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- Title
In obese individuals dexfenfluramine corrects molecular derangements reflecting insulin resistance.
- Authors
Piccinini, M; Rabbone, I; Novi, R F; Alberto, G; Mostert, M; Musso, A; Vai, S; Gamba, S; Rinaudo, M T
- Abstract
BACKGROUND: Circulating lymphocytes of obese individuals with and without type 2 diabetes have derangements of pyruvate dehydrogenase (PDH) that are described as reflecting a disorder underlying systemic insulin resistance, namely basal activity below normal and, in vitro, unresponsiveness to insulin at 33 pmol/I and activation at 330 pmol/I instead of activation and inhibition as in controls. OBJECTIVE: To explore whether the above enzyme derangements are overcome in obese individuals on dexfenfluramine treatment, known to improve poor peripheral insulin sensitivity. METHODS: Fifteen obese diabetic patients and 15 age-matched euglycaemic obese subjects with normal glucose tolerance were enrolled for a trial composed of two 21-day periods; in the first (D[sub -21]-D[sub 0]), participants received a placebo, and in the second (D[sub 0]-D[sub 21]), dexfenfluramine (30 mg/day). At D[sub -21], D[sub 0] and D[sub 21] participants were evaluated for weight, BMI, fasting glycaemia (FG), fasting insulinaemia (FI), fasting insulin resistance index (FIRI), area under the glycaemic (G-AUC) and insulinaemic (I-AUC) curves from an OGT test, and for PDH activity assayed in their circulating lymphocytes before (basal activity) and after incubation with 33 or 330 pmol/I insulin. At D[sub 2], basal PDH activity and clinical parameters were assayed. RESULTS: In both groups of participants at Do all parameters tested were constant with respect to D[sub -21]; at D[sub 2], only basal PDH activity rose significantly; at D[sub 21], basal and insulin stimulated PDH activities were normalized and weight decreased significantly, as did FG, FI, FIRI and G-AUC in the diabetic, and FI, FIRI, G-AUC and I-AUC in the non-diabetic participants. CONCLUSION: In obese, non-diabetic and diabetic individuals on dexfenfluramine treatment, amelioration of clinical parameters and indexes of poor insulin sensitivity of blood glucose homeostasis are preceded by correction, in their circulating...
- Subjects
DEXFENFLURAMINE; OBESITY; LYMPHOCYTES; INSULIN
- Publication
International Journal of Obesity & Related Metabolic Disorders, 2000, Vol 24, Issue 6, p735
- ISSN
0307-0565
- Publication type
Article
- DOI
10.1038/sj.ijo.0801212