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Curcumin Extract for Prevention of
Type 2 Diabetes
SOMLAK CHUENGSAMARN,MD
1,2
SUTHEE RATTANAMONGKOLGUL,MD
3
RATAYA LUECHAPUDIPORN,PHD
4
CHADA PHISALAPHONG,PHD
5
SIWANON JIRAWATNOTAI,PHD
6,7
OBJECTIVEdTo assess the efficacy of curcumin in delaying development of type 2 diabetes
mellitus (T2DM) in the prediabetic population.
RESEARCH DESIGN AND METHODSdThis randomized, double-blinded, placebo-
controlled trial included subjects (n= 240) with criteria of prediabetes. All subjects were ran-
domly assigned to receive either curcumin or placebo capsules for 9 months. To assess the T2DM
progression after curcumin treatments and to determine the number of subjects progressing to
T2DM, changes in b-cell functions (homeostasis model assessment [HOMA]-b,C-peptide,and
proinsulin/insulin), insulin resistance (HOMA-IR), anti-inflammatory cytokine (adiponectin),
and other parameters were monitored at the baseline and at 3-, 6-, and 9-month visits during the
course of intervention.
RESULTSdAfter 9 months of treatment, 16.4% of subjects in the placebo group were di-
agnosed with T2DM, whereas none were diagnosed with T2DM in the curcumin-treated group.
In addition, the curcumin-treated group showed a better overall function of b-cells, with higher
HOMA-b(61.58 vs. 48.72; P,0.01) and lower C-peptide (1.7 vs. 2.17; P,0.05). The
curcumin-treated group showed a lower level of HOMA-IR (3.22 vs. 4.04; P,0.001) and higher
adiponectin (22.46 vs. 18.45; P,0.05) when compared with the placebo group.
CONCLUSIONSdA 9-month curcumin intervention in a prediabetic population signifi-
cantly lowered the number of prediabetic individuals who eventually developed T2DM. In
addition, the curcumin treatment appeared to improve overall function of b-cells, with very
minor adverse effects. Therefore, this study demonstrated that the curcumin intervention in a
prediabetic population may be beneficial.
Diabetes Care 35:2121–2127, 2012
The impacts of type 2 diabetes melli-
tus (T2DM) on global health care
and economy are enormous (1). Ac-
cording to the World Health Organiza-
tion, there are ;311 million people
worldwide who live with T2DM. This
number continues to rise, especially in
the newly developing and poorer coun-
tries in Asia and elsewhere. Because
T2DM is currently incurable, a common
treatment approach is to try to control the
disease with lifelong use of antidiabetes
drugs. Limiting the number of newly de-
veloped T2DM cases should be one of the
better key strategies to restrict the global
impacts of T2DM (2). In order to limit the
number of new T2DM cases, the lifestyle
of the prediabetic population has to be
changed. However, this has been shown
to be challenging (3). One of the
alternative approaches to prevent devel-
opment of T2DM is to intervene with the
prediabetic population before disease
progresses into fully developed T2DM
(3). The intervention approach is appeal-
ing. It relies on timely identification of
prediabetic individuals and provision of
preventive treatment before the disease
fully progresses. The intervention rep-
resents a chance for the diabetes-prone
population to halt the disease progression
and maintain a normal and healthy life. In
recent years, several effective T2DM inter-
vention regimens have been developed,
with encouraging results (3–5). However,
these regimens are not usually economi-
cally accessible, and they are not well-
tolerated because of treatment-related
toxicities (4,5). The focus now is to iden-
tify new effective therapeutic agents,
with relatively low cost and low toxicity,
that can be used regularly to control a
progression of T2DM in the prediabetic
population.
Curcumin is the principal curcumi-
noid found in turmeric (Curcuma longa
Linn.), a popular spice in Asian cuisine.
It is widely consumed and generally be-
lieved to be beneficial for human health
(6). Curcumin extract from rhizomes of
turmeric has been shown to contain anti-
inflammation and antidiabetic properties
(7–13). In addition, it could delay devel-
opment of T2DM, improve b-cell func-
tions, prevent b-cell death, and reduce
insulin resistance in animals (8–16).
This study aimed to determine the effec-
tiveness of curcumin extract as an interven-
tion agent to prevent T2DM development.
We assessed T2DM progression and sev-
eral indicative T2DM parameters in a large
randomized, double-blinded, and pla-
cebo-controlled cohort. We found that
curcumin extract effectively reduced the
number of prediabetic individuals who
progressed toward T2DM as well as im-
proved functions of b-cells.
RESEARCH DESIGN AND
METHODS
Study design and participants
This randomized, double-blinded, placebo-
controlled trial was conducted at HRH
Princess Maha Chakri Sirindhorn Medical
ccccccccccccccccccccccccccccccccccccccccccccccccc
From the
1
Division of Endocrinology and Metabolism, Faculty of Medicine, HRH Princess Maha Chakri
Sirindhorn Medical Center, Srinakharinwirot University, Nakornnayok, Thailand; the
2
Division of Endo-
crinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Boston, Massachusetts; the
3
De-
partment of Preventive and Social Medicine, Faculty of Medicine, HRH Princess Maha Chakri Sirindhorn
Medical Center, Srinakharinwirot University, Nakornnayok, Thailand; the
4
Department of Pharmacology
and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand; the
5
Research and Development Institute, Thai Government Pharmaceutical Organization, Bangkok, Thailand;
the
6
Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhon Pratom, Thailand; and the
7
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Corresponding author: Somlak Chuengsamarn, somlukc@hotmail.com.
Received 18 January 2012 and accepted 9 May 2012.
DOI: 10.2337/dc12-0116. Clinical trial reg. no. NCT01052025, clinicaltrials.gov.
This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10
.2337/dc12-0116/-/DC1.
© 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly
cited, the use is educa tional and not for profit, and the work is not alte red. See http://creativecommons.org/
licenses/by-nc-nd/3.0/ for details.
care.diabetesjournals.org DIABETE S CARE,VOLUME 35, NOVEMB ER 2012 2121
Clinical Care/Education/Nutrition/Psychosocial Research
ORIGINAL ARTICLE
Center of Srinakharinwirot University (Na-
kornnayok, Thailand). Two hundred forty
patients were selected to participate in this
study by inclusion and exclusion criteria
(for a complete flow chart, see Supple-
mentary Fig. 1). The subjects were en-
rolled in the 12-month–long study. We
educated all subjects to perform in the
same protocols for diet and exercise
during a 3-month period after the enroll-
ment (before the randomization). Stan-
dard lifestyle recommendations were
provided for all subjects in written form.
All of the subjects took part in a 20–30-
min one-on-one workshop that empha-
sized the importance of a healthy lifestyle.
Participants were encouraged to follow the
Medical Nutrition Therapy and physical
activity (17). To avoid any interference
from other medications, during the re-
cruitment process, we excluded all of pa-
tients who were taking any other
medicines, as shown in the exclusion cri-
teria. Only prediabetic subjects aged $35
years were included in this study. Predia-
betes was diagnosed following the Ameri-
can Diabetes Association (ADA) practice
guidelines. Subjects who fit into at least
one of these three criteria were included:
subjects with a fasting plasma glucose
(FPG) between 100 and 124 mg/dL (indi-
cating impaired fasting glucose), an oral
glucose tolerance test (OGGT) plasma glu-
cose at 2 h postglucose load (OGTT at 2 h)
between 140 and 199 mg/dL (indicating
impaired glucose tolerance), and a glyca-
ted hemoglobin (HbA
1c
) range from 5.7 to
6.4%. Diagnosis of prediabetes was con-
firmed by a second repeating test of all of
the above-listed criteria on a different day.
Subjects diagnosed with diabetes ac-
cording to the new ADA guidelines
(18,19) were excluded from the study
(subjects who are positive for any one of
these following criteria: FPG level $126
mg/dL, OGTT at 2 h $200 mg/dL, and
HbA
1c
$6.5%. The following subjects
were also excluded from the study: sub-
jects receiving oral hypoglycemic agents,
antiplatelet drugs, angiotensin-converting
enzyme inhibitors, angiotensin II receptor
antagonists, fenofibrate, atorvastatin, ro-
suvastatin, and fluvastatin; subjects with
serum creatinine $2.0 mg/dL or on dial-
ysis; subjects with the liver enzyme alanine
aminotransferase (ALT) $3 folds of upper
limit of normal value range; subjects re-
ceiving other herbal medicines; subjects
with secondary causes of hyperglycemia
(receiving steroids or with pancreatic can-
cer); subjects with acute infections or
chronic inflammatory diseases (cancer,
rheumatoid arthritis); and subjects with
gall bladder disease or history of cholecys-
tectomy. This study (clinical trial reg. no.
NCT01052025) was approved by the
Ethic Committee of Faculty of Medicine,
Srinakharinwirot University, Bangkok,
Thailand (serial number SWUEC 9/
2552) in accordance with the Declaration
of Helsinki. Participants were informed
and gave their consent before enrollment.
Randomization procedures
After steps of screening, consenting, and
diet and lifestyle training, all subjects
were randomly assigned to either the
curcumin-treated group (intervention
treatment condition) or placebo-treated
group (control condition) using a fixed
randomization scheme with assignment
based on computer-generated random
numbers performed by an independent
researcher. The allocation scheme was
sealed in opaque and consecutively num-
bered envelopes. Envelopes were opened
sequentially by the independent person.
The participants were informed that two
types of interventions were being com-
pared.
The intervention
All participants were instructed to take
three capsules with blinded labels of
either curcumin or placebo twice a day
(total of six capsules per day) for 9
months continuously. Each curcumin
capsule has curcuminoid content of 250
mg. Curcumin and identical placebo cap-
sules were manufactured by the Govern-
ment Pharmaceutical Organization of
Thailand. Patients were asked to bring
all capsules back at the follow-up visit at
3, 6, and 9 months for assessing their
compliance. Numbers of capsules taken
by the subjects were recorded (Supple-
mentary Table 3).
Preparation of curcuminoids
capsules
Dried rhizomes of turmeric (Curcuma
longa Linn.) grown in Kanchanaburi
province, Thailand, were ground into
powder. The turmeric powder was extrac-
tedwithethanolandevaporatedatlow
pressure to obtain ethanol extract in the
form of semisolid containing oleoresin
and curcuminoids. The oleoresin was re-
moved to yield curcuminoid extract (total
curcuminoids content between 75 and
85%). The peak ratio of curcumin:deme-
thoxycurcumin and bisdemethoxycurcu-
min in the extract was determined by high-
performance thin-layer chromatography.
The extract (calculated for 250 mg of cur-
cuminoids) was filled into capsules under
the Good Manufacturing Procedures
standard. Fingerprints of the extract
and a detailed analysis of the chemical
composition of the preparation in the ex-
tract are shown in Supplementary Fig. 2.
Study outcomes
The primary outcome was assessed by
numbers of the subjects in the curcumin-
treated or placebo-treated groups diag-
nosed with T2DM according to the ADA
guidelines (18,19). Secondary outcomes
were also measured as follows: changes of
the b-cell functions (homeostasis model
assessment [HOMA]-b, C-peptide, and
proinsulin/insulin ratio), insulin resis-
tance (IR) by HOMA-IR, obesity (body
weight), abdominal obesity (waist cir-
cumference [WC]), and anti-inflammatory
cytokine (adiponectin). Adverse effects of
curcumin were determined by elevated
creatinine $1.2 mg/dL and aspartate ami-
notransferase (AST)/ALT $3 times the up-
per limit of normal value range, and any
symptoms of patient complaints were re-
corded (20). Other adverse effects related
to peroxisome proliferator–activated re-
ceptor-gin curcumin action were as-
sessed, including bone mineral density
(BMD), signs of edema, and coronary
arterial disease (CAD) event.
Data collection and measurement
methods
Measurements were made at baseline (be-
fore treatment) and at 3, 6, and 9 months
after the intervention start. We recorded
demographic data at the baseline; the
researchers administered a questionnaire
on medical history and medication, and
measured body weight, height, and vital
signs. The abdominal obesity/WC were
measured by tape horizontally, midway
between the inferior margin of the wrist
and the superior border of the iliac crest
(21). Histories of CAD and cerebrovascular
disease were tracked from the subjects’
medical records. The diagnosis of CAD,
based on the presence of angina symptoms
and abnormalities in resting electrocardio-
gram, was also assessed at baseline and dur-
ing each follow-up visit (at 3, 6, and 9
months). Hypertension was determined
by history of high blood pressure ($130/
85 mmHg). Dyslipidemia was defined by
any of the following: total cholesterol
$200 mg/dL, triglycerides $150 mg/dL,
LDL cholesterol $100 mg/dL, and/or HDL
cholesterol #35 mg/dL or taking lipid-
lowering drugs. BMD, a known fracture
2122 DIABETES CARE,VOLUME 35, NOVEMBER 2012 care.diabetesjournals.org
Preventive type 2 diabetes and curcumin extract
risk, was analyzed at the baseline and at 9
months after starting the intervention by
dual X-ray absorptiometry (QDR 4500;
Hologic) at the level of the lumbar spine
region. OGTT at 2 h was performed in all
subjects by taking 75 g oral glucose solu-
tion after overnight fasting; and then 2 h
later, blood glucose level was measured.
Blood was collected at 8:00 AM from the
antecubital vein while the subjects were in
the recumbent position after an overnight
fasting. Plasma samples for insulin, proin-
sulin, C-peptide, and adiponectin assays
were frozen and stored at 2808C until
the analysis of hormones were measured.
FPG, HbA
1c
, total cholesterol, LDL choles-
terol, HDL cholesterol, and triglyceride
levels were measured according to the
standard procedures. Plasma insulin, pro-
insulin, C-peptide, and adiponectin con-
centrations were determined using the
radioimmunoassay kits from Millipore
(St. Charles, MO) with a gscintillation
counter, which is calibrated for
125
I mea-
surement. HOMA-b, C-peptide, and the
proinsulin/insulin ratio were measured
for b-cell functions (22,23). HOMA-IR
was calculated to assess change of IR
(22,24).
Sample size
We estimated the size of the sample for
this study based on data from the study by
Nauck et al. (25). Calculations used an SD
of 46.3. We needed to enroll at least 117
subjects in each treatment group to detect a
difference of 17 in HOMA-bwith 80%
power at the 5% level of significance (26).
Statistical analysis
Demographic data at baseline were ana-
lyzed and presented as mean 6SEM for
continuous variables and number with
percent for categorical variables. Two-tailed
Student ttest and x
2
test were, respectively,
used for continuous and categorical varia-
bles in comparisons between the two
groups, using P,0.05 for statistically sig-
nificant difference. We used two-sided sig-
nificance tests throughout. For analysis of
outcome variables, values of mean 6SEM
at 3, 6, and 9 months were presented for
both groups. The analyses were performed
on an intention-to-treat basis. Two-tailed
Student ttest was used to assess the statis-
tical significant differences between means
of the two groups at 3, 6, and 9 months,
separately. Statistical analysis was per-
formed using the Statistical Package for So-
cial Sciences 11.5 software (SPSS Inc.,
Chicago, IL).
RESULTSdAflow chart of the trial is
presented (Supplementary Fig. 1). A total
of 240 subjects were initially enrolled in
the study. The baseline characteristics of
237 subjects who were randomly allo-
cated into the two groups are presented
in Table 1. All parameters at the baseline
between placebo-treated group and cur-
cumin-treated group were not statistically
different.
Intervention outcomes
The means of diabetes-related blood
chemistries used to assess the diabetic
progression, such as HbA
1c
,FPG,and
OGTT at 2 h were significantly lower in
the curcumin-treated group when com-
pared with the placebo group (P,0.01)
in all visits at 3, 6, and 9 months (Table 2).
Differences from baselines for these three
variables comparing the two groups are il-
lustrated in the Fig. 1A–C.
b-Cell function outcomes
HOMA-b, C-peptide, and proinsulin/in-
sulin ratio were examined as outcomes
related to b-cell functions (Table 2 and
Fig. 1). Figure 1Dshows that HOMA-b
in the curcumin-treated group was increas-
ingly elevated in all follow-up visits (at 3, 6,
and 9 months) and became statistically sig-
nificant at the final visit (9 months). Blood
levels of C-peptide (Fig. 1E) were found to
be significantly lower in curcumin-treated
group when compared with those of pla-
cebo group. Although not significant, pro-
insulin/insulin ratio showed a lower trend
in the curcumin-treated group (Table 2).
Insulin resistance and inflammatory
cytokine outcomes
HOMA-IR level is a clinical representative
of insulin resistance (22). HOMA-IR from
both placebo and curcumin-treated
groups was examined. The means of
HOMA-IR of the curcumin-treated group
were lower than those of placebo group at
all follow-up visits (3, 6, and 9 months)
(Fig. 1F). The differences were significant,
particularly at the 6- and 9-month visits.
Levels of adiponectin, an anti-inflamma-
tory cytokine, in the placebo-treated
group were virtually unchanged, whereas
those of the curcumin-treated group were
gradually elevated (at 3 and 6 months)
and became significantly different from
that of placebo-treated group at the final
visit (9 months) (Table 2).
Diabetes prevention
At 6, 9, and 12 months after the subjects
were first identified with prediabetes con-
ditions (at 3-, 6-, and 9-month visits), a
number of subjects in the placebo-treated
Table 1dBaseline characteristics of subjects
Variables
Placebo mean
(SEM)
Curcumin mean
(SEM) Pvalue*
Sex (%) (male:female) 35.6:64.4% 35.1:64.9% 0.94†
Age (years) 57.93 (1.18) 56.95 (1.10) 0.57
BMI (kg/m
2
) 26.62 (0.51) 26.66 (0.48) 0.96
Body weight (kg) 67.8 (1.5) 67.7 (1.3) 0.92
WC (cm) 88.9 (1.2) 89.0 (1.0) 0.94
FPG (mg/dL) 103.24 (0.98) 103.65 (0.99) 0.26
OGTT at 2 h (mg/dL) 140.91 (3.24) 143.48 (3.6) 0.36
HbA
1c
(%) 5.83 (0.03) 5.86 (0.04) 0.37
Insulin (pmol/L) 109.71 (6.1) 110.25 (6.29) 0.95
Proinsulin (pmol/L) 16.8 (1.42) 15.31 (1.3) 0.44
Proinsulin per insulin 0.18 (0.02) 0.17 (0.01) 0.52
HOMA-IR 3.85 (0.21) 4.03 (0.23) 0.57
HOMA-b(%) 51.08 (3.23) 49.11 (3.12) 0.66
Adiponectin (ng/mL) 18.68 (1.25) 18.18 (1.20) 0.29
C-peptide (ng/mL) 2.14 (0.17) 2.1 (0.13) 0.88
Creatinine (mg/dL) 1.15 (0.06) 1.07 (0.04) 0.27
AST (U/L) 27.21 (1.53) 26.50 (1.65) 0.75
ALT (U/L) 43.42 (1.85) 44.04 (1.94) 0.82
History of cerebrovascular disease 5 (4.3%) 3 (2.5%) 0.46†
History of coronary arterial disease 8 (6.8%) 9 (7.0%) 0.96†
History of hypertension 78 (67.2%) 83 (70.3%) 0.61†
History of dyslipidemia 105 (90.5%) 107 (90.7%) 0.97†
*Data were evaluated by independent sample ttest, except sex (%). †x
2
test.
care.diabetesjournals.org DIABETE S CARE,VOLUME 35, NOVEMB ER 2012 2123
Chuengsamarn and Associates
group developed T2DM: 11 subjects (9.5%)
at 6 months, 18 (15.5%) at 9 months, and
19 (16.4%) at 12 months (Table 3 and Sup-
plementary Table 1). However, none of the
subjects in the curcumin-treated group de-
veloped T2DM (Table 3).
Adverse effects
To monitor possible adverse effects of
curcumin intervention, we determined
kidney and liver functions, BMD, body
weights, and WCs (Supplementary Table
2 and Table 2). We found no significant
differences in the means of AST, ALT, cre-
atinine, and BMD between the curcumin-
treated and placebo-treated group. In
addition, during the course of our study,
none of the subjects newly developed
CADoranysignsofedema(datanot
shown). A few subjects from the curcu-
min-treated group reported minor symp-
toms such as itching (one subject),
constipation (two subjects), and vertigo
(one subjects). None in the curcumin-
treated group showed hypoglycemia
symptoms. Interestingly, at the last fol-
low-up visit (9 months after interven-
tion), we noticed a slight reduction of
mean body weight and WC from the
group of subjects treated with curcumin.
We did not see such reductions in the
placebo-treated group (Table 2).
Altogether, these results indicated
that curcumin extract can be used for
intervention, at least during a period of 9
months, without serious adverse effect.
At each follow-up visit, we counted
numbers of remaining capsules brought
to us by subjects. Numbers of the capsule
consumed by subjects from both groups
were very comparable (Supplementary
Table 3). Therefore, the effects observed
by us were not a result of different levels of
compliance between two groups.
CONCLUSIONSdIn an attempt to
find safe, well-tolerated, and easily avail-
able intervention agents for the predia-
betic population, we tested a potential
candidate, ethanol-extracted curcumin,
becauseofitsknowninvitroandinvivo
Table 2dLevels of blood chemistries indicating b-cell functions and obesity parameters
Outcomes Follow-up period
Placebo Curcumin
PvalueMean Minimum –maximum Mean Minimum –maximum
Body weight (kg) 3 months 67.8 34–130 67.7 42–118 NS
6 months 68.9 36–136 66.0 38–114 NS
9 months 70.1 38–144 63.8 34–110 ,0.05
WC (cm) 3 months 88.9 59–134 88.0 68–121 NS
6 months 89.8 62–130 86.6 64–118 NS
9 months 91.6 65–144 84.4 60–110 ,0.05
FPG (mg/dL) 3 months 106.88 80–129 96.11 80–122 ,0.01
6 months 108.03 80–138 90.76 73–122 ,0.01
9 months 108.21 80–138 86.47 73–122 ,0.01
OGTT at 2 h (mg/dL) 3 months 150.87 90–250 135.44 75–190 ,0.01
6 months 155.06 90–290 127.23 75–180 ,0.01
9 months 155.09 90–290 123.35 75–178 ,0.01
HbA
1c
(%) 3 months 5.92 5.2–7.1 5.77 4.9–6.3 ,0.01
6 months 5.99 5.2–7.4 5.68 4.9–6.2 ,0.01
9 months 6.02 5.2–7.5 5.60 4.9–6.8 ,0.01
Proinsulin 3 months 17.77 0.5–121 14.58 1–98.2 NS
6 months 16.83 0.5–85.6 14.06 0.9–98 NS
9 months 16.80 0.5–85.6 13.57 0.8–97 NS
Proinsulin per insulin 3 months 0.19 0–1.6 0.16 0–0.9 NS
6months 0.20 0–1.2 0.15 0–0.9 NS
9months 0.21 0–1.2 0.14 0–0.9 NS
Insulin (pmol/L) 3 months 109.52 82–140 109.49 80–136 NS
6 months 109.65 83–144 108.73 76–132 NS
9 months 109.68 83–144 107.62 72–128 ,0.05
HOMA-IR 3 months 3.97 0.3–13.3 3.60 0.4–11.6 NS
6 months 4.03 0.3–16.2 3.39 0.4–11.3 ,0.05
9 months 4.08 0.3–16.6 3.22 0.4–11 ,0.001
HOMA-b(%) 6 months 49.32 0.8–238.9 54.71 3.1–259.7 NS
9 months 48.78 0.8–238.0 58.54 3.1–266.4 NS
3 months 48.72 0.8–237.6 61.58 3.1–268.3 ,0.01
Adiponectin (ng/mL) 3 months 18.59 31–110.8 18.3 5.5–60.0 NS
6 months 18.52 31–110.8 20.71 6.0–65.0 NS
9 months 18.45 31–110.2 22.46 6.5–69.5 ,0.05
C-peptide (ng/mL) 3 months 2.15 0.5–13.8 1.97 0.4–10.0 NS
6 months 2.16 0.5–13.8 1.8 0.3–9.5 NS
9 months 2.17 0.1–13.8 1.7 0.3–9.0 ,0.05
Pvalues were calculated by an independent sample ttest (P$0.05).
2124 DIABETES CARE,VOLUME 35, NOVEMBER 2012 care.diabetesjournals.org
Preventive type 2 diabetes and curcumin extract
antidiabetes activity (10–12,15,16).
In this randomized, double-blinded,
placebo-controlled clinical trial, we found
that curcumin extract was able to sub-
stantially 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 curcu-
min intervention improved b-cell func-
tions, indicated by an increased HOMA-b
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
b-cell function in the prediabetic popula-
tion. HOMA-IR clinically represents IR.
We found that in the curcumin-treated
group, HOMA-IR was significantly lower
Figure 1dMean of parameters with SEM at baseline, 3, 6, and 9 months were compared between placebo- and curcumin-treated group. A:FPG.
*P ,0.01. B: OGTT at 2 h. *P,0. 01. C:HbA
1c
.*P,0.01. D:HOMA-b.*P ,0.01. E: C-peptide. *P ,0.05. F: HOMA-IR. *P ,0.001, #P ,0.05.
care.diabetesjournals.org DIABETE S CARE,VOLUME 35, NOVEMB ER 2012 2125
Chuengsamarn and Associates
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 b-cell functions.
Adiponectin is an anti-inflammatory
cytokine known to play a positive role in
pathogenesis of T2DM (27,28). It has
been shown that a higher adiponectin
level is associated with a lower risk of
T2DM (28). Our study showed that cur-
cumin intervention significantly increases
adiponectin levels. Curcumin has also
been shown to reduce inflammation by
downregulating other inflammatory cyto-
kines, such as tumor necrosis factor-a,
leptin, and resistin (7). In an in vivo dia-
betic mouse model, curcumin treatment
significantly reduced macrophage infiltra-
tion of white adipose tissue and reversed
many of the inflammatory derangements
(8). Because inflammation is one of the
main causes of b-cell degradation, we hy-
pothesize that the anti-inflammation activ-
ity 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 sub-
jects. 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 devel-
oped from a Thai cohort of 2,677 individ-
uals (29). The EGAT study identified a set
of strong risk factors that accelerate the de-
velopment of T2DM among the Thai pop-
ulation; 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 base-
line in Table 1). Our subjects are mostly
of old age, with high BMI (according to
Asianstandards),highWC,andsome
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 (nor-
malized 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 tra-
ditional Chinese herbs and dietary sup-
plements may have potential antidiabetic
activity (6,30–32). Although promising,
most of these studies could not be easily
interpreted, quite often because of inade-
quate study designs, such as lack of ran-
domized control trials (30–32), small
sample size (30–32), or lack of safety
information (30–32). Our study was de-
signed and set up specifically to overcome
those previous problems. Our study
showed that the curcumin extract can ef-
fectively prevent the prediabetic popula-
tion 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.
Despitelosingsomebodyweightand
WC, all of the subjects treated with
curcumin appeared to be healthy. Be-
cause of its benefits and safety, we
propose that curcumin extract may be
used for an intervention therapy for the
prediabetic population.
AcknowledgmentsdThis study was sup-
ported by a grant from Thai Traditional Medical
Knowledge Fund and the Department for De-
velopment of Thai Traditional and Alternative
Medicine, Ministry of Public Health (to S.C.).
No potential conflicts of interest relevant to
this article were reported.
S.C. designed the study, screened and ex-
amined all the recruited subjects, researched
and analyzed data, and wrote and reviewed the
manuscript. S.R. analyzed data and performed
the statistical analysis. R.L. and C.P. provided
trial advice. S.J. designed the study and wrote
and reviewed the manuscript. S.R. is the
guarantor of this work and, as such, had full
access to all the data in the study and takes
responsibility for the integrity of the data and
the accuracy of the data analysis.
The authors thank the Thai Government
Pharmaceutical Organization for the gift of the
curcumin extract and placebo. The authors
also thank all of the subjects for participating
in this study and the team of the outpatient
clinic at HRH Princess Maha Chakri Sirind-
horn Medical Center of Srinakharinwirot
University, Nakornnayok, Thailand.
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