Breastfeeding at night is rarely followed by hypoglycaemia in women with type 1 diabetes using carbohydrate counting and flexible insulin therapy.

AIMS/HYPOTHESIS: Hypoglycaemia in association with breastfeeding is a feared condition in mothers with type 1 diabetes. Thus, routine carbohydrate intake at each breastfeed, particularly at night, is often recommended despite lack of evidence. We aimed to evaluate glucose levels during breastfeeding, focusing on whether night-time breastfeeding induced hypoglycaemia in mothers with type 1 diabetes. METHODS: Of 43 consecutive mothers with type 1 diabetes, 33 (77%) were included prospectively 1 month after a singleton delivery. Twenty-six mothers (mean [SD] age 30.7 [5.8] years, mean [SD] duration of diabetes 18.6 [10.3] years) were breastfeeding and seven mothers (mean [SD] age 31.7 [5.6] years, mean [SD] duration of diabetes 20.4 [6.2] years) were bottle-feeding their infants with formula. All were experienced in carbohydrate counting using individually tailored insulin therapy with insulin analogues (45% on insulin pump, 55% on multiple daily injections). Thirty-two women with type 1 diabetes, matched for age ±1 year and BMI ±1 kg/m2, who had not given birth or breastfed in the previous year, served as a control group. Blinded continuous glucose monitoring (CGM) for 6 days was applied at 1, 2 and 6 months postpartum in the breastfeeding mothers who recorded breastfeeds and carbohydrate intake at each CGM period. CGM was applied at 1 month postpartum in the formula-feeding mothers and once in the control women. The insulin dose was individually tailored after each CGM period. RESULTS: The percentage of night-time spent with CGM <4.0 mmol/l was low (4.6%, 3.1% and 2.7% at each CGM period in the breastfeeding mothers vs 1.6% in the control women, p = 0.77), and the breastfeeding mothers spent a greater proportion of the night-time in the target range of 4.0-10.0 mmol/l (p = 0.01). Symptomatic hypoglycaemia occurred two or three times per week at 1, 2 and 6 months postpartum in both breastfeeding mothers and the control women. Severe hypoglycaemia was reported by one mother (3%) during the 6 month postpartum period and by one control woman (3%) in the previous year (p = 0.74). In breastfeeding mothers at 1 month, the insulin dose was 18% (-67% to +48%) lower than before pregnancy (p = 0.04). In total, carbohydrate was not consumed in relation to 438 recorded night-time breastfeeds, and CGM <4.0 mmol/l within 3 h occurred after 20 (4.6%) of these breastfeeds. CONCLUSIONS/INTERPRETATION: The percentage of night-time spent in hypoglycaemia was low in the breastfeeding mothers with type 1 diabetes and was similar in the control women. Breastfeeding at night-time rarely induced hypoglycaemia. The historical recommendation of routine carbohydrate intake at night-time breastfeeding may be obsolete in mothers with type 1 diabetes who have properly reduced insulin dose with sufficient carbohydrate intake. TRIAL REGISTRATION: ClinicalTrials.gov NCT02898428.

The impact of restricted gestational weight gain by dietary intervention on fetal growth in women with gestational diabetes mellitus.

AIMS/HYPOTHESIS: We aimed to investigate the impact of maternal gestational weight gain (GWG) during dietary treatment on fetal growth in pregnancies complicated by gestational diabetes (GDM). METHODS: This was a retrospective cohort study of 382 women consecutively diagnosed with GDM before 34 weeks' gestation with live singleton births in our centre (Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark) between 2011 and 2017. The women were stratified into three groups according to restricted (53%), appropriate (16%) and excessive (31%) weekly GWG during dietary treatment (using the Institute of Medicine guidelines) to estimate compliance with an energy-restricted 'diabetes diet' (6000 kJ/day [1434 kcal/day], with approximately 50% of energy intake coming from carbohydrates with a low glycaemic index, and a carbohydrate intake of 175 g/day). Insulin therapy was initiated if necessary, according to local clinical guidelines. RESULTS: Glucose tolerance, HbA1c, weekly GWG before dietary treatment (difference between weight at GDM diagnosis and pre-pregnancy weight, divided by the number of weeks) and SD score for fetal abdominal circumference were comparable across the three groups at diagnosis of GDM at 276 ± 51 weeks (gestation time is given as weeksdays). The women were followed for 100 ± 51 weeks, during which 54% received supplementary insulin therapy and the average (mean) GWG during dietary treatment was 0 kg, 3 kg and 5 kg in the three groups, respectively. Excessive weekly GWG during dietary treatment, reflecting poor dietary adherence was associated with increasing HbA1c (p = 0.014) from diagnosis of GDM to late pregnancy and infants with a birthweight-SD score of 0.59 ± 1.6. In contrast, restricted weekly GWG during dietary treatment, reflecting strict dietary adherence, was associated with decreasing HbA1c (p = 0.001) from diagnosis of GDM to late pregnancy and infants with a birthweight-SD score of 0.15 ± 1.1, without increased prevalence of infants born small for gestational age. Excessive GWG during dietary treatment and late-pregnancy HbA1c were identified as potentially modifiable clinical predictors of infant birthweight-SD score (p = 0.02 for both variables) after correction for confounders. CONCLUSIONS/INTERPRETATION: Restricted GWG during dietary treatment was associated with healthier fetal growth in women with GDM. GWG during dietary treatment and late-pregnancy HbA1c were identified as potentially modifiable clinical predictors of infant birthweight-SD score.

Translating HbA1c measurements into estimated average glucose values in pregnant women with diabetes.

AIMS/HYPOTHESIS: This study aimed to examine the relationship between average glucose levels, assessed by continuous glucose monitoring (CGM), and HbA1c levels in pregnant women with diabetes to determine whether calculations of standard estimated average glucose (eAG) levels from HbA1c measurements are applicable to pregnant women with diabetes. METHODS: CGM data from 117 pregnant women (89 women with type 1 diabetes; 28 women with type 2 diabetes) were analysed. Average glucose levels were calculated from 5-7 day CGM profiles (mean 1275 glucose values per profile) and paired with a corresponding (±1 week) HbA1c measure. In total, 688 average glucose-HbA1c pairs were obtained across pregnancy (mean six pairs per participant). Average glucose level was used as the dependent variable in a regression model. Covariates were gestational week, study centre and HbA1c. RESULTS: There was a strong association between HbA1c and average glucose values in pregnancy (coefficient 0.67 [95% CI 0.57, 0.78]), i.e. a 1% (11 mmol/mol) difference in HbA1c corresponded to a 0.67 mmol/l difference in average glucose. The random effects model that included gestational week as a curvilinear (quadratic) covariate fitted best, allowing calculation of a pregnancy-specific eAG (PeAG). This showed that an HbA1c of 8.0% (64 mmol/mol) gave a PeAG of 7.4-7.7 mmol/l (depending on gestational week), compared with a standard eAG of 10.2 mmol/l. The PeAG associated with maintaining an HbA1c level of 6.0% (42 mmol/mol) during pregnancy was between 6.4 and 6.7 mmol/l, depending on gestational week. CONCLUSIONS/INTERPRETATION: The HbA1c-average glucose relationship is altered by pregnancy. Routinely generated standard eAG values do not account for this difference between pregnant and non-pregnant individuals and, thus, should not be used during pregnancy. Instead, the PeAG values deduced in the current study are recommended for antenatal clinical care.

Vitamin D insufficiency, preterm delivery and preeclampsia in women with type 1 diabetes - an observational study.

INTRODUCTION: The aim of this study was to evaluate whether vitamin D insufficiency is associated with preterm delivery and preeclampsia in women with type 1 diabetes. MATERIAL AND METHODS: An observational study of 198 pregnant women with type 1 diabetes. 25-Hydroxy-Vitamin D and HbA1c were measured in blood samples in early (median 8 weeks, range 5-14) and late (34 weeks, range 32-36) pregnancy. Kidney involvement (microalbuminuria or nephropathy) at inclusion, smoking status at inclusion, preterm delivery (<37 weeks) and preeclampsia (blood pressure ≥140/90 mmHg and proteinuria) were registered. Vitamin D supplementation of 10 µg daily was routinely recommended. RESULTS: Thirty-nine (20%) of the 198 women delivered preterm and 16 (8%) developed preeclampsia. Vitamin D insufficiency (<50 nmol/L) was present in 68 women (34%) in early pregnancy and in 73 women (37%) in late pregnancy. Preterm delivery occurred more frequently in women with vitamin D insufficiency in late pregnancy (27% vs. 15%, crude odds ratio 2.1; 95% confidence interval 1.0-4.3, p = 0.04). After adjustment for preexisting kidney involvement, HbA1c in late pregnancy and smoking the association became nonsignificant (adjusted odds ratio 1.8; 95% confidence interval 0.8-3.7). Preeclampsia developed in 11% of women with vitamin D insufficiency vs. 6% of the remaining women (crude odds ratio 1.8; 95% confidence interval 0.9-4.1, p = 0.25). CONCLUSION: In women with type 1 diabetes, preterm delivery was twice as frequent in women with vitamin D insufficiency in late pregnancy in crude analysis, but in this small study, low vitamin D was not independently associated with preterm birth or preeclampsia.

Quality of life, anxiety and depression symptoms in early and late pregnancy in women with pregestational diabetes.

INTRODUCTION: The aim of this study was to explore changes in health-related quality of life, anxiety and depression symptoms during pregnancy in women with pregestational diabetes. MATERIAL AND METHODS: An observational cohort study including 137 pregnant women with pregestational diabetes (110 with type 1 and 27 with type 2). To evaluate changes from early to late pregnancy, the internationally validated questionnaires 36-Item Short-Form Health Survey (SF-36) and Hospital Anxiety and Depression Scale (HADS) were completed at 8 and 33 gestational weeks. RESULTS: From early to late pregnancy, the SF-36 scales Physical Function, Role Physical, Bodily Pain and Physical Component Summary worsened (p < 0.0001 for all scales). Physical Component Summary score deteriorated from mean 52.3 (SD 6.5) to 40.0 (9.7) (p < 0.0001) and the deterioration was negatively associated with gestational weight gain in multiple linear regression (ß = -0.34/kg, p = 0.03). The SF-36 scale Mental Health improved (p = 0.0009) and the Mental Component Summary score increased moderately from 47.6 (10.6) to 53.5 (8.6) (p < 0.0001). Greater improvement in Mental Component Summary score was seen with lower HbA1c in late pregnancy. The HADS anxiety score improved slightly from 5.0 (3.3) to 4.5 (3.4) (p = 0.04) whereas the HADS depression score remained unchanged. The prevalence of women with HADS anxiety or depression score ≥8 did not change. CONCLUSIONS: Physical quality of life deteriorated whereas mental quality of life improved slightly during pregnancy in women with pregestational diabetes. A minor reduction in anxiety and stable depression symptoms was observed. The results on mental health are reassuring, considering the great demands that pregnancy places on women with pregestational diabetes.

Fetal sonographic characteristics associated with shoulder dystocia in pregnancies of women with type 1 diabetes.

INTRODUCTION: Shoulder dystocia is a rare but severe complication of vaginal delivery and diabetic women are at high risk. The aim of this study was to identify fetal sonographic and maternal glycemic characteristics associated with shoulder dystocia in pregnant women with type 1 diabetes. MATERIAL AND METHODS: Twelve cases (5%) of shoulder dystocia among 241 consecutive vaginal deliveries in women with type 1 diabetes followed at Rigshospitalet University Hospital in 2009-2013 were retrospectively identified in a local database. Fetal sonographic and clinical data were compared with 69 women with type 1 diabetes and uncomplicated vaginal deliveries. RESULTS: Women experiencing shoulder dystocia compared with women with uncomplicated deliveries had a higher glycated hemoglobin (HbA1c) in early pregnancy [median 7.0% (range 5.9-8.1) vs. 6.6% (range 5.4-10.0, P = 0.04)], whereas in late pregnancy, HbA1c in the two groups of women was comparable [6.1% (range 5.5-6.9) vs. 6.0% (range 4.7-8.4, P = 0.30)]. Fetal biometry at 36 weeks showed a higher estimated fetal weight of 3597 g (range 3051-4069) vs. 2989 g (range 2165-4025), P < 0.001, corresponding to 20% (4-41%) vs. 5% (-20 to 44%) above the mean estimated fetal weight for gestational age (P = 0.002) and a greater abdominal circumference SD score of 2.51 (range 1.56-4.20) vs. 1.33 (range -1.08 to 4.25), P = 0.001). Head circumference was comparable. Vacuum extraction was more frequent during deliveries with shoulder dystocia (58 vs. 17%, P = 0.005). Seven (58%) newborns with shoulder dystocia had brachial plexus injuries, fractures, intra-abdominal bleeding or needed resuscitation. CONCLUSIONS: Excessive estimated fetal weight and abdominal circumference at 36 weeks' sonographic examination may help in identifying diabetic women at high risk of later shoulder dystocia.

Continuous glucose monitoring-enabled insulin-pump therapy in diabetic pregnancy.

We describe the feasibility of continuous glucose monitoring (CGM)-enabled insulin-pump therapy during pregnancy in a woman with type 1 diabetes, who was treated with CGM-enabled insulin-pump therapy in her third pregnancy. During her first pregnancy, the woman was treated with multiple daily injections and baseline HbA1c was 8.9%. Due to pre-eclampsia, the child was born preterm, and had neonatal hypoglycemia. In the planning of the second pregnancy, insulin-pump therapy was initiated, resulting in an HbA1c of 6.8% in early pregnancy. Due to pre-eclampsia, the second child was born preterm, but without neonatal morbidity. Before her third pregnancy, CGM-enabled insulin-pump therapy was introduced, and HbA1c was 6.4% in early pregnancy. The patient was satisfied with this therapy, pre-eclampsia did not occur, and the child was born at term without neonatal morbidity. CGM-enabled insulin-pump therapy appears feasible in diabetic pregnancies.

Analysis of Continuous Glucose Monitoring in Pregnant Women With Diabetes: Distinct Temporal Patterns of Glucose Associated With Large-for-Gestational-Age Infants.

OBJECTIVE: Continuous glucose monitoring (CGM) is increasingly used to assess glucose control in diabetes. The objective was to examine how analysis of glucose data might improve our understanding of the role temporal glucose variation has on large-for-gestational-age (LGA) infants born to women with diabetes. RESEARCH DESIGN AND METHODS: Functional data analysis (FDA) was applied to 1.68 million glucose measurements from 759 measurement episodes, obtained from two previously published randomized controlled trials of CGM in pregnant women with diabetes. A total of 117 women with type 1 diabetes (n = 89) and type 2 diabetes (n = 28) who used repeated CGM during pregnancy were recruited from secondary care multidisciplinary obstetric clinics for diabetes in the U.K. and Denmark. LGA was defined as birth weight ≥90th percentile adjusted for sex and gestational age. RESULTS: A total of 54 of 117 (46%) women developed LGA. LGA was associated with lower mean glucose (7.0 vs. 7.1 mmol/L; P < 0.01) in trimester 1, with higher mean glucose in trimester 2 (7.0 vs. 6.7 mmol/L; P < 0.001) and trimester 3 (6.5 vs. 6.4 mmol/L; P < 0.01). FDA showed that glucose was significantly lower midmorning (0900-1100 h) and early evening (1900-2130 h) in trimester 1, significantly higher early morning (0330-0630 h) and throughout the afternoon (1130-1700 h) in trimester 2, and significantly higher during the evening (2030-2330 h) in trimester 3 in women whose infants were LGA. CONCLUSIONS: FDA of CGM data identified specific times of day that maternal glucose excursions were associated with LGA. It highlights trimester-specific differences, allowing treatment to be targeted to gestational glucose patterns.

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/m(2); 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/m(2) (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) (ß = 19; P = 0.02) and birth weight SD score (ß = 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.

Changes in basal rates and bolus calculator settings in insulin pumps during pregnancy in women with type 1 diabetes.

OBJECTIVE: To explore insulin pump settings in a cohort of pregnant women with type 1 diabetes on insulin pump therapy with a bolus calculator. METHODS: Twenty-seven women with type 1 diabetes on insulin pump therapy were included in this study. At 8, 12, 21, 27 and 33 weeks, insulin pump settings and HbA1c were recorded. Results were compared with 96 women with type 1 diabetes on multiple daily injection therapy. RESULTS: Throughout pregnancy, the carbohydrate-to-insulin ratio decreased at all three main meals. The most pronounced decrease was observed at breakfast, where the carbohydrate-to-insulin ratio was reduced, from median 12 (range 4-20) in early pregnancy to 3 (2-10) g carbohydrate per unit insulin in late pregnancy. Basal insulin delivery increased by ∼50%, i.e. from 0.8 (0.5-2.2) to 1.2 (0.6-2.5) IU/h at 5 a.m. and from 1.0 (0.6-1.5) to 1.3 (0.2-2.3) IU/h at 5 p.m. during pregnancy. HbA1c levels during pregnancy, the occurrence of severe hypoglycemia and pregnancy outcomes were similar in the two groups. CONCLUSIONS: In women with type 1 diabetes on insulin pump therapy with a bolus calculator, the carbohydrate-to-insulin ratio declined 4-fold from early to late pregnancy, whereas changes in basal insulin delivery were smaller.

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.

[Continuous glucose monitoring in pregnancies complicated by diabetes]. / Kontinuerlig glukosemonitorering kan have betydning hos gravide med diabetes.

In this review the use of continuous glucose monitoring (CGM) in pregnancy complicated by type 1 and type 2 diabetes is examined. Fourteen relevant articles were identified. Observational studies demonstrated that CGM was feasible during pregnancy without severe side effects. One randomised controlled trial resulted in improved metabolic control and reduced risk of macrosomia in women randomised to CGM. Future studies on the use of CGM in pregnancy are awaited with interest.