Medicine Marrow Pg No 915-924 (Endocrinology)
50 Questions
0 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Which of the following factors is considered the initiating factor in the pathophysiology of insulin resistance?

  • Liver function
  • Adipose tissue (correct)
  • Gastrointestinal hormones
  • Renal function

    • The accumulation of fatty acyl Co-A occurs due to the absence of CPT-1 in the liver.

    True

    What is the main substrate for increased gluconeogenesis in patients with insulin resistance?

    Free Fatty Acids (FFA)

    The __________ receptor is responsible for insulin-dependent glucose uptake in skeletal muscle.

    <p>GLUT-1</p> Signup and view all the answers

    Match the following locations with their respective GLUT receptor:

    <p>Skeletal muscle = GLUT-1 Heart = GLUT-4 Adipose tissue = GLUT-4 Brain = GLUT-3</p> Signup and view all the answers

    Which of the following features is associated with Type A Resistance in diabetes mellitus?

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

    MODY is characterized by an inappropriate response of β cells to rising blood glucose levels.

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

    What are the characteristic features of MODY 4 diabetes?

    <p>Presents with renal cysts and genital anomalies.</p> Signup and view all the answers

    Type C Resistance includes features like HAIR AN syndrome, childhood DM, and ________ hair.

    <p>rapidly growing</p> Signup and view all the answers

    Match the following types of MODY with their associated gene defects:

    <p>MODY 1 = HNF-4α MODY 2 = Glucokinase MODY 3 = HNF-1α MODY 4 = IPF-1</p> Signup and view all the answers

    Which of the following comorbidities is NOT associated with Type 2 DM?

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

    Impaired Fasting Glucose (IFG) is defined as a glucose level greater than 100mg/dL.

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

    What waist circumference measurement is considered obese for males according to Indian criteria?

    <p>greater than 90 cm</p> Signup and view all the answers

    The least important factor in the metabolic syndrome criteria is triglycerides, with a level greater than ______ mg/dL.

    <p>150</p> Signup and view all the answers

    Match the following metabolic syndrome criteria with their corresponding values:

    <p>Waist Circumference (Male) = &gt; 102cm HDL (Female) = &lt; 50mg/dL Blood Pressure = &gt; 130/85 Triglycerides = &gt; 150mg/dL</p> Signup and view all the answers

    What is the purpose of starting metformin in pre-diabetes treatment?

    <p>To improve glycemic control and reduce diabetes risk</p> Signup and view all the answers

    Screening for pre-diabetes is recommended only once a year regardless of risk factors.

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

    What hemoglobin level (HbA1c) indicates the need for starting metformin?

    <p>≥ 6.5%</p> Signup and view all the answers

    Pioglitazone acts on PPAR-γ to combat __________ resistance.

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

    Match the following conditions with their respective screening indications:

    <p>Gestational DM = High chance of developing diabetes Stroke = High-risk population screening PCOS = Insulin resistance indication Population ≥ 35 years = Increased screening frequency</p> Signup and view all the answers

    Which of the following factors is commonly associated with Type 2 diabetes mellitus?

    <p>Presence of Acanthosis Nigricans</p> Signup and view all the answers

    Dawn phenomenon is commonly observed in Type 1 diabetes mellitus.

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

    What is the primary cause of beta cell destruction in Type 1 diabetes mellitus?

    <p>T cell-mediated destruction</p> Signup and view all the answers

    Type 1 diabetes is more frequently diagnosed in ______ individuals, while Type 2 diabetes is more common in ______ individuals.

    <p>younger, older</p> Signup and view all the answers

    Match the following diabetes characteristics with their corresponding type:

    <p>Presence of antibodies = Type 1 DM Higher C-Peptide levels = Type 2 DM Commonly associated with obesity = Type 2 DM Rare family history = Type 1 DM</p> Signup and view all the answers

    Which of the following is included in the 'Treacherous 13' of diabetes pathophysiology?

    <p>Increased hormone sensitive lipase</p> Signup and view all the answers

    The diagnostic criteria for diabetes include an HbA1c level of 6.0% or higher.

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

    What percentage of patients with pre-diabetes progress to diabetes each year?

    <p>10-15%</p> Signup and view all the answers

    A fasting plasma glucose level of __________ mg/dL indicates pre-diabetes.

    <p>100-125</p> Signup and view all the answers

    Match the glucose measurement with its corresponding classification:

    <p>HbA1c &lt; 5.7% = Normal Fasting plasma glucose 100-125 mg/dL = Pre-diabetes 2hr Postprandial plasma glucose ≥ 200 mg/dL = Diabetes HbA1c ≥ 6.5% = Diabetes</p> Signup and view all the answers

    Which of the following conditions is associated with an increased TSH level?

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

    Subacute thyroiditis is characterized by the absence of pain.

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

    What medication is considered the drug of choice (DOC) for recovery management in thyroid issues?

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

    Postpartum thyroiditis is associated with ______ autoimmune conditions.

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

    Match the following features to Subacute and Postpartum Thyroiditis:

    <p>Pain Present = Subacute Thyroiditis Associated with pregnancy = Postpartum Thyroiditis Autoimmune = Postpartum Thyroiditis ESR ↑ = Subacute Thyroiditis</p> Signup and view all the answers

    What is the primary cause of Type-1 Diabetes mellitus?

    <p>Immune-mediated destruction of the pancreas</p> Signup and view all the answers

    Type-2 Diabetes mellitus accounts for 90-95% of all diabetes cases.

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

    What type of diabetes is often referred to as ketosis-prone diabetes?

    <p>Type-1.5 Diabetes</p> Signup and view all the answers

    The abbreviation GDM stands for __________.

    <p>Gestational Diabetes mellitus</p> Signup and view all the answers

    Match the following types of diabetes with their descriptions:

    <p>Type-3 Diabetes = Associated with Alzheimer's disease Type 4 Diabetes = Mild age-related diabetes Type-1 Diabetes = Immune-mediated pancreas destruction GDM = Diabetes that occurs during pregnancy</p> Signup and view all the answers

    What phenomenon is associated with Type-I thyrotoxicosis induced by amiodarone?

    <p>Jod-basedow phenomenon</p> Signup and view all the answers

    Type-II thyrotoxicosis is characterized by the presence of antibodies related to Graves' disease.

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

    What is the primary treatment for Type-I amiodarone-induced thyrotoxicosis?

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

    The duration of symptoms in Graves' disease typically lasts for __________.

    <p>2-3 months</p> Signup and view all the answers

    Match the following thyroid conditions with their respective features:

    <p>Subacute Thyroiditis = Presence of neck pain Graves' Disease = Ophthalmopathy present Toxic MNG = Common in elderly Thyrotoxicosis Type II = No antibodies present</p> Signup and view all the answers

    What characterizes Ketosis-prone Diabetes/Flatbush Diabetes?

    <p>Often presents in males around early age with insulin dependence and obesity.</p> Signup and view all the answers

    Latent Autoimmune Diabetes in Adults (LADA) typically requires insulin treatment immediately upon diagnosis.

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

    What does GAD stand for in the context of autoantibodies used for diagnosing diabetes?

    <p>Glutamic acid decarboxylase</p> Signup and view all the answers

    Type 1 Diabetes Mellitus behaves like ______ diabetes in a significant number of cases.

    <p>Type 2</p> Signup and view all the answers

    Match the autoantibodies with their features:

    <p>GAD = Most sensitive and specific Autoantibody ICA = Islet cell antibodies IAA = Not valid after therapy in new onset T1DM 2nT8 = Zinc transporter 8</p> Signup and view all the answers

    Study Notes

    Pathophysiology of Diabetes

    • Glucose and Lipid Toxicity: A key factor in the development of diabetes.
      • Increases glucose output.
      • Causes toxic effects on beta cells.
      • Leads to defective insulin secretion from beta cells.
    • Ominous Octet of Defronzo: A set of eight factors that contribute to insulin resistance.
      • A: Adipose Tissue: Responsible for initiating the process of fat storage. This includes:
        • Centripetal obesity: Increased fat storage in the abdomen.
        • Adipose tissue converts free fatty acids (FFAs) to glycerol.
        • Increased sensitivity of beta-2 receptors leads to increased lipolysis by hormone sensitive lipase, resulting in increased FFAs.
      • G: Gastrointestinal Tract:
        • Increased incretin effect.
        • Increased glucagon production.
      • P: Pancreas:
      • R: Renal:
        • Increased activation of SGLT-2.
        • Increased sodium and water absorption, leading to edema.
    • FFA (Free Fatty Acids): The main substrate for gluconeogenesis.
      • Increased FFAs lead to increased gluconeogenesis (production of glucose from non-carbohydrate sources).
    • Insulin Resistance: Leads to the accumulation of fatty acyl Co-A in the liver.
      • CPT-1: A key enzyme for the breakdown of fatty acids (beta-oxidation) is absent in the liver.
    • Beta-Oxidation: The normal pathway for breaking down fatty acids.
      • Impaired beta-oxidation leads to FFA accumulation.
    • GLUT-4: An insulin-dependent glucose transporter found in skeletal muscle, heart, and adipose tissue.
      • Insulin resistance impairs the normal glucose uptake process in the body.

    Genetic Syndromes Associated with Diabetes

    • Type A Resistance: Primarily seen in females, characterized by:
      • Acanthosis nigricans (darkening of skin in certain areas).
      • Hyperandrogenism (excess male hormones).
      • Often linked to Polycystic Ovary Syndrome (PCOS).
      • Pathogenesis: Insulin receptor resistance.
    • Type C Resistance:
      • HAIR AN Syndrome: A syndrome associated with hyperinsulinism, acanthosis nigricans, and rapid growth.
      • Presents with childhood diabetes, acanthosis nigricans, rapid hair growth, and abnormal dentition.
      • Pathogenesis: Post-binding defect in insulin action, involving mutations of the insulin receptor.

    Other Types of Diabetes

    • Type 4 DM (Middle Age Related DM (MARD)):
      • Characterized by an increased number of T regulatory cells, which have a role in preventing autoimmune diseases like Type 1 Diabetes.
      • Leads to a milder form of diabetes.
    • MODY (Maturity-Onset Diabetes of the Young):
      • A group of monogenic forms of diabetes.
      • It is not insulin-dependent, manifests before 25 years old, and is characterized by an increased activity of the SGLT2 transporter, resulting in glycosuria (glucose in urine).
      • Patients do not typically experience major complications associated with diabetes.

    Treatment for Pre-Diabetes

    • ADA Recommendations:
      • Start metformin for individuals:
        • Age 60 years or older.
        • HbA1c ≥ 6.5%.
        • Fasting blood sugar (FBS) ≥ 110 mg/dL.
        • Overweight.
        • With gestational diabetes.
      • Add pioglitazone to manage diabetes.
        • Pioglitazone acts on the PPAR-gamma receptor, which helps fight insulin resistance.
        • Slows the progression of cardiovascular disease risk.
        • Decreases the risk of stroke.

    Screening for Diabetes

    • Indications for Screening:

      • Every 6 months:
        • Individuals with a history of gestational diabetes (due to the high risk of developing diabetes later).
        • Pre-diabetic population (previously diagnosed with pre-diabetes).
        • Individuals at high risk:
          • Stroke.
          • Cardiovascular disease.
          • HIV.
          • PCOS.
          • Signs of insulin resistance.
          • People over 35 years old.

    • Screening Tests:

      • HbA1c:
        • Offers the best sensitivity and specificity for detecting pre-diabetes.
        • Provides a 6-8 week window of blood glucose control.
        • Shows an average blood glucose value over time.
        • Limitation: Provides average values over a long period, not real-time data.

    Factors Interfering with HbA1c Levels

    • False Lower Values:
      • Hemoglobinopathies (abnormal hemoglobin in red blood cells).
      • Hemolytic anemia (red blood cell breakdown).
      • Malnutrition.
      • Blood loss.
      • Chronic liver disease.
    • False Elevated Values:
      • Renal failure.
      • Iron deficiency.
      • Anemia.
      • Elevated bilirubin levels.
      • Elevated triglycerides.

    Type 2 & Type 1 DM

    • Natural History of the Disease:

      • Common complications:
        • Non-alcoholic fatty liver disease (NAFL).
        • Hypogonadism (impaired hormone production).
        • Periodontal disease.
        • Fractures.
        • Atherosclerosis (hardening of arteries).

    • Metabolic Syndrome Criteria:

      • Meeting three or more of the following criteria indicates metabolic syndrome:
        • Waist Circumference (WC):
          • Male (m) > 102 cm
          • Female (F) > 88 cm
        • Triglycerides (TG): > 150 mg/dL (Least important factor in the criteria).
        • HDL Cholesterol:
          • Male (m) < 40 mg/dL
          • Female (F) < 50 mg/dL
        • Blood Pressure (BP): > 130/85 mmHg
        • Impaired Fasting Glucose (IFG): > 100 mg/dL

    • BMI (Body Mass Index):

      • WHO Criteria (World Health Organization):
        • Normal: 18.5 - 24.9
        • Overweight: 25 - 29.9
        • Obese: ≥ 30
      • Indian Criteria:
        • Normal: 18 - 22.9
        • Overweight: 23 - 24.9
        • Obese: ≥ 25

    • Diabesity/Adiposopathy (Common in Indian populations):

      • Waist Circumference (WC) :
        • Male (m) > 90cm
        • Female (F) > 80cm
      • Hyperglycemia
      • Hypertension
      • Hyperlipidemia
      • Increased CRP (C-reactive protein) - a marker of inflammation.
      • Decreased adiponectin (a hormone with anti-inflammatory properties).
      • Prothrombotic state (increased likelihood of blood clotting).

    Type 1 vs Type 2 Diabetes Mellitus

    • Type 1 DM: Caused by the autoimmune destruction of beta cells.
      • Characterized by insulitis (inflammation of pancreatic islets).
      • Markers: Auto-antibodies such as GAD (glutamic acid decarboxylase) and ZNT-8 (zinc transporter 8, found in >95% of patients).
      • HLA association: Strong association with HLA DRB1-04.
    • Type 1 vs Type 2 DM Chart*
    Factors Type 1 DM Type 2 DM
    Age Younger Older
    Weight Thinner (due to weight loss) Obese
    Family history Rare Common
    Symptoms Osmotic symptoms (frequent urination, excessive thirst, weight loss) Variable
    DKA (Diabetic Ketoacidosis) Common Rare
    C-Peptide Low Higher
    Acanthosis Nigricans Absent Present
    Dyslipidemia Absent Present
    Hyperuricemia Absent Present
    PCOS Rare Present
    Antibodies Present Absent
    HLA association (HLA DR3/4) Stronger Weaker
    Genetic factor association Weaker Stronger
    Risk of Developing DM if: * Either parent has DM * Both parents have DM 5% 15% 25% 40%
    Twin to twin concordance 40% 70-90%

    Newer Discoveries in Diabetes

    • Dirty Dozen:
      • The eight factors from the "Ominous Octet" plus four more.
      • D: Decreased dopamine levels.
      • Vit-D: Decreased Vitamin D levels.
      • G: Hypogonadism (decreased testosterone levels).
      • R: Renin-aldosterone system activation.
    • Treacherous 13:
      • Dirty dozen plus one more.
      • Serotonin: Increased serotonin levels lead to increased hormone sensitive lipase (HSL).
    • Faithless 14:
      • Treacherous 13 plus one more.
      • Iron in beta-cell: Toxicity and resistance.

    Diagnostic Criteria for Diabetes and Pre-diabetes

    • Diabetes*
    HbA1c Fasting plasma glucose 2hr Postprandial plasma glucose (PPBG) RBS Clinical Symptoms
    ≥ 6.5% ≥ 126 mg/dL ≥ 200 mg/dL (75mg glucose) ≥ 200 mg/dL Polyurea, Polydypsia, Weight Loss
    • Pre-Diabetes/Impaired Glucose Tolerance*
    Normal Value Pre-diabetes/Impaired Glucose Tolerance
    Fasting Glucose < 100 mg/dL 100-125 mg/dL
    2hr PPBG (75g) < 140 mg/dL 140-199 mg/dL
    HbA1c < 5.7% 5.7 - 6.4%

    Introduction to Diabetes Mellitus and Classification

    • Classification:

      • Type-1 Diabetes mellitus: Immune-mediated destruction of pancreatic beta cells leading to insulin deficiency.
      • Type-2 Diabetes mellitus (most common): Insulin resistance (cells do not respond to insulin properly).
      • Hybrid Diabetes mellitus (Type-1.5):
        • Ketosis-prone diabetes (KPD).
        • Latent Autoimmune diabetes in adults (LADA).
      • Type-3 Diabetes mellitus:
        • Alzheimer's disease: The accumulation of APO-B2 protein is linked to Alzheimer's disease.
        • Type 3 C: Pancreatic Diabetes.
        • Type 3 D: Drug-induced Diabetes.
      • Type 4 Diabetes mellitus: Mild, age-related diabetes (MARD).
      • GDM (Gestational Diabetes mellitus): Diabetes developing during pregnancy.

    • Artificial pancreas:

      • A device that automatically monitors glucose levels and delivers insulin.

    Thyroid Gland Issues

    • Mechanisms of Hormone Release:

      • Stored hormone release.
      • Increased free T3, increased free T4, decreased TSH (thyroid-stimulating hormone), and a T3/T4 ratio.
      • Symptoms: Neck pain, sore throat, ear pain, and elevated ESR (erythrocyte sedimentation rate).

    • Recovery Management:

      • Aspirin 600mg every 6 hours (DOC - drug of choice).
      • NSAIDs (nonsteroidal anti-inflammatory drugs).
      • Steroids.

    Thyroid Levels

    • TSH levels:
      • Elevated TSH: Hypothyroidism (low thyroid hormone).
      • Normal TSH: Central hypothyroidism (problem with the pituitary gland that regulates the thyroid).
      • Decreased TSH and Elevated FT3/FT4: Graves' disease (overactive thyroid), Toxic multinodular goiter (MNG), adenoma (thyroid tumor), or thyrotoxicosis (high levels of thyroid hormone).

    Types of Thyroiditis

    • Postpartum thyroiditis: Also known as painless/silent thyroiditis.
      • Often occurs in patients with underlying autoimmune conditions, like systemic lupus erythematosus (SLE) or Sjogren's syndrome.
    • Subacute Thyroiditis v. Postpartum Thyroiditis*
    Feature Subacute Thyroiditis Postpartum Thyroiditis
    Pain Present Absent/silent
    Association with pregnancy No Post Partum
    Autoimmune No Yes
    ESR ↑ Normal
    Anti TPO Ab -ve +ve
    Role of Steroid Yes No
    β-blocker Yes No

    Effects Of Amiodarone On Thyroid

    • Amiodarone: A medication that can disrupt thyroid function.

    Thyrotoxicosis

    • Type-1:
      • Amiodarone is started in a patient with pre-existing thyroid disease (e.g., Graves or MNG).
      • Jod-basedow phenomenon occurs (increase in thyroid hormone production due to iodine exposure).
      • Treatment: Stop amiodarone treatment and start thionamide (DOC).
      • Color Doppler: Reduced thyroid vascularity (blood flow).
    • Type-II:
      • Occurs in patients without pre-existing thyroid disease.
      • Amiodarone-induced destruction of the thyroid gland (lysosomal mediated).
      • No antibodies (no Graves' disease).
      • Color Doppler: Reduced thyroid vascularity.
      • Treatment: Stop amiodarone; Treat with steroids.

    Hypothyroidism

    • Transient hypothyroidism (temporary).
    • Caused by the Wolff-Chaikoff phenomenon (iodine excess temporarily inhibits thyroid hormone production).

    Subacute Thyroiditis vs Graves' vs Toxic MNG

    Features Subacute Thyroiditis Graves' Disease Toxic MNG
    Duration Days to weeks 2-3 months Months to years
    Age and sex Anytime 20-40 years (F > m) Commonly in elderly (F > m)
    Symptoms Very severe Severe Mild to moderate
    Neck pain Present Absent Absent
    Goiter Small Diffuse Nodular
    Ophthalmopathy/Dermopathy Absent Present Absent
    Thyroid function test TSH↓ T4↑ T3 (N)/↑ TSH↓ T4↑ T3↑↑ TSH↓ T4↑ T3↑↑
    T3/T4 ratio ≦15 >20 >20
    TSH-R stimulating Ab Absent Present Absent
    Ultrasound Not significant Diffusely enlarged gland Enlarged nodules
    Colour doppler Vascularity decrease ↑↑ vascularity (Best test to diagnose) Variable
    Radioiodine uptake Low uptake ↑↑ Uptake Depends on functional status of nodules (cold or hot nodules)

    Type 1.5 Diabetes

    • Features of Type-1 and Type-2 Diabetes:
    Feature Ketosis-prone Diabetes/Flatbush Diabetes Latent Autoimmune Diabetes of Adults
    Gender M > F m = F
    Course Early age (~20y): Ketosis (Started on Insulin) 5-10 years in requirement of Insulin- Obesity- Good response to OHA. Asymptomatic patient (~30y) accidentally found to be hyperglycemicTreated as T₁ DM, not requiring insulin5-10 years ↑Insulin requirement- C-peptide value: slightly decreased (Slower than TIDM)- ↑↑ Antibodies level.
    Presentation T₁ DM behaves like TIDM.Dark, hirsuit and obese male- Acanthosis nigricans, balanoposthitis (Stigmata of insulin resistance)- Hyperinsulinemia (Resistance). T₁ DM behaves like T₂ DM- 1/3 cases of diagnosed T₁ DM are in reality LADA- Lean, fair with stigmata of autoimmune illness.
    • Diagnostic Algorithm - Autoantibodies in LADA/TIDM*
    Autoantibody Sensitivity Specificity Additional Features
    GAD (Glutamic acid decarboxylase) 70-90% 99% most sensitive and specific antibody Earliest to appear Disappears after few years
    ICA (Islet cell antibodies) 44-100% 96%
    IAA (Insulin autoantibody) 40-70% 99% Not valid after therapym/c in new onset TIDM
    2nT8 (Zinc transporter 8) 50-70% 99%

    Studying That Suits You

    Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

    Quiz Team

    Description

    This quiz focuses on the pathophysiology of insulin resistance, its connection to diabetes, and the features of different types of MODY. Test your knowledge on the mechanisms behind glucose uptake and metabolism in the context of diabetes. Perfect for students studying endocrinology or diabetes management.

    More Like This

    Use Quizgecko on...
    Browser
    Open
    Browser
    Browser