Heterogeneous effect of gestational weight gain on birth weight: quantile regression analysis from a population-based screening.

PURPOSE: Classical regression models might give an incomplete picture of the associations between predictors and outcomes. We investigated associations between gestational weight gain (GWG) and birth weight along the entire birth weight distribution with quantile regression and estimated effects of hypothetical prevention strategies. METHODS: The GWG-birth weight association was analyzed using quantile and classical regression models on data from a population-based gestational diabetes screening (n = 4760) at the Szent Imre Teaching Hospital in Budapest, Hungary (2002-2005). Birth weight distributions were modeled based on hypothetical GWG changes. RESULTS: At a body mass index of 20 kg/m(2), a 1-kg difference in GWG was associated with a 14.2 g (95% confidence interval, 10.0-20.9) higher birth weight at the fifth percentile of the birth weight distribution and a 29.0 g (21.3-35.6) higher birth weight at the 95th percentile. The coefficient from linear regression was 20.7 (17.5-24.0). Estimates differed modestly between the two regressions at a body mass index of 30 kg/m(2). A population-wide 2-kg decrease in GWG would rather affect the risk of macrosomia (-1.8%) than that of low birth weight (+0.4%). In contrast, a 3-kg decrease in GWG among overweight and obese women would lower macrosomia more modestly (-0.8%). CONCLUSIONS: A population-wide lowering of GWG would lead to greater improvements in the right tail of the birth weight distribution.

Maternal glycemia and risk of large-for-gestational-age babies in a population-based screening.

OBJECTIVE: Gestational diabetes is a risk factor for large-for-gestational-age (LGA) newborns, but many LGA babies are born to mothers with normal glucose tolerance. We aimed to clarify the association of maternal glycemia across the whole distribution with birth weight and risk of LGA births in mothers with normal glucose tolerance. RESEARCH DESIGN AND METHODS: We undertook a population-based gestational diabetes screening in an urban area of Hungary in 2002-2005. All singleton pregnancies of mothers >or=18 years of age, without known diabetes or gestational diabetes (World Health Organization criteria) and data on a 75-g oral glucose tolerance test at 22-30 weeks of gestation, were included (n = 3,787, 78.9% of the target population). LGA was determined as birth weight greater than the 90th percentile using national sex- and gestational age-specific charts. RESULTS: Mean +/- SD maternal age was 30 +/- 4 years, BMI was 22.6 +/- 4.0 kg/m(2), fasting blood glucose was 4.5 +/- 0.5 mmol/l, and postload glucose was 5.5 +/- 1.0 mmol/l. The mean birth weight was 3,450 +/- 476 g at 39.2 +/- 1.2 weeks of gestation. There was a U-shaped association of maternal fasting glucose with birth weight (P(curve) = 0.004) and risk of having an LGA baby (lowest values between 4 and 4.5 mmol/l, P(curve) = 0.0004) with little change after adjustments for clinical characteristics. The association of postload glucose with birth weight (P = 0.03) and the risk of an LGA baby (P = 0.09) was weaker and linear. CONCLUSIONS: Both low and high fasting glucose values at 22-30 weeks of gestation are associated with increased risk of an LGA newborn. We suggest that the excess risk related to low glucose reflects the increased use of nutrients by LGA fetuses that also affects the mothers' fasting glucose.

Abnormal glucose tolerance is associated with diminished postload change in leptin levels in women.

BACKGROUND: It is generally accepted that the metabolic effects of leptin are diminished in the obese due to leptin resistance. Hormone resistance may develop if diurnal (including meal-related) changes in hormone levels are disrupted. We sought to describe leptin changes after a 75 g oral glucose tolerance test (OGTT) in women with a prior diagnosis of gestational diabetes mellitus (a high risk group for the metabolic syndrome) compared to that in healthy controls. METHODS: In 2000 a retrospective cohort study was performed on women who had been diagnosed with gestational diabetes mellitus (WHO criteria 1985, n = 57) between 1996 and 1998 and on a healthy control female group (n = 36) all of whom had had a prior pregnancy without any diagnosis of diabetes. All the women underwent a standard 75 g OGTT. Serum leptin was measured by radioimmunoassay before and 90 min after the OGTT. RESULTS: Using multilevel models of change, fasting leptin levels were shown to be associated with body mass index; 10.1% (95% CI 8.1-12.1%) increase per 1 kg/m(2) increase in body mass index), homeostasis model assessment insulin sensitivity; 0.4% (95% CI 0.2-0.7%) decrease per 1% increase in insulin sensitivity); abnormal glucose tolerance (24% decrease, 95% CI 8-37%); and smoking (31% decrease, 95% CI 16-44%). Postload (90 min) leptin levels decreased significantly in women with normal glucose tolerance by 13% (95% CI 8-18%), while no significant change in postload leptin level was apparent in women with abnormal glucose tolerance (3% increase, 95% CI -4% to 29%). CONCLUSIONS: Disturbed leptin changes were found following an OGTT in women with abnormal glucose tolerance that might be either a cause or a consequence of leptin resistance.

Carbohydrate metabolism and cardiovascular risk factors 4 years after a pregnancy complicated by gestational diabetes.

AIMS: The aim of the present study was to determine the prevalence of abnormal glucose tolerance and the metabolic syndrome in a cohort of previously gestational diabetic (GDM) women 4 years after delivery. METHODS: Sixty-eight prior GDM and a control group of 39 women with normal glucose tolerance during pregnancy were invited to participate in a follow-up study. RESULTS: The prevalence of diabetes, impaired glucose tolerance and impaired fasting glucose (IFG) was 21%, 16%, and 6% among prior GDM women and 0%, 15%, and 0% among controls respectively (P=0.0039). Independently of the metabolic syndrome criteria used this status was found more frequently among women with prior GDM (all P<0.05). The prevalence of the metabolic syndrome showed a dose-response relationship with the level of weight categories (P<0.005) as well as with the level of glucose intolerance (P=0.024). CONCLUSION: According to our results a disturbed carbohydrate metabolism and a clustering of cardiovascular risk factors might be observed in previous GDM women 4 years after delivery.

[Metabolic syndrome after pregnancy complicated with gestational diabetes: four-year follow-up]. / Metabolikus szindróma gesztációs diabéteszt követôen: négyéves utánkövetés.

Although clustering of cardiovascular risk factors is unquestionable, the importance of the "metabolic syndrome" as a distinct cardiovascular risk marker has been debated recently. In the authors' previous report a high frequency of glucose intolerance was described 8 years after a pregnancy complicated by gestational diabetes, often associated with other unfavorable metabolic parameters. In the present study the objective was to estimate the prevalence of metabolic syndrome in a cohort of previously gestational diabetes women, using different diagnostic criteria, 4 years after delivery. Those data were compared to a control group of 39 women with normal glucose tolerance during pregnancy. Irrespective of the criteria used, metabolic syndrome was found more frequently among women with prior gestational diabetes. The prevalence of metabolic syndrome increased by degree of deterioration of glucose tolerance in the prior gestational diabetes group. Overweight women in both group had 10-fold increased risk of metabolic syndrome compared to normal-weight women. According to our results a clustering of cardiovascular risk factors might be observed in previous gestational diabetes women, 4 yrs after delivery. These data highlight the importance of regular follow-up of these women, and the possible advantage of early and aggressive treatment of each component of metabolic syndrome.

Combination therapy with rosiglitazone and glibenclamide compared with upward titration of glibenclamide alone in patients with type 2 diabetes mellitus.

AIM: To compare the efficacy of combination therapy using rosiglitazone (8 mg per day) and glibenclamide (7.5 mg per day) with upward titration of glibenclamide as monotherapy (maximum dose=15 mg per day) in reducing HbA(1c) levels over 26 weeks in patients with type 2 diabetes mellitus (T2DM). METHODS: Three hundred and forty patients with T2DM inadequately controlled (FPG > or =7.0 and < or =15.0 mmol/l) on glibenclamide 7.5 mg per day were randomised to either additional treatment with rosiglitazone 8 mg per day or up-titration of the glibenclamide dose (maximum dose=15 mg per day). RESULTS: After 26 weeks, treatment with rosiglitazone combination reduced HbA(1c) by 0.81% (P<0.0001) and FPG by 2.4 mmol/l (P<0.0001) compared with glibenclamide monotherapy. HOMA-S and HOMA-B increased by 12 and 28%, respectively (P<0.0001 for both) with combination compared with glibenclamide monotherapy. With rosiglitazone combination and glibenclamide monotherapy, total cholesterol: HDL ratio reduced by 5 and 13%, triglycerides reduced by 6 and 2%, and FFAs reduced by 15 and 8%, respectively. Both treatments were well tolerated and had predictable safety profiles. CONCLUSION: For patients inadequately controlled on glibenclamide, addition of rosiglitazone provides significantly improved glycaemic control compared with uptitration of glibenclamide. This may be preferable to continued monotherapy with higher doses of glibenclamide.

Effect of pioglitazone compared with metformin on glycemic control and indicators of insulin sensitivity in recently diagnosed patients with type 2 diabetes.

Pioglitazone, a thiazolidinedione, improves glycemic control primarily by increasing peripheral insulin sensitivity in patients with type 2 diabetes, whereas metformin, a biguanide, exerts its effect primarily by decreasing hepatic glucose output. In the first head-to-head, double-blind clinical trial comparing these two oral antihyperglycemic medications (OAMs), we studied the effect of 32-wk monotherapy on glycemic control and insulin sensitivity in 205 patients with recently diagnosed type 2 diabetes who were naive to OAM therapy. Subjects were randomized to either 30 mg pioglitazone or 850 mg metformin daily with titrations upward to 45 mg (77% of pioglitazone patients) and 2550 mg (73% of metformin patients), as indicated, to achieve fasting plasma glucose levels of less than 7.0 mmol/liter (126 mg/dl). Pioglitazone was comparable to metformin in improving glycemic control as measured by hemoglobin A1C and fasting plasma glucose. At endpoint, pioglitazone was significantly more effective than metformin in improving indicators of insulin sensitivity, as determined by reduction of fasting serum insulin (P = 0.003) and by analysis of homeostasis model assessment for insulin sensitivity (HOMA-S; P = 0.002). Both OAM therapies were well tolerated. Therefore, pioglitazone and metformin are equally efficacious in regard to glycemic control, but they exert significantly different effects on insulin sensitivity due to differing mechanisms of action. The more pronounced improvement in indicators of insulin sensitivity by pioglitazone, as compared with metformin monotherapy in patients recently diagnosed with type 2 diabetes who are OAM-naive, may be of interest for further clinical evaluation.

Current controversies in the mechanisms and treatment of gestational diabetes.

Gestational diabetes mellitus (GDM) is a heterogeneous entity, including carbohydrate intolerance of variable severity with onset or first recognition during pregnancy. Insulin resistance and beta-cell dysfunction are thought to be major determinants of its development. Its pathomechanism in many ways resembles that of type 2 diabetes. There is an evolving body of evidence from the last decade presenting similarities between gestational diabetes and the metabolic (insulin resistance) syndrome. These new observations suggest that GDM might be an early manifestation of the metabolic syndrome. The desired treatment target of GDM is normoglycemia. It can be reached by dietary treatment; however, if it fails, maternal glycemic monitoring or combined fetal-maternal monitoring, or even insulin (if required) can help reach it. Multiple daily insulin regimens are becoming more widely accepted for the treatment of GDM. Insulin analogues, however, need some more evidence to support their usefulness and safety during pregnancy. The screening for GDM, the reclassification, regular care, and follow-up of these women after pregnancy are of the utmost importance to delay or prevent not only type 2 diabetes but cardiovascular complications as well.