Metabolic and therapeutic assessment of gestational diabetes by two-hour and twenty-four-hour isocaloric meal tolerance tests.

Lean and obese women with gestational diabetes (GDM) were given two different isocaloric meal challenge tests to assess glucose and insulin responses. Forty-three pregnant women received a 400-kcal isocaloric breakfast meal tolerance test (mini-MTT). Twenty of the subjects were also given a 2000-kcal isocaloric diet with three meals and three snacks during a 24-h period (maxi-MTT). This was the first study to utilize the physiologic challenge of mixed meals to compare insulin and glucose responses of both obese and lean normal pregnant women and women with GDM around the clock. Normal obese pregnant women had higher integrated glucose and insulin values around the 24-h clock (P less than 0.003 and less than 0.03, respectively) than lean pregnant women. Lean and obese women with GDM also responded differently to the physiologic challenge of mixed meals. Some, but not all, obese diabetic subjects were markedly hyperinsulinemic in contrast to lean diabetic women who were relatively insulin deficient. One normoglycemic massively obese 18-yr-old pregnant woman was unexpectedly found to be severely hyperinsulinemic. The two meal tolerance tests clearly defined a delay in the release of insulin in women with GDM (lean and obese) and markedly different quantitative insulin responses to identical meal challenges in obese diabetic subjects. Maternal hyperinsulinemia was positively correlated with prepregnancy body mass index (kg/m2) and heavier infants, but not with plasma glucose levels. These studies provide evidence that GDM is a heterogeneous syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Nutritional management of pregnancy complicated by diabetes: historical perspective.

The important role of diet in the management of pregnancies complicated by diabetes has been recognized since the nineteenth century. In this historical review we have traced the evolution of the diabetic diet from the pre-insulin era, when diabetic pregnancies were not only rare, but accompanied by high maternal mortality and fetal loss to 1981, when the nutritional management of carbohydrate intolerance during gestation is again raising provocative questions. Our recent understanding of diabetes as a heterogeneous syndrome, the 1979 dietary guidelines of the American Diabetes Association (ADA), and the 1980 revised Recommended Dietary Allowances (RDA) for pregnant and lactating women are summarized as representative of the current approach to the nutritional management of diabetic pregnancies. Many questions remain unanswered. These include the hundred-year-old debate concerning the optimal amount of carbohydrate in the diabetic diet, the possible beneficial role of large amounts of dietary fiber, and the nagging concern about total caloric intake in type I insulin-dependent diabetes mellitus (IDDM) versus type II non-insulin-dependent diabetes mellitus (NIDDM) pregnant diabetic women. We suggest that nutritional counseling during gestation in the future may need to be more highly individualized as metabolic distinctions between different types of patients with carbohydrate intolerance are more clearly delineated.

Diabetes in pregnancy in Mexican Americans.

Diabetes in pregnant Mexican-American women is a serious and expensive health problem. At the University of California, San Diego Medical Center, 44% of pregnant women are Mexican American. In the Diabetes in Pregnancy Clinic, only 7% of women with insulin-dependent diabetes are in this ethnic group compared with 66% of non-insulin-dependent diabetic patients and 51% of those with gestational diabetes mellitus (GDM). GDM is the most common complication of pregnancy in Mexican Americans with a prevalence approximately three times higher than that of whites (4.5 vs. 1.5%). Mexican-American obese GDM subjects had more frequent cesarean sections and were more likely to have complications of premature rupture of membranes and preterm labor (NS). Polycythemia and sepsis also occurred more often in their infants. Anthropometric measurements in infants of both lean and obese GDM subjects differed from those of infants of mothers without GDM. Infants of lean mothers with GDM were heavier and longer than those of lean mothers without GDM. In addition, they had increased waist-hip ratio and triceps and subscapular skin folds. Infants of obese mothers with GDM were heavier than those of lean mothers with GDM. Moreover, they were longer (P less than 0.04); had a higher body mass index (P less than 0.04); and larger waist and hip circumferences (P less than 0.03) and buccal (P less than 0.01), subscapular (P less than 0.01), and sum of skin-fold measurements (P less than 0.03). Our observations indicate that pregnant diabetic Mexican-American women have predominantly GDM and non-insulin-dependent diabetes. They represent a major public health problem because of increased maternal and neonatal morbidity.

Decreased insulin requirement and improved control of diabetes in pregnant women given a high-carbohydrate, high-fiber, low-fat diet.

Five quantitative measures of diabetic control [HbA1c determinations, mean 24-h plasma glucose values, mean amplitude of glycemic excursions (MAGE), mean 24-h urinary loss of glucose, and daily exogenous insulin requirement] were compared in 20 pregnant women who were randomly assigned to either a high-carbohydrate, high-fiber diet (HCF) that was low in fat or to a control diet commonly prescribed for pregnancy. Eleven women followed the HCF diet and nine subjects, the control diet, from baseline entry into the study until delivery. Dietary compliance was excellent, with 78% of the women in each group rated good or acceptable. HbA1c values were similar in both groups at baseline (HCF: 11.0 +/- 0.5% versus control: 10.2 +/- 0.6%), with no different predelivery values (8.6 +/- 0.4%). Mean 24-h plasma glucose levels improved in patients on both diets, with lower values noted in the HCF group at predelivery. MAGE values and standard deviations did not differ significantly in the two groups. Glycosuria decreased markedly in both dietary groups, but differences between groups were not significant. Improved control of diabetes on the HCF diet was achieved with significantly lower increments in insulin dose during gestation (HCF baseline: 32 +/- 8 U/24 h to 66 +/- 10 U/24 h versus control baseline: 27 +/- 9 U/24 h to 108 +/- 12 U/24 h, P less than 0.03). Outcome of pregnancy did not differ in the two groups of patients, but women on the HCF diet gained less weight than those on the control diet (26 +/- 3 lb versus 35 +/- 5 lb, P less than 0.05). Mean newborn gestational age was similar in the two groups (HCF: 37.2 +/- 0.7 wk versus control: 36.5 +/- 0.7 wk). Mean birth weight in infants of HCF mothers was 3809 +/- 248 g versus 3313 +/- 278 g in infants of control mothers (P less than 0.05). We conclude that although marked improvement of diabetic control occurred on both regimens, patients on the HCF diet achieved better control of diabetes with significantly lower increments in exogenous insulin.

Amniotic fluid concentrations of iodothyronines and thyrotropin do not reliably predict fetal thyroid status in pregnancies complicated by maternal thyroid disorders or anencephaly.

In this study we report measurements of amniotic fluid (AF) concentrations of iodothyronines and TSH in 69 normal and 16 complicated pregnancies. The latter group included 2 women with untreated hyperthyroidism, 1 patient with untreated hypothyroidism, 5 hyperthyroid patients who received propylthiouracil (3 with Graves' disease, 1 with a multinodular goiter, and 1 with chronic thyroiditis), 3 women with Graves' disease who were hypothyroid after treatment, but who were receiving replacement therapy, and 5 anencephalic pregnancies. AF hormone levels could not be correlated with either maternal or cord serum values, neonatal serum measurements, and/or the clinical status of the infant. AF TSH and T4 levels were markedly elevated in 1 patient with Graves' disease and severe Rh isoimmunization and in 2 pregnancies complicated by anencephaly without identifiable pituitary tissue in the fetus. We conclude that measurements of AF concentrations of thyroid hormones and TSH do not reliably predict fetal or neonatal thyroid status.

Glycosylated and nonglycosylated prolactin in serum during pregnancy.

To study the pattern of release of glycosylated (G-PRL) and nonglycosylated (PRL) under various physiological conditions, we studied normal women from the first trimester of pregnancy through the postpartum period. Immunoreactive PRL variants were immunoprecipitated from 100-microL aliquots of serum, and the precipitates were subjected to gel electrophoresis in the presence of sodium dodecyl sulfate, electrotransferred to nitrocellulose paper, immunoblotted with anti-PRL serum and [125I]protein-A, and autoradiographed. The relative concentrations of the two forms of PRL were indicated by the intensity of the electrophoretic bands. Before pregnancy, serum G-PRL was the predominant PRL form. As pregnancy progressed, increasing amounts of PRL, compared to G-PRL, appeared in the serum, and it reached a maximum by the third trimester. G-PRL was found at all stages of pregnancy, even when the amount of PRL was greatest. After parturition in nonnursing mothers the PRL band again decreased; however, in nursing mothers the PRL band remained prominent. We conclude that the G-PRL and PRL variants may fulfill different physiological roles and, under certain conditions, such as pregnancy and lactation, more of the nonglycosylated PRL may be produced to fill special requirements.

Moderate caloric restriction in obese women with gestational diabetes.

The effect of moderate caloric restriction on weight gain during pregnancy and fetal outcome in 22 obese women with gestational diabetes mellitus was assessed. A new tool was used to assess dietary compliance in an outpatient setting. The authors observed that obese gestational diabetics gained less weight during pregnancy than ten normal pregnant women or 31 lean women with gestational diabetes. Paradoxically, the placentas of obese gestational diabetics were larger (P not significant), and infants of these mothers were significantly heavier than those of normal women or lean women with gestational diabetes (P less than .03). The authors suggest that the currently recommended daily caloric allowances for normal women may be excessive for obese gestational diabetics who are not prone to ketosis but have a complex metabolic problem characterized by hyperinsulinemia and insulin resistance.

Continuous subcutaneous insulin infusion in an obese insulin-resistant pregnant woman with type II diabetes: accelerated fetal growth and neonatal complications.

This is the first report to describe prolonged continuous subcutaneous insulin infusion in a massively obese insulin-resistant pregnant woman with type II diabetes. Maternal 24-hour plasma glucose levels became normal by 48 hours, and normoglycemia was maintained with high daily doses of insulin (530 U-333 U/24 hours) from 29 weeks' gestation until delivery at 38.5 weeks. Excellent diabetic control was associated with euglycemia, normal glycosylated hemoglobin concentration, and a significant decrease in mean 24-hour plasma C-peptide (P less than .004) and glucagon (P less than .003) levels. Unexpectedly, fetal growth accelerated during constant insulin infusion despite normal maternal plasma glucose levels. The newborn infant was large (4530 g), with a striking truncal accumulation of fat, hypoglycemia (30-minute plasma glucose 11 mg/dL), and polycythemia (central venous hematocrit 71%). Normalization of maternal plasma glucose levels failed to ameliorate established macrosomia, and did not prevent the neonatal complications that are common in infants of diabetic mothers.

Impaired surfactant production in cretin lambs.

Midgestation ovine fetal thyroidectomy resulted in profound congenital hypothyroidism and severe respiratory distress at term. Amniotic fluid obtained at delivery revealed low lecithin: sphingomyelin (L:S) ratios in all animals with a predominantly acidic phosphatide pulmonary phospholipid profile. Surfactant was diminished in the lung effluent of cretins at birth as compared with normal lambs. The acidic phosphatides and low L:S ratios persisted in the pharyngeal aspirates of the cretin lambs following attempted air breathing and the onset of severe respiratory distress. Conversely, normal lambs released considerable surfactant at birth that contained nonacidic phosphatides dominated by dipalmitoyl lecithin and yielding strongly positive L:S ratios. Comparative histologic studies revealed poor alveolar differentiation in certain lambs and persistence of the midgestation canalicular stage of lung development.

Endocrine and metabolic homeostasis in diabetic pregnancy.

Diabetic pregnancies involve complex alterations in maternal-placental and fetal compartments. This article discusses the unique features of diabetic pregnancies as they pertain to the maternal changes that must occur to accommodate the fetus.

Alterations of maternal metabolism in normal and diabetic pregnancies: differences in insulin-dependent, non-insulin-dependent, and gestational diabetes.

In normal and diabetic pregnancies, the placenta functions as a complex endocrine gland that modulates all classes of maternal nutrients to the fetus. The metabolic alterations of normal pregnancy are diabetogenic and associated with modest resistance to endogenous insulin. Pregnant women with carbohydrate intolerance represent three metabolically heterogeneous groups: type I (insulin-dependent), type II (non-insulin-dependent), and gestational diabetes. Patients with type I diabetes are at risk for ketosis and require replacement therapy because of a deficient production of insulin. They have decreased 24-hour, around-the-clock levels of C-peptide and glucagon, and lower nocturnal cortisol values and higher 24-hour prolactin levels than those of women with type II diabetes. Type II pregnant diabetic patients are not prone to ketosis and are more resistant to endogenous and exogenous insulin. They have higher fasting and meal-stimulated levels of C-peptide, accentuated fasting hypertriglyceridemia, and significantly lower high-density lipoprotein cholesterol levels than those of normal or type I women. In gestational diabetes, the metabolic stress of pregnancy evokes reversible hyperglycemia which may be associated with either a surfeit or a deficiency of insulin. These metabolic differences among diabetic pregnant women could have implications for placental structure and function that might influence fetal growth.

Postprandial walking exercise in pregnant insulin-dependent (type I) diabetic women: reduction of plasma lipid levels but absence of a significant effect on glycemic control.

In this study 42 pregnant women with type I diabetes and 28 nondiabetic controls were recruited to participate in a postprandial walking exercise program. Exercise patients were instructed to walk 20 minutes (1 mile) after each meal and were divided into two groups: group 1 were normal nondiabetic controls and group 2 were women with type I diabetes. There were two nonexercise comparison groups: group 3, nondiabetic controls, and group 4, women with type I diabetes. Diabetic women were followed weekly in an intensive perinatal program. Glycemic control was assessed by serial hemoglobin A1 concentration measurements, home blood glucose monitoring, 24-hour glucose profiles, and 24-hour quantitative urinary glucose loss. Glycemic control was modestly but not significantly superior in the diabetic exercise group 2 compared with the diabetic nonexercise group 4. Exercise was associated with lower fasting cholesterol and triglyceride values in both controls and diabetic women, with significantly lower fasting plasma triglyceride levels in the diabetic exercise group (p less than 0.02). There were no adverse effects of postprandial walking exercise in mothers or infants.