The impact of risk factors and more stringent diagnostic criteria of gestational diabetes on outcomes in central European women.

OBJECTIVES: In the face of the ongoing discussion on the criteria for the diagnosis of gestational diabetes (GDM), we aimed to examine whether the criteria of the Fourth International Workshop Conference of GDM (WC) select women and children at risk better than the World Health Organization (WHO) criteria. DESIGN AND SETTING: This was a prospective longitudinal open study in five tertiary care centers in Austria. PATIENTS AND OUTCOME MEASURES: The impact of risk factors, different thresholds (WC vs. WHO), and numbers of abnormal glucose values (WC) during the 2-h, 75-g oral glucose tolerance test on fetal/neonatal complications and maternal postpartum glucose tolerance was studied in 1466 pregnant women. Women were treated if at least one value according to the WC (GDM-WC1) was met or exceeded. RESULTS: Forty-six percent of all women had GDM-WC1, whereas 29% had GDM-WHO, and 21% of all women had two or three abnormal values according to WC criteria (GDM-WC2). Eighty-five percent of the GDM-WHO were also identified by GDM-WC1. Previous GDM [odds ratio (OR) 2.9], glucosuria (OR 2.4), preconceptual overweight/obesity (OR 2.3), age 30 yr or older (OR 1.9), and large-for-gestational age (LGA) fetus (OR 1.8) were the best independent predictors of the occurrence of GDM. Previous GDM (OR 4.4) and overweight/obesity (OR 4.0) also independently predicted diabetes postpartum. GDM-WC1 had a higher rate of obstetrical complications (LGA neonates, neonatal hypoglycemia, cesarean sections; P < 0.001) and impaired postpartum glucose tolerance (P < 0.0001) than GDM-WHO. CONCLUSION: These results suggest the use of more stringent WC criteria for the diagnosis of GDM with the initiation of therapy in case of one fasting or stimulated abnormal glucose value because these criteria detected more LGA neonates with hypoglycemia and mothers with impaired postpartum glucose metabolism than the WHO criteria.

Value of the intravenous and oral glucose tolerance tests for detecting subtle impairments in insulin sensitivity and beta-cell function in former gestational diabetes.

OBJECTIVE: Women with former gestational diabetes mellitus (fGDM) often show defects in both insulin sensitivity and beta-cell function but it is not clear which defect plays the major role or which appears first. This might be because fGDM women are often studied as a unique group and not divided according to their glucose tolerance. Different findings might also be the result of using different tests. Our aim was to study insulin sensitivity and beta-cell function with two independent glucose tolerance tests in fGDM women divided according to their glucose tolerance. DESIGN AND PATIENTS: A total of 108 fGDM women divided into normal glucose tolerance (IGT; N = 82), impaired glucose metabolism (IGM; N = 20) and overt type 2 diabetes (T2DM; N = 6) groups, and 38 healthy control women (CNT) underwent intravenous (IVGTT) and oral glucose tolerance tests (OGTT). Measurements Insulin sensitivity and beta-cell function were assessed by both the IVGTT and the OGTT. RESULTS: Both tests revealed impaired insulin sensitivity in the normotolerant group compared to controls (IVGTT: 4.2 +/- 0.3 vs. 5.4 +/- 0.4 10(-4) min(-1) (microU/ml)(-1); OGTT: 440 +/- 7 vs. 472 +/- 9 ml min(-1) m(-2)). Conversely, no difference was found in beta-cell function from the IVGTT. However, some parameters of beta-cell function by OGTT modelling analysis were found to be impaired: glucose sensitivity (106 +/- 5 vs. 124 +/- 7 pmol min(-1) m(-2) mm(-1), P = 0.0407) and insulin secretion at 5 mm glucose (168 +/- 9 vs. 206 +/- 10 pmol min(-1) m(-2), P = 0.003). CONCLUSIONS: Both insulin sensitivity and beta-cell function are impaired in normotolerant fGDM but the subtle defect in beta-cell function is disclosed only by OGTT modelling analysis.

Elevated concentrations of asymmetric dimethylarginine are associated with deterioration of glucose tolerance in women with previous gestational diabetes mellitus.

OBJECTIVE: Women with previous gestational diabetes mellitus (GDM) have a high risk for development of type 2 diabetes mellitus. The endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) could be related to disorders of the glucose metabolism. To evaluate if ADMA predicts deterioration of glucose tolerance in women with previous GDM and to assess concentration changes we analysed ADMA in women with previous GDM after delivery and after a median follow-up of 2.75 years (interquartile range: 1.47-4.60). DESIGN: Prospective cohort study. Subjects and methods. ADMA, symmetric dimethylarginine (SDMA) and L-arginine were determined in 77 women with previous GDM who underwent a 75-g oral glucose tolerance test 4 months after delivery and at follow-up. RESULTS: Deterioration in glucose tolerance was observed in 36% of the women with ADMA above and 11% of those with ADMA below the median (0.56 micromol L(-1); P = 0.008, log-rank test). ADMA correlated significantly with mean arterial blood pressure and nonsignificantly with body mass index (P = 0.050) but not with insulin resistance, fasting glucose, lipids or glomerular filtration rate. The fully adjusted hazard ratio for a decline of glucose tolerance during follow-up was 3.94 (95% CI: 1.16-13.37; P = 0.028) for subjects with ADMA above the median. SDMA and L-arginine were not associated with changes in the glucose tolerance status. ADMA and L-arginine decreased significantly during follow-up. CONCLUSIONS: High serum ADMA after delivery is associated with deterioration in glucose tolerance in women with previous GDM and declines in the following years.

Gestational diabetes mellitus is associated with increased C-reactive protein concentrations in the third but not second trimester.

OBJECTIVE: Serum C-reactive protein (CRP) concentrations were measured longitudinally throughout pregnancy to test the hypothesis that CRP could relate more closely to glucose tolerance than to adiposity. METHODS: The CRP concentrations in pregnant women with normal glucose tolerance (NGT) and those with gestational diabetes mellitus (GDM) were measured at the same time as the oral glucose tolerance test (OGTT), at the 24th and 28th weeks of gestation and between the 37th and 38th weeks of gestation. RESULTS: At the end of the third trimester, women with GDM had significantly higher CRP levels than women with NGT [median (interquartile range), 9.7 mg L(-1) (5.4-16.0) and 5.7 mg L(-1) (5.1-7.2); P < 0.001, respectively], but at the time of the diagnostic OGTT no significant difference between the two groups was observed. This was owing to a significant increase of CRP in women with GDM between the time of the OGTT and the 37th-38th gestational weeks [median (interquartile range), 1.9 mg L(-1) (-2.2, 6.7); P = 0.01]; whereas, no change in CRP was found in women with NGT [median (interquartile range), -0.1 mg L(-1) (-2.4, 3.1); P = 0.76]. Multiple linear regression analysis showed only a significant independent influence of GDM (P < 0.001) on maternal CRP concentrations in the 37th-38th gestational weeks and a significant influence of body mass index (P < 0.007), but no influence of GDM at the time of the OGTT. CONCLUSION: These data suggest that in women with gestational diabetes the CRP concentration is primarily related to the degree of adiposity until the second trimester and that thereafter impaired glucose metabolism appears to be the predominant predictor of changes in CRP.