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Erschienen in: Diabetologia 12/2013

01.12.2013 | Article

Prediction of type 2 diabetes in women with a history of gestational diabetes using a genetic risk score

verfasst von: Soo Heon Kwak, Sung Hee Choi, Kyunga Kim, Hye Seung Jung, Young Min Cho, Soo Lim, Nam H. Cho, Seong Yeon Kim, Kyong Soo Park, Hak C. Jang

Erschienen in: Diabetologia | Ausgabe 12/2013

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Abstract

Aims/hypothesis

Women with a history of gestational diabetes mellitus (GDM) are at increased risk of future development of type 2 diabetes. Recently, over 65 genetic variants have been confirmed to be associated with diabetes. We investigated whether this genetic information could improve the prediction of future diabetes in women with GDM.

Methods

This was a prospective cohort study consisting of 395 women with GDM who were followed annually with an OGTT. A weighted genetic risk score (wGRS), consisting of 48 variants, was assessed for improving discrimination (C statistic) and risk reclassification (continuous net reclassification improvement [NRI] index) when added to clinical risk factors.

Results

Among the 395 women with GDM, 116 (29.4%) developed diabetes during a median follow-up period of 45 months. Women with GDM who went on to develop diabetes had a significantly higher wGRS than those who did not (9.36 ± 0.92 vs 8.78 ± 1.07; p < 1.56 × 10−7). In a complex clinical model adjusted for age, prepregnancy BMI, family history of diabetes, blood pressure, fasting glucose and fasting insulin concentration, the C statistic marginally improved from 0.741 without the wGRS to 0.775 with the wGRS (p = 0.015). The addition of the wGRS to the clinical model resulted in a modest improvement in reclassification (continuous NRI 0.430 [95% CI 0.218, 0.642]; p = 7.0 × 10−5).

Conclusions/interpretation

In women with GDM, who are at high risk of diabetes, the wGRS was significantly associated with the future development of diabetes. Furthermore, it improved prediction over clinical risk factors.
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Literatur
1.
Zurück zum Zitat Bellamy L, Casas JP, Hingorani AD, Williams D (2009) Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet 373:1773–1779PubMedCrossRef Bellamy L, Casas JP, Hingorani AD, Williams D (2009) Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet 373:1773–1779PubMedCrossRef
2.
Zurück zum Zitat Kwak SH, Choi SH, Jung HS et al (2013) Clinical and genetic risk factors for type 2 diabetes at early or late post partum after gestational diabetes mellitus. J Clin Endocrinol Metab 98:E744–E752PubMedCrossRef Kwak SH, Choi SH, Jung HS et al (2013) Clinical and genetic risk factors for type 2 diabetes at early or late post partum after gestational diabetes mellitus. J Clin Endocrinol Metab 98:E744–E752PubMedCrossRef
3.
Zurück zum Zitat Buchanan TA, Xiang A, Kjos SL et al (1998) Gestational diabetes: antepartum characteristics that predict postpartum glucose intolerance and type 2 diabetes in Latino women. Diabetes 47:1302–1310PubMed Buchanan TA, Xiang A, Kjos SL et al (1998) Gestational diabetes: antepartum characteristics that predict postpartum glucose intolerance and type 2 diabetes in Latino women. Diabetes 47:1302–1310PubMed
4.
Zurück zum Zitat Metzger BE, Cho NH, Roston SM, Radvany R (1993) Prepregnancy weight and antepartum insulin secretion predict glucose tolerance five years after gestational diabetes mellitus. Diabetes Care 16:1598–1605PubMedCrossRef Metzger BE, Cho NH, Roston SM, Radvany R (1993) Prepregnancy weight and antepartum insulin secretion predict glucose tolerance five years after gestational diabetes mellitus. Diabetes Care 16:1598–1605PubMedCrossRef
5.
Zurück zum Zitat Jang HC (2011) Gestational diabetes in Korea: incidence and risk factors of diabetes in women with previous gestational diabetes. Diabetes Metab J 35:1–7PubMedCrossRef Jang HC (2011) Gestational diabetes in Korea: incidence and risk factors of diabetes in women with previous gestational diabetes. Diabetes Metab J 35:1–7PubMedCrossRef
6.
Zurück zum Zitat Kwak SH, Jang HC, Park KS (2012) Finding genetic risk factors of gestational diabetes. Genomics Inform 10:239–243PubMedCrossRef Kwak SH, Jang HC, Park KS (2012) Finding genetic risk factors of gestational diabetes. Genomics Inform 10:239–243PubMedCrossRef
7.
Zurück zum Zitat Buchanan TA, Xiang AH, Peters RK et al (2002) Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women. Diabetes 51:2796–2803PubMedCrossRef Buchanan TA, Xiang AH, Peters RK et al (2002) Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women. Diabetes 51:2796–2803PubMedCrossRef
8.
Zurück zum Zitat Ratner RE, Christophi CA, Metzger BE et al (2008) Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab 93:4774–4779PubMedCrossRef Ratner RE, Christophi CA, Metzger BE et al (2008) Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab 93:4774–4779PubMedCrossRef
9.
Zurück zum Zitat Morris AP, Voight BF, Teslovich TM et al (2012) Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet 44:981–990PubMedCrossRef Morris AP, Voight BF, Teslovich TM et al (2012) Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet 44:981–990PubMedCrossRef
10.
Zurück zum Zitat Manolio TA, Collins FS, Cox NJ et al (2009) Finding the missing heritability of complex diseases. Nature 461:747–753PubMedCrossRef Manolio TA, Collins FS, Cox NJ et al (2009) Finding the missing heritability of complex diseases. Nature 461:747–753PubMedCrossRef
11.
Zurück zum Zitat Meigs JB, Shrader P, Sullivan LM et al (2008) Genotype score in addition to common risk factors for prediction of type 2 diabetes. N Engl J Med 359:2208–2219PubMedCrossRef Meigs JB, Shrader P, Sullivan LM et al (2008) Genotype score in addition to common risk factors for prediction of type 2 diabetes. N Engl J Med 359:2208–2219PubMedCrossRef
12.
Zurück zum Zitat Lyssenko V, Jonsson A, Almgren P et al (2008) Clinical risk factors, DNA variants, and the development of type 2 diabetes. N Engl J Med 359:2220–2232PubMedCrossRef Lyssenko V, Jonsson A, Almgren P et al (2008) Clinical risk factors, DNA variants, and the development of type 2 diabetes. N Engl J Med 359:2220–2232PubMedCrossRef
13.
Zurück zum Zitat Talmud PJ, Hingorani AD, Cooper JA et al (2010) Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II Prospective Cohort Study. BMJ 340:b4838PubMedCrossRef Talmud PJ, Hingorani AD, Cooper JA et al (2010) Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II Prospective Cohort Study. BMJ 340:b4838PubMedCrossRef
14.
Zurück zum Zitat Vassy JL, Durant NH, Kabagambe EK et al (2012) A genotype risk score predicts type 2 diabetes from young adulthood: the CARDIA study. Diabetologia 55:2604–2612PubMedCrossRef Vassy JL, Durant NH, Kabagambe EK et al (2012) A genotype risk score predicts type 2 diabetes from young adulthood: the CARDIA study. Diabetologia 55:2604–2612PubMedCrossRef
15.
Zurück zum Zitat Kwak SH, Kim SH, Cho YM et al (2012) A genome-wide association study of gestational diabetes mellitus in Korean women. Diabetes 61:531–541PubMedCrossRef Kwak SH, Kim SH, Cho YM et al (2012) A genome-wide association study of gestational diabetes mellitus in Korean women. Diabetes 61:531–541PubMedCrossRef
16.
Zurück zum Zitat Metzger BE (1991) Summary and recommendations of the Third International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes 40(Suppl 2):197–201PubMedCrossRef Metzger BE (1991) Summary and recommendations of the Third International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes 40(Suppl 2):197–201PubMedCrossRef
17.
Zurück zum Zitat American Diabetes Association (2013) Diagnosis and classification of diabetes mellitus. Diabetes Care 36(Suppl 1):S67–S74CrossRef American Diabetes Association (2013) Diagnosis and classification of diabetes mellitus. Diabetes Care 36(Suppl 1):S67–S74CrossRef
18.
Zurück zum Zitat 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 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
19.
Zurück zum Zitat Kanat M, Winnier D, Norton L et al (2011) The relationship between β-cell function and glycated hemoglobin: results from the Veterans Administration Genetic Epidemiology Study. Diabetes Care 34:1006–1010PubMedCrossRef Kanat M, Winnier D, Norton L et al (2011) The relationship between β-cell function and glycated hemoglobin: results from the Veterans Administration Genetic Epidemiology Study. Diabetes Care 34:1006–1010PubMedCrossRef
20.
Zurück zum Zitat Li Y, Willer C, Sanna S, Abecasis G (2009) Genotype imputation. Annu Rev Genomics Hum Genet 10:387–406PubMedCrossRef Li Y, Willer C, Sanna S, Abecasis G (2009) Genotype imputation. Annu Rev Genomics Hum Genet 10:387–406PubMedCrossRef
21.
Zurück zum Zitat Hosmer DW, Lemeshow S (1989) Applied logistic regression. Wiley, New York Hosmer DW, Lemeshow S (1989) Applied logistic regression. Wiley, New York
22.
Zurück zum Zitat Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, Vasan RS (2008) Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 27:157–172, discussion 207-112PubMedCrossRef Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, Vasan RS (2008) Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 27:157–172, discussion 207-112PubMedCrossRef
23.
Zurück zum Zitat Purcell S, Neale B, Todd-Brown K et al (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575PubMedCrossRef Purcell S, Neale B, Todd-Brown K et al (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575PubMedCrossRef
24.
Zurück zum Zitat Kundu S, Aulchenko YS, van Duijn CM, Janssens AC (2011) PredictABEL: an R package for the assessment of risk prediction models. Eur J Epidemiol 26:261–264PubMedCrossRef Kundu S, Aulchenko YS, van Duijn CM, Janssens AC (2011) PredictABEL: an R package for the assessment of risk prediction models. Eur J Epidemiol 26:261–264PubMedCrossRef
25.
Zurück zum Zitat de Miguel-Yanes JM, Shrader P, Pencina MJ et al (2011) Genetic risk reclassification for type 2 diabetes by age below or above 50 years using 40 type 2 diabetes risk single nucleotide polymorphisms. Diabetes Care 34:121–125PubMedCrossRef de Miguel-Yanes JM, Shrader P, Pencina MJ et al (2011) Genetic risk reclassification for type 2 diabetes by age below or above 50 years using 40 type 2 diabetes risk single nucleotide polymorphisms. Diabetes Care 34:121–125PubMedCrossRef
26.
Zurück zum Zitat Vassy JL, Meigs JB (2012) Is genetic testing useful to predict type 2 diabetes? Best Pract Res Clin Endocrinol Metab 26:189–201PubMedCrossRef Vassy JL, Meigs JB (2012) Is genetic testing useful to predict type 2 diabetes? Best Pract Res Clin Endocrinol Metab 26:189–201PubMedCrossRef
27.
Zurück zum Zitat Vassy JL, Dasmahapatra P, Meigs JB et al (2012) Genotype prediction of adult type 2 diabetes from adolescence in a multiracial population. Pediatrics 130:e1235–e1242PubMedCrossRef Vassy JL, Dasmahapatra P, Meigs JB et al (2012) Genotype prediction of adult type 2 diabetes from adolescence in a multiracial population. Pediatrics 130:e1235–e1242PubMedCrossRef
28.
Zurück zum Zitat Buchanan TA (2001) Pancreatic B cell defects in gestational diabetes: implications for the pathogenesis and prevention of type 2 diabetes. J Clin Endocrinol Metab 86:989–993PubMedCrossRef Buchanan TA (2001) Pancreatic B cell defects in gestational diabetes: implications for the pathogenesis and prevention of type 2 diabetes. J Clin Endocrinol Metab 86:989–993PubMedCrossRef
29.
Zurück zum Zitat Kwak SH, Park KS (2013) Genetics of type 2 diabetes and potential clinical implications. Arch Pharm Res 36:167–177PubMedCrossRef Kwak SH, Park KS (2013) Genetics of type 2 diabetes and potential clinical implications. Arch Pharm Res 36:167–177PubMedCrossRef
Metadaten
Titel
Prediction of type 2 diabetes in women with a history of gestational diabetes using a genetic risk score
verfasst von
Soo Heon Kwak
Sung Hee Choi
Kyunga Kim
Hye Seung Jung
Young Min Cho
Soo Lim
Nam H. Cho
Seong Yeon Kim
Kyong Soo Park
Hak C. Jang
Publikationsdatum
01.12.2013
Verlag
Springer Berlin Heidelberg
Erschienen in
Diabetologia / Ausgabe 12/2013
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-013-3059-x

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