<jats:title>Abstract</jats:title><jats:sec><jats:title>Aims/Introduction</jats:title><jats:p>We aimed to examine the association between diabetes‐related parameters and hippocampal and parahippocampal gyrus atrophy (HPGA) in patients with type 2 diabetes mellitus to elucidate the risk factors for HPGA, which is often accompanied by Alzheimer’s disease.</jats:p></jats:sec><jats:sec><jats:title>Materials and methods</jats:title><jats:p>A total of 137 patients aged ≥50 years with type 2 diabetes mellitus (mean age 67.8 ± 9.8 years) underwent brain magnetic resonance imaging scans and comprehensive health examinations. We measured the volume of interest – a portion of the inner temporal lobe that includes the hippocampus, amygdala and entorhinal cortex (frontal part of the parahippocampal gyrus) – using the voxel‐based specific regional analysis system for Alzheimer’s disease in each patient. The diabetes‐related parameters included glycated hemoglobin, fasting plasma glucose, C‐peptide (CPR) index (serum CPR / fasting plasma glucose × 100) and duration of diabetes.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The mean glycated hemoglobin was 9.3 ± 2.2%, the median CPR index was 1.29 (interquartile range 0.85–1.74) and the median duration of diabetes was 10 years (interquartile range 3–20 years). The severity score of volume of interest atrophy was >1.0 in 36 patients. Using multivariate logistic regression analysis, we found that age (odds ratio 1.09, 95% confidence interval 1.02–1.15) and CPR index (odds ratio 0.451, 95% confidence interval 0.216–0.940) were significantly associated with HPGA.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Lower insulin secretion was significantly associated with HPGA in patients with type 2 diabetes mellitus. The results of this study support the hypothesis that insulin‐signaling abnormalities are involved in the pathophysiology of Alzheimer’s disease.</jats:p></jats:sec>