Immunogenetic analysis suggests different pathogenesis for obese and lean African-Americans with diabetic ketoacidosis.

Umpiérrez, Guillermo E.; Woo, Whc; Hagopian, William; Isaacs, Scott; Palmer, JL; Gaur, Lakshmi K.; Nepom, Gerald T.; Clark, William S.; Mixon, P S; Kitabchi, Abbas E.

doi:10.2337/diacare.22.9.1517

Cited by 119 publications

(98 citation statements)

References 3 publications

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“…Banerji et al (2) reported a higher frequency of HLA DR3/DR4 in GAD65 autoantibodynegative African-American patients with type 2 diabetes (65%) compared with nondiabetic control subjects (30%). Umpierrez et al (6) reported that all those with GAD autoantibodies in a cohort of predominantly African-American KPD patients possessed the DQB1*0201 allele. Wang et al (34) found that the frequency of the autoimmune type 1 diabetes susceptibility genotype DR3-DQ2/ DR4-DQ8 was 10-fold higher and that of the protective allele DQB1*0602 10-fold lower among newly diagnosed younger children with autoantibodies.…”

Section: Methodsmentioning

confidence: 99%

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HLA Class II Alleles Specify Phenotypes of Ketosis-Prone Diabetes

et al. 2008

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OBJECTIVE -Ketosis-prone diabetes (KPD) comprises four subgroups based on the presence or absence of ␤-cell autoantibodies (Aϩ or AϪ) and ␤-cell functional reserve (␤ϩ or ␤Ϫ). Genetic factors could contribute to their distinctive phenotypes. Our aim was to specify the role of HLA class II alleles associated with susceptibility or resistance to autoimmune type 1 diabetes in determining KPD phenotypes.RESEARCH DESIGN AND METHODS -A total of 185 adults presenting with diabetic ketoacidosis were followed longitudinally for a mean of 5.5 years, with measurements of autoantibodies, ␤-cell functional reserve, insulin sensitivity, and insulin requirement. Frequencies of susceptibility and resistance alleles at HLA DQA1, DQB1, and DRB1 loci were correlated with clinical and phenotypic features of KPD subgroups and compared with those of ethnic-specific population control subjects.RESULTS -Susceptibility alleles were more frequent (P Ͻ 0.0001) in the two Aϩ than the two AϪ KPD subgroups; in the latter, the frequency was no greater than in population control subjects (except for DQB1*0302). Susceptibility alleles differentiated the two clinically similar ␤Ϫ subgroups (more frequent in Aϩ␤Ϫ than AϪ␤Ϫ KPD; P Ͻ 0.01). Resistance alleles were more frequent in the two ␤ϩ than the two ␤Ϫ KPD subgroups (P Ͻ 0.01). The frequencies of certain susceptibility (e.g., DQB1*02) and resistance (DQB1*0602) alleles were higher in African-American AϪ␤ϩ KPD patients than in African-American control subjects. DQB1*0302 was more frequent in all KPD subgroups compared with control subjects.CONCLUSIONS -HLA class II alleles associated with susceptibility or resistance to autoimmune type 1 diabetes help specify the four subgroups of KPD. Inheritance of these alleles may influence long-term ␤-cell functional reserve.

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Section: Methodsmentioning

confidence: 99%

“…etosis-prone diabetes (KPD), an emerging form of diabetes defined by presentation with diabetic ketoacidosis (DKA) (1)(2)(3)(4)(5)(6)(7), is phenotypically heterogeneous (1)(2)(3)(4)(5)(6). KPD patients may have variable ␤-cell function and clinical outcomes after the initial presentation with DKA.…”

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confidence: 99%

HLA Class II Alleles Specify Phenotypes of Ketosis-Prone Diabetes

et al. 2008

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“…Patients with ketosis-prone type 2 diabetes were once described as having "atypical diabetes;" however, increasing evidence indicates that this subtype of diabetes accounts for more than half of newly diagnosed black and Hispanic patients with DKA (3,6,17,42,43). These subjects are usually obese, have a strong family history of diabetes, have a low prevalence of autoimmune markers, and lack HLA genetic association (9 …”

Section: E D I T O R I a L S E D I T O R I A L ( S E E B A L A S U B mentioning

confidence: 99%

“…For this test, C-peptide levels are measured before and within 10 min after the intravenous administration of glucagon (1 mg) (6,7,10). In agreement with this report, fasting C-peptide levels Ͼ1.0 ng/dl (0.33 nmol/l) and stimulated Cpeptide levels Ͼ1.5 ng/dl (0.5 nmol/l) shortly after presentation is predictive of long-term remission (6 -8,10,12,14, 36,37).…”

Section: E D I T O R I a L S E D I T O R I A L ( S E E B A L A S U B mentioning

confidence: 99%

Ketosis-Prone Type 2 Diabetes

Umpiérrez

2006

Diabetes Care

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“…Latent autoimmune diabetes is not plausible since late appearance of islet-cell autoimmunity has not been reported. Obesity, which is an exceptional finding in classic Type I diabetes, is found in up to 56 % of the cohorts of patients with this atypical presentation [8] and mean BMI varies between 26 and 37 kg/m 2 [1,2,9,10].…”

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confidence: 99%