Abstract
Objectives: Objectives
To investigate patients' views about their lowest tolerable blood glucose level and explore symptoms they may develop below that level.
Design
A semi-structured patient interview.
Setting
Outpatient clinic for older people (≥75 years) with diabetes.
Participants
Patients attending an outpatient clinic over a six months period who are monitoring their blood glucose at home and able to participate in interview.
Results
Sixty one patients gave answers to the interview questions. Mean (SD) age was 82.3 (3.9) years and 33 (54%) were females. All patients indicated that they were usually aware when hypoglycaemia occurs but the symptoms reported were mostly non specific. The threshold for hypoglycaemia was 5 mmol/L in 13 (21%) patients, 6 mmol/L in 14 (23%) patients, 7 mmol/L in 13 (21%) patients, 8 mmol/L in 17 (28%) patients and 9 mmol/L in 4 (7%) patients. There was no significant difference between patients who were symptomatic at a higher blood glucose level (>6mmo/L) and those who developed symptoms at a lower level (≤6mmol/L).
Conclusion
Older people with diabetes who seem to be aware of hypoglycaemia report mostly non specific symptoms. The threshold of experiencing hypoglycaemic symptoms appears to be higher than the usually defined <4mmol/L.
Key words: Diabetes, older people, hypoglycaemia
Introduction
Diabetes mellitus affects about one third of older people (≥70 years old) in Europe (1) and one quarter in the United States (2) and the majority of these patients are treated with oral hypoglycaemic agents and/or insulin. Hypoglycaemia is a critical limiting factor in achieving glycaemic targets in these patient (3). Older people are particularly vulnerable to hypoglycaemia because of the higher level of polypharmacy and multiple comorbidities in this age group (4). Symptoms of hypoglycaemia are generally classified as either autonomic, such as palpitations, tremors and sweating, or neuroglycopaenic such as behavioural changes, confusion, seizure, and coma (5). With increasing age, the symptoms of hypoglycaemia may become less intense, particularly autonomic symptoms (6), and the symptom profile may be modified (7). Symptoms of hypoglycaemia are usually described by patients exposed to experimental hypoglycaemia which may result in a different symptom profile to that experienced by ambulant patients in everyday life (8). The reduction in autonomic symptoms perceived by older people with diabetes has been recognised as hypoglycaemia unawareness (9). However, only a few previous studies of hypoglycaemia have considered the effects of age on responses to hypoglycaemia and very few have included patients aged over 75 years (6, 9). As disease presentation tends to be atypical with increasing age, older people with hypoglycaemia may present atypically and their threshold of hypoglycaemic symptoms may be different from the currently defined threshold as <4 mmol/L (5).
Aim
To investigate patients’ views about their lowest tolerable blood glucose level and explore symptoms they may develop below that level.
Methods
Design
A semi-structured patient interview
Setting
Outpatient diabetes clinic for older people (>75 years old) in a District General Hospital in the United Kingdom. The clinic is run by a geriatrician with a special interest in diabetes mellitus. Older patients attending the clinic have access to care provided by diabetes specialist nurse, physiotherapist, occupational therapist, dietician and chiropodist to provide a holistic approach to patients needs as well as on site vascular surgery and psychogeriatric services. The clinic runs weekly and accepts referrals from the community, other hospital based outpatients’ clinics and follow up from inpatient departments after hospital discharge.
Study sample
The population comprised all patients who attended the outpatient clinic over a six month period and who were monitoring their blood glucose at home and able to participate in the interview. Patients unable to participate in the interview due to cognitive dysfunction or those who do not monitor their blood glucose were excluded.
Interview and data collection
Patients were asked about their lowest tolerable blood glucose level and any symptoms they may develop if their blood glucose dropped below that level. The question was phrased as the lowest blood glucose level they feel well at and below which they may develop symptoms. If patients reported a range, rather than a single figure, of the least tolerated blood glucose level the lower limit was taken as an answer. Baseline characteristics such as age, gender, comorbidities, number of medications and social circumstances were recorded as well as last HbAlc result, duration of diabetes and history of serious (requiring assistance or leading to hospital admission) hypoglycaemia.
Blood glucose level
Patients were divided into two groups, one either side of the mean of the lowest tolerated blood glucose level: Group I=patients who were symptomatic at blood glucose level ≤6mmol/L and group II=patients who developed symptoms at a higher glucose level >6mmol/L. We have compared demographics of both groups to identify any probable differences that may explain their answers. The cut off level of 6mmol/L was chosen as it was closer to the mean and gave a reasonable number of patients in each group for a valid statistical comparison.
Statistical analysis
Continuous variables are presented as means and standard deviations (SD) and categorical ones as percentages. Chi-squared test was used to compare categorical variables, Fisher exact test when expected cell value was <5, t test for continuous variables and two sided p value of <0.05 was considered significant. Statistical analysis was performed using the statistical software package “Stata version 10”, StataCorp LP, College station, Texas, USA.
Results
Baseline characteristics and lowest tolerable blood glucose level
A total of 281 patients attended the outpatient clinic over the six months period. The majority of patients (163 patients) did not monitor their blood glucose at home and were excluded. Another 32 patients were excluded due to cognitive dysfunction. Twenty five patients stated that their blood glucose was not low at any time and were not able to give specific answers to questions. The remaining 61 patients gave full answers to the interview questions and formed the study population. Baseline characteristics are summarised in Table 1. All patients were above 75 years old with a mean (SD) of 82.3 (3.9) years and the majority (77%) were on insulin treatment. Most patients lived in their own home (93%) and had a long duration of diabetes, mean (SD) 17.1 (10) years. The lowest tolerable blood glucose level they felt well at and below which symptoms developed was >4mmo/L in all patients. The lowest tolerable blood glucose level stated by patients was as follows: 5 mmol/L by 13 (21%) patients, 6 mmol/L by 14 (23%) patients, 7 mmol/L by 13 (21%) patients, 8 mmol/L by 17 (28%) patients and 9 mmol/L by 4 (7%) patients. (Figure 1) The mean (SD) lowest tolerable blood glucose level was 6.7 (1.3) mmol/L.
Table 1.
Baseline characteristics
| Total number | 61 |
|---|---|
| Age, mean (SD) | 82.3 (3.9) |
| Range | 75-92 |
| Sex (female %) | 33 (54) |
| Mean (SD) number of comorbidities | 3.9 (1.3) |
|
|
| Range | 4-14 |
| Patients on insulin (%) | 47 (77) |
| Self administration (%) | 41 (87) |
| Living status: | |
| Care home | 4 (7) |
| Home (%) | 57 (93) |
| Alone | 30 (53) |
| Carers | 17 (30) |
| History of severe hypoglycaemia | 26 (43) |
| Duration of diabetes, mean (SD) | 17.1 (10) |
| Range | 5-49 |
| lowest tolerable blood glucose, mean (SD) | 6.7 (1.3) |
| Range | 5-9 |
| HbA1c, mean (SD) | 7.6% (1.4) |
| Range | 4.8%-11.9% |
Figure 1.
The least tolerated blood glucose levels stated by patients
Symptoms of hypoglycaemia
Hypoglycaemia symptoms reported by patients were generally non specific (Table 2). There was no significant difference between patients who were symptomatic at a higher blood glucose level (>6mmo/L) and those who developed symptoms at a lower level (≤6mmol/L) regarding age, gender, number of comorbidities or medications, insulin therapy, living status or presence of carers (Table 3).
Table 2.
Symptoms reported when blood glucose drops below least tolerable level (number of patients)*
| Generally unwell (38) | Grey (1) |
|---|---|
| Shaky (8) | Hungry (1) |
| Sleepy (7) | Droopy face (1) |
| Dizzy (5) | Odd (1) |
| Sweaty (3) | Sick (1) |
| Headache (3) | Hazy (1) |
| Tired (3) | Hot (1) |
| Lightheaded (2) | Cross legged (1)** |
| Clammy (2) | No control (1) |
| Imbalanced (2) | Staring (1) |
| Off colour (2) | Lifeless (1) |
| Wobbly (2) | Detached (1) |
| Drowsy (2) | Not self (1) |
| Confused (2) | Jittery (1) |
Some patients reported more than one symptom.
Patient meant loss of balance.
Table 3.
Comparison between patients symptomatic at low vs high blood glucose levels
| Parameter | Group I | Group II | Difference (95% CI), p |
|---|---|---|---|
| Number (%) | 27 (44) | 34 (56) | |
| Mean (SD) age | 81.9 (3.6) | 82.5 (4.3) | 0.6 (−1.4 to 2.7), 0.6 |
| Sex (female %) | 16 (59) | 17 (50) | 0.1 (−0.2 to 0.3), 0.5 |
| Mean (SD) number of comorbidities | 3.6 (1.1) | 4.0 (1.4) | 0.4 (−0.3 to 1.1), 0.9 |
| Mean (SD) number of medications | 7.9 (2.2) | 7.8 (2.9) | 0.1 (−1.4 to 1.3), 0.9 |
| Patients on insulin (%) | 19 (70) | 28 (82) | 0.2 (−0.1 to 0.5), 0.3 |
| Patients self administer insulin | 7 (26) | 11 (32) | 0.1 (−0.3 to 0.2), 0.6 |
| Patients living at home | 26 (96) | 31 (91) | 0.2 (−0.2 to 0.5), 0.4 |
| Patients living alone | 15 (56) | 15 (44) | 0.1 (−0.1 to 0.4), 0.4 |
| Patients with carers | 7 (26) | 10 (29) | 0.1 (−0.3 to 0.2), 0.8 |
| Mean (SD) duration of diabetes | 15.9 (8.4) | 18.1 (9.1) | 2.2 (−3.1 to 7.3), 0.8 |
| History of serious hypoglycaemia | 13 (48) | 13 (38) | 0.1 (−0.2 to 0.4), 0.4 |
| Mean (SD) HbAlc | 7.6% (1.5) | 7.7% (1.3) | 0.1 (−0.6 to 0.9), 0.7 |
Patients were divided into two groups, one either side of the mean of the lowest tolerated blood glucose level: Group Inpatients who were symptomatic at blood glucose level <6mmol/L, group II=patients who developed symptoms at a higher glucose level >6mmol/L, CI=confidence interval.
Discussion
This study has shown that in a group of older people with diabetes who are aware of symptoms of hypoglycaemia, the cut off level of hypoglycaemia symptoms is higher than the usually defined level (<4 mmo/L) and their symptoms, although included autonomic and neuroglycopenic features, are generally non specific. With advancing age symptoms of hypoglycaemia may be less intense or symptom profile becomes modified (7). The most prominent symptom of hypoglycaemia reported by our cohort (generally unwell) is not a classic hypoglycaemia symptom and could potentially be unrecognized or not perceived as early warning symptoms of hypoglycaemia. This may be because, in older people with diabetes, blood glucose level drops too low before specific symptoms of hypoglycaemia develop. Nonspecific symptoms like light headedness and unsteadiness have also been reported previously as the predominant symptoms of hypoglycaemia in an elderly cohort (7). A previous survey of 45 elderly patients with diabetes revealed that the symptoms of hypoglycaemia that were most commonly recognised were non specific in nature and included weakness, unsteadiness, sleepiness and faintness (10). Therefore, although the symptoms may be present, they may not be attributed to hypoglycaemia by health care professionals and these patients may be labelled as hypoglycaemia unaware which could lead to more severe hypoglycaemia. It has been shown that the prevalence of impaired awareness of hypoglycaemia is associated with 17-fold higher frequencies of severe hypoglycaemia (0.83 vs. 0.05, p < 0.001) and 5-fold higher biochemical hypoglycaemia (2.43 vs. 0.46, p < 0.001 episodes per patient) compared to those with normal hypoglycaemia awareness (11). Importantly there was no correlation between hypoglycaemia unawareness and age or duration of diabetes (11). Additionally, the non specific symptoms of hypoglycaemia may be misinterpreted in older patients because of coexisting illnesses, such as cerebrovascular disease or dementia. Lack of awareness of hypoglycaemia in older people has always been claimed to be due to reduced counter regulatory hormones (12). However, it has been shown that counter regulation remains intact in older people with a good response which is similar, in time and magnitude, to younger people. A recent study has shown subjective unawareness (diminished autonomic and neuroglycopenic symptom scores, p<0.01) of hypoglycaemia in older (>65 years) patients with diabetes but equal hormonal counter regulatory responses compared to middle aged (39-64 years) patients (9). In both groups however, the reaction time was prolonged up to 30 min after restoration of euglycaemia. The authors suggested that older people with diabetes may have diminished end organ sensitivity to the counter regulatory hormones resulting in fewer symptoms. This may support our suggestion that older people with diabetes develop fewer specific symptoms of hypoglycaemia but they do generate other non specific symptoms which may not be perceived as hypoglycaemia leading to them being labelled as hypoglycaemia unaware. Our results suggest that hypoglycaemic thresholds for older people with diabetes experiencing non specific symptoms is higher than the usually defined <4 mmol/L. The use of a cut off level of <4mmo/L is due to the fact that it is the glycaemic threshold at which activation of counter regulatory response occurs. (13) However, the glycaemic thresholds responsible for the activation of the physiological defences against hypoglycaemia are dynamic rather than static with an expected higher threshold in patients with uncontrolled diabetes and lower threshold in intensively controlled individuals (1 4). The arbitrary biochemical value of blood glucose that can be used to define hypoglycaemia is debated (15). The American Diabetes Association defined hypoglycaemia in diabetes as all episodes of an abnormally low plasma glucose concentration that expose the individual to potential harm (5). Therefore, it is not possible to state a single plasma glucose concentration that defines hypoglycaemia because the glycaemic thresholds for responses to falling glucose levels are dynamic in nature and vary between individuals. In our study we have not demonstrated any factors such as duration or control of diabetes to explain a higher glucose threshold of hypoglycaemic symptoms experienced by patients suggesting that this was their genuine threshold below which they felt unwell. The strength of this study is the open approach given to patients to express their tolerance to a blood glucose level. Previous studies have used a pre-designed questionnaire (11) or a pre-defined checklist of hypoglycaemic symptoms (7) which may have some limitations or restrictions for patients to freely express their symptoms. Also patients may only recognise severe symptoms of hypoglycaemia when their blood glucose is very low and not perceive other early warning symptoms which tend to be nonspecific and not included in the checklist, such as feeling unwell, when their blood glucose is only mildly reduced. In other words older people may not have reduced awareness of hypoglycaemia but instead hypoglycaemia presents atypically in this age group in a general subtle or nonspecific way. In addition, induction of hypoglycaemia using a glucose clamp technique does not simulate how hypoglycaemia occurs naturally when blood glucose falls continuously and is not held at a plateau for predetermined intervals. In real life, when blood glucose level drops sufficiently it triggers a profound autonomic reaction which illustrates the sudden onset of symptoms of hypoglycaemia. Such an effect does not occur during a glucose clamp because of the slower method of lowering blood glucose. Also patients included in this study were older compared to those included in clinical studies therefore the present data is likely to be representative of patients in clinical practice.
Conclusion
From our patients’ perspective, the hypoglycaemic threshold for older patients with diabetes appears to be higher than the usually defined <4mmo/L. Some older people with diabetes seem to be aware of hypoglycaemia and hypoglycaemic symptoms tend to be largely non specific.
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