Progression to insulin-requiring diabetes in seronegative prediabetic subjects: the role of two HLA-DQ high-risk haplotypes

HLA-DQB1 genotypes, islet antibodies and beta cell function in the classification of recent-onset diabetes among young adults in the nationwide Diabetes Incidence Study in Sweden

“…This corresponds to the previous findings regarding risk genotype presence in Ab-patients that conferred an increased risk of insulin requirement at a later follow-up [22]. However, antibodies not detected by current assays may be present in patients without islet antibodies, with risk HLA-DQB1 genotypes and low F-P-C-peptide.…”

Islet Cell Autoimmunity in a Triethnic Adult Population of the Third National Health and Nutrition Examination Survey

“…Given the crosssectional nature of this study and that both new and prevalent diabetic individuals were identified, we believed that GAD65 AAs would be the first antibody marker of choice to detect in this population. Although data on sequential determination of GAD65 AAs are not available for this study, there is strong evidence to suggest that GAD AAs are stable for a number of years or even decades in patients who present with both type 1 (44,45) and type 2 diabetes (31,46).…”

Gene- and cell-based therapeutics for type I diabetes mellitus

“…In humans, the disease is associated with the inheritance of DR3/DR4 haplotypes (DR3: DQA1*0501, DQB1*0201 and DR4: DQA1*0301, DQB1*0302). 2,3 IDDM2 has been mapped to a variable number of tandem repeats (VNTR) polymorphism upstream of the insulin gene promoter, which can determine thymic levels of insulin. 4,5 In fact, a recent study demonstrated that the number of active copies of insulin in a transgenic mouse can influence the degree of immune cell reactivity towards insulin, a putative autoantigen.…”

“…This is the main reason for the ongoing debates on prevention based on genetic screening. 2,64 While outright prevention based only on genetic screening may not be yet acceptable, other strategies that fall inside the realm of 'prevention' can be acceptable. There are data indicating that newly onset diabetics still possess adequate b-cell mass to sustain normoglycemia if the autoimmune inflammation can be promptly controlled.…”