A 10-Year Prospective Study of Bone Mineral Density and Bone Turnover in Males and Females With Type 1 Diabetes.

Context: In a previous community-based, cross-sectional study, males with type 1 diabetes (T1D) had lower bone mineral density (BMD) than did matched people without diabetes but females with T1D had normal BMD. Objective: To determine whether BMD in the males continued to decline, the neutral effect of T1D on BMD in females persisted, and whether temporal BMD changes reflected changes in bone turnover markers. Design: Longitudinal observational study. Setting: Urban community. Patients: Forty-eight of the original 102 original cross-sectional study participants (20 males, 28 females) of mean age 42.0 years and median diabetes duration 14.6 years at baseline who were restudied a mean of 10.3 years later. Main Outcome Measures: BMD at total hip, femoral neck, lumbar spine (L1 to L4), and distal forearm. Biochemical bone turnover markers. Results: After adjustment for age, body mass index (BMI), and renal function, there was no temporal change in BMD at the hip or forearm in the males (P ≥ 0.12), but lumbar spine BMD increased (P = 0.009). Females exhibited no statistically significant change in BMD in similar multivariable models that also included postmenopausal status, except a mild increase at the forearm (P = 0.046). Age- and sex-related changes in bone turnover markers paralleled those in general population studies. Conclusions: There is a reduction in BMD in males with T1D that occurs early in the course of the disease but then stabilizes. BMD in females with T1D remains similar to that expected for age, BMI, and postmenopausal status.

Circulating osteocalcin is unrelated to glucose homoeostasis in adults with type 1 diabetes.

AIMS: To assess the relationship between total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC) and a range of markers of glucose homeostasis in type 1 diabetes. METHODS: One hundred and eight community-based Caucasian adults (53 males, 55 females) without a history of osteoporosis and with a mean±SD age 39.1±15.1years and median [inter-quartile range] type 1 diabetes duration of 14.3 [6.6-20.4] years participated in a cross-sectional study of bone health. Fasting serum glucose and HbA1c, and serum tOC, ucOC, total adiponectin and procollagen type 1N-terminal propeptide (P1NP) were measured using validated assays, and daily insulin dose and estimated glucose disposal rate (eGDR) were calculated. Multiple linear regression was used to determine independent associates of markers of glucose homoeostasis (HbA1c, fasting serum glucose, daily insulin dose, eGDR and serum total adiponectin). RESULTS: In sex-adjusted multivariable regression analyses, ln(serum P1NP) was independently and inversely associated with ln(HbA1c) and ln(serum adiponectin) (P≤0.013). Other associations included those between ln(serum vitamin D) and ln(HbA1c) (inversely), daily insulin dose (inversely) and eGDR (positively) (P≤0.035), as well as an inverse relationship between overweight by waist circumference and ln(serum adiponectin) (P<0.001). Ln(serum tOC) and ln(serum ucOC) were not independently associated with any glucose homoeostasis marker. CONCLUSIONS: These data from well characterized community-based adults with type 1 diabetes do not suggest that there is a role for osteocalcin in the potentially complex interplay between the skeleton and energy homoeostasis in type 1 diabetes.

A five-year prospective study of bone mineral density in men and women with diabetes: the Fremantle Diabetes Study.

To examine longitudinally the effect of diabetes on bone structure and metabolism, we measured bone mineral density (BMD) and turnover markers in 26 type 1 (mean age 49 years) and 27 type 2 (mean age 65 years) diabetic patients without known osteoporosis from a community-based sample at baseline and 5 years later. In the 17 type 1 men, BMD fell at the femoral neck (0.804 ± 0.145 vs. 0.769 ± 0.129 g/cm(2); P = 0.003) with no change at lumbar spine or forearm. In the 11 type 2 women, BMD decreased at all sites except spine (femoral neck 0.779 ± 0.119 vs. 0.742 ± 0.090 g/cm(2); P = 0.019). BMD did not fall at any site in type 1 women or type 2 men. There was an increase in serum alkaline phosphatase and trend to higher serum beta carboxyl-terminal type I collagen telopeptide concentrations in the type 1 patients, and a decrease in free testosterone in the type 1 men. These data show that the rate of demineralization at the femoral neck in type 1 men is similar to that in older post-menopausal type 2 women. Changes in biochemical markers suggest that, in type 1 men, there is ineffective bone formation associated with accelerated bone resorption and lower sex steroid bioavailability. These findings may have implications for the clinical management of young male adults with diabetes.