Lois Jovanovic

American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus.

Acknowledgments We would like to recognize Elliot Sternthal, MD, FACE, and Joseph Vassalotti, MD, for their review of these guidelines and thoughtful comments.

Diabetes and Pregnancy: An Endocrine Society Clinical Practice Guideline

OBJECTIVE Our objective was to formulate a clinical practice guideline for the management of the pregnant woman with diabetes. PARTICIPANTS The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, 5 additional experts, a methodologist, and a medical writer. EVIDENCE This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. CONSENSUS PROCESS One group meeting, several conference calls, and innumerable e-mail communications enabled consensus for all recommendations save one with a majority decision being employed for this single exception. CONCLUSIONS Using an evidence-based approach, this Diabetes and Pregnancy Clinical Practice Guideline addresses important clinical issues in the contemporary management of women with type 1 or type 2 diabetes preconceptionally, during pregnancy, and in the postpartum setting and in the diagnosis and management of women with gestational diabetes during and after pregnancy.

A retrospective cohort study of diabetes mellitus and antipsychotic treatment in the United States.

Treatment-emergent diabetes mellitus (DM) has been described for conventional and atypical antipsychotics. In our study, antipsychotic prescription claims from AdvancePCSs database were used to identify patients starting antipsychotic monotherapy. The relative risk of developing DM was determined using prescription claims for antidiabetic agents in the following cohorts: AdvancePCS general patient population, combined conventional antipsychotics, and combined atypical antipsychotics. Cox proportional hazards regression was used to adjust for differences in age, gender, and duration of antipsychotic exposure between cohorts in the estimation of risk of developing diabetes. Hazard ratios for developing DM in the combined conventional, combined atypical, and individual conventional and atypical antipsychotic treatment cohorts were greater than the AdvancePCS general patient population cohort. An increased risk of developing diabetes compared with the AdvancePCS general patient population was observed during treatment with conventional or atypical antipsychotics.

Relationship of Fasting and Hourly Blood Glucose Levels to HbA1c Values: Safety, accuracy, and improvements in glucose profiles obtained using a 7-day continuous glucose sensor

OBJECTIVE—In this study, we evaluated the safety and efficacy of 7-day transcutaneous, real-time, continuous glucose monitoring (CGM) in subjects with insulin-requiring diabetes. RESEARCH DESIGN AND METHODS—Eighty-six subjects were enrolled at five U.S. centers. Subjects wore a sensor inserted under the skin of the abdomen for 7 days during each of three consecutive periods. Data were blinded during period 1 and unblinded during periods 2 and 3. RESULTS—Of the 6,811 matched self-monitoring of blood glucose to sensor values prospectively analyzed, 97.2% fell in the Clarke error grid zones A and B, and median absolute relative difference was 11.4%. After unblinding, subjects reduced time spent at <55 mg/dl by 0.3 h/day, reduced time spent at >240 mg/dl by 1.5 h/day, and increased time in the target zone (81–140 mg/dl) by 1.4 h/day (P < 0.05 for all three comparisons). Improvements were seen in both types 1 and 2 diabetes and with use of both multiple daily injections and continuous subcutaneous insulin infusion. Modal day graphs were generated in six groups of subjects based on HbA1c (A1C) (≤6, 6–7, 7–8, 8–9, 9–10, and >10%). Mean glucose levels from midnight to 7:00 a.m. (fasting and dawn phenomenon periods) were only normal for subjects with A1C ≤6%. All other groups were hyperglycemic during this and all periods. Reductions in overall mean glucose were achieved for the four highest A1C groupings with unblinded device use. CONCLUSIONS—This is the first report of a real-time, transcutaneous glucose sensor that functioned for 7 days. The use of CGM in the unblinded phase resulted in improvements in target-range glycemia across all A1C values.

Feasibility of maintaining normal glucose profiles in insulin-dependent pregnant diabetic women.

This study was designed to test the feasibility of a patient-monitored glucose determination program to establish and maintain normal blood glucose levels. Ten pregnant women, who were insulin-dependent diabetics prior to becoming pregnant and who were in their eighth week or less of pregnancy, were offered the program. All 10 accepted and continued the program for the duration of their pregnancy. Normal plasma glucose (60 to 140; mean = 80 mg/dl) levels were achieved after one week of the program and were maintained throughout the pregnancy as documented by 5 to 8 blood glucose determinations a day. The hemoglobin A1c level, which was elevated in all 10 patients at the start (9.4 +/- 1.6 per cent) of the program, fell into the normal range (2 to 5.0 per cent) five weeks after glucose values became normal. Serum estradiol (0.8 +/- 0.6 ng/ml), serum prolactin (10 +/- 9 ng/ml) and serum human chorionic gonadotropin (5,500 +/- 1,700 ng/ml), although all abnormal at the start of the program, became normal after glucose control was achieved (program weeks 4, 5 and 6, respectively). The infants showed no signs of macrosomnia (2,988 +/- 959 g), hypoglycemia, hyperbilirubinemia, hypocalcemia, erythremia or respiratory distress. Therefore, a program to maintain normal blood glucose levels during a diabetic patients pregnancy is not only possible but may also improve the pregnancy and the outcome.

Maternal Efficacy and Safety Outcomes in a Randomized, Controlled Trial Comparing Insulin Detemir With NPH Insulin in 310 Pregnant Women With Type 1 Diabetes

OBJECTIVE This randomized, controlled noninferiority trial aimed to compare the efficacy and safety of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) (both with prandial insulin aspart) in pregnant women with type 1 diabetes. RESEARCH DESIGN AND METHODS Patients were randomized and exposed to IDet or NPH up to 12 months before pregnancy or at 8–12 weeks gestation. The primary analysis aimed to demonstrate noninferiority of IDet to NPH with respect to A1C at 36 gestational weeks (GWs) (margin of 0.4%). The data were analyzed using linear regression, taking several baseline factors and covariates into account. RESULTS A total of 310 type 1 diabetic women were randomized and exposed to IDet (n = 152) or NPH (n = 158) up to 12 months before pregnancy (48%) or during pregnancy at 8–12 weeks (52%). The estimated A1C at 36 GWs was 6.27% for IDet and 6.33% for NPH in the full analysis set (FAS). IDet was declared noninferior to NPH (FAS, –0.06% [95% CI –0.21 to 0.08]; per protocol, –0.15% [–0.34 to 0.04]). Fasting plasma glucose (FPG) was significantly lower with IDet versus NPH at both 24 GWs (96.8 vs. 113.8 mg/dL, P = 0.012) and 36 GWs (85.7 vs. 97.4 mg/dL, P = 0.017). Major and minor hypoglycemia rates during pregnancy were similar between groups. CONCLUSIONS Treatment with IDet resulted in lower FPG and noninferior A1C in late pregnancy compared with NPH insulin. Rates of hypoglycemia were comparable.

Serum 1,5-Anhydroglucitol (GlycoMark™): A Short-Term Glycemic Marker

1,5-Anhydroglucitol (1,5-AG), the 1-deoxy form of glucose, has been measured and used clinically in Japan for over a decade to monitor short-term glycemic control. Evaluation of glucose control otherwise requires measuring plasma glucose or glycated proteins whose levels reflect average glucose concentration over the half-life of the protein analyzed. Hemoglobin A1c measurements reflect blood glucose levels over that past 2-3 months, while fructosamine can be used to evaluate glycemic control over 10-14 days. In contrast, 1,5-AG levels in blood respond within 24 h as a result of glucoses competitive inhibition of 1,5-AG reabsorption in the kidney tubule. When glucose levels rise, even transiently, urinary loss of 1,5-AG occurs, and circulating levels fall. Because of changes in renal hemodynamics in normal pregnancies, 1,5-AG appears of limited usefulness in evaluation of gestational diabetes. However, the characteristics of 1,5-AG levels in patients with moderate to near-normal glycemic control suggest that it may be a valuable complement to frequent self-monitoring or continuous monitoring of plasma glucose to confirm stable glycemic control. Measurements performed daily or weekly in a given patient would suggest that overall glycemic control has been stable or improved if 1,5-AG levels are stable or increasing. If 1,5-AG levels fall, greater attention to glucose monitoring and both lifestyle and medical management could be prescribed to correct the glycemic excursions that would underlie such changes. The behavior of this analyte is different from all others used in the management of diabetes, creating potential opportunities for its use in clinical practice.

Physiological Reduction in Fasting Plasma Glucose Concentration in the First Trimester of Normal Pregnancy: The Diabetes in Early Pregnancy Study

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.

Screening for Gestational Diabetes: Optimum Timing and Criteria for Retesting

Because of the morbidity associated with undiagnosed gestational diabetes (GDM), screening programs are advocated in all pregnancy clinics. The purpose of this study was to elucidate the optimum time to test for diabetes during gestation, the indication for retesting, and the predictive value of a positive screening test for a large (>4000 g) infant. Women (N = 300) were screened at three time points: 9–20 wk, 27–31 wk, and 33–36 wk. An additional group of 300 women were screened at two time points: 27–31 wk and 33–36 wk. The prevalence of GDM in this group was 3.2%. The optimum timing for screening for highest yield was 27–31 wk. Retesting at 33–36 wk appeared cost effective if (1) maternal age was ≥33 yr, (2) a positive screen was present at 27–31 wk, and (3) the mother was obese (>120% ideal body wt).

The Role of Continuous Glucose Monitoring in Gestational Diabetes Mellitus

S-67 GESTATIONAL DIABETES MELLITUS (GDM), defined as “carbohydrate intolerance of variable severity with onset or first recognition during pregnancy,”1 occurs in nearly 4% of all pregnancies in the United States.2 The actual prevalence may differ with ethnicity and maternal age.2,3 Women with diabetes who have high blood glucose levels throughout pregnancy experience greater incidence of adverse maternal and infant outcomes, including preeclampsia, cesarean delivery, macrosomia, congenital anomalies, and increased risk for future development of type 2 diabetes or other metabolic abnormalities.