Diabetes Vascular Complications
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Questions and Answers

What is one of the consequences of damaged blood vessel walls and capillary basement membranes?

  • Improved vascular stability
  • Enhanced nutrient transport to adjacent areas
  • Increased oxygen supply to tissues
  • Ischaemia due to reduced blood flow (correct)

Which condition is associated with the vascular complications resulting from diabetes?

  • Diabetic nephropathy (correct)
  • Hypertension
  • Hyperlipidemia
  • Acute metabolic syndrome

What histological feature is observed in the kidney glomerulus indicative of diabetic nephropathy?

  • Thinning of capillary membranes
  • Absence of PAS staining
  • Decreased protein deposition in mesangium
  • Thickening of capillary basement membranes (correct)

Which of the following is a proposed mechanism of hyperglycemia-induced tissue damage?

<p>Genetic factors (C)</p> Signup and view all the answers

What additional independent accelerating factor can contribute to tissue damage in individuals with diabetes?

<p>Hypertension (C)</p> Signup and view all the answers

What is the estimated increased risk of myocardial infarction (MI) in individuals with macrovascular complications?

<p>3-5X risk (C)</p> Signup and view all the answers

Which of the following is NOT a risk factor for cardiovascular disease in people with diabetes?

<p>Normal blood pressure (A)</p> Signup and view all the answers

What is the main contributing factor to the increased risk of amputation in diabetic patients with peripheral vascular disease?

<p>Neuropathy and infection (C)</p> Signup and view all the answers

Which of the following strategies is recommended for the prevention of macrovascular disease in individuals with diabetes?

<p>Weight loss and exercise (C)</p> Signup and view all the answers

What percentage of total costs for diagnosed diabetes in 2017 was attributed to hospital inpatient care?

<p>30% (D)</p> Signup and view all the answers

Which of the following is a consequence of poor glucose control in patients with diabetes?

<p>Higher risk of macrovascular complications (A)</p> Signup and view all the answers

What is the role of GLP-1 agonists and SGLT-2 inhibitors in patients with atherosclerotic cardiovascular disease (ASCVD)?

<p>They are treatment options for those with ASCVD. (C)</p> Signup and view all the answers

Which symptom is typical of gangrene in diabetic patients?

<p>Isolated toe or heel infection (B)</p> Signup and view all the answers

What is the leading cause of renal failure associated with diabetes?

<p>Diabetic kidney disease (C)</p> Signup and view all the answers

Which of the following complications is NOT primarily categorized as a microvascular complication?

<p>Cardiovascular disease (B)</p> Signup and view all the answers

What impact does diabetes have on life expectancy?

<p>Reduces by 5-10 years (A)</p> Signup and view all the answers

Which condition is NOT associated with the complications of diabetes?

<p>Gout (B)</p> Signup and view all the answers

What is the main relationship between hyperglycemia and disease?

<p>Strong correlation with microvascular disease (A)</p> Signup and view all the answers

Which risk factor significantly increases the likelihood of developing complications from diabetes?

<p>Age (C)</p> Signup and view all the answers

What occurs to the protein basement membrane in diabetes?

<p>It becomes abnormally thickened (B)</p> Signup and view all the answers

Which of the following best describes the risk for cardiovascular disease among diabetics?

<p>It increases 2 to 4 times (D)</p> Signup and view all the answers

Which of the following is a characteristic of nodular glomerulosclerosis?

<p>Presence of Kimmelstiel-Wilson nodules (B)</p> Signup and view all the answers

What is one risk factor for the progression of diabetic nephropathy?

<p>Poor glucose control (D)</p> Signup and view all the answers

Which of the following treatments is primarily used to improve or normalize albuminuria in diabetic nephropathy?

<p>ACE Inhibitor or Angiotensin II Receptor Blocker (C)</p> Signup and view all the answers

Which type of diabetic neuropathy is prevalent among patients in developed countries?

<p>Diabetic polyneuropathy (C)</p> Signup and view all the answers

What is a common symptom of distal symmetric polyneuropathy?

<p>Decreased sensation (D)</p> Signup and view all the answers

What therapeutic class does Duloxetine belong to for the treatment of painful neuropathy?

<p>Serotonin Norepinephrine Reuptake Inhibitors (A)</p> Signup and view all the answers

Which of the following is a recommendation to prevent foot ulcers in diabetic patients?

<p>Trimming toenails to avoid sharp edges (B)</p> Signup and view all the answers

Which macrovascular complication of diabetes is considered the leading cause of death?

<p>Coronary artery disease (A)</p> Signup and view all the answers

Which factor has the greatest influence on the development of diabetic neuropathy?

<p>Duration of diabetes (B)</p> Signup and view all the answers

What is the primary goal of management strategies for diabetic nephropathy?

<p>To prevent the progression of kidney disease (A)</p> Signup and view all the answers

What is a significant consequence of decreased NADPH in the polyol pathway?

<p>Increased oxidative stress (D)</p> Signup and view all the answers

Which factor is known to contribute to the pathophysiology of diabetic retinopathy?

<p>Dysregulated retinal blood flow (A)</p> Signup and view all the answers

Which of the following is NOT a risk factor for diabetic nephropathy?

<p>Low body weight (B)</p> Signup and view all the answers

What is a key characteristic of non-proliferative retinopathy?

<p>Cotton wool spots (C)</p> Signup and view all the answers

Which of the following treatments is indicated for high-risk proliferative diabetic retinopathy?

<p>Vascular endothelial growth factor inhibitors (B)</p> Signup and view all the answers

What are advanced glycosylation end-products primarily associated with?

<p>Modification of proteins (D)</p> Signup and view all the answers

Which type of diabetic retinopathy is characterized by the presence of microaneurysms and dot hemorrhages?

<p>Mild non-proliferative retinopathy (A)</p> Signup and view all the answers

What is an evidence-backed cornerstone of therapy for preventing diabetic retinopathy?

<p>Antihypertensive therapy (D)</p> Signup and view all the answers

Which of the following is a common symptom of diabetic retinopathy in its later stages?

<p>Decreased visual acuity (D)</p> Signup and view all the answers

What is a common consequence of diabetic nephropathy?

<p>Albuminuria (B)</p> Signup and view all the answers

Which pathway diverts from glycolysis and is associated with altered gene expression in diabetes?

<p>Hexosamine pathway (D)</p> Signup and view all the answers

Which of the following factors is NOT included in the risk factors for diabetic retinopathy?

<p>Strenuous exercise (D)</p> Signup and view all the answers

What is the primary risk factor for developing diabetic retinopathy?

<p>Duration of diabetes (D)</p> Signup and view all the answers

In the context of diabetic nephropathy, what does microalbuminuria indicate?

<p>Early kidney damage (C)</p> Signup and view all the answers

Which factor primarily contributes to the thickening of capillary basement membranes in diabetes?

<p>Hyperglycemia-induced metabolic changes (C)</p> Signup and view all the answers

What is a significant consequence of ischaemia resulting from damaged blood vessels in diabetes?

<p>Reduced tissue oxygenation (C)</p> Signup and view all the answers

Which mechanism is considered an independent accelerating factor of hyperglycemia-induced tissue damage?

<p>Hyperlipidemia (A)</p> Signup and view all the answers

What histological change is most indicative of diabetic glomerulosclerosis in kidney tissue?

<p>Thickening of capillary walls (C)</p> Signup and view all the answers

In which tissue is the abnormal response to hyperglycemia most prominently observed?

<p>Kidney glomerulus (A)</p> Signup and view all the answers

Which complication of diabetes is primarily responsible for increased risk of blindness?

<p>Retinopathy (C)</p> Signup and view all the answers

What is a major consequence of diabetic kidney disease?

<p>Increased likelihood of renal failure (C)</p> Signup and view all the answers

Which factor significantly contributes to the development of neuropathy in diabetic patients?

<p>Chronic hyperglycemia (B)</p> Signup and view all the answers

Which of the following best describes the impact of diabetes on life expectancy?

<p>Reduces life expectancy by 5 to 10 years (D)</p> Signup and view all the answers

What underlying mechanism is primarily involved in the thickening of the protein basement membrane in diabetes?

<p>Formation of glycosylated proteins (D)</p> Signup and view all the answers

Which of the following is a common sign of diabetic neuropathy?

<p>Difficulty in perception of pain and temperature (B)</p> Signup and view all the answers

What is the leading cause of nontraumatic amputations in diabetic patients?

<p>Peripheral vascular disease (A)</p> Signup and view all the answers

Which type of infections are particularly common in diabetic patients?

<p>Fungal infections (B)</p> Signup and view all the answers

What is a typical characteristic of peripheral vascular disease in diabetic patients?

<p>Multiple diffuse lesions in lower limb arteries (D)</p> Signup and view all the answers

Which of the following factors is NOT a component of risk factor management for macrovascular disease in diabetes?

<p>Maintaining high glucose levels (B)</p> Signup and view all the answers

Which statement accurately reflects the cost implications of diagnosed diabetes?

<p>Inpatient hospital care comprises a significant portion of diabetes-related costs. (D)</p> Signup and view all the answers

What disproportionate risk do individuals with diabetes face regarding myocardial infarction (MI)?

<p>3-5 times higher risk compared to non-diabetic individuals (B)</p> Signup and view all the answers

Which lifestyle change is NOT recommended for the prevention of macrovascular disease in diabetes?

<p>Increased sedentary behavior (A)</p> Signup and view all the answers

What is the primary reason individuals with diabetes should manage lipid levels effectively?

<p>To reduce the risk of stroke and myocardial infarction (B)</p> Signup and view all the answers

What is a contributing factor to the significantly increased risk of amputation in patients with peripheral vascular disease due to diabetes?

<p>Higher likelihood of foot ulcers (A), Greater susceptibility to infections (C), Less pain sensation leading to unnoticed injuries (D)</p> Signup and view all the answers

Which of the following statements regarding aspirin use in diabetes management is accurate?

<p>Aspirin may be advised for secondary prevention or high-risk individuals. (B)</p> Signup and view all the answers

What is the typical nature of diabetic neuropathy associated with diabetic patients?

<p>Distal symmetric polyneuropathy (D)</p> Signup and view all the answers

What effect does renin-angiotensin system inhibition have on diabetic nephropathy?

<p>It improves or normalizes albuminuria levels (B)</p> Signup and view all the answers

How does microalbuminuria relate to the progression of diabetic nephropathy?

<p>It may regress to normoalbuminuria under certain circumstances (C)</p> Signup and view all the answers

Which treatment is not typically used for managing painful diabetic neuropathy?

<p>Statins (A)</p> Signup and view all the answers

What is a crucial lifestyle modification for the prevention of diabetic neuropathy?

<p>Regular blood pressure monitoring and control (B)</p> Signup and view all the answers

What type of dietary modification is important in the management of diabetic nephropathy?

<p>Restriction of sodium intake (B)</p> Signup and view all the answers

Which factor is associated with the worsening of neuropathy and microvascular complications in diabetes?

<p>Poor glucose control over time (C)</p> Signup and view all the answers

What is the primary method used to screen for diabetic nephropathy?

<p>Measurement of spot urine microalbumin to creatinine ratio (B)</p> Signup and view all the answers

Which neuropathy type is often characterized by a 'stocking-glove' distribution?

<p>Distal symmetric polyneuropathy (C)</p> Signup and view all the answers

Which treatment is recognized for managing foot ulcers in diabetic patients?

<p>Daily foot inspection (A)</p> Signup and view all the answers

Which of the following correctly describes the impact of the hexosamine pathway in diabetic complications?

<p>It diverts glucose from glycolysis, increasing altering gene expression. (A)</p> Signup and view all the answers

What key symptom differentiates severe NPDR from mild NPDR?

<p>Cotton wool spots (A)</p> Signup and view all the answers

Which treatment is primarily indicated for patients with high-risk proliferative diabetic retinopathy?

<p>Panretinal photocoagulation (PRP) (B)</p> Signup and view all the answers

What mechanism is primarily responsible for increased oxidative stress in diabetic retinopathy?

<p>Hyperglycemia-induced inflammation (C)</p> Signup and view all the answers

In diabetic nephropathy, what underlying structural change is characterized by glomerular disease?

<p>Glomerular sclerosis (D)</p> Signup and view all the answers

Which of these factors is considered a weaker piece of evidence regarding prevention therapies for retinopathy?

<p>Lipid-lowering therapy (D)</p> Signup and view all the answers

Which factor is NOT a direct risk factor for the development of diabetic nephropathy?

<p>Duration of fasting (D)</p> Signup and view all the answers

What is a primary characteristic of proliferative diabetic retinopathy?

<p>Neovascularization of the optic disc (C)</p> Signup and view all the answers

Which growth factor is associated with increased vascular permeability in the pathophysiology of diabetic retinopathy?

<p>Vascular Endothelial Growth Factor (VEGF) (A)</p> Signup and view all the answers

Which of the following conditions represents a common symptom of diabetic nephropathy?

<p>Microalbuminuria (D)</p> Signup and view all the answers

What condition is characterized by changes such as mesangial expansion and albuminuria?

<p>Diabetic nephropathy (C)</p> Signup and view all the answers

Which of the following is a primary cornerstone of therapy for the prevention of retinopathy?

<p>Glycemic control measures (B)</p> Signup and view all the answers

Which classification of diabetic retinopathy involves the presence of clinically significant macular edema?

<p>Severe non-proliferative retinopathy (NPDR) (B)</p> Signup and view all the answers

Which approach effectively reduces glucose levels in diabetic patients, suitable for preventing complications?

<p>Comprehensive glycemic control management (D)</p> Signup and view all the answers

Flashcards

Diabetic vascular complications

Diabetes can cause blood vessel damage in various parts of the body.

Diabetic microangiopathy

Thickening of the basement membrane in capillaries, leading to reduced blood flow and fragility.

Diabetic nephropathy

Damage to the blood vessels in the kidney, resulting in kidney disease.

Diabetic neuropathy

Damage to the blood vessels in the nerves, causing nerve damage.

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Diabetic retinopathy

Damage to the blood vessels in the eyes, leading to vision problems.

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How does diabetes damage tissues?

The process of abnormally high glucose levels in the blood damaging proteins and tissues in the body, leading to complications like thickened basement membranes.

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What is the relationship between hyperglycemia and microvascular diseases?

Hyperglycemia is strongly linked to microvascular diseases, which are diseases affecting small blood vessels.

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What are cardiovascular complications?

A group of complications affecting the circulatory system, specifically related to the hardening and narrowing of arteries due to plaque buildup.

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What is microangiopathy?

A type of cardiovascular complication where small blood vessels are affected, leading to issues like retinopathy (eye damage), kidney disease, and neuropathy (nerve damage).

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What are the potential coma-related complications of diabetes?

High blood sugar, ketoacidosis, and hyperosmolar non-ketotic states are just some of the potential complications associated with diabetes. Remember that individuals with diabetes are also susceptible to all other causes of coma that affect non-diabetics.

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What are the major health impacts of diabetes?

Diabetes is the leading cause of new cases of blindness, nontraumatic amputations, and renal failure.

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What is the impact of diabetes on life expectancy?

Increases in cardiovascular disease, renal failure, blindness, and amputations are all linked to diabetes.

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What are the major categories of complications of diabetes?

Atheroma, microangiopathy, renal failure, sepsis and infections, eye complications, and complications during pregnancy are all potential complications associated with diabetes.

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What is nodular glomerulosclerosis?

Nodular glomerulosclerosis is a specific type of kidney damage seen in diabetic nephropathy characterized by abnormal clumps of tissue (Kimmelstiel-Wilson nodules) within the glomeruli, which are the filtering units of the kidneys.

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Define diabetic nephropathy.

Diabetic nephropathy is kidney damage caused by diabetes. It involves the small blood vessels in the kidneys, leading to the formation of scar tissue and reduced kidney function over time.

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What is microalbuminuria?

Microalbuminuria is the presence of a small amount of protein in the urine. It's a sign of early kidney damage and a key marker for diabetic nephropathy.

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Explain hyperfiltration in diabetic nephropathy.

Hyperfiltration is an increased rate of blood filtering in the kidneys. It can happen in early stages of diabetic nephropathy, leading to larger-than-normal kidneys.

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What is macroalbuminuria?

Macroalbuminuria is a significant amount of protein in the urine, indicating more advanced kidney damage and a higher risk of progression to kidney failure.

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What medications are commonly used to manage diabetic nephropathy?

ACE inhibitors and angiotensin II receptor blockers are medications that can slow down the progression of diabetic nephropathy by lowering blood pressure and reducing protein in the urine.

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What is the 'stocking-glove' distribution in diabetic neuropathy?

The 'stocking-glove' distribution of diabetic neuropathy refers to the pattern of nerve damage in the legs and feet, often affecting the toes and hands.

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Define diabetic neuropathy.

Diabetic neuropathy is a nerve damage caused by diabetes. It can affect various nerves throughout the body, leading to pain, numbness, tingling, and other symptoms.

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What is Charcot arthropathy?

Charcot arthropathy is a specific type of joint destruction that can occur in the feet of individuals with diabetic neuropathy. It's caused by nerve damage and repeated trauma.

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What are diabetic foot ulcers?

Diabetic foot ulcers are sores or wounds on the feet that are difficult to heal due to nerve damage, poor blood circulation, and other complications.

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How does diabetes affect heart attack risk?

Diabetes significantly increases the risk of heart attacks, with individuals with diabetes experiencing three to five times the risk compared to the general population.

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How does diabetes affect stroke risk?

Stroke risk is doubled or tripled in individuals with diabetes, primarily due to blood clots and blockages in the brain's blood vessels.

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How does diabetes affect peripheral vascular disease?

Peripheral vascular disease (PVD) involves narrowing of blood vessels in the legs, making circulation difficult. It's significantly more common in people with diabetes, with a 40 times higher risk of amputation.

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What is "silent ischemia" in diabetes?

Diabetes can lead to silent ischemia, meaning heart attacks can occur without noticeable symptoms, making it crucial to have regular checkups and monitor risk factors.

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What are the main strategies for preventing cardiovascular complications in diabetes?

Maintaining good blood sugar control, managing blood pressure, and cholesterol levels are crucial for preventing cardiovascular complications. This includes weight loss, exercise and smoking cessation.

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What are the major financial impacts of diabetes?

Diabetes has a significant financial impact, with the total annual cost in the US exceeding $327 billion, largely due to hospital stays, medications, and diabetes supplies.

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How much more do people with diabetes spend on medical expenses?

Diabetes significantly increases healthcare expenditures, with individuals with diabetes incurring an average of $16,752 per year, which is nearly three times higher than those without diabetes.

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What is the key focus for managing diabetes-related cardiovascular complications?

Early intervention and proactive management of risk factors, including blood sugar control, blood pressure, cholesterol, weight loss, exercise and smoking cessation, are essential for managing cardiovascular complications associated with diabetes.

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Polyol Pathway

A metabolic pathway that converts glucose into sorbitol. Reduced NADPH leads to decreased glutathione and oxidative stress.

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Advanced Glycosylation End Products (AGEs)

A protein modification pathway occurring in the presence of high glucose levels. AGE molecules can alter protein structure and function, contributing to inflammation and vascular damage.

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Protein Kinase C (PKC) Activation

A signaling pathway that gets activated by high glucose levels. It plays a key role in diabetic complications by altering gene expression and regulating inflammation.

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Hexosamine Pathway

A metabolic pathway that diverts glucose away from glycolysis. Increased levels of N-acetyl glucosamine affect gene expression, promoting factors like TGF-β and PAI-1.

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Microaneurysms

The presence of small, red blood vessel bulges in the retina, a sign of early diabetic retinopathy.

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Proliferative Diabetic Retinopathy (PDR)

A type of retinopathy where new blood vessels grow on the retina, potentially leading to bleeding and vision loss.

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Nonproliferative Diabetic Retinopathy (NPDR)

A type of retinopathy that does not involve new blood vessel growth, but can still lead to vision loss due to swelling and leakage.

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Albuminuria

The presence of excess protein in the urine, a hallmark of diabetic nephropathy.

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Glomerular Disease

A condition where the blood vessels in the kidneys become thickened and damaged, leading to kidney disease.

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Hyperglycemia

A significant risk factor for diabetic retinopathy, characterized by high blood sugar levels over an extended period.

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Hypertension

A major risk factor for developing diabetic retinopathy, often accompanied by hyperglycemia in diabetes.

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Glycemic Control

A cornerstone treatment for diabetic retinopathy, aiming to reduce the risk of progression and complications.

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Photocoagulation

A type of treatment for diabetic retinopathy, using laser to destroy abnormal blood vessels in the eye.

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Anti-VEGF Therapy

A therapeutic strategy for diabetic retinopathy, targeting the growth and proliferation of abnormal blood vessels.

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What are capillary basement membranes?

Capillary basement membranes are the thin layers surrounding blood vessels. In diabetes, these membranes thicken due to high blood sugar levels, making it harder for blood to flow through the vessels.

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Health Impact of Diabetes

Diabetes is the leading cause of blindness, amputations, and kidney failure, impacting life expectancy and healthcare costs.

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How Diabetes Damages Tissues

High blood sugar levels damage blood vessels, leading to complications in various organs. Thickening of basement membranes and excess protein in the urine are key signs.

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Diabetic Foot Ulcers

Diabetic foot ulcers are sores that can easily get infected and are difficult to heal due to poor blood circulation and nerve damage.

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Cardiovascular Complications of Diabetes

Diabetes can lead to heart attacks, strokes, and peripheral vascular disease, making it crucial to manage blood sugar, blood pressure, and cholesterol.',

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Diabetic Ketoacidosis

Diabetic ketoacidosis is a serious complication of diabetes, characterized by high blood sugar, ketones in the urine, and dehydration. It requires immediate medical attention.

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How does diabetes increase heart attack risk?

Diabetes significantly increases the risk of heart attacks, with individuals with diabetes experiencing 3 to 5 times the risk compared to the general population. This means that people with diabetes are far more likely to have a heart attack than those without.

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How does diabetes increase stroke risk?

Stroke risk is doubled or tripled in individuals with diabetes. This is primarily due to blood clots and blockages in the brain's blood vessels, which are more likely to occur with diabetes.

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What is the link between diabetes and peripheral vascular disease?

Peripheral vascular disease (PVD) involves narrowing of blood vessels in the legs, making circulation difficult. It's significantly more common in people with diabetes, with a 40 times higher risk of amputation. This means people with diabetes are much more likely to experience poor circulation and potential limb loss.

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What are the financial impacts of diabetes?

Diabetes has a significant financial impact, with the total annual cost in the US exceeding $327 billion. This is partly due to hospital stays, medications, and diabetes supplies.

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How can we prevent macrovascular complications?

Maintaining good blood sugar control, managing blood pressure, and cholesterol levels are essential for preventing cardiovascular complications. This includes weight loss, exercise, and smoking cessation.

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What is the key focus for managing cardiovascular complications in diabetes?

Early intervention and proactive management of risk factors, including blood sugar control, blood pressure, cholesterol, weight loss, exercise, and smoking cessation are essential for managing cardiovascular complications associated with diabetes.

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What is silent ischemia, and why is it important?

Diabetes can lead to silent ischemia, meaning heart attacks can occur without noticeable symptoms, making it crucial to have regular checkups and monitor risk factors.

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Microalbuminuria

A marker of early kidney damage, usually indicating the presence of small amounts of protein in the urine.

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Macroalbuminuria

The presence of significant amounts of protein in the urine, indicating a more advanced stage of kidney damage.

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Distal Symmetric Polyneuropathy

A type of diabetic neuropathy that affects nerves throughout the body, often presenting as a symmetrical 'stocking-glove' pattern of numbness and tingling in the feet and hands.

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Charcot Arthropathy

A joint destruction that occurs in the feet of individuals with diabetic neuropathy, often due to repeated injury and poor blood supply.

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Macrovascular Complications

A group of complications that affect larger blood vessels, like the heart, brain, and legs, often caused by plaque buildup and atherosclerosis.

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ACE Inhibitors and ARBs

A crucial medication class used in diabetic nephropathy to reduce pressure and protect the kidneys, often including drugs like lisinopril and losartan.

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Neuropathic Foot Ulcer

A type of diabetic foot ulcer that can develop in the absence of a clear injury, often due to sensory neuropathy and poor blood circulation.

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Study Notes

Complications of Diabetes

  • Diabetes is the 5th leading cause of death.
  • Life expectancy is reduced by 5-10 years.
  • Cardiovascular disease is 2 to 4 times more likely.
  • Nerve damage occurs in 60-70% of patients.
  • Diabetes is the leading cause of renal failure, blindness, and nontraumatic amputations.

Learning Outcomes

  • The microvascular and macrovascular complications of diabetes should be listed.
  • The pathophysiology of each complication needs to be explained.
  • The risk factors for the development of complications should be outlined.
  • The common signs and symptoms of each complication should be outlined.
  • The overarching principles of investigation and management of diabetic complications should be outlined.
  • The impact of diabetic complications on quality of life, healthcare costs, and mortality rates should be analyzed.

Health Impact of the Disease

  • Hyperglycemia is strongly correlated with microvascular disease.
  • Sustained progression of retinopathy, progression to albuminuria (>300 mg/dL), progression to clinical neuropathy, and progression to microalbuminuria (>40 mg/dL) are all related to HbA1c levels.
  • HbA1c levels are strongly correlated with the progression of microvascular diseases, as shown in the NEJM 1993 data.

Summary of Pathological Complications of Diabetes

  • Coma can be caused by hypoglycemia, ketoacidosis, or hyperosmolar non-ketotic conditions.
  • Cardiovascular complications include atherosclerosis, stroke, and peripheral vascular disease (limb amputation).
  • Microangiopathy leads to cardiac failure, retinopathy, diabetic kidney disease, and neuropathy.
  • Renal failure is associated with diabetic kidney disease or pyelonephritis & renal papillary necrosis.
  • Infections such as tuberculosis, bronchopneumonia, Covid-19, skin infections (diabetic foot) and fungal infections are possible.
  • Eye complications include retinopathy, cataracts, macular edema, and glaucoma.
  • Pregnancy complications include gestational diabetes; pre-existing diabetes increasing risk of developmental abnormalities and complications for the mother.
  • Diabetes can lead to generalized (systemic) protein basement membrane thickening, reducing blood flow, creating ischemia and making the lining of blood vessels more fragile, therefore causing hemorrhage.
  • Overall, the summary highlights the wide range of organ systems that can be affected by diabetes and its complications.

How Diabetes Damages Tissues

  • In diabetes, the protein basement membrane thickens, reducing blood flow and causing ischemia.
  • The lining of blood vessels becomes fragile, leading to hemorrhage.

Proteins Damaged in Blood Vessel Walls and Capillary Basement Membranes

  • Capillary basement membranes thicken throughout the body.
  • These vessels function poorly, supplying insufficient blood to surrounding tissues.
  • They become fragile and prone to bleeding.
  • Vessels in the kidney become damaged, leading to diabetic glomerulosclerosis and renal papillary necrosis.
  • Vessels supplying the nerves are damaged, resulting in neuropathy.
  • Vessels in the eyes are damaged, causing diabetic retinopathy and resulting in vision loss.
  • Vessels in skin, particularly the feet, are damaged, leading to ulcers.

Diabetic Nephropathy

  • The abnormal capillaries in the kidney are best observed using a PAS stain.
  • An image of a kidney glomerulus may show thickening of the capillary basement membranes and increased protein deposition in the mesangium. More detailed study of this will be included in a later lecture.
  • Diabetic nephropathy significantly impacts kidney function leading to complications such as end-stage kidney disease(ESKD) requiring dialysis or transplantation.

Proposed Mechanisms of Hyperglycemia-Induced Tissue Damage

  • Hyperglycemia, through repeating acute changes in cellular metabolism and cumulative long-term changes in stable macromolecules, leads to tissue damage.
  • Genetic factors are involved as independent accelerating factors.

Molecular Pathways Implicated in Diabetic Tissue Damage

  • Aldose Reductase converts glucose to sorbitol, decreasing NADPH and glutathione (increasing oxidative stress).
  • Advanced Glycosylation End-products (AGE) modify intra- and extracellular proteins.
  • Increased inflammatory cytokines and growth factors, and altered gene expression are related to protein Kinase C activation, decreasing endothelial nitric oxide synthase (eNOS), increased endothelin-1, TGF-β, PAI-1, VEGF, and NFKB.
  • The hexosamine pathway diverts glycolysis and increases N-acetylglucosamine, altering gene expression of TGF-β and PAI-1.

Microvascular Complications of DM

  • Retinopathy
  • Nephropathy
  • Neuropathy

Diabetic Retinopathy (DR)

  • Between 20-74 years, DR is one of the common causes of blindness.
  • Many patients have no symptoms, meaning treatment may be too late.
  • Visual acuity decreases progressively, correlating with the duration of the disease.
  • Type 1 diabetes frequently affects patients 15-20 years after diagnosis.
  • About 20% prevalence at the time of diagnosis is seen for Type 2 diabetes, with an average onset 4-7 years beforehand, and 50-80% incidence after 20 years.

Risk Factors for Diabetic Retinopathy

  • Duration of diabetes
  • Level of glycemic control
  • Hypertension
  • Other microvascular complications (e.g., nephropathy & neuropathy)
  • Dyslipidemia
  • Pregnancy, temporarily increasing risk and progression.

Pathophysiology of Diabetic Retinopathy

  • Hyperglycemia dysregulates retinal blood flow, causing oxidative stress and inflammation.
  • Vascular permeability increases, leading to edema.
  • Microthrombosis causes ischemia.
  • Growth factors (IGF-1, PDGF, VEGF) result in increased proliferation.
  • Genetic factors increase incidence in first-degree relatives & association with nephropathy (in T1DM).
  • Hypertension and dyslipidemia may also be contributing factors.

Classification of Retinopathy

  • Two major categories:
    • Non-proliferative retinopathy (NPDR): Mild/Moderate/Severe
    • Proliferative retinopathy (PDR): Early/High-Risk/Severe
  • Macular edema can occur at any stage: Clinically significant macular edema (CSME) is diagnosed based on size of area affected and proximity to the macula.

Eye Findings in Retinopathy

  • Mild: Microaneurysms, dot hemorrhages, hard exudates
  • Moderate/Severe: Mild findings plus soft exudates (cotton wool spots), venous beading, intraretinal microvascular abnormalities (IRMA), occluded/dilated tortuous capillaries

Mild NPDR

  • Shown in fundoscopic images of Normal Fundus and Non-proliferative Retinopathy, NPDR is identified as possessing retinal microaneurysms and dot hemorrhages with lipid exudates.
  • Progressively transitioning into PDR, there is a 5% annual increase in transition to the disease.

Severe NPDR

  • Shown in fundoscopic images of Severe NPDR characterized by transition from NPDR (50-75% annual), there's a progression to PDR.

PDR

  • Fundoscopic images of PDR demonstrates Neovascularization of the Optic Disc (NVD) and Neovascularization Elsewhere on Retina (NVE).

Prevention of Retinopathy

  • Cornerstones of therapy: Glycemic control (DCCT, UKPDS Trials), antihypertensive therapy.
  • Weaker evidence: Lipid lowering therapy, Antiplatelet agents, Carbonic anhydrase inhibitors.

Treatment of Retinopathy

  • NPDR with CSME: Focal laser photocoagulation
  • High-risk and severe PDR: Panretinal photocoagulation (PRP) (600-1600 laser burns, grid pattern) and medical therapy (intravitreal glucocorticoids, VEGF inhibitors).
  • Vitrectomy is indicated for non-clearing vitreous hemorrhage, traction retinal detachment involving the fovea, and severe PDR not responsive to PRP.

(Remainder of the study notes are identical to the original)

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