Utilities for treatment-related adverse events in type 2 diabetes

Abstract

Objectives:

The impact of Type 2 diabetes mellitus (T2DM) on health-related quality-of-life (HRQoL) is complex due to the burden of disease, lifelong treatment requirements, and comorbidities. This study aimed to capture UK societal utility values for health states associated with T2DM and treatment-related adverse events (AEs) to assess the burden of the disease and common AEs.

Methods:

Nine health state descriptions were developed (from a literature review and patient and clinician qualitative input) depicting the burden associated with T2DM and treatment-related AEs. These were mild/moderate urinary tract infection (UTI); severe UTI; mycotic infection; moderate hypoglycemic events; severe hypoglycemic events; fear of hypoglycemia; gastrointestinal symptoms; and hypovolemic events. Members of the UK general public (n = 100) valued these states using the time trade-off (TTO) methodology to elicit utility values (between 0 = dead, 1 = full health). Regression analysis was conducted to understand the influence of age and gender.

Results:

All treatment-related AEs were found to have a significant effect on utility. From the T2DM baseline state (0.92), the experience of AEs was associated with the following disutility: T2DM with hypovolemic events (0.08); T2DM with mild/moderate UTIs (0.09); T2DM with moderate hypoglycemic events (0.11); T2DM with severe hypoglycemic events (0.15); T2DM with fear of hypoglycemia (0.15); T2DM with severe UTIs (0.19); T2DM with GI symptoms (0.24); and T2DM with mycotic infection (0.25); Males consistently scored the states with significantly lower utility values, but no significant age effects emerged.

Conclusions:

Findings suggest that adverse events in T2DM can be a burden for some individuals. The study indicates the potential importance of including information regarding AEs in economic evaluations. Although some states were rated severely in terms of utility; in reality, many of these only last a few days, therefore having a minimal quality-adjusted life year (QALY) impact.

Keywords::

• Type 2 diabetes
• Quality-of-life
• Utility
• Co-morbidities

Introduction

Understanding the impact of T2DM on HRQoL can be complex due to the wide ranging effects of the disease, treatments, and associated comorbidities. Treatments for T2DM can be associated with a wide range of AEs, including hypoglycemia and gastrointestinal problems, which can be an additional burden for people with T2DM. There is no cure for T2DM and so treatment remains a lifelong commitment.

A substantial amount of work already exists exploring the burden of T2DM. Studies have demonstrated that the disease can significantly impact HRQoL both physically and emotionally1–4. HRQoL is usually assessed using patient reported outcome (PRO) measures such as the EQ-5D5^,6. The scores elicited when using the EQ-5D not only measure HRQoL, but also reflect the value of the health state that the patient is in because the scores reflect societal preferences or utilities. Utility values vary from 1.0 (full health) to 0 (dead) and the scores are said to lie on a cardinal (or ratio) scale. This quality of life (QoL) weight or utility value is used for the estimation of quality adjusted life years (QALY). A QALY is the product of time and QoL and is commonly used as the main measure of benefit in a cost-effectiveness analysis7^,8. This method for assessing treatment benefit is preferred by some reimbursement bodies, such as the National Institute for Health and Care Excellence (NICE) in the UK7.

T2DM is one area that has been widely researched in terms of its impact on HRQoL and utilities more specifically. The UK Prospective Diabetes Study (UKPDS) can be considered a benchmark study for understanding the impact of T2DM and its comorbidities on HRQoL6. Table 1 presents data from the UKPDS and other studies surrounding the impact of T2DM and of the co-morbidities which this study focusses on.

Table 1. Previous utility values for T2DM and comorbidities.

Health state	Study	Study methodology	Utility values
T2DM	Zhang et al.7	EQ-5D (USA)	0.80
	Shaw et al.8	Time Trade Off (US)	0.80
		Time Trade Off (UK)	0.82
	Evans et al.9	Time Trade Off (Canada, Germany, Sweden, UK, and US)	0.84
UTI without T2DM	Ellis and Verma10	Mapped SF-36 to EQ-5D (Canada)	0.72
	Abrahamian et al.11	Mapped SF-36 to EQ-5D (US)	0.56 (susceptible/treatment resistant UTI–0.58 (population norm)
	Vogel et al.12	Mapped SF-12 to EQ-5D (US and Canada)	0.78 (mild/moderate)–0.73 (severe)
MI	No data available
Hypoglycemia without T2DM	Evans et al.9	Time Trade Off (Canada, Germany, Sweden, UK, and US)	0.73–0.81
Fear of hypoglycemia with T2DM	Matza et al.13	Standard Gamble (UK)	0.72
GI with T2DM	Matza et al.13	Standard Gamble (UK)	0.57 (weight gain and nausea)–0.71 (no weight gain and nausea)
Hypovolemic events	No data available

Four of the included studies have employed the TTO methodology and are therefore closer for comparison to the current study’s methodology rather than those which used the standard gamble technique.

It is important to note that, generally, the addition of a complication causes a greater burden to HRQoL than the experience of T2DM alone in nearly all cases. The GI symptoms reported in Matza et al.13 show a large decrement in HRQoL (−0.43 from full health). Experiencing T2DM alone appeared to only show a relatively small burden to HRQoL, with decrements from full health between 0.16–0.2. While this study focuses on comorbidities, it does not provide any data on the impact of treatment-related AEs. Since the publication of this study new treatments have continued to emerge. Most recently, inhibitors of the renal sodium-glucose co-transporter 2 (SGLT-2) have been developed to elicit glucosuria, thus reducing plasma glucose levels and leading to weight loss. These oral anti-diabetic agents have been shown to improve glycemic control while avoiding hypoglycemia, and resulting weight loss, but may also be associated with an increased rate of UTIs and genital mycotic infections14. Evaluating the net benefit of these treatments should incorporate review of the burden of the AEs. The present study was designed to elicit utility values from members of the UK general public related to co-morbidities associated with T2DM and treatment-related AEs.

Materials and methods

Ideally, quality-of-life data for health states and treatment AEs would be solicited directly from patients with T2DM, preferably using instruments such as the EQ-5D. A vignette approach was adopted, whereby health state descriptions were developed and assessed by members of the UK public in a valuation exercise using the time trade-off (TTO) method15. The vignette approach has been criticized because the content of the descriptions is often not empirically determined and is not formally assessed for validity16. Poorly designed vignettes can lead participants to focus on very specific aspects of HRQoL which causes exaggerated differences in the resulting scores. However, this current study followed several steps which can maximize the quality of the vignettes, in order to bring it closer to the NICE reference case17. The health states were developed using information from rounds of in-depth interviews and review with patients and clinicians. An overview of the methodology is presented in Figure 1.

Figure 1. Flow chart to show study methodology.

In total, nine health states were developed; one depicting T2DM without any co-morbidity, and eight that characterized T2DM plus additional information concerning comorbidities and treatment-related AEs related to novel and existing anti-hyperglycemic agents (AHAs).

• Urinary tract infection (mild/moderate);

• Urinary tract infection (severe);

• Genital mycotic infection;

• Hypoglycemic event (moderate);

• Hypoglycemic event (severe);

• Fear of hypoglycemic event;

• Gastrointestinal (GI) symptoms (nausea, vomiting, and diarrhea); and

• Hypovolemic event.

Although utility values existed for T2DM, it was decided to include a vignette depicting stable, controlled T2DM to act as a reference case for the additional eight vignettes. During analysis, this allowed for a better estimate of the decrement (or dis-utility) associated for the AE states (if any were to exist). The values that exist may not describe the type of T2DM in a way felt relevant for this study, and it was difficult to assess how these states (where TTO/SG had been used) had been developed and, therefore, how clinically accurate they were.

Health state development

Literature review

A brief literature review was conducted to specifically identify qualitative data (e.g., data from interviews or focus groups) exploring the HRQoL impact of T2DM co-morbidities and treatment AEs. The web-based platform Ovid was used to conduct the search. The search was restricted to journal articles, written in English, published between 2003–2013, and was run on 21 March 2013. The search strategy included terms associated with HRQoL, burden of illness, psychological adaptation, and diabetes. This original T2DM search strategy was then adapted to search for literature associated with the other eight states, to include terms related to the co-morbidities and AEs of interest, such as keywords associated with UTI, genital mycotic infection, etc.

Abstracts were reviewed by two researchers. Thirteen articles were retrieved, based on an abstract review. The studies provided some evidence regarding the impact of T2DM in general. It was found that daily management of T2DM can be demanding on patients, affecting many areas of HRQoL. Many of the studies included PRO measures and the results demonstrated a reduction in HRQoL, specifically in areas of physical function and emotion (anxiety/worry). Being restricted in food and drink options and having to monitor blood glucose were also commonly raised as reasons why HRQoL was impacted. However, there was a paucity of research concerning the impact of the individual treatment-related AEs within patients with T2DM (UTI, n = 2; genital mycotic infection, n = 0; hypoglycemic events, n = 5; GI symptoms, n = 1; and hypovolemic events, n = 1). Wider keyword searches were conducted using online search engines to better understand how these AEs may affect patients, especially in terms of symptoms and presentation. The results of this review were used to inform the patient and clinician interview guides and to construct the health states.

Patient interviews

Eight patients with T2DM who had reported experiencing at least one of the eight AEs were recruited to undertake one-to-one, semi-structured telephone interviews using an interview guide to help structure the discussion. The interview guide included questions specifically in relation to how HRQoL is affected in terms of the EQ-5D dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression18. Participants reported considerable individual variation in their experiences of living with T2DM. There was agreement, however, that living with T2DM led to frustration and/or anxiety relating to future health and current management. It also affected usual activities, specifically the need to plan activities, especially in terms of when to eat and drink to allow blood glucose management.

Data from the literature review and patient interviews were combined to draft the health states (T2DM base state, and T2DM plus each of the eight co-morbidities/AEs). These provided a description of how a typical patient may be affected for each of the five EQ-5D dimensions.

Clinician interviews and review

Four healthcare professionals from primary and secondary care were sent the draft health states for review. They were interviewed in a one-to-one, semi-structured telephone interview. The interviews aimed to gain feedback from the clinicians on clinical relevancy and accuracy of the states. The clinicians were in agreement that the health states accurately characterized T2DM co-morbidities and treatment-related AEs. Some minor revisions were suggested.

Cognitive debriefing

Three members of the public participated in a face-to-face interview to explore their interpretation and understanding of the health states’ wording and meaning. This check was included. Following minor word changes, the health states were deemed suitable for use in the TTO exercise. The final health states are available in Appendix A.

Valuation study

One hundred members of the UK general public were recruited to participate in the valuation exercise to elicit utility values for the nine vignettes. The sample aimed to be broadly representative of the UK general public19. No hypothesis was being tested; therefore, no formal sample size calculation was conducted. Previous studies using this methodology, which have been reviewed by bodies such as NICE, have used similar sample sizes and reported results with relatively low levels of variance around the estimates20^,21.

Time trade off exercise

The TTO interviews were conducted by four experienced TTO interviewers based around the UK who used convenience sampling to recruit participants for interviews. Participants were ≥18 years of age, resided in the UK, and provided written informed consent. Participants completed a socio-demographic form and the EQ-5D, to allow for comparison between the HRQoL of this sample population compared to the UK general population.

Participants were presented with each of the nine vignettes in a random order and asked initially to rank them on a 0 (representing worst state) to 100 (representing best state) visual analog scale (VAS). This process not only elicited VAS ratings for each state but also familiarized the participants with the vignettes. If they chose to do so, participants were able to rank the states as being equal to, or worse than dead on the VAS. If this occurred, the ‘worse than dead’ TTO methodology was used to elicit utility values for these vignettes22.

During the TTO interview the participant was presented with the vignettes in a random order. Each vignette was presented alongside the state of full health and participants were asked whether they would prefer to live in the proposed health state or full health for (10–x) years. The time in full health was varied until the participant was indifferent between the two choices. The amount of time someone was willing to trade (lose) rather than live with the described health indicated the utility value of the state. For vignettes valued as equal to or worse than dead in the VAS exercise, a similar methodology was used, but, this time, years spent in a mixture of the health state and full health was varied and the participant was asked to choose between this or being dead.

Statistical analysis

Regression analyses were conducted on both the TTO utility values and the VAS scores. The raw scores were subtracted from the full health value to find the disutility score (e.g., {1 – TTO utility score} or {100 – VAS score}), which was used as the response variable. This was done to transpose left-skewed utility data into right-skewed disutilities so that commonly used distributions could be fit to the data. The health state, gender, and age were entered as explanatory variables.

The analysis was carried out in the General Estimating Equations (GEE) framework. Several forms of the correlation matrix between the repeated measurements were fitted: independent, exchangeable, and unstructured correlation matrix. Furthermore, four different specifications of the model were estimated:

• Model 1: general linear model with link = ID, distribution = normal;

• Model 2: general linear model with link = log, distribution = normal;

• Model 3: general linear model with link = log, distribution = Poisson; and

• Model 4: general linear model with link = log, distribution = Gamma.

Each participant rated nine states in the valuation tasks and so, therefore, it’s reasonable to assume that the same person’s valuations are correlated. A repeated-measurement structure with a correlation matrix between the measurements is the most appropriate way to estimate the utilities. Ignoring the intra-participant correlations would be equivalent to saying that all the utility valuations come from different participants (100 × 9 = 900 participants instead of the actual 100). Not all correlation matrices are appropriate in this setting; the one with a uniform correlation matrix (exchangeable) is the most intuitive one, suggesting a fixed correlation between each pair of utility valuations. The independent matrix means no correlation between responses; the unstructured matrix implies a different correlation between each pair of responses. In our analysis the exchangeable matrix was found to be the best fitting one, as is often the case in this type of analysis.

These four models were tested against each other using the QIC statistic, which works similarly to the Akaike Information criterion but is applicable for the GEE environment (analysis of correlated data). The parameter estimates from each model represent the disutility of each health state and need to be back-transposed in order to obtain the utility value associated with a health state (i.e. 1 − disutility = utility).

Results

One hundred members of the UK general public took part in the TTO interview. No missing data was found and all data was checked and cleaned prior to analyses. Table 2 outlines the sample characteristics, which were generally representative of the UK. This demonstrates that the sample was relatively comparable to the UK population in terms of gender, age, and ethnicity. There was, however, an over-representation of participants who had been to university. This may have influenced the results somewhat, but is unlikely to have had a large impact.

Table 2. Participant characteristics.

Participant characteristics	n = 100	UK norms (ONS, 2011)^a
Male, % (n)	49 (49)	49%
Mean age (SD)	40.42 years (14.75)	38.2 years
Ethnicity, %
White	90	92%
Mixed race	3	2%
Asian	6	4%
Black	1	2%
Main activity, %
Employed	52	73%
Student	17	5%
Retired	11	3%
Stay at home	3	5%
Self-employed	13	–
Seeking work	1	–
Other	3	7%
Qualifications, %
No formal qualifications	4	23%
Left school with qualifications	19	40%
Technical/vocational qualifications	13	4%
Completed university	53	27%
Other	11	6%
Marital status, %
Single	30	36%
Partnership	20	–
Married	47	48%
Divorced/separated	3	10%
EQ-5D (% of moderate problems)
Mobility	4	18%^b
Self-care	0	4%
Usual activities	6	14%
Pain/discomfort	12	29%
Anxiety/depression	11	19%

^aBased on Office of National Statistics data (2013)21

^bBased on Kind et al.25

With regards to the EQ-5D, the study sample had fewer moderate and no extreme problems when compared to the published sample23, suggesting a slightly better self-reported HRQoL compared to the UK general public. This is to be expected for such a study employing the TTO methodology, which includes face-to-face interviewing techniques.

Table 3 reports the VAS and utility values elicited from the regression analysis for each of the health states.

Table 3. Mean VAS and TTO utility scores.

Health states	TTO mean score (SD)	95% CI	VAS mean score (SD)	95% CI
T2DM	0.92 (0.01)	0.90–0.94	76.9 (1.52)	73.81–79.95
T2DM with hypovolemic events	0.84 (0.01)	0.81–0.87	64.5 (1.83)	60.79–68.19
T2DM with mild/moderate UTIs	0.83 (0.01)	0.80–0.86	59.3 (1.79)	55.63–62.87
T2DM with moderate hypoglycemic events	0.81 (0.02)	0.77–0.84	58.9 (1.86)	55.13–62.65
T2DM with severe hypoglycemic events	0.77 (0.02)	0.73–0.81	53.5 (1.83)	49.82–57.22
T2DM with fear of hypoglycemia	0.77 (0.02)	0.74–0.81	54.9 (1.88)	51.09–58.69
T2DM with severe UTIs	0.73 (0.02)	0.69–0.77	50.8 (1.83)	47.12–54.52
T2DM with GI symptoms	0.68 (0.02)	0.64–0.73	50.6 (1.91)	46.70–54.42
T2DM with mycotic infection	0.67 (0.03)	0.62–0.72	49.7 (1.99)	45.69–53.73

The T2DM reference state was valued most highly compared to other states by the study participants in the VAS and TTO tasks (76.9 and 0.92, respectively), demonstrating an apparent lack of burden to HRQoL. As previously discussed, this health state was included in order to demonstrate the decrement in utility if experiencing a co-morbidity or AE associated with T2DM (i.e., a base state). Of the health states that described co-morbidities and AEs of T2DM, hypovolemic events were valued as having the least burden on HRQoL (disutility from base state = 0.08). The two states which were valued as having the greatest impact on HRQoL by participants were T2DM with genital mycotic infection (disutility = 0.25) and T2DM with GI symptoms (nausea, vomiting, and diarrhea) (disutility = 0.24).

The disutilities of the co-morbidity and AE health states, calculated from regression analysis, are demonstrated in Figure 2. The regression analyses explored the influence of gender and age on the utility values for each state (Figure 3). The results show that females valued states significantly higher (+0.0748, p = 0.0035) than males when using the TTO method. There was no significant effect of age on the TTO derived values (p = 0.45). However, older participants did rate states significantly higher on the VAS scale (+8.12, p = 0.004), but there was no effect of gender on VAS ratings (p = 0.23) (results not shown).

Figure 2. Graph to show utility decrement by health state.

Figure 3. Graph to show the difference between genders and ages.

Discussion

This study captured utilities and VAS ratings of states related to T2DM and anti-hyperglycemic therapies. The disutilities associated with some of the co-morbid and treatment-related AE states show how important it is to consider the influence of AEs on HRQoL in any decision-making context. All of the co-morbidities and AEs had the effect of lowering utility scores when compared to the base state of T2DM also included in this study; the relative impact of these differed, however, from what was anticipated at the start of the study. Health states which included a suggestion of hospital admission (e.g., severe UTI and severe hypoglycemic event) were not rated as the most burdensome states. Everyday fear of hypoglycemia seemed to have a more substantial impact on HRQoL than was expected, especially when this result is considered alongside the disutility of actual hypoglycemia24.

The results also indicated that female members of the public consistently rated the states as less severe than the male participants did. One possible explanation for this is that the female participants may have had more experience of the co-morbidities and treatment-related AEs than men did. There is evidence for example that genital mycotic infections are more common in women compared to men and so the women in our sample may have had more experience of these infections than the male participants25. It may also be that coping strategies vary between genders and that females are able to deal with such AEs in a way that they do not find as burdensome compared to men. Alternatively, it is possible that men find the prospect of genital mycotic infections more of a concern than women do.

When reviewing the results of this study, it is important to consider that some of the more burdensome states may actually only be experienced for a short period of time (such as genital mycotic infections). While some of the states are rated quite severely, the net impact of these AEs may not be as great as other AEs which are chronic in nature. When considering the impact of an AE, it’s important to consider the severity of the AE and its duration. The QALY framework accommodates this well. At the individual patient level it would be possible to combine these values with the actual amount of time that patients experienced AEs for in trials or other clinical studies. It should also be remembered that not all possible co-morbidities or AEs that may impact HRQoL were included in the health state descriptions. This type of methodology only permits a limited number of health states to be included, and this may be seen as a limitation to this study; however, the states that were included were deemed relevant and important to capture utility values on for the aims of this study.

T2DM is a commonly studied area, and, as demonstrated, utility values exist for a number of health states associated with the disease, T2DM (with no complication/AEs) especially. In this study a state describing T2DM with no complications or AEs was included to provide a reference value to assess the impact of specific AEs. The T2DM reference case value elicited in this study was higher than other values referenced in the literature. Previous mean utility values found for T2DM (range = 0.80–0.84) presented in previous studies7–9 were lower than the value (0.92) found in this study. It’s not clear if the present value is too high or previous values have over-estimated the burden of T2DM. It is possible that the vignette description used in the present study described the condition as less burdensome than it is in reality. There could also be some important differences in the way that T2DM was described in the present study compared with previous studies. Equally, the estimates from previous studies may be too low. In the absence of the very significant complications in T2DM, the main symptoms experienced are thirst, hunger, and increased urination26. Previous studies may have recorded lower quality-of-life scores for T2DM because the states or the data reflected some of the longer term sequelae also. The states developed in the present study were based on a careful development process which relied upon rounds of detailed feedback from T2DM patients and specialist clinicians.

Utility values have not previously been reported for the majority of the health states included within this study, but some similar states have been explored previously. Some of these mean values did differ to that found in this study. Evans et al.10 reported the impact of hypoglycemic events (diurnal and nocturnal), using the TTO methodology from a mixed sample including participants from the general population, and patients with Type 1 diabetes and T2DM. They reported the baseline T2DM utility diabetes state (0.84). A health state described as non-severe symptomatic hypoglycemic events experienced once every 3 months had a value of 0.74, which is lower than the closest equivalent in the present study (0.81). These differences probably relate to small differences in the content of the vignettes or equally may reflect the mixed sample of the general public and patients in the Evans et al. study.

Values in the present study for fear of hypoglycemia and GI upset are similar to values reported previously by Matza et al.13. A T2DM health state describing worry regarding hypoglycemia had a value of 0.72, which is similar to the fear of hypoglycemia health state in the current study (0.77). The same study reported GI values from 0.57 (weight gain and nausea) to 0.71 (no weight gain and nausea), which span the GI utility value generated from this study (0.68).

A systematic review11 included studies which examined the utility values for UTI events10–12 without T2DM and reported mapped EQ-5D values for UTIs (ranging from 0.56–0.78). These values reflect those currently reported for experiencing diabetes plus UTI events in this study (0.83 = mild-to-moderate UTI and 0.73 = severe UTI).

Ideally, utility values would have been elicited directly from patients with diabetes who have experienced these co-morbidities where patients can indicate the impact using a standardized measure of HRQoL. Such a study would be a very valuable way of taking this research forward. Recruiting sufficient numbers of people who are experiencing each AE/complication would be a challenge. Clinical trials and registries provide opportunities to capture such data.

In the present study, values were estimated for the experience of a long-term complication or AE in the context of T2DM. The mixed model analysis was undertaken to estimate the influence of each component separately. However, this does not mean that a simple additive or arithmetic approach can necessarily be used to understand the impact of two complications/AEs or to estimate the combined effect of one of the joint states included (e.g., T2DM with mycotic infection) and a comorbidity such as obesity. This issue has been explored previously and different methods exist. These range from some very simple approaches (simply take the minimum value of two states) to more complex regression-based approaches. Ara and Wailoo27 summarize the important issues here.

The observations derived from this study may have a variety of implications from both the clinical and health economic perspectives. In clinical practice terms these data can provide clinicians with an assessment of the impact of T2DM co-morbidities and treatment-related AEs. This may help to inform decision-making in clinical practice. The values can also help decision-making at a national reimbursement level. The experience of AEs may influence the cost-effectiveness of a treatment.

In conclusion, the findings suggest that T2DM can be associated with a significant burden for individuals, even when they are not experiencing AEs. The addition of a co-morbidity or treatment-related AE adds to the burden on HRQoL, reflected in the lower utility scores. The utility states derived from this study have face validity based on previously published data, and any treatment that may help manage the disease effectively without causing a significant number of severe AEs could be seen as highly beneficial.

Transparency

Declaration of funding and financial relationships

ICON PRO was paid a fixed fee to design and conduct this research project from Janssen, UK.

Declaration of financial relationships

MS & GT are employees of Janssen Scientific, UK. JME Peer Reviewers on this manuscript have no relevant financial relationships to disclose.

Acknowledgments

We would like to give thanks to the following clinicians for their help in developing and reviewing the health states: Dr Richard Brice, Whitstable Medical Practice, UK; Dr Dunford, Birmingham, UK; and Dr Kedia, London, UK.

Appendix

T2DM

• You have an on-going illness for which you are required to take regular medication. You also need to think carefully about and closely monitor what you eat and drink, which may require you to adapt your lifestyle.

• You have no problems walking about or washing and dressing yourself.

• You have no problems doing your usual activities, although due to tiredness you are limited with the amount of activity you can do.

• You occasionally worry about the future and have some concerns about your disease getting worse.

T2DM with mild/moderate UTIs

• You have an on-going illness for which you are required to take regular medication. You also need to think carefully about and closely monitor what you eat and drink, which may require you to adapt your lifestyle.

• You have no problems walking about or washing and dressing yourself.

• You have no problems doing your usual activities, although due to tiredness you are limited with the amount of activity you can do.

• You can experience some dull, lower back and abdominal discomfort. You need to urinate frequently which can cause sharp pain. You are required to take a course of antibiotics from your doctor.

• You occasionally worry about the future and have some concerns about your disease getting worse. You worry that you will be required to take more antibiotics in the near future to treat your urinary symptoms should they re-occur.

T2DM with severe UTIs

• You have an on-going illness for which you are required to take regular medication. You also need to think carefully about and closely monitor what you eat and drink, which may require you to adapt your lifestyle.

• You recently spent a few days in hospital due to an infection. You received antibiotics through a drip, directly into a vein and so were limited in your usual activities. You experienced a fever and felt confused, although this has now subsided.

• You have no problems walking about or washing and dressing yourself.

• You currently have no problems doing your usual activities, although due to tiredness you are limited with the amount of activity you can do.

• You can experience some dull, lower back and abdominal discomfort. You need to urinate frequently which can cause sharp pain.

• You occasionally worry about the future and have some concerns about your disease getting worse or returning. You worry that you will be re-admitted to hospital if the infection does not get better completely. You also have concerns that you will be required to take more antibiotics in the near future to reduce your chances of infection.

T2DM with mycotic infection

• You have an on-going illness for which you are required to take regular medication. You also need to think carefully about and closely monitor what you eat and drink, which may require you to adapt your lifestyle.

• You currently have no problems walking about or washing and dressing yourself.

• You currently have no problems doing your usual activities, although due to tiredness you are limited with the amount of activity you can do.

• You do not feel like going out as much to socialize with friends or family.

• You have an infection in your genitals which can be sore, red, and itchy. This can affect your sex life and can require that you see your doctor to receive treatment.

• You occasionally worry about the future and have some concerns about your disease getting worse. Your mood can be down about the infection in your genital area and you worry that you may experience similar infections in the future. 

T2DM with moderate hypoglycemic events

• You have an on-going illness for which you are required to take regular medication. You also need to think carefully about and closely monitor what you eat and drink, which may require you to adapt your lifestyle.

• You currently have no problems walking about or washing and dressing yourself.

• You currently have no problems doing your usual activities, although due to tiredness you are limited with the amount of activity you can do.

• You do not feel like going out and socializing with friends or family.

• You can occasionally experience feelings of shakiness, dizziness, sweating, and hunger. These episodes do not last for long and you can usually stop the symptoms by eating or drinking something sweet.

• You occasionally worry about the future and have some concerns about your disease getting worse. You worry about having further episodes of feeling shaky, dizzy, and hungry in the future, which can cause you to feel anxious and fearful.

T2DM with severe hypoglycemic events

• You have an on-going illness for which you are required to take regular medication. You also need to think carefully about and closely monitor what you eat and drink, which may require you to adapt your lifestyle.

• You recently spent a few days in hospital due to an episode of illness which caused you to become unconscious. Before you were admitted, you experienced feelings of shakiness, dizziness, sweating, hunger, and confusion. You received injectable treatment.

• You currently have no problems walking about or washing and dressing yourself.

• You currently have no problems doing your usual activities, although due to tiredness you are limited with the amount of activity you can do.

• You occasionally worry about the future and have some concerns about your disease getting worse. You are concerned and fearful that you will be re-admitted to hospital if another episode of illness occurs. Because of this you sometimes feel depressed.

T2DM with fear of hypoglycemia

• You have an on-going illness for which you are required to take regular medication. You also need to think carefully about and closely monitor what you eat and drink, which may require you to adapt your lifestyle.

• You have no problems walking about or washing and dressing yourself.

• You have no problems doing your usual activities, although due to tiredness you are limited with the amount of activity you can do.

• You are very anxious about having an episode of illness which requires you to be admitted to hospital for treatment. You have already experienced this and are scared it will happen again. You also worry that you will become ill whilst no one else is around, making it difficult for you to receive medical help.

• You feel the need to eat more frequently and larger amounts in order to reduce your chances of becoming unwell again.

• You worry about the future and have some concerns about your disease getting worse.

T2DM with GI symptoms

• You have an on-going illness for which you are required to take regular medication. You also need to think carefully about and closely monitor what you eat and drink, which may require you to adapt your lifestyle.

• You currently have no problems walking about or washing and dressing yourself.

• You are sometimes limited in the type and amount of activity you can do because you feel tired and nauseous.

• You do not feel like going out and socializing with friends or family.

• You frequently feel nauseous and sometimes vomit.

• You sometimes also experience episodes of diarrhea.

• You occasionally worry about the future and have some concerns about your disease getting worse.

T2DM with hypovolemic events

• You have an on-going illness for which you are required to take regular medication. You also need to think carefully about and closely monitor what you eat and drink, which may require you to adapt your lifestyle.

• You have no problems walking about or washing and dressing yourself, although you can sometimes feel dizzy when you move around.

• You have no problems doing your usual activities, although due to tiredness you are limited with the amount of activity you can do.

• You can sometimes feel lightheaded and dizzy when moving around, especially if you have been sitting for a long period of time.

• You occasionally worry about the future and have some concerns about your disease getting worse. You sometimes worry about falling over or passing out when you experience symptoms of dizziness which could lead to injury.

Full health

• You do not have any diseases and you are not receiving any treatments.

• You have no problems walking around.

• You have no problems in caring for yourself.

• You have no problems in completing your usual activities.

• You have no pain or discomfort.

• You are not anxious or depressed.

Dead

• You are dead.