Carolyn F. Pedley

The Healthy Living Partnerships to Prevent Diabetes Study: 2-Year Outcomes of a Randomized Controlled Trial

BACKGROUND Since the Diabetes Prevention Project (DPP) demonstrated that lifestyle weight-loss interventions can reduce the incidence of diabetes by 58%, several studies have translated the DPP methods to public health-friendly contexts. Although these studies have demonstrated short-term effects, no study to date has examined the impact of a translated DPP intervention on blood glucose and adiposity beyond 12 months of follow-up. PURPOSE To examine the impact of a 24-month, community-based diabetes prevention program on fasting blood glucose, insulin, insulin resistance as well as body weight, waist circumference, and BMI in the second year of follow-up. DESIGN An RCT comparing a 24-month lifestyle weight-loss program (LWL) to an enhanced usual care condition (UCC) in participants with prediabetes (fasting blood glucose=95-125 mg/dL). Data were collected in 2007-2011; analyses were conducted in 2011-2012. SETTING/PARTICIPANTS 301 participants with prediabetes were randomized; 261 completed the study. The intervention was held in community-based sites. INTERVENTION The LWL program was led by community health workers and sought to induce 7% weight loss at 6 months that would be maintained over time through decreased caloric intake and increased physical activity. The UCC received two visits with a registered dietitian and a monthly newsletter. MAIN OUTCOME MEASURES The main measures were fasting blood glucose, insulin, insulin resistance, body weight, waist circumference, and BMI. RESULTS Intent-to-treat analyses of between-group differences in the average of 18- and 24-month measures of outcomes (controlling for baseline values) revealed that the LWL participants experienced greater decreases in fasting glucose (-4.35 mg/dL); insulin (-3.01 μU/ml); insulin resistance (-0.97); body weight (-4.19 kg); waist circumference (-3.23 cm); and BMI (-1.40), all p-values <0.01. CONCLUSIONS A diabetes prevention program administered through an existing community-based system and delivered by community health workers is effective at inducing significant long-term reductions in metabolic indicators and adiposity.

Intensive Blood Pressure Treatment Does Not Improve Cardiovascular Outcomes in Centrally Obese Hypertensive Individuals With Diabetes: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial

OBJECTIVE The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial reported no differences in most cardiovascular disease (CVD) outcomes between intensive and standard blood pressure therapy in individuals with diabetes mellitus (DM) and hypertension. Many such individuals are centrally obese. Here we evaluate whether the trial outcomes varied by the level of central obesity. RESEARCH DESIGN AND METHODS The cohort included 4,687 people (47.7% women) with DM and hypertension. Mean age was 62.2, and mean follow-up was 4.7 years. Participants were randomly assigned to one of two blood pressure treatment strategies: intensive (systolic <120 mmHg) or standard (systolic <140 mmHg). Sex-specific quartiles of waist-to-height ratio were used as the measure of central obesity. The primary ACCORD outcome (a composite of nonfatal myocardial infarction [MI], nonfatal stroke, or CVD death) and three secondary outcomes (nonfatal MI, fatal or nonfatal stroke, and CVD death) were examined using proportional hazard models. RESULTS There was no evidence that the effect of intensively lowering blood pressure differed by quartile of waist-to-height ratio for any of the four outcomes (P > 0.25 in all cases). Controlling for waist-to-height quartile had no significant impact on previously published results for intensive blood pressure therapy. Waist-to-height ratio was significantly related to CVD mortality (hazard ratio 2.32 [95% CI 1.40–3.83], P = 0.0009 comparing the heaviest to lightest quartiles), but not to the other outcomes (P > 0.09 in all cases). CONCLUSIONS Intensive lowering of blood pressure versus standard treatment does not ameliorate CVD risk in individuals with DM and hypertension. These results did not vary by quartile of waist-to-height ratio.

Orthostatic Hypotension in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) Blood Pressure Trial Prevalence, Incidence, and Prognostic Significance

Orthostatic hypotension (OH) is associated with hypertension and diabetes mellitus. However, in populations with both hypertension and diabetes mellitus, 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 ACCORD (Action to Control Cardiovascular Risk in Diabetes) BP trial, seated BP was measured 3×, 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 months, and 48 months. The relationship between OH and clinical outcomes (total and cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization or death and the primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) was assessed using proportional hazards analysis. Consensus OH, defined by orthostatic decline in systolic BP ≥20 mm Hg 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 (hazard ratio, 1.61; 95% confidence interval, 1.11–2.36) and heart failure death/hospitalization (hazard ratio, 1.85, 95% confidence interval, 1.17–2.93), but not with the primary outcome or other prespecified outcomes. In patients with type 2 diabetes mellitus and hypertension, OH was common, not associated with intensive versus standard BP treatment goals, and predicted increased mortality and heart failure events.

Prevalence of Nephropathy in Black Patients with Type 2 Diabetes mellitus

The prevalence of nephropathy in black patients with type 2 diabetes mellitus is poorly defined. We performed a cross-sectional analysis of 98 unrelated and unselected black type 2 diabetic patients treated in indigent care internal medicine clinics to determine the prevalence of proteinuria and nephropathy. Serum creatinine, blood urea nitrogen, urine albumin and urine creatinine concentrations were measured. A Spearman’s rank correlation was computed to test for a relationship between diabetes duration and continuous outcomes. For binary outcomes, an odds ratio and 95% confidence interval were computed for a change of 10 years diabetes duration based on logistic regression. Cases were 61% female, and had mean (± SD) age 59.9 ± 12.5 years, diabetes duration 12.6 ± 9.4 years, body mass index 32.4 ± 9.3 kg/m2, hemoglobin A1C (HbA1C) 9.2 ± 2.3%, and serum creatinine concentration 1.60 ± 1.1 mg/dl. For continuous variables, diabetes duration was positively associated with albuminuria (r = 0.31; p = 0.0017), serum creatinine (r = 0.36; p = 0.0003) and blood urea nitrogen concentration (r = 0.36; p = 0.0003). For binary variables, cases with longer diabetes duration were at increased risk for urinary albumin:creatinine >300 µg/mg (p = 0.006), elevated serum creatinine concentration (≧1.4 mg/dl in women or ≧1.6 mg/dl in men; p = 0.045), elevated blood urea nitrogen concentration (≧20 mg/dl; p = 0.026), and clinical cerebrovascular disease (p = 0.028). HbA1C, body mass index, and blood pressure did not correlate with diabetes duration in this population. Among the cases, 33.7% had elevated serum creatinine concentration and 71.5% had abnormal levels of albuminuria (27.6% > 300 µg albumin/mg Cr and 43.9% 30–300 µg albumin/mg Cr). Abnormal proteinuria was seen in the majority of black patients with poorly controlled type 2 diabetes mellitus treated in indigent care clinics. This prevalence may be conservative, due to the widespread use of angiotensin-converting enzyme inhibitor therapy and exclusion of cases treated only by nephrologists. Approximately 70% of black patients with type 2 diabetes cared for in indigent care clinics have abnormal proteinuria and are at heightened risk for ESRD and death.

Longitudinal changes in dietary fat intake and associated changes in cardiovascular risk factors in adults with type 2 diabetes: The ACCORD trial

AIMS To measure dietary fat intake using the Puget Sound Eating Patterns (PEP) questionnaire, a validated 19-item food questionnaire, and to quantify how reduced dietary fat intake affects cardiovascular risk factors in adults with type 2 diabetes. METHODS Randomized controlled trial including a subsample of 1781 Action to Control Cardiovascular Risk in Diabetes (ACCORD) participants. Participants received dietary counseling to consume a reduced-fat diet. Outcome measures included HbA1c, fasting lipid profile, blood pressure, and weight. Longitudinal linear regression analyses were used to evaluate relationships between baseline and follow-up PEP scores and cardiovascular risk factors. RESULTS PEP scores decreased significantly from baseline to 12-month follow up with a mean difference of -0.09 ± 0.39, P<0.001. All of the fat intake subscales showed significant improvement at 12 months from baseline. White race, female gender, and more hours per week of physical activity were correlated with a decline in PEP scores at 1-year. A longitudinal decrease in dietary fat intake was associated with significantly less weight gain at 12- and 36-months and lower serum triglycerides at 1 year. CONCLUSIONS Reduced fat intake as measured by a brief questionnaire was associated with significant improvement in some cardiovascular risk factors (triglycerides and weight), but not in others.

The Lifestyle Intervention for the Treatment of Diabetes study (LIFT Diabetes): Design and baseline characteristics for a randomized translational trial to improve control of cardiovascular disease risk factors

The prevalence of type 2 diabetes continues to increase in minority and underserved patients, who are also more likely to have poorer control of diabetes and related risk factors for complications. Although the Look AHEAD trial has demonstrated improved risk factor control among overweight or obese diabetes patients who received an intensive lifestyle intervention, translating such findings into accessible programs is a major public health challenge. The purpose of this paper is to report the design and baseline characteristics of the Lifestyle Interventions for the Treatment of Diabetes study (LIFT Diabetes). The overall goal is to test the impact of a community-based lifestyle weight loss (LWL) intervention adapted from Look AHEAD on cardiovascular disease risk at 12-months and 24-months among minority and lower income diabetes patients. Secondary outcomes include body weight, physical activity, medication use, cost, resource utilization, and safety. The primary hypothesis being tested is that the LWL will result in 10% relative reduction in CVD risk compared to the DSM. We have randomized 260 overweight or obese adults with diabetes one of two 12-month interventions: a LWL condition delivered by community health workers or a diabetes self-management (DSM) education condition. The baseline demographic characteristics indicate that our sample is predominantly female, obese, low income, and ethnic minority. Translating evidence-based, lifestyle strategies, and targeting minority and underserved patients, will yield, if successful, a model for addressing the burden of diabetes and may favorably impact health disparities.

The 24-month metabolic benefits of the healthy living partnerships to prevent diabetes: A community-based translational study

AIMS Large-scale clinical trials and translational studies have demonstrated that weight loss achieved through diet and physical activity reduced the development of diabetes in overweight individuals with prediabetes. These interventions also reduced the occurrence of metabolic syndrome and risk factors linked to other chronic conditions including obesity-driven cancers and cardiovascular disease. The Healthy Living Partnerships to Prevent Diabetes (HELP PD) was a clinical trial in which participants were randomized to receive a community-based lifestyle intervention translated from the Diabetes Prevention Program (DPP) or an enhanced usual care condition. The objective of this study is to compare the 12 and 24 month prevalence of metabolic syndrome in the two treatment arms of HELP PD. MATERIALS AND METHODS The intervention involved a group-based, behavioral weight-loss program led by community health workers monitored by personnel from a local diabetes education program. The enhanced usual care condition included dietary counseling and written materials. RESULTS HELP PD included 301 overweight or obese participants (BMI 25-39.9kg/m2) with elevated fasting glucose levels (95-125mg/dl). At 12 and 24 months of follow-up there were significant improvements in individual components of the metabolic syndrome: fasting blood glucose, waist circumference, HDL, triglycerides and blood pressure and the occurrence of the metabolic syndrome in the intervention group compared to the usual care group. CONCLUSIONS This study demonstrates that a community diabetes prevention program in participants with prediabetes results in metabolic benefits and a reduction in the occurrence of the metabolic syndrome in the intervention group compared to the enhanced usual care group.

Orthostatic Hypotension in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) Blood Pressure Trial

Orthostatic hypotension (OH) is associated with hypertension and diabetes mellitus. However, in populations with both hypertension and diabetes mellitus, 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 ACCORD (Action to Control Cardiovascular Risk in Diabetes) BP trial, seated BP was measured 3×, 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 months, and 48 months. The relationship between OH and clinical outcomes (total and cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization or death and the primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) was assessed using proportional hazards analysis. Consensus OH, defined by orthostatic decline in systolic BP ≥20 mm Hg 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 (hazard ratio, 1.61; 95% confidence interval, 1.11–2.36) and heart failure death/hospitalization (hazard ratio, 1.85, 95% confidence interval, 1.17–2.93), but not with the primary outcome or other prespecified outcomes. In patients with type 2 diabetes mellitus and hypertension, OH was common, not associated with intensive versus standard BP treatment goals, and predicted increased mortality and heart failure events.

Comment on Kahn and Davidson. The Reality of Type 2 Diabetes Prevention. Diabetes Care 2014;37:943–949

Kahn and Davidson (1) conclude that inadequacies in the evidence base support inaction on diabetes prevention in the community. Because we lack evidence from randomized controlled trials of community-based translations of the Diabetes Prevention Program (DPP) showing long-term maintenance of weight loss and prevention of diabetes and diabetes complications, they state that “… it is premature to siphon off precious national health care resources or revenue going into health plans toward an intervention that has no clear clinical benefit” (1). Fortunately, Kahn and Davidson are not responsible for developing public health policy. Many sound health policies are based on evidence that would fall short …

Clinical Outcomes by Race and Ethnicity in the Systolic Blood Pressure Intervention Trial (SPRINT): A Randomized Clinical Trial

Abstract BACKGROUND The Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure (SBP) of ≤ 120 mm Hg (intensive treatment) reduced cardiovascular disease (CVD) events compared to SBP of ≤ 140 mm Hg (standard treatment); however, it is unclear if this effect is similar in all racial/ethnic groups. METHODS We analyzed SPRINT data within non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic subgroups to address this question. High-risk nondiabetic hypertensive patients (N = 9,361; 30% NHB; 11% Hispanic) 50 years and older were randomly assigned to intensive or standard treatment. Primary outcome was a composite of the first occurrence of a myocardial infarction, acute coronary syndrome, stroke, decompensated heart failure, or CVD death. RESULTS Average postbaseline SBP was similar among NHW, NHB, and Hispanics in both treatment arms. Hazard ratios (HRs) (95% confidence interval) (intensive vs. standard treatment groups) for primary outcome were 0.70 (0.57–0.86), 0.71 (0.51–0.98), 0.62 (0.33–1.15) (interaction P value = 0.85) in NHW, NHB, and Hispanics. CVD mortality HRs were 0.49 (0.29–0.81), 0.77 (0.37–1.57), and 0.17 (0.01–1.08). All-cause mortality HRs were 0.61 (0.47–0.80), 0.92 (0.63–1.35), and 1.58 (0.73–3.62), respectively. A test for differences among racial/ethnic groups in the effect of treatment assignment on all-cause mortality was not significant (Hommel-adjusted P value = 0.062) after adjustment for multiple comparisons. CONCLUSION Targeting a SBP goal of ≤ 120 mm Hg compared to ≤ 140 mm Hg led to similar SBP control and was associated with similar benefits and risks among all racial ethnic groups, though NHBs required an average of ~0.3 more medications. CLINICAL TRIALS REGISTRATION Trial Number NCT01206062, ClinicalTrials.gov Identifier at https://clinicaltrials.gov/ct2/show/NCT01206062.