ABSTRACT
The direct involvement of the human leukocyte antigen class II DR-DQ genes in type 1 diabetes (T1D) is well established, and these genes display a complex hierarchy of risk effects at the genotype and haplotype levels. We investigated, using data from 38 studies, whether the DR-DQ haplotypes and genotypes show the same relative predispositional effects across populations and ethnic groups. Significant differences in risk within a population were considered, as well as comparisons across populations using the patient/control (P/C) ratio. Within a population, the ratio of the P/C ratios for two different genotypes or haplotypes is a function only of the absolute penetrance values, allowing ranking of risk effects. Categories of consistent predisposing, intermediate ('neutral'), and protective haplotypes were identified and found to correlate with disease prevalence and the marked ethnic differences in DRB1-DQB1 frequencies. Specific effects were identified, for example for predisposing haplotypes, there was a statistically significant and consistent hierarchy for DR4 DQB1*0302s: DRB1*0405 =*0401 =*0402 > *0404 > *0403, with DRB1*0301 DQB1*0200 (DR3) being significantly less predisposing than DRB1*0402 and more than DRB1*0404. The predisposing DRB1*0401 DQB1*0302 haplotype was relatively increased compared with the protective haplotype DRB1*0401 DQB1*0301 in heterozygotes with DR3 compared with heterozygotes with DRB1*0101 DQB1*0501 (DR1). Our results show that meta-analyses and use of the P/C ratio and rankings thereof can be valuable in determining T1D risk factors at the haplotype and amino acid residue levels.
Subject(s)
Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , Genetic Predisposition to Disease , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Haplotypes , Europe , Genotype , HLA-DQ beta-Chains , HLA-DRB1 Chains , HumansABSTRACT
AIMS: To determine prospectively, the reproducibility of individualized coronary heart disease (CHD) risk estimations in a high-risk (diabetic) population. METHODS: One hundred and three patients attending a hospital diabetes clinic who were in the primary prevention category for CHD had measurements of cholesterol, HDL-cholesterol and systolic blood pressure (SBP) performed in one of 13 general practices and then 2 weeks later in the hospital clinic. The data were combined with age, sex, smoking history and diabetic status data to produce a 10-year CHD risk estimate for each occasion using the Framingham algorithm. RESULTS: The coefficients of variation for cholesterol, HDL and SBP were 6.0%, 9.4% and 7.0%, respectively. When classified by treatment thresholds of 15% and 30% 10-year CHD risk, 88% of patients were classified in the same category on both occasions. Kappa values for the 15% and 30% risk thresholds were 0.71 and 0.82. This indicates good interobserver agreement for the estimation of CHD risk. The use of a single BP rather than the mean of two, resulted in seven of 206 estimations of CHD risk performed in 103 patients crossing a risk threshold, with 6/7 being placed in a higher risk category. CONCLUSIONS: Estimation of CHD risk on a single occasion is sufficient to make robust treatment decisions based on risk thresholds. Use of a single BP measurement rather than the mean of two overestimates the risk category in around 3% of cases.
Subject(s)
Blood Pressure , Coronary Disease/epidemiology , Diabetes Mellitus/epidemiology , Diabetic Angiopathies/epidemiology , Hypertension/epidemiology , Adult , Aged , Analysis of Variance , Cholesterol/blood , Cholesterol, HDL/blood , Coronary Disease/blood , Coronary Disease/physiopathology , Diabetes Mellitus/blood , Diabetes Mellitus/physiopathology , Diabetic Angiopathies/blood , Diabetic Angiopathies/physiopathology , England/epidemiology , Family Practice , Female , Humans , Male , Middle Aged , Observer Variation , Reproducibility of Results , Risk Assessment , Smoking/epidemiology , SystoleABSTRACT
BACKGROUND: Charcot neuroarthropathy is well recognized in diabetes, although it typically affects the joints of the forefoot and ankle. Neuroarthropathy affecting the knee in diabetes is extremely rare. The surgical options for treatment of Charcot neuroarthropathy remain poorly defined, particularly the use of arthroplasty with knee involvement. METHODS: We describe a case of neuroarthropathy of the knee in a patient with Type 1 diabetes. We also describe the successful management of the disorder with total knee arthroplasty-only the third such description. RESULTS: The case illustrates some of the typical radiological features of this uncommon condition, which may aid early diagnosis and limit morbidity.
