Multi-tissue insulin resistance despite near-normoglycemic remission in Africans with ketosis-prone diabetes

  1. Simeon Pierre Choukem, MD1,2,
  2. Eugene Sobngwi, MD, PhD1,2,7,
  3. Lila-Sabrina Fetita, MD1,
  4. Philippe Boudou, PhD3,5,
  5. Eric De Kerviler, MD4,
  6. Yves Boirie, MD, PhD6,
  7. Isabelle Hainault, PhD5,
  8. Patrick Vexiau, MD1,
  9. Franck Mauvais-Jarvis, MD, PhD8,
  10. Fabien Calvo, MD, PhD2 and
  11. Jean-François Gautier, MD, PhD (jean-francois.gautier{at}sls.aphp.fr)1,2,5
  1. 1Department of Diabetes and Endocrinology
  2. 2INSERM, Clinical Investigation Center CIC9504
  3. 3Unit of Transfer in Molecular Oncology and Hormonology, and
  4. 4Department of Radiology and Medical Imaging, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, University Paris-Diderot Paris-7
  5. 5INSERM UMRS 872, Cordeliers Research Center; Paris, France
  6. 6UMR1019, University of Clermont 1, CRNH-Auvergne, Clermont-Ferrand, France
  7. 7Institute of Health and Society, University of Newcastle, Newcastle upon Tyne, UK
  8. 8Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University School of Medicine, Chicago, IL, USA

    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 of 10.5 months insulin-free near-normoglycemic remission period (mean HbA1c 6.2%) were compared to 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 non-esterified fatty acids (NEFA) were studied using a 200-min two-step (10mU.m-2 body surface.min-1 and 80mU.m-2.min-1 insulin infusion rates) euglycemic clamp with [6,6-2H2]glucose as tracer. Early phase insulin secretion was determined during an OGTT.

    Results: The total glucose disposal was reduced in patients compared with control subjects (7.5 ± 0.8 [mean ± SEM] 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 (10mU.m-2.min-1: 1.6 ± 0.2 vs. 0.6 ± 0.1, p = 0.004; 80mU.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 (1936.7 ± 161.4 vs. 1230.0 ± 174.1 μmol/l; p = 0.002) and remained higher after 100-min 10mU.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

      • Received May 17, 2008.
      • Accepted September 14, 2008.

    This Article

    1. Published online before print September 22, 2008, doi: 10.2337/dc08-0914
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