Lois Jovanovic-Peterson

Maternal postprandial glucose levels and infant birth weight: The Diabetes in Early Pregnancy Study

The cause of macrosomia in the infant of the diabetic woman is still not completely defined. The National Institute of Child Health and Human Development--Diabetes in Early Pregnancy Study, which recruited insulin-dependent diabetic and control women before conception, provided an opportunity to address the relationship between maternal glycemia and percentile birth weight. Data were analyzed from 323 diabetic and 361 control women. Fasting and nonfasting venous plasma glucose were measured on alternate weeks in the first trimester and monthly thereafter. Glycosylated hemoglobin was measured weekly in the first trimester and monthly thereafter. More infants of the diabetic women were at or above the 90th percentile for birth weight than infants of control women (28.5% versus 13.1%, p less than 0.001). Although first-trimester nonfasting glucose and glycosylated hemoglobin levels were positively correlated with infant birth weight (p less than 0.001 and p = 0.008), when the analyses were adjusted for the variables of the subsequent trimesters the values became insignificant, whereas the third-trimester nonfasting glucose levels adjusted for values in prior trimesters emerged as the stronger predictor of percentile birth weight (p = 0.001). After adjusting for maternal hypertension, smoking, and ponderal index, the above relationships remained. In conclusion, monitoring of nonfasting glucose levels rather than the fasting levels, which are more commonly monitored in clinical practice, are necessary to prevent macrosomia.

Lack of Relation of Increased Malformation Rates in Infants of Diabetic Mothers to Glycemic Control during Organogenesis

To determine how much insulin-dependent diabetes increases a womans risk of giving birth to a malformed infant and how that risk is influenced by metabolic control, we followed 347 diabetic and 389 control women who enrolled in the study within 21 days of conception (the early-entry group) and 279 diabetic women who entered later (the late-entry group). We detected major malformations in the infants of 4.9 percent of the early-entry diabetic women, 2.1 percent of the controls, and 9.0 percent of the late-entry diabetic women. Malformation rates were significantly higher among offspring of early-entry diabetic women than among those of controls (odds ratio, 2.45; lower one-sided 95 percent confidence limit, 1.12; P = 0.027), and higher among late-entry than among early-entry diabetic women (odds ratio, 1.91; lower one-sided 95 percent confidence limit, 1.07; P = 0.032). Mean blood glucose and glycosylated hemoglobin levels during organogenesis were not significantly higher in women whose infants were malformed. Hypoglycemia (glucose, less than or equal to 50 mg per deciliter [2.8 mmol per liter]) was not significantly more common in the same group. Hyperglycemia and glycosylated hemoglobin were not correlated with malformation. The data suggest that more sensitive measures are needed to identify the teratogenic mechanisms, or that not all malformation can be prevented by good glycemic control. Despite the increased malformation rate among infants of the early-entry diabetic women, as compared with the controls, the more favorable outcome seen in the former group as compared with the late-entry group justifies the attempt to achieve good metabolic control around the time of conception.

Incidence of Spontaneous Abortion among Normal Women and Insulin-Dependent Diabetic Women Whose Pregnancies Were Identified within 21 Days of Conception

Whether pregnant women with insulin-dependent diabetes mellitus have an increased risk of spontaneous abortion is controversial. To address this question, we enrolled 386 women with insulin-dependent diabetes and 432 women without diabetes before or within 21 days after conception and followed both groups prospectively. Sixty-two diabetic women (16.1 percent) and 70 control women (16.2 percent) had pregnancy losses (odds ratio, 0.99; 95 percent confidence interval, 0.67 to 1.46). After adjustment for known risk factors for spontaneous abortion, the rate was still not significantly higher in the diabetic group (odds ratio, 0.91; 95 percent confidence interval, 0.59 to 1.40). Nonetheless, among the diabetic women, most of whom had good metabolic control, those who had spontaneous abortions had higher fasting and postprandial glucose levels in the first trimester than those whose pregnancies continued to delivery (P = 0.01 for fasting glucose levels and P = 0.005 for postprandial levels). In the small subgroup of diabetic women with poor control, who had elevated values for glycosylated hemoglobin in the first trimester, each increase of 1 SD above the normal range was associated with an increase of 3.1 percent in the rate of pregnancy loss (95 percent confidence interval, 0.6 to 5.6). We conclude that diabetic women with good metabolic control are no more likely than nondiabetic women to lose a pregnancy, but that diabetic women with elevated blood glucose and glycosylated hemoglobin levels in the first trimester have a significantly increased risk of having a spontaneous abortion.

Metabolic Control and Progression of Retinopathy: The Diabetes in Early Pregnancy Study

OBJECTIVE To evaluate the role of metabolic control in the progression of diabetic retinopathy during pregnancy. RESEARCH DESIGN AND METHODS We conducted a prospective cohort study of 155 diabetic women in the Diabetes in Early Pregnancy Study followed from the periconceptional period to 1 month postpartum. Fundus photographs were obtained shortly after conception (95% within 5 weeks of conception) and within 1 month postpartum. Glycosylated hemoglobin was measured weekly during the 1st trimester and monthly thereafter. RESULTS In the 140 patients who did not have proliferative retinopathy at baseline, progression of retinopathy was seen in 10.3, 21.1, 18.8, and 54.8% of patients with no retinopathy, microaneurysms only, mild nonproliferative retinopathy, and moderate-to-severe nonproliferative retinopathy at baseline, respectively. Proliferative retinopathy developed in 6.3% with mild and 29% with moderate-to-severe baseline retinopathy. Elevated glycosylated hemoglobin at baseline and the magnitude of improvement of glucose control through week 14 were associated with a higher risk of progression of retinopathy (adjusted odds ratio for progression in those with glycohe-moglobin ≥ 6 SD above the control mean versus those within 2 SD was 2.7; 95% confidence interval was 1.1-7.2; P = 0.039). CONCLUSIONS The risk for progression of diabetic retinopathy was increased by initial glycosylated hemoglobin elevations as low as 6 SD above the control mean. This increased risk maybe due to suboptimal control itself or to the rapid improvement in metabolic control that occurred in early pregnancy. Excellent metabolic control before conception may be required to avoid this increase in risk. Those with moderate-to-severe retinopathy at conception need more careful ophthalmic monitoring, particularly if their diabetes was suboptimally controlled at conception.

Randomized trial of diet versus diet plus cardiovascular conditioning on glucose levels in gestational diabetes.

We studied the impact of a training program on glucose tolerance in gestational diabetes mellitus. Women with gestational diabetes mellitus (N = 19) were randomized into either group I, a 6-week diet alone group (24 to 30 kcal/kg/24 hours; 20% protein, 40% carbohydrate, 40% fat), or group II, which followed the same diet plus exercise (20 minutes three times a week for 6 weeks). An arm ergometer was used to maintain heart rate in the training range. Glycemic response was monitored by glycosylated hemoglobin, a 50 gm oral glucose challenge with a fasting and 1-hour plasma glucose, and blood glucose self-monitoring, fasting and 1 hour after meals. Week 1 glycemic parameters were the same for both groups. Week 6 data (mean +/- SD) were as follows: group I glycosylated hemoglobin, 4.7% + 0.2% versus group II, 4.2% +/- 0.2%; p less than 0.001. The group I glucose challenge fasting value was 87.6 +/- 6.2 versus 70.1 +/- 6.6 mg/dl, p less than 0.001 for group II. The group I 1-hour plasma glucose challenge result was 187.5 +/- 12.9 mg/dl versus 105.9 +/- 18.9 mg/dl for group II, p less than 0.001. The glycemic levels diverged between the groups at week 4. We conclude that arm ergometer training is feasible in women with gestational diabetes mellitus and results in lower glycosylated hemoglobin, fasting, and 1-hour plasma glucose concentrations than diet alone. Arm ergometer training may provide a useful treatment option for women with gestational diabetes mellitus and may obviate insulin treatment.

Randomized Crossover Study of Effect of Resistance Training on Glycemic Control, Muscular Strength, and Cholesterol in Type I Diabetic Men

The goal of this study was to evaluate a program of resistance weight training on cardiovascular risk factors, blood glucose management, and overallstrength in diabetic subjects. A randomized crossover design was performed on eight male type I (insulin-dependent) diabetic subjects (mean ± SD age 31 ± 3.5 yr, height 176 ± 5.6 cm, body wt 80 ± 15 kg, duration of diabetes 12.3 ± 9.8 yr, and insulin dose 24 U NPH/day and 21 U regular/day). The program consisted of heavy-resistance weight training 3 days/wk for 10 wk, concentrating on the strengthening of major muscle groups through progressive resistance. Blood tests included total cholesterol, triglycerides, very-low-density lipoprotein and high-densitylipoprotein cholesterol, and HbA1c. These tests were repeated atthree time points during the program. Field-strength testing was performed before and after training. An improvement was seen in the squat (93.6% increase, P < 0.0001) and bench press (58% increase, P < 0.005). HbA1c and triglyceride levels showed no change during the resting portion ofthe experiment but showed a significant change with the training program: HbA1c 6.9 ± 1 . 4 vs. 5.8 ± 0.9% (P = 0.05) and triglyceride 5.044 ± 1.06 vs. 4.628 ± 0.88 mM (P = 0.01). Self-monitored glucose (taken pre- and postexercise) showed a decrease from 7.85 ± 3.13 to 7.05 ± 2.91 mM (P = 0.0001). Very-low-density lipoprotein cholesterol and triglycerides did not change after training. Analysis of variance showed no significant differences over time from the three time points with regard to reductions in cardiovascular risk factors or HbA1c. Heavy-resistance strength training may be associated with a decrease inglycosylated hemoglobin and cholesterol in type I diabetic men after training, in addition to increasing overall strength.

The Diabetes in Early Pregnancy Study: Changes incholesterol, triglycerides, body weight, and blood pressure

Summary This study examined changes in cholesterol, triglycerides, body weight, and blood pressure duringpregnancy in 312 diabetic and 356 control women recruited within 21 days after conception. Cholesterol values rose in both groups but were significantly lower in diabetic women at each time point (166 vs 178 mg/dl at week 12, p=0.0004). Triglyceride values also rose in both groups. Triglyceride levels did not differ between groups up to week 8 of gestation, but by weeks 10 to 12 they were significantly lower in diabetic women than in controls (75 vs 89 mg/dl at week 12, p = 0.0004). Although they were no heavier at entry, diabetic women gained significantly more weight between weeks 6 and 8 ( p p = 0.0006 at term). Diastolic blood pressure was higher in diabetic women on entry (70.7 vs 67.3 mm Hg, p = 0.0006) and throughout gestation. Significant correlations were found in the diabetic group between maternal blood pressure and lipids and infant birth weight. These newly found differences in cholesterol and triglyceride levels, weight gain, and blood pressure between type I diabetic and control women during gestation may have long-term cardiovascular implicationsThis study examined changes in cholesterol, triglycerides, body weight, and blood pressure during pregnancy in 312 diabetic and 356 control women recruited within 21 days after conception. Cholesterol values rose in both groups but were significantly lower in diabetic women at each time point (166 vs 178 mg/dl at week 12, p = 0.0004). Triglyceride values also rose in both groups. Triglyceride levels did not differ between groups up to week 8 of gestation, but by weeks 10 to 12 they were significantly lower in diabetic women than in controls (75 vs 89 mg/dl at week 12, p = 0.0004). Although they were no heavier at entry, diabetic women gained significantly more weight between weeks 6 and 8 (p less than 0.001), resulting in a mean difference between groups of 1 kg. Systolic blood pressure increased steadily and significantly in the diabetic but not the control women (115.8 +/- 16.2 SD vs 109.3 +/- 11.8 mm Hg, p = 0.0006 at term). Diastolic blood pressure was higher in diabetic women on entry (70.7 vs 67.3 mm Hg, p = 0.0006) and throughout gestation. Significant correlations were found in the diabetic group between maternal blood pressure and lipids and infant birth weight. These newly found differences in cholesterol and triglyceride levels, weight gain, and blood pressure between type I diabetic and control women during gestation may have long-term cardiovascular implications.

Percentage of carbohydrate and glycemic response to breakfast, lunch, and dinner in women with gestational diabetes.

We studied the relationship between 1-h glucose response and the percentage of carbohydrates in a given meal in 14 gestational diabetic women who did not require insulin therapy and were between 32 and 36 wk gestation. Each subject was > 130% ideal body weight and was placed on a diet of 24 kcal · kg−1 · 24 h−1, with 12.5% of calories at breakfast and 28% of the calories at lunch and again at dinner, with other calorie intake divided among three snacks. Glycemic response was monitored by self-monitoring of blood glucose 1 h after the start of each meal. Ten postprandial values for each meal were averaged for each of the 14 women. The correlation between percentage of carbohydrates and postprandial glucose level at 1 h was strongest for dinner (r = 0.95, P < 0.001), with more variability seen at breakfast (r = 0.75, P = 0.002) and lunch (r = 0.86, P = 0.001). To maintain a 1-h postprandial whole-blood glucose level <7.78 mM required the following percentages of carbohydrates in each meal: 45% at breakfast, 55% at lunch, and 50% at dinner. If 1-h postprandial whole-blood glucose level was to remain <6.67 mM, then the respective values were 33, 45, and 40%. We conclude that the glycemic response to a mixed meal in subjects with gestational diabetes is highly correlated with the percentage of carbohydrates of the ingested meal and varies among individuals and among breakfast, lunch, and dinner. These results emphasize the potential hazard of rote prescription of diets relatively high in carbohydrates during pregnancy complicated by gestational diabetes and the need to validate diet prescriptions with blood glucose monitoring.

Rapid association of acetaldehyde with hemoglobin in human volunteers after low dose ethanol

A fluorigenic high performance liquid chromatographic (HPLC) method was used to determine plasma (PA) and hemoglobin-associated (HbAA) acetaldehyde levels following a pulse of 0.3 g/kg ethanol to volunteers from whom bloods were drawn serially for 8 hours on the clinical research unit. On discharge from the research unit, the volunteers were instructed to avoid ethanol for 28 days. The results were compared to previously published results in teetotalers and alcoholic individuals reporting for treatment at an inpatient detoxification facility. Following ethanol ingestion, the peak levels of ethanol and both plasma and hemoglobin-associated acetaldehyde were detected at the 30 min time point and plasma levels were less than those associated with hemoglobin (31 +/- 16 S.D. and 159 +/- 48 S.D. nmol/g respectively, p less than 0.001). PA and HbAA returned to baseline values following ethanol ingestion within 3.5 hours. PA returned to within 1 standard deviation of levels found in teetotalers by 5 days, whereas HbAA remained elevated for the 28 days of the study. These data provide evidence that measurement of PA and HbAA may provide a useful marker for relatively acute and chronic ethanol ingestion respectively.

De novo clinical hypothyroidism in pregnancies complicated by and type I diabetes, subclinical hypothyroidism, proteinuria: A new syndrome

Fifty-one women with type I diabetes who had normal thyroxine values before becoming pregnant were evaluated. Abnormalities of thyroid tests other than thyroxine were encountered in 26 women, of whom 8 developed a low serum thyroxine level, an elevated thyroid-stimulating hormone level, and a low insulin requirement in the second trimester subsequent to an increase in 24-hour urinary protein excretion to greater than 4 gm/24 hr. Thyroid replacement led to an increase in insulin requirement to levels appropriate for gestational age. It is concluded that the woman with type I diabetes who develops proteinuria greater than 4 gm/24 hr during gestation is at risk for the development of de novo hypothyroidism during pregnancy, evidenced by a low serum thyroxine level, an elevated thyroid-stimulating hormone level, and a drop in insulin requirement.