Effect of treatment of gestational diabetes mellitus on pregnancy outcomes.

BACKGROUND: We conducted a randomized clinical trial to determine whether treatment of women with gestational diabetes mellitus reduced the risk of perinatal complications. METHODS: We randomly assigned women between 24 and 34 weeks' gestation who had gestational diabetes to receive dietary advice, blood glucose monitoring, and insulin therapy as needed (the intervention group) or routine care. Primary outcomes included serious perinatal complications (defined as death, shoulder dystocia, bone fracture, and nerve palsy), admission to the neonatal nursery, jaundice requiring phototherapy, induction of labor, cesarean birth, and maternal anxiety, depression, and health status. RESULTS: The rate of serious perinatal complications was significantly lower among the infants of the 490 women in the intervention group than among the infants of the 510 women in the routine-care group (1 percent vs. 4 percent; relative risk adjusted for maternal age, race or ethnic group, and parity, 0.33; 95 percent confidence interval, 0.14 to 0.75; P=0.01). However, more infants of women in the intervention group were admitted to the neonatal nursery (71 percent vs. 61 percent; adjusted relative risk, 1.13; 95 percent confidence interval, 1.03 to 1.23; P=0.01). Women in the intervention group had a higher rate of induction of labor than the women in the routine-care group (39 percent vs. 29 percent; adjusted relative risk, 1.36; 95 percent confidence interval, 1.15 to 1.62; P<0.001), although the rates of cesarean delivery were similar (31 percent and 32 percent, respectively; adjusted relative risk, 0.97; 95 percent confidence interval, 0.81 to 1.16; P=0.73). At three months post partum, data on the women's mood and quality of life, available for 573 women, revealed lower rates of depression and higher scores, consistent with improved health status, in the intervention group. CONCLUSIONS: Treatment of gestational diabetes reduces serious perinatal morbidity and may also improve the woman's health-related quality of life.

The prevalence of the metabolic syndrome in a danish population of women with previous gestational diabetes mellitus is three-fold higher than in the general population.

CONTEXT: Diabetes and obesity, components of the metabolic syndrome, are common characteristics of women with prior gestational diabetes mellitus (GDM). Due to increasing incidence of diabetes and obesity, the metabolic syndrome might comprise a major health problem among these women. OBJECTIVE: The objective was to estimate the prevalence of the metabolic syndrome by three different criteria [World Health Organization 1999 (WHO), The National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults 2001, and European Group for the Study of Insulin Resistance 2002] among women with previous GDM. DESIGN: We conducted a follow-up study of a Danish cohort of women admitted in 1978-1996 to the Diabetes and Pregnancy Center, Rigshospitalet, Copenhagen University Hospital, with diet-treated GDM. The follow-up took place in 2000-2002 at median 9.8 yr (interquartile range 6.4-17.2) after pregnancy. Results were compared with a control group of 1000 age-matched women from a population-based sample (Inter99). PARTICIPANTS: Four hundred eighty-one women at median age 43 yr (interquartile range 38-48) participated. MAIN OUTCOME MEASURES: The main outcome measures were body mass index (BMI), glucose tolerance, blood pressure, lipid profile, and insulin resistance. RESULTS: Independent of the criteria, the prevalence of the metabolic syndrome was three times higher in the prior GDM group, compared with the control group (e.g. WHO: 38.4 vs. 13.4%, P < 0.0005). Age- and BMI-adjusted odds ratio for having the WHO-defined metabolic syndrome was 3.4 (95% confidence interval 2.5-4.8) for the prior GDM group vs. the control group. Obese women (BMI > 30 kg/m(2)) with previous GDM had a more than 7-fold increased prevalence of the metabolic syndrome (WHO), compared with normal-weight prior GDM women (BMI < 25 kg/m(2)). In glucose-tolerant women, the prevalence was doubled in the prior GDM group, compared with control group. CONCLUSION: The prevalence of the metabolic syndrome was three times as high in women with prior diet-treated GDM, compared with age-matched control subjects.

Subclinical inflammation and vascular dysfunction in women with previous gestational diabetes mellitus.

CONTEXT: A history of gestational diabetes (GDM) significantly increases the risk of developing type 2 diabetes, an independent risk factor for cardiovascular disease (CVD). It is not known whether nondiabetic women with prior GDM are also at increased risk of CVD. OBJECTIVE: The aim of this study was to compare biochemical and hemodynamic surrogate markers of CVD in nondiabetic women with and without a history of GDM who were at least 1 yr post delivery. DESIGN: This was a single center cross-sectional study. SETTING: The study was performed in an academic referral center. SUBJECTS: Forty-eight premenopausal healthy women with a history of GDM (n = 25) or a history of normal pregnancy (n = 23) were studied in the follicular phase of the menstrual cycle. MAIN OUTCOME MEASURES: The main outcome measures were: 1) inflammatory markers associated with CVD including C-reactive protein, IL-6, and plasminogen activator inhibitor-1; 2) the adipokine adiponectin; and 3) conduit vessel stiffness. RESULTS: When compared to normal controls, women with prior GDM had higher mean levels of C-reactive protein (3.58 +/- 3.86 vs. 0.52 +/- 0.16 mg/liter; P < 0.001), IL-6 (1.81 +/- 1.04 vs. 0.99 +/- 0.52 pg/ml; P = 0.001), plasminogen activator inhibitor-1 (29.6 +/- 17.6 vs. 16.5 +/- 14.0 ng/ml; P = 0.001), and lower levels of adiponectin (8.9 +/- 3.9 vs. 15.9 +/- 7.3 microg/ml; P = 0.001). Women with prior GDM also had significantly (P

Obstetric complications with GDM. Effects of maternal weight.

Obstetric complications recorded prospectively were assessed retrospectively in 150 women with gestational diabetes mellitus (GDM) and 305 control subjects matched for age, parity, and ethnicity. Intensive diet therapy and self-monitoring of capillary blood glucose were used to obtain postprandial euglycemia; 22% of GDM subjects required insulin. GDM and control subjects were grouped by body mass index to detect any influence of maternal prepregnancy weight on outcome. Polyhydramnios, preterm labor, and pyelonephritis were not more frequent in GDM, but hypertension without proteinuria (7.3 vs. 3.3%) and preeclampsia (8 vs. 3.9%) were more frequent in GDM. The frequency of hypertensive complications in GDM was not totally attributable to being overweight. Abnormalities of labor, birth trauma, and fetal macrosomia were not more common in GDM; 6.7% of the infants of mothers with GDM weighed greater than 4200 g at birth compared with 3.6% of control infants (NS), and 10% were large for gestational age and sex compared with 6.6% of control infants (NS). Despite this, cesarean delivery was more common in GDM (35.3 vs. 22%, P less than 0.01), mostly due to significantly more cesarean births without labor.

Defects in insulin secretion and action in women with a history of gestational diabetes.

Gestational diabetes mellitus (GDM) is associated with defects in insulin secretion and insulin action, and women with a history of GDM carry a high risk for the development of non-insulin-dependent diabetes mellitus (NIDDM). Assessment of subjects with a history of GDM who are currently normoglycemic should help elucidate some of the underlying defects in insulin secretion or action in the evolution of NIDDM. We have studied 14 women with normal oral glucose tolerance who had a history of GDM. They were compared with a group of control subjects who were matched for both body mass index (BMI) and waist-to-hip ratio (WHR). All subjects underwent tests for the determination of oral glucose tolerance, ultradian oscillations in insulin secretion during a 28-h glucose infusion, insulin secretion in response to intravenous glucose, glucose disappearance after intravenous glucose (Kg), and insulin sensitivity (SI) as measured by the Bergman minimal model method. The BMI in the post-GDM women was similar to that in the control subjects (24.9 +/- 1.2 vs. 25.4 +/- 1.4 kg/m2, respectively), as was the WHR ratio (0.80 +/- 0.01 vs. 0.76 +/- 0.01, respectively). The post-GDM women were slightly older (35.2 +/- 0.9 vs. 32.1 +/- 1.4 years, P = 0.04). The fasting plasma glucose levels were significantly higher in the post-GDM group than in the control group (4.9 +/- 0.1 vs. 4.4 +/- 0.1 mmol/l, respectively, P < 0.001) and remained higher at each of the subsequent determinations during the oral glucose tolerance test, although none had a result indicative of either diabetes or impaired glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of type 1 diabetes postpartum in patients with gestational diabetes mellitus by combined islet cell autoantibody screening: a prospective multicenter study.

Women with gestational diabetes mellitus (GDM) have a considerable risk of developing diabetes later in life. To determine the predictive value of autoantibody markers in gestational diabetic pregnancy for the development of type 1 diabetes postpartum, we tested 437 patients with GDM (289 women treated with diet only [GDM-A] and 148 requiring insulin treatment during pregnancy [GDM-B]) for antibodies to islet cells (ICAs), GAD (GADAs), and tyrosine phosphatase ICA512/IA-2 (IA2As). We prospectively followed them with repeated oral glucose tolerance tests and antibody determinations for up to 7 years postpartum (mean, 1.6 years; range, 0-7.2 years). The cumulative risk of diabetes up to 5 years postpartum was 17% (95% CI 12-22%). The risk of type 1 diabetes was 3% (2-5%) by 9 months and 7% (4-9%) 2 years after delivery. At delivery, 8.5% of all patients were ICA+, 9.5% were GADA+, 6.2% were IA2A+, and 18.1% were positive for at least one antibody (12.6% for GDM-A vs. 30.4% for GDM-B, P < 0.0001). During follow-up, GADAs persisted in 75%, ICAs in 35%, and IA2As in 30% of the subjects positive for the respective marker at delivery. By 2 years postpartum, 29% (19-39%) of patients positive for at least one antibody developed type 1 diabetes, compared with 2% (1-4%) of antibody-negative patients (P < 0.0001). Thereby, the risk for type 1 diabetes 2 years postpartum increased with the number of antibodies present at delivery from 17% (6-28%) for one antibody, to 61% (30-91%) for two antibodies, and to 84% (55-100%) for 3 antibodies. Risk of progression to type 1 diabetes postpartum was also associated with the status of parity. Women with one or more pregnancies before the index pregnancy had a higher risk for type 1 diabetes 2 years after delivery (14.7% [4.9.-24.5%]) than women having their first (i.e., index) pregnancy (5% [2.9-7.1%]) (P < 0.006). A comparison of different prediction strategies showed that single antibody screening with GADA yielded the highest sensitivity of 63% (45-75%), compared with ICA (48% [31-65%]) and IA2A (34% [13-47%]). Combined screening with two autoantibodies increased sensitivity to 74% (58-90%) and 75% (60-92%) when using GADA plus ICA or GADA plus IA2A, respectively. Screening with all three markers improved sensitivity further to 82% (67-100%). Beta-cell autoantibodies determined at delivery in women with GDM are highly predictive for the development of type 1 diabetes postpartum. Autoantibody screening in pregnant women with GDM from populations at high risk for type 1 diabetes should therefore be considered to allow early diagnosis and appropriate therapy.

Predicting future diabetes in Latino women with gestational diabetes. Utility of early postpartum glucose tolerance testing.

We tested 32 routine clinical parameters for their ability to discriminate between a high risk and a low risk of non-insulin-dependent diabetes mellitus (NIDDM) within 5-7 years after pregnancies complicated by gestational diabetes mellitus (GDM). Latino women (n = 671) with GDM who did not have diabetes 4-16 weeks after delivery returned for at least one 75-g oral glucose tolerance test (OGTT) within 7.5 years. Multivariate analysis was used to identify parameters ascertained during or immediately after the index pregnancy that were independently associated with the development of diabetes during follow-up. Life table analysis revealed a 47% cumulative incidence rate of NIDDM 5 years after delivery for this cohort of patients who did not have diabetes at the initial postpartum examination. Four variables were identified as independent predictors of NIDDM: the area under the OGTT glucose curve at 4-16 weeks postpartum, the gestational age at the time of diagnosis of GDM, the area under the OGTT glucose curve during pregnancy, and the highest fasting serum glucose concentration during pregnancy. Examination of relative risks (RRs) of NIDDM between the highest and lowest quartiles of the cohort for each variable, adjusted for the other three variables, revealed that the postpartum OGTT provided the best discrimination between high-risk and low-risk individuals (adjusted RR = 11.5 [95% confidence interval 4.5-29.1] compared with adjusted RRs of only 0.5-2.5 for the other three variables).(ABSTRACT TRUNCATED AT 250 WORDS)

Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk hispanic women.

Type 2 diabetes frequently results from progressive failure of pancreatic beta-cell function in the presence of chronic insulin resistance. We tested whether chronic amelioration of insulin resistance would preserve pancreatic beta-cell function and delay or prevent the onset of type 2 diabetes in high-risk Hispanic women. Women with previous gestational diabetes were randomized to placebo (n = 133) or the insulin-sensitizing drug troglitazone (400 mg/day; n = 133) administered in double-blind fashion. Fasting plasma glucose was measured every 3 months, and oral glucose tolerance tests (OGTTs) were performed annually to detect diabetes. Intravenous glucose tolerance tests (IVGTTs) were performed at baseline and 3 months later to identify early metabolic changes associated with any protection from diabetes. Women who did not develop diabetes during the trial returned for OGTTs and IVGTTs 8 months after study medications were stopped. During a median follow-up of 30 months on blinded medication, average annual diabetes incidence rates in the 236 women who returned for at least one follow-up visit were 12.1 and 5.4% in women assigned to placebo and troglitazone, respectively (P < 0.01). Protection from diabetes in the troglitazone group 1) was closely related to the degree of reduction in endogenous insulin requirements 3 months after randomization, 2) persisted 8 months after study medications were stopped, and 3) was associated with preservation of beta-cell compensation for insulin resistance. Treatment with troglitazone delayed or prevented the onset of type 2 diabetes in high-risk Hispanic women. The protective effect was associated with the preservation of pancreatic beta-cell function and appeared to be mediated by a reduction in the secretory demands placed on beta-cells by chronic insulin resistance.

Gestational diabetes leads to the development of diabetes in adulthood in the rat.

We have developed a model of gestational diabetes in the rat to determine whether an altered metabolic intrauterine milieu is directly linked to the development of diabetes later in life. Uteroplacental insufficiency is induced in the pregnant rat on day 19 of gestation. Sham-operated animals serve as controls. Offspring are growth retarded at birth; however, they catch up by 5-7 weeks of age. At approximately 8 weeks of age, they are bred to normal males. During pregnancy, these animals develop progressive hyperglycemia and hyperinsulinemia accompanied by impaired glucose tolerance and insulin resistance. Offspring, designated as infants of a diabetic mother (IDMs), are heavier at birth and remain heavy throughout life. IDMs are insulin resistant very early in life, and glucose homeostasis is progressively impaired. Defects in insulin secretion are detectable as early as 5 weeks of age. By 26 weeks of age, IDMs are overtly diabetic. These data demonstrate that the altered metabolic milieu of the diabetic pregnancy causes permanent defects in glucose homeostasis in the offspring that lead to the development of diabetes later in life.

Response of pancreatic beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes.

The purpose of this study was to examine the response of pancreatic beta-cells to changes in insulin sensitivity in women at high risk for type 2 diabetes. Oral glucose tolerance tests (OGTTs) and frequently sampled intravenous glucose tolerance tests (FSIGTs) were conducted on Latino women with impaired glucose tolerance and a history of gestational diabetes before and after 12 weeks of treatment with 400 mg/day troglitazone (n = 13) or placebo (n = 12). Insulin sensitivity was assessed by minimal model analysis, and beta-cell insulin release was assessed as acute insulin responses to glucose (AIRg) and tolbutamide (AIRt) during FSIGTs and as the 30-min incremental insulin response (30-min dINS) during OGTTs. Beta-cell compensation for insulin resistance was assessed as the product (disposition index) of minimal model insulin sensitivity and each of the 3 measures of beta-cell insulin release. In the placebo group, there was no significant change in insulin sensitivity or in any measure of insulin release, beta-cell compensation for insulin resistance, or glucose tolerance. Troglitazone treatment resulted in a significant increase in insulin sensitivity, as reported previously. In response, AIRg did not change significantly, so that the disposition index for AIRg increased significantly from baseline (P = 0.004) and compared with placebo (P = 0.02). AIRt (P = 0.001) and 30-min dINS (P = 0.02) fell with improved insulin sensitivity during troglitazone treatment, so that the disposition index for each of these measures of beta-cell function did not change significantly from baseline (P > 0.20) or compared with placebo (P > 0.3). Minimal model analysis revealed that 89% of the change from baseline in insulin sensitivity during troglitazone treatment was accounted for by lowered plasma insulin concentrations. Neither oral nor intravenous glucose tolerance changed significantly from baseline or compared with placebo during troglitazone treatment. The predominant response of beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes was a reduction in insulin release to maintain nearly constant glucose tolerance.

Metabolic and vascular abnormalities in subjects at risk for type 2 diabetes: the early start of a dangerous situation.

Various groups at risk for type 2 diabetes have been identified, including individuals with family history of type 2 diabetes, obesity, prior gestational diabetes, polycystic ovary syndrome, metabolic syndrome, hypertension, dyslipidemia and particularly those with pre-diabetes (impaired glucose tolerance and/or impaired fasting glucose). To various degrees, all these groups have also been identified with significant vascular abnormalities that range from endothelial dysfunction and low-grade or sub-clinical inflammation to evident atherosclerosis. The mechanisms involved in establishing a link between the risk of type 2 diabetes and vascular dysfunction are multiple and complex. The presence in the circulation of various cytokines, hormones and substrates associated with increased visceral fat and insulin resistance, the frequent appearance of associated cardiovascular risk factors and/or the possibility of some genetically determined intrinsic vascular abnormalities are all explanatory mechanisms that are being evaluated in clinical research. Whereas the possibility of appreciating a significant reduction in cardiovascular outcomes in long-term prospective clinical trials in all these groups at risk for type 2 diabetes is still lacking, understanding these mechanisms and recognizing how various interventions may improve vascular health is a worthwhile area of research that may translate into important clinical strategies to reduce the burden of type 2 diabetes and cardiovascular disease.

Screening for gestational diabetes mellitus.

The term 'gestational diabetes mellitus' is unsatisfactory as it refers to a heterogeneous group of women, including those with minimal abnormality of carbohydrate metabolism and those with undiagnosed type II diabetes. However, perinatal morbidity is increased even in the group of women who have only impaired glucose tolerance; the mothers are at increased risk of subsequent development of diabetes, and there may also be long-term implications for the offspring. Current research is aiming to define the blood glucose levels at which risks increase so that clinical management can be appropriately directed. When available, the criteria required to justify population screening in pregnancy should be satisfied. The glucose challenge and fasting glucose tests are the leading contenders as appropriate screening tests to determine who should have the diagnostic glucose tolerance test. However, until this is reviewed, the widely used scheme of risk factors as a screening method should continue, as it detects at least 50% of women with gestational diabetes.

Are plasma total homocysteine and other amino acids associated with glucose intolerance in uncomplicated pregnancies and preeclampsia?

OBJECTIVE: To evaluate the possible association between plasma total homocysteine or other amino acid concentrations and gestational diabetes or glucose intolerance (GI), in normotensive and preeclamptic pregnant women. STUDY DESIGN: Prospective study including 243 pregnant women without previous risk factors. O'Sullivan test (plus oral glucose tolerance test when necessary) was performed, and homocysteine, B vitamins and plasma amino acids (AA) were measured at 24-25 weeks. Homocysteine and other amino acids were also measured in the third trimester. RESULTS: Significant differences were observed in the incidence of preeclampsia in relation to abnormal glucose tolerance (P < 0.012). In normotensive patients, the glucose intolerance group showed significantly lower tHcy (P = 0.021) and increased plasma alanine concentrations in comparison with controls (P = 0.046), although no correlation was observed between both amino acid concentrations. CONCLUSIONS: (a) A higher incidence of preeclampsia was observed in abnormal glucose tolerance patients, (b) total homocysteine and alanine were the only individual amino acids whose plasma concentrations varied according to the glucose tolerance classes, and (c) an association between hyperhomocysteinemia and glucose intolerance in our preeclamptic patients could not be demonstrated.

Diagnostic controversy: gestational diabetes and the meaning of risk for pima Indian women.

Gestational diabetes is the one form of this well known, chronic disease of development that disappears. After the birth of the child, the mother's glucose levels typically return to normal. As a harbinger of things to come, gestational diabetes conveys greater risk for later type 2 (previously "non-insulin dependent") diabetes in both the mother and child. Thus, pregnant women have become a central target for prevention of this disease in the entire Pima population. Based on ethnographic interviews conducted between 1999 and 2000, I discuss the negotiated meanings of risk, "borderline" diabetes, and women's personal knowledge and experiences of diabetes, particularly during the highly surveilled period of pregnancy. I also highlight the heterogeneity of professional discourse pertaining to gestational diabetes, most notably the debate surrounding its diagnosis. Significantly, women's narratives reveal the same set of questions as is raised in the professional debate. Implications for diabetes prevention and for balancing the increased surveillance of pregnant women with clinical strategies that privilege their experience and perspectives are also discussed.

Infant outcomes of gestational diabetes mellitus.

This study was carried out in Mymensingh Medical College and Hospital, Mymensingh. The work, which lasted for one year commencing in July 2003, was designed to find out and compare the infant outcomes of gestational diabetes mellitus (GDM) with a view to reducing the complications. Forty cases of GDM with single pregnancy were selected as experimental group, while forty other cases of pregnant women without GDM constituted the control group. Questionnaire and observation charts were the research instruments. Statistical analyses were done manually. It was retrieved that the offspring of GDM mothers had a higher risk of macrosomia, neonatal jaundice and respiratory complications. The perinatal mortality rate was also more in GDM cases. However, befitting measures for prevention, treatment and management of GDM may be taken up to ameliorate the situation.

Growth patterns of large-for-gestational-age and appropriate-for-gestational-age infants of gestational diabetic mothers and control mothers at age 1 year.

OBJECTIVE: The purpose of this study was to explore the development of adiposity in macrosomic and normosomic infants of mothers with gestational diabetes mellitus (GDM) and control subjects between birth and age 1 year, and assess its relation to maternal prenatal factors and neonatal factors. RESEARCH DESIGN AND METHODS: This was a prospective observational study of 192 infants, including 47 large-for-gestational-age (LGA) infants of GDM mothers, 47 appropriate-for-gestational-age (AGA) infants of GDM mothers, 55 LGA control infants, and 44 AGA control infants who were evaluated at birth and age 1 year. Maternal prenatal and pregnancy anthropometric measurements were recorded. Multiple infant anthropometric measurements, including skinfold thicknesses, were obtained at birth and age 1 year. Regression models were run to detect the independent effects of various maternal and infant factors on 1-year child adiposity, adjusting for their effects at birth. RESULTS: LGA infants of GDM mothers had a higher BMI, waist circumference, and abdominal skinfold at age 1 year compared with all other study groups. Among infants of GDM mothers, the mean 2-h postprandial glucose value for the second and third trimester correlated with waist circumference (r = 0.28, P < 0.04) and subscapular skinfold (r = 0.37, P < 0.007), and correlated marginally with 1-year sum of four skinfolds. Among infants of GDM mothers, a regression of 1-year sum of four skinfolds was significantly related to maternal prepregnancy weight after controlling for sum of skinfolds at birth. For control infants, the maternal glucose screen value was significantly associated with 1-year sum of skinfolds adjusted for the birth sum of skinfolds. CONCLUSIONS: We concluded that macrosomic infants of GDM mothers have unique patterns of adiposity that are present at birth and persist at age 1 year. Further, we concluded that maternal factors, including adiposity and intrauterine fuel environment, influence the presence and distribution of adiposity for both infants of GDM mothers and control infants.

Hypertension in women with gestational diabetes.

Hypertension in pregnancy and gestational diabetes have in common a lack of universally accepted classification and nomenclature that hinders comparison of data between research groups and contributes to the lack of consensus in the literature on these conditions. The inter-relationship of hypertension and gestational diabetes can be considered from three viewpoints according to whether hypertension is present before, during, or after the pregnancy. The first question is whether hypertension predating pregnancy predisposes to gestational diabetes. Epidemiological evidence and physiological argument based on the common etiologic factor of insulin resistance would suggest that gestational diabetes should be more common in the presence of preexisting hypertension. The limited clinical data available support this hypothesis. There are three issues concerning the coexistence of hypertension and gestational diabetes: whether gestational diabetes predisposes to pregnancy-induced hypertension, whether pregnancy-induced hypertension predisposes to gestational diabetes and what effect the combination has on morbidity and mortality. A number of studies have investigated whether pregnancy-induced hypertension is more common in women with gestational diabetes, but no consensus has been reached. There is little direct clinical evidence on the reverse issue, but data are presented to suggest that pregnancy-induced hypertension may only predispose to gestational diabetes when its etiology is gestational hypertension and not preeclampsia. The issue of how the coexistence of pregnancy-induced hypertension and gestational diabetes affects maternal or neonatal morbidity and mortality is largely unanswered. The last question is whether gestational diabetes has any prognostic significance with regard to the future development of hypertension in the mother. It is well known that gestational diabetes predisposes to subsequent NIDDM and that NIDDM is associated with a high incidence of essential hypertension. Once again insulin resistance may be a unifying factor. However, there is no direct clinical evidence that gestational diabetes predisposes to future hypertension.

Maternal and fetal outcomes if gestational impaired glucose tolerance is not treated.

OBJECTIVE: To evaluate whether there is increased maternal or neonatal morbidity in connection with impaired glucose tolerance (IGT) during pregnancy when the condition is not treated. RESEARCH DESIGN AND METHODS: During the study period of 1997-2001, in a defined geographical area in Sweden, the diagnostic criteria for gestational diabetes mellitus (GDM) were limited to the criteria for diabetes. Prospectively, 213 women who were identified with IGT during pregnancy were undiagnosed and untreated. Data on maternal and fetal outcome was collected from records. For each case subject, four control subjects were taken from the same delivery department. RESULTS: The proportion of women who underwent cesarean section was significantly higher in the case subjects than in the control subjects and was independently associated with IGT. The adjusted odds ratio (OR) was 1.9 (95% CI 1.2-2.9). The proportion of infants who were large for gestational age (LGA), defined as birth weight >2 SDs greater than the mean for gestation and sex, was independently significantly associated with untreated IGT during pregnancy (OR 7.3, 95% CI 4.1-12.7). Admission to a neonatal intensive care unit (NICU) for 2 days or longer was more common (adjusted OR 2.0, 95% CI 1.1-3.8). However, 71.3% of the children in the IGT group and 87.3% of the control subjects had no neonatal complications. CONCLUSIONS: There is increased independent association between cesarean section rate, prematurity, LGA, and macrosomic infants born to mothers with untreated IGT. Most of the children were healthy, but there is still increased morbidity. Therefore, to evaluate the effects of treatment, there is a need for a randomized study.

Diabetes and abnormal glucose tolerance in women with previous gestational diabetes.

OBJECTIVE: In Spanish women with gestational diabetes mellitus (GDM), we aimed to study the progression to diabetes and abnormal glucose tolerance (AGT) and identify predictive factors. RESEARCH DESIGN AND METHODS: In 696 women with GDM and 70 control women, glucose tolerance was evaluated postpartum and at 5-year intervals. RESULTS: In the GDM group, the cumulative risk for diabetes and AGT was 13.8 and 42.4% after 11 years compared with 0 and 2.8% in control women, respectively (P < 0.05). Independent predictive factors for diabetes were previous hyperglycemia, four abnormal glucose values on the diagnostic oral glucose tolerance test (OGTT) or overt diabetes during pregnancy, 2-h blood glucose on the diagnostic OGTT >/=11.7 mmol/l, gestational age at diagnosis <24 weeks, and prepregnancy BMI >/=26.4 kg/m(2). All of these factors (some with different cutoff points) in addition to fasting glycemia were predictors of AGT also. The risk was nonlinear. Four abnormal glucose values on the diagnostic OGTT or overt diabetes during pregnancy was the strongest predictive factor for diabetes (relative risk 3.92), and prepregnancy BMI was the predictive factor with the highest attributable fraction in the whole group (13.3%). When first postpartum OGTT data were included in the analysis, predictors changed, but the overall prediction was similar. CONCLUSIONS: Spanish women with GDM have an increased risk of diabetes and AGT. Predictive factors display a nonlinear relationship. The strongest predictive factor for diabetes was four abnormal glucose values on the diagnostic OGTT or overt diabetes during pregnancy; the factor with the highest attributable fraction in the whole group was prepregnancy BMI.

Total sialic acid and associated elements of the metabolic syndrome in women with and without previous gestational diabetes.

OBJECTIVE: Inflammatory markers predict type 2 diabetes and relate to the metabolic syndrome. Gestational diabetes mellitus (GDM) predicts type 2 diabetes and may be part of this syndrome. To examine the association of inflammatory markers with GDM, we investigated total sialic acid (TSA) in women with and without previous GDM. RESEARCH DESIGN AND METHODS: All women with GDM and a random sample of women from one center of the Brazilian Study of Gestational Diabetes were invited to return 7 years after their index pregnancy. After an interview, an oral glucose tolerance test and anthropometry were performed. A total of 46 women with and 50 women without previous GDM completed the protocol. RESULTS: Mean TSA was significantly higher in women with (71.8 +/- 11.1 mg/dl) than without (67.5 +/- 9.8 mg/dl) previous GDM (P < 0.05). In a linear regression model, TSA was 4 mg/dl (P < 0.05) higher in women with previous GDM, after adjustment for BMI, fasting insulin sensitivity, and number of years spent in school. In a similar model, current 2-h plasma glucose levels were associated with higher TSA levels after adjustment for waist-to-hip ratio and the log of triglycerides. TSA was strongly correlated with individual components and aggregates (r = 0.55, P < 0.001) of the metabolic syndrome. CONCLUSIONS: Increased TSA levels are associated with previous GDM and are strongly linked to the metabolic syndrome. These findings in young women suggest that a chronic mild systemic inflammatory response is an early feature of the metabolic syndrome and that GDM may be a window for its investigation.