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Objective: To characterise early metabolic abnormalities and the impact of ethnicity following gestational diabetes mellitus (GDM)., Design: Women with a history of GDM belonging to three different ethnic groups were evaluated. Using the insulin-modified, frequently-sampled intravenous glucose tolerance test (FSIVGTT) and HOMA we studied 34 European, 16 South Asian and 10 Afro-Caribbean women with normal fasting glucose following GDM and 44 European, 16 South Asian and 19 Afro-Caribbean controls to assess insulin action and secretion., Results: European post-GDM women had lower insulin sensitivity by FSIVGTT [0.6 (0.1-5.1) vs 1.5 (0.8-2.8) x10(-4).min(-1).pmol(-1).l(-1), p=0.010, adjusted for BMI p=0.054] and by HOMA [72(22-235) vs 153(55-421)%, p=0.004, adjusted for BMI p=0.006], and reduced -cell function [lower disposition index 0.05(0.01-0.40) vs 0.11(0.05-0.25)min(-1), p=0.017] compared with controls. South Asian post-GDM women had decreased -cell function [lower HOMA (%B) (73 (37-147) vs 124 (59-262) %, p=0.048 and acute insulin response to glucose (463 (131-1639) vs 1039 (393-2748) pmol/l h, p=0.052] than controls. Afro-Caribbean post-GDM women had lower glucose disappearance rate [1.3(0.6-2.8) vs 2.6 (1.8-3.8) 10(-2)/min, p=0.003] than controls, suggesting subtle glucose intolerance., Conclusions: Women with a history of GDM of three different ethnic groups, even in the presence of normal fasting glucose, display a range of metabolic abnormalities, including -cell dysfunction with variable insulin resistance. These derangements may be influenced by ethnicity.

Aims/hypothesis: We assessed the impact of ethnic origin on metabolism in women following gestational diabetes mellitus (GDM)., Materials and Methods: Glucose regulation and other features of the metabolic syndrome were studied at 20.0 (18.2-22.1) months (geometric mean [95% CI]) post-partum in women with previous GDM (185 European, 103 Asian-Indian, 80 African-Caribbean). They were compared with the same features in 482 normal control subjects who had normal glucose regulation during and following pregnancy., Results: Impaired glucose regulation or diabetes by WHO criteria were present in 37% of women with previous GDM (diabetes in 17%), especially in those of African-Caribbean and Asian-Indian origin (50 and 44%, respectively vs 28% in European, p=0.009). BMI, waist circumference, diastolic blood pressure, fasting triglyceride and insulin levels, and insulin resistance by homeostatic model assessment (HOMA), were increased following GDM (p<0.001 for all, vs control subjects). Where glucose regulation was normal following GDM, basal insulin secretion (by HOMA) was high (p<0.001 vs control subjects). Irrespective of glucose regulation in pregnancy, Asian-Indian origin was associated with high triglyceride and low HDL cholesterol levels, and African-Caribbean with increased waist circumference, blood pressure, and insulin levels, together with insulin resistance and low triglyceride concentrations. Nonetheless, the GDM-associated features were consistent within each ethnic group. The metabolic syndrome by International Diabetes Federation criteria was present in 37% of women with previous GDM, especially in non-Europeans (Asian-Indian 49%, African-Caribbean 43%, European 28%, p=0.001), and in 10% of controls., Conclusions/interpretation: Following GDM, abnormal glucose regulation and the metabolic syndrome are common, especially in non-European women, indicating a need for diabetes and cardiovascular disease prevention strategies.

Objective: Women with previous gestational diabetes (GDM) are at increased risk of subsequent type 2 diabetes. To characterize early metabolic abnormalities associated with this increased risk, we studied normoglycaemic women with a history of GDM., Patients and Measurements: We performed an insulin-modified, frequently sampled intravenous glucose tolerance test (FSIVGTT) in 34 normoglycaemic European women with previous GDM and 44 European control women, deriving measures of insulin sensitivity, glucose effectiveness, glucose disappearance rate and acute insulin response to glucose., Results: Post-GDM women were more obese than controls [body mass index (BMI), geometric mean (95% confidence interval); 25.3 kg/m2 (23.8-27.1 kg/m2) vs. 23.1 kg/m2 (21.9-24.3 kg/m2), P = 0.03]. Evidence of insulin resistance was provided by their lower insulin sensitivity as measured by FSIVGTT [0.6 x 10-4/min/pmol/l (0.3-1.2 x 10-4/min/pmol/l) vs. 1.5 x 10-4/min/pmol/l (1.2-1.8 x 10-4/min/pmol/l), P = 0.01] and by homeostatic model assessment [72% (49-107%) vs. 153% (113-206%), P = 0.004]; and by their higher fasting triglycerides [1.0 mmol/l (0.7-1.5 mmol/l) vs. 0.7 mmol/l (0.6-0.8 mmol/l), P = 0.001]. Though there was no difference between groups in fasting NEFA levels, acute NEFA suppression was diminished in the post-GDM group (P = 0.01). Concomitant beta-cell dysfunction in the post-GDM women was revealed by their lower disposition index [0.05/min (0.02-0.10/min) vs. 0.11/min (0.09-0.14/min), P = 0.02] compared to controls. The differences in insulin sensitivity, but not those of beta-cell function, were partly, though not completely, attributable to differences in regional and total adiposity., Conclusions: European normoglycaemic women with previous GDM display both glucoregulatory and antilipolytic insulin resistance, reduced beta-cell function and dyslipidaemia. These metabolic abnormalities are likely to contribute to their increased risk of future type 2 diabetes.

We assessed postprandial thermogenesis (PPT) for 3 h following a mixed meal in 29 normoglycemic European women with previous gestational diabetes (GDM), compared with 37 control women. Given the potential role of catecholamines and insulin in the regulation of PPT, we assessed insulin and catecholamine responses to the meal. There was no significant difference between the two groups in resting energy expenditure, PPT (although lower in the GDM group), or catecholamine levels. However, we observed a difference in the shape of the PPT curve between groups, and by applying a mathematical model, there was a consistent delay in PPT, insulin, and noradrenaline responses to the meal in the GDM group (T: fitted time constant, geometric mean (95% confidence interval), T(PPT) 58 (47-72) vs. 42 (37-48) min, P = 0.006; T(ins) 32 (28-37) vs. 22 (19-27) min, P = 0.002; T(NA) 30 (23-38) vs. 18 (14-23) min, P = 0.01, respectively). Fidgeting activity during the study was assessed by a novel technique and was lower in the GDM group, resting [427 (381-477) vs. 511 (466-560) kJ/min, P = 0.02] but not postprandially. These delayed PPT, insulin, and noradrenaline responses to the meal in post-GDM women represent early metabolic changes. The decrease in fidgeting activity while resting, observed in the post-GDM group, may have physiological significance for energy balance.

Objective: Increased levels of the soluble adhesion molecule sE-selectin have been reported in normoglycaemic women with previous gestational diabetes but not in other groups at increased risk of future type 2 diabetes. To explore the basis for these discrepant findings, we studied the relationship between sE-selectin and glucose regulation in a large group of women with previous gestational diabetes., Design: Comparison of sE-selectin levels between a study cohort ascertained on the basis of recent gestational diabetes and suitable control subjects., Patients: One hundred and forty women with recent gestational diabetes (104 European, 20 South Asian and 16 Afro-Caribbean) and 125 normoglycaemic control women (90 European, 19 South Asian and 16 Afro-Caribbean)., Measurements: sE-selectin, fasting lipids, insulin and current glucose regulation status., Results: There was no overall difference in sE-selectin levels between women with a history of gestational diabetes and control women among the 3 ethnic groups. European post-GDM women with abnormal glucose regulation postpartum (n = 30) had higher sE-selectin than control women (67 (54-91) ng/ml vs. 57 (43-75) ng/ml, P = 0.049). There was no difference in sE-selectin between normoglycaemic European women with a history of gestational diabetes (n = 74) and control women, even though the former displayed metabolic abnormalities predictive of diabetes. In those European post-GDM women with normal glucose regulation postpartum, sE-selectin levels were negatively correlated with time since delivery (r = -0.25, P = 0.04), suggesting that the previously described elevation of sE-selectin following GDM pregnancies slowly resolves postpartum. There was no correlation between sE-selectin levels and features of insulin resistance., Conclusions: In contrast to previous findings, this larger study does not support a role for sE-selectin as a marker, independent of prevailing glucose levels, of early metabolic abnormalities or future diabetes risk in women with previous gestational diabetes.

Objective: To assess the prevalence and characteristics of islet cell autoimmunity amongst women with gestational diabetes selected from South Asian and Afro-Caribbean as well as European populations., Design: Cross-sectional retrospective survey of subject cohort., Population: Three hundred and twenty-one women with a recent history of gestational diabetes (173 European, 86 South Asian and 62 Afro-Caribbean), a median (range) of 22 (1-150) months postpartum., Results: Antibodies to Glutamic acid decarboxylase were found in 13 (4%) of these women. There was no difference in the prevalence of anti-glutamic acid decarboxylase positivity between the three ethnic groups (European 4.6%, South Asian 3.5%, Afro-Caribbean 3.2%). Anti-glutamic acid decarboxylase positive women were leaner than anti-glutamic acid decarboxylase negative women (body mass index, median (upper-lower quartile) 23.9 (22.5-26.7) vs 26.6 (23.4-30.5)kg/m2, P = 0.03, P = 0.049 allowing for ethnicity). There was no difference between glutamic acid decarboxylase-positive and glutamic acid decarboxylase-negative women for age, family history of diabetes, waist/hip ratio, prevalence of insulin treatment during pregnancy, postpartum glucose status, lipid profile and indices of insulin action and beta-cell function., Conclusions: Markers of islet cell autoimmunity are found as frequently in gestational diabetes women of South Asian and Afro-Caribbean origin, as they are in European subjects. Identification of future risk of type 1 diabetes is relevant to the planning of clinical management and intervention strategies in women with gestational diabetes of all major ethnic groups.

Aims: It has been reported that short individuals are more likely to have abnormalities of glucose homeostasis. The aim of this study was to examine the relationship between adult height and gestational diabetes mellitus (GDM), taking into account possible artefactual or confounding explanations., Methods: Three hundred and forty-six women with previous GDM (169 European, 102 South Asian, 75 Afro-Caribbean) and 470 control women with no previous history of GDM (282 European, 94 South Asian and 94 Afro-Caribbean) were studied. Post-partum glucose status and height were measured., Results: European and South Asian women with previous GDM were shorter than control women from the same ethnic groups (European: (mean +/- SD) 162.9 +/- 6.1 vs. 165.3 +/- 6.8 cm, P < 0.0001; South Asian: 155.2 +/- 5.4 vs. 158.2 +/- 6.3 cm, P = 0.003, adjusted for age). A similar, but non-significant trend was observed among Afro-Caribbean women (162.2 +/- 6.2 vs. 163.7 +/- 6.1 cm, P = 0.1). Similar, significant height differences were observed in Europeans and South Asians when analysis was restricted to those GDM women who had received insulin during pregnancy. There was no association between height and glucose tolerance postpartum within the GDM group., Conclusions: European and South Asian women with previous GDM are shorter than control women from the same ethnic groups. The data demonstrate that this is unlikely to be an artefact resulting from the use of an fixed 75 g load in women of differing sizes, and suggest that there are likely to be common pathophysiological mechanisms underlying GDM and the determination of final adult height.

Objective: To determine the consequences of applying revised American Diabetes Association (ADA) (1997) and World Health Organization (WHO) (1998) recommendations for the classification of glucose intolerance in women with previous gestational diabetes mellitus (GDM)., Research Design and Methods: There were 192 women with previous GDM who took an oral glucose tolerance test (OGTT) 1-86 months after delivery and were classified by WHO (1985), ADA (1997, fasting glucose), and revised WHO (1998) guidelines., Results: Among the 165 women without a preexisting diagnosis of diabetes, WHO-1985 and ADA-1997 provided similar estimates of diabetes prevalence (13.3% vs. 11.5%) but widely differing estimates of impaired glucose homeostasis (31.5% impaired glucose tolerance [IGT] by WHO-1985 vs. 10.9% impaired fasting glucose by ADA-1997 criteria). Overall, 56 women (34%) showed a classification discrepancy between WHO-1985 and ADA-1997 criteria, including 44 with normal fasting glucose by ADA-1997 criteria, but abnormal 2-h glucose by WHO-1985 criteria (40 IGT, 4 diabetes). The cardiovascular risk profile of these women was more favorable than that of 18 women with impaired fasting glucose. WHO-1998 recommendations reproduced ADA-1997 findings when used as a fasting screen, but behaved similarly to WHO-1985 criteria when 2-h glucose values were also analyzed., Conclusions: All criteria produced similar estimates of diabetes prevalence. However, analyses based on a single fasting glucose screen (and a threshold of 6.1 mmol/l) failed to identify 60% of women with abnormal 2-h glucose levels. Screening women with previous GDM (and by analogy, other groups at high risk of diabetes) with a single fasting glucose has low sensitivity for the detection of abnormal glucose tolerance. Recent guidelines recommending this approach require reevaluation.