Association of glucose metabolism and blood pressure during pregnancy with subsequent maternal blood pressure.

The goal of this study was to examine associations of measures of maternal glucose metabolism and blood pressure during pregnancy with blood pressure at follow-up in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. The HAPO Follow-Up Study included 4747 women who had a 75-g oral glucose tolerance test (OGTT) at ~28 weeks' gestation. Of these, 4572 women who did not have chronic hypertension during their pregnancy or other excluding factors, had blood pressure evaluation 10-14 years after the birth of their HAPO child. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (SBP ≥ 140 and/or DBP ≥ 90 or treatment for hypertension) at follow-up. Blood pressure during pregnancy was associated with all blood pressure outcomes at follow-up independent of glucose and insulin sensitivity during pregnancy. The sum of glucose z-scores was associated with blood pressure outcomes at follow-up but associations were attenuated in models that included pregnancy blood pressure measures. Associations with SBP were significant in adjusted models, while associations with DBP and hypertension were not. Insulin sensitivity during pregnancy was associated with all blood pressure outcomes at follow-up, and although attenuated after adjustments, remained statistically significant (hypertension OR 0.79, 95%CI 0.68-0.92; SBP beta -0.91, 95% CI -1.34 to -0.49; DBP beta -0.50, 95% CI -0.81 to -0.19). In conclusion, maternal glucose values at the pregnancy OGTT were not independently associated with maternal blood pressure outcomes 10-14 years postpartum; however, insulin sensitivity during pregnancy was associated independently of blood pressure, BMI, and other covariates measured during pregnancy.

Excessive gestational weight gain in the first trimester among women with normal glucose tolerance and resulting neonatal adiposity.

OBJECTIVE: To assess whether weight gain above or below Institute of Medicine (IOM) recommended amounts in an ethnically diverse obstetric population with normal glucose tolerance is associated with differences in neonatal adiposity. STUDY DESIGN: In this prospective cohort study, healthy women with normal glucose tolerance based on the International Association of Diabetes and Pregnancy Study Groups guidelines were enrolled. Gestational weight at multiple time points were collected. Neonatal adiposity was measured by air displacement plethysmography at 24 to 72 h of life. Analyses included Fisher's exact test, analysis of variance and a trajectory analysis using a group-based weight gain trajectory model with a censored normal distribution. RESULTS: Overweight and obese women were more likely to exceed IOM weight gain guidelines. Regardless, there was no significant difference in %body fat of neonates born to mothers who either met or exceeded gestational weight gain (GWG) guidelines. GWG timing influenced neonatal anthropometrics: women who gained excessively by the first prenatal visit had neonates with significantly higher birth weight (3.91 vs 3.45 kg, P<0.001) and %body fat (13.7 vs 10.9%, P=0.0001) compared with women who had steady and moderate GWG. CONCLUSION: Avoidance of excessive GWG in the first trimester may prevent high amounts of neonatal adiposity.

The chromosome 3q25 locus associated with fetal adiposity is not associated with childhood adiposity.

Increased newborn adiposity is associated with later adverse metabolic outcomes. Previous genome-wide association studies (GWAS) demonstrated strong association of a locus on chromosome 3 (3q25.31) with newborn sum of skinfolds, a measure of overall adiposity. Whether this locus is associated with childhood adiposity is unknown. Genotype and sum of skinfolds data were available for 293 children at birth and age 2, and for 350 children at birth and age 6 from a European cohort (Belfast, UK) who participated in the Hyperglycemia and Adverse Pregnancy Outcome GWAS. We examined single nucleotide polymorphisms (SNPs) at the 3q25.31 locus associated with newborn adiposity. Linear regression analyses under an additive genetic model adjusting for maternal body mass index were performed. In both cohorts, a positive association was observed between all SNPs and sum of skinfolds at birth (P=2.3 × 10(-4), ß=0.026 and P=4.8 × 10(-4), ß=0.025). At the age of 2 years, a non-significant negative association was observed with sum of skinfolds (P=0.06; ß =-0.015). At the age of 6 years, there was no evidence of association (P=0.86; ß=0.002). The 3q25.31 locus strongly associated with newborn adiposity had no significant association with childhood adiposity suggesting that its impact may largely be limited to fetal fat accretion.

Maternal testosterone levels are associated with C-peptide levels in the Mexican American subset of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study cohort.

Altered sex hormone levels are thought to play an important role in adult-onset diseases including obesity, cardiovascular disease, and diabetes. They contribute to these complex diseases through changes in their availability, which is influenced, in part, by binding proteins. Insulin resistance, which is characteristic of these diseases, along with increased insulin secretion, is a physiologic change that occurs normally during pregnancy. To determine the relationship between insulin resistance and sex hormone levels, we examined the associations of sex hormone-binding globulin (SHBG) and testosterone with measures of glycemia and insulinemia in a healthy pregnant population. We measured fasting serum SHBG and testosterone levels in 215 Hispanic mothers of Mexican ancestry from the HAPO Study cohort and tested for associations between SHBG and testosterone levels and maternal plasma glucose and C-peptide. After adjusting for confounding variables, serum total testosterone (TT) was positively associated with fasting C-peptide (0.18 µg/l higher for TT higher by 1 SD, p=0.001) and 1-h C-peptide (0.79 µg/l higher for TT higher by 1 SD, p<0.001). Free testosterone (FT) was also positively associated with fasting C-peptide (0.19 µg/l higher for FT higher by 1 SD, p<0.001), and 1-h C-peptide (0.83 µg/l higher for FT higher by 1 SD, p<0.001). Although these findings are from a single cohort, this study provides evidence for an association between testosterone and C-peptide during pregnancy in a nondiabetic Hispanic obstetric population.

Excessive weight gain in women with a normal pre-pregnancy BMI is associated with increased neonatal adiposity.

BACKGROUND: More than 40% of women with a normal pre-pregnancy body mass index (BMI) exceed the 2009 Institute of Medicine (IOM) guidelines' recommended weight gain of 25-35 lb. Excessive gestational weight gain is one modifiable factor that may be contributing to childhood overweight and obesity. OBJECTIVE: The objective of this study was to evaluate differences in adiposity from neonates born to mothers with a normal pre-pregnancy BMI who either gained within or above IOM guidelines. METHODS: Neonatal adiposity was measured within 72 h of birth by the method of air displacement plethysmography. RESULTS: Compared with mothers who gained within IOM guidelines (N = 27), mothers with excessive gestational weight gain (N = 11) (mean 29.0 vs. 45.2 lb) had neonates with 50% more fat mass (348 vs. 525 g) and 3% greater body fat (10.7 vs. 13.9%). CONCLUSIONS: Increased adiposity at birth may predispose these children to increased risk of obesity and highlight the importance that women avoid gaining excessive weight in pregnancy.

The role of the polycystic ovary syndrome susceptibility locus D19S884 allele 8 in maternal glycemia and fetal size.

CONTEXT: The high incidence of insulin resistance, type 2 diabetes, and metabolic syndrome in Western societies and their impact on quality of life emphasize the importance of identifying underlying susceptibility loci for metabolic diseases. The polycystic ovary syndrome (PCOS) susceptibility locus D19S884 allele 8 (A8) is associated with measures of insulin resistance, beta-cell dysfunction, and other metabolic phenotypes in PCOS families. We now investigate the role of D19S884 A8 in pregnancy. OBJECTIVE: Using the multiethnic Hyperglycemia and Adverse Pregnancy Outcome cohort, we assessed the associations of D19S884 A8 with measures of maternal glycemia and fetal size. DESIGN: We tested for association of maternal D19S884 A8 with maternal outcomes (fasting, 1-h, and 2-h plasma glucose, and fasting and 1-h C-peptide from an oral glucose tolerance test) and fetal and maternal D19S884 A8 with fetal outcomes (birth weight, length, head circumference, sum of skin folds, fat mass, cord C-peptide, and 2-h neonatal plasma glucose). SUBJECTS: We analyzed 4424 Caucasian mothers and 3347 offspring of northern European ancestry, 1957 Thai mothers and 2089 offspring from Bangkok, 1208 Afro-Caribbean mothers and 1209 offspring from Barbados, and 774 Hispanic mothers and 762 offspring from Bellflower, California. RESULTS: After adjusting for confounding variables and multiple testing, neither maternal nor fetal D19S884 A8 showed significant evidence for association with any of the outcomes tested. CONCLUSIONS: The PCOS susceptibility locus, D19S884 A8, is not a major factor contributing to glycemia during pregnancy or fetal size in a general obstetric population.

Declining insulin requirement in the late first trimester of diabetic pregnancy.

OBJECTIVE: To investigate whether pregnancies complicated by type 1 diabetes are associated with a decrease in first-trimester insulin requirement. RESEARCH DESIGN AND METHODS: We examined the weekly insulin requirement (as units per kilogram per day) during the first trimester of pregnancy in diabetic women in the Diabetes in Early Pregnancy Study (DIEP) with accurate gestational dating, regular glucose monitoring, daily insulin-dose recording, and monthly glycohemoglobin measurements. RESULTS: In pregnancies that resulted in live-born full-term singleton infants, a significant 18% increase in mean weekly dosage was observed between weeks 3 and 7 (P = 0.000), followed by a significant 9% decline from week 7 through week 15 (P = 0.000). Further testing localized a significant change in insulin dose in the interval beginning weeks 7-8 and ending weeks 11-12 (P = 0.014). Within this interval, the maximum decrease was between weeks 9 and 10 (mean), 10 and 11 (median), and 8 and 9 (most frequent maximal decrease). To determine whether prior poor glucose control exaggerated these trends, we categorized the women based on their glycohemoglobin values: <2 SDs above the mean of a normal population (subgroup 1), 2-4 SDs (subgroup 2), and >4 SDs (subgroup 3) at baseline. Late first-trimester declines in dosage were statistically significant in subgroup 2 (P = 0.002) and subgroups 2 and 3 together (P = 0.003). Similarly, women with BMI >27.0 had a greater initial insulin rise and then fall compared with leaner women. CONCLUSIONS: Observations in the DIEP cohort disclose a mid-first-trimester decline in insulin requirement in type 1 diabetic pregnant women. Possible explanations include overinsulinization of previously poorly controlled diabetes, a transient decline in progesterone secretion during the late first-trimester luteo-placental shift in progesterone secretion, or other hormonal shifts. Clinicians should anticipate a clinically meaningful reduction in insulin requirement in the 5-week interval between weeks 7 and 12 of gestation.

Correlations between the intrauterine metabolic environment and blood pressure in adolescent offspring of diabetic mothers.

OBJECTIVE: To investigate associations between maternal diabetes and blood pressure (BP), obesity, impaired glucose tolerance, and serum lipids in offspring and whether these parameters correlate with metabolism during pregnancy. STUDY DESIGN: Body mass index, BP, serum glucose, and insulin during an oral glucose tolerance test, and lipid concentrations were measured in 99 offspring of diabetic mothers (ODM) and 80 members of a control group. RESULTS: ODM were more obese (body mass index 22.5 +/- 5.6 vs 20.3 +/- 4.0 kg/m(2)) and had higher systolic (8 mm Hg) and mean arterial BP (4 mm Hg) but similar diastolic BP compared with the control group. ODM had higher 2-hour glucose (6.6 +/- 1.3 vs 5.7 +/- 0.9 mmol/L) and insulin (580 +/- 544 vs 377 +/- 239 pmol/L) concentrations but lower fasting concentrations of low-density lipoprotein (2.54 +/- 0.67 vs 2.82 +/- 0.70 mmol/L) and total cholesterol (4.01 +/- 0.80 vs 4.40 +/- 0.78 mmol/L). In both groups body mass index, triglycerides, and fasting and 2-hour glucose concentrations showed correlations with BP measurements. Fasting insulin was correlated with BP readings only in the ODM. Correlations were found between second- and third-trimester maternal free fatty acid concentrations and diastolic and mean arterial BP. Third-trimester beta-hydroxybutyrate was correlated with mean arterial BP. CONCLUSIONS: In ODM, abnormalities in weight and glucose tolerance are associated with abnormal maternal metabolism. Higher BP is an additional abnormality associated with fetal overnutrition.

The Diabetes in Early Pregnancy Study: beta-hydroxybutyrate levels in type 1 diabetic pregnancy compared with normal pregnancy. NICHD-Diabetes in Early Pregnancy Study Group (DIEP). National Institute of Child Health and Development.

OBJECTIVE: The objective was to assess relationships between beta-hydroxybutyrate (beta-OHB) level and pregnancy outcome in human pregnancy in light of the fact that high levels of beta-OHB cause malformations and growth retardation in in vitro studies. RESEARCH DESIGN AND METHODS: We analyzed beta-OHB in prospectively collected specimens from the National Institute of Child Health and Human Development-Diabetes in Early Pregnancy Study, in gestational weeks 6-12 in diabetic (n = 204-239) and nondiabetic (n = 316-332) pregnant women. RESULTS: Levels of beta-OHB in diabetic women were 2.5-fold higher than in nondiabetic pregnant women at 6 weeks' gestation and declined to 1.6-fold above nondiabetic women by 12 weeks' gestation (P < 0.0001 at all times). beta-OHB was positively correlated with glucose levels (P < 0.0001) in diabetic mothers, probably reflecting degree of diabetic control. beta-OHB correlated inversely with glucose (P < 0.0003) (gestational week 6 only) in nondiabetic mothers, possibly reflecting caloric intake. beta-OHB tended to be lower (not higher) in diabetic and nondiabetic mothers with malformed infants or pregnancy losses, but the difference was not statistically significant. beta-OHB in diabetic mothers at 8, 10, and 12 weeks correlated inversely with birth weight (P = 0.004-0.02), even after adjusting for maternal glucose levels. beta-OHB levels were also generally lower in diabetic mothers of macrosomic infants, and week 12 ultrasound crown-rump measurements were inversely related to beta-OHB levels. CONCLUSIONS: The lst trimester beta-OHB is significantly higher in diabetic than nondiabetic pregnant women. In both groups, beta-OHB tended to be lower, not higher, in mothers who had a malformed infant or pregnancy loss. beta-OHB was inversely related to crown-rump length and birth weight. The modest beta-OHB elevation in the 1st trimester of reasonably well-controlled diabetic pregnancy is not associated with malformations, probably because beta-OHB levels causing malformations in embryo culture models are 20- to 40-fold higher. The mechanism of the beta-OHB association with impaired fetal growth is unknown.

Long-term effects of the intrauterine environment. The Northwestern University Diabetes in Pregnancy Center.

We sought to test the hypothesis that long-term postnatal development may be modified by metabolic experiences in utero. We enrolled offspring of women with pregestational diabetes (this included type 1 and type 2 diabetes) and gestational diabetes in a prospective study from 1977 to 1983. Fetal beta-cell function was assessed by measurement of amniotic fluid insulin (AFI) concentration at 32-38 weeks' gestation. Postnatally, offspring were seen yearly for neuropsychological testing, measurement of anthropometrics, and modified glucose tolerance testing. Neuropsychological control subjects were followed longitudinally. Additional control subjects had anthropometrics measured once, and a random subset of these had a single oral glucose challenge at 10-16 years. The rates of major neuropsychological disturbances in our cohort did not differ significantly from national estimates. However, aberrant maternal metabolism was associated with poorer intellectual performance and psychomotor development. The macrosomia observed at birth in offspring of diabetic mothers (ODM) resolves by 1 year of age. Obesity recurs in childhood; and by 14-17 years, the mean BMI is 24.6 +/- 5.8 kg/m2 in ODM versus 20.9 +/- 3.4 kg/m2 in control subjects. Obesity in adolescence is associated with sex, mother's weight, and AFI concentration. Impaired glucose tolerance (IGT) is found in 36% of ODM and is also associated with elevated amniotic fluid insulin in utero. In confirmation of our original hypothesis, aberrant maternal metabolism is associated with poorer intellectual and psychomotor development, obesity, and IGT in offspring. Excessive insulin secretion in utero, as assessed by AFI concentration, is a predictor of both obesity and IGT in adolescence. This study is a long-term prospective evaluation of the effects of maternal diabetes on pregnant women and their offspring. In this article, we report the results of the correlations between indexes of maternal and fetal metabolism during pregnancy and the offspring's subsequent physical, metabolic, and psychological development from birth through adolescence.

Short stature in Korean women: a contribution to the multifactorial predisposition to gestational diabetes mellitus.

We examined the associations between demographic characteristics including short stature and the prevalence of gestational diabetes mellitus (GDM) in Korean women. In this study, a total of 9005 pregnant women underwent universal screening for GDM. Oral glucose tolerance tests (100 g OGTT) were performed in positive screenees (1 h plasma glucose > or = 7.2 mmol/l) and GDM was diagnosed using National Diabetes Data Group criteria. Women with GDM were older and heavier than those with a positive screen and normal OGTT, as well as those with a negative screen. However, height of women with GDM was significantly shorter than those with a positive screen and normal OGTT, and a negative screen. When the study subjects were stratified according to height quartiles, the plasma glucose at the screening test decreased as height increased. Furthermore, the prevalence of GDM was highest in the shortest quartile (< or = 157 cm) group; the odds ratio for GDM was two times greater compared with the highest quartile (> or = 163 cm) group, even after controlling for age and body mass index (BMI). In addition, multiple logistic regression analysis revealed that greater prepregnancy BMI, age, weight gain, a parental history of diabetes mellitus, and shorter maternal height were directly and independently associated with the prevalence of GDM. We have found that short stature is an independent risk factor for GDM in the racially homogeneous population of Seoul, Korea. It is suggested that this propensity may be conveyed primarily by environmental influences. However, genetic factors may also modify the response to the environmental insult. Our findings also emphasize the heterogeneity of factors which predispose to GDM.

Behavioral adjustment in children of diabetic mothers.

The aim of this study was to evaluate whether maternal diabetes in pregnancy may adversely affect the children's behavioral adjustment, in a sample of 201 mothers (68 with pre-gestational diabetes, 50 with gestational diabetes, and 83 with non-diabetic pregnancies) and their singleton offspring. After accounting for socioeconomic status, ethnicity and maternal attitudes, none of the Child Behavior Checklist ratings correlated significantly with maternal patient group or several indices of antepartum maternal metabolism. Child obesity, a common sequela of diabetic pregnancies, correlated positively with Internalizing Behavior problems and three narrow-band sub-scales: Somatic Complaints, Anxious/Depressed, and Social Problems. Results suggest that children of diabetic mothers are at increased risk for a variety of developmental disturbances. Screening for learning and behavioral difficulties should be made at regular pediatric visits, with follow-up evaluations warranted by positive indications, excessive weight gain, or other evolving medical concerns.

Increased macrosomia and perinatal morbidity independent of maternal obesity and advanced age in Korean women with GDM.

OBJECTIVE: To examine the impact of gestational diabetes mellitus(GDM) on perinatal outcome in a setting where influences of maternal age and obesity would be minimal. RESEARCH DESIGN AND METHODS: A case-control study was done to compare the outcome of pregnancy in 65 women with GDM and 153 women with normal carbohydrate metabolism matched for age, height, and prepregnancy weight. RESULTS: The frequencies of preeclampsia and primary cesarean sections were higher and delivery was earlier in pregnancies complicated by GDM. Birth weight, symmetry index, and chest circumference were greater, and macrosomia and need for phototherapy were more common in offspring of mothers with GDM. Cord-serum C-peptide and insulin concentrations were higher in the infants of mothers with GDM and were strongly correlated with birth weight and symmetry index. However, maternal age, prepregnancy weight, and prepregnancy BMI were not correlated with birth weight. Postprandial glucose levels during the first 2 weeks after diagnosis of GDM had associations with the infants' birth weight, symmetry index, and cord insulin concentration in the diet-treated patients with GDM. CONCLUSIONS: Antepartum maternal glucose metabolism was significantly associated with fetal hyperinsulinemia and excessive fetal growth in relatively nonobese Korean women. These findings support a direct role for metabolic factors in the adverse outcomes in pregnancies complicated by GDM.

Early malnutrition and child neurobehavioral development: insights from the study of children of diabetic mothers.

In this study we sought to discern whether disturbances in mothers' metabolism during pregnancy may exert long-range effects on the neurobehavioral development of the progeny. Participants were 139 women with diabetes in pregnancy and their singleton offspring. Serial estimates of circulating maternal fuels were obtained for each pregnancy, along with detailed records of perinatal course and outcome. Offspring were administered the Wechsler Intelligence Scale for Children--Revised (WISC-R) and Kaufman Test of Educational Achievement: Short Form (KTEA) at ages 7 to 11 years. The rate of WISC-R full-scale IQ scores below 70 in our cohort did not differ significantly from national estimates. Nonetheless, after statistically controlling for other influences, WISC-R verbal, performance, and full-scale IQ scores, and Bannatyne's indices of Verbal Conceptualization Ability, Acquired knowledge, Spatial Ability, and Sequencing Ability were inversely correlated with measures of maternal lipid and glucose metabolism in the second and third trimesters. KTEA Arithmetic scores were similarly correlated with measures of maternal lipids in the third trimester. All correlations indicate that poorer maternal metabolic regulation was attended by poorer child performance. The effects of maternal metabolism on fetal brain and neurobehavioral development are discussed as potential intermediary factors.

Diabetes, asymptomatic hyperglycemia, and 22-year mortality in black and white men. The Chicago Heart Association Detection Project in Industry Study.

OBJECTIVE: To assess relationships of diabetes and asymptomatic hyperglycemia at baseline to the risk of cardiovascular disease (CVD) and all-cause (ALL) mortality in employed, white and black middle-aged men. RESEARCH DESIGN AND METHODS: A prospective cohort study of 11,554 white men and 666 black men between the ages 35 and 64 from 1967 to 1973 was conducted using data from the Chicago Heart Association (CHA) Detection Project in Industry 22-year mortality follow-up. cox proportional hazards models, adjusted fro age and other CVD risk factors, were used to estimate the relative risk (RR) and the 95% CI of mortality associated with baseline glycemic status. RESULTS: Age-adjusted baseline prevalence of clinical diabetes was similar in white (3.7%) and black (4.3%) men; asymptomatic hyperglycemia (glucose post-50-g load > or = 11.1 mmol/l) was present in 11.1% of whites and 7.8% of blacks. After controlling for age, lifestyle, and other CVD risk factors, mortality risk was increased among white men with clinical diabetes (CVD: RR 2.51, CI 2.08-3.02; ALL: RR 1.88, CI 1.63-2.17) and asymptomatic hyperglycemia (CVD: RR 1.18, CI 1.01-1.37; ALL: RR 1.24, CI 1.11-1.37), compared with men with postload glucose < 8.9 mmol/l. Risks were similarly, though nonsignificantly (owing to low statistical power), increased among black men with clinical diabetes (CVD: RR 1.60, CI 0.60-4.29; ALL: RR 1.78, CI 0.97-3.25) and asymptomatic hyperglycemia (CVD: RR 1.29, CI 0.61-2.72; ALL: RR 1.37, CI 0.85-2.20). CONCLUSIONS: Asymptomatic hyperglycemia and clinical diabetes appear to confer increased mortality risk in both white and black men. In addition, mortality risk is increased with increased severity of glycemia. These findings indicate the importance of applying efforts to reduce risk factors and prevent diabetes in both blacks and whites.

Metabolic response to meal eating and extended overnight fast in twin gestation.

OBJECTIVE: Our purpose was to compare the metabolic response to normal meal eating and the vulnerability to starvation ketosis in twin versus singleton gestation. STUDY DESIGN: Data are reported on 10 twin and 10 singleton nondiabetic gestations enrolled in a 40-hour metabolic study. Singletons were age (+/- 5 years) and prepregnancy weight (+/- 10% ideal body weight) matched with twins. The diet (35 kcal/kg ideal body weight for singletons, 40 kcal/kg ideal body weight for twins) was distributed as one fifth at 8 AM, two fifths at 1 PM, and two fifths at 6 PM. An overnight fast was extended until noon the following day. Glucose and beta-hydroxybutyrate measurements were made hourly except at night, when they were made every 2 hours. Insulin values were obtained before and after dinner and on the day when breakfast was delayed. RESULTS: The glucose, beta-hydroxybutyrate, and insulin excursions in response to meal eating from 8 AM to 12:00 noon on day 1 were similar in twin and singleton pregnancies (analysis of variance for repeated measures, p < 0.05). On day 2, when breakfast was delayed, a progressive decrement in glucose was observed in both twins and singletons (p = 0.4682). Concurrently, there was a progressive rise in beta-hydroxybutyrate in both twins and singletons, which was significantly greater for twins compared with singletons (p = 0.002). CONCLUSIONS: These data indicate that twin gestations are more vulnerable to the accelerated starvation of late normal pregnancy than singletons are in spite of additional caloric intake. We speculate that the observed difference may be the result of the increased metabolic demands of twin gestation.

Effect of pregnancy on renal function in patients with moderate-to-severe diabetic renal insufficiency.

OBJECTIVE: Previous studies of patients with diabetic nephropathy and mild renal impairment have suggested no determination in renal function as a result of pregnancy. The objective of this study was to determine whether pregnancy may permanently worsen renal function in women with diabetic nephropathy and moderate-to-severe renal insufficiency. RESEARCH DESIGN AND METHODS: Eleven patients were identified with diabetic nephropathy and moderate-to-severe renal dysfunction (creatinine [Cr] > or = 124 mumol/l [1.4 mg/dl]) at pregnancy onset by retrospective chart review. Alterations in glomerular filtration rate were estimated by using linear regression of the reciprocal of Cr over time. An equal number of nonpregnant premenopausal type 1 diabetic women with similar degrees of renal dysfunction served as a comparison group for nonpregnant rate of decline of renal function and potential contributing factors. RESULTS: Mean serum Cr rose from 159 mumol/l (1.8 mg/dl) prepregnancy to 221 mumol/l (2.5 mg/dl) in the third trimester. Renal function was stable in 27%, showed transient worsening in pregnancy in 27%, and demonstrated a permanent decline in 45%. Proteinuria increased in pregnancy in 79%. Exacerbation of hypertension or preeclampsia occurred in 73%. Seven patients progressed to dialysis 6-57 months postpartum, with 71% (five of seven) of these cases attributed to acceleration of disease during the pregnancy. Student's tests and repeated-measures analysis of variance support a pregnancy-induced acceleration in the rate of decline of renal function. CONCLUSIONS: In this series, patients with diabetic nephropathy and moderate-to-severe renal insufficiency were found to have a > 40% chance of accelerated progression of their disease as a result of pregnancy.