Cancer, cardiovascular disease, and all-cause mortality in Iraqi- and Swedish-born individuals in Sweden: the MEDIM cohort study.

Immigrants from the Middle East to Sweden have a twice as high prevalence of type 2 diabetes (T2D) and obesity as native-born Swedes. Both obesity and T2D have been linked to increased incidence of cancer, cardiovascular disease (CVD) and all-cause mortality (ACM); however, data on differences between ethnicities are scarce. In a population-based cohort we aimed to study the impact of Middle Eastern and European ethnicity on ACM, cancer- and CVD related mortality, incidence of cancer and CVD in an eight-year follow-up study. Methods: People born in Iraq or Sweden, who were 30-75 years of age, were invited from 2010 to 2012 to participate in the population based MEDIM study including a health exam, fasting blood sampling, assessment of insulin secretion and action (through oral glucose tolerance test) and questionnaires assessing history of CVD, cancer and T2D. Register data were retrieved from baseline until the 31st of December 2018 from the Swedish National Patient Register and Cause of Death register regarding CVD diagnosis, cancer diagnosis and cause of death. Information regarding diabetes diagnosis was retrieved from the National Diabetes Register. Individuals with a history of cancer or CVD at baseline were excluded. Cox regression analysis was assessed to study the adjusted hazard ratios (HR) for the relationships between ethnicity and ACM, cancer events, CVD events, death from cancer, and death from CVD, with adjustments for age, sex, anthropometrical measures, T2D and lifestyle. A total of 1398 Iraqi- and 757 Swedish-born residents participated in the study. ACM was considerably lower in Iraqi- compared to Swedish-born individuals HR 0.32 (95% CI 0.13-0.79) (p < 0.05). Furthermore, cancer related morbidity and mortality HR 0.39 (0.22-0.69) (p < 0.01) as well as CVD related morbidity and mortality HR 0.56 (0.33-0.95) (p < 0.05) were lower in the Iraqi-born group compared to the Swedish-born group for. The differences in mortality and cancer rates across ethnicities are not fully explained by anthropometric, environmental or metabolic measures but lie elsewhere. Further studies are needed to increase the understanding of contributing mechanisms.

Insulin secretion and action with increasing age - A comparison between Middle Eastern immigrants and native Swedes.

Aims: Little is known how insulin secretion and action change over time in populations of different ethnicities. We studied changes in insulin secretion and action with increasing age in Iraqi-born immigrants and native Swedes, and investigated if the changes were modified by region of origin. Methods: Residents of Malmö, 30-75 years of age born in Iraq or Sweden, were invited to participate in this population-based, cross-sectional study. Health examination, medical history, lifestyle, sociodemographic data, and fasting blood samples were assessed. Oral glucose tolerance tests were performed and insulin secretion (disposition index, DIo) and insulin sensitivity index (ISI) calculated using the Matsuda indices. Results: In total 1881 people participated; 1193 Iraqi- and 688 Swedish born. DIo decreased with increasing age in the total study population (ß for the effect of age on ln DIo: -0.018, 95% CI -0.023 to -0.013, P < 0.001), adjusted for origin, lifestyle and anthropometric measures. DIo was generally lower in Iraqis vs. Swedes (median: 12,712.9 vs. 14,659.2, P = 0.004), but the difference disappeared when adjusted for BMI.Further, ISI declined with increasing age in both Iraqis and Swedes. ISI was generally lower among Iraqis compared to Swedes, (median: 76.9 vs. 102.3, p < .001). The difference could not be fully explained by age, sex, lifestyle, and anthropometric measures. No significant interactions were observed. Conclusions: The levels of DIo and ISI were lower among Iraqis compared to Swedes and declined with increasing age, irrespective of origin.

Association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus.

BACKGROUND: This study investigated whether single nucleotide polymorphisms (SNPs) reported by previous genome-wide association studies (GWAS) to be associated with impaired insulin secretion, insulin resistance, and/or type 2 diabetes are associated with disposition index, the homeostasis model assessment of insulin resistance (HOMA-IR), and/or development of diabetes following a pregnancy complicated by gestational diabetes mellitus (GDM). METHODS: Seventy-two SNPs were genotyped in 374 women with previous GDM from Southern Sweden. An oral glucose tolerance test was performed 1-2 years postpartum, although data on the diagnosis of diabetes were accessible up to 5 years postpartum. HOMA-IR and disposition index were used to measure insulin resistance and secretion, respectively. RESULTS: The risk A-allele in the rs11708067 polymorphism of the adenylate cyclase 5 gene (ADCY5) was associated with decreased disposition index (beta = - 0.90, SE 0.38, p = 0.019). This polymorphism was an expression quantitative trait loci (eQTL) in islets for both ADCY5 and its antisense transcript. The risk C-allele in the rs2943641 polymorphism, near the insulin receptor substrate 1 gene (IRS1), showed a trend towards association with increased HOMA-IR (beta = 0.36, SE 0.18, p = 0.050), and the T-allele of the rs4607103 polymorphism, near the ADAM metallopeptidase with thrombospondin type 1 motif 9 gene (ADAMTS9), was associated with postpartum diabetes (OR = 2.12, SE 0.22, p = 0.00055). The genetic risk score (GRS) of the top four SNPs tested for association with the disposition index using equal weights was associated with the disposition index (beta = - 0.31, SE = 0.29, p = 0.00096). In addition, the GRS of the four SNPs studied for association with HOMA-IR using equal weights showed an association with HOMA-IR (beta = 1.13, SE = 0.48, p = 9.72874e-11). All analyses were adjusted for age, body mass index, and ethnicity. CONCLUSIONS: This study demonstrated the genetic susceptibility of women with a history of GDM to impaired insulin secretion and sensitivity and, ultimately, to diabetes development.

Glycemic, maternal and neonatal outcomes in women with type 1 diabetes using continuous glucose monitoring during pregnancy - Pump vs multiple daily injections, a secondary analysis of an observational cohort study.

INTRODUCTION: Continuous glucose monitoring (CGM) provides detailed information about glucose level fluctuations over time. The method is increasingly being used in pregnant women with type 1 diabetes. However, only one previous study compared CGM results related to pregnancy outcomes in women using insulin pumps with those administering multiple daily injections (MDI). We performed a secondary analysis of CGM metrics from an observational cohort of pregnant women with type 1 diabetes and compared insulin pump and MDI therapies in relation to maternal and neonatal outcomes. MATERIAL AND METHODS: The study included 185 pregnant Swedish women with type 1 diabetes undergoing CGM throughout pregnancy. Women were divided according to insulin administration mode, ie MDI (n = 131) or pump (n = 54). A total of 91 women used real-time CGM and 94 women used intermittently viewed CGM. Maternal demographics and maternal and neonatal outcome data were collected from medical records. CGM data were analyzed according to predefined glycemic indices: mean glucose; standard deviation; percentage of time within, below and above glucose target range; mean amplitude of glycemic excursion; high and low glucose indices; and coefficient variation in percent. Associations between insulin administration mode and CGM data, on the one hand, and maternal and neonatal outcomes, on the other, were analyzed with analysis of covariance and logistic regression, respectively, adjusted for confounders. RESULTS: There were no differences in maternal characteristics or glycemic indices between the MDI and pump groups, except for a longer duration of type 1 diabetes and higher frequencies of microangiopathy and real-time CGM among pump users. Despite improvement with each trimester, glucose levels remained suboptimal throughout pregnancy in both groups. There were no differences between the MDI and pump groups concerning the respective associations with any of the outcomes. The frequency of large for gestational age was high in both groups (MDI 49% vs pump 63%) and did not differ significantly. CONCLUSIONS: Pregnant women with type 1 diabetes did not differ in glycemic control or pregnancy outcome, related to MDI or pump administration of insulin. Glycemic control remained suboptimal throughout pregnancy, regardless of insulin administration mode.

Association between the rs1544410 polymorphism in the vitamin D receptor (VDR) gene and insulin secretion after gestational diabetes mellitus.

BACKGROUND AND AIMS: Genetic variants involved in vitamin D metabolism have been associated with diabetes and related syndromes/diseases. We wanted to investigate possible associations of polymorphisms in genes involved in vitamin D metabolism with indices of insulin resistance and insulin secretion, and also with development of diabetes after gestational diabetes mellitus (GDM). MATERIALS AND METHODS: We have studied 376 women with previous GDM. Eight single nucleotide polymorphisms (SNPs) in the genes for vitamin D receptor (VDR) [rs731236, rs7975232, rs10735810, and rs1544410], vitamin D binding protein (DBP) [rs7041 and rs4588], and cytochrome P450 family 27 subfamily B member 1 (CYP27B1) [rs10877012 and rs4646536] were genotyped by TaqMan Allelic Discrimination Assay using the Quantstudio 7 Flex system. A 75-g oral glucose tolerance test (OGTT) was performed 1-2 years postpartum. The homeostasis model assessment of insulin resistance (HOMA-IR) and the disposition index [(insulinogenic index: I30/G30)/HOMA-IR] were used to calculate insulin resistance and insulin secretion, respectively. Serum samples for determination of 25(OH)D3 were collected at the time of the OGTT. Manifestation of diabetes was followed up to five years postpartum. RESULTS: After adjustment for BMI, age, and ethnicity, the A-allele of the VDR rs1544410 polymorphism was found to be associated with increased disposition index (difference per allele = 3.56, 95% CI: 0.4567-6.674; p = 0.03). The A-allele of the DBP rs7041 polymorphism was found to be associated with 25(OH)D3 levels (difference [in nmol/L] per allele = -5.478, 95% CI: -8.315 to -2.641; p = 0.0002), as was the T-allele of the DBP rs4588 polymorphism (OR = -6.319, 95% CI: -9.466 to -3.171; p = 0.0001). None of the SNPs were significantly associated with HOMA-IR or postpartum diabetes. CONCLUSIONS: This study provides evidence that the rs1544410 polymorphism of the VDR gene may be associated with increased insulin secretion in women after pregnancy complicated by GDM. Further studies in other populations are needed to confirm the results.

Diagnosis of Gestational Diabetes Mellitus with Point-of-Care Methods for Glucose versus Hospital Laboratory Method Using Isotope Dilution Gas Chromatography-Mass Spectrometry as Reference.

BACKGROUND: In Sweden, both glucose analyzers in accredited laboratories and point-of-care glucose devices are used for gestational diabetes mellitus (GDM) diagnosis. The aim of this study was to compare the diagnostic performance of the HemoCue Glucose 201+ (HC201+) and RT (HC201RT) systems with that of the hospital central laboratory hexokinase method (CL) based on lyophilized citrate tubes, using the isotope dilution gas chromatography-mass spectrometry (ID GC-MS) as reference. METHODS: A 75 g oral glucose tolerance test was performed on 135 women screened positive for GDM. Diagnosis was based on the World Health Organization 2013 diagnostic thresholds for fasting (n = 135), 1 h (n = 135), 1 h (n = 135), 1 h (. RESULTS: Significantly more women were diagnosed with GDM by HC201+ (80%) and CL (80%) than with the reference (65%, P < 0.001) based on fasting and/or 2 h thresholds, whereas the percentage diagnosed by HC201RT (60%) did not differ significantly from the reference. In Bland-Altman analysis, a positive bias was observed for HC201+ (4.2%) and CL (6.1%) and a negative bias for HC201RT (-1.8%). In the surveillance error grid, 95.9% of the HC201+ values were in the no-risk zone as compared to 98.1% for HC201RT and 97.5% for CL. CONCLUSIONS: A substantial positive bias was found for CL measurements resulting in overdiagnosis of GDM. Our findings suggest better performance of HC201RT than HC201+ in GDM diagnosis. The results may have possible implications for GDM diagnosis in Sweden and require further elucidation.

Continuous glucose monitoring in pregnant women with type 1 diabetes: an observational cohort study of 186 pregnancies.

AIMS/HYPOTHESIS: The aim of this study was to analyse patterns of continuous glucose monitoring (CGM) data for associations with large for gestational age (LGA) infants and an adverse neonatal composite outcome (NCO) in pregnancies in women with type 1 diabetes. METHODS: This was an observational cohort study of 186 pregnant women with type 1 diabetes in Sweden. The interstitial glucose readings from 92 real-time (rt) CGM and 94 intermittently viewed (i) CGM devices were used to calculate mean glucose, SD, CV%, time spent in target range (3.5-7.8 mmol/l), mean amplitude of glucose excursions and also high and low blood glucose indices (HBGI and LBGI, respectively). Electronic records provided information on maternal demographics and neonatal outcomes. Associations between CGM indices and neonatal outcomes were analysed by stepwise logistic regression analysis adjusted for confounders. RESULTS: The number of infants born LGA was similar in rtCGM and iCGM users (52% vs 53%). In the combined group, elevated mean glucose levels in the second and the third trimester were significantly associated with LGA (OR 1.53, 95% CI 1.12, 2.08, and OR 1.57, 95% CI 1.12, 2.19, respectively). Furthermore, a high percentage of time in target in the second and the third trimester was associated with lower risk of LGA (OR 0.96, 95% CI 0.94, 0.99 and OR 0.97, 95% CI 0.95, 1.00, respectively). The same associations were found for mean glucose and for time in target and the risk of NCO in all trimesters. SD was significantly associated with LGA in the second trimester and with NCO in the third trimester. Glucose patterns did not differ between rtCGM and iCGM users except that rtCGM users had lower LBGI and spent less time below target. CONCLUSIONS/INTERPRETATION: Higher mean glucose levels, higher SD and less time in target range were associated with increased risk of LGA and NCO. Despite the use of CGM throughout pregnancy, the day-to-day glucose control was not optimal and the incidence of LGA remained high.

Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables.

BACKGROUND: Diabetes is presently classified into two main forms, type 1 and type 2 diabetes, but type 2 diabetes in particular is highly heterogeneous. A refined classification could provide a powerful tool to individualise treatment regimens and identify individuals with increased risk of complications at diagnosis. METHODS: We did data-driven cluster analysis (k-means and hierarchical clustering) in patients with newly diagnosed diabetes (n=8980) from the Swedish All New Diabetics in Scania cohort. Clusters were based on six variables (glutamate decarboxylase antibodies, age at diagnosis, BMI, HbA1c, and homoeostatic model assessment 2 estimates of ß-cell function and insulin resistance), and were related to prospective data from patient records on development of complications and prescription of medication. Replication was done in three independent cohorts: the Scania Diabetes Registry (n=1466), All New Diabetics in Uppsala (n=844), and Diabetes Registry Vaasa (n=3485). Cox regression and logistic regression were used to compare time to medication, time to reaching the treatment goal, and risk of diabetic complications and genetic associations. FINDINGS: We identified five replicable clusters of patients with diabetes, which had significantly different patient characteristics and risk of diabetic complications. In particular, individuals in cluster 3 (most resistant to insulin) had significantly higher risk of diabetic kidney disease than individuals in clusters 4 and 5, but had been prescribed similar diabetes treatment. Cluster 2 (insulin deficient) had the highest risk of retinopathy. In support of the clustering, genetic associations in the clusters differed from those seen in traditional type 2 diabetes. INTERPRETATION: We stratified patients into five subgroups with differing disease progression and risk of diabetic complications. This new substratification might eventually help to tailor and target early treatment to patients who would benefit most, thereby representing a first step towards precision medicine in diabetes. FUNDING: Swedish Research Council, European Research Council, Vinnova, Academy of Finland, Novo Nordisk Foundation, Scania University Hospital, Sigrid Juselius Foundation, Innovative Medicines Initiative 2 Joint Undertaking, Vasa Hospital district, Jakobstadsnejden Heart Foundation, Folkhälsan Research Foundation, Ollqvist Foundation, and Swedish Foundation for Strategic Research.

Fetal overgrowth in women with type 1 and type 2 diabetes mellitus.

OBJECTIVES: Despite improved glycemic control, the rate of large-for-gestational-age (LGA) infants remains high in pregnancies complicated by diabetes mellitus type 1 (T1DM) and type 2 (T2DM). Poor glycemic control, obesity, and excessive gestational weight gain are the main risk factors. The aim of this study was to determine the relative contribution of these risk factors for LGA in women with T1DM and T2DM, after controlling for important confounders such as age, smoking, and parity. METHODS: In this retrospective chart review study, we analyzed the medical files of pregnant women with T1DM and T2DM who attended the antenatal care program at Skåne University Hospital during the years 2006 to 2016. HbA1c was used as a measure of glycemic control. Maternal weight in early pregnancy and at term was registered. LGA was defined as birth weight > 2 standard deviations of the mean. Univariable and multivariable logistic regression analysis was used to calculate odds ratios (OR's) and 95% confidence intervals (CIs) for LGA. RESULTS: Over the 11-year period, we identified 308 singleton pregnancies in 221 women with T1DM and in 87 women with T2DM. The rate of LGA was 50% in women with T1DM and 23% in women with T2DM. The multivariable regression model identified gestational weight gain and second-trimester HbA1c as risk factors for LGA in T1DM pregnancies (OR = 1.107, 95% CI: 1.044-1.17, and OR = 1.047, 95% CI: 1.015-1.080, respectively) and gestational weight gain as a risk factor in T2DM pregnancies (OR = 1.175, 95% CI: 1.048-1.318), independent of body mass index. CONCLUSIONS: Gestational weight gain was associated with LGA in women with T1DM and T2DM, independent of maternal body mass index. The findings suggest that monitoring and regulation of gestational weight gain is important in the clinical care of these women, to minimize the risk of fetal overgrowth.

Glucose homeostasis, beta cell function, and insulin resistance in relation to vitamin D status after gestational diabetes mellitus.

INTRODUCTION: We wanted to determine vitamin D status after gestational diabetes mellitus (GDM) and to evaluate whether levels of 25-hydroxyvitamin D3 (25OHD3 ) are associated with beta cell function, insulin resistance or a diagnosis of diabetes after GDM. MATERIAL AND METHODS: Glucose homeostasis was assessed during a 75-g oral glucose tolerance test one to two years after delivery in 376 women with previous GDM (287 European and 78 non-European, including 33 Arab and 35 Asian women). Insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR). The insulinogenic index (I/G30) and the disposition index [(I/G30)/HOMA-IR] were used to calculate insulin secretion. Concentrations of serum 25OHD3 were determined. RESULTS: Mean (±SD) 25OHD3 concentration was 50.0 ± 22.3 nmol/L and differed significantly among subgroups of body mass index, ethnicity, and glucose tolerance status; 53% had 25OHD3 levels <50 nmol/L and 87% had 25OHD3 levels <75 nmol/L. There was a negative correlation between 25OHD3 concentration and HOMA-IR (p < 0.001) and a positive correlation between 25OHD3 and disposition index (p = 0.002) in univariable regression analysis. Correlations attenuated after adjustment for body mass index. In univariable regression analysis, 25OHD3 concentrations were significantly associated with diabetes after GDM (p = 0.004). However, in a multivariable model, non-European origin, HOMA-IR and insulinogenic index were significantly associated with postpartum diabetes, whereas 25OHD3 concentrations were not. CONCLUSION: Vitamin D deficiency/insufficiency in previous GDM cases appears to be associated with beta cell dysfunction and insulin resistance, but not with postpartum diabetes when factors well known to influence type-2 diabetes were adjusted for.

HbA1c as a predictor of diabetes after gestational diabetes mellitus.

AIM: We wanted to investigate third-trimester HbA1c as a predictor of diabetes after gestational diabetes mellitus (GDM). METHODS: Women with GDM were followed up prospectively for five years from pregnancy to detect the development of diabetes. The ability of HbA1c to predict diabetes was evaluated with receiver-operating characteristic (ROC) curves and logistic regression analysis. RESULTS: By five years, 73 of 196 women had been diagnosed with diabetes. An optimal cut-off point for HbA1c of 36mmol/mol (5.4%) could predict diabetes with 45% sensitivity and 92% specificity. For HbA1c ≥39mmol/mol (≥5.7%), sensitivity, specificity, and positive predictive value were 30%, 97%, and 91%, respectively. In logistic regression analysis, adjusting for the diagnostic glucose concentration during pregnancy, HbA1c levels in the upper quartile (≥36mmol/mol) were associated with a 5.5-fold increased risk of diabetes. CONCLUSION: Third-trimester HbA1c levels in the pre-diabetes range revealed women with post-partum diabetes with high specificity and high positive predictive value. HbA1c testing could be used as a strategy to select high-risk women for lifestyle interventions aimed at prevention of diabetes starting during pregnancy. The results should encourage further validation in other populations using new diagnostic criteria for GDM.

Seasonal Pattern in the Diagnosis of Gestational Diabetes Mellitus in Southern Sweden.

Aim. The aim of this study was to examine seasonal patterns in glucose tolerance and in the diagnosis of gestational diabetes mellitus (GDM). Methods. Altogether, 11 538 women underwent a 75-g oral glucose tolerance test (OGTT) in the twenty-eighth week of pregnancy during the years 2003-2005 in southern Sweden. GDM was defined by the 2-h capillary glucose concentration in the OGTT (≥8.9 mmol/L). Chi-squared test, analysis of variance, and regression analyses were used for statistical evaluations. Results. The seasonal frequency of GDM ranged from 3.3% in spring to 5.5% in summer (p < 0.0001). Mean 2-h glucose concentrations followed the same seasonal trend, with a difference of 0.15 mmol/L between winter and summer (p < 0.0001). The 2-h glucose level increased by 0.009 mmol/L for every degree increase in temperature (p < 0.0001). In regression analysis, summer (June-August) was associated with increased 2-h glucose level (p < 0.001) and increased frequency of GDM compared to the other seasons (odds ratio 1.51, 95% confidence interval 1.24-1.83, and p < 0.001). Conclusions. Our findings suggest seasonal variation in the 2-h glucose concentration in the OGTT and in the proportion of women diagnosed with GDM, with a peak in the summer.

The impact of ethnicity on glucose homeostasis after gestational diabetes mellitus.

The objective of this study was to examine measures of insulin resistance and beta cell function in relation to ethnicity and the development of diabetes after gestational diabetes mellitus (GDM). Glucose homeostasis was assessed during a 75 g oral glucose tolerance test 1-2 years after delivery in 456 women with previous GDM (362 European, 94 non-European; including 41 Arab and 43 Asian women) and 133 control women. Insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR). The insulinogenic index (I/G30) and the disposition index [(I/G30)/HOMA-IR] were used to quantify insulin secretion. Women developing diabetes after GDM were characterized by increased HOMA-IR [p = 0.010, adjusted for body mass index (BMI)], whereas the disposition index was decreased in all women with previous GDM irrespective of glucose tolerance, most pronounced in the presence of diabetes (BMI-adjusted p = 1 × 10(-5)). Non-European origin was associated with increased HOMA-IR (p = 0.001 vs. European), strengthened by adjustment for BMI in Asian women (p = 0.046 vs. p = 0.016), but eradicated among Arab women (p = 0.004 vs. p = 0.65). Non-European women exhibited an increased frequency of diabetes after GDM (17 % vs. European 4 %, p = 2 × 10(-5)). In addition to BMI, non-European and Asian origin was associated with the development of diabetes after GDM in a multivariate logistic regression analysis, whereas Arab origin was not. Our results highlight the importance of preventive measures to ensure a healthy lifestyle in women with GDM, particularly in high-risk ethnic groups.

Evidence of still-ongoing convergence evolution of the lactase persistence T-13910 alleles in humans.

A single-nucleotide variant, C/T(-13910), located 14 kb upstream of the lactase gene (LCT), has been shown to be completely correlated with lactase persistence (LP) in northern Europeans. Here, we analyzed the background of the alleles carrying the critical variant in 1,611 DNA samples from 37 populations. Our data show that the T(-13910) variant is found on two different, highly divergent haplotype backgrounds in the global populations. The first is the most common LP haplotype (LP H98) present in all populations analyzed, whereas the others (LP H8-H12), which originate from the same ancestral allelic haplotype, are found in geographically restricted populations living west of the Urals and north of the Caucasus. The global distribution pattern of LP T(-13910) H98 supports the Caucasian origin of this allele. Age estimates based on different mathematical models show that the common LP T(-13910) H98 allele (approximately 5,000-12,000 years old) is relatively older than the other geographically restricted LP alleles (approximately 1,400-3,000 years old). Our data about global allelic haplotypes of the lactose-tolerance variant imply that the T(-13910) allele has been independently introduced more than once and that there is a still-ongoing process of convergent evolution of the LP alleles in humans.

Genetics of gestational diabetes mellitus.

About 2-5% of all pregnant women develop gestational diabetes mellitus (GDM) during their pregnancies and the prevalence has increased considerably during the last decade. GDM is a heterogeneous disorder that is defined as carbohydrate intolerance with onset or first recognition during pregnancy. It is manifested when pancreatic beta cells are no longer able to compensate for the increased insulin resistance during pregnancy, but the pathogenesis of the disease is still largely unknown. GDM is considered to result from interaction between genetic and environmental risk factors. Genetic predisposition to GDM has been suggested since GDM clusters in families. Also, women with mutations in MODY (Maturity onset diabetes of the young) genes often present with GDM. In addition, common variants in several candidate genes (e.g. potassium inwardly rectifying channel subfamily J, member 11 [KCNJ11], Glucokinase [GCK], Hepatocyte nuclear factor-1alpha [HNF1A] etc.) have been demonstrated to increase the risk of GDM. Old age, obesity and high fat diet represent some important non-genetic factors. There are several approaches to search for genes predisposing to a polygenic disease like GDM including linkage and association studies, expression profiling and animal models. A combination of several methods is usually necessary. Identification of the underlying genetic causes of GDM will eventually give a better view of the mechanisms that contribute to the pathophysiology of the disease. Furthermore, it may improve options to possibly prevent GDM and complications for the mother and her child. This review focuses on the genetics of GDM and possible implications in clinical practice.