European Journal of Cardiovascular Medicine

Diabetes Mellitus (DM) is considered one of the main threats to human health in recent times. It is the most prevalent disease distributed all over the globe and is the fourth leading cause of death in developed countries.^(1–3) India has witnessed a sharp rise in cases of Type 2 Diabetes Mellitus (T2DM) with about 2.4% in the rural and 11.6% in the urban population.⁽⁴⁾ Diabetes Mellitus (DM) is a group of long-term heterogeneous metabolic disorders that is characterized by hyperglycemia due to impaired insulin secretion combined with insulin resistance or not.^(5,6) It is a chronic disease associated with many complications that severely affect the patient’s quality of life in all aspects of physical, social, and behavioural limitations. This affects the psychoemotional status of the patient along with the alteration in the patient’s mental state.^(4,7)

Numerous researches have documented the relationship between the elements of psychoemotional distress and mental status with quality of life.⁽⁸⁾ The risk of psychoemotional distress is 1.5 to 2 times higher in patients with Type 2 Diabetes Mellitus (T2DM) than in the normal population, and about 80% of T2DM patients are diagnosed with depressive and anxiety disorders.^(4,9) Due to vascular and metabolic damage to the cerebral tissues, diabetes patients are at greater risk of developing cognitive disorders, which accelerate cognitive impairment and eventually lead to dementia.^(10,11)

Non-adherence to medications in patients with T2DM has a significant consequence of these negative diabetic outcomes i.e. psychoemotional distress and cognitive impairment, that decreases patient quality of life.^(12–14) There is a complex relationship between mental state, psychoemotional status, non-adherence to medication, and quality of life.⁽⁷⁾ Non-adherence to medication worsens the disease condition of the patient by developing chronic diabetic complications.^(15,16) This study mainly focuses on how much extent of depression, anxiety, and cognitive symptoms experienced by T2DM patients in the Indian diabetic population and their association with medication non-adherence and the quality of life of the patients.

It was a descriptive cross-sectional mono-center study conducted at a tertiary care teaching hospital, Konaseema Institute of Medical Sciences and Research Foundation (KIMS) Hospital (Amalapuram, Andhra Pradesh, India) from July 2022 to December 2022 and included all the patients with T2DM.

Patients aged 18-75 years of both genders and with a confirmed diagnosis of Type 2 DM for at least one year before the study and currently on medication with oral hypoglycemic agents for at least 3 months before participating in the study were included in the study. This study was conducted upon approval by the Institutional Ethics Committee (IEC) and all the patients signed the informed consent form before their inclusion into the study. The patients unable to complete the proposed questionnaire and follow the study procedures due to any reason, and patients with a known history of psychiatric and cognitive disorders were excluded from the study.

In this study, all the patients were personally interviewed and asked to complete a set of standardized questionnaires, which included a mini-mental state examination (MMSE), European quality of life questionnaire (EQ-5D-5L), and hospital anxiety and depression scale (HADS). All the patients also provided information about their socio-demographic data (age, sex, social habits, family history, etc.), duration of diabetes, chronic diabetic complications, HbA1c levels, and self-reported adherence to diabetic medication (‘yes’ or ‘no’).

The MMSE is a standardized 30-point questionnaire test that is used in clinical practice to assess the cognitive functioning of the patients.⁽¹⁷⁾ This scale allows the comprehensive assessment of the cognitive function of the patient through ten structured questions (orientation to place and time, object registration, attention and calculation, recall, language, and praxis).⁽⁷⁾ The results of the scale are obtained by simply adding the scores obtained by the patient for each completed task in the questionnaire. A score of 30 points is the maximum which states the absence of cognitive disorders in the patient, whereas a score of 0 is the minimum which states that the patient is unable to perform any task given in the questionnaire. A total score obtained by the patient in this test defines the cognitive condition of the patient: 24-30 (no cognitive impairment), 18-23 (mild cognitive impairment), and 0-17 (severe cognitive impairment).⁽¹⁸⁾

Hospital anxiety and depression scale (HADS) is mainly used in clinical studies and general medical practice to assess the psychoemotional status of patients. The sale consists of separate subscales for anxiety (HADS-A) and depression (HADS-D) and the results are obtained by simple addition of the scores.⁽¹⁹⁾ A total score of, 0-7 indicates normal (absence of significant depression and anxiety symptoms), 8-10 indicates borderline abnormal (sub-clinical symptoms), and 11-21 indicates abnormal (symptoms of clinical anxiety or depression).

The European Quality of Life questionnaire (EQ-5D-5L) is widely used for measuring the health-related quality of life of patients. The questionnaire in this scale mainly focuses on the assessment of the subjective health of the patient in five main categories (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). It is also accomplished with a visual analog health scale (VAS) which is a self-assessment scale of health condition by the patient.⁽²⁰⁾ The final VAS score ranges from 0-100, where 0 indicates worst health and 100 indicates best health. The final EQ-5D-5L index score ranges from 0 to 1. All the scoring of the scale is done as per the standardized method and EQ index scores were calculated using the EQ-index value sets for India from the prior studies conducted by research scholars.⁽²¹⁾

All the above-mentioned questionnaires were translated into the local language (Telugu) to facilitate the accuracy of the study and convenience to the patient while participating in the study. The patient is allowed to complete all the standard questionnaires simultaneously. Data was entered into MS Excel Spreadsheet and analyzed for descriptive statistics (Mean, Median, Standard Deviation, and Percentage). The results are obtained in the form of tables, figures, and graphs. A linear regression correlation was obtained between HADS, MMSE, and EQ-5D-5L values.

A total of 200 patients with T2DM were included in the study, aged 53.73 ± 12.0 years and males 56% were more in number compared to females 44%. 60% of patients reported a family history of T2DM, 70% lacked exercise, 32% had obesity, 58% reported a stressful lifestyle, 20% were smokers, 18% were alcoholic, 40% had frequent urination, and 45% suffered from decreased or lack of sleep.

The study results showed that the majority 60% of the T2DM patients were non-adherent to the prescribed antidiabetic medication whereas, 40% were adherent to the prescribed medications. The MMSE results showed that the majority of the patients, 50.5% had mild cognitive impairment, 48% of patients reported no cognitive impairment, and 1.5% of patients reported severe cognitive impairment. HADS scores reported that the majority of the T2DM patients had mild depression 39.5% (HADS-D borderline abnormal), and normal anxiety score 61% (HADS-A normal). The patients who are non-adherent to the anti-diabetic drugs reported low MMSE and quality of life scores and high HADS scores. The quality of life scores obtained by EQ-5D-5L were EQ VAS score 78.25 ± 14.6 and the EQ index score distribution level 1 to 5 by dimensions is given in table 1.

The statistical analysis of the data showed the strongest correlation between MMSE and EQ-5D-5L scores, whereas a similar correlation was also observed between HADS-A, HADS-D scores, and EQ-5D-5L, but to a smaller extent. The description of the statistical analysis for correlations is given in Table 3. The quality of life scores were positively correlated with MMSE scores (p < 0.0001) whereas, the quality of life scores negatively correlated with HADS scores (p < 0.0001).

In our study, most of the type 2 diabetic patients were non-adherent to the medications prescribed by the physician, these people showed low MMSE scores and high HADS scores. Patients with medication non-adherence are associated with an increased risk of developing diabetic complications, cognitive impairment, and psychoemotional distress, which is observed similarly to the study results conducted by Eirini Belsi et al.⁽²²⁾

The hospital anxiety and depression (HADS) scale scores reported that the majority of the patients showed depressive symptoms (39.5%) and a significant number of patients also showed abnormal symptoms of anxiety (20%). These results showed a similarity with the study conducted by Kalpana Sharma et al.⁽²³⁾ Psychoemotional distress is associated with the treatment non-adherence in diabetic patients. The depression symptoms in diabetic patients along with non-adherence to medication deteriorate the mental health of the patient thereby causing cognitive impairment. The mini-mental state examination (MMSE) score of the study participants revealed that the majority of the diabetic patients have mild cognitive impairment (50.5%) which is similar to the study conducted by Yi Zhou et al.⁽²⁴⁾ Patients with low MMSE scores are associated with non-adherence to medications which is also observed in similar to the results of the study done by Daisy Smith at al.⁽²⁵⁾ Cognitive impairment increases the risk of dementia and severe psychiatric disorders in patients. It can further decrease the quality of life of the patient to a greater extent.⁽²⁶⁾

The health-related quality of life (QoL) was assessed using a standard EQ-5D-5L questionnaire. The EQ index and VAS scores are affected by the presence of depression, anxiety, and cognitive impairment. The patients with depression, anxiety, and cognitive impairment showed low EQ index and VAS scores, which is similar to the studies conducted by Francis Creed et al.⁽²⁷⁾ and Elena Gomez-Pimienta et al.⁽⁸⁾ The lowest scores of EQ index and VAS were identified in patients with high HADS-D and HADS-A scores and low MMSE scores. The quality of life of the patients is further affected by medication non-adherence and the presence of diabetic complications. These study results also were identified as similar to the study conducted by K. Venkataraman et al.⁽²⁸⁾ The health-related quality of life is greatly affected by cognitive impairment, psychoemotional distress (depression and anxiety), and the presence of long-term complications of diabetes mellitus.^(20,29,30)

In our study, the relationship between the psychoemotional state, cognitive state of the type 2 diabetes patients, and their quality of life and adherence to medication were determined. The linear regression analysis showed the relationship between the patient’s cognitive function, psychoemotional state, and quality of life. The results of our study show that patients with type 2 diabetes have a poor quality of life when measured using EQ-5D-5L. There is a correlation between the cognitive and psychoemotional status and patient quality of life. The patient’s quality of life is decreased with the decrease in the MMSE score and increase in HADS scores. These findings were observed similar to the results of the study conducted by Alina Y Babenko et al.⁽⁷⁾ Many factors such as age, gender, lack of exercise, family history, duration of diabetes, uncontrolled disease, and the presence of long-term complications and comorbidities can further worsen the quality of life of the patient.^(12,31,32)

Our study concluded that the quality of life in type 2 diabetes patients is decreased with depression, anxiety, and cognitive impairment. These may be developed due to treatment non-adherence by the patients. There is a complex relationship between the patient’s psychoemotional state, mental status, and quality of life of the patient. There is a need for special concern while treating patients with type 2 diabetes mellitus and the cognitive and psychoemotional determinants of the patients should be assessed and treated to increase the quality of life of the patient and to provide effective optimal drug therapy. Medication adherence is crucial to avoid long-term complications, deterioration of cognitive functions, and psychiatric disorders. The importance of the clinical pharmacist’s role in providing medical care and patient counselling services by educating and encouraging medication adherence and lifestyle modifications is understood.