Case 4: Susanna Green Pt 2 - Diabetes Complications

DM: Description

Metabolic disorder causing chronic hyperglycemia

DM: Types

T1D: Insulin-dependent

• 1A: Autoimmune

• 1B: Idiopathic

T2D: Non-insulin-dependent

Gestational: During pregnancy

Maturity-Onset Diabetes of the Young (MODY): Autosomal dominant genetic defect → Beta-cell dysfunction

DM: Treatment/Management

Lifestyle changes

Glucose monitoring

Pharmacological

DM Management: Lifestyle Changes

• Weight loss

• Balanced diet

• Exercise

• Smoking cessation

• Vaccinations

DM Management: Glucose Monitoring

Self: At fixed times

Continuous: Subcutaneous device

Importance:

• Evaluate treatment response

• Avoid hypoglycemia

  • Insulin titration

DM Management: Pharmacological

Non-insulin anti-hyperglycemics

• Indications: HbA1c > 7%

• Goal: HbA1c < 6.5%

Classes:

• Biguanides

• Dipeptidyl peptidase (DPP)-4 inhibitor

• SGLT-2 inhibitor

• GLP-1 agonist

• Sulfonylurea

• Thiazolidinedione

• Insulin

DM Management: Biguanide

Ex: Metformin

• First-line

MOA: Modify glucose pathways + increase insulin sensitivity

Contraindications:

• Renal failure

• CHF

• Liver failure

  • Alcohol

DM Management: DPP-4 Inhibitor

Ex: -gliptin

• Sitagliptin

• Saxagliptin

MOA: Delay gastric emptying + increase insulin secretion

Contraindications:

• CHF

• Renal failure

• Liver failure

DM Management: SGLT-2 Inhibitor

Ex: -gliflozin

• Empagliflozin

MOA: Decrease glucose reabsorption

Contraindications:

• Recurrent UTIs

DM Management: GLP-1 Agonist

Ex: -glutide

• Emaglutide

• Liraglutide

MOA: Delay gastric emptying + increase insulin secretion

Contraindications:

• GI motility disorders

• Pancreatitis

• MEN hx

DM Management: Sulfonylurea

Ex: Glimepiride, gliclazide

MOA: Increase insulin secretion

Contraindications:

• Beta blockers

• CVD

• Obesity

• Sulfa allergy

• Renal failure

• Liver failure

DM Management: Thiazolidinedione

Ex: -glitazone

• Pioglitazone

MOA: Increase glucose + FFA storage + use

Contraindications:

• CHF

• Liver failure

• Bladder cancer

DM Management: Insulin

Indications:

• Glycemic targets not met with non-insulin medications (> 9.5%)

• Poor kidney function

• Hyperglycemic crisis

• Gestational DM

Types:

• Basal: Long-acting insulin

  • Administration: 1-2 times/day

• Prandial: Short-acting insulin

  • Administration: Bolus before meals

• Mixed: Intermediate-acting + short-acting insulin

• Insulin Pump: Automated subcutaneous delivery

  • Anticipate glucose levels = Administer bolus dose

DM Complications

Microvascular

Macrovascular

DM Microvascular Complications

Pathophysiology: Chronic hyperglycemia = Protein/lipid glycation = Thickened basal membrane = Tissue damage + organ dysfunction

Types:

• Nephropathy

• Retinopathy

• Polyneuropathy

• Foot ulcers

DM Microvascular: Nephropathy

Types:

• CKD

• Nephrosclerosis

• Glomerulosclerosis

Clinical Presentation:

• Asymptomatic

• Albuminuria

• Decreased eGFR

Screening:

• Urine albumin-to-creatinine ratio

  • Normal < 3

• eGFR

  • Normal ≥ 90

Treatment:

• ACE inhibitor or ARB

• SGLT2 inhibitor

• GLP-1 receptor agonist

DM Microvascular: Retinopathy

Types:

• Edema

• Hemorrhage

• Retinal detachment

Clinical Presentation: Vision changes

Screening: Dilated eye exam

Treatment:

• Laser photocoagulation

• Anti-VEGF

DM Microvascular: Polyneuropathy

Types:

• Peripheral nerve damage

• Gastroparesis

Clinical Presentation:

• Distal symmetrical sensory loss

• Dysthesia (burning)

• Weakness

Screening:

• Sensation testing (temp, monofilament, vibration)

• Foot exam

Treatment:

• Glycemic control

• Pain control

  • SNRIs: Duloxetine

  • Gabapentinoid: Pregabalin/gabapentin

  • TCA: Amitriptyline

DM Microvascular: Foot Ulcers

Clinical Presentation:

• Ulcers

• Osteomyelitis

• Charcot arthropathy

Screening: Same as polyneuropathy

Treatment:

• Therapeutic footwear

• Infection management

DM Macrovascular Complications

Pathophysiology: Metabolic dysfunction = Increase vascular inflammation = Increase plaque formation

Types:

• Atherosclerosis + CAD

• Cerebrovascular disease

• Peripheral vascular disease

DM Macrovascular: Atherosclerosis + CAD

Types:

• Angina

• MI

DM Macrovascular: Cerebrovascular Disease

Types:

• Stroke

• Carotid artery stenosis

• Aneurysms

DM Macrovascular: Peripheral Vascular Disease

Peripheral artery disease (PAD)

Chronic venous insufficiency

PAD: Epidemiology

Risk factors…

• Smoking

• CAD

• DM

PAD: Pathophysiology

Atherosclerosis = Decreased tissue perfusion = PAD

PAD: Clinical Presentation

Claudication

• Worse with exertion

• Relieved by rest + lowering limbs

Pain at rest

Ischemic ulcers

PAD: Investigations

Ankle-brachial index (ABI): Ankle SBP/Brachial SBP

• Normal: 0.9-1.2

• PAD: < 0.9

Imaging: US + Angiography (MR, catheter)

PAD: Complications

Arterial ulcers

• Well-defined borders

• Pressure points

Acute limb ischemia

Gangrene

Wound healing complications

• Decreased perfusion = Decreased O2, nutrients, immune cells = Impair tissue repair

Chronic Venous Insufficiency: Pathophysiology

Venous valve incompetence = Venous HTN + stasis = Inflammation = Elastin, smooth muscle, collagen remodelling + hypertrophy = Varicose veins

Chronic Venous Insufficiency: Clinical Presentation

Pain + cramping

Edema

Pruritis

• Stasis dermatitis: Scaly pruritic rash

Telangiectasia + varicose veins

Yellow/red/brown skin

Chronic Venous Insufficiency: Investigations

Imaging: Venous duplex US

• Venous reflux

DM Macrovascular: Treatment/Management

Lifestyle changes

• Physical activity

• Smoking cessation

• Compression stockings

Pharmacological

Revascularization

DM Macrovascular Management: Pharmacological

Statins: Lipid control

ACE inhibitors or ARBs: BP control

Antiplatelet/anticoagulant therapy: Prevent thrombus formation

• ASA 

• Rivaroxaban

DM Macrovascular Management: Revascularization

Percutaneous angioplasty

Stent placement

Peripheral artery bypass surgery

CKD: Description

Abnormal kidney structure/function for > 3 months

CKD: Etiology

DM

HTN

Glomerulonephritis

CKD: Pathophysiology

1. Nephron loss + damage

• Glomerulonephritis: Inflammation

• Diabetic + HTN Nephropathy: Hypertrophy = Decreased renal blood flow = Ischemia

• Older Age: Natural loss

2. Decreased renal function = Low GFR

• Low urine production = Volume overload and decreased waste

• Decreased acid-base + electrolyte balance = Metabolic acidosis + electrolyte imbalances

3. Decreased endocrine activity

• Decreased calcitriol production + phosphate excretion = Low serum Ca2+ = Increase PTH

• Decreased erythropoietin = Decreased RBC production

CKD: Investigations

Blood tests

Urinalysis

Imaging

CKD Investigation: Blood Tests

eGFR: < 60

Creatinine: Increased

• Normal: 22-75 umol/L (F) and 49-93 umol/L (M)

Cystatin C: Increased

• Normal ≤ 1.20 mg/L

BUN: Increased

PTT/INR: Increased

CKD Investigation: Urinalysis

Proteinuria

• Urine ACR > 3 ng/mmol

Waxy cast

CKD Investigation: Imaging

US

• Deceased kidney length

• Decreased parenchymal + cortical thickness

• Increased echogenicity (white)

• Cysts

CKD: Treatment/Management

Nonpharmacological

Pharmacological

Renal replacement therapy

CKD Management: Nonpharmacological

Diet

• Vit D supplements

  • Prevent bone-mineral disorders

• Plant-based (DASH, Mediterranean)

  • Prevent CVD + diabetic neuropathy

• Decrease protein intake

  • Prevent CVD

• Restrict Na+, K+, phosphate

  • Prevent CVD + diabetic neuropathy

Physical activity

• Prevent diabetic neuropathy

Weight loss

• Prevent CD + diabetic neuropathy

CKD Management: Pharmacological

RAAS inhibitors

Statins

SGLT2 inhibitors

Medication changes

CKD Management: RAAS Inhibitors

Ex: ACE inhibitors (ramipril), ARBs (lorsartan, valsartan)

Manage HTN

Decrease proteinuria

CKD Management: Statins

Ex: Rosuvostatin

Decrease lipids = Decrease CVD risk

CKD Management: SGLT2 Inhibitors

Ex: Empagflozin

DM management = Decrease CVD risk

CKD Management: Medication Changes

Avoid nephrotoxic drugs

Ex: NSAIDs, Metformin, cisplatin/carboplatin, aminoglycosides, vancomycin, cephalosporins

CKD Management: Renal Replacement Therapy

Indications: AEIOU

• A: Acidosis

  • Severe metabolic acidosis pH < 7.1

• E: Electrolyte abnormalities

• I: Ingestion

  • Toxins/poisons

  • Medications

• O: Overload fluids (refractory)

• U: Uremia

Types:

• Dialysis: Remove solutes + water from blood through diffusion bypassing kidneys

  • Hemodialysis: Diffusion across semipermeable membrane outside body

  • Peritoneal Dialysis: Diffusion across peritoneum (membrane)

• Kidney transplantation: Place donated kidney in iliac fossa

CKD: Complications

Anemia

Bone + mineral disorders

HTN

Dyslipidemia

CKD Complications: Anemia

Pathophysiology: Low erythropoietin synthesis = Decrease RBC production = Anemia

Treatment: Erythropoietin-stimulating agents + Fe replacement therapy

CKD Complications: Bone + Mineral Disorder

Pathophysiology: Decreased renal phosphate excretion = Increased blood phosphate = Ca2+ phosphate precipitation into tissue = Hypocalcemia

Treatment: Normalize phosphate, Ca2+, PTH

CKD Complications: HTN

Pathophysiology: Decreased urine excretion = Increase water retention 

Treatment: ACE inhibitor or ARB

CKD Complications: Dyslipidemia

Treatment: Statins

Skin + Soft Tissue Infections (SSTI): Description

Infection affecting epidermis, dermis, subcutaneous tissue, or superficial fascia

SSTI: Conditions

Impetigo

• Nonbullous

• Bullous

Nonpurulent

• Erysipelas

• Cellulitis

Purulent

• Skin abscess

• Folliculitis

• Furuncles

• Carbuncles

Necrotizing

• Necrotizing cellulitis

• Necrotizing fasciitis

• Necrotizing myositis

Impetigo: Etiology

S. aureus

• Exotoxins = Staphylococcal scalded skin syndrome

S. pyogenes

Impetigo: Tissue Involvement

Superficial epidermis

Impetigo: Common Location

Nonbullous:

• Face

• Limbs

Bullous:

• Trunk

• Upper limbs

Impetigo: Clinical Presentation

Bullae

Honey yellow crust

Erysipelas: Etiology

GAS

Erysipelas: Tissue Involvement

Superficial dermis

Lymphatic vessels

Erysipelas: Common Locations

Lower limbs

Face

Erysipelas: Clinical Presentation

Raised + sharply demarcated lesion

Cellulitis: Etiology

GAS

S. aureus

Cellulitis: Tissue Involvement

Deep dermis

Cellulitis: Common Location

Lower limbs

Face

Cellulitis: Clinical Presentation

Poorly defined lesion

Skin Abscess: Etiology

S. aureus

• MRSA

Skin Abscess: Tissue Involvement

Deeper layers

Skin Abscess: Common Location

Anywhere

Skin Abscess: Clinical Presentation

Walled-off infection

Pus collection

Folliculitis, Furuncles, Carbuncles: Etiology

S. aureus

Peudomonas aeruginosa

Folliculitis, Furuncles, Carbuncles: Tissue Involvement

Hair follicles

Folliculitis, Furuncles, Carbuncles: Common Location

Anywhere

Genitals

Folliculitis, Furuncles, Carbuncles: Clinical Presentation

Localized tender papules + pustules

• Around hair follicles

Necrotizing SSTIs: Etiology

GAS + anerobic bacteria

Clostridium spp.

Necrotizing Cellulitis: Tissue Involvement

Deep dermis + subcutaneous

Necrotizing Fasciitis: Tissue Involvement

Superficial fascia

Necrotizing Myositis: Tissue Involvement

Muscle

Necrotizing SSTIs: Common Location

Anywhere

Necrotizing SSTIs: Clinical Presentation

Rapidly progressing

Necrosis

• Skin discoloration

Crepitus

Bullae

Pain out of proportion

SSTIs: Epidemiology

Risk factors…

• Chronic lymphedema

• Local skin defects

• DM

• Immunodeficiency

• IV drug use

SSTIs: Pathophysiology

Minor skin injury = Pathogen entry = Infection + spread through lymph vessels

SSTIs: General Clinical Presentation

General

• Rubor: Redness

• Calor: Heat

• Tumor: Swelling

• Dolor: Pain

• Functio Laesa: Loss of function

Systemic symptoms

• Fever

• Chills

• Nausea

• Headache

SSTIs: Other Clinical Presentation

Purulent exudate

Lymphangitis: Red streaks radiating from lesion following lymphatic vessels

Lymphadenitis: Swollen + tender lymph nodes

Sinus Tracts: Channel opening into deep soft tissue/abscess cavity

SSTIs: Investigations

Blood tests

Imaging

Culture

SSTIs Investigation: Blood Tests

CBC

• Leukocytosis

CRP + ESR

• Increased

CK

• Necrotizing: Elevated

SSTIs Investigation: Imaging

US: Soft tissue

CT/MRI: For complications + necrotizing

• Gas in soft tissue

XR: Gas in soft tissue

SSTIs Investigation: Culture

Location: Advancing lesion margin

Specimen:

• Tissue

  • Biopsy

• Fluid

  • Blood

  • Pus

• Aspirate

  • Abscess

• Swab: Last choice

SSTIs: Treatment/Management

Nonpharmacological

Pharmacological

Surgical

SSTIs Management: Nonpharmacological

Proper wound dressing + cleaning

Elevate affected limb

Warm compress

Incision + drain

• Purulent

• Abscess

SSTIs Nonpharmacological: Wound Dressing + Cleaning

Saline wash + irrigation

Topical antiseptic

• Sodium hypochlorite

• Mafenide

• Polyhexidine

Dressing

• Moist: Film, petrolatum, hydrogel, cellulose/collagen

• Antimicrobial: Silver, iodine, chlorhexidine, honey

SSTIs Management: Pharmacological

Antimicrobials

SSTIs Pharmacological: Antimicrobials

Empiric: Systemic signs

• Necrotizing: Daptomycin, linezolid, or vancomycin +

  • Carbapendem

  • Piperacillin/tazobactum

  • Fluoroquinolone + metronidazole

  • Ceftriaxone + metronidazole

Specific: After culture + sensitivity

SSTIs Antimicrobials: Administration

Mild: Topical, oral

Moderate: Oral, IV

Severe: IV

SSTIs Management: Surgical

Necrotizing: Immediate

• Exploration + debridement

• Tissue sample for microscopy + culture

Amputation

SSTIs Surgical: Amputation

Indications:

• Debridement insufficient for source control

• Necrotizing soft tissue infections

  • Gas gangrene

  • Necrotizing fasciitis

  • Severe osteomyelitis

• Severe diabetic foot infections

Post-Op Care:

• Wound care

  • Negative-pressure wound therapy (VAC): Promote granulation

• Analgesics

• Antibiotics: Broad-spectrum

• Prosthetics/wheelchair

• PT/OT

SSTIs: Complications

Sepsis

Osteomyelitis

Gangrene

Osteomyelitis: Description

Bone infection from hematogenous pathogen spread