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

Diabetes Metab Res Rev. 2016 Sep;32(6):589-95. doi: 10.1002/dmrr.2772. Epub 2016 Jan 26.

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: IGF1; IGF1R; TGFB1; low BMD; mRNA expression; type 1 diabetes.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / analysis
  • Blood Glucose / analysis
  • Bone Density*
  • Case-Control Studies
  • Child
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology*
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin / analysis
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Prognosis
  • Receptor, IGF Type 1
  • Receptors, Somatomedin / genetics
  • Receptors, Somatomedin / metabolism*
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • IGF1 protein, human
  • IGF1R protein, human
  • Receptors, Somatomedin
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • hemoglobin A1c protein, human
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1