Model for individual prediction of diabetes up to 5 years after gestational diabetes mellitus

Ignell et al. SpringerPlus (2016) 5:318 DOI 10.1186/s40064-016-1953-7 Open Access RESEARCH Model for individual prediction of diabetes up to 5 years after gestational diabetes mellitus Claes Ignell1,2*, Magnus Ekelund1,3, Eva Anderberg4 and Kerstin Berntorp1,5 *Correspondence: Claes. 2 Department of Obstetrics and Gynecology, Helsingborg Hospital, SE‑251 87 Helsingborg, Sweden Full list of author information is available at the end of the article Abstract Aims: To identify predictors of diabetes development up to 5 years after gestational diabetes mellitus (GDM) and to develop a prediction model for individual use. Methods: Five years after GDM, a 75-g oral glucose tolerance test (OGTT) was performed in 362 women, excluding women already diagnosed with diabetes at 1- to 2-year follow-up or later (n = 45). All but 21 women had results from follow-up at 1–2 years, while 84 women were lost from that point. Predictive variables were identified by logistic regression analysis. Results: Five years after GDM, 28/362 women (8 %) were diagnosed with diabetes whereas 187/362 (52 %) had normal glucose tolerance (NGT). Of the latter, 139/187 (74 %) also had NGT at 1- to 2-year follow-up. In simple regression analysis, using NGT at 1–2 years and at 5 years as the reference, diabetes at 1- to 2-year follow-up or later was clearly associated with easily assessable clinical variables, such as BMI at 1- to 2-year follow-up, 2-h OGTT glucose concentration during pregnancy, and non-European origin (P < 0.0001). A prediction model based on these variables resulting in 86 % correct classifications, with an area under the receiver-operating characteristic curve of 0.91 (95 % CI 0.86–0.95), was applied in a function-sheet line diagram illustrating the individual effect of weight on diabetes risk. Conclusions: The results highlight the importance of BMI as a potentially modifiable risk factor for diabetes after GDM. Our proposed prediction model performed well, and should encourage validation in other populations in future studies. Keywords: Diabetes mellitus, Follow-up, Gestational diabetes mellitus, Glucose tolerance, Prediction Background The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide. Currently, it affects about 2.6 % of pregnant women in southern Sweden (Hunt and Schuller 2007; Ignell et al. 2014). GDM is an important risk factor for type-2 diabetes and cardiovascular disease (Bellamy et al. 2009; Harreiter et al. 2014). A cumulative diabetes incidence of 30–50 % within 5–10 years after GDM has been described (Kim et al. 2002; Ekelund et al. 2010). GDM and type-2 diabetes have many risk factors in common (Dornhorst and Rossi 1998), and both are characterized by insulin resistance and an inability of the beta cells to compensate by a sufficient increase in insulin secretion © 2016 Ignell et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Ignell et al. SpringerPlus (2016) 5:318 (Buchanan et al. 2007; Retnakaran et al. 2008). However, the incidence of GDM and type-2 diabetes following GDM is dependent of the screening activity and the diagnostic criteria used to define GDM. In southern Sweden, universal screening with a 75-g oral glucose tolerance test (OGTT) has been used since 1995. Using the World Health Organization (WHO) criteria from 1999 to define GDM, we have previously reported a diabetes incidence of 6 % 1–2 years after delivery (Anderberg et al. 2011; World Health Organization 1999). Here we report the results of 5-year follow-up of these women. As intervention studies have shown that type-2 diabetes can be prevented by modification of lifestyle (Knowler et al. 2002; Lindstrom et al. 2003), even in women with a history of GDM (Ratner et al. 2008; Aroda et al. 2015), a major challenge in public healthcare is to identify individuals who have the highest risk (Noble et al. 2011). The aim of the present study was to identify risk factors associated with diabetes development up to 5 years after pregnancy and to explore the possibility of establishing a model for diabetes prediction that could be used in clinical practice on an individual basis when counseling women after GDM. Methods Study population The present study was part of the Mamma Study, which was conducted in four of the five delivery departments in the county of Skåne in southern Sweden. The design of the study has been described in detail elsewhere (Anderberg et al. 2011; Ignell et al. 2013). Briefly, during the years 2003–2005, all pregnant women, representing different glucose categories according to an OGTT, were invited to take part in a 5-year follow-up program postpartum. A 75-g OGTT was offered to all women in the 28th week of gestation, and also in gestational week 12 if they had had a history of GDM in previous pregnancies or a first-degree relative with diabetes. The diagnostic criteria for GDM used in the present study were a modification of those recommended by the WHO in 1999, defining GDM as the joint category of diabetes and impaired glucose tolerance (IGT) based on the 2-h capillary plasma glucose concentration (World Health Organization 1999). A 2-h capillary plasma glucose concentration below the limit for IGT was considered to be normal glucose tolerance (NGT) during pregnancy (GNGT) (World Health Organization 1999). The first follow-up appointment took place 1–2 years after delivery (Anderberg et al. 2011; Ignell et al. 2013). A 75-g OGTT was performed after overnight fasting in 470 women with previous GDM, and in 166 women with previous GNGT. Fasting and 2-h venous blood samples were drawn in duplicate for determination of plasma glucose concentration, and the mean value was calculated. Diagnostic criteria were those proposed by the WHO (World Health Organization 1999). Weight and height were measured and body mass index (BMI) calculated (kg/m2). Information on first-grade family history of diabetes, earlier pregnancies, smoking/snuff habits, and ethnic affiliation was obtained. Based on the stated country of origin of at least three grandparents, women were grouped according to whether they were of European or non-European origin. Using this definition, 14 women with previous GDM were unclassifiable. In all, 32 women were diagnosed with diabetes 1–2 years after delivery (all GDM) and were referred to primary care for clinical surveillance. During the two subsequent years, 13 other women with previous GDM (3 NGT and 10 IGT at 1–2 years) were given a diabetes diagnosis. Page 2 of 11 Ignell et al. SpringerPlus (2016) 5:318 Page 3 of 11 The second and final follow-up took place 5 years after pregnancy and followed (...truncated)