Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes

doi:10.4239/wjd.v15.i8.1717

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Aug 15, 2024 (publication date) through Aug 31, 2024

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World Journal of Diabetes

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1948-9358

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Diabetes. Aug 15, 2024; 15(8): 1717-1725
Published online Aug 15, 2024. doi: 10.4239/wjd.v15.i8.1717

Table 1 Demographic characteristics by insulin dependence, mean ± SD

Variable	Total (n = 132)	No insulin dependence (n = 64)	Insulin dependence (n = 68)	P value
Sex (M) (%)	71 (53.8)	34 (53.1)	37 (54.4)	0.51
Age (years)	15.9 ± 1.3	15.98 ± 1.3	15.9 ± 1.4	0.85
Weight (kg)	73.4 ± 10.1	72.2 ± 10.4	74.5 ± 9.8	0.06
Height (cm)	165.3 ± 6.4	164.7 ± 6.5	165.9 ± 6.3	0.11
BMI (kg/m²)	25.2 ± 3.5	24.9 ± 3.8	25.5 ± 3.1	0.09
BMI z-score	1.39 ± 0.44	1.35 ± 0.46	1.43 ± 0.41	0.42
WC (cm)	87.4 ± 9.9	85.1 ± 10.6	89.1 ± 8.9	0.22
WHtR	0.52 ± 0.05	0.52 ± 0.06	0.53 ± 0.04	0.08
SBP (mm/Hg)	111.6 ± 11.2	110.3 ± 10.7	112.9 ± 11.6	0.05
DBP (mm/Hg)	72.0 ± 8.5	70.6 ± 7.8	73.3 ± 9.0	0.1
DD (years)	4.49 ± 0.88	4.73 ± 0.09	4.27 ± 0.70	0.03

BMI: Body mass index; WC: Waist circumference; WHtR: Waist-to-height ratio; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; DD: Diabetes duration in years.

Table 2 Metabolic characteristics by insulin dependence, mean ± SD

Variable	Total (n = 132)	No insulin dependence (n = 64)	Insulin dependence (n = 68)	P value
TC (mg/dL)	175.9 ± 48.3	164.2 ± 37.4	186.9 ± 54.8	0.54
HDL-C (mg/dL)	44.1 ± 9.3	44.6 ± 7.5	43.6 ± 10.8	0.11
LDL-C (mg/dL)	107.1 ± 41.1	93.3 ± 28.8	118.3 ± 47.5	0.1
TG (mg/dL)	158.5 ± 21.1	148.5 ± 14.0	187.9 ± 19.9	0.18
Fasting glucose (mmol/L)	10.95 ± 0.55	7.62 ± 0.37	14.07 ± 0.51	0.08
HbA1c (%)	8.8 ± 2.9	6.7 ± 1.6	10.8 ± 2.3	0.001
Insulin (mUI/mL)	11.4 ± 7.7	12.7 ± 9.6	10.3 ± 5.0	0.3
C- peptide (ng/dL)	1.4 ± 1.3	2.53 ± 1.2	0.41 ± 0.36	0.001
HOMA-β	85.38 ± 16.6	125.5 ± 15.6	50.9 ± 16.8	0.022

TC: Total cholesterol; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein-cholesterol; TG: Triglycerides; HbA1c: Glycated hemoglobin A1c; HOMA-β: Homeostatic model assessment of beta cell function.

Table 3 Demographic characteristics by autoimmunity

Variable	At the time of diagnosis	NID		P value	At the time of diagnosis	ID		P value
Variable	NID (n = 64)	(Ab+) (n = 16)	(Ab-) (n = 48)	P value	ID (n = 68)	(Ab+) (n = 27)	(A-) (n = 41)	P value
Sex (F) (%)		8 (50.0)	26 (54.1)	0.77		16 (59.2)	21 (51.2)	0.51
Age (years)	12.9 ± 0.7	15.9 ± 1.4	16.0 ± 1.3	0.87	13.1 ± 0.9	16.1 ± 1.4	15.7 ± 1.4	0.3
Weight (kg)	68.9 ± 13.9	67.2 ± 11.2	73.9 ± 9.6	0.04	74.6 ± 10.5	73.6 ± 8.4	75.0 ± 10.6	0.57
Height (cm)	159.2 ± 6.0	161.7 ± 7.6	165.7 ± 5.9	0.03	162.2 ± 5.96	165.9 ± 6.2	166.0 ± 6.5	0.95
BMI (kg/m²)	26.0 ± 5.0	24.8 ± 3.3	25.0 ± 4.0	0.81	26.6 ± 4.2	25.6 ± 2.5	25.4 ± 3.5	0.85
BMI z-score	1.61 ± 0.6	1.25 ± 0.4	1.38 ± 0.4	0.31	1.68 ± 0.4	1.40 ± 0.3	1.46 ± 0.4	0.52
WC (cm)	92.6 ± 9.4	85.9 ± 9.5	85.1 ± 11.1	0.91	94.6 ± 10.8	89.0 ± 7.1	89.1 ± 10.0	0.95
WHtR (cm)	0.56 ± 0.06	0.53 ± 0.05	0.51 ± 0.07	0.47	0.56 ± 0.06	0.53 ± 0.03	0.53 ± 0.50	0.94
SBP (mmHg)	112 ± 12.2	109.8 ± 10.0	110.5 ± 11.0	0.82	18 ± 14.6	112.3 ± 13.2	113.2 ± 10.6	0.75
DBP (mmHg)	74.5 ± 8.4	70.7 ± 7.0	70.6 ± 8.1	0.96	78.8 ± 9.2	73.1 ± 10.2	73.5 ± 8.2	0.86
DD (years)		4.76 ± 0.95	4.72 ± 0.09	0.87		4.38 ± 0.82	4.19 ± 0.73	0.34

NID: No insulin dependence; ID: Insulin dependent; Ab: Antibodies; BMI: Body mass index; WC: Waist circumference; WHtR: Waist-to-height ratio; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; DD: Diabetes duration in years.

Table 4 Metabolic characteristics of the groups by autoimmunity

Variable	At the time of diagnosis	NID		P value	At the time of diagnosis	ID		P value
Variable	NID (n = 64)	Ab+) (n = 16)	(Ab-) (n = 48)	P value	ID (n = 68)	(Ab+) (n = 27)	(A-) (n = 41)	P value
TC (mg/dL)	164.8 ± 39	170 ± 32.9	162.1 ± 38.8	0.44	170 ± 37.5	189.2 ± 60.7	185.3 ± 51.3	0.77
HDL-C (mg/dL)	41.9 ± 11.4	45.8 ± 6.9	44.1 ± 7.7	0.42	43.6 ± 8.0	42.2 ± 8.0	44.5 ± 12.4	0.39
LDL-C (mg/dL)	97.9 ± 30	96.8 ± 23.2	94.8 ± 30.6	0.82	96.2 ± 29.3	124.8 ± 51.6	114.0 ± 44.8	0.38
TG (mg/dL)	136.4 ± 28	162.5 ± 21.1	143.8 ± 11.0	0.65	153.3 ± 22	172.6 ± 9.8	164.8 ± 10.9	0.75
Glucose (mmol/L)	14.77 ± 2.16	7.58 ± 2.93	7.64 ± 3.97	0.96	13.27 ± 2.55	13.66 ± 0.54	14.68 ± 0.25	0.43
HbA1c (%)	9.7 ± 2.7	6.8 ± 1.8	6.3 ± 0.9	0.91	9.2 ± 2.2	11.4 ± 2.6	10.4 ± 2.1	0.09
Insulin (mUI/mL)	16.7 ± 1.6	9.3 ± 4.8	13.8 ± 9.5	0.02	21.1 ± 2.8	9.5 ± 3.7	10.7 ± 5.7	0.04
C-peptide (ng/mL)	0.3 ± 0.09	2.3 ± 1.2	2.6 ± 1.2	0.42	1.1 ± 0.26	0.30 ± 0.25	0.40 ± 0.04	0.19
HOMA-β	72.3 ± 33.9	64.8 ± 45.3	125.7 ± 15.8	0.02	91.5 ± 30.6	25.8 ± 34.6	61.3 ± 20.2	0.02

NID: No insulin dependence; ID: Insulin dependent; TC: total cholesterol; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein-cholesterol; TG: Triglycerides; HbA1c: Glycated hemoglobin A1c; HOMA-β: Homeostatic model assessment of beta-cell function.

Table 5 Frequency of antibody positivity, n (%)

Variable	Total (n = 132)	No insulin dependence (n = 64)	Insulin dependent (n = 68)	P value
Anti-GAD 65	39 (29.5)	13 (20.3)	26 (38.2)	0.02
Anti-IA2	24 (18.2)	8 (12.5)	16 (23.5)	0.07
Anti-Zn8T	21 (15.9)	3 (4.7)	18 (26.5)	0
Anti-GAD65 + anti-IA2	20 (15.2)	5 (7.8)	15 (22.1)	0.02
Anti-GAD65 + anti-Zn8T	15 (11.4)	3 (4.7)	12 (17.6)	0.01
Anti-IA2 + anti-Zn8T	12 (9.1)	2 (3.1)	10 (14.7)	0.02
Three antibodies	12 (9.1)	2 (3.1)	10 (14.7)	0.02

GAD65: Glutamic acid decarboxylase; IA2: Islet antigen 2; Zn8T: Zinc transporter 8.

Table 6 Antibody titers according to insulin dependence

Variable	Total (n = 132)	No insulin dependence (n = 64)	Insulin dependent (n = 68)	P value
Anti-GAD65 (UI/mL)	11.0 (5-543)	6.8 (5-543)	12.0 (5-186)	0.69
Anti-IA2 (UI/mL)	14.6 (5-245)	8.45 (5-111)	21.6 (5-245)	0.6
Anti-Zn8T (UI/mL)	68.5 (15.9-178.2)	64.5 (47-74.5)	73.7 (15.9-178.2)	0.68

Median and minimum and maximum ranges. Mann–Witney U test. GAD65: Glutamic acid decarboxylase; IA2: Islet antigen 2; Zn8T: Zinc transporter 8.

Table 7 Estimation of risks according to antibodies

Variable	Odds ratio early insulin requirements (n = 132)
Variable	OR adj (95%CI)	P value
Anti-GAD65	2.42 (1.112- 5.303)	0.026
Anti-IA2	1.55 (0.859- 2.818)	0.101
Anti-Zn8T	7.32 (2.039-26.279)	0.002
Anti-GAD65 + Anti-IA2	3.34 (1.136- 9.814)	0.028
Anti-GAD65 + anti-Zn8T	4.35 (1.168-16.248)	0.028
Anti-IA2 + anti-Zn8T	5.34 (1.123-25.431)	0.035
Anti-GAD65 + Anti-IA2 + anti-Zn8T	5.34 (1.123-25.431)	0.035

Adjusted for age, body mass index, and time of evolution of diabetes. GAD65: Glutamic acid decarboxylase; IA2: Islet antigen 2; Zn8T: Zinc transporter 8.

Citation: Molina JM, Medina PG, Gomez RA, Herrera JR, Martínez NL, Hernández B, García Y. Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes. World J Diabetes 2024; 15(8): 1717-1725
URL: https://www.wjgnet.com/1948-9358/full/v15/i8/1717.htm
DOI: https://dx.doi.org/10.4239/wjd.v15.i8.1717