Abstract
ObjectiveMetabolic syndrome (MetS), type 1 diabetes (T1D), and type 2 diabetes, are associated with an increased risk of fractures; however, the impact of obesity on bone deficits in diabetes is unknown. We aimed to compare markers of bone structure, bone density, and bone turnover in non-diabetic overweight men with MetS and overweight men with T1D or T2D.Methods and Research DesignIn this cross-sectional study we included participants from two previously described study cohorts consisting of participants with diabetes and participants with MetS. Participants underwent dual-energy X-ray absorptiometry measuring areal bone mineral density (aBMD) at the hip and lumbar spine, High Resolution peripheral Quantitative (HRpQCT) scan of the tibia and radius and measurement of circulating bone turnover markers. We compared groups with unpaired t test and performed multiple linear regression with adjustment for age, body mass index, and smoking.ResultsWe included 33 participants with T1D, 25 participants with T2D, and 34 participants with MetS. Bone turnover markers levels were comparable between T1D and MetS. aBMD at the hip was lower in T1D compared to MetS, also after adjustment. P1NP and Osteocalcin levels were lower among individuals with T2D compared to MetS, whereas aBMD were similar between the groups after multiple adjustments. We observed no difference in volumetric BMD at the tibia or radius between MetS and T1D and T2D, respectively. Participants with T2D had a higher trabecular number and lower trabecular separation compared to individuals with MetS at the tibia, which remained signficant after multiple adjustments.ConclusionIn conclusion, we observed no clinically important differences in bone density or structure between men with T2D, T1D, or MetS. However, men with T2D displayed lower bone turnover compared to MetS highlighting that T2D per se and not obesity, is associated with low bone turnover.
Highlights
The incidence of bone fracture is expected to increase in the coming years as the prevalence of diabetes increases, and diabetes per se is associated with an increased risk of fracture, e.g., a metaanalysis reported a 7-fold and 1.4-fold increased risk of hip fracture for type 1 diabetes (T1D) and type 2 diabetes (T2D), respectively [1] and another meta-analysis reported a 1.2-fold increased risk for non-hip, non-vertebral fractures for T2D and a non-significant 1.9-fold increased risk for T1D [2].The mechanisms of the increased fracture risk in patients with T1D and T2D are not fully elucidated
Impaired glucose tolerance is linked to insulin resistance which is associated with a lower bone turnover [8]; in observational studies that excluded individuals with diabetes neither insulin resistance or impaired glucose tolerance are associated with an increased fracture risk [9, 10]
In a study from our group we found no difference in HRpQCT parameters between patients with T1D and T2D [19]; another study reported lower vBMD in patients with T1D and microvascular complications compared to healthy controls with similar age, gender and body mass index (BMI) [20]
Summary
The incidence of bone fracture is expected to increase in the coming years as the prevalence of diabetes increases, and diabetes per se is associated with an increased risk of fracture, e.g., a metaanalysis reported a 7-fold and 1.4-fold increased risk of hip fracture for type 1 diabetes (T1D) and type 2 diabetes (T2D), respectively [1] and another meta-analysis reported a 1.2-fold increased risk for non-hip, non-vertebral fractures for T2D and a non-significant 1.9-fold increased risk for T1D [2].The mechanisms of the increased fracture risk in patients with T1D and T2D are not fully elucidated. Several factors may influence fracture risk in MetS and an observational study reported a strong association between MetS and increased fracture risk in individuals with increasing number of MetS characteristics [7]. Impaired glucose tolerance is linked to insulin resistance which is associated with a lower bone turnover [8]; in observational studies that excluded individuals with diabetes neither insulin resistance or impaired glucose tolerance are associated with an increased fracture risk [9, 10]. Obesity is associated with a decreased risk of fracture at the hip and spine, but associated with an increased risk for humerus-, femoral-, and ankle fractures [6, 11]. Bone mineral density (BMD) is increased in T2D and in overweight and obese individuals, whereas BMD is decreased in T1D [1, 12]. Individuals with T1D and T2D have impaired bone formation which is likely to be a contributing factor to increased fracture risk [15]
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