Ketosis-prone type 2 diabetes in patients of sub-Saharan African origin: clinical pathophysiology and natural history of beta-cell dysfunction and insulin resistance.
Nonautoimmune ketosis-prone diabetic syndromes are increasingly frequent in nonwhite populations. We have characterized a cohort of patients of sub-Saharan African origin who had ketosis-prone type 2 diabetes (n = 111), type 1 diabetes (n = 21), and type 2 diabetes (n = 88) and were admitted to a hospital for management of uncontrolled diabetes. We compared epidemiological, clinical, and metabolic features at diabetes onset and measured insulin secretion (glucagon-stimulated C-peptide) and insulin action (short intravenous insulin tolerance test) during a 10-year follow-up. Ketosis-prone type 2 diabetes shows a strong male predominance, stronger family history, higher age and BMI, and more severe metabolic decompensation than type 1 diabetes. In ketosis-prone type 2 diabetes, discontinuation of insulin therapy with development of remission of insulin dependence is achieved in 76% of patients (non-insulin dependent), whereas only 24% of patients remain insulin dependent. During evolution, ketosis-prone type 2 diabetes exhibit specific beta-cell dysfunction features that distinguish it from type 1 and type 2 diabetes. The clinical course of non-insulin-dependent ketosis-prone type 2 diabetes is characterized by ketotic relapses followed or not by a new remission. Progressive hyperglycemia precedes and is a strong risk factor for ketotic relapses (hazard ratio 38). The probability for non-insulin-dependent ketosis-prone type 2 diabetes to relapse is 90% within 10 years, of whom approximately 50% will become definitively insulin dependent. Insulin sensitivity is decreased in equal proportion in both ketosis-prone type 2 diabetes and type 2 diabetes, but improves significantly in non-insulin-dependent ketosis-prone type 2 diabetes, only after correction of hyperglycemia. In conclusion, ketosis-prone type 2 diabetes can be distinguished from type 1 diabetes and classical type 2 diabetes by specific features of clinical pathophysiology and also by the natural history of beta-cell dysfunction and insulin resistance reflecting a propensity to glucose toxicity.
Mauvais-Jarvis
Franck
F
Department of Endocrinology & Diabetes, Saint-Louis Hospital and University of Paris VII School of Medicine, Paris, France. fmjarvis@bcm.tmc.edu
Sobngwi
Eugène
E
Porcher
Raphaël
R
Riveline
Jean-Pierre
JP
Kevorkian
Jean-Philippe
JP
Vaisse
Christian
C
Charpentier
Guillaume
G
Guillausseau
Pierre-Jean
PJ
Vexiau
Patrick
P
Gautier
Jean-François
JF
D000328:Adult; D017954:Africa South of the Sahara; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000145:classification / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000145:classification / Q000503:physiopathology*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007330:Insulin Antibodies / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism* / Q000503:physiopathology; D009765:Obesity
D001786:Blood Glucose; D007328:Insulin; D007330:Insulin Antibodies