Increased Skeletal Muscle Tumor Necrosis Factor- and Impaired Insulin Signaling Persist in Obese Women With Gestational Diabetes Mellitus 1 Year Postpartum

Department of Pediatrics, University of Colorado Denver, P.O. Box 6511, MS-8106, Aurora, CO 80045, USA.
Diabetes (Impact Factor: 8.1). 03/2008; 57(3):606-13. DOI: 10.2337/db07-1356
Source: PubMed


Women with gestational diabetes mellitus (GDM) demonstrate chronic and progressive insulin resistance and a markedly increased risk of converting to type 2 diabetes after pregnancy. However, the cellular mechanisms underlying this insulin resistance are unknown.
We investigated the progression of insulin resistance in nine obese women with GDM during late pregnancy (30-36 weeks) and 1 year postpartum. Skeletal muscle biopsies were obtained at each visit, and insulin resistance was determined by the hyperinsulinemic-euglycemic clamp technique.
Insulin resistance was not significantly improved in GDM women (4.1 +/- 0.4 vs. 5.8 +/- 1.1 10(-2) mg x kg FFM x min(-1)/microU x ml(-1)). Subjects did not experience significant weight loss postpartum. Body weight, fat mass, fasting glucose, and plasma tumor necrosis factor (TNF)-alpha remained higher 1 year postpartum than seen in previously studied normal glucose-tolerant women. Skeletal muscle TNF-alpha mRNA was elevated five- to sixfold in GDM women and remained higher 1 year postpartum. While levels of insulin receptor (IR), IR substrate (IRS)-1, and p85 alpha improved postpartum, insulin-stimulated IR tyrosine phosphorylation and receptor tyrosine kinase activity did not significantly improve postpartum in GDM. The levels of (312)Ser-IRS-1 also did not improve postpartum and correlated with TNF-alpha mRNA (r(2) = 0.19, P < 0.03), consistent with a state of subclinical inflammation and chronic skeletal muscle insulin resistance.
These results suggest the mechanisms underlying chronic insulin resistance in GDM women may be driven by increased inflammation that impinges on the IR and IRS-1 signaling cascade in skeletal muscle. These findings have important implications for the health of GDM women during subsequent pregnancies and their risk for progression to type 2 diabetes.

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    • "Gestational diabetes mellitus (GDM) can be defined as an impaired carbohydrate metabolism observed for the first time in pregnant woman irrespective of insulin or diet modification required.[1] Globally, the prevalence of GDM has been increasing rapidly at a rate proportionate to type-2 diabetes. "
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    ABSTRACT: Aim: To assess the safety and efficacy of insulin lispro in improving glycemic control in patients with gestational diabetes. Materials and Methods: A retrospective observational study was conducted at a single center on 201 gestational women with diabetes. Subjects who received insulin lispro performed blood glucose self-monitoring and recorded the readings in the fasting state and 1 h after each meal. At each contact (in person or telephonic contact), the insulin dose was adjusted based on the readings measured. A total of 53 subjects also recorded glucose levels post-partum. Pregnancy and post-delivery glucose level and insulin requirements of these 53 patients were compared. Results: Analysis of glucose levels both fasting and post-prandial glucose levels revealed that after using insulin lispro, the number of episodes of post-prandial hyperglycemia (1 h plasma glucose >120 mg/dL) was minimal and so was the incidence of hypoglycemia. Hypoglycemia was defined as a blood sugar value of. There was neither any congenital abnormality except for a poorly formed pinna in the right ear of one baby nor any post-partum complications of note. Conclusion: Insulin lispro is an effective and safe treatment option in gestational diabetes.
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    • "It is especially important to introduce healthy lifestyle changes, as well as a proper diet based on individualized caloric needs and weight gain [22]. It should be pointed out, that limiting excessive growth of fatty tissue may also decrease the adverse effect of adipokines on the insulin secretion [23] and reduce the intensity of insulin resistance of skeletal muscles [6]. "
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    • "Human leukocyte antigen (HLA) class I, HLA class II and secretion of inflammatory cytokine increase when a proinflammatory stimulus is given to normal muscle tissues [15]. TNF-α mRNA expression after delivery was higher in gestational diabetes patients than in patients with normal glucose tolerance, and this was also related to insulin resistance [16]. The inflammatory process was observed in the skeletal muscle of diabetes patients, in whom chronic systemic inflammation is known to be present. "
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