Lene Ringholm

The Effect of Real-Time Continuous Glucose Monitoring in Pregnant Women With Diabetes: A randomized controlled trial

OBJECTIVE To assess whether intermittent real-time continuous glucose monitoring (CGM) improves glycemic control and pregnancy outcome in unselected women with pregestational diabetes. RESEARCH DESIGN AND METHODS A total of 123 women with type 1 diabetes and 31 women with type 2 diabetes were randomized to use real-time CGM for 6 days at 8, 12, 21, 27, and 33 weeks in addition to routine care, including self-monitored plasma glucose seven times daily, or routine care only. To optimize glycemic control, real-time CGM readings were evaluated by a diabetes caregiver. HbA1c, self-monitored plasma glucose, severe hypoglycemia, and pregnancy outcomes were recorded, with large-for-gestational-age infants as the primary outcome. RESULTS Women assigned to real-time CGM (n = 79) had baseline HbA1c similar to that of women in the control arm (n = 75) (median 6.6 [range 5.3–10.0] vs. 6.8% [5.3–10.7]; P = 0.67) (49 [34–86] vs. 51 mmol/mol [34–93]). Forty-nine (64%) women used real-time CGM per protocol. At 33 weeks, HbA1c (6.1 [5.1–7.8] vs. 6.1% [4.8–8.2]; P = 0.39) (43 [32–62] vs. 43 mmol/mol [29–66]) and self-monitored plasma glucose (6.2 [4.7–7.9] vs. 6.2 mmol/L [4.9–7.9]; P = 0.64) were comparable regardless of real-time CGM use, and a similar fraction of women had experienced severe hypoglycemia (16 vs. 16%; P = 0.91). The prevalence of large-for-gestational-age infants (45 vs. 34%; P = 0.19) and other perinatal outcomes were comparable between the arms. CONCLUSIONS In this randomized trial, intermittent use of real-time CGM in pregnancy, in addition to self-monitored plasma glucose seven times daily, did not improve glycemic control or pregnancy outcome in women with pregestational diabetes.

Pregnancy-induced sight-threatening diabetic retinopathy in women with Type 1 diabetes

Diabet. Med. 27, 431–435 (2010)

Pregnancy in women with type 1 diabetes: Have the goals of St. Vincent declaration been met concerning foetal and neonatal complications?

Abstract Objective: In 1989 the St. Vincent declaration set a five-year target for approximating outcomes of pregnancies in women with diabetes to those of the background population. We investigated and quantified the risk of adverse pregnancy outcomes in pregnant women with type 1 diabetes (T1DM) to evaluate if the goals of the 1989 St. Vincent Declaration have been obtained concerning foetal and neonatal complications. Methods: Twelve population-based studies published within the last 10 years with in total 14 099 women with T1DM and 4 035 373 women from the background population were identified. The prevalence of four foetal and neonatal complications was compared. Results: In women with T1DM versus the background population, congenital malformations occurred in 5.0% (2.2–9.0) (weighted mean and range) versus 2.1% (1.5–2.9), relative risk (RR) = 2.4, perinatal mortality in 2.7% (2.0–6.6) versus 0.72% (0.48–0.9), RR = 3.7, preterm delivery in 25.2% (13.0–41.7) versus 6.0% (4.7–7.1), RR = 4.2 and delivery of large for gestational infants in 54.2% (45.1–62.5) versus 10.0%, RR = 4.5. Early pregnancy HbA1c was positively associated with adverse pregnancy outcomes. Conclusion: The risk of adverse pregnancy outcomes was two to five times increased in women with T1DM compared with the general population. The goals of the St. Vincent declaration have not been achieved.

Hypoglycaemia during pregnancy in women with Type 1 diabetes

Diabet. Med. 29, 558–566 (2012)

Stillbirth in diabetic pregnancies

Pregnancy in women with pregestational diabetes is associated with high perinatal morbidity and mortality. Stillbirth accounts for the majority of cases with perinatal death. Intrauterine growth restriction, pre-eclampsia, foetal hypoxia and congenital malformations may be contributing factors, but more than 50% of stillbirths are unexplained. Majority of stillbirths are characterised by suboptimal glycaemic control during pregnancy. Foetal hypoxia and cardiac dysfunction secondary to poor glycaemic control are probably the most important pathogenic factors in stillbirths among pregnant diabetic women. There is thus a need for new strategies for improving glycaemic control to near-normal levels throughout pregnancy and for preventing and treating hypertensive disorders in pregnancy. Antenatal surveillance tests including ultrasound examinations of the foetal growth rate, kick counting and non-stress testing of foetal cardiac function are widely used. However, future research should establish better antenatal surveillance tests to identify the infants susceptible to stillbirth before it happens.

Higher Gestational Weight Gain Is Associated With Increasing Offspring Birth Weight Independent of Maternal Glycemic Control in Women With Type 1 Diabetes

OBJECTIVE We evaluate the association between gestational weight gain and offspring birth weight in singleton term pregnancies of women with type 1 diabetes. RESEARCH DESIGN AND METHODS One hundred fifteen consecutive women referred at <14 weeks were retrospectively classified as underweight (prepregnancy BMI <18.5 kg/m2; n = 1), normal weight (18.5–24.9; n = 65), overweight (25.0–29.9; n = 39), or obese (≥30.0; n = 10). Gestational weight gain was categorized as excessive, appropriate, or insufficient according to the Institute of Medicine recommendations for each BMI class. Women with nephropathy, preeclampsia, and/or preterm delivery were excluded because of restrictive impact on fetal growth and limited time for total weight gain. RESULTS HbA1c was comparable at ∼6.6% (49 mmol/mol) at 8 weeks and ∼6.0% (42 mmol/mol) at 36 weeks between women with excessive (n = 62), appropriate (n = 37), and insufficient (n = 16) gestational weight gain. Diabetes duration was comparable, and median prepregnancy BMI was 25.3 (range 18–41) vs. 23.5 (18–31) vs. 22.7 (20–30) kg/m2 (P = 0.05) in the three weight gain groups. Offspring birth weight and birth weight SD score decreased across the groups (3,681 [2,374–4,500] vs. 3,395 [2,910–4,322] vs. 3,295 [2,766–4,340] g [P = 0.02] and 1.08 [−1.90 to 3.25] vs. 0.45 [−0.83 to 3.18] vs. −0.02 [−1.51 to 2.96] [P = 0.009], respectively). In a multiple linear regression analysis, gestational weight gain (kg) was positively associated with offspring birth weight (g) (β = 19; P = 0.02) and birth weight SD score (β = 0.06; P = 0.008) when adjusted for prepregnancy BMI, HbA1c at 36 weeks, smoking, parity, and ethnicity. CONCLUSIONS Higher gestational weight gain in women with type 1 diabetes was associated with increasing offspring birth weight independent of glycemic control and prepregnancy BMI.

Managing type 1 diabetes mellitus in pregnancy—from planning to breastfeeding

Type 1 diabetes mellitus in pregnant women increases the risk of adverse outcomes for mother and offspring. Careful preconception counselling and screening is important, with particular focus on glycaemic control, indications for antihypertensive therapy, screening for diabetic nephropathy, diabetic retinopathy and thyroid dysfunction, as well as review of other medications. Supplementation with folic acid should be initiated before conception in order to minimize the risk of fetal malformations. Obtaining and maintaining tight control of blood glucose and blood pressure before and during pregnancy is crucial for optimizing outcomes; however, the risk of severe hypoglycaemia during pregnancy is a major obstacle. Although pregnancy does not result in deterioration of kidney function in women with diabetic nephropathy and normal serum creatinine levels, pregnancy complications such as pre-eclampsia and preterm delivery are more frequent in these women than in women with T1DM and normal kidney function. Rapid-acting insulin analogues are considered safe to use in pregnancy and studies on long-acting insulin analogues have provided reassuring results. Immediately after delivery the insulin requirement declines to approximately 60% of the prepregnancy dose, and remains 10% lower than before pregnancy during breastfeeding.

Fetal growth in relation to gestational weight gain in women with type 2 diabetes: an observational study.

To evaluate fetal growth in relation to gestational weight gain in women with Type 2 diabetes.

Obstetric Nephrology: Pregnancy in Women with Diabetic Nephropathy—The Role of Antihypertensive Treatment

This review highlights factors of importance for the clinical care of pregnant women with pregestational diabetes and microalbuminuria or diabetic nephropathy with particular focus on the role of intensive antihypertensive treatment during pregnancy. Most information in the literature comes from women with type 1 diabetes and diabetic nephropathy, but this is probably also valid for women with type 2 diabetes. Careful counseling of women with diabetic nephropathy before pregnancy with estimation of the risk for the mother and fetus is important. Pregnancy does not result in worsening of kidney function in women with diabetic nephropathy and normal serum creatinine, but pregnancy complications such as pre-eclampsia and preterm delivery are common. Intensive metabolic control before and during pregnancy, low-dose aspirin from 12 gestational weeks onward, and intensive antihypertensive treatment are important. Methyldopa, labetalol, and nifedipine are regarded safe in pregnancy, whereas angiotensin converting enzyme inhibitors, AngII antagonists, or statins should be paused before pregnancy. Case series and pathophysiological studies support the use of a stringent goal for BP and albumin excretion in pregnant women with diabetic nephropathy. Screening for diabetic retinopathy before and during pregnancy is mandatory and laser treatment should be performed if indicated. Pregnancy outcome in women with diabetic nephropathy has improved considerably with a take-home-baby rate of approximately 95%. Further research on the benefits and risks of intensive antihypertensive treatment in this population is needed.

Patient satisfaction and barriers to initiating real-time continuous glucose monitoring in early pregnancy in women with diabetes

Diabet. Med. 29, 272–277 (2012)