Article

Insulin pump dosing across gestation in women with well-controlled type 1 diabetes mellitus

Division of Perinatology, Department of Reproductive Medicine, UC San Diego Health System, San Diego, CA.
American journal of obstetrics and gynecology (Impact Factor: 4.7). 10/2012; 207(4):324.e1-5. DOI: 10.1016/j.ajog.2012.06.029
Source: PubMed

ABSTRACT

We hypothesized that bolus and basal insulin doses in women with type 1 diabetes mellitus who use insulin pumps would increase 2-fold to maintain hemoglobin A1c <6.5% across gestation.
This was a retrospective study of 9 women with type 1 diabetes mellitus with preconceptional hemoglobin A1c ≤7.4% using insulin pumps. The primary outcome was absolute and percentage change of basal and bolus insulin from preconception to delivery.
Total daily dose of insulin increased from 33.3 ± 7.8 U/d before conception to 93.5 ± 27.9 U/d at delivery. Basal rates rose modestly (50% increase, from 16.2 ± 6.5 U/d to 24.0 ± 9 U/d); bolus insulin doses quadrupled from 17.1 ± 6.1 U/d to 69.5 ± 29.6 U/d (P = .0001). Bolus insulin increased from approximately 50% of total daily dose of insulin before conception to 75% of total daily dose of insulin at 36 weeks' gestation.
In well-controlled type 1 diabetes mellitus, insulin requirements increased 3-fold from before conception to 36 weeks' gestation. Most of this requirement was attributed to an increase in bolus rates that are required for control with meals.

0 Followers
 · 
15 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Both oxidative stress and endoplasmic reticulum stress (ER stress) are causal events in diabetic embryopathy. We test whether oxidative stress causes ER stress. Wild-type (WT) and superoxide dismutase 1 (SOD1) overexpressing Day 8.75 embryos from nondiabetic WT control (NDC) with SOD1 transgenic male and diabetic WT female with SOD1 transgenic male were analyzed for ER stress markers: C/EBP-homologous protein (CHOP), calnexin, eukaryotic initiation factor 2α (eIF2α), protein kinase RNA-like ER kinase (PERK), binding immunoglobulin protein (BIP), protein disulfide isomerase family A member 3 (PDIA3), kinases inositol-requiring protein-1α (IRE1α), and the X-box binding protein (XBP1) mRNA splicing. Maternal diabetes significantly increased the levels of CHOP, calnexin, phosphorylated (p)-eIF2α, p-PERK and p-IRE1α; triggered XBP1 mRNA splicing; and enhanced ER chaperone gene expression in WT embryos. Thus, SOD1 overexpression blocked these diabetes-induced ER stress markers. Mitigating oxidative stress via SOD1 overexpression blocks maternal diabetes-induced ER stress in vivo.
    Full-text · Article · Jun 2013 · American journal of obstetrics and gynecology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract 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 to 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) grams carbohydrate per unit insulin in late pregnancy. Basal insulin delivery increased by approximately 50%, i.e. from 0.8 (0.5-2.2) to 1.2 (0.6-2.5) international units (IU)/hour at 5 a.m., and from 1.0 (0.6-1.5) to 1.3 (0.2-2.3) /hour 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 four-fold from early to late pregnancy, while changes in basal insulin delivery were smaller.
    Full-text · Article · Aug 2013 · The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Maternal diabetes is a significant risk factor for structural birth defects, including congenital heart defects and neural tube defects (NTDs). With the rising prevalence of type 2 diabetes and obesity in women of childbearing age, diabetes-induced birth defects have become an increasingly significant public health problem. Maternal diabetes in vivo and high glucose in vitro induce yolk sac injuries by damaging the morphology of cells and altering the dynamics of organelles. The yolk sac vascular system is the first system to develop during embryogenesis, therefore, it is the most sensitive to hyperglycemia. The consequences of yolk sac injuries include impairment of nutrient transportation due to vasculopathy. Although the functional relationship between yolk sac vasculopathy and structural birth defects has not yet been established, a recent study reveals that the quality of yolk sac vasculature is inversely related to embryonic malformation rates. Studies in animal models have uncovered key molecular intermediates of diabetic yolk sac vasculopathy, including hypoxia-inducible factor-1α (HIF-1α), apoptosis signal-regulating kinase 1 (ASK1) and its inhibitor thioredoxin-1 (Trx), c-Jun-N-terminal kinases (JNK), nitric oxide (NO) and nitric oxide synthase (NOS). Yolk sac vasculopathy is also associated with abnormalities in arachidonic acid and myo-inositol. Dietary supplementation with fatty acids that restore lipid levels in the yolk sac lead to reduction in diabetes-induced malformations. Although the role of the human yolk in embryogenesis is less extensive than in rodents, nevertheless, human embryonic vasculogenesis is negatively affected by maternal diabetes. Mechanistic studies have identified potential therapeutic targets for future intervention against yolk sac vasculopathy, birth defects, and other complications associated with diabetic pregnancies.
    Full-text · Article · Oct 2015 · American journal of obstetrics and gynecology
Show more