OBJECTIVE: To prospectively determine the turnover (gain or loss) of gastrointestinal (GI) symptoms in diabetic subjects in relation to glycemic control, autonomic neuropathy and psychiatric disease over a 2-year follow-up. METHODS: Type 1 and type 2 diabetic subjects were recruited from the community, as were community controls. Individual GI symptoms were examined by a validated questionnaire and classified as diarrhea, irritable bowel syndrome, upper GI symptoms, and any GI symptoms at baseline, 12 and 24 months. Glycemic control (glycated hemoglobin), autonomic function (using standardized tests), and psychiatric disease (using the Composite International Diagnostic Interview) were also assessed at these time points. RESULTS: Baseline and 2-year follow-up data were available for 139 diabetic subjects and 55 controls. Glycated hemoglobin at baseline was 7.7% (±1.36) in the diabetic group; 5% had severe autonomic dysfunction. There was a significantly higher prevalence of diarrhea in the diabetic subjects. GI symptom turnover varied between 15% and 25% in the diabetic group and was not significantly different from the controls. There was no clear association between turnover of GI symptoms and either glycemic control or autonomic neuropathy. The appearance of depression was associated with gaining of most symptoms apart from irritable bowel syndrome, although the associations did not always reach significance. The univariate results were confirmed after adjusting for age, gender, body mass index, and metformin use. CONCLUSION: The turnover of GI symptoms in diabetic subjects was not associated with glycemic control but there was a positive association with change in depression.