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

Abstract

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 +/- 3.4 years and mean glycosylated hemoglobin (HbA(1c)) level over 12 months was 9.8 +/- 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 +/- 7.7 vs. 107 +/- 5.7%, P = 0.005; 0.32 +/- 0.08 vs. 0.36 +/- 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 +/- 6613 vs. 24145 +/- 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.

Bone status in adolescents with type 1 diabetes

“…A negative influence of type 1 diabetes on bone has been observed in a number of case-control studies conducted in adults [2,22] as well as in children and adolescents [1,4,6,[23][24][25], where peripheral and axial DXA and QCT were employed. It has been suggested that observed differences in adults may result from mineralisation disorders, which operate during rapid skeletal development in puberty.…”

MECHANISMS IN ENDOCRINOLOGY: Mechanisms and evaluation of bone fragility in type 1 diabetes mellitus

“…Some studies, however, documented the presence of osteopenia at diagnosis of diabetes (35). As depicted in Table 1, BMD correlated poorly with glycaemic control in most (29,33,34,35,36,37), but not all (28,31,32), studies. However many studies reported an association between the presence of microvascular complications of diabetes and the presence and/or progression of a decreased BMD (27,28,38,40,42,50).…”

“…Although the decreased BMD reported in subjects with T1DM (27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,50,58) may largely explain the higher fracture risk observed in these patients (17,18,19,20,21,22,26), alterations in bone quality, as described below, may also contribute and actually confer its specific nature to diabetic bone disease.…”

“…Most (27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44), although not all (45,46,47,48,49), studies report a significant decrease in BMD at either the spine, hip or total body. The magnitude of the decrease in BMD varied quite markedly from 8 to 67%, and large gender differences appear to be present, with many studies documenting changes in BMD in either males or females only.…”

Osteoporosis in diabetes mellitus: Possible cellular and molecular mechanisms

“…Type 1 DM, also known as insulindependent DM, results from insulin insufficiency which leads to hyper glycemia in the young [20] . Besides the usual neurovascular complications, both male and female patients with type 1 DM manifest low bone mass at the hip, femoral neck and spine (Table 1), which may eventually lead to an increased incidence of bone fractures [2225,28,29] . In contrast, data on skeletal abnormalities in type 2 DM, or non insulin-dependent DM, appear conflicting, and the exact explanation of this is still unknown [26,27,30] .…”