Is it time to reduce the length of postgraduate training for physician-scientists in internal medicine?

Physician-scientists play a crucial role in advancing medical knowledge and patient care, yet the long periods of time required to complete training may impede expansion of this workforce. We examined the relationship between postgraduate training and time to receipt of NIH or Veterans Affairs career development awards (CDAs) for physician-scientists in internal medicine. Data from NIH RePORTER were analyzed for internal medicine residency graduates who received specific CDAs (K08, K23, K99, or IK2) in 2022. Additionally, information on degrees and training duration was collected. Internal medicine residency graduates constituted 19% of K awardees and 28% of IK2 awardees. Of MD-PhD internal medicine-trained graduates who received a K award, 92% received a K08 award; of MD-only graduates who received a K award, a majority received a K23 award. The median time from medical school graduation to CDA was 9.6 years for K awardees and 10.2 years for IK2 awardees. The time from medical school graduation to K or IK2 award was shorter for US MD-PhD graduates than US MD-only graduates. We propose that the time from medical school graduation to receipt of CDAs must be shortened to accelerate training and retention of physician-scientists.

Clinical effectiveness and cost-impact after 2 years of a ketogenic diet and virtual coaching intervention for patients with diabetes.

AIM: We previously evaluated the impacts at 5 months of a digitally delivered coaching intervention in which participants are instructed to adhere to a very low carbohydrate, ketogenic diet. With extended follow-up (24 months), we assessed the longer-term effects of this intervention on changes in clinical outcomes, health care utilization and costs associated with outpatient, inpatient and emergency department use in the Veterans Health Administration. MATERIALS AND METHODS: We employed a difference-in-differences model with a waiting list control group to estimate the 24-month change in glycated haemoglobin, body mass index, blood pressure, prescription medication use, health care utilization rates and associated costs. The analysis included 550 people with type 2 diabetes who were overweight or obese and enrolled in the Veterans Health Administration for health care. Data were obtained from electronic health records from 2018 to 2021. RESULTS: The virtual coaching and ketogenic diet intervention was associated with significant reductions in body mass index [-1.56 (SE 0.390)] and total monthly diabetes medication usage [-0.35 (SE 0.054)]. No statistically significant differences in glycated haemoglobin, blood pressure, outpatient visits, inpatient visits, or emergency department visits were observed. The intervention was associated with reductions in per-patient, per-month outpatient spending [-USD286.80 (SE 97.175)] and prescription drug costs (-USD105.40 (SE 30.332)]. CONCLUSIONS: A virtual coaching intervention with a ketogenic diet component offered modest effects on clinical and cost parameters in people with type 2 diabetes and with obesity or overweight. Health care systems should develop methods to assess participant progress and engagement over time if they adopt such interventions, to ensure continued patient engagement and goal achievement.

Effects of the DASH diet and losartan on serum urate among adults with hypertension: Results of a randomized trial.

Serum urate is a risk factor for hypertension and gout. The DASH diet and losartan independently lower blood pressure (BP); however, their effects on serum urate are understudied. We performed a post-hoc analysis of the DASH-losartan trial, which randomized participants with hypertension in parallel fashion to the DASH diet or a standard American diet (control) and in crossover fashion to 4-week losartan or placebo. Serum urate was measured at baseline and after each 4-week period. Diets were designed to maintain weight constant. We examined the effects of DASH (vs control) and/or losartan (vs placebo) on serum urate, overall and among those with baseline serum urate ≥6 mg/dL, using generalized estimating equations. Of 55 participants (mean age 52 years, 58% women, 64% Black), mean (±SD) baseline ambulatory SBP/DBP was 146±12/91±9 and mean (±SD) serum urate was 5.2±1.2 mg/dL. The DASH diet did not significantly reduce urate levels overall (mean difference -0.05 mg/dL; 95%CI: -0.39, 0.28), but did decrease levels among participants with baseline hyperuricemia (-0.33 mg/dL; 95%CI: -0.87, 0.21; P-interaction=0.007 across hyperuricemia groups). Losartan significantly decreased serum urate (-0.23 mg/dL; 95%CI: -0.40, -0.05) with greater effects on serum urate among adults <60 years old versus adults ≥60 years old (-0.33 mg/dL vs 0.16 mg/dL, P interaction = 0.003). In summary, the DASH diet significantly decreased serum urate among participants with higher urate at baseline, while losartan significantly reduced serum urate, especially among younger adults. Future research should examine the effects of these interventions in patients with hyperuricemia or gout.

The Growing Role of Technology in the Care of Older Adults With Diabetes.

The integration of technologies such as continuous glucose monitors, insulin pumps, and smart pens into diabetes management has the potential to support the transformation of health care services that provide a higher quality of diabetes care, lower costs and administrative burdens, and greater empowerment for people with diabetes and their caregivers. Among people with diabetes, older adults are a distinct subpopulation in terms of their clinical heterogeneity, care priorities, and technology integration. The scientific evidence and clinical experience with these technologies among older adults are growing but are still modest. In this review, we describe the current knowledge regarding the impact of technology in older adults with diabetes, identify major barriers to the use of existing and emerging technologies, describe areas of care that could be optimized by technology, and identify areas for future research to fulfill the potential promise of evidence-based technology integrated into care for this important population.

Association of hemoglobin A1c stability with mortality and diabetes complications in older adults with diabetes.

INTRODUCTION: Hemoglobin A1c (A1c) treatment goals in older adults should be individualized to balance risks and benefits. It is unclear if A1c stability over time within unique target ranges also affects adverse outcomes. RESEARCH DESIGN AND METHODS: We conducted a retrospective observational cohort study from 2004 to 2016 of veterans with diabetes and at least four A1c tests during a 3-year baseline. We generated four distinct categories based on the percentage of time that baseline A1c levels were within patient-specific target ranges: ≥60% time in range (TIR), ≥60% time below range (TBR), ≥60% time above range (TAR), and a mixed group with all times <60%. We assessed associations of these categories with mortality, macrovascular, and microvascular complications. RESULTS: We studied 397 634 patients (mean age 76.9 years, SD 5.7) with an average of 5.5 years of follow-up. In comparison to ≥60% A1c TIR, mortality was increased with ≥60% TBR, ≥60% TAR, and the mixed group, with HRs of 1.12 (95% CI 1.11 to 1.14), 1.10 (95% CI 1.08 to 1.12), and 1.06 (95% CI 1.04 to 1.07), respectively. Macrovascular complications were increased with ≥60% TBR and ≥60% TAR, with estimates of 1.04 (95% CI 1.01 to 1.06) and 1.06 (95% CI 1.03 to 1.09). Microvascular complications were lower with ≥60% TBR (HR 0.97, 95% CI 0.95 to 1.00) and higher with ≥60% TAR (HR 1.11, 95% CI 1.08 to 1.14). Results were similar with higher TIR thresholds, shorter follow-up, and competing risk of mortality. CONCLUSIONS: In older adults with diabetes, mortality and macrovascular complications are associated with increased time above and below individualized A1c target ranges. Higher A1c TIR may identify patients with lower risk of adverse outcomes.

The National Clinical Care Commission Report to Congress: Summary and Next Steps.

The U.S. is experiencing an epidemic of type 2 diabetes. Socioeconomically disadvantaged and certain racial and ethnic groups experience a disproportionate burden from diabetes and are subject to disparities in treatment and outcomes. The National Clinical Care Commission (NCCC) was charged with making recommendations to leverage federal policies and programs to more effectively prevent and control diabetes and its complications. The NCCC determined that diabetes cannot be addressed simply as a medical problem but must also be addressed as a societal problem requiring social, clinical, and public health policy solutions. As a result, the NCCC's recommendations address policies and programs of both non-health-related and health-related federal agencies. The NCCC report, submitted to the U.S. Congress on 6 January 2022, makes 39 specific recommendations, including three foundational recommendations that non-health-related and health-related federal agencies coordinate their activities to better address diabetes, that all federal agencies and departments ensure that health equity is a guiding principle for their policies and programs that impact diabetes, and that all Americans have access to comprehensive and affordable health care. Specific recommendations are also made to improve general population-wide policies and programs that impact diabetes risk and control, to increase awareness and prevention efforts among those at high risk for type 2 diabetes, and to remove barriers to access to effective treatments for diabetes and its complications. Finally, the NCCC recommends that an Office of National Diabetes Policy be established to coordinate the activities of health-related and non-health-related federal agencies to address diabetes prevention and treatment. The NCCC urges Congress and the Secretary of Health and Human Services to implement these recommendations to protect the health and well-being of the more than 130 million Americans at risk for and living with diabetes.

The National Clinical Care Commission Report to Congress: Recommendations to Better Leverage Federal Policies and Programs to Prevent and Control Diabetes.

The National Clinical Care Commission (NCCC) was established by Congress to make recommendations to leverage federal policies and programs to more effectively prevent and treat diabetes and its complications. The NCCC developed a guiding framework that incorporated elements of the Socioecological and Chronic Care Models. It surveyed federal agencies and conducted follow-up meetings with representatives from 10 health-related and 11 non-health-related federal agencies. It held 12 public meetings, solicited public comments, met with numerous interested parties and key informants, and performed comprehensive literature reviews. The final report, transmitted to Congress in January 2022, contained 39 specific recommendations, including 3 foundational recommendations that addressed the necessity of an all-of-government approach to diabetes, health equity, and access to health care. At the general population level, the NCCC recommended that the federal government adopt a health-in-all-policies approach so that the activities of non-health-related federal agencies that address agriculture, food, housing, transportation, commerce, and the environment be coordinated with those of health-related federal agencies to affirmatively address the social and environmental conditions that contribute to diabetes and its complications. For individuals at risk for type 2 diabetes, including those with prediabetes, the NCCC recommended that federal policies and programs be strengthened to increase awareness of prediabetes and the availability of, referral to, and insurance coverage for intensive lifestyle interventions for diabetes prevention and that data be assembled to seek approval of metformin for diabetes prevention. For people with diabetes and its complications, the NCCC recommended that barriers to proven effective treatments for diabetes and its complications be removed, the size and competence of the workforce to treat diabetes and its complications be increased, and new payment models be implemented to support access to lifesaving medications and proven effective treatments for diabetes and its complications. The NCCC also outlined an ambitious research agenda. The NCCC strongly encourages the public to support these recommendations and Congress to take swift action.

The National Clinical Care Commission Report to Congress: Leveraging Federal Policies and Programs to Improve Diabetes Treatment and Reduce Complications.

The Treatment and Complications subcommittee of the National Clinical Care Commission focused on factors likely to improve the delivery of high-quality care to all people with diabetes. The gap between available resources and the needs of people living with diabetes adversely impacts both treatment and outcomes. The Commission's recommendations are designed to bridge this gap. At the patient level, the Commission recommends reducing barriers and streamlining administrative processes to improve access to diabetes self-management training, diabetes devices, virtual care, and insulin. At the practice level, we recommend enhancing programs that support team-based care and developing capacity to support technology-enabled mentoring interventions. At the health system level, we recommend that the Department of Health and Human Services routinely assess the needs of the health care workforce and ensure funding of training programs directed to meet those needs. At the health policy level, we recommend establishing a process to identify and ensure pre-deductible insurance coverage for high-value diabetes treatments and services and developing a quality measure that reduces risk of hypoglycemia and enhances patient safety. We also identified several areas that need additional research, such as studying the barriers to uptake of diabetes self-management education and support, exploring methods to implement team-based care, and evaluating the importance of digital connectivity as a social determinant of health. The Commission strongly encourages Congress, the Department of Health and Human Services, and other federal departments and agencies to take swift action to implement these recommendations to improve health outcomes and quality of life among people living with diabetes.

The National Clinical Care Commission Report to Congress: Background, Methods, and Foundational Recommendations.

Since the first Federal Commission on Diabetes issued its report in 1975, the diabetes epidemic in the U.S. has accelerated, and efforts to translate advances in diabetes treatment into routine clinical practice have stalled. In 2021, the National Clinical Care Commission (NCCC) delivered a report to Congress that provided recommendations to leverage federal policies and programs to more effectively prevent and treat diabetes and its complications. In the five articles in this series, we present the NCCC's evidence-based recommendations to 1) reduce diabetes-related risks, prevent type 2 diabetes, and avert diabetes complications through changes in federal policies and programs affecting the general population; 2) prevent type 2 diabetes in at-risk individuals through targeted lifestyle and medication interventions; and 3) improve the treatment of diabetes and its complications to improve the health outcomes of people with diabetes. In this first article, we review the successes and limitations of previous federal efforts to combat diabetes. We then describe the establishment of and charge to the NCCC. We discuss the development of a hybrid conceptual model that guided the NCCC's novel all-of-government approach to address diabetes as both a societal and medical problem. We then review the procedures used by the NCCC to gather information from federal agencies, stakeholders, key informants, and the public and to conduct literature reviews. Finally, we review the NCCC's three foundational recommendations: 1) improve the coordination of non-health-related and health-related federal agencies to address the social and environmental conditions that are accelerating the diabetes epidemic; 2) ensure that all Americans at risk for and with diabetes have health insurance and access to health care; and 3) ensure that all federal policies and programs promote health equity in diabetes.

Association of hemoglobin A1c time in range with risk for diabetes complications.

INTRODUCTION: We assessed the association between hemoglobin A1c time in range (A1c TIR), based on unique patient-level A1c target ranges, with risks of developing microvascular and macrovascular complications in older adults with diabetes. RESEARCH DESIGN AND METHODS: We used a retrospective observational study design and identified patients with diabetes from the Department of Veterans Affairs (n=397 634). Patients were 65 years and older and enrolled in Medicare during the period 2004-2016. Patients were assigned to individualized A1c target ranges based on estimated life expectancy and the presence or absence of diabetes complications. We computed A1c TIR for patients with at least four A1c tests during a 3-year baseline period. The association between A1c TIR and time to incident microvascular and macrovascular complications was studied in models that included A1c mean and A1c SD. RESULTS: We identified 74 016 patients to assess for incident microvascular complications and 89 625 patients to assess for macrovascular complications during an average follow-up of 5.5 years. Cox proportional hazards models showed lower A1c TIR was associated with higher risk of microvascular (A1c TIR 0% to <20%; HR=1.04; 95%) and macrovascular complications (A1c TIR 0% to <20%; HR=1.07; 95%). A1c mean was associated with increased risk of microvascular and macrovascular complications but A1c SD was not. The association of A1c TIR with incidence and progression of individual diabetes complications within the microvascular and macrovascular composites showed similar trends. CONCLUSIONS: Maintaining stability of A1c levels in unique target ranges was associated with lower likelihood of developing microvascular and macrovascular complications in older adults with diabetes.

Pearls of wisdom for aspiring physician-scientist residency applicants and program directors.

Postgraduate physician-scientist training programs (PSTPs) enhance the experiences of physician-scientist trainees following medical school graduation. PSTPs usually span residency and fellowship training, but this varies widely by institution. Applicant competitiveness for these programs would be enhanced, and unnecessary trainee anxiety relieved, by a clear understanding of what factors define a successful PSTP matriculant. Such information would also be invaluable to PSTP directors and would allow benchmarking of their admissions processes with peer programs. We conducted a survey of PSTP directors across the US to understand the importance they placed on components of PSTP applications. Of 41 survey respondents, most were from internal medicine and pediatrics residency programs. Of all components in the application, two elements were considered very important by a majority of PSTP directors: (a) having one or more first-author publications and (b) the thesis advisor's letter. Less weight was consistently placed on factors often considered more relevant for non-physician-scientist postgraduate applicants - such as US Medical Licensing Examination scores, awards, and leadership activities. The data presented here highlight important metrics for PSTP applicants and directors and suggest that indicators of scientific productivity and commitment to research outweigh traditional quantitative measures of medical school performance.

A novel dataset of predictors of mortality for older Veterans living with type II diabetes.

The dataset summarized in this article includes a nationwide prevalence sample of U.S. military Veterans who were aged 65 years or older, dually enrolled in the Veterans Health Administration and traditional Medicare and had a previous diagnosis of diabetes (diabetes mellitus) as of December 2005 (N = 275,190) [1]. Our data were originally used to develop and validate prognostic indices of 5- and 10-year mortality among older Veterans with diabetes. We include various potential predictors including demographics (e.g., sex, age, marital status, and VA priority group), healthcare utilization (e.g., # of outpatient visits, # days of inpatient stays), medication history, and major comorbidities. This novel dataset provides researchers with an opportunity to study the associations between a large variety of individual-level risk factors and longevity for patients living with diabetes.

Effectiveness of a ketogenic diet and virtual coaching intervention for patients with diabetes: A difference-in-differences analysis.

AIM: To test the effectiveness of a ketogenic diet and virtual coaching intervention in controlling markers of diabetes care and healthcare utilization. MATERIALS AND METHODS: Using a difference-in-differences analysis with a waiting list control group-a quasi-experimental methodology-we estimated the 5-month change in HbA1c, body mass index, blood pressure, prescription medication use and costs, as well as healthcare utilization. The analysis included 590 patients with diabetes who were also overweight or obese, and who regularly utilize the Veterans Health Administration (VA) for healthcare. We used data from VA electronic health records from 2018 to 2020. RESULTS: The ketogenic diet and virtual coaching intervention was associated with significant reductions in HbA1c (-0.69 [95% CI -1.02, -0.36]), diabetes medication fills (-0.38, [-0.49, -0.26]), body mass index (-1.07, [-1.95, -0.19]), diastolic blood pressure levels (-1.43, [-2.72, -0.14]), outpatient visits (-0.36, [-0.70, -0.02]) and prescription drug costs (-34.54 [-48.56, -20.53]). We found no significant change in emergency department visits (-0.02 [-0.05, 0.01]) or inpatient admissions (-0.01 [-0.02, 0.01]). CONCLUSIONS: This real-world assessment of a virtual coaching and diet programme shows that such an intervention offers short-term benefits on markers of diabetes care and healthcare utilization in patients with diabetes.

Increased Hemoglobin A1c Time in Range Reduces Adverse Health Outcomes in Older Adults With Diabetes.

OBJECTIVE: Short- and long-term glycemic variability are risk factors for diabetes complications. However, there are no validated A1C target ranges or measures of A1C stability in older adults. We evaluated the association of a patient-specific A1C variability measure, A1C time in range (A1C TIR), on major adverse outcomes. RESEARCH DESIGN AND METHODS: We conducted a retrospective observational study using administrative data from the Department of Veterans Affairs and Medicare from 2004 to 2016. Patients were ≥65 years old, had diabetes, and had at least four A1C tests during a 3-year baseline period. A1C TIR was the percentage of days during the baseline in which A1C was in an individualized target range (6.0-7.0% up to 8.0-9.0%) on the basis of clinical characteristics and predicted life expectancy. Increasing A1C TIR was divided into categories of 20% increments and linked to mortality and cardiovascular disease (CVD) (i.e., myocardial infarction, stroke). RESULTS: The study included 402,043 veterans (mean [SD] age 76.9 [5.7] years, 98.8% male). During an average of 5.5 years of follow-up, A1C TIR had a graded relationship with mortality and CVD. Cox proportional hazards models showed that lower A1C TIR was associated with increased mortality (A1C TIR 0 to <20%: hazard ratio [HR] 1.22 [95% CI 1.20-1.25]) and CVD (A1C TIR 0 to <20%: HR 1.14 [95% CI 1.11-1.19]) compared with A1C TIR 80-100%. Competing risk models and shorter follow-up (e.g., 24 months) showed similar results. CONCLUSIONS: In older adults with diabetes, maintaining A1C levels within individualized target ranges is associated with lower risk of mortality and CVD.

Association between hemoglobin A1c variability and hypoglycemia-related hospitalizations in veterans with diabetes mellitus.

INTRODUCTION: To study the impact of hemoglobin A1c (A1c) variability on the risk of hypoglycemia-related hospitalization (HRH) in veterans with diabetes mellitus. RESEARCH DESIGN AND METHODS: 342 059 veterans with diabetes aged 65 years or older were identified for a retrospective cohort study. All participants had a 3-year baseline period from January 1, 2005 to December 31, 2016, during which they had at least four A1c tests. A1c variability measures included coefficient of variation (A1c CV), A1c SD, and adjusted A1c SD. HRH was identified during a 2-year follow-up period from Medicare and the Veterans Health Administration through validated algorithms of International Classification of Diseases (ICD)-9 and ICD-10 codes. Logistic regression modeling was used to evaluate the relationship between A1c variability and HRH risk while controlling for relevant clinical covariates. RESULTS: 2871 patients had one or more HRH in the 2-year follow-up period. HRH risk increased with greater A1c variability, and this was consistent across A1c CV, A1c SD, and adjusted A1c SD. Average A1c levels were also independently associated with HRH, with levels <7.0% (53 mmol/mol) having lower risk and >9% (75 mmol/mol) with greater risk. The relationships between A1c variability remained significant after controlling for average A1c levels and prior HRH during the baseline period. CONCLUSION: Increasing A1c variability and elevated A1c levels are associated with a greater risk of HRH in older adults with diabetes. Clinicians should consider A1c variability when assessing patients for risk of severe hypoglycemia.

Diabetes in ageing: pathways for developing the evidence base for clinical guidance.

Older adults with diabetes are heterogeneous in their medical, functional, and cognitive status, and require careful individualisation of their treatment regimens. However, in the absence of detailed information from clinical trials involving older people with varying characteristics, there is little evidence-based guidance, which is a notable limitation of current approaches to care. It is important to recognise that older people with diabetes might vary in their profiles according to age category, functional health, presence of frailty, and comorbidity profiles. In addition, all older adults with diabetes require an individualised approach to care, ranging from robust individuals to those residing in care homes with a short life expectancy, those requiring palliative care, or those requiring end-of-life management. In this Review, our multidisciplinary team of experts describes the current evidence in several important areas in geriatric diabetes, and outlines key research gaps and research questions in each of these areas with the aim to develop evidence-based recommendations to improve the outcomes of interest in older adults.

Predicting 5- and 10-Year Mortality Risk in Older Adults With Diabetes.

OBJECTIVE: Several diabetes clinical practice guidelines suggest that treatment goals may be modified in older adults on the basis of comorbidities, complications, and life expectancy. The long-term benefits of treatment intensification may not outweigh short-term risks for patients with limited life expectancy. Because of the uncertainty of determining life expectancy for individual patients, we sought to develop and validate prognostic indices for mortality in older adults with diabetes. RESEARCH DESIGN AND METHODS: We used a prevalence sample of veterans with diabetes who were aged ≥65 years on 1 January 2006 (N = 275,190). Administrative data were queried for potential predictors that included patient demographics, comorbidities, procedure codes, laboratory values and anthropomorphic measurements, medication history, and previous health service utilization. Logistic least absolute shrinkage and selection operator regressions were used to identify variables independently associated with mortality. The resulting odds ratios were then weighted to create prognostic indices of mortality over 5 and 10 years. RESULTS: Thirty-seven predictors of mortality were identified: 4 demographic variables, prescriptions for insulin or sulfonylureas or blood pressure medications, 6 biomarkers, previous outpatient and inpatient utilization, and 22 comorbidities/procedures. The prognostic indices showed good discrimination, with C-statistics of 0.74 and 0.76 for 5- and 10-year mortality, respectively. The indices also demonstrated excellent agreement between observed outcome and predictions, with calibration slopes of 1.01 for both 5- and 10-year mortality. CONCLUSIONS: Prognostic indices obtained from administrative data can predict 5- and 10-year mortality in older adults with diabetes. Such a tool may enable clinicians and patients to develop individualized treatment goals that balance risks and benefits of treatment intensification.

2019 Endocrine Society Measures Set for Older Adults With Type 2 Diabetes Who Are at Risk for Hypoglycemia.

CONTEXT: Hypoglycemia in the outpatient setting has a significant financial impact on the health care system and negative impact on a person's quality of life. Primary care physicians must address a multitude of issues in a visit with a person with type 2 diabetes mellitus (T2DM), often leaving little time to ask about hypoglycemia. OBJECTIVE: To develop quality measures that focus on outpatient hypoglycemia episodes for patients 65 and older with T2DM, which facilitate a clinician's ability to identify opportunities to improve the quality of care and reduce hypoglycemic episodes. PARTICIPANTS AND PROCESS: A technical expert panel established by the Endocrine Society in March 2019, which includes endocrinologists, primary care physicians, a diabetes care and education specialist/pharmacist, and a patient, developed 3 outpatient hypoglycemia quality measures. The measure set is intended to improve quality of care for patients with T2DM who are at greatest risk for hypoglycemia. The measures were available for public comment in July 2019. A fourth measure on shared decision-making was removed from the final measure set based on public feedback. CONCLUSION: A lack of outpatient hypoglycemia measures focusing on older adults with T2DM is a barrier to improving care of people with diabetes and reducing hypoglycemic episodes. This paper provides measure specifications for 3 measures that may be used to focus quality improvement efforts on patients at greatest risk for hypoglycemia.

Interactions of the DASH Diet with the Renin-Angiotensin-Aldosterone System.

BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet is widely recommended to lower blood pressure, but its mechanisms of action are unclear. Lines of evidence suggest an interaction with the renin-angiotensin-aldosterone system (RAAS). OBJECTIVE: We conducted a randomized, controlled, cross-over feeding trial to test RAAS-related mechanisms underlying the DASH diet in patients with isolated systolic hypertension. METHODS: Participants entered a 1-wk run-in period on a control (CON) diet and then consumed the DASH or CON diets for 4 wk each in randomized sequence. Calorie content was controlled to maintain weight, and sodium intake was set at 3 g daily. After each diet, participants had hormonal and hemodynamic assessments obtained at baseline, in response to RAAS inhibition with captopril (CAP) 25 mg, and to graded angiotensin II (AngII) infusions (1 ng/kg and 3 ng/kg × 45 min). Primary outcomes were mean arterial pressure (MAP) and renal blood flow (RBF), and secondary outcomes were diastolic function, pulse wave velocity (PWV), plasma renin activity (PRA), and aldosterone (ALDO) responses by diet. RESULTS: In total, 44 (19 female) participants completed the study. DASH + CAP significantly lowered MAP compared with CON + CAP (83 ± 11 mmHg compared with 88 ± 14 mmHg, P <0.01). RBF was increased with DASH + CAP compared with CON + CAP (486 ± 149 cc/min compared with 451 ± 171 cc/min, P <0.001). Study diet did not change PWV but CAP reduced diastolic function on the DASH diet (P <0.05). DASH + CAP significantly increased PRA compared with CON + CAP (1.52 ± 1.78 ng/mL/min compared with 0.89 ± 1.17 ng/mL/min; P <0.001). ALDO sensitivity to AngII infusion was greater with DASH when compared to CON (17.4 ± 7.7 ng/mL compared with 13.8 ± 6.2 ng/dL, P <0.05) as was DASH + CAP compared with CON + CAP (15.1 ± 5.3 ng/dL compared with 13.1 ± 5.9 ng/mL, P <0.05). CONCLUSIONS: The DASH diet interacts with the RAAS resulting in vascular and hormonal responses similar to a natriuretic effect, which appears to augment the hypotensive effect of angiotensin-converting enzyme (ACE) inhibition in individuals with isolated systolic hypertension. This trial was registered at clinicaltrials.gov as NCT00123006.