Lower bone mineral density in children with type 1 diabetes is associated with poor glycemic control and higher serum ICAM-1 and urinary isoprostane levels

The purpose of the study was to investigate bone mineral density (BMD) in children with type 1 diabetes (DM1) and to establish the relationships between BMD, physical activity, glycemic control, and markers of systemic oxidative stress and inflammation. We studied 30 children with DM1, aged 4.7-18.6 years, and 30 healthy subjects, matched by sex, age, and body mass index (BMI). Mean duration of DM1 was 5.4 +/- A 3.4 years and mean glycosylated hemoglobin (HbA(1c)) level over 12 months was 9.8 +/- A 1.5%. Lumbar and total bone mineral density (BMD, g/cm(2)) were measured by dual-energy X-ray absorptiometry (DXA). We calculated the apparent volumetric lumbar BMD (BMDvol, g/cm(3)) and total mineral content adjusted for age and height (BMCadj), and measured plasma intercellular adhesion molecule-1 (ICAM-1), high sensitivity C-reactive protein (hs-CRP), and urinary 8-iso-prostaglandin F(2a) (F(2)-IsoPs). Calcium (Ca) intake was assessed by questionnaire and physical activity by questionnaire and accelerometer (ActiGraph, count/h). Total BMCadj and lumbar BMDvol were significantly lower in children with DM1 than in controls (101.8 +/- A 7.7 vs. 107 +/- A 5.7%, P = 0.005; 0.32 +/- A 0.08 vs. 0.36 +/- A 0.09 g/cm(3), P = 0.05, respectively). These differences were mostly caused by the differences in boys. Plasma ICAM-1 and hs-CRP levels were significantly higher in the DM1 group compared to the controls. Ca intake and urine F(2)-IsoPs levels were similar between the groups. Diabetic boys were less active than controls (18231 +/- A 6613 vs. 24145 +/- A 7449 count/h, P = 0.04). In the DM1 group, lumbar BMDvol correlated inversely with urinary F(2)-IsoPs (r = -0.5; P = 0.005) and plasma ICAM-1 levels (r = -0.4; P = 0.02), and also with HbA(1c) levels after adjustment for age (r = -0.45; P < 0.05). Total BMCadj correlated inversely with HbA(1c) levels (r = -0.4; P = 0.02). We conclude that children with DM1, particularly boys, have lower BMD. Poor glycemic control, elevated markers of oxidative stress, and inflammation are associated with lower BMD.