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Diagnosis and management of type 1 diabetes

Peter Hammond
MA MD FRCP
Consultant Physician Harrogate District Hospital
Harrogate
N Yorks

In the UK the annual incidence of type 1 diabetes is 10-15 cases per 100,000 children and adolescents under the age of 19, and this is increasing. The peak age of onset is 12 years, but the diagnosis should not be overlooked in older age groups; 10% of diagnosed diabetics over the age of 65 are type 1.

Diagnosis
Diagnosis of type 1 diabetes is not usually a problem. Individuals are young and have the classic symptoms of:

  • Polyuria (excessive urine output) because of the osmotic diuresis associated with glycosuria.
  • Polydipsia (thirst and excessive drinking) because of the body's response to polyuria.
  • Weight loss from increased catabolism.
  • Blurred vision owing to distortion of the lens following the osmotic movement of water in response to hyperglycaemia.

Symptoms become apparent once residual insulin secretion is insufficient to control blood glucose levels, usually when about 90% of cells have been destroyed. However, onset of the disease may be insidious, causing other symptoms, such as growth failure in children and susceptibility to infections such as candidiasis. On rare occasions, when the diagnosis goes undetected, patients present with acute, life- threatening ketoacidosis.
Older individuals with type 1 diabetes may cause diagnostic confusion. Type 2 diabetes is more common in this age group. However, type 1 diabetes can present at any age and occasionally in obese individuals. If these individuals are wrongly classified and treated with oral hypoglycaemic agents, stimulation of residual pancreatic insulin secretion will prevent ketoacidosis developing, but blood glucose control remains poor and they remain symptomatic until insulin therapy is commenced.
Where there is diagnostic uncertainty, a number of features may help in distinguishing between the two types of diabetes (Table 1). Ketonuria is the most compelling indication of type 1 diabetes, since it occurs only when circulating insulin levels are very low; hence it is extremely rare in type 2 diabetes. Definitive confirmation of the diagnosis may be obtained by checking blood for islet cell autoantibodies, present in 80% of patients with type 1 diabetes, and C-peptide deficiency (C-peptide is produced with insulin in the pancreas).

[[NIP02_table1_50]]

Management
The objective of treatment in type 1 diabetes is to:

  • Avoid marked swings in blood glucose.
  • Avoid hypoglycaemia.
  • Maintain a level of blood glucose control that reduces chronic complications (Table 2).

[[NIP02_table2_50]]

Blood glucose control is usually assessed by measurement of glycosylated haemoglobin (HbA(1c)), which gives an indication of average blood glucose levels over the prior 6-8 weeks in most individuals. The Diabetes Control and Complications Trial (DCCT) demonstrated that reduction in HbA(1c) by intensive insulin therapy resulted in a significant decrease in microvascular complications.(1) Recently, interest has focused on the importance of postprandial hyperglycaemia in the genesis of complications, particularly macrovascular disease. There is increasing evidence that assessment of control should consider this in addition to HbA(1c).(2) An increased risk of hypoglycaemia is almost always a consequence of intensive insulin therapy, unless this is achieved by using continuous subcutaneous insulin infusion (CSII) - pump therapy. Hypoglycaemia is distressing to patients and their families. It is frightening and has implications for driving(3) and employment. Frequent severe episodes can have a significant effect on cognitive function.(4) Every attempt should be made to minimise hypoglycaemia. Blood glucose levels should be maintained between 4mmol/l and 8mmol/l with HbA(1c) In normal individuals there are low basal circulating insulin concentrations, with glucose-stimulated secretion resulting in peaks after meals. The aim of insulin therapy should be to replicate this physiological profile. However, subcutaneous injection of insulin can never be expected to match the secretion of insulin by the normal pancreas. It can be highly variable and depends on subcutaneous blood flow, which can be affected by, for example, temperature, exercise and drugs.
The rapid-acting insulin analogues Lispro (Humalog(®): Lilly) and Insulin Aspart (Novorapid(®): Novo Nordisk) have been modified to allow the insulin molecules to be absorbed more rapidly. This may help to reduce variability in absorption.(5)
Conventional insulin therapy uses a twice-daily regimen of mixed intermediate-acting insulin, either a fixed mixture (such as Mixtard 30 [Novo Nordisk]or Humulin M3 [Lilly]) or a self-mixed combination of short and intermediate insulin before breakfast and supper. This results in an excess of insulin between meals, necessitating snacking to avoid hypoglycaemia, and insufficient insulin before meals, particularly lunch.
A closer approximation to physiological insulin release can be obtained by using intensive insulin (basal-bolus) regimens. An intermediate or long-acting insulin is injected once or twice a day to give the baseline level, and then injections of short-acting insulin or rapid-acting analogue are given before each meal. This reduces the necessity for snacks, particularly if a rapid-acting insulin is used, but accumulation of insulin can still occur between meals and cause hypoglycaemia, less so with rapid-acting analogues. Novel long-acting analogues that provide a more constant basal insulin level will shortly be available.
Finally, the best approximation to physiological insulin profiles can be achieved using an insulin pump delivering a rapid-acting insulin analogue. Infusion pumps are very sophisticated. The rate of insulin infusion can be varied each hour. Bolus insulin can be delivered before meals, adjusted to the carbohydrate content, or to correct high blood-glucose levels. The pump delivers insulin through a catheter and needle inserted into the abdominal wall. The advantages of this method of administration are:

  • Achievement of tight blood-glucose control without hypoglycaemia.
  • Variable insulin delivery at night, avoiding nocturnal hypoglycaemia and reducing morning hyperglycaemia (the "dawn phenomenon").
  • Reduction in swings in blood-glucose levels, which has a significant impact on quality of life.(6)

There is widespread use of these pumps in Europe and the USA, and increasing interest in the UK.

Five-year forecast
Wider use of continuous subcutaneous insulin infusion (pump therapy) in the UK
Introduction of long-acting insulin analogues: insulin glargine (Lantus(®): Aventis Pharma) already available in USA; UK release imminent
Introduction of inhaled insulin to replace injections of short-acting insulin; recent reports indicate comparable efficacy(7)
Wider use of islet transplantation to cure type 1 diabetes(8)

References

  1. The 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.
  2. The Diabetes Control and Complications Trial Research Group. The relationship of glycaemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes 1995;44:968-83.
  3. Cox DJ, Gonder-Frederick LA, Kovatchev BP, Julian DM, Clarke WL. Progressive hypoglycaemia's impact on driving simulation performance: occurrence, awareness, and correction. Diabetes Care 2000;23:163-70.
  4. Deary IJ. Effects of hypoglycaemia on cognitive function. In: Frier BM, Fisher BM, editors. Hypoglycaemia and diabetes: clinical and physiological aspects. London: Edward Arnold; 1993. p. 80-92.
  5. Bolli GB, Di Marchi RD, Park GD, Pramming S, Koivisto VA. Insulin analogues and their potential in the management of diabetes mellitus. Diabetologia 1999;42:1151-67.
  6. Boland EA, Grey M, Oesterle A, Fredrickson L,Tamborlane WV. Continuous subcutaneous insulin infusion: a new way to lower risk of severe hypoglycaemia, improve metabolic control and enhance coping in adolescents with type-1 diabetes. Diabetes Care 1999;22(1):1779-84.
  7. Skyler JS, Cefalu WT, Kourides IA, et al. Efficacy of inhaled human insulin in type 1 diabetes mellitus: a randomised proof-of-concept study. Lancet 2001;357:331-5.
  8. Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000;343:230-8.

Resources
Diabetes UK
W:www.diabetes.org.uk

Pump
A group that supports professionals who use insulin pumps
E:diabetes.team@hhc-tr.northy.nhs.uk

Federation of European Nurses in Diabetes (FEND)
E:info@fend.org
W:www.fend.org