CHAPTER 1
Diagnosing Diabetes

Tim Holt1 and Sudhesh Kumar2

1Nuffield Department of Primary Care Health Sciences, Oxford University, UK

2Warwick Medical School, University of Warwick; and WISDEM, University Hospital, Coventry, UK

OVERVIEW

• Diabetes produces a variety of clinical presentations, from acute to gradual onset.
• The diagnosis should be based on two separate tests, unless the patient is clearly symptomatic, in which case only one positive test is required.
• A combination of genetic and environmental factors contribute to the risk of diabetes.
• Impaired glucose regulation is an important risk factor, both for future diabetes and cardiovascular disease.
• Distinction between random and fasting samples is essential in interpreting the significance of borderline blood glucose levels.

Introduction

Diabetes mellitus is a common metabolic disorder that is defined by chronic hyperglycaemia. There are myriad underlying causes for the hyperglycaemia but, currently, much of our approach to treatment is empirical. Besides symptoms related to hyperglycaemia itself, such as thirst, polyuria and weight loss, it may also cause potentially life-threatening acute hyperglycaemic emergencies. It is a major cause of morbidity and premature mortality from long-term complications such as cardiovascular disease, blindness, renal failure, amputations and stroke. With good control of hyperglycaemia established early on, and continued life-long, an individual with diabetes can enjoy a good quality of life and reduce the risk of these long-term complications that are so detrimental to their life and wellbeing.

Prevalence of diabetes

In the United Kingdom, we have an estimated 2.9 million people with diabetes. The prevalence of both type 1 and type 2 diabetes is increasing. Type 2 diabetes is increasing far more rapidly, driven by increasing life expectancy and the epidemic of obesity. It is believed that there will be as many as 300 million people with diabetes worldwide by the year 2025. Most of this increase will occur in developing countries. The majority of children have insulin-requiring type 1 diabetes, while the vast majority of those aged over 25 years will have type 2 diabetes (Figure 1.1).

Figure 1.1 Projected prevalence of diabetes in 2025.

Source: World Health Organisation (1998). Reproduced with permission of World Health Organisation.

Types of diabetes

The types of diabetes have been classified by the WHO. Type 1 diabetes (previously referred to as insulin-dependent diabetes mellitus or IDDM) is due to absolute insulin deficiency and is usually an autoimmune disease, leading to the destruction of the insulin-secreting beta cells in the pancreas. In some cases, the cause of destruction of the beta cells is not known.

Type 2 (previously known as non-insulin dependent diabetes mellitus or NIDDM) results from relative insulin deficiency that may be associated with varying degrees of insulin action defects, known collectively as insulin resistance.

For a practising clinician, the implication of this diagnosis is that patients with type 1 diabetes require insulin straight away and insulin should not be stopped, as it is life-preserving. Type 2 patients can progress through several stages, and may require insulin later on in their disease.

Risk factors for diabetes

Genetics

Genetic susceptibility is important for both types of diabetes. Family history of type 1 diabetes, or other autoimmune diseases such as autoimmune thyroid disease, is associated with a higher risk of developing type 1 diabetes in the family. Inheritance in type 2 diabetes is far more complex, as there are many underlying causes. Furthermore, the risk varies according to the particular sub-type of type 2 diabetes. A family history of type 2 diabetes in a first degree relative is a strong risk factor for diabetes in that individual.

Obesity

Apart from family history, obesity is a very important risk factor for diabetes. For a given degree of obesity, central or 'apple-shaped' obesity is associated with a much higher risk of progression to type 2 diabetes than for those who have lower body obesity or are 'pear-shaped'. Those with a body mass index (BMI) of more than 25?kg/m2 or high waist circumference (Table 1.1) are at a higher risk of developing diabetes, and they should be encouraged to take regular exercise and eat healthily (Figure 1.2).

Table 1.1 The International Classification of adult underweight, overweight and obesity according to BMI (adapted from WHO guidelines, http://apps.who.int/bmi/index.jsp?introPage=intro_3.html).

Source: Adapted from World Health Organisation 1995, 2000, 2004.

Figure 1.2 'Apple'-shaped fat distribution (central obesity with intra-abdominal adiposity) carries a higher cardiovascular and diabetes risk than 'pear'-shaped fat distribution.

Age

Beta cell function declines with age. Indeed, if we live long enough, all of us have the potential to develop diabetes at some stage. With an aging population, an increase in prevalence of diabetes can be expected.

Ethnicity

People of South Asian or Afro-Caribbean origin are at higher risk of developing diabetes. They are also more likely to have type 2 diabetes presenting at a young age, and usually have poorer risk factor control. South Asian patients have a high risk of developing diabetic renal disease and also coronary artery disease. Afro-Caribbean patients are more likely to have strokes, and have a higher risk of gestational diabetes. South Asian and Hispanic children may develop type 2 diabetes.

Initial presentation and diagnosis

The commonest presentation is tiredness, thirst, polyuria, weight loss, pruritus vulvae or balanitis. It is not uncommon for this diagnosis to be missed for years, and a significant proportion of those with type 2 diabetes remain undiagnosed. Insidious symptoms mean that the patients generally tend to ignore them. This is one reason why complications are often seen at diagnosis in patients with type 2 diabetes. A number of cases with type 2 diabetes are now diagnosed at insurance examinations, or through opportunistic testing, when the patient has presented for some other problem to the general practice or hospital.

The diagnosis of diabetes must not be taken lightly by a clinician, as the consequences for the individual are significant and life-long. For those presenting with severe symptoms, evidence of long-term complications or severe hyperglycaemia at presentation, the diagnosis is quite straightforward and can be made using only one diagnostic blood glucose or HbA1c measurement. In asymptomatic individuals presenting with mild hyperglycaemia, the diagnosis should only be established on the basis of at least two abnormal test results. One may use either glucose or HbA1c testing for diagnosis of diabetes (Box 1.1).

Box 1.1 Recommendation of the International Expert Committee

For the diagnosis of diabetes:

• The HbA1c assay is an accurate, precise measure of chronic glycaemic levels and correlates well with the risk of diabetes complications.
• The HbA1c assay has several advantages over laboratory measures of glucose.
• Diabetes should be diagnosed when HbA1c is = 48 mmol/mol. Diagnosis should be confirmed with a repeat HbA1c test. Confirmation is not required in symptomatic subjects with plasma glucose levels = 11.1?mmol/l.
• If HbA1c testing is not possible, previously recommended diagnostic methods (e.g. FPG or two-hour OGTT, with confirmation) are acceptable.
• HbA1c should not be used to diagnose diabetes in certain circumstances, namely: pregnancy; children, young people or anyone following a type 1...