Article Dans Une Revue Diabetes Care Année : 2017

Diabetes, Associated Clinical Spectrum, Long-term Prognosis, and Genotype/Phenotype Correlations in 201 Adult Patients With Hepatocyte Nuclear Factor 1B ( HNF1B ) Molecular Defects

Résumé

Molecular defects of hepatocyte nuclear factor 1B (HNF1B) are associated with a multiorgan disease, including diabetes (maturity-onset diabetes of the young 5) and kidney abnormalities. The HNF1B-syndrome is related to HNF1B mutations or to a 17q12 deletion spanning 15 genes, including HNF1B. Here, we described HNF1Brelated diabetes and associated phenotypes and assessed genotype/phenotype correlations at diagnosis and in the long-term. RESEARCH DESIGN AND METHODS This multicenter retrospective cohort study included 201 patients, aged 18 or older at follow-up, with HNF1B mutations (n = 101) or deletion (n = 100). RESULTS Diabetes was present in 159 patients. At diagnosis, clinical symptoms of diabetes were present in 67 of 144 patients, and HNF1B-renal disease in 64 of 102. Although responsiveness to sulfonylureas/repaglinide was observed in 29 of the 51 tested, 111 of 140 patients (79%) were treated with insulin at follow-up. Diabetic retinopathy and/or neuropathy were present in 46 of 114 patients. Renal cysts were present in 122 of 166 patients, chronic kidney disease (CKD) stages 3-4 in 75 of 169 (44%), and end-stage renal disease (ESRD) in 36 of 169 (21%). Compared with the patients with mutations, those with HNF1B deletion had less often CKD3-4/ESRD at diagnosis (11 of 43 vs. 27 of 35, P < 10 24) and in the long-term (40 of 78 vs. 71 of 91, P = 0.0003). They were leaner and more frequently treated with insulin. CONCLUSIONS In patients with HNF1B-syndrome, diabetes complications, cardiovascular risk factors, CKD3-4, and ESRD are highly prevalent. At diabetes diagnosis, the presence of morphological and/or functional kidney disease may help etiological diagnosis. Genotype/phenotype correlations may have implications for the care and the prognosis of these patients.

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hal-03121409 , version 1 (28-01-2021)

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Danièle Dubois-Laforgue, Erika Cornu, Cécile Saint-Martin, Joël Coste, Christine Bellanné-Chantelot, et al.. Diabetes, Associated Clinical Spectrum, Long-term Prognosis, and Genotype/Phenotype Correlations in 201 Adult Patients With Hepatocyte Nuclear Factor 1B ( HNF1B ) Molecular Defects. Diabetes Care, 2017, 40 (11), pp.1436-1443. ⟨10.2337/dc16-2462⟩. ⟨hal-03121409⟩
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