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Diabetes and Endocrine System - Vocabulary Flashcards

Overview of Diabetes

  • Diabetes is a group of diseases characterized by abnormalities in fat, carbohydrate, and protein metabolism that lead to hyperglycemia and can cause microvascular changes and neuropathic complications.

  • Increasing frequency in the US is linked to obesity and diet; lifestyle and cultural factors influence prevalence and management.

  • Education and ongoing management are essential for prevention of complications, especially in patients with cardiac disease, hypertension, or other comorbidities.

Pathophysiology and Mechanisms

  • Mechanisms (general): defects in secretion of insulin and/or insulin action, after metabolism of carbohydrates, fats, and proteins.

  • Type 1 diabetes: autoimmune destruction of pancreatic beta cells leading to absolute insulin deficiency.

  • Type 2 diabetes: insulin resistance with progressive insulin deficiency (impaired secretion and/or insulin resistance; may involve β-cell burnout over time).

  • Other specific types: genetic defects of beta cell function, genetic defects in insulin action, disease of the pancreas (e.g., cystic fibrosis), or drug-induced/organ transplant–related diabetes (e.g., steroids).

  • Gestational diabetes: occurs during pregnancy; increases risk of developing diabetes later in life.

  • Organ transplant and steroids can induce hyperglycemia or diabetes due to glucocorticoid effects on glucose metabolism.

  • Typical presentation varies; undiagnosed adults may present with few symptoms but hyperglycemia is detected via testing.

Classic Clinical Presentation and Signs

  • Three hallmark symptoms (polys):

    • Polyuria (frequent urination)

    • Polydipsia (excessive thirst)

    • Polyphagia (increased hunger)

    • The trio is often referred to as the three polys.

  • Other symptoms/signs: fatigue, weight loss, blurred vision, infections, slow wound healing.

  • In late hyperglycemia or poorly controlled diabetes, patients may report fatigue, blurred vision, and weight loss due to poor glucose utilization and dehydration.

Diagnostic and Monitoring Measures

  • Finger-stick glucose testing in acute settings; immediate reading helps triage.

  • Critical thresholds observed in practice (example values from the transcript):

    • Critical high: reading above 600 (for some monitors).

    • Critical low: reading below 60.

  • Laboratory tests commonly used:

    • CBC and CMP for general assessment and electrolyte status.

    • Fasting blood glucose thresholds mentioned: normal below 100\%? (clarification needed). In the discussion, fasting glucose under 100 mg/dL is described as normal; values around 101 mg/dL are noted as borderline; above 120 mg/dL is not normal.

    • Hemoglobin A1c (HbA1c) measures average blood glucose over about 3\text{ months}.

    • Normal HbA1c is described as below 5.6\%. An HbA1c of 8.9\% indicates poor control and a need for treatment adjustment.

  • Home monitoring and data sharing:

    • Patients may use home glucose monitoring devices; some systems allow clinicians to read data remotely.

    • Regular follow-up labs include fasting glucose and HbA1c to assess control over time.

Goals and Interpretation of Key Numbers

  • Fasting blood glucose goals in the discussion:

    • Target: below 100 \text{ mg/dL} (normal range).

    • Borderline/acceptable reading: around 101\ \text{mg/dL}.

    • Not normal: above 120 \text{ mg/dL}.

  • HbA1c goals and interpretation:

    • HbA1c reflects average glucose over about 3 months.

    • A reduction of HbA1c by about 1\% is typical with effective therapy such as metformin, depending on baseline values.

    • An HbA1c of 8.9\% indicates suboptimal control and a need for therapy adjustment.

Pharmacologic Treatments (Overview)

  • Medication classes are chosen based on where the patient’s metabolic defect lies (insulin deficiency vs insulin resistance) and severity.

  • Goals include lowering blood glucose, minimizing hypoglycemia, and improving long-term outcomes; therapy often involves lifestyle changes plus pharmacotherapy.

Metformin (Biguanide) – First-line for Type 2 Diabetes (as discussed)

  • Mechanism: decreases hepatic glucose production via reduced gluconeogenesis and glycogenolysis; enhances insulin-mediated glucose uptake in peripheral tissues (e.g., muscle); overall reduces hyperglycemia.

  • Efficacy: lowers HbA1c by about 1\% on average.

  • Benefits: generally not associated with weight gain; may cause weight loss of 2-3\text{ kg} in some patients.

  • Safety and tolerability: not associated with hypoglycemia when used alone; GI side effects (nausea, diarrhea, abdominal discomfort) and metallic taste; vitamin B12 malabsorption may occur and require monitoring/supplementation.

  • Dosing and titration: start low and go slow; typical titration is +500\text{ mg every 2 weeks}; the majority of glucose-lowering effect is achieved around 1500\text{ mg/day} with little additional benefit above that dose.

  • Renal considerations: eliminated by the kidneys; renal function should be assessed before starting and periodically thereafter (renal clearance calculations).

  • Contraindications/risks: generally avoided in significant renal impairment, hepatic impairment, heart failure in some contexts, alcohol use disorder, and other hypoxic states due to risk of lactic acidosis.

  • Drug interactions: alcohol may increase risk of hypoglycemia; interactions with other antidiabetic agents exist but are limited.

  • Special notes from evidence: a Cochrane review (3,347 studies, >70,000 subjects) found no overall increase in lactic acidosis with metformin vs other therapies, though high-risk groups require careful consideration.

  • Practical tips: take with meals to reduce GI side effects; monitor B12; assess renal function periodically.

Sulfonylureas – Insulin Secretagogues

  • Mechanism: close ATP-sensitive potassium channels in pancreatic beta cells, leading to cell depolarization, calcium influx, and increased insulin secretion.

  • Generations:

    • First generation: e.g., tolbutamide.

    • Second generation: e.g., glipizide (glipizide is still widely used).

    • Third generation: newer agents (examples discussed include glipizide; the note suggests third-generation options exist).

  • Role in therapy: often used in combination with metformin; can reduce HbA1c by up to about 0.5-1.0\% in some regimens.

  • Key drawback: higher risk of hypoglycemia compared to other agents.

  • Real-world mechanism explanation (from transcript): in type 2 diabetes, impaired ATP-sensitive K+ channel closure reduces insulin secretion; sulfonylureas help close these channels to restore insulin release.

Incretin-Based Therapies and GLP-1 Pathway

  • Incretins: hormones released by the gut in response to meals that enhance insulin secretion and suppress glucagon, contributing to better postprandial glucose control.

  • GLP-1 (glucagon-like peptide-1):

    • Increases insulin secretion and suppresses glucagon when nutrients are present in the gut.

    • Slows gastric emptying, producing a more gradual rise in glucose after meals.

    • Suppresses appetite, aiding weight management.

  • DPP-4 inhibitors (gliptins):

    • Mechanism: inhibit DPP-4 enzyme, which degrades GLP-1, thereby prolonging endogenous incretin action.

    • Example: Januvia (sitagliptin).

  • GLP-1 receptor agonists (GLP-1 mimetics):

    • Examples discussed include exenatide (BYETTA), injected subcutaneously, typically before meals; dosing can be twice daily.

    • They mimic GLP-1 action but are resistant to DPP-4 degradation.

  • Summary of role: incretin-based therapies help lower glucose with potential weight loss benefits and a lower risk of hypoglycemia compared to secretagogues when used alone.

SGLT2 Inhibitors and Other Oral Agents

  • SGLT2 inhibitors (incretin-independent glucose lowering): block renal glucose reabsorption in the proximal tubule, promoting glucosuria and reducing plasma glucose.

  • Examples discussed include Jardiance (empagliflozin) and Steglatro (ertugliflozin).

  • They provide cardiovascular and renal benefits in many patients, though not all patients are eligible due to kidney function and other factors.

Insulin Therapy – Types and Use

  • Indications: required for Type 1 diabetes and often added for Type 2 diabetes when other meds do not achieve control.

  • Types of insulin:

    • Rapid-acting insulins: Lispro, Aspart (often used around meals or as part of a bolus regimen).

    • Long-acting insulins: Glargine (Lantus), Detemir; used for basal coverage (usually given at night or once daily).

    • Mixed insulins: e.g., 70/30 mixtures (70% Intermediate-acting to cover basal plus 30% rapid-acting for meals).

  • Typical regimen considerations: insulin regimens are often tailored based on patient needs, with combinations of basal and bolus insulin or premixed regimens.

  • Goal: achieve blood glucose control while avoiding hypoglycemia; monitor regularly and adjust dosing as needed.

Hypoglycemia: Recognition and Emergency Management

  • Early signs/symptoms: shakiness, sweating (diaphoresis), confusion, dizziness, hunger, irritability.

  • Management for awake patients: provide fast-acting carbohydrates (e.g., orange juice or oral glucose) and recheck glucose after 15 minutes; repeat if still low; avoid giving by mouth if patient is unconscious or at risk of choking.

  • Management for unconscious or unable to swallow: administer glucagon (emergency kit) or, if IV access is available, IV dextrose (e.g., dextrose 50% solution) can be given; call emergency services (EMS) if there is any concern about the patient’s ability to maintain airway or consciousness.

  • Practical tips: have quick source of glucose available; educate patients to recognize early hypoglycemia and to carry fast-acting carbs; ensure caregivers know when and how to administer glucagon.

Patient Education, Adherence, and Lifestyle Counseling

  • Education is a key role for nurses and physicians: diet, exercise, and medication adherence significantly impact outcomes.

  • Barriers to adherence discussed:

    • Cost/insurance access and affordability.

    • Access to pharmacies and medication availability.

    • Side effects leading to reluctance to take meds.

    • Preference for home remedies or alternative therapies in some cultures.

  • Importance of follow-up and monitoring:

    • Regular monitoring of fasting glucose, HbA1c, lipids, and renal/hepatic function as appropriate.

    • Reassessing medications based on lifestyle, weight, and comorbidities.

    • Education on proper insulin administration techniques and safe storage.

  • Lifestyle factors:

    • Diet: emphasis on balanced diet; discussion of low-carbohydrate/low-sugar approaches as part of glucose control.

    • Exercise: planning activity around insulin dosing and meals to avoid hypoglycemia.

    • Weight management: addressing obesity and its role in Type 2 diabetes risk and control.

  • Cultural and personal factors: varying beliefs about medications and therapies; need for culturally sensitive education and shared decision-making.

Diabetes Subtypes and Key Distinctions (Recap)

  • Type 1 diabetes:

    • Autoimmune beta-cell destruction; absolute insulin deficiency; often younger individuals.

  • Type 2 diabetes:

    • Insulin resistance with progressive deficiency; often older individuals; strongly linked to obesity and lifestyle.

  • Gestational diabetes:

    • Occurs during pregnancy; increases risk of type 2 diabetes later in life for the mother and child.

  • Other specified types:

    • Genetic defects of beta-cell function, insulin action; pancreatic disease (e.g., CF); drug/therapy-induced diabetes (e.g., steroids, transplant-related).

Practical Takeaways for Exam Preparation

  • Be able to distinguish type 1 vs type 2 diabetes in terms of pathophysiology and typical patient demographics.

  • Recognize the classic triad of diabetes symptoms: polyuria, polydipsia, polyphagia, plus fatigue, weight loss, and blurred vision.

  • Understand the purpose, mechanism, and typical side effects of major drug classes: metformin, sulfonylureas, GLP-1 mimetics, DPP-4 inhibitors, SGLT2 inhibitors, and insulin (rapid-acting, long-acting, and mixed regimens).

  • Know the key monitoring metrics: fasting glucose targets, HbA1c targets, and the use of home glucose monitoring data to guide therapy adjustments.

  • Be prepared to discuss hypoglycemia management steps and the importance of timely education and follow-up for medication adherence and lifestyle changes.

  • Understand how comorbidities (hypertension, hyperlipidemia, obesity) interact with diabetes management and why integrated care is critical.

  • Appreciate the broader context: the social determinants of health affecting diabetes care (insurance, access to healthy foods, cultural beliefs about medications).

Quick References (LaTeX-formatted for study notes)

  • Fasting blood glucose goals described: <100\ \text{mg/dL (normal)}, \approx 101\ \text{mg/dL (acceptable)}, >120\ \text{mg/dL (not normal)}

  • HbA1c: measures average glucose over \approx 3\text{ months}; normal HbA1c described as <5.6\%; typical HbA1c reduction with metformin: \approx -1\%

  • Metformin dosing guidance: start at low dose, titrate by +500\ \text{mg every 2 weeks}; most effect around 1500\ \text{mg/day}; monitor renal function due to renal clearance; avoid in significant renal/hepatic impairment; lactic acidosis risk discussed with comorbid conditions

  • Insulin regimens: rapid-acting (Lispro/Aspart), long-acting (Glargine/Lantus, Detemir), mixed (e.g., 70/30)); basal-bolus strategy common in Type 1 and many Type 2 cases

  • Hypoglycemia management: if awake—provide fast-acting carbohydrate (e.g., orange juice or oral glucose); if unconscious—glucagon or IV dextrose with EMS activation; avoid oral intake if risk of airway compromise

  • Incretin-based therapies:

    • DPP-4 inhibitors (e.g., Januvia) prolong endogenous GLP-1 activity

    • GLP-1 receptor agonists (e.g., exenatide) mimic GLP-1 action

  • SGLT2 inhibitors (e.g., Jardiance, Steglatro) promote glucosuria and reduce plasma glucose