Administration of Lispro Insulin with Meals Improves Glycemic Control, Increases Circulating Leptin, and Suppresses Ghrelin, Compared with Regular/NPH Insulin in Female Patients with Type 1 Diabetes

Department of Nutrition, University of California, Davis, Davis, California, United States
Journal of Clinical Endocrinology & Metabolism (Impact Factor: 6.21). 03/2006; 91(2):485-91. DOI: 10.1210/jc.2005-1338
Source: PubMed


Overweight and obesity are overrepresented in adolescents with type 1 diabetes mellitus (T1DM). Exogenous insulin administration often poorly reproduces normal insulin patterns and may less effectively regulate leptin and ghrelin, two hormones involved in the control of appetite and adiposity.
The objective of the study was to determine whether insulin regimens that better replicate normal insulin patterns and augment postprandial nutrient disposal may help normalize leptin and ghrelin and improve body weight regulation.
Ten young women with T1DM were studied in this 2-wk prospective, balanced crossover-design study at the University of California, Davis.
Participants received either a single injection of regular + NPH insulin (R+N) or two mealtime injections of Lispro insulin in randomized order on 2 separate days. Meal composition and total insulin administered were the same on both treatment days.
Plasma glucose, insulin, leptin, and ghrelin concentrations were monitored over the 10-h study period.
Lispro produced two distinct mealtime peaks of insulin, compared with one prolonged rise with R+N. Lispro reduced postprandial hyperglycemia and total glucose area under the curve. Leptin increased more on the Lispro (2.7 +/- 0.7 vs. 0.7 +/- 0.5 ng/ml, P = 0.02). Ghrelin was more suppressed after lunch with Lispro (P = 0.004).
Injection of Lispro insulin with meals produces more physiological insulin patterns, better glucose control, and improved leptin and ghrelin regulation than R+N. More closely mimicking normal insulin, leptin, and ghrelin responses to meals with fast-acting insulin may have implications for body weight regulation in T1DM.

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    • "Changes in plasma ghrelin concentrations have been reported in animal models of diabetes and in human diabetes type 1 and type 2. It has been shown in a model of streptozotocin-induced diabetes that plasma ghrelin concentration and preproghrelin mRNA expression in the stomach of the diabetic rats increased significantly whereas their gastric ghrelin level and the number of ghrelin-immunoreactive cells in the gastric fundus decreased significantly [114]. In type 1 diabetic patients decreased plasma ghrelin levels have been documented [115–117], and after prolonged insulin treatment or food intake, a suppression of plasma ghrelin in these patients has been shown [118, 119]. Also in children with insulin-treated type 1 diabetes, the plasma ghrelin levels were found to be lower than those measured in controls with a negative association of their plasma ghrelin levels with daily insulin dosage [116]. "
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