WP 2018-389

Recent research has found, in some groups of Americans, dramatic increases in deaths due to drug overdose and suicide and an overall stagnation of trends toward increased longevity. This study examines the link between mortality of older working age (45 to 64) adults and local economic downturns in the U.S. to evaluate the role of economic shifts in various causes of death and their related mortality trends. Specifically, we estimate regression models to test the hypotheses that the longevity effects of poor economic prospects are reflected through (1) increased suicide, drug overdose, and other “deaths of despair” and (2) other causes of death linked to exposure to economic and social stress such as heart and cerebrovascular disease. To avoid the problem of endogeneity of local economic conditions to mortality conditions, we measure the local economic shock of lost employment with predicted employment based on baseline industrial composition and national trends in employment by industry. We find evidence consistent with prior research that among non-Hispanic white adults, midlife mortality has increased since 1990, particularly among those with low educational attainment. We also find that “deaths of despair” are important contributors to that trend. However, we find that while distress in local, area economies does predict increased mortality for chronic disease, it predicts decreased mortality from suicides, opioids, and other substance abuse. This finding suggests caution in the application of the construct of despair in explaining recent mortality patterns.Social Security Adminstration, Award number RRC08098401-10, R-UM18-07https://deepblue.lib.umich.edu/bitstream/2027.42/148126/1/wp389.pdfDescription of wp389.pdf : Working pape

Robust implications on Dark Matter from the first FERMI sky gamma map

We derive robust model-independent bounds on DM annihilations and decays from the first year of FERMI gamma-ray observations of the whole sky. These bounds only have a mild dependence on the DM density profile and allow the following DM interpretations of the PAMELA and FERMI electron/positron excesses: primary channels mu+ mu-, mu+ mu-mu+mu- or e+ e- e+ e-. An isothermal-like density profile is needed for annihilating DM. In all such cases, FERMI gamma spectra must contain a significant DM component, that may be probed in the future.Comment: 16 pages, 8 figures. Final versio

Relationships of the early insulin secretory response and oral disposition index with gastric emptying in subjects with normal glucose tolerance

The oral disposition index, the product of the early insulin secretory response during an oral glucose tolerance test and insulin sensitivity, is used widely for both the prediction of, and evaluation of the response to interventions, in type 2 diabetes. Gastric emptying, which determines small intestinal exposure of nutrients, modulates postprandial glycemia. The aim of this study was to determine whether the insulin secretory response and the disposition index (DI) related to gastric emptying in subjects with normal glucose tolerance. Thirty-nine subjects consumed a 350 mL drink containing 75 g glucose labeled with 99mTc-sulfur colloid. Gastric emptying (by scintigraphy), blood glucose (G) and plasma insulin (I) were measured between t = 0-120 min. The rate of gastric emptying was derived from the time taken for 50% emptying (T50) and expressed as kcal/min. The early insulin secretory response was estimated by the ratio of the change in insulin (∆I0-30) to that of glucose at 30 min (∆G0-30) represented as ∆I0-30/∆G0-30 Insulin sensitivity was estimated as 1/fasting insulin and the DI was then calculated as ∆I0-30/∆G0-30 × 1/fasting insulin. There was a direct relationship between ∆G0-30 and gastric emptying (r = 0.47, P = 0.003). While there was no association of either ∆I0-30 (r = -0.16, P = 0.34) or fasting insulin (r = 0.21, P = 0.20), there were inverse relationships between the early insulin secretory response (r = -0.45, P = 0.004) and the DI (r = -0.33, P = 0.041), with gastric emptying. We conclude that gastric emptying is associated with both insulin secretion and the disposition index in subjects with normal glucose tolerance, such that when gastric emptying is relatively more rapid, both the early insulin secretory response and the disposition index are less. These findings should be interpreted as "hypothesis generating" and provide the rationale for longitudinal studies to examine the impact of baseline rate of gastric emptying on the prospective risk of type 2 diabetes.Chinmay S. Marathe, Christopher K. Rayner, Kylie Lange, Michelle Bound, Judith Wishart, Karen L. Jones, Steven E. Kahn and Michael Horowit

Effective Binding of Methane Using a Weak Hydrogen Bond

The weak hydrogen bond is an important type of noncovalent interaction, which has been shown to contribute to stability and conformation of proteins and large biochemical membranes, stereoselectivity, crystal packing, and effective gas storage in porous materials. In this work, we systematically explore the interaction of methane with a series of functionalized organic molecules specifically selected to exhibit a weak hydrogen bond with methane molecules. To enhance the strength of hydrogen bond interactions, the functional groups include electron-enriched sites to allow sufficient polarization of the C–H bond of methane. The binding between nine functionalized benzene molecules and methane has been studied using the second order Møller–Plesset perturbation theory to reveal that benzenesulfonic acid (C6H5–SO3H) and phenylphosphonic acid (C6H5–PO3H2) have the greatest potential for efficient methane capture through hydrogen bonding interactions. Both acids exhibit efficient binding potential with up to three methane molecules. For additional insight, the atomic charge distribution associated with each binding site is presented

Comparative effect of intraduodenal and intrajejunal glucose infusion on the gut-incretin axis response in healthy males

The region of enteral nutrient exposure may be an important determinant of postprandial incretin hormone secretion and blood glucose homoeostasis. We compared responses of plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon, and blood glucose to a standardised glucose infusion into the proximal jejunum and duodenum in healthy humans. Ten healthy males were evaluated during a standardised glucose infusion (2 kcal min−1 over 120 min) into the proximal jejunum (50 cm post pylorus) and were compared with another 10 healthy males matched for ethnicity, age and body mass index who received an identical glucose infusion into the duodenum (12 cm post pylorus). Blood was sampled frequently for measurements of blood glucose and plasma hormones. Plasma GLP-1, GIP and insulin responses, as well as the insulin:glucose ratio and the insulinogenic index 1 (IGI1) were greater (P<0.05 for each) after intrajejunal (i.j.) than intraduodenal glucose infusion, without a significant difference in blood glucose or plasma glucagon. Pooled analyses revealed direct relationships between IGI1 and the responses of GLP-1 and GIP (r=0.48 and 0.56, respectively, P<0.05 each), and between glucagon and GLP-1 (r=0.70, P<0.001). In conclusion, i.j. glucose elicits greater incretin hormone and insulin secretion than intraduodenal glucose in healthy humans, suggesting regional specificity of the gut–incretin axis.T Wu, S S Thazhath, C S Marathe, M J Bound, K L Jones, M Horowitz and C K Rayne

Effects of a D-xylose preload with or without sitagliptin on gastric emptying, glucagon-like peptide-1, and postprandial glycemia in type 2 diabetes

OBJECTIVE Macronutrient “preloads” can reduce postprandial glycemia by slowing gastric emptying and stimulating glucagon-like peptide-1 (GLP-1) secretion. An ideal preload would entail minimal additional energy intake and might be optimized by concurrent inhibition of dipeptidyl peptidase-4 (DPP-4). We evaluated the effects of a low-energy d-xylose preload, with or without sitagliptin, on gastric emptying, plasma intact GLP-1 concentrations, and postprandial glycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS Twelve type 2 diabetic patients were studied on four occasions each. After 100 mg sitagliptin (S) or placebo (P) and an overnight fast, patients consumed a preload drink containing either 50 g d-xylose (X) or 80 mg sucralose (control [C]), followed after 40 min by a mashed potato meal labeled with 13C-octanoate. Blood was sampled at intervals. Gastric emptying was determined. RESULTS Both peak blood glucose and the amplitude of glycemic excursion were lower after PX and SC than PC (P < 0.01 for each) and were lowest after SX (P < 0.05 for each), while overall blood glucose was lower after SX than PC (P < 0.05). The postprandial insulin-to-glucose ratio was attenuated (P < 0.05) and gastric emptying was slower (P < 0.01) after d-xylose, without any effect of sitagliptin. Plasma GLP-1 concentrations were higher after d-xylose than control only before the meal (P < 0.05) but were sustained postprandially when combined with sitagliptin (P < 0.05). CONCLUSIONS In type 2 diabetes, acute administration of a d-xylose preload reduces postprandial glycemia and enhances the effect of a DPP-4 inhibitor.Tongzhi Wu, Michelle J. Bound, Beiyi R. Zhao, Scott D. Standfield, Max Bellon, Karen L. Jones, Michael Horowitz, Christopher K. Rayne