Person:

James-Todd, Tamarra

Background: In severely obese type 2 diabetes patients, gastric bypass surgery (GB) reduces body mass index (BMI) and hemoglobin A1c (HbA1c) and allows reduced doses of insulin and other medications. Data regarding the effects of GB on severely obese patients with type 1 diabetes are limited. Methods: Severely obese women with type 1 diabetes (n = 9) were studied immediately before and after GB (7.7 ± 5.8 weeks, mean ± SD). Results: On average, GB reduced mean BMI by 11 % and mean HbA1c by 0.9 % (from 8.0 to 7.1 %), with a parallel 38 % decrease in basal insulin requirements (expressed per kilogram of body weight). Conclusion: GB rapidly decreased BMI, HbA1c, and insulin requirements in severely obese women with type 1 diabetes. However, physiologic insulin replacement remains necessary in patients with type 1 diabetes.

Background: More women are entering pregnancy with pre-existing diabetes. Disease severity, glycaemic control, and predictors of pregnancy complications may differ by race/ethnicity or educational attainment, leading to differences in adverse pregnancy outcomes. Methods: We used linked New York City hospital record and birth certificate data for 6291 singleton births among women with pre-existing diabetes between 1995 and 2003. We defined maternal race/ethnicity as non-Hispanic white, non-Hispanic black, Hispanic, South Asian, and East Asian, and education level as <12, 12, and >12 years. Our outcomes were pre-eclampsia, preterm birth (PTB) (<37 weeks gestation and categorised as spontaneous or medically indicated), as well as small-for-gestational age (SGA) and large-for-gestational age (LGA). Using multivariable binomial regression, we estimated the risk ratios for pre-eclampsia, SGA, and LGA. We used multivariable multinomial regression to estimate odds ratios (OR) for PTB. Results: Compared with non-Hispanic white women with pre-existing diabetes, non-Hispanic black and Hispanic women with pre-existing diabetes had a 1.50-fold increased risk of pre-eclampsia compared with non-Hispanic whites with pre-existing diabetes, after full adjustment. Non-Hispanic black and Hispanic women with pre-existing diabetes had adjusted ORs of 1.72 [adj. 95% confidence interval (CI) 1.38, 2.15] and 1.65 [adj.95% CI 1.32, 2.05], respectively, for medically indicated PTB. South Asian women with pre-existing diabetes had the highest risk for having an SGA infant [adj. OR: 2.29; adj. 95% CI 1.73, 3.03]. East Asian ethnicity was not associated with these pregnancy complications. Conclusions: Non-Hispanic black, Hispanic, and South Asian women with pre-existing diabetes may benefit from targeted interventions to improve pregnancy outcomes.

Aim To examine the association of pre-pregnancy BMI and postpartum weight retention with postpartum HbA1c levels in women with Type 1 diabetes.

Methods We longitudinally evaluated 136 women with Type 1 diabetes who received prenatal, pregnancy, and postpartum care through Joslin Diabetes Center's Diabetes and Pregnancy Program between 2004 and 2009. Weight, BMI and HbA1c concentrations were assessed before the index pregnancy and repeatedly monitored after delivery until 12 months postpartum. We used linear mixed models to assess the association of postpartum HbA1c with pre-pregnancy BMI and postpartum weight retention.

Results The mean HbA1c concentration increased from 49 mmol/mol (6.6%) at 6 weeks postpartum to 58 mmol/mol (7.5%) by 10 months postpartum, a level similar to the mean pre-pregnancy HbA1c concentration. Postpartum weight retention showed a linearly decreasing trend of 0.06 kg/week (P < 0.0001), with −0.1 kg average postpartum weight retention by 1 year postpartum. Compared with women with a pre-pregnancy BMI ≥ 25 kg/m2, women with a lower pre-pregnancy BMI maintained a 3.4 mmol/mol (0.31%) lower HbA1c concentration, after adjusting for several sociodemographic, reproductive and diabetes-related factors (P = 0.03). There was a suggestion of a time-varying positive association between HbA1c and postpartum weight retention, with the most significant difference of 3.7 mmol/mol (0.34%; P = 0.05) at 30 weeks postpartum among women with postpartum weight retention ≥ 5 kg vs those with postpartum weight retention < 5 kg.

Conclusions Pre-pregnancy BMI and postpartum weight retention were positively associated with HbA1c during the first postpartum year in women with Type 1 diabetes. Interventions to modify the behaviours associated with these body weight factors before pregnancy and after delivery may help women with Type 1 diabetes maintain good glycaemic control after pregnancy.

Objective: To assess whether glycemic control, soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) were associated with the development of preeclampsia (PE) or gestational hypertension (GHTN) in women with preexisting diabetes. Methods: Maternal circulating angiogenic factors (sFlt1 and PlGF) measured on automated platform were studied at four time points during pregnancy in women with diabetes (N = 159) and reported as multiples of the median (MOM) of sFlt1/PlGF ratio (median, 25th–75th percentile) noted in non-diabetic non-hypertensive control pregnant population (N = 139). Diagnosis of PE or GHTN was determined by review of de-identified clinical data. Results: PE developed in 12% (N = 19) and GHTN developed in 23% (N = 37) of the women with diabetes. Among diabetic women without PE or GHTN, median sFlt1/PlGF levels at 35–40 weeks was threefold higher than in non-diabetic controls [MOM 3.21(1.19–7.24), p = 0.0001]. Diabetic women who subsequently developed PE had even greater alterations in sFlt1/PlGF ratio during the third trimester [MOM for PE at 27–34 weeks 15.18 (2.37–26.86), at 35–40 weeks 8.61(1.20–18.27), p ≤ 0.01 for both windows compared to non-diabetic controls]. Women with diabetes who subsequently developed GHTN also had significant alterations in angiogenic factors during third trimester; however, these findings were less striking. Among women with diabetes, glycosylated hemoglobin (HbA1c) during the first trimester was higher in subjects who subsequently developed PE (7.7 vs 6.7%, p = 0.0001 for diabetic PE vs diabetic non-PE). Conclusions: Women with diabetes had a markedly altered anti-angiogenic state late in pregnancy that was further exacerbated in subjects who developed PE. Altered angiogenic factors may be one mechanism for the increased risk of PE in this population. Increased HbA1c in the first trimester of pregnancies in women with diabetes was strongly associated with subsequent PE.

Objective: Determine the independent association between time-specific placental growth factor (PIGF)—a marker of placental vasculature—and infant birth weight in offspring of mothers with preexisting type 1 and 2 diabetes. Methods: A total of 150 women were recruited from Joslin Diabetes Center’s/Beth Israel Deaconess Medical Center’s Diabetes in Pregnancy Program. PlGF was measured up to four times during pregnancy. Infant birth weight and covariate data were collected from medical records. Hemoglobin A1c was assessed from drawn blood samples. We used generalized linear and log-binomial models to calculate the change in continuous birth weight, as well as macrosomia for every unit change in time-specific ln-transformed PlGF, respectively. Models were adjusted for potential confounders. Results: Approximately 75% of women had type 1 diabetes. Third trimester PlGF levels were significantly associated with infant birth weight (r = 0.24, p = 0.02 at 27–34 weeks; r = 0.26, p < 0.009 for 36–40 weeks). After full adjustment, there was a 6.1% and 6.6% increase in birth weight for gestational age percentile for each unit increase in ln-transformed PlGF level at 27–34 weeks and 35–40 weeks, respectively (95% CI for 27–34 weeks gestation: 1.1, 11.0, and 95% CI for 35–40 weeks gestation: 0.7%, 12.5%). We found a statistically significant increased risk of macrosomia among women with higher ln-transformed PlGF levels (RR: 1.72; 95% CI: 1.09, 2.70). Associations were not mediated by hemoglobin A1c. Conclusions: Third trimester PlGF levels were associated with higher birth weight in women with preexisting diabetes. These findings may provide insight to the pathophysiology of fetal overgrowth in women with diabetes.