Introduction to Diabetes

Diabetes is defined as an elevation of blood glucose above a diagnostic threshold

Pathophysiology

Disorders of insulin action

  • Pure disorders are rare and mostly genetic e.g. Donohue syndrome, Rabson-Mendenhall syndrome
  • Insulin resistance
    • Feature of obesity
    • Type 2 diabetes
    • NAFLD
  • Endocrinopathies
    • Cushing's syndrome
    • Acromegaly
    • Phaeochromocytoma
    • Glucagonoma
  • Steriod induced - exogenous glucocorticoids

Disorders of insulin secretion

  • Type I diabetes
  • Genetic disorders
    • MODY
    • Neonatal diabetes
  • Pancreatic disease
    • Alcoholic and chronic pancreatitis
    • Acute pancreatitis
    • Pancreatectomy
    • Pancreatic cancer
    • Cystic fibrosis (genetic)
    • Haemochromatosis (genetic)

Mixed

  • Type 2 diabetes - ranging from predominant beta cell deficiency to predominant insulin resistance

Clinical presentation

  • Often asymptomatic - especially type 2 diabetes

Symptoms of high blood glucose

  • Polyuria
  • Thirst and polydipsia
  • Blurred vision
    • Hyperglycaemia results in changes to osmotic pressures in the anterior chamber of the eye in front of the lens
  • Genital thrush
  • Fatigue
  • Weight loss

Presentation with diabetic emergencies

  • Diabetic ketacidosis - most commonly due to type 1
  • Hyperosmolar hyperglycaemic state - extreme presentation of new type 2 diabetes

Symptoms/signs of complications (rarely)

  • Loss of vision/retinal bleed or retinal changes found by optician

Investigations

Blood glucose

  • Defining the threshold for diabetes is based upon risk of developing diabetic retinopathy
  • EXCEPTION: in gestational diabetes threshold levels are not set by retinopathy risk but rather by risk to the foetus/neonate (threshold much lower)
Diagnosis requires:
  • Fasting glucose >/= 7mmol/L OR
  • Random or 2 hr (after 75g oral glucose) glucose >/= 11.1 OR
  • HbA1c >/= 48 mmol/mol
  • If asymptomatic a repeat confirmatory test is required
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C-peptide

  • Co-secreted with insulin and is not part of injected insulin
  • Can be used to measure 'endogenous' insulin secretion as if c-peptide is present in the blood it must be coming from the person's beta cells

HbA1c

  • Haemoglobin exposed to glucose becomes glycated
  • The amount of glycation is proportional to the glucose
  • As a RBC survives for ~90 days the HbA1 gives a measure of glucose exposure over the last 90 days - used in diagnosis and monitoring
  • Caution in conditions of increased or reduced RBC turnover e.g. haemolytic anaemia

Complications

  • Diabetes needs to be managed to prevent acute symptoms and life threatening illness, but also to reduce the 'burden of diabetes' (complications)

Microvascular complications

  • 'Diabetes specific'
  • Largely driven by chronic hyperglycaemia
  • Retinopathy, neuropathy, nephropathy
  • Prevention: aim for HbA1c <53 mmol/mol

Macrovascular complications

  • Due to hyperglycaemia, high blood pressure and dyslipidaemia
  • MI/ACS, stroke, PVD
  • Prevention: cholesterol control, BP control, antiplatelet therapy

Screening for other complications

  • Eye disease (laser)
  • Neuropathy (podiatry)
  • Kidney disease (BP management, ACEi)