Serum Sclerostin and Bone Turnover in Latent Autoimmune Diabetes in Adults.
Napoli N., Strollo R., Defeudis G., Leto G., Moretti C., Zampetti S., D'Onofrio L., Campagna G., Palermo A., Greto V., Manfrini S., Hawa MI., Leslie RD., Pozzilli P., Buzzetti R., NIRAD (NIRAD 10) and Action LADA Study Groups None.
Purpose:Bone formation is impaired in both type 1 diabetes and type 2 diabetes (T2D), whereas sclerostin, an antagonist of bone formation, is increased in T2D only. No data are available on latent autoimmune diabetes in adults (LADA), an autoimmune type of diabetes that may clinically resemble T2D at diagnosis. We evaluated serum sclerostin and bone turnover markers in LADA compared with those in T2D and whether metabolic syndrome (MetS) affects sclerostin in T2D or LADA. Methods:This cross-sectional study included 98 patients with T2D and 89 with LADA from the Action LADA and Non Insulin Requiring Autoimmune Diabetes cohorts. Patients were further divided according to MetS status. Nondiabetic participants (n = 53) were used as controls. Serum sclerostin, bone formation (pro-collagen type 1 N-terminal propeptide [P1NP]), and bone resorption (C-terminal telopeptide of type I collagen [CTX]) were analyzed. Results:Patients with T2D had higher sclerostin than did those with LADA [P = 0.0008, adjusted for sex and body mass index (BMI)], even when analysis was restricted to patients with MetS (adjusted P = 0.03). Analysis of T2D and LADA groups separately showed that sclerostin was similar between those with and those without MetS. However, a positive trend between sclerostin and number of MetS features was seen with T2D (P for trend = 0.001) but not with LADA. Patients with T2D or LADA had lower CTX than did controls (P = 0.0003) and did not have significantly reduced P1NP. Sclerostin was unrelated to age or hemoglobin A1c but was correlated with BMI (ρ = 0.29; P = 0.0001), high-density lipoprotein (ρ = -0.23; P = 0.003), triglycerides (ρ = 0.19; P = 0.002), and time since diagnosis (ρ = 0.32; P < 0.0001). Conclusions:Patients with LADA presented lower bone resorption than did controls, similar to patients with T2D. Sclerostin is increased in T2D but not in LADA, suggesting possible roles on bone metabolism in T2D only.