Current understandings of the pathogenesis of type 1 diabetes: Genetics to environment

Table 1 Genetic risk and protective factors of type 1 diabetes¹

Risk factors[16,17]	Protective factors[18,19]
HLA DR3/DQ2	DRB1*15:01
HLA-DR4/DQ8	DQA1*01:02
HLA-A*02:01	DQB1*06:02
Increased PTPN22 activity	Rare variant of IFIH1
INS polymorphisms
IL2RA variants
Increased expression of common variant IFIH1
1st degree relative with T1D

¹These genetic factors represent more prevalent risk factors associated with type 1 diabetes and is not all inclusive. PTPN22: Protein tyrosine phosphatase non-receptor type 22; INS: Insulin gene; IL2RA: Interluekin-2 receptor alpha; IFIH1: Interferon-induced with helicase C domain 1; T1D: Type 1 diabetes.

Table 2 Concordance rate of monozygotic and dizygotic twins in the indicated countries

Study population	Relation	No. of twin pairs	No. of concordant pairs	Probandwise concordance rate (%)
Australia[95]	Monozygotic	14	6	61
	Dizygotic	32	2	12
Finland[28]	Monozygotic	44	12	42.90
	Dizygotic	183	7	7.40
Japan[96]	Monozygotic	19	7	53.81
	Dizygotic	13	1	14.31
United States[25]	Monozygotic	53	12	36.91
	Dizygotic	30	0	0
Denmark[97]	Monozygotic	26	10	53
	Dizygotic	69	4	11
Finland[98]	Monozygotic	26	3	23.10
	Dizygotic	83	2	4.80
North America[27]	Monozygotic	132	38	45
	Dizygotic	92	13	25
United Kingdom[99]	Monozygotic	49	15	25 (1 yr)1
				40 (5 yr)1
				50.7 (10 yr)1

¹Rate not listed in original study, but calculated here based on the equation (2C/2C+D), where C is the number of concordant twin pairs and D is the number of discordant twin pairs.

Table 3 Progression to type 1 diabetes in siblings within 3 years based on number of autoantibodies at screening

Relation	0 Autoantibodies		1 Autoantibody		≥ 2 Autoantibodies
	No. of individuals	Progressed to T1D	No. of individuals	Progressed to T1D	No. of individuals	Progressed to T1D
Monozygotic Twins	89	1.50%	25	69%	29	69%
Dizygotic Twins	231	0%	22	13%	17	72%
Full Siblings	13944	0.50%	1456	12%	900	47%

T1D: Type 1 diabetes.

Table 4 Environmental risk and protective factors of type 1 diabetes

Risk factor	Protective factors
Group B Coxsackieviruses[42,44,45]	Longer breastfeeding duration[78-80]
Early introduction of cow’s milk duration[76,77]	Vitamin D intake supplements[68,69]
Early cereal introduction[72,87]	Polyunsaturated fatty acids[89,90]
High latitudes[18,31]	Intestinal microbiome[36-38]
Cold seasons[55-57]	Multiple living siblings[35]
Acceleated linear growth and weight gain[32-34]
White ethnicity[35]
Maternal age > 35 yr[35]