Blinded comparison of cervical portio length measurements by digital examination vs Cervilenz.

OBJECTIVE: Cervical length (CL) examinations may identify patients in preterm labor or those who may benefit from prophylactic therapy. We sought to compare the accuracy of clinician digital CL examinations with objective measurements using the Cervilenz device in women presenting with symptoms of preterm labor. STUDY DESIGN: Forty-two patients with singleton gestation from 24 to 34 weeks' gestation and cervical dilation less than 3 cm underwent speculum examination and Cervilenz measurement. A second examiner, blinded to results, digitally measured CL. Pearson's correlation coefficient, Student t tests and McNemar's tests were used to compare digital and Cervilenz measures. RESULTS: Digital CL was significantly less than Cervilenz (2.88 vs 3.40 cm; P < .001), and in 36% of subjects, this difference exceeded 1 cm. The discrepancy in CL estimates persisted whether women were multiparous or had soft cervices or a history of preterm delivery. CONCLUSION: Digital assessment underestimates CL, whereas the Cervilenz device permits a visualized and objective CL measure in patients with preterm labor.

Coordinate changes in plasma glucose and pancreatic beta-cell function in Latino women at high risk for type 2 diabetes.

The purpose of this study was to examine longitudinally the relationship among glucose levels, pancreatic beta-cell function, and insulin resistance in women at high risk for type 2 diabetes. Oral glucose tolerance tests (OGTTs) and intravenous glucose tolerance tests (IVGTTs) were performed at 15-month intervals for up to 5 years or until fasting plasma glucose exceeded 140 mg/dl in Hispanic women with recent gestational diabetes. Data were analyzed 1) to compare changes in insulin sensitivity, beta-cell function, and glucose levels between women who had diabetes at one or more visits and women who remained diabetes free and 2) to determine longitudinal patterns of change in glucose levels and acute beta-cell compensation for insulin resistance. Seventy-one women provided data from a total of 280 paired OGTTs and IVGTTs during a median follow-up of 46 months. Compared with the 47 women who remained free of diabetes, the 24 who either had diabetes (n = 9) or developed it during follow-up (n = 15) had higher baseline glucose levels and lower acute beta-cell compensation for insulin resistance. Baseline insulin sensitivity was low in both groups and did not change significantly during follow-up. Fasting and 2-h glucose levels increased more rapidly in the diabetic group despite a decline in acute beta-cell compensation that was significantly slower than the decline in women who did not develop diabetes. This paradox was explained by an accelerated rise in glucose levels for any decline in beta-cell compensation when beta-cell compensation reached approximately 10% of normal, a level that was reached in the women who had or developed diabetes but not in the women who remained diabetes free. These findings define a pathogenesis for type 2 diabetes in one high-risk group that is characterized by a relatively long-term decline in acute beta-cell compensation for chronic insulin resistance that is attended by slowly rising glucose levels. Only relatively late in this process do glucose levels rise rapidly and into the diabetic range.

Effect of pioglitazone on pancreatic beta-cell function and diabetes risk in Hispanic women with prior gestational diabetes.

The Pioglitazone In Prevention Of Diabetes (PIPOD) study was conducted to evaluate beta-cell function, insulin resistance, and the incidence of diabetes during treatment with pioglitazone in Hispanic women with prior gestational diabetes who had completed participation in the Troglitazone In Prevention Of Diabetes (TRIPOD) study. Women who completed the TRIPOD study were offered participation in the PIPOD study for a planned 3 years of drug treatment and 6 months of postdrug washout. Oral glucose tolerance tests were performed annually on pioglitazone and at the end of the postdrug washout. Intravenous glucose tolerance tests (IVGTTs) for assessment of insulin sensitivity and beta-cell function were conducted at baseline, after 1 year on pioglitazone, and at the end of the postdrug washout. Of 95 women who were not diabetic at the end of the TRIPOD study, 89 enrolled in the PIPOD study, 86 completed at least one follow-up visit, and 65 completed all study visits, including the postdrug tests. Comparison of changes in beta-cell compensation for insulin resistance across the TRIPOD and PIPOD studies revealed that pioglitazone stopped the decline in beta-cell function that occurred during placebo treatment in the TRIPOD study and maintained the stability of beta-cell function that had occurred during troglitazone treatment in the TRIPOD study. The risk of diabetes, which occurred at an average rate of 4.6% per year, was lowest in women with the largest reduction in total IVGTT insulin area after 1 year of treatment. The similarity of findings between the PIPOD and TRIPOD studies support a class effect of thiazolidinedione drugs to enhance insulin sensitivity, reduce insulin secretory demands, and preserve pancreatic beta-cell function, all in association with a relatively low rate of type 2 diabetes, in Hispanic women with prior gestational diabetes.

After pregnancy complicated by diabetes: postpartum care and education.

The postpartum period in women with pregestational or gestational diabetes allows the physician and mother to switch from intensive medical and obstetric management into a proactive and preventive mode, and to jointly develop a reproductive health plan. The woman's individual needs regarding contraception and breastfeeding, an appropriate diet to achieve healthy weight goals, the medical management of diabetes, daily exercise, and future pregnancy planning must be considered. Essential is the active participation of the woman, who, through education, gains an understanding of the far-reaching effects her active participation will have on her subsequent health, her newborn child's health, and possibly that of her future children.

Long-acting injectable progestin contraception and risk of type 2 diabetes in Latino women with prior gestational diabetes mellitus.

OBJECTIVE: To investigate the impact of a long-acting injectable progestin, depo-medroxyprogesterone acetate (DMPA), compared with combination oral contraceptives (COCs) on the risk of diabetes in Latino women with prior gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: An observational cohort study of 526 Hispanic women with prior GDM who were not diabetic in their postpartum visit during January 1987 to October 1997 and who elected DMPA (n = 96) or COCs (n = 430) as initial contraception were followed for a maximum of 9.2 years with a median follow-up of approximately 12 months. Oral glucose tolerance tests were performed and choice of contraception method was recorded at each visit as part of routine clinical care. RESULTS: Annual diabetes incidence rates were 19% in the DMPA group and 12% in the COC group, with an unadjusted hazard ratio (HR) of 1.58 (95% CI 1.00-2.50; P = 0.05) for DMPA compared with COCs. Adjustment for baseline imbalances reduced the HR to 1.18 (0.67-2.28; P = 0.57). Additional adjustment for weight gain during follow-up, which was on average 1.8 kg higher in the DMPA group (P < 0.0001), reduced the HR to 1.07. DMPA interacted with baseline serum triglyceride levels and, separately, with breast-feeding to increase the diabetes risk. CONCLUSIONS: DMPA use was associated with an increased risk of diabetes that appeared to be explained by three factors: 1) use in women with increased baseline diabetes risk, 2) weight gain during use, and 3) use with high baseline triglycerides and/or during breast-feeding.

Insulin resistance and preeclampsia in gestational diabetes mellitus.

OBJECTIVE: To compare the degree of insulin resistance in women with gestational diabetes mellitus (GDM) who do and do not develop preeclampsia. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of initially normotensive women with GDM who underwent oral glucose tolerance tests (OGTTs), intravenous glucose tolerance tests (IVGTTs), and glucose clamp studies in the early third trimester (n = 150) and 15 months postpartum (n = 89). After delivery, the women were categorized as nonpreeclamptic or preeclamptic (systolic blood pressure [SBP] > or = 140 mmHg, diastolic blood pressure [DBP] > or = 90 mmHg, and at least >1+ proteinuria or >300 mg/24 h). Metabolic parameters between the groups were compared by chi2 or Fisher's exact tests and ANOVA with P < 0.05 as significant. RESULTS: A total of 29 women (19%) developed preeclampsia, which was mild in 21 and severe in 8 women. At entry, there were no differences in age, weight indexes, and glycemic measures between the nonpreeclamptic and preeclamptic groups. Those with preeclampsia were significantly taller (61.5 +/- 2.4 vs. 60.1 +/- 2.3 in, P = 0.003), were more often nulliparous (38 vs. 16%, P = 0.01), and had higher entry SBP (112 +/- 10 vs. 103 +/- 6.9 mmHg, P < 0.0001) and DBP (64 +/- 9 vs. 59 +/- 5 mmHg, P = 0.002). No significant differences between the groups were found in any measures of the OGTT glucose levels, insulin sensitivity index, glucose effectiveness, acute response to glucose, or disposition index, nor were there any differences found in the euglycemic clamp measures of basal or steady-state levels of glucose, insulin, free fatty acid, hepatic glucose output, peripheral glucose clearance, C-peptide, or glucagon. At 15 months postpartum, blood pressure levels remained significantly higher in the preeclamptic group (n = 19) compared with the nonpreeclamptic group (n = 70). No differences in any glycemic or insulin resistance measures were found. CONCLUSIONS: Women with GDM were uniformly insulin resistant. Those who developed preeclampsia, when compared with those who remained nonpreeclamptic, were not more insulin resistant in either the third trimester or 15 months postpartum. However, women who developed preeclampsia had blood pressure levels that were significantly higher, although still in the normal range, than those of women who remained nonpreeclamptic.

Effect of thiazolidinedione treatment on progression of subclinical atherosclerosis in premenopausal women at high risk for type 2 diabetes.

We tested the effects of treatment with a thiazolidinedione drug on rates of progression of carotid intima-media thickness (CIMT) and some putative determinants of CIMT in young women at high risk for type 2 diabetes. A total of 266 nondiabetic, Hispanic women with recent gestational diabetes were randomized to placebo or troglitazone. CIMT measurements were made at baseline, annually, and at study end, together with measurements of obesity, serum lipids, and glucose and insulin levels during oral glucose tolerance tests. Insulin sensitivity (minimal model analysis) was measured at baseline and 3 months later. Data were analyzed to compare CIMT progression rates between treatment groups and investigate potential determinants of differences in CIMT progression. One hundred ninety-two women had a CIMT measurement at baseline and at least one follow-up visit. The mean rate of CIMT change was 31% lower in women assigned to troglitazone (P = 0.048). This intergroup difference was not explained by baseline or on-trial differences in obesity, lipids, glucose, or insulin. The reduction in CIMT progression developed gradually, occurred only in women who had an increase in insulin sensitivity, and was unrelated to the presence of the metabolic syndrome at baseline. Troglitazone reduced the progression of subclinical atherosclerosis via a mechanism that involved unmeasured mediators of atherosclerosis, either in the circulation or directly in the arterial wall.

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.

A randomized trial evaluating a predominantly fetal growth-based strategy to guide management of gestational diabetes in Caucasian women.

OBJECTIVE: To compare the management of Caucasian women with gestational diabetes (GDM) based predominantly on monthly fetal growth ultrasound examinations with an approach based solely on maternal glycemia. RESEARCH DESIGN AND METHODS: Women with GDM who attained fasting capillary glucose (FCG) <120 mg/dl and 2-h postprandial capillary glucose (2h-CG) <200 mg/dl after 1 week of diet were randomized to management based on maternal glycemia alone (standard) or glycemia plus ultrasound. In the standard group, insulin was initiated if FCG was repeatedly >90 mg/dl or 2h-CG was >120 mg/dl. In the ultrasound group, thresholds were 120 and 200 mg/dl, respectively, or a fetal abdominal circumference >75th percentile (AC>p75). Outcome criteria were rates of C-section, small-for-gestational-age (SGA) or large-for-gestational-age (LGA) infants, neonatal hypoglycemia (<40 mg/dl), and neonatal care admission. RESULTS: Maternal characteristics and fetal AC>p75 (36.0 vs. 38.4%) at entry did not differ between the standard (n = 100) and ultrasound groups (n = 99). Assignment to (30.0 vs. 40.4%) and mean duration of insulin treatment (8.3 vs. 8.1 weeks) did not differ between groups. In the ultrasound group, AC>p75 was the sole indication for insulin. The ultrasound-based strategy, as compared with the maternal glycemia-only strategy, resulted in a different treatment assignment in 34% of women. Rates of C-section (19.0 vs. 18.2%), LGA (10.0 vs. 12.1%), SGA (13.0 vs. 12.1%), hypoglycemia (16.0 vs. 17.0%), and admission (15.0 vs. 14.1%) did not differ significantly. CONCLUSIONS: GDM management based on fetal growth combined with high glycemic criteria provides outcomes equivalent to management based on strict glycemic criteria alone. Inclusion of fetal growth might provide the opportunity to reduce glucose testing in low-risk pregnancies.

Determinants of fetal growth at different periods of pregnancies complicated by gestational diabetes mellitus or impaired glucose tolerance.

OBJECTIVE: To determine maternal parameters with the strongest influence on fetal growth in different periods of pregnancies complicated by an abnormal glucose tolerance test (GTT). RESEARCH DESIGN AND METHODS: Retrospective study of 368 women with gestational diabetes mellitus (GDM; > or = 2 abnormal GTT values, n = 280) and impaired glucose tolerance (IGT; one abnormal value, n = 88) with 869 ultrasound examinations at entry to and during diabetic care. Both groups were managed comparably. Abdominal circumference (AC) > or = 90th percentile defined fetal macrosomia. Maternal historical and clinical parameters, and diagnostic and glycemic values of glucose profiles divided into five categories of 4 weeks of gestational age (GA; <24 weeks, 24 weeks/0 days to 27 weeks/6 days, 28/0-31/6, 32/0-35/6, and 36/0-40/0 [referred to as <24 GA, 24 GA, 28 GA, 32 GA, and 36 GA categories, respectively]) were tested by univariate and multiple logistic regression analysis for their ability to predict an AC > or = 90th percentile at each GA group and large-for-gestational-age (LGA) newborn. Data obtained at entry were also analyzed separately irrespective of the GA. RESULTS: Maternal weight, glycemia after therapy, rates of fetal macrosomia, and LGA were not significantly different between GDM and IGT; thus, both groups were analyzed together. LGA in a previous pregnancy, (odds ratio [OR] 3.6; 95% CI 1.8-7.3) and prepregnancy obesity (BMI > or = 30 kg/m(2); 2.1; 1.2-3.7) independently predicted AC > or = 90th percentile at entry. When data for each GA category were analyzed, no predictors were found for <24 GA. Independent predictors for each subsequent GA category were as follows: at 24 GA, LGA history (OR 9.8); at 28 GA, LGA history (OR 4.2), and obesity (OR 3.3); at 32 GA, fasting glucose of 32 GA (OR 1.6 per 5-mg/dl increase); at 36 GA, fasting glucose of 32 GA (OR 1.6); and for LGA at birth, LGA history (OR 2.7), and obesity (OR 2.4). CONCLUSIONS: In the late second and early third trimester, maternal BMI and LGA in a previous pregnancy appear to have the strongest influence on fetal growth, while later in the third trimester coincident with the period of maximum growth described in diabetic pregnancies, maternal glycemia predominates.

Pharmacological treatment of insulin resistance at two different stages in the evolution of type 2 diabetes: impact on glucose tolerance and beta-cell function.

The purpose of this study was to compare the impact of treating insulin resistance with a thiazolidinedione drug before vs. at the onset of diabetes on glucose levels and beta-cell function. Nondiabetic Hispanic women of Mexican or Central American descent with prior gestational diabetes mellitus (GDM) were randomized to troglitazone (early intervention), 400 mg/d, or placebo (later intervention). Women who developed diabetes were placed on open-label troglitazone. Glucose tolerance, insulin resistance, and beta-cell function were measured at randomization, at the diagnosis of diabetes, and 8 months post trial to determine the long-term impact of the two treatment strategies on glucose levels and beta-cell function. During a mean follow-up of 4.3 yr between baseline and posttrial tests, glucose tolerance (oral glucose tolerance test glucose area, P = 0.04) and insulin resistance (MINMOD SI, P = 0.02) worsened more in women randomized to late intervention (n = 69) than to early intervention (n = 57). Insulin secretion (acute insulin response in the iv glucose tolerance test, P = 0.09) and beta-cell compensation for insulin resistance (disposition index, P = 0.07) also tended to worsen more in the late intervention group. Among women in the late intervention group who developed diabetes, oral glucose tolerance test glucose area (P = 0.0001) and beta-cell function (P < or = 0.04) deteriorated significantly during development of diabetes on placebo and then did not change significantly (P > 0.50) during treatment with troglitazone and posttreatment washout. In high-risk Hispanic women, amelioration of insulin resistance can stabilize glycemia at the time diabetes develops. These findings highlight the role of insulin resistance in the genesis of progressive beta-cell dysfunction during the evolution of type 2 diabetes.

Comparison of point-of-care-testing glucose meters with standard laboratory measurement of the 50g-glucose-challenge test (GCT) during pregnancy.

OBJECTIVES: Although glucose meters are well-established instruments for self-monitoring blood glucose levels, diagnostic and screening procedures should be performed using standard laboratory methods. In addition to standard laboratory methods, HemoCue is authorized for screening and diagnostic purposes in Germany. The rapid development of other glucose meters makes it necessary to re-evaluate this recommendation. Our objective was to test the usefulness of glucose meters in screening pregnant patients for gestational diabetes. METHODS: The 50-g glucose challenge test was administered to one hundred and ninety-three pregnant patients whose blood glucose levels were then simultaneously measured with five portable meters and the HemoCue. The results were compared to our standard method (Hexokinase). A cut-off of 7.8 mmol/L was used and sensitivity, specificity, accuracy, the Youden index, and the Kappa index were calculated. The tests were performed by well-trained personnel (C.D. and U.S.). RESULTS: 1212 measurements were performed on 193 patients. All glucose meters showed a very good correlation (r > 0.90). None of the measurements showed an extreme deviation necessitating the error grid analysis. The GlucoTouch (5.93% +/- 7.4) and the HemoCue (-9.04% +/- 5.9) showed a mean deviation greater than 5%. None of the meters had a mean deviation greater than 10%. The accuracy fluctuated between 0.85 and 0.94. The Kappa index was between 66 to 85. In our clinical trial, the Accu-Chek, Glucotouch, OneTouch, and Precision demonstrated greater accuracy and a higher Kappa index than the HemoCue. CONCLUSIONS: Our data showed good concordance in statistical and clinical parameters for most of the six glucose meters. The HemoCue, recommended as a standard method in several countries, did not show better concordance than most of the tested glucose meters. When used by well-trained personnel, the accuracy of the Accu-Chek, Glucotouch, One-Touch, and Precision was acceptable for use in gestational diabetes screening.

Gestational diabetes mellitus alters apoptotic and inflammatory gene expression of trophobasts from human term placenta.

AIM: Increased placental growth secondary to reduced apoptosis may contribute to the development of macrosomia in GDM pregnancies. We hypothesize that reduced apoptosis in GDM placentas is caused by dysregulation of apoptosis related genes from death receptors or mitochondrial pathway or both to enhance placental growth in GDM pregnancies. METHODS: Newborn and placental weights from women with no pregnancy complications (controls; N=5), or with GDM (N=5) were recorded. Placental villi from both groups were either fixed for TUNEL assay, or snap frozen for gene expression analysis by apoptosis PCR microarrays and qPCR. RESULTS: Maternal, placental and newborn weights were significantly higher in the GDM group vs. Controls. Apoptotic index of placentas from the GDM group was markedly lower than the Controls. At a significant threshold of 1.5, seven genes (BCL10, BIRC6, BIRC7, CASP5, CASP8P2, CFLAR, and FAS) were down regulated, and 13 genes (BCL2, BCL2L1, BCL2L11, CASP4, DAPK1, IκBκE, MCL1, NFκBIZ, NOD1, PEA15, TNF, TNFRSF25, and XIAP) were unregulated in the GDM placentas. qPCR confirmed the consistency of the PCR microarray. Using Western blotting we found significantly decreased placental pro-apoptotic FAS receptor and FAS ligand (FASL), and increased mitochondrial anti-apoptotic BCL2 post GDM insult. Notably, caspase-3, which plays a central role in the execution-phase of apoptosis, and its substrate poly (ADP-ribose) polymerase (PARP) were significantly down regulated in GDM placentas, as compared to non-diabetic Control placentas. CONCLUSION: Maternal GDM results in heavier placentas with aberrant placental apoptotic and inflammatory gene expression that may account, at least partially, for macrosomia in newborns.

Does the use of fetal fibronectin in an algorithm for preterm labor reduce triage evaluation times?

OBJECTIVE: To determine the effectiveness of a novel algorithm based on fetal fibronectin (FFN) for management of preterm labor (PTL). METHODS: A randomized trial was performed on patients who presented with symptoms of PTL at 24-34 weeks. Patients were randomized to algorithms with cervical exams only versus cervical exams plus FFN. In this algorithm, physicians had to discharge patients with a negative FFN result. The primary outcome was the evaluation time for triage. The secondary outcomes were admission to the hospital for PTL, preterm birth <34 weeks and preterm birth <37 weeks. RESULTS: A total of 76 patients were enrolled and randomized (control n = 32, FFN n = 44). There were no differences in triage time, hospital admissions or preterm deliveries (PTDs) between the two groups. CONCLUSION: An algorithm based on FFN for management of PTL does not reduce evaluation times for triage, hospital admissions or PTDs.

Cervilenz assessment of cervical length compared to fetal fibronectin in the prediction of preterm delivery in women with threatened preterm labor.

OBJECTIVE: To determine whether cervical length (CL) measured by the Cervilenz™ measuring device is an effective screening tool for the prediction of preterm delivery (PTD) compared to fetal fibronectin (fFN). METHODS: We evaluated fFN and CL among women who enrolled into a randomized control trial (RCT) comparing management algorithms for threatened preterm labor between 24 and 34 weeks' gestation. In all subjects, fFN was collected, with CL determined in blinded fashion. The sensitivity, specificity, and positive and negative predictive values (NPV) for fFN or Cervilenz in prediction of PTD within 7 days or prior to 37 weeks were determined. RESULTS: Fifty-two subjects were evaluated. CL <30 mm correlated with PTD <7 days (r = 0.31, p = 0.04) and fFN positivity (r = 0.43, p = 0.006). CL <30 mm and fFN had excellent NPV for PTD <7 days (97.1 vs. 97.3%), and the area under the receiver operator characteristic curves were similar for prediction of PTD <7 days (76.6 vs. 75.2%, p = 0.71) or <37 weeks (56.7 vs. 55.2%, p = 0.71). CONCLUSIONS: Measurement of CL with Cervilenz appears to be equivalent to fFN in screening symptomatic women for PTD within 7 days or prior to 37 weeks. Given cost and turnaround time with fFN testing, Cervilenz represents a promising new tool for real time, clinically useful results in the management of women with threatened preterm labor.

Declining beta-cell compensation for insulin resistance in Hispanic women with recent gestational diabetes mellitus: association with changes in weight, adiponectin, and C-reactive protein.

OBJECTIVE: To identify factors associated with declining beta-cell compensation for insulin resistance. RESEARCH DESIGN AND METHODS: In a cohort of Hispanic women with recent gestational diabetes mellitus, oral glucose tolerance tests (OGTTs), intravenous glucose tolerance tests (IVGTTs), and bioelectrical impedance measurements were performed at 15-month intervals for up to 5 years, or until fasting plasma glucose exceeded 140 mg/dl (7.8 mmol/l). Data were analyzed to identify predictors of declining beta-cell compensation for insulin resistance (the disposition index [DI]) and to examine the mechanism of weight gain and changes in circulating levels of selected adipokines and inflammatory markers on beta-cell compensation decline. RESULTS: A total of 60 nondiabetic women had a median of four sets of OGTT + IVGTT during a median follow-up of 52 months. Fourteen of the women developed diabetes. None of the baseline characteristics were significantly predictive of a decline in DI. There were significant univariate associations between declining DI and weight gain (specifically fat gain), declining adiponectin and rising C-reactive protein. Multivariate analysis showed that the weight gain was the most significant factor associated with declining DI. The amount of association between weight gain and declining DI was explained 31% by changes in adiponectin and C-reactive protein and 40% by changes in insulin resistance. CONCLUSIONS: These results identify weight gain as the strongest factor associated with declining beta-cell compensation for insulin resistance in Hispanic women at high risk for type 2 diabetes. Such effect may be mediated through at least two effects: alterations in adipokine levels and increasing insulin resistance.