Martin Montoro

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). Women who met World Health Organization criteria for impaired glucose tolerance at the early postpartum examination had a 5-year unadjusted 80% risk of diabetes, which was much higher than the risk of NIDDM that has been reported for Latino people with impaired glucose tolerance who were not selected for a history of GDM. Our findings indicate that postpartum glucose tolerance testing is superior to other routine clinical parameters in defining the risk of NIDDM within 5–7 years after pregnancies complicated by GDM. Furthermore, a history of GDM appears to impart a specific risk for NIDDM that cannot be explained by the degree of glucose tolerance observed when patients are not pregnant.

Managing preexisting diabetes for pregnancy: Summary of evidence and consensus recommendations for care

This document presents consensus panel recommendations for the medical care of pregnant women with preexisting diabetes, including type 1 and type 2 diabetes. The intent is to help clinicians deal with the broad spectrum of problems that arise in management of diabetes before and during pregnancy, and to prepare diabetic women for treatment that may reduce complications in the years after pregnancy. A thorough discussion of the evidence supporting the recommendations is presented in the book, Management of Preexisting Diabetes and Pregnancy , authored by the consensus panel and published by the American Diabetes Association (ADA) in 2008 (1). A consensus statement on obstetrical and postpartum management will appear separately. The recommendations are diagnostic and therapeutic actions that are known or believed to favorably affect maternal and perinatal outcomes in pregnancies complicated by diabetes. The grading system adapted by the ADA was used to clarify and codify the evidence that forms the basis for the recommendations (2). Unfortunately there is a paucity of randomized controlled trials (RCTs) of the different aspects of management of diabetes and pregnancy. Therefore our recommendations are often based on trials conducted in nonpregnant diabetic women or nondiabetic pregnant women, as well as on peer-reviewed experience before and during pregnancy in women with preexisting diabetes (3–4). We also reviewed and adapted existing diabetes and pregnancy guidelines (5–10) and guidelines on diabetes complications and comorbidities (2,3,11–14). ### A. Organization of preconception and pregnancy care #### Recommendations

A comparison of propylthiouracil versus methimazole in the treatment of hyperthyroidism in pregnancy

OBJECTIVE Our purpose was to demonstrate that propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism during pregnancy. STUDY DESIGN Between 1974 and 1990 records were available on 185 pregnant patients with a history or diagnosis of hyperthyroidism. Ninety-nine patients were treated with propylthiouracil and 36 with methimazole. The response to therapy was compared with respect to the time to normalization of the free thyroxine index and the incidences of congenital anomalies and hypothyroidism. RESULTS The time to normalization of the free thyroxine index was compared in the two groups by means of survival analysis. The median time to normalization of the free thyroxine index on propylthiouracil and methimazole was 7 and 8 weeks, respectively (p = 0.34, log-rank test). The incidence of major congenital malformations in mothers treated with propylthiouracil and methimazole was 3.0% and 2.7%, respectively. No neonatal scalp defects were seen. One infant was overtly hypothyroid at delivery. CONCLUSION Propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism in pregnancy.

Use of Fetal Ultrasound to Select Metabolic Therapy for Pregnancies Complicated by Mild Gestational Diabetes

OBJECTIVE To determine whether fetal ultrasound early in the third trimester can identify Latina with mild gestational diabetes mellitus (GDM) whose fetuses are at risk for macrosomia and, if so, whether maternal insulin therapy can reduce that risk. RESEARCH DESIGN AND METHODS Study subjects included 303 consecutive women with GDM and a fasting serum glucose level <5.8 mM on diet therapy who had a fetal ultrasound between 29 and 33 weeks gestation. Of the women, 98 (32%) had a fetal AC ≥ 75th percentile for gestational age, and 59 women completed a randomized trial of diet therapy (n = 29) or diet plus twice daily insulin (n = 30). Maternal nutrient levels were assessed by meal tolerance testing (MTT) before and during therapy and by capillary glucose monitoring four to seven times a day. Birth weights corrected for gestational age and neonatal glycemia and skin folds were the primary outcome variables compared between treatment groups. RESULTS Diet and diet-plus-insulin groups were well matched for maternal age, prepregnancy relative weight, weight gain during pregnancy, and glycemia at entry. Insulin therapy reduced maternal capillary (P < 0.005) and MTT (P < 0.001) glucose levels and prevented a diet-associated rise in MTT triglyceride levels (P < 0.002). Gestational age at delivery was similar in insulin- and diet-treated groups (39.6 ± 0.2 vs. 39.5 ± 0.2 weeks). Birth weights (3,647 ± 67 vs. 3,878 ± 84 g; P < 0.02), the prevalence of large-for-gestational age infants (13 vs. 45%, P < 0.02), and neonatal skin-fold measurements at three sites (P < 0.005) were reduced in the insulin-treated group. Rates of transient neonatal hypoglycemia were low in both treatment groups (14 and 18%, respectively) and didnot differ significantly between groups. CONCLUSIONS Fetal ultrasound early in the third trimester identified women with mild GDM whose infants were at high risk for fetal macrosomia in the absence of standard glycemic criteria for insulin therapy. Insulin treatment reduced the macrosomia, indicating that fetal ultrasound can be used to guide metabolic therapy in pregnancies complicated by mild GDM.

Gestational diabetes mellitus : the prevalence of glucose intolerance and diabetes mellitus in the first two months post partum

To determine the prevalence of abnormal carbohydrate metabolism in the early postpartum period in women with gestational diabetes mellitus, we performed 2-hour oral glucose tolerance tests between 5 and 8 weeks post partum in 246 women with recent gestational diabetes mellitus. Patients were stratified into three study groups based on their fasting serum glucose level during pregnancy: (1) group A1: all fasting serum glucose levels during pregnancy less than 105 mg/dl without insulin therapy; (2) group A2: any fasting serum glucose levels greater than 105 and less than 140 mg/dl before insulin therapy; (3) group B1: any pregnancy with fasting serum glucose levels greater than 140 mg/dl. Overall, 48 (19%) of the patients had an abnormal oral glucose tolerance test in the early postpartum period; 25 (10%) had impaired glucose tolerance and 23 (9%) had diabetes mellitus. The prevalence of postpartum diabetes mellitus (2% in group A1, 9% in group A2 and 44% in group B1) increased in parallel with the degree of maternal metabolic decompensation during pregnancy (p less than 0.05 for A1 versus A2; p less than 0.001 for A2 versus B1). The prevalence of impaired glucose tolerance was likewise greater in the B1 group (26%) than in either the A1 or the A2 group (p less than 0.05). Gestational age less than 24 weeks at diagnosis of gestational diabetes mellitus was an additional risk factor for postpartum glucose intolerance. Our findings support the use of an oral glucose tolerance test in the early puerperium, especially for patients with elevated fasting serum glucose levels during pregnancy.

Successful Outcome of Pregnancy in Women with Hypothyroidism

Published data on the influence of hypothyroidism on fertility, gestation, and the offspring are controversial. We studied nine hypothyroid women during 11 pregnancies. Mean serum values for thyroxine, triiodothyronine (T3), resin T3 uptake ratio, and thyroid-stimulating hormone were 2.3 microgram/dL, 82 ng/dL, 0.64, and 105 mU/mL, respectively. Four patients had iatrogenic hypothyroidism (three remote thyroidectomy, one remote 131I therapy), two Hashimotos thyroiditis, and three idiopathic primary hypothyroidism. Seven patients first presented untreated after the 24th week of gestation. Two patients needed cesarean section; seven delivered vaginally. There was one stillborn infant in the only patient with pre-eclampsia. Another infant had Downs syndrome and an ostium primum defect (mothers age, 41 years). The remaining nine infants were normal at birth. All placentas were normal. Follow-up in seven infants up to 2.7 years showed normal thyroid function and somatic development. Infants of hypothyroid mothers may be normal because their hypothalamic-pituitary thyroid axis develops independently from the mother.

Prevalence and etiology of respiratory distress in infants of diabetic mothers: Predictive value of fetal lung maturation tests

Abstract The purpose of this study was to investigate the prevalence of respiratory distress syndrome attributable to surfactant deficiency in infants of diabetic mothers tested for fetal lung maturation. Three tests were assessed: (1) lecithin/sphingomyelin ratio, (2) phosphatidylglycerol concentration, and (3) optical density at 650 nm. From January 1987 through June 1989, 526 diabetic gestations were delivered within 5 days of fetal lung maturation testing. Surfactant-deficient respiratory distress syndrome was present in five infants (0.95%); all were n = 5), hypertrophic cardiomyopathy ( n = 4), pneumonia ( n = 2), polycythemia ( n = 1), and meconium aspiration syndrome ( n = 1). The use of standard maturity values of lecithin/sphingomyelin ratio ≥ 2.0, phosphatidylglycerol > 2% to 5%, and optical density at 650 nm ≥ 0.150 were evaluated. Each test had a 100% sensitivity in identifying surfactant-deficient respiratory distress syndrome and a 100% negative predictive value in identifying the absence of disease. All three tests had a low positive predictive value: 15% for lecithin/sphingomyelin ratio, 9% for phosphatidylglycerol, and 3% for optical density at 650 nm. We concluded that most cases of respiratory distress in the infants of diabetic mothers were unrelated to surfactant deficiency. The standard maturity values used in fetal lung maturation tests were valid in the diabetic gestation. The optical density at 650 nm was useful as a first-line test to predict the absence of surfactant-deficient respiratory distress syndrome.

The role of nonstress tests, fetal biophysical profile, and contraction stress tests in the outpatient management of insulin-requiring diabetic pregnancies

Antepartum fetal surveillance methods applicable in a home glucose-monitored population of pregnant diabetic women have been evaluated. A testing sequence of nonstress heart rate testing, backed up by either the fetal biophysical profile or contraction stress testing employed at a twice weekly interval, in 107 outpatients was compared with the management of 140 historic control patients by weekly nonstress tests and daily plasma estriols. There were 617 of 672 (91.8%) reactive nonstress tests in outpatients compared to 566 of 626 (90.4%) reactive tests in hospitalized control patients. Of 13 contraction stress tests performed in the outpatient group, only one was positive. Although 2,670 estriol determinations were done on hospitalized control patients, none was used for outpatients. No losses were attributed to unexplained antenatal stillbirth in either group. A fetal biophysical score of 8 was found to be at least as reliable as a reactive nonstress test. Antenatal surveillance in the well-controlled, insulin-requiring diabetic woman can be safely achieved with a testing sequence that consists of twice weekly nonstress tests backed up by the fetal biophysical profile and contraction stress tests.

Alteration of endothelial function markers in women with gestational diabetes and their fetuses.

Objective: We tested the hypothesis that women with gestational diabetes mellitus (GDM) and their fetuses would demonstrate alterations in markers of endothelial nitric oxide synthase (eNOS) uncoupling, oxidative stress, and endothelial dysfunction and these changes would correlate with the levels of hyperglycemia through a pilot observational case-control study of women with GDM and their fetuses. Methods: Levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), C-reactive protein (CRP), nitric oxide (NO), eNOS, p22-phox, and SOD gene expression, and endothelial progenitor cells (EPC) counts in both maternal and cord blood were measured at the time of delivery in women with and without GDM. Results: We demonstrated the presence of decreased maternal circulating EPC counts, increased soluble adhesion molecules in maternal blood, decreased SOD expression in both maternal and cord blood and increased eNOS expression in both maternal and cord blood in women with GDM. Conclusions: These data suggest that the molecular mechanisms behind oxidative stress in women with GDM and their fetuses appear similar to those hypothesized for non-pregnant adults with type 2 diabetes mellitus (DM).

Serum Lipids Within 36 mo of Delivery in Women With Recent Gestational Diabetes

We prospectively evaluated fasting serum total cholesterol (chol), low- and high-density lipoprotein cholesterol (LDL-chol and HDL-chol), and triglycerides (TGs) in a large cohort of Hispanic women during the first 36 mo after pregnancies complicated by gestational diabetes mellitus (GDM). In 1340 women studied 6–12 wk postpartum (PP-GDM group), chol and LDL-chol were similar to levels in 43 postpartum control subjects without prior GDM. Compared with control subjects (2.01 ± 1.24 mM), TG was elevated in the PP-GDM women with diabetes mellitus (DM) (2.86 ± 2.21 mM, P < 10−5) and impaired glucose tolerance (IGT) (2.64 ± 1.68 mM, P = 0.02) but not in those with normal glucose tolerance (2.00 ± 1.21 mM). HDL-chol was decreased in PP-GDM women with DM compared with those with normal glucose tolerance. A subgroup of 157 women with prior GDM returned for at least one annual follow-up test on nonhormonal contraception (FU-GDM: n = 60 at 3–11 mo after delivery, n = 78 at 12–23 mo, and n = 39 at 24–35 mo). The cumulative prevalence of DM by 36 mo was 40%. Chol or LDL-chol levels did not significantly change during the 1-yr intervals in the FU-GDM group and were similar to a control group of 36 women without prior GDM. TG was elevated and HDL-chol was decreased in the FU-GDM women with DM at 3–11 mo but not thereafter. Overall, the prevalence of moderateand high-risk LDL-chol in the FU-GDM group was not different from that of control subjects. These findings suggest that lipid abnormalities are uncommon during the first 36 mo after delivery in women with recent GDM. The abnormalities found consisted of increased TG and decreased HDL-chol in subjects who had developed DM during the study period.