JC33, 34 (Medicine) - Diabetes Flashcards

Question

Treatment outline for Type 1 and II DM

Answer 1

T1DM: lifestyle measures + insulin T2DM: → Lifestyle measures alone in early stages (1st line) → Lifestyle measures + oral hypoglycaemics if relative insulin insufficiency → Lifestyle measures + insulin if absolute insulin insufficiency (advanced) * First line: Metformin * High risk CVD and CKD \> SGLT2 inhibitor or GLP-1 * No CVD or CKD: DDP-4 inhibitor, SGLT2 inhibitor, TZD, GLP-1RA * Need weight loss: SGLT2 inhibitor or GLP-1RA

Answer 2

Energy content: 30kcal/kg ideal body weight per day Composition: → 40-50% carbohydrates, 30% fat (\<7% saturated/trans fat), 20-30% protein → 20-35g/d fibre intake Other advice: → Personalized according to individual preference and culture → Consistency of meal timing and quantity → Emphasis on ↑fibre food, low-fat dairy products and fresh fish → Minimize high energy food, esp those with high glycemic index (GI) and glycemic load (GL) → Hypocaloric diet for obese T2DM pt

Answer 3

1. Insulin secretagogues 2. Incretin mimetics 3. DDP-4 inhibitors 4. Insulin sensitizers 5. a-glucosidase inhibitors 6. SGLT2 inhibitors

Answer 4

Sulfonylureas (SUs) - 1G: chlorpropamide, tolbutamide - 2G: gliclazide (Diamicron), glibenclamide, glipizide Meglitinide analogues - Repaglinide - Nateglinide MoA Blocks K+ ATP channel of pancreatic β cells → ↑depolarization → ↑insulin secretion

Answer 5

**Sulfonylureas:** * Risk of **weight gain** * High risk **Hypoglycaemia** * **C/O poor renal function (high risk hypoGly)** * No cardiovascular or renal benefits **Meglitinide analogues** * Risk of **weight gain** * Small risk of **Hypoglycaemia** * No cardiovascular or renal benefits

Answer 6

GLP-1 analogues - Exenatide (weekly) - Liraglutide (QD) Mimics endogenous incretin action → ↑insulin secretion from pancreatic β cells Slow gastric emptying and weight loss

Answer 7

Benefits: * Atherosclerotic CVD (dulaglutide, liraglutide) * Slow progression of Diabetic nephropathy S/E: Pancreatitis Injection site reaction Thyroid C-cell tumor C/O very poor renal function (eGFR \< 35)

Answer 8

DPP-4 inhibitors - Sitagliptin (Januvia) - Linagliptin (Trajenta) - Vildagliptin (Galvus) Inhibits DPP-4-mediated breakdown of endogenous incretins → prolong incretin action on β cells S/E ↑risk of acute pancreatitis and pancreatic CA or neuroendocrine tumours ↑risk of IBD, deranged LFT and rarely joint pain Caution: Dose adjustment in CKD (except linagliptin) Risk of HF (saxagliptin only)

Answer 9

Biguanides - Metformin HCl (Glucophage) ↑AMPK activity → ↓gluconeogenesis, ↑FA utilization, ↓FA synthesis Thiazolidinediones - Rosiglitazone - Pioglitazone (Actos) ↑PPARγ action in adipocytes → ↓inflammation, ↑insulin sensitivity, preferential differentiation of pre-adipocytes to increase FA uptake

Answer 10

Benefits: * Weight loss * Benefit against ASCVD S/E * GI S/E (dyspepsia, diarrhea) and B12 deficiency Caution * Risk of lactic acidosis: eGFR \<30, alcohol abuse, severe liver disease, unstable HFrEF or uncontrolled sepsis at risk of hypoperfusion * Dose adjustment at eGFR 30-45 * Withhold 48h before and after contrast CT

Answer 11

S/E: * weight gain * derange LFT * Increase LDL-C (Rosiglitazone) * Bladder Cancer (Pioglitazone) Caution: * Increase fluid retention and risk of congestive HF * C/O Chronic kidney disease

Answer 12

α-glucosidase inhibitors - Miglitol - Acarbose Competitive inhibitors of GI α-glucosidase → ↓digestion and absorption of starch and disaccharides from small intestines → ↓postprandial blood glucose level Lower risk of ASCVD S/E: Flatulence and diarrhea due to high glucose in feces Poor hypoglycaemic effect/ performance

Answer 13

SGLT2 inhibitor - Canaglifozin - Dapaglifozin (Forxiga) - Empaglifozin (Jardiance) Inhibits SGLT2 in PCT of kidney tubule → ↓glucose reabsorption → ↑glucose excretion Benefits: * Weight loss * No hypoglycaemia * Reduce ASCVD and Diabetic nephropathy S/E: * Urogenital infections * Postural hypotension (osmotic diuresis) * Osteoporosis (Canagliflozin) * CA bladder (Dapagliflozin) * High LDL-C * Euglycaemic DKA

Answer 14

T1DM: Immediately from Dx T2DM: → Features of absolute insulin insufficiency, eg. marked recent weight loss, marked ketosis → Failed oral Tx → Clinically ill, eg. dehydrated, infection, MI → Pregnancy Features of absolute insulin deficiency: Ketosis, Marked recent weight loss, Underweight/ critically ill Severe hyperglycemia at Dx: HbA1c \>10%, Fasting glucose \>16.7mmol/L

Answer 15

□ **Rapid**-acting analogues, eg. insulin Aspart (Novorapid), insulin Lispro (Humalog) □ **Short**-acting insulins, i.e. regular human insulin eg. Actrapid, Humulin R □ **Intermediate**-acting analogues, eg. insulin NPH (protaphane) □ **Long**-acting analogues, eg. insulin degludec (Tresiba), insulin glargine (Lantus) □ **Pre-mixed** insulins, eg. Protamine/Aspart (Novolog 70/30), Lispro protamine/Lispro (Humalog mix 75/25 and 50/50), NPH/regular (Humulin mix 70/30, Novolin mix 70/30)

Answer 16

Basal insulin only: suitable for patients with fasting hyperglycemia only → Examples: protaphane bedtime, Tresiba/Lantus OM/bedtime Daily/BD insulin: suitable for patients with daytime hyperglycemia → Examples: protaphane , pre-mixed Basal-bolus insulin: suitable for patients with difficult titration or T1DM or long term type 2 DM with worsening insulin deficiency → Examples: Tresiba + Novorapid fasting Haemstix for fasting glycemic control Regular HbA1c for postprandial control

Answer 17

 Diabetic ketoacidosis (DKA) ± coma  Hyperglycaemic hyperosmolar state (HHS) ± hyperosmolar nonketotic coma (HONK)  Hypoglycaemia  Infections: pulmonary TB (due to ↓WBC function), UTI (glycosuria), others

Answer 18

Reason: inability to ↑insulin appropriately to compensate for stress hyperglycaemia Triggers: → Physiological stress: infection, operation, trauma, MI, stroke (esp if elderly) → Emotional stress if severe → Drug administration, eg. steroids

Answer 19

Presentation: 1. Usually T1DM or in advanced, insulin-deficient T2DM 2. Presenting manifestation of undiagnosed T1DM 3. Inadequate insulin Tx in known T1DM Precipitating factors: 1. Infections (30-40%) 2. Non-compliance with treatment (25%) 3. Alterations to insulin dose (13%) 4. Newly diagnosed DM (10-20%) 5. MI (\<1%) Severity: Mild: pH 7.25-7.3, HCO3 15-18, alert Moderate: pH 7-7.25, HCO3 10-15, mild drowsiness Severe: pH \<7, HCO3 \<10, stupor/coma

Answer 20

□ Ketoacidosis: hyperketonemia and ketonuria with metabolic acidosis □ Hyperglycaemia: ≥11mmol/L □ Dehydration and electrolyte disturbances Mild: pH 7.25-7.3, HCO3 15-18, alert Moderate: pH 7-7.25, HCO3 10-15, mild drowsiness Severe: pH \<7, HCO3 \<10, stupor/coma

Answer 21

1. Acute insulin deficiency → unrestrained lipolysis → ↑blood FFA → ↑hepatic ketogenesis → ↑↑blood ketones (a fasting state response) → metabolic acidosis 2. HyperGly → profound osmotic diuresis → dehydration + Na/K loss * 2o hyperaldosteronism → ↑↑K loss → net K deficit * Metabolic acidosis → H+/K+ intracellular shift * ↑↑Glc/ketones → hyperosmolar hyponatremia or normonatremia

Answer 22

Clinical presentation: can be fulminant or mild but generally evolve rapidly □ S/S of hyperglycaemia: polyuria, polydipsia, polyphagia, marked fatigue □ S/S of dehydration/electrolyte disturbance: orthostatic hypotension or even shock □ S/S of ketoacidosis: → Fruity smelling breath → Kussmaul’s respiration, leg cramps → Acute abdomen: diffuse abdominal pain, nausea, vomiting (due to ileus, usu only if severe acidosis) → Altered mentation: ↓consciousness, confusion, coma

Answer 23

□ Hyperglycaemia: plasma glucose \>14mmol/L □ HAGMA: arterial pH \<7.3, plasma HCO3- \<15mmol/L ± ↑AG □ Ketosis: moderate ketonuria or ketonaemia or ↑serum β-hydroxybutyrate (BHBA)

Answer 24

* Urine and plasma glucose * Urine ± plasma ketones or BHBA (urine ketone is useless) * Na, K, PO4 ± Mg * Anion gap (AG) * Urea, creatinine, Hb * ABG If indicated, look for underlying cause: - CXR, ECG (MI) - Blood and MSU C/ST (Infection\*) - Urine/serum osmolality (New DM) - PT, aPTT

Answer 25

Q1H: 1. BP/P, 2. RR, 3. GCS, 4. UO (Urine output) 5. ± CVP (Central venous pressure) Temperature - Q2H Aspirate stomach if unconscious or vomiting ± ETT for airway protection if necessary Foley’s catheter and set CVP as indicated Abx if evidence of infection, treat hypotension and shock as appropriate

Answer 26

**Rehydration** - 1-2L 0.9% normal saline * Monitor serum Na * Keep under 10% body weight infusion over 12h * Watch out for fluid overload and CHF **Insulin** - Regular human insulin * IV bolus + Infusion by insulin pump * Aim to decrease plasma glucose by 3-4mmol/L/h * Change to maintenance insulin when Anion Gap normalize **Potassium** - 10-20mmol/h * Maintain serum K at 4-5mmol/L * Calcium gluconate * First priority of treatment **Sodium Bicarbonate** * Only if pH under 7.0 * Monitor serum K, maintain until over pH 7.0

Answer 27

Early T2DM with relative insulin deficiency At risk: Elderly with difficulty drinking water, on diuretics, decreased sense of thirst, sudden copious intake of glucose-containing fluid Pathogenesis: Severe Hyperglycemia \> osmotic diuresis exacerbated by insulin deficiency causing impaired tubular sodium reabsorption \> Severe dehydration/ Hyperosmolarity _But no ketosis_ (unlike DKA): insulin still present + severe hyperosmolar state → suppress lipolysis

Answer 28

Clinical presentation: **typically insidious** □ Predisposition: Hx of ↓fluid intake or ingestion of large amounts of glucose-containing fluid □ S/S of hyperglycaemia: polyuria, polydipsia, polyphagia, marked fatigue □ S/S of dehydration/electrolyte disturbance: orthostatic hypotension or even shock □ Neurological: focal neurological signs, seizures, general consciousness decrease, confusion, coma

Answer 29

□ Hyperglycaemia: **blood glucose \>33mmol/L** (different from DKA) □ **Non-ketotic: arterial pH \>7.3, serum HCO3- \>15mmol/L**, mild ketonuria/ketonaemia only (complete opposite direction from DKA) □ **Hyper-osmolar**: effective serum **osmolality** **\>320mOsm/kg** (2[Na] + [Glc])

Answer 30

Rehydration with normal saline Insulin: less aggressive than DKA, switch to maintenance insulin when alert, tolerating diet, osmo \<315

Answer 31

Same as DKA panel * Urine and plasma glucose * Urine ± plasma ketones or BHBA (urine ketone is useless) * Na, K, PO4 ± Mg * Anion gap (AG) * Urea, creatinine, Hb * ABG If indicated, look for underlying cause: - CXR, ECG (MI) - Blood and MSU C/ST (Infection\*) - Urine/serum osmolality (New DM) - PT, aPTT

Answer 32

Complications: → Risk of thrombosis esp in Caucasians + hyperosmolality → Risk of overshoot hypoglycemia and hypokalemia → Risk of cerebral oedema in children

Answer 33

□ Overtreatment: excessive insulin or insulin secretagogues (sulphonylureas or meglitinides) □ Treatment with anti-diabetics precipitated by renal impairment □ Insufficient carbohydrate intake □ Excessive exercise

Answer 34

**Adrenergic symptoms** from ANS activity (usually occur first) → Palpitation, sweating, anxiety, tremor, tachycardia → Gradual decrease awareness in recurrent hypoglycaemia (eg. chronic DM) **Neuroglycopenic symptoms** from ↓CNS activity due to hypoGly (usually occur later) → Hunger sensation → Periorbital and finger paraesthesia, seizures → Focal weakness, ↓sensation, clouding of vision → Depressed consciousness, drowsiness, coma

Answer 35

_Whipple’s triad_ □ Symptoms compatible with hypoglycemia □ Low blood glucose coinciding with time of symptoms □ Resolution of symptoms with correction of hypoglycemia Table below is for DM patients, not normal people

Answer 36

* Oral carbohydrates: sweet drink, early meal or snack, 15-20g oral glucose * IV dextrose if unconscious * IM glucagon if cannot obtain IV access * Monitoring: Haemstix Q1-2h until stable → duration depends on L/RFT and type of insulin/drug (in case of overdose)

Answer 37

□ Education to keep good balance between exercise, meals and antidiabetic Tx □ Revise glycaemic target if frequent asymptomatic hypoGly □ Consider pre-emptive glucagon prescription for those at risk of level 2-3 hypoGly

Answer 38

 Lacrimal system: ↓tear production  EOM: CN III, IV, VI palsies (as part of mononeuritis multiplex)  Lens: fluctuating refractive errors, cataract  Glaucoma: idiopathic or due to rubeosis iridis  Retina: retinopathy, papillopathy  Others: ↑eye infections, ↑eye inflammation after ocular operations

Answer 39

□ Diabetic retinopathy (DMR): non-proliferative or proliferative □ Diabetic macular oedema: retinal thickening and oedema involving macula → Can occur at any stage of DR → Commonest cause of vision loss in DM patients

Answer 40

□ Long duration of DM: 80% have DMR after 20y of disease □ Poor DM control □ Vascular comorbidities, esp HTN, smoking □ Others: pregnancy, rapid implementation of tight glycemic control

Answer 41

□ **Retinal microangiopathy**: chronic hyperGly → metabolic changes in retinal vessels → impaired vascular autoregulation → microaneurysm + retinal haemorrhage (‘dot-and-blot’) □ **Retinal ischaemia**: endothelial damage → microthrombosis or occlusion → ischaemia → cotton wool spots (retinal nerve infarct) + venous beading (due to ischaemia) + intra-retinal microvascular abnormalities (IRMA) (anastomosis between arterioles and venules) □ **Breakdown of blood-retinal barrier**: microangiopathy + microthrombosis → ↑capillary leakage → hard exudates (lipoprotein leakage) + macular edema (if occurring near macula) + retinal edema □ **Vasoproliferative** substances: ischaemia → vasoproliferative factor secretion (eg. VEGF) → neovascularization (PDMR) + exacerbates ischaemia + breakdown of B-R barrier □ **Proliferative DMR**: neovascularization w/ fragile vessels → vitreous haemorrhage

Answer 42

Asymptomatic: majority with DMR shows no symptoms until very late stages 1. **Blurred vision** of gradual onset: usually due to macular oedema 2. **Sudden visual loss** indicates complications → **Vitreous haemorrhage** due to neovascularization into vitreous → **Rubeotic glaucoma** due to neovascularization of iris leading to acute angle closure → **Tractional Retinal detachment** due to fibrosis of abnormal vessels

Answer 43

Pathogenesis: □ Mechanism: hyperglycaemia → ↑ROS production → chronic damage to glomerular epithelium □ Histology: → Nodular glomerulosclerosis with Kimmelstiel-Wilson nodules → Diffuse glomerulosclerosis with ↑mesangial matrix

Answer 44

□ Onset: microalbuminuria develops 5-15y after T1DM and 15-20y after T2DM dx □ Albuminuria: slowly progressive from microalbuminuria (30-300mg/d) then to macroalbuminuria (\>300mg/d) □ Progressive CKD with gradual ↓GFR

Answer 45

□ CVD risk factors control: stop smoking… □ Glycaemic control: aim A1c \<7-8% → Prefer SGLT2i and GLP1a □ BP control (esp by ACEI/ARB) □ Treat hyperlipidemia (by statins or fibrates) □ Renal replacement therapy if ESRD

Answer 46

Acute diabetic **mononeuropathy** **Proximal** diabetic neuropathy (diabetic amyotrophy, lumbosacral plexopathy) Diabetic **peripheral** neuropathy Diabetic **autonomic** neuropathy

Answer 47

□ Cause: likely ischaemic infarction of peripheral nerves □ Site: most commonly CN III, CN VI, median and common peroneal palsies □ Clinical presentation: acute onset, usually transient → Ptosis and divergent squint (CN III) (typically pupil-sparing) → Lateral rectus palsy (CN VI) → Upper facial and eye pain (ocular) → Foot drop (peroneal n.) □ Mx: generally supportive but may require MRI to r/o stroke

Answer 48

□ Cause: likely **ischaemic infarction** of lumbosacral nerve roots and peripheral nerves □ Site: asymmetrical, proximal, usually LL (but can affect UL) □ Clinical presentation: progressive, typically transient, lasting weeks to months → Acute severe asymmetrical progressive proximal weakness and wasting → Hyperaesthesia and paraesthesia → Associated autonomic failure and weight loss □ Dx: NCV (axonal degeneration), MRI pelvis (to r/o alternative causes) □ Mx: 60% with good functional recovery in 12-24mo but mild residual weakness may remain → controlling underlying hyperglycaemia → Gabapentin/pregabalin/amitriptyline for neuropathic pain

Answer 49

□ Cause: **metabolic or osmotic neurotoxicity** due to chronic hyperglycaemia □ Site: symmetrical, distal, usually begins in LL □ Clinical presentation: → **Sensory** polyneuropathy: glove-and-stocking sensory loss of all modalities or paraesthesia → **Motor** polyneuropathy: ↓tendon reflexes in LL ± weakness, wasting (generally later) → **Skin** and joint: foot ulcers, foot deformities, Charcot arthropathy □ Screening: by symptoms and **monofilament (small fibre) and tuning fork (large fibre) tests** □ Workup: clinical ± NCV study and blood test (to r/o alternative causes, eg. B12) □ Mx: → Optimize glycemic control as mainstay → Gabapentinoids (gabapentin/pregabalin) and antidepressants (amitriptyline) for pain

Answer 50

 **Impaired CO control:** resting tachycardia (early), failure of exercise-induced ↑HR resulting in exercise intolerance  **Orthostatic hypotension** due to central/peripheral sympathetic denervation  **Postural tachycardia** with lightheadedness, dizziness, presyncope

Answer 51

 Distal hypohidrosis with compensatory proximal hyperhidrosis (abnormal excessive sweating)  Thermoregulatory impairment and hyperthermia  Diabetic dermopathy (dryness, itching) and Charcot arthropathy

Answer 52

 GERD  Gastroparesis: N/V, early satiety, bloating, upper abd pain  Diarrhoea: painless watery nocturnal diarrhoea

Answer 53

 Bladder dysfunction: ↓ability to sense full bladder, incomplete emptying, recurrent UTI, overflow incontinence  Ejactulatory dysfunction: retrograde ejaculation, erectile dysfunction  Dyspareunia due to ↓vaginal lubrication

Answer 54

Cause: Diabetic peripheral neuropathy Common manifestation: □ Foot ulcers: 25% lifestyle risk, annual risk 2%/y □ Diabetic foot infections: cellulitis, osteomyelitis RFs of foot ulcer development: □ Previous foot ulceration (most important) □ Neuropathy (80%): loss of monofilament sensation, neuropathy disability score □ Foot deformity □ Concomitant vascular disease

Answer 55

General foot care recommendations: □ Annual comprehensive foot examination to identify RFs incl inspection + palpation of pulses → Refer vascular surgery for patients with significant claudication or +ve ABI □ General foot self-care □ Multidisciplinary approach (refer podiatry)

Answer 56

Pathogenesis: Lack of proprioception + ligament laxity + joint instability + deformity → **prone to damage by minor trauma** **vasomotor changes due to autonomic neuropathy** lead to exaggerated local inflammatory response → **arthropathy**

Answer 57

Clinical features: generally painless □ **Acute arthritis:** sudden onset unilateral warmth, erythema, swelling over foot/ankle (often ppt by minor trauma) → Joint involved: tarsal/TMTJ \> MTPJ/ankle □ **Chronic arthritis**: slowly progressing arthropathy with insidious swelling ± acute attacks □ **Foot deformity**: collapse of midfoot arch, bony prominences in peculiar places ± pressure ulcerations

Answer 58

□ Early: soft tissue swelling, loss in joint spaces □ Late: forefoot bone resorption, disappearance in MT heads, pencil-pointing of phalangeal/MT shafts □ Complication features: stress fractures, subluxation/dislocations

Answer 59

□ **Short-term immobilization** (3-6mo): proven to ↓long-term joint damage and progression □ Consider **antiresorptive agents** (bisphosphonates, calcitonin) as adjunct □ Orthopaedic **surgical correction** in severe cases

JC33, 34 (Medicine) - Diabetes Flashcards

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