A one-time algorithmic adjustment of open-loop settings did not alter glucose control in a relatively short duration outpatient closed-loop study. The CLC system proved very robust and adaptable, with minimal (<2%) time spent in the hypoglycemic range in either arm.

-To determine the effects of exercise on postprandial glucose metabolism and insulin action in type 1 diabetes (T1D), we applied the triple tracer technique to study 16 T1D subjects on insulin pump therapy before, during, and after 75 min of moderate-intensity exercise (50% V O2max) that started 120 min after a mixed meal containing 75 g of labeled glucose. Prandial insulin bolus was administered as per each subject's customary insulin/carbohydrate ratio adjusted for meal time meter glucose and the level of physical activity. Basal insulin infusion rates were not altered. There were no episodes of hypoglycemia during the study. Plasma dopamine and norepinephrine concentrations rose during exercise. During exercise, rates of endogenous glucose production rose rapidly to baseline levels despite high circulating insulin and glucose concentrations. Interestingly, plasma insulin concentrations increased during exercise despite no changes in insulin pump infusion rates, implying increased mobilization of insulin from subcutaneous depots. Glucagon concentrations rose before and during exercise. Therapeutic approaches for T1D management during exercise will need to account for its effects on glucose turnover, insulin mobilization, glucagon, and sympathetic response and possibly other blood-borne feedback and afferent reflex mechanisms to improve both hypoglycemia and hyperglycemia. exercise; postprandial glucose kinetics; insulin mobilization EXERCISE INCREASES PERIPHERAL GLUCOSE UPTAKE [rate of glucose disappearance (R d )] via insulin-dependent and -independent mechanisms. Simultaneously, rates of endogenous glucose production (EGP) increase to minimize risks of hypoglycemia (5, 9, 31, 33). These changes in glucose fluxes are facilitated by falling insulin and rising glucagon and catecholamine (34) concentrations in plasma together with emerging roles for potential blood-borne feedback and afferent reflex mechanisms in stimulating glucose rate of appearance (R a ) (6,18,19) and pancreatic islet hormone secretion (24).However, the increment in EGP may not sufficiently compensate for the increase in glucose disposal, thus predisposing to exercise-induced hypoglycemia in type 1 diabetes (T1D) (27). This could, at least in part, be due to impaired glucagon and/or catecholamine secretion and responsiveness because of concomitant dysfunction of ␣-cell or autonomic systems, respectively, that often afflicts patients with T1D (8, 17). Furthermore, the increase in insulin sensitivity can persist for several hours after cessation of exercise, according to a study in rats (14), hence, further predisposing individuals with T1D to delayed hypoglycemia (20,22). Although there have been numerous reports (11,12,25) evaluating glucose kinetics during and after exercise in individuals without diabetes, a comprehensive assessment of glucose turnover during and immediately after exercise applying state-of-the-art isotope dilution techniques has, to the best of our knowledge, not been conducted in individuals with T1D. In this context, in...

Quantifying the effect size of acute exercise on insulin sensitivity (SI exercise) and simultaneous measurement of glucose disappearance (R d), endogenous glucose production (EGP), and meal glucose appearance in the postprandial state has not been developed in humans. To do so, we studied 12 healthy subjects [5 men, age 37.1 Ϯ 3.1 yr, body mass index 24.1 Ϯ 1.1 kg/m 2 , fat-free mass (FFM) 50.9 Ϯ 3.9 kg] during moderate exercise at 50% V O2max for 75 min, 120 -195 min after a triple-tracer mixed meal consumed at time 0. Tracer infusion rates were adjusted to achieve constant tracer-to-tracee ratio and minimize non-steadystate errors. Glucose turnover was estimated by accounting for the nonstationary kinetics introduced by exercise. Insulin sensitivity index was calculated in each subject both in the absence [time (t) ϭ 0 -120 min, SI rest] and presence (t ϭ 0 -360 min, SIexercise) of physical activity. EGP at t ϭ 0 min (13.4 Ϯ 1.1 M·kg FFM Ϫ1 ·min Ϫ1 ) fell at t ϭ 120 min (2.4 Ϯ 0.4 M·kg FFM Ϫ1 ·min Ϫ1 ) and then rapidly rose almost eightfold at t ϭ 180 min (18.2 Ϯ 2.6 M·kg FFM Ϫ1 ·min Ϫ1 ) before gradually falling at t ϭ 360 min (10.6 Ϯ 0.9 M·kg FFM Ϫ1 ·min Ϫ1 ). Rd rapidly peaked at t ϭ 120 min at the start of exercise (89.5 Ϯ 11.6 M·kg FFM Ϫ1 ·min Ϫ1 ) and then gradually declined at t ϭ 195 min (26.4 Ϯ 3.3 M·kg FFM Ϫ1 ·min Ϫ1 ) before returning to baseline at t ϭ 360 min. SI exercise was significantly higher than SI rest (21.6 Ϯ 3.7 vs. 12.5 Ϯ 2.0 10 Ϫ4 dl·kg Ϫ1 ·min Ϫ1 per U/ml, P Ͻ 0.0005). Glucose turnover was estimated for the first time during exercise with the triple-tracer technique. Our results, applying stateof-the-art techniques, show that moderate exercise almost doubles postprandial insulin sensitivity index in healthy subjects.oral minimal model; exercise; insulin sensitivity IT IS WELL ESTABLISHED THAT exercise increases rates of glucose uptake (R d ) and that rates of endogenous glucose production (EGP) must increase to meet the increased metabolic demands of the exercising muscle to prevent hypoglycemia (13,16,38,40). These changes in glucose fluxes are facilitated by falling insulin and rising glucagon and catecholamine levels during exercise in healthy individuals (43). Although numerous studies have demonstrated increased R d and EGP during physical activity in individuals with and without diabetes (19,25) in the postabsorptive state, very few have examined the effects of exercise in the postprandial state in individuals with and without type 2 diabetes (8, 9, 23, 26 -28) and none in individuals with type 1 diabetes. Furthermore, very few studies (12) have used methods that minimize fluctuations in tracer-totracee specific activity to enable accurate continuous (every 10 min) measurement of glucose turnover and during the transition from rest to exercise in nondiabetic subjects. This latter point is important when developing a mathematical model for the next-generation artificial pancreas for type 1 diabetes.Models of insulin action and secretion in response to physiological perturbations...

e Although much is known about vancomycin-resistant (VR) Enterococcus faecium, little is known about the epidemiology of VR Enterococcus faecalis. The predilection of VR E. faecalis to transfer the vancomycin resistance determinant to Staphylococcus aureus is much greater than that of VR E. faecium. The epidemiology of VR E. faecalis has important implications regarding the emergence of vancomycin-resistant S. aureus (VRSA); 8 of 13 reported VRSA cases have been from Michigan. A retrospective case-case-control study was conducted at the Detroit Medical Center, located in southeastern Michigan. Unique patients with VR E. faecalis infection were matched to patients with strains of vancomycin-susceptible (VS) E. faecalis and to uninfected controls at a 1:1:1 ratio. Five hundred thirty-two VR E. faecalis cases were identified and were matched to 532 VS E. faecalis cases and 532 uninfected controls. The overall mean age of the study cohort (n ‫؍‬ 1,596) was 63.0 ؎ 17.4 years, and 747 (46.8%) individuals were male. Independent predictors for the isolation of VR E. faecalis (but not VS E. faecalis) compared to uninfected controls were an age of >65 years, nonhome residence, diabetes mellitus, peripheral vascular disease, exposure to cephalosporins and fluoroquinolones in the prior 3 months, and immunosuppressive status. Invasive procedures and/or surgery, chronic skin ulcers, and indwelling devices were risk factors for both VR E. faecalis and VS E. faecalis isolation. Cephalosporin and fluoroquinolone exposures were unique, independent predictors for isolation of VR E. faecalis. A majority of case patients had VR E. faecalis present at the time of admission. Control of VR E. faecalis, and ultimately VRSA, will likely require regional efforts focusing on infection prevention and antimicrobial stewardship.