OBJECTIVE 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 HNF1B-related 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 < 10−4) 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.
This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc16-2462/-/DC1.
↵* The list of the participant investigators of the Monogenic Diabetes Study Group, Société Francophone du Diabète can be found in the Supplementary Data online.
- Received November 18, 2016.
- Accepted March 21, 2017.
- © 2017 by the American Diabetes Association.