ObjectivesCoffee consumption is associated with a reduced risk of Type-2 Diabetes. A bioactive compound in coffee, cafestol, has shown potential preventive effects for Type-2 Diabetes in cell and animal studies, but its potential benefits in humans have not been examined.MethodsIn this randomized, double- blinded crossover intervention study, 15 healthy participants with increased waist circumference and thus elevated risk of developing Type-2 Diabetes underwent three oral glucose tolerance tests one week apart, with placebo, 7 mg- or 14 mg cafestol capsules ingested with the glucose load.ResultsThere were no substantial differences in area under the curve (AUC) for glucose, insulin, glucagon-like peptide 1 (GLP-1) or gastric inhibitory peptide (GIP) on placebo or cafestol intervention study days. Among participants with impaired glucose tolerance and/or elevated fasting glucose (n=8, 53%), ingestion of 14 mg of cafestol resulted in an 11% larger AUC for GIP (p=0.046) and a 5% smaller AUC for glucose (p=0.14), compared to placebo.ConclusionsOur results suggest that cafestol may contribute to coffee's inverse association with risk of Type-2 Diabetes, particularly in subjects with impaired glucose tolerance, possibly through increased GIP secretion. Further studies are needed to confirm these novel findings in participants with impaired glucose metabolism, both after acute and longer-term cafestol intervention.