Abstract
Aims:
To evaluate the long-term effects of behavioral treatments on glycemic and psychological outcomes for patients with major depressive disorder (MDD) and type 2 diabetes (T2D).
Methods:
Program ACTIVE II was a multicenter randomized controlled comparative effectiveness trial of cognitive behavioral therapy (CBT), exercise (EXER), combination treatment (CBT+EXER) and usual care (UC) for adults with MDD and T2D.
Results:
Primary outcomes: change in A1c and depressive symptoms at 6- (N=87) and 12-months (N=75) from baseline. In those with a baseline A1c ≥7.0%, CBT+EXER showed lasting A1c benefit at 6- (-1.2%; SE: 0.6; p=.032) and 12-months (-1.4%; SE: 0.6; p=.025) compared to UC. All groups had clinically significant improvements in depressive symptoms. At 6 months, CBT+EXER had significant improvements in diabetes-related distress regimen burden (p=.005); and social support (CIRS, p=.043) compared to UC.
Conclusions:
The Program ACTIVE II CBT+EXER intervention demonstrated a sustained improvement in A1c for a subgroup of study participants with a baseline A1c ≥7.0%. However, this finding should be considered preliminary because of small sample size. All 3 behavioral intervention groups demonstrated improvements in psychosocial outcomes one-year post-intervention. These findings point to the enduring benefits of community-based interventions to extend the availability of depression treatment for T2D patients.
Keywords: Depression, Type 2 Diabetes, Glycemic Management
Introduction
More than 37.3 million U.S. adults have diabetes mellitus 1 resulting in annual diabetes-related costs of more than $412 billion in direct and indirect costs in 2022.2 Further, people with type 1 and type 2 diabetes have higher rates of depression than the general population.3, 4
There is a bidirectional relationship between diabetes and depression where a lifetime history of depression confers increased risk of developing type 2 diabetes and the presence of type 2 diabetes increased the risk of developng subsequent depression.5,6 Patients with type 2 diabetes are two times more likely to experience depressive symptoms than their non-diabetes peers, with one in four patients reporting elevated depressive symptoms and 11.4% meeting criteria for Major Depressive Disorder (MDD).3 Depressive symptoms are associated with worsened diabetes outcomes including blood glucose levels7 diabetes complications,8 decreased adherence to diabetes care regimens,9 increased functional disability,10 increased health care costs,11 decreased quality of life12–13 and earlier mortality attributable to all causes.14–15
Few randomized controlled behavioral interventions tailored for the treatment of depression in people with type 2 diabetes have examined whether there was a sustained effect over time.16–21 Lustman and colleagues conducted a randomized controlled trial (N=51 type 2 diabetes participants) of a 10-week individualized cognitive behavioral therapy (CBT) compared to diabetes education. Although no group differences in baseline-adjusted HbA1c levels were found at post-treatment assessment, the CBT arm showed a 0.7% improvement in HbA1c at the 6-month follow-up assessment compared to controls.16
Piette and colleagues tested a combination of telephone-based CBT and a prescribed walking program compared to enhanced usual care in 291 veterans with type 2 diabetes and depressive symptoms.21 At the 12-month follow-up, 58% of participants in the intervention group reported improvements in depressive symptoms. No changes were observed in HbA1c at the 12-month follow-up assessment.21
While rates of depression relapse have been observed to be as high as 79% over a 5 year period16, few studies have documented the effectiveness of behavioral interventions on glycemic outcomes in the treatment of depression over long-term follow-up. Distinct from prior clinical trials, Program ACTIVE II was designed to test the comparative effectiveness of two behavioral interventions on depression and glycemic outcomes in adults with type 2 diabetes by engaging community-based behavioral health and exercise professionals to work synergistically with medical care providers. Program ACTIVE II primary study was conducted with a 2 x 2 factorial design to test the comparative effectiveness of community-based cognitive behavioral therapy (CBT) and/or exercise (EXER) against usual care (UC) at 12 weeks.22 The key findings included a remission in MDD of 60% in the CBT group, 72% in EXER and 71% in the combination group compared to 32% in the UC group.22 There were no significant pre- to post-intervention differences in HbA1c overall, but subgroup analysis showed a 1.3% HbA1c more reduction in those with baseline HbA1c above 7.0% compared with the UC group. The results of the 12-week intervention are published elsewhere.22 In this manuscript the authors report findings on the effects of these interventions on depression, glycemic control and quality of life outcomes at 6- and 12-months post-intervention.
Subjects, Materials and Methods
Program ACTIVE II was a multi-center repeated measures randomized controlled trial conducted in three states (Appalachian Ohio, West Virginia and Indiana). The study used a community-engaged research approach in which community organizations participated in recruitment, intervention implementation, and dissemination of findings. The full study design is described in elsewhere;22 a synopsis is provided below. The study protocol was approved by the institutional review boards of Indiana University, Ohio University and West Virginia University. A Data Safety and Monitoring Panel provided ethical and safety oversight.
Inclusion criteria are detailed elsewhere but are summarized as follows: adults with medical diagnosis of type 2 diabetes for at least 1 year and meeting DSM-IVTR criteria for Major Depressive Disorder for at least 2 weeks. Primary exclusion criteria included bipolar disorder, suicidality, psychotic features, substance abuse, significant diabetes-related complications that limit physical activity, or a history of DKA.22 Advertising was conducted through primary care and specialty medical practices, newspapers, radio stations, community centers, partnering community organizations and community events.23
Participants were randomly assigned to one of four study arms: 10 sessions of manualized CBT delivered by trained master’s and doctoral-level community mental health professionals (CBT), 12-weeks of community-based exercise (EXER) using manualized materials and delivered by trained community exercise professionals, concurrent CBT and EXER interventions (CBT+EXER) or usual care (UC). Details of the content of interventions have been published elsewhere23. Briefly, the CBT intervention consisted of 10 individual sessions with a trained therapist providing psychoeducation on the cognitive behavioral therapy model, introduction to automatic thoughts, cognitive distortions, and cognitive restructuring of automatic thoughts and core beliefs. The exercise intervention was patterned from the lifestyle arm of the Diabetes Prevention Program. Participants met with a trained personal coach for 6 sessions across the 12-week intervention period. They received didactic and experiential training in exercise strategies tailored for their current state of health, consistent with ACSM guidelines. Between classes, participants were asked to engage in aerobic activity at a minimum of 100–150 minutes per week. All participants were offered Dining with Diabetes, a U.S. Centers for Disease Control certified nutrition education program offered through county extension programs in their state during the 12-week intervention period.
Measures
Psychological, behavioral and physiologic measures were administered at baseline, post intervention, 6- and 12-month follow-up time points. The Structured Clinical Interview for the DSM-IV-TR (SCID) was used to establish MDD diagnostic eligibility and diagnosis status at post-intervention. The SCID has been shown to have validity and adequate inter-rater reliability (kappa = 0.61–0.68) and test-retest reliability (r = 0.64–0.69) for diagnosis of major depression.24–25 A case conference diagnosis assignment process was used to achieve consensus on psychiatric diagnosis.
The Beck Depression Inventory-II (BDI) was used to assess severity of depressive symptoms.26 The BDI-II has been shown to have excellent test-retest reliability and validity when used in populations with type 2 diabetes. 27 The Automatic Thoughts Questionnaire was collected to assess severity of depression cognitions.28 General quality of life was measured using the SF-12 Quality of Life Measure (SF-12).29 Internal consistency in adult samples has been found to be r=0.81–0.88 with acceptable validity in type 2 diabetes samples.30 The Physical Component Score and Mental Component Score subscales were calculated. The Diabetes Quality of Life Measure (DQOL) was used to assess diabetes-specific quality of life.31 It has demonstrated acceptable levels of reliability, internal consistency and external validity in type 2 diabetes samples.32
Medical variables included current and past medical history data such as type 2 diabetes duration, prescribed diabetes medication treatment regimen, medication history, and number and severity of diabetes complications. HbA1c samples were drawn via non-fasting venipuncture and analyzed at CLIA-certified clinical testing facilities.
Exercise variables included the Six-Minute Walk Test (6MWT) to evaluate aerobic capacity. Total distance covered was measured in meters with a distance measuring wheel.33–34 Resting, exercise and recovery blood pressures were measured via auscultation with a calibrated sphygmomanometer at rest and peak performance by fitness directors during the exercise intervention, in conjunction with collection of Borg exertion ratings for clinical monitoring purposes.35–34
Anthropometric measurements were taken to estimate body composition and regional adipose distribution. Body mass index was calculated. Height and weight were measured on a Detecto Physician’s Scale with stadiometer, measuring height to the nearest half inch and weight to the pound. Waist circumference (girth) was assessed with a constant tension tape measure (Gulick tape) at the narrowest portion of the torso, while a hip measurement was made at the maximum posterior extension of the buttocks. The waist-to-hip ratio was calculated.37
Interventions are described elsewhere.23 All interventions were delivered within a 12-week period post-randomization. CBT and Exercise were offered concurrently to participants randomized to the combination treatment group.
Descriptive statistics (mean and standard deviation) were used to summarize all continuous variables. Baseline clinical and demographic data were compared among the four treatment groups. Dichotomous and ordinal variables were examined using either chi-square test or Fishers exact test. Continuous measures were examined using ANOVA. Baseline comparisons included only those subjects who had non-missing primary outcomes data at 6-month and/or 12-month.
The primary outcomes of the 12-week intervention trial were the change in Beck Depression Inventory total score to assess the effect of CBT and the change in HbA1c to assess the main effect of exercise at post-treatment. Secondary outcomes included change in BDI at 6 months and 12 months, change of A1c in 6 and 12 months and also changes in psychological and medical outcomes. The changes in all outcomes were analyzed by a repeated measures ANCOVA model. Treatment group specific least square means were estimated from the ANCOVA model and each of the three treatment groups, CBT, EXER and CBT+ EXER, were compared with the UC group. Group comparisons were adjusted for baseline value of the outcome variable, age and education status. Sensitivity analysis was performed to account for missing data at 6- and 12-month assessment and included the multiple imputation method with the assumption that missing data at follow-up was a function of treatment group and baseline value of the response variable.
Results
Sample Characteristics
At baseline, N=140 participants enrolled. Of these, N=87 (62.1%) participants continued at 6-month follow-up with the remaining 53 either withdrawn (N=36) or lost to follow-up (N=17). The 12-month follow-up sample size was N=75, with the remaining 65 either withdrawn (N=41) or lost to follow-up (N=24). For the purposes of evaluating the primary outcomes, N=87 (62.1%) and N=75 (53.6%) were included at the 6- and 12-month time points. Demographics of the enrolled sample are shown in Table 1. The mean age range was 53.4–61.4 years in four treatment groups and groups had significantly different mean ages. The UC group had significantly higher proportion of subjects with 4-year college degree or higher education. These variables were entered as covariates in subsequent analyses. Groups were similar on all other baseline demographic characteristics.
Table 1.
Baseline Demographic Characteristics for Program ACTIVE II
| Outcome | CBT (N = 21) | CBT+EXERCISE (N = 21) | EXERCISE (N = 22) | USUAL CARE (N = 23) | P-Value |
|---|---|---|---|---|---|
| Age in years, Mean (SD) | 61.43 (7.97) | 56.67 (9.81) | 53.55 (11.57) | 53.39 (11.50) | 0.037 |
| Gender | 0.681 | ||||
| Male | 6 (28.6) | 3 (14.3) | 6 (27.3) | 6 (26.1) | |
| Female | 15 (71.4) | 18 (85.7) | 16 (72.7) | 17 (73.9) | |
| Race | 0.653 | ||||
| White | 18 (85.7) | 16 (76.2) | 17 (77.3) | 16 (69.6) | |
| Not White | 3 (14.3) | 5 (23.8) | 5 (22.7) | 7 (30.4) | |
| Marital Status | 0.941 | ||||
| Now Married | 13 (61.9) | 10 (47.6) | 14 (63.6) | 13 (56.5) | |
| Never Married | 1 (4.8) | 4 (19.0) | 3 (13.6) | 4 (17.4) | |
| Divorced | 4 (19.0) | 5 (23.8) | 3 (13.6) | 4 (17.4) | |
| Separated/Windowed/Other | 3 (14.3) | 2 (9.5) | 2 (9.1) | 2 (8.7) | |
| Education | 0.007 | ||||
| Less Than or Equal to High School | 8 (38.1) | 5 (23.8) | 0 (0.0) | 1 (4.3) | |
| Trade School/Part College | 5 (23.8) | 7 (33.3) | 12 (54.5) | 7 (30.4) | |
| 4-Year College or higher | 8 (38.1) | 9 (42.9) | 10 (45.5) | 15 (65.2) | |
| Income | 0.925 | ||||
| <= $20,000 | 4 (19.0) | 5 (23.8) | 4 (18.2) | 4 (18.2) | |
| $21,000 - $40,000 | 8 (38.1) | 9 (42.9) | 9 (40.9) | 6 (27.3) | |
| $41,000 - $60,000 | 5 (23.8) | 2 (9.5) | 4 (18.2) | 4 (18.2) | |
| >= $61,000 | 4 (19.0) | 5 (23.8) | 5 (22.7) | 8 (36.4) | |
| Home Ownership (Yes) | 15 (71.4) | 14 (66.7) | 15 (71.4) | 19 (82.6) | 0.668 |
| Work Outside Home (Yes) | 8 (38.1) | 11 (52.4) | 15 (68.2) | 14 (60.9) | 0.226 |
| Household Size, Mean SD | 2.76 (1.26) | 2.05 (1.07) | 2.41 (1.22) | 2.27 (1.08) | 0.232 |
| Difficulty Making Ends Meet | 0.660 | ||||
| Hard or Very Hard | 11 (52.4) | 7 (33.3) | 10 (45.5) | 13 (56.5) | |
| 50/50 | 6 (28.6) | 10 (47.6) | 10 (45.5) | 7 (30.4) | |
| Easy or Very Easy | 4 (19.0) | 4 (19.0) | 2 (9.1) | 3 (13.0) | |
| Health Insurance (Yes) | 19 (90.5) | 19 (90.5) | 20 (90.9) | 17 (73.9) | 0.264 |
| Current PCP (Yes) | 21 (100.0) | 20 (95.2) | 20 (90.9) | 21 (91.3) | 0.544 |
| Current Endocrinologist (Yes) | 7 (33.3) | 4 (19.0) | 4 (18.2) | 5 (21.7) | 0.623 |
Note: Figures are counts (percent) until mentioned otherwise
Glycemic and Lipid Outcomes
There were no differences in A1c at 6- and 12-month overall. However, CBT+EXER had a significant and clinically important lasting A1c benefit at 6-month (-1.2%; SE: 0.6; p=0.032) and 12-month (-1.4%; SE: 0.6; p=0.025) compared to UC in those with baseline A1c ≥ 7.0%, after controlling for baseline covariates (Tables 3 and 5). We consider this as a preliminary finding because of small sample size in each of the two groups. Medical outcomes are presented in Tables 3 and 5. None of the three intervention groups showed differences in other medical outcomes with compared to the UC group except for the CBT+EXER group in total cholesterol and the EXER group in HDL at 12-month.
Table 3:
Change in Secondary Outcomes at 6-Month
| Treatment, Least Square Mean (SE) | P-Value Comparisons to USUAL CARE | ||||||
|---|---|---|---|---|---|---|---|
| Outcome1 | CBT (N=21) | CBT+ EXERCISE (N=21) | EXERCISE (N=22) | USUAL CARE (N=23) | CBT | CBT+ EXERCISE | EXERCISE |
| Change in Psychosocial Outcomes | |||||||
| Automatic Thoughts Questionnaire | −11.4 (2.7) | −10.3 (2.8) | −15.6 (2.9) | −5.5 (2.7) | 0.132 | 0.197 | 0.006 |
| Diabetes Distress Regimen Burden | −0.6 (0.3) | −1.2 (0.3) | −0.8 (0.3) | −0.1 (0.3) | 0.217 | 0.005 | 0.061 |
| CIRS Personal Support | 3.8 (1.1) | 3.3 (1.2) | 1.4 (1.2) | 0.1 (1.1) | 0.020 | 0.043 | 0.350 |
| CIRS Community Support | 0.2 (0.7) | −0.4 (0.7) | 1.0 (0.7) | −1.7 (0.7) | 0.052 | 0.169 | 0.005 |
| SF-12: PCS | −3.2 (1.9) | 0.6 (2.0) | −1.4 (2.0) | −2.8 (1.9) | 0.898 | 0.215 | 0.590 |
| Diabetes Quality of Life (Total) | 7.6 (2.5) | 11.7 (2.8) | 14.0 (2.8) | 6.7 (2.8) | 0.812 | 0.185 | 0.042 |
| Change in Medical Outcomes | |||||||
| Fasting Glucose | −1.0 (13.2) | 1.6 (13.9) | −7.4 (14.0) | −4.1 (13.4) | 0.872 | 0.760 | 0.857 |
| Total Cholesterol | −6.5 (8.6) | −12.3 (9.1) | −0.4 (9.0) | 4.6 (8.7) | 0.378 | 0.168 | 0.666 |
| High Density Lipoprotein | −0.2 (1.5) | 2.3 (1.6) | 2.0 (1.6) | 1.1 (1.5) | 0.544 | 0.566 | 0.682 |
| Low Density Lipoprotein | −3.6 (5.9) | −1.7 (6.2) | −1.6 (6.2) | 4.9 (6.0) | 0.325 | 0.434 | 0.419 |
| Triglycerides | 28.7 (22.6) | −26.7 (23.8) | 14.0 (23.9) | −13.0 (23.0) | 0.206 | 0.672 | 0.383 |
| BMI | 0.4 (0.7) | 0.1 (0.8) | −0.3 (0.7) | 0.8 (0.7) | 0.708 | 0.507 | 0.260 |
| 6 Minute Walk Test Distance (Ft) | −10.1 (36.8) | 14.3 (41.8) | 75.8 (40.3) | 54.0 (40.5) | 0.255 | 0.479 | 0.675 |
Treatment group comparisons were adjusted for baseline education status, age and baseline outcome values.
Table 5:
Change in Secondary Outcomes at 12-Month
| Treatment, Least Square Mean (SE) | P-Value for Comparisons to USUAL CARE | ||||||
|---|---|---|---|---|---|---|---|
| Outcome1 | CBT (N=17) | CBT+ EXERCISE (N=17) | EXERCISE (N=21) | USUAL CARE (N=20) |
CBT | CBT+ EXERCISE | EXERCISE |
| Change in Psychosocial Outcomes | |||||||
| Automatic Thoughts Questionnaire | −13.2 (2.8) | −12.8 (2.9) | −14.0 (2.9) | −9.6 (2.8) | 0.368 | 0.407 | 0.231 |
| Diabetes Distress Regimen Burden | −0.8 (0.3) | −1.1 (0.3) | −0.6 (0.3) | −0.8 (0.3) | 0.955 | 0.436 | 0.562 |
| CIRS Provider Support | 1.6 (1.5) | 1.7 (1.6) | 1.4 (1.6) | −3.0 (1.5) | 0.032 | 0.029 | 0.033 |
| SF-12: PCS | −1.1 (2.1) | 0.8 (2.2) | −3.1 (2.2) | −5.3 (2.0) | 0.160 | 0.040 | 0.441 |
| Diabetes Quality of Life | 7.8 (2.6) | 12.6 (2.9) | 10.1 (2.8) | 8.5 (2.9) | 0.862 | 0.299 | 0.670 |
| Change in Medical Outcomes | |||||||
| Fasting Glucose | −6.5 (15.4) | −18.1 (14.5) | 7.5 (14.0) | 0.3 (14.4) | 0.751 | 0.358 | 0.699 |
| Total Cholesterol | −5.1 (9.3) | −20.4 (9.3) | −12.9 (9.0) | 6.5 (9.0) | 0.379 | 0.035 | 0.100 |
| High Density Lipoprotein | 1.3 (1.7) | 2.5 (1.6) | −1.9 (1.6) | 3.7 (1.6) | 0.314 | 0.573 | 0.009 |
| Low Density Lipoprotein | −6.2 (6.7) | −8.2 (6.4) | −10.1 (6.2) | 2.3 (6.5) | 0.369 | 0.235 | 0.137 |
| Triglycerides | 62.2 (26.6) | −17.7 (25.0) | 9.5 (24.0) | 13.6 (24.7) | 0.188 | 0.364 | 0.900 |
| BMI | −0.5 (0.7) | −0.2 (0.8) | 0.2 (0.7) | 0.3 (0.7) | 0.441 | 0.637 | 0.936 |
| 6 Minute Walk Test Distance (Ft) | −35.1 (38.7) | 1.4 (42.5) | 15.4 (40.3) | 13.5 (43.2) | 0.416 | 0.837 | 0.972 |
Treatment group comparisons were adjusted for baseline education status, age and baseline outcome values.
Sensitivity Analyses
We conducted sensitivity analyses by imputing missing values on the primary outcomes, improvement in depression and HbA1c as well as key secondary outcomes, diabetes quality of life, in order to assess the robustness of our findings. The sensitivity analyses showed results very similar to the results without imputation.
Depression and Psychosocial Outcomes
At 6- and 12-month, all four groups showed improvement in depressive symptoms with a range of mean improvement in BDI score from 10.6 to 16.4 points (Tables 2 and 4). Although the CBT and EX groups had greater improvement (at 6-month) compared to the UC group, this did not reach statistical significance.
Table 2:
Change in Primary Outcomes at 6-Month
| Outcome | Treatment, Least Square Mean (SE) | P-Value Comparisons to USUAL CARE | |||||
|---|---|---|---|---|---|---|---|
| CBT (N=21) | CBT+ EXERCISE (N=21) | EXERCISE (N=22) | USUAL CARE (N=23) | CBT | CBT+ EXERCISE | EXERCISE | |
| Beck Depression Inventory | −16.4 (2.2) | −11.8 (2.3) | −16.0 (2.3) | −10.6 (2.2) | 0.077 | 0.714 | 0.070 |
| HbA1c* | |||||||
| (N=14) | (N=6) | (N=12) | (N=11) | ||||
| −0.2 (0.4) | −1.2 (0.6) | −0.8 (0.4) | 0.3 (0.4) | 0.350 | 0.032 | 0.058 | |
ANCOVA. Treatment group comparisons were adjusted for baseline education status, age and baseline outcome values.
Subjects with baseline A1c >= 7% were included for the analysis. Treatment group comparisons for A1c were adjusted for baseline education status, age, baseline outcome values, and change in antidiabetic medication (0 if no change, 1 if an increase, −1 if a decrease) at 6 Month Assessment.
Table 4:
Change in Primary Outcomes at 12 Months
| Outcome | Treatment, Least Square Mean (SE) | P-Value Comparisons to USUAL CARE | |||||
|---|---|---|---|---|---|---|---|
| CBT (N=17) | CBT+EXERCISE (N=17) | EXERCISE (N=21) | USUAL CARE (N=20) | CBT | CBT+ EXERCISE | EXERCISE | |
| Beck Depression Inventory | −16.4 (2.2) | −15.9 (2.3) | −14.0 (2.3) | −12.3 (2.3) | 0.219 | 0.255 | 0.558 |
| HbA1c* | |||||||
| (N=11) | (N=6) | (N=12) | (N=9) | ||||
| −0.4 (0.4) | −1.4 (0.6) | −0.4 (0.4) | 0.3 (0.4) | 0.315 | 0.025 | 0.273 | |
ANCOVA. Treatment group comparisons were adjusted for baseline education status, age and baseline outcome values.
Subjects with baseline A1c >= 7% were included for the analysis. Treatment group comparisons for A1c were adjusted for baseline education status, age, baseline outcome values, and change in antidiabetic medication (0 if no change, 1 if an increase, −1 if a decrease) at 6-Month Assessment.
At 6-month (Table 3), CBT+EXER had significant improvements in diabetes-related distress regimen burden (p=0.005); and personal support for health (p=0.043) compared to UC. EXER had higher improvements in negative thoughts (p=0.006), community social support (p=0.005) and diabetes-specific quality of life (DQOL; p=0.042) compared to UC. CBT had improvements over UC in personal support for health (p=0.020). At 12 months, all 3 treatment groups reported improved support from health care providers (p=0.03 CBT, EXER and CBT+EXER) compared to UC. CBT+EXER had improved SF-12 Physical Component Scores (p=0.04) compared to UC.
At 12-month (Table 5), all three intervention groups had significantly higher improvement in provider support compared with the UC group (p < 0.05).
Discussion
Type 2 diabetes is a public health (noncommunicable) epidemic. Co-morbid depression substantially complicates diabetes self-care and resultant glucose regulation and complications.3–8 Evidence for the long-term effectiveness of behavioral interventions on glycemic outcomes have been mixed in prior studies.17–21 This study demonstrates the effectiveness of a manualized combined behavioral approach to treat depression in adults with type 2 diabetes and MDD. This study also suggests a likely synergistic effect of CBT and exercise as evidenced by a prolonged benefit in A1c compared to UC. These treatments can be effectively delivered using existing community resources in both rural and urban environments. With modest training and support, resources that already exist in rural and underserved urban communities can affect considerable improvement in health outcomes for adults with type 2 diabetes and MDD.
In subgroup analyses, we observed a significant improvement in HbA1c in the CBT+EXER group among those with baseline HbA1c values above 7.0% without diabetes medication intervention. Prior trials have showed either delayed change in HbA1c or changes in HbA1c attributable to changes in diabetes medications.20–21,38 However, this finding should be interpreted with caution because of small sample size in each of the CBT+Exercise and Usual Care groups and should be confirmed in a large-scale study.
The observed improvement in HbA1c both at 6- and 12-months is clinically meaningful in terms of reducing the risk of diabetes complications such as nephropathy and diabetic retinopathy in type 2 diabetes adults.39
We observed significant improvements in depressive symptoms in all arms at the 6- and 12-month time points. The lack of statistically significant differences from UC at these follow-up time points is not surprising given the episodic nature of MDD and likelihood of eventual remission in the untreated UC arm. It is important to note that the active interventions continued to have higher rates of MDD remission, though not statistically significant.
The study’s limitations include a predominantly female, white, and married sample and relatively small sample sizes due to attrition from the primary sample. This may limit the generalizability to other populations. There were also baseline differences in the mean age between the treatment groups. Further, the results here present the original secondary endpoints for the observational follow-up time points at 6 and 12 months. While our retention rates are comparable to many clinical trials in patient populations with major medical diagnoses, the small sample size limited the power to detect effects.40 However, sensitivity analyses did not show bias due to sample attrition suggesting the durability of these findings. Finally, the sample represented socioeconomic and geographic diversity but had limited ethnic diversity as it did not include Latinos and Asian Americans.
In summary, the Program ACTIVE community-based intervention is the first to demonstrate clinically meaningful improvements in glycemic outcomes in adults with type 2 diabetes as long as 12 months post-intervention in patients with elevated glycemia. These interventions enable behavioral health and exercise professionals to deliver interventions to concurrently improve depression and type 2 diabetes in patients with both disorders. These data demonstrate both effectiveness and, in separate analyses, cost-effectiveness41, suggesting value of adoption of these interventions by exercise and healthcare organizations at the national level.
Highlights.
Comorbid depression and type 2 diabetes is associated with worsened diabetes outcomes and diabetes complications.
Community-based interventions for depression and diabetes have the potential to extend reach of treatment in collaboration with medical care.
6- and 12-Month outcomes of Program ACTIVE II demonstrated that sustained changes in A1c were observed at 6-and 12-months from baseline in those with a baseline A1c ≥7.0%, in those randomized to the combination (CBT+EXER) group. This group also showed significant improvements in diabetes-related distress regimen burden (p=.005); and social support (CIRS, p=.043) compared to UC.
These findings point to the enduring benefits of community-based interventions to extend the availability of depression treatment for T2D patients.
Acknowledgements
Program ACTIVE II was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (R18DK092765 & R34DK071545). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
We thank all of the participants of Program ACTIVE II who gave generously of their time and energy to engage in a new research activity. We are grateful for their generosity of spirit and their willingness to try something new.
Footnotes
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The following conflicts of interest apply to the co-authors: Dr. Mary de Groot is a faculty consultant to Mediflix, Inc. Dr. Kieren Mather is an employee of Eli Lilly, Inc.
The Program ACTIVE Research Team thanks the participants of Program ACTIVE II who gave generously of time and energy to be involved in this study. The authors also thank the community partners who delivered the interventions to the participants and for referring health care providers for collaboration. The Program ACTIVE Research Team also thanks the following individuals for their many contributions to this study: Dr. Karen Fitzpatrick, Barb Myers, Chelsea Holbert, Debby Wimer, Kelly Chaudoin, Sarah Mielens, Ellen Knapp, Kent Crick, Kellie Givens, Tracey Garrett, Trenity Taylor, Danielle Epler, Michelle Weinstein, Kasey Goodpaster, Brett McKinney, and Kisha Wilkerson (Indiana University); Rachel Clift, Frank Schwartz, Cammie Starner, Lynn Petrik, and Melinda Ruberg (Ohio University Heritage College of Osteopathic Medicine); Susan Eason, David Donley, Lindsey Sams, Jaclyn Babe, Christian Abildso, and Daniel Bonner (West Virginia University); and Bernadette Heckman (University of Georgia). The authors also thank the community partners who delivered interventions to the participants: Richard Nulter, Kim Johnson, Adrianne Garrett, Bonnie de Lange, and Cassandra Watt (Hopewell Health Center, Belpre and Athens, OH); Suzy Zumwalde and Dave Vogel (Marietta Family YMCA, Marietta, OH); Sharon Sheets, Jason Weber, and Sheila Williams (private practitioners, Athens, OH); Priscilla Leavitt, Stephen Givens, and Rick Stanley (Counseling & Wellness Center, Parkersburg, WV); Noah Albrecht, Joe Leaman, Erin Weber, Allison Burner, Dan Braatz, Cassy Offenberger, and Jonathan Rodriquez (Mountain River Physical Therapy, Parkersburg and Vienna, WV); Pat Perine and Louie Haer (Family Fitness, Parkersburg, WV); Jo sh Christen (Wellworks, Athens, OH); McKenzie Walter, Flynt Smathers, and Rich Campitelli (Athens Community Center, Athens, OH); Karen Newton, Eric Murphy, Jennifer Murray, Lauren Prinzo, and Rebecca Smith (West Virginia University County Extension Program); Kathy Dodrill (The Ohio State University Washington County Extension Program); Christina Ferroli and Lydia Armstrong (Purdue University Marion County Extension Program); Brian Sharp, Dana Nugent, and Mark Tipton (United Summit Center, Clarksburg, WV); Kimberly Yingling (private practitioner, Morgantown, WV); Eric Shaw and Rick Williams (Tygart Valley Rehabilitation and Fitness Center, Grafton, WV); Kellie Snyder (Fairmont General HealthPlus, Fairmont, WV); Shane Trivigno and Beth Burleson (Pro Performance, Morgantown, WV); Rob Cress and Jesse Halldin (Rob’s Fitness Factory, Morgantown, WV); Whitney Hickman (Harrison County YMCA, Lodgeville Branch, Bridgeport, WV); James Brummett, Kathi Bledsoe, Allison White, Ella Vinci, Cynthia Donel, Monica Staples, Tina Wiesert, Carol Hendricks, Krisha MacDonald, and Cindy Wilson (Midtown Community Mental Health, Indianapolis, IN); Gary Brown, Chelsy Winters, Anne Graves, Evan Heald, Latisha Idlewine, Julie Kenny, Matt Larson, and LaRona Dixon (YMCA of Greater Indianapolis, Indianapolis, IN); Allison Plopper, Natalie Johann, and Denise Sayasit (Physically Active Residential Communities and Schools [PARCS] Program, Indianapolis, IN); and Ben Jones (Chase Near Eastside Legacy Center, Indianapolis, IN).
We also wish to acknowledge our community partners who delivered interventions to our participants: Hopewell Health Center, Belpre and Athens, OH; Marietta Family YMCA, Marietta, OH; Sharon Sheets, Athens, OH; Jason Weber, Athens, OH; Sheila Williams, Athens, OH; Counseling & Wellness Center, Parkersburg, WV; Mountain River Physical Therapy, Parkersburg and Vienna, WV; Family Fitness, Parkersburg, WV; Wellworks, Athens, OH; Athens Community Center, Athens, OH; West Virginia University County Extension Program; The Ohio State University Washington County Extension Program; Purdue University Marion County Extension Program; United Summit Center, Clarksburg, WV; Kimberly Yingling, M.A., NCC, LPC, Morgantown, WV; Tygart Valley Rehabilitation and Fitness Center, Grafton, WV; Fairmont General HealthPlus, Fairmont, WV; Pro Performance, Morgantown, WV; Rob’s Fitness Factory, Morgantown, WV; Harrison County YMCA, Lodgeville Branch, Bridgeport, WV; Eskenazi Midtown Community Mental Health, Indianapolis, IN; YMCA of Greater Indianapolis, Indianapolis, IN; Physically Active Residential Communities and Schools (PARCS) Program, Indianapolis, IN; Chase Near Eastside Legacy Center, Indianapolis, IN; Natalie Johann; Denise Sayasit; Evan Heald; Latisha Idlewine; Julie Kenny; Matt Larson; Gary Brown; Chelsy Winters; Anne Graves; Christina Ferroli; Lydia Armstrong; LaRona Dixon; Allison Plopper; Ben Jones; James Brummett; Kathi Bledsoe; Allison White; Ella Vinci; Cynthia Donel; Monica Staples; Tina Wiesert; Carol Hendricks; Cindy Wilson; Richard Nulter; Kim Johnson, M.A.; Adryanne Garrett; Bonnie de Lange; Cassandra Watt; Priscilla Leavitt, Ph.D.; Rick Stanley, Ph.D.; Stephen Givens, Psy.D.; Sharon Sheets, M.A.; Suzy Zumwalde; Dave Vogel; Noah Albrecht; Joe Leaman; Erin Weber; Allison Burner; Dan Braatz; Cassy Offenberger; Eric Weber; Jonathan Rodriquez; Pat Perine; Louie Haer; Josh Christen; McKenzie Walter; Flynt Smathers; Rich Campitelli; Kathy Dodrill; Brian Sharp, Ph.D.; Dana Nugent, Psy.D; Mark Tipton, M.A., A.A.D.C, LPC; Eric Shaw, M.P.T; Rick Williams, C.D.M., M.P.F.T; Shane Trivigno, B.S.; Kellie Snyder, B.S., M.B.A, C.P.T; Beth Burleson, B.S. C.P.T; Brad Wright, B.S, C.P.T; Rob Cress M.S., C.S.C.S; Jesse Halldin, B.A, CPT; Whitney Hickman, B.S., A.C.S.M; Karen Newton, B.A; Eric Murphy, M.S, M.A; Jennifer Murray, M.S; Lauren Prinzo, M.P.A; Rebecca Smith, M.B.A.
Author Statement
The following conflicts of interest apply to the co-authors: Dr. Mary de Groot is a faculty consultant to Mediflix, Inc. Dr. Kieren Mather is an employee of Eli Lilly, Inc. No artificial intelligence was used in the creation or revision of this manuscript.
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