BackgroundCoronary heart disease (CHD) and lacunar infarction (LI) are the most common cardio- cerebrovascular complications of type 2 diabetes mellitus (T2DM) and a recognized risk factor for renal injury. Although a unidirectional association of CHD or LI with T2DM or the kidney has been demonstrated, however, it remains unknown whether there is an interactive effect of the coexistence of CHD and LI on renal function in T2DM patients. The aim of our study was to investigate the interaction between CHD and LI on renal function in gender-specific patients with T2DM and the association between cardio-cerebrovascular disease-related conventional serum markers and the estimated glomerular filtration rate (eGFR). MethodsWe conducted a cross-sectional study in Beijing and Tianjin from April 2019 to August 2021. Participants with T2DM aged ≥18 years were asked to complete a one-to-one questionnaire and physical examination. ResultsIn this study, 389 eligible patients with T2DM were included, with a mean age of 63.04 ± 9.41 years, of whom 200 (51.41 %) were male. The proportions of patients with CHD, LI, and both CHD and LI were 28.53 %, 24.42 %, and 11.05 %, respectively. Compared to T2DM patients without either CHD or LI, those with both CHD and LI were found to have a significantly greater risk of reduced eGFR (OR: 12.82, 95 % CI 5.06–32.52, P < 0.001) than those with CHD alone (OR: 2.42, 95 % CI 1.37–3.00, P = 0.004) or LI alone (OR: 1.15, 95 % CI 0.61–2.18, P = 0.664). The combined presence of CHD and LI is associated with a significantly greater risk of decreased eGFR in female T2DM patients compared to their male counterparts. We found both multiplicative and additive effects in all T2DM patients; however, when stratified by sex, only multiplicative effects were observed. After controlling for interference from CHD, LI, and age, we found that total cholesterol (TC) was negatively correlated with eGFR in females (r = −0.156, P = 0.034), and low-density lipoprotein cholesterol (LDL-C) was negatively correlated with eGFR in males (r = −0.229, P = 0.001). ConclusionThis study provides novel evidence that the synergistic effect of CHD and LI on renal injury in patients with T2DM is significantly greater than their individual effects. Women with T2DM who have both CHD and LI are at a 4.85-fold higher risk of decreased eGFR than men. Therefore, increased clinical attention should be given to preventing and treating vascular complications in T2DM patients, as well as aggressively reducing lipid levels, particularly TC and LDL-C, to delay or prevent renal dysfunction in T2DM patients.