- Email: [email protected]
Management of Type 1 Diabetes
MANAGEMENT OF DIABETES
replacement is aimed at lowering plasma glucose levels below the renal threshold. The third reason for insulin replacement therapy (avoidance of the microvascular complications associated with longterm hyperglycaemia) is more difficult to achieve and harder for patients to accept. Until the publication of the results of the Diabetes Control and Complications Trial (DCCT), this reason for treating type 1 diabetes was assumed rather than based on evidence. The landmark findings of the DCCT showed clinically significant reductions in the development and/or progression of retinopathy, nephropathy and neuropathy in patients randomized to the intensive control arm of the trial, and proved that near-normal plasma glucose levels impact on complications. One interpretation of the DCCT data is that therapy aimed at avoiding symptoms (as in the conventionally treated group) is insufficient to prevent adverse outcomes over the lifetime of patients with the disease. The DCCT was an efficacy study; that is, the setting in which the intervention was evaluated was optimized to increase the likelihood of a beneficial outcome. For example, patients in the intensive arm of the trial were seen as often as monthly, and had weekly telephone contact with members of the study team including diabetes nurse educators, dietitians and psychologists. The challenge for most doctors is to translate the results of the DCCT into the ‘real world’, with its constraints on resources and time. The first step in this task should be to engage the patient in the challenge. As discussed below, the work involved in achieving and maintaining near-normal plasma glucose levels over a lifetime is enormous. At a minimum, it involves daily attention to lifestyle (diet and exercise), and monitoring of glucose levels and insulin dosing. Patients with newly diagnosed type 1 diabetes can now anticipate a long life free of complications, but it is important to recognize that this is achieved at a price. The price of intensive control may be acceptable to many patients, if they are given the tools and skills to achieve this. For those who fail to appreciate or achieve the benefits of good glycaemic control, the role of the diabetes care team is to help find a balance between what is acceptable to the patient (in terms of quality of life) and an acceptable degree of control. The third justification for insulin therapy (avoidance of complications) is undoubtedly the greatest management challenge.
Management of Type 1 Diabetes Sean F Dinneen
Failure of the thyroid gland requires thyroid hormone replacement therapy, which is relatively easily adjusted to replicate the normal physiological state by monitoring plasma levels of thyroxine and/or thyroid-stimulating hormone. In contrast, failure of pancreatic β-cells requires insulin therapy, and optimal replacement requires monitoring, not of the absent hormone (insulin), but of its major substrate (glucose). The fact that glucose levels are also regulated by several other (counter-regulatory) hormones, by nutrient ingestion, by energy expenditure and by many poorly understood psychosocial stressors, plus the inadequacy of current insulin replacement regimens, means that truly physiological insulin replacement remains an elusive goal almost 80 years after the discovery of insulin. This contribution focuses on the role of self-management in type 1 diabetes and the tools available to achieve management goals.
Aims of management Without insulin therapy, patients with type 1 diabetes develop profound hyperglycaemia leading to ketosis, ketoacidosis, coma and death. Insulin therapy is therefore a life-saving intervention, and easy for patients, family members and health-care providers to accept. It also alleviates the unpleasant symptoms associated with hyperglycaemia, making the patient feel better. When plasma glucose levels are persistently above the renal threshold (about 10 mmol/litre), glycosuria leads to osmotic diuresis, and the classical triad of polydipsia, polyuria and weight loss ensues. The weight loss associated with insulin deficiency results partly from loss of calories (in the form of glucose) in the urine and partly from a catabolic state associated with insulin deficiency. Insulin
Self-management education Initial diabetes education Initial diabetes education to achieve the first two objectives outlined above is often referred to as ‘survival skills’ training. It focuses on the knowledge and skills needed to avoid symptomatic hyperglycaemia and hypoglycaemia. It typically comprises: • general facts about diabetes and the need for insulin • the mechanics of self-monitoring of blood glucose and insulin self-administration • recognition and treatment of low blood sugar reactions • the role of diet and exercise in treating diabetes. This information is first delivered in the setting of recently diagnosed diabetes and therefore often requires reinforcement
Sean F Dinneen is Consultant Diabetologist at Addenbrooke’s Hospital, Cambridge, UK. He qualified from University College Cork Medical School, Cork, Ireland, and trained in diabetes and endocrinology at the Mayo Clinic, Rochester, USA, and in clinical epidemiology at McMaster University, Hamilton, Canada. His interests include clinical trials and systematic reviews of the diabetes literature, and developing optimal models for community-based diabetes care.
MEDICINE
16
© 2002 The Medicine Publishing Company Ltd
MANAGEMENT OF DIABETES
ment), increasing the target to 6–8 mmol/litre preprandial and 8–10 mmol/litre at bedtime should be considered. • Women who are pregnant or planning pregnancy should aim for less than 5 mmol/litre preprandial and less than 8 mmol/litre 2 hours post-prandial. Setting of treatment targets should take into account both the overall clinical setting and the patient’s capabilities and understanding. In some patients (e.g. those with a terminal illness), avoidance of symptomatic hyperglycaemia or hypoglycaemia may be a reasonable target. In all cases, establishment of targets should be discussed with the patient early in the development of a self-management education programme.
once the patient has come to terms with the diagnosis. Even in patients who have had diabetes for many years, it is often worthwhile reviewing this basic knowledge. Management of diabetes during intercurrent illness poses problems for many patients, and the following principles must be taught and constantly reinforced. Patients should: • never stop taking their insulin, even if they are unable to eat or are nauseated and vomiting • monitor blood sugar more frequently and monitor for ketonuria on sick-days • know how to adjust their insulin doses for hyperglycaemia and for ketonuria • avoid dehydration by drinking plenty of fluids • know how and when to call for help from the health-care team.
Life-long learning The patient is now ready to embark on what should be a programme of life-long learning in how to master his or her diabetes. Proper self-management education requires commitment on the part of both patient and health-care team. Patients differ in their willingness to engage in mastering their disease, and their commitment to self-management may vary over time. Self-management education cannot be delivered in the course of a single visit to an out-patient clinic. Different teaching strategies are available and may be suited to individual patients; ideally, a number of strategies (e.g. one-on-one teaching, group education, self-study) should be available. The main components of a comprehensive self-management skills training programme are outlined in Figure 1. The aim is to provide patients with the knowledge and skills they need to control their diabetes. The underlying philosophy is a team approach to the delivery of care, with the patient at the centre of the team. Traditional medical school edu-cation has centred on a physician-centred rather than a patient-centred model of care, but this is suited more to the
Determining management targets After starting an appropriate insulin programme, the next step in self-management is to decide on appropriate treatment targets. These vary, depending on clinical parameters including the age of the patient, the presence of co-morbidity, the willingness and/or ability of the patient to participate in diabetes self-management, and the skills and attitude of the health-care team in supporting a self-management approach. When agreeing targets, it is essential to assess (in all patients) the degree of hypoglycaemic awareness and (in women of childbearing age) the patient’s plans for future conception. • In most patients, a standard preprandial blood glucose of 4–6 mmol/litre and a bedtime level of 6–8 mmol/litre is ideal. A 2-hour post-prandial target of less than 10 mmol/litre is reasonable, though monitoring at this time is seldom recommended. • In patients with hypoglycaemia unawareness (arbitrarily defined as the occurrence of one or more episodes of hypoglycaemia requiring the assistance of another person for treat-
Components of a self-management education programme • • • • • • • • • • • • • • • • •
General facts Nutrition Exercise Insulin Monitoring Glycaemic targets Hypoglycaemia Intercurrent illness Chronic complications Foot care Pre-pregnancy counselling Safety issues Family involvement Use of health-care system Stress and psychosocial issues Additional resources The future
What diabetes is and what it is not Optimizing meal plans Effects on glucose and the need to plan exercise and activity Action, duration and administration technique Technique, available meters, importance of maintaining a record Use of self-monitoring of blood glucose, exercise and diet to achieve and maintain agreed targets Recognition, avoidance and treatment, including the role of glucagon Sick-day rules, monitoring for ketones, when and how to call for help Aetiology, avoidance by maintaining good control, importance of screening Regular inspection, appropriate footwear, role of the chiropodist Emphasis on tight control and planning of conception Driving, wearing an identity badge Harnessing social support system to help with diabetes care Knowledge of entitlements, importance of annual review, contact information for health-care team Recognizing that fear, denial, anger and frustration can all be part of having diabetes Diabetes websites, support groups, local and national organizations Pumps, sensors, islet transplantation
1 MEDICINE
17
© 2002 The Medicine Publishing Company Ltd
MANAGEMENT OF DIABETES
24-hour insulin time-course Meals and snacks Twice-daily soluble and isophane insulin regimen
Insulin
SE DO
1
+
SE DO
SE DO
2
3
+
SE DO
4
Basal–bolus regimen A wide range of blood glucose meters and insulin delivery devices is available to help patients mimic the activity of the healthy β-cell.
management of acute diseases such as those seen in the hospital environment. Management of chronic disease requires a different approach. Health professionals must recognize this and change their systems of delivering care, to best meet the needs of their patients.
Insulin
SE DO
1
SE DO
2
SE DO
3
SE DO
4
Short-acting (soluble) insulin Intermediate-acting (e.g. isophane) insulin
Management tools
2
Insulin replacement therapy For many years, clinicians and scientists have grappled with the task of delivering insulin in a truly physiological manner. This amounts to provision of a basal or background level of insulin (ideally at a steady state over 24 hours) combined with boluses of insulin at times of calorie ingestion. Physiological insulin replacement has not been fully realized, but important steps towards this goal have been made. These include: • delaying absorption of insulin from its subcutaneous depot by combining it with preparations of zinc (lente insulin) or protamine (NPH, isophane insulin) • mass producing the peptide by recombinant DNA methods, thus making human insulin widely available • chemical manipulation of the insulin molecule to alter its pharmacokinetic properties, producing the so-called insulin analogues with rapid (lispro or aspart) or delayed (glargine) onset and duration of action. These advances, combined with novel insulin delivery systems (e.g. pen devices, continuous subcutaneous insulin infusion pumps, metered-dose inhalers in the future) mean that patients can be offered several options for insulin replacement therapy. There is no single best method for delivering subcutaneous insulin, and all methods have major limitations. Programmes must be tailored to individual patients, based on their needs and their willingness to engage in selfmanagement and dose adjustment.
The two principal programmes in current use are: • twice-daily mixtures of intermediate and fast-acting insulin (sometimes called a ‘split-mixed’ programme) • multiple daily injections combining meal-time fast-acting insulin with a bedtime injection of intermediate or longacting insulin (the so-called ‘basal–bolus’ programme, Figure 2). Both programmes have advantages and disadvantages. When fewer injections and less tight glycaemic control are desirable (e.g. in elderly or very young patients), the twice-daily option may be preferable. When greater lifestyle flexibility and tighter glycaemic control are desirable (e.g. in young adults, during pregnancy), the basal–bolus programme is preferred. Although total daily insulin doses must be tailored to the individual patient, a good ‘rule-of-thumb’ for commencing a twice-daily split-mixed programme is to provide two-thirds of the dose in the morning injection and one-third in the evening injection; each injection should comprise about twothirds intermediate-acting insulin and one-third fast-acting insulin. A similar rule-of-thumb for commencement of a basal–bolus programme is to give about 50% of the total daily insulin dose as basal insulin, and the remaining 50% divided equally among the three mealtime boluses. Pen devices are popular in Europe but not in the USA, where free-mixing of insulin using vials and syringes is the
MEDICINE
18
© 2002 The Medicine Publishing Company Ltd
MANAGEMENT OF DIABETES
The bicycle model of diabetes care
m st e sy He
alt h
Fam
ily
ds Frien
Patient
Foot care
Quality of life
Glucose self-monitoring
Work
Health-care team
Diet
Exercise
Adherence to treatment plan
The bicycle model of diabetes care emphasizes the role of the health-care team (giving direction), the patient (providing momentum) and various support systems linking the two. Source: Montori V M, Smith S A. Exp Clin Endocrinol Diabetes 2001; 108: (Suppl. 2): 351–65.
norm. Pump therapy is more popular in the USA; advantages over multiple daily injection programmes include the ability to alter the basal insulin infusion rate in response to diurnal fluctuations in insulin sensitivity (e.g. the early morning ‘dawn phenomenon’).
common dietary educational tool. Modern variations on this approach include use of the glycaemic index, in which foods are ranked on the basis of their glycaemic effect compared with a standard food. A similar approach (carbohydrate counting) has become popular in patients on basal–bolus insulin regimens or continuous subcutaneous insulin infusion pump therapy. This method requires an understanding of the number of grams of carbohydrate ingested and the likely impact on the glucose response to that meal. The popularity of this approach is partly related to its liberal nature compared with its more restrictive forerunners.
Nutrition The aim of nutritional education is to help patients learn how their calorie intake influences day-to-day fluctuations in blood glucose, and how to use this knowledge to establish a meal plan appropriate to their management goals. The approach to dietary management of type 1 diabetes has changed dramatically over the last few decades. In the pre-insulin era and the early post-insulin era, the recommended diet was extremely low in carbohydrate and high in fat. A gradual reduction in the recommended daily fat intake (with a concomitant increase in carbohydrate content) has since occurred – the most recent recommendations from the American Diabetes Association emphasize a diet in which less than 10% of calories are derived from saturated fat. Early insulin regimens were less physiological than modern regimens and required rigid adherence to meal and snack times. An emphasis on distribution of carbohydrate calories (‘carbohydrate exchanges’) throughout the day was a
MEDICINE
Exercise In non-diabetic individuals, exercise is associated with increased insulin sensitivity, decreased insulin secretion and increased counter-regulatory hormone secretion. The latter two responses offset any decrease in plasma glucose that might result from increased insulin sensitivity; the net result is that plasma glucose concentrations are maintained within the normal range. The principles of education on exercise in diabetes are to enable patients to plan activity and to have a good understanding of their individual response. If this is accomplished, exercise can be a useful tool in achieving good glycaemic control.
19
© 2002 The Medicine Publishing Company Ltd
MANAGEMENT OF DIABETES
• delayed hypoglycaemia (several hours after cessation of exercise), which is related to replenishment of glycogen stores in the exercised muscles • the need to avoid injection in exercised limbs, because of increased blood flow and resultant increased insulin absorption • the importance of planning exercise, using a reduction in insulin dose beforehand and/or snacks to deal with hypoglycaemia.
Unplanned exercise in a patient with type 1 diabetes results in increased counter-regulatory hormone secretion; because the β-cell is unable to alter the amount of circulating insulin, the plasma glucose response to exercise depends entirely on the prevailing amount of exogenous insulin. If this is excessive, hypoglycaemia can result; if it is insufficient, hyperglycaemia can occur. Patients must learn what their ‘comfort zone’ is for a given degree of exercise; for example, vigorous physical activity (e.g. 45 minutes of competitive squash) may be ‘safe’ at a pre-exercise plasma glucose level of 10 mmol/litre, but may lead to hypoglycaemia at 6 mmol/ litre. Patients must also understand that exercise can sometimes raise blood glucose (generally at plasma glucose levels > 15 mmol/litre). Additional considerations include:
Monitoring Clinical trial evidence supporting the efficacy of self-monitoring of blood glucose is weak, but this is likely to be related to difficulties in designing trials of complex interventions
Glucose sensor data Non-diabetic individual Day 1
Day 2
Day 3
20
15
10
5
0 4
8
12
4
8
4
8
12
Time
4
8
4
8
Time
12
4
8
4
8
Time
Individual with type 1 diabetes Day 1
Day 2
Day 3
20
15
10
5
0 4
8
12
4
8
4
8
12
Time Meal
4
8
Time Insulin
Hyperglycaemic limit
4
8
12
Time Hypoglycaemic limit
Continuous glucose monitoring system data illustrate the striking contrast between the healthy β-cell and the absent β-cell replaced by exogenous insulin injections. 3 MEDICINE
20
© 2002 The Medicine Publishing Company Ltd
MANAGEMENT OF DIABETES
Patient education in type 1 diabetes hypoglycaemia (for at least 6 years), reduced numbers of sick-days and hospitalizations, and improvements in preference-weighted quality-of-life variables. Quality-control of DTTP is essential, and comprises re-evaluating representative patients 6–12 months after the intervention. u
Effective therapeutic education in diabetes is oriented towards therapeutic objectives defined for each individual patient. Minimizing the effects of the disease and its treatment on quality of life and avoiding acute metabolic decompensations are therapeutic goals for every individual with diabetes, regardless of age, accompanying conditions and preferences. Prevention of microangiopathic complications by achieving near-normoglycaemia is important, except in patients who are very elderly or who have otherwise limited life expectancy, and strict normoglycaemia must be achieved during pregnancy. Based on such individual objectives, therapeutic education aims at training and motivating patients to undertake their treatment as independently and self-responsibly as individually possible. In type 1 diabetes, this usually requires self-monitoring of glycaemia and adapting insulin doses within the framework of intensified insulin therapy (twice-daily NPH and preprandial regular insulin, or insulin pump therapy). Patients are trained and encouraged to adapt their insulin therapy to their preferred nutrition and lifestyle, rather than vice versa. The educational programme underlying such a therapeutic strategy must be elaborate. A structured treatment and teaching programme (DTTP) for groups of five to ten type 1 diabetic patients, comprising 25 hours of interactional learning and practice during five consecutive days on an in-patient or out-patient basis, has been shown to be effective. The DTTP is delivered by a team of health-care providers, usually comprising a physician, a diabetes educator and a dietitian. A central element of the programme is to train and encourage patients to continuously adapt their insulin doses to their needs by following certain rules, without relying on fixed algorithms or so-called sliding scales. Proof of the efficacy and cost-effectiveness of DTTP has been based on uncontrolled and controlled studies in university hospitals, in city and country hospitals, and in diabetes clinics in several health-care systems, and includes the recent positive experience with DAFNE in the UK. DTTP results in significant improvements in outcome measures; for example, decreased HbA1c levels associated with a reduction (or no increase) in the incidence of severe
Michael Berger, Professor of Medicine and Head of the Department of Metabolic Diseases and Nutrition (WHO Collaborating Centre for Diabetes), Heinrich-Heine University, Düsseldorf, Germany Ingrid Mühlhauser, Professor of Health Sciences, University of Hamburg, Germany
REFERENCES AND FURTHER READING Assal J P, Mühlhauser I, Pernet A, Gfeller R, Jörgens V, Berger M. Patient Education as the Basis for Diabetes Care in Clinical Practice and Research. Diabetologia 1985; 28: 602–13. Berger M. To Bridge Science and Patient Care in Diabetes. Diabetologia 1996; 39: 749–57. Berger M, Mühlhauser I. Diabetes Care and Patient-oriented Outcomes. JAMA 1999; 281: 1676–8. Jörgens V, Grüßer M, Bott U, Mühlhauser I, Berger M. Effective and Safe Translation of Intensified Insulin Therapy to General Internal Medicine Departments. Diabetologia 1993; 36: 99–105. Mühlhauser I, Berger M. Evidence Based Patient Information in Diabetes. Diabetic Med 2000; 17: 823–9. Mühlhauser I, Berger M. Diabetes Education and Insulin Therapy: When Will They Ever Learn? J Int Med 1993; 233: 321–6. Mühlhauser I, Bruckner I, Berger M et al. Evaluation of an Intensified Insulin Treatment and Teaching Programme as Routine Management of Type 1 (Insulin-dependent) Diabetes. The Bucharest–Düsseldorf Study. Diabetologia 1987; 30: 681–90. Müller U A, Femerling M, Reinauer K M et al. Intensified Treatment and Education of Type 1 Diabetes Mellitus in Clinical Routine. Diabetes Care 1999; 22: (Suppl. 2): B29–34. WHO. Therapeutic Patient Education. Copenhagen: WHO, 1998.
rather than to a true lack of efficacy. The fact that a patient monitors his or her blood glucose on a regular basis does not in itself lead to improvement in glycaemic control – the selfmanagement skills needed to interpret and act on the meter readings are often lacking. Sophisticated software for memory meter download or continuous glucose sensing (Figure 3) helps with pattern recognition and can be a useful tool in self-management, but these methods do not inform the patient what insulin to deliver, and many patients do not make optimal use of the information they obtain from their meter. A common situation is for patients to supplement their mealtime insulin dose according to the prevailing blood sugar at the time of the injection. This approach is conceptually easy for patients to grasp and is the basis of the ‘sliding-scale’ approach that is widely used by hospital doctors in managing in-patient diabetes. This approach is
MEDICINE
fundamentally flawed, however, because it incorrectly attributes hyperglycaemia to lack of insulin in the injection about to be taken, rather than in the preceding injection. An alternative and often more useful approach to dose adjustment is ‘pattern recognition’. This emphasizes the setting of blood sugar targets, agreeing fixed doses of insulin and adjusting these doses only if the blood sugar pattern (over several days) shows a clear trend towards being high or low. Dose adjustments usually amount to 10% of the fixed dose. The ‘sliding-scale’ approach is so ingrained in the minds of patients (and health-care providers) that a pragmatic solution to optimizing dose adjustment is required, combining the two methods. This can be accomplished by agreeing a supplement scale with patients and encouraging them to record their insulin doses as ‘fixed dose’ plus (or minus) ‘supplement’ (Figure 4); patients then learn how to respond
21
© 2002 The Medicine Publishing Company Ltd
MANAGEMENT OF DIABETES
Insulin dose adjustment
16/7 17/7 18/7 19/7 20/7
5 5 5 5 6
6+1 6+2 6 6+2 6
7 7 7 7 7
14 14 14 14 14
6.1 4.8 5.2 4.2 5.0
12.1 14.2 15.1 7.2
5.2 8.2 7.1 8.4
10.0 7.2 8.1 6.1 10.1
During night
Before bed
2 hours after evening meal
Before evening meal
2 hours after mid-day meal
Before mid-day meal
2 hours after breakfast
Before breakfast
Breakfast Lunch Dinner Bed Actrapid Actrapid Actrapid Insulatard
Date
Time
Insulin injection Blood glucose
Key events
Comments
Supplement scale <3 4–8 9 –12 13 –15 > 15
–1 0 +1 +2 +3
Dose adjustment of breakfast insulin after 3 days of supplementing at lunchtime This home monitoring diary illustrates the combined use of a supplement scale and pattern recognition to help inform insulin dose adjustment decision-making. 4
to patterns of supplementation at certain times of the day by adjusting the preceding insulin dose. Experienced patients learn to combine this dose-adjustment strategy with a carbohydrate-counting approach, whereby they know on average how much insulin is required for a given amount of carbohydrate consumed with a meal. Urinary or blood ketone measurement is also possible with current technology, and kits for measurement of glycosylated haemoglobin are available. As with self-monitoring of blood glucose, maximum benefit from these methods requires a well-informed and motivated patient. u
American Diabetes Association. Diabetes Mellitus and Exercise. Diabetes Care 2001; 24: (Suppl. 1): S51–5. Diabetes Control and Complications Trial Research Group. The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-term Complications in Insulin-dependent Diabetes Mellitus. N Engl J Med 1993; 329: 977–86. Owens D R, Zinman B, Bolli G B. Insulins Today and Beyond. Lancet 2001; 358: 739–46. Paterson B, Sloan J. A Phenomenological Study of the Decision-making Experience of Individuals with Long-standing Diabetes. Can J Diabetes Care 1994; 18: 10–19. www.shodor.org/aida/ (This interactive website simulates the blood glucose profiles of patients on various insulin regimens; changes to insulin dose, carbohydrate intake, insulin sensitivity and the renal threshold for glucose can be made – a useful tool for teaching and learning the complexity of day-to-day management.)
FURTHER READING American Diabetes Association. Nutrition Recommendations and Principles for People with Diabetes Mellitus. Diabetes Care 2001; 24: (Suppl. 1): S44–7.
MEDICINE
22
© 2002 The Medicine Publishing Company Ltd
replacement is aimed at lowering plasma glucose levels below the renal threshold. The third reason for insulin replacement therapy (avoidance of the microvascular complications associated with longterm hyperglycaemia) is more difficult to achieve and harder for patients to accept. Until the publication of the results of the Diabetes Control and Complications Trial (DCCT), this reason for treating type 1 diabetes was assumed rather than based on evidence. The landmark findings of the DCCT showed clinically significant reductions in the development and/or progression of retinopathy, nephropathy and neuropathy in patients randomized to the intensive control arm of the trial, and proved that near-normal plasma glucose levels impact on complications. One interpretation of the DCCT data is that therapy aimed at avoiding symptoms (as in the conventionally treated group) is insufficient to prevent adverse outcomes over the lifetime of patients with the disease. The DCCT was an efficacy study; that is, the setting in which the intervention was evaluated was optimized to increase the likelihood of a beneficial outcome. For example, patients in the intensive arm of the trial were seen as often as monthly, and had weekly telephone contact with members of the study team including diabetes nurse educators, dietitians and psychologists. The challenge for most doctors is to translate the results of the DCCT into the ‘real world’, with its constraints on resources and time. The first step in this task should be to engage the patient in the challenge. As discussed below, the work involved in achieving and maintaining near-normal plasma glucose levels over a lifetime is enormous. At a minimum, it involves daily attention to lifestyle (diet and exercise), and monitoring of glucose levels and insulin dosing. Patients with newly diagnosed type 1 diabetes can now anticipate a long life free of complications, but it is important to recognize that this is achieved at a price. The price of intensive control may be acceptable to many patients, if they are given the tools and skills to achieve this. For those who fail to appreciate or achieve the benefits of good glycaemic control, the role of the diabetes care team is to help find a balance between what is acceptable to the patient (in terms of quality of life) and an acceptable degree of control. The third justification for insulin therapy (avoidance of complications) is undoubtedly the greatest management challenge.
Management of Type 1 Diabetes Sean F Dinneen
Failure of the thyroid gland requires thyroid hormone replacement therapy, which is relatively easily adjusted to replicate the normal physiological state by monitoring plasma levels of thyroxine and/or thyroid-stimulating hormone. In contrast, failure of pancreatic β-cells requires insulin therapy, and optimal replacement requires monitoring, not of the absent hormone (insulin), but of its major substrate (glucose). The fact that glucose levels are also regulated by several other (counter-regulatory) hormones, by nutrient ingestion, by energy expenditure and by many poorly understood psychosocial stressors, plus the inadequacy of current insulin replacement regimens, means that truly physiological insulin replacement remains an elusive goal almost 80 years after the discovery of insulin. This contribution focuses on the role of self-management in type 1 diabetes and the tools available to achieve management goals.
Aims of management Without insulin therapy, patients with type 1 diabetes develop profound hyperglycaemia leading to ketosis, ketoacidosis, coma and death. Insulin therapy is therefore a life-saving intervention, and easy for patients, family members and health-care providers to accept. It also alleviates the unpleasant symptoms associated with hyperglycaemia, making the patient feel better. When plasma glucose levels are persistently above the renal threshold (about 10 mmol/litre), glycosuria leads to osmotic diuresis, and the classical triad of polydipsia, polyuria and weight loss ensues. The weight loss associated with insulin deficiency results partly from loss of calories (in the form of glucose) in the urine and partly from a catabolic state associated with insulin deficiency. Insulin
Self-management education Initial diabetes education Initial diabetes education to achieve the first two objectives outlined above is often referred to as ‘survival skills’ training. It focuses on the knowledge and skills needed to avoid symptomatic hyperglycaemia and hypoglycaemia. It typically comprises: • general facts about diabetes and the need for insulin • the mechanics of self-monitoring of blood glucose and insulin self-administration • recognition and treatment of low blood sugar reactions • the role of diet and exercise in treating diabetes. This information is first delivered in the setting of recently diagnosed diabetes and therefore often requires reinforcement
Sean F Dinneen is Consultant Diabetologist at Addenbrooke’s Hospital, Cambridge, UK. He qualified from University College Cork Medical School, Cork, Ireland, and trained in diabetes and endocrinology at the Mayo Clinic, Rochester, USA, and in clinical epidemiology at McMaster University, Hamilton, Canada. His interests include clinical trials and systematic reviews of the diabetes literature, and developing optimal models for community-based diabetes care.
MEDICINE
16
© 2002 The Medicine Publishing Company Ltd
MANAGEMENT OF DIABETES
ment), increasing the target to 6–8 mmol/litre preprandial and 8–10 mmol/litre at bedtime should be considered. • Women who are pregnant or planning pregnancy should aim for less than 5 mmol/litre preprandial and less than 8 mmol/litre 2 hours post-prandial. Setting of treatment targets should take into account both the overall clinical setting and the patient’s capabilities and understanding. In some patients (e.g. those with a terminal illness), avoidance of symptomatic hyperglycaemia or hypoglycaemia may be a reasonable target. In all cases, establishment of targets should be discussed with the patient early in the development of a self-management education programme.
once the patient has come to terms with the diagnosis. Even in patients who have had diabetes for many years, it is often worthwhile reviewing this basic knowledge. Management of diabetes during intercurrent illness poses problems for many patients, and the following principles must be taught and constantly reinforced. Patients should: • never stop taking their insulin, even if they are unable to eat or are nauseated and vomiting • monitor blood sugar more frequently and monitor for ketonuria on sick-days • know how to adjust their insulin doses for hyperglycaemia and for ketonuria • avoid dehydration by drinking plenty of fluids • know how and when to call for help from the health-care team.
Life-long learning The patient is now ready to embark on what should be a programme of life-long learning in how to master his or her diabetes. Proper self-management education requires commitment on the part of both patient and health-care team. Patients differ in their willingness to engage in mastering their disease, and their commitment to self-management may vary over time. Self-management education cannot be delivered in the course of a single visit to an out-patient clinic. Different teaching strategies are available and may be suited to individual patients; ideally, a number of strategies (e.g. one-on-one teaching, group education, self-study) should be available. The main components of a comprehensive self-management skills training programme are outlined in Figure 1. The aim is to provide patients with the knowledge and skills they need to control their diabetes. The underlying philosophy is a team approach to the delivery of care, with the patient at the centre of the team. Traditional medical school edu-cation has centred on a physician-centred rather than a patient-centred model of care, but this is suited more to the
Determining management targets After starting an appropriate insulin programme, the next step in self-management is to decide on appropriate treatment targets. These vary, depending on clinical parameters including the age of the patient, the presence of co-morbidity, the willingness and/or ability of the patient to participate in diabetes self-management, and the skills and attitude of the health-care team in supporting a self-management approach. When agreeing targets, it is essential to assess (in all patients) the degree of hypoglycaemic awareness and (in women of childbearing age) the patient’s plans for future conception. • In most patients, a standard preprandial blood glucose of 4–6 mmol/litre and a bedtime level of 6–8 mmol/litre is ideal. A 2-hour post-prandial target of less than 10 mmol/litre is reasonable, though monitoring at this time is seldom recommended. • In patients with hypoglycaemia unawareness (arbitrarily defined as the occurrence of one or more episodes of hypoglycaemia requiring the assistance of another person for treat-
Components of a self-management education programme • • • • • • • • • • • • • • • • •
General facts Nutrition Exercise Insulin Monitoring Glycaemic targets Hypoglycaemia Intercurrent illness Chronic complications Foot care Pre-pregnancy counselling Safety issues Family involvement Use of health-care system Stress and psychosocial issues Additional resources The future
What diabetes is and what it is not Optimizing meal plans Effects on glucose and the need to plan exercise and activity Action, duration and administration technique Technique, available meters, importance of maintaining a record Use of self-monitoring of blood glucose, exercise and diet to achieve and maintain agreed targets Recognition, avoidance and treatment, including the role of glucagon Sick-day rules, monitoring for ketones, when and how to call for help Aetiology, avoidance by maintaining good control, importance of screening Regular inspection, appropriate footwear, role of the chiropodist Emphasis on tight control and planning of conception Driving, wearing an identity badge Harnessing social support system to help with diabetes care Knowledge of entitlements, importance of annual review, contact information for health-care team Recognizing that fear, denial, anger and frustration can all be part of having diabetes Diabetes websites, support groups, local and national organizations Pumps, sensors, islet transplantation
1 MEDICINE
17
© 2002 The Medicine Publishing Company Ltd
MANAGEMENT OF DIABETES
24-hour insulin time-course Meals and snacks Twice-daily soluble and isophane insulin regimen
Insulin
SE DO
1
+
SE DO
SE DO
2
3
+
SE DO
4
Basal–bolus regimen A wide range of blood glucose meters and insulin delivery devices is available to help patients mimic the activity of the healthy β-cell.
management of acute diseases such as those seen in the hospital environment. Management of chronic disease requires a different approach. Health professionals must recognize this and change their systems of delivering care, to best meet the needs of their patients.
Insulin
SE DO
1
SE DO
2
SE DO
3
SE DO
4
Short-acting (soluble) insulin Intermediate-acting (e.g. isophane) insulin
Management tools
2
Insulin replacement therapy For many years, clinicians and scientists have grappled with the task of delivering insulin in a truly physiological manner. This amounts to provision of a basal or background level of insulin (ideally at a steady state over 24 hours) combined with boluses of insulin at times of calorie ingestion. Physiological insulin replacement has not been fully realized, but important steps towards this goal have been made. These include: • delaying absorption of insulin from its subcutaneous depot by combining it with preparations of zinc (lente insulin) or protamine (NPH, isophane insulin) • mass producing the peptide by recombinant DNA methods, thus making human insulin widely available • chemical manipulation of the insulin molecule to alter its pharmacokinetic properties, producing the so-called insulin analogues with rapid (lispro or aspart) or delayed (glargine) onset and duration of action. These advances, combined with novel insulin delivery systems (e.g. pen devices, continuous subcutaneous insulin infusion pumps, metered-dose inhalers in the future) mean that patients can be offered several options for insulin replacement therapy. There is no single best method for delivering subcutaneous insulin, and all methods have major limitations. Programmes must be tailored to individual patients, based on their needs and their willingness to engage in selfmanagement and dose adjustment.
The two principal programmes in current use are: • twice-daily mixtures of intermediate and fast-acting insulin (sometimes called a ‘split-mixed’ programme) • multiple daily injections combining meal-time fast-acting insulin with a bedtime injection of intermediate or longacting insulin (the so-called ‘basal–bolus’ programme, Figure 2). Both programmes have advantages and disadvantages. When fewer injections and less tight glycaemic control are desirable (e.g. in elderly or very young patients), the twice-daily option may be preferable. When greater lifestyle flexibility and tighter glycaemic control are desirable (e.g. in young adults, during pregnancy), the basal–bolus programme is preferred. Although total daily insulin doses must be tailored to the individual patient, a good ‘rule-of-thumb’ for commencing a twice-daily split-mixed programme is to provide two-thirds of the dose in the morning injection and one-third in the evening injection; each injection should comprise about twothirds intermediate-acting insulin and one-third fast-acting insulin. A similar rule-of-thumb for commencement of a basal–bolus programme is to give about 50% of the total daily insulin dose as basal insulin, and the remaining 50% divided equally among the three mealtime boluses. Pen devices are popular in Europe but not in the USA, where free-mixing of insulin using vials and syringes is the
MEDICINE
18
© 2002 The Medicine Publishing Company Ltd
MANAGEMENT OF DIABETES
The bicycle model of diabetes care
m st e sy He
alt h
Fam
ily
ds Frien
Patient
Foot care
Quality of life
Glucose self-monitoring
Work
Health-care team
Diet
Exercise
Adherence to treatment plan
The bicycle model of diabetes care emphasizes the role of the health-care team (giving direction), the patient (providing momentum) and various support systems linking the two. Source: Montori V M, Smith S A. Exp Clin Endocrinol Diabetes 2001; 108: (Suppl. 2): 351–65.
norm. Pump therapy is more popular in the USA; advantages over multiple daily injection programmes include the ability to alter the basal insulin infusion rate in response to diurnal fluctuations in insulin sensitivity (e.g. the early morning ‘dawn phenomenon’).
common dietary educational tool. Modern variations on this approach include use of the glycaemic index, in which foods are ranked on the basis of their glycaemic effect compared with a standard food. A similar approach (carbohydrate counting) has become popular in patients on basal–bolus insulin regimens or continuous subcutaneous insulin infusion pump therapy. This method requires an understanding of the number of grams of carbohydrate ingested and the likely impact on the glucose response to that meal. The popularity of this approach is partly related to its liberal nature compared with its more restrictive forerunners.
Nutrition The aim of nutritional education is to help patients learn how their calorie intake influences day-to-day fluctuations in blood glucose, and how to use this knowledge to establish a meal plan appropriate to their management goals. The approach to dietary management of type 1 diabetes has changed dramatically over the last few decades. In the pre-insulin era and the early post-insulin era, the recommended diet was extremely low in carbohydrate and high in fat. A gradual reduction in the recommended daily fat intake (with a concomitant increase in carbohydrate content) has since occurred – the most recent recommendations from the American Diabetes Association emphasize a diet in which less than 10% of calories are derived from saturated fat. Early insulin regimens were less physiological than modern regimens and required rigid adherence to meal and snack times. An emphasis on distribution of carbohydrate calories (‘carbohydrate exchanges’) throughout the day was a
MEDICINE
Exercise In non-diabetic individuals, exercise is associated with increased insulin sensitivity, decreased insulin secretion and increased counter-regulatory hormone secretion. The latter two responses offset any decrease in plasma glucose that might result from increased insulin sensitivity; the net result is that plasma glucose concentrations are maintained within the normal range. The principles of education on exercise in diabetes are to enable patients to plan activity and to have a good understanding of their individual response. If this is accomplished, exercise can be a useful tool in achieving good glycaemic control.
19
© 2002 The Medicine Publishing Company Ltd
MANAGEMENT OF DIABETES
• delayed hypoglycaemia (several hours after cessation of exercise), which is related to replenishment of glycogen stores in the exercised muscles • the need to avoid injection in exercised limbs, because of increased blood flow and resultant increased insulin absorption • the importance of planning exercise, using a reduction in insulin dose beforehand and/or snacks to deal with hypoglycaemia.
Unplanned exercise in a patient with type 1 diabetes results in increased counter-regulatory hormone secretion; because the β-cell is unable to alter the amount of circulating insulin, the plasma glucose response to exercise depends entirely on the prevailing amount of exogenous insulin. If this is excessive, hypoglycaemia can result; if it is insufficient, hyperglycaemia can occur. Patients must learn what their ‘comfort zone’ is for a given degree of exercise; for example, vigorous physical activity (e.g. 45 minutes of competitive squash) may be ‘safe’ at a pre-exercise plasma glucose level of 10 mmol/litre, but may lead to hypoglycaemia at 6 mmol/ litre. Patients must also understand that exercise can sometimes raise blood glucose (generally at plasma glucose levels > 15 mmol/litre). Additional considerations include:
Monitoring Clinical trial evidence supporting the efficacy of self-monitoring of blood glucose is weak, but this is likely to be related to difficulties in designing trials of complex interventions
Glucose sensor data Non-diabetic individual Day 1
Day 2
Day 3
20
15
10
5
0 4
8
12
4
8
4
8
12
Time
4
8
4
8
Time
12
4
8
4
8
Time
Individual with type 1 diabetes Day 1
Day 2
Day 3
20
15
10
5
0 4
8
12
4
8
4
8
12
Time Meal
4
8
Time Insulin
Hyperglycaemic limit
4
8
12
Time Hypoglycaemic limit
Continuous glucose monitoring system data illustrate the striking contrast between the healthy β-cell and the absent β-cell replaced by exogenous insulin injections. 3 MEDICINE
20
© 2002 The Medicine Publishing Company Ltd
MANAGEMENT OF DIABETES
Patient education in type 1 diabetes hypoglycaemia (for at least 6 years), reduced numbers of sick-days and hospitalizations, and improvements in preference-weighted quality-of-life variables. Quality-control of DTTP is essential, and comprises re-evaluating representative patients 6–12 months after the intervention. u
Effective therapeutic education in diabetes is oriented towards therapeutic objectives defined for each individual patient. Minimizing the effects of the disease and its treatment on quality of life and avoiding acute metabolic decompensations are therapeutic goals for every individual with diabetes, regardless of age, accompanying conditions and preferences. Prevention of microangiopathic complications by achieving near-normoglycaemia is important, except in patients who are very elderly or who have otherwise limited life expectancy, and strict normoglycaemia must be achieved during pregnancy. Based on such individual objectives, therapeutic education aims at training and motivating patients to undertake their treatment as independently and self-responsibly as individually possible. In type 1 diabetes, this usually requires self-monitoring of glycaemia and adapting insulin doses within the framework of intensified insulin therapy (twice-daily NPH and preprandial regular insulin, or insulin pump therapy). Patients are trained and encouraged to adapt their insulin therapy to their preferred nutrition and lifestyle, rather than vice versa. The educational programme underlying such a therapeutic strategy must be elaborate. A structured treatment and teaching programme (DTTP) for groups of five to ten type 1 diabetic patients, comprising 25 hours of interactional learning and practice during five consecutive days on an in-patient or out-patient basis, has been shown to be effective. The DTTP is delivered by a team of health-care providers, usually comprising a physician, a diabetes educator and a dietitian. A central element of the programme is to train and encourage patients to continuously adapt their insulin doses to their needs by following certain rules, without relying on fixed algorithms or so-called sliding scales. Proof of the efficacy and cost-effectiveness of DTTP has been based on uncontrolled and controlled studies in university hospitals, in city and country hospitals, and in diabetes clinics in several health-care systems, and includes the recent positive experience with DAFNE in the UK. DTTP results in significant improvements in outcome measures; for example, decreased HbA1c levels associated with a reduction (or no increase) in the incidence of severe
Michael Berger, Professor of Medicine and Head of the Department of Metabolic Diseases and Nutrition (WHO Collaborating Centre for Diabetes), Heinrich-Heine University, Düsseldorf, Germany Ingrid Mühlhauser, Professor of Health Sciences, University of Hamburg, Germany
REFERENCES AND FURTHER READING Assal J P, Mühlhauser I, Pernet A, Gfeller R, Jörgens V, Berger M. Patient Education as the Basis for Diabetes Care in Clinical Practice and Research. Diabetologia 1985; 28: 602–13. Berger M. To Bridge Science and Patient Care in Diabetes. Diabetologia 1996; 39: 749–57. Berger M, Mühlhauser I. Diabetes Care and Patient-oriented Outcomes. JAMA 1999; 281: 1676–8. Jörgens V, Grüßer M, Bott U, Mühlhauser I, Berger M. Effective and Safe Translation of Intensified Insulin Therapy to General Internal Medicine Departments. Diabetologia 1993; 36: 99–105. Mühlhauser I, Berger M. Evidence Based Patient Information in Diabetes. Diabetic Med 2000; 17: 823–9. Mühlhauser I, Berger M. Diabetes Education and Insulin Therapy: When Will They Ever Learn? J Int Med 1993; 233: 321–6. Mühlhauser I, Bruckner I, Berger M et al. Evaluation of an Intensified Insulin Treatment and Teaching Programme as Routine Management of Type 1 (Insulin-dependent) Diabetes. The Bucharest–Düsseldorf Study. Diabetologia 1987; 30: 681–90. Müller U A, Femerling M, Reinauer K M et al. Intensified Treatment and Education of Type 1 Diabetes Mellitus in Clinical Routine. Diabetes Care 1999; 22: (Suppl. 2): B29–34. WHO. Therapeutic Patient Education. Copenhagen: WHO, 1998.
rather than to a true lack of efficacy. The fact that a patient monitors his or her blood glucose on a regular basis does not in itself lead to improvement in glycaemic control – the selfmanagement skills needed to interpret and act on the meter readings are often lacking. Sophisticated software for memory meter download or continuous glucose sensing (Figure 3) helps with pattern recognition and can be a useful tool in self-management, but these methods do not inform the patient what insulin to deliver, and many patients do not make optimal use of the information they obtain from their meter. A common situation is for patients to supplement their mealtime insulin dose according to the prevailing blood sugar at the time of the injection. This approach is conceptually easy for patients to grasp and is the basis of the ‘sliding-scale’ approach that is widely used by hospital doctors in managing in-patient diabetes. This approach is
MEDICINE
fundamentally flawed, however, because it incorrectly attributes hyperglycaemia to lack of insulin in the injection about to be taken, rather than in the preceding injection. An alternative and often more useful approach to dose adjustment is ‘pattern recognition’. This emphasizes the setting of blood sugar targets, agreeing fixed doses of insulin and adjusting these doses only if the blood sugar pattern (over several days) shows a clear trend towards being high or low. Dose adjustments usually amount to 10% of the fixed dose. The ‘sliding-scale’ approach is so ingrained in the minds of patients (and health-care providers) that a pragmatic solution to optimizing dose adjustment is required, combining the two methods. This can be accomplished by agreeing a supplement scale with patients and encouraging them to record their insulin doses as ‘fixed dose’ plus (or minus) ‘supplement’ (Figure 4); patients then learn how to respond
21
© 2002 The Medicine Publishing Company Ltd
MANAGEMENT OF DIABETES
Insulin dose adjustment
16/7 17/7 18/7 19/7 20/7
5 5 5 5 6
6+1 6+2 6 6+2 6
7 7 7 7 7
14 14 14 14 14
6.1 4.8 5.2 4.2 5.0
12.1 14.2 15.1 7.2
5.2 8.2 7.1 8.4
10.0 7.2 8.1 6.1 10.1
During night
Before bed
2 hours after evening meal
Before evening meal
2 hours after mid-day meal
Before mid-day meal
2 hours after breakfast
Before breakfast
Breakfast Lunch Dinner Bed Actrapid Actrapid Actrapid Insulatard
Date
Time
Insulin injection Blood glucose
Key events
Comments
Supplement scale <3 4–8 9 –12 13 –15 > 15
–1 0 +1 +2 +3
Dose adjustment of breakfast insulin after 3 days of supplementing at lunchtime This home monitoring diary illustrates the combined use of a supplement scale and pattern recognition to help inform insulin dose adjustment decision-making. 4
to patterns of supplementation at certain times of the day by adjusting the preceding insulin dose. Experienced patients learn to combine this dose-adjustment strategy with a carbohydrate-counting approach, whereby they know on average how much insulin is required for a given amount of carbohydrate consumed with a meal. Urinary or blood ketone measurement is also possible with current technology, and kits for measurement of glycosylated haemoglobin are available. As with self-monitoring of blood glucose, maximum benefit from these methods requires a well-informed and motivated patient. u
American Diabetes Association. Diabetes Mellitus and Exercise. Diabetes Care 2001; 24: (Suppl. 1): S51–5. Diabetes Control and Complications Trial Research Group. The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-term Complications in Insulin-dependent Diabetes Mellitus. N Engl J Med 1993; 329: 977–86. Owens D R, Zinman B, Bolli G B. Insulins Today and Beyond. Lancet 2001; 358: 739–46. Paterson B, Sloan J. A Phenomenological Study of the Decision-making Experience of Individuals with Long-standing Diabetes. Can J Diabetes Care 1994; 18: 10–19. www.shodor.org/aida/ (This interactive website simulates the blood glucose profiles of patients on various insulin regimens; changes to insulin dose, carbohydrate intake, insulin sensitivity and the renal threshold for glucose can be made – a useful tool for teaching and learning the complexity of day-to-day management.)
FURTHER READING American Diabetes Association. Nutrition Recommendations and Principles for People with Diabetes Mellitus. Diabetes Care 2001; 24: (Suppl. 1): S44–7.
MEDICINE
22
© 2002 The Medicine Publishing Company Ltd