Clinical aspects of diabetes

• Symptoms common to all forms of diabetes:

  • Excessive urination
  • Thirst
  • Hunger
  • Blurred vision
• Signs a patient may notice:

  • Problems with immunity and recovery
  • Inability to control blood sugars (if they are monitoring)
  • Weight loss (if Type 1)
  • Neuropathies
• Methods of checking glucose control:

  • Urine glucose
  • Plasma glucose
  • Glycated haemoglobin
• Diagnostic criteria for a positive diagnosis of diabetes:

  • Fasting plasma glucose >7mM
  • 2-hour post OGTT blood glucose over >11.1mM
  • HbA1c >48mmol/mol (sometimes reported as 6.5% if using DCCT units)
  • Classic symptoms of hyperglycaemia and random plasma glucose >11.1mM
• Type 1 diabetes:

  • Characterized by complete inability to secrete insulin
  • Fatal without exogenous insulin
  • Early onset, typically presents with short symptom history or DKA
  • Genetic component, with environmental modifiers
• Type 1.5 diabetes (Latent Autoimmune Diabetes of Adulthood):

  • Estimated incidence 6-10%
  • Easily mis-diagnosed as Type 2
  • Oral treatments may be effective at first
  • Diagnosed by presence of DM and pancreatic auto-antibodies
  • Try to preserve islet cell function
  • Ketoacidosis possible, especially when on insulin
  • CVD and microvascular risks similar to Type 2
• Gestational Diabetes:

  • Cause unknown, tested for between weeks 24-28
  • 2-12% of pregnancies with non-diabetic mothers
  • Diet and exercise fundamental, 15% need insulin
  • May respond to metformin or glibenclamide
  • Usually resolves post-partum
  • Increases the mother's risk of developing DM in the future
• Iatrogenic diabetes:

  • Mostly caused by medication
  • Common culprits: steroids, antiretrovirals, diuretics, antipsychotics
• Correct subtype identification is crucial for correct management

  • Type 1 patients must always be on a full insulin regimen
  • Type 2 patients can be managed with lifestyle, oral medication, or insulin
  • Iatrogenic diabetes may require management if the causative drug cannot be removed
  • Gestational diabetes will have a known finite duration, but must still be managed
• Complications of poor diabetes control are long-term consequences linked to persistent elevated blood sugar levels
• Aim for an HbA1c of 48mmol/mol or less to prevent complications
• High blood pressure and abnormal lipids are also linked to high blood glucose levels
• Medications important for prevention include ACE inhibitors, statins, and oral hypoglycemic agents
• Symptom relief for diabetes complications can involve emollients, PDE5 inhibitors, analgesics, and antiepileptics
• KNIVES is a mnemonic for common complications of diabetes:

  • K: Kidney (nephropathy, proteinuria, kidney failure)
  • N: Neuromuscular (neuropathies, erectile dysfunction, gastroparesis)
  • I: Infective (chronic ulcers, recurrent infections)
  • V: Vascular (diabetic foot, hypertension, PAD, CVD, CHD)
  • E: Eyes (retinopathy, macular degeneration)
  • S: Skin (skin tags, lipodystrophy, necrobiosis lipodica, ulcers)
• Kidney complications in diabetes can progress from microalbuminuria to proteinuria, haematuria, and renal failure
• Neuromuscular symptoms in diabetes depend on the affected nerves and can include sensory, autonomic, and motor issues
• Infections in diabetes are more common due to compromised immune function, high tissue glucose, and poor circulation
• (Macro)Vascular complications in diabetes are caused by endothelial damage, abnormal clotting, and inflammation, leading to atherosclerosis, coronary artery disease, peripheral arterial disease, and stroke
• Eye complications in diabetes include diabetic macular oedema, retinopathy, cataracts, and glaucoma
• Skin complications in diabetes can manifest as skin tags, acanthosis nigricans, and necrobiosis lipoidica
• Diabetic foot complications can result from neuropathies, vascular issues, poor eyesight, and slow healing
• Annual testing for diabetics should include weight/BMI, smoking status, blood pressure, glycated haemoglobin, urine albumin/protein, serum lipids, creatinine, fundoscopy, and vibration testing
• During sickness, diabetics should have a plan in place, adjust insulin doses, monitor glucose levels more frequently, stay hydrated, eat normally, and be cautious with certain medications like SGLT2 inhibitors
• Biguanides


  • Metformin only UK agent available
  • Phenformin available in Europe
• Biguanides


  • Useful first-line agent for most patients
  • Mechanism not fully clear: increases insulin sensitivity and reduces gluconeogenesis
  • Demonstrated positive effect on cardiovascular complications
  • Causes weight loss
  • Does not cause hypos
  • Linked to lactic acidosis (caution in renal or heart failure)
  • Chronic use may cause B12 deficiency
  • GI ADRs
• Sodium-glucose co-Transporter 2 Inhibitors (SGLT2i aka "flozins")


  • Canagliflozin
  • Dapagliflozin
  • Empagliflozin
  • Ertugliflozin
• Sodium-glucose co-Transporter 2 Inhibitors (SGLT2i aka "flozins")


  • Dapagliflozin for HFrEF as reduces fluid volume and pre-load leading to lower BP and afterload
  • Reduces hypertrophy and cardiac re-modelling
  • Increases renal loss of glucose
  • Requires adequate renal function
  • Will not cause hypos
  • Raises incidence of genital infections / UTIs
  • May cause DKA and normoglycaemic ketosis
• Sulphonylureas (SFU)


  • Tolbutamide
  • Glipizide
  • Gliclazide
  • Glimepiride
• Sulphonylureas (SFU)


  • Often 2nd or 3rd line
  • Stimulate insulin secretion, possibly also reduce resistance
  • Less effect on CV mortality than metformin
  • Shorter acting agents with inactive metabolites preferred in renal disease
  • Glipizide and glimepiride short acting
  • Hypo, weight gain (1.54kg over 6.3 years)
  • Sulphonamide allergy
• Meglitinides


  • Stimulate insulin secretion
  • Structurally distinct from SFU so no cross-allergy
  • Can replace sulphonylureas in therapy
  • Adverse effects similar to SFU
  • 2C8, 3A4 and UGT metabolised, clopidogrel can lead to hypo because decrease clearance of repag
  • Rapid onset of effect and short duration
• Dipepylpeptidase-4 inhibitors (DPP4i aka "Gliptins")


  • Linagliptin
  • Sitagliptin
  • Saxagliptin
  • Vildagliptin
  • Alogliptin
• Dipepylpeptidase-4 inhibitors (DPP4i aka "Gliptins")


  • Inhibit DPP4 so endogenous incretins
  • Slow gastric emptying
  • Reduces appetite
  • Reduces glucagon secretion
  • Increases insulin secretion
  • Second-line add-on therapy
  • Will not cause hypo
• Glucagon-like-peptide-1 (GLP1) analogues (incretin mimetics)

  • Exenatide
  • Liraglutide
  • Dulaglitide
  • Lixisenatide
  • Oral semaglutide
  • Tirzepatide
• Glucagon-like-peptide-1 (GLP1) analogues (incretin mimetics)


  • DPP4 resistant analogues of GLP
  • Not used in T1 patients in spite of some pancreas independent effects
  • Pancreatitis
  • Caution if patient already has slowed gastric emptying
  • GI ADR common but may be beneficial
  • No additive effects with
• Non-insulin agents


  • GLP-1 GIP mimetic
  • DPP4 resistant analogues of GLP
  • Glucosidase Inhibitors
  • Thiazolidinediones (TZD aka "glitazones")
  • MR preparations
  • Combination preparations
• Oral semaglutide and Tirzepatide are dual GLP-1 GIP mimetic
• Caution if patient already has slowed gastric emptying. GI ADR common but may be beneficial
• Acarbose is the sole agent in the Glucosidase Inhibitors class
• Acarbose is used as add-on therapy