A tincture of time does not turn the tide: type 2 diabetes trends in offspring of type 2 diabetic mothers.
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Biomedical subjects
Publications and source records attributed to L Jovanovic.
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Uncontrolled gestational diabetes is associated with infant macrosomia and a lifelong risk of developing diabetes. Prompt diagnosis and aggressive management is therefore critical. All pregnant women should be screened for carbohydrate intolerance. Women with even minor abnormalities in blood sugar levels should be trained to monitor their glucose levels, rigorously control their diet, and use insulin if necessary. Exercise is also very beneficial.
CONTEXT: Intensive diabetes management using frequent blood glucose measurements to guide therapy has been shown to significantly improve short- and long-term outcomes. Development of a device that makes possible frequent, automatic, painless, and accurate measurements of glucose would facilitate intensive management. OBJECTIVE: To determine the accuracy of the GlucoWatch automatic glucose biographer (Cygnus Inc) compared with that of serial blood glucose measurements. DESIGN: Multicenter comparative study of the GlucoWatch biographer and the HemoCue blood glucose analyzer (Aktiebolaget Leo) performed between August 29 and October 17, 1998. Participants wore up to 2 biographers during the 15-hour study session and performed 2 fingersticks per hour for comparative blood glucose measurements. The biographers were calibrated with a single HemoCue measurement after a 3-hour warm-up period. Diet and insulin were manipulated to produce a broad glycemic range during the study. SETTING: Controlled clinical environment at 2 diabetes centers and 3 contract research organizations in the United States. PARTICIPANTS: A total of 92 subjects (mean [SD] age, 42.1 [15.1] years; 59.8% women) with type 1 or 2 diabetes requiring treatment with insulin. MAIN OUTCOME MEASURES: Mean error, mean absolute error, correlation, slope, and intercept using Deming regression, and clinical significance of differences between biographer readings and blood glucose measurements using the Clarke error grid. RESULTS: Results showed close tracking of blood glucose over a range of 2.2 to 22.2 mmol/L (40-400 mg/dL) for up to 12 hours using a single point calibration. The biographer readings lagged behind serial blood glucose values by a mean of 18 minutes. An analysis of 2167 data pairs shows a linear relationship (r = 0.88; slope = 1.03; intercept = -0.33 mmol/L [-6 mg/dL]) between biographer readings and serial glucose measurements. The mean absolute error between the 2 measurements was 15.6% (mean error [SD], -0.07 [1.82] mmol/L [-1 [33] mg/dL]), and 96.8% of the data fell in the therapeutically relevant regions of the error grid analysis. CONCLUSION: These results demonstrate close agreement between GlucoWatch biographer readings and blood glucose measurements using repeated fingerstick blood samples. The automatic, frequent, and noninvasive measurements obtained with the biographer provides more information about glucose levels than the current standard of care.
The goal of this study was to determine whether the type of fat plays a role in the glucose response to a meal, independent of the carbohydrate content. Ten gestational diabetic women (gestational weeks 29-34) who were well controlled on diet alone were randomized as to the order in which they would eat a meal, after overnight fast, containing saturated fat (SF) or monounsaturated fat (MUFA). Blood was drawn at 0, 60, 120, and 180 min for plasma glucose, insulin, lipid profile (triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol) and free fatty acids. After 2 weeks, each patient received the other type of meal. The test meal was composed of 20% of the total daily caloric needs based on ideal body weight. The area under the curve showed a significantly lower glucose concentration for SF meal (p = 0.001). Serum insulin concentrations followed the glucose response with the peak at the 60-min time point and a significantly lower concentration at the 180-min time point in the SF than in the MUFA group. The present study demonstrated that the addition of SF to the meal resulted in lower postprandial glucose and insulin than when the meal contained MUFA. Thus, SF may be useful in controlling postprandial glucose.
Infant macrosomia is a serious medical concern. Pregnant women who do not meet the specific diagnosis for gestational diabetes may still have glucose-mediated macrosomia. In Santa Barbara County all pregnant women are screened for gestational diabetes at 24-28 weeks with a 50-g, 1-hr glucose challenge test (GCT). All patients who fail this test are placed on a standard euglycemic diet (40% carbohydrate, 20% protein, 40% fat) and perform home glucose monitoring of fasting and postprandial glucose levels. The objective of this study was to examine the effectiveness of this treatment program in decreasing infant macrosomia, maternal and infant morbidity, maternal complications, and operative delivery. We studied 103 women who had a positive GCT, but a negative 100-g, 3-hr oral glucose tolerance test (OGTT). The women were randomly assigned to either experimental or control groups with experimental women receiving dietary counseling and home glucose monitoring instruction (HBGM). HBGM diaries were reviewed weekly by clinic nurses. All women had hemoglobin A1c (HbA1c) tests at 28 and 32 weeks. Maternal and fetal charts were reviewed to determine delivery type and complications, indications for cesarean section (C-section), and infant gestational age, gender, Apgar scores, birth weight, morbidities, and congenital anomalies. Of the 103 women, 5 women required insulin treatment, 1 woman had an abortion, and 14 women were indeterminate regarding compliance or were control women who received diet counseling and HBGM. The results are based on 83 women--48 control and 35 experimental. There were no significant differences between the groups for age, parity, or weight at 28-30 weeks or 37 weeks to delivery, or HbA1c at 28 weeks. HbA1c was significantly higher in control women at 32 weeks. Birth weight expressed in grams or as a percentile specific for gender, ethnicity, and gestational age was significantly higher in control infants. Birth weight was significantly correlated with maternal intake weight, weight at 28-30 weeks, and weight at delivery and with HbA1c at 32 weeks' gestation. There were no significant differences between groups for maternal complications. Groups were significantly different for mode of delivery with experimental women having more induced vaginal deliveries but fewer repeat C-sections than control women. Groups were not different for primary C-sections. Women who fail the GCT, but not the OGTT and thus do not receive the diagnosis of GDM are still at risk for delivering a macrosomic infant and operative delivery. Our program of treatment for all women who fail the GCT improves outcome by reducing infant birth weight and the number of cesarean sections.
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OBJECTIVE: To compare the immunologic response to insulin lispro with that to regular human insulin, thereby assuring its safety for use in women with gestational diabetes, and to verify that it is effective. RESEARCH DESIGN AND METHODS: We compared the metabolic and immunologic effects of insulin lispro and regular human insulin in 42 women >18 years of age diagnosed with gestational diabetes by oral glucose tolerance testing at 14-32 weeks of gestation. Patients were randomized to receive regular human insulin or insulin lispro before consuming a test meal. Serum insulin, blood glucose, and C-peptide concentrations were measured. Throughout the remainder of gestation, patients received premeal insulin lispro or regular human insulin combined with basal insulin and performed blood glucose self-monitoring before and after each meal. Insulin antibodies and HbA1c were determined at enrollment and 6 weeks later. In addition, 10 patients received continuous intravenous insulin (4 lispro, 6 regular human insulin) and dextrose infusions intrapartum to assess placental insulin transfer. RESULTS: Anti-insulin antibody levels were similar in the two groups. Insulin lispro was not detectable in the cord blood. During a meal test, areas under the curve for glucose, insulin, and C-peptide were significantly lower in the lispro group. Mean fasting and postprandial glucose concentrations and end point HbA1c were similar in the two groups. The lispro group demonstrated fewer hypoglycemic episodes (symptoms and blood glucose concentrations <55 mg/dl). No fetal or neonatal abnormalities were noted in either treatment group. CONCLUSIONS: Insulin lispro may be considered a treatment option for women with gestational diabetes.
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This multicenter, randomized, placebo-controlled study of glimepiride, a new oral sulfonylurea, was conducted in patients with type 2 diabetes for whom dietary treatment was unsuccessful (fasting plasma glucose [FPG] = 151-300 mg/dL) during a 1-week screening period. Patients were randomized to receive glimepiride (n = 123) or placebo (n = 126) once daily for a 10-week dose-titration period, then maintained on an individually determined optimal dose (1-8 mg of glimepiride or placebo) for 12 weeks. Glimepiride lowered FPG by 46 mg/dL, hemoglobin A1C (HbA1C) by 1.4%, and 2-hour postprandial glucose by 72 mg/dL more than placebo. Glimepiride improved postprandial insulin and C-peptide responses without producing clinically meaningful increases in fasting insulin or C-peptide levels. Good glycemic control (HbA1C < or = 7.2%) was achieved by 69% of the patients taking glimepiride versus 32% of those taking placebo. The overall incidence of adverse events was similar in both groups. No clinically noteworthy abnormal laboratory values or hypoglycemia (blood glucose < 60 mg/dL) occurred. Glimepiride is safe and effective for treatment of patients with type 2 diabetes for whom diet therapy is unsuccessful.
Previous studies indicate that fasting plasma glucose decreases during gestation, but the timing and extent are not consistent from study to study. We had an opportunity to examine this question in the normal pregnancy cohort of women studied in the Diabetes in Early Pregnancy Study. Subjects were monitored to identify pregnancy by human chorionic gonadotropin testing, enrolled within 21 days of conception, and screened to rule out gestational diabetes at the juncture of the second and third trimesters. All subjects were instructed to fast overnight for 10 to 12 hours. Three hundred sixty-one women were studied between 6 and 12 weeks of gestation. A median decrease in plasma glucose of 2 mg/dL was observed between weeks 6 and 10 (P=.007). In a smaller group of subjects evaluated through the third trimester, little further glucose reduction was observed. A reduction in glycosylated hemoglobin levels between 10 and 20 weeks (P=.002) followed the earlier reduction in first trimester glucose levels. Analysis by body mass index (BMI) showed a smaller first trimester reduction with increasing BMI, and none among severely obese women (BMI > 29.9 kg/m2). The decline in fasting plasma glucose in pregnancy begins early in the first trimester, well before fetal glucose requirements can contribute to the decline in the glucose level. Thereafter, plasma glucose levels decrease little. These results suggest that in the setting in which this study was performed (an overnight fast) maternal physiologic adjustments account for a reduction in plasma glucose early in the first trimester of pregnancy, and possibly even later in gestation as well.
OBJECTIVE: To determine if introduction of a low carbohydrate diet might be a useful option for type 2 diabetic patients who do not achieve glucose target levels despite conventional treatment. METHODS: Subjects with type 2 diabetes, either treated with diet alone (n=9) or second generation sulfonylurea agents (n= 19), which were discontinued, were placed on a diet based on ideal body weight and comprised of 25% carbohydrate. After a mean of 8 weeks, they were then switched to a caloricly equivalent diet, but composed of 55% carbohydrate. RESULTS: Compared to baseline diet, after 8 weeks of a 25% diet, subjects showed significantly improved glycemia as evidenced by fasting blood glucose values (p<0.005) and hemoglobin A1c levels (p<0.05). Those previously treated with oral hypoglycemic agents showed, in addition, a significant decrease in weight and diastolic blood pressure despite the discontinuation of the oral agent. When then placed on a 55% carbohydrate diet, the hemoglobin A1c rose significantly over the ensuing next 12 weeks (p<0.05). CONCLUSION: A low carbohydrate, caloricly-restricted diet has beneficial short-term effects in subjects with type 2 who have failed either diet or sulfonylurea therapy and may obviate the necessity for insulin. Our study also affirms the need for reassessing the role of diet whenever type 2 diabetic patients manifests hyperglycemia, despite conventional oral treatment or diet management.
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.
This review summarizes Session IV: Therapeutic Interventions of the Fourth International Gestational Diabetes Workshop and suggests intervention protocols based on the presentations at this meeting and the literature. The opinions of the six presenters and their interpretation of the review of the literature in their specific areas, the synthesis of the 30 abstracts presented at this symposium on therapeutic interventions, and my interpretations of the literature to date on these strategies are discussed. Also, the suggested intervention protocols are outlined as to medical nutritional therapy, weight gain, insulin prescriptions, and the utility of an exercise program for gestational diabetes mellitus. The goals of an intervention protocol for the gestational diabetic women are to achieve and maintain normoglycemia and thus to minimize the risk of maternal or fetal morbidity.
An unusual triclonal IgG combination in the serum of a 56-year old male with clinical stage IIIB multiple myeloma is reported. The patient initially had an IgG4(lambda) monoclonal protein in his serum and later developed an IgG2(kappa) and an IgG (kappa) which possessed the characteristics of both IgG1 and IgG3 subclasses with an unusual combination of allotypic markers. Three M-proteins did not share idiotypic determinants. A rare class-switch recombination followed by mutation has been considered as a possible mechanism leading to this combination.
The measurement of umbilical and uterine artery velocity waveforms was used to study pregnancies complicated by diabetes. Continuous wave Doppler velocimetry was used to identify the umbilical and uterine artery velocity waveforms. A systolic:end diastolic ratio (S:D ratio) was calculated to analyze the obtained velocity waveforms. We treated 33 tightly controlled and monitored diabetic gravidas. The mean blood sugar value for this population was 95 +/- 8 mg/dL, and the mean umbilical artery S:D ratio was 2.5 +/- 0.3. That group of patients was compared to a group on which we reported previously. Statistically significant differences were found between the well-controlled and poorly controlled populations in third-trimester S:D ratios, number of stillbirths and neonatal morbidity. Uterine artery velocimetry allowed the identification of a patient who developed preeclampsia. This study seems to have indicated that umbilical and uterine artery velocimetry may have an adjunctive role in the surveillance of pregnancies complicated by diabetes.
Once pregnancy is recognized clinically, it is accepted that 12% to 15% undergo spontaneous abortion. However, the actual time of fetal demise has not yet been determined. To address this question, the outcomes of pregnancies identified before 21 days of conception by serum beta-human chorionic gonadotropin assays were studied. All subjects underwent ultrasound examinations at eight and 12 weeks' gestation. Among 220 women who had a viable pregnancy at eight weeks, only seven (3.2%) experienced a fetal loss thereafter. The results of this study suggest that most clinically recognized spontaneous abortions manifested after eight weeks actually represent pregnancies in which fetal demise occurred before eight weeks. These findings have important implications with respect to the safety of chorionic villi sampling and to the identification of exogenous agents that cause fetal wastage.
Dizygotic twins developed cloacogenic carcinoma of the anus almost simultaneously. The patients, although separated from the time they were 20-years-old, had very similar life styles. There are several reports in the medical literature of synchronous tumors in mono and dizygotic twins. It is recommended that if a cancer diagnosis is made in one twin, the other undergo workup to exclude the presence of a tumor with similar histology. The establishment of state or national twin registries would provide valuable information regarding the role of genetic and environmental factors in the development of not only cancer but also of various nonmalignant disorders.