Research
Hormonal
Obesity drives insulin resistance and type 2 diabetes through the accumulation of free fatty acids and pro-inflammatory cytokines in non-adipose tissues, which activate kinases (PKC, JNK, IKKβ) that inhibit insulin receptor signaling.
If you have obesity, your risk for type 2 diabetes is significantly higher due to biological changes in your fat tissue and blood. This isn't just about 'eating less'; it's about how your body processes energy. Addressing obesity through sustainable lifestyle changes can mitigate these specific biological risks.
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Elevated levels of FFAs are observed in obese individuals. High level of FFAs in the circulation become deposited in insulin-sensitive non-adipose tissues, resulting in lipotoxicity, which is an important cause of insulin resistance. Lipid metabolites from FFA, such as long-chain fatty acyl CoAs, diacylglycerol (DAG) and ceramides, activate some forms of PKC, the inhibitor of nuclear factor kB kinase β (IKKβ), and Jun kinase (JNK), which induce Ser/Thr phosphorylation of IRS-1 and in turn inhibit normal insulin-stimulated tyrosine phosphorylation of IRS-1, resulting in the impairment of insulin signaling.
Why this rating
The paper cites multiple mechanistic studies and meta-analyses linking obesity to T2DM.
Source
Pathophysiology of obesity and its associated diseases
Xin Jin et al. · Acta Pharmaceutica Sinica B · 2023
DOI 10.1016/j.apsb.2023.01.012
narrative_reviewCited 427×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
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