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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 Endocrinology (S.C.G.) and Pediatrics (D.M.S., N.G., M.H.C.), School of Medicine, and Department of Nutrition (K.O., K.L.S., J.G., P.J.H.), University of California, Davis, Davis, California 95616; and Division of Endocrinology (D.E.C.), University of Washington Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98108

Address all correspondence to: Steven C. Griffen, University of California, Davis, Medical Center, Patient Support and Services Building Suite G-400, 4150 V Street, Sacramento, California 95817. E-mail: scgriffen{at}ucdavis.edu.

Context: 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.

Objective: 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.

Design, Setting, and Participants: Ten young women with T1DM were studied in this 2-wk prospective, balanced crossover-design study at the University of California, Davis.

Intervention: 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.

Main Outcome Measures: Plasma glucose, insulin, leptin, and ghrelin concentrations were monitored over the 10-h study period.

Results: 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).

Conclusions: 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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