The Beneficial Effects of a Multispecies Probiotic Supplement on Glycaemic Control and Metabolic Profile in Adults with Type 1 Diabetes: A Randomised, Double-Blinded, Placebo-Controlled Pilot-Study

Figures & data

Table 1 General Baseline Characteristics of the Study Participants

	Total (N=50)	Placebo (N=23)	Probiotics (N=27)	p-value
Age (years)	39±11	39±8	38±14	0.834
Sex, female/male, n (%)	23 (36.0)/27 (54.0)	10 (43.5)/13 (56.5)	13 (48.1)/14 (51.9)	0.741
Diabetes duration (years)	10 (6, 16)	10(7, 16)	10 (4, 16)	0.718
Daily insulin dose (U)	38.7±18.3	34.7±21.2	42.4±14.6	0.154
Body weight (kg)	57.8±8.6	56.2±8.0	59.3±9.0	0.216
BMI (kg/m^2)	21.1±2.4	20.5±2.4	21.7±2.2	0.085
SBP (mmHg)	114±14	111±13	116±15	0.147
DBP (mmHg)	74±10	74±9	75±10	0.608
HbA1c (%)	7.5±1.5	7.3±1.5	7.8±1.5	0.251
HbA1c (mmol/mol)	58.65±16.55	55.76±16.76	61.31±16.24	0.251
Fasting C-peptide (ng/ml)	0.17±0.35	0.14±0.40	0.19±0.31	0.616
Hs-CRP (mg/L)	0.75±0.55	0.63±0.50	0.86±0.58	0.132
ALT (U/L)	17.8±13.8	20.3±18.6	15.5±6.6	0.258
AST (U/L)	21.2±10.9	21.7±11.0	20.8±10.9	0.759
TG (mmol/L)	1.05±1.98	0.757±0.23	1.32±2.73	0.312
TC (mmol/L)	5.19±1.00	5.31±0.98	5.08±1.03	0.422
HDL-c (mmol/L)	1.80±0.45	1.91±0.42	1.69±0.45	0.098
LDL-c (mmol/L)	3.01±0.78	3.11±0.85	2.92±0.72	0.403
eGFR (mL/min/1.73 m2)	107.51±16.82	104.09±15.94	110.65±17.30	0.178
FBG (mmol/L)	8.7±4.0	7.6±3.5	9.8±4.2	0.052
30min PBG (mmol/L)	12.8±3.6	11.9±3.0	13.6±4.0	0.098
2h PBG (mmol/L)	23.1±4.4	22.6±4.4	23.5±4.5	0.521
SDBG (mmol/L)	2.85 (2.15, 3.39)	2.85 (2.08, 3.09)	2.81 (2.28, 3.80)	0.410
LAGE (mmol/L)	12.50(10.05~16.40)	11.80(9.70~15.33)	12.95(11.40~16.78)	0.471
MAGE (mmol/L)	6.45 (5.03, 7.90)	6.10 (5.13, 7.65)	6.55 (5.08, 8.40)	0.520
MODD (mmol/L)	2.85 (2.20, 3.40)	2.70 (2.20, 3.93)	2.95 (2.18, 3.33)	0.767
CV(%)	34.0±9.92	33.3±9.35	34.6±10.6	0.674
MSG(mmol/L)	8.58±2.34	8.47±2.51	8.69±2.22	0.752
TAR (%)	29.9±24.5	28.4±24.6	31.3±24.8	0.701
TBR (%)	4.82±7.29	5.13±7.63	4.53±7.11	0.782
TIR (%)	65.3±23.5	66.4±23.6	64.2±23.8	0.754

Note: Normally distributed quantitative variables are presented as the mean ± s.d., and nonnormally distributed quantitative variables are presented as the median (interquartile range, IQR).

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CV, coefficient of variation; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FBG fasting blood glucose; HbA1c, haemoglobin A1c; HDL-C, high-density lipoprotein cholesterol; Hs-CRP, high sensitivity C-reactive protein; LAGE, largest amplitude of glycaemic excursions; LDL-C, low-density lipoprotein cholesterol; MAGE, mean amplitude of glucose excursions; MODD, mean of daily differences; SBP, systolic blood pressure; SDBG, standard deviation of blood glucose; TC, total cholesterol; TG, total triglyceride; TAR, time above range; TBR, time below range; TIR, time in range, 2h PBG, 2-hour postprandial blood glucose;30min PBG, 30 minutes postprandial blood glucose.

Figure 1 Diagram of clinical trials in participants with type 1 diabetes mellitus. f/u, follow-up.

Table 2 The Between-Group Comparisons of Metabolic Profiles, CGM Data, and Hs-CRP After Supplementation

	Placebo (N=23)	Probiotics (N=25)	p-value
ΔHbA1c (%)	−0.22±0.60	−0.49±1.15	0.310
ΔHbA1c (mmol/mol)	−2.38±6.59	−5.33±12.60	0.310
ΔFasting C-peptide (ng/mL)	−0.02±0.28	−0.01±0.14	0.979
Δ30 minutes postprandial C-peptide (ng/mL)	−0.07±0.39	0.01±0.11	0.406
Δ2 hour postprandial C-peptide (ng/mL)	−0.17±0.71	−0.01±0.15	0.302
ΔFBG (mmol/L)	1.8±4.7	−1.0±4.7	0.048
Δ30min PBG (mmol/L)	1.9±3.3	−0.5±4.6	0.050
Δ2h PBG (mmol/L)	0.5±4.7	0.1±5.0	0.727
ΔSDBG (mmol/L)	0.40 (0.02, 0.81)	0.11 (−0.44, 0.81)	0.296
ΔLAGE (mmol/L)	1.30 (−1.68, 2.93)	−0.05 (−3.23, 2.33)	0.281
ΔMAGE (mmol/L)	0.60 (−0.65, 1.88)	−0.00 (−2.53, 1.65)	0.195
ΔMODD (mmol/L)	0.45 (−0.48, 1.05)	0.850 (−0.08, 1.18)	0.448
ΔCV (%)	1.97 (−1.63, 7.33)	1.92 (−7.19, 5.37)	0.624
ΔMSG (mmol/L)	0.40 (−0.56, 1.41)	−0.15 (−1.24, 1.43)	0.725
ΔTAR (%)	2.26 (−2.21, 7.52)	0.82 (−11.82, 21.29)	0.991
ΔTBR (%)	0.00 (−2.41, 3.10)	0.00 (−2.12, 2.73)	0.965
ΔTIR (%)	−1.66 (−7.44, 3.43)	−1.84 (−20.33, 11.98)	0.700
ΔTG (mmol/L)	0.00±0.20	0.52±2.39	0.297
ΔTC (mmol/L)	0.52±1.05	0.16±0.64	0.156
ΔHDL-C (mmol/L)	0.00±0.21	0.00±0.13	0.925
ΔLDL-C (mmol/L)	0.32±0.78	−0.07±0.45	0.041
ΔHs-CRP (mg/L)	0.08±0.47	0.20±0.43	0.374

Notes: Normally distributed quantitative variables are presented as the mean ± s.d., and nonnormally distributed quantitative variables are presented as the median (interquartile range, IQR). Delta (Δ) value = 3-month value – baseline value.

Abbreviations: CV, coefficient of variation; FBG fasting blood glucose; HbA1c, haemoglobin A1c; HDL-C, high-density lipoprotein cholesterol; Hs-CRP, high sensitivity C-reactive protein; LAGE, largest amplitude of glycaemic excursions; LDL-C, low-density lipoprotein cholesterol; MAGE, mean amplitude of glucose excursions; MODD, mean of daily differences; SDBG, standard deviation of blood glucose; TC, total cholesterol; TG, total triglyceride; TAR, time above range; TBR, time below range; TIR, time in range; 2h PBG, 2-hour postprandial blood glucose;30min PBG, 30 minutes postprandial blood glucose.

Figure 2 Probiotics improved fasting blood glucose (FBG) and 30 minutes postprandial blood glucose (PBG) as well as low-density lipoprotein cholesterol (LDL-C). (A) Change in FBG (mmol/L) in response to Probiotics group vs Placebo group. (B) Change in 30 minutes PBG (mmol/L) in response to Probiotics group vs Placebo group. (C) Change in LDL-C (mmol/L) in response to Probiotics group vs Placebo group. Significant reductions inFBG, 30minutesPBG as well as LDL-C were observed in the patients in the Probiotics group, and the changes were significantly different compared with those in Placebo group.

Table 3 Subgroup Analysis of C-Peptide and Glucose Level in the Probiotics Group After Intervention

	ΔFasting C-Peptide (ng/mL)	Δ30 Minutes Postprandial C-Peptide (ng/mL)	Δ2 Hour Postprandial C-Peptide (ng/mL)	ΔFBG (mmol/L)	Δ30Min PBG (mmol/L)	Δ2h PBG (mmol/L)
BMI (kg/m^2)
>20.8	−0.04±0.10	0.00±0.09	−0.01±0.17	−1.5±3.5	−0.6±4.5	0.3±5.1
≤20.8	0.02±0.17	0.01±0.15	−0.02±0.12	−0.2±6.1	−0.2±5.0	−0.2±5.1
P-value	0.307	0.965	0.774	0.558	0.850	0.835
Sex
Male	−0.05±0.13	−0.03±0.08	−0.04±0.15	−0.33±5.00	−0.16±5.23	−0.20±4.65
Female	0.02±0.14	0.04±0.13	0.02±0.15	−1.61±4.34	−0.80±4.03	0.37±5.52
P-value	0.245	0.125	0.354	0.501	0.736	0.784
Hba1c (%)
>7.35	−0.02±0.09	0.01±0.10	−0.00±0.16	−2.34±4.75	−1.60±5.29	−0.77±5.89
≤7.35	−0.01±0.18	0.00±0.13	−0.03±0.14	0.83±4.04	0.98±3.23	1.14±3.52
P-value	0.835	0.917	0.670	0.085	0.148	0.325
FBG (mmol/L)
>8.62	−0.03±0.09	−0.01±0.10	−0.03±0.14	−2.87±4.53	−2.16±4.98	−1.37±5.60
≤8.62	0.00±0.19	0.03±0.13	0.01±0.17	1.51±3.65	1.69±3.09	1.91±3.51
P-value	0.676	0.388	0.440	0.013	0.027	0.087

Notes: Data are the mean ± s.d. Delta (Δ) value = 3-month value – baseline value.

Abbreviations: FBG, fasting blood glucose; 30min PBG, 30 minutes postprandial blood glucose; 2h PBG, 2-hour postprandial blood glucose.

Table 4 Subgroup Analysis of Glycaemic Variability and Glycaemic Control in the Probiotics Group After Intervention

	ΔSDBG (mmol/L)	ΔLAGE (mmol/L)	ΔMAGE (mmol/L)	ΔMODD (mmol/L)	ΔCV (%)	ΔMSG (mmol/L)	ΔTAR (%)	ΔTBR (%)	ΔTIR (%)
BMI (kg/m^2)
>20.8	0.08 (−0.47, 0.44)	−0.80 (−3.25, 2.15)	−0.40 (−2.90, 0.95)	0.20 (−0.35, 0.90)	2.58 (−0.38, 5.11)	−0.37 (−1.88, 0.55)	−0.95 (−16.44, 6.78)	0.56 (−0.25, 2.78)	0.68 (−12.56, 12.39)
≤20.8	0.30 (−0.34, 1.24)	1.00 (−2.70, 3.60)	0.40 (−0.60, 3.50)	1.10 (1.00, 1.40)	−6.36 (−9.75, 9.33)	0.95 (−0.02, 2.52)	14.47 (2.66, 23.37)	−1.74 (−3.99, 0.35)	−19.58 (−20.95, 7.87)
P-value	0.519	0.796	0.114	0.374	0.848	0.120	0.121	0.100	0.197
Sex
Male	−0.20 (−0.44, 0.26)	−0.45 (−3.23, 1.33)	−0.50 (−2.75, 0.15)	0.30 (−0.33, 1.03)	3.57 (−1.76, 5.23)	−0.75 (−2.11, 0.48)	−5.47 (−20.13, 3.04)	0.99 (−0.13, 2.92)	9.32 (−4.84, 16.6)
Female	0.44 (−0.54, 1.00)	1.00 (−3.33, 3.30)	1.05 (−1.98, 3.20)	0.95 (0.43, 1.43)	−0.14 (−10.50, 6.28)	1.51 (−0.37, 2.74)	18.92 (−1.11, 35.56)	−1.37 (−4.25, 0.88)	−19.85 (−31.39, 0.69)
P-value	0.588	0.941	0.076	0.660	0.367	0.010	0.006	0.317	0.005
Hba1c (%)
>7.35	−0.20 (−0.49, 0.70)	−0.25 (−3.53, 2.30)	−0.50 (−2.40, 1.50)	0.35 (−0.23, 1.33)	−0.14 (−8.90, 3.76)	0.015 (−1.25, 2.67)	0.62 (−13.25, 26.78)	4.28 (−22.22, 13.02)	−1.07 (−4.57, 1.39)
≤7.35	0.36 (−0.13, 0.71)	−0.05 (−2.35, 2.30)	0.25 (−1.85, 1.33)	0.95 (0.65, 1.00)	4.64 (−3.43, 9.19)	−0.15 (−0.38, 0.65)	2.20 (−1.44, 13.89)	−9.67 (−17.93, 1.30)	1.09 (0.09, 4.59)
P-value	0.526	0.521	0.968	0.727	0.170	0.531	0.843	0.764	0.039
FBG (mmol/L)
>8.62	0.015 (−0.40, 0.89)	−0.50 (−3.53, 2.98)	−0.50 (−2.58, 1.43)	0.85 (0.13, 1.33)	1.92 (−8.90, 5.66)	0.17 (−1.21, 2.16)	2.03 (−11.03, 22.68)	−1.07 (−4.57, 0.26)	−1.84 (−20.74, 12.32)
≤8.62	0.22 (−0.43, 0.45)	−0.05 (−2.23, 2.23)	0.25 (−1.23, 1.33)	0.55 (−0.38, 1.00)	1.57 (−4.21, 4.92)	−0.15 (−1.39, 0.48)	0.03 (−13.08, 11.90)	2.43 (0.41, 5.19)	−3.25 (−17.93, 9.17)
P-value	0.931	0.675	0.735	0.579	0.478	0.479	0.509	0.007	0.931

Notes: Data are the median (interquartile range, IQR). Delta (Δ) value = 3-month value – baseline value.

Abbreviations: CV, coefficient of variation; LAGE, largest amplitude of glycaemic excursions; MAGE, mean amplitude of glucose excursions; MODD, mean of daily differences; MSG, mean sensor glucose; SDBG, standard deviation of blood glucose; TAR, time above range; TBR time below range; TIR, time in range.