General characteristics of the subjects
A total of 160 eligible participants (80 each intervention group) with prediabetes (n=90) or newly diagnosed diabetes (n=70) were included in this trial. Baseline characteristics of all the randomized participants are presented in Supplemental Table 1. Participants in anthocyanins and placebo groups were comparable in terms of age, gender, education, lifestyle factors, dietary intakes and physical activities. Twenty participants (12.5%) lost from the study and two participants were in poor compliance, resulting in 138 cases finally analyzed. Relatively more dropouts were observed in the placebo group (n =13) than in the anthocyanins group (n = 3). The flow chart presented in Figure 1 shows the allocation and finally available for each group.
More than 90% of the participants in each group consumed at least 85% of the supplements provided, and no significant difference was observed in the proportion of poor compliance between the two groups. Participants reported a total of 10 adverse events to the intervention, and the proportion of adverse events did not significantly different between the two groups (Supplemental Table 2). There are 3 participants reported abdominal pain (n = 1), diarrhea (n = 1) and skin rash (n = 1) in the placebo groups; 7 participants reported black stool (n = 5) insomnia (n = 1) and dizziness (n= 1) in the anthocyanins group. Within the subgroup of prediabetes and newly diagnosed diabetes, comparisons for baseline values indicated that the subjects among the two intervention groups had similar metabolic parameters (Table 1). No significant difference was observed between the anthocyanins and placebo groups in dietary intakes and nutrients in either the baseline or the end of the study (Supplemental Table 3).
Table 1 Baseline values of adiponectin and glucolipid metabolic parameters between the anthocyanins and placebo group
for the participants classified with prediabetes and newly diabetes
|
Prediabetes
|
Newly diabetes
|
|
Anthocyanins (n=41)
|
Placebo (n=49)
|
P
|
Anthocyanins (n=39)
|
Placebo (n=31)
|
P
|
Adiponectin (ug/mL)
|
6.05±2.48
|
6.49±2.28
|
0.41
|
5.93±2.4
|
5.77±1.62
|
0.762
|
Glucose metabolism
|
|
|
|
|
|
|
Hemoglobin A1c (%)
|
5.8±0.42
|
5.63±0.43
|
0.074
|
6.49±0.53
|
6.46±0.48
|
0.854
|
Fasting glucose (mmol/L)
|
5.68±0.68
|
5.87±0.44
|
0.145
|
6.62±0.82
|
6.48±0.66
|
0.418
|
2-h glucose (mmol/L)
|
7.66±2.03
|
7.05±1.8
|
0.144
|
12.08±3.03
|
11.74±3.34
|
0.661
|
Fasting insulin (μU/mL)
|
11.58±5.79
|
11.22±5.6
|
0.773
|
11.49±7.12
|
13.21±6.6
|
0.314
|
2-h insulin (μU/mL)
|
81.45±53.51
|
82.12±71.98
|
0.961
|
102.56±68.11
|
109.42±71.86
|
0.686
|
Fasting C-peptide (ng/mL)
|
2.27±0.92
|
2.29±0.81
|
0.943
|
2.58±1.1
|
2.81±1.26
|
0.424
|
2-h C-peptide (ng/mL)
|
10.9±3.68
|
10.56±3.7
|
0.674
|
12.14±3.86
|
12.45±4.25
|
0.754
|
AUC Glucose
|
23.7±4.04
|
23.96±3.76
|
0.785
|
33.66±6.01
|
32.56±5.55
|
0.465
|
AUC Insulin
|
195.77±95.64
|
208.35±105.93
|
0.608
|
211.23±126.83
|
260.78±129.8
|
0.142
|
AUC C-peptide
|
25.72±7.44
|
25.47±6.22
|
0.875
|
26.64±7.35
|
29.86±8.47
|
0.121
|
HOMA-IR
|
2.94±1.6
|
2.91±1.39
|
0.937
|
3.41±2.39
|
3.91±2.18
|
0.383
|
HOMA-β
|
112.65±68.82
|
104.3±97.25
|
0.664
|
77.31±41.61
|
87.36±38.99
|
0.316
|
Lipids
|
|
|
|
|
|
|
Total cholesterol (mmol/L)
|
5.99±1.2
|
5.99±1.03
|
0.996
|
6.24±1.17
|
6.06±1.46
|
0.57
|
Triglycerides (mmol/L)
|
1.7±0.9
|
1.69±1
|
0.949
|
1.73±1.14
|
1.8±1.58
|
0.822
|
HDL cholesterol (mmol/L)
|
1.45±0.39
|
1.48±0.34
|
0.693
|
1.48±0.37
|
1.43±0.34
|
0.528
|
LDL cholesterol (mmol/L)
|
3.35±0.88
|
3.28±0.82
|
0.67
|
3.43±0.94
|
3.33±0.99
|
0.654
|
Apo A-1 (g/L)
|
1.55±0.3
|
1.66±0.28
|
0.073
|
1.64±0.34
|
1.63±0.34
|
0.907
|
Apo B (g/L)
|
1.17±0.25
|
1.13±0.22
|
0.506
|
1.16±0.22
|
1.14±0.28
|
0.836
|
LDLHDL ratio
|
2.44±0.76
|
2.34±0.82
|
0.554
|
2.46±0.86
|
2.46±0.94
|
0.998
|
TGHDL ratio
|
1.33±0.93
|
1.29±1.08
|
0.848
|
1.32±1.21
|
1.42±1.49
|
0.77
|
AUC, area under the curve by 3-hour oral glucose tolerance test, were calculated according the trapezoidal rule.
HOMA-IR, homoeostasis model assessment of insulin resistance; HOMA-IR= FIns (mU/mL) ×FG (mmol/L)/22.5.
HOMA-β, homoeostasis model assessment of β-cell function; HOMA-β= FIns×20/(FG-3.5).
HDL, high-density lipoprotein; LDL, low-density lipoprotein; apo A-1, apolipoprotein A-1; apo B, apolipoprotein B; TG, Triglycerides.
P value was for the differences between the two groups, compared by independent student’s t-test.
Changes in serum adiponectin
After 12 weeks intervention, serum adiponectin reduced both in the placebo group (-0.31 ug/mL [-0.55, -0.06], p=0.015) and anthocyanins group (-0.29 ug/mL [-0.53, -0,05], p=0.021). There was no significant difference in the net change of serum adiponectin between the anthocyanins and placebo group in the overall subjects (0.02 ug/mL [-0.32, 0.36], p=0.906) (Figure 2 A).
In the subgroup of prediabetes, serum adiponectin reduced in the anthocyanins group (-0.51 ug/mL [-0.86, -0.16], p=0.006) but not in placebo group (-0.17 ug/mL [-0.53, 0.2], p=0.365), and the net change between the two groups was nonsignificant (-0.35 ug/mL [-0.85, 0.16], p=0.174) (Figure 2 B). In the subgroup of newly diabetes, there was a significant reduction of serum adiponectin in the placebo group (-0.48 ug/mL [-0.8, -0.16], p=0.004), whereas a null change in the anthocyanins group (-0.02 ug/mL [-0.33, 0.3], p=0.917), and the net change of adiponectin between the two groups was statistically significant (0.46 ug/mL [0.03, 0.90], p=0.038) (Figure 2 C).
Changes in markers for glucose and lipid metabolism
Compared with placebo, anthocyanins decreased fasting glucose (-0.5 mmol/L [-1, -0.04], p=0.035) in the subjects with newly diagnosed diabetes (Supplemental Table4), and increased serum apo A-1 (0.15 g/L [0.03, 0.26], p=0.016), decreased apo B (-0.1 g/L [-0.17, -0.03], p=0.008) in the subjects with prediabetes (Supplemental Table5). Similar changes in apo A-1 and apo B were observed in the overall subjects. No significant change was observed in the inflammatory marker such as C-reactive protein, the anthropometric measurements such as the body weight, BMI, waist and hip circumferences, and blood pressures either in the overall subjects or in the subgroups (data will be submitted on request).