Associations of maternal BMI and insulin resistance with the maternal metabolome and newborn outcomes.

AIMS/HYPOTHESIS: Maternal obesity increases the risk for large-for-gestational-age birth and excess newborn adiposity, which are associated with adverse long-term metabolic outcomes in offspring, probably due to effects mediated through the intrauterine environment. We aimed to characterise the maternal metabolic milieu associated with maternal BMI and its relationship to newborn birthweight and adiposity. METHODS: Fasting and 1 h serum samples were collected from 400 European-ancestry mothers in the Hyperglycaemia and Adverse Pregnancy Outcome Study who underwent an OGTT at ∼28 weeks gestation and whose offspring had anthropometric measurements at birth. Metabolomics assays were performed using biochemical analyses of conventional clinical metabolites, targeted MS-based measurement of amino acids and acylcarnitines and non-targeted GC/MS. RESULTS: Per-metabolite analyses demonstrated broad associations with maternal BMI at fasting and 1 h for lipids, amino acids and their metabolites together with carbohydrates and organic acids. Similar metabolite classes were associated with insulin resistance with unique associations including branched-chain amino acids. Pathway analyses indicated overlapping and unique associations with maternal BMI and insulin resistance. Network analyses demonstrated collective associations of maternal metabolite subnetworks with maternal BMI and newborn size and adiposity, including communities of acylcarnitines, lipids and related metabolites, and carbohydrates and organic acids. Random forest analyses demonstrated contribution of lipids and lipid-related metabolites to the association of maternal BMI with newborn outcomes. CONCLUSIONS/INTERPRETATION: Higher maternal BMI and insulin resistance are associated with broad-based changes in maternal metabolites, with lipids and lipid-related metabolites accounting, in part, for the association of maternal BMI with newborn size at birth.

Genetics of Gestational Diabetes Mellitus and Maternal Metabolism.

Gestational diabetes mellitus (GDM) is defined as abnormal glucose tolerance with onset or first recognition during pregnancy. Women with a history of GDM are at long-term risk for developing type 2 diabetes (T2DM), raising the question to what extent GDM and T2DM share a common genetic architecture. Meta-analysis of candidate gene studies and genome-wide association analysis (GWAS) have identified a number of genes which are reproducibly associated with GDM, including TCF7L2, GCK, KCNJ11, KCNQ1, CDKAL1, IGF2BP2, MTNR1B, and IRS1. These genes are also associated with T2DM. Candidate gene and GWAS have also identified genes associated with maternal metabolic traits, most of which are also associated with metabolic traits in the general population. Two genes, BACE2 and HKDC1, are uniquely associated with maternal metabolic traits. These studies suggest that there are similarities and differences between the genetic architecture of GDM and T2DM and metabolic quantitative traits in pregnant and non-pregnant populations.

Recovery of pituitary function following treatment of an unruptured giant cavernous carotid aneurysm using Surpass flow-diverting stents.

Giant aneurysms arising from the cavernous internal carotid artery (ICA) can mimic pituitary adenomas and may cause pituitary dysfunction due to their mass effect on the pituitary gland. We report a case of a 56-year-old man presenting with impotence, fatigue and panhypopituitarism who was found to have a giant unruptured aneurysm arising from the right cavernous ICA with severe mass effect on the pituitary gland. The patient underwent endovascular treatment of the giant aneurysm using two telescoping Surpass flow-diverting stents. At 6-month follow-up, repeat cerebral angiography showed Raymond grade II occlusion of the aneurysm with a small neck remnant. At the 10-month follow-up the patient showed full recovery of his pituitary function and clinical resolution of impotence and fatigue. This is the first report of occlusion of a giant cavernous carotid aneurysm using next generation Surpass flow-diverting stents leading to complete recovery of pituitary function.

Reducing the risk of hypoglycemia associated with intravenous insulin: experience with a computerized insulin infusion program in 4 adult intensive care units.

Computerized insulin infusion protocols have facilitated more effective blood glucose (BG) control in intensive care units (ICUs). This is particularly important in light of the risks associated with hypoglycemia. End stage renal disease (ESRD) increases the risk of insulin-induced hypoglycemia. We evaluated BG control in 210 patients in 2 medical ICUs and in 2 surgical ICUs who were treated with a computerized insulin infusion program (CIIP). Our CIIP was programmed for a BG target of 140-180 mg/dL for medical ICU patients or 120-160 mg/dL for surgical ICU patients. In addition, we focused on BG control in the 11% of our patients with ESRD. Mean BG was 147 ± 20 mg/dL for surgical ICU patients and 171 ± 26 mg/dL for medical ICU patients. Of both surgical and medical ICU patients, 17% had 1 or more BG 60-79 mg/dL, while 3% of surgical ICU and 8% of medical ICU patients had 1 or more BG < 60 mg/dL. Mean BG in ESRD patients was 147 ± 16 mg/dL similar to 152 ± 23 mg/dL in patients without ESRD. Of ESRD patients, 41% had 1 or more BG < 79 mg/dL as compared with 17.8% of non-ESRD patients (P < .01). A higher BG target for medical ICU patients as compared with surgical ICU patients yielded comparably low rates of moderate or severe hypoglycemia. However, hypoglycemia among ESRD patients was more common compared to non-ESRD patients, suggesting a need for a higher BG target specific to ESRD patients.

Recovery of pituitary function following treatment of an unruptured giant cavernous carotid aneurysm using Surpass flow-diverting stents.

Giant aneurysms arising from the cavernous internal carotid artery (ICA) can mimic pituitary adenomas and may cause pituitary dysfunction due to their mass effect on the pituitary gland. We report a case of a 56-year-old man presenting with impotence, fatigue and panhypopituitarism who was found to have a giant unruptured aneurysm arising from the right cavernous ICA with severe mass effect on the pituitary gland. The patient underwent endovascular treatment of the giant aneurysm using two telescoping Surpass flow-diverting stents. At 6-month follow-up, repeat cerebral angiography showed Raymond grade II occlusion of the aneurysm with a small neck remnant. At the 10-month follow-up the patient showed full recovery of his pituitary function and clinical resolution of impotence and fatigue. This is the first report of occlusion of a giant cavernous carotid aneurysm using next generation Surpass flow-diverting stents leading to complete recovery of pituitary function.