ß-Cell function during a high-fat meal in young versus old adults: role of exercise.

The acute effect of exercise on ß-cell function during a high-fat meal (HFM) in young adults (YA) versus old adults (OA) is unclear. In this randomized crossover trial, YA (n = 5 M/7 F, 23.3 ± 3.9 yr) and OA (n = 8 M/4 F, 67.7 ± 6.0 yr) underwent a 180-min HFM (12 kcal/kg body wt; 57% fat, 37% CHO) after a rest or exercise [∼65% heart rate peak (HRpeak)] condition ∼12 h earlier. After an overnight fast, plasma lipids, glucose, insulin, and free fatty acid (FFA) were determined to estimate peripheral, or skeletal muscle, insulin sensitivity (Matsuda index) as well as hepatic [homeostatic model assessment of insulin resistance (HOMA-IR)] and adipose insulin resistance (adipose-IR). ß-Cell function was derived from C-peptide and defined as early-phase (0-30 min) and total-phase (0-180 min) disposition index [DI, glucose-stimulated insulin secretion (GSIS) adjusted for insulin sensitivity/resistance]. Hepatic insulin extraction (HIE), body composition [dual-energy X-ray absorptiometry (DXA)], and peak oxygen consumption (V̇o2peak) were also assessed. OA had higher total cholesterol (TC), LDL, HIE, and DI across organs as well as lower adipose-IR (all, P < 0.05) and V̇o2peak (P = 0.056) despite similar body composition and glucose tolerance. Exercise lowered early-phase TC and LDL in OA versus YA (P < 0.05). However, C-peptide area under the curve (AUC), total phase GSIS, and adipose-IR were reduced postexercise in YA versus OA (P < 0.05). Skeletal muscle DI increased in YA and OA after exercise (P < 0.05), whereas adipose DI tended to decline in OA (P = 0.06 and P = 0.08). Exercise-induced skeletal muscle insulin sensitivity (r = -0.44, P = 0.02) and total-phase DI (r = -0.65, P = 0.005) correlated with reduced glucose AUC180min. Together, exercise improved skeletal muscle insulin sensitivity/DI in relation to glucose tolerance in YA and OA, but only raised adipose-IR and reduced adipose-DI in OA.NEW & NOTEWORTHY High-fat diets may induce ß-cell dysfunction. This study compared how young and older adults responded to a high-fat meal with regard to ß-cell function and whether exercise comparably impacted glucose regulation. Older adults secreted more insulin during the high-fat meal than younger adults. Although exercise increased ß-cell function adjusted for skeletal muscle insulin sensitivity in relation to glucose tolerance, it raised adipose insulin resistance and reduced pancreatic ß-cell function relative to adipose tissue in older adults. Additional work is needed to discern nutrient-exercise interactions across age to mitigate chronic disease risk.

Acute Exercise and the Systemic and Airway Inflammatory Response to a High-Fat Meal in Young and Older Adults.

The purpose of the present study was to determine fasting and high-fat meal (HFM)-induced post-prandial systemic inflammation and airway inflammation (exhaled nitric oxide (eNO)) in older adults (OAs) compared to younger adults (YAs) before and after acute exercise. Twelve YAs (23.3 ± 3.9 y n = 5 M/7 F) and 12 OAs (67.7 ± 6 y, n = 8 M/4 F) completed two HFM challenges. After an overnight fast, participants underwent an HFM session or pre-prandial exercise (EX, 65% VO2Peak to expend 75% of the caloric content of the HFM) plus HFM (EX + HFM) in a randomized order. Systemic inflammatory cytokines were collected at 0, 3, and 6 h, while eNO was determined at 0, 2, and 4 h after the HFM (12 kcal/kg body weight: 61% fat, 35% CHO, 4% PRO). TNF-α was higher in OAs compared to YAs (p = 0.005) and decreased across time from baseline to 6 h post-HFM (p = 0.007). In response to the HFM, IL-6 decreased from 0 to 3 h but increased at 6 h regardless of age or exercise (p = 0.018). IL-8 or IL-1ß did not change over the HFM by age or exercise (p > 0.05). eNO was also elevated in OAs compared to YAs (p = 0.003) but was not altered by exercise (p = 0.108). There was a trend, however, towards significance post-prandially in OAs and YAs from 0 to 2 h (p = 0.072). TNF-α and eNO are higher in OAs compared to YAs but are not elevated more in OAs post-prandially compared to YAs. Primary systemic inflammatory cytokines and eNO were not modified by acute exercise prior to an HFM.

Acute exercise improves glucose and TAG metabolism in young and older adults following high-fat, high-carbohydrate meal intake.

A single high-fat, high-carbohydrate meal (HFHC) results in elevated postprandial glucose (GLU), triglycerides (TAG) and metabolic load index (MLI; TAG (mg/dl) + GLU (mg/dl)) that contributes to chronic disease risk. While disease risk is higher in older adults (OA) compared to younger adults (YA), the acute effects of exercise on these outcomes in OA is understudied. Twelve YA (age 23.3 ± 3.9 yrs, n = 5 M/7 F) and 12 OA (age 67·7 ± 6.0 yrs, n = 8 M/4 F) visited the laboratory in random order to complete a HFHC with no exercise (NE) or acute exercise (EX) condition. EX was performed 12 hours prior to HFHC at an intensity of 65 % of maximal heart rate to expend 75 % of the kcals consumed in HFHC (Marie Callender's Chocolate Satin Pie; 12 kcal/kgbw; 57 % fat, 37 % CHO). Blood samples were taken at 0, 30, 60, 90 minutes, and then every hour until 6 hours post-meal. TAG levels increased to a larger magnitude in OA (Δ∼61 ± 31 %) compared to YA (Δ∼37 ± 34 %, P < 0·001), which were attenuated in EX compared to NE (P < 0·05) independent of age. There was no difference in GLU between OA and YA after the HFM, however, EX had attenuated GLU independent of age (NE: Δ∼21 ± 26 %; EX: Δ∼12 ± 18 %, P = 0·027). MLI was significantly lower after EX compared to NE in OA and YA (P < 0·001). Pre-prandial EX reduced TAG, GLU and MLI post-HFHC independent of age.

Different Patterns of Hearing Loss among Tinnitus Patients: A Latent Class Analysis of a Large Sample.

BACKGROUND: The heterogeneity of tinnitus is a major challenge for tinnitus research. Even if a complex interaction of many factors is involved in the etiology of tinnitus, hearing loss (HL) has been identified as the most relevant etiologic factor. Here, we used a data-driven approach to identify patterns of hearing function in a large sample of tinnitus patients presenting in a tinnitus clinic. METHODS: Data from 2,838 patients presenting at the Tinnitus Center of the University Regensburg between 2007 and 2014 have been analyzed. Standard audiometric data were frequency-wise categorized in four categories [a: normal hearing (0-20 dB HL); b: moderate HL (25-50 dB HL; representing outer hair cell loss); c: severe HL (>50 dB HL; representing outer and inner hair cell loss); d: no data available] and entered in a latent class analysis, a statistical method to find subtypes of cases in multivariate categorical data. To validate the clinical relevance of the identified latent classes, they were compared with respect to clinical and demographic characteristics of their members. RESULTS: The classification algorithm identified eight distinct latent classes with an excellent separation. Patient classes differed with respect to demographic (e.g., age, gender) and clinical characteristics (e.g., tinnitus location, tinnitus severity, gradual, or abrupt onset, etc.). DISCUSSION: Our results demonstrate that data-driven categorization of hearing function seems to be a promising approach for profiling tinnitus patients, as it revealed distinct subtypes that reflect prototypic forms of HL and that differ in several relevant clinical characteristics.

Temporal Changes in Alcohol-Related Morbidity and Mortality in Germany.

AIMS: Trends in morbidity and mortality, fully or partially attributable to alcohol, for adults aged 18-64 were assessed for Germany. METHODS: The underestimation of population exposure was corrected by triangulating survey data with per capita consumption. Alcohol-attributable fractions by sex and two age groups were estimated for major disease categories causally linked to alcohol. Absolute numbers, population rates and proportions relative to all hospitalizations and deaths were calculated. RESULTS: Trends of 100% alcohol-attributable morbidity and mortality over thirteen and eighteen years, respectively, show an increase in rates of hospitalizations and a decrease in mortality rates. Comparisons of alcohol-attributable morbidity including diseases partially caused by alcohol revealed an increase in hospitalization rates between 2006 and 2012. The proportion of alcohol-attributable hospitalizations remained constant. Rates of alcohol-attributable mortality and the proportion among all deaths decreased. CONCLUSIONS: The increasing trend in mortality due to alcohol until the mid-1990s has reversed. The constant proportion of all hospitalizations that were attributable to alcohol indicates that factors such as improved treatment and easier health care access may have influenced the general increase in all-cause morbidity. To further reduce alcohol-related mortality, efforts in reducing consumption and increasing treatment utilization are needed.

Rasch Mixture Models for DIF Detection: A Comparison of Old and New Score Specifications.

Rasch mixture models can be a useful tool when checking the assumption of measurement invariance for a single Rasch model. They provide advantages compared to manifest differential item functioning (DIF) tests when the DIF groups are only weakly correlated with the manifest covariates available. Unlike in single Rasch models, estimation of Rasch mixture models is sensitive to the specification of the ability distribution even when the conditional maximum likelihood approach is used. It is demonstrated in a simulation study how differences in ability can influence the latent classes of a Rasch mixture model. If the aim is only DIF detection, it is not of interest to uncover such ability differences as one is only interested in a latent group structure regarding the item difficulties. To avoid any confounding effect of ability differences (or impact), a new score distribution for the Rasch mixture model is introduced here. It ensures the estimation of the Rasch mixture model to be independent of the ability distribution and thus restricts the mixture to be sensitive to latent structure in the item difficulties only. Its usefulness is demonstrated in a simulation study, and its application is illustrated in a study of verbal aggression.

Alcohol-attributable mortality in Switzerland in 2011--age-specific causes of death and impact of heavy versus non-heavy drinking.

BACKGROUND: Alcohol use causes high burden of disease and injury globally. Switzerland has a high consumption of alcohol, almost twice the global average. Alcohol-attributable deaths and years of life lost in Switzerland were estimated by age and sex for the year 2011. Additionally, the impact of heavy drinking (40+grams/day for women and 60+g/day for men) was estimated. METHODS: Alcohol consumption estimates were based on the Addiction Monitoring in Switzerland study and were adjusted to per capita consumption based on sales data. Mortality data were taken from the Swiss mortality register. Methodology of the Comparative Risk Assessment for alcohol was used to estimate alcohol-attributable fractions. RESULTS: Alcohol use caused 1,600 (95% CI: 1,472 - 1,728) net deaths (1,768 deaths caused, 168 deaths prevented) among 15 to 74 year olds, corresponding to 8.7% of all deaths (men: 1,181 deaths; women: 419 deaths). Overall, 42,627 years of life (9.7%, 95% CI: 40,245 - 45,008) were lost due to alcohol. Main causes of alcohol-attributable mortality were injuries at younger ages (15-34 years), with increasing age digestive diseases (mainly liver cirrhosis) and cancers (particularly breast cancers among women). The majority (62%) of all alcohol-attributable deaths was caused by chronic heavy drinking (men: 67%; women: 48 %). CONCLUSION: Alcohol is a major cause of premature mortality in Switzerland. Its impact, among young people mainly via injuries, among men mainly through heavy drinking, calls for a mix of preventive actions targeting chronic heavy drinking, binge drinking and mean consumption.

The revolving door phenomenon revisited: time to readmission in 17'145 [corrected] patients with 37'697 hospitalisations at a German psychiatric hospital.

OBJECTIVE: Despite the recurring nature of the disease process in many psychiatric patients, individual careers and time to readmission rarely have been analysed by statistical models that incorporate sequence and velocity of recurrent hospitalisations. This study aims at comparing four statistical models specifically designed for recurrent event history analysis and evaluating the potential impact of predictor variables from different sources (patient, treatment process, social environment). METHOD: The so called Andersen-Gil counting process model, two variants of the conditional models of Prentice, Williams, and Peterson (gap time model, conditional probability model), and the so called frailty model were applied to a dataset of 17'145 [corrected] patients observed during a 12 years period starting from 1996 and leading to 37'697 psychiatric hospitalisations Potential prognostic factors stem from a standardized patient documentation form. RESULTS: Estimated regression coefficients over different models were highly similar, but the frailty model best represented the sequentiality of individual treatment careers and differing velocities of disease progression. It also avoided otherwise likely misinterpretations of the impact of gender, partnership, historical time and length of stay. A widespread notion of psychiatric diseases as inevitably chronic and worsening could be rejected. Time in community was found to increase over historical time for all patients. Most important protective factors beyond diagnosis were employment, partnership, and sheltered living situation. Risky conditions were urban living and a concurrent substance use disorder. CONCLUSION: Prognostic factors for course of diseases should be determined only by statistical models capable of adequately incorporating the recurrent nature of psychiatric illnesses.

Estimating uncertainty of alcohol-attributable fractions for infectious and chronic diseases.

BACKGROUND: Alcohol is a major risk factor for burden of disease and injuries globally. This paper presents a systematic method to compute the 95% confidence intervals of alcohol-attributable fractions (AAFs) with exposure and risk relations stemming from different sources. METHODS: The computation was based on previous work done on modelling drinking prevalence using the gamma distribution and the inherent properties of this distribution. The Monte Carlo approach was applied to derive the variance for each AAF by generating random sets of all the parameters. A large number of random samples were thus created for each AAF to estimate variances. The derivation of the distributions of the different parameters is presented as well as sensitivity analyses which give an estimation of the number of samples required to determine the variance with predetermined precision, and to determine which parameter had the most impact on the variance of the AAFs. RESULTS: The analysis of the five Asian regions showed that 150 000 samples gave a sufficiently accurate estimation of the 95% confidence intervals for each disease. The relative risk functions accounted for most of the variance in the majority of cases. CONCLUSIONS: Within reasonable computation time, the method yielded very accurate values for variances of AAFs.