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Genetic interaction between Type 1 and Type 2 diabetes

Li, Haiyan LU (2002)
Abstract
There are two major types of diabetes, type 1 and type 2 diabetes. Similarly characterized by hyperglycaemia and long term micro- and macrovascular complications, type 1 and type 2 diabetes have different underlying pathophysiologic processes. In Scandinavia, type 1 diabetes is common; type 2 diabetes accounts for 85% of all cases with diabetes. There is emerging evidence that type 1 and type 2 diabetes cluster in the same families. 10% of patients diagnosed with type 2 diabetes have autoantibodies against GAD65 (GADabs). The presence of GADabs predicts the development of insulin deficiency in patients with type 2 diabetes (latent autoimmune diabetes in adults, i.e. LADA). The aim of the thesis was to study whether genetic interaction... (More)
There are two major types of diabetes, type 1 and type 2 diabetes. Similarly characterized by hyperglycaemia and long term micro- and macrovascular complications, type 1 and type 2 diabetes have different underlying pathophysiologic processes. In Scandinavia, type 1 diabetes is common; type 2 diabetes accounts for 85% of all cases with diabetes. There is emerging evidence that type 1 and type 2 diabetes cluster in the same families. 10% of patients diagnosed with type 2 diabetes have autoantibodies against GAD65 (GADabs). The presence of GADabs predicts the development of insulin deficiency in patients with type 2 diabetes (latent autoimmune diabetes in adults, i.e. LADA). The aim of the thesis was to study whether genetic interaction exists between type 1 and type 2 diabetes.



In a population-based study in Finland, the prevalence of families with both type 1 and type 2 diabetes (mixed type 1/type 2 diabetes families, or mixed type 1/2) among type 2 diabetes families was 14%. 5% of type 2 diabetic probands had a first-degree relative with type 1 diabetes. Type 2 diabetic patients from the mixed families had more often GADabs (18% vs. 8%; p<0.0001) and HLA DQB1*0302/X genotype (25% vs. 12%; p=0.005) associated with an increased risk for type 1 diabetes than those from the common type 2 diabetes families. However, compared with adult onset type 1 diabetic patients (GADabs, 65%), mixed type 1/2 patients had lower frequencies of GADabs (p<0.0001) and DQB1*02/0302 genotype (4% vs. 27%, p<0.0001) conferring the highest risk for type 1 diabetes. Despite similar age and lipid profile, type 1/2 patients had a more severe beta cell dysfunction, but less features of metabolic syndrome than the common type 2 diabetic patients. Sharing a risk HLA haplotype at the IDDM1 locus with a type 1 diabetic family member could explain most of the genetic influence of type 1 on type 2 diabetes. Insulin gene VNTR at the IDDM2 locus modified the risk conferred by the HLA locus in patients with type 2 diabetes.



The data point to a genetic interaction between type 1 and type 2 diabetes that is mediated by the type 1 diabetes susceptibility genes. Combined information from the clinical and genetic studies in the subgroup of type 1/2 patients could have important therapeutic implications for type 2 diabetes. (Less)
Please use this url to cite or link to this publication:
author
opponent
  • Professor Pociot, Flemming, M.D. Steno Diabetes Center, Niels Steensensvej 2, DK-2820 Gentofte, Denmark
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Endocrinology, IDDM2., Insulin gene VNTR, HLA, IDDM1, mixed type 1/2, Mixed type 1/type 2 diabetes families, LADA, GADabs, Autoantibodies against GAD65, Type 1 diabetes, Type 2 diabetes, diabetology, secreting systems, sekretion, diabetologi, Endokrinologi
pages
162 pages
publisher
Haiyan Li, Wallenberg Laboratory ing 46, Malmö University Hospital, 20502 Malmö, Sweden,
defense location
The Medical Research Centre (Jubileumsaulan), Malmö University Hospital
defense date
2002-09-25 09:15
external identifiers
  • Other:ISRN: LUMEDW/MEEK 02/1019-SE
ISBN
91-628-5326-0
language
English
LU publication?
yes
id
f994e9eb-07ba-4be7-8efa-cd4a73f27b73 (old id 464852)
date added to LUP
2007-10-02 14:03:36
date last changed
2016-09-19 08:45:15
@phdthesis{f994e9eb-07ba-4be7-8efa-cd4a73f27b73,
  abstract     = {There are two major types of diabetes, type 1 and type 2 diabetes. Similarly characterized by hyperglycaemia and long term micro- and macrovascular complications, type 1 and type 2 diabetes have different underlying pathophysiologic processes. In Scandinavia, type 1 diabetes is common; type 2 diabetes accounts for 85% of all cases with diabetes. There is emerging evidence that type 1 and type 2 diabetes cluster in the same families. 10% of patients diagnosed with type 2 diabetes have autoantibodies against GAD65 (GADabs). The presence of GADabs predicts the development of insulin deficiency in patients with type 2 diabetes (latent autoimmune diabetes in adults, i.e. LADA). The aim of the thesis was to study whether genetic interaction exists between type 1 and type 2 diabetes.<br/><br>
<br/><br>
In a population-based study in Finland, the prevalence of families with both type 1 and type 2 diabetes (mixed type 1/type 2 diabetes families, or mixed type 1/2) among type 2 diabetes families was 14%. 5% of type 2 diabetic probands had a first-degree relative with type 1 diabetes. Type 2 diabetic patients from the mixed families had more often GADabs (18% vs. 8%; p&lt;0.0001) and HLA DQB1*0302/X genotype (25% vs. 12%; p=0.005) associated with an increased risk for type 1 diabetes than those from the common type 2 diabetes families. However, compared with adult onset type 1 diabetic patients (GADabs, 65%), mixed type 1/2 patients had lower frequencies of GADabs (p&lt;0.0001) and DQB1*02/0302 genotype (4% vs. 27%, p&lt;0.0001) conferring the highest risk for type 1 diabetes. Despite similar age and lipid profile, type 1/2 patients had a more severe beta cell dysfunction, but less features of metabolic syndrome than the common type 2 diabetic patients. Sharing a risk HLA haplotype at the IDDM1 locus with a type 1 diabetic family member could explain most of the genetic influence of type 1 on type 2 diabetes. Insulin gene VNTR at the IDDM2 locus modified the risk conferred by the HLA locus in patients with type 2 diabetes.<br/><br>
<br/><br>
The data point to a genetic interaction between type 1 and type 2 diabetes that is mediated by the type 1 diabetes susceptibility genes. Combined information from the clinical and genetic studies in the subgroup of type 1/2 patients could have important therapeutic implications for type 2 diabetes.},
  author       = {Li, Haiyan},
  isbn         = {91-628-5326-0},
  keyword      = {Endocrinology,IDDM2.,Insulin gene VNTR,HLA,IDDM1,mixed type 1/2,Mixed type 1/type 2 diabetes families,LADA,GADabs,Autoantibodies against GAD65,Type 1 diabetes,Type 2 diabetes,diabetology,secreting systems,sekretion,diabetologi,Endokrinologi},
  language     = {eng},
  pages        = {162},
  publisher    = {Haiyan Li, Wallenberg Laboratory ing 46, Malmö University Hospital, 20502 Malmö, Sweden,},
  school       = {Lund University},
  title        = {Genetic interaction between Type 1 and Type 2 diabetes},
  year         = {2002},
}