Independent predictors of cesarean delivery in women with diabetes.

OBJECTIVES: To identify independent risk factors for Cesarean delivery in women with pregnancy complicated by diabetes. METHODS: Retrospective analysis of pregnancies from 5735 diabetic women delivering liveborn infants. Maternal demographic, medical, obstetric historical factors and index pregnancy obstetric, glycemic and neonatal outcome parameters were evaluated for association with Cesarean delivery after a trial of labor. Individual risk factors were analyzed for association by chi2 and ANOVA. Independent predictors of Cesarean delivery and adjusted relative risk (RR) were identified by stepwise logistic regression. RESULTS: Trial of labor was permitted in 90.8% and 59.4% of women without (n = 4643) and with prior Cesarean delivery (n = 1092) and was successful in 85.2% and 56.9%, respectively. Eleven independent predictors were found. Five were related to obstetric history and maternal age: prior Cesarean delivery (RR 5.34, 95% CI 3.94-7.25), no prior live birth (RR 3.17, 95% CI 1.98-5.07), no prior vaginal delivery (RR 2.28, 95% CI 1.50-3.44), prior stillbirth (RR 1.71, 95% CI 1.09-2.68%) and maternal age > or = 35 years (RR 1.53, 95% CI 1.20-1.93). Two were related to the severity of diabetes at entry to diabetes care: requiring insulin (RR 1.53, 95% CI 1.20-1.93) and highest fasting plasma glucose level (RR 1.04, 95% CI 1.01-1.07). Two were related to obstetric factors: pre-eclampsia/hypertension (RR 2.56, 95% CI 2.00-3.27) and labor induction (RR 3.32, 95% CI 2.70-4.10). The remaining two were birth weight (per 250 g, RR 1.12, 95% CI 1.09-1.17) and pre-delivery body mass index (RR, 1.03, 95% CI 1.00-1.05). CONCLUSION: The majority of predictors were not modifiable, relating to obstetric history, maternal age and diabetes severity. Possible modifiable interventions to avoid/improve labor induction, and decrease birth weight and maternal weight gain might decrease risk of Cesarean delivery. Future studies must address these multiple predictors.

Prospective delivery of reliably dated term infants of diabetic mothers without determination of fetal lung maturity: comparison to historical control.

OBJECTIVE: To determine whether omitting fetal lung maturity (FLM) testing prior to delivery in term pregnancies complicated by gestational (GDM) and pregestational diabetes mellitus would increase the risk of neonatal respiratory distress syndrome (RDS). METHODS: In a 2-year study (1990-91), 1,457 pregnant women with accurately dated pregnancies were enrolled after 37 completed weeks and prospectively followed through delivery without FLM testing (study group). The prevalence of RDS and other neonatal outcomes was compared with a historical control group (n = 713, 1988-89) who had undergone determination of lecithin/sphingomyclin ratio prior to delivery at term. Logistic regression analysis was performed to determine independent predictors of RDS. RESULTS: The study group compared to the control group had less severe diabetes: diet-controlled GDM, 35% vs. 18%, respectively; insulin-requiring GDM, 42% vs. 42%, respectively; undiagnosed type-2 diabetes, 14% vs. 31%, respectively; and pre-existing diabetes, 9.6% vs. 8.8%, respectively, p < 0.001. RDS rates in the study group (0.8%) and control group (1.0%) were not significantly different, nor were rates of resuscitation at delivery, neonatal intensive care admission or hospitalization days. Logistic regression analysis found only Cesarean delivery to be independently predictive (adjusted OR 2.21, 95% CI 2.04-2.27) of RDS. Non-predictive variables included FLM testing, diabetic classification, insulin use, poor third-trimester glycemic control, chronic hypertension, pre-eclampsia, labor, neonatal gender, gestational age or large-for-gestational-age fetuses. CONCLUSIONS: Routine FLM testing did not change the RDS prevalence in reliably dated, term infants of diabetic mothers and should be abandoned. Delivery by Cesarean section was associated with increased RDS.

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.

Trauma-induced Kaposi's sarcoma of the hallux. An unusual case.

Kaposi's sarcoma is the most common malignant lesion in patients who test seropositive for the human immunodeficiency virus. Although many cases of this tumor have been described in the literature, only a few cases have been related to Koebner's phenomenon following trauma. Biopsy of lesions remains the standard method of diagnosis, but the numerous treatment options available today require treatment to be determined on a case-by-case basis. The authors present an unusual case of trauma-induced, acquired immunodeficiency syndrome-related Kaposi's sarcoma of the hallux with successful treatment through radiotherapy.

The challenge of exercise: practical advice for implementation into clinical practice.

Regular physical activity has important physiological and psychological benefits for all people. There are, however, special concerns for people with diabetes that require consideration before recommending an exercise program. Risks associated with exercise include exercise-induced hypoglycemia or hyperglycemia and worsening of long-term complications. Safe participation in all forms of exercise is possible through proper screening and teaching specific diabetes self-management skills.

Utility of fetal measurements in the management of gestational diabetes mellitus.

The metabolic management of gestational diabetes mellitus (GDM) during pregnancy traditionally has focused on maintenance of circulating maternal glucose concentrations in all patients within a range that is associated with a low rate of perinatal morbidity, especially morbidity related to excessive fetal growth and macrosomia. Clinical data reviewed elsewhere in this supplement provide guidelines for glycemic targets that appear to eliminate the excess risk to the fetus. However, because only a minority of infants are at risk for perinatal morbidity over the range of glycemia generally encountered in patients with GDM, attainment of those strict glycemic targets in all women with GDM requires implementation of self-monitoring of glucose and exogenous insulin therapy in many pregnancies that are not at risk. In this article, we review management approaches that take into account not only maternal glycemia, but also fetal growth and metabolic parameters in selecting GDM pregnancies for intensive metabolic therapy. The approaches can reduce the number of women with mild GDM who require self-monitoring of glucose and/or exogenous insulin therapy, thereby providing the potential to improve cost-effectiveness of antepartum management of GDM.

TRIPOD (TRoglitazone In the Prevention Of Diabetes): a randomized, placebo-controlled trial of troglitazone in women with prior gestational diabetes mellitus.

The TRoglitazone In the Prevention Of Diabetes (TRIPOD) trial is a single-center, randomized, placebo-controlled, double-masked study. The primary aim of the TRIPOD trial is to test the hypothesis that chronic administration of troglitazone to nondiabetic women with prior gestational diabetes mellitus (GDM) will improve whole-body insulin sensitivity and reduce the incidence of non-insulin-dependent diabetes (NIDDM). Because troglitazone is already known to lower blood glucose concentrations in persons who have developed NIDDM, an additional aim of the project will be to determine whether early intervention with troglitazone will achieve better final glycemic control than can be achieved by later intervention. In addition, since troglitazone treatment is expected to improve insulin sensitivity and may prevent or delay a decline in glucose tolerance, we also plan to determine whether long-term troglitazone treatment alters the development or progression of atherosclerosis. In this article we describe the experiment's design, the study's endpoints and methods for determining those endpoints, methods for assessing quality of life, and proposed methods for statistical analyses. The unique two-phase study design of the TRIPOD trial will permit testing not only of the biological question about reversal of insulin resistance and prevention of diabetes, but also of the clinical question about whether early intervention is superior to late intervention. Results from this trial will have an important impact on the monitoring and treatment of patients at high risk for NIDDM.

Insulin resistance and preeclampsia.

Insulin resistance appears to be a causative mechanism for the development of essential hypertension. Insulin resistance syndrome consists of a cluster of abnormalities that aggravate preexisting tendencies to develop hypertension, resulting in a cascade of physiologic alterations and ultimately leading to increased rates of heart attack, stroke, and peripheral vascular disease. Like hypertension, NIDD is mediated by insulin resistance and is expressed in individuals with limited beta-cell reserve. Episodes of increased insulin resistance, such as aging, weight gain, and pregnancy, cannot be compensated for in these states, and glucose intolerance results. In the case of pregnancy, the temporary state of insulin resistance unmasks individuals with an early beta-cell defect and allows for identification of high-risk groups at a time when therapeutic interventions could result in primary prevention of disease. Evidence is beginning to accumulate that preeclampsia is at least partially mediated by insulin resistance as well, and that individuals with preeclampsia may have clinically silent but persistent alterations in insulin resistance. If this condition proves a corollary to gestational diabetes, there may be an opportunity to intervene for primary prevention of some forms of essential hypertension as well. The availability of new pharmacologic agents to enhance insulin sensitivity represents a true opportunity effectively to prevent the long-term complications associated with insulin resistance and hyperinsulinemia. To achieve this goal, early and accurate identification of populations at risk is essential. A complete understanding of the role of insulin resistance in the generation of preeclampsia will aid significantly in the discovery of the genetic polymorphisms and intracellular pathways by which insulin resistance is translated into cardiovascular disease, stroke, and nephropathy.

Congenital malformations in offspring of women with hyperglycemia first detected during pregnancy.

OBJECTIVES: Our aim was to determine risk factors for congenital malformations in offspring of women with hyperglycemia first detected during pregnancy (i.e., women with gestational diabetes). STUDY DESIGN: A total of 3743 pregnancies complicated by gestational diabetes mellitus delivered at > 20 weeks of gestation were reviewed for the presence of congenital malformations diagnosed before hospital discharge. Anomalies were categorized as major, minor, or absent. Pregnancies with genetic syndromes and aneuploidies were excluded. In addition to maternal clinical and historic parameters, diagnostic glycemic parameters (fasting and post-glucose-challenge levels from the diagnostic glucose tolerance test, highest fasting serum glucose level, and hemoglobin A1c level before insulin therapy) were examined by logistic regression for predictive risk of major anomalies. RESULTS: One or more major congenital anomalies were present in 108 (2.9%) of the newborns; an additional 91 (2.4%) had only minor anomalies. None of the maternal variables were associated with the risk of minor anomalies. By contrast, parity, a history of gestational diabetes mellitus, and several glycemic parameters were associated with the risk of major anomalies. The highest fasting serum glucose level was the best independent predictor (odds ratio 1.13/10 mg/dl, 95% confidence interval 1.09 to 1.34). The fasting serum glucose level at diagnosis, a parameter that is almost uniformly available to clinicians, gave similar predictive information about the risk of major anomalies (odds ratio 1.13, 95% confidence interval 1.08 to 1.14). Stratification of women into subgroups of fasting serum glucose level at diagnosis revealed the incidence of major anomalies to be as follows: 2.1% with a fasting serum glucose level < 120 mg/dl (2973 pregnancies), 5.2% with a fasting serum glucose level of 121 to 260 mg/dl (747 pregnancies), and 30.4% with a fasting serum glucose level > 260 mg/dl (23 pregnancies). CONCLUSION: In a large population of women without a diagnosis of diabetes before pregnancy, the maternal fasting serum glucose concentration at diagnosis was a useful predictor of the risk of major but not minor anomalies. The rate of major anomalies doubled with a fasting glucose level > 120 mg/dl. Thus a fasting glucose level below that of overt diabetes outside of pregnancy carries an important risk of major anomalies that must be considered in the counseling and management of these patients.

Fetal lung maturation. Comparison of biochemical indices in gestational diabetic and nondiabetic pregnancies.

OBJECTIVE: To compare the biochemical maturation of the components of the lung profile according to gestational age between reliably dated gestational diabetic and nondiabetic pregnancies. STUDY DESIGN: Lung maturation was compared in reliably dated pregnancies in 501 gestational diabetic women and 561 nondiabetic women. Lecithin/sphingomyelin ratio (L/S) and phosphatidylglycerol (PG) were evaluated by analysis of variance according to the presence or absence of diabetes and weeks of gestational age. The effect of gestational diabetes on fetal lung maturation was determined by analysis of variance. RESULTS: The gestational diabetic group had no clinical or statistical differences in L/S ratios as compared to the nondiabetic patients at any gestational age. There were no differences in mean percent PG between the diabetic and nondiabetic groups at any gestational age. By 37 completed weeks, 86% of the L/S ratios and 78% of the PG values were mature in the diabetic group as compared to 80% of the L/S ratios and 78% of the PG values in the control group (P = .33 and .43, respectively). CONCLUSION: In reliably dated gestational diabetic pregnancies, biochemical maturation of the fetal lung strongly correlates with gestational age and does not appear to be significantly delayed when compared to a nondiabetic control group.

Effect of troglitazone on insulin sensitivity and pancreatic beta-cell function in women at high risk for NIDDM.

We conducted a randomized placebo-controlled study to determine the effects of the thiazolidinedione compound troglitazone on whole-body insulin sensitivity (SI), pancreatic beta-cell function, and glucose tolerance in 42 Latino women with impaired glucose tolerance (IGT) and a history of gestational diabetes mellitus (GDM), characteristics that carry an 80% risk of developing NIDDM within 5 years. After baseline oral (OGTT) and intravenous (IVGTT) glucose tolerance testing, subjects were assigned to take placebo or 200 or 400 mg troglitazone daily for 12 weeks (14 subjects per treatment group). An OGTT and IVGTT were repeated during the 12th week of treatment. Five subjects failed to complete the trial for personal reasons, and medication compliance averaged 90% in the remaining subjects, none of whom experienced a serious adverse event. SI, calculated by minimal model analysis of IVGTT results, changed by only 4 +/- 14% during 12 weeks of placebo administration, but increased 40 +/- 22 and 88 +/- 22% above basal during treatment with 200 and 400 mg troglitazone, respectively (P = 0.01 among groups). Troglitazone administration was also associated with a dose-dependent reduction in the total insulin area during IVGTTs, which was highly significant (P < 0.001), and with a reduction during OGTTs, which approached statistical significance (P = 0.09). Glucose tolerance improved slightly in all groups, but the magnitude of change did not differ significantly among groups, whether it was assessed as the number of subjects who continued to manifest IGT at 12 weeks (P = 0.64 among groups), the change in total glucose area during OGTTs (P = 0.58), or the change in fractional glucose disappearance rates during IVGTTs (P = 0.28). Among the women who received troglitazone, the greatest improvement in SI occurred in the women who had the highest diastolic blood pressures and the best IVGTT insulin responses during baseline testing. Our findings indicate that troglitazone improved whole-body insulin sensitivity and lowered circulating insulin concentrations in women with prior GDM who are at very high risk for NIDDM. The lack of improvement in glucose tolerance despite improved insulin sensitivity may be a manifestation of the beta-cell defect that predisposes the women to NIDDM. The overall pattern of response to troglitazone in our high-risk patients indicates that the drug is an ideal agent with which to test whether the amelioration of insulin resistance can delay or prevent diabetes in women with limited beta-cell reserve.

Local anesthetics. Is there an advantage to mixing solutions?

The advantages to using a 50/50 mixture of lidocaine and bupivacaine with respect to onset and duration of local anesthesia instead of using the solutions independently were evaluated. In a double-blind randomized experiment, 12 subjects, each volunteering both feet, were studied. One foot was injected with 1 ml of one of the following three solutions: 1% plain lidocaine, 0.25% plain bupivacaine (Marcaine), or a 50/50 mixture of 1% lidocaine and 0.25% bupivacaine; and in the other foot, a 1-ml injection of normal saline as a blinded control. A 5.07 (10 g) Semmes-Weinstein monofilament wire was used for testing for sensory blockade, and the onset and duration of anesthesia was recorded for each subject. It was determined that there was no significant difference in the mean onset times for the three solutions, and no significant difference between the durations of anesthesia of plain lidocaine and the 50/50 mixture. Additionally, it was determined that bupivacaine had a prolonged duration of anesthesia compared with the other two solutions. The results of this preliminary study suggest that there is no clinical advantage, with respect to onset and duration of local blockade, to using a 50/50 mixture of plain lidocaine and plain bupivacaine in place of their independent use.

Naturally occurring insulin autoantibodies in neonates of normal pregnancies and their relationship to insulinemia and birth weight.

OBJECTIVE: The objectives of this study were to determine whether insulin autoantibodies are present in umbilical cord blood from normal pregnancies, determine whether cord blood insulin autoantibody levels correlate with respective maternal levels at delivery, determine whether cord blood insulin autoantibody levels are related to cord blood or maternal insulin levels, and to determine what relationship neonatal birth weight has with either cord blood insulin autoantibody and insulin levels or maternal insulin autoantibody and insulin levels. STUDY DESIGN: Paired umbilical cord and maternal serum samples were taken from 70 normal subjects at delivery. Measurements of serum insulin autoantibody (competitive charcoal radiobinding assay) and insulin (radioimmune inhibition assay) levels were performed. Multiple linear regression analysis and paired t tests were used for data analyses. RESULTS: Neonatal insulin autoantibody levels (120 nU/ml) were more than two times higher than maternal levels (49 nU/ml) (p < 0.001). No correlation was observed between neonatal and maternal insulin autoantibody levels (r = 0.14, p = 0.25). A positive correlation of both neonatal and maternal insulin with birth weight was observed (r = 0.28, p < 0.02; and r = 0.36, p < 0.01, respectively). CONCLUSIONS: These results suggest that the insulin autoantibody levels in fetal cord blood are not related to maternal levels in normal uncomplicated pregnancies. In addition, insulin levels in both maternal and neonatal circulations were positively correlated with increased birth weight in the normal pregnancies studied.

Factors affecting the yield of acid-fast sputum smears in patients with HIV and tuberculosis.

OBJECTIVE: To evaluate the sensitivity of acid-fast sputum smears in the diagnosis of pulmonary Mycobacterium tuberculosis (MTB). DESIGN: Retrospective chart and radiographic film review. SETTING: Department of Veterans Affairs Medical Center in New York City. PATIENTS: All patients with positive sputum cultures for MTB during 1989 to 1991, including 100 with HIV, and 76 without HIV infection. PARAMETERS: The likelihood of a positive acid-fast sputum smear, related to chest radiograph findings, CD4 cell counts, drug sensitivity, and the presence of disseminated disease. RESULTS: Overall, 60 percent of patients with HIV had positive acid-fast smears, compared with 57 percent of non-HIV-infected patients. A relative absence of cavitary infiltrates did not substantially reduce the frequency of acid-fast smears in patients with and without HIV. Patients with HIV and CD4 count < 50, 50 to 200, and > 200 had positive acid-fast smear rates of 58 percent, 60 percent, and 56 percent, respectively; HIV-infected patients with drug-resistant organisms had 65 percent positive smears. Smear positivity was 96 percent in patients with HIV infection and disseminated MTB, CONCLUSIONS: Positive acid-fast sputum smears in culture-proven MTB occur with similar frequency in patients with and without HIV. The absence of cavitary disease did not significantly reduce the frequency of positive acid-fast smears. For patients with HIV, the likelihood of a positive smear was also independent of CD4 cell counts and drug resistance. Patients with HIV and disseminated MTB had positive sputum smears in nearly all cases.