Diabetes Care 32:e86, author reply e87PubMedCrossRef

33.

Elbein SC, Sun J, Scroggin E, Teng K, Hasstedt SJ (2001) Role of common sequence variants in insulin secretion in familial type 2 diabetic kindreds: the sulfonylurea receptor, glucokinase, and hepatocyte nuclear factor 1alpha genes. Diabetes Care 24:472–478PubMedCrossRef

34.

Gjesing AP, Hornbak M, Allin KH et al (2014) High heritability and genetic correlation of intravenous glucose- and tolbutamide-induced insulin secretion among non-diabetic family members of type 2 diabetic patients. Diabetologia 57:1173–1181PubMedCrossRef

35.

Nolan CJ, Damm P, Prentki M (2011) Type 2 diabetes across generations: from pathophysiology to prevention and management. Lancet 378:169–181PubMedCrossRef

36.

Lingwood BE, Henry AM, d'Emden MC et al (2011) Determinants of body fat in infants of women with gestational diabetes mellitus differ with fetal sex. Diabetes Care 34:2581–2585PubMedCrossRefPubMedCentral

37.

Pettitt DJ, Baird HR, Aleck KA, Bennett PH, Knowler WC (1983) Excessive obesity in offspring of Pima Indian women with diabetes during pregnancy. N Engl J Med 308:242–245PubMedCrossRef

38.

Weiss R, Dufour S, Taksali SE et al (2003) Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning. Lancet 362:951–957PubMedCrossRefPubMedCentral

Title: A low disposition index in adolescent offspring of mothers with gestational diabetes: a risk marker for the development of impaired glucose tolerance in youth
Authors: Tara Holder
Cosimo Giannini
Nicola Santoro
Bridget Pierpont
Melissa Shaw
Elvira Duran
Sonia Caprio
Ram Weiss
Publication date: 01-11-2014
Publisher: Springer Berlin Heidelberg
Published in: Diabetologia / Issue 11/2014
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-014-3345-2

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