We have previously reported the beneficial effects of Caiapo, the extract of white-skinned sweet potato (ipomoea batatas), on fasting plasma glucose, as well as on total and low-density lipoprotein (LDL) cholesterol in type 2 diabetic patients. The present study aimed to describe the underlying mechanism responsible for the improvement in metabolic control following administration of Caiapo in those type 2 subjects. A total of 18 male patients (age=58+/-8 years, body mass index [BMI]=27.7+/-2.7 kg/m2, mean +/- SEM) treated only by diet were randomized into 3 groups (placebo, low-dose Caiapo, 2 g/d, and high-dose, 4 g/d). Parameters related to glucose tolerance, glucose disappearance, and insulin secretion were obtained by performing both frequently sampled intravenous glucose tolerance test (FSIGT) and oral glucose tolerance test (OGTT) before and after 6 weeks of treatment with Caiapo. Following treatment with high dose Caiapo, insulin sensitivity significantly ameliorated when assessed both with OGTT (from 308+/-13 mg/min/m2 to 334+/-10, P=.048) and FSIGT (from 1.21+/-0.32 10(4) min(-1)/(microU/mL) to 1.73+/-0.40, P=.021). Improvement of insulin sensitivity with the low dose was observed only with the FSIGT (from 2.02+/-0.70 10(4) min(-1)/(microU/mL) to 2.76+/-0.89, P<.05). Glucose effectiveness did not change. While no changes in glucose tolerance were observed in the placebo and low-dose groups, it increased from 0.85+/-0.13 %min(-1) to 1.46+/-0.13 (P<.02) in patients on high dose. No significant changes were seen in any of the parameters related to insulin dynamics: insulin secretion (from C-peptide), distribution, clearance, and hepatic extraction remained virtually the same after the treatment. In conclusion, short-term treatment with 4 g/d of the nutraceutical Caiapo consistently improved metabolic control in type 2 diabetic patients by decreasing insulin resistance without affecting body weight, glucose effectiveness, or insulin dynamics. No side effects related to the treatment were observed. Thus these results indicate that Caiapo could potentially play a role in the treatment of type 2 diabetes.