Type 1 diabetes and LADA--occurrence of HLA-DRB1 *03 and DRB1 *04 alleles in two age different groups of diabetics

Adv Gerontol. 2010;23(2):243-8.

Abstract

Type 1 Diabetes Mellitus (T1D) with an onset in adulthood and Late Autoimmune Diabetes of Adults (LADA) are connected with autoimmune insulitis (associated with islet cell autoantibodies) and the specific high-risk HLA class II genotype. The study was aimed at analyzing time and clinical characteristics of the diabetics with an onset of the disease after 35 y. (T1D and LADA). Main target of the study was to assess possible role of the old age onset and compare it with diabetics with the onset in the middle age (incl. analyzing HLA-DRB1 genotype). In the study, we included 103 diabetics with an onset of autoimmune diabetes at 35+ y. who were hospitalized and afterwards long-term observed in the diabetological outpatient department. 46 men and 57 women of the average age 65.7 +/- 13.8 y. (range 35-93 y.) were out of this number. 41 were assessed as the T1D patients and 61 as the LADA ones. As a control group we used 99 healthy individuals. Patients of the T1D subgroup developed diabetes in the age of 50.8 +/- 15.1 y. and of the LADA subgroup in the age of 52.6 +/- 12.8 y. Its duration in the time of this study was 10.7 +/- 11.6 y.; respectively 5.3 +/- 7.1 y. Fasting and postprandial C-peptide levels were statistically higher (p < 0.01) in the LADA subgroup vs. T1D. Obesity 1st and 2nd grade were present together only in 12.6%. BMI was not statistically significantly different between both groups. We found in our diabetic patients the predisposition alleles HLA-DRB1*03, HLA-DRB1*04 and particularly their combination. The occurrence of these HLA alleles is significantly higher in T1D patients in comparison to control groups (p = 0.01, OR = 4.0). In our study, the occurrence of the susceptible HLA-DRB1*03 and HLA-DRB1*04 alleles in T1D patients is higher than in LADA. The presence of these alleles identifies patients of high risk and requirement of insulin therapy. Since risk alleles are similarly present in middle and old age, environmental factors probably play similar role in these onsets of autoimmune diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Alleles
  • C-Peptide / blood
  • Case-Control Studies
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Glycated Hemoglobin / analysis
  • HLA-DR Antigens / genetics*
  • HLA-DRB1 Chains
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use
  • Insulin / administration & dosage
  • Insulin / therapeutic use
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Predictive Value of Tests
  • Risk

Substances

  • C-Peptide
  • Glycated Hemoglobin A
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Hypoglycemic Agents
  • Insulin
  • hemoglobin A1c protein, human