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  • Martinez, Maria MånssonLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Celiac Disease and Diabetes Unit,Lund University Research Groups,Skåne University Hospital (author)

Heterogeneity of beta-cell function in subjects with multiple islet autoantibodies in the TEDDY family prevention study - TEFA

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-01-05
  • Springer Science and Business Media LLC,2022
  • 10 s.

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  • LIBRIS-ID:oai:lup.lub.lu.se:366310e4-0447-4d61-86cc-6f1a6ee4fbab
  • https://lup.lub.lu.se/record/366310e4-0447-4d61-86cc-6f1a6ee4fbabURI
  • https://doi.org/10.1186/s40842-021-00135-6DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • BACKGROUND: Individuals with multiple islet autoantibodies are at increased risk for clinical type 1 diabetes and may proceed gradually from stage to stage complicating the recruitment to secondary prevention studies. We evaluated multiple islet autoantibody positive subjects before randomisation for a clinical trial 1 month apart for beta-cell function, glucose metabolism and continuous glucose monitoring (CGM). We hypothesized that the number and type of islet autoantibodies in combination with different measures of glucose metabolism including fasting glucose, HbA1c, oral glucose tolerance test (OGTT), intra venous glucose tolerance test (IvGTT) and CGM allows for more precise staging of autoimmune type 1 diabetes than the number of islet autoantibodies alone.METHODS: Subjects (n = 57) at 2-50 years of age, positive for two or more islet autoantibodies were assessed by fasting plasma insulin, glucose, HbA1c as well as First Phase Insulin Response (FPIR) in IvGTT, followed 1 month later by OGTT, and 1 week of CGM (n = 24).RESULTS: Autoantibodies against GAD65 (GADA; n = 52), ZnT8 (ZnT8A; n = 40), IA-2 (IA-2A; n = 38) and insulin (IAA; n = 28) were present in 9 different combinations of 2-4 autoantibodies. Fasting glucose and HbA1c did not differ between the two visits. The estimate of the linear relationship between log2-transformed FPIR as the outcome and log2-transformed area under the OGTT glucose curve (AUC) as the predictor, adjusting for age and sex was - 1.88 (- 2.71, - 1.05) p = 3.49 × 10-5. The direction of the estimates for all glucose metabolism measures was positive except for FPIR, which was negative. FPIR was associated with higher blood glucose. Both the median and the spread of the CGM glucose data were significantly associated with higher glucose values based on OGTT, higher HbA1c, and lower FPIR. There was no association between glucose metabolism, autoantibody number and type except that there was an indication that the presence of at least one of ZnT8(Q/R/W) A was associated with a lower log2-transformed FPIR (- 0.80 (- 1.58, - 0.02), p = 0.046).CONCLUSIONS: The sole use of two or more islet autoantibodies as inclusion criterion for Stage 1 diabetes in prevention trials is unsatisfactory. Staging type 1 diabetes needs to take the heterogeneity in beta-cell function and glucose metabolism into account.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02605148 , November 16, 2015.

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  • Spiliopoulos, LamprosLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine,Skåne University Hospital(Swepub:lu)la3078sp (author)
  • Salami, FalastinLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Celiac Disease and Diabetes Unit,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-fss (author)
  • Agardh, DanielLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Celiac Disease and Diabetes Unit,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-dia (author)
  • Toppari, JormaTurku University Hospital,University of Turku (author)
  • Lernmark, ÅkeLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Celiac Disease and Diabetes Unit,Lund University Research Groups,Skåne University Hospital(Swepub:lu)endo-ale (author)
  • Kero, JukkaUniversity of Turku,Turku University Hospital(Swepub:lu)ju1247ke (author)
  • Veijola, RiittaOulu University Hospital,University of Oulu(Swepub:lu)ri3323ve (author)
  • Tossavainen, PäiviOulu University Hospital,University of Oulu(Swepub:lu)pa6174to (author)
  • Palmu, SauliTampere University Hospital(Swepub:lu)sa4103pa (author)
  • Lundgren, MarkusLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine,Skåne University Hospital(Swepub:lu)med-mn2 (author)
  • Borg, HenrikLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine,Skåne University Hospital(Swepub:lu)endo-hbo (author)
  • Katsarou, AnastasiaLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Celiac Disease and Diabetes Unit,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-ask (author)
  • Larsson, Helena EldingLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine,Skåne University Hospital(Swepub:lu)pedi-hla (author)
  • Knip, MikaelUniversity of Helsinki (author)
  • Maziarz, MarlenaLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Celiac Disease and Diabetes Unit,Lund University Research Groups,Skåne University Hospital(Swepub:lu)ma4353ma (author)
  • Törn, CarinaLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Celiac Disease and Diabetes Unit,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-cto (author)
  • Institutionen för kliniska vetenskaper, MalmöMedicinska fakulteten (creator_code:org_t)
  • The TEDDY Family (TEFA) Study Group

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  • In:Clinical diabetes and endocrinology: Springer Science and Business Media LLC7:12055-8260

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