Diabetes mellitus (DM) is a systemic disease that affects a number of sensory systems and is a major public health concern. A common, but under-recognized complication of DM is hearing difficulty. However, research on DM-related auditory deficits is relatively sparse. Recent data shows over a two-fold higher prevalence of hearing impairment in diabetic patients compared to non-diabetic individuals, further solidifying this strong association between diabetes and hearing loss. However, the nature of these hearing difficulties has not been clearly elucidated. In the present study, the auditory processing abilities of a group of adults (N = 9; mean age = 53.3) with type 2 DM was compared to an age matched control group (N = 9; mean age= 47.6). In addition, visual processing abilities of the participants were examined to determine if the hearing difficulties associated with DM were a function of a more global sensory deficit. The selection criteria for the DM group included age, duration of diabetes (> 5 years), and recent measures of diabetic control (hemoglobin A1C and blood sugar). Further, all participants in the test and control groups had a comprehensive hearing evaluation and had hearing (measured with pure tones 250-4000 Hz) within normal limits bilaterally. The following test measures were recorded. The Michigan Neuropathy Screening Instrument (MNSI) was administered to screen each subject for peripheral neuropathy symptoms. The Speech, Spatial & Qualities (SSQ12) questionnaire was administered to attain a measure of each individuals subjective hearing complaints. Subtle deficits in the peripheral auditory system were examined using (a) Extended high frequency audiometry, that assessed ultra high frequencies from 9000-16000 Hz bilaterally, (b) The Threshold Equalizing Noise (TEN) test, to assess for potential dead regions within the cochlea, and (c) Distortion product otoacoustic emissions (DPOAE) were collected bilaterally to assess frequency specific cochlear outer hair cell function. Higher-order auditory processing was examined with the Quick Speech in Noise Test (QuickSIN), the Listening in Spatial Noise test-Sentences (LiSN-S) and the Random gap detection, to measure temporal processing abilities. Further, the Text Reception Threshold Test (TRT) was employed to examine visual processing abilities. The results revealed that individuals with DM had significantly (a) Elevated high frequency (> 4 kHz) pure tone thresholds; (b) Increased self-reported hearing difficulties based on SSQ12 scores (c) Poorer spatial listening in noise skills based on LiSN results, (d) Lower DPOAE amplitudes for higher frequencies, and (e) Poorer temporal processing skills based on the average gap detection thresholds, when compared to the age-matched controls. These findings not only support the strong association between diabetes and hearing loss, they suggest that that even individuals with controlled diabetes potentially suffer with subclinical auditory processing deficits that may affect their quality of life. These findings have implications in the management of DM in the future. Further research is needed in order to determine clinically feasible means of evaluating DM subjects.

Abstract available in The FASEB Journal.

C1q TNF Related Protein 3 (CTRP3) is a novel adipose tissue derived secreted factor, or adipokine, which has been linked to a number of beneficial biological effects on metabolism, inflammation, and survival signaling in a variety of tissues. However, very little is known about CTRP3 in regards to human health. The purpose of this project was to examine circulating CTRP3 levels in a clinical population, patients with symptoms requiring heart catheterization in order to identify the presence of obstructive coronary artery disease (CAD). It was hypothesized that serum CTRP3 levels would be decreased in the presence of CAD. Methods Body mass index (BMI), diabetes status, and plasma samples were collected from 100 patients who were >30 years of age and presented at the East Tennessee State University Heart Clinic with symptoms requiring heart catheterization in order to identify the presence of cardiovascular blockages (n = 52 male, n = 48 female). Circulating CTRP3 levels were quantified using commercially available ELISA. Results Circulating CTRP3 levels had no relationship to the presence of CAD regardless of gender. However, circulating concentrations of CTRP3 were significantly higher in normal weight (BMI < 30) females (0.88 ± 0.12 µg/ml) compared with males (0.54 ± 0.06 µg/ml). Further, obesity (BMI > 30) resulted in an increase in circulating CTRP3 levels in male subjects (0.74 ± 0.08 µg/ml) but showed a significant decrease in female subjects (0.58 ± 0.07 µg/ml). Additionally, there was a significant reduction in circulating CTRP3 levels in female subjects who were diagnosed with Type 2 diabetes compared with patients without (0.79 ± 0.08 vs. 0.42 ± 0.10 µg/ml). There was no relationship between diabetes status and circulating CTRP3 levels in male subjects. Conclusion Circulating CTRP3 levels had a different relationship with diabetes and obesity status between male and female patients. It is possible that circulating CTRP3 levels are controlled by hormonal status, however more research is needed to explore this relationship. Nevertheless, future studies examining the relationship between CTRP3 levels and disease status should treat gender as an independent variable.

Abstract available in The FASEB Journal.

Background: Diabetes is the seventh leading cause of death in the United States. More and more people have suffered from diabetes and its serious complications including heart disease, blindness, etc. The U.S. Department of Veterans Affairs (VA) reported that nearly 25% of veterans, enrolled in the Veterans Health Administration (VHA), have diabetes, which is much higher than the general population. Objective: This study aimed to estimate the prevalence of diabetes in the U.S. veterans using the up-to-date National Health and Nutrition Examination Survey (NHANES) data since VHA has a relatively low coverage (less than 30% of veterans each year were enrolled). Methods: Five biennial cross sectional surveys (NHANES) between 2005-2014 were used in this study. Total 2,940 veterans were included to estimate the prevalence of diabetes. Total diabetes was defined as any participant who had at least one of four conditions: (1) a hemoglobin A1c at least 6.5%, (2) fasting plasma glucose (FPG) at least 126mg/dL, (3) a 2-hour plasma glucose (PG) at least 200mg/dL, (4) diagnosed with diabetes by a doctor or other health professional. Results: The overall prevalence of total diabetes (including diagnosed and undiagnosed diabetes), undiagnosed diabetes and obesity were 20.54%, 3.37% and 40.68%, respectively. The family poverty level and education were significantly associated with the presence of diabetes with p=0.005 and 0.03, respectively. Highest prevalence diabetes and obesity existed in veterans aged 65yrs and over and 45-64yrs, respectively. The overall prevalence trend of diabetes significantly increased from 15.52% (95%CI: 12.36-18.68%) in 2005-2006 to 20.54% (95%CI: 15.92-25.17%) (p=0.04 for trend test) and prevalence significantly increased in male veterans ( p=0.04) and those who did not finish high school education (p=0.04) and who had college education (p=0.03). Conclusion: In 2013-2014, the estimated prevalence of diabetes was 20.54% among U.S. veterans, with higher prevalence among participants who were 65 years old or older, and had low socioeconomics status (including less education and poverty status).

Background Over the long term, unhealthy lifestyles can lead to many health problems, especially type 2 diabetes (T2D). The aim of the present study was to determine associations between lifestyle factors (smoking, alcohol consumption, physical activity, and diet) and T2D in American adults (aged ≥20 years) in a nationally representative sample. Methods Data for 12 987 American adults participating in the National Health and Nutrition Examination Survey 2005–2014 were evaluated. Weighted multiple logistic regression models were used to examine associations between the four lifestyle factors and T2D after adjusting for demographics and socioeconomic status (SES). Prevalence trends for T2D were examined using Cochran–Armitage tests. Results There was a significant increasing prevalence trend for T2D among American adults. Smokers and individuals consuming >12 alcoholic drinks in the past year were less likely to report having T2D than non-smokers (odds ratio [OR] 0.41; 95% confidence interval [CI] 0.35–0.48) and those consuming Conclusion All four lifestyle factors were significantly associated with T2D among American adults. The findings of the present study provide useful information for healthcare providers that may help them promote specific lifestyle modifications.

Background: Diabetes type 2 is a chronic system disease which has a huge impact on the patient’s life. The disease can lead to many sequalae and involves different types of sufferings for the patient. The treatment consists of both medical and lifestyle changes where self-care has great importance. Previous researches have made evident that life with diabetes type 2 means a great change in lifestyle that affects the patient psychologically, physically, spiritually and socially. In addition, there were many people who had difficulty making these changes. Patients experienced shame because diabetes type 2 is seen as a lifestyle disease. Aim: The aim of this study was to describe patient experiences of living with diabetes type 2. Method: A systematic qualitative literature study was conducted with an inductive approach. A manifest content analysis was conducted on 13 articles. Result: People with type 2 diabetes experienced negative emotions such as fear, depression, anxiety and loneliness. Living with a changed body hindered everyday life and triggered feelings of dissatisfaction and frustration. The participants experienced restrictions in travel, career and social outlooks. Furthermore, patients with type 2 diabetes blamed themselves of getting diabetes. They also felt judged and blamed by others for getting diabetes type 2 because it is seen as a lifestyle disease. The consequence of this was that many participants hid their illness from others. Conclusions:  Many factors must work together, for life with type 2 diabetes to workout. It is the nurse’s responsibility support and provide the patient with the information needed to cope with the management of the disease, however, it is the patient’s responsibility to implement it. Furthermore, there is a lot of stigma against type 2 diabetes and more education is needed for patients, health care professionals and relatives/ the public in order to fight it. / Bakgrund: Diabetes typ 2 är en kronisk systemsjukdom som har en stor påverkan på patientens liv. Sjukdomen kan leda till många följdsjukdomar och innebär olika typer av lidande för patienten. Behandlingen består av både medicin och livsstilsförändringar där egenvården har en stor betydelse. Tidigare forskning visar att livet med diabetes typ 2 innebär en stor förändring som berör personen psykiskt, fysiskt, andligt och socialt. Dessutom finns det många människor som hade svårigheter att göra dessa förändringar. Patienter upplever skamkänslor eftersom diabetes typ 2 ses som en livsstilssjukdom. Syfte: Syftet var att beskriva patienters upplevelser av att leva med diabetes typ 2. Metod: En systematisk kvalitativ litteraturstudie genomfördes med induktiv ansats. En manifest innehållsanalys gjordes på 13 artiklar. Resultat: Människor med diabetes typ 2 upplevde negativa känslor som bland annat rädsla, depression, oro och ensamhet. Att leva med en förändrad kropp hindrade det vardagliga livet och triggade igång känslor av missnöje och frustration. Deltagarna upplevde restriktioner i resor, karriär och sociala utsikter. Vidare, anklagade patienter med diabetes typ 2 sig själva för att ha fått diabetes. De kände sig även dömda och anklagade av andra för att ha fått diabetes genom att ha en dålig livsstil. Konsekvensen av detta blev att många deltagare dolde sin sjukdom för andra.  Slutsats: Många faktorer måste samverka för att livet med diabetes typ 2 ska fungera. Det är sjuksköterskans ansvar att stötta och ge patienten informationen som krävs för att klara av hanteringen av sjukdomen dock är det patientens ansvar att genomföra det. Det finns mycket stigmatisering mot diabetes typ 2 patienter och det krävs mer utbildning för patienter, vårdpersonal och närstående/allmänheten för att kunna kämpa emot det.

Sleep is a fundamental and essential component of vertebrate life, although its exact function remains unknown. Animals that are deprived of sleep typically show reduced neurobiological performance, health, and in some cases, survival. However, a number of animals exhibit adaptations that permit them to carry out normal activities even when sleep is restricted or deprived. Lapland longspurs (Calcarius lapponicus), arctic-breeding passerine birds, exhibit around-the-clock activity during their short breeding season, with an inactive period of only 3–4 h/day (71°N). Whether these birds suffer behavioral and physiological costs associated with acute sleep loss (SL) is unknown. To assess the effects of SL, wild-caught male longspurs were placed in captivity (12L:12D) and trained for 2 months using a series of memory tests, including color association and spatial learning to assess executive function. Birds were then placed in automated sleep fragmentation cages that utilize a moving wire to force movement every 1 min (60 arousals/h) during 12D (inactive period) or control conditions (during 12L; active period). After a single round of SL (or control) treatment, color association and spatial learning tests were conducted. Baseline plasma corticosterone concentration, body mass, and satiety were also assessed. SL significantly elevated corticosterone levels and increased accuracy during the color association test, but not the overall time required to complete the test. SL had no effect upon spatial learning, body mass, or satiety. Taken together, these results suggest that Lapland longspurs exhibit a behavioral, but not a physiological, resilience to acute SL.

Insulin plays a vital role in whole-body metabolism and provides a major anabolic stimulus for cellular signaling pathways, including those involved in the metabolism of glucose and protein. Consequently, insulin dysregulation (ID) is known to alter molecular signal transduction in insulin-sensitive tissues such as skeletal muscle, thereby disrupting glucose metabolism and compromising protein synthetic capacity. Our first objective was to induce ID in healthy horses by administering dexamethasone (DEX), a potent glucocorticoid, for 21 days. We evaluated the effects on insulin-stimulated muscle protein signaling components involved in the mammalian target of rapamycin (mTOR) pathway. DEX-induced ID reduced insulin-stimulated activation of downstream (rpS6, 4EBP-1) mTOR signaling and increased atrogin-1 abundance, a marker for protein breakdown (P < 0.05). Additionally, 21 days of DEX elevated plasma amino acids levels in insulin-stimulated conditions, indicative of reduced uptake or increase release into circulation (P < 0.05). The second objective was to evaluate the short-term effects of DEX treatment in healthy horses. Plasma insulin, glucose and amino acid dynamics and activation of mTOR signaling pathways following an oral sugar test (OST) or intake of a high protein meal were evaluated before and after 7 days of DEX treatment, and after 7 days of no treatment. Seven days of DEX treatment increased basal levels of glucose, insulin and several amino acids (P < 0.05). Additionally horses treated with DEX had an exacerbated insulin response to the OST and consumption of the high protein meal in comparison to control horses (P < 0.05). The majority of blood metabolites returned to basal levels after 7 days of recovery from DEX treatment, indicating these effects were transient. Short-term DEX treatment decreased overall activation of mTOR and FoxO3 but increased total FoxO3 and IRS-1 abundance (P < 0.05). Postprandial activation of rpS6 was greater in horses treated with DEX for 7 days but was lower in those horses after 7 days of recovery from treatment (P < 0.05). Postprandial activation of ULK and AMPK tended to be greater in DEX treated horses (P < 0.1). Akt phosphorylation and mysotatin abundance were lower after the OST in DEX treated horses (P < 0.05). The final objective was to evaluate whether similar changes in postprandial metabolic responses would be seen in horses with naturally occurring ID. Plasma insulin, glucose and amino acid responses following ingestion of a high protein meal were determined in mature horses with equine metabolic syndrome (EMS). Horses with EMS had higher basal plasma insulin concentrations but lower levels of aspartate, glutamate, asparagine and plasma urea nitrogen in comparison to healthy controls (P < 0.05). Consumption of a high protein meal resulted in a 9-fold greater insulin response and higher postprandial levels of various amino acids (P < 0.05). Together this research indicates that ID affects whole body protein metabolism by altering cellular signaling pathways in healthy and diseased horses.

The first goal of the current research was to determine whether gene expression profiles differed between whole pituitaries of growing beef steers grazing pastures containing high (HE) or low (LE) amounts of toxic endophyte-infected tall fescue. The global (microarray analysis) and selected targeted (RT-PCR) mRNA expression patterns of pituitaries collected from beef steers (BW = 266 ± 15.5 kg) that had been randomly assigned to undergo summer-long grazing (89 to 105 d) of either HE (0.52 ppm ergot alkaloids) or LE (< 0.03 ppm ergot alkaloids) pastures were compared. Gene expression data were subjected to one-way ANOVA. The pituitaries of HE steers had 542 differentially expressed genes, and the pattern of altered gene expression was dependent on treatment. Targeted RT-PCR analysis corroborated these findings, including decreased expression of DRD2, PRL, POU1F1, GAL, and VIP and that of POMC and PCSK1, respectively. Canonical pathway analysis (Integrated Pathway Analysis, IPA) identified HE-dependent alteration in signaling of additional pituitary-derived hormones, including growth hormone and GnRH. In conclusion, consumption of endophyte-infected tall fescue alters the pituitary transcriptome profiles of steers in a manner consistent with their negatively affected physiological parameters. The second goal of this project was to test the hypothesis that sodium selenite (ISe), SEL-PLEX (OSe), vs. a 1:1 blend (MIX) of ISe and OSe in a basal vitamin-mineral (VM) mix would differentially alter pituitary transcriptome profiles in growing beef steers (BW = 183 ± 34 kg) commonly grazing an endophyte-infected tall fescue (HE) pasture. Steers were randomly selected from herds of fall-calving cows grazing HE pasture and consuming VM mixes that contained 35 ppm Se as either ISe, OSe, or MIX forms. Steers were weaned, depleted of Se for 98 d, and subjected to summer-long common grazing of a 10.1 ha HE pasture containing 0.51 ppm ergot alkaloids. Steers were assigned (n = 8) to the same Se-form treatments on which they were raised. Selenium treatments were administered by daily top-dressing 85 g of VM mix onto 0.23 kg soyhulls, using in-pasture Calan gates. Pituitaries were collected at slaughter and changes in global (microarray) and selected (RT-PCR) mRNA expression patterns determined. The effects of Se treatment on relative gene expression were subjected to one-way ANOVA. The form of Se affected the expression of 542 annotated genes. Integrated Pathway Analysis found a canonical pathway network between prolactin and POMC/ACTH/ α-MSH synthesis-related proteins, and that mitochondrial dysfunction was a top-affected canonical pathway. Targeted RT-PCR analysis found that the relative abundance of mRNA encoding prolactin and POMC/ACTH/ α-MSH synthesis-related proteins was affected by the form of Se, as were mitochondrial dysfunction-related proteins OSe steers appeared to have a greater prolactin synthesis capacity vs. ISe steers through decreased dopamine receptor D2 signaling, whereas MIX steers had a greater prolactin synthesis capacity and release potential by increasing TRH concentrations than ISe steers. OSe steers also had a greater ACTH and α-MSH synthesis potential than ISe steers. We conclude that form of Se in VM mixes affected genes responsible for prolactin and POMC/ACTH/α-MSH synthesis, and mitochondrial function in pituitaries of growing beef steers commonly grazing an HE pasture. The third goal was to test the hypothesis that sodium selenite (ISe), SEL-PLEX (OSe), vs. a 1:1 blend (MIX) of ISe and OSe in a basal vitamin-mineral (VM) mix would differentially alter selenoprotein profiles in pituitaries and livers of growing beef steers commonly grazing an endophyte-infected tall fescue (HE) pasture (i.e., the same steers used in Goal 2). The effects of Se treatment on relative gene expression were subjected to one-way ANOVA. The mRNA content of 6 selenoproteins in the pituitary was affected by Se treatments, along with two selenoprotein P receptors, whereas the expression of two selenoproteins was altered in the liver. We conclude that the change in selenoprotein gene expression in pituitaries indicates that OSe steers have a greater potential capacity to manage against oxidative damage, maintain cellular redox balance, and have a better quality control of protein-folding in their pituitaries than ISe steers. The change in selenoprotein gene expression by the liver indicates that MIX steers have a greater redox signaling capacity and capacity to manage oxidative damage than ISe steers.