Diabetes Mellitus and Complications

16/07/2013 by admin | Endocrine

Diabetes mellitus

  1. Chronically elevated glucose
  2. Fasting glucose:
  3. Normal <6mmol/L
  4. Impaired glucose tolerance 6-7mmol/L
  5. Diabetes >7mmol/L
  6. 2-hours post 75g glucose challenge:
  7. Normal <7.8mmol/L
  8. Impaired glucose tolerance 7.8-11.1mmol/L
  9. Diabetes >11.1mmol/L


DM T1 (insulin dependent):

  1. Rare disease of white northern Europeans 25:100,000
  2. p/c: <30yo (average age of presentation = 13yo), FH of other autoimmune conditions (pernicious anaemia, thyroid disease, addison’s disease, coeliac disease), polyuria, polydipsia, thin, weight loss, fatigue, infections (abscesses, candidiasis). Acutely = ketoacidosis = N&V, drowsiness, tachypnoea.
  3. Cause: Autoimmune beta-bell destruction in pancreas
  4. Average age of death = 49 years with macrovascular/microvascualr complications


DM T2 (non-insulin dependent):

  1. Common. Prevalence of 2% in UK. Increasing in prevalence due to lifestyle/dietary factors.
  2. p/c: middle aged or elderly, overweight, 20% will have IHD/CVA/renal failure/visual impairment/PVD at diagnosis, polyuria, polydipsia.
  3. Can also present with symptoms of hyperglycaemia, hyperosmolar non-ketosis (HONK), asymptomatic screening
  4. Cause: peripheral resistance to actions of insulin. Reduced insulin secretion may exist late on, but absolute insulin production is rarely found.
  5. Genetic factors exist
  6. Mx: most can be managed with dietary/lifestyle advice and hypoglycaemic drugs. Some may require insulin.

Other types of diabetes:

  1. Exocrine pancreas failure: pancreatitis, pancreatectomy, destruction of pancreas (=CF, carcinoma, haemochromatosis)
  2. Endocrine disease: Cushing’s syndrome, acromegaly, glucagonoma, phaechromocytoma
  3. GDM: in 3rd trimester – similar pathophysiology to DM T2. 30-50% go on develop DM T2 within 10 years
  4. Malnutrition
  5. Genetic syndromes
    1. o Maturity onset diabetes in the young (MODY): relates to defects in beta-bell function
    2. o MODY type 1: abnormal hepatocyte nuclear factor HNF-1alpha
    3. o MODY type 2: glucokinase defect
    4. o MODY type 3: abnormal HNF-1alpha


Mx of diabetes:

  1. Patient education
  2. Tx of acute metabolic complications
  3. Long-term hypoglycaemic therapy
  4. Assessment of end organ damage every 6-12months: eyes (retinopathy and cataracts), CV system (peripheral pulses, HF, HTN), nervous system (peripheral sensory, autonomic neuropathy), feet (ulcers, gangrene, infections), renal function (creatinine, albuminuria).
  5. Best prognosis in those with excellent blood glucose control, stopping smoking, BP <130/80, and good lipid profile (statins advised to keep cholesterol <5mmol/L).


Specific Tx options:

  1. Dietary advice: healthy BMI (as obesity increases insulin resistance), reduce sat fats, reduce alcohol etc.
  2. Oral hypoglycaemics: give in DM T2 if diet and lifestyle not sufficient.
    1. o Sulphonylureas: gliclazide, glibenclamide, tolbutamide. Increase insulin release from b-cells (closes K channels). May cause weight gain or hypoglycaemia.
    2. o Biguanides: metformin. Mech of action unknown. Mild anorectic action – therefore indicated in obese individuals. Reduces insulin resistance and hepatic gluconeogenesis (stop sugar being made in liver). s/e: GI upset and lactic acidosis.
    3. o Alpha-glucosidase inhibitors: Acarbose. Inhibits carbohydrate digestion. s/e: diarrhoea and bloating.
    4. o Post-prandial glucose regulators (PPGR’s): Repaglinide. Stimulates insulin release from b-cells. Shorter action than Sulphonylureas, so less chance of hypoglycaemic episodes. s/e: hepatic dysfunction.
    5. o Thiazolidinediones: Rosiglitazone, pioglitazone. Insulin sensitizing agents which activate the peroxisome proliferator-activated receptor (PPAR-y), stimulating transcription of the glucose transporter molecule (Glut-1) = increased glucose uptake into tissues. S/e: hepatoxicty.
    6. o Insulin: subcut used in all T1 and some T2. There are several types:
    7. Recombinant human insulin: most common, can be short/medium/long acting. Some preps have a combination of short +med/long acting components.
    8. Insulin analogues: chemically modified forms of insulin (=lispro – which rapid onset and short duration) – ideal to be taken before meal.
    9. Hypoglycaemic agents can be added in in DM T2 to improve insulin sensitivity.
    10. S/e of insulin: hypoglycaemia, weight gain, lipohypertrophy at injection sites.

Assessing for diabetic complications:

  1. Eyes: visual acuity (maculopathy), fundal exam (retinopathy)
  2. BP: sittingstanding = postural/orthostatic change (for autonomic neuropathy)
  3. ECG: silent MI
  4. Renal: creatinine, GFR, proteinuria (dipstick, 12hour)
  5. Bruits over femoral artery
  6. Injection sites: lipohypertrophy, infections, abscesses, pain.
  7. Feet: pulses (PVD), ulceration
  8. Vibration senses: neuropathy
  9. Also check BMs, CVD RFs, weight.


Monitoring BMs in DM:

  1. Tight control = improved outcome
  2. On oral agents – check fasting BMs
  3. On insulin – check more frequently (before meals)
  4. Monotoring should be more frequent if pt is unwell. You can test BMs in urine but this is unreliable.
  5. HbA1c is a good marker of longer term glycaemic control (~6 weeks). Diabetes diagnosed if HbA1c ≥ 48 mmol/mol (≥6.5%).


Complications of DM:

  1. Acute: metabolic derangement = hypo/hyperglycaemia
  2. Later on = micro/macrovascular disease
  3. Good lifestyle, tight BM control, no smoking, <130/80, low cholesterol – all improve survival.


Microvascular complications:

  1. Hallmark of DM and takes ~10 years to develop



  1. 1/3 have retinopathy at 30yo and 5% are blind.
  2. Due to capillary basement membrane thickening = leaking of vessels (hard exudates and haemorrhage), occluded vessels (retinal ischaemia and unstable neovascularisation), and macular oedema.
  3. Background retinopathy: blot haemorrhage, dot aneurysms, hard exudates, no change in sight
  4. Maculopathy: macular oedema, haemorrhages, hard exudates,
  5. Pre-proliferative retinopathy: CWS (=retinal ischaemia interrupts axoplasmic transport), venous bleeding, intra-retinal microvascular abnormalities due to dilated capillaries.
  6. Proliferative retinopathy: ischaemia induces new vessels, fragile, bleed easily, retinal detachment from traction scars occur
  7. Cataracts: occur 10-15 years earlier in DM than in those without DM
  8. Mx: annual eye check, laser retinal photocoagulation in maculopathy, pre-proliferative and proliferative retinopathy.



  1. Occurs 15-25 years after diagnosis in 35-45% of patients with DM T1 and <20% with DM T2
  1. Initial lesion = glomerular hyperfiltration (increased GFR) leads to diffuse thickening of glomerular basement membrane (GBM).
  2. Manifests as microalbuminuria (urinary albumin 30-300mg/d). An accurate of CVD risk
  3. Next – Persistent albuminuria (>300mg/d) is usually associated with normal GFR
  4. Next overt proteinuria (>0.5g protein/d) develops – GFR progressively falls = overt renal failure (end stage renal disease) follows.


  1. 1. microalbuminuria
  2. 2. albuminuria
  3. 3. proteinuria
  4. 4. ESRD


  1. Clinical features: asymptomatic early on, then HTN, oedema, and uraemia
  2. Mx: ACEi for HTN. ACEi also useful if proteinuria – regardless of BP. Chronic renal failure requires renal replacement therapy with dialysis or transplantation.



  1. Due to damage to small blood vessels nourishing the peripheral nerves. Also due to abnormal sugar metabolism.
  2. Several manifestations:
  3. Loss of peripheral vibration senseglove and stocking neuropathy.
  4. Mononeuropathies: any nerve, but most often oculomotor, with pupillary reactions spared.
  5. Amyotrophy: painful wasting of thigh muscles
  6. Automic neuropathy: postural hypotension, absent cardiac vagal tone (no NSR), gustatory sweating, gastroparesis, nocturnal diarrhoea, bladder dysfunction (increased infections, incontinence, ED)
  7. Mx: supportive.


Macrovascular complications of DM:

  1. DM is a major RF for the development of atherosclerosis
  2. DM strongly synergizes with all other CVD RFs!
  3. CVA risk x 2
  4. CAD risk x 3-5
  5. PVD x 40
  1. Foot disease: as result of PVD (=cold painful foot), peripheral neuropathy (=warm, painless foot), or as increased risk of infections (cellulitis, osteomyelitis) and leading to ulceration, gangrene and Charcot’s foot (=warm/hot foot with destruction to the joint).
  2. Mx of foot disease: patient education, good footwear, podiatry, Abx for infections, debridement of ulcers, reconstructive arterial wall surgery for PVD. Amputation in gangrene/acute ischaemia.



  1. Common complication in those treated with insulin and occasionally in those on sulphonylureas.
  2. Symptoms occur when BM is <2.2mmol/L, although in pts who are used to high BMs, symptoms can start at ~4mmol/L (‘4 to the floor’).
  3. Causes other than hypoglycaemic agents include:
    1. o Alcohol
    2. o Renal or hepatic failure
    3. o Reactive hypoglycaemia: rebound hypo after a glucose load
    4. o Insulinoma: pancreatic tumour producing insulin inappropriately
    5. o Endocrine disease: adrenocortical failure, hypopituitarism
    6. o Insulin-like growth factor II (IGF-II) producing tumours: pleural fibroma, sarcoma.
  4. p/c: anxiety, poor concentration, impaired cognition, decreased consciousness, coma, seizures. Sweating, tremor, tachycardia, extensor plantar response.
  5. Ix:
    1. o In DM – often due to over-treatment
    2. o If not DM – glucose, insulin and C-peptide to be measured before giving glucose.
    3. o Raised insulin and raised C-peptide = insulinoma
    4. o Raised insulin and low C-peptide = exogenous insulin administration
    5. o If no obvious cause – rule our Addison’s disease
    6. o If this is negative, look for IGF-II tumours, with pancreatic MRI and chest CT.
  6. Tx: glucose PO, otherwise IV 50mL of 50% in a large vein. In emergency IM glucagon can be helpful.  
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