Trabecular bone score in type 1 diabetes--a cross-sectional study.

UNLABELLED: Trabecular bone score (TBS) seems to provide additive value on BMD to identify individuals with prevalent fractures in T1D. TBS did not significantly differ between T1D patients and healthy controls, but TBS and HbA1c were independently associated with prevalent fractures in T1D. A TBS cutoff <1.42 reflected prevalent fractures with 91.7 % sensitivity and 43.2 % specificity. INTRODUCTION: Type 1 diabetes (T1D) increases the risk of osteoporotic fractures. TBS was recently proposed as an indirect measure of bone microarchitecture. This study aimed at investigating the TBS in T1D patients and healthy controls. Associations with prevalent fractures were tested. METHODS: One hundred nineteen T1D patients (59 males, 60 premenopausal females; mean age 43.4 ± 8.9 years) and 68 healthy controls matched for gender, age, and body mass index (BMI) were analyzed. The TBS was calculated in the lumbar region, based on two-dimensional (2D) projections of DXA assessments. RESULTS: TBS was 1.357 ± 0.129 in T1D patients and 1.389 ± 0.085 in controls (p = 0.075). T1D patients with prevalent fractures (n = 24) had a significantly lower TBS than T1D patients without fractures (1.309 ± 0.125 versus 1.370 ± 0.127, p = 0.04). The presence of fractures in T1D was associated with lower TBS (odds ratio = 0.024, 95 % confidence interval (CI) = 0.001-0.875; p = 0.042) but not with age or BMI. TBS and HbA1c were independently associated with fractures. The area-under-the curve (AUC) of TBS was similar to that of total hip BMD in discriminating T1D patients with or without prevalent fractures. In this set-up, a TBS cutoff <1.42 discriminated the presence of fractures with a sensitivity of 91.7 % and a specificity of 43.2 %. CONCLUSIONS: TBS values are lower in T1D patients with prevalent fractures, suggesting an alteration of bone strength in this subgroup of patients. Reliable TBS cutoffs for the prediction of fracture risk in T1D need to be determined in larger prospective studies.

High serum pentosidine but not esRAGE is associated with prevalent fractures in type 1 diabetes independent of bone mineral density and glycaemic control.

UNLABELLED: Fracture risk in type 1 diabetes (T1D) is supposed to be underestimated by bone mineral density (BMD). Individuals with T1D had more prevalent fractures in a cross-sectional study. Serum levels of pentosidine, an advanced glycation end product, and poor glycaemic control were associated with prevalent fractures independent of BMD. INTRODUCTION: Type 1 diabetes (T1D) is associated with increased fracture risk. Bone mineral density (BMD) underestimates the risk of fractures in some individuals. The accumulation of advanced glycation end products (AGEs) impairs bone matrix and reduces bone strength. METHODS: In a cross-sectional study, 128 men and premenopausal women with T1D were evaluated. We compared traditional risk factors for fractures, BMD, parameters of bone metabolism and AGEs in individuals with and without prevalent fractures. An independent association of serum AGE levels with prevalent fractures was investigated. RESULTS: Individuals with prevalent fractures exhibited a longer duration of T1D, higher HbA1c and more diabetic-related complications. BMD at the femoral neck (z-score -0.76 ± 0.94 vs. -0.23 ± 1.02; p = 0.031) and total hip (z-score -0.54 ± 0.93 vs. 0.11 ± 1.11; p = 0.017) was lower in those with prevalent fractures. Individuals with fractures had higher pentosidine levels (164.1 ± 53.6 vs. 133.2 ± 40.4; p = 0.002). The levels of N-ε-(carboxymethyl)-lysine (CML) and endogenous secretory receptor for AGEs (esRAGE) did not significantly differ. Multivariate logistic regression analysis adjusted for age, BMI, family history of fractures, smoking, vitamin D deficiency, BMD at lumbar spine, femoral neck and total hip identified pentosidine levels and HbA1c as independent factors associated with prevalent fractures (odds ratio 1.02, 95% CI 1.00-1.03/pmol/ml increase of pentosidine; p = 0.008 and odds ratio 1.93, 95% CI 1.16-3.20 per percentage increase of HbA1c; p = 0.011). CONCLUSIONS: The pentosidine levels but not BMD are independently associated with prevalent fractures. Impaired bone quality in T1D may result from increased AGE formation.

Glycaemic control is positively associated with prevalent fractures but not with bone mineral density in patients with Type 1 diabetes.

AIM: There are conflicting data regarding the risk of osteoporosis in patients with Type 1 diabetes. We investigated an association between diabetes, bone mineral density and prevalent fractures. METHODS: A single-centre, cross-sectional study of men and pre-menopausal women with Type 1 diabetes (n = 128) and a matched control group (n = 77) was conducted. The primary outcome measure was bone mineral density and secondary measures were markers of bone metabolism and prevalent fractures. RESULTS: Hip and total body bone mineral densities were significantly lower in women with diabetes compared with control subjects. In men, no difference in bone mineral density was found. A multivariate regression analysis in women with diabetes revealed higher BMI as the strongest predictor of higher total hip, femoral neck and total body bone mineral density, whereas previous fractures were inversely associated with total hip bone mineral density and C-terminal telopeptide of type I collagen with total body bone mineral density. Poor long-term glycaemic control was not associated with low bone mineral density. Fracture frequency was higher in patients with diabetes compared with control subjects (1.64 vs. 0.62 per 100 patient-years; P < 0.05). In a multivariable model, long-term HbA(1c) control was associated with increased clinical fracture prevalence (OR 1.92; 95% CI 1.09-2.75) in those with diabetes. CONCLUSIONS: Type 1 diabetes contributes to low bone mineral density in women. Previous fractures and low BMI were strong predictors of impaired bone mineral density and should therefore be considered in risk estimation. Fractures are more frequent in Type 1 diabetes. Long-term hyperglycaemia may account for impaired bone strength, independently from bone mineral density.

Osteocalcin, adipokines and their associations with glucose metabolism in type 1 diabetes.

To determine osteocalcin (OC) and adipokines in type 1 diabetes (T1D) and healthy controls, and to explore possible associations between glucose and bone metabolism, body composition and adipokines. Serum levels of total OC, undercarboxylated (UC-OC), leptin, adiponectin, and other parameters of glucose and bone metabolism were measured in 128 patients with T1D (mean duration 21.2years) and in 77 healthy controls, matched for gender, age, and body mass index (BMI). Partial correlations (adjusted for age and gender) with parameters of body composition (BMI, fat body mass [derived from bone mineral density scans]), glycaemic control (hemoglobin A1c (HbA1c), daily insulin dose in T1D), skeletal homeostasis (osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), all measured in serum), and serum insulin-like growth factor 1 (IGF-1) were also examined. Independent predictors of total and UC-OC were then explored. Total OC was lower in males with T1D (16.3±6.4 vs. 22.2±9.9ng/ml; p=0.001), whereas UC-OC did not show group differences. Adiponectin was higher in T1D patients, both for males and females (8.9±6.6 vs. 5.7±2.5µg/ml; p=0.004 and 13.8±6.4 vs. 8.8±4.0µg/ml; p<0.001). IGF-1 was lower only in females with T1D (146.6±68.8 vs. 203.0±74.4ng/ml; p<0.001). BMI and fat body mass were similar in T1D and controls. In T1D patients, total OC was inversely correlated with BMI and HbA1c, and UC-OC inversely correlated with HbA1c. In T1D patients, leptin positively correlated with BMI, fat body mass and daily insulin dose, while adiponectin inversely correlated with BMI and daily insulin dose. Multivariate regression modelling showed that determinants of higher total OC levels were male gender (p=0.04, ß-coefficient=2.865) and lower HbA1c (p=0.04, ß-coefficient=-0.117), whereas determinants of UC-OC levels were T1D (p=0.016, ß-coefficient=2.015), higher IGF-1 (p=0.004, ß-coefficient=0.011) and lower HbA1c (p=0.011, ß-coefficient=- 0.061). Total OC and UC-OC are associated with good glycaemic control in T1D, with gender-specific differences for total-OC. The association of leptin and adiponectin with glycaemic control, as observed in controls, does not seem to be a feature in T1D, although both adipokines appear to be related to the insulin demand. This article is part of a Special Issue entitled "Bone and diabetes".