Cardiac repolarization and depolarization in people with Type 1 diabetes with normal ejection fraction and without known heart disease: a case-control study.

AIMS: To investigate depolarization and repolarization durations in people with Type 1 diabetes, including the relationship to age. METHODS: 855 persons with Type 1 diabetes without known heart disease were included and matched with 1710 participants from a general population study. Clinical examinations, questionnaires and biochemistry were assessed. A 10-second 12-lead ECG was performed and analysed digitally. RESULTS: QTc was longer in people with Type 1 diabetes compared to controls (414±16 vs. 411±19 ms, P <0.001), and particularly so in young people with Type 1 diabetes. The fully adjusted increase was 13.8 ms (95% confidence interval (CI): 8.6-19.0 ms, P <0.001) at age 20 years and 3.4 ms (CI: 1.5-5.3 ms, P<0.001) at age 40 years. The rate-corrected QRSc was increased in people with Type 1 diabetes (97±11 vs. 95±11 ms, P <0.001) and was age-independent (P =0.5). JTc was increased in the young people with Type 1 diabetes (10.7 ms (CI: 5.4-16.0 ms, P <0.001) at age 20 years), but not in older people with Type 1 diabetes (interaction age-diabetes, P <0.01). CONCLUSIONS: For people with Type 1 diabetes, cardiac depolarization is increased at all ages, whereas repolarization is increased only relatively in young people with Type 1 diabetes. Hence, young people with Type 1 diabetes may be more prone to ventricular arrhythmias. The findings contribute to the understanding of sudden cardiac death in young people with Type 1 diabetes.

Near-normalization of glycaemic control with glucagon-like peptide-1 receptor agonist treatment combined with exercise in patients with type 2 diabetes.

AIMS: To investigate the effects of exercise in combination with a glucagon-like peptide-1 receptor agonist (GLP-1RA), liraglutide, or placebo for the treatment of type 2 diabetes. METHODS: Thirty-three overweight, dysregulated and sedentary patients with type 2 diabetes were randomly allocated to 16 weeks of either exercise and liraglutide or exercise and placebo. Both groups had three supervised 60-minute training sessions per week including spinning and resistance training. RESULTS: Glycated haemoglobin (HbA1c) levels dropped by a mean ± standard deviation of 2.0% ± 1.2% (from 8.2% ± 1.4%) in the exercise plus liraglutide group vs 0.3% ± 0.9% (from 8.0% ± 1.2%) in the exercise plus placebo group ( P < .001), and body weight was reduced more with liraglutide (-3.4 ± 2.9 kg vs -1.6 ± 2.3 kg; P < .001). Compared with baseline, similar reductions were seen in body fat (exercise plus liraglutide: -2.5% ± 1.4% [ P < .001]; exercise plus placebo: -2.2% ± 1.9% [ P < .001]) and similar increases were observed in maximum oxygen uptake (exercise plus liraglutide: 0.5 ± 0.5 L O2 /min [ P < .001]; exercise plus placebo: 0.4 ± 0.4 L O2 /min [ P = .002]). Greater reductions in fasting plasma glucose (-3.4 ± 2.3 mM vs -0.3 ± 2.6 mM, P < .001) and systolic blood pressure (-5.4 ± 7.4 mm Hg vs -0.6 ± 11.1 mm Hg, P < .01) were seen with exercise plus liraglutide vs exercise plus placebo. The two groups experienced similar increases in quality of life during the intervention. CONCLUSIONS: In obese patients with type 2 diabetes, exercise combined with GLP-1RA treatment near-normalized HbA1c levels and caused a robust weight loss when compared with placebo. These results suggest that a combination of exercise and GLP-1RA treatment is effective in type 2 diabetes.

Glycated haemoglobin and the risk of cardiovascular disease, diabetes and all-cause mortality in the Copenhagen City Heart Study.

OBJECTIVE: Individuals with diabetes mellitus (DM) have a considerably elevated risk of developing serious health problems including cardiovascular disease (CVD). Long-term elevated levels of blood glucose in nondiabetic individuals may also be associated with increased risk of CVD. The aim of this study was to investigate the relationships between glycated haemoglobin A(1c) (HbA(1c) ) and CVD, DM and all-cause mortality. SUBJECTS AND DESIGN: The Copenhagen City Heart Study is a prospective study of individuals from the Danish general population. The cohort was followed for 10 years via national registers with respect to incident CVD, DM and all-cause mortality. Follow-up was 100% complete. RESULTS: A total of 5127 subjects were included, of whom 597 had DM. In the nondiabetic population, HbA(1c) was significantly associated with incident CVD events in both univariate [hazard ratio (HR) 1.38, 95% CI 1.11-1.71] and multivariate analyses (HR 1.31, 95% CI 1.05-1.64). In the nondiabetic population, increased levels of HbA(1c) were correlated with developing DM. There was a threefold increase in risk of incident DM per unit increase in HbA(1c) with a univariate HR of 3.83 (95% CI 1.96-7.51). This relationship was essentially unchanged after multivariate adjustments (HR 4.19, 95% CI 2.01-8.71). Furthermore, we found that net reclassification improvement for diagnosed DM and CVD was significantly improved with the addition of HbA(1c) in the analyses. Although not statistically significant, we found a strong trend towards an association between HbA(1c) and all-cause mortality (HR 1.21, 95% CI 0.99-1.47). We did not find the same associations amongst the population with DM. CONCLUSION: In the Danish general population, HbA(1c) was strongly associated with CVD in individuals without DM.

A diet high in omega-3 fatty acids does not improve or protect cognitive performance in Alzheimer's transgenic mice.

Although a number of epidemiologic studies reported that higher intake of omega-3 fatty acids (largely associated with fish consumption) is protective against Alzheimer's disease (AD), other human studies reported no such effect. Because retrospective human studies are problematic and controlled longitudinal studies over decades are impractical, the present study utilized Alzheimer's transgenic mice (Tg) in a highly controlled study to determine whether a diet high in omega-3 fatty acid, equivalent to the 13% omega-3 fatty acid diet of Greenland Eskimos, can improve cognitive performance or protect against cognitive impairment. Amyloid precursor protein (APP)-sw+PS1 double transgenic mice, as well as nontransgenic (NT) normal littermates, were given a high omega-3 supplemented diet or a standard diet from 2 through 9 months of age, with a comprehensive behavioral test battery administered during the final 6 weeks. For both Tg and NT mice, long-term n-3 supplementation resulted in cognitive performance that was no better than that of mice fed a standard diet. In NT mice, the high omega-3 diet increased cortical levels of omega-3 fatty acids while decreasing omega-6 levels. However, the high omega-3 diet had no effect on cortical fatty acid levels in Tg mice. Irrespective of diet, no correlations existed between brain omega-3 levels and cognitive performance for individual NT or Tg mice. In contrast, brain levels of omega-6 fatty acids were strongly correlated with cognitive impairment for both genotypes. Thus, elevated brain levels of omega-3 fatty acids were not relevant to cognitive function, whereas high brain levels of omega-6 were associated with impaired cognitive function. In Tg mice, the omega-3 supplemental diet did not induce significant changes in soluble/insoluble Abeta within the hippocampus, although strong correlations were evident between hippocampal Abeta(1-40) levels and cognitive impairment. While these studies involved a genetically manipulated mouse model of AD, our results suggest that diets high in omega-3 fatty acids, or use of fish oil supplements (DHA+EPA), will not protect against AD, at least in high-risk individuals. However, normal individuals conceivably could derive cognitive benefits from high omega-3 intake if it corrects an elevation in the brain level of n-6 fatty acids as a result. Alternatively, dietary fish may contain nutrients, other than DHA and EPA, that could provide some protection against AD.

Lifelong immunization with human beta-amyloid (1-42) protects Alzheimer's transgenic mice against cognitive impairment throughout aging.

Although both active and passive beta-amyloid (Abeta) immunotherapy have been shown to protect against or lessen cognitive impairment in various Alzheimer's transgenic mouse lines, these studies have focused on a single task and involved standard statistical analysis. Because Alzheimer's disease impacts multiple cognitive domains, the current study employed an extensive behavioral battery and multimetric analysis therein to determine the impact of Abeta immunization given throughout most of adult life (from 2-16 1/2 months of age) to APP+PS1 transgenic mice. At both adult (4 1/2-6 month) and aged (15-16 1/2 month) test points, the same 6-week behavioral battery was administered. Results indicate that Abeta immunotherapy partially or completely protected APP+PS1 mice at both test points from otherwise impaired performance in a variety of tasks spanning multiple cognitive domains (reference learning/memory, working memory, search/recognition). At both adult and aged test points, the cognitive benefits of Abeta immunotherapy were evident even when behavioral measures were analyzed collectively (as "overall" performance) through discriminant function analysis. Since behavioral protection at the 15-16 1/2 month test point occurred without a decrease in (or correlation to) Abeta deposition, the mechanism of Abeta immunotherapy's action most likely involves neutralization/removal of small Abeta oligomers from the brain. However, in factor analysis performed at this aged test point, brain Abeta deposition measures loaded heavily with key cognitive measures. Collectively, our results suggest that the entire process of Abeta deposition deleteriously impacts cognitive performance and that Abeta-based preventative strategies can provide long-term cognitive benefits extending well into older age.

Chromatographic separation of gram quantities of immunoglobulins from porcine colostrium against transmissible gastroenteritis virus.

Similar immunoglobulin (Ig) classes were obtained from porcine colodtral whey by either column or batch chromatographic procedures; a stepwise buffer elution technique was used. Specific transmissible gastroenteritis virus neutralizing antibody was found in the 4 major fractions eluted comprising of IgG1, IgG2, IgA, and IgM. The IgG1, and IgG2 were essentially homogeneous, and the IgA- AND IgM-rich fractions had to be recycled several times through Sephadex G-200 to obtain pure IgA and IgM that had specific virus neutralizing activities per mg of protein of 342.1 and 302. 4, compared with 7.6 for IgG. By a combination of the batch chromatographic procedures and gel filtration, gram amounts of specific Ig could be fractionated from the same colostrum.

Serum antibody responses of neonatal and young adult pigs to transmissible gastroenteritis coronavirus.

Serum titers of virus-neutralizing (VN) antibody were 10 to 16 times higher in neonatal pigs than in young adult pigs, after single oral doses of virulent transmissible gastroenteritis virus (TGEV). To determine the reason for this higher response, sera from neonatal and young adult pigs, 18 to 21 days after exposure to TGEV, were collected and assayed for VN antibody by plaque reduction. In addition, sera of VN-positive and VN-negative neonatal pigs were analyzed for immunoglobulin classes by radial immunodiffusion technique. The competence of neonatal pigs to produce VN antibody with increased IgG levels was demonstrated. The higher antibody response seen in neonatal pigs, when compared to sera of young adult pigs, may be attributed to the increased replication of TGEV in the intestinal tracts of neonatal pigs or to the lack of other immunogens that may interfere or compete with the production of specific antibody.

Partial characterization of procomplementary activity of porcine serum and its relationship to the fifth component of complement.

The procomplementary factor (PCF) of porcine serum, a component that enhances the hemolytic activity of guinea pig complement, was purified by precipitation with methanol and then by diethylaminoethyl-cellulose chromatography. The PCF substituted for the 5th complement component (C5) in the complement cascade in tests with functionally purified guinea pig complement components. In contrast to human C5, PCF is heat stable at 56 C.

Effect of Brussels sprouts and inulin/rape seed cake on the sensory profile of pork M. longissimus dorsi.

The objective of the present study was to evaluate the influence of two diets containing either Brussels sprouts or inulin/rape seed cake, compared with a standard diet (control) for slaughter pigs on flavour and odour attributes and sensory profile of cooked pork. Three weeks prior to slaughter 24 female pigs were allocated to three diets: (1) a standard grower-finishing diet (control) for slaughter pigs containing barley, wheat and soy-bean meal, (2) the control diet containing 11 energy percent Brussels sprouts and (3) a diet containing 25% inulin and 55% rape seed cake. The odour and flavour of the cooked meat from inulin/rape seed cake-fed pigs differed significantly from the other two diets, showing reduced meat odour, increased pig and acrid odour, increased pig flavour, reduced fresh flavour and total impression. Meat from the Brussels sprouts-fed pigs deviated only slightly from the control-fed pigs.

Methanol precipitation of transmissible gastroenteritis virus.

Methanol precipitation of transmissible gastroenteritis virus was tested at Ph 4.0, 5.0, 6.0, and 7.0 and at methanol concentrations of 15%, 25%, and 30%. Supernatant and precipitate fractions were tested for complement-fixing and agar-diffusion soluble antigens and plaque-forming units, and were examined by electron microscopy. Virus could be obtained free of detectable agar-diffusion antigens and most of the complement-fixing antigens. Most of the virions were without peplomers after methanol treatment but they retained infectivity.