Development Of Diabetes In Women Research Articles

Amelioration of Insulin Resistance after Delivery Is Associated with Reduced Risk of Postpartum Diabetes in Women with Gestational Diabetes Mellitus.

Identifying risk factors for postpartum type 2 diabetes in women with gestational diabetes mellitus (GDM) is crucial for effective interventions. We examined whether changes in insulin sensitivity after delivery affects the risk of type 2 diabetes in women with GDM. This prospective cohort study included 347 women with GDM or gestational impaired glucose tolerance, who attended the follow-up visits at 2 months postpartum and annually thereafter. Changes in insulin sensitivity were calculated using the Matsuda index at GDM diagnosis and at 2 months postpartum (ΔMatsuda index). After excluding women with pregestational diabetes or those followed up only once, we analyzed the risk of postpartum type 2 diabetes based on the ΔMatsuda index tertiles. The incidence of type 2 diabetes at the two-month postpartum visit decreased with increasing ΔMatsuda index tertiles (16.4%, 9.5%, and 1.8%, P=0.001). During a 4.1-year follow-up, 26 out of 230 women who attended more than two follow-up visits (11.3%) developed type 2 diabetes. Compared to the lowest tertile, subjects in the highest ΔMatsuda index tertile showed a significantly reduced risk of type 2 diabetes (hazard ratio, 0.33; 95% confidence interval, 0.12 to 0.93; P=0.036) after adjusting for confounders. Improvement in insulin sensitivity after delivery is associated with a reduced risk of postpartum type 2 diabetes in women with GDM. Postpartum changes in insulin sensitivity could be a useful prediction for future type 2 diabetes development in women with GDM.

842: Comparisons of perinatal and postpartum outcomes between women with early- and late-diagnosed gestational diabetes

The difference in the risk of perinatal outcomes and postpartum development of diabetes in women diagnosed with gestational diabetes (GDM) during early pregnancy is unclear. We investigated the risk of perinatal adverse outcomes and the development of postpartum diabetes in women with early-diagnosed GDM compared with women diagnosed at 24 weeks or later. In this multicenter prospective observational study, we included singleton pregnant women with GDM who were diagnosed before 20 weeks’ gestation (early GDM) and women diagnosed at 24 weeks or later (late GDM) by the IADPSG criteria. They underwent the first postpartum follow-up 75-g oral glucose tolerance test (OGTT) at 6-9 weeks, repeating the test every 6-12 months. We compared their perinatal outcomes and the prevalence of postpartum diabetes between women with early and late GDM. We included 307 women diagnosed at 13.1±2.3 weeks’ gestation and 808 women diagnosed at 27.6±3.2 weeks’ gestation in the in the early-GDM and late-GDM groups, respectively. Although the rate of insulin requirement during pregnancy was similar, women in the early-GDM group delivered earlier and had lower birthweight infants than those in the late-GDM group. The prevalence of postpartum diabetes was not markedly different between the groups (Table). Women with early GDM delivered earlier and had lighter-weight infants, than those with late GDM, suggesting the possibility of over-treatment. The risk of postpartum development of diabetes seems to be similar between the groups.

858: Leptin and the association between breastfeeding and insulin resistance in women with current gestational diabetes

Although breastfeeding is considered to have a protective effect against the development of diabetes in women with gestational diabetes (GDM), the mechanism remains obscure. In this pilot study, we investigated factors associated with breastfeeding and insulin resistance (IR) at six months postpartum. In this prospective observational study, we included Japanese singleton pregnant women with a diagnosis of GDM. At 6 months postpartum when they underwent a follow-up 75-g oral glucose tolerance tests (OGTT), we collected serum samples for the measurement of serum factors, including TNF-alpha, leptin, adiponectin, prolactin (PRL), oxytocin, and IgA, as well as insulin, in the fasting state. We used homeostasis model of assessment (HOMA)-IR as a surrogate index of IR. We defined the condition in which infants were fed by breastfeeding greater than 80% of the volume as high-intensity breastfeeding (HIB), while other statuses, including partial and non-breastfeeding, were non-HIB. We investigated the association between HOMA-IR, breastfeeding status, and endocrine factors. In 72 women with current GDM, we found that the breastfeeding status and body mass index (BMI) were independently associated with HOMA-IR at 6 months postpartum. The TNF-alpha (p< 0.0001), leptin (p< 0.0001) and IgA (p< 0.05) levels were also significantly and positively associated with HOMA-IR in a multivariate analysis after adjusting for the age and BMI. Among those factors, only leptin (p< 0.05) was associated with breastfeeding status (HIB vs. non-HIB: 14.9±9.0 vs. 21.3±17.3, p< 0.05), and it remained significant after adjusting for the age and BMI. PRL and oxytocin were significantly associated with the breastfeeding status but not with HOMA-IR. Adiponectin was associated with neither HOMA-IR nor the breastfeeding status. Breastfeeding is significantly and independently associated with decreasing insulin resistance at six months postpartum. Leptin may play a key role in the association between breastfeeding and insulin sensitivity.

The Incidence of Glutamic Acid Decarboxylase Autoantibodies and its Association With Clinical Features in Pregnant Women With Gestational Diabetes Mellitus

Introduction: The association between the incidence of glutamic acid decarboxylase antibodies(GADAs) and risk of diabetes in pregnant women is controversial. Here, our aim was to investigate the incidence and clinical relevance of GADA and its association with development of post-delivery diabetes in women with gestational diabetes mellitus (GDM).Methods: This cohort study was conducted in Torbat–e Heydarieh (Khorasan Razavi, Iran) from October 2015 to March 2017. A total of 147 pregnant women with GDM were included in case group. The control group consisted of 147 healthy controls. A GAD diagnostic kit (Diametra Co.,Italy) was used for diagnosis of GADA. The history of insulin therapy and the development of diabetes one year after delivery were investigated.Results: Of 147 pregnant women with GDM, 9 (6.1%) had GADA in their sera. 14.3% (21 out of 147) of women with GDM had history of insulin therapy. 33.3% (7 of 21) of women who had received insulin developed diabetes one year after delivery. Type 1 and type 2 diabetes were observed in, respectively, 1 (0.7%) and 7 (4.8%) of women with GDM at one year after delivery.At one year after delivery, no women in GADA negative women was diagnosed with type 1 diabetes. However, type 2 diabetes was observed in 2.9% of GADA negative pregnant women.Type 1 and type 2 diabetes were also noticed in, respectively, 11.1% and 33.3% of GADA positive mothers at one year after delivery.Conclusion: The prevalence of GADA was 6.1% in diabetic pregnant women. The GADA positivity and history of insulin therapy during pregnancy were significant risk factors for diabetes at one year after delivery. In addition, development of type 1 diabetes was higher in GADA positive pregnant women with GDM than GADA negative women.

Oral Glucose Tolerance Testing Allows Better Prediction of Diabetes in Women with a History of Gestational Diabetes Mellitus.

BackgroundWe aimed to identify the postpartum metabolic factors that were associated with the development of diabetes in women with a history of gestational diabetes mellitus (GDM). In addition, we examined the role of the oral glucose tolerance test (OGTT) in the prediction of future diabetes.MethodsWe conducted a prospective study of 179 subjects who previously had GDM but did not have diabetes at 2 months postpartum. The initial postpartum examination including a 75-g OGTT and the frequently sampled intravenous glucose tolerance test (FSIVGTT) was performed 12 months after delivery, and annual follow-up visits were made thereafter.ResultsThe insulinogenic index (IGI30) obtained from the OGTT was significantly correlated with the acute insulin response to glucose (AIRg) obtained from the FSIVGTT. The disposition indices obtained from the OGTT and FSIVGTT were also significantly correlated. Women who progressed to diabetes had a lower insulin secretory capacity including IGI30, AIRg, and disposition indices obtained from the FSIVGTT and OGTT compared with those who did not. However, the insulin sensitivity indices obtained from the OGTT and FSIVGTT did not differ between the two groups. Multivariate logistic regression analysis showed that the 2-hour glucose and disposition index obtained from the FSIVGTT were significant postpartum metabolic risk factors for the development of diabetes.ConclusionWe identified a crucial role of β-cell dysfunction in the development of diabetes in Korean women with previous GDM. The 2-hour glucose result from the OGTT is an independent predictor of future diabetes. Therefore, the OGTT is crucial for better prediction of future diabetes in Korean women with previous GDM.

Predicting diabetes risk among HIV-positive and HIV-negative women.

To assess the performance of an adapted American Diabetes Association (ADA) risk score and the concise Finnish Diabetes Risk Score (FINRISC) for predicting type 2 diabetes development in women with and at risk of HIV infection. Longitudinal analysis of the Women's Interagency HIV Study. The women's Interagency HIV Study is an ongoing prospective cohort study of women with and at risk for HIV infection. Women without prevalent diabetes and 3-year data on fasting blood glucose, hemoglobin A1c, self-reported diabetes medication use, and self-reported diabetes were included. ADA and FINRISC scores were computed at baseline and their ability to predict diabetes development within 3 years was assessed [sensitivity, specificity and area under the receiver operating characteristics (AUROC) curve]. A total of 1111 HIV-positive (median age 41, 60% African American) and 454 HIV-negative women (median age 38, 63% African-American) were included. ADA sensitivity did not differ between HIV-positive (77%) and HIV-negative women (81%), while specificity was better in HIV-negative women (42 vs. 49%, P = 0.006). Overall ADA discrimination was suboptimal in both HIV-positive [AUROC = 0.64 (95% CI: 0.58, 0.70)] and HIV-negative women [AUROC = 0.67 (95% CI: 0.57, 0.77)]. FINRISC sensitivity and specificity did not differ between HIV-positive (72 and 49%, respectively) and HIV-negative women (86 and 52%, respectively). Overall FINRISC discrimination was suboptimal in HIV-positive [AUROC = 0.68 (95% CI: 0.62, 0.75)] and HIV-negative women [AUROC = 0.78 (95% CI: 0.66, 0.90)]. Model performance was suboptimal in women with and at risk of HIV, while greater misclassification was generally observed among HIV-positive women. HIV-specific risk factors known to contribute to diabetes risk should be explored in these models.

The postpartum effect of maternal diabetes on the circulating levels of sirtuins and superoxide dismutase.

Gestational diabetes mellitus (GDM) is a glucose intolerance disorder which occurs during pregnancy as a result of insulin insensitivity; it usually disappears after delivery. However, some women with GDM can develop type 2 diabetes (T2D) after delivery, and the mechanisms by which this occurs remain unknown. This study compared the levels of sirtuins (NAD‐dependent deacetylases) and antioxidative enzymes in postpartum women with previous GDM (pGDM) or T2D and in postpartum women with a previous healthy pregnancy (controls). Women with pGDM showed upregulated levels of sirtuin 1 (SIRT1) mRNA and protein, with reduced expression levels of sirtuin 3 (SIRT3) and superoxide dismutase 2 (SOD2), relative to the controls. Women with T2D similarly showed a lower level of SIRT3 mRNA than the controls. Lipid peroxidation (malondialdehyde) was higher in women with pGDM than in the controls. These data show that in women with pGDM, the reduced level of SIRT3 may play a role in the reduced SOD2 level, possibly leading to oxidative stress, which, in turn, upregulates the level of SIRT1. These results might confer the risk of future diabetes development in women with pGDM, as a similar reduction in SIRT3 was found in women with T2D.

Low serum creatinine is a type 2 diabetes risk factor in men and women: The Yuport Health Checkup Center cohort study

AimType 2 diabetes (T2D) is a risk factor for muscle loss and subsequent frailty. The reverse association, however, may also happen. This study examined whether serum creatinine level, an indicator of muscle mass, predicted diabetes development. In addition, a role for body mass index (BMI) as an effect modifier of creatinine levels was evaluated. MethodsThis cohort study included 9667 subjects without diabetes or hypertension and with normal creatinine levels at baseline. Multiple-adjusted hazard ratios (HRs) for associations between baseline creatinine and diabetes development were estimated using the Cox proportional-hazards model. Stratified analyses based on BMI were also performed. ResultsDuring the follow-up period (mean: 5.6 years), 287 (5.5%) men and 115 (2.3%) women developed T2D. HR in men with serum creatinine≤0.7mg/dL compared with 0.9–1.2mg/dL was 1.40 (95% CI: 1.05–1.87) after adjusting for age, BMI, blood pressure and fasting plasma glucose at baseline, whereas the adjusted HR in women with creatinine≤0.5mg/dL compared with 0.7–1.1mg/dL was 1.69 (95% CI: 1.04–2.76). In a subgroup analysis stratified by BMI, interactions between BMI and baseline creatinine levels for T2D were statistically significant in women with the lowest creatinine levels (P=0.08 for interaction). ConclusionLow serum creatinine levels, a surrogate marker of muscle mass, predict T2D development in both genders, even after excluding the effect of diabetic and prediabetic glomerular hyperfiltration. BMI modified the association between creatinine and diabetes development in women.

Is waist circumference ≥102/88cm better than body mass index ≥30 to predict hypertension and diabetes development regardless of gender, age group, and race/ethnicity? Meta-analysis.

Between body mass index (BMI) ≥30 and waist circumference (WC) ≥102/88cm, we investigated which of the two measures is a better predictor of two of the most common chronic diseases - diabetes mellitus and hypertension while also examining differential association by gender, age group, and race/ethnicity. Meta-analysis was conducted for all longitudinal studies with at least 12months of follow-up published up to April 2015. Ratio of relative risk (rRR) and relative risk of diseases were computed and compared by baseline obesity measurement. The final sample included 23 longitudinal observation studies involving 62 study arms with 259,200 individuals. WC≥102/88cm was a better predictor than BMI≥30 for development of diabetes (rRR=0.81, 95% CI=0.68-0.96), but not for hypertension (rRR=0.92, 95% CI=0.80-1.06). Subgroup analyses showed WC≥102/88cm was a better predictor for diabetes in women than men, and for ages 60 and older than other ages. Only WC≥102/88cm, not BMI≥30, predicted development of hypertension among Hispanic/Latinos. Neither BMI≥30 nor WC≥102/88cm were significant predictors of hypertension when age group was controlled. Central obesity may be a more serious risk factor for diabetes development in women and for older ages. The predictive power of BMI≥30 or WC≥102/88cm in hypertension development should not be emphasized as either could mask the effect of age.

Pre-eclampsia is associated with a twofold increase in diabetes: a systematic review and meta-analysis.

Aims/hypothesisPre-eclampsia is a pregnancy-specific multisystem disorder and a state of physiological insulin resistance. Our aim was to systematically evaluate and quantify the evidence on the relationship between pre-eclampsia and the future risk of diabetes.MethodsWe conducted a systematic review and meta-analysis of studies that evaluated diabetes in women with and without pre-eclampsia. We performed a systematic search of MEDLINE and EMBASE to identify relevant studies. Independent double data extractions were conducted by four reviewers. Random-effects meta-analysis was used to estimate the risk of future diabetes following pre-eclampsia.ResultsA total of 21 studies were identified with more than 2.8 million women, including more than 72,500 women with pre-eclampsia. Meta-analysis of studies that adjusted for potential confounders demonstrated that pre-eclampsia was independently associated with an increased risk of future diabetes (RR 2.37 [95% CI 1.89, 2.97]). This risk appeared in studies that followed women from less than 1 year postpartum (RR 1.97 [95% CI 1.35, 2.87]) and persisted to more than 10 years postpartum (RR 1.95 [95% CI 1.28, 2.97]). After adjusting for BMI or gestational diabetes, pre-eclampsia remained linked with an increased risk of future diabetes (RR 2.38 [95% CI 1.74, 3.24] and RR 2.36 [95% CI 1.94, 2.88], respectively).Conclusions/interpretationPre-eclampsia is independently associated with a twofold increase in future diabetes. Our study highlights the importance of clinical risk assessment for the future development of diabetes in women with pre-eclampsia. We recommend detailed evaluation of a screening programme for diabetes in this high-risk population.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-016-4098-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus

To examine if periodontal disease is associated with later development of impaired glucose metabolism in women with a recent history of gestational diabetes (GDM). Women with (n = 19) and without (n = 20) a history of GDM were prospectively followed at 22 months postpartum. All subjects underwent: a) a 75-gram oral glucose tolerance test (OGTT); and b) an oral examination for measuring periodontal disease. Insulin sensitivity and pancreatic β-cell secretory capacity derived from fasting (HOMA-IR) and glucose-stimulated measures (SI(OGTT) and IGI/HOMA-IR) were determined. Periodontitis was defined as the presence of any site with a probing depth ≥ 4 mm or a clinical attachment loss ≥ 4 mm. Compared to women without a history of GDM, prior GDM women had significantly higher fasting glucose and insulin concentrations, increased insulin resistance and decreased β-cell function. Although not statistically significant, prior GDM women had a higher prevalence of periodontal disease (42.1%) than women without a history of GDM (25.0%). Women with periodontal disease showed greater insulin resistance and lower β-cell function. Women with both prior GDM and periodontal disease had the most impaired glucose metabolism; the insulin secretion-sensitivity index was significantly lower in women with both prior GDM and periodontal disease (208.20 ± 2.60) than in women without prior GDM and periodontal disease (742.93 ± 1.78) (P < 0.05). Women with prior GDM show reduced insulin sensitivity and inadequate β-cell secretory function at 22 months postpartum. Periodontal disease may contribute to their impaired glucose metabolism and future risk of developing 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.

Potentiation of abnormalities in myocardial metabolism with the development of diabetes in women with obesity and insulin resistance

BackgroundBecause studies in animal models of type-2 diabetes mellitus (DM) show that excessive myocardial fatty acid (FA) metabolism (at the expense of glucose metabolism) cause cardiac dysfunction, we hypothesized that women with DM would have more FA and less glucose myocardial metabolism than normal or even obese (OB) women. Research Design and MethodsWomen who were lean volunteers (NV) (N = 14; age 35 ± 17 years, body mass index 23 ± 1 kg/m2), OB (N = 28;31 ± 6 years, BMI 39 ± 7 kg/m2), and DM (n = 22; 54 ± 11 years, BMI 38 ± 5 kg/m2) were studied. Cardiac positron emission tomography was performed for the determination of myocardial blood flow, oxygen consumption, FA and glucose metabolism. Cardiac work was measured by echocardiography and efficiency by the ratio of work to myocardial oxygen consumption. ResultsFractional glucose uptake was comparable between NV and OB but lower in DM (P < .05 versus NV). Myocardial FA utilization and oxidation were both higher in DM compared with NV and OB (P < .0001). Myocardial FA utilization and oxidation had positive correlations with HOMA (R = 0.35, P = .005 and R = 0.40, P = .001, respectively) whereas fractional glucose uptake exhibited an inverse correlation (R = −.31, P = .01). Cardiac work and efficiency were similar among the three groups. ConclusionsIn women, the presence of OB and DM compared with OB alone is associated with a greater reliance on myocardial FA metabolism at the expense of glucose metabolism. These perturbations in myocardial metabolism are not associated in a decline left ventricular efficiency or function suggesting that the metabolic perturbations may precede an eventual decline left ventricular function as is seen in animal models of DM.

Risk of diabetes after gestational diabetes and preeclampsia. A registry-based study of 230,000 women in Norway

This study aimed to use a population-based Prescription Database to explore later development of diabetes in women registered with gestational diabetes mellitus (GDM) and/or preeclampsia in the Medical Birth Registry of Norway (MBRN) during 2004–8. We used two nationwide Norwegian registries, the Norwegian Prescription Database and the MBRN, to explore the onset of later diabetes after pregnancy complications, indicated by receiving prescriptions of drugs used to treat diabetes, in 230,000 women giving birth in 2004–8. The mean follow-up of the study cohort was 3.7 years. Five years after pregnancy, about 19 and 2% of women with GDM and preeclampsia, respectively, received drugs used to treat diabetes, compared to 0.5% of those without these complications. The risk of being dispensed drugs used to treat diabetes within the first years after pregnancy was estimated to be 41 times (95% CI: 35–47) and 3.0 times (95% CI: 2.4–3.6) higher in women with GDM and preeclampsia, respectively, compared to women without these pregnancy complications. Women with pregnancies complicated with preeclampsia or GDM had an increased risk of later diabetes, especially those having GDM. If the increase in frequency of GDM observed in MBRN in recent years is real, a further increase in diabetic women can be expected.

Markers of oxidative stress and risk of type 2 diabetes mellitus: Results from the MONICA/KORA Augsburg Study 1984–2002

Background: We sought to elucidate the role of oxidative stress in the development of incident type 2 diabetes by measuring oxidized LDL (ox-LDL) and myeloperoxidase (MPO) in a large cohort study. Methods: Using a case-cohort design, serum levels of ox-LDL and MPO were measured in 460 cases with incident type 2 diabetes and 1,474 non-cases selected from a source population of 7,936 middle-aged men and women who participated in the population-based MONICA/KORA Augsburg studies between 1984–1995. The mean follow-up time was 10.9±4.7 years. Results: After adjustment for age, survey, and lifestyle factors, elevated ox-LDL was significantly associated with the risk of type 2 diabetes in both sexes. Hazard ratios (HR) and 95% confidence intervals (CI) were 2.39 (1.63–3.52) for men and 3.02 (1.81–5.03) for women, respectively, comparing tertile extremes. MPO, however, was significantly associated with type 2 diabetes development in women only (HR [95% CI] 1.77 [1.18–2.65]). Further adjustment for body mass index, systolic blood pressure, total cholesterol/HDL-cholesterol, family history of diabetes and markers of inflammation attenuated the observed HR and they became clearly non-significant for ox-LDL (p-trend=0.178 for men and 0.920 for women), but remained borderline significant for MPO in women (p-trend=0.063). Conclusions: Our findings indicate that markers of oxidative stress predict incident type 2 diabetes. However, the effect is not independent of other known risk factors for type 2 diabetes including lipids and markers of inflammation. Further studies should also consider potential sex differences.

IGF-binding protein 1 and abdominal obesity in the development of type 2 diabetes in women

ObjectiveLow levels of IGF-binding protein 1 (IGFBP1) are associated with metabolic syndrome and predict diabetes development in men. The aim of this study was to determine the levels of IGFBP1 in women who later develop diabetes, in relation to abdominal obesity, and to compare these levels with those of men.MethodsIGFBP1 levels were determined at baseline and after 8 years in a case–control, prospective study of Swedish women aged 35–56 years. Individuals with normal oral glucose tolerance test (OGTT) who developed abnormal glucose regulation (n=240) were pair matched to controls for age and family history of diabetes and also compared to men of the same age (n=355).ResultsLow fasting IGFBP1 and increased waist measurement predicted development of diabetes in women (n=60; odds ratio (OR) 70, 95% confidence interval (CI) 8–661, lowest tertile and OR 27, 95% CI 5–141, highest tertile). In women developing diabetes, baseline IGFBP1 levels were lower than expected for fasting insulin values, were associated with impaired suppression after OGTT and increased during 8 years despite an increase in fasting insulin. All individuals in the highest tertile for waist and with ≤40% suppression of IGFBP1 developed diabetes within 8 years. Circulating IGFBP1 concentrations were higher in women compared to men. Women and men who developed diabetes had a similar degree of abdominal obesity, corrected for height.ConclusionsWe conclude that low IGFBP1 and elevated waist measurement predict diabetes development and that IGFBP1 production is suppressed by a novel factor(s) in women developing diabetes. Increasing levels of IGFBP1 during the emergence of diabetes in men and women suggest the emergence of hepatic insulin resistance.

Relationship of serum adiponectin with blood lipids, HbA1c, and hs‐CRP in type II diabetic postmenopausal women

Adipose tissue has been considered an important endocrine organ. Adiponectin secretes from adipose tissue and plays an important role in the regulation of glycemia, beta-oxidation in muscle, and decreased insulin resistance in the liver. The objectives of this study were to compare the levels of adiponectin, hs-C-reactive protein (CRP), HbA1c, and blood lipids among diabetic and healthy postmenopausal women, and to determine the relationship between circulating adiponectin and development of type II diabetes. This case-control study was performed on 28 diabetic and 42 age-matched healthy women. All participants were postmenopausal. Serum adiponectin concentrations, serum triglycerides (TG), cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) concentrations were determined. Blood HbA1c and serum hs-CRP were also measured. Adiponectin levels were significantly decreased (P<0.01) in the diabetic patients as compared to normal control subjects. Adiponectin levels were negatively associated with hs-CRP, LDL-C, HbA1c, TG, and total cholesterol (TC). A positive correlation was observed between adiponectin and HDL-C. The obtained data indicate that diabetic women have lower adiponectin levels compared to healthy women. HbA1c as an indicator of glycemic control has a negative correlation with serum adiponectin. Adiponectin may play an important role in the pathogenesis of diabetes, and may be an independent predictor of the development of diabetes in women.

Elevated Homocysteine as a Risk Factor for the Development of Diabetes in Women With a Previous History of Gestational Diabetes Mellitus: A 4-year Prospective Study

Gestational diabetes mellitus (GDM) is a state of carbohydrate intolerance that first becomes apparent during pregnancy. An estimated 3% to 8% of all pregnancies in North America may be complicated by GDM. Affected women are at increased risk of later developing type 2 diabetes. Elevated blood levels of homocysteine have recently been recognized as a risk factor for cardiovascular disease. Both endothelial dysfunction and oxidative damage may be involved. The authors performed a prospective study designed to clarify the relationship between homocysteine and diabetes in 170 women with a history of GDM who had normal or impaired glucose tolerance, but not diabetes, at baseline (6 weeks postpartum). They were followed at annual intervals for up to 4 postpartum years by, among other measures, a 2-hour, 75-g oral glucose tolerance test. Diabetes developed in 18 women (10.6%) during a mean follow up of 2.94 years; 9 had normal glucose tolerance at baseline, and 9 had impaired glucose tolerance. At last follow up, another 43 (25.3%) had impaired glucose tolerance; 20 had normal glucose tolerance and 23 had impaired tolerance at baseline. The later development of diabetes was associated with prepregnancy obesity, early diagnosis of GDM, and high blood glucose. The women who developed diabetes also required insulin for GDM more often than others, but the difference did not meet statistical significance (P = 0.056). Fasting glucose and homocysteine levels were significantly higher in women who later developed diabetes than in those with impaired or normal glucose tolerance. The latest homocysteine level correlated positively with the fasting insulin level in women with diabetes or impaired glucose tolerance. The best predictor of future diabetes was the fasting blood glucose at the time GDM was diagnosed, but a homocysteine level above 6.4 mmol/L at baseline also was a relatively sensitive and specific predictive factor. Compared with women with relatively low homocysteine levels at baseline, those with higher levels had a greater than 3-fold increase in the risk of developing diabetes during follow up. In this prospective study, early postpartum elevation of the blood homocysteine level in a woman with a history of GDM was a risk factor for diabetes developing in the postpartum period. The authors suggest that measuring blood homocysteine 6 weeks postpartum will help to identify women with previous GDM who are at high risk of developing type 2 diabetes.

Elevated Homocysteine as a Risk Factor for the Development of Diabetes in Women With a Previous History of Gestational Diabetes Mellitus

To investigate the potential use of the plasma homocysteine level as a predictor of diabetes in women with a previous history of gestational diabetes mellitus (GDM). At 6 weeks' postpartum, baseline examination was performed in 177 GAD-negative subjects. Of these subjects, 7 who were diagnosed with diabetes at baseline were excluded from further evaluation, and 170 with normal or impaired glucose tolerance (IGT) at baseline were followed annually over 4 years. The follow-up examinations included 2-h 75-g oral glucose tolerance tests (OGTTs), lipid profiles, homocysteine levels, anthropometric measurements, history taking, diet, and lifestyle. During the OGTTs, insulin and glucose levels were assayed every 30 min. Plasma homocysteine levels were determined by ion-exchange chromatography. Of the 170 women, 18 (10.6%) converted to diabetes during the 4-year follow-up period. Mean age, BMI, fasting insulin, and total cholesterol at baseline (6 weeks' postpartum test) were similar in the three study groups (i.e., normal, IGT, and diabetes). Fasting glucose levels, insulin-to-glucose ratios, and homocysteine levels were significantly higher in the diabetic group (P < 0.05). Higher glucose at the time of the diagnosis of GDM and higher homocysteine levels at baseline were independently associated with the onset of postpartum diabetes. These relationships were independent of age, BMI, and family history of diabetes. This prospective study identified homocysteine level as a significant risk factor for development of diabetes in women with previous GDM.

Secretion of incretin hormones and the insulinotropic effect of gastric inhibitory polypeptide in women with a history of gestational diabetes

The insulinotropic effect of gastric inhibitory polypeptide (GIP) is reduced in patients with type 2 diabetes and around 50% of their first-degree relatives under hyperglycaemic conditions. It is unknown whether this is a result of a specific defect in GIP action or of a general reduction in beta cell function. Moreover, impaired secretion of glucagon-like peptide 1 (GLP-1) has been described in patients with type 2 diabetes. Therefore, we studied the insulinotropic effect of GIP in women with previous gestational diabetes (pGDM) under euglycaemic fasting conditions and during a hyperglycaemic clamp experiment. The secretion of GIP and GLP-1 was assessed following oral glucose ingestion. On separate occasions we performed an OGTT and administered an i.v. bolus of 20 pmol GIP/kg body weight in 20 women with pGDM and 20 control women. An additional hyperglycaemic clamp experiment (140 mg/dl [7.8 mmol/l] over 120 min) with i.v. infusion of GIP (2 pmol kg(-1) min(-1); 30-90 min) was performed in 14 women in each group. Capillary and venous blood samples were drawn for the measurement of glucose (glucose oxidase), insulin, C-peptide, GIP and GLP-1 (specific immunoassays). Indices of insulin sensitivity and beta cell function were calculated. Statistical analyses were carried out using repeated measures ANOVA. Following oral glucose ingestion, plasma glucose, insulin and C-peptide concentrations increased to higher levels in the women with pGDM than in the control women (p<0.05). The women with pGDM were characterised by a higher degree of insulin resistance than the control women (p=0.007 for the Matsuda index), but showed no overt defects in glucose-stimulated insulin secretion (p=0.40 for the insulinogenic index following i.v. glucose). The secretion of GLP-1 and GIP was not different between the groups (p=0.87 and p=0.57, respectively). The insulin secretory response to GIP administration was similar in the two groups both after GIP bolus administration and during the hyperglycaemic clamp experiment (p=0.99 and p=0.88, respectively). A hyperbola-like relationship was found between the degree of insulin sensitivity (Matsuda index) and the insulin secretory response to GIP and i.v. glucose administration. These results do not support the hypothesis of an early defect in GIP action as a risk factor for subsequent development of diabetes in women with previous gestational diabetes. The inverse relationship between insulin resistance and the insulin secretory response to glucose or GIP suggests that beta cell secretory function in response to different stimuli increases adaptively when insulin sensitivity is diminished.