Multitissue Insulin Resistance Despite Near-Normoglycemic Remission in Africans With Ketosis-Prone Diabetes
- Simeon-Pierre Choukem, MD12,
- Eugene Sobngwi, MD, PHD123,
- Lila-Sabrina Fetita, MD1,
- Philippe Boudou, PHD45,
- Eric De Kerviler, MD6,
- Yves Boirie, MD, PHD7,
- Isabelle Hainault, PHD5,
- Patrick Vexiau, MD1,
- Franck Mauvais-Jarvis, MD, PHD8,
- Fabien Calvo, MD, PHD2 and
- Jean-François Gautier, MD, PHD125
- 1Department of Diabetes and Endocrinology, Saint-Louis Hospital, Assistance Publique–Hôpitaux de Paris, University Paris-Diderot Paris 7, Paris, France
- 2INSERM, Clinical Investigation Center CIC9504, Saint-Louis Hospital, Assistance Publique–Hôpitaux de Paris, University Paris-Diderot Paris 7, Paris, France
- 3Institute of Health and Society, University of Newcastle, Newcastle upon Tyne, U.K.
- 4Unit of Transfer in Molecular Oncology and Hormonology, Saint-Louis Hospital, Assistance Publique–Hôpitaux de Paris, University Paris-Diderot Paris 7, Paris, France
- 5INSERM UMRS 872, Cordeliers Research Center, Paris, France
- 6Department of Radiology and Medical Imaging, Saint-Louis Hospital, Assistance Publique–Hôpitaux de Paris, University Paris-Diderot Paris 7, Paris, France
- 7UMR1019, University of Clermont 1, CRNH-Auvergne, Clermont-Ferrand, France
- 8Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University School of Medicine, Chicago, Illinois
- Corresponding author: Jean-François Gautier, jean-francois.gautier{at}sls.aphp.fr
Abstract
OBJECTIVE—To characterize insulin action in Africans with ketosis-prone diabetes (KPD) during remission.
RESEARCH DESIGN AND METHODS—At Saint-Louis Hospital, Paris, France, 15 African patients with KPD with an average 10.5-month insulin-free near-normoglycemic remission period (mean A1C 6.2%) were compared with 17 control subjects matched for age, sex, BMI, and geographical origin. Insulin stimulation of glucose disposal, and insulin suppression of endogenous glucose production (EGP) and nonesterified fatty acids (NEFAs), was studied using a 200-min two-step (10 mU · m−2 body surface · min−1 and 80 mU · m−2 · min −1 insulin infusion rates) euglycemic clamp with [6,6-2H2]glucose as the tracer. Early-phase insulin secretion was determined during an oral glucose tolerance test.
RESULTS—The total glucose disposal was reduced in patients compared with control subjects (7.5 ± 0.8 [mean ± SE] vs. 10.5 ± 0.9 mg · kg−1 · min−1; P = 0.018). EGP rate was higher in patients than control subjects at baseline (4.0 ± 0.3 vs. 3.0 ± 0.1 mg · kg−1 · min−1; P = 0.001) and after 200-min insulin infusion (10 mU · m−2 · min−1: 1.6 ± 0.2 vs. 0.6 ± 0.1, P = 0.004; 80 mU · m−2 · min−1: 0.3 ± 0.1 vs. 0 mg · kg−1 · min−1, P = 0.007). Basal plasma NEFA concentrations were also higher in patients (1,936.7 ± 161.4 vs. 1,230.0 ± 174.1 μmol/l; P = 0.002) and remained higher after 100-min 10 mU · m−2 · min−1 insulin infusion (706.6 ± 96.5 vs. 381.6 ± 55.9 μmol/l; P = 0.015).
CONCLUSIONS—The triad hepatic, adipose tissue, and skeletal muscle insulin resistance is observed in patients with KPD during near-normoglycemic remission, suggesting that KPD is a form of type 2 diabetes.
Footnotes
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Published ahead of print at http://care.diabetesjournals.org on 22 September 2008.
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- Accepted September 14, 2008.
- Received May 17, 2008.
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