Type 2 Diabetes

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Overview

Diabetes mellitus is characterised by prolonged hyperglycaemia. Type 2 diabetes mellitus (T2DM) occurs due to insulin resistance and the inability of the beta cells to release sufficient amounts of insulin.

To help make sense of this chapter, it may be helpful to refer to Endocrine and Metabolic Physiology.

Maturity-Onset Diabetes of the Young (MODY)

MODY describes the development of T2DM in adolescence or early adulthood (usually <25 years) that is inherited in an autosomal dominant manner. There are many different monogenic mutations associated with MODY.

Epidemiology

  • T2DM is one of the most common chronic diseases in the UK
  • T2DM can occur in all age groups and is increasingly being diagnosed in children
  • 90% of patients diagnosed with diabetes have T2DM

Risk Factors

  • Obesity
  • Inactivity
  • Increased age
  • Family history
  • People of Asian, African, or Afro-Caribbean ethnicity
  • Hypertension
  • Dyslipidaemia
  • Cardiovascular disease
  • Previous gestational diabetes
  • Some drugs (e.g. corticosteroids)
  • Polycystic ovary syndrome

Presentation

The presentation of T2DM tends to be milder and more subacute. T2DM is often incidentally picked up on routine tests. Features may be:

  • Asymptomatic
  • Polyuria
  • Polydipsia
  • Recurrent urinary tract infections
  • Recurrent skin infections
  • Candida infections
  • Fatigue
  • Acanthosis nigricans – a sign of insulin resistance:
    • Velvety dark skin usually on the neck, underarms, or groin

Differential Diagnoses

Type 1 diabetes mellitus

  • Patients are generally younger and the onset is quicker over hours – days
  • Weight loss is common
  • C-peptide levels are low/undetectable
  • Autoantibodies are present
  • Ketonuria is common

Maturity onset diabetes of the young (MODY)

  • MODY is due to an autosomal dominant mutation – family history is likely to be present
  • C-peptide levels are normal/raised
  • Autoantibodies are absent

Latent autoimmune diabetes in adults (LADA)

  • The onset is generally after 30 years of age
  • Patients are often misdiagnosed as having type 2 diabetes
  • C-peptide levels are low-normal
  • Some autoantibodies may be present

Investigations

All patients

  • Fasting plasma glucose:
    • ≥7.0 mmol/L – see Diagnosis section on diagnosing T2DM
  • Random plasma glucose:
    • ≥11.1 mmol/ L – see Diagnosis section on diagnosing T2DM
    • A helpful way to remember the thresholds for fasting and random blood glucose in diabetes is ‘7-11 fr (For Real)’ for Fasting blood glucose and Random respectively. 
  • HbA1c:
    • Shows hyperglycaemia over the preceding 3 months
    • ≥48 mmol/mol – see Diagnosis section on diagnosing T2DM
    • Not useful in haemoglobinopathies as red blood cells may have a reduced lifespan, causing falsely low results
    • Not useful in splenic dysfunction as red blood cells may have an increased lifespan, causing falsely high results
  • Oral glucose tolerance test (OGTT):
    • Plasma glucose is measured 2 hours after giving the patient a 75 g oral glucose solution
  • ≥ 11.1 mmol/ L – see Diagnosis section on diagnosing T2DM

Other investigations

Other investigations to consider are:

Diagnosis

World Health Organisation (WHO) criteria

T2DM is diagnosed if:

  • The patient is symptomatic and has one of the following on one occasion:
    • Raised fasting glucose (≥7.0 mmol/L)
    • Raised random glucose (≥11.1 mmol/L)
    • OGTT (≥11.1 mmol/L)
  • The patient is asymptomatic but one of the above criteria has been demonstrated on two separate occasions.

Prediabetes and impaired glucose regulation

A patient has impaired fasting glucose if their fasting glucose is between 6.1 – 7.0 mmol/L. they have impaired glucose tolerance if their OGTT result is between 7.8 – 11.1 mmol/L.

Management

Treatment targets

Treatment targets are set according to one’s HbA1c levels. They can vary depending on what stage of management a patient is on:

  • Lifestyle changes: 48 mmol/mol
  • Lifestyle changes + drug that does not cause hypoglycaemia (metformin): 48 mmol/mol
  • Lifestyle changes + drug that does cause hypoglycaemia (sulfonylurea): 53 mmol/mol
  • If already taking 1 drug but HbA1c is ≥58 mmol/mol: 53 mmol/mol

Metformin not contraindicated

  • 1st-line: metformin + check cardiovascular disease (CVD) status:
    • If they have heart failure, established CVD, or are at high risk for CVD (QRISK >10%): add an SGLT-2 inhibitor after the metformin has been established and titrated up
    • If metformin is not tolerated, switch to a modified-release form
    • If the patient develops heart failure, or CVD, or becomes at high risk for CVD at any point: add an SGLT-2 inhibitor regardless of HbA1c
  • 2nd-line: dual therapy – if the HbA1c has risen to 58 mmol/mol, then another drug is indicated, which may be one of the following:
    • Metformin + DPP-4 inhibitor
    • Metformin + pioglitazone
    • Metformin + sulfonylurea
    • Metformin + SGLT-2 inhibitor if a sulfonylurea is contraindicated/not tolerated, or the person is at risk of hypoglycaemia or its consequences
  • 3rd-line: triple therapy – one of the following:
    • Metformin + DPP-4 inhibitor + sulfonylurea
    • Metformin + pioglitazone + sulfonylurea
    • Metformin + pioglitazone or sulfonylurea + canagliflozin or empagliflozin (specific SGLT-2 inhibitors)
    • Metformin + DPP-4 inhibitor + ertugliflozin (SGLT-2 inhibitor) if sulfonylurea or pioglitazone is inappropriate
    • Start insulin-based treatment
  • 4th-line: one of the following:
    • If taking triple therapy, consider metformin + sulfonylurea + GLP-1 agonist for people with either:
      • BMI ≥35 kg/m2 + psychological/other medical conditions associated with obesity
      • BMI <35 kg/m2 and insulin therapy would have occupational implications or weight loss would benefit over other obesity-related comorbidities
    • If on insulin-based treatment, refer to a specialist for consideration of GLP-1 agonist + insulin

Metformin contraindicated

  • 1st-line: check CVD status:
    • If they have heart failure, established CVD, or are at high-risk for CVD: SGLT-2 inhibitor monotherapy
    • If no heart failure, established CVD, or are not at high-risk for CVD then consider:
      • Pioglitazone, sulfonylurea, or a DPP-4 inhibitor
      • Offer an SGLT-2 inhibitor if none of the above is appropriate
  • 2nd-line: dual therapy – one of the following:
    • DPP-4 inhibitor + pioglitazone
    • DPP-4 inhibitor + sulfonylurea
    • Pioglitazone + sulfonylurea
  • 3rd-line: insulin-based treatment

Antihypertensive treatment

If patients with diabetes develop hypertension, regardless of age, they should be offered:

  • 1st-line: ACE inhibitors or angiotensin II receptor blockers (ARB)
    • ARBs are preferred if the patient is of black African or Caribbean origin
  • The blood pressure targets for those who have diabetes are the same as those without

Lipid modification

If the patient does not have established CVD offer atorvastatin 20 mg once daily for primary prevention of CVD if:

  • They are <85 years of age and their QRISK score is ≥10%
  • They are ≥85 years of age
  • They have a diagnosis of chronic kidney disease

Antiplatelet treatment

  • NICE does not recommend giving antiplatelet treatment (e.g. aspirin or clopidogrel) for the primary prevention of CVD in patients with T2DM. Patients with diabetes are managed the same way as the general population regarding antiplatelet treatment.

Immunisation

  • Patients should be offered an annual influenza vaccination and one-off pneumococcal vaccination.

Monitoring

  • HbA1c is measured at 3-6 monthly intervals while initiating treatment, then every 6 months after
  • Screening for complications is arranged at diagnosis and then annually after. This involves:
    • Diabetic eye screening for diabetic retinopathy
    • Diabetic foot problems
    • Diabetic kidney disease:
    • This is done by measuring the albumin:creatinine ratio (ACR) using an early morning first-void urine sample
    • eGFR is also calculated
  • Cardiovascular risk factors (e.g. smoking, blood pressure, full lipid profile etc.)
  • Peripheral and autonomic neuropathy

Patient Advice

  • Patients and their carers/family should know how to contact the specialist diabetes team
  • Patients should be provided advice on lifestyle and cultural aspects such as driving, fasting, ‘sick day rules’ etc.
  • Patients should be offered advice on lifestyle measures (e.g. diet, exercise, weight loss etc.) 

Complications

Microvascular complications

  • Diabetic retinopathy – due to damage to small blood vessels in the kidney
  • Diabetic retinopathy – due to damage to small blood vessels in the retina
  • Diabetic neuropathy – due to direct damage due to hyperglycaemia and decreased blood flow due to damage to small blood vessels supplying the nerves. This includes:
    • Painful diabetic neuropathy
    • Diabetic foot disease
    • Autonomic neuropathy – late-stage complication where there is autonomic nervous system dysfunction. This can lead to reduced hypoglycaemia awareness.
  • Erectile dysfunction
  • Sexual dysfunction in women

Macrovascular complications

  • Atherosclerosis and increased risk of cardiovascular diseases such as myocardial infarction, stroke, heart failure, and peripheral arterial disease

Other complications

Prognosis

  • With optimal treatment, most people can live a near-normal life but carry an increased risk of the aforementioned complications
  • The longer diabetes has been present, the more likely the mortality rates and risks of complications are.

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