Type-2 diabetes

1. Epidemiology and aetiology
The prevalence of both type-1 and type-2 diabetes is rising, and the latter accounts for 95 per cent of all diabetes worldwide. The number of people with diabetes in the UK is now over 2 million.

Type-2 diabetes is now being diagnosed in children and young adults and is prevalent across the socio-economic range, with a growing preponderance among the less well off.

Increasing recognition that genetic background influences the likelihood of developing type-2 diabetes suggest  that more attention should be paid to family history and ethnicity in order to facilitate earlier diagnosis.

Pathophysiology
Type-2 diabetes is a heterogeneous and progressive disease, the onset of which can be very slow, typically developing over a period of 10 years or more. A reduction in insulin action — known as insulin resistance — is an early feature in the development of type-2 diabetes. This insulin resistance is initially overcome by a compensatory rise in insulin levels which maintains normal or near normal glucose homeostasis.

However, over time the ability to cope with a glucose load is compromised and impaired glucose tolerance (IGT) develops.

Obesity is a cause of insulin resistance and if adequate weight loss can be achieved at this early stage, the progression to diabetes might be halted — perhaps permanently.

Early stages
In the early stages of type-2 diabetes, beta cell dysfunction is evident: the first phase of meal-induced insulin release is lost and the second phase is generated slowly.

Often, there is an increase in the amount of insulin released in the second phase and it may be protracted to compensate for the insulin resistance.

Eventually, the beta cells are unable to sustain the compensatory rise in insulin levels, insulin secretion is then diminished as the beta cells exhaust and escalating hyperglycaemia occurs. 

Insulin resistance
By the time diabetes has developed and been diagnosed, insulin resistance is usually well established. The progressive loss of glycaemic control, even with good treatment, is largely due to declining beta cell function, and so insulin therapy becomes necessary in the later stages of the condition.

2. Diagnosis
In many cases diabetes is diagnosed during a routine medical or an emergency hospital admission (for example, for acute MI), rather than presentation with classic symptoms.

Lifestyle changes
A diagnosis of diabetes, even when anticipated, has far reaching ramifications for the patient and implementation of coping strategies is individual.

Ideally patients should take exercise and consume a balanced diet and in most cases they should attempt to lose weight. Some will face the additional challenge of quitting smoking. This approach is the foundation and a continuing requirement of diabetes treatment, upon which pharmacological therapies are built.

Although the lifestyle approach alone is unlikely to achieve adequate glycaemic control, it is important to cultivate good habits. To this end the provision of information, education of the patient and motivational reinforcement must not be underestimated.

At diagnosis 20–25 per cent of patients will have diabetes-associated microvascular and/or macrovascular complications requiring attention.

Cardiovascular risk
Type-2 diabetes is a component of the metabolic syndrome. Therefore conditions that increase cardiovascular risk should be investigated. Almost always this results in patients requiring aspirin and medications for hypertension and dyslipidaemia, in addition to antidiabetic agents.

Since the majority of patients with type-2 diabetes are overweight at diagnosis, prescription of an anti-obesity agent might also be warranted.

Team approach
Patients need to believe in the value of their recommended treatment and to be motivated to maintain adherence to prescribed medication and lifestyle changes.

The establishment of a therapeutic alliance should facilitate compliance, enhance patient empowerment and ideally improve health outcomes.

3. Treatment
Type-2 diabetes is a dual deficit disorder that is characterised by both insulin resistance and beta cell failure.

The aim of treatment is to achieve glycaemic control that is as near to normal as possible because this reduces the onset, progression and severity of complications. A 1 per cent decrease in HbA1c over 12 years substantially reduces morbidity and mortality, highlighting the value of intensive therapeutic intervention. 

Monotherapy
The natural history of the condition dictates the intensity of initial treatment, for example in addition to lifestyle changes an HbA1c <8 per cent may be effectively treated by monotherapy with a sulphonlyurea or metformin.

A selection of sulphonlyureas is available with different onsets and durations of action.

For example, the most-used sulphonylurea in the UK is gliclazide, which is of intermediate duration of action, usually given twice daily up to a maximum of 320mg/day. A long-acting formulation of gliclazide offers the advantage of simple once-daily dosing (120mg/day max).

Metformin (up to 2–3g/day in divided doses) is the only biguanide available but many patients find the gastrointestinal discomfort unacceptable. A recently introduced formulation reduces this side-effect and offers convenient once-daily dosing. 

Combination therapy
As type-2 diabetes progresses, or if it is well advanced at diagnosis (of HbA1c >10 per cent), monotherapy will not suffice and drug therapy may be initiated with a combination of agents that have complementary modes of action.

An advantage of combination therapy is that lower doses of both agents may be used, and this reduces the risk of side-effects associated with each agent.

To aid adherence by reducing the pill burden combination tablets are being introduced in many countries.

Insulin therapy
Eventually beta cell failure may be so severe that glycaemic control cannot be achieved with a combination of oral agents.

At this stage, it is important to move swiftly to insulin therapy to
prevent the patient being exposed unnecessarily to excessive hyperglycaemia.

In terms of health outcomes, delaying the introduction of insulin therapy is a false economy.

Annual review
The annual review ensures regular monitoring of people with diabetes, but most patients will have more frequent consultations.

Multifactorial interventions are required to reduce morbidity and mortality in patients with type-2 diabetes.

The POEM (Practice of Evidence-based Medicine) strategy provides a useful reminder for their routine clinical care.

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