GW BGZ 2025 Case 10 - ‘Sporty’ office workers

What are the reference values for cholesterol?

Lipid parameter	Optimal/reference value	Clinical meaning
Total cholesterol	< 200 mg/dL (< 5.2 mmol/L)	Desirable cardiovascular risk profile
LDL cholesterol	< 100 mg/dL (< 2.6 mmol/L)	Lower values reduce atherosclerosis risk
HDL cholesterol	> 40 mg/dL men; > 50 mg/dL women (> 1.5 mmol/L)	Protective against CVD

• HDL (“good cholesterol”) removes excess cholesterol from peripheral tissues and transports it to the liver for excretion.

• LDL (“bad cholesterol”) deposits cholesterol into arterial walls, promoting atherosclerosis.

• Triglycerides are elevated in metabolic dysfunction and increase cardiovascular risk.

• VLDL mainly transports triglycerides from the liver to tissues.

High LDL and triglycerides together with low HDL are characteristic of sedentary individuals and metabolic syndrome.

What are blood pressure categories?

Blood pressure reflects the force exerted by blood on arterial walls and is a major determinant of cardiovascular risk.

• Systolic pressure = pressure during ventricular contraction.

• Diastolic pressure = pressure during ventricular relaxation.

Classification	Systolic BP (mmHg)	Diastolic BP (mmHg)
Normal	< 120	and < 80
Elevated / Prehypertension	120–129	and < 80
Hypertension stage 1	130–139	or 80–89
Hypertension stage 2	≥ 140	or ≥ 90

What are BMI categories?

BMI is a screening measure used to classify body weight relative to height.

BMI Category	BMI (kg/m²)
Underweight	< 18.5
Normal weight	18.5–24.9
Overweight	25.0–29.9
Obesity class I	30.0–34.9
Obesity class II	35.0–39.9
Obesity class III	≥ 40

Higher BMI values are associated with increased cardiometabolic risk, insulin resistance, hypertension, dyslipidemia, and several forms of cancer.

What are normal, prediabetes, and diabetes glucose values?

Measurement	Normal	Prediabetes	Diabetes
Fasting plasma glucose	< 5.6 mmol/L	5.6–6.9 mmol/L	≥ 7.0 mmol/L

Elevated glucose reflects insulin resistance or insufficient insulin production.

What is a sedentary lifestyle?

A sedentary lifestyle refers to prolonged periods of physical inactivity with low energy expenditure, such as sitting for long durations and insufficient participation in structured exercise or daily physical activity. <1.5 METS

Physical inactivity negatively affects multiple physiological systems and is considered a major modifiable risk factor for chronic disease.

How does sedentary behavior affect diabetes risk?

• Reduces GLUT-4 activity in muscles

• Lowers glucose uptake

• Increases insulin resistance

• Increases visceral fat and inflammation

Result: higher risk of type 2 diabetes.

How does sedentary behavior affect cardiovascular disease?

• Increases LDL and decreases HDL

• Increases blood pressure via vascular stiffness

• Promotes endothelial dysfunction

• Increases atherosclerosis progression

Result: higher risk of heart attack and stroke.

How does sedentary behavior affect dyslipidemia?

Sedentary behavior worsens dyslipidemia by disrupting normal lipid metabolism and reducing the body’s ability to clear and use fats.

It decreases lipoprotein lipase (LPL) activity in skeletal muscle, which normally breaks down triglycerides and allows fatty acid uptake into muscles. As a result, triglycerides and VLDL increase in the blood.

It also reduces HDL (good cholesterol) production and impairs reverse cholesterol transport, meaning less cholesterol is removed from tissues and arteries back to the liver.

In addition, sedentary behavior reduces LDL receptor activity in the liver, leading to decreased LDL clearance and therefore higher LDL levels in circulation.

Overall, the typical dyslipidemia pattern in sedentary individuals is:

• LDL increased

• Triglycerides increased

• VLDL increased

• HDL decreased

This lipid profile increases the risk of atherosclerosis, cardiovascular disease, and metabolic syndrome.

How does sedentary behavior affect obesity?

• Reduces energy expenditure

• Causes positive energy balance

• Increases visceral fat

• Lowers metabolic rate via muscle loss

Result: obesity and metabolic syndrome.

How does sedentary behavior affect hypertension?

• Increases sympathetic nervous system activity

• Increases vascular resistance

• Reduces nitric oxide (vasodilation)

• Promotes arterial stiffness

Result: chronic high blood pressure.

How does sedentary behavior affect cancer risk?

• Increases chronic inflammation (TNF-α, IL-6)

• Increases oxidative stress (DNA damage)

• Increases insulin/IGF-1 (cell growth stimulation)

• Weakens immune surveillance

Result: higher risk of breast, colon, and endometrial cancer.

What are risk factors for type 2 diabetes?

• Obesity → increases insulin resistance

• Sedentary lifestyle → lowers glucose use by muscles

• High-sugar diet → chronically raises blood glucose

• Family history → genetic predisposition

• Aging → reduced insulin sensitivity

What are risk factors for cardiovascular disease?

• High LDL → plaque buildup in arteries

• Hypertension → damages vessel walls

• Smoking → causes inflammation and vessel damage

• Diabetes → accelerates atherosclerosis

• Obesity → increases cardiac workload and inflammation

What are risk factors for dyslipidemia?

• Poor diet → increases LDL and triglycerides

• Obesity → alters fat metabolism

• Physical inactivity → lowers HDL (“good” cholesterol)

• Smoking → worsens lipid profile

• Genetics → inherited lipid metabolism disorders

What are risk factors for obesity?

• Excess calories → fat storage exceeds energy use

• Sedentary lifestyle → low energy expenditure

• Poor sleep → disrupts hunger hormones

• Stress → increases cortisol and overeating

• Genetics → influences metabolism and appetite

What are risk factors for hypertension?

• High salt intake → increases water retention and pressure

• Obesity → increases vascular resistance

• Smoking → constricts blood vessels

• Stress → increases sympathetic activity

• Kidney disease → impairs blood pressure regulation

What are risk factors for cancer?

• Smoking → causes DNA mutations

• UV/radiation → damages DNA

• Obesity → promotes inflammation and hormone changes

• Alcohol → toxic metabolites damage cells

• Chronic inflammation → increases abnormal cell growth

• Genetics → inherited mutations increase susceptibility

How does exercise reduce diabetes risk?

• Increases insulin sensitivity

• Increases GLUT-4 glucose uptake

• Reduces visceral fat

• Lowers blood glucose

Strength training increases muscle mass; endurance training improves glucose use and insulin sensitivity.

How does exercise reduce cardiovascular disease risk?

• Improves endothelial function

• Reduces inflammation

• Lowers LDL and increases HDL

• Reduces blood pressure

Endurance training has the strongest effect on heart and vascular health.

How does exercise improve dyslipidemia?

• Lowers triglycerides

• Lowers LDL

• Raises HDL

• Increases fat oxidation

Endurance training is most effective for lipid improvement.

How does exercise reduce obesity?

• Increases calorie expenditure

• Increases resting metabolic rate (strength training)

• Reduces visceral fat

• Improves energy balance

How does exercise reduce hypertension?

• Decreases peripheral resistance

• Improves arterial elasticity

• Reduces sympathetic nervous activity

• Increases nitric oxide production

Result: lower resting blood pressure.

How does exercise reduce cancer risk?

• Lowers inflammation

• Reduces insulin and IGF-1

• Improves immune function

• Reduces obesity

Risk reduction:

• Colon cancer: ~20–50%

• Breast cancer: ~10–40%

• Prostate cancer: ~10%

Why does exercise lower blood pressure long-term?

• Lower peripheral resistance (more elastic vessels)

• Stronger heart → higher stroke volume, lower resting heart rate

• Reduced sympathetic nervous system activation

Together these reduce resting blood pressure.

What is the difference between strength and endurance training effects?

Strength training:

• Increases muscle mass

• Improves glucose uptake

• Increases resting metabolic rate

• Supports diabetes prevention

Endurance training:

• Improves cardiovascular fitness

• Strongly lowers blood pressure

• Improves lipid profile

• Reduces fat mass

Endurance training has broader effects on cardiovascular risk factors, while strength training is essential for muscle and glucose metabolism.

What is Type 2 Diabetes Mellitus?

Type 2 diabetes is a chronic metabolic disorder characterized by insulin resistance and progressive β-cell dysfunction, leading to persistent hyperglycemia.

In insulin resistance, body cells (especially muscle, liver, and fat tissue) respond less effectively to insulin, meaning higher levels of insulin are required to achieve normal glucose uptake. Over time, pancreatic β-cells cannot maintain sufficient insulin production, causing blood glucose levels to rise chronically.

Main physiological features:

• Reduced glucose uptake in muscle and fat cells

• Increased hepatic glucose production

• Elevated fasting and postprandial blood glucose

• Progressive insulin secretory failure

Long-term complications involve damage to blood vessels, nerves, kidneys, and eyes due to chronic hyperglycemia and metabolic stress.

What is Cardiovascular Disease (CVD)?

Cardiovascular disease refers to a group of disorders affecting the heart and blood vessels, most commonly caused by atherosclerosis, a progressive narrowing and hardening of arteries due to plaque formation.

Atherosclerosis develops through:

1. Endothelial dysfunction (damage to vessel lining)

2. LDL cholesterol infiltration into arterial walls

3. LDL oxidation and inflammatory response

4. Monocyte migration and transformation into macrophages

5. Foam cell formation

6. Smooth muscle proliferation and fibrous plaque formation

7. Plaque rupture and thrombosis

Consequences include:

• Coronary artery disease (angina, myocardial infarction)

• Cerebrovascular disease (stroke)

• Peripheral artery disease

The main pathological issue is reduced blood flow and oxygen delivery due to arterial narrowing or blockage.

What are the steps for atherosclerosis development?

Atherosclerosis is a disease of the large and medium-sized arteries in which fatty plaques develop on the inside of the arterial wall. Steps in the development of atherosclerosis:

1. It begins with endothelial dysfunction which is a change in the phenotype of the endothelium due to many different conditions (hypertension, smoking, hyperlipidaemia). This leads to increased permeability of the blood vessel wall, leukocyte adhesion, ,and thrombosis.

2. Subsequently, lipoproteins (LDL) accumulate in the blood vessel wall.

3. Monocytes bind to the endothelium, allowing them to migrate to the tunica intima (inner layer of the blood vessel). There, they differentiate into macrophages and foam cells (macrophages that carry fat)

4. Platelets bind to the assembly

5. The activated platelets, macrophages, and endothelial cells release various factors. This leads to the recruitment of smooth muscle cells to the tunica intima. These can originate from the tunica media (middle layer of the blood vessels) or circulating precursors

6. Smooth muscle cells proliferate, extracellular matrix is formed, and T-cells are attracted. The proliferation of smooth muscle cells and the formation of extracellular matrix (collagen) lead to the formation of an atheroma. This process is driven by platelet-derived growth factors (PDGF) released by platelets, macropahges, endothelial cells, and smooth muscle.

7. Both within macrophages and smooth muscle cells, as well as extracellular, fat accumulation

8. The extracellular matrix calcifies, and later in the disease, necrosis occurs.

What is Dyslipidemia?

Dyslipidemia is an abnormal lipid profile in the blood, typically involving elevated LDL cholesterol, elevated triglycerides, and/or reduced HDL cholesterol.

It reflects an imbalance in lipid transport and metabolism.

Key abnormalities:

• Increased LDL (cholesterol delivery to tissues)

• Increased triglycerides (energy storage fats in blood)

• Increased VLDL (triglyceride transport particles)

• Decreased HDL (cholesterol removal from tissues)

Pathophysiologically, dyslipidemia promotes:

• Cholesterol accumulation in arterial walls

• Oxidation of LDL

• Formation of atherosclerotic plaques

It is a major risk factor for cardiovascular disease.

What is Obesity?

Obesity is a chronic condition characterized by excess body fat accumulation, resulting from long-term imbalance between energy intake and energy expenditure.

It is commonly defined using BMI, but physiologically it reflects excessive adipose tissue storage.

Key mechanisms:

• Increased fat storage in adipose tissue

• Expansion of visceral (abdominal) fat depots

• Hormonal dysregulation (leptin, insulin, ghrelin)

• Chronic low-grade inflammation

Visceral fat is especially metabolically active and contributes to:

• Insulin resistance

• Dyslipidemia

• Increased cardiovascular risk

Obesity is a central driver of many metabolic and cardiovascular diseases.

What is Hypertension?

Hypertension is a chronic condition characterized by persistently elevated arterial blood pressure, defined by increased systolic and/or diastolic pressure.

Blood pressure depends on:

• Cardiac output

• Peripheral vascular resistance

• Blood volume

• Arterial elasticity

• Autonomic nervous system activity

Pathophysiological mechanisms include:

• Increased vascular resistance due to arterial stiffening

• Endothelial dysfunction and reduced vasodilation (low nitric oxide)

• Increased sympathetic nervous system activity

• Structural changes in blood vessel walls

Sustained hypertension damages blood vessels and increases workload on the heart, contributing to heart failure, stroke, and kidney disease.

What is Cancer (Oncology-related disease)?

Cancer is a group of diseases characterized by uncontrolled cell growth and division due to genetic mutations and failure of normal cell regulatory mechanisms.

Cancer development involves:

• DNA damage and mutations

• Uncontrolled cellular proliferation

• Avoidance of apoptosis (programmed cell death)

• Ability to invade surrounding tissues and metastasize

Key biological mechanisms:

• Chronic inflammation promoting DNA damage and cell proliferation

• Oxidative stress causing genetic instability

• Hormonal signals (e.g., insulin, IGF-1, estrogen) stimulating growth

• Immune system evasion by tumor cells

Cancer can develop in almost any tissue and becomes dangerous when cells invade or spread to other organs, disrupting normal function.