Clinical expression and insulin sensitivity in type 2 diabetic patients with heterozygous mutations for haemochromatosis.
BACKGROUND
Elevated iron metabolism indices as well as liver enzymes abnormalities have been reported in type 2 diabetic patients. The aim of this study was to determine the clinical and biological characteristics of overweight or obese type 2 diabetic subjects, with and without heterozygosity for HFE gene mutation (C282Y or H63D). We also assessed their insulin sensitivity and B cell function.


METHODS
90 patients (age and diabetes duration: 61 +/- 11 and 12 +/- 8 years [mean +/- 1 SD]) were included. BMI was 32 +/- 6 kg/m(2). HbA(1c) was 8.9 +/- 1.8%. HFE genotyping was performed by PCR and restriction enzyme cleavage. Insulin sensitivity and B cell function were measured by the Homeostasis Model Assessment (HOMA).


RESULTS
Heterozygosity for C282Y (wt/C282Y) or H63D (wt/H63D) allele was found in 11 and 12 subjects respectively. There were no major differences in clinical status and iron parameters according to the single allelic presence of C282Y or H63D. However, systolic blood pressure [BP] was lower when such mutation was present. Insulin sensitivity and B cell function (HOMA) were comparable. When the cohort was divided according to gender, we found higher serum iron in females with than in those without HFE mutation (91 +/- 27 vs 73 +/- 25 microgram/dl;P=0.049), while a transferrin saturation index above 45% was observed in 36% of females with a mutation (vs 7% in wt/wt;P=0.06). When analysis was performed according to the presence of each particular mutation, we observed a transferrin saturation index higher than 45% in 60% of wt/C282Y patients vs 21% in the wt/wt group (P=0.008). A significantly lower BP was also identified in wt/C282Y patients. Cholesterol-HDL was 38 +/- 11 vs 46 +/- 12 mg/dl in wt/C282Y and wt/wt subjects, respectively (P=0.045). There were no differences in iron status, BP or lipids between wt/wt and wt/H63D subjects.


CONCLUSIONS
Type 2 diabetic patients, in particular females, with mono-allelic C282Y mutation, had slightly increased iron parameters. Systolic BP and cholesterol-HDL were also lower in wt/C282Y subjects. No difference in insulin sensitivity or B cell function was observed in the presence of mono-allelic HFE mutations.
Van Lerberghe
S
S
Service d'Endocrinologie et Nutrition, Cliniques Universitaires St Luc, Université Catholique de Louvain, B-1200 Bruxelles, Belgique.
Hermans
M P
MP
Dahan
K
K
Buysschaert
M
M
D000328:Adult; D017668:Age of Onset; D000483:Alleles; D019943:Amino Acid Substitution; D001530:Belgium; D001794:Blood Pressure / Q000235:genetics; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D007501:Iron / Q000097:blood; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation; D012727:Sex Characteristics; D044465:White People
C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D007328:Insulin; D008565:Membrane Proteins; D007501:Iron