Racial differences of incident diabetes postpartum in women with a history of gestational diabetes

AimsThe aim of the present study was to investigate the race-specific association between a history of gestational diabetes mellitus (GDM) and incidence of type 2 diabetes and evaluate how the risk changed over different years after delivery.MethodsWe performed two large cohorts - the Coronary Artery Risk Development in Young Adults (CARDIA) cohort and the Tianjin GDM Observational Study. The multivariate cox regression model was used to assess the risk of incident postpartum diabetes between women with and without prior GDM.ResultsDuring a mean follow-up of 13.8 years, 405 women developed type 2 diabetes. After adjustment for multiple confounding factors, Chinese women with GDM had a higher risk of incident diabetes within 5 years postpartum than African Americans with GDM compared with Chinese and African Americans without GDM (Hazard ratio 71.5 in Chinese vs. 9.29 in African Americans). When the risk of incident diabetes was analyzed within 10 years, white women with GDM seemed to have a higher hazard ratio than African American and Chinese women with GDM compared with non-GDM women of different races. In comparison to African American women without GDM, the highest risk of type 2 diabetes over 10 years postpartum appeared in Chinese women with GDM, followed by African American women with GDM, and the smallest risk was seen in white women with GDM.ConclusionsDifferent genetic backgrounds and other risk factors among women of different races might contribute to the racial differences in the incidence of diabetes postpartum among women with GDM.     

Inflammatory markers in women with a recent history of gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is a risk factor for both Type 2 diabetes (DM2) and insulin-resistance syndrome (IRS). C-reactive protein (CRP), fibrinogen and leukocyte count are increased in the IRS and predict DM2 and cardiovascular disease (CVD). The chemochine monocyte chemoattractant protein-1 (MCP-1/CCL2) is also elevated in DM2 and CVD. Recent evidence suggests a relation between chronic inflammation and GDM, but post-delivery information on inflammatory markers in these high-risk women is lacking. Serum levels of CRP, fibrinogen, MCP-1/ CCL2, and leukocyte blood count have been assessed in 26 women with and 26 women without a recent history of GDM, matched for age, body mass index (BMI), post-partum duration and parity. DM2 was excluded in all the participants by an oral glucose tolerance test (OGTT). Women with previous GDM showed significantly higher CRP (p=0.007) and fibrinogen (p=0.02) serum concentrations, whereas MCP-1/CCL2 serum levels and leukocyte blood count were comparable in the two groups. Overall, CRP levels significantly correlated with BMI (r=0.40, p=0.03), waist-to-hip ratio (WHR) (r=0.44, p=0.001), fasting insulin (r=0.27, p=0.04), insulin-resistance assessed by means of the homeostatic model (HOMA) (r=0.28, p=0.04), and fibrinogen concentration (r=0.49, p=0.0001). At linear regression analysis, only WHR and fibrinogen were independently associated with CRP levels. In conclusion, the increase of inflammatory markers may be one of the first detectable disorders in healthy women at high risk of DM2 and IRS, like those with a GDM history.     

The prevalence of polycystic ovaries in women with a history of gestational diabetes

OBJECTIVE: Women with a history of gestational diabetes mellitus (GDM) and women with polycystic ovary syndrome (PCOS) both demonstrate abnormalities in insulin action and secretion, and both are at increased risk of developing type 2 diabetes. To determine whether these similarities reflect a common pathophysiological basis, we examined the prevalence of ultrasound-based polycystic ovarian morphology in a large multiethnic group of women with a history of GDM and a group of women who had normal glucose tolerance during pregnancy. PATIENTS AND DESIGN: We studied 91 women with previous GDM (48 European, 20 South Asian, 10 Afro-Caribbean and 13 of other or mixed ethnicity) and 73 normoglycaemic control women (56 European, one South Asian, 14 Afro-Caribbean and two of other or mixed ethnicity), a median (interquartile range) of 20 (11-36) and 29 (17-49) months postpartum, respectively. A detailed history was taken, and the prevalence of PCO morphology on ultrasound scan was assessed. Fasting lipids, insulin, glucose status, gonadotrophins and testosterone were measured. Estimates of beta-cell function (%B) and insulin sensitivity (%S) were derived using the HOMA algorithm. RESULTS: Women with previous GDM had higher fasting glucose (5.4 (4. 8-6.0) vs. 4.7 (4.4-5.0) mmol/l, P<0.0001) and features reminiscent of syndrome X: higher BMI (26.4 (22.8-31.4) vs. 23.8 (21. 0-27.5) kg/m2, P = 0.002), waist/hip ratio (0.82 (0.79-0.88) vs. 0. 77 (0.73-0.81), P<0.0001), fasting insulin (165 (68-299) vs. 54 (24-156) pmol/l, P<0.0001), triglycerides (1.1 (0.8-1.6) vs. 0.8 (0.6-1.1) mmol/l, P<0.0001) and lower insulin sensitivity (%S) (27 (16-62) vs. 86 (34-139)%, P<0.0001) compared to control women. The prevalence of PCO was higher in the previous GDM group than in the control subjects (47/91 (52%) vs. 20/73 (27%), chi2 = 9.86, P = 0. 002 overall, odds ratio 2.7, P = 0.007 by logistic regression allowing for ethnicity). There was no difference in any metabolic parameter between the post-GDM PCO group and the post-GDM normal ovaries group, but irregular cycles were more prevalent in the PCO group (22/47 (47%) vs. 9/44 (21%), chi2 = 7.03, P = 0.008). CONCLUSIONS: We found a higher prevalence of polycystic ovarian morphology in women with a history of gestational diabetes. Among the women with previous gestational diabetes, irregular cycles were more prevalent in the PCO group than in the women with normal ovarian morphology, but no other differences in endocrine or metabolic parameters were detected. These findings confirm an association between PCO and gestational diabetes and suggest that women with gestational diabetes display metabolic abnormalities irrespective of ovarian morphology.     

Prevalence of type 2 diabetes among women with a previous history of gestational diabetes mellitus

We compared the prevalence of diabetes in women who experienced gestational diabetes mellitus (GDM) with that in the general population and identified risk factors for the development of diabetes.The analysis included 868 subjects (620 GDM and 248 single positive (SP) for one of the diagnostic criteria). The post-partum examinations included 2 h 75 g oral glucose tolerance tests, lipid profiles, anthropometric measurements, and documentation of medical history, diet, and lifestyle. All participants were followed up at 6 weeks after parturition and subsequent follow-ups were conducted annually. General population subjects were identified from the 2001 Korean National Health and Nutrition Survey and age-matched for case–control analysis.Eleven (4.4%) and 71 (11.5%) subjects in the SP and GDM groups, respectively, developed diabetes, while 22 (2.5%) subjects in the general population group presented with diabetes. The risk of developing diabetes was 3.5 times greater for GDM subjects than for general population subjects, after adjusting for confounding factors. A multiple logistic regression model revealed that GDM, a family history of diabetes, and waist circumference were independently associated with the development of diabetes.We concluded that GDM women in Korea are at high risk of diabetes irrespective of the absence of putative risk factors.     

Beta-cell function and visceral fat in lactating women with a history of gestational diabetes

Lactation has been recommended as beneficial for the maternal metabolic abnormalities associated with glucose intolerance and diabetes risk, although associations between breastfeeding (BF), glucose tolerance, and adipose tissue distribution are unknown. Therefore, a population of women with recent gestational diabetes (GDM) was evaluated with comparison of results for lactating versus nonlactating women. A total of 26 women participated (14 BF and 12 nonbreastfeeding [nonBF]) with a singleton vaginal delivery after 36 weeks gestation. At 3 months postpartum, each woman completed a 75-g oral glucose tolerance test (OGTT), a frequently sampled intravenous glucose tolerance test (FSIGT), and computed tomography (CT) scanning for adipose distribution and mass. Insulin sensitivity was not significantly different between BF and nonBF groups (4.97 +/- 0.78 v 3.44 +/- 1.0 x 10(-4) min(-1)/(microU/mL) nor was glucose effectiveness (1.92 +/- 0.22 v 1.56 +/- 0.19 x 10(-2) min(-1)). However, the disposition index (DI) (insulin sensitivity [S(I)] x acute insulin response to glucose [AIRg]) was higher in the BF group (129.9 +/- 26.0 v 53.4 +/- 18.0 x 10(-4) min(-1); P =.03). Visceral fat (103 +/- 14 v 97 +/- 15 cm(2)) and subcutaneous fat (362 +/- 36 v 460 +/- 68 cm(2)) were similar between the groups. We conclude that 3 months of BF in a population with previous GDM was associated with improved pancreatic beta-cell function, but not with any difference in measures of adiposity.     

Prediction of type 2 diabetes in women with a history of gestational diabetes using a genetic risk score

Aims/hypothesis

Women with a history of gestational diabetes mellitus (GDM) are at increased risk of future development of type 2 diabetes. Recently, over 65 genetic variants have been confirmed to be associated with diabetes. We investigated whether this genetic information could improve the prediction of future diabetes in women with GDM.

Methods

This was a prospective cohort study consisting of 395 women with GDM who were followed annually with an OGTT. A weighted genetic risk score (wGRS), consisting of 48 variants, was assessed for improving discrimination (C statistic) and risk reclassification (continuous net reclassification improvement [NRI] index) when added to clinical risk factors.

Results

Among the 395 women with GDM, 116 (29.4%) developed diabetes during a median follow-up period of 45 months. Women with GDM who went on to develop diabetes had a significantly higher wGRS than those who did not (9.36?±?0.92 vs 8.78?±?1.07; p?<?1.56?×?10^?7). In a complex clinical model adjusted for age, prepregnancy BMI, family history of diabetes, blood pressure, fasting glucose and fasting insulin concentration, the C statistic marginally improved from 0.741 without the wGRS to 0.775 with the wGRS (p?=?0.015). The addition of the wGRS to the clinical model resulted in a modest improvement in reclassification (continuous NRI 0.430 [95% CI 0.218, 0.642]; p?=?7.0?×?10^?5).

Conclusions/interpretation

In women with GDM, who are at high risk of diabetes, the wGRS was significantly associated with the future development of diabetes. Furthermore, it improved prediction over clinical risk factors.     

Insulin resistance syndrome in women with prior history of gestational diabetes mellitus

The purpose of this study was to determine the prevalence of insulin resistance syndrome (IRS) and the risk factors for developing IRS among women with a history of gestational diabetes mellitus (GDM), compared with controls over 11 postdelivery years. Assessments of 106 women with a prior history of GDM and 101 controls were done on six occasions from 4-11 yr after delivery. Tests included glucose, insulin, lipids, blood pressure, and body measurements. The risk of IRS was analyzed by Cox regression. The results were that 27.2% of GDM and 8.2% of controls developed IRS by 11 yr after delivery. The hazard of developing IRS was 5.6 times (95% confidence interval = 2.6-12.3) among women with prepregnant obesity (body mass index >27.3 kg/m(2)), compared with women without prepregnant obesity and 4.4 times (95% confidence interval = 1.7-11.1) in women with a history of GDM, compared with controls. At 11 yr after delivery, the cumulative hazard for developing IRS in the next 2 yr was 26 times higher among GDM with prepregnant obesity, compared with controls without prepregnant obesity. We concluded that obesity and GDM in a prior pregnancy are significant risk factors for developing IRS over time. Early detection of markers of IRS is vital for possible prevention of type 2 diabetes and cardiovascular adverse events in women.     

Insulin clearance is altered in women with a history of gestational diabetes progressing to type 2 diabetes

Background and aimsInsulin clearance is a relevant process in glucose homeostasis. In this observational study, we aimed to assess insulin clearance (Cl_INS) in women with former gestational diabetes (fGDM) both early after delivery and after a follow-up.Methods and resultsWe analysed 59 fGDM women, and 16 women not developing GDM (CNT). All women underwent an oral glucose tolerance test (OGTT) yearly, and an insulin-modified intravenous glucose tolerance test (IVGTT) at baseline and at follow-up end (until 7 years). Both IVGTT and OGTT Cl_INS was assessed as insulin secretion to plasma insulin ratio. We also defined IVGTT first (0–10 min) and second phase (10–180 min) Cl_INS. We found that 14 fGDM women progressed to type 2 diabetes (PROG), whereas 45 women remained diabetes-free (NONPROG). At baseline, IVGTT Cl_INS showed alterations in PROG, especially in second phase (0.88 ± 0.10 l·min⁻¹ in PROG, 0.60 ± 0.06 in NONPROG, 0.54 ± 0.07 in CNT, p ≤ 0.03). Differences in Cl_INS were not found from OGTT. Cox regression analysis showed second phase Cl_INS as significant type 2 diabetes predictor (hazard ratio = 1.90, 95% confidence interval 1.09–3.30, p = 0.02).ConclusionThis study showed that insulin clearance derived from an insulin-modified IVGTT is notably altered in women with history of GDM progressing towards type 2 diabetes.     

Investigation of a lifestyle change strategy for high-risk women with a history of gestational diabetes

Fifty-nine women with recent gestational diabetes participated in a randomized controlled trial to assess the feasibility and efficacy of a pragmatic diabetes risk reduction intervention. Intervention participants achieved improvements in energy, total and saturated fats, and carbohydrate intake, but no change in physical activity. Recruitment was challenging and below expectations.     

Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions

CONTEXT: A past history of gestational diabetes mellitus (GDM) confers a very high risk of postpartum development of diabetes, particularly type 2 diabetes. OBJECTIVE: The Diabetes Prevention Program (DPP) sought to identify individuals with impaired glucose tolerance (IGT) and intervene in an effort to prevent or delay their progression to diabetes. This analysis examined the differences between women enrolled in DPP with and without a reported history of GDM. DESIGN: The DPP was a randomized, controlled clinical trial. SETTING: The study was a multicenter, National Institutes of Health-sponsored trial carried out at 27 centers including academic and Indian Health Services sites. Patients: A total of 2190 women were randomized into the DPP and provided information for past history of GDM. This analysis addressed the differences between those 350 women providing a past history of GDM and those 1416 women with a previous live birth but no history of GDM. INTERVENTIONS: Subjects were randomized to either standard lifestyle and placebo or metformin therapy or to an intensive lifestyle intervention. MAIN OUTCOMES: The primary outcome was the time to development of diabetes ascertained by semiannual fasting plasma glucose and annual oral glucose tolerance testing. Assessments of insulin secretion and insulin sensitivity were also performed. RESULTS: Whereas entering the study with similar glucose levels, women with a history of GDM randomized to placebo had a crude incidence rate of diabetes 71% higher than that of women without such a history. Among women reporting a history of GDM, both intensive lifestyle and metformin therapy reduced the incidence of diabetes by approximately 50% compared with the placebo group, whereas this reduction was 49 and 14%, respectively in parous women without GDM. These data suggest that metformin may be more effective in women with a GDM history as compared with those without. CONCLUSIONS: Progression to diabetes is more common in women with a history of GDM compared with those without GDM history despite equivalent degrees of IGT at baseline. Both intensive lifestyle and metformin are highly effective in delaying or preventing diabetes in women with IGT and a history of GDM.     

Preventing diabetes in women with gestational diabetes

The immediate consequences of gestational diabetes on pregnancy are well known but the complications decades later for the mother and child are just now emerging. This trio of papers discuss the long-term consequences of gestational diabetes, the importance of screening this high risk group of women for type 2 diabetes, and the evidence for lifestyle, medications and breastfeeding for the prevention of type 2 diabetes in these women.     

Relationship between insulin responses tod-glucose and tol-arginine in women with a history of gestational diabetes

The relationship between insulin responses to glucose and to arginine was studied in non-obese women with previous gestational diabetes (PGD). One group,n=10, had normal glucose tolerance (NGT) by WHO criteria and another,n=8, had impaired glucose tolerance (IGT). A third group of women without PGD,n=12, was also studied. A hyperglycaemic clamp (blood glucose level 11 mM) and an arginine stimulation test (150 mg/kgl-arginine followed by 10 mg/kg · min) were performed on separate days. The ratios of arginine to glucose responses 0–10 min differed: they were 1.00 for non-PGD, 1.29 for NGT and 1.46 for IGT (P<0.02 vs non-PGD). A further difference between groups was the ratio between first- and second-phase glucose-induced insulin secretion, which was significantly decreased in IGT, 0.72, compared with NGT, 0.98 (P<0.01), and non-PGD, 1.05 (P<0.005). However, within each group insulin responses 0–10 min to glucose and arginine were strongly correlated: for NGT (r=0.75,P<0.05), for IGT (r=0.85,P<0.01) and for women without PGD (r=0.69,P<0.05). Insulin sensitivity, as assessed by the M/I ratio, was non-significantly decreased in IGT (0.18±0.03 mg/kg·min per mU/l vs 0.26 ±0.03 in NGT and 0.28±0.03 in non-PGD,P<0.1). Conclusions are: (1) insulin responses to glucose and arginine are linked both in PGD and non-PGD women, but (2) the relative potency of these secretagogues as well as the time-dynamics of glucose-induced insulin secretion may be altered in PGD with IGT.     

Insulin resistance and beta-cell dysfunction in normoglycaemic European women with a history of gestational diabetes

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.     

Avoiding the slippery slope: preventing the development of diabetes in women with a history of gestational diabetes

Women with a history of gestational diabetes are at increased risk of developing type 2 diabetes. By identifying this high-risk group who has not yet developed the disease, we have the opportunity to try to prevent this progression to diabetes. In this article, we review the evidence for different strategies used to prevent the onset of diabetes in women with a history of gestational diabetes. These strategies include lifestyle changes, medications and breastfeeding.     

Increased prevalence of non-alcoholic fatty liver disease in European women with a history of gestational diabetes

Aims/hypothesis  

Non-alcoholic fatty liver disease (NAFLD) is common in type 2 diabetes but it is unknown whether NAFLD is prevalent in European women at risk of type 2 diabetes. We studied the prevalence of, and risk factors for, NAFLD in European women with previous gestational diabetes (GDM) at high risk of type 2 diabetes.     

Transforming growth factor-beta 1 levels in women with prior history of gestational diabetes mellitus

It is known that women with prior history of gestational diabetes mellitus (pGDM) feature obesity, insulin resistance and endothelial dysfunction which cause premature atherosclerosis. Transforming growth factor-beta 1 (TGF-beta1) is a key cytokine in obesity and insulin resistance and also play important roles in the development of atherosclerosis. This study was conducted to demonstrate the serum TGF-beta1 levels of people with pGDM. Thirty women with pGDM, 20 women with type 2 diabetes mellitus (T2DM) and 20 healthy women were enrolled. Serum TGF-beta1 levels of people with pGDM were found to be significantly higher than healthy controls and significantly lower than women with T2DM. TGF-beta1 levels were found to be correlated with postprandial glucose and age and inversely correlated with body mass index (BMI) and waist circumference. On multiple regression analysis postprandial glucose level, age and BMI were determined as the most important factors affecting TGF-beta1 levels. This study demonstrates elevated TGF-beta1 levels in pGDM. The inflammatory response to hyperglycemia and insulin resistance could be the major factors for the increased expression of TGF-beta1.     

Changing psychosocial determinants of physical activity and diet in women with a history of gestational diabetes mellitus

Background

To investigate how a behavioural lifestyle intervention influences psychosocial determinants of physical activity and dietary behaviours in a population at risk of type 2 diabetes (T2DM).

Methods

Fifty‐nine women with a body mass index of ≥25 kg/m² and a history of gestational diabetes mellitus (GDM) participated in a randomized controlled study. The intervention group (n = 29) received 2 face‐to‐face and 5 telephone lifestyle‐counselling sessions with a health professional. The control group (n = 30) received care as usual. At baseline and 6 months, psychosocial determinants related to physical activity and diet were measured with a self‐administrated questionnaire. Linear regression analyses were applied to test for intervention effects.

Results

The intervention was effective in improving social support (β = 3.5, P < 0.001; β = 2.1, P = 0.02), modifying self‐efficacy (β = ‐2.2, P = 0.02; β = ‐4.3, P < 0.001), and reducing barriers (β = ‐3.5, P = 0.01; β = ‐3.8, P = 0.01) for, respectively, physical activity and diet from baseline to 6‐month follow‐up in the intervention group compared with the control group. The intervention reduced the following barriers to a physically active lifestyle: lack of energy and lack of motivation. Physical activity barriers like lack of time and lack of childcare were unchanged. The intervention reduced the following barriers to a healthy diet: lack of time, costs, having unhealthy snacks at home, and having cravings for sweets.

Conclusion

This lifestyle intervention influenced psychosocial determinants relevant for overweight women with a history of gestational diabetes mellitus (GDM) in prevention of T2DM.