Key Points
Question
What are the effects of a Dietary Approaches to Stop Hypertension (DASH)–style diet and sodium reduction on blood pressure in adults with type 2 diabetes?
Findings
In this randomized clinical trial of 102 individuals with type 2 diabetes, the combination of sodium reduction and a DASH-style diet optimized for diabetes lowered systolic blood pressure by 4.6 mm Hg.
Meaning
The trial results found that for adults with type 2 diabetes, most of whom were treated with multiple antihypertensive medications, a lower sodium DASH-style diet achieved a clinically meaningful reduction in blood pressure, primarily from sodium reduction.
Abstract
Importance
People with type 2 diabetes and hypertension are at high risk for blood pressure–related cardiovascular events. Few trials have tested the blood pressure–lowering effects of dietary interventions other than weight loss in this population.
Objective
To determine the effects of dietary patterns and sodium reduction on blood pressure in adults with type 2 diabetes.
Design, Setting, and Participants
Dietary Approaches to Stop Hypertension for Diabetes (DASH4D) was a randomized 4-period crossover feeding study conducted at a community-based study center from June 2021 to June 2024. It included adults with type 2 diabetes, a systolic blood pressure of 120 to 159 mm Hg, and a diastolic blood pressure of less than 100 mm Hg. The DASH4D diet is a Dietary Approaches to Stop Hypertension (DASH)–style diet optimized for people with type 2 diabetes (lower carbohydrates, higher unsaturated fats, and lower potassium than the original DASH diet). Participants were provided all of their food and ate no outside food. Weight was held constant. Data analysis was completed in November 2024.
Interventions
Participants were randomized to a sequence of 4 diets, each for 5 weeks: (1) DASH4D diet with lower sodium, (2) DASH4D diet with higher sodium, (3) comparison (typical US) diet with lower sodium, and (4) comparison diet with higher sodium (reference).
Main Outcomes and Measures
The primary and secondary outcomes were end-of-period systolic and diastolic blood pressure, respectively. The primary dietary contrast compared the DASH4D lower sodium diet vs a comparison higher sodium diet.
Results
Of 102 participants, 85 (83.3%) completed all diet periods. The mean (SD) age was 66 (8.8) years, 67 (66%) were women, 6 (6%) were self-reported Asian, 89 (87%) were Black, 2 (2%) were Hispanic, 6 (6%) were White, mean (SD) baseline blood pressure was 135 (9)/75 (9) mm Hg, and 67 (66%) used 2 or more antihypertensive medications. Compared with the comparison diet with higher sodium, the DASH4D diet with lower sodium reduced end-of-period systolic blood pressure by 4.6 mm Hg (95% CI, 7.2-2.0; P < .001) and diastolic blood pressure by 2.3 mm Hg (95% CI, 3.7-0.9). Most blood pressure reduction occurred during the first 3 weeks of each diet, and the effect of sodium reduction appeared stronger than the effect of the DASH4D diet. Adverse events were infrequent in each diet.
Conclusions and Relevance
This randomized clinical trial found that, for adults with type 2 diabetes, most of whom were treated with multiple antihypertensive medications, the DASH4D diet combined with sodium reduction achieved a clinically relevant reduction in blood pressure, primarily from sodium reduction.
Trial Registration
ClinicalTrials.gov Identifier: NCT04286555
This randomized clinical trial examines the effects of dietary patterns and sodium reduction on blood pressure in adults with type 2 diabetes.
Introduction
Four in 5 US adults with diabetes have hypertension.1,2 Hypertension is a major contributor to atherosclerotic cardiovascular disease, the leading cause of morbidity and mortality in people with diabetes.3 Among people with type 2 diabetes (T2D) and hypertension, blood pressure (BP) lowering with antihypertensive medications substantially reduces all-cause mortality, cardiovascular events, stroke, and nephropathy.4,5,6 Consuming a healthy diet that lowers BP is recommended for all people with hypertension and T2D, but few achieve guideline-recommended BP goals.1,2,7,8,9
The Dietary Approaches to Stop Hypertension (DASH) diet is rich in fruits, vegetables, and low-fat dairy products and reduced in saturated fat and cholesterol.10,11 The DASH diet, combined with dietary sodium reduction, is recommended for hypertension management in people with T2D, but with limited evidence.8,9,10,11 Among healthy individuals, the DASH diet is associated with lowered BP and improved cardiometabolic risk factors12,13; trial evidence is extremely limited in people with T2D.14,15,16 Further, the DASH diet was not developed for the nutritional needs of people with T2D, including those with chronic kidney disease, for whom caution is recommended to avoid hyperkalemia.17,18,19
In this context, we developed the Dietary Approaches to Stop Hypertension for Diabetes (DASH4D) diet, a DASH-style dietary pattern optimized for the nutritional needs of adults with T2D. This article reports the main results of the DASH4D randomized feeding study that tested the effects of the DASH4D diet and dietary sodium reduction on BP among adults with T2D.
Methods
Study Design
DASH4D was a single-site, 4-period crossover feeding study that tested the effects of the DASH4D (vs comparison) diet and lower (vs higher) sodium intake on BP (NCT04286555) (Supplement 1). Participants were recruited from June 2, 2021, to December 19, 2023; data collection was completed on June 17, 2024. This trial was approved by the Johns Hopkins University School of Medicine institutional review board, and all participants provided written informed consent.
Setting and Population
DASH4D was conducted at the community-based Johns Hopkins ProHealth Clinical Research Unit in Baltimore, Maryland. Participants were primarily recruited through mass mailings of brochures, letters to previous participants, electronic health record messages, newspaper advertisements, and word of mouth. Major inclusion criteria were being 18 years or older, having T2D, systolic blood pressure (SBP) of 120 to 159 mm Hg, and diastolic blood pressure (DBP) less than 100 mm Hg. This BP range was selected to include individuals with a BP greater than the normal range and for whom dietary change affecting BP would be safe. T2D was defined as a hemoglobin A1c level of 6.5% or greater (48 mmol/mol; to convert to the proportion of total hemoglobin, multiply by 0.01) and/or treatment with diabetes medications. Major exclusion criteria were type 1 diabetes; hemoglobin A1c level of greater than 9.0% (75 mmol/mol); use of rapid-acting insulin; unstable doses of antihypertensive medications; estimated glomerular filtration rate of less than 30 mL/min/1.73 m2; potassium supplementation; serum potassium level of 5.2 or greater or less than 3.5 mEq/L (to convert to mmol/L, multiply by 1); recent weight loss or gain of more than 5.0% of body weight; weight loss medications, including glucagon-like peptide-1 (GLP-1) receptor agonists at higher doses; or serious illness that could interfere with study participation.
Intervention Diets
The 4 intervention diets were the DASH4D diet with lower sodium, DASH4D diet with higher sodium, comparison diet with lower sodium, and comparison diet with higher sodium (reference diet). Diets were developed by a multidisciplinary team with specific targets for macronutrients, fiber, potassium, magnesium, and calcium (Table 1).19,20,21 The DASH4D diet was adapted from the original DASH diet (eTable 1 in Supplement 2) for people with type 2 diabetes.10,11 Major adaptations were (1) lower carbohydrates and higher unsaturated fats, which should enhance BP and cholesterol lowering,13 and (2) lower potassium content as appropriate for chronic kidney disease and consistent with current dietary reference intakes for potassium.22 The comparison diet was based on the average macronutrient distribution of intake for US adults with diabetes, with micronutrient targets near the 25th percentile of US intake to contrast with the DASH4D diet, as done in the original DASH trial.23 The macronutrient composition of the DASH4D and comparison diets was similar, as to our knowledge there is no specific recommended macronutrient balance for people with diabetes.9
Table 1. Daily Nutrient Targets and Content of the 4 Study Diets at the 2000-Kilocalorie Level.
| Targeta | Diets | |||||
|---|---|---|---|---|---|---|
| DASH4D | Comparison | |||||
| Targets for DASH4D diets | Menu calculations | Targets for comparison diets | Menu calculations | |||
| DASH4D lower sodium | DASH4D higher sodium | Comparison lower sodium | Comparison higher sodium | |||
| Energy, kilocalories | 2000 | 1992 | 2009 | 2000 | 2011 | 2006 |
| Percentage from protein | 18 | 19 | 19 | 15 | 15 | 15 |
| Percentage from carbohydrate | 45 | 45 | 44 | 48 | 48 | 48 |
| Percentage from fat | 37 | 36 | 37 | 37 | 37 | 37 |
| Percentage from saturated fat | <10 | 9 | 9 | <10 | 11 | 10 |
| Fiber, g | 30 | 32 | 32 | 13 | 13 | 13 |
| Cholesterol, mg | NA | 242 | 238 | NA | 294 | 298 |
| Potassium, mg | 3900 | 3812 | 3801 | 1950 | 2033 | 2028 |
| Magnesium, mg | 476 | 494 | 483 | 238 | 247 | 239 |
| Calcium, mg | 1200 | 1154 | 1182 | 600 | 602 | 607 |
| Sodium, mg | ||||||
| Lower sodium diet | 1500 | 1513 | NA | 1500 | 1525 | NA |
| Higher sodium diet | 3700 | NA | 3617 | 3700 | NA | 3552 |
| Food groups, No. of servings per day | ||||||
| Fruits | NA | 5.3 | 4.5 | NA | 1.9 | 1.7 |
| Vegetables | NA | 5.7 | 6.1 | NA | 2.8 | 2.8 |
| Grains | NA | 3.8 | 4.2 | NA | 5.3 | 7.0 |
| Meat, fish, poultry, eggs, nuts, and seeds | NA | 8.5 | 8.3 | NA | 7.4 | 7.4 |
| Dairy and nondairy alternatives | NA | 2.0 | 2.1 | NA | 1.1 | 0.9 |
| Fats | NA | 5.7 | 5.7 | NA | 7.4 | 7.1 |
| Sweets | NA | 2.2 | 2.8 | NA | 3.4 | 2.5 |
Abbreviations: DASH4D, Dietary Approaches to Stop Hypertension for Diabetes; NA, no target.
Seven-day average nutrient and food group calculations of the 4 study diets are shown at the 2000 kilocalorie level. Prespecified tolerances for each 7-day menu cycle were ±2% kilocalorie for total fat, saturated fat, carbohydrates, and protein; ±5% mg for sodium, potassium, and calcium; and ±10% mg for magnesium and fiber. Diets were prepared at 5 levels: 1500, 2000, 2500, 3000, and 3500 kilocalories. Sodium, potassium, calcium, and magnesium were adjusted in increments per kilocalorie, maintaining an approximately 50% difference between the higher vs lower sodium diets for sodium, or between the DASH4D vs comparison diet for other nutrients.
The lower and higher sodium levels for a 2000-kcal menu were 1500 mg per day and 3700 mg per day, respectively. The lower sodium level was selected to maximize BP lowering, as seen in prior studies, aligning with guidelines from the American Heart Association and American Diabetes Association.8,9,10,11 The higher sodium level approximated the 75th percentile of US sodium intake to be typical of what many people with diabetes eat and provide a similar sodium contrast as in the DASH Sodium trial.11,23 A 7-day menu cycle was developed for each diet at 5 calorie levels: 1500, 2000, 2500, 3000, and 3500 kcal (Table 1).
Participant Flow
Potential participants completed a telephone prescreening, 3 on-site screening visits, and an 8-day run-in period consuming 2 days of meals from each study diet. Participants who continued after the run-in were randomized to 1 of 24 possible sequences of 4 feeding periods (eTable 2 in Supplement 2). Each period lasted 5 weeks, during which participants ate lunch or dinner on site 3 days per week; for the remaining meals, participants were provided individually packaged meals to consume at home. Feeding periods were separated by a break of at least 1 week of ad libitum intake (median [IQR] break duration, 14 [14-15] days). During the run-in and feeding periods, participants were provided all of their food, which was prepared in the study metabolic kitchen, and instructed to eat all study food and no outside food other than approved beverages. Diets maintained participants’ starting weight, with initial calorie levels determined using the Mifflin St. Jeor equation.24 Participants underwent weight measurement at on-site meals, with calories adjusted to maintain a stable weight.
Outcomes and Diet Contrasts
The primary outcome was end-of-period SBP, as measured on 5 separate days during the last 2 weeks of the feeding period. The secondary outcome was end-of-period DBP. BP was measured using American Heart Association–recommended procedures: triplicate measures (separated by 30 seconds) by trained staff using an OMRON 907XL device25 after participants sat for 5 minutes in a quiet room. The average of the triplicate readings was used in analyses.
The primary diet contrast tested the difference of end-of-period SBP between the DASH4D diet with lower sodium and the comparison diet with higher sodium. The secondary contrasts compared the effects on SBP and DBP of the 2 sodium levels within each diet and the 2 dietary patterns within each sodium level.
Other Measurements
Self-reported race, ethnicity, sex, and health history were ascertained by questionnaire. Adherence to study diets was assessed by self-report, using a daily diary form completed on each day of feeding. Adherence was defined as complete consumption of the study food and no consumption of outside food or unallowed beverages, as analyzed from feeding period day 1 until completion of the BP outcome assessment. Adherence was also measured objectively by 24-hour urinary excretion of sodium, potassium, and creatinine collected during feeding period week 4 or 5.
Safety Monitoring and Adverse Events
Study staff ascertained serious adverse events and the following prespecified adverse events of special interest: (1) SBP greater than 180 mm Hg or DBP greater than 110 mm Hg; (2) SBP of 171 to 180 mm Hg or DBP of 106 to 110 mm Hg; (3) serum potassium level of 5.5 mEq/L or greater; and (4) blood glucose level less than 70 mg/dL (to convert to mmol/L, multiply by 0.0555).26 Monitoring for an SBP less than 90 mm Hg was added during the study. Potassium was measured at the end of each study period for all participants and additionally during period week 2 for participants with chronic kidney disease stage 3 or greater and those taking potassium-sparing diuretics. Participants were withdrawn for potassium levels of 5.5 mEq/L or greater as confirmed on recheck. Participants taking insulin, sulfonylureas, or meglitinides recorded self-monitored blood glucose levels, which were reviewed by a study clinician, with protocolized medication adjustment if needed to prevent hypoglycemia.
Randomization and Masking
The randomization schedule was generated via a computer algorithm by the study statistician, with equal allocation to the 24 possible 4-diet sequences with a block size of 1. Investigators and outcome assessors were masked to intervention assignment, and intervention staff were masked to BP measurements.
Statistical Analysis
Statistical power was evaluated based on the single, primary contrast for SBP. A sample size of 100 participants provided 90% power to detect a clinically meaningful difference of 4.7 mm Hg in SBP, with a 2-sided α of .05, assuming the mean SBP had a standard deviation of 14 mm Hg and within-person correlation of 0.5.13,20
All analyses were conducted in the modified intention-to-treat population, which was defined as those who completed at least 1 end-of-period BP measurement. Three participants who withdrew shortly after randomization, including 2 who withdrew before initiating any diet intervention, were not analyzed (Figure 1). The testing of the primary and secondary contrasts used a repeated-measure observed data likelihood approach implemented through a linear mixed-effects model, with indicators for diet, feeding period, baseline SBP (or DBP for the secondary outcome model), and covariates associated with missing outcome data (Black or African American race and diabetes medication use) (eTable 3 in Supplement 2). To evaluate the appropriateness of the primary model, parameters for period effects, carryover effects, and period-by-diet pattern interactions were explored; no statistically or clinically relevant period or carryover effects were observed. Prespecified subgroup analyses were conducted by age, sex, race, baseline SBP, baseline chronic kidney disease, and number of antihypertensive medications. Prespecified sensitivity analyses are presented in eTable 8 in Supplement 2. All analyses were conducted using SAS, version 9.4 (SAS Institute), and P < .05 was considered statistically significant.
Figure 1. Participant Screening, Randomization, and Study Diet Completion.
DASH4D indicates Dietary Approaches to Stop Hypertension for Diabetes; DL, DASH4D diet with lower sodium.
Results
Study Participants
Of the 102 participants in the modified intention-to-treat population, 97 (95%) completed 2 or more diet periods, and 85 (83%) completed all 4 periods (Figure 1). The mean (SD) age was 66 (8.8) years, 67 (66%) were women, 89 (87%) were self-reported Black, 2 (2%) were Hispanic, and the mean (SD) baseline BP was 135 (9)/75 (9) mm Hg (Table 2). Two thirds of participants used 2 or more antihypertensive medications, and 56 (55%) used 2 or more glucose-lowering medications (eTable 4 in Supplement 2). During the study, antihypertensive medications were decreased or discontinued for 10 participants and increased or initiated for 5 (eTable 5 in Supplement 2).
Table 2. Baseline Characteristics for the 102 Participants.
| Characteristic | No. (%) |
|---|---|
| Age, mean (SD), y | 66.0 (8.8) |
| Sex | |
| Female | 67 (65.7) |
| Male | 35 (34.3) |
| Race | |
| Asian | 6 (5.9) |
| Black or African American | 89 (87.3) |
| White | 6 (5.9) |
| Multiracial | 1 (1.0) |
| Hispanic ethnicity | 2 (2.0) |
| Systolic blood pressure, mean (SD), mm Hg | 135.2 (9.0) |
| Diastolic blood pressure, mean (SD), mm Hg | 74.6 (9.0) |
| Systolic blood pressure categories, mm HG | |
| 120-129 | 32 (31.4) |
| 130-139 | 39 (38.2) |
| 140-159 | 31 (30.4) |
| Diastolic blood pressure categories, mm Hg | |
| <80 | 70 (68.6) |
| 80-89 | 27 (26.5) |
| 90-99 | 5 (4.9) |
| eGFR, mean (SD), mL/min/1.73 m2 | 77.6 (18.2) |
| eGFR categories, mL/min/1.73 m2 | |
| 30-59 | 21 (20.6) |
| ≥60 | 81 (79.4) |
| Ratio of urinary albumin to urinary creatinine, mean (SD), mg/g | 35.4 (153.1) |
| Ratio of urinary albumin to urinary creatinine ≥30, mg/mg | 13 (13.5) |
| Hemoglobin A1c, mean (SD), % | 7.0 (0.8) |
| Fasting glucose, mean (SD), mg/dL | 125.9 (28.9) |
| Serum potassium, mean (SD), mEq/L | 4.4 (0.4) |
| BMI, mean (SD) | 32.7 (6.5) |
| BMI categories | |
| <25 | 8 (7.8) |
| 25-29.9 | 32 (31.4) |
| ≥30 | 62 (60.8) |
| No. of antihypertensive medications used | |
| 0 | 7 (6.9) |
| 1 | 28 (27.5) |
| 2 | 41 (40.2) |
| ≥3 | 26 (25.5) |
| No. of antihypertensive medications among medication users, mean (SD) | 2.1 (1.0) |
| No. of glucose-lowering medications used | |
| 0 | 8 (7.8) |
| 1 | 38 (37.3) |
| 2 | 33 (32.4) |
| ≥3 | 23 (22.5) |
| No. glucose-lowering medications among medication users, mean (SD) | 1.9 (0.9) |
| Insulin use | 15 (14.7) |
| GLP-1 receptor agonist use | 29 (28.4) |
| SGLT-2 inhibitor use | 17 (16.7) |
| Any lipid-lowering medication use | 82 (80.4) |
| Mean (SD) No. lipid-lowering medications if used ≥1 medication | 1.1 (0.3) |
| Smoking status | |
| Current | 5 (4.9) |
| Former | 38 (37.3) |
| Never | 59 (57.8) |
| Any alcohol use | 23 (22.6) |
| Annual household income, $ | |
| <30 000 | 18 (17.7) |
| 30 000-59 999 | 22 (21.6) |
| ≥60 000 | 34 (33.3) |
| Prefer not to answer/missing | 28 (27.5) |
| Education | |
| High school or less | 22 (21.6) |
| Some college | 33 (32.4) |
| College graduate or more | 47 (46.1) |
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); eGFR, estimated glomerular filtration rate; GLP-1, glucagon-like peptide-1; SGLT-2, sodium-glucose cotransporter 2.
SI conversion factor: To convert glucose to mmol/L, multiply by 0.0555; for hemoglobin A1c to the proportion of total hemoglobin, multiply by 0.001; for potassium to mmol/L, multiply by 1.
Adherence
Participants reported complete adherence to the study diet for a mean of 96% of study days in all diets (eTable 6 in Supplement 2). Urinary sodium excretion averaged 2.3 to 2.4 g per day in the lower sodium diets and 3.3 g per day in the higher sodium diets. Urinary potassium excretion was higher in the DASH4D diets than the comparison diets. Participants’ weight and calories were similar across diets and by GLP-1 receptor agonist use (eTable 7 in Supplement 2).
Blood Pressure Outcomes
Most BP reduction occurred over the first 3 weeks of each diet (Figure 2). In the primary contrast (Table 3), the mean end-of-period SBP was significantly lower on the DASH4D diet with lower sodium than corresponding SBP on the comparison diet with higher sodium (mean difference, −4.6 mm Hg; 95% CI, −7.2 to −2.0; P < .001). Findings for DBP paralleled those for SBP, with a −2.3 mm Hg mean difference in DBP (95% CI, −3.7 to −0.9) comparing the DASH4D diet with lower sodium with the comparison diet with higher sodium.
Figure 2. Mean Weekly Systolic Blood Pressure and Diastolic Blood Pressure by Study Diet.
Shown are the observed mean weekly systolic (A) and diastolic (B) blood pressures across the 5-week feeding period while consuming each of the 4 study diets. The first point labeled “Start of feeding period” indicates the period baseline measurement taken before the diet was initiated. The last point labeled “End of feeding period” indicates the average of the measurements taken during period weeks 4 and 5, the time of data collection for the primary outcome. DASH4D indicates Dietary Approaches to Stop Hypertension for Diabetes.
Table 3. Effect of the DASH4D Diet and Sodium Reduction on Systolic and Diastolic Blood Pressure by Diet Contrast.
| Diet contrasta | Observed mean (SD) end-of-period systolic blood pressure | Modeled effect, difference (95% CI) |
|---|---|---|
| Systolic blood pressure (primary outcome), mm Hg | ||
| Effect of DASH4D diet and sodium reduction (primary contrast) | ||
| DASH4D lower sodium (n = 89) | 122.4 (13.3) | −4.6 (−7.2 to −2.0) |
| Comparison higher sodium (n = 97) | 127.0 (13.5) | |
| Effects of sodium reduction (secondary contrasts) | ||
| Effects of sodium reduction in comparison diet | ||
| Comparison lower sodium (n = 95) | 124.8 (15.2) | −2.3 (−4.8 to 0.3) |
| Comparison higher sodium (n = 97) | 127.0 (13.5) | |
| Effects of sodium reduction in DASH4D diet | ||
| DASH4D lower sodium (n = 89) | 122.4 (13.3) | −4.8 (−7.4 to −2.2) |
| DASH4D higher sodium (n = 92) | 127.2 (13.7) | |
| Effects of the DASH4D diet (secondary contrasts) | ||
| Effects of DASH4D diet at lower sodium | ||
| DASH4D lower sodium (n = 89) | 122.4 (13.3) | −2.3 (−4.9 to 0.2) |
| Comparison lower sodium (n = 95) | 124.8 (15.2) | |
| Effects of DASH4D diet at higher sodium | ||
| DASH4D higher sodium (n = 92) | 127.2 (13.7) | 0.2 (−2.3 to 2.8) |
| Comparison higher sodium (n = 97) | 127.0 (13.5) | |
| Diastolic blood pressure (secondary outcome), mm Hg | ||
| Effect of DASH4D diet and sodium reduction | ||
| DASH4D lower sodium (n = 89) | 67.4 (10.0) | −2.3 (−3.7 to −0.9) |
| Comparison higher sodium (n = 97) | 69.4 (9.5) | |
| Effects of sodium reduction | ||
| Effects of sodium reduction in comparison diet | ||
| Comparison lower sodium (n = 95) | 68.8 (11.2) | −0.9 (−2.3 to 0.5) |
| Comparison higher sodium (n = 97) | 69.4 (9.5) | |
| Effects of sodium reduction in DASH4D diet | ||
| DASH4D lower sodium (n = 89) | 67.4 (10.0) | −2.5 (−3.9 to −1.1) |
| DASH4D higher sodium (n = 92) | 69.9 (10.0) | |
| Effects of the DASH4D diet | ||
| Effects of DASH4D diet at lower sodium | ||
| DASH4D lower sodium (n = 89) | 67.4 (10.0) | −1.4 (−2.8 to 0.04) |
| Comparison lower sodium (n = 95) | 68.8 (11.2) | |
| Effects of DASH4D diet at higher sodium | ||
| DASH4D higher sodium (n = 92) | 69.9 (10.0) | 0.2 (−1.1 to 1.6) |
| Comparison higher sodium (n = 97) | 69.4 (9.5) | |
Abbreviation: DASH4D, Dietary Approaches to Stop Hypertension for Diabetes.
Shown are the observed mean end-of-period blood pressure measures for each study diet and the between-diet difference in blood pressure measures from the primary analysis using linear mixed-effects regression adjusted for baseline systolic blood pressure (or diastolic blood pressure for the secondary outcome model) and covariates found associated with missing outcome data: Black or African American race and diabetes medication use.
The within-diet effect of sodium reduction on SBP was −4.8 mm Hg (95% CI, −7.4 to −2.2) in the DASH4D diet and −2.3 mm Hg (95% CI, −4.8 to 0.3) in the comparison diet. At the lower sodium level, mean SBP was modestly lower with the DASH4D diet vs the comparison diet (−2.3 mm Hg; 95% CI, −4.9 to 0.2). There was no significant SBP difference between the DASH4D and comparison diets at the higher sodium level. Analyses within prespecified subgroups (eFigures 1 and 2 in Supplement 2), post hoc subgroup analyses by GLP-1 receptor agonist and sodium-glucose cotransporter 2 inhibitor use (eFigure 3 in Supplement 2), and sensitivity analyses (eTable 8 in Supplement 2) showed no substantial difference from the primary analysis.
Adverse Events
There were 2 serious adverse events (eTable 9 in Supplement 2): 1 hospitalized myocardial infarction that occurred near the start of the DASH4D lower sodium diet, and 1 hospitalized heart failure during the break period after the comparison lower sodium diet. Regarding adverse events of special interest, elevated SBP to 171 to 180 mm Hg or DBP to 106 to 110 mm Hg occurred for 3 participants during the comparison higher sodium diet, 3 participants during the comparison lower sodium diet, and no participants in the DASH4D diets. SBP less than 90 mm Hg occurred for 6 participants during the comparison lower sodium diet, 5 during the DASH4D lower sodium diet, 2 during the comparison higher sodium diet, and 1 during the DASH4D higher sodium diet. Elevated serum potassium levels of 5.5 mEq/L or greater occurred for 2 participants during the DASH4D lower sodium diet and 1 participant during the comparison lower sodium diet. There were no occurrences of severe hypoglycemia.
Discussion
In this randomized clinical trial of people with T2D, dietary sodium reduction combined with the DASH4D diet, a DASH-style diet tailored for diabetes, significantly lowered BP compared with a higher sodium typical US diet control. Sodium reduction appeared to lower BP to a greater degree than the DASH4D dietary pattern. The dietary intervention lowered BP in the context of antihypertensive drug therapy, with more than 90% of participants treated with antihypertensive medications. These results supported the use of the DASH4D diet with lower sodium as a means to lower BP in people with T2D, consistent with food as medicine initiatives to improve health.27
DASH4D was one of the largest controlled feeding studies conducted among people with T2D. The reductions in SBP and DBP of 4.6 and 2.3 mm Hg, respectively, from the DASH4D diet with lower sodium were clinically meaningful. In people with diabetes, a 5–mm Hg reduction in SBP lowered the risk of stroke by 14%, cardiovascular events by 6%, and heart failure by 8%.28 Recently, a large trial documented that a 3–mm Hg SBP reduction was associated with an approximately 12% reduction in stroke and total mortality.29
Adverse events due to the DASH4D diet and sodium reduction as operationalized in this study were infrequent. A few participants experienced an SBP reading less than 90 mm Hg, which was more common with the lower sodium diets; the occurrence of low BP readings has commonly been observed in trials of antihypertensive medications.30 Two participants consuming the DASH4D diet experienced confirmed hyperkalemia, with serum potassium levels of 5.5 mEq/L or greater, which was a small absolute risk compared with initiating angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.31,32 Future research is needed to quantify the risks of the DASH4D diet and sodium reduction in higher-risk individuals, such as those with advanced kidney disease.
The BP-lowering effect of the DASH4D lower sodium diet was smaller than seen in prior efficacy studies, and the DASH4D trial did not establish a BP-lowering effect of the DASH4D dietary pattern alone. In the original DASH study, the DASH diet at a fixed sodium intake of 3000 mg per day lowered SBP and DBP by 5.5 and 3.0 mm Hg, respectively.10 The subsequent DASH Sodium trial combined the DASH diet with sodium reduction from approximately 3450 to 1150 mg per day, which lowered SBP and DBP by 8.9 and 4.5 mm Hg, respectively.11
Sodium reduction appeared responsible for much of the BP-lowering effect of the DASH4D lower sodium diet. DASH4D tested a lower sodium intake of 1500 mg per day, which is the sodium target recommended by the American Heart Association. The American Diabetes Association recommends a daily sodium intake of less than 2300 mg for people with diabetes, and the Kidney Disease: Improving Global Outcomes group recommends less than 2000 mg for people with high BP and kidney disease.8,9,17 Of 4 prior feeding studies that tested dietary sodium reduction in people with T2D, 3 found a clinically significant reduction in BP; all were limited by short duration (1 week) and exclusion of chronic antihypertensive therapy.14 A 1-week crossover feeding study of adults without diabetes, half taking antihypertensives, found that a large reduction in dietary sodium lowered SBP by 7 mm Hg.33 In the current study, sodium reduction lowered BP quickly and appeared to plateau by 5 weeks. Analysis of the DASH Sodium feeding study suggested that a maximal BP-lowering effect of sodium reduction takes longer than 4 weeks; more long-term studies are needed.34
Several factors may have limited the magnitude of the BP-lowering effect in the DASH4D trial. The potassium content of the DASH4D diet was approximately 400 mg per day lower at the 2000 kcal level than the original DASH diet to minimize the risk for hyperkalemia, which may have attenuated BP lowering.20 The effect of dietary change on BP may be smaller for people with T2D compared with the generally healthy population examined in prior feeding studies due to physiologic differences and/or concurrent pharmacotherapy. Approximately one-third of DASH4D participants were treated with diuretics, which may attenuate the BP-lowering effect of dietary sodium reduction.35 Additionally, a substantial minority of DASH4D participants were treated with GLP-1 receptor agonists or sodium-glucose cotransporter 2 inhibitors, which lower BP and have unknown interactions with diet.36 Finally, approximately 1 in 5 DASH4D participants had changes to antihypertensive therapy during the trial, which may have affected the BP outcomes.
The findings in DASH4D have public health implications. First, they provide evidence of the efficacy of BP lowering through dietary change in people with T2D, including those treated with multiple antihypertensive and glucose-lowering medications. High adherence to the DASH4D lower sodium diet suggests that the diet is acceptable. Nonetheless, sodium reduction to 1500 mg per day is difficult to achieve given the current food environment, and further research, including implementation research in community settings, is needed.37 Second, the magnitude of BP lowering has clinical and public health relevance for reducing cardiovascular and kidney outcomes. Third, our results highlight the importance of dietary sodium reduction in people with T2D, for which there are cost-effective population-level interventions.38
Strengths and Limitations
Strengths of the DASH4D trial included its efficient crossover design, with participants serving as their own controls, high adherence to study diets, a low level of dropout (with >80% of participants completing all 4 study periods), and inclusion of people with kidney disease and medication-treated hypertension. The feeding study design minimized the confounding effects of variable dietary adherence, which is commonplace in behavioral intervention trials. Limitations included insufficient power to detect the effects of the DASH4D diet and sodium reduction separately. Additionally, this was a single-center study, and the study population was not as diverse as planned. Nonetheless, the trial enrolled many individuals identifying as Black, an important population given their disproportionately lower rates of hypertension control and greater risk of cardiovascular complications.39,40,41 A particular challenge of this study was the COVID-19 pandemic, which interrupted participant feeding at several points.
Conclusions
In this randomized clinical trial, the DASH4D diet combined with sodium reduction achieved a clinically significant reduction in BP in adults with T2D, primarily from sodium reduction. The observed effects on BP may contribute to a meaningful reduction in the risk of BP-related outcomes.
Trial protocol
eFigure 1. Forest plot of the effect of the DASH4D diet combined with sodium reduction on systolic blood pressure among prespecified participant subgroups
eFigure 2. Forest plot of the effect of the DASH4D diet combined with sodium reduction on diastolic blood pressure among prespecified participant subgroups
eFigure 3. Forest plot of the effect of the DASH4D diet combined with sodium reduction on systolic blood pressure among subgroups of baseline GLP-1 receptor agonist and SGLT2 inhibitor use
eTable 1. Daily nutrient targets and content of the DASH4D diets and the original DASH diet at the 2000 kilocalorie level
eTable 2. Number of participants randomized to each of 24 diet sequences, and feeding period completion (N=105)
eTable 3. Association of participant baseline characteristics with missing blood pressure outcome data in the modified intention-to-treat population
eTable 4. Baseline antihypertensive, glucose lowering, and lipid lowering medication use in the modified intention-to-treat population
eTable 5. Number of participants with antihypertensive medication changes during the study
eTable 6. Measures of dietary adherence, 24-hour urine metabolite excretion, and weight and calories at baseline and on the four study diets
eTable 7. Baseline and end of period weight, calories, and caloric adjustments, stratified by baseline GLP1 receptor agonist use
eTable 8. The effect of the DASH4D diet combined with sodium reduction (primary contrast) on systolic blood pressure—sensitivity analyses
eTable 9. Adverse events of special interest and serious adverse events
Nonauthors collaborators
Data sharing statement
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Trial protocol
eFigure 1. Forest plot of the effect of the DASH4D diet combined with sodium reduction on systolic blood pressure among prespecified participant subgroups
eFigure 2. Forest plot of the effect of the DASH4D diet combined with sodium reduction on diastolic blood pressure among prespecified participant subgroups
eFigure 3. Forest plot of the effect of the DASH4D diet combined with sodium reduction on systolic blood pressure among subgroups of baseline GLP-1 receptor agonist and SGLT2 inhibitor use
eTable 1. Daily nutrient targets and content of the DASH4D diets and the original DASH diet at the 2000 kilocalorie level
eTable 2. Number of participants randomized to each of 24 diet sequences, and feeding period completion (N=105)
eTable 3. Association of participant baseline characteristics with missing blood pressure outcome data in the modified intention-to-treat population
eTable 4. Baseline antihypertensive, glucose lowering, and lipid lowering medication use in the modified intention-to-treat population
eTable 5. Number of participants with antihypertensive medication changes during the study
eTable 6. Measures of dietary adherence, 24-hour urine metabolite excretion, and weight and calories at baseline and on the four study diets
eTable 7. Baseline and end of period weight, calories, and caloric adjustments, stratified by baseline GLP1 receptor agonist use
eTable 8. The effect of the DASH4D diet combined with sodium reduction (primary contrast) on systolic blood pressure—sensitivity analyses
eTable 9. Adverse events of special interest and serious adverse events
Nonauthors collaborators
Data sharing statement
