Effect of vitamin E supplementation on HDL function by haptoglobin genotype in type 1 diabetes: results from the HapE randomized crossover pilot trial.

AIMS: Haptoglobin (Hp) genotype 2-2 increases cardiovascular diabetes complications. In type 2 diabetes, α-tocopherol was shown to lower cardiovascular risk in Hp 2-2, potentially through HDL function improvements. Similar type 1 diabetes data are lacking. We conducted a randomized crossover pilot of α-tocopherol supplementation on HDL function [i.e., cholesterol efflux (CE) and HDL-associated lipid peroxides (LP)] and lipoprotein subfractions in type 1 diabetes. METHODS: Hp genotype was assessed in members of two Allegheny County, PA, type 1 diabetes registries and the CACTI cohort; 30 were randomly selected within Hp genotype, and 28 Hp 1-1, 31 Hp 2-1 and 30 Hp 2-2 were allocated to daily α-tocopherol or placebo for 8 weeks with a 4-week washout. RESULTS: Baseline CE decreased with the number of Hp 2 alleles (p-trend = 0.003). There were no differences in LP or lipoprotein subfractions. In intention-to-treat analysis stratified by Hp, α-tocopherol increased CE in Hp 2-2 (ß = 0.79, p = 0.03) and LP in Hp 1 allele carriers (ß Hp 1-1 = 0.18, p = 0.05; ß Hp 2-1 = 0.21, p = 0.07); reduced HDL particle size (ß = -0.07, p = 0.03) in Hp 1-1 carriers; increased LDL particle concentration in Hp 1-1; and decreased it in Hp 2-2 carriers. However, no significant interactions were observed by Hp. CONCLUSIONS: In this type 1 diabetes study, HDL function worsened with the number of Hp 2 alleles. α-Tocopherol improved HDL function in Hp 2-2 carriers and appeared to adversely affect lipid peroxides and lipoprotein subfractions among Hp 1 allele carriers. As no significant interactions were observed, findings require replication in larger studies.

The Patient Perspective on Living with Acute Myeloid Leukemia.

INTRODUCTION: Acute myeloid leukemia (AML) imposes significant burden on patients, their families, and the healthcare system. Published literature has reported many AML signs and symptoms, as well as their impact on patients. However, there are no publications on the experience of living with AML from the patient's perspective. In this study, we performed qualitative interviews with patients with AML to understand their experience. METHODS: Participants were recruited from the US and Japan. All patients were screened to assess eligibility, and were divided into four subgroups (i.e., newly-diagnosed, high-intensity chemotherapy; newly-diagnosed, low-intensity chemotherapy; relapse/refractory; and post-transplant). Patients were interviewed over the phone by a trained researcher and asked about their day-to-day experience with AML. Signs/symptoms and impacts were coded, analyzed using Atlas.ti software, and reported as frequencies, with the medians of patient-reported disturbance levels (0-10) computed for each symptom and impact. RESULTS: The most commonly reported sign/symptom in the US was fatigue (95.7%), followed by bruising and weakness (both 78.3%), and in Japan, nausea (94.4%), followed by fatigue and headache (both 88.9%). The most commonly reported impact in the US was a decreased ability to maintain social/familial roles (91.3%), followed by anxiety and a decreased ability to function (both 87.0%), and most commonly reported in Japan was anxiety, a decreased ability to function, and remission uncertainty (94.4%). CONCLUSION: Although the frequency of signs/symptoms and their level of disturbance varied between the US and Japan, there was remarkable consistency in the types of signs/symptoms and impacts reported across all patients. The consistency in the experience of the disease across patients suggests that measurement of AML experience can be achieved by using the same tool for most, if not all, of these patients. FUNDING: Astellas Pharma Inc., Northbrook, IL, USA.

Type A behavior and risk of all-cause mortality, CAD, and CAD-related mortality in a type 1 diabetic population: 22 years of follow-up in the Pittsburgh Epidemiology of Diabetes Complications Study.

OBJECTIVE: To determine whether type A behavior predicts all-cause mortality and incident coronary artery disease (CAD) in a type 1 diabetic population. RESEARCH DESIGN AND METHODS: Follow-up data (22 years) from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood-onset type 1 diabetes were analyzed for the 506 participants who completed the Bortner Rating Scale (measuring type A behavior) and Beck Depression Inventory (BDI) at baseline (1986-1988). CAD comprised myocardial infarction as determined by hospital records/Q waves on electrocardiogram (ECG), CAD death (determined by a mortality classification committee), angiographic stenosis, ischemic ECG, and angina. RESULTS: There were 128 deaths (25.3%) during follow-up. Univariate analysis showed an inverse relationship between Bortner scores and all-cause mortality (P=0.01), which remained significant after allowing for age, sex, duration, HbA1c, education, smoking, BMI, and physical activity (P=0.03). However, the addition of BDI scores attenuated the relationship (P=0.11) with a significant interaction (P=0.03) such that any protective effect against mortality was limited among individuals with lower BDI scores (bottom three quintiles) (P=0.07), whereas no effect was seen in those with higher BDI scores (P=0.97). Bortner scores showed only a borderline association with incident CAD (P=0.09). CONCLUSIONS: Those with higher type A behavior have lower all-cause mortality in our type 1 diabetic population, an effect that interacts with depressive symptomatology such that it is only operative in those with low BDI scores. Further research should focus on understanding this interaction.