Diabetes mellitus refers to a condition in which circulating blood glucose is chronically elevated. As with (for example) anaemia, there are many possible causes for a high blood glucose. Equally, there can be wide variety of possible consequences, such that a physician specializing in diabetes must have some familiarity with almost every system in the body. Investigation of diabetes itself can be divided into the study of its causes, natural history, epidemiology, genetic basis, pathophysiological mechanism and biochemical consequences, and each of its many complications requires investigating along similar lines. This entry provides a brief introduction to the way in which research findings have over the years been translated into the clinical investigation of diabetes.
Figure 1As shown in the Figure 1, understanding a disease involves an iterative cycle of learning and investigation. This begins with careful clinical observation of the natural history of the condition, leading on to the ability to make predictions about its course and prognosis. Clinical interventions are developed and tested, in modern times by randomized controlled trials (RCTs). Aetiological research seeks to identify possible causes, to examine their genetic basis and mechanism in humans and (as necessary) in experimental animals, and thereby feeds into possible new approaches to intervention. Functional studies examine the way in which disease mechanisms are mediated and translate into clinical outcomes. Epidemiological analysis considers disease at a a population level, allowing investigation of potential environmental causes and correlates, of the impact of the disease, of its association with other disease states, and of its wider consequences.
Investigation of the Newly Diagnosed Patient
This follows a logical sequence: - establishing the diagnosis of diabetes - assigning a cause or classification - examination for possible early complications - screening for associated disorders - review of other aspects of health
Establishing the Diagnosis
This is based upon confirmation of diabetes by a reliable method, which would normally entail a laboratory (rather than stick) test for plasma glucose. A single positive test is generally considered reliable in people with typical symptoms, but a confirmatory test is prudent in asymptomatic people to exclude the possibility of laboratory error.
The diagnosis is confirmed by a random blood glucose >11 mmol/l (>200 mg/dl), or by a fasting glucose >7.0 mmol/l (126 mg/dl). It may also be confirmed by measurement of HbA1c >6.5% (48 mmol/mol). The oral glucose tolerance test (OGTT) may be useful in special circumstances, but is not generally necessary.
Investigating the Cause
Although the great majority of people have primary (idiopathic,unknown cause) diabetes, some 3-5% have diabetes secondary to some other condition. See Other types of diabetes mellitus for a full list of the possibilities. Consideration should be given to the possibility of Monogenic diabetes, Pancreatic disorders, Endocrine disorders and Drug-induced diabetes.
The distinction between Type 1 diabetes mellitus and Type 2 diabetes mellitus is generally straightforward and can be made on clinical grounds, but the two conditions blur at the margins, especially as early onset type 2 diabetes becomes more common in children and adolescents. Equally, autoimmune diabetes can masquerade as type 2 diabetes in later life; see LADA- Latent Autoimmune Diabetes of the Adult.
Special tests including measurement of C-peptide and islet autoantibodies may be needed in case of doubt.
Examination for possible early complications
Microvascular disease is the direct cause of diabetic retinopathy or diabetic nephropathy, and contributes to diabetic neuropathy. Young patients with acute onset of diabetes are unlikely to have evidence of tissue damage at diagnosis, although regular long-term monitoring is needed. Evidence of early microvascular complications is not however uncommon in older people with slower onset of diabetes and (often) exposure to subclinical hyperglycaemia over many years.
Screening for Diabetic Retinopathy is performed by ophthalmoscopy through dilated pupils or retinal photography. Nephropathy is tested for by urinary testing for proteinuria or microalbuminuria. Neuropathy is tested for by standard clinical tests.
Older patients with type 2 diabetes are at high risk of cardiovascular or peripheral arterial disease, and will, as indicated, be investigated with ECGs, treadmill tests, doppler studies and so forth.
Screening for associated disorders
Type 1 diabetes is An autoimmune condition that overlaps with a number of other autoimmune disorders including autoimmune thyroid disease, coeliac disease, autoimmune Addison's disease and pernicious anaemia, and many centres perform an autoimmune screen to exclude these possibilities.
Type 2 diabetes is associated with a disease complex, often known as the metabolic syndrome, which is characterized by central obesity, dylipidaemia, hypertension, and insulin resistance. Obese individuals are at increased risk of some types of cancer, and diabetes may sometimes be the presenting symptom of Pancreatic cancer.
Lipids and blood pressure are routinely measured in the new-onset patient with type 2 diabetes, and further investigation may be required according to the clinical findings.
Review of other aspects of health
Evaluation of a newly diagnosed person with diabetes is incomplete without careful review of their general health. In older patients, especially, it is not uncommon to find evidence of other unrelated or indirectly related illness.
Thus, general systems review and physical examination is required, together with standard screening tests including a full blood count, renal and liver function tests, and other general screening tests including CXR, ECG, etc, according to local guidelines.
Investigation of diabetes should always be undertaken in a directed fashion, rather than by the routine deployment of standard tests. The investigator should actively question the possibility of unusual causes for diabetes, should reflect upon the relative contribution of insulin deficiency and pathogenesis (and thus the most appropriate approach to therapy), and should carefully evaluate the future risk of vascular disease and the best means of mitigating this. Nor should s/he fail to consider the person affected, whose future is at stake, and whose adaptation to a diagnosis of diabetes will so powerfully influence the success or otherwise of medical intervention.