EHS 260: Exam II Review Notes

EHS 260: Exam II Review Pt 1

Overview of Class Focus

  • The first section of this class concentrated on EXPOSURES related to health outcomes.
      - Physical Activity: Decreases mortality risk
      - Sedentary Time: Increases mortality risk
        - Associated with increased obesity, which subsequently increases mortality risk.
      - Physical Activity: Increases physical fitness
        - Increased physical fitness leads to decreased mortality risk.

Major Causes of Death Related to Exposures

  • The primary causes of death that were emphasized:
      - Cardiovascular Disease (CVD)
      - Diabetes
      - Metabolic Syndrome
      - Cancer

  • The ultimate OUTCOME of concern is mortality, influenced by various underlying factors.

  • Discussion on whether all sources of mortality are included: Car accidents, snake bites, reckless behavior, etc.

Cardiometabolic Disease Pathophysiology

  • Emphasis on the progression from Healthy to death from cardiovascular disease is not straightforward.
      - Most individuals progress through a series of pre-disease symptoms before reaching severe disease states.
      - Pathophysiology can progress:
        - Slowly over years, but can be expedited by negative overloads (stressors such as obesity).
        - There are notable differences in disease progression by race/ethnicity.

  • Behaviors and Choices:
      - Personal behaviors impact physiological health across multiple pathways.
      - Starting point for discussion is excess body fat (Obesity).

Visceral Adipose Tissue (VAT)

  • Distinction made between types of fat: Subcutaneous vs Visceral.

  • Visceral Adipose Tissue (VAT):
      - Also known as Central adiposity or Central obesity.
      - Defined as:
        - Fat that accumulates around and interspersed between the organs (Rennie et al. Int J Epidemiol 2003).

Inflammation, Oxidative Stress, and Insulin Resistance

  • Inflammation:
      - Described as a shorthand term for pro-inflammatory cytokines/chemokines.
      - Cell signaling pathways react as if the body is experiencing illness, which promotes disease development.

  • Reactive Oxygen Species (ROS):
      - Produced by visceral fat cells.
      - They degrade cellular integrity, likened to rusting metal or decaying fruit.
      - Damaged cells through oxidative stress contribute to cardiovascular disease.

Insulin and Glucose Regulation

  • Insulin's Role:
      - Released by the pancreas following carbohydrate ingestion.
      - Its primary purpose is to stimulate glucose uptake in muscles and prevent the liver from continuing glucose production.

  • Insulin Resistance:
      - Normal insulin signaling facilitates glucose uptake; however, inactivity and inflammation disrupt this process.
      - Muscles and the liver may become resistant to insulin signals, compromising metabolic health.

Consequences of Insulin Resistance

  • When insulin’s effects become inadequate:
      - The pancreas compensates by producing more insulin but this is not a comprehensive solution.

  • Prediabetes:
      - Characterized by slight increases in blood glucose levels that fall short of diabetes classification.

Lipid Profiles and Cardiovascular Health

  • High Triglycerides and Cholesterol:
      - Poor dietary habits, inactivity, and energy surplus lead to plaque accumulation in arteries.
      - Triglycerides: Transport fats throughout the body; can indicate metabolic issues.
      - Cholesterol: Offers structural support but, in high levels, can contribute to cardiovascular disease risk.
      - HDL Cholesterol: Known as “good cholesterol”; lower levels increase health risks.

High Blood Pressure Implications

  • Plaque formation narrows blood vessels, leading to increased systemic pressure.

  • This causes the heart to work harder to maintain blood circulation.

Metabolic Syndrome: Overview

  • Defined as a pre-disease state characterized by a collection of symptoms.
      - Requires the presence of at least three of the five following criteria:
        - High Visceral/Abdominal Obesity
        - High Blood Pressure
        - High Blood Sugar
        - High Triglycerides
        - Low HDL Cholesterol/High LDL Cholesterol
        - Or use of medications related to metabolic control (e.g., diabetes, antihypertensive, cholesterol-lowering drugs).

Mechanical Assessments of Metabolic Syndrome

  • Measurement of Visceral Adiposity:
      - BMI not suitable for assessing visceral fat; waist circumference is preferred.
      - Common measurement cut-off: >90 cm (Male) and >80 cm (Female).

  • Blood Pressure Measurement:
      - Measured with a sphygmomanometer during the heart's contraction (systole) and relaxation (diastole).
      - Normal systolic pressure is <120 mmHg, diastolic pressure is <80 mmHg; MS cut-point defined as >130 and >85 respectively.

Biomarker Assessments for Metabolic Syndrome

  • Fasting Blood Glucose:
      - Normal range: >70 but <100 mg/dL; elevated levels indicate metabolic risk (cut-point >100 mg/dL).

  • Triglycerides: Cut-point >110 mg/dL indicates higher metabolic risk.

  • HDL Cholesterol Levels:
      - Cut-points: <40 mg/dL for males and <50 mg/dL for females signal increased risk.

Importance of Addressing Metabolic Syndrome

  • Metabolic syndrome represents a transitional health state.
      - Denotes when lifestyle choices significantly impact health; intervention is crucial to prevent progression to disease.
      - Conditions previously deemed significant have seen changes in their perception, with a trend towards describing states of pre-disease for targeted approaches.

Progression from Insulin Resistance to Type II Diabetes

  • Prolonged insulin resistance strains pancreatic function, potentially leading to its failure (i.e., pancreas 'quits').

  • Resultant condition reveals elevated blood glucose levels and loss of control over blood sugar leading to Type II Diabetes.

Diagnosing Type II Diabetes

  • Defined by fasting blood glucose levels exceeding 125 mg/dL or hemoglobin A1c levels >6.5%.

  • Consequences associated with poor glycemic control include vascular damage, retinopathy, nephropathy, and peripheral vascular complications.

The 'Perfect Storm'

  • Clinical representation of multiple cardio-metabolic stressors:
      - Narrowed blood vessels (Atherosclerosis)
      - Elevated blood pressure (Hypertension)
      - Increased blood viscosity (Diabetes)
      - Greater risk of arterial blockage and subsequent ischemia affecting various organs.

Consequences of Ischemia

  • Heart Ischemia: Results in angina, shortness of breath, and myocardial infarction.

  • Cerebral Ischemia: Leads to stroke and potential brain tissue death.

  • Peripheral Ischemia: Affects blood flow to limbs, impacting physical capability.

Heart Failure Due to Chronic Conditions

  • Years of chronic conditions (atherosclerosis, diabetes, hypertension) place extreme stress on the heart.
      - The heart must pump harder which may lead to structural and functional deterioration (e.g., decreased ejection fraction, positive feedback loop towards heart failure).

Epidemiological Data on Diabetes and Cardiovascular Disease

  • Diabetes and cardiovascular disease incidence statistics with significant values above 12% in certain demographics.

  • Stroke death rates in specific counties during the timeframe of 2000-2006, with rates varying significantly by state.

Breast Cancer and Obesity

  • Obesity related to cancer risk:
      - Certain cancers show strong correlations with obesity classifications.
      - The National Cancer Institute highlights risks associated with various forms of cancer relative to body weight.

Mutational Drivers in Cancer

  • Descriptive insight into the genetic mutations associated with cancer development:
      - Gas/Brake mechanism: describing mutations accelerating or inhibiting cellular functions leading to neoplastic transformation.

  • Most cancers are diseases of aging, with increased incidence in older populations due to accumulation of mutagenic damage over time.

Summary of Hormonal Influences in Cancer Development

  • Hyperinsulinemia and associated growth factors like IGF-1 drive tumorigenic activity by stimulating cellular proliferation.

  • Insulin resistance corresponds with increased levels of circulating insulin amplifying cancer risk.

Conclusion: Pathophysiology of Cancer and Cardiometabolic Disease

  • A cascade effect of unhealthy behaviors leads to obesity, insulin resistance, chronic inflammation, and ultimately heart disease and cancer.

  • The significance of physical activity and dietary habits in reversing these trends is emphasized, marking the importance of preventative health behaviors.