Hypoglycaemia can be prevented by proactive self-care including regular blood glucose monitoring, appropriate nursing care, and recognising impending hypoglycaemia and managing it appropriately. The prevalence of hypoglycaemia is increasing due to the focus on achieving blood glucose levels as close to normal as possible.

Hypoglycaemia is the most common and the most serious side effect of insulin. The prevalence of hypoglycaemia has increased since the results of the Diabetes Control and Complications Trial DCCT (DCCT 1997 and 2003) and the United Kingdom Prospective Diabetes Study (UKPDS) (UKPDS 1998) demonstrated that keeping blood glucose in the normal range reduced the risk of long-term complications and glucose targets were revised.

Severe hypoglycaemia was three times more frequent in the intensive insulin treatment group compared to conventional treatment in the DCCT (61 events per 100 people). Hypoglycaemia was more common in men than women and in adolescents than adults. The risk of severe hypoglycaemia was 1 in 3 and the risk of coma 1 in 10 (DCCT 1991). Concern about hypoglycaemia was thought to contribute to the difficulty achieving glycaemic targets. Likewise, Pramming et al. (1991) reported mild hypoglycaemia was 1.8 episodes per patient per week and 1.4 episodes of severe hypoglycaemia per patient per year.

The increased rate of hypoglycaemia is largely due to the focus on achieving normoglycaemia by intensifying management in both Type 1 and Type 2 and transferring people with Type 2 diabetes onto insulin sooner since the results of these studies were released. In early reports from the UKPDS, major hypoglycaemia occurred between 0.4 and 2.3% of insulin-treated patients per year compared with 0.4% of those treated with diet or sulphonurylureas (UKPDS). Later studies also show the frequency and severity of hypoglycaemia in people with Type 2 diabetes is lower than Type 1 (Yki-Jarvinen et al. 1999).

Wright et al. (2006) recorded self-reported hypoglycaemia rates and severity grade (transient (1), temporarily incapacitated (2), requiring assistance (3), requiring medical attention (4) in various treatment groups who remained on their allotted therapy for six years from diagnosis as part of the UKPDS). Grades 1 and 2 occurred in 0.8% in the diet and 1.7% in the metformin groups per year and 0.1% and 0.3% respectively for grades 2–4 per year. Rates for those on sulphonylureas were 7.9% and 1.2%; 21.2% and 3.65 on basal insulin and 32% and 5.5% on basal and pre-meal insulin.

Younger people (<45 years), women, those with HbA_lc <7%, and islet autoantibody-positive people were twice as likely to report hypoglycaemia. Wright et al. claimed the low rates of hypoglycaemia in Type 2 diabetes was unlikely to have a major negative impact on people’s ability to achieve glycaemic targets. Despite ∼30% of people initially recruited were lost from the study, possibly due to intensifying treatment to achieve optimal glycaemic control so the numbers of people in each treatment group was small, the overall hypoglycaemia rate was low. Not surprisingly, hypoglycaemia risk was greater in people on insulin with poorer control but lower doses of insulin were associated with a 35% lower rate of hypoglycaemia. Older people (>65) were not included in the study, thus their risk and ability to recognise hypoglycaemia is unclear from the study.

A number of researchers suggest the rate of mild and severe hypoglycaemia is lower in insulin-treated Type 2 diabetes than in Type 1. However, hypoglycaemia risk increases once insulin is commenced and with increasing duration of diabetes (Henderson et al. 2003). Hypoglycaemic unawareness is uncommon in Type 2 diabetes, but when present, it is associated with a higher incidence of severe hypoglycaemia. Ziemer et al. (2007) suggested intensifying insulin treatment is not associated with increased hypoglycaemia, even when the HbA_lc is close to the target.

The rate of severe hypoglycaemia is higher in young children: 0.49 in children <6 years compared to 0.16 in children >6 (Davis et al. 1997). Daneman et al. (1989) reported 31% of children (n = 311); mean age 11.6 and mean duration of diabetes 4.6 years, had at least one coma or convulsion since diagnosis. Other researchers report rates ranging from 6.8 to 12%.

In contrast, Nordfeldt & Ludvigsson (1997) stated the incidence of hypoglycaemic coma did not increase when HbA_lc improved from 8.1% to 6.9%, but episodes of severe hypoglycaemia increased from 1.01 to 1.26 per patient per year. Early recognition and treatment of hypoglycaemia in young children is essential because their brains are vulnerable to hypoglycaemia, which may cause permanent cognitive deficits (Tattersall 1999).

Normal glucose homeostasis was discussed in Chapter 1. Counter-regulatory hormones, especially glucagon, the catecholamines, growth hormone, and cortisol are released when the blood glucose falls below the normal range to maintain the blood glucose level and ensure a constant supply of energy to the brain. Glucagon and the catecholamines stimulate gluconeogenesis and reduce glucose utilisation. The severity and duration of hypoglycaemia determines the magnitude of the counter-regulatory response and begins as the blood glucose falls to ∼3.5–3.7 mmol/L before cognitive function is impaired around 3.0 mmol/L (Heller & Macdonald 1996).

The counter-regulatory hormones are largely responsible for the signs and symptoms of hypoglycaemia through activating the autonomic nervous system. Several researchers have compiled lists of hypoglycaemic symptoms (Hepburn 1993; Cox et al. 1993). Recognising the signs enables early treatment to be initiated. Significantly, symptoms are specific to the individual and are interpreted differently from health professionals. For example, people report symptoms differently if they are asked to indicate the relevance of each symptom to themselves (Tattersall 1999, p. 57). In the author’s experience, some people think ‘a hypo means you go into a coma’ and do not associate mild symptoms with hypoglycaemia, other people and their relatives associate trembling, vagueness and aggressive behaviour as ‘having a fit’, which suggests some information included in hypoglycaemia education programmes may not be appropriate to everybody. The most commonly reported symptoms are: sweating, trembling, difficulty concentrating, nervousness, feeling tense, light-headedness and dizziness (Cox et al. 1993).

When the blood glucose is <3.0 mmol/L, fine motor coordination, mental speed and concentration, and some memory functions become impaired. Reaction times are slower especially when the individual needs to make decisions: mental arithmetic and short-term verbal memory and working memory are impaired (Sommerfield et al. 2003). McAulay et al. (2001) also demonstrated significant impairment of attentional abilities during hypoglycaemia but found fluid intelligence (problem-solving ability) was not impaired. Thus, many everyday tasks appear to be impaired during hypoglycaemia including the individual’s ability to manage the episode.

Factors associated with increased cognitive deficits include male gender, hypoglycaemic unawareness, Type 1 diabetes, and high IQ. These findings have implications for effective hypoglycaemia self-management and safety. For example, people drive slowly, swerve more, steer inappropriately, spend more time driving off the road and position the car badly on the road when the blood glucose is <2.6 mmol/L (Cox et al. 1993). The counter–regulatory response to recurrent hypoglycaemia may be blunted in subsequent hypoglycaemia and the individual may not recognise the signs and symptoms. Often, people do not recall severe hypoglycaemic episodes.

Results from continuous glucose monitoring systems (CSII) suggest people taking four insulin injections per day have at least one blood glucose level <2.8 mmol/L of varying duration per day, which may not cause symptoms (Thorsteinsson et al. 1986). This is affected by a number of factors including the number of injections per day, the type of insulin, variations in absorption within individuals and among injection sites.

Emotions are also affected and mood changes in the three basic mood types: energetic arousal (feel active), tense arousal (feel anxious), and hedonic state (feel happy) occur during or in anticipation of hypoglycaemia. People with diabetes fear hypoglycaemia, which can lead them to inappropriately lower their insulin doses to reduce the risk of hypoglycaemia, see Chapter 15.

Thus, the effects of hypoglycaemia are complex and multifactorial. Education and strategies to prevent/manage hypoglycaemia should be individualised and accompany changes in medication management and include family and significant others.

Hypoglycaemia is defined in several ways:

• Biochemical: blood glucose below a specific level, which is common especially overnight and is often unrecognised.
  
• Mild symptomatic where the individual is able to self-treat. The symptoms are often vague and may not be related to the actual blood glucose level. The most commonly reported initial symptoms that closely reflect the actual blood glucose level are trembling, sweating, tiredness, difficulty concentrating and hunger.
  
• Severe symptomatic associated with neuroglycopenia where help is required to treat. People do not always remember a severe hypoglycaemic episode because of retrograde amnesia or denial. Severe hypoglycaemia can occur without coma.
  
• Profound associated with coma and sometimes convulsions (Tattersall 1999, pp. 55–87). Some experts associate severe hypoglycaemia with coma and convulsions.

In addition, a grading system is often used, especially in research, as follows:

• Grade 1 – mild: the person recognises and self-treats.
  
• Grade 2 – moderate: the person requires assistance but oral treatment normalises the blood glucose.
  
• Grade 3 – severe: the person is semiconscious and requires assistance, and glucagon or IV glucose may be needed.

Clinically, hypoglycaemia is often defined as blood glucose low enough to cause hypoglycaemia signs and symptoms and/or a blood glucose level of <3.0 mmol/L in people with diabetes treated with insulin or oral hypoglycaemic agents.

Although hypoglycaemia is associated with insulin and OHA use, the relationship among these agents and food intake, exercise, and a range of other contributory factors is not straightforward. Some episodes can be explained by altered awareness or mismatch between food intake and/or food absorption and insulin. It should be noted that serum insulin levels and glucose clearance following insulin injections varies in the same individual even when the same dose is injected at the same time, dose and approximate site each day (Galloway & Chance 1994), even with modern purified insulins.

Exercise is also a contributing factor in many cases but the effect of exercise is also difficult to predict and depends on exercise intensity and duration, planned or spontaneous, time of the day, previous food intake, when it occurred in relation to insulin/OHA dose, and the insulin injection site. For example, absorption is enhanced if exercise commences immediately after injecting insulin but not if exercise commences >35 minutes after injecting.

As indicated, sulphonylureas cause hypoglycaemia but less commonly than insulin. However, when it does occur it causes significant morbidity and mortality, may be prolonged and may accompany or precipitate a stroke or myocardial infarction. Interactions with other medicines including complementary medicines should be considered especially in the setting of compromised renal function, see Chapters 8 and 19. Alcohol may be a contributing factor.

Frequent hypoglycaemia might indicate changing renal function and insulin doses may need to be reduced. OHAs may be contraindicated. Lowered appetite and nausea accompanying renal disease may contribute to hypoglycaemia risk.

If no reasonable common contributing factor can be identified less common causes such as endocrine disorders, gastroparesis, and coeliac disease should be considered. Psychological factors need to be considered, see Chapter 15.

A specific reason for the episode cannot always be found, which makes prevention difficult; unknown rates ranging between 19 and 38% have been reported.

Various authors attribute hypoglycaemia to ‘patient non-compliance’ such as manipulating insulin doses, reducing intake, or omitting meals. While these behaviours do occur, health professionals need to understand the reason for the behaviour rather than attaching a label to the individual. They need to appreciate the complexity of achieving diabetes balance and the frustration it causes many people with diabetes. The view that achieving blood glucose balance is an equation where:

insulin/OHAs + appropriate diet + appropriate exercise = target glucose

is simplistic, and ignores significant individual factors.

Hypoglycaemic unawareness means people no longer recognise the early autonomic hypoglycaemic signs and do not recognise hypoglycaemia thus do not treat it and are at risk of severe hypoglycaemia and coma. Recurrent episodes of hypoglycaemia reduce the counter-regulatory response, associated symptoms and cognitive responses, which affects the individual’s ability to recognise and treat the episode. People with Type 1 diabetes have compromised counter-regulatory response and a cycle of hypoglycaemia where each episode becomes increasingly severe may develop. If counterregulation is compromised endogenous insulin secretion is not inhibited. Significantly, glucagon release in response to hypoglycaemia is impaired soon after diagnosis of diabetes and becomes progressively defective in Type 1 diabetes. Adrenaline release is also reduced, which ultimately results in hypoglycaemic unawareness (DCCT Research Group 1991).

Hypoglycaemic unawareness may develop when the usual blood glucose is in the low/normal range and people may begin to recognise the symptoms again if the blood glucose targets are raised. Chronic hypoglycaemic unawareness develops with long duration of diabetes usually as a result of autonomic neuropathy and diminished counter-regulatory response. Both acute and chronic hypoglycaemic unawareness can be aggravated by medicines such as non-selective beta blockers, alcohol, and stimulants such as caffeine. Hypoglycaemic unawareness increases the risk of severe and profound hypoglycaemia and is one criterion for islet cell transplants.

Indicators that chronic hypoglycaemia might be present in elderly people, especially those on OHAs, include failing mental function, personality changes, and disordered behaviour and must be distinguished from other less easily reversible causes of these signs. Accurately monitoring the blood glucose levels is important to detect chronic hypoglycaemia and CGMS can be useful. Management consists of revising the care plan and checking:

• That carbohydrate intake is adequate and evenly distributed;
  
• The individual is able to accurately prepare and administer their insulin;
  
• Whether any new medications or complementary therapies were commenced and reviewing the individual’s medication self-management practices;
  
• Teeth/dentures to ensure there is no infection or mouth ulcers and that false teeth fit and are worn;
  
• Presence of diabetic complications or comorbidities that can affect self-care ability.
  
• Knowledge, which might mean relatives and friends need information about managing hypoglycaemia including how and when to use. People may benefit from education programmes such as BGATT and some regain the ability to recognise hypoglycaemia or new body cues after a period free from hypoglycaemia.

Nocturnal hypoglycaemia is particularly worrying in children because they have a blunted counter-regulatory response (Jones et al. 1998). It is defined as blood glucose, 3.3 mmol/L occurring during the night and mainly occurs in Type 1 diabetes, usually as a consequence of relative insulin excess and impaired glucose production overnight. Increased insulin sensitivity overnight plays a role. More than 80% of people treated with insulin experience nocturnal hypoglycaemia; 40% of these episodes are severe and are associated with significant morbidity and rarely, death. Continuous blood glucose monitoring (CGSM) suggests the prevalence of nocturnal hypoglycaemia is 10–56%, lasts for ∼6 hours, the time of the lowest level (nadir) depends on the insulin type and regimen (Raju et al. 2006). Raju et al. (2006) did not find differences in mean nocturnal blood glucose or mean nadir using CGSM to compare four insulin regimens in people with Type 1 diabetes with HbA_lc <7.1%, but detected high rates of under- and overestimation of the glucose level.

Pramming et al. (1985) tried to identify predictors of early morning hypoglycaemia. They suggested if the blood glucose was <6 mmol/L at 11 pm there was an 80% chance of nocturnal hypoglycaemia compared to 12% risk if the blood glucose was >5 mmol/L. Other researchers report similar predictive blood glucose levels but the likelihood increases if multiple injections are used compared to CSII (Whincup & Milner 1987; Bendtson et al. 1988). Vervoort et al. (1996) found the bedtime blood glucose level predicted hypoglycaemia in the early part of the night but not hypoglycaemia occurring in the early morning. They also found a fasting blood glucose (before breakfast) <5.5 mmol/L indicated early morning hypoglycaemia.

However, the only risk factor Young et al. (2007) identified in a study to determine the amount of glucose needed to prevent exercise-induced hypoglycaemia was frequent exercise. In Young et al.’s study, nocturnal hypoglycaemia occurred on both exercise and sedentary nights. Blood glucose 7.2 mmol/L at 9 pm predicted overnight hypoglycaemia on sedentary days. Exercise has multifactorial effects on fuel utilisation and mobilisation. Initially, in the first 5–10 minutes muscle glycogen is the primary fuel source, followed by circulating glucose and then fuel derived from gluconeogenesis and oxidation of fatty acids (Silverstein 2008). Due to the counterregulatory deficits, children with Type 1 diabetes are unable to mobilise glucose stores for gluconeogenesis.

In many cases the individual does not recognise the signs of nocturnal hypoglycaemia and does not wake up especially in Type 1 (Veneman et al. 1993; Raju et al. 2006). Repeated episodes of nocturnal hypoglycaemia reduce the counter-regulatory response to hypoglycaemia. Undetected autonomic dysfunction and nocturnal hypoglycaemia can increase the risk of fatal cardiac ventricular dysrrhythmias (‘dead in bed’ syndrome).

Indicators of nocturnal hypoglycaemia

• Night sweats.
  
• Nightmares or vivid dreams.
  
• Unaccustomed snoring.
  
• Morning lethargy or chronic fatigue.
  
• Headaches or ‘hung over’ feeling.
  
• Mood change, particularly depression.
  
• High blood glucose before breakfast (Somogyi effect).
  
• Morning ketouria.

Factors that contribute to nocturnal hypoglycaemia include preceding physical activity that may have occurred many hours previously, insufficient carbohydrate in meals, excess insulin as a result of these factors, enhanced sensitivity to insulin and/or inappropriate insulin dose, alcohol consumption.

The Somogyi effect refers to pre-breakfast hyperglycaemia following an overnight hypoglycaemic episode. If any of the above symptoms occur, the blood glucose should be measured at 2 to 3 am over several nights to establish whether nocturnal hypoglycaemia is occurring. The insulin is then adjusted accordingly by decreasing the morning long-acting dose for those on a daily insulin, the afternoon long-acting dose for those on BD insulin or the pre-evening meal or bedtime dose for basal bolus regimes.