Peter Wein

Gestational Diabetes Mellitus: Clinical Predictors and Long-Term Risk of Developing Type 2 Diabetes A retrospective cohort study using survival analysis

OBJECTIVE—We sought to determine the long-term risk of type 2 diabetes following a pregnancy complicated by gestational diabetes mellitus (GDM) and assess what maternal antepartum, postpartum, and neonatal factors are predictive of later development of type 2 diabetes. RESEARCH DESIGN AND METHODS—This was a retrospective cohort study using survival analysis on 5,470 GDM patients and 783 control subjects who presented for postnatal follow-up at the Mercy Hospital for Women between 1971 and 2003. RESULTS—Risk of developing diabetes increased with time of follow-up for both groups and was 9.6 times greater for patients with GDM. The cumulative risk of developing type 2 diabetes for the GDM patients was 25.8% at 15 years postdiagnosis. Predictive factors for the development of type 2 diabetes were use of insulin (hazard ratio 3.5), Asian origin compared with Caucasian (2.1), and 1-h blood glucose (1.3 for every 1 mmol increase above 10.1 mmol). BMI was associated with an increased risk of developing type 2 diabetes but did not meet the assumption of proportional hazards required for valid inference when using Cox proportional hazards. CONCLUSIONS—While specific predictive factors for the later development of type 2 diabetes can be identified in the index pregnancy, women with a history of GDM, as a group, are worthy of long-term follow-up to ameliorate their excess cardiovascular risk.

Identification and Treatment of Women with Hyperglycaemia Diagnosed During Pregnancy Can Significantly Reduce Perinatal Mortality Rates

Summary: We wished to determine whether gestational diabetes was associated with an increased perinatal mortality rate, and to investigate the cause for the observed increase in the incidence of gestational diabetes. We therefore reviewed the results of glucose tolerance tests and pregnancy outcome in 116,303 pregnancies, 1971–1994, at the Mercy Hospital for Women. The main outcome measurements were the presence or absence of gestational diabetes, and perinatal mortality. Over the entire period of the study, gestational diabetes was associated with an increased risk of perinatal mortality (Mantel‐Haenszel adjusted odds ratio 1.53, 95% CI 1.13‐2.06, p=0.0069). Women with gestational diabetes that was only diagnosed retrospectively had a higher perinatal mortality rate than their contemporaries with normal glucose tolerance (OR 2.31,95% CI 1.37‐3.91, p=0.0025). Women in whom a glucose tolerance test was not performed continued to have a higher perinatal mortality rate than women who were tested (adjusted OR 2.21,95% CI 1.56‐3.12, p<0.00001). There has been an increase in the prevalence of gestational diabetes from 2.9% to 8.8%. Some of this is due to changes in population characteristics (increases in maternal age, obesity and proportion from South‐East Asia), but there was still an independent increase over time. We conclude that identification and treatment of women with gestational diabetes can reduce perinatal mortality rates. Similarly to diabetes mellitus in the total population, the prevalence of gestational diabetes has increased over time.

A Trial of Simple versus Intensified Dietary Modification for Prevention of Progression to Diabetes Mellitus in Women with Impaired Glucose Tolerance

Summary: Women with impaired glucose tolerance are at high risk of developing noninsulin dependent diabetes mellitus (NIDDM). The Mercy Hospital for Women has a long‐term follow‐up programme for women with gestational diabetes, which identifies many women with impaired glucose tolerance. Two hundred of these women were entered into a randomized controlled trial of intensive versus routine dietary advice. Seven women were lost to follow‐up. The annual incidence rates of diabetes mellitus for the 2 groups were 6.1% (intervention) and 7.3% (control), an incident rate ratio of 0.83, 95% confidence interval 0.47–1.48, p = 0.50. Overall, there was a return to normal glucose tolerance in 44% of patients. Multivariate analysis showed that body mass index, fasting and 2‐hour plasma glucose levels at trial entry were significantly associated with an increased risk of diabetes mellitus. Impaired glucose tolerance is an important condition that should be treated with advice about lifestyle modification (diet and/or exercise). We consider that future trials in the management of women with previous gestational diabetes who have impaired glucose tolerance should investigate the effect of pharmacological intervention in addition to diet and/or exercise, the latter providing a therapy that it would be unethical to exclude on the evidence presently available.

Prevalence of antibodies to glutamic acid decarboxylase in women who have had gestational diabetes

OBJECTIVESnOur purpose was to determine the prevalence of autoantibodies to glutamic acid decarboxylase in women who had had gestational diabetes, including those in whom insulin-requiring or non-insulin-requiring diabetes mellitus has since developed.nnnSTUDY DESIGNnThe study group comprised 734 women with previous gestational diabetes who were consecutive attendees to a follow-up clinic. These women were tested for autoantibodies to glutamic acid decarboxylase with a radioimmunoprecipitation assay. We similarly tested 104 women in whom permanent diabetes mellitus developed after gestational diabetes, of whom 20 were using insulin and 84 were not. Those using insulin also had fasting C-peptide levels measured.nnnRESULTSnThirteen of the 734 (1.8%, 95% confidence interval 0.9% to 3.0%) women with previous gestational diabetes were positive for autoantibodies to glutamic acid decarboxylase. Of the 20 women with diabetes treated with insulin, 12 had insulin deficiency confirmed by low levels of C peptide; all 12 were positive for autoantibodies to glutamic acid decarboxylase. Of the 84 women with diabetes not requiring insulin, 6 (7.1%, 95% confidence interval 2.7% to 14.9%) were positive for autoantibodies to glutamic acid decarboxylase.nnnCONCLUSIONSnThe prevalence of autoantibodies to glutamic acid decarboxylase in women with previous gestational diabetes was 1.8%. Our data also showed that insulin-dependent diabetes mellitus will develop in 1.7% of women with gestational diabetes. A positive test for autoantibodies to glutamic acid decarboxylase may help in the early identification of insulin-dependent diabetes mellitus. Adult-onset insulin-dependent diabetes mellitus developed in only 5.2% (12/230) of women with previous gestational diabetes who later had diabetes mellitus.

GESTATIONAL DIABETES IN TWIN PREGNANCY : PREVALENCE AND LONG-TERM IMPLICATIONS

Summary: During the period 1971–1991 at the Mercy Hospital for Women, gestational diabetes (GDM) was diagnosed in 3,447 of 61,914 tested singleton pregnancies (5.6%) and 59 of 798 tested twin pregnancies (7.4%, p = 0.025). A difference was apparent in the period 1971–1980, when the prevalences of GDM in singleton and twin pregnancies were 3.0% and 5.6% respectively (p = 0.012), but not in the period 1981–1991 when the corresponding prevalences were 7.4% and 8.4% (p = 0.36). Of the 59 patients in whom a diagnosis of GDM in a twin pregnancy was made, 27 attended the follow‐up programme. These patients were matched to a control group of 27 patients who had GDM in a singleton pregnancy with similar characteristics for known risk factors for the development of permanent diabetes mellitus. On WHO criteria diabetes mellitus occurred in 5 (18.5%) of the subjects and 2 (7.4%) of the controls (p = 0.21).

Why do Asian-born Women Have a Higher Incidence of Gestational Diabetes? An Analysis of Racial Differences in Body Habitus, Lipid Metabolism and the Serum Insulin Response to an Oral Glucose Load

Summary: We have observed a higher incidence of gestational diabetes (GDM) in Asian‐born than in Caucasian women. Body habitus, serum lipid levels and the serum insulin response to a glucose load in pregnancy were compared in 15 women with normal glucose tolerance, 16 Caucasian women with GDM and 19 Asian‐born women with GDM. Caucasian women with GDM, unlike Asian‐born women with GDM, were obese compared with control women as measured by body mass index (p = 0.022). Both groups of GDM women had similar patterns of insulin response to oral glucose with a delayed insulin peak and an elevated 2‐hour insulin level (p = 0.0021). In addition, the insulin response per unit of glycaemic stimulus (incremental insulin area/incremental glucose area at 1 hour) was reduced in both GDM groups (p = 0.035). Fasting serum triglyceride levels were higher in women with GDM although this was only significant in the

Severe folate deficiency masquerading as the syndrome of hemolysis, elevated liver enzymes, and low platelets.

Background Although folate deficiency is common in pregnancy, progresion to megaloblastosis is not. Hemolytic anemia, thrombocytopenia, and coagulopathy due to folate deficiency may mimic the sundrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). Cases Two women presented in the second trimester with abdominal pain and severe thrombocytopenia. These symptoms were ministerpreted in the first woman as the HELLP syndrome, leading to an emergency cesarean delivery. Subsequent investigation revealed folate deficiency; treatment resulted in rapid normalization of all abnormalities. In the second woman, folate deficiency was diagnosed antenatally. Treatment allowed continuation of the pregnancy to term. Conclusion The serious complications of folate deficiency make a strong case for supplementation in pregnancy. Careful scrutiny of clinical and laboratory findings may help discriminate the HELLP syndrome from its mimics, avoiding preterm delivery.

Value of Early Glucose Tolerance Testing in Women Who had Gestational Diabetes in Their Previous Pregnancy

Summary: The patterns of glucose tolerance, clinical characteristics, and follow‐up results of 1,027 pregnant women who had gestational diabetes diagnosed in their previous pregnancy, were analyzed. Glucose tolerance testing was performed before 24 weeks (mean 16.6 ±4.5 weeks) in 180 women (group 1); when the result was normal the test was repeated at 26–30 weeks gestation. In this group the incidence of recurrent gestational diabetes was 49.4%, and early testing diagnosed 61.8% of cases. Group 2 consisted of 685 women in whom glucose tolerance was tested only at 26–30 weeks gestation. In this group the incidence of recurrent gestational diabetes was 34.0%. Group 3 consisted of 162 women in whom glucose tolerance was not tested in the subsequent pregnancy. Perinatal mortality rates in Groups 1 to 3 were 2.2%, 0.6% and 3.1% respectively in the pregnancy subsequent to that in which gestational diabetes was first diagnosed.

Studies of Postnatal Diabetes Mellitus in Women Who Had Gestational Diabetes

Summary: This study investigated the prevalence of undiagnosed diabetes in women in the reproductive age group in a Victorian population by analysis of the results of glucose tolerance testing in 57,563 pregnancies. Gestational diabetes (GD) was diagnosed in 4,243 pregnancies and in 2,957 (69.7%) of these, postnatal glucose tolerance testing was performed. Diabetes mellitus was diagnosed within 26 weeks of delivery in 59 women, 55 of whom were diagnosed by the postnatal glucose tolerance test (GTT). There were 4 women with GD who developed diabetic ketosis during pregnancy (3) or within 12 weeks of delivery (1). By consideration of the results of the antenatal and postnatal GTTs, it was deduced that 53% (31 of 59) of the women with diabetes diagnosed after delivery may have had unrecognized prepregnancy diabetes. Consideration of the entire glucose‐tolerance tested population led to the conclusion that approximately 1 in 1,031 women in the reproductive age group in our community have unrecognized prepregnancy diabetes mellitus.

Amniotic Fluid Insulin Values in Women with Gestational Diabetes as a Predictor of Emerging Diabetes Mellitus

Summary: Amniotic fluid insulin levels were estimated in 30 women with insulin‐dependent diabetes, 216 with gestational diabetes and 27 with normal glucose tolerance. Results were correlated with birth‐weight, incidences of fetal macrosomia and neonatal hypoglycaemia, and the risk of the mothers with gestational diabetes developing diabetes mellitus on follow‐up.