Future risk of metabolic syndrome in women with a previous LGA delivery stratified by gestational glucose tolerance: a prospective cohort study.

BACKGROUND: Whether the delivery of a large-for-gestational-age (LGA) infant predicts future maternal metabolic syndrome (MetS) is not known. To this aim, we investigated the incidence of MetS and its components in women with or without a history of gestational diabetes mellitus (GDM) with a view to the birth weight of the offspring. METHODS: Eight hundred seventy six women treated for their pregnancies in Kuopio University Hospital in 1989-2009 underwent a follow-up study (mean follow-up time 7.3 (SD 5.1) years), of whom 489 women with GDM and 385 normoglycemic controls. The women were stratified into two groups according to the newborn's birth weight: 10-90th percentile (appropriate-for-gestational-age; AGA) (n = 662) and > 90th percentile (LGA) (n = 116). MetS and its components were evaluated in the follow-up study according to the International Diabetes Federation criteria. RESULTS: LGA vs. AGA delivery was associated with a higher incidence of MetS at follow-up in women with a background of GDM (54.4% vs. 43.6%), but not in women without GDM. CONCLUSION: An LGA delivery in women with GDM is associated with a higher risk of future MetS and this group is optimal to study preventive measures for MetS. In contrast, an LGA delivery after a normoglycemic pregnancy was not associated with an increased future maternal MetS risk.

Delivery of an LGA infant and the maternal risk of diabetes: A prospective cohort study.

AIMS: Was to determine whether the birth weight of the infant predicts prediabetes (impaired fasting glucose, impaired glucose tolerance, or both) and type 2 diabetes (T2DM) during long-term follow-up of women with or without gestational diabetes mellitus (GDM). METHODS: The women with or without GDM during their pregnancies in Kuopio University Hospital in 1989-2009 (n=876) were contacted and invited for an evaluation. They were stratified into two groups according to the newborn's birth weight: 10-90th percentile (appropriate-for-gestational-age; AGA) (n=662) and >90th percentile (large-for-gestational-age; LGA) (n=116). Glucose tolerance was investigated with an oral glucose tolerance test after a mean follow-up time of 7.3 (SD 5.1) years. RESULTS: The incidence of T2DM was 11.8% and 0% in the women with and without GDM, respectively, after an LGA delivery. The incidence of prediabetes increased with offspring birth weight categories in the women with and without GDM: from 46.3% and 26.2% (AGA) to 52.9% and 29.2% (LGA), respectively. CONCLUSIONS: GDM women with LGA infants are at an increased risk for subsequent development of T2DM and therefore represent a target group for intervention to delay or prevent T2DM development. In contrast, an LGA delivery without GDM does not increase T2DM risk.

The risk of metabolic syndrome in women with previous GDM in a long-term follow-up.

The aim of this study was to evaluate the incidence of metabolic syndrome (MetS) during long-term follow-up of women with gestational diabetes (GDM). Furthermore, we evaluated the glycemic measures from an oral glucose tolerance test (OGTT) during pregnancy as predictors of incident MetS. Women diagnosed with GDM were divided into two groups according to the results of OGTT: one abnormal value = GDM1 (n = 338) and two abnormal values = GDM2 (n = 151), while women with normal glucose tolerance (n = 385) served as controls. MetS and its components were evaluated in a follow-up study (mean follow-up time 7.3 ± 5.1 years) according to the International Diabetes Federation (IDF) criteria. Fasting plasma glucose in OGTT was the best predictor of incident MetS in ROC (area under the curve) analysis. The incidence of MetS during a <5-year follow-up was 22.2% in controls, 39.3% in GDM1 and 60.4% in GDM2; and >10-year follow-up 24.2%, 46.2% and 62.5%, respectively. In controls and GDM2, the incidence of MetS remained nearly constant during the follow-up, whereas in GDM1 it increased. In conclusion, already mild gestational glucose intolerance may progress to MetS and therefore merits intervention measures to prevent future cardiovascular disease.

Post-challenge glycemia during pregnancy as a marker of future risk of type 2 diabetes: a prospective cohort study.

The aim of this study was to evaluate the glycemic measures from an oral glucose tolerance test (OGTT) during pregnancy as predictors of incident type 2 diabetes mellitus (T2DM). Patients diagnosed with gestational diabetes mellitus (GDM) were divided into two groups according to the results of OGTT: one abnormal value = GDM1 (n = 338) and two abnormal values = GDM2 (n = 151), while women with normal glucose tolerance served as controls (n = 385). Glucose tolerance was re-evaluated with an OGTT in a follow-up study (average follow-up time 7.3 ± 5.1 years). The incidence of T2DM after 10 years follow-up increased progressively by the degree of the glycemic abnormality during pregnancy: 0.8% in controls, 3.8% in GDM1 (adjusted HR 17.6, 95% CI 1.9-162.3) and 25.0% in GDM2 (adjusted HR 72.9, 95% CI 9.6-553.7), respectively (p = <0.0001). The risk of T2DM is significantly increased in women with two or more abnormal values in OGTT during pregnancy. Post-challenge glucose levels in OGTT were the best predictors of the incident T2DM in ROC analysis and they therefore identify the greatest risk group for targeted prevention of T2DM after GDM.

Long-term changes in glucose metabolism after gestational diabetes: a double cohort study.

BACKGROUND: Gestational diabetes (GDM) has been associated with an elevated risk of type 2 diabetes in women after the pregnancy. Recognition of the factors differentiating the women at highest risk of progression to overt disease from those who remain normoglycemic after gestational diabetes is of key importance for targeted prevention programmes. To this aim, we investigated the incidence and risk factors of prediabetes and type 2 diabetes with a view to the underlying pathophysiological mechanisms in a long-term follow-up of women with a history of gestational diabetes. METHODS: 489 women with GDM and 385 normoglycemic controls attended a follow-up study after pregnancy (mean follow-up time 7.3, SD 5.1 years) in Kuopio, Finland. Glucose tolerance was evaluated with an oral glucose tolerance test, insulin sensitivity by Matsuda insulin sensitivity index (ISI), and insulin secretion by Disposition Index 30 (DI30). RESULTS: GDM increased risk of pre-diabetes and diabetes (HR 3.7, 95% C.I. 2.8-4.7 and HR 40.7, 95% C.I. 5.3-310.1, respectively, after adjustment for confounding factors) and was associated with both increased fasting (P < 0.001) and 2-hour plasma glucose (P < 0.001) during OGTT at the follow-up study. This effect was attenuated when adjusted for Matsuda ISI but abolished after adjustments with DI30 suggesting insulin secretion is the key defect leading to type 2 diabetes after GDM pregnancy. Increase in waist circumference and weight after pregnancy predicted the development of hyperglycemic conditions in women with a history of GDM (P < 0.001, and P = 0.002, respectively). CONCLUSIONS: Pre-diabetic stages after GDM pregnancy are frequent and reflect the progressive risk of type 2 diabetes in long-term follow-up. Hyperglycemia after GDM pregnancy results from beta cell failure and inability to compensate the increased insulin resistance by insulin secretion. Importantly, increase in waist circumference and as well as weight gain during the follow-up is associated with progression to prediabetes and type 2 diabetes in women with a history GDM.

Association of risk variants for type 2 diabetes and hyperglycemia with gestational diabetes.

OBJECTIVE: The aim of this study was to investigate the association of risk variants for type 2 diabetes (T2D) and hyperglycemia with gestational diabetes (GDM). DESIGN AND METHODS: Five hundred and thirty-three Finnish women who were diagnosed with GDM and 407 controls with normal glucose tolerance during the pregnancy were genotyped for 69 single-nucleotide polymorphisms (SNPs) which have been previously verified as susceptibility risk variants for T2D and hyperglycemia. All participants underwent an oral glucose tolerance test at the follow-up study after the index pregnancy. RESULTS: Risk variants rs10830963 and rs1387153 of MTNR1B were significantly associated with GDM (odds ratio (OR)=1.62 (95% CI 1.34-1.96), P=4.5 × 10⁻7 and 1.38 (1.14-1.66), P=7.6 × 10⁻4 respectively). Both SNPs of MTNR1B were also significantly associated with elevated fasting glucose level and reduced insulin secretion at follow-up. Additionally, risk variants rs9939609 of FTO, rs2796441 of TLE1, rs560887 of G6PC2, rs780094 of GCKR, rs7903146 of TCF7L2 and rs11708067 of ADCY5 showed nominally significant associations with GDM (OR range from 1.25 to 1.30). CONCLUSIONS: Our study suggests that GDM and T2D share a similar genetic background. Our findings also provide further evidence that risk variants of MTNR1B are associated with GDM by increasing fasting plasma glucose and decreasing insulin secretion.

Cumulative baby take-home rate among women with PCOS treated by IVF.

OBJECTIVE: This study was designed to evaluate cumulative live birth rates after an in vitro fertilisation (IVF) programme in polycystic ovary syndrome (PCOS) women. SUBJECTS AND METHODS: IVF outcomes of 66 women with PCOS diagnosed via Rotterdam criteria, who failed to conceive after ovulation induction, were compared with 106 women with tubal factor infertility. One hundred and twenty-five cycles were analysed in the PCOS group and 225 cycles in the control group (1-4 cycles per woman). Results of frozen-thawed cycles, occurrence of ovarian hyperstimulation syndrome (OHSS) and drop-outs were also included. RESULTS: Despite a lower pregnancy rate among women with PCOS versus controls, the cumulative baby take-home rate did not differ between the groups (48.5% and 44.3%). The first cycle was the most successful cycle for living birth rate in PCOS group. One-third of PCOS women, who did not continue after unsuccessful treatment, had more miscarriage but not more OHSS compared to those who continued. CONCLUSIONS: Although the baby take-home rate was similar among women with PCOS, and controls, the outcomes of consecutive cycles were not equal. Cumulative data give more realistic information than pooled cycles.