Abstract

ABSTRACTThere 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.

Highlights

  • Diabetes is a major public health problem; worldwide estimates show that 463 million people were living with diabetes in 2019—equivalent to 9.3% of the global population [1]

  • The primary outcomes were changes in fasting glucose, HbA1c, and 2-h glucose following a glucose-tolerance test (GTT). These outcomes represent the 3 clinical markers used in the diagnosis of type 1 diabetes, type 2 diabetes, prediabetes, and gestational diabetes [31, 32]

  • Twenty studies were included in the data synthesis—7 studies in mice (n = 132 mice), 9 studies in rats (n = 159 rats), and 4 human studies (n = 172 participants)—providing data for 2 primary outcomes and 3 additional outcomes [fasting insulin, HOMA-IR, and homeostatic model assessment for steady-state βcell function (HOMA-β)]

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Summary

Introduction

Diabetes is a major public health problem; worldwide estimates show that 463 million people were living with diabetes in 2019—equivalent to 9.3% of the global population [1]. A hallmark of type 2 diabetes is poor glycemic control and insulin resistance [2], which present earlier in life as impaired fasting glucose or impaired glucose tolerance ( known as prediabetes). This represents a high-risk state that requires intervention, as a 45-y-old with prediabetes has a 74% lifetime risk of progression to type 2 diabetes [3]. It is essential to develop lowcost, novel therapies to improve glycemic control and help prevent or delay disease progression

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