Clinical review: Type 2 diabetes

Section 1: Epidemiology and aetiology
Section 2: Making the diagnosis
Section 3: Managing the condition
Section 4: Prognosis
Section 5: Case study
Section 6: Evidence base

Section 1: Epidemiology and aetiology

It is estimated that 3.6m people have been diagnosed with diabetes in the UK.¹ However, using QOF figures with estimates from the Diabetes Prevalence Model 2016 (Public Health England) and 2012 APHO Diabetes Prevalence Model, there are an estimated 4.5 million people with diabetes in the UK. This includes 1 million people with type 2 diabetes who do not know they have it because they have not been diagnosed. This overall figure is projected to reach 5m by 2025.

DH data shows that 90% of adults with diabetes in the UK have type 2 diabetes. Current estimates suggest the NHS already spends about 10% of its budget on diabetes (~£21bn) and this is expected to rise to £35.6bn in 2035, driven by rising trends in diabetes-specific expenditure associated with treatment costs and acute hospital care.²

Studies in the UK and the US have reported that the age of diagnosis of type 2 diabetes – traditionally diagnosed more commonly in older individuals – has also decreased over time.³

As such, we are seeing more and more patients diagnosed with type 2 diabetes before the age of 40 years. Its prevalence among children in the UK is also rising.

Globally, the five countries with the largest numbers of people with diabetes are China, India, the US, Russia and Brazil, according to International Diabetes Federation estimates.⁴ The highest prevalence of diabetes however are seen in Mauritius, countries situated in the western pacific islands and in the middle East.

Type 2 diabetes is a heterogeneous disorder caused by a combination of environmental and genetic factors, which adversely affect pancreatic beta-cell function and insulin sensitivity of tissues.⁵

Longitudinal and cross-sectional studies have demonstrated that people who develop type 2 diabetes pass through five stages, which include:

• Birth – glucose homeostasis is normal, but there is genetic predisposition for type 2 diabetes
• Decreased insulin sensitivity owing to lifestyle and environmental factors
• Beta-cell function deteriorates to a point that postprandial glucose tolerance becomes abnormal
• Further beta-cell dysfunction, leading to a rise in fasting plasma glucose
• Fasting and postprandial glucose reach levels that are diagnostic of type 2 diabetes, owing to overall decline in beta-cell function.^6-10

Criteria for diagnosing diabetes mellitus^11,12

Patients with symptoms of diabetes

• Random venous plasma glucose ≥11.1mmol/L or
• Fasting plasma glucose ≥7mmol/L or
• Two-hour plasma glucose after 75g oral glucose tolerance test (OGTT) ≥11.1mmol/L or
• Laboratory HbA1c >48mmol/mol (6.5%)*

*There are some caveats for using HbA1c to diagnose diabetes. HbA1c results can be affected by haemolysis and other conditions of increased cell turnover (that reduce HbA1c) or conditions with reduced cell turnover, for example, iron deficiency anaemia (that increase HbA1c), or in any chronic disease states.

Patients without symptoms of diabetes

• Two samples, either random, fasting, or after OGTT, are needed to confirm diagnosis. Samples should be taken on different days. Most cases can be confirmed with a random glucose measurement and OGTT is often not necessary

Section 2: Making the diagnosis

The typical symptoms of type 2 diabetes are polyuria, polydipsia and weight loss occurring over months, but it may be asymptomatic and may only be diagnosed on a routine examination or laboratory test.

These symptoms result from an osmotic diuresis as a consequence of hyperglycaemia.

Type 2 diabetes may present with vascular complications, which may affect the small blood vessels (microvascular - such as eyes, kidneys and nerves) or large blood vessels (macrovascular - affecting the heart, brain and arteries of the lower limb). As such, an initial diagnosis of type 2 diabetes during acute heart attack (MI) or stroke is not uncommon. Similarly, foot ulceration or loss of vision can sometimes be a presenting feature of type 2 diabetes.

Gestational diabetes, which occurs during pregnancy and usually resolves after delivery, is associated with a high risk for future type 2 diabetes.

Screening
Although routine screening for type 2 diabetes has important implications for individual health, day-to-day clinical practice and public health policy, there is currently no direct evidence that this strategy will reduce the vascular risk for affected individuals.

There is, however, some merit in screening individuals at risk of developing type 2 diabetes.

Risk factors
Risk factors associated with type 2 diabetes are increasing age, obesity (especially central), dietary excess, dietary factors such as increased intake of animal fats and carbonated drinks, sedentary lifestyle, positive family history, history of gestational diabetes, polycystic ovary syndrome, severe mental illness, hypertension, hyperlipidaemia and cardiometabolic risk factors.

Central obesity is a major risk factor for developing type 2 diabetes and accounts for 80-85% of the overall risk and underlies the global spread of the disease.

Type 2 diabetes usually appears in middle-aged or older people, although it is being diagnosed more frequently in younger overweight people and is known to affect South Asian people at a younger age. It is very important to identify diabetes as early as possible, because data suggest that up to 50% of patients with newly diagnosed type 2 diabetes already have one or more complications at the time of diagnosis.¹³

Section 3: Managing the condition

The treatment approach should involve patient-centred and individualised care, which means management should take into account individual needs and preferences.¹⁴

Good communication is essential, supported by evidence-based information, to allow patients to reach informed decisions about their care.

Structured care plan
A structured care plan for patients with type 2 diabetes is described below.

Patient education
Provide structured education to every patient (and carer); review and reinforce annually.

Dietary advice
Dietary advice should be provided in a form that is sensitive to the patient’s needs, culture and beliefs, being sensitive to their willingness to change and their quality of life.

Integrate other lifestyle modification, such as physical exercise and individualised weight loss targets, into the care plan.

Blood glucose target
Achievement of an appropriate blood glucose target (as measured using HbA1c) is associated with a significant reduction in long-term vascular complications of diabetes.

This needs to be balanced against the risk of hypoglycaemia and any individual adverse effects of glucose-lowering therapy.

The HbA1c target level should therefore be individualised, which may be above the general target of 48mmol/mol.

For example, among patients who are on insulin therapy or who have cardiovascular disease, a target HbA1c of 58mmol/mol may be appropriate.

Offer appropriate therapy (lifestyle and medication) to help patients to achieve and maintain the HbA1c target.

Monitor blood glucose every two to six months (according to individual needs) until stable on unchanging therapy.

Offer self-monitoring of plasma glucose to a patient who has been newly diagnosed with type 2 diabetes only as an integral part of self-management education.

Oral glucose control therapies
Use appropriate oral glucose control therapies as recommended to control blood glucose.

Glucose control may deteriorate continually with the passage of time, so therapy has to be stepped up over time, one drug added to another until the stage where only exogenous insulin replacement will suffice.¹⁴

A variety of glucose-lowering agents are available (see box 1). Large-scale RCT data for alpha-glucosidase inhibitors and insulin secretagogues is limited.

Insulin therapy
If any (or a combination) of these measures do not keep the patient’s HbA1c to the agreed target, insulin therapy may be required.

This should be initiated with a structured programme and begun with human NPH (neutral protamine hagedorn) insulin taken at bedtime or twice daily according to need.

Alternatively, consider a once-daily long-acting insulin analogue (insulin detemir, insulin glargine) if twice-daily insulin is difficult for the patient to manage.

Bariatric surgery
NICE recommends that patients diagnosed with type 2 diabetes who are overweight should be considered for bariatric surgery if their BMI is >35.¹⁵

Complications
Patients with type 2 diabetes are at high risk of cardiovascular disease, eye damage and renal disease. These adverse outcomes are known to be reduced by lowering HbA1c and improved by BP control.

Aim to reduce the patient’s BP to <140/80mmHg (<135/75mmHg if there is kidney, eye or cerebrovascular damage) with lifestyle changes and an antihypertensive agent. First-line therapy should be a once-daily ACE inhibitor or ARB.

Exceptions to this are people of African-Caribbean descent or women for whom there is a possibility of becoming pregnant, where alternative agents may need to be considered.

Review cardiovascular risk status annually by assessment of the patient’s risk factors and start them on statins according to guidelines.

Annual measurement of the albumin:creatinine ratio, creatinine and eGFR is paramount and consider treating albuminuria with ACE inhibitors or ARBs.

Arrange for structured eye screening annually, because eye damage from diabetes is the single largest cause of blindness before old age, with a progressive incidence in people with type 2 diabetes.

Consider appropriate management of other complications, such as foot disease, neuropathic pain and erectile dysfunction.

New developments
There is a continuing need for new and improved agents to manage patients with type 2 diabetes. The progressive, multifactorial nature of the disease poses a continuing challenge and the requirement for novel and additional blood glucose lowering therapies.

Recent interest has emerged regarding the role of very low calorie diets or bariatric surgery to potentially cure diabetes.^15,16

New insulins are also now available, which may have a better action profile. In addition, novel glucose-lowering therapies, for example, GLP-1 analogues, DPP4 inhibitors and SGLT2 inhibitors, have a reduced risk of the patient developing hypoglycaemia or gaining weight. More recently, evidence from large randomised controlled trials have shown that SGLT2 inhibitors and GLP-1 analogues therapies are associated with reduction in mortality and/or cardiovascular events.^17,18

Section 4: Prognosis

The prognosis for patients with type 2 diabetes predominantly depends on the degree of glucose control, as well as appropriate and effective management of cardiovascular risk factors.

On the whole, mortality is two to three times higher among people with type 2 diabetes than it is for the general population.

There has been increasing evidence that individuals who are diagnosed before the age of 40 years may have a higher risk of cardiovascular disease compared with those diagnosed in later years.

The most common cause of death in people with type 2 diabetes is cardiovascular disease. For every 1% increase in HbA1c, the risk of death from a diabetes-related cause increases by 21%.¹⁹

Approximately half of all patients in whom type 2 diabetes cannot be controlled by diet alone will require more than one glucose-lowering drug at three years after diagnosis.

This proportion increases to three-quarters of patients by nine years after diagnosis²⁰ and is likely to be due to the natural progression of the disease.

Section 5: Case study

HS is a 49-year-old man with type 2 diabetes. He complains of tiredness, daytime somnolence, frequently waking up at night to pass urine and is significantly overweight, with a body mass index of 41.2.

He takes metformin 500mg three times a day and gliclazide 80mg twice a day. His HbA1c remains high at 79mmol/mol.

The patient has poor glucose control, so requires intensification of his glucose-lowering therapy. His excess weight, however, raises concerns about starting a thiazolidinedione or introducing insulin therapy as the next-line agent. Moreover, his ongoing gliclazide therapy is associated with weight gain and hypoglycaemia.

In this case, consideration should be given to a glucose-lowering agent with limited risks of weight gain or hypoglycaemia. DPP4 inhibitor is not associated with weight loss, but is generally weight neutral and well tolerated. Meanwhile, GLP-1 analogue or SGLT2 inhibitor therapy is associated with weight loss.

Any therapy should only be implemented in combination with appropriate lifestyle and dietary advice and intervention. In view of his high BMI, bariatric surgery should also be considered if the patient is motivated and willing to make lifestyle and eating behavioural changes. This patient is also at high risk of obstructive sleep apnoea and should be referred for a sleep study assessment.

If the patient’s blood glucose control does not improve with these measures, the addition of an intermediate/long-acting insulin can still be considered, but he would then have to take extra precautions to prevent hypoglycaemia.

Section 6: Evidence base

Guidelines

• NICE. Type 2 diabetes: The management of type 2 diabetes. NG28. London, NICE, May 2017.

The algorithm on stepping up therapy over time is a useful resource for patients who need to intensify their glucose control.

• NICE. Obesity: Guidance on the prevention of overweight and obesity in adults and children. CG43. London, NICE, December 2006. 
• NICE. Obesity: prevention and lifestyle weight management in children and young people. QS94. London, NICE, 2015
• NICE. Obesity: identification, assessment and management of overweight and obesity in children, young people and adults. CG189. London, NICE, 2014

Online

• Diabetes UK. Guide to diabetes. https://www.diabetes.org.uk/Guide-to-diabetes/
• International Diabetes Federation. IDF Clinical Practice Guidelines. http://www.idf.org/guidelines

Professor Iskandar Idris is associate professor in diabetes and honorary consultant physician, Royal Derby Hospital and University of Nottingham

This is an updated version of an article that was first published in October 2015.

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