Intensive Glycemic Control and Skeletal Health

描述（由申请人提供）：老年2型糖尿病患者骨折风险较高，增加了该疾病的健康负担。糖尿病患者更频繁的跌倒和可能降低的骨骼强度被认为是关键因素。然而，目前尚不清楚更好地控制糖尿病是否足以降低骨折风险，或者是否应该给予骨质疏松症的额外治疗。观察性研究表明，改善血糖控制可以通过防止跌倒、降低跌倒的严重程度和减少骨质流失来降低骨折风险。先前的试验表明，改善控制可以减少糖尿病并发症，特别是周围神经病变和视网膜病变，这是跌倒的危险因素。强化血糖控制可以通过降低骨中晚期糖基化终产物的水平、改善骨细胞功能和减少骨质流失来保持骨强度。另一方面，在严格控制血糖的同时，低血糖发作的增加可能会促进老年糖尿病人群的跌倒，从而增加骨折的风险。为了确定强化血糖控制是否有助于预防老年糖尿病患者骨折、跌倒和/或骨质流失，我们建议在最近启动的临床试验Action to control Cardiovascular Risk In Diabetes （ACCORD）中增加骨折、跌倒和骨密度的测量。ACCORD将对10,000名中老年人（平均年龄63岁）2型糖尿病患者进行平均5.6年的随访，以确定强化（糖化血红蛋白< 6%）与标准（糖化血红蛋白约7.5%）血糖控制是否能减少心血管事件。我们假设，与随机分配到标准对照组的患者相比，随机分配到强化对照组的患者骨折率更低，摔倒次数更少，骨质流失也更少。在7145名ACCORD参与者中，骨折和跌倒将通过每12个月的自我报告来确定，报告的骨折将通过医疗记录来集中裁决。两年内髋骨和腰椎骨密度的变化将通过双能量吸收测定法（DEXA）在一个亚样本（N=240）中测定。

DESCRIPTION (provided by applicant): Older adults with type 2 diabetes have a higher risk of fractures, adding to the health burden of this disease. More frequent falls and perhaps reduced bone strength in those with diabetes are thought to be key contributing factors. However, it is not clear whether better control of diabetes is sufficient to reduce fracture risk or whether additional treatment for osteoporosis should be given. Observational studies suggest that improved glycemic control may reduce fracture risk by preventing falls, decreasing the severity of falls, and reducing bone loss. Previous trials have demonstrated that improved control reduces diabetic complications, particularly peripheral neuropathy and retinopathy, that are risk factors for falls. Intensive glycemic control may preserve bone strength through reduced levels of advanced glycation endproducts in the bone, improved bone cell function, and reduced bone loss. On the other hand, increased hypoglycemic episodes accompanying tight glycemic control could promote falls in the older diabetic population, resulting in an increased risk of fracture. In order to determine whether intensive glycemic control is useful as a prevention measure for fractures, falls and/or bone loss in older diabetic adults, we propose adding measures of fractures, falls and bone mineral density to the recently initiated clinical trial Action to Control Cardiovascular Risk in Diabetes (ACCORD). ACCORD will follow 10,000 middle-aged and older adults (average age 63 years) with type 2 diabetes for an average of 5.6 years to determine if cardiovascular events are reduced by intensive (A1C < 6%) versus standard (A1C approximately 7.5%) glycemic control. We hypothesize that those randomized to intensive control will have a lower rate of fractures, less frequent falls, and reduced bone loss compared with those randomized to standard control. In 7,145 of the ACCORD participants, fractures and falls will be determined by self-report every 12 months, with reported fractures adjudicated centrally using medical records. Change in bone mineral density over two years at the hip and lumbar spine will be determined in a subsample (N=240) using dual energy absorptiometry (DEXA).