However, those with later onset type 1 diabetes had a modestly lower type 1 diabetes genetic risk score (0.268 vs 0.279; p < 0.001 [expected type 2 diabetes population median, 0.231]), a higher islet autoantibody prevalence (GAD-, islet antigen 2 [IA2]- or zinc transporter protein 8 [ZnT8]-positive) of 78% at 13 years vs 62% at 26 years of diabetes duration; (p = 0.02), and were less likely to identify as having type 1 diabetes (79% vs 100%; p < 0.001) vs those with young-onset disease.
Subjects were assigned into one of the following groups: control (n = 25, non-diabetic non-smokers with no history of periodontitis), CP (n = 26, non-diabetic non-smokers with CP), DMCP (n = 30, non-smokers with DM and CP), SCP (n = 27, non-diabetic smokers with CP), and SDMCP (n = 22, smokers with type 2 DM and CP).
We aimed to improve the genetic characterisation of LADA and hypothesised that type 2 diabetes-associated gene variants also predispose to LADA, and that the associations would be strongest in LADA patients with low levels of GAD autoantibodies (GADA).
In 509 GAD-negative patients with newly diagnosed type 2 diabetes, we 1) genotyped six single nucleotide polymorphisms in GCKR genomic region: rs6717980, rs1049817, rs6547626, rs780094, rs2384628, and rs8731; 2) assessed clinical phenotypes, insulin sensitivity by the euglycemic insulin clamp, and β-cell function by state-of-the-art modeling of glucose/C-peptide curves during an oral glucose tolerance test; and 3) estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease formula.
ZnT8As were measured by a radioimmunoprecipitation assay using recombinant ZnT8 COOH-terminal or NH(2)-terminal proteins in 193 patients with adult-onset autoimmune diabetes having antibodies to either GAD (GADAs) or IA-2 (IA-2As) and in 1,056 antibody-negative patients with type 2 diabetes from the Non Insulin Requiring Autoimmune Diabetes (NIRAD) study.
Of type 2 diabetes-associated genes, the CC/CT genotypes of rs7961581 (TSPAN8) and the obesity-linked AA/AC genotypes of rs8050136 (FTO) were associated with LADA in general, but mainly in low anti-GAD LADA patients (P = 0.004 and P = 0.004, respectively).
In conclusion, GAD positive subjects initially diagnosed with Type 2 diabetes are unable to compensate for insulin resistance due to more pronounced beta-cell impairment.
We investigated the clinical aspects and genetic background of 13 diabetic patients with high-titers (>10,000 U/ml) of anti-glutamic acid decarboxylase antibody (Group A) and compared these 28 middle-aged (35-51 years, Group B) and 13 elderly (66-79 years, Group C) patients with anti-GAD(+) (<1100 U/ml) who were diagnosed initially as having type 2 diabetes.
A Diabetes Outcome Progression Trial (ADOPT) is a randomized, double-blind clinical trial in recently diagnosed drug-naive patients with type 2 diabetes that allows for the evaluation of GAD positivity in the context of anthropometric and biochemical characteristics.
Furthermore, we studied the frequency of GAD antibodies (GADabs), HLA-DQB1 risk genotypes, and the presence of coronary heart disease (CHD) according to family history in unrelated patients with type 2 diabetes from 787 families (148 FH-, 546 FH+(TYPE2) and 93 FH+(MIXED)).
In addition, a combination of serological marker (anti-GAD) and genetic marker (HLA-DRB1) is useful for predicting clinical course of NIDDM patients with secondary failure of sulfonylurea agents.
We determined GAD and islet cell (ICA512) autoantibodies from 215 NIDDM individuals and from 14 individuals with impaired glucose tolerance (IGT) of 68 families, including 1 family with maturity-onset diabetes of the young (MODY) and 3 families ascertained specifically for a mixture of NIDDM and IDDM.
The overall prevalence of anti-GAD antibodies was 1.7% (2 of 121) in patients with previously undiagnosed NIDDM, whereas 1 of 100 controls had positive antibodies.
The overall prevalence of anti-GAD antibodies was 1.7% (2 of 121) in patients with previously undiagnosed NIDDM, whereas 1 of 100 control subjects had a positive test for antibodies.