Sport, Health, and Performance Enhancement (SHAPE) Research Centre, Musculoskeletal Physiology Research Group, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.
Research Centre for Life and Sport Sciences (CLaSS), School of Health and Life Sciences, Department of Sport and Exercise, Birmingham City University, Birmingham, United Kingdom.
Adv Nutr. 2021 Dec 1;12(6):2216-2231. doi: 10.1093/advances/nmab087.
There is growing evidence that supplementation with carnosine, or its rate-limiting precursor β-alanine, can ameliorate aspects of metabolic dysregulation that occur in diabetes and its related conditions. The purpose of this systematic review and meta-analysis was to evaluate the effect of carnosine or β-alanine supplementation on markers of glycemic control and insulin resistance in humans and animals. We performed a systematic search of 6 electronic databases up to 31 December 2020. Primary outcomes were changes in 1) fasting glucose, 2) glycated hemoglobin (HbA1c), and 3) 2-h glucose following a glucose-tolerance test. A set of additional outcomes included fasting insulin and homeostatic model assessment of β-cell function (HOMA-β) and insulin resistance (HOMA-IR). We assessed risk of bias using the Cochrane risk of bias (RoB) 2.0 (human studies) and the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) RoB (animal studies) tools; and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess certainty. We used Bayesian hierarchical random-effects models, with informative priors for human data and noninformative priors for animal data. Inferences were made on posterior samples generated by Hamiltonian Markov Chain Monte Carlo using 90% credible intervals (90% CrI) and calculated probabilities. Twenty studies (n = 4 human, n = 16 rodent) were included, providing data for 2 primary outcomes (fasting glucose and HbA1c) and 3 additional outcomes (fasting insulin, HOMA-β, and HOMA-IR). The model provides evidence that supplementation decreases fasting glucose [humans: mean difference (MD)0.5 = -0.95 mmol · L-1 (90% CrI: -2.1, 0.08); rodent: MD0.5 = -2.26 mmol · L-1 (90% CrI: -4.03, -0.44)], HbA1c [humans: MD0.5 = -0.91% (90% CrI: -1.46, -0.39); rodents: MD0.5 = -1.05% (90% CrI: -1.64, -0.52)], HOMA-IR [humans: standardized mean difference (SMD)0.5 = -0.41 (90% CrI: -0.82, -0.07); rodents: SMD0.5 = -0.63 (90% CrI: -1.98, 0.65)], and fasting insulin [humans: SMD0.5 = -0.41 (90% CrI: -0.77, -0.07)]. GRADE assessment showed our certainty in the effect estimate of each outcome to be moderate (human outcomes) or very low (rodent outcomes). Supplementation with carnosine or β-alanine may reduce fasting glucose, HbA1c, and HOMA-IR in humans and rodents, and fasting insulin in humans; both compounds show potential as therapeutics to improve glycemic control and insulin resistance. This review was registered at PROSPERO as CRD42020191588.
越来越多的证据表明，补充肌肽或其限速前体β-丙氨酸，可以改善糖尿病及其相关疾病中发生的代谢失调的各个方面。本系统评价和荟萃分析的目的是评估肌肽或β-丙氨酸补充对人类和动物的血糖控制和胰岛素抵抗标志物的影响。我们对 6 个电子数据库进行了系统搜索，截至 2020 年 12 月 31 日。主要结局是 1）空腹血糖，2）糖化血红蛋白（HbA1c），以及 3）葡萄糖耐量试验后 2 小时血糖的变化。一组额外的结局包括空腹胰岛素和稳态模型评估的β细胞功能（HOMA-β）和胰岛素抵抗（HOMA-IR）。我们使用 Cochrane 偏倚风险（RoB）2.0（人体研究）和系统评价中心实验室动物实验（SYRCLE）RoB（动物研究）工具评估偏倚风险；并使用推荐评估、制定与评估（GRADE）方法评估确定性。我们使用贝叶斯分层随机效应模型，对人体数据使用信息性先验，对动物数据使用非信息性先验。在推断时，我们使用 Hamilton 马尔可夫链蒙特卡罗法生成的后验样本进行推断，使用 90%可信区间（90% CrI）和计算概率。共纳入 20 项研究（n=4 项人体，n=16 项啮齿动物），提供了 2 项主要结局（空腹血糖和 HbA1c）和 3 项额外结局（空腹胰岛素、HOMA-β和 HOMA-IR）的数据。该模型提供的证据表明，补充剂可以降低空腹血糖[人体：平均差值（MD）0.5=-0.95mmol·L-1（90% CrI：-2.1，0.08）；啮齿动物：MD0.5=-2.26mmol·L-1（90% CrI：-4.03，-0.44）]、HbA1c[人体：MD0.5=-0.91%（90% CrI：-1.46，-0.39）；啮齿动物：MD0.5=-1.05%（90% CrI：-1.64，-0.52）]、HOMA-IR[人体：标准化平均差值（SMD）0.5=-0.41（90% CrI：-0.82，-0.07）；啮齿动物：SMD0.5=-0.63（90% CrI：-1.98，0.65）]和空腹胰岛素[人体：SMD0.5=-0.41（90% CrI：-0.77，-0.07）]。GRADE 评估表明，我们对每个结局的效应估计的确定性为中度（人体结局）或非常低（啮齿动物结局）。肌肽或β-丙氨酸补充可能会降低人类和啮齿动物的空腹血糖、HbA1c 和 HOMA-IR，以及人类的空腹胰岛素；这两种化合物都有可能成为改善血糖控制和胰岛素抵抗的治疗药物。本综述在 PROSPERO 上注册为 CRD42020191588。
