In an attempt to find safe, well-tolerated, and easily available intervention agents for the prediabetic population, we tested a potential candidate, ethanol-extracted curcumin, because of its known in vitro and in vivo antidiabetes activity (10
). In this randomized, double-blinded, placebo-controlled clinical trial, we found that curcumin extract was able to substantially and significantly prevent T2DM development in the prediabetic population (0% of curcumin-treated subjects developed DM, whereas 16.4% of placebo-treated subjects developed DM). In addition, we found that curcumin intervention improved β-cell functions, indicated by an increased HOMA-β and reduced C-peptide. Meanwhile, although not statistically significant, curcumin intervention tended to decrease proinsulin/insulin ratio. These indicated that curcumin treatment may result in better β-cell function in the prediabetic population. HOMA-IR clinically represents IR. We found that in the curcumin-treated group, HOMA-IR was significantly lower when compared with that of the placebo group. From these results, we believe that curcumin intervention in the prediabetic population can prevent T2DM conversion and lower the IR level by maintaining healthy β-cell functions.
Adiponectin is an anti-inflammatory cytokine known to play a positive role in pathogenesis of T2DM (27
). It has been shown that a higher adiponectin level is associated with a lower risk of T2DM (28
). Our study showed that curcumin intervention significantly increases adiponectin levels. Curcumin has also been shown to reduce inflammation by downregulating other inflammatory cytokines, such as tumor necrosis factor-α, leptin, and resistin (7
). In an in vivo diabetic mouse model, curcumin treatment significantly reduced macrophage infiltration of white adipose tissue and reversed many of the inflammatory derangements (8
). Because inflammation is one of the main causes of β-cell degradation, we hypothesize that the anti-inflammation activity of curcumin is a key factor for the curcumin’s antidiabetic property.
Of note, we observed from our study the conversion rate of the placebo-treated group during a period of 12 months (from first screening to the end of study) to be 16.7%, which is significantly higher than that in a well-known American study (3
). We reasoned that the high conversion rate may be specific to the ethnicity of the subjects. However, because of a lack of data on conversion rate in Thai prediabetes, we cannot directly verify our data. We then compared our result to a diabetes study conducted in a large Thai cohort by Aekplakorn et al. (29
), the Electric Generating Authority of Thailand (EGAT) study. In this study, risk scores were developed from a Thai cohort of 2,677 individuals (29
). The EGAT study identified a set of strong risk factors that accelerate the development of T2DM among the Thai population; these are old age, high BMI, high WC, hypertension, and history of diabetes in parent or sibling. We found that these factors also influenced our study (see the health parameter of the subject at the baseline in ). Our subjects are mostly of old age, with high BMI (according to Asian standards), high WC, and some with hypertension and a history of diabetes in parent or sibling.
When we analyzed data based on the instruction from the EGAT study, we found that the prediabetic subjects from our study were assigned with high-risk scores (Supplementary Tables 4–6
). When we followed the EGAT calculation, the estimated overall incidence rate (normalized to a period of 12 months) from our study would be 21.8% (within 12 months, an estimation of 21.8% of the prediabetic subjects would develop T2DM). We observed 16.4%, which is well within the estimation (not higher than expected).
Therefore, we believe that the high conversion rates found in the present study are a common characteristic of Thai prediabetes.
Several studies have shown that traditional Chinese herbs and dietary supplements may have potential antidiabetic activity (6
). Although promising, most of these studies could not be easily interpreted, quite often because of inadequate study designs, such as lack of randomized control trials (30
), small sample size (30
), or lack of safety information (30
). Our study was designed and set up specifically to overcome those previous problems. Our study showed that the curcumin extract can effectively prevent the prediabetic population from developing T2DM. Although we found that the results were quite remarkable, a longer trial may be required to see if the curcumin-treated prediabetic population will eventually develop T2DM.
We found that a 9-month treatment of curcumin was rather safe. We have not found any significant adverse effect caused by curcumin treatment when compared to the placebo treatment. Despite losing some body weight and WC, all of the subjects treated with curcumin appeared to be healthy. Because of its benefits and safety, we propose that curcumin extract may be used for an intervention therapy for the prediabetic population.