Type 2 diabetes mellitus

T2DM

Diabetes mellitus describes a condition which notoriously leads to chronically elevated levels of blood sugar (hyperglycaemia).

Type II DM - peripheral insulin resistance leads to reduced glucose uptake. The pancreas compensates temporarily with increased insulin production via β-cell hyperplasia and hypertrophy, eventually leading to β-cell dysfunction → relative insulin deficiency.

Epidemiology

Type II DM is far more common than type I DM; it makes up 90% of diabetes mellitus cases in the UK.

Presentation

Typically affects adults, with incidence rising in those >40 years of age. In contrast to type I DM.

These patients usually present with

• Weight gain, polyuria and polydipsia.
• Maye be an incidental finding.
  

There is an osmotic diuresis, leading to the polyuria. Which subsequently leads to polydipsia.

Aetiology

Factors which increase insulin resistance:

• Obesity
• Physical inactivity
• Ageing
  

Family Hx - especially first-degree relatives

Ethnicity - Hispanics and Afro-Caribbeans are at increased risk

Clinical features

• Polyuria
• Polydipsia
• Polyphagia
• Poor wound healing
• Recurrent infections - in particular cellulitis and candidiasis
• Acanthosis nigricans, associated with hyperglycaemic states.

Investigations

There are three main investigations used to investigate and diagnose diabetes mellitus:

• Serum glucose - this can be a fasted (no food or drink aside from water for 8-10 hours beforehand) or non-fasted reading.
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• HbA1c (glycated haemoglobin) - represents the average blood glucose over the past 2-3 months.
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• OGTT (oral glucose tolerance test) - fasting blood glucose reading is taken, 75g load of glucose is then given and 2 hours after that, blood glucose is measured again.

The following diagnostic criteria for diabetes mellitus has been issued by the World Health Organisation (WHO):

Blood glucose levels:

If the patient is symptomatic:

• Fasting glucose reading ≥7mmol/l
• Random glucose reading ≥11.1mmol/l (or after an OGTT)

If the patient is asymptomatic:

• The above criteria applies, however it will have to be demonstrated on two separate occasions.

HbA1c:

If the patient is symptomatic:

• HbA1c of ≥48mmol/mol (6.5%) is diagnostic of diabetes mellitus in symptomatic patients.

If the patient is asymptomatic:

• Repeat test.

It is recommended that the HbA1c level is repeated within 2 weeks of the original reading.

HbA1c reliability

It is important to note that several conditions may impact HbA1c levels, and thus it may not always be an accurate representation of average blood glucose levels. HbA1c value depends on 2 factors:

• Red blood cell lifespan: reduced = lower HbA1c, increased = higher HbA1c.
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• Average blood glucose concentration
  

Causes of an underestimated HbA1c:

• Sickle-cell anaemia
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• G6PD
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• Hereditary spherocytosis

All of these involve haemolysis of RBCs, thereby reducing their lifespan.

Causes of an overestimated HbA1c:

• Anaemia - RBC lifespan increased to hold onto as much Hb in the body as possible
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• Splenectomy - RBC lifespan increased because the spleen is not destroying them.
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• Alcoholism - RBC lifespan increased to compensate for lack of erythropoiesis in the bone marrow, due to excess alcohol intake.

Management

There are three very simple principles underlying the management of diabetes mellitus:

1. Control of blood glucose levels using medication.
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2. Lifestyle modifications - to increase the chances of achieving glycaemic control, while reducing the risk of developing other health complications related to DM.
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3. Screening for and managing complications of DM. This will be covered on another learning card.

Lifestyle changes

Dietary advice:

• Eat a diet high in fibre (slow down the absorption of glucose)
• Low-glycaemic index sources of carbohydrates
• Intake of foods containing saturated and trans fatty acids should be controlled
• Discourage the use of foods marketed specifically for people with diabetes. For example, studies have found that artificial sweetener is associated with impaired glucose tolerance.

Smoking and alcohol:

Advice is the same as that given for patients with type I diabetes.

Exercise:

Patients are recommended to engage in 150 minutes of moderate-intensity exercise during the week. Alternatively, similar benefits can be seen by doing 75 minutes of high-intensity exercise throughout the week.

• Exercise is crucial in type II diabetes, because studies show that it improves peripheral insulin sensitivity.

Medication

Important HbA1c cut-offs to remember:

• HbA1c of ≥48mmol/mol (6.5%) - despite lifestyle management = offer metformin
• Patient already on medication, HbA1c rises to ≥58mmol/mol (7.5%) - move up ladder

HbA1c monitoring

The target HbA1c level depends on which medication the patient is taking.

• Lifestyle modifications only: ≤48mmol/mol (6.5%)
• Lifestyle modifications and a drug which does not cause hypoglycaemia: ≤48mmol/mol (6.5%)
• People taking a drug associated with hypoglycaemia: ≤53mmol/mol (7.0%)

HbA1c should be measured every 3-6 months, and once stable, it should be measured every 6 months.

Blood glucose monitoring

Regular blood glucose monitoring is not usually needed, unless taking insulin.