Intensive Glycemic Control and Skeletal Health

描述(申请人提供)：患有2型糖尿病的老年人有更高的骨折风险，增加了这种疾病的健康负担。糖尿病患者更频繁的跌倒和骨骼强度的降低被认为是关键因素。然而，目前还不清楚更好地控制糖尿病是否足以降低骨折风险，或者是否应该对骨质疏松症进行额外的治疗。观察性研究表明，改善血糖控制可能通过预防跌倒、降低跌倒严重程度和减少骨丢失来降低骨折风险。以前的试验已经证明，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，这些都是跌倒的危险因素。强化血糖控制可能通过降低骨骼中晚期糖基化终末产物的水平，改善骨细胞功能，减少骨丢失来保持骨强度。另一方面，伴随着严格的血糖控制而增加的低血糖发作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的骨折、跌倒和/或骨丢失，我们建议在最近启动的临床试验行动控制糖尿病心血管风险(ACCORD)中增加骨折、跌倒和骨密度的测量。ACCORD将对10,000名患有2型糖尿病的中老年人(平均年龄63岁)进行平均5.6年的跟踪调查，以确定强化(A1C&lt；6%)与标准(A1C约7.5%)血糖控制是否能减少心血管事件。我们假设，与随机接受标准对照的患者相比，随机接受强化控制的患者骨折发生率更低，跌倒的频率更低，骨丢失也更少。在7145名ACCORD参与者中，骨折和跌倒将每12个月通过自我报告进行确定，报告的骨折将使用医疗记录进行集中判断。髋部和腰椎骨密度在两年内的变化将在子样本(N=240)中使用双能量吸收法(DEXA)来确定。

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).