Changhee Lee

Background:  Type-2 diabetes mellitus (T2DM) is among the most common metabolic conditions worldwide, with an estimated prevalence of 463 milllion adults globally as of 2019¹. Intermittent fasting (IF), which involves modified timing of caloric intake without intentional change in overall intake, has demonstrated promise as a non-pharmacologic means of improving glycemic control in T2DM through multiple randomized trials to date, with effect sizes comparable to medical therapy in one trial^2,3,4. While the molecular mechanisms underlying this benefit are incompletely understood, the adipokine adiponectin has come to the forefront as an important biomarker for insulin resistance in T2DM⁵. This analysis seeks to synthesize a narrative of recent experimental findings as they relate to the potential role of adiponectin in the glycemic effects of intermittent fasting on T2DM.

Methods:  PubMed was searched to identify original research articles as well as meta-analyses of trials studying the effects of IF in patients with T2DM. Search keywords used included “intermittent fasting AND diabetes mellitus”, “adiponectin AND intermittent fasting”, and “adiponectin AND fasting”. Articles were selected for review based on relevance to the scope of the current analysis.

Results:  A central process implicated in the development of insulin resistance is abnormal fatty acid buildup in non-adipocyte tissues, especially skeletal muscle⁵. Adiponectin is known to both stimulate fatty acid oxidation in muscle and impact GLUT4 translocation in muscle cells^5,6. Adiponectin may thus play a central role in reducing the burden of fatty acids in muscle tissue, allowing restoration of insulin sensitivity. A recent study supports the relationship between increased adiponectin levels and decreased muscle adipose tissue content in healthy Japanese older adults⁷. The Whitehall II longitudinal study has previously demonstrated decreased adiponectin levels to precede onset of T2DM in both male and female adults in the UK⁸. When looking at adiponectin levels directly, however, the association becomes more complex, with statistically significant increases in adiponectin seen with IF regimens in healthy adults but not adults with T2DM based on meta-analyses to date^9,10.

Conclusions:  Adiponectin may play a central role in the pathogenesis of T2DM as well as mediation of glyemic benefits seen in IF. The association between adiponectin and glycemic benefits, however, is likely complex, and further studies are needed to more precisely elucidate its role in T2DM.

Works Cited

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2. Guo L, Xi Y, Jin W, et al. A 5:2 Intermittent Fasting Meal Replacement Diet and Glycemic Control for Adults with Diabetes The EARLY Randomized Clinical Trial. JAMA Netw Open. 2024;7(6):e2416786. doi: 0.1001/jamanetworkopen.2024.16786.
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9. Cho Y, Hong N, Kim KW, et al. The Effectiveness of Intermittent Fasting to Reduce Body Mass Index and Glucose Metabolism: A Systematic Review and Meta-Analysis. J Clin Med. 2019;8(10):1645. doi: 10.3390/jcm8101645.
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