Diabetes Mellitus: Regulation of Insulin Secretion
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Questions and Answers

What is the typical characteristic of Diabetic Ketoacidosis?

  • Absence of ketonuria and presence of metabolic acidosis
  • Presence of ketonuria and absence of metabolic acidosis
  • Presence of ketonemia and metabolic acidosis (correct)
  • Absence of ketonemia and metabolic acidosis

    • What is the primary cause of coma in Hyperosmolar Coma?

  • Ketonemia
  • Cellular dehydration in the brain (correct)
  • Hypoglycemia
  • Metabolic acidosis

    • What is the common symptom of Hypoglycemia and Hyperglycemia?

  • Blurred vision (correct)
  • Polydipsia
  • Nausea and vomiting
  • Polyphagia

    • What is the cause of Leukocytosis in Diabetic Ketoacidosis?

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

    What is the typical characteristic of Hyperglycemia in Diabetic Ketoacidosis?

    <p>Glucose levels around 500 mg/dL</p> Signup and view all the answers

    What is the cause of hyperosmolality in Hyperosmolar Coma?

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

    What is the characteristic of Kussmaul breathing in Diabetic Ketoacidosis?

    <p>Deep and rapid respiration</p> Signup and view all the answers

    What is the characteristic laboratory finding in steatohepatitis due to alcohol-related fatty liver disease?

    <p>AST : ALT &gt; 2:1</p> Signup and view all the answers

    Which of the following is a risk factor for the development of nonalcoholic fatty liver disease (NAFLD)?

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

    What is the characteristic histopathological feature of micronodular cirrhosis?

    <p>Continual subdivision of nodules</p> Signup and view all the answers

    What is the consequence of decreased production of adiponectin by adipocytes in NAFLD?

    <p>Increased release of free fatty acids</p> Signup and view all the answers

    What is the characteristic clinical feature of steatosis due to alcohol-related fatty liver disease?

    <p>Asymptomatic with hepatomegaly</p> Signup and view all the answers

    What is the consequence of insulin resistance in NAFLD?

    <p>Increased uptake of FFA by hepatocytes</p> Signup and view all the answers

    What is the characteristic laboratory finding in steatosis due to nonalcoholic fatty liver disease?

    <p>AST : ALT &lt; 1</p> Signup and view all the answers

    What is the consequence of activation of inflammasome in NAFLD?

    <p>Increased release of IL-1</p> Signup and view all the answers

    Study Notes

    Regulation of Insulin Secretion

    • Glucose is the primary physiologic stimulant of insulin release, entering β cells via glucose transporter (GLUT 2)
    • Glucokinase, an enzyme regulated by glucose, controls the first step in glucose metabolism
    • Stimulators of insulin release include:
      • Vagal stimulation
      • β-adrenergic stimulation
      • GLP1
      • Amino acids
    • Inhibitors of insulin release include:
      • Catecholamines
      • α-adrenergic stimulation
      • Somatostatin

    Diabetes Mellitus

    • Defined as a heterogeneous disorder characterized by hyperglycemia
    • Criteria for diagnosis:
      • Fasting plasma glucose ≥ 126 mg/dL (7.0 mmol/L)
      • Symptoms of DM plus a random plasma glucose ≥ 200 mg/dL (11.1 mmol/L)
      • Plasma glucose ≥ 200 mg/dL after OGTT
    • Classification:
      • Normal fasting plasma glucose: 70-99 mg/dL (3.4-5.5 mmol/L)
      • Impaired fasting glucose (IFG): 100-125 mg/dL (5.6-6.9 mmol/L)
      • Impaired glucose tolerance (IGT): plasma glucose 140-199 mg/dL (7.8-11 mmol/L) after 2-hour OGTT
      • Prediabetes: IFG or IGT
      • Diabetes: symptoms of hyperglycemia and casual plasma glucose ≥ 200 mg/dL (11.1 mmol/L)

    Etiology of Diabetes Mellitus

    • Functional deficiency of insulin action → hyperglycemia
    • Decreased insulin secretion by β cells of pancreas (DM 1)
    • Decreased response to insulin by target tissues → insulin resistance (DM 2)
    • Increase in counterregulatory hormones that oppose the effects of insulin (DM in endocrinopathies, gestational DM)

    Types of Diabetes Mellitus

    • Type I DM
      • Selective destruction of over 90% of pancreatic β cells with severe insulin deficiency
      • Immune-mediated (autoimmune DM 1) → 90%
      • Idiopathic → 10%
    • Type II DM
      • Insulin resistance with relative insulin deficiency
      • Genetic predisposition stronger than in DM 1
      • Polygenic origin of disease
    • Gestational Diabetes Mellitus (GDM)
      • Any hyperglycemic state that occurs or is recognized for the first time during pregnancy
      • Occurs in 4% of pregnant women
      • May recur with subsequent pregnancies (in ~30%)
      • Tends to resolve at parturition
      • Associated with obesity

    Complications of Diabetes Mellitus

    • Acute Complications

      • Diabetic ketoacidosis
      • Hyperosmolar coma
      • Hypoglycemia

    • Chronic Complications

      • Macrovascular:
        • Atherosclerosis
        • Stroke
        • Heart disease
        • Hypertension
      • Microvascular:
        • Retinopathy
        • Nephropathy
        • Neuropathy### Morphology of Steatofibrosis/Cirrhosis

    • Gross findings: nodular surface, greenish color

    • Microscopic findings:

      • Central vein sclerosis
      • Perisinusoidal scarring
      • Central portal fibrous septa
      • Continual subdivision of nodules (micronodular cirrhosis)
      • With abstinence, regeneration occurs, forming macronodules

    Steatosis

    • Asymptomatic, but may present with hepatomegaly
    • Mild increase in serum bilirubin and alkaline phosphatase
    • Resolves with abstinence

    Steatohepatitis

    • Weeks to months of heavy alcohol consumption
    • Possible acute onset
    • Symptoms: malaise, anorexia, tender hepatomegaly, fever
    • Laboratory findings:
      • Hyperbilirubinemia
      • Increased serum alkaline phosphatase
      • AST & ALT < 500 U/mL
      • AST : ALT > 2:1
    • Increased risk of cirrhosis and death

    Chronic Liver Failure/Cirrhosis

    Pathogenesis of NAFLD

    • Contributing factors:
      • Diabetes type II
      • Central obesity
      • Dyslipidemia (high TG & LDL, low HDL)
      • Hypertension
    • Mechanisms:
      • Insulin resistance → increased activity of lipoprotein lipase → increased release of free fatty acids
      • Decreased production of adiponectin by adipocytes
      • Decreased oxidation of FFA by skeletal muscle
      • Increased uptake of FFA by hepatocytes
      • Activation of inflammasome (release of IL-1)
      • Products of lipid metabolism → hepatocytes injury → stellate cell activation → fibrosis

    Clinical Features of NAFLD

    • Transaminase elevation (AST : ALT < 1)
    • Steatosis: usually asymptomatic
    • Steatohepatitis: asymptomatic or presents with fatigue, malaise, discomfort in right upper quadrant
    • Low progression to NASH / cirrhosis

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    Description

    This quiz covers the regulation of insulin secretion, including the role of glucose, glucokinase, and stimulators of insulin release in diabetes mellitus.

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