Diabetes Mellitus Flashcards
What is diabetes mellitus (DM)?
group of metabolic disorders typified by hyperglycaemia resulting from defects in insulin secretion, insulin action or both. Chronic hyperglycaemia is associated with long-term damage, dysfunction and failure of various organs such as: eyes (retinopathy), kidneys (nephropathy), nerves (neuropathy), heart (CV) and BVs (CVI/MI/ASCVD)
How is DM diagnosed?
Glycated Hb (HbA1c) > 48 mmol/L (7%)
FBG > 7.0mmol/L
OGTT 2 hr blood glucose > 11.1mmol/L
Random blood glucose > 11.1mmol/L in presence of symptoms
List 5 types of Diabetes.
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Gestational Diabetes Mellitus
Diabetes Mellitus secondary to Pancreatitis
Diabetes Mellitus Secondary to Cushing’s disease/Steroids
MODY
Diabetes Insipidus (Central and Peripheral)
What is T1DM?
insulin-dependent DM caused by immune-mediated ß-cell destruction or idiopathic ß-cell destruction; both may be caused by environmental factors e.g. viral infection. Symptoms present when ≈ 80% ß-cell mass lost
What is the pathophysiology of T1DM?
HLA associations + Autoantibodies (islet cells/insulin/GAD/Tyrosine phosphatases)
List 3 types of autoantibodies you may find in type 1 diabetes mellitus
Anti-insulin
Anti-islet antigens (IA2 and IA2-ß)
Anti-GAD
Anti-Tyrosine Phosphatases
Outline 3 clinical presentation of T1DM.
Polydipsia
Lens change
Nocturia
Polyuria
Polydipsia
Weight loss
Fatigue
(4 T’s: Tired/Thirst/Toilet/Thinning)
Why does osmotic lens change occur in DM?
Sugar is a powerful osmolyte which draws water into the lens ≈ swelling ≈ lens change
How may you assess if a patient is clinically dry?
Blood pressure
Dry oral mucosa
Skin turgor
How do you monitor glucose?
- Blood glucometer: FBG > 7.0mmol/L or OGTT or random > 11.1mmol/L
- Wearable technology e.g. Freestyle Libre - measures interstitial glucose and plots
- Sensor + Pump: Sensor detects ∆s in interstitial glucose then pump adjusts insulin levels
- Glycated haemoglobin (HbA1c): diagnostics + monitoring which measures non-enzymatic glycation of haemoglobin for previous 120 days ≈ 3 months ≈ RBC lifetime whereby HbA1c > 48 mmol/L
What two general formulations are there for insulin therapy?
Insulin can be administered as:
1) a quick release formulation
2) longer/slow-release formulation as a mixture
3) Basal bolus regime
What is the basal bolus regime?
Replicate natural, endogenous physiology by eating, estimating activity levels and calculating amount of insulin then injecting insulin as a basal bolus to keep insulin at constant levels in order to reduce risk of hypoglycaemic periods
What device can be used to automate the basal bolus regime?
Continuous subcutaneous insulin infusion is a sensor measuring interstitial fluid [glucose], relaying the information in feedback to the pump which changes its output of insulin administered subcutaneously
What is T2DM?
metabolic disease of the diabetes mellitus metabolic diseases which is typified by IR, hyperglycaemia, polyuria and polydipsia which is generally presenting in older patients with interplay between genetics and environmental risk factors
What is T2DM the result of?
T2DM is the result of genetic factors and environmental factors
i) Genetic factors:
- Defect of ß-cell
- IR
ii) Environmental factors:
- Obesity: visceral fat distribution
- Stress
- Reduced PA
- Diet
Outline the classical presentation of T2DM.
- Polydipsia
- Polyuria
- Weight gain
- Malaise
- Fatigue
- Infections
- Blurred vision
- Incidental findings: Nephropathy/Neuropathy
What is the main fat depot which differs in volume between normal and T2DM pt?
Visceral fat distribution
What is the progression of T2DM like?
Insulin resistance increases causing plasma insulin to increase along with blood glucose which precipitate symptoms and are raised in diagnosis and then plasma insulin falls sharply as ß-cell failure occurs and blood glucose continues to rise which elicits complications and increases morbidity and mortality
List 5 drugs to treat Diabetes.
Insulin
Sulphonylureas (clorpropamide/glipzide/gliclazide)
Biguanides (Metformin)
a-Glucosidase inhibitors
Thiazolidinediones (Pioglitazone)
GLP-1 agonists (Exanitide)
DPP-4 inhibitors
SGLT2 inhibitors
What are the categories of complications of diabetes mellitus?
1) Acute
- DKA
- Hypoglycaemia
- Other emergencies e.g. MALA, HONK coma
2) Chronic:
i) Microvascular
- Retinopathy
- Nephropathy
- Neuropathy
ii) Macrovascular
- CVD
- ASCCVD
- CVI
What are the clinical features of DKA?
Hyperglycemic + Acidosis
Hyperglycaemia:
- Dehydration
- Polydipsia
- Tachycardia
- Hypotension
- Clouding of consciousness
Acidosis:
- Air hunger (Kussmaul’s respiration)
- Acetone on breath
- Abdominal pain
- Vomiting
What is the ketone body metabolism?
Long term fasting state ≈ ∆ metabolism ≈ catabolic breaking down of skeletal muscle + WAT ≈ AAs + FAs ≈ liver ≈ produce ketone bodies ≈ end organ
List 3 ketones present in DKA.
- Acetoacetate
- Acetate - 3ß-hydroxybutyrate
Which of the following is not actually a ketone body by chemical structure?
A. Acetoacetate
B. Acetate
C. 3ß-hydroxybutyrate
C. 3ß-hydroxybutyrate
How many protons are produced for each of the following ketone bodies?
A. Acetoacetate
B. Acetate
C. 3ß-hydroxybutyrate
A. 1
B. 1
C. 1
What is the pathogenesis of DKA?
Insulin deficiency —>
i) Hyperglycaemia ≈ glycosuria ≈ osmotic diuresis ;
ii) Ketosis ≈ acidosis ≈ gastroparesis…
volume depletion ≈ renal hypoperfusion —> impaired excretion of H+ and Ketone bodies
How can you test for ketones?
Urinalysis
Blood ketone meter
Ketometer (breathalyser)
Outline the Rx for DKA.
1) Hyperglycaemia
- IV insulin 6U/Hr (then by Sliding scale)
2) Dehydration
- N/Saline 4-6L
- Dextrose
3) Electrolyte (e.g. Potassium) losses
- Monitor K+
- Replace
What is hypoglycaemia?
Low blood glucose concentrations < 2.2 mmol/L h/e 4 is the floor (educating patients)
What are the causes of hypoglycaemia?
- Hyperinsulinemia
- Low food intake
- Strenuous exercise
What are the symptoms of hypoglycaemia?
1) Adrenergic: Fight or flight symptoms
- Tachycardia
- Palpitations
- Diaphoresis
- Tremor
- Hunger
2) Neuroglycopenic
- Dizziness
- Confusion
- Somnolence
- Coma
- Seizure
What are the counter-regulatory mechanisms involved in hypoglycaemia?
Hypoglycaemia detected which elicits vagal stimulation, leading to parasympathetic drive, and adrenal medulla stimulation ≈ sympathetic stimulation ≈ adrenaline release
What is the treatment for hypoglycaemia?
IV 50% Dextrose Or IM or SC dextrose
What is HONK?
Hyperglycaemic HyperOsmolar Non-Ketotic Coma which occurs in elderly patients which can often be undiagnosed
What is MALA?
Metformin-Associated Lactic Acidosis
What are the chronic complications of DM?
Microvascular + Macrovascular
Why do chronic complications of DM occur? Outline the general pathological process.
Chronic inflammatory processes such as AGEs, immune infiltration, ROS and ∆ transcription lead to hypoxia, cell death, haemodynamic changes + ECM changes
What is nephropathy?
deterioration of the kidney ≈ impaired function
What is the main pathologic marker of nephropathy?
Kimmelstiel-Wilson nodules which involve thickening of the BM, widening of slit membranes of podocytes, matrix invading glomerular capillaries and deposition of mesanglial matrix
Which eponymous pathological marker denotes a nephropathy?
Kimmelstiel-Wilson nodules - thickening of BM, widening slit of procure membranes and matrix invading glomerular capillaries with deposition of mesangial matrix
Outline the stages of nephropathy
- Hyperfiltration
- Normal
- Microalbuminuria
- Overt nephropathy
- Chronic Renal Failure
Outline the management of nephropathy.
1) Screening:
- Microalbuminuria
- Albustix
- GFR
2) BP:
- ACEi/ARB
3) Hyperlipidemia:
- Statins
4) Glycaemic control
- Metformin
5) Diet:
- Balanced diet
What is neuropathy?
disease or dysfunction of one or more peripheral nerves typically causing numbness or weakness
What is microangiopathy?
Microvascular disease which affects small blood vessels in the body with a narrowed lumen, reduced blood flow, turbulent not laminar flow and nerve damage
What is diabetic foot?
Pathology of the foot resulting from diabetes or chronic complications of diabetes mellitus which is the result of a combination of microvascular and macrovascular disease
Outline how you would examine a diabetic? patient’s foot.
0) Screening Questions: Reach feet + any pain in feet
1) Vascular/Skeletal:
i) Look: all surfaces, heel, plantar surface and interdigital space; check for hallux valgus, calluses,
ii) Palpate: temperature, pulses (dorsalis pedis + posterior tibial) + capillary refill
2) Neurological:
i) Look: muscle tone, temperature + sweating
ii) Palpate: Vibration (128Hz @ bony prominences) + Pressure (10mg monofilament at 1,3,5 metatarsal heads, plantar surface of big toe + apex of 3rd digit)
3) Footwear: wear patterns + suitability
What are some pathologies looking to be observed in a diabetic foot examination?
- Hallux vulgus
- Plantar ulcer (Arterial: tips of toes, phalangeal heads, lateral malleolus; deep, pale and necrotic with minimal granulation tissue, dry, minimal drainage and high pain vs Venous: medial lower leg, medial malleolus, irregular wound margins, shallow, moderate to large drainage amounts)
- Amputation
- Gangrene
- Osteomyelitis
- Charcot Foot
What is retinopathy?
disease of the retina causing changes to vision of the eye
What are the stages of diabetic retinopathy?
- Background
- Preproliferative
- Proliferative
- Advanced eye disease
How do you screen for diabetic retinopathy?
- Screening: Annual if no previous DR or more frequent as necessary
- Methods: Opthalmascope or Retinal camera
- System: Recall or referral
What may be seen in diabetic retinopathy when using an opthalmascope?
- Papilloedema
- Neovascularisation
- Rubiosis Iridis - Fibrosis/Scarring
What intervention may be required and what major side-effect does this have?
Burn out peripheral retina ≈ fine vision in macula however may lose visual fields
What is macrovascular disease?
pathology affecting large (macro) blood vessels in the body - coronary arteries, aorta, arteries in the brain and limbs
What macrovascular disease complications are there?
1) CHD: atherosclerosis, MI
2) CVI: stroke
3) PVD
List all the processes of care for a patient with Diabetes Mellitus.
1) Weight: BMI
2) BP: 140/80mmHg
3) Smoking status
4) Glycaemic control: HbA1c < 58mmol
5) Urinary albumin: < 2.5mg (M) or < 3.5mg (F)
6) SCr
7) Lipid control < 4mmol/L and LDL < 2mmol/L
8) Eye test
9) Foot exam
Why may HbA1c not be the best indicator of glycaemic control?
- Cost
- Anaemic
- Haemaglobinopathies: Sick;e Cell, Thalassaemias, Haemolytic anaemia
