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The Association between Hyperglycemia and Fracture Risk in Middle Age. A Prospective, Population-Based Study of 22,444 Men and 10,902 Women

Lund University, Department of Clinical Sciences, Clinical and Molecular Osteoporosis Research Unit (A.H.H., J-A.N., K.A.), and Medicine (P.M.N.), Malmö University Hospital, S-205 02 Malmö, Sweden

Address all correspondence and requests for reprints to: Anna H. Holmberg, M.D., Ph.D., Department of Orthopaedics, Malmö University Hospital, S-205 02 Malmö, Sweden. E-mail: Anna.Holmberg{at}skane.se.

Aims: Type 1 diabetes mellitus is associated with increased fracture risk, whereas the risk associated with type 2 diabetes is less obvious. Elevated fasting blood glucose and high 2-h glucose during an oral glucose tolerance test indicate impaired glucose tolerance or diabetes. The associations among fasting blood glucose, 2-h glucose, and the risk of fracture were investigated.

Methods: The Malmö Preventive Project consists of 22,444 men (44 ± 6.6 yr) and 10,902 women (50 ±7.4 yr), with a follow-up of 19 yr (±3.9) and 15 yr (±4.5) for incident fractures. Baseline assessment included multiple examinations and lifestyle information. A logistic regression model was used. Adjustments were made for age, body mass index (BMI), and smoking.

Results: Low-energy fractures were recorded in 1246 men and 1236 women. A 2-h glucose measurement between 4.3 and 6.2 mmol/liter in men (second and third quartile), and above 6.5 mmol/liter in women (third and fourth quartile), adjusted for age, BMI, and smoking, was significantly associated with a decreased risk of multiple fractures, in men [odds ratios (ORs) 0.57–0.71] and women (ORs 0.38–0.66). In women, a 2-h glucose measurement above 7.5 mmol/liter was associated with a decreased risk of osteoporotic fractures (OR 0.57, 95% confidence interval 0.44–0.74).

Conclusions: In middle-aged men and women, elevated 2-h glucose levels were associated with decreased risks of multiple and osteoporotic fractures, independent of age, BMI, and smoking. A high 2-h glucose level is characterized by peripheral insulin resistance with a high insulin level. Our findings indirectly suggest a positive effect on bone from hyperglycemia.