Early Metformin in Gestational Diabetes: A Randomized Clinical Trial.

Importance: Gestational diabetes is a common complication of pregnancy and the optimal management is uncertain. Objective: To test whether early initiation of metformin reduces insulin initiation or improves fasting hyperglycemia at gestation weeks 32 or 38. Design, Setting, and Participants: Double-blind, placebo-controlled trial conducted in 2 centers in Ireland (one tertiary hospital and one smaller regional hospital). Participants were enrolled from June 2017 through September 2022 and followed up until 12 weeks' postpartum. Participants comprised 510 individuals (535 pregnancies) diagnosed with gestational diabetes based on World Health Organization 2013 criteria. Interventions: Randomized 1:1 to either placebo or metformin (maximum dose, 2500 mg) in addition to usual care. Main Outcomes And Measures: The primary outcome was a composite of insulin initiation or a fasting glucose level of 5.1 mmol/L or greater at gestation weeks 32 or 38. Results: Among 510 participants (mean age, 34.3 years), 535 pregnancies were randomized. The primary composite outcome was not significantly different between groups and occurred in 150 pregnancies (56.8%) in the metformin group and 167 pregnancies (63.7%) in the placebo group (between-group difference, -6.9% [95% CI, -15.1% to 1.4%]; relative risk, 0.89 [95% CI, 0.78-1.02]; P = .13). Of 6 prespecified secondary maternal outcomes, 3 favored the metformin group, including time to insulin initiation, self-reported capillary glycemic control, and gestational weight gain. Secondary neonatal outcomes differed by group, with smaller neonates (lower mean birth weights, a lower proportion weighing >4 kg, a lower proportion in the >90% percentile, and smaller crown-heel length) in the metformin group without differences in neonatal intensive care needs, respiratory distress requiring respiratory support, jaundice requiring phototherapy, major congenital anomalies, neonatal hypoglycemia, or proportion with 5-minute Apgar scores less than 7. Conclusion and relevance: Early treatment with metformin was not superior to placebo for the composite primary outcome. Prespecified secondary outcome data support further investigation of metformin in larger clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02980276; EudraCT: 2016-001644-19.

Atlantic DIP: is weight gain less than that recommended by IOM safe in obese women with gestational diabetes mellitus?

BACKGROUND/OBJECTIVES: The Institute of Medicine (IOM) recommends gestational weight gain (GWG) of 5-9 kg in women with a body mass index (BMI) ≥ 30 kg/m2. Debate continues as to whether GWG less than that recommended is safe in women with gestational diabetes mellitus (GDM). The study objective was to examine maternal and infant outcomes for obese women with GDM who lost weight or gained 0-5 kg during pregnancy. SUBJECTS/METHODS: A 7-year retrospective cohort study of pregnancy outcomes for obese women with GDM recorded in the Atlantic Diabetes in Pregnancy database was conducted. We examined pregnancy outcomes for mothers with GDM and a BMI ≥ 30 who either lost weight or gained 0-5 kg (Group 1, n = 237) and women who gained 5-9 kg (Group 2, n = 77). We further divided groups 1 and 2 into women treated by diet only (GDM-D) (n = 120) and those requiring additional treatment with insulin (GDM-I) (n = 194). RESULTS: GDM-D women in Group 1 were more likely to deliver earlier (38.9 vs 39.8 weeks, p < 0.01), to develop pregnancy induced hypertension (PIH) (15.4% v 0%; p = 0.02) or have a post-partum haemorrhage (PPH) (13.2% vs 0, p = 0.03) compared to women in Group 2. Rates of prematurity were higher in group 1 vs 2 (14.3% vs 0%, p = 0.03). However, further logistic regression analysis adjusted for smoking status, family history of diabetes, ethnicity and age determined no significant difference in maternal or infant outcomes for women in Group 1 compared to those in Group 2. CONCLUSION: In our population, weight gain less than IOM guideline appears safe and is not associated with any further increase in adverse outcomes. However, validation through a prospective study with a larger obese GDM cohort is required before the findings presented here could be recommended for routine clinical use.

Sleep duration and physical function in people with severe obesity: a prospective cross-sectional study.

BACKGROUND: Subjects with severe obesity (BMI > 40 kg/m2) have worse physical function and sleep less than lean people (BMI 18.5-25 kg/m2). METHODS: In 554 subjects with severe obesity, we compared physical function in those with normal sleep duration (NSD, 6-9 h/night), short sleep duration (SSD, ≤ 6 h/night) and long sleep duration (LSD, ≥ 9 h/night). RESULTS: The mean (±SD) age and BMI were 43.1 (± 11.1) years and 50.9 ± 8.6 kg/m2 respectively. One hundred ninety-six (35.4%) were male. More subjects in the NSD group (n = 256) were able to ascend and descend a step 50 times than in the SSD group (n = 247) or the LSD group (n = 51, 75.5% vs 62.8% vs 56.9%, p = 0.002). A similar observation was made for step speed (0.45 ± 0.11 vs 0.43 ± 0.10 vs 0.40 ± 0.11 steps/s respectively, p = 0.001). NSD participants were less likely to have fallen in the preceding year compared to LSD participants (21.1% vs 39.2%, p = 0.007) and also reported less low back pain compared to SSD participants (60.8% vs 75.9%, p = 0.004). CONCLUSIONS: In conclusion, abnormal sleep duration is associated with reduced physical function in non-elderly severely obese subjects. The effects of sleep hygiene interventions in this cohort warrant further assessment and may be beneficial to their physical function.

Pregnancy in acromegaly is safe and is associated with improvements in IGF-1 concentrations.

Pregnancy is rarely reported in acromegaly. Many patients are diagnosed in later life and younger patients may have subfertility due to hypopituitarism. We present a case series of 17 pregnancies in 12 women with acromegaly. Twelve women with acromegaly who completed pregnancy were identified from centres involved in the Irish Pituitary Study. Eleven women had pituitary macroadenomas and one woman had a microadenoma. Only 5/17 pregnancies had optimal biochemical control of acromegaly preconception, as defined by IGF-1 concentration in the age-related reference level and plasma GH concentration of <2 µg/L. In 6/17 pregnancies, dopamine agonist treatment was continued during pregnancy; all other acromegaly treatments were discontinued during pregnancy. Effect of pregnancy on acromegaly: No patient developed new visual field abnormalities, or symptoms suggestive of tumour expansion during pregnancy. In 9/12 patients, plasma IGF-1 concentrations that were elevated preconception normalised during pregnancy. There was a reduction in plasma IGF-1 concentrations, though not into the normal range, in a further two pregnancies. Effect of acromegaly on pregnancy: 15 healthy babies were born at term; one patient underwent emergency C-section at 32 weeks for pre-eclampsia, and one twin pregnancy had an elective C-section at 35 weeks' gestation. Blood pressure remained within normal limits in the remainder of the pregnancies. Gestational diabetes did not develop in any pregnancy. Our data suggests that pregnancy in women with acromegaly is generally safe, from a maternal and foetal perspective. Furthermore, biochemical control tends to improve despite the withdrawal of somatostatin analogue therapy during pregnancy.