Multitissue insulin resistance despite near-normoglycemic remission in Africans with ketosis-prone diabetes.
OBJECTIVE
To characterize insulin action in Africans with ketosis-prone diabetes (KPD) during remission.


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 x m(-2) body surface x min(-1) and 80 mU x m(-2) x min (-1) insulin infusion rates) euglycemic clamp with [6,6-(2)H(2)]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 x kg(-1) x 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 x kg(-1) x min(-1); P = 0.001) and after 200-min insulin infusion (10 mU x m(-2) x min(-1): 1.6 +/- 0.2 vs. 0.6 +/- 0.1, P = 0.004; 80 mU x m(-2) x min(-1): 0.3 +/- 0.1 vs. 0 mg x kg(-1) x 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 micromol/l; P = 0.002) and remained higher after 100-min 10 mU x m(-2) x min(-1) insulin infusion (706.6 +/- 96.5 vs. 381.6 +/- 55.9 micromol/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.
Choukem
Simeon-Pierre
SP
Department of Diabetes and Endocrinology, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, University Paris-Diderot Paris 7, Paris, France.
Sobngwi
Eugene
E
Fetita
Lila-Sabrina
LS
Boudou
Philippe
P
De Kerviler
Eric
E
Boirie
Yves
Y
Hainault
Isabelle
I
Vexiau
Patrick
P
Mauvais-Jarvis
Franck
F
Calvo
Fabien
F
Gautier
Jean-François
JF
D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000328:Adult; D044383:Black People; D003920:Diabetes Mellitus / Q000208:ethnology* / Q000378:metabolism / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology / Q000378:metabolism / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000378:metabolism / Q000503:physiopathology; D016883:Diabetic Ketoacidosis / Q000208:ethnology* / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D012074:Remission Induction