Long-term effects of intensive glycemic and blood pressure control and fenofibrate use on kidney outcomes

Background and objectives In people with type 2 diabetes, aggressive control of glycemia, BP, and lipids have resulted in conflicting short-term (<5 years) kidney outcomes. We aimed to determine the long-term kidney effects of these interventions. Design, setting, participants, & measurements The Action to Control Cardiovascular Risk in Diabetes (ACCORD) was a multifactorial intervention study in people with type 2 diabetes at high risk for cardiovascular disease (n=10,251), to examine the effects of intensive glycemic control (hemoglobin A1c <6.0% versus 7%-7.9%), BP control (systolic BP <120 mm Hg versus <140 mm Hg) or fenofibrate versus placebo added to simvastatin on cardiovascular events and death. The glycemia trial lasted 3.7 years and participants were followed for another 6.5 years in ACCORDION, the ACCORD Follow-On Study. The post hoc primary composite kidney outcome was defined as incident macroalbuminuria, creatinine doubling, need for dialysis, or death by any cause. Cox proportional hazards regression estimated the effect of each intervention on the composite outcome and individual components. In secondary outcome analyses, competing risk regression was used to account for the risk of death in incident kidney outcomes. Analyses were adjusted for sociodemographics, randomization groups, and clinical factors. Results There were 988 cases of incident macroalbuminuria, 954 with doubling of creatinine, 351 requiring dialysis, and 1905 deaths. Hazard ratios (HRs) for the composite outcome with intensive glycemic, BP control, and fenofibrate use compared with standard therapy were 0.92 (95% confidence interval [95% CI], 0.86 to 0.98), 1.16 (95% CI, 1.05 to 1.28), and 1.16 (95% CI, 1.06 to 1.27). Multivariable, secondary outcome analyses showed that in the glycemia trial, only macroalbuminuria was significantly decreased (HR, 0.68; 95% CI, 0.59 to 0.77). In the BP and lipid trials, only creatinine doubling was affected (HR, 1.64; 95% CI, 1.30 to 2.06 and HR, 2.00; 95% CI, 1.61 to 2.49, respectively). Conclusions In people with type 2 diabetes at high risk for cardiovascular disease, intensive glycemic control may result in a long-term reduction in macroalbuminuria; however, intensive BP control and fenofibrates may increase the risk for adverse kidney events

The Plasma Environment of Comets

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138863/1/rog199129s2976.pd

Near-Simultaneous Polar and DMSP Measurements of Topside Ionosphere Field - Aligned Flows at High Latitudes

Near-simultaneous observations of topside 0' parallel flows are presented for four periods of measurement by POLAR and DMSP satellites during April 1996. The POLAR measurements are from Southern perigee measurements near 5000 km altitude, while the DMSP measurements were from 840 km altitude. These observations provide a view of wide-spread upward/downward ionospheric O(+) flows over the broad polar region along extended and multiple distinct satellite tracks. In general, the velocities are upward toward expected cleft and auroral latitudes, typically about a 2-10 km/s at 5000 km altitude, and 0-2 km/s at 840 km altitudes. At the highest, polar cap latitudes, downward velocities are more frequent at both altitudes, but especially at the lower 840 km altitude. The downward velocities were typically a few hundred d s at 840 altitude, and 0-1 km/s at 5000 km altitude. In some instances, apparently downward velocities were observed at 840 km altitudes while upward 0' flows were observed at 5000 km altitude on the same flux tube. The O+ density were characteristically 1-10 O(+)/cu cm at 5000 km altitude and 10(exp 3) - 10(exp 40 O(+)/cu cm at 840 km altitude, while the O(+) flux were characteristically 1 10(exp 5) - 10(exp 7) O(+)+/sq cm -sec at 5000 km altitudes and characteristically 10(exp 7) - 10(exp 9) O(+)/sq cm -sec at 840 km altitude. We have also examined the dual altitude parameter measurements for a polar cap field line, the POLAR and DMSP measurements approximately 30 minutes apart, and compared them with results from a transport simulation in which a flux tube was subjected to a brief pulse of soft electron precipitation and topside transverse ion heating. The simulated density and velocity altitude profiles for 5 minutes later generally matched the observations, except that the observed downward velocities (500 - 600 m/s) at 840 km altitude were much larger than those simulated

Patient health utility equations for a type 2 diabetes model.

OBJECTIVE: To estimate the health utility impact of diabetes-related complications in a large, longitudinal U.S. sample of people with type 2 diabetes. RESEARCH DESIGN AND METHODS: We combined Health Utilities Index Mark 3 data on patients with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Look AHEAD (Action for Health in Diabetes) trials and their follow-on studies. Complications were classified as events if they occurred in the year preceding the utility measurement; otherwise, they were classified as a history of the complication. We estimated utility decrements associated with complications using a fixed-effects regression model. RESULTS: Our sample included 15,252 persons with an average follow-up of 8.2 years and a total of 128,873 person-visit observations. The largest, statistically significant (P &lt; 0.05) health utility decrements were for stroke (event, -0.109; history, -0.051), amputation (event, -0.092; history, -0.150), congestive heart failure (event, -0.051; history, -0.041), dialysis (event, -0.039), estimated glomerular filtration rate (eGFR) &lt;30 mL/min/1.73 m2 (event, -0.043; history, -0.025), angina (history, -0.028), and myocardial infarction (MI) (event, -0.028). There were smaller effects for laser photocoagulation and eGFR &lt;60 mL/min/1.73 m2. Decrements for dialysis history, angina event, MI history, revascularization event, revascularization history, laser photocoagulation event, and hypoglycemia were not significant (P ≥ 0.05). CONCLUSIONS: With use of a large study sample and a longitudinal design, our estimated health utility scores are expected to be largely unbiased. Estimates can be used to describe the health utility impact of diabetes complications, improve cost-effectiveness models, and inform diabetes policies