1. IntroductionThe prevalence of type 2 diabetes (T2D) in Japan is a major health concern and is predicted to further increase over coming decades due to an aging population [[1]Goto A. Noda M. Inoue M M. Goto M. Charvat H. Increasing number of people with diabetes in Japan: Is this trend real?.]. In addition to lifestyle changes such as diet, exercise, and weight management, treatment for T2D comprises oral antidiabetic and/or injectable medications [2Davies M.J. D’Alessio D.A. Fradkin J. et al.Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)., 3American Diabetes Association Standards of medical care in diabetes-2019 abridged for primary care providers., 4Haneda M. Noda M. Origasa H. et al.Japanese clinical practice guideline for diabetes 2016., ]. Due to its progressive nature, most people with T2D (PWT2D) will eventually require insulin to maintain glycemic control [[6]Defining and characterizing the progression of type 2 diabetes.]. Although insulin treatment is associated with higher rates of adequate glycemic control [3American Diabetes Association Standards of medical care in diabetes-2019 abridged for primary care providers., ], initiation of insulin therapy is often delayed. This delay, known as psychological insulin resistance (PIR), has been examined in several studies [7Polonsky W.H. Hajos T.R. Dain M.P. Snoek F.J. Are patients with type 2 diabetes reluctant to start insulin therapy? An examination of the scope and underpinnings of psychological insulin resistance in a large, international population., 8Ng C.J. Lai P.S. Lee Y.K. Azmi S.A. Teo C.H. Barriers and facilitators to starting insulin in patients with type 2 diabetes: a systematic review., 9Nakar S. Yitzhaki G. Rosenberg R. Vinker S. Transition to insulin in type 2 diabetes: family physicians’ misconception of patients’ fears contributes to existing barriers., 10Peyrot M. Barnett A.H. Meneghini L.F. Schumm-Draeger P.M. Insulin adherence behaviours and barriers in the multinational global attitudes of patients and physicians in insulin therapy study., 11Oliveria S.A. Menditto L.A. Ulcickas Yood M. et al.Barriers to the initiation of, and persistence with, insulin therapy.]. PIR is documented to be due to physician-related factors such as clinical inertia [12Shah B.R. Hux J.E. Laupacis A. Zinman B. van Walraven C. Clinical inertia in response to inadequate glycemic control: do specialists differ from primary care physicians?., 13Parchman M.L. Pugh J.A. Romero R.L. Bowers K.W. Competing demands or clinical inertia: the case of elevated glycosylated hemoglobin.] and lack of knowledge concerning insulin [[9]Nakar S. Yitzhaki G. Rosenberg R. Vinker S. Transition to insulin in type 2 diabetes: family physicians’ misconception of patients’ fears contributes to existing barriers.], and patient-related factors including fear of injections [[11]Oliveria S.A. Menditto L.A. Ulcickas Yood M. et al.Barriers to the initiation of, and persistence with, insulin therapy.], fear of weight gain and hypoglycemia, misconceptions regarding the benefits of insulin, and feelings of personal failure [10Peyrot M. Barnett A.H. Meneghini L.F. Schumm-Draeger P.M. Insulin adherence behaviours and barriers in the multinational global attitudes of patients and physicians in insulin therapy study., 14Polonsky W.H. Arsenault J. Fisher L. et al.Initiating insulin: how to help people with type 2 diabetes start and continue insulin successfully., 15Brod M. Kongso J.H. Lessard S. Christensen T.L. Psychological insulin resistance: patient beliefs and implications for diabetes management.].Limited research exists regarding effective strategies that help PWT2D begin insulin treatment. Several groups [14Polonsky W.H. Arsenault J. Fisher L. et al.Initiating insulin: how to help people with type 2 diabetes start and continue insulin successfully., 16Krall J. Gabbay R. Zickmund S. Hamm M.E. Williams K.R. Siminerio L. Current perspectives on psychological insulin resistance: primary care provider and patient views., 17Brod M. Lessard Alolga S. Meneghini L. Barriers to initiating insulin in type 2 diabetes patients: development of a new patient education tool to address myths, misconceptions and clinical realities., 18Polonsky W.H. Jackson R.A. What’s so tough about taking insulin? Addressing the problem of psychological insulin resistance in type 2 diabetes.] have put forward recommendations to address PIR, including the need to focus on injection-related fears and misconceptions concerning insulin, as well as interventions targeting health care providers (HCPs) [[19]Linetzky B. Jiang D. Funnell M.M. Curtis B.H. Polonsky W.H. Exploring the role of the patient-physician relationship on insulin adherence and clinical outcomes in type 2 diabetes: insights from the MOSAIc study.]; however, interventional studies are currently lacking. Furthermore, there are limited studies describing PIR among Japanese PWT2D [20Transition of psychological and behavioral reactions to insulin treatment in patients with type 2 diabetes., 21Yoshioka N. Ishii H. Tajima N. Iwamoto Y. Dawn Japan group Differences in physician and patient perceptions about insulin therapy for management of type 2 diabetes: the DAWN Japan study., 22Odawara M. Ishii H. Tajima N. Iwamoto Y. Impact of patient attitudes and beliefs to insulin therapy upon initiation, and their attitudinal changes after initiation: the DAWN Japan study.].To further understand factors associated with reluctance to commence insulin, a multinational, non-interventional study was conducted with insulin-using PWT2D who were initially reluctant to commence insulin treatment [[23]Polonsky W.H. Fisher L. Hessler D. et al.Identifying solutions to psychological insulin resistance: an international study.]. The EMOTION (AccEpting Insulin TreatMent for Reluctant PeOple with Type 2 DIabetes Mellitus – A GlObal Study to IdeNtify Effective Strategies) study [[23]Polonsky W.H. Fisher L. Hessler D. et al.Identifying solutions to psychological insulin resistance: an international study.] was conducted in 3 phases: (1) qualitative interviews with PWT2D and HCPs (2) quantitative surveys, and (3) follow-up interviews. EMOTION identified certain HCP actions and life events that were helpful in initiating insulin among the total multinational population. These included efforts to address injection concerns by demonstrating the insulin injection process, explaining the benefits of insulin, and adopting a collaborative communication style [[23]Polonsky W.H. Fisher L. Hessler D. et al.Identifying solutions to psychological insulin resistance: an international study.]. The perceived helpfulness of these actions was linked with earlier insulin initiation and greater insulin persistence over time [[23]Polonsky W.H. Fisher L. Hessler D. et al.Identifying solutions to psychological insulin resistance: an international study.].A subanalysis of Japanese participants from phase 2 of EMOTION has been previously described [[24]Okazaki K. Shingaki T. Cai Z. Perez-Nieves M. Fisher L. Successful healthcare provider strategies to overcome psychological insulin resistance in Japanese patients with type 2 diabetes.], outlining the frequency and level of helpfulness of HCP actions and life events that impact the decision to initiate insulin amongst Japanese PWT2D. Overall, practical demonstrations by HCPs on how to use insulin were rated by Japanese participants as most helpful. Examples of such practical demonstrations, reported as helping moderately or a lot, were ‘HCP walked patient through the process of exactly how to take insulin’, ‘HCP showed an insulin pen’, and ‘HCP helped patient to see how simple it was to inject insulin’ [[23]Polonsky W.H. Fisher L. Hessler D. et al.Identifying solutions to psychological insulin resistance: an international study.].

The present study builds on the current literature by describing the results of qualitative research on a subgroup of Japanese participants from phase 3 of EMOTION. We aim to identify key factors that motivated reluctant Japanese PWT2D to initiate insulin treatment in order to further elucidate potential clinical interventions for helping Japanese PWT2D overcome PIR, and to clarify actions/events from the phase 2 quantitative studies.

2. Methods2.1 Study design and populationData included in the study were derived from the EMOTION study. The study design and procedures have been described elsewhere [[23]Polonsky W.H. Fisher L. Hessler D. et al.Identifying solutions to psychological insulin resistance: an international study.]. Briefly, phase 1 of EMOTION involved qualitative interviews with a total of 29 insulin-using adults with T2D and 29 HCPs across 6 countries (Brazil, Canada, Germany, Spain, United Kingdom, and United States of America) to inform survey content and design. Phase 2 involved a 30-minute survey, derived from the qualitative interviews, with PWT2D from these same nations plus Japan. At the end of phase 2, participants were asked if they could be contacted for a follow-up qualitative phone interview (phase 3). This 45- to 60-minute interview involved an in-depth discussion about factors influencing the participants’ decision to initiate insulin, and the effects of these factors on other outcomes such as satisfaction, diabetes distress, care management, and quality of life. This report focuses on phase 3 of EMOTION in Japanese PWT2D.

The EMOTION study was performed in accordance with principles of the Declaration of Helsinki. Regulatory approval was provided by the Western Institutional Review Board (Puyallup, WA, USA), Pennsylvania State University College of Medicine IRB (Hershey, PA, USA) as well as Nagoya University IRB (Nagoya, Japan). All participants provided informed consent.

PWT2D were selected from Survey Sampling International (SSI) and their local partners’ market research panels or online communities. Eligible participants were adults (≥ 21 years old), diagnosed with T2D ≥ 1 year before initiating basal insulin, used basal insulin for ≥ 30 days and < 3 years before the survey, and who reported at screening that they were initially “not willing” to start insulin treatment after the first HCP recommendation. Individuals were ineligible if they had type 1 or gestational diabetes, had experience with insulin therapy before initiation of basal insulin therapy, had initiated insulin using a pre-mix product or basal bolus therapy, or if they had initiated insulin after surgical procedures involving the pancreas.

2.2 InterviewsThe semi-structured participant interview guide was developed in accordance with findings from the first 2 phases of the EMOTION study, the current literature, and the experience of the experts and advisors leading the study. The open-ended questions were structured for a 45- to 60-min interview and designed to gain a deeper perspective relevant to the research questions (see Supplementary materials). Participants were asked questions pertaining to the following areas of exploration: a) participants’ thoughts and perceptions about insulin before and after initiation and any related factors (e.g., through observation of other family members using insulin); b) reasons behind participants’ responses to the individual PIR Action Survey questions (e.g., responses that were answered on a particular end of the spectrum such as, (1) not helpful or (2) little helpful and (4) moderately helpful or (5) helped a lot); c) other actions their HCP may have taken that convinced them to commence insulin treatment; and d) what advice, if any, they would give to other PWT2D facing a similar PIR. If all questions in a section were answered the same, the section was further analyzed by asking which action was the most or least helpful out of those checked. This approach aimed to give an in-depth summary of the survey questions and reasons behind responses.

Training sessions for interviewers were conducted by HS and KO. Data analysis was conducted by KO and NT. The informed consent documentation and the interview guide were translated into Japanese by SSI. Interviews were conducted and analyzed in Japanese, with the results translated into English. All translated materials were reviewed by advisors for appropriateness.

2.3 Data analysis

Demographics and clinical characteristics of participants were collected, including age, gender, educational level, HbA1c, and body mass index (self-reported).

Interviews were recorded, transcribed, and analyzed by Steps for Coding and Theorization (SCAT), a qualitative data analysis method [, 26SCAT: steps for coding and theorization., 27Concept of Qualitative Research – From Research Methodology to SCAT Analysis.]. SCAT is a 4-step coding process used to identify themes and constructs, and to develop a storyline by weaving these themes and constructs together. This method is applicable for analyzes of small-scale data, including open-ended questionnaire responses. SCAT is based on theory development from data that are collected and analyzed systematically and iteratively. In detail, data integration and analysis from each interview was performed to generate coding. Japanese interview data and the primary EMOTION analyses were reviewed and analyzes of data in line with the purpose of the study were performed followed by the development of a theoretical description. Data saturation was reached when no new findings were emerging [28The use of saturation in qualitative research., ]. Following this, Japanese interview data were checked and re-analyzed based on the theoretical description. Meanwhile, the theoretical description was revised by not only focusing on the sections that could be explained using the theory already generated, but also identifying those sections that did not correspond with the theoretical description. Thus, the theoretical description is modified to meet the research purpose.The significance of the method is suggested in its explicit process of analysis, its smooth guidance towards the steps of analysis, the enhancement of the reflective quality of critique and falsifiability, and the integration of theoretical coding and qualitative data analysis []. Interviews were transcribed and coded as follows:1.

Noteworthy words and phrases from the text.

2.

Paraphrases of 1.

3.

Concepts that account for number 2.

4.

Themes and constructs in consideration of context.

A storyline was described based on the themes and constructs, then a theory provided from the storyline.

4. Discussion

We report the findings of exploratory interviews with Japanese participants from the global EMOTION study. Our study identified 3 major themes which influence Japanese PWT2D to commence insulin therapy. Our study findings add to the limited literature regarding PIR in Japanese PWT2D, providing a greater understanding of the factors which assist with the decision to commence insulin.

This study determined that HCP actions have significant influence on Japanese PWT2D in initiating insulin treatment. Reluctant Japanese participants valued the advice given by their primary physician regarding the benefits and risks of insulin. A good patient–HCP relationship and having trust in the HCP was also highly valued, with Japanese participants reporting that a collaborative approach between patient and HCP was preferred over an authoritarian relationship. This is supported by evidence that a patient’s relationship with their HCP is closely related to self-management behavior [30Rubin R.R. Peyrot M. Siminerio L.M. Health care and patient-reported outcomes: results of the cross-national Diabetes Attitudes, Wishes and Needs (DAWN) study., 31Piette J.D. Schillinger D. Potter M.B. Heisler M. Dimensions of patient-provider communication and diabetes self-care in an ethnically diverse population.]. Specifically, a positive patient–physician relationship has been shown to be associated with reduced diabetes-related distress and improved insulin adherence and glycemic control [[19]Linetzky B. Jiang D. Funnell M.M. Curtis B.H. Polonsky W.H. Exploring the role of the patient-physician relationship on insulin adherence and clinical outcomes in type 2 diabetes: insights from the MOSAIc study.].Demonstration of the insulin pen/needle and the injection process were important to Japanese participants, who valued practical demonstrations over explanations. This theme was also apparent in the global population of EMOTION [[32]Stuckey H. Fisher L. Polonsky W.H. et al.Key factors for overcoming psychological insulin resistance: an examination of patient perspectives through content analysis.], and is consistent with previous findings in Japanese participants from part 2 of the EMOTION study, where actions such as ‘HCP walked participant through the process of exactly how to take insulin’ and ‘HCP showed an insulin pen’ were rated as the most helpful factors in deciding to initiate insulin therapy [[24]Okazaki K. Shingaki T. Cai Z. Perez-Nieves M. Fisher L. Successful healthcare provider strategies to overcome psychological insulin resistance in Japanese patients with type 2 diabetes.]. Practical demonstrations are likely to dispel preconceived negative assumptions, such as the perceived large size of the needle and pain associated with the injection, the stigma attached to using insulin and people’s anxiety regarding the use of insulin, helping to build a strong and trusting relationship between patient and physician.An interesting observation was the theme of resignation/surrender/acceptance of insulin. The underlying concept of ‘resignation’ has cultural differences; implied to be a negative and weakened state of mind in Western culture but with more complex meaning in Eastern culture and generally regarded as a desired quality [[33]The Japanese psychology of resignation, akirame, and the writings of Kawabata.]. As explained by Meaders, surrender/resignation (called ‘akirame’ in Japan) is a specific form of defense with multilayered psychological and cultural meanings; a culture-specific adaptive defensive operation of the ego [[33]The Japanese psychology of resignation, akirame, and the writings of Kawabata.]. In the current study, Japanese participants reported that they felt there was no choice other than to commence insulin treatment, because alternative therapies were not effective at controlling blood glucose, or due to a new life event (such as the diagnosis of comorbid diseases). Once the participant initiated insulin treatment with their physician’s support, they may have a positive experience relative to their expectations [[23]Polonsky W.H. Fisher L. Hessler D. et al.Identifying solutions to psychological insulin resistance: an international study.].Overall, our findings are in alignment with previous studies that suggest a stepwise approach to diabetes and insulin education [14Polonsky W.H. Arsenault J. Fisher L. et al.Initiating insulin: how to help people with type 2 diabetes start and continue insulin successfully., 17Brod M. Lessard Alolga S. Meneghini L. Barriers to initiating insulin in type 2 diabetes patients: development of a new patient education tool to address myths, misconceptions and clinical realities.], although our findings should be interpreted with caution due to limited participants. In a recent UK subgroup analysis of the EMOTION study, the most helpful strategies for reluctant individuals were demonstration of the injection process, a collaborative approach with HCPs, explanation of the benefits of insulin, and addressing patients' concerns. Our current findings in Japanese participants are in alignment with the UK findings in terms of theme 1 (advice from HCP) and theme 2 (demonstration) [[31]Piette J.D. Schillinger D. Potter M.B. Heisler M. Dimensions of patient-provider communication and diabetes self-care in an ethnically diverse population.]. There is consensus in the literature that assisting people get off to a ‘good start’ with insulin is critical, and that this should be complemented with appropriate clinical support and follow-up over the initial few months [[14]Polonsky W.H. Arsenault J. Fisher L. et al.Initiating insulin: how to help people with type 2 diabetes start and continue insulin successfully.]. An optimal start to insulin treatment may have additional benefits such as an increased likelihood of people maintaining long-term treatment, thereby successfully reaching the recommended glycemic target. In terms of clinical practice recommendations for reluctant Japanese PWT2D, theme 1 (advice from HCP) and theme 2 (demonstration) are indicated as helpful for the initiation of insulin. It is inevitable that theme 1 precedes theme 2; however, theme 3 (resignation/surrender/acceptance of insulin) may occur independently. In some Japanese people, HCPs should consider that theme 3 may be necessary for the acceptance of insulin therapy, hence a level of patience and support from HCPs may be required.

The results of this study highlight the importance of understanding and addressing PWT2D perceptions regarding insulin therapy, and of providing a supportive environment to help facilitate insulin initiation. However, the study has some limitations. The number of Japanese participants was small, with the majority being male. Increased female participation may have resulted in varied perspectives, and this could be the subject of further investigation. Survey respondents were recruited from online panels of individuals who volunteer to participate in studies and may therefore be more involved in their T2D care compared with the broader population of reluctant PWT2D. In addition, self-reported data may not be accurate and may be subject to recall bias. The present study is exploratory in nature, providing a conceptual framework regarding key factors that motivate reluctant Japanese PWT2D to initiate insulin treatment. Further research is required, particularly regarding other factors that may influence PIR in Japanese PWT2D such as age, comorbid conditions, and mental health. A further area of study may relate to our findings regarding ‘surrender/resignation’, potentially applicable to Japanese people with other health conditions.