Diabetes Lecture 4

Course Overview

• Course No 4: Chronic Complications of Diabetes

Agenda

• Chronic Complications of Diabetes:

  • Definition

  • Pathogenesis

  • Diagnosis

  • Treatment

• Microvascular Complications in Diabetes:

  • Retinopathy

  • Nephropathy

  • Neuropathy

• Macrovascular Complications in Diabetes:

  • Coronary Artery Disease

  • Cerebrovascular Disease

  • Peripheral Vascular Disease

• Diabetic Foot

Characteristics of Chronic Complications of DM

Microvascular Complications

• Characterized by thickening of the basement membrane of small blood vessels and capillaries.

  • Types:

    • Diabetic Retinopathy

    • Diabetic Nephropathy

    • Diabetic Neuropathy

Macrovascular Complications

• Associated with atherosclerosis, leading to:

  • Hardening of arteries

  • Types:

    • Coronary Artery Disease

    • Cerebrovascular Disease

    • Peripheral Vascular Disease

Diabetic Foot

• A significant issue related to complications.

Long-term Complications

• Increasingly common as more people live longer with diabetes.

• Affect nearly all organ systems of the body.

• Occur in both Type 1 and Type 2 diabetes, generally within 5 to 10 years following hyperglycemia.

Pathogenesis of Chronic Complications

Key Pathways

• Polyol Pathway:

  • Glucose converted to sorbitol and fructose via NADPH pathway.

• Hexosamine Pathway:

  • Alters various cell metabolic functions.

• AGE Pathway (Advanced Glycation End Products):

  • Contributes to vascular and nerve damage.

Important Factors in Pathogenesis

• AGEs: Advanced Glycation End products

• eNOS: Endothelial Nitric Oxide Synthase

• NF-kB: Nuclear Factor Kappa B

• ROS: Reactive Oxygen Species

• TGF-β: Transforming Growth Factor Beta

• PAI-1: Plasminogen Activator Inhibitor-1

• ET-1: Endothelin-1

Epidemiology and Impact

• Increased risk of blindness in working-age adults by 2-4 times.

• Significant mortality rates related to diabetic conditions.

• Leading causes of end-stage renal disease and non-traumatic amputations due to diabetic complications.

Diabetic Retinopathy

Definition

• A specific microvascular complication of diabetes.

  • Leading cause of blindness in adults.

Risk Factors

• Longer duration of diabetes

• Chronic hyperglycemia

• Frequent hypoglycemia

• Pregnancy

• Smoking

Diagnosis

• Fundus examination (Ophthalmoscopy)

• Fluorescein Angiography for preclinical changes.

Classification

• Non-proliferative Diabetic Retinopathy (NPDR):

  • Mild

  • Moderate

  • Severe

• Proliferative Diabetic Retinopathy (PDR)

• Diabetic Maculopathy

• Advanced Diabetic Eye Diseases:

  • Vitreous/Preretinal Hemorrhage

  • Retinal Detachment

  • Rubeosis Iridis

  • Neovascular Glaucoma

Signs and Symptoms

• Blurred vision, Floaters, Loss of vision, Shadows in vision, Eye pain.

Screening Recommendations

• T1DM: Annually, starting 5 years post-onset.

• T2DM: Every 1-2 years from diagnosis.

Management and Treatment

• For Proliferative Diabetic Retinopathy:

  • Laser therapy (panretinal photocoagulation)

  • Intraocular pharmacological intervention (VEGF antagonists)

• For Diabetic Macular Edema:

  • Focal laser therapy

  • Vitrectomy if necessary

Diabetic Nephropathy

Definition

• Progressive increase in proteinuria leading to declining renal function, risking end-stage renal disease.

Risk Factors

• Long-standing diabetes

• Family history of hypertension and cardiovascular diseases

• Hyperglycemia

• Hypertension

• Male Gender

• Smoking

Pathological Patterns

• Diffuse Glomerular Basement Membrane Thickening: Most common.

• Nodular Form (Kimmelstiel-Wilson Lesion): Accumulation of specific materials in glomeruli.

Treatment

• Control Measures:

  • Glycemic control

  • Blood pressure management

  • ACE inhibitors or ARBs for patients with urinary albumin excretion ≥30 mg/24 h.

Diabetic Neuropathy

Types

• Sensorimotor Neuropathy

• Proximal Motor Neuropathy

• Acute Mononeuropathy

• Autonomic Neuropathy

Importance of Early Recognition

• Improving life quality by reducing symptoms and sequelae.

• Up to 50% may be asymptomatic.

Distal Symmetric Peripheral Neuropathy Symptoms

• Numbness, Tingling, Sharp pains, Loss of balance.

• Complications may include painless ulceration.

Screening Recommendations

• 10-g monofilament test for all patients at diagnosis and at least annually.

Treatment

• Tight glycemic control

• Vitamin B supplementation

• Alpha-lipoic acid

Macrovascular Complications

Definition

• A significant threat in diabetes, affecting heart and vascular systems.

Risk Factors

• Advancing age, Chronic hyperglycemia, Dyslipidemia, Obesity, Sedentary lifestyle.

Cardiovascular Risks in Diabetes

• 4-fold increase in risk of cardiovascular events compared to non-diabetic individuals.

• Increased risk for strokes and lower-extremity amputations.

Screening for CVD

• Assess for atypical cardiovascular symptoms.

• Evaluate for cerebrovascular and peripheral disease.

Diabetic Foot

Overview

• Major causes of morbidity and disability stemming from neuropathy and vascular disease.

• Annual foot exams recommended for all diabetes patients.

Management of Diabetic Foot Ulcers

• Tight glycemic control, Infection treatment, Diabetic arterial disease management, Proper footwear education, and supportive therapies.