Consequences of a family history of type 1 and type 2 diabetes on the phenotype of patients with type 2 diabetes.
OBJECTIVE
To investigate the impact of a family history of type 1 and type 2 diabetes on the phenotype of patients with type 2 diabetes.


METHODS
In a population-based study, we compared the phenotype in 3 groups of patients with type 2 diabetes. The first group had no family history of diabetes (FH-, n = 148); the second group had a family history of type 2 diabetes only (FH+(TYPE2), n = 1,211); and the third group had a family history of both type 1 and type 2 diabetes (FH+(MIXED), n = 240). Furthermore, we studied the frequency of GAD antibodies (GADabs), HLA-DQB1 risk genotypes, and the presence of coronary heart disease (CHD) according to family history in unrelated patients with type 2 diabetes from 787 families (148 FH-, 546 FH+(TYPE2) and 93 FH+(MIXED)).


RESULTS
Patients with no family history of diabetes were older at the onset of the disease, had a better beta-cell function (P = 0.004), and had higher HDL cholesterol concentrations (P = 0.006) than patients with a family history of diabetes. Patients with a family history of only type 2 diabetes had higher BMI and fasting C-peptide concentrations (P = 0.031) but lower frequency of GADab (11 vs. 23%, P = 0.001) and DQB1 risk genotypes (37 vs. 54%, P = 0.003) compared with patients with a family history of both type 1 and type 2 diabetes. In addition, hypertension (P = 0.05) and CHD (P = 0.031) were more common in FH+(TYPE2) than in FH+(MIXED) patients. In patients <60 years old, a family history of type 1 diabetes was associated with a reduced risk of CHD independent of age, hypertension, and HDL cholesterol concentrations. The results were similar when the GADab+ patients were excluded from the analysis.


CONCLUSIONS
A family history of both type 1 and type 2 diabetes had a profound influence on the phenotype of patients with type 2 diabetes, which suggests a genetic interaction between type 1 and type 2 diabetes.
Li
H
H
Department of Endocrinology, Lund University, Malmö, Sweden.
Isomaa
B
B
Taskinen
M R
MR
Groop
L
L
Tuomi
T
T
D000368:Aged; D001323:Autoantibodies / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003327:Coronary Disease / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005968:Glutamate Decarboxylase / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors
D001323:Autoantibodies; D008076:Cholesterol, HDL; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D005968:Glutamate Decarboxylase