Clinical Implication of Alterations in Serum Klotho Levels in Type 2 Diabetes Mellitus with Differential C-Peptide...

Klotho is relevant to glucose and lipid metabolism and may be involved in insulin resistance (IR), which is a hallmark of type 2 diabetes mellitus (T2DM). This study aimed to elucidate the alterations in serum Klotho levels and their relationship with IR in T2DM with varying C-peptide patterns.

690 T2DM subjects with different levels of serum C-peptide were enrolled. Blood samples were analyzed for FPG, HbA1c, C-peptide, FINS, and Klotho. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated as HOMA-IR=FINS (μU/ml)×FPG (mmol/L)/22.5. Finally, receiver operating characteristic (ROC) analysis was used to explore the diagnostic performance based on β-cell function in T2DM.

Klotho levels were significantly lower in T2DM patients compared to in controls, with decreasing maximum in the hyper-C-peptidemia group, while the HOMA-IR exhibited an inverse tendency across T2DM subgroups. In addition, Klotho was inversely correlated with HOMA-IR, FINS, FPG, and HbA1c, especially in T2DM with hyper-C-peptidemia. Moreover, the relationship remained significant even after additional adjustment for FGF23 and eGFR. Finally, Klotho displayed a good ability in distinguishing T2DM patients with different C-peptide patterns from controls, although its performance was marginal among T2DM subgroups.

In T2DM, serum Klotho levels were negatively correlated with HOMA-IR, and Klotho showed a good ability in distinguishing T2DM patients with differential C-peptide level patterns from healthy controls.