CLINICAL RISK REDUCTION
DIABETES MELLITUS
Making the diagnosis M
Professor Mark Strachan highlights some pitfalls for the unwary diagnostician
AKING a diagnosis of diabetes is, on the face of it, easy. One needs simply to demonstrate that an individual has an elevated blood glucose concentration. However, there are
potential pitfalls for the unwary and I shall consider several of these in this article.
Using HbA1c as a diagnostic test Te traditional diagnostic criteria for diabetes (a fasting plasma glucose ≥ 7.0 mmol/l and/or a random or two hour post glucose-challenge plasma glucose ≥ 11.1 mmol/l) are based around epidemiological data that essentially identify individuals at a higher risk of diabetic retinopathy. Te World Health Organisation has also approved glycated haemoglobin (HbA1c) as a diagnostic test for diabetes, with the diagnosis confirmed if HbA1c is ≥ 48 mmol/mol (6.5 per cent). HbA1c is more familiarly used as a tool to monitor the degree of
glycaemic control in individuals with confirmed diabetes. Glucose binds irreversibly to haemoglobin in red blood cells in direct proportion to the prevailing plasma glucose concentration. Red blood cells have an average lifespan of 120 days and so HbA1c broadly gives a measure of average glycaemic control over that period. Tere are very strong epidemiological data linking HbA1c to risk of
diabetes complications and the HbA1c level is a powerful driver in making alterations to antidiabetic treatment. Terefore, it makes logical sense that HbA1c should also be used as a diagnostic test for diabetes. HbA1c has the additional advantages that it can be measured without the need for fasting and obviates the need for a glucose tolerance test. Many areas of the country are already using HbA1c as a diagnostic test for diabetes, despite its increased cost in relation to plasma glucose, and it is likely that its use will become more common. Te implications of making a diagnosis of diabetes for an individual
can be profound – the individual is turned into a “patient”. Getting travel insurance, life assurance and critical illness cover may be more difficult and more expensive and there may be an impact on employment. It is important to get the diagnosis right and it must be remembered that HbA1c is not a perfect diagnostic test. Anything that alters haemoglobin or the lifespan of a red blood cell
will alter the relationship between HbA1c and average glycaemia. Tus, haemolytic anaemia, haemoglobinopathies, acute blood loss, splenomegaly and some antiretroviral drugs can result in an artificially low HbA1c. Te result may also be lower in renal dialysis patients and be altered by iron and vitamin B12 deficiency. HbA1c will also give a falsely reassuring result if there has been a recent rapid rise in blood glucose; therefore it cannot be used as a diagnostic test for gestational
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diabetes, steroid-induced diabetes and type 1 diabetes. Whatever diagnostic test for diabetes is used, it is important to send
a second confirmatory test in asymptomatic individuals. Samples can be mislabelled and laboratory errors can occur. To avoid confusion in interpretation, the second confirmatory test should be the same as the first, i.e. if HbA1c has been used on the first occasion it should also be tested on the second. Do not delay seeking an urgent opinion though (waiting on a second confirmatory test result) if the individual is ill, has significant symptoms or is a child.
What type of diabetes? Confirming that an individual has diabetes is only part of the job. Te key question to answer next is: “what type of diabetes does this person have?” At its extremes, diabetes is a consequence either of insulin deficiency or insulin resistance, though many individuals with diabetes probably have a bit of both. Insulin deficiency is the hallmark of type 1 diabetes, where there is
autoimmune destruction of the insulin-producing cells of the pancreas. Type 1 diabetes classically presents in children and young adults and there is oſten a short history of increasing osmotic symptoms and weight loss. Central obesity is the commonest substrate of insulin resistance and predisposes to type 2 diabetes, with its trusty lieutenants of hypertension and dyslipidaemia. It is important to be alert to other potential causes of diabetes:
pancreatic pathology (most commonly chronic pancreatitis or post-pancreatic surgery, but more rarely tumours), drugs (including steroid therapy and some antipsychotic medications), endocrine disorders (classically Cushing’s syndrome, acromegaly and phaeochromocytoma) and the reasonably common monogenic forms of diabetes. Monogenic diabetes, oſten referred to as maturity onset diabetes of the young (MODY), is inherited in an autosomal dominant fashion and classically presents in young adults, with hyperglycaemia that can be managed with dietary modification or oral antidiabetic therapy. I always say to my registrars in diabetes and endocrinology that,
when seeing an individual with newly diagnosed diabetes, they should ask themselves: “Why has this person developed diabetes?” Type 1 diabetes can occur in overweight individuals as well as slim people and can present at any age. Te consequences of missing a diagnosis of type 1 diabetes can be extremely serious because insulin deficiency can lead to diabetic ketoacidosis. Terefore, testing for elevated urine or blood ketone concentrations is essential in all people with newly diagnosed diabetes.
SUMMONS
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