This refers to those relatively uncommon causes of diabetes in which the underlying defect or disease process can be specifically identified.
These include genetic defects of β-cell function or insulin action, diseases of the exocrine pancreas (pancretitis, pancreatectomy) as well as diabetes induced by other endocrinopathies (Cushing’s syndrome, acromegaly, glucagonoma, phaeochromocytoma, hyperthyroidism), drugs (nicotinic acid, glucocorticoids, thiazides, interferon, diazoxide), toxins and infections (congenital rubella, cytomegalovirus).
Monogenetic defects of β-cell function, of which several subtypes exist, are characterised by early age of onset of hyperglycaemia, strong family history of diabetes displaying autosomal dominant pattern of inheritance, absence of autoimmunity and usually low insulin requirement with relative ease in achieving glycaemic control with sulphonylureas (Maturity Onset Diabetes of the Young – MODY). Genetic testing is available locally only in certain research laboratories.
2.3 Summary
Diabetes mellitus is classified according to aetiological types:
a) Type 1 diabetes mellitus (immune-mediated β-cell destruction, usually leading to absolute insulin deficiency).
b) Type 2 diabetes mellitus (may range from predominantly insulin resistance with relative insulin deficiency to predominantly secretory defect, together with insulin resistance), including a variant who are susceptible to ketoacidosis.
c) Gestational diabetes mellitus (onset or recognition of glucose intolerance in pregnancy).
d) Other specific types (conditions in which the underlying defect or disease process is specifically defined).
3 Diagnosis and screening of diabetes mellitus in Singapore
3.1 Introduction
In the 2010 National Health Survey,9 diabetes mellitus was found to affect 11.3% of our population, up from 8.2% in 2004. It is associated with considerable mortality and morbidity from chronic complications.
In Singapore, it is associated with a 3-fold increase in mortality10 (most of which is related to cardiovascular disease) and a three to seven-fold increase in the risk of coronary artery disease.11
Early and aggressive treatment of diabetes mellitus and its associated metabolic derangements (hyperglycaemia, dyslipidaemia, hypertension and obesity) can prevent or delay the progression of the major chronic complications including both macrovascular disease (coronary heart disease)12-19 and microvascular disease (retinopathy, nephropathy, neuropathy).15,20-28 Intensive lifestyle modifications, treatment of hyperlipidaemia with statins, counselling for smoking cessation, control of blood pressure with a Angiotensin-Converting Enzyme Inhibitor (ACE inhibitor) or a Angiotensin Receptor Blocker (ARB) has been found to be cost-effective in the prevention of potential complications of diabetes mellitus.29
It is therefore important to detect individuals with diabetes mellitus so that appropriate therapeutic measures can be taken to minimise the morbidity caused by this devastating disease. At the same time, when a diagnosis of diabetes mellitus is made, the clinician must feel confident that the diagnosis is fully established since the consequences for the individual are considerable and life-long.
3.2 Objective
It is the objective of the workgroup to provide recommendations regarding the screening and diagnosis of diabetes mellitus that are appropriate for our population. To achieve this, the workgroup closely examined the recommendations of the American Diabetes Association30
3.3 Diagnosis of diabetes mellitus
D
In patients with hyperglycaemic crisis, diabetes mellitus can be diagnosed without further testing. 30Grade D, Level 4
B
In patients with typical symptoms, diabetes mellitus can be diagnosed if any one of the following is present. 32-341. Casual plasma glucose ≥11.1 mmol/l 2. Fasting plasma glucose ≥7.0 mmol/l
3. 2-hour post-challenge plasma glucose ≥11.1 mmol/l Other individuals should have a repeat test on a subsequent day.
Grade B, Level 2++
D
When two different tests are available for the same patient and the results for both tests are above the diagnostic thresholds, the diagnosis of diabetes is confirmed. 35Grade D, Level 4
D
When two different tests are available in an individual and the results are discordant, the test whose result is above the diagnostic cut point (usually the fasting plasma glucose or 2-hour post-challenge glucose) should be repeated. 30Grade D, Level 4
Fasting is defined as no consumption of food or beverage except water for at least 8 hours. Casual plasma glucose refers to plasma glucose at any time of the day, without regard to the interval since the last meal.
Oral glucose tolerance test (75 g glucose) is performed in accordance to WHO recommendations. The 1-hour post-challenge glucose is not
glucose ≥11.1 mmol/l as non-diabetic.36 Therefore, in line with the recommendations of the World Health Organization,31 we recommend that all subjects FPG from 6.1 to 6.9 mmol/l be subjected to an oral glucose tolerance test (OGTT) to determine the glycaemic status precisely.
D
Fasting plasma glucose measured in an accredited laboratory is the preferred test for the diagnosis of diabetes mellitus.1Grade D, Level 4
B
All subjects with fasting plasma glucose from 6.1 to 6.9 mmol/l should undergo a 75 g oral glucose tolerance test to determine if they have impaired glucose tolerance or diabetes mellitus.31, 36Grade B, Level 2++
D
If a second test fails to confirm the diagnosis, barring a laboratory error, such patients are likely to have test results near the margins of the threshold for a diagnosis. The healthcare professional might opt to follow the patient closely and repeat the testing in 6-12 months.30Grade D, Level 4
GPP
HbA1c is not recommended as a screening and diagnostic tool for diabetes mellitus until its performance in our multi-ethnic population has been evaluated.GPP
In coming to this conclusion, the committee considered the incomplete correlation between HbA1c and average glucose in certain individuals, including those of different ethnic groups.37-42 In addition, the HbA1c can be misleading in patients with certain forms of anaemia and haemoglobinopathies, which may also have unique ethnic or geographic distributions. The impact of these factors has not yet been established in our population. Furthermore, in rapidly evolving diabetes, such as the development of type 1 diabetes in some children, HbA1c may not be significantly elevated despite frank diabetes.
Figures 1 and 2 are flow charts which show a recommended diagnostic strategy.