Biobehavioral Bases & Management of Type 2 Diabetes

This project will be conducted on type 2 diabetic patients. Patients meeting eligibility criteria will be randomized to SC or the CALM-D condition, which includes diet and exercise counseling and coping skills training that in part is intended to facilitate medication adherence. Both CALM-D and SC patients will be prescribed antidepressant as well as other medications.

Because patient retention and adherence to protocol will be a major emphasis in this project, we intend to use a 3 session "run-in" prior to randomization. Patients who appear to be medically eligible, meet study criteria for major depression, and who express willingness to participate return for a session in which the patient completes a medical history form, undergoes a brief physical exam, takes a maximum exercise stress test, is given a standardized dietary assessment, and is taught how to use a food diary and activity monitor. At the beginning of the third run-in session, the patient returns the completed food diary, and data from the activity monitor is recorded. The patient then takes a 2 hour oral glucose tolerance test (OGTT) during which time he or she answers questions about health habits, psychosocial functioning and health quality of life. After a brief rest and snack the patient is escorted to the Ultrasound Laboratory for assessment of echocardiography, carotid artery imaging and brachial artery endothelial functioning. Patients who satisfactorily complete all three run-in sessions, meet eligibility requirements and are interested in participating, are then asked to provide informed consent and are randomized into the CALM-D or SC conditions.

Randomization will be implemented using a stratified randomized block design. Eight strata will be designated on the basis of age (<50 vs ≥ 50 years), severity of depression (<24 vs ≥ 24 on the HRSD), and glycemic control (<8 vs ≥ HbA1c) at baseline. Within each stratum, random sequences will be generated in blocks of sizes 2, 4 or 6. The block size will also be randomly chosen. In this manner the resulting sequence will look purely random, but will be fairly closely balanced with respect to the critical variables of age, depression and severity of diabetes (Piantadosi, 1997). Elements in the random sequences will be paired with the subject number of participants assigned to each stratum. The number of sequences generated for each stratum will vary depending on the number of eligible participants in that stratum. These sequences will be concealed until the treatment conditions are actually assigned.

The SC patients will be treated in accordance with ADA Clinical Practice Guidelines (2005), which will include at least 2 HbA1c tests, lipid profile, test for microalbuminuria, dilated retinal eye exam, complete foot exam and influenza immunization each year plus prescribed aspirin therapy, and a screen for readiness to stop smoking if they smoke. Smokers are encouraged to stop, using ADA recommendations in the Guidelines. In addition, each patient's physician will receive after baseline, 6 months and 1 year, a report including OGTT, insulin resistance, oxidative stress, inflammation, lipid profile, endothelial function, resting blood pressure, cardiac and vascular function, cardiac morphology, psychosocial functioning and health quality of life. Participants in the CALM-D condition will receive all of the above, but also 2 individual counseling sessions on (a) getting started, being active, losing weight and managing stress; and (b) negative thoughts and emotions including a discussion of ways to curb emotional eating. Following the 2 individual sessions there will be 2 weekly group sessions followed by 4 bi-weekly sessions and then 9 monthly sessions. Each session in CALM-D will be 1 hour long and will include deep breathing relaxation (5 min), homework review including medication adherence, activity level, and fat and caloric intake (10 min), session topics and homework assignment (45 min). The group topics include such issues as "Where's the Fat?/Three Ways to Eat Less Fat" and "Taking Your Medications/Stress and You." Although participants and interventionists will be aware of the patient's treatment assignment, all staff who collect, verify or classify end point data or follow-up assessments will be masked as much as possible.

The primary outcomes of the study will be: a) depression; (b) weight and waist circumference; (c) HbA1c; and (d) medication adherence. Secondary outcomes will include: (a) glucose tolerance, (b) insulin resistance, (c) inflammation, (d) fibrinolysis, (e) lipid profile, (f) oxidative stress, (g) endothelial function, (h) resting blood pressure, (i) cardiac and vascular function, (j) cardiac morphology, (k) psychosocial functioning, and (l) health quality of life. The above variables will be assessed at baseline, after 6 months and after 1 year. Data will be analyzed using mixed-model analyses to determine change over time as a function of experimental condition. This will be done using the PROC Mixed module of SAS software (Littell, Milliken, Stroup, & Wolfinger, 1996). This methodology is useful for intent to treat analyses in that it does not require complete data across multiple time points.