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Background: Left ventricular diastolic dysfunction (LVDD) is considered a precursor of diabetic cardiomyopathy, while insulin resistance (IR) is a precursor of type 2 diabetes mellitus (T2DM) and independently predicts heart failure (HF). We assessed whether IR and abnormalities of the glucose metabolism are related to LVDD., Methods: We included 208 patients with normal ejection fraction, 57 (27%) of whom had T2DM before inclusion. In subjects without T2DM, an oral glucose tolerance test (oGTT) was performed. IR was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The lower limit of the top quartile of the HOMA-IR distribution (3.217) was chosen as threshold for IR. LVDD was verified according to current guidelines., Results: IR was diagnosed in 38 (18%) patients without a history of diabetes. The prevalence of LVDD was 92% in subjects with IR vs. 72% in patients without IR (n = 113), respectively (p = 0.013). In the IR group, the early diastolic mitral inflow velocity (E) in relation to the early diastolic tissue Doppler velocity (averaged from the septal and lateral mitral annulus, E'av) ratio (E/E'av) was significantly higher compared to those without IR (9.8 [8.3-11.5] vs. 8.1 [6.6-11.0], p = 0.011). This finding remains significant when patients with IR and concomitant T2DM based on oGTT results were excluded (E/E'av ratio 9.8 [8.2-11.1)] in IR vs. 7.9 [6.5-10.5] in those without both IR and T2DM, p = 0.014). There were significant differences among patients with and without LVDD regarding the HOMA-IR (1.71 [1.04-3.88] vs. 1.09 [0.43-2.2], p = 0.003). The HOMA-IR was independently associated with LVDD on multivariate logistic regression analysis, a 1-unit increase in HOMA-IR value was associated with an odds ratio for prevalent LVDD of 2.1 (95% CI 1.3-3.1, p = 0.001). Furthermore, the E/E'av ratio increases along the glucose metabolism status from normal glucose metabolism (7.6 [6.2-10.1]) to impaired glucose tolerance (8.8 [7.4-11.0]) and T2DM (10.5 [8.1-13.2]), respectively (p < 0.001)., Conclusions: Insulin resistance is independently associated with LVDD in subjects without overt T2DM. Patients with IR and glucose metabolism disorders might represent a target population to prevent the development of HF. Screening programs for glucose metabolism disturbances should address the assessment of diastolic function and probably IR.