title: Low bone mineral density in patients with type 1 diabetes: association with reduced expression of IGF1, IGF1R and TGF B 1 in peripheral blood mononuclear cells.
abstract: The negative effects of type 1 diabetes (T1D) on growth factors of bone metabolism lead to a reduction in bone mineral density. This study aimed to evaluate the association between bone mineral density and insulin-like growth factor 1 (IGF1), insulin-like growth factor 1 receptor (IGF1R) and transforming growth factor beta 1 (TGFB1) expressions in children and adolescents with T1D. Moreover, the influences of age at diagnosis, time since diagnosis, glycaemic control and albuminuria on bone mineral density were investigated.
  
  
  
  Eighty-six T1D children/adolescents (T1D group) and ninety normoglycaemic controls (normoglycaemic group) were included. T1D patients were analysed as a whole and also in subsets of patients with good glycaemic control (glycated hemoglobin concentration ≤7.5%) and with poor glycaemic control (glycated hemoglobin concentration >7.5%). Bone mineral density was assessed by dual energy x-ray absorptiometry. Glycaemic control, renal function and bone markers were also assessed. IGF1, IGF1R and TGFB1 expressions were determined in peripheral blood mononuclear cells by real-time polymerase chain reaction.
  
  
  
  Patients with T1D showed low bone mineral density and poor glycaemic control. Serum total calcium and urinary albumin-to-creatinine ratio were higher in patients with poor glycaemic control compared to those with good glycemic control (p = 0.003 and p = 0.035, respectively). There was a reduction of IGF1, IGF1R and TGFB1 expressions in the T1D patients and in the subset with poor glycaemic control compared to normoglycaemic controls (p < 0.05).
  
  
  
  The decreased IGF1, IGF1R and TGFB1 expressions in the T1D patients, who presented with T1D at an early age, had been diagnosed with T1D for a longer time, had poor glycaemic control and albuminuria may contribute to low bone mineral density. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: Karla Simone Costa
authors.initials: KS
authors.lastname: de Souza
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: Marcela Abbott Galvão
authors.initials: MA
authors.lastname: Ururahy
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: Yonara Monique
authors.initials: YM
authors.lastname: da Costa Oliveira
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: Melina Bezerra
authors.initials: MB
authors.lastname: Loureiro
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: Heglayne Pereira Vital
authors.initials: HP
authors.lastname: da Silva
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: Raul Hernandes
authors.initials: RH
authors.lastname: Bortolin
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: Fabricio
authors.initials: F
authors.lastname: Melo Dos Santos
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: André Ducati
authors.initials: AD
authors.lastname: Luchessi
authors.affiliation: Radiology Center, Onofre Lopes University Hospital of Federal University of Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: José Jorge Maciel
authors.initials: JJ
authors.lastname: Neto
authors.affiliation: Department of Pediatrics, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Ricardo Fernando
authors.initials: RF
authors.lastname: Arrais
authors.affiliation: Department of Clinical and Toxicological Analyses, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Rosario Dominguez Crespo
authors.initials: RD
authors.lastname: Hirata
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: Maria
authors.initials: M
authors.lastname: das Graças Almeida
authors.affiliation: Department of Clinical and Toxicological Analyses, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Mario Hiroyuki
authors.initials: MH
authors.lastname: Hirata
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: Adriana Augusto
authors.initials: AA
authors.lastname: de Rezende
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D015519:Bone Density; D016022:Case-Control Studies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D011379:Prognosis; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin; D053773:Transforming Growth Factor beta1; C583557:IGF1 protein, human; C000597236:IGF1R protein, human; C508960:TGFB1 protein, human; C517652:hemoglobin A1c protein, human
keywords: IGF1; IGF1R; TGFB1; low BMD; mRNA expression; type 1 diabetes