Genetic interaction between Type 1 and Type 2 diabetes

Research output: ThesisDoctoral Thesis (compilation)

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.

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.

Details

Authors
  • Haiyan Li
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes

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
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
  • [unknown], [unknown], Supervisor, External person
Award date2002 Sep 25
Publisher
  • Haiyan Li, Wallenberg Laboratory ing 46, Malmö University Hospital, 20502 Malmö, Sweden,
Print ISBNs91-628-5326-0
Publication statusPublished - 2002
Publication categoryResearch

Bibliographic note

Defence details Date: 2002-09-25 Time: 09:15 Place: The Medical Research Centre (Jubileumsaulan), Malmö University Hospital External reviewer(s) Name: Pociot, Flemming Title: Professor Affiliation: M.D. Steno Diabetes Center, Niels Steensensvej 2, DK-2820 Gentofte, Denmark --- Article: Paper ILi H, Isomaa B, Taskinen MR, Groop L, Tuomi T"Consequences of a family history of type 1 and type 2 diabetes on the phenotype of patients with type 2 diabetes"Diabetes Care 2000 May; 23(5):589-94. Article: Paper IILi H, Lindholm E, Almgren P, Gustafsson Å, Forsblom C, Groop L, Tuomi T"Possible human leukocyte antigen (HLA)-mediated genetic interaction between type 1 and type 2 diabetes"J Clin Endocrinol Metab 2001 Feb;86(2):574-82 Article: Paper IIILi H, Groop L, Nilsson A, Weng J, Tuomi T"A combination of HLA DQB1*02 and the TNFa promoter G308A polymorphism predisposes to a type 1 diabetes like phenotype in patients with type 2 diabetes" Preliminarily acceptance for publication in J Clin Endocrinol Metab 2002 June Article: Paper IVTuomi T, Li H, Altshuler D, Hirschhorn J, Nilsson A and Groop L"The insulin gene VNTR affects body-mass and insulin concentration in patients with type 2 diabetes"Preliminarily acceptance for publication in Diabetes 2002 June The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Endocrinology (013241500), Pediatrics/Urology/Gynecology/Endocrinology (013240400)