Treatment update: thiazolidinediones in combination with metformin for the treatment of type 2 diabetes

Type 2 diabetes mellitus (DM2) is characterized by excessive hepatic gluconeogenesis, increased insulin resistance and a progressive inability of pancreatic beta cells to produce sufficient insulin. DM2 evolves as a progression from normal glucose tolerance, to impaired glucose tolerance (IGT) to frank diabetes mellitus, reflecting the establishment of insulin resistance and beta cell dysfunction. Insulin resistance not only contributes to impaired glycemic control in DM2, but to the development of hypertension, dyslipidemia and endothelial dysfunction. Cardiovascular disease is the primary morbidity for patients with DM2. The onset of insulin resistance and cardiovascular insult likely occurs well before the onset of IGT is detected clinically. Biguanides and thiazolidinediones (TZDs) are two classes of oral agents for the management of DM2 that improve insulin resistance, and thus have potential cardiovascular benefits beyond glycemic control alone. Metformin additionally inhibits hepatic gluconeogenesis. The combined use of two of these agents targets key pathophysiologic defects in DM2. Single pill combinations of rosiglitazone/metformin and pioglitazone/metformin have recently been approved for use in the US and Europe. This article reviews the clinical data behind the use of metformin in combination with TZDs for the management of diabetes, its impact on vascular health, side effects and potential mechanisms of action for combined use

High-Fat Feeding Does Not Disrupt Daily Rhythms in Female Mice Because of Protection by Ovarian Hormones

Obesity in women is increased by the loss of circulating estrogen after menopause. Shift work, which disrupts circadian rhythms, also increases the risk for obesity. It is not known whether ovarian hormones interact with the circadian system to protect females from obesity. During high-fat feeding, male C57BL/6J mice develop profound obesity and disruption of daily rhythms. Since C57BL/6J female mice did not develop diet-induced obesity (during 8 weeks of high-fat feeding), we first determined if daily rhythms in female mice were resistant to disruption from high-fat diet. We fed female PERIOD2:LUCIFERASE mice 45% high-fat diet for 1 week and measured daily rhythms. Female mice retained robust rhythms of eating behavior and locomotor activity during high-fat feeding that were similar to chow-fed females. In addition, the phase of the liver molecular timekeeping (PER2:LUC) rhythm was not altered by high-fat feeding in females. To determine if ovarian hormones protected daily rhythms in female mice from high-fat feeding, we analyzed rhythms in ovariectomized mice. During high-fat feeding, the amplitudes of the eating behavior and locomotor activity rhythms were reduced in ovariectomized females. Liver PER2:LUC rhythms were also advanced by ~4 h by high-fat feeding, but not chow, in ovariectomized females. Together these data show circulating ovarian hormones protect the integrity of daily rhythms in female mice during high-fat feeding

Employment and Disability Policy: the role of the psychologist

Persons with minor or major disabilities represent a significant portion of the U.S. working-age population. Based on the 1993 Survey of Income and Program Participation (SIPP), approximately 30 million (19%) men and women 18 to 64 years of age report some type of physical or mental limitation. For approximately 55% of these individuals (about 10% of those 18 to 64), the limitations are severe

ATP10A deficiency results in male-specific infertility in mice

Over 8% of couples worldwide are affected by infertility and nearly half of these cases are due to male-specific issues where the underlying cause is often unknown. Therefore, discovery of new genetic factors contributing to male-specific infertility in model organisms can enhance our understanding of the etiology of this disorder. Here we show that murine ATP10A, a phospholipid flippase, is highly expressed in male reproductive organs, specifically the testes and vas deferens. Therefore, we tested the influence of ATP10A on reproduction by examining fertility of Atp10A knockout mice. Our findings reveal that Atp10A deficiency leads to male-specific infertility, but does not perturb fertility in the females. The Atp10A deficient male mice exhibit smaller testes, reduced sperm count (oligozoospermia) and lower sperm motility (asthenozoospermia). Additionally, Atp10A deficient mice display testes and vas deferens histopathological abnormalities, as well as altered total and relative amounts of hormones associated with the hypothalamic-pituitary-gonadal axis. Surprisingly, circulating testosterone is elevated 2-fold in the Atp10A knockout mice while luteinizing hormone, follicle stimulating hormone, and inhibin B levels were not significantly different from WT littermates. The knockout mice also exhibit elevated levels of gonadotropin receptors and alterations to ERK, p38 MAPK, Akt, and cPLA2-dependent signaling in the testes. Atp10A was knocked out in the C57BL/6J background, which also carries an inactivating nonsense mutation in the closely related lipid flippase, Atp10D. We have corrected the Atp10D nonsense mutation using CRISPR/Cas9 and determined that loss of Atp10A alone is sufficient to cause infertility in male mice. Collectively, these findings highlight the critical role of ATP10A in male fertility in mice and provide valuable insights into the underlying molecular mechanisms

Robots with Display Screens: A Robot with a More Humanlike Face Display Is Perceived To Have More Mind and a Better Personality

It is important for robot designers to know how to make robots that interact effectively with humans. One key dimension is robot appearance and in particular how humanlike the robot should be. Uncanny Valley theory suggests that robots look uncanny when their appearance approaches, but is not absolutely, human. An underlying mechanism may be that appearance affects users’ perceptions of the robot’s personality and mind. This study aimed to investigate how robot facial appearance affected perceptions of the robot’s mind, personality and eeriness. A repeated measures experiment was conducted. 30 participants (14 females and 16 males, mean age 22.5 years) interacted with a Peoplebot healthcare robot under three conditions in a randomized order: the robot had either a humanlike face, silver face, or no-face on its display screen. Each time, the robot assisted the participant to take his/her blood pressure. Participants rated the robot’s mind, personality, and eeriness in each condition. The robot with the humanlike face display was most preferred, rated as having most mind, being most humanlike, alive, sociable and amiable. The robot with the silver face display was least preferred, rated most eerie, moderate in mind, humanlikeness and amiability. The robot with the no-face display was rated least sociable and amiable. There was no difference in blood pressure readings between the robots with different face displays. Higher ratings of eeriness were related to impressions of the robot with the humanlike face display being less amiable, less sociable and less trustworthy. These results suggest that the more humanlike a healthcare robot’s face display is, the more people attribute mind and positive personality characteristics to it. Eeriness was related to negative impressions of the robot’s personality. Designers should be aware that the face on a robot’s display screen can affect both the perceived mind and personality of the robot

First trimester serum biomarkers to predict gestational diabetes in a high-risk cohort: Striving for clinically useful thresholds

Objectives: Screening and diagnosis of gestational diabetes (GDM) has been a source of controversy. The prevalence has increased in line with an obesity epidemic and a trend towards delayed child-bearing. Treatment of even modest glycaemic impairment in pregnancy has been shown to be beneficial in preventing its clinical sequalae. However the cumbersome nature and timing of the oral glucose tolerance test coupled with debate around universal versus risk factor based screening have been problematic. This group aimed to investigate a panel of biomarkers which have shown promise in the literature to predict GDM from the first trimester in a group of high risk women. Methods: Serum samples were drawn on 248 women deemed at risk of GDM before 15 weeks\u27 gestation to measure C-reactive protein, sex hormone binding globulin, adiponectin and 1,5 anhydroglucitol. Patients underwent an oral glucose tolerance test as per IADPSG criteria at 28 weeks\u27 gestation. Multiple logistic regression was used to examine the link between incidence of GDM and early pregnancy serum biomarkers. Results: Adiponectin levels in the first trimester are independently linked to the risk of GDM. Serum adiponectin \u3c8.9 μg/ml gives an odds ratio of 3.3 for GDM.Mean 1,5 AG levels are significantly lower in those that go on to develop GDM. SHBG levels measured in the first trimester were linked to the risk of GDM. However, this was no longer statistically significant once BMI, ethnicity and family history were taken into consideration. First trimester measurement of CRP is not a useful indicator of GDM risk. Conclusions: First trimester measurement of Adiponectin and 1,5 Anhydroglucitol are potential early biomarkers for the later onset of GDM. Risk stratification using these biomarkers may facilitate early diagnosis and management of GDM to mitigate against its complications