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01.02.2008 | Article

Loss of 50% of excess weight using a very low energy diet improves insulin-stimulated glucose disposal and skeletal muscle insulin signalling in obese insulin-treated type 2 diabetic patients

verfasst von: I. M. Jazet, G. Schaart, A. Gastaldelli, E. Ferrannini, M. K. Hesselink, P. Schrauwen, J. A. Romijn, J. A. Maassen, H. Pijl, D. M. Ouwens, A. E. Meinders

Erschienen in: Diabetologia | Ausgabe 2/2008

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Abstract

Aims/hypothesis

Both energy restriction (ER) per se and weight loss improve glucose metabolism in obese insulin-treated type 2 diabetic patients. Short-term ER decreases basal endogenous glucose production (EGP) but not glucose disposal. In contrast the blood glucose-lowering mechanism of long-term ER with substantial weight loss has not been fully elucidated. The aim of this study was to investigate the effect of loss of 50% of excess weight [50% excess weight reduction (EWR)] on EGP, whole-body insulin sensitivity and the disturbed myocellular insulin-signalling pathway in ten obese insulin-treated type 2 diabetic patients.

Methods

A euglycaemic–hyperinsulinaemic clamp with stable isotopes ([6,6-²H₂]glucose and [²H₅]glycerol) combined with skeletal muscle biopsies was performed during a very low energy diet (VLED; 1,883 kJ/day) on day 2 and again after 50% EWR. Oral blood glucose-lowering agents and insulin were discontinued 3 weeks prior to the VLED and at the start of the VLED, respectively.

Results

Loss of 50% EWR (20.3 ± 2.2 kg from day 2 to day of 50% EWR) normalised basal EGP and improved insulin sensitivity, especially insulin-stimulated glucose disposal (18.8 ± 2.0 to 39.1 ± 2.8 μmol kg fat-free mass⁻¹ min⁻¹, p = 0.001). The latter was accompanied by improved insulin signalling at the level of the recently discovered protein kinase B/Akt substrates AS160 and PRAS40 along with a decrease in intramyocellular lipid (IMCL) content.

Conclusions/interpretation

Considerable weight loss in obese, insulin-treated type 2 diabetic patients normalises basal EGP and improves insulin sensitivity resulting from an improvement in insulin signal transduction in skeletal muscle. The decrease in IMCL might contribute to this effect.

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Titel: Loss of 50% of excess weight using a very low energy diet improves insulin-stimulated glucose disposal and skeletal muscle insulin signalling in obese insulin-treated type 2 diabetic patients
verfasst von: I. M. Jazet
G. Schaart
A. Gastaldelli
E. Ferrannini
M. K. Hesselink
P. Schrauwen
J. A. Romijn
J. A. Maassen
H. Pijl
D. M. Ouwens
A. E. Meinders
Publikationsdatum: 01.02.2008
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 2/2008
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-007-0862-2

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