BACKGROUND There is no evidence from randomized trials to support a strategy of lowering systolic blood pressure below 135 to 140 mm Hg in persons with type 2 diabetes mellitus. We investigated whether therapy targeting normal systolic pressure (i.e., <120 mm Hg) reduces major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events. METHODS A total of 4733 participants with type 2 diabetes were randomly assigned to intensive therapy, targeting a systolic pressure of less than 120 mm Hg, or standard therapy, targeting a systolic pressure of less than 140 mm Hg. The primary composite outcome was nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years. RESULTS After 1 year, the mean systolic blood pressure was 119.3 mm Hg in the intensive-therapy group and 133.5 mm Hg in the standard-therapy group. The annual rate of the primary outcome was 1.87% in the intensive-therapy group and 2.09% in the standard-therapy group (hazard ratio with intensive therapy, 0.88; 95% confidence interval [CI], 0.73 to 1.06; P = 0.20). The annual rates of death from any cause were 1.28% and 1.19% in the two groups, respectively (hazard ratio, 1.07; 95% CI, 0.85 to 1.35; P = 0.55). The annual rates of stroke, a prespecified secondary outcome, were 0.32% and 0.53% in the two groups, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P = 0.01). Serious adverse events attributed to antihypertensive treatment occurred in 77 of the 2362 participants in the intensive-therapy group (3.3%) and 30 of the 2371 participants in the standard-therapy group (1.3%) (P <0.001). CONCLUSIONS In patients with type 2 diabetes at high risk for cardiovascular events, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events. (ClinicalTrials.gov number, NCT00000620.)

The targeted literature search included evidence related to the effectiveness of 5 U.S. Food and Drug Administration-approved pharmacologic therapies for dementia for outcomes in the domains of cognition, global function, behavior/mood, and quality of life/activities of daily living. RECOMMENDATION 1: Clinicians should base the decision to initiate a trial of therapy with a cholinesterase inhibitor or memantine on individualized assessment. (Grade: weak recommendation, moderate-quality evidence.) RECOMMENDATION 2: Clinicians should base the choice of pharmacologic agents on tolerability, adverse effect profile, ease of use, and cost of medication. The evidence is insufficient to compare the effectiveness of different pharmacologic agents for the treatment of dementia. (Grade: weak recommendation, low-quality evidence.) RECOMMENDATION 3: There is an urgent need for further research on the clinical effectiveness of pharmacologic management of dementia.

OBJECTIVE -The purpose of this study was to determine whether implementation of a multicomponent organizational intervention can produce significant change in diabetes care and outcomes in community primary care practices.RESEARCH DESIGN AND METHODS -This was a group-randomized, controlled clinical trial evaluating the practical effectiveness of a multicomponent intervention (TRANSLATE) in 24 practices. The intervention included implementation of an electronic diabetes registry, visit reminders, and patient-specific physician alerts. A site coordinator facilitated previsit planning and a monthly review of performance with a local physician champion. The principle outcomes were the percentage of patients achieving target values for the composite of systolic blood pressure (SBP) Ͻ130 mmHg, LDL cholesterol Ͻ100 mg/dl, and A1C Ͻ7.0% at baseline and 12 months. Six process measures were also followed.RESULTS -Over 24 months, 69,965 visits from 8,405 adult patients with type 2 diabetes were recorded from 238 health care providers in 24 practices from 17 health systems. Diabetes process measures increased significantly more in intervention than in control practices, giving net increases as follows: foot examinations 35.0% (P Ͻ 0.0.001); annual eye examinations 25.9% (P Ͻ 0.001); renal testing 28.5% (P Ͻ 0.001); A1C testing 8.1%(P Ͻ 0.001); blood pressure monitoring 3.5% (P ϭ 0.05); and LDL testing 8.6% (P Ͻ 0.001). Mean A1C adjusted for age, sex, and comorbidity decreased significantly in intervention practices (P Ͻ 0.02). At 12 months, intervention practices had significantly greater improvement in achieving recommended clinical values for SBP, A1C, and LDL than control clinics (P ϭ 0.002).CONCLUSIONS -Introduction of a multicomponent organizational intervention in the primary care setting significantly increases the percentage of type 2 diabetic patients achieving recommended clinical outcomes.

Germline mutations in SPRTN cause Ruijs–Aalfs syndrome (RJALS), a disorder characterized by genome instability, progeria and early onset hepatocellular carcinoma. Spartan, the protein encoded by SPRTN, is a nuclear metalloprotease that is involved in the repair of DNA–protein crosslinks (DPCs). Although Sprtn hypomorphic mice recapitulate key progeroid phenotypes of RJALS, whether this model expressing low amounts of Spartan is prone to DPC repair defects and spontaneous tumors is unknown. Here, we showed that the livers of Sprtn hypomorphic mice accumulate DPCs containing Topoisomerase 1 covalently linked to DNA. Furthermore, these mice exhibited DNA damage, aneuploidy and spontaneous tumorigenesis in the liver. Collectively, these findings provide evidence that partial loss of Spartan impairs DPC repair and tumor suppression.

Orthostatic hypotension (OH) is associated with hypertension and diabetes mellitus. However, in populations with both hypertension and diabetes, its prevalence, the effect of intensive versus standard systolic blood pressure (BP) targets on incident OH, and its prognostic significance are unclear. In 4266 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) BP trial, seated BP was measured 3 times, followed by readings every minute for 3 minutes after standing. Orthostatic BP change, calculated as the minimum standing minus the mean seated systolic BP and diastolic BP, was assessed at baseline,12, and 48 months. The relationship between OH and clinical outcomes (total and cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, heart failure hospitalization or death and the primary composite outcome of non-fatal myocardial infarction, non-fatal stroke and cardiovascular death) was assessed using proportional hazards analysis. Consensus OH, defined by orthostatic decline in systolic BP ≥20 mm Hg and/or diastolic BP ≥10 mm Hg, occurred at ≥1 time point in 20% of participants. Neither age nor systolic BP treatment target (intensive, <120 mm Hg versus standard, <140 mm Hg) was related to OH incidence. Over a median follow-up of 46.9 months, OH was associated with increased risk of total death (HR=1.61, 95% CI 1.11–2.36) and heart failure death/hospitalization (HR=1.85, 95% CI 1.17–2.93), but not with the primary outcome or other prespecified outcomes. In patients with type 2 diabetes and hypertension, OH was common, not associated with intensive versus standard BP treatment goals, and predicted increased mortality and heart failure events.

PURPOSE We wanted to describe how primary care clinicians care for patients with type 2 diabetes.METHODS We undertook a cross-sectional study of 95 primary care clinicians and 822 of their established patients with type 2 diabetes from 4 practice-based, primary care research networks in the United States. Clinicians were surveyed about their training and practice. Patients completed a self-administered questionnaire about their care, and medical records were reviewed for complications, treatment, and diabetes-control indicators. RESULTSParticipating clinicians (average age, 45.7 years) saw an average of 32.6 adult patients with diabetes per month. Patients (average age, 59.7 years) reported a mean duration of diabetes of 9.1 years, with 34.3% having had the disease more than 10 years. Nearly one half (47.5%) of the patients had at least 1 diabetes-related complication, and 60.8% reported a body mass index greater than 30. Mean glycosylated hemoglobin (HbA 1c ) level was 7.6% (SD 1.73), and 40.5% of patients had values <7%. Only 35.3% of patients had adequate blood pressure control (<130/85 mm Hg), and only 43.7% had low-density lipoprotein cholesterol (LDL-C) levels <100 mg/dL. Only 7.0% of patients met all 3 control targets. Multilevel models showed that patient ethnicity, practice type, involvement of midlevel clinicians, and treatment were associated with HbA 1c level; patient age, education level, and practice type were associated with blood pressure control; and patient ethnicity was associated with LDL-C control.CONCLUSIONS Only modest numbers of patients achieve established targets of diabetes control. Reengineering primary care practice may be necessary to substantially improve care.

About 75% of the total P in conventional soybean [Glycine max (L.) Merr.] seed is phytate P, which cannot be readily digested by nonruminant livestock, such as swine and poultry. The phytate P in soybean lines homozygous for the recessive alleles pha1 and pha2 is reduced to about 25% of the total P. The objective of this study was to determine the influence of low phytate (LP) on agronomic and seed traits of soybean. Three populations were developed by crossing three cultivars with normal phytate (NP) to the LP line CX1834‐1‐6. From each population, 10 LP and 10 NP lines were selected and grown in replicated tests at three Iowa environments during 2003. The mean total P of the LP and NP lines was not significantly different, but the mean phytate P, inorganic P, and other P were significantly different for the two types of lines in the three populations. The mean seedling emergence of the LP lines was 45% compared with 68% for the NP lines. The mean differences between the LP and NP lines for the other agronomic and seed traits were not significant in one or more of the populations. On the basis of these results, reduced seedling emergence will be a major factor to consider in the development of commercially viable cultivars with the pha1pha1pha2pha2 genotype for LP.

Workshop participants strongly advocated developing new systems to address common barriers to glycemic control and recommended several initial steps toward this goal. These recommendations included further studies to establish the clinical value of pharmacological therapies, continuing basic research to elucidate the nature and mechanisms of beta-cell failure in type 2 diabetes mellitus, and exploring new educational approaches to promote pathophysiology-based clinical practices. The Endocrine Society has launched a new website to continue the discussion between endocrinologists and primary care physicians on beta-cell pathophysiology in type 2 diabetes and its clinical implications. Join the conversation at http://www.betacellsindiabetes.org