Background and justification: Nearly 29 million Americans (9.3% of the population) have type 2 Diabetes Mellitus (T2DM) and another 86 million are considered prediabetic, 20-30% of whom will develop diabetes within five years.4,5 T2DM disproportionately affects those from lower socioeconomic status (SES) and rural backgrounds. Appalachian residents represent an extreme version of this already vulnerable population, with rates of diabetes 46% higher than national averages.6,7 The investigators have developed, pilot tested (N=41) and refined (N=48 in-depth interviews, 4 focus groups with 31 participants, and 2 CAB meetings with 16 members), a culturally appropriate, feasible, and promising intervention that combines diabetes self-management education and tailored patient navigation intervention., Goal: Our goal focuses on reducing HbA1c, BMI, blood pressure, lipids, and waist circumference and improving T2DM self-management and clinic attendance. Leveraging local assets, including faith communities, local health facilities, trained community health workers, and social support, the investigators will expand a promising and refined pilot study and assess outcomes, satisfaction and cost effectiveness. Innovation and impact: The proposed project is among the first RCT to combine the two most influential approaches to diabetes control-- self-management education and tailored patient navigation in a community setting. The Community to Clinic Navigation (CCN) intervention has the potential to sustainably empower hard to reach populations with effective self-management education and enhance the quality of healthcare in traditionally underserved communities, greatly improving T2DM outcomes.

1. Background: Appalachian residents maintain disproportionately high rates of Type 2 Diabetes Mellitus (T2DM) and suffer tremendous burdens from diabetic complications. The main challenges to stemming adverse outcomes from T2DM involve ensuring optimal clinical care and self-management. Because the prevalence of diabetes has tripled since 2005, the already low supply of primary care physicians combined with this tremendous chronic disease burden places huge demands on providers in rural Appalachia. Enhancing the quality and efficiency of these practices by linking to community health workers has the potential of mitigating the adverse effects of these shortages.

   Patient navigation, particularly a clinic to community navigation (CCN) model offers an innovative approach to address these inequities. Patient navigation has been implemented almost exclusively in the cancer setting, despite being promising for chronic disease management. The proposed project is, to our knowledge, the first to test a hybrid model of clinic (health promotion professional) plus community (community health worker) navigation among rural residents. Clinical patient navigation has been shown to facilitate appointment setting and return visits, may improve goal setting, and enhances some adherence (medication taking, blood glucose testing), but does not address some key psychosocial (self-efficacy, patient activation) and practical concerns (transportation, childcare, self-management) challenges. Community-based navigation programs have been shown to enhance self-efficacy, decrease community barriers to care (e.g., transportation), and improved self-management, but may be less effective in ensuring return visits and working collaboratively with the doctor.

2. Objectives: The investigators aim to test a CCN program that may improve the most salient influences on diabetes outcomes and self-management, the health care context and the patient's home context. Specifically, the investigators will (1) recruit 1200 participants from community settings with T2DM and HbA1c levels between 9-11% and randomize them to one of three arms, DSMP; PN, or combined CCN intervention; (2) the investigators will administer three quantitative assessments. All activities will take place in Appalachia. Outcomes include physiologic data (HbA1C levels, blood pressure, lipids, waist circumference and BMI, obtained by research staff); quantitative data collection of self-management (medication taking, blood glucose, appointment adherence, diet, physical activity, foot and eye care, obtained by interviewer); and psychosocial variables (self-efficacy, patient activation, obtained by interviewer).

3. Study Design: Behavioral randomized controlled trial, single blind design.

4. Study Population: Eligibility criteria: Adults 18+; Appalachian residence, and HBA1c levels between 9-11%. Those who do not meet these inclusion criteria, are cognitively impaired, or who do not wish to participate will be excluded. All race/ethnicities and both genders will be included. Participants will be enrolled on a rolling basis from June 1, 2014-June 2, 2019. Participants will be involved in the study for approximately one year. The investigators anticipate a total of 1200 participants.

5. Subject Recruitment Methods and Privacy: Participants will be recruited through churches and other community settings. If eligible (see above), project staff will call potential participants within five days to verify eligibility and determine their interest in participating in the study.

6. Informed Consent Process: For those indicating an interest in participating, staff will visit potential participants at their home or a location of their choosing and administer the informed consent document. Study personnel for all phases of the project will provide a clear explanation of the project and invite questions. Our informed consent forms are written in a basic language. Interested participants will be asked to provide their signature on the informed consent forms. A copy of the signed consent will be provided for all participants. All forms will be read to participants to allay concerns about limited literacy. No non-English speaking or cognitively impaired participants will be recruited.

7. Research Procedures: The consort diagram (Figure 1) below provides an estimation and visual description of the recruitment and sampling frame.

   Fig 1: Consort diagram of enrollment

   1. Once informed consent documents are completed, participants (N=1200) will undergo the baseline assessment. Baseline, posttest, and exit assessments will consist of the same measures highlighted in Table 3.

   2. There will be three arms. For those randomized to the diabetes self management program (n=435), within two weeks of initial recruitment and baseline assessment, project staff will schedule the participant to attend a group Diabetes Self-management Program, a six week, lay lead and en evidence-based diabetes home self-management program (See Table 1, DSMP contents). Staff will arrange for the group sessions of the DSMP. One session will take place every other week. Upon completion of the DSMP program, approximately three month later, clinic navigation will be implemented. For those randomized to the Patient Navigation group, within two weeks of initial recruitment and baseline assessment, project staff will schedule the participant to meet with the Community Health Worker who will strategize about insuring that patients make their doctors' appointments as scheduled. The CHW/Patient Navigator will make at least 4 calls to each participant randomized to this group. For those randomized to the combined Community to Clinic Navigation, CCN (n=435), both of the activities for the Diabetes self management education group and the Patient navigation will be conducted. At month 5-6, the posttest will take place. To assess sustainability, 3-4 months later, navigation again will take place. An interviewer will complete the exit interview in month 10-11 using the same assessments. All throughout the intervention, standard medical visits will take place.

      Fig 2: Flow diagram of intervention and control activities by month

      Table 1: DSMP contents and conduct:

      Class Number Content/Objectives./Activities

      1. Diabetes: causes, diagnosis, incidence, and prevalence Discussion using a pancreas model and the handout "Understanding Diabetes". How to talk with your doctor and being a proactive patient. Goal setting
      2. Blood glucose testing, hyperglycemia, and hypoglycemia Discussion of the blood glucose-testing procedure, review of the handouts "Hyperglycemia" and "Hypoglycemia. Goal check in
      3. Eating right for diabetes, discussion of the food pyramid and dietary strategies ; Review of handouts. Goal check in
      4. Avoiding complications: Eye care, dental care, neuropathy, hypertension Discussion of appropriate eye care, dental care, kidney care. Review of how to talk with your doctor. Goal check in
      5. Getting active: review of physical activity and foot care. Goal check in
      6. Empowerment and goal check in. Class discussion.

      Table 2: Timeline

      Activity Q1 Q2 Q3 Q4 Staff training Recruitment, informed consent, enrollment, randomization Baseline medical record review/ interview 0 CCN arm participants receive DSM sessions (6 sessions total) and navigation to clinic X X Posttest 1 0 CCN arm Navigation X Exit interview 0 CCN= clinic to community navigation (intervention arm); DSM= diabetes self-management; X= intervention activity; 0= assessment

8. Resources: The research and intervention activities will be conducted in participants' homes, community sites, and the health clinics.

9. Potential Risks: The potential risks from participating in the study are very small. Some risk of pain from a finger prick or psychological upset could result from responding to interview questions or the emotional distress from questions about diabetes management. The most significant risk involves any threat to confidentiality. However, all project staff will be human subjects trained and have extensive experience maintaining participant confidentiality.

10. Safety Precautions: In each stage of the research, the investigators will make every effort to provide protection against risks. Study personnel will provide a clear explanation of the project and invite questions during enrollment. In the rare event that a participant experiences psychological distress resulting from the interview questions or from the intervention, our staff will contact Dr. Van Breeding, internal medicine physician at the MCHC. Dr. Breeding will consult with the participant, debrief and discuss the participant's concerns, and refer participants to any additional support. In addition, all project staff will receive training on how to respond to a participant who needs additional assistance with diabetes management.

11. Benefit vs. Risk Participation in the study involves little risk for subjects in comparison to the potential benefits of adopting improving diabetes outcomes. Participants in the intervention group will receive their usual care, plus navigation from a staff person at MCHC and an evidence-based diabetes self-management program at no cost. If they are not assigned to the intervention arm, they will receive their usual diabetes care. Given the disproportionate diabetes burden experienced by Appalachian populations, implementing and evaluating this novel, theory based intervention has the potential to save many lives while advancing intervention science.

12. Available Alternative Treatment(s): Participants will be randomized to the intervention (the standard of care plus navigation with a clinic employee and community-based navigation) OR will receive the standard treatment, which involves brief clinically-based consultation with the health care provider.

13. Research Materials, Records, and Privacy: Two sources of data will be collected: physiologic data collection (HbA1C levels, blood pressure, lipids, and BMI); and quantitative assessments (surveys). Table 3 highlights the specific data to be collected.

Table 3: Variables Data sources and collector Main outcomes HbA1C, blood pressure, lipids, waist circumference, BMI Additional outcomes: Self-management outcomes Medication taking, blood glucose testing, appointment adherence, diet, physical activity, foot and eye care.

Assessments by UK project staff Diabetes Empowerment Scale (self-efficacy), patient activation Assessments by UK project staff Sociodemographic, self-perceived health status, depression, Clinic attendance, assessments by UK project staff

14. Confidentiality Confidentiality of all data will be maintained by never linking paper or computer copy of data with the participants' names. A sheet with the participant's name, address, telephone number, and identification number will be kept by the Project Director and Principal Investigator separately in a locked file. Only staff members who are authorized to review files will be permitted access to the data. As part of our training, each lay health adviser and interviewer will be asked to sign a confidentiality pledge promising never to reveal, alter, or falsify survey data. This pledge is especially important in small, tight-knit rural communities. Data are held in password-protected computers and secure servers at University of Kentucky which have extensive firewalls and security measures. The investigator will keep all records (tapes, informed consent documents, and other records like completed questionnaires) for a minimum of six years after the completion of the study.

16. Costs to Subjects: N/A for program participation. Some costs associated with transportation may occur.

17. Data and Safety Monitoring: N/A 18. Subject Complaints: Participants will be asked to contact the investigator, Dr. Nancy Schoenberg at 859-323-8175 should they have any complaints. If they have any questions about their rights as a volunteer in this research, they will be asked to contact the staff in the Office of Research Integrity at the University of Kentucky at 859-257-9428 or toll free at 1-866-400-9428.

19. Research Involving Non-English Speaking Subjects or Subjects from a Foreign Culture: N/A 20. HIV/AIDS Research: N/A 20. PI-Sponsored FDA-Regulated Research: N/A

Two main revisions for this trial were implemented.

1. Timelines: Reduced the 18 month follow up to 9 months and then, ultimately, from 9 months to 6 months.

2. Data collection for several secondary outcomes:

   1. Data for HDL, LDL, cholesterol was not collected for two reasons:

1) lack of a scientific evidence base on the association between lipids and diabetes self-management and diabetes outcomes.

2) The extremely high cost of such data collection. b. We ceased collecting data on clinic attendance. At baseline, we collected data on clinic attendance within the standard guideline of 3 months. To our surprise, 87% of our sample had clinic appointments consistent with recommended guidelines. Thus, we could not realistically expect any significant improvements in subsequent time periods. Such a revelation, in conjunction with the cessation of clinical operations due to COVID, made clinic attendance data collection unnecessary and unfeasible. When the project began in 2017, the uninsured population of Appalachian Kentucky dropped from 25% to 6.7%. This coverage resulted in most participants adhering to the recommendations for clinic attendance.

Several significant events undermined the original data collection plan including:

• 24 month cessation of recruitment, data collection and intervention implementation due to COVID
• Episodic cessation of recruitment, data collection and intervention implementation due to COVID
• Major interruption of recruitment, data collection and intervention implementation due to natural disaster (flooding July 2022)
• Lack of NIH approval of two supplement requests to support data collection

Inclusion Criteria:

• Adults (age 18+);
• Appalachian residence, no plans to relocate out of the area in the next 18 months,
• Willingness and ability to participate (i.e., no major cognitive impairment)
• HbA1c levels at least 6.5% or Diagnosis of Diabetes.

Exclusion Criteria:

-

9 months

Participant files were reviewed monthly from enrollment through the final follow up