Familial early-onset type 2 diabetes in Chinese patients: obesity and genetics have more significant roles than autoimmunity

Diabetes Care. 2001 Apr;24(4):663-71. doi: 10.2337/diacare.24.4.663.

Abstract

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.

Research design and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Amino Acid Substitution
  • Amyloid / genetics
  • Asian People* / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DNA, Mitochondrial / genetics
  • DNA-Binding Proteins / genetics
  • Diabetes Mellitus / epidemiology*
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus / immunology
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / immunology
  • Exons
  • Female
  • Glucokinase / genetics
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 1-beta
  • Hepatocyte Nuclear Factor 4
  • Hong Kong / epidemiology
  • Humans
  • Islet Amyloid Polypeptide
  • Male
  • Middle Aged
  • Mutation*
  • Nuclear Proteins*
  • Obesity*
  • Pedigree
  • Phosphoproteins / genetics
  • Point Mutation
  • Promoter Regions, Genetic
  • Registries
  • Transcription Factors / genetics

Substances

  • Amyloid
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DNA, Mitochondrial
  • DNA-Binding Proteins
  • HNF1A protein, human
  • HNF1B protein, human
  • HNF4A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 4
  • Islet Amyloid Polypeptide
  • MLX protein, human
  • Nuclear Proteins
  • Phosphoproteins
  • Transcription Factors
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta
  • Glucokinase