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Reversal of Nonalcoholic Hepatic Steatosis, Hepatic Insulin Resistance, and Hyperglycemia by Moderate Weight Reduction in Patients With Type 2 Diabetes
Ist Teil von
Diabetes (New York, N.Y.), 2005-03, Vol.54 (3), p.603-608
Ort / Verlag
Alexandria, VA: American Diabetes Association
Erscheinungsjahr
2005
Quelle
MEDLINE
Beschreibungen/Notizen
Reversal of Nonalcoholic Hepatic Steatosis, Hepatic Insulin Resistance, and Hyperglycemia by Moderate Weight Reduction in
Patients With Type 2 Diabetes
Kitt Falk Petersen 1 ,
Sylvie Dufour 1 2 ,
Douglas Befroy 1 ,
Michael Lehrke 3 ,
Rosa E. Hendler 1 and
Gerald I. Shulman 1 2 4
1 Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut
2 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut
3 Department of Internal Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
4 Department of Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut
Address correspondence and reprint requests to Kitt Falk Petersen, MD, Yale University School of Medicine, Department of Internal
Medicine, 300 Cedar St., S263 TAC, P.O. Box 9812, New Haven, CT 06520-8020. E-mail: kitt.petersen{at}yale.edu
Abstract
To examine the mechanism by which moderate weight reduction improves basal and insulin-stimulated rates of glucose metabolism
in patients with type 2 diabetes, we used 1 H magnetic resonance spectroscopy to assess intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) content in conjunction
with hyperinsulinemic-euglycemic clamps using [6,6- 2 H 2 ]glucose to assess rates of glucose production and insulin-stimulated peripheral glucose uptake. Eight obese patients with
type 2 diabetes were studied before and after weight stabilization on a moderately hypocaloric very-low-fat diet (3%). The
diabetic patients were markedly insulin resistant in both liver and muscle compared with the lean control subjects. These
changes were associated with marked increases in IHL (12.2 ± 3.4 vs. 0.6 ± 0.1%; P = 0.02) and IMCL (2.0 ± 0.3 vs. 1.2 ± 0.1%; P = 0.02) compared with the control subjects. A weight loss of only ∼8 kg resulted in normalization of fasting plasma glucose
concentrations (8.8 ± 0.5 vs. 6.4 ± 0.3 mmol/l; P < 0.0005), rates of basal glucose production (193 ± 7 vs. 153 ± 10 mg/min; P < 0.0005), and the percentage suppression of hepatic glucose production during the clamp (29 ± 22 vs. 99 ± 3%; P = 0.003). These improvements in basal and insulin-stimulated hepatic glucose metabolism were associated with an 81 ± 4% reduction
in IHL ( P = 0.0009) but no significant change in insulin-stimulated peripheral glucose uptake or IMCL (2.0 ± 0.3 vs. 1.9 ± 0.3%; P = 0.21). In conclusion, these data support the hypothesis that moderate weight loss normalizes fasting hyperglycemia in patients
with poorly controlled type 2 diabetes by mobilizing a relatively small pool of IHL, which reverses hepatic insulin resistance
and normalizes rates of basal glucose production, independent of any changes in insulin-stimulated peripheral glucose metabolism.
APE, atom percent enrichment
GCRC, General Clinical Research Center
IHL, intrahepatic lipid
IL-6, interleukin-6
IMCL, intramyocellular lipid
IRS, insulin receptor substrate
MRS, magnetic resonance spectroscopy
Footnotes
Accepted November 29, 2004.
Received August 2, 2004.
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