Potential of Creatine in Glucose Management and Diabetes
Abstract
:1. Introduction
2. Insulin resistance in the Context of the Interplay between Creatine and Glucose Metabolism
3. Effects of Creatine Supplementation Alone on Glycemic Control
4. Effects of Creatine Supplementation Combined with Exercise on Glycemic Control
5. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Reference | Model | Creatine Protocol | Main Findings |
---|---|---|---|
Ferrante et al. [17] | Transgenic mice model of Huntington’s disease | Diet supplemented with 1, 2, or 3% of Cr for 21 d | ↑ glucose tolerance; ↑ neuroprotective effect; ↑ body weight; ↑ motor performance on the rotarod test. |
Op’t Eijnde et al. [9] | Male Wistar rats | Powdered rat chow with 5% of Cr for 5 d | ↑ Cr and PCr muscle content; ↔ muscle GLUT-4 content; ↔ glucose transport rate; ↔ plasma insulin; ↔ blood glucose. |
Young and Young, [48] | Male Sprague Dawley rats | 300 mg∙kg−1∙d−1 for 5 wk | ↑ Cr and PCr muscle content; ↔ basal rates of glucose uptake; ↔ insulin-stimulated rates of glucose uptake. |
Rooney et al. [31] | Male Wister rats | Chow containing 2% of Cr for 2, 4, or 8 wk | ↔ fasting plasma glucose; ↔ plasma glucose after oral glucose load; ↑ fasting plasma insulin levels; ↑ pancreatic TCr content. |
Ju et al. [10] | Female Wistar rats | Chow containing 2% of Cr for 3 wk | ↑ glycogen content; ↑ muscle GLUT-4 content; ↑ GLUT-4 mRNA; ↑ AMPK phosphorylation; ↑ Acetyl-Coa carboxylase phosphorylation. |
Op’t Eijnde et al. [32] | Male Goto-Kakizaki rats | Pallets enriched with 2% of Cr for 8 wk | ↑ muscle Cr content only in young rats (but not in older rats); ↓ plasma insulin concentration; ↔ Blood D-glucose concentration after OGTT; ↓ insulinogenic index. |
Nicastro et al. [49] | Male Wistar rats | 5 g∙Kg−1∙d−1 of Cr for 7 d + 5 mg∙kg−1∙d−1 of DXM | ↑ serum glucose and insulin after Cr + DXM; ↑ HOMA-IR after Cr + DXM; ↓ GLUT-4 translocation after Cr + DXM |
Reference | Sample (n) | Study Design | Creatine Protocol | Main Findings |
---|---|---|---|---|
Newman et al. [16] | Healthy, active, untrained, male adults (17) | Sigle-blind, placebo-controlled trial | Loading phase: 20 g∙d−1 (4 × 5 g) of Cr for 5 d + Maintenance phase: 3 g∙d−1 for 28 d | ↑ muscle TCr; ↔ muscle glycogen content; ↔ plasma glucose and insulin during OGTT; ↔ glucose-insulin index; ↔ index of insulin sensitivity. |
Rooney et al. [51] | Healthy, vegetarian adults (14) | Controlled-trial | 5 g∙d−1 of Cr for 42 d | ↑ plasma total Cr concentration; ↑ plasma glucose response; ↔ plasma insulin. |
Van Loon et al. [33] | Young, nonvegetarians adults (20) | Double-blind placebo-controlled trial | Loading phase: 20 g∙d−1 (4 × 5 g) of Cr for 5 d + Maintenance phase: 2 g∙d−1 for 6 wk | ↑ muscle glycogen, Cr and PCr after loading phase, with a decline in maintenance phase; ↔ GLUT-4 mRNA; ↔ total muscle GLUT-4 protein content. |
Safdar et al. [34] | Young, healthy, nonobese men (12) | Double-blind, crossover, randomized, placebo-controlled trial | Loading phase: 20 g∙d−1 (4 × 5 g) of Cr for 3 d + Maintenance phase: 5 g∙d−1 for 7 d | ↑ muscle total Cr ↑ PKB/Akt1 expression and protein; ↑ MAPK expression; ↔ GLUT-4 mRNA |
Rocic et al. [52] | Recently diagnosed T2DM patients, without anti-diabetic treatment (30) | Open-label, cross-over | 6 g∙d−1 of Cr or 1000 mg∙d−1 of metformin for 5 d | ↓ glucose concentration in both groups; ↔ insulin, C-peptide and, HbA1c. |
Reference | Model | Creatine and Training Protocol | Main Findings |
---|---|---|---|
Souza et al. [59] | Male Wistar rats | Loading phase: 5 g∙kg−1 body weight of Cr for 7 d + Maintenance phase: 1 g∙d−1 for 8 wk Training: swimming | ↓ plasma glucose levels during 1–4 wk after Cr alone; ↓ plasma glucose levels during 1–8 wk after Cr and exercise protocol. |
Freire et al. [61] | Male Wistar rats | Pallets enriched with 2% of Cr for 4 or 8 wk Training: swimming | ↔ glucose uptake; ↔ glucose AUC during OGTT; ↔ liver and quadriceps glycogen content. |
Vaisy et al. [62] | Male Wistar rats | Cafeteria diet enriched with 2.5% of Cr for 12 wk Training: swimming | ↔ fasting blood glucose concentration; ↓ fasting plasma insulin level after training and training + creatine; ↓ whole body insulin level. |
Araújo et al. [60] | Male Wistar rats | Loading phase: Chow containing 13% of Cr for 7d + Maintenance phase: Chow containing 2% of Cr for 55 d Training: high intensity treadmill running | ↔ glucose uptake; ↓ glucose AUC during OGTT after Cr and exercise protocol. |
Reference | Sample (n) | Study Design | Creatine and Training Protocol | Main Findings |
---|---|---|---|---|
Op’t Eijnde et al. [9] | Young, healthy subjects (22) | Double-blind placebo-controlled trial | Loading phase: 20 g∙d−1 during immobilization period (2 wk) + Maintenance phase: 15 g∙d−1 for 3 wk followed by 5 g∙d−1 for 7 wk during rehabilitation training Program training: knee-extensor resistance training (3 times∙wk−1) | Immobilization period: ↓ 20% GLUT-4 in placebo group, but not in Cr group; ↔ glycogen and Cr muscle content in both groups. Rehabilitation period: ↑ 40% GLUT-4 in Cr group; ↑ glycogen and Cr muscle content after Cr. |
Derave et al. [63] | Young, healthy subjects (22) | Double-blind, placebo-controlled trial | Loading phase: 15 g∙d−1 during immobilization period (2 wk) combined or not with protein supplementation + Maintenance phase: 2.5 g∙d−1 for 6 wk during rehabilitation training Program training: knee-extensor resistance training (3 times∙wk−1) | Immobilization period: ↓ GLUT-4 in placebo and Cr group, but not in Cr + protein group; ↔ glycogen and Cr muscle content in all groups. Rehabilitation period: ↑ 24% GLUT-4 in Cr group and ↑ 33% in Cr + protein group; ↑ glycogen and Cr muscle content after Cr and Cr + protein supplementation. |
Gualano et al. [18] | Healthy, sedentary male (22) | Double-blind, randomized-placebo-controlled trial | Loading phase: 0.3 g∙kg−1∙d−1 of Cr for 1 wk + Maintenance phase: 0.15 g∙kg−1∙d−1 for 11 wk Program training: aerobic training at 70% of the VO2max | ↓ glucose AUC after OGTT; ↔ fasting insulin; ↔ HOMA-IR. |
Gualano et al. [19] | T2DM patients (25) | Double-blind, randomized-placebo-controlled trial | 5 g∙d−1 of Cr for 12 wk Program training: Aerobic training and resistance training | ↓ HbA1c in Cr group; ↓ glycemia during MTT (0, 30 and 60 min) in Cr group; ↑ muscle PCr content in Cr group; ↑ muscle strength and function in Cr group |
Alves et al. [38] | T2DM patients (25) | Double-blind, randomized-placebo-controlled trial | 5 g∙d−1 of Cr for 12 wk Program training: Aerobic training and resistance training | ↑ AMPK protein expression; ↔ IR-β, Akt1 and MAPK. |
Oliveira et al. [64] | Healthy, older adults (32) | randomized, double-blind, placebo-controlled, parallel-group clinical trial | 5 g∙d−1 of Cr for 12 wk Program training: resistance training | ↔ inflammatory biomarkers ↔ fasting blood glucose; ↔ fasting insulin; ↔ HOMA-IR. |
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Solis, M.Y.; Artioli, G.G.; Gualano, B. Potential of Creatine in Glucose Management and Diabetes. Nutrients 2021, 13, 570. https://doi.org/10.3390/nu13020570
Solis MY, Artioli GG, Gualano B. Potential of Creatine in Glucose Management and Diabetes. Nutrients. 2021; 13(2):570. https://doi.org/10.3390/nu13020570
Chicago/Turabian StyleSolis, Marina Yazigi, Guilherme Giannini Artioli, and Bruno Gualano. 2021. "Potential of Creatine in Glucose Management and Diabetes" Nutrients 13, no. 2: 570. https://doi.org/10.3390/nu13020570