Familial early-onset type 2 diabetes in Chinese patients: obesity and genetics have more significant roles than autoimmunity.
OBJECTIVE
We examined the prevalence of different forms of diabetes in Hong Kong Chinese patients with familial early-onset type 2 diabetes and compared their clinical features with patients with familial late-onset type 2 diabetes.


METHODS
A total of 145 young patients with early-onset diabetes (age and age at diagnosis < or = 40 years) and a family history of diabetes were studied. They were screened for mutations in the genes encoding glucokinase, hepatocyte nuclear factor (HNF)-4alpha, and HNF-1alpha. The mitochondrial DNA A-->G at nucleotide 3243 (mt3243) and amyLin S20G mutations were studied, and antibodies to GAD (anti-GADs) were also examined.


RESULTS
The prevalence of putative diabetogenic gene mutations and autoimmune markers were 4% for glucokinase, 0% for HNF-4alpha, 5% for HNF-1alpha, 3% for mt3243, 2% for amylin 520G, and 4% for anti-GAD. Compared with late-onset patients, the patients with early-onset diabetes had a higher prevalence of a parental history of diabetes and were generally more obese. When classified by obesity indexes (BMI and waist circumference), the obese patients, especially those with early-onset diabetes, had a clustering of cardiovascular risk factors and increased rates of retinopathy and albuminuria. CONCLUSIONS; Genetic factors (up to 14%) and obesity (55%) play more significant roles than autoimmunity (4%) in familial type 2 diabetes in young Chinese patients. The significance of obesity-related genes and other gene-gene and gene-environment interactions in these young patients remains to be determined.
Ng
M C
MC
Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, SAR. maggieng@cuhk.edu.hk
Lee
S C
SC
Ko
G T
GT
Li
J K
JK
So
W Y
WY
Hashim
Y
Y
Barnett
A H
AH
Mackay
I R
IR
Critchley
J A
JA
Cockram
C S
CS
Chan
J C
JC
D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D000682:Amyloid / Q000235:genetics; D044466:Asian People / Q000235:genetics; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004272:DNA, Mitochondrial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003920:Diabetes Mellitus / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D005091:Exons; D005260:Female; D005941:Glucokinase / Q000235:genetics; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051557:Hepatocyte Nuclear Factor 4; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins; D009765:Obesity; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D012042:Registries; D014157:Transcription Factors / Q000235:genetics
D000682:Amyloid; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; C496592:HNF4A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D058228:Islet Amyloid Polypeptide; C403128:MLX protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D005941:Glucokinase