Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA.
Department of Public Health Laboratory Sciences, West China School of Public Health, Sichuan University, Chengdu, Sichuan Province, China.
Diabetes Care. 2019 Aug;42(8):1365-1371. doi: 10.2337/dc19-0134. Epub 2019 May 21.
Type 2 diabetes is related to obesity and altered bone health, and both are affected by gut microbiota. We examined associations of weight loss diet-induced changes in a gut microbiota-related metabolite trimethylamine N-oxide (TMAO), and its precursors (choline and l-carnitine), with changes in bone mineral density (BMD) considering diabetes-related factors.
In the 2-year Preventing Overweight Using Novel Dietary Strategies trial (POUNDS Lost), 264 overweight and obese participants with measurement of BMD by DXA scan were included in the present analysis. The participants were randomly assigned to one of four diets varying in macronutrient intake. Association analysis was performed in pooled participants and different diet groups. Changes in blood levels of TMAO, choline, and l-carnitine from baseline to 6 months after the dietary intervention were calculated.
We found that a greater reduction in plasma levels of TMAO from baseline to 6 months was associated with a greater loss in whole-body BMD at 6 months and 2 years ( = 0.03 and = 0.02). The greater reduction in TMAO was also associated with a greater loss in spine BMD ( = 0.005) at 2 years, independent of body weight changes. The associations were not modified by baseline diabetes status and glycemic levels. Changes in l-carnitine, a precursor of TMAO, showed interactions with dietary fat intake in regard to changes of spine BMD and hip BMD at 6 months (all < 0.05). Participants with the smallest decrease in l-carnitine showed less bone loss in the low-fat diet group than the high-fat diet group ( = 0.03 and = 0.02).
TMAO might protect against BMD reduction during weight loss, independent of diet interventions varying in macronutrient content and baseline diabetes risk factors. Dietary fat may modify the relation between change in plasma l-carnitine level and changes in BMD. Our findings highlight the importance of investigating the relation between TMAO and bone health in patients with diabetes.
2 型糖尿病与肥胖和骨骼健康改变有关，而这两者均受肠道菌群的影响。我们研究了与体重减轻相关的肠道菌群代谢物三甲胺 N-氧化物（TMAO）及其前体（胆碱和左旋肉碱）的变化与考虑到糖尿病相关因素的骨密度（BMD）变化之间的关联。
在为期 2 年的使用新型饮食策略预防超重试验（POUNDS Lost）中，共有 264 名超重和肥胖参与者接受了 DXA 扫描测量 BMD，他们被纳入本分析。参与者被随机分配到四种不同宏量营养素摄入量的饮食组之一。在汇总的参与者和不同的饮食组中进行了关联分析。从基线到饮食干预后 6 个月，计算了 TMAO、胆碱和左旋肉碱的血液水平变化。
我们发现，从基线到 6 个月时 TMAO 水平的降低幅度与 6 个月和 2 年时全身体 BMD 的降低幅度更大相关（ = 0.03 和 = 0.02）。TMAO 的更大降幅也与 2 年时脊柱 BMD 的更大降幅相关（ = 0.005），与体重变化无关。这些关联不受基线糖尿病状态和血糖水平的影响。TMAO 的前体左旋肉碱的变化与 6 个月时脊柱 BMD 和髋部 BMD 的饮食脂肪摄入量之间存在交互作用（均 < 0.05）。在低脂饮食组中，左旋肉碱降幅最小的参与者的骨丢失量小于高脂肪饮食组（ = 0.03 和 = 0.02）。
TMAO 可能独立于宏量营养素含量和基线糖尿病危险因素不同的饮食干预，防止减肥期间 BMD 降低。膳食脂肪可能会改变血浆左旋肉碱水平变化与 BMD 变化之间的关系。我们的研究结果强调了在糖尿病患者中研究 TMAO 与骨骼健康之间关系的重要性。
