In antibody-positive first-degree relatives of patients with type 1 diabetes, HLA-A*24 and HLA-B*18, but not HLA-B*39, are predictors of impending diabetes with distinct HLA-DQ interactions.

Diabetologia. 2013 May 28;

Authors: Mbunwe E, Van der Auwera BJ, Weets I, Van Crombrugge P, Crenier L, Coeckelberghs M, Seret N, Decochez K, Vandemeulebroucke E, Gillard P, Keymeulen B, van Schravendijk C, Wenzlau JM, Hutton JC, Pipeleers DG, Gorus FK, The Belgian Diabetes Registry

Abstract
AIMS/HYPOTHESIS: Secondary type 1 diabetes prevention trials require selection of participants with impending diabetes. HLA-A and -B alleles have been reported to promote disease progression. We investigated whether typing for HLA-B*18 and -B*39 may complement screening for HLA-DQ8, -DQ2 and -A*24 and autoantibodies (Abs) against islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8) for predicting rapid progression to hyperglycaemia. METHODS: A registry-based group of 288 persistently autoantibody-positive (Ab(+)) offspring/siblings (aged 0-39 years) of known patients (Ab(+) against insulin, GAD, IA-2 and/or ZnT8) were typed for HLA-DQ, -A and -B and monitored from the first Ab(+) sample for development of diabetes within 5 years. RESULTS: Unlike HLA-B*39, HLA-B*18 was associated with accelerated disease progression, but only in HLA-DQ2 carriers (p < 0.006). In contrast, HLA-A*24 promoted progression preferentially in the presence of HLA-DQ8 (p < 0.002). In HLA-DQ2- and/or HLA-DQ8-positive relatives (n = 246), HLA-B*18 predicted impending diabetes (p = 0.015) in addition to HLA-A*24, HLA-DQ2/DQ8 and positivity for IA-2A or ZnT8A (p ≤ 0.004). HLA-B*18 interacted significantly with HLA-DQ2/DQ8 and HLA-A*24 in the presence of IA-2 and/or ZnT8 autoantibodies (p ≤ 0.009). Additional testing for HLA-B*18 and -A*24 significantly improved screening sensitivity for rapid progressors, from 38% to 53%, among relatives at high Ab-inferred risk carrying at least one genetic risk factor. Screening for HLA-B*18 increased sensitivity for progressors, from 17% to 28%, among individuals carrying ≥3 risk markers conferring >85% 5 year risk. CONCLUSIONS/INTERPRETATION: These results reinforce the importance of HLA class I alleles in disease progression and quantify their added value for preparing prevention trials.

PMID: 23712485 [PubMed - as supplied by publisher]

Comparison of low density lipoprotein cholesterol concentrations by direct measurement and Friedewald formula in diabetic patients with and without hemoglobin E disorders.

J Med Assoc Thai. 2013 Apr;96(4):407-15

Authors: Srisurin W

Abstract
BACKGROUND: Low density lipoprotein cholesterol (LDL) levels were significantly lower in diabetic patients with homozygous hemoglobin E (HbEE) measured by a homogeneous assay.
OBJECTIVE: Comparison of direct measurement of LDL (dLDL) determined by a homogeneous assay and calculated LDL (cLDL) determined by the Friedewald formula in diabetic patients with and without hemoglobin E disorders.
MATERIAL AND METHOD: The hemoglobin E (HbE) screening test and hemoglobin (Hb) typing were conducted in diabetic patients at Surin Hospital. In 2,973 cases with triglyceride (TG) levels under 400 mg/dL, classification was determined into three groups, negative screening (NS), HbE trait (HbEA), and HbEE. The measurements of total cholesterol (TC) and TG were performed using enzymatic methods. The direct measurements of high density lipoprotein cholesterol (HDL) andLDL were performed using homogeneous methods.
RESULTS: The prevalence of HbEE and HbEA were 7.6% and 35.7% respectively. The means of TG, CHOL, dLDL, cLDL, and non-HDL cholesterol (non-HDL-C) were significantly lower in HbEE (p = 0.009, p<0.001, p< 0.001, p< 0.001, and p< 0.001 respectively). The mean of cLDL in each group was significantly lower than the mean of dLDL (p< 0.001 at all). By the Passing-Bablok regression, the interception with 95% confidence interval (95% CI) ofNS, HbEA, and HbEE were 4.322 (3.082 to 5.485), 6.625 (5.094 to 7.981), and 6.60 (3.347 to 10.356) respectively. The slope with 95% CI were 1.017 (1.007 to 1.027), 1.002 (0.991 to 1.016), and 1.0 (0.963 to 1.033) respectively. Using the Bland-Altman method, the mean with standard deviation of the difference between dLDL and cLDL in NS, HbEA, and HbEE were 6.758 (7.856) mg/dL, 7.350 (8.212) mg/dL, and 7.225 (7.129) mg/dL respectively. The 95% limits of agreement between the dLDL and cLDL in NS, HbEA, and HbEE were -8.640 to 22.156 mg/dL, -8.746 to 23.446 mg/dL, and-6.748 to 21.197 mg/dL respectively. The statistically significant difference of having more patients with cLDL <100 mg/dL than dLDL <100 mg/dL in each group were observed in most of the subgroups of TG levels at 100 mg/dL to <200 mg/dL and higher HbEE had more patients of dLDL <100 mg/dL and cLDL <100 mg/dL than NS. The adjusted odds ratio and 95% CI were 1.383 (1.022 to 1.871) with p = 0. 036 and 1.838 (1.375 to 2.456) with p< 0.001 respectively.
CONCLUSION: The direct homogeneous method showed a higher LDL concentration than the Friedewald formula indicated in diabetes and diabetes with HbE disorders. The percentage of higher LDL levels by direct method than Friedewald formula significantly increased along the subgroups of higher TG levels. The dissociation occurred at TG levels of 100 mg/dL and higher Systematic biases between both methods were found in all groups but the proportional difference between both methods was only observed in diabetes without HbE disorders.

PMID: 23691694 [PubMed - in process]

Pregnancy outcomes amongst thalassemia traits.

Arch Gynecol Obstet. 2013 May 17;

Authors: Hanprasertpong T, Kor-Anantakul O, Leetanaporn R, Suntharasaj T, Suwanrath C, Pruksanusak N, Pranpanus S

Abstract
OBJECTIVE: To compare the pregnancy outcome between pregnancies affected and not affected by thalassemia trait. METHODS: A retrospective case-control cohort study was conducted on singleton pregnant women who attended antenatal care and delivered at Songklanagarind Hospital. All of the participating thalassemia trait pregnant women were diagnosed based on hemoglobin typing and/or DNA analysis. A ratio of around 1-1 was used to compare their pregnancy outcomes with normal pregnant women. RESULTS: Seven hundred thirty-nine thalassemia trait and 799 normal pregnant women were included in the study. All of the women were Thai nationals living in the Southern Region of Thailand and nearly all of them had spontaneously conceived. Maternal complication rates of gestational diabetes, preterm birth, antepartum bleeding, postpartum bleeding, shoulder dystocia and puerperal morbidity, and the rates of neonatal complications: macrosomia, fetal weight <2,000 g, intrauterine growth restriction (IUGR), stillbirth, low Apgar score (<7) at 1 and 5 min and NICU admission, were not significantly different between the two groups. The rate of pre-eclampsia, however, was significantly different, with RRs of 1.73 (CI 1.01-3.00). CONCLUSION: The thalassemia trait condition did not affect the risk of gestational diabetes, postpartum hemorrhage, stillbirth, preterm birth and puerperal morbidity. However, pre-eclampsia should be warranted especially among nulliparous and high-BMI pregnant women.

PMID: 23681496 [PubMed - as supplied by publisher]

Association of the HLA-DQA1 and HLA-DQB1 Alleles in Type 2 Diabetes Mellitus and Diabetic Nephropathy in the Han Ethnicity of China.

J Diabetes Res. 2013;2013:452537

Authors: Ma ZJ, Sun P, Guo G, Zhang R, Chen LM

Abstract
HLA gene system is one of the most polymorphic regions of the human genome. The association of HLA class II genes in T1DM pathogenesis has been reported for several ethnicities. Associations of HLA class II genes with T2DM have revealed inconsistent results. Moreover, correlations between DN and HLA alleles remain unclear. We carried out DNA typing chip by specific medium resolution typing probes in 310 T2DM subjects (including 210 patients with DN and 100 patients without DN) in addition to 100 healthy controls. Differences were found between patients with T2DM and the control group in the frequencies of the HLA-DQA1∗0301 (15.5% versus 8.0%, P < 0.01) and the HLA-DQA1∗0501 alleles (16.6% versus 8.5%, P < 0.01). Differences were found between patients with DN and without DN in the frequencies of the HLA-DQA1∗0302 (6.9% versus 13.5%, P < 0.01) and HLA-DQB1∗0501 alleles (5.8% versus 14.5%, P < 0.01). Diabetes duration and systolic blood pressure were independent risk factors associated with DN (OR = 2.277 and 1.366, resp., P < 0.05), whereas the HLA-DQB1∗0501 llele had a protective effect on DN (OR = 0.53, P < 0.05). These data suggest the HLA-DQA1∗0301 and HLA-DQA1∗0501 alleles are markers of susceptibility for T2DM, and the HLA-DQB1∗0501 allele is associated with a protective effect on DN in Han ethnicity of China.

PMID: 23671871 [PubMed - in process]