Heterogeneity in young adult onset diabetes: aetiology alters clinical characteristics.
OBJECTIVE
To describe the characteristics of hepatocyte nuclear factor (HNF) 1 alpha mutation carriers diagnosed with diabetes after 25 years and compare them with young-onset Type 2 diabetic patients (YT2D) diagnosed at the same age.


METHODS
We studied 44 (21 male, 23 female) patients with HNF-1 alpha mutations diagnosed with diabetes at ages 25-45 years and 44 YT2D subjects matched for sex and age of diagnosis.


RESULTS
Median age of onset of diabetes was 35 years in both groups. The HNF-1 alpha group demonstrated: lower body mass index (25.1 vs. 30.7 kg/m2; P < 0.001) and lower fasting triglycerides (1.37 vs. 2.96 mmol/l; P = 0.001) with similar fasting cholesterol level. They had lower glycated haemoglobin A1c (7.3 vs. 8.5%; P = 0.015) despite greater duration of diabetes (24 vs. 16 years; P = 0.02) and less frequent treatment with insulin (21% vs. 55%; P = 0.002). They were less likely to be treated for hypertension (13.3% vs. 56.3%; P = 0.009). Importantly, no difference was observed in reported parental history of diabetes between the two groups (65.9% vs. 63.6%; P = 0.92). Logistic regression showed that triglyceride levels and presence of anti-hypertensive treatment were the most important independent variables.


CONCLUSIONS
Patients with HNF-1 alpha mutations may present with diabetes as young adults between the ages of 25-45 years. In this age range a wide differential diagnosis of diabetes is observed. Conventional criteria of age of onset and family history will not differentiate HNF-1 alpha mutation carriers from YT2D subjects in this age range, but features of the metabolic syndrome, in particular fasting triglycerides and hypertension, are helpful. In patients diagnosed before 45 years without features of insulin resistance the diagnosis of HNF-1 alpha should be considered.
Centre for Molecular Genetics, School of Postgraduate Medicine and Health Sciences, University of Exeter, Exeter, UK. K.R.Owen@exeter.ac.uk
K R
KR
Owen
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M
Shepherd
A
A
Stride
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S
Ellard
A T
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Hattersley
D000328:Adult; D017668:Age of Onset; D000959:Antihypertensive Agents / Q000627:therapeutic use; D004268:DNA-Binding Proteins; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins; D014157:Transcription Factors / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
D000959:Antihypertensive Agents; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D007004:Hypoglycemic Agents; D007328:Insulin; D009687:Nuclear Proteins; D014157:Transcription Factors; D014280:Triglycerides; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta