caa a22 4500 475770994 CHVBK 20180406123617.0 cr unu---uuuuu 170329e20000101xx s 000 0 eng 10.1007/s001259900177 doi (NATIONALLICENCE)springer-10.1007/s001259900177 Impaired insulin secretion in non-diabetic offspring of probands with latent autoimmune diabetes mellitus in adults [Elektronische Daten] [I. Vauhkonen, L. Niskanen, M. Knip, J. Ilonen, E. Vanninen, S. Kainulainen, M. Uusitupa, M. Laakso] Aims/hypothesis. This study was undertaken to investigate metabolic and genetic characteristics of latent autoimmune diabetes in adults (LADA).¶Methods. We evaluated insulin secretory capacity with oral and intravenous glucose tolerance tests (early insulin response) and hyperglycaemic clamp (insulin secretory capacity) and the rates of whole body glucose uptake with the euglycaemic clamp, HLA-DQB1 genotypes (time-resolved fluorescence) and islet cell antibodies (ICA) (immunofluoresence) and antibodies to glutamic acid decarboxylase (GAD) (radio-immunoprecipitation) in 36 non-diabetic offspring (LADA-offspring) of patients with Type II (non-insulin-dependent) diabetes mellitus who tested positive for ICA and/or GAD antibodies during the 10-year follow-up from the diagnosis and in 19 healthy control subjects without a family history of diabetes.¶Results. The early insulin response during the first 10 min of an intravenous glucose tolerance test was about 40 % lower in the LADA-offspring than in the control group (p = 0.008). Insulin secretory capacity in the hyperglycaemic clamp was also about 30 % lower in the LADA-offspring (p = 0.048). The rates of whole body glucose uptake were similar in both groups. The frequency of low risk HLA-DQB1 genotypes was higher in the LADA-offspring than among Finnish healthy blood donors (p = 0.033). The risk conferring genotypes were associated with the lowest tertile of insulin secretory capacity in the LADA-offspring (p = 0.032). There were no associations between the autoantibodies and early insulin response or insulin secretory capacity within the study groups.¶Conclusion/interpretation. We conclude that LADA is a familial disease involving most likely gene defects leading to a slow progressive beta-cell destruction and insulin deficiency. [Diabetologia (2000) 43: 69-78] Springer-Verlag Berlin Heidelberg, 2000 Keywords Islet cell antibodies, glutamic acid decarboxylase antibodies, HLA-DQB1, relatives of Type II diabetic patients, insulin sensitivity nationallicence Vauhkonen I. Department of Medicine, Kuopio University Hospital and University of Kuopio, Kuopio, Finland, FI aut Niskanen L. Department of Medicine, Kuopio University Hospital and University of Kuopio, Kuopio, Finland, FI aut Knip M. Department of Paediatrics, University of Oulu, Oulu, Finland, FI aut Ilonen J. Turku Immunology Center and Department of Virology, University of Turku, Turku, Finland, FI aut Vanninen E. Department of Clinical Physiology, Kuopio University Hospital and University of Kuopio, Kuopio, Finland, FI aut Kainulainen S. Department of Clinical Radiology, Kuopio University Hospital and University of Kuopio, Kuopio, Finland, FI aut Uusitupa M. Department of Clinical Nutrition, Kuopio University Hospital and University of Kuopio, Kuopio, Finland, FI aut Laakso M. Department of Medicine, Kuopio University Hospital and University of Kuopio, Kuopio, Finland, FI aut https://doi.org/10.1007/s001259900177 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001259900177 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Vauhkonen I. Department of Medicine, Kuopio University Hospital and University of Kuopio, Kuopio, Finland, FI aut NATIONALLICENCE 700 1- Niskanen L. Department of Medicine, Kuopio University Hospital and University of Kuopio, Kuopio, Finland, FI aut NATIONALLICENCE 700 1- Knip M. Department of Paediatrics, University of Oulu, Oulu, Finland, FI aut NATIONALLICENCE 700 1- Ilonen J. Turku Immunology Center and Department of Virology, University of Turku, Turku, Finland, FI aut NATIONALLICENCE 700 1- Vanninen E. Department of Clinical Physiology, Kuopio University Hospital and University of Kuopio, Kuopio, Finland, FI aut NATIONALLICENCE 700 1- Kainulainen S. Department of Clinical Radiology, Kuopio University Hospital and University of Kuopio, Kuopio, Finland, FI aut NATIONALLICENCE 700 1- Uusitupa M. Department of Clinical Nutrition, Kuopio University Hospital and University of Kuopio, Kuopio, Finland, FI aut NATIONALLICENCE 700 1- Laakso M. Department of Medicine, Kuopio University Hospital and University of Kuopio, Kuopio, Finland, FI aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer