Editorial disclosure: This article is original educational commentary based on the cited literature. It summarizes and interprets published evidence rather than reproducing source text. Clinical decisions should be based on the full original publications, current guidelines, regulatory status, and individual patient factors.
Beyond a prediabetes framework
Insulin resistance is usually framed as a metabolic problem that precedes type 2 diabetes. Emerging evidence supports a broader view: insulin and compensatory hyperinsulinemia have direct effects on kidney physiology and may contribute to CKD progression in people with and without diabetes.
Insulin contributes to podocyte integrity, regulates tubular sodium handling and participates in renal gluconeogenesis. Abnormal signaling may contribute to glomerular hyperfiltration, proteinuria and sodium retention, linking obesity, insulin resistance, hypertension and CKD.
Implications for cardiorenal–metabolic care
A patient with albuminuria and preserved eGFR may already have substantial metabolic and renal risk before overt diabetes develops. Treatments aimed at weight, insulin resistance and metabolic risk may have renal implications beyond glucose lowering. GLP-1 receptor agonists, newer metabolic hormone therapies, SGLT2 inhibitors and mineralocorticoid receptor antagonists target complementary pathways.
Mechanistic plausibility does not automatically establish outcome benefit. Kidney effects should be judged using randomized outcome data whenever available.
Key clinical takeaways
- Insulin has direct renal physiological effects.
- Insulin resistance may contribute to hyperfiltration, proteinuria and sodium retention.
- Metabolic risk should be integrated into CKD assessment.
References
- Zaitoon H, Abdul-Ghani M, DeFronzo RA. Insulin resistance and hyperinsulinaemia in kidney disease: mechanisms and metabolic effects. Nat Rev Nephrol. 2026;22:474–486. DOI.
- Alicic RZ, Neumiller JJ, Tuttle KR. GLP-1 receptor agonists and next-generation metabolic hormone therapies in chronic kidney disease. Nat Rev Nephrol. 2026;22:265–282. DOI.