Denice S. Feig

Risk of development of diabetes mellitus after diagnosis of gestational diabetes

Background: It is generally appreciated that gestational diabetes is a risk factor for type 2 diabetes. However, the precise relation between these 2 conditions remains unknown. We sought to determine the incidence of diabetes mellitus after diagnosis of gestational diabetes. Methods: We used a population-based database to identify all deliveries in the province of Ontario over the 7-year period from Apr. 1, 1995, to Mar. 31, 2002. We linked these births to mothers who had been given a diagnosis of gestational diabetes through another administrative database that records people with diabetes on the basis of either physician service claims or hospital admission records. We examined database records for these women from the time of delivery until Mar. 31, 2004, a total of 9 years. We determined the presence of diabetes mellitus according to a validated administrative database definition for this condition. Results: We identified 659 164 pregnant women who had no pre-existing diabetes. Of these, 21 823 women (3.3%) had a diagnosis of gestational diabetes. The incidence of gestational diabetes rose significantly over the 9-year study period, from 3.2% in 1995 to 3.6% in 2001 (p < 0.001). The probability of diabetes developing after gestational diabetes was 3.7% at 9 months after delivery and 18.9% at 9 years after delivery. After adjustment for age, urban or rural residence, neighbourhood income quintile, whether the woman had a previous pregnancy, whether the woman had hypertension after the index delivery, and primary care level before the index delivery, the most significant risk factor for diabetes was having had gestational diabetes during the index pregnancy (hazard ratio 37.28, 95% confidence interval 34.99–40.88; p < 0.001). Age, urban residence and lower income were also important factors. When analyzed by year of delivery, the rate of development of diabetes was higher among the latest subcohort of women with gestational diabetes (delivery during 1999–2001) than among the earliest subcohort (delivery during 1995 or 1996) (16% by 4.7 years after delivery v. 16% by 9.0 years). Interpretation: In this large population-based study, the rate of development of diabetes after gestational diabetes increased over time and was almost 20% by 9 years. This estimate should be used by clinicians to assist in their counselling of pregnant women and by policy-makers to target these women for screening and prevention

Effect of Home Blood Pressure Telemonitoring With Self-Care Support on Uncontrolled Systolic Hypertension in Diabetics

Lowering blood pressure reduces cardiovascular risk, yet hypertension is poorly controlled in diabetic patients. In a pilot study we demonstrated that a home blood pressure telemonitoring system, which provided self-care messages on the smartphone of hypertensive diabetic patients immediately after each reading, improved blood pressure control. Messages were based on care paths defined by running averages of transmitted readings. The present study tests the systems effectiveness in a randomized, controlled trial in diabetic patients with uncontrolled systolic hypertension. Of 244 subjects screened for eligibility, 110 (45%) were randomly allocated to the intervention (n=55) or control (n=55) group, and 105 (95.5%) completed the 1-year outcome visit. In the intention-to-treat analysis, mean daytime ambulatory systolic blood pressure, the primary end point, decreased significantly only in the intervention group by 9.1±15.6 mmHg (SD; P<0.0001), and the mean between-group difference was 7.1±2.3 mmHg (SE; P<0.005). Furthermore, 51% of intervention subjects achieved the guideline recommended target of <130/80 mmHg compared with 31% of control subjects (P<0.05). These improvements were obtained without the use of more or different antihypertensive medications or additional clinic visits to physicians. Providing self-care support did not affect anxiety but worsened depression on the Hospital Anxiety and Depression Scale (baseline, 4.1±3.76; exit, 5.2±4.30; P=0.014). This study demonstrated that home blood pressure telemonitoring combined with automated self-care support reduced the blood pressure of diabetic patients with uncontrolled systolic hypertension and improved hypertension control. Home blood pressure monitoring alone had no effect on blood pressure. Promoting patient self-care may have negative psychological effects.

Trends in Incidence of Diabetes in Pregnancy and Serious Perinatal Outcomes: A Large, Population-Based Study in Ontario, Canada, 1996–2010

OBJECTIVE Women with diabetes in pregnancy have high rates of pregnancy complications. Our aims were to explore trends in the incidence of diabetes in pregnancy and examine whether the risk of serious perinatal outcomes has changed. RESEARCH DESIGN AND METHODS We performed a population-based cohort study of 1,109,605 women who delivered in Ontario, Canada, between 1 April 1996 and 31 March 2010. We categorized women as gestational diabetes (GDM) (n = 45,384), pregestational diabetes (pre-GDM) (n = 13,278), or no diabetes (n = 1,050,943). The annual age-adjusted rates of diabetes in pregnancy were calculated, and rates of serious perinatal outcomes were compared between groups and by year using Poisson regression. RESULTS The age-adjusted rate of both GDM (2.7–5.6%, P < 0.001) and pre-GDM (0.7–1.5%, P < 0.001) doubled from 1996 to 2010. The rate of congenital anomalies declined by 23%, whereas the rate of perinatal mortality did not change significantly. However, compared with women with no diabetes, women with pre-GDM and GDM faced an increased risk of congenital anomalies (relative risk 1.86 [95% CI 1.49–2.33] and 1.26 [1.09–1.45], respectively), and perinatal mortality remained elevated in women with pre-GDM (2.33 [1.59–3.43]). CONCLUSIONS The incidence of both GDM and pre-GDM in pregnancy has doubled over the last 14 years, and the overall burden of diabetes in pregnancy on society is growing. Although congenital anomaly rates have declined in women with diabetes, perinatal mortality rates remain unchanged, and the risk of both remains significantly elevated compared with nondiabetic women. Increased efforts are needed to reduce these adverse outcomes.

Insulin Glargine Safety in Pregnancy: a Transplacental Transfer Study

OBJECTIVE Insulin glargine (Lantus) is an extended-action insulin analog with greater stability and duration of action than regular human insulin. The long duration of action and decreased incidence of hypoglycemia provide potential advantages for its use in pregnancy. However, the placental pharmacokinetics of insulin glargine have not been studied. Therefore, the objective of this study was to determine whether insulin glargine crosses the human placenta using the human perfused placental lobule technique. RESEARCH DESIGN AND METHODS Placentae were obtained with informed consent after elective cesarean section delivery of noncomplicated term pregnancies. Insulin glargine, at a therapeutic concentration of 150 pmol/l (20 μU/ml) was added to the maternal circulation. Additional experiments were carried out at insulin glargine concentrations 1,000-fold higher than therapeutic levels (150, 225, and 300 nmol/l). A subsequent perfusion for which the maternal circuit remained open and insulin glargine was continuously infused at 150 pmol/l was completed for further confirmation of findings. The appearance of insulin glargine in the fetal circulation was analyzed by a chemiluminescence immunoassay. RESULTS Results from perfusions carried out at therapeutic concentrations (150 pmol/l) of insulin glargine showed no detectable insulin glargine in the fetal circuit. After perfusion with very high insulin glargine concentrations of 150, 225, and 300 nmol/l, the rate of transfer remained low at 0.079 ± 0.01, 0.14, and 0.064 pmol · min−1 · g tissue−1, respectively. CONCLUSIONS Insulin glargine, when used at therapeutic concentrations, is not likely to cross the placenta.

Preeclampsia as a Risk Factor for Diabetes: A Population- Based Cohort Study

Denice Feig and colleagues assess the association between gestational diabetes, gestational hypertension, and preeclampsia and the development of future diabetes in a database analysis of pregnant women in Ontario, Canada.

Missed opportunities for type 2 diabetes testing following gestational diabetes: a population-based cohort study

Please cite this paper as: Shah B, Lipscombe L, Feig D, Lowe J. Missed opportunities for type 2 diabetes testing following gestational diabetes: a population‐based cohort study. BJOG 2011;118:1484–1490.

Safety of Insulin Glargine Use in Pregnancy: A Systematic Review and Meta-Analysis:

Background The prevalence of diabetes in women of childbearing age is increasing. As such, the number of pregnancies complicated by diabetes will inevitably increase. New insulin analogues such as the long-acting analogue Insulin glargine may represent beneficial treatment options in pregnancy by ensuring that patients achieve excellent glycemic control without risk of maternal hypoglycemia. Objective To determine the fetal safety of insulin glargine use in the treatment of diabetes in pregnancy compared with NPH insulin therapy. Methods A systematic review and meta-analysis was performed of all original human studies that reported neonatal outcomes among women with pregestational or gestational diabetes who were managed with either insulin glargine or NPH insulin during pregnancy. A systematic literature search was conducted using MEDLINE, EMBASE, CINAHL, the Cochrane Central Register for Controlled Trials database, and Web of Science from 1980 to June 1, 2010. Outcomes included large size for gestational age, macrosomia, neonatal hypoglycemia, neonatal intensive care unit admissions, birth trauma, congenital anomalies, preterm delivery, perinatal mortality, respiratory distress, and hyperbilirubinemia. Relative risk ratios and weighted mean differences were computed with 95% confidence intervals. Results: Eight studies reporting on a total of 702 women with pregestational or gestational diabetes in pregnancy treated with either insulin glargine (n = 331) or NPH insulin (n = 371) met the inclusion criteria. There were no statistically significant differences in the occurrence of fetal outcomes studied with the use of insulin glargine compared to NPH insulin. Conclusions: No evidence has been documented for increased adverse fetal outcomes with the use of insulin glargine in pregnancy compared to the use of NPH insulin. These results increase the choices for women requiring basal insulin therapy in pregnancy.

Association between serum 25‐hydroxyvitamin D in early pregnancy and risk of gestational diabetes mellitus

Diabet. Med. 29, e25–e32 (2012)

Maternal-fetal transport of hypoglycaemic drugs.

Due to legal, ethical and monetary problems, drug studies in pregnancy are rare. Numerous pharmacokinetic and pharmacodynamic changes occur in pregnancy that can affect the efficacy and safety of drugs, and these are difficult to predict without appropriate studies.Drugs potentially useful and safe in pregnancy have to either not cross the placenta and/or be harmless to the fetus at clinically relevant concentrations. The first characteristic can be predicted using in vitro models such as the placenta perfusion model. In the case of glibenclamide (glyburide), in vitro experiments showed minimal maternal-fetal transfer, leading to completion of a successful clinical trial of this drug in gestational diabetes. Insulin, the main drug used in diabetes during pregnancy, has also been shown not to cross the placenta in vitro, as has insulin lispro. Animal insulin may cross the placenta when complexed with anti-insulin antibodies. Other sulphonylurea drugs (tolbutamide and chlorpropamide) have been shown to cross the placenta both in vitro and in vivo and to produce toxicity in the fetus.This review summarises the pharmacokinetic data available for hypoglycaemic drugs during pregnancy, as well as the potential role for the in vitro placenta perfusion model in the preclinical evaluation of drugs with potential usefulness in pregnancy.

Screening for type 2 diabetes mellitus to prevent vascular complications: updated recommendations from the Canadian Task Force on Preventive Health Care

In developing these recommendations, the Canadian Task Force on Preventive Health Care drew heavily on a recent systematic review prepared for the US Preventive Services Task Force of the evidence for screening asymptomatic people for type 2 diabetes mellitus to prevent cardiovascular events.[1][1]