Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Biochemistry, Rigshospitalet, Kobenhavn, Denmark.
Eur J Endocrinol. 2019 Sep;181(3):221-231. doi: 10.1530/EJE-19-0309.
Bone turnover has a diurnal variation influenced by food intake, incretin hormones, the sympathetic nervous system and osteocyte function. The aim of the study was to compare diurnal variation in bone turnover in patients with diabetes and controls.
A clinical 24-h study with patients with type 1 diabetes (n = 5), patients with type 2 diabetes (n = 5) and controls (n = 5).
Inclusion criterion: age >50 years. Exclusion criteria: diseases/medication that affect bone metabolism or recent use of incretin-based drugs. We drew blood samples hourly during the day and every 3 h during the night. We served an identical diet on all study days. We used repeated-measures one-way ANOVA to compare the levels of the investigated markers, and we quantified the effect of time by comparing group mean standard deviations.
The bone formation marker procollagen type 1 N-terminal propeptide showed a significant interaction between time and group (P = 0.01), and the mean standard deviation was lower in patients with type 2 diabetes compared with controls (P = 0.04) and patients with type 1 diabetes (P = 0.02). Other markers of bone formation and resorption showed significant effect of time. Levels of glucagon-like peptide-2, glucose-dependent insulinotropic peptide and sclerostin only showed significant effect of time (all P values 0.01), but levels of sclerostin tended to being highest in type 2 diabetes and lowest in controls.
The diurnal variation in bone formation is attenuated in patients with type 2 diabetes. This is not explained by changes in incretin hormone levels, but possibly mediated by sclerostin.
骨转换具有受饮食摄入、肠降血糖素激素、交感神经系统和骨细胞功能影响的昼夜变化。本研究的目的是比较糖尿病患者和对照组的骨转换昼夜变化。
一项针对 1 型糖尿病患者（n=5）、2 型糖尿病患者（n=5）和对照组（n=5）的临床 24 小时研究。
纳入标准：年龄>50 岁。排除标准：影响骨代谢的疾病/药物或近期使用肠促胰岛素药物。我们在白天每小时抽取一次血样，夜间每 3 小时抽取一次。所有研究日均提供相同的饮食。我们使用重复测量的单向方差分析比较了研究标志物的水平，并通过比较组平均值的标准差来量化时间的影响。
骨形成标志物 1 型前胶原 N 端前肽显示时间和组之间存在显著交互作用（P=0.01），与对照组（P=0.04）和 1 型糖尿病患者（P=0.02）相比，2 型糖尿病患者的平均标准差较低。其他骨形成和吸收标志物也显示出显著的时间效应。胰高血糖素样肽-2、葡萄糖依赖性胰岛素释放肽和骨硬化蛋白的水平仅显示出时间的显著效应（所有 P 值均<0.01），但骨硬化蛋白的水平似乎在 2 型糖尿病中最高，在对照组中最低。
2 型糖尿病患者的骨形成昼夜变化减弱。这不能用肠降血糖素激素水平的变化来解释，但可能是由骨硬化蛋白介导的。
