Prospective clinical trial of hepatitis B vaccination in adults with and without type-2 diabetes mellitus

Figures & data

Table 1. Demographic characteristics at screening (according-to-protocol immunogenicity cohort).

Characteristic	Categories	Diabetes group N = 378	Control group N = 189
Age (years)	Median (range)	54.0 (20–82)	53.0 (21–81)
	Mean (SD)	53.7 (12.07)	53.1 (12.88)
Gender n(%)	Female	168 (44.4)	111 (58.7)
	Male	210 (55.6)	78 (41.3)
Geographic Ancestry n(%)	White - Caucasian / European Heritage	319 (84.4)	177 (93.7)
	African Heritage / African American	16 (4.2)	2 (1.1)
	American Indian or Alaskan Native	17 (4.5)	1 (0.5)
	Other*	26 (6.7)	9 (4.8)
BMI (kg/m^2)	Median (range)	32.1 (19.3–63.5)	30.8 (16.7–51.6)
	<30 n (%)	161 (42.6)	80 (42.3)
	≥30 n (%)	217 (57.4)	109 (57.7)
HbA1c (%)	Median (range)	6.5 (4.8–13.9)	5.5 (4.2–6.3)
HbA1c (mmol/mol)	Median (range)	48 (29–127)	37 (22–45)
eGFR (mL/min/1.73m^2)	Median (range)	88 (50–127)	82 (50–135)
	50–80 n (%)	131 (34.7)	86 (45.5)
	80–120 n (%)	239 (63.2)	100 (52.9)
	>120 n (%)	8 (2.1)	3 (1.6)
Age/BMI distribution n(%)	Age 20–39 y and <BMI 30 kg/m^2	14 (3.7)	7 (3.7)
	Age 20–39 y and ≥BMI 30 kg/m^2	38 (10.1)	19 (10.1)
	Age 40–49 y and <BMI 30 kg/m^2	26 (6.9)	13 (6.9)
	Age 40–49 y and ≥BMI 30 kg/m^2	59 (15.6)	31 (16.4)
	Age 50–59 y and <BMI 30 kg/m^2	61 (16.1)	31 (16.4)
	Age 50–59 y and ≥ BMI 30 kg/m^2	58 (15.3)	31 (16.4)
	Age ≥60 years and < BMI 30 kg/m^2	60 (15.9)	29 (15.3)
	Age ≥60 years and ≥ BMI 30 kg/m^2	62 (16.4)	28 (14.8)

N = total number of subjects.

n/% = number / percentage of subjects in a given category.

SD = standard deviation.

BMI = body mass index, HbA1c = glycated hemaglobin.

eGFR =Estimated Glomerular Filtration Rate.

* Other includes Asian, Japanese, Native Hawaiian or Other Pacific Islander, Arabic and North African Heritage.

Table 2. Antibody response to hepatitis B vaccination in the diabetes and control groups and in subgroups according to age and BMI, one month post-dose 3 (according-to-protocol immunogenicity cohort).

	Diabetes N = 378			Controls
	N	n	% (95% CI)	N	n	% (95% CI)
All participants
≥ 6.2 mIU/mL	378	293	77.5 (73.0; 81.6)	189	160	84.7 (78.7; 89.5)
≥ 10 mIU/mL	378	285	75.4 (70.7; 79.7)	189	155	82.0 (75.8; 87.2)
≥ 100 mIU/mL	378	203	53.7 (48.5; 58.8)	189	135	71.4 (64.4; 77.8)
GMC	378	—	147.6 (110.2; 197.8)	189	—	384.2 (254.5; 580.0)
Anti-HBs antibodies ≥ 10 mIU/mL by age
Age 20–39 years	52	46	88.5 (76.6; 95.6)	26	26	100 (86.8; 100)
Age 40–49 years	85	69	81.2 (71.2; 88.8)	44	38	86.4 (72.6; 94.8)
Age 50–59 years	119	99	83.2 (75.2; 89.4)	62	51	82.3 (70.5; 90.8)
Age ≥60 years	122	71	58.2 (48.9; 67.1)	57	40	70.2 (56.6; 81.6)
Anti-HBs antibodies ≥ 10 mIU/mL by BMI
BMI <30 kg/m^2	161	128	79.5 (72.4; 85.5)	80	66	82.5 (72.4; 90.1
BMI ≥30 kg/m^2	217	157	72.4 (65.9; 78.2)	109	89	81.7 (73.1; 88.4)
Anti-HBs antibodies ≥ 10 mIU/mL by age and BMI
Age 20–39 years, BMI <30 kg/m^2	14	12	85.7 (57.2; 98.2)	7	7	100 (59.0; 100)
Age 20–39 years, BMI ≥30 kg/m^2	38	34	89.5 (75.2; 97.1)	19	19	100 (82.4; 100)
Age 40–49 years, BMI <30 kg/m^2	26	21	80.8 (60.6; 93.4)	13	13	100 (75.3; 100)
Age 40–49 years, BMI ≥30 kg/m^2	59	48	81.4 (69.1; 90.3)	31	25	80.6 (62.5; 92.5)
Age 50–59 years, BMI <30 kg/m^2	61	55	90.2 (79.8; 96.3)	31	26	83.9 (66.3; 94.5)
Age 50–59 years, BMI ≥30 kg/m^2	58	44	75.9 (62.8; 86.1)	31	25	80.6 (62.5; 92.5)
Age ≥60 years, BMI <30 kg/m^2	60	40	66.7 (53.3; 78.3)	29	20	69.0 (49.2; 84.7)
Age ≥60 years, BMI ≥30 kg/m^2	62	31	50.0 (37.0; 63.0)	28	20	71.4 (51.3; 86.8)

GMC = geometric mean antibody concentration calculated on all subjects.

N = number of subjects with available results.

n/% = number/percentage of subjects with concentration ≥ specified value.

95% CI = 95% confidence interval.

GMC = geometric mean antibody concentration.

BMI = body mass index.

Thresholds: 6.2 mIUmL = assay level of detection defining seropositivity 10 mIU/ml = threshold defining seroprotection.

Table 3. Estimated coefficients of the regression analyses on anti-HBs antibody seroprotection status and geometric mean antibody concentrations (GMCs) (according-to-protocol immunogenicity cohort).

		Logistic regression analysis on seroprotection status		Stepwise multiple linear regression analysis on GMCs
		Odds ratio (95% CI)	p value	GMC ratio (95% CI)	p value
Saturated Model	Presence of diabetes	0.61 (0.36; 1.05)	0.0741	0.47 (0.27; 0.82)	0.0078
	Increased BMI (per 10kg/m^2)	0.52 (0.39; 0.71)	<0.0001	0.33 (0.24; 0.45)	<0.0001
	Female gender	1.15 (0.76; 1.77)	0.5061	1.75 (1.12; 2.72)	0.0136
	Older age (per decade)	0.56 (0.44; 0.70)	<0.0001	0.47 (0.37; 0.58)	<0.0001
	Caucasian ancestry	0.92 (0.45; 1.91)	0.8331	0.62 (0.31; 1.23)	0.1720
	Decreased eGFR	1.00 (0.99; 1.02)	0.5835	1.00 (0.98; 1.01)	0.5694
	Increased HbA1c	1.21 (0.95; 1.53)	0.1206	1.16 (0.94; 1.43)	0.1558
Final model	Increased BMI (per 10kg/m^2)	0.53 (0.40; 0.71)	<0.0001	0.33 (0.24; 0.45)	<0.0001
	Older age (per decade)	0.54 (0.45; 0.65)	<0.0001	0.47 (0.39; 0.56)	<0.0001
	Presence of diabetes	—	—	0.59 (0.37; 0.95)	0.0301
	Female gender	—	—	1.71 (1.10; 2.66)	0.0173

Characteristics were coded in the following order: diabetes group as 1, control group as 0; female as 1, male as 0; Caucasian / European heritage as 1, non-Caucasian / European heritage as 0; age per 10 years; BMI per 10 kg/m²; eGFR as mL/min/1.73m²; HbA1c as %. Odds ratio: for binary co variable this represents the ratio of odds between the category coded 1 over the category code 0. For continuous co variable this represents the ratio of odds associated to a co variable increase by one unit. A value above 1 is associated to an increase in seroprotection. GMC ratio: for binary covariables this represents the ratio of GMC between the category coded 1 over the category code 0. For continuous covariables this represents the ratio of GMC associated to a covariable increase by one unit. A value above 1 is associated to an increase in antibody concentration. The p-value for each term tests the null hypothesis that the coefficient is = 0 (no effect). Note: Saturated model is without considering stepwise elimination strategy and final model is after consideration of stepwise elimination strategy.

Table 4. Percentage of participants reporting solicited local and general symptoms within 4 d after vaccination (all doses, total vaccinated cohort).

	Diabetes Group (N = 413)		95 % CI		Control Group (N = 257)		95 % CI
	n	%	LL	UL	n	%	LL	UL
Solicited local symptom
Pain	160	38.7	34.0	43.6	115	44.7	38.6	51.1
Redness	84	20.3	16.6	24.5	51	19.8	15.1	25.3
Swelling	49	11.9	8.9	15.4	19	7.4	4.5	11.3
Solicited general symptom
Fatigue	118	28.6	24.3	33.2	69	26.8	21.5	32.7
Gastrointestinal symptoms	83	20.1	16.3	24.3	47	18.3	13.8	23.6
Headache	97	23.5	19.5	27.9	71	27.6	22.3	33.5
Fever /(Oral) (°C)	15	3.6	2.0	5.9	8	3.1	1.4	6.0

Diabetes Group = Subjects diagnosed with type 2 diabetes within the past 5 y.

Control Group = Subjects with no diagnosis or documented history of diabetes.

N = number of subjects with at least one documented dose.

n/% = number/percentage of subjects reporting the symptom at least once.

95% CI = Exact 95% confidence interval; LL = lower limit, UL = upper limit.