BACKGROUND: The transition from normal glucose tolerance and insulin sensitivity to overt type 2 diabetes (T2D) encompasses a variety of glycemic abnormalities that are commonly referred to as 'prediabetes'. In 2003, 314 million people (8.2% of the adult population) had prediabetes, and this number is projected to increase to 472 million (9.0% of the adult population) by 2025. Approximately 40-50% of individuals with prediabetes have been reported to develop T2D within 10 years.~While intensive lifestyle interventions remain the cornerstone of T2D prevention, targeted pharmacotherapy has been shown to be effective and may be considered in high-risk patients. Several antidiabetic medications prevent or, at least, delay the progression from prediabetes to diabetes, including metformin, α-glucosidase inhibitors or pioglitazone. However, cost, potential adverse effects, and secondary failure in the long-term have often limited the widespread use of these and other newer antidiabetic drugs in patients with prediabetes. For instance 10 to 20% of metformin-treated patients experience gastrointestinal side effects (nausea, vomiting, and diarrhea) leading to its discontinuation, whereas the use pioglitazone is often complicated by weight gain and increased risk of fractures.~In this context, efficacious, cost-effective, and safe adjunct therapeutics for T2D prevention are highly desirable. The present trial proposes to test the effects of cinnamon in patients with prediabetes.~RATIONALE: Several randomized controlled studies have addressed the effects of cinnamon on changes in glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) in adult patients with T2D. Almost all studies showed a significant 10-20% decrease in FPG from baseline and improvements in HbA1c, although the latter change often did not achieve statistical significance. These findings in patients with T2D provide the rational to test whether cinnamon exerts similar beneficial effects in patients with prediabetes.~STUDY DESIGN: This is a multi-center placebo-controlled, randomized (1:1), double masked trail to assess the effects of cinnamon (cinnamomum burmannii) on glucose homeostasis over a 12- week period. FPG, HbA1c, and other measures of glucose metabolism will be collected at baseline, after 6 weeks, and at the end of the 12-week study period. Participants will be prompted to report Adverse Events (AE) at the study visits or anytime during the study period.~OUTCOMES: The primary outcome for the Cinnamon Trial is a change in the FPG level from baseline to week 12 of treatment, as compared to placebo. Secondary outcomes include change in the FPG from baseline to week 6 of treatment, and change from baseline in plasma glucose at 2 hours and area under the curve-glucose during a 75-gram oral glucose tolerance test to week 12. Data will be analyzed using the intent-to-treat approach, which includes all randomized subjects with at least one post-baseline FPG measurement; the supplementation group assignment will not be altered based on the subject's adherence to the regimen.~SAMPLE SIZE DETERMINATION: Anticipating an absolute change in FPG smaller than what observed in previous studies in patients with T2D, 10 patients with prediabetes in total entering a two-treatment parallel-design study will provide 90% probability of detecting a true between-treatment difference in FPG means of 22 mg/dl with standard deviation of 10 mg/dl, using a paired two-sided comparison with type 1 error of 0.05. To allow for up to 20% dropout, 12 patients in total will be recruited.
The transition from normal glucose tolerance to overt type 2 diabetes mellitus (T2D) encompasses a variety of glycemic abnormalities that are commonly referred to as 'prediabetes'. While intensive lifestyle interventions are the cornerstone of T2D prevention, developing safe, cost-effective adjunct therapeutic strategies is a clinically relevant goal. Cinnamon supplementation has been shown to improve fasting plasma glucose in patients with T2D. This placebo-controlled, randomized study will determine if cinnamon improves glucose homeostasis in patients with prediabetes over a 12-week period.