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Biomedical subjects

T A Buchanan

Publications and source records attributed to T A Buchanan.

At least 37 records · Page 2Linked to original sources
PubMed1999

Antepartum predictors of the development of type 2 diabetes in Latino women 11-26 months after pregnancies complicated by gestational diabetes.

In this study, we sought to identify antepartum characteristics that predict the de novo development of diabetes 11-26 months after the index pregnancy in a carefully characterized cohort of women with gestational diabetes mellitus (GDM). Oral and frequently sampled intravenous glucose tolerance tests (OGTTs and FSIGTs), hyperinsulinemic-euglycemic clamps with labeled glucose, and body composition studies were performed on 91 islet cell antibody-negative Latino women with GDM during the third trimester of pregnancy. The women were documented to be diabetes-free within 6 months postpartum. Their diabetes status was ascertained again between 11 and 26 months postpartum. Logistic regression analysis was used to identify independent predictors of the development of diabetes within that interval. Fourteen of the women developed diabetes by World Health Organization criteria 11-26 months after delivery of the index pregnancy. Three antepartum variables were independent predictors of diabetes: the 1-h postchallenge plasma glucose concentration from the 100-g OGTT at which GDM was diagnosed (higher = increased risk; P = 0.003); an index of pancreatic beta-cell compensation for insulin resistance, defined as the product of the 30-min incremental plasma insulin:glucose ratio on a 75-g OGTT and the insulin sensitivity index from a hyperinsulinemic-euglycemic clamp (lower = increased risk, P = 0.009); and the basal glucose production rate after an overnight fast (higher = increased risk; P = 0.04). We conclude that postchallenge hyperglycemia, poor pancreatic beta-cell compensation for insulin resistance, and elevated endogenous glucose production during pregnancy precede the development of type 2 diabetes in young Latino women by at least 1-2 years.

Adult↗
PubMed1999

Multiple metabolic defects during late pregnancy in women at high risk for type 2 diabetes.

Detailed metabolic studies were carried out to compare major regulatory steps in glucose metabolism in vivo between 25 normal pregnant Latino women without and 150 pregnant Latino women with gestational diabetes mellitus (GDM). The two groups were frequency-matched for age, BMI, and gestational age at testing in the third trimester. After an overnight fast, women with GDM had higher fasting plasma glucose (P = 0.0001) and immunoreactive insulin (P = 0.0003) concentrations and higher glucose production rates (P = 0.01) but lower glucose clearance rates (P = 0.001) compared with normal pregnant women. During steady-state hyperinsulinemia (approximately 600 pmol/l) and euglycemia (approximately 4.9 mmol/l), women with GDM had lower glucose clearance rates (P = 0.0001) but higher glucose production rates (P = 0.0001) and plasma free fatty acid (FFA) concentrations (P = 0.0002) than the normal women. These intergroup differences persisted when a subgroup of 116 women with GDM who were not diabetic < or = 6 months after pregnancy were used in the analysis. When all subjects were considered, there was a very close correlation between glucose production rates and plasma FFA concentrations throughout the glucose clamps in control (r = 0.996) and GDM (r = 0.995) groups. Slopes and intercepts of the relationships were nearly identical, suggesting that blunted suppression of FFA concentrations contributed to blunted suppression of glucose production in the GDM group. In addition to these defects in insulin action, women with GDM had a 67% impairment of pancreatic beta-cell compensation for insulin resistance compared with normal pregnant women. These results demonstrate that women with GDM have multiple defects in insulin action together with impaired compensation for insulin resistance. Our findings suggest that defects in the regulation of glucose clearance, glucose production, and plasma FFA concentrations, together with defects in pancreatic beta-cell function, precede the development of type 2 diabetes in these high-risk women.

Adult↗
PubMed1998

Contraception and the risk of type 2 diabetes mellitus in Latina women with prior gestational diabetes mellitus.

CONTEXT: Effective contraception is essential in women with prior gestational diabetes mellitus (GDM) but should not increase their already substantial risk of developing type 2 diabetes. OBJECTIVE: To determine whether exposure to low-dose oral contraceptives increases the risk of developing type 2 diabetes mellitus in women with recent GDM. DESIGN: Retrospective cohort study of 904 Latinas with GDM who gave birth between January 1987 and March 1994, in whom postpartum diabetes was excluded at 4 to 16 weeks post partum. INTERVENTIONS: At their initial postpartum visit, 443 women selected a nonhormonal form of contraception, 383 received a low-dose, estrogen-progestin combination oral contraceptive (OC), and 78 breast-feeding women received the progestin-only OC. When breast-feeding ended, patients initially taking progestin-only OCs were switched to combination OCs. Patients were followed up periodically with oral glucose tolerance tests for up to 7 1/2 years. MAIN OUTCOME MEASURES: Person time was used to compute unadjusted average annual incidence rates of developing diabetes mellitus, as defined by the National Diabetes Data Group Criteria. Survival analysis was used to compute the unadjusted cumulative incidence rates and adjusted relative risks of diabetes mellitus. RESULTS: The unadjusted average annual incidence rates of type 2 diabetes mellitus were 8.7%, 10.4%, and 26.5%, respectively, for patients using nonhormonal forms of contraception, combination OCs, and progestin-only OCs. Cumulative incidence rates were virtually identical for patients with uninterrupted use of combination OCs and nonhormonal forms of contraception, but patients using progestin-only OCs developed diabetes mellitus more rapidly during the first 2 years of use. After adjustment for potential confounding factors, the use of progestin-only OCs almost tripled the risk of type 2 diabetes mellitus compared with equivalent use of low-dose combination OCs (adjusted relative risk, 2.87; 95% confidence interval, 1.57-5.27). The magnitude of this risk increased with duration of uninterrupted use. CONCLUSION: Progestin-only OCs were associated with an increased risk of diabetes in breast-feeding Latinas with recent GDM and probably should be prescribed with caution, if at all, in these women. Long-term use of low-dose combination OCs did not increase the risk of type 2 diabetes compared with use of nonhormonal contraception. Thus, combination OCs do not appear to increase the risk of diabetes in non-breast-feeding women with recent GDM.

Cohort Studies↗
PubMed1998

Metabolic effects of troglitazone monotherapy in type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Troglitazone is a new insulin-sensitizing agent used to treat type 2 diabetes mellitus. The mechanism by which troglitazone exerts its effect on systemic glucose metabolism is unknown. OBJECTIVE: To determine the effects of 6 months of troglitazone monotherapy on glucose metabolism in patients with type 2 diabetes mellitus. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Six general clinical research centers at university hospitals. PATIENTS: 93 patients (mean age, 52 years) with type 2 diabetes mellitus (mean fasting plasma glucose level, 11.2 mmol/L) who were being treated with diet alone or who had discontinued oral antidiabetic medication therapy. INTERVENTION: Patients were randomly assigned to one of five treatment groups (100, 200, 400, or 600 mg of troglitazone daily or placebo) and had metabolic assessment before and after 6 months of treatment. MEASUREMENTS: Plasma glucose and insulin profiles during a meal tolerance test; basal hepatic glucose production and insulin-stimulated glucose disposal rate during a hyperinsulinemic-euglycemic clamp procedure. RESULTS: Troglitazone at 400 and 600 mg/d decreased both fasting (P < 0.001) and postprandial (P = 0.016) plasma glucose levels by approximately 20%. All four troglitazone dosages also decreased fasting (P = 0.012) and postprandial (P < 0.001) triglyceride levels; 600 mg of the drug per day decreased fasting free fatty acid levels (P = 0.018). Plasma insulin levels decreased in the 200-, 400-, and 600-mg/d groups (P < 0.001), and C-peptide levels decreased in all five study groups (P < 0.001). Basal hepatic glucose production was suppressed in the 600-mg/d group compared with the placebo group (P = 0.02). Troglitazone at 400 and 600 mg/d increased glucose disposal rate by approximately 45% above pretreatment levels (P = 0.003). Stepwise regression analysis showed that troglitazone therapy was the strongest predictor of a decrease in fasting (P < 0.001) or postprandial (P = 0.01) glucose levels. Fasting C-peptide level was the next strongest predictor (higher C-peptide level equaled greater glucose-lowering effect). CONCLUSION: Troglitazone monotherapy decreased fasting and postprandial glucose levels in patients with type 2 diabetes, primarily by augmenting insulin-mediated glucose disposal.

Adult↗
PubMed1998

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.

Adolescent↗
PubMed1998

Hyperinsulinism, neonatal obesity and placental immaturity in infants born to women with one abnormal glucose tolerance test value.

Several groups have reported a risk of fetal macrosomia in pregnancies with maternal glucose intolerance which is intermediate between gestational diabetes (GDM) and normal glucose tolerance. The present study was designed to determine whether these pregnancies are also at risk for fetal obesity, hyperinsulinism and placental villous immaturity. 325 women with risk factors for GDM underwent a 75 g OGTT interpreted according to the O'Sullivan criteria. All women who met the criteria for GDM were managed with diet therapy. Insulin therapy was added for women with a mean serum glucose value > 100 mg/dl on a 24 hour glucose profile. Patients not meeting the GDM criteria were managed without special intervention. Primary outcome variables were measures of neonatal weight and skinfold thickness, fetal and neonatal insulin and glucose concentration, and placental villous maturation. Outcome parameters were compared among three groups: pregnancies with normal OGTT (control, n = 95), 1 abnormal value in the OGTT (1 abnl, n = 76) and GDM (n = 154). The outcome of pregnancies with 1 abnormal value in the OGTT was different from those with normal OGTT. Regarding fetal growth, rates of LGA were approximately twice as high in groups with one abnormal value and GDM (21% and 24%) compared to women with normal OGTTs (11%: p < 0.05 vs GDM and p = 0.07 vs 1 abnormal value). The percent of infants with skinfold thickness > 90th percentile was also greater in the 1 abnormal value and GDM groups (31.1 and 31.6% respectively) compared to controls (19.2%; p < 0.05 for GDM vs control only). Regarding fetal hyperinsulinism, AFI concentrations were similar in control and GDM groups (3.1 +/- 0.4 and 3.4 +/- 0.8 microU/ml, respectively), but were higher in the group with one abnormal OGTT value (4.3 +/- 1.2 microU/ml, p < 0.05 vs controls). Cord blood insulin: glucose ratios were elevated in both the 1 abnormal value and GDM groups (0.22 +/- 0.05 and 0.20 +/- 0.02 microU/ml per mg/dl), compared to controls (0.12 +/- 0.01 microU/ml per mg/dl, p < 0.05 vs 1 abnormal value). Neonatal glycemia < 30 mg/dl was significantly more common in the one abnormal value than in the control group (49% vs 34% of infants) and intermediate in the GDM group (40%). Severe placental villous immaturity was more than twice as frequent in the 1 abnormal value group compared to controls (24% vs 9%, p < 0.05) and the most frequent in the GDM group (33%; p < 0.001 vs controls). Pregnancies with glucose intolerance below the thresholds for diagnosis of GDM have an increased risk for fetal obesity, hyperinsulinism, postpartum hypoglycemia and placental immaturity. These findings indicate the continuum of risk for fetal morbidity associated with increasing maternal glucose intolerance in pregnancy.

Adult↗
PubMed1998

Gestational diabetes: antepartum characteristics that predict postpartum glucose intolerance and type 2 diabetes in Latino women.

We examined antepartum clinical characteristics along with measures of glucose tolerance, insulin sensitivity, pancreatic beta-cell function, and body composition in Latino women with gestational diabetes mellitus (GDM) for their ability to predict type 2 diabetes or impaired glucose tolerance (IGT) within 6 months after delivery. A total of 122 islet cell antibody-negative women underwent oral and intravenous glucose tolerance tests (OGTT; IVGTT), hyperinsulinemic-euglycemic clamps, and measurement of body fat between 29 and 36 weeks' gestation and returned between 1 and 6 months postpartum for a 75-g OGTT. Logistic regression analysis was used to examine the relationship between antepartum variables and glucose tolerance status postpartum. At postpartum testing, 40% of the cohort had normal glucose tolerance, 50% had IGT, and 10% had diabetes by American Diabetes Association criteria. Independent antepartum predictors of postpartum diabetes were the 30-min incremental insulin:glucose ratio during a 75-g OGTT (P = 0.0002) and the total area under the diagnostic 100-g glucose tolerance curve (P = 0.003). Independent predictors of postpartum IGT were a low first-phase IVGTT insulin response (P = 0.0001), a diagnosis of GDM before 22 weeks' gestation (P = 0.003), and weight gain between prepregnancy and the postpartum examination (P = 0.03). All subjects had low insulin sensitivity during late pregnancy, but neither glucose clamp nor minimal model measures of insulin sensitivity in the 3rd trimester were associated with the risk of IGT or diabetes within 6 months' postpartum. These results highlight the importance of pancreatic beta-cell dysfunction, detectable under conditions of marked insulin resistance in late pregnancy, to predict abnormalities of glucose tolerance soon after delivery in pregnancies complicated by GDM. Moreover, the association of postpartum IGT with weight gain and an early gestational age at diagnosis of GDM suggests a role for chronic insulin resistance in mediating hyperglycemia outside the 3rd trimester in women with such a beta-cell defect.

Adult↗
PubMed1998

Mapping genes for NIDDM. Design of the Finland-United States Investigation of NIDDM Genetics (FUSION) Study.

OBJECTIVE: To map and identify susceptibility genes for NIDDM and for the intermediate quantitative traits associated with NIDDM. RESEARCH DESIGN AND METHODS: We describe the methodology and sample of the Finland-United States Investigation of NIDDM Genetics (FUSION) study. The whole genome search approach is being applied in studies of several different ethnic groups to locate susceptibility genes for NIDDM. Detailed description of the study materials and designs of such studies are important, particularly when comparing the findings in these studies and when combining different data sets. RESULTS: Using a careful selection strategy, we have ascertained 495 families with confirmed NIDDM in at least two siblings and no history of IDDM among the first-degree relatives. These families were chosen from more than 22,000 NIDDM patients, representative of patients with NIDDM in the Finnish population. In a subset of families, a spouse and offspring were sampled, and they participated in a frequently sampled intravenous glucose tolerance test (FSIGT) analyzed with the Minimal Model. An FSIGT was completed successfully for at least two nondiabetic offspring in 156 families with a confirmed nondiabetic spouse and no history of IDDM in first-degree relatives. CONCLUSIONS: Our work demonstrates the feasibility of collecting a large number of affected sib-pair families with NIDDM to provide data that will enable a whole genome search approach, including linkage analysis.

Age of Onset↗
PubMed1998

Hormonal choices after gestational diabetes. Subsequent pregnancy, contraception, and hormone replacement.

The effects of subsequent states of excess hormone exposure, for example, subsequent pregnancy, hormonal contraception, and hormonal replacement therapy, on the development of diabetes in women with prior gestational diabetes were assessed. Current literature examining the effect of parity, hormonal contraception, and hormonal replacement therapy in healthy women and women with previous gestational diabetes and current diabetes was reviewed. Subsequent pregnancy in women with prior GDM appears to triple the risk of subsequent diabetes. Low-dose progestin and estrogen combination oral contraceptives do not appear to clinically increase the risk of diabetes. Hormonal replacement therapy appears to provide the greatest reduction in coronary artery disease to women at greatest risk, i.e., those who have developed diabetes. Careful follow-up and metabolic surveillance should be provided when prescribing hormonal contraception or replacement therapy. In women with prior gestational diabetes, exposure to repeat pregnancy poses a greater risk for subsequent diabetes than does either an exposure to low-dose progestin and estrogen combination oral contraceptives or to postmenopausal hormonal therapy, both of which do not appear to increase the risk of diabetes.

Contraceptives, Oral↗
PubMed1998

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.

Birth Weight↗
PubMed1997

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.

Adult↗
PubMed1997

Insulin sensitivity and insulin secretion in lean and obese normal pregnant women.

An insulin-modified frequently sampled intravenous glucose tolerance test with minimal model analysis was performed in normal pregnant women between 28-32 weeks of gestation, to assess insulin sensitivity and insulin secretion. Insulin sensitivity in the pregnant group (no. 26) was reduced to approximately 50% that of nonpregnant group (no. 27) (p < 0.05). This increased insulin resistance was compensated by an enhancement of the first phase of insulin secretion, which was increased more than twofold in the pregnant women when compared with the nonpregnant women (p < 0.05). There was a trend toward greater insulin resistance and insulin secretion in the obese pregnant women (no. 7) as compared with the lean pregnant women (no. 19) although this difference was not statistically significant. Our findings confirm that late pregnancy is a state of physiologic insulin resistance compensated by an increase of insulin secretion.

Adult↗
PubMed1996

Long-term diabetogenic effect of single pregnancy in women with previous gestational diabetes mellitus.

BACKGROUND: Pregnancy is associated with marked insulin resistance that seems to have little, if any, impact on the long-term risk of non-insulin-dependent diabetes mellitus (NIDDM) in the general population. The aim of this study was to test whether pregnancy would alter the risk of NIDDM among women with a high prevalence of pancreatic beta-cell dysfunction, as indicated by a history of gestational diabetes mellitus. METHODS: The cohort consisted of 666 Latino women with gestational diabetes attending a high-risk family planning clinic. They were followed up for up to 7.5 years, during which time they were weighed and underwent an oral glucose-tolerance test annually. The effect of an additional pregnancy, and of other risk factors for diabetes, was examined. FINDINGS: 87 (13%) of the women completed an additional pregnancy. 80 of those women did not have NIDDM immediately after the additional pregnancy and their subsequent annual incidence rate of NIDDM was 30.9% (95% CI 12.7-49.1), more than 2.5 times the annual incidence rate of NIDDM in the cohort overall (11.9%; 95% CI 10.0-13.8). Proportional hazards regression analysis using the presence or absence of an additional pregnancy as a time-dependent variable confirmed that an additional pregnancy increased the rate ratio of NIDDM to 3.34 (95% CI 1.80-6.19), compared with women without an additional pregnancy after adjustment for other potential diabetes risk factors during the index pregnancy (antepartum oral glucose tolerance, highest fasting glucose, gestational age at diagnosis of gestational diabetes) and during follow-up (postpartum body mass index [BMI], and glucose tolerance, weight change, breast feeding, and months of contraceptive use). Weight gain also was independently associated with an increased risk of NIDDM; the rate ratio was 1.95 (95% CI 1.63-2.33) for each 10 lb (4.5 kg) gained during follow-up after adjustment for the additional pregnancy and the other potential risk factors. INTERPRETATION: The study showed that a single pregnancy, independent of the well-known effect of weight gain, accelerated the development of NIDDM in a group of women with a high prevalence of pancreatic beta-cell dysfunction. This finding implies that episodes of insulin resistance may contribute to the decline in beta-cell function that leads to NIDDM in many high-risk individuals.

Body Weight↗
PubMed1996

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.

Adult↗