Human adenovirus-36 is uncommon in type 2 diabetes and is associated with increased insulin sensitivity in adults in Sweden

Figures & data

Figure 1. Study groups. The study groups were selected from the population-based Stockholm Diabetes Prevention Program (SDPP). BMI = body mass index kg/m².

Table I. Clinical characteristics of the SDPP study groups. Data are from the follow-up if nothing else is specified.

	Type 2 diabetes (T2DM)		Normal glucose tolerance (NGT)
		Prediabetes	BMI < 25 kg/m^2	BMI ≥ 28 kg/m^2
nfemales, nmales	106, 183	211, 290	255, 219	252, 218
ELISA (nfemales, nmales)^a	104, 176	199, 286	251, 217	244, 212
Females
Age (years)	59 (55, 61)	58 (55, 61)	57 (52, 60)	57 (52, 60)
BMI (kg/m^2)	31.2 (26.7, 35.2)	29.1 (25.9, 32.9)	22.4 (21.2, 23.8)	30.0 (28.8, 31.9)
FHD (n)	14 FHD–, 91 FHD+	53 FHD–, 155 FHD+	225 FHD–, 30 FHD+	210 FHD–, 41 FHD+
IFG, IGT, both, at baseline (n)	12, 28, 6	7, 21, 2	All NGT	All NGT
IFG, IGT, both, at follow-up (n)		46, 142, 23	All NGT	All NGT
Glucose (mM)	6.8 (5.9, 7.6)	5.7 (5.1, 6.2)	4.6 (4.3, 4.8)	4.9 (4.6, 5.2)
Insulin (pM)	141 (102, 204)	114 (84, 150)	72 (60, 90)	96 (78, 119)
HOMA-IR	7.2 (4.7, 10.2)	4.7 (3.3, 6.3)	2.4 (2.0, 3.1)	3.6 (2.8, 4.4)
HOMA-β	147 (108, 212)	182 (138, 256)	222 (175, 320)	233 (187, 306)
Treatment for T2DM (n)	47
Males
Age (years)	59 (55, 62)	58 (55, 61)	57 (53, 61)	57 (53, 59)
BMI (kg/m^2)	29.2 (26.8, 32.0)	28.4 (26.1, 31.4)	23.3 (22.4, 24.1)	29.9 (28.7, 31.8)
FHD (n)	41 FHD–, 137 FHD+	98 FHD–, 184 FHD+	203 FHD–, 15 FHD+	202 FHD–, 12 FHD+
IFG, IGT, both, at baseline (n)	16, 40, 16	9, 26, 1	All NGT	All NGT
IFG, IGT, both, at follow-up (n)		88, 147, 55	All NGT	All NGT
Glucose (mM)	7.3 (6.2, 8.6)	6.0 (5.3, 6.3)	4.8 (4.6, 5.1)	5.1 (4.8, 5.3)
Insulin (pM)	144(108, 198)	114 (96, 150)	69 (54, 96)	108 (84, 132)
HOMA-IR	8.4 (5.4, 12.1)	5.0 (4.1, 6.5)	2.6 (1.9, 3.4)	4.0 (3.0, 5.1)
HOMA-β	125 (82, 196)	177 (131, 253)	224 (180, 300)	225 (174, 307)
Treatment for T2DM (n)	77

BMI = body mass index; FHD = family history of diabetes (first-degree relative or second-degree relatives with diabetes); IFG, IGT, both = impaired fasting glucose, impaired glucose tolerance, IFG+ IGT.

Values are median (25th, 75th percentile), Fasting serum levels.

^aNumber of those with successful ELISA.

Figure 2. Prevalence of seropositivity for human adenovirus-36 (Adv36) in serum samples from adults with normal glucose tolerance, prediabetes, and type 2 diabetes. Seropositivity was lower in females and males with type 2 diabetes (T2DM; black bars) and females with prediabetes (PreT2DM; impaired fasting glucose and/or impaired glucose tolerance; grey bars) compared to those with normal glucose tolerance (NGT; white bars). Error bars indicate standard error of proportion. Statistical significance of differences was tested using Pearson's chi-square test.

Table II. Unadjusted and adjusted relationships odds ratios for Adv36 seronegativity in females and males with prediabetes and type 2 diabetes compared to those with normal glucose tolerance (NGT).

Study group	Adv36pos % (n)	Adv36neg % (n)	OR (95% CI), chi-square , P vs NGT	ORadj (95% CI), Padj vs NGT
Normal glucose tolerance (NGT):
Females	14.3 (71)	85.7 (424)	Reference
Males	17.5 (75)	82.5 (354)	Reference
Prediabetes:
Females	8.5 (17)	91.5 (182)	1.8 (1.1–3.1), 4.0, 0.043	1.7 (0.96–3.0), 0.070
Males	16.8 (48)	83.2 (238)	1.1 (0.62–1.4), 0.06, 1.0	0.93 (0.63–1.45), 0.73
Diabetes:
Females	1.0 (1)	99.0 (103)	17.2 (4.0–74.3), 13.3, 0.0003	15.7 (2.1–112.7), 0.007
Males	5.7 (10)	94.3 (166)	3.5 (1.8–6.7), 13.4, 0.0003	3.1 (1.5–6.2), 0.002

Significance tests were made in each sex separately, comparing patients with normal-glucose-tolerant controls.

OR, P: Pearson's chi-square test was used. OR_adj, P_adj: logistic regression with BMI and age as covariates was used.

CI = confidence interval; OR = odds ratio.

Figure 3. Relationship of Adv36 seropositivity to: (A) fasting serum triglyceride levels; (B) IGFBP-1; and (C) HOMA-IR levels in females with normal glucose tolerance (NGT) at baseline who had NGT at follow-up, or had developed prediabetes or type 2 diabetes at follow-up. Bars indicate the back-transformed mean of ln-transformed clinical parameter. Error bars indicate the back-transformed 95% confidence interval of ln-transformed clinical parameter. Statistical significance of differences was tested using the t test. White bars = Adv36-negative; black bars = Adv36-positive.

Table III. Unadjusted and adjusted relationships for Adv36 positivity to triglycerides, IGFBP-1, and measures of insulin resistance in persons with normal glucose tolerance (NGT) at baseline who had NGT at follow-up, or had developed prediabetes or type 2 diabetes at follow-up.

Status at follow-up	Adv36neg mean (95% CI)^an	Adv36pos mean (95% CI)^a n	% diff^b pos vs neg	P value pos vs neg	Padj pos vs neg
Normal glucose tolerance (n = 134):
Triglycerides (mM)	1.2 (1.1, 1.3) 112	1.2 (1.0, 1.5) 22	0.3↑	NS	NS
IGFBP-1 (μg/L)	41 (38, 45) 112	37 (30, 44) 22	11.8↓	NS	NS
HOMA-IR	2.7 (2.5, 2.9) 112	2.9 (2.4, 3.4) 22	7.0↑	NS	NS
Diabetes (n = 58) and IGT-prediabetes patients (n = 131):
Triglycerides (mM)	1.8 (1.7, 1.9) 178	1.5 (1.3, 1.8) 11	16.2↓	0.054	0.52
IGFBP-1 (μg/l)	28 (25, 30) 178	40 (30, 52) 11	44.3↑	0.034	0.099
IGT-prediabetes (n = 131):
Triglycerides (mM)	1.8 (1.6, 1.9) 120	1.5 (1.3, 1.8) 11	14.7↓	0.084	0.52
IGFBP-1 (μg/l)	27 (24, 29) 120	40 (30, 52) 11	49.9↑	0.018	0.049
HOMA-IR	4.4 (4.0, 4.9) 120	2.7 (2.2, 3.4) 11	38.0↓	0.003	0.028
Insulin (pM)	111 (102, 121) 120	72 (57, 90) 11	35.5↓	0.003	0.020

Significance tests between Adv36-positive and Adv36-negative groups were made applying unpaired t test on natural logarithm-transformed HOMA-IR, IGFBP-1, and insulin (P value), and confirmed applying ANCOVA, on natural logarithm-transformed HOMA-IR and IGFBP-1 adjusting for age and natural logarithm of BMI (P_adj).

Data are fasting serum levels at follow-up; NS: P > 0.2

^aMean and 95% confidence interval of the mean (CI) are back-transformed values of corresponding mean and 95% CI of natural logarithm (ln)-transformed clinical parameter values.

^b% diff is (HOMA-IR_Adv36pos–HOMA-IR_Adv36neg)/HOMA-IR_Adv36neg where the values were back-transformed means of ln-transformed HOMA-IR, and corresponding for IGFBP-1 and insulin. Calculations are based on more value digits than those two or three given in the Table.

HOMA-IR = homeostatic model assessment of insulin resistance; IGFBP-1 = insulin-like growth factor binding protein-1; IGT = impaired glucose tolerance.