Glucose Intolerance and Type 2 Diabetes
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Questions and Answers

What is the primary goal of treatment for type 2 diabetes?

  • To increase lipolysis in adipose tissue
  • To enhance insulin production
  • To completely eradicate diabetes
  • To minimize fluctuations in blood glucose levels (correct)

    • Which of the following pharmacotherapies is a key drug used for treating type 2 diabetes?

  • Acarbose
  • Insulin
  • Sulfonylureas
  • Metformin (correct)

    • What is a primary consequence of insulin resistance in the liver?

  • Enhanced glucose uptake from the bloodstream
  • Increased lipid synthesis
  • Inhibition of gluconeogenesis
  • Unregulated hepatic glucose production (correct)

    • Which lifestyle intervention is NOT typically recommended for managing type 2 diabetes?

    <p>Increased sugar intake</p> Signup and view all the answers

    Which complication is NOT considered a metabolic complication of type 2 diabetes?

    <p>Neuropathies</p> Signup and view all the answers

    Which of the following tissues is primarily affected by insulin resistance regarding glucose uptake?

    <p>Skeletal muscle</p> Signup and view all the answers

    How does insulin resistance affect lipolysis in adipose tissue?

    <p>It leads to increased lipolysis.</p> Signup and view all the answers

    What vascular complication is associated with type 2 diabetes?

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

    What is the initial physiological change that occurs in response to insulin resistance?

    <p>Compensatory increase in insulin secretion</p> Signup and view all the answers

    What aspect of glucose metabolism is impaired leading to profound hyperglycemia in type 2 diabetes?

    <p>Increased glucose production in the liver</p> Signup and view all the answers

    Which of the following best describes the effect of insulin on amino acids?

    <p>It promotes the uptake of amino acids and protein synthesis.</p> Signup and view all the answers

    What is a potential result of microvascular complications in individuals with type 2 diabetes?

    <p>Diabetic foot ulcers</p> Signup and view all the answers

    Which of the following is a complication of type 2 diabetes that could lead to serious health risks?

    <p>Hyperosmolarity</p> Signup and view all the answers

    What happens during beta cell failure in the context of type 2 diabetes?

    <p>Insulin secretion begins to decrease.</p> Signup and view all the answers

    What is one of the major metabolic disturbances caused by insulin resistance?

    <p>Increased circulating free fatty acids.</p> Signup and view all the answers

    What effect does insulin resistance have on the GLUT4 transporter in skeletal muscle?

    <p>It prevents translocation of the GLUT4 transporter.</p> Signup and view all the answers

    What happens to insulin levels when the body experiences insulin resistance?

    <p>Insulin secretion increases to compensate.</p> Signup and view all the answers

    Which of the following accurately characterizes the progression of type 2 diabetes?

    <p>Beta cells eventually fail to meet insulin demand.</p> Signup and view all the answers

    What is the primary condition that leads to glucose intolerance?

    <p>Insulin resistance.</p> Signup and view all the answers

    What results from prolonged insulin resistance if beta cells cannot keep up?

    <p>Decline in insulin secretion.</p> Signup and view all the answers

    During the early stages of glucose intolerance, how is blood glucose managed?

    <p>By elevated insulin secretion.</p> Signup and view all the answers

    What phenomenon occurs when insulin sensitivity begins to plateau?

    <p>Insulin levels begin to decline.</p> Signup and view all the answers

    What is hyperinsulinemia a result of?

    <p>Compensatory insulin secretion due to insulin resistance.</p> Signup and view all the answers

    Which condition is characterized by the inability to effectively metabolize glucose?

    <p>Glucose intolerance.</p> Signup and view all the answers

    What is the initial response of adipose tissue to an energy surplus?

    <p>Expansion to store the surplus</p> Signup and view all the answers

    Which of the following conditions occurs as a consequence of excessive lipid accumulation in skeletal muscle?

    <p>Decreased glucose uptake</p> Signup and view all the answers

    Which lipid species directly inhibits the phosphorylation of AKT in insulin signaling?

    <p>Ceramides</p> Signup and view all the answers

    What impact do diacylglycerols (DAG) have on insulin signaling pathways?

    <p>Block the phosphorylation of IRS</p> Signup and view all the answers

    What happens to liver function in the presence of excess lipids?

    <p>Increased glucose production</p> Signup and view all the answers

    How does ectopic lipid accumulation affect the heart?

    <p>Increases heart disease risk</p> Signup and view all the answers

    What is the primary fate of free fatty acids entering skeletal muscle cells?

    <p>Formation of ceramides and DAG</p> Signup and view all the answers

    What is one consequence of insulin resistance in skeletal muscle associated with obesity?

    <p>Impaired glucose uptake</p> Signup and view all the answers

    At what age does the prevalence of type 2 diabetes begin to significantly increase?

    <p>45 to 49</p> Signup and view all the answers

    What is the likelihood of individuals in the lower obese category (BMI 30–39) developing type 2 diabetes?

    <p>Four times more likely</p> Signup and view all the answers

    Which mechanism describes the effect of insulin on hepatic glucose production?

    <p>Inhibits gluconeogenesis</p> Signup and view all the answers

    What is the primary metabolic site for glucose uptake in the body?

    <p>Skeletal muscle</p> Signup and view all the answers

    What correlation exists between fat mass and insulin sensitivity?

    <p>Inverse correlation</p> Signup and view all the answers

    Which sex has a higher prevalence of type 2 diabetes?

    <p>Males</p> Signup and view all the answers

    What is consistently associated with improved insulin sensitivity?

    <p>Greater fat loss</p> Signup and view all the answers

    Which category of obesity has the highest odds ratio for developing type 2 diabetes?

    <p>Morbidly obese category</p> Signup and view all the answers

    Study Notes

    Glucose Intolerance and Type 2 Diabetes

    • Glucose intolerance occurs when the body is unable to effectively metabolize glucose.
    • Insulin resistance is a hallmark of glucose intolerance, where the body cannot respond effectively to insulin.
    • Insulin resistance is initially compensated by increased insulin secretion from the pancreas, leading to hyperinsulinemia.
    • Type 2 diabetes develops when the beta cells of the pancreas can no longer produce sufficient insulin, often as a result of prolonged insulin resistance.

    Pathophysiological Progression of Type 2 Diabetes

    • Insulin sensitivity declines in the early stages of glucose intolerance and insulin resistance.
    • As insulin sensitivity decreases, insulin secretion elevates to compensate.
    • Once the beta cells can no longer maintain the demand, insulin levels decrease.
    • Blood glucose levels remain stable during the early stages due to elevated insulin secretion, however, these levels rise when insulin secretion declines marking the progression to type 2 diabetes.

    Effects of Insulin Resistance on Glucose Metabolism

    • Insulin resistance prevents insulin from inhibiting hepatic glucose production.
    • This leads to unregulated gluconeogenesis, resulting in elevated hepatic glucose production, which contributes to hyperglycemia.
    • Insulin resistance impairs glucose uptake in skeletal muscle, hindering the body's primary site for glucose clearance.
    • This effect is due to the inability of insulin to promote the translocation of the GLUT4 transporter, inhibiting glucose uptake and contributing to hyperglycemia.

    Impact of Insulin Resistance on Lipid Metabolism

    • Insulin resistance increases lipolysis, leading to a surge in circulating free fatty acids.
    • This disrupts blood lipid levels in addition to affecting glucose metabolism.

    Progression from Glucose Intolerance to Type 2 Diabetes

    • Insulin resistance triggers a compensatory increase in insulin secretion during initial stages.
    • Beta cell failure occurs when the pancreas cannot produce sufficient insulin, leading to decreased insulin secretion.
    • This decline in insulin secretion is a defining characteristic of type 2 diabetes.

    Prevalence of Type 2 Diabetes

    • The prevalence of type 2 diabetes increases significantly between the ages of 45 to 49 and 55 to 59.
    • 92% of individuals with type 2 diabetes are 45 years or older.
    • The proportion of individuals with type 2 diabetes is higher in males compared to females.

    Relationship Between Obesity and Type 2 Diabetes

    • There is a strong link between overweight and obesity and the onset of diabetes.
    • The prevalence of type 2 diabetes rises significantly with increasing weight, especially prominent in the overweight and obese categories.
    • Prevalence becomes exceptionally high in individuals with morbid obesity.
    • Individuals in the lower obese category (BMI 30–39) are four times more likely to develop type 2 diabetes.
    • This likelihood increases to just under eight times more likely in the morbidly obese category.

    Insulin Sensitivity and Fat Mass

    • There is an inverse relationship between fat mass and insulin sensitivity.
    • Increased fat mass (adiposity) correlates with reduced insulin sensitivity and increased insulin resistance.
    • Weight loss, regardless of the method, consistently leads to improved insulin sensitivity, particularly with greater fat loss.

    Insulin's Actions in the Periphery

    • Insulin, secreted from the beta cells of the pancreas, affects three major metabolic sites: the liver, skeletal muscle, and adipose tissue.
    • In the liver, insulin inhibits gluconeogenesis, reducing hepatic glucose production.
    • Skeletal muscle is the primary site for glucose uptake, where insulin promotes glucose uptake and its conversion to glycogen.
    • In adipose tissue, insulin promotes glucose uptake, though less efficiently compared to skeletal muscle, and inhibits lipolysis, promoting triglyceride synthesis.

    Lipotoxicity and Insulin Resistance in Skeletal Muscle

    • Diabetes is also a disease of defective lipid metabolism.
    • Excess energy surplus results in lipid accumulation in white adipose tissue.
    • Adipose tissue expansion eventually reaches its limit, and with insulin resistance's inability to suppress lipolysis, free fatty acids spill over into other peripheral tissues.
    • This excess lipid can have detrimental effects on various tissues, including:
      • Adipose Tissue: increased lipolysis and production of unfavorable adipokines
      • Muscle: lipid accumulation reduces glucose uptake
      • Liver: increased glucose production, decreased insulin clearance, and enhanced cholesterol synthesis (LDL)
      • Pancreas: decreased insulin secretion and potential beta cell death
      • Heart: ectopic lipid accumulation can lead to increased heart disease risk and mortality

    Mechanisms of Lipotoxicity and Insulin Resistance

    • Free fatty acids entering the skeletal muscle myocytes (muscle cells) are converted into long-chain fatty acids.
    • These long-chain fatty acids form triacylglycerides, which can produce either ceramides (a sphingolipid) or diacylglycerol (DAG).
    • Ceranides and DAGs inhibit the insulin signaling cascade:
      • DAGs, via protein kinase C, block the phosphorylation of insulin response substrate (IRS).
      • Ceramides prevent the phosphorylation of AKT.
    • These disruptions prevent the activation of downstream signaling pathways that regulate glucose metabolism.

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    Lecture 13: Insulin Resistance and Type 2 Diabetes PDF

    Description

    This quiz explores the critical pathophysiological aspects of glucose intolerance and the progression to Type 2 diabetes. Learn about insulin resistance, hyperinsulinemia, and the role of beta cells in glucose metabolism. Test your understanding of how these factors interact in the development of diabetes.

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