R Hjort1, L Alfredsson2, T Andersson3, P-O Carlsson4, V Grill5, L Groop6, M Martinell7, B Rasouli8, P Storm6, T Tuomi9, S Carlsson8. 1. Unit of epidemiology, institute of environmental medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: rebecka.hjort@ki.se. 2. Unit of cardiovascular epidemiology, institute of environmental medicine, Karolinska Institutet, Stockholm, Sweden. 3. Unit of epidemiology, institute of environmental medicine, Karolinska Institutet, Stockholm, Sweden; Centre for occupational and environmental medicine, Stockholm County Council, Sweden. 4. Department of medical sciences, Uppsala university, Uppsala, Sweden. 5. NTNU institute of cancer research and molecular medicine, Norwegian university of science and technology, Trondheim, Norway; Department of endocrinology, Trondheim university hospital, Trondheim, Norway. 6. Department of clinical sciences in Malmö, clinical research centre, Lund university, Malmö, Sweden. 7. Department of public health and caring sciences, Uppsala university, Uppsala, Sweden. 8. Unit of epidemiology, institute of environmental medicine, Karolinska Institutet, Stockholm, Sweden. 9. Division of endocrinology, abdominal centre, Finnish institute for molecular medicine and research program for diabetes and obesity, university of Helsinki and Folkhälsan research centre, Helsinki university hospital, Helsinki, Finland.
Abstract
BACKGROUND: A family history of diabetes (FHD) is a strong predictor of diabetes risk, yet has rarely been investigated in latent autoimmune diabetes in adults (LADA). This study therefore investigated the risk of LADA and type 2 diabetes (T2D) in relation to FHD, taking into account the type of diabetes in relatives. METHODS: Data from a population-based study were used, including incident cases of LADA [glutamic acid decarboxylase antibody (GADA)-positive, n=378] and T2D (GADA-negative, n=1199), and their matched controls (n=1484). First-degree relatives with disease onset at age<40 years and taking insulin treatment were classified as type 1 diabetes (T1D) or, if otherwise, as T2D. Odds ratios (ORs) were adjusted for age, gender, BMI, education and smoking. Cases were genotyped for high- and low-risk HLA genotypes. RESULTS: Both FHD-T1D (OR: 5.8; 95% CI: 3.2-10.3) and FHD-T2D (OR: 1.9; 95% CI: 1.5-2.5) were associated with an increased risk of LADA, whereas the risk of T2D was associated with FHD-T2D (OR: 2.7; 95% CI: 2.2-3.3), but not FHD-T1D. In LADA patients, FHD-T1D vs FHD-T2D was associated with higher GADA but lower C-peptide levels, lower prevalence of low-risk HLA genotypes (5.0% vs 28.6%, respectively; P=0.038) and a tendency for higher prevalence of high-risk genotypes (90.0% vs 69.1%, respectively; P=0.0576). CONCLUSION: The risk of LADA is substantially increased with FHD-T1D but also, albeit significantly less so, with FHD-T2D. This supports the idea of LADA as a mix of both T1D and T2D, but suggests that the genes related to T1D have greater impact. LADA patients with FHD-T1D had more T1D-like features, emphasizing the heterogeneity of LADA.
BACKGROUND: A family history of diabetes (FHD) is a strong predictor of diabetes risk, yet has rarely been investigated in latent autoimmune diabetes in adults (LADA). This study therefore investigated the risk of LADA and type 2 diabetes (T2D) in relation to FHD, taking into account the type of diabetes in relatives. METHODS: Data from a population-based study were used, including incident cases of LADA [glutamic acid decarboxylase antibody (GADA)-positive, n=378] and T2D (GADA-negative, n=1199), and their matched controls (n=1484). First-degree relatives with disease onset at age<40 years and taking insulin treatment were classified as type 1 diabetes (T1D) or, if otherwise, as T2D. Odds ratios (ORs) were adjusted for age, gender, BMI, education and smoking. Cases were genotyped for high- and low-risk HLA genotypes. RESULTS: Both FHD-T1D (OR: 5.8; 95% CI: 3.2-10.3) and FHD-T2D (OR: 1.9; 95% CI: 1.5-2.5) were associated with an increased risk of LADA, whereas the risk of T2D was associated with FHD-T2D (OR: 2.7; 95% CI: 2.2-3.3), but not FHD-T1D. In LADA patients, FHD-T1D vs FHD-T2D was associated with higher GADA but lower C-peptide levels, lower prevalence of low-risk HLA genotypes (5.0% vs 28.6%, respectively; P=0.038) and a tendency for higher prevalence of high-risk genotypes (90.0% vs 69.1%, respectively; P=0.0576). CONCLUSION: The risk of LADA is substantially increased with FHD-T1D but also, albeit significantly less so, with FHD-T2D. This supports the idea of LADA as a mix of both T1D and T2D, but suggests that the genes related to T1D have greater impact. LADA patients with FHD-T1D had more T1D-like features, emphasizing the heterogeneity of LADA.
Authors: Raffaella Buzzetti; Ernesto Maddaloni; Jason Gaglia; R David Leslie; F Susan Wong; Bernhard O Boehm Journal: Nat Rev Dis Primers Date: 2022-09-22 Impact factor: 65.038