Diabetes Mellitus: Pathophysiology and Complications
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Questions and Answers

What is the primary characteristic of diabetes mellitus?

  • Chronically elevated blood glucose (correct)
  • Deficiency of insulin in the pancreas
  • Chronic hyperglycemia
  • Abnormal protein metabolism

    • What can occur without effective treatment of diabetes mellitus?

  • Acute complications such as diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome (correct)
  • Macrovascular complications
  • Neuropathic complications
  • Microvascular complications

    • What type of complications can chronic hyperglycemia cause?

  • Only microvascular complications
  • Microvascular, macrovascular, and neuropathic complications (correct)
  • Only macrovascular complications
  • Only neuropathic complications

    • What is the usual cause of type 1 DM?

    <p>Autoimmune destruction of pancreatic β-cells</p> Signup and view all the answers

    At what age does type 1 DM usually present?

    <p>In children and adolescents, but can occur at any age</p> Signup and view all the answers

    What is a major feature of Type 2 diabetes mellitus related to insulin action in the body?

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

    Which of these factors greatly contributes to hyperglycemia in Type 2 diabetes mellitus?

    <p>Upregulated sodium-glucose cotransporter-2 (SGLT-2)</p> Signup and view all the answers

    Which class of diabetes mellitus occurs specifically during pregnancy?

    <p>Gestational diabetes (GDM)</p> Signup and view all the answers

    Retinopathy is a complication related to which part of the diabetes mellitus pathology?

    <p>Microvascular complications</p> Signup and view all the answers

    Which of the following is considered a macrovascular complication of diabetes mellitus?

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

    What is a common initial presentation sign of Type 1 Diabetes Mellitus?

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

    Which condition are individuals with Type 1 Diabetes Mellitus prone to develop without adequate insulin?

    <p>Diabetic Ketoacidosis (DKA)</p> Signup and view all the answers

    What often triggers the onset of Type 1 Diabetes Mellitus symptoms?

    <p>Psychological stress</p> Signup and view all the answers

    How are most Type 2 Diabetes Mellitus patients found to have the disease?

    <p>Through routine laboratory testing</p> Signup and view all the answers

    Why are complications often present at the time of Type 2 Diabetes Mellitus diagnosis?

    <p>Mild hyperglycemia may exist for years prior to the diagnosis</p> Signup and view all the answers

    What is the minimum A1C level for diagnosing diabetes mellitus?

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

    Which of the following is a criterion for diagnosing diabetes mellitus?

    <p>Fasting plasma glucose ≥126 mg/dL</p> Signup and view all the answers

    What is the term for a condition where blood glucose levels are abnormal but not high enough to be classified as diabetes mellitus?

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

    Who should be screened for type 2 diabetes mellitus?

    <p>Asymptomatic adults who are overweight and have at least one other risk factor</p> Signup and view all the answers

    How often should adults without risk factors be screened for type 2 diabetes mellitus?

    <p>Every 3 years starting at 45 years old</p> Signup and view all the answers

    At what age should children at risk for developing type 2 diabetes mellitus undergo screening?

    <p>10 years old</p> Signup and view all the answers

    What is the primary goal of diabetes treatment?

    <p>To prevent microvascular and macrovascular complications</p> Signup and view all the answers

    What should be the initial weight loss goal for type 2 DM patients who are overweight or obese?

    <p>5% of body weight</p> Signup and view all the answers

    How often should resistance/strength training be performed for patients without proliferative diabetic retinopathy?

    <p>2 times/week</p> Signup and view all the answers

    What level of exercise is recommended for adults with type 2 diabetes?

    <p>150 min/week of moderate intensity exercise</p> Signup and view all the answers

    What aspect should be individualized when setting glycemic targets?

    <p>Glycemic targets</p> Signup and view all the answers

    Which of the following is an additional goal of diabetes treatment?

    <p>Minimizing hyperglycemia</p> Signup and view all the answers

    What is the main advantage of insulin over other antihyperglycemic agents?

    <p>The dose can be individualized based on glycemic levels</p> Signup and view all the answers

    What is a characteristic of inhaled human insulin?

    <p>It is a dry powder of regular insulin inhaled and absorbed through pulmonary tissue</p> Signup and view all the answers

    What is the purpose of basal insulin?

    <p>To regulate BG levels in between meals</p> Signup and view all the answers

    What is a disadvantage of NPH insulin?

    <p>It has a distinct peak and usually requires twice daily dosing</p> Signup and view all the answers

    What are the characteristics of insulin products that are important to understand?

    <p>Onset, peak, and duration of action</p> Signup and view all the answers

    What is the primary characteristic of the rapid-acting insulins aspart, lispro, and glulisine?

    <p>Faster onset and shorter duration of action than regular insulin</p> Signup and view all the answers

    What is the difference between ultra-rapid acting insulins and rapid-acting insulins?

    <p>Ultra-rapid acting insulins have a faster onset of action</p> Signup and view all the answers

    What is the advantage of using ultra-rapid acting insulins over rapid-acting insulins?

    <p>They have a faster onset of action</p> Signup and view all the answers

    What is the characteristic of inhaled human insulin and fast-acting insulin aspart (Fiasp)?

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

    What is the potential benefit of using ultra-rapid acting insulins?

    <p>They may more closely mimic prandial endogenous insulin release</p> Signup and view all the answers

    What is a challenge posed by premixed insulin products containing both a basal and a prandial component?

    <p>They have a fixed mixed formulation that makes it difficult to tailor the dosing regimen.</p> Signup and view all the answers

    What is the approximate average daily insulin requirement for individuals with type 1 DM?

    <p>0.5-0.6 units/kg</p> Signup and view all the answers

    What is a common adverse effect of insulin therapy?

    <p>Dose-dependent weight gain</p> Signup and view all the answers

    What can be prevented by routinely rotating injection sites when administering insulin via SC administration?

    <p>Lipoatrophy or lipohypertrophy</p> Signup and view all the answers

    What is the usual proportion of basal insulin in the daily insulin requirement for individuals with type 1 DM?

    <p>50%</p> Signup and view all the answers

    What is the primary effect of metformin on hepatic glucose production?

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

    What is the primary advantage of metformin in terms of weight loss?

    <p>It may lead to a modest weight loss of 2-3 kg</p> Signup and view all the answers

    What is the primary reason why metformin is associated with a low risk of hypoglycemia?

    <p>It does not directly increase pancreatic insulin secretion</p> Signup and view all the answers

    What is the primary effect of metformin on lipid profiles?

    <p>It decreases plasma triglycerides and LDL-C and increases HDL-C</p> Signup and view all the answers

    What is the primary strategy for minimizing gastrointestinal side effects associated with metformin?

    <p>Taking metformin with or immediately after meals</p> Signup and view all the answers

    What is the primary concern with using metformin in patients with renal insufficiency?

    <p>It may accumulate in the body and cause acute renal failure</p> Signup and view all the answers

    What is the primary indication for withholding metformin therapy?

    <p>Use of IV contrast dye</p> Signup and view all the answers

    What is the primary characteristic of extended-release metformin in terms of gastrointestinal side effects?

    <p>It lessens gastrointestinal side effects</p> Signup and view all the answers

    What is the mechanism by which SGLT-2 inhibitors decrease plasma glucose levels?

    <p>Blocking the reabsorption of glucose in the kidneys</p> Signup and view all the answers

    Which of the following conditions are SGLT-2 inhibitors recommended for due to their additional benefits?

    <p>Heart failure and chronic kidney disease (CKD)</p> Signup and view all the answers

    Which adverse effect is most commonly associated with SGLT-2 inhibitors?

    <p>Genital mycotic infections</p> Signup and view all the answers

    Why are SGLT-2 inhibitors unlikely to cause hypoglycemia when used alone?

    <p>They do not increase insulin release</p> Signup and view all the answers

    Which additional medication classes may increase the risk of hypoglycemia when used with SGLT-2 inhibitors?

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

    What is the effect of GLP-1 RAs on gastric emptying and satiety?

    <p>Decrease gastric emptying and increase satiety</p> Signup and view all the answers

    Which GLP-1 RAs are FDA approved to reduce the risk of major adverse CV events?

    <p>Dulaglutide, liraglutide, and semaglutide</p> Signup and view all the answers

    What is the difference in the effects of short-acting and long-acting GLP-1 RAs on glucose levels?

    <p>Short-acting agents lower PPG, while long-acting agents lower both FPG and PPG</p> Signup and view all the answers

    Which GLP-1 RA is available in both SC and oral preparations?

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

    In which patients can GLP1-RAs be used as monotherapy?

    <p>Patients who are unable to tolerate or take first-line therapy</p> Signup and view all the answers

    What is the effect of DPP-4 inhibitors on gastric emptying?

    <p>They do not alter gastric emptying</p> Signup and view all the answers

    What is a characteristic of DPP-4 inhibitors in terms of weight?

    <p>They are weight neutral</p> Signup and view all the answers

    What is the typical frequency of dosing for DPP-4 inhibitors?

    <p>Once daily</p> Signup and view all the answers

    What is a benefit of using DPP-4 inhibitors as monotherapy?

    <p>They decrease the risk of hypoglycemia</p> Signup and view all the answers

    What is the typical position of DPP-4 inhibitors in therapy for diabetes mellitus?

    <p>Second- or third-line therapy</p> Signup and view all the answers

    Which receptor do thiazolidinediones (TZDs) primarily bind to?

    <p>Peroxisome proliferator-activated receptor-γ (PPAR-γ)</p> Signup and view all the answers

    What is a common consequence of fluid retention caused by TZDs?

    <p>Peripheral edema</p> Signup and view all the answers

    After how many months of therapy are the maximum effects of TZDs typically observed?

    <p>3-4 months</p> Signup and view all the answers

    In which patients are TZDs contraindicated?

    <p>Patients with New York Heart Association Class III or IV heart failure</p> Signup and view all the answers

    What factors contribute to weight gain associated with TZDs?

    <p>Fluid retention and fat accumulation</p> Signup and view all the answers

    What is the mechanism of action of sulfonylureas on pancreatic β-cells?

    <p>Binding to the sulfonylurea receptor SUR1</p> Signup and view all the answers

    What is a common side effect of sulfonylureas, which is a concern in their use?

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

    What is a characteristic of sulfonylureas that may lead to poor long-term durability of response in most patients?

    <p>Tachyphylaxis to insulin secretion effect</p> Signup and view all the answers

    What is the typical weight gain associated with sulfonylureas?

    <p>1-2 kg</p> Signup and view all the answers

    What is the risk of cross-reactivity in patients with sulfa allergy who take sulfonylureas?

    <p>Low risk</p> Signup and view all the answers

    What is the primary effect of α-glucosidase inhibitors on carbohydrate absorption?

    <p>Prolonging carbohydrate absorption</p> Signup and view all the answers

    What is the primary advantage of meglitinides over sulfonylureas?

    <p>Faster onset and shorter duration of action</p> Signup and view all the answers

    Which patients are good candidates for α-glucosidase inhibitors?

    <p>Those with near target A1C levels and near-normal FPG but high PPG levels</p> Signup and view all the answers

    What is the primary side effect of meglitinides?

    <p>Hypoglycemia and weight gain</p> Signup and view all the answers

    When should meglitinides be taken?

    <p>With each meal</p> Signup and view all the answers

    What is the primary mechanism of action of pramlintide in reducing glucose levels?

    <p>Reducing glucagon secretion</p> Signup and view all the answers

    What is the FDA-approved indication for 1-bromocriptine mesylate?

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

    What is the primary benefit of using pramlintide in patients with type 1 diabetes mellitus?

    <p>Allowing for lower mealtime insulin doses</p> Signup and view all the answers

    What is the role of colesevelam in lowering plasma glucose levels?

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

    In what type of patients is pramlintide used primarily as adjunctive therapy?

    <p>Patients with type 1 diabetes mellitus</p> Signup and view all the answers

    What should be implemented upon diagnosis of type 2 diabetes?

    <p>Comprehensive lifestyle modifications</p> Signup and view all the answers

    Which of the following is advised for a patient with heart failure (HF) and type 2 diabetes?

    <p>SGLT2 inhibitor</p> Signup and view all the answers

    What is recommended when a patient's initial A1C level is very high (>10%)?

    <p>Introduce basal insulin early</p> Signup and view all the answers

    What should be considered if a patient's initial A1C is close to the goal (≤7.5%)?

    <p>Consider initial treatment with lifestyle modifications alone</p> Signup and view all the answers

    How frequently should patients who are not meeting their glucose targets be seen?

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

    What is the role of setting a patient-specific A1C target?

    <p>Individualize treatment and management goals</p> Signup and view all the answers

    What is the recommended course of action if a patient’s A1C target is not achieved after 3 months of dual therapy?

    <p>Start triple therapy with a drug from another class</p> Signup and view all the answers

    What is a preferred treatment for extreme hyperglycemia (A1C >10%) or symptomatic hyperglycemia?

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

    Why are GLP-1 RAs preferred over basal insulin when insulin is not immediately necessary?

    <p>They have equal or superior A1C lowering efficacy and lead to weight loss</p> Signup and view all the answers

    When should basal insulin be initiated in the treatment plan?

    <p>After GLP-1 RA therapy has been maximized but additional glucose lowering is still needed</p> Signup and view all the answers

    What treatment options are considered if the A1C target is not reached by maximally titrating basal insulin?

    <p>GLP-1 RA or SGLT-2 inhibitor and possibly prandial insulin</p> Signup and view all the answers

    In what scenario might prandial insulin be added to a patient’s regimen?

    <p>If PPG levels remain elevated despite maximally titrating basal insulin</p> Signup and view all the answers

    What is the purpose of basal insulin in intensive insulin regimens?

    <p>To maintain consistent insulin secretion throughout the day</p> Signup and view all the answers

    What is a common multiple daily injection (MDI) approach for type 1 diabetes management?

    <p>One injection of long-acting insulin and three injections of rapid-acting insulin</p> Signup and view all the answers

    Why does the ADA recommend using rapid-acting insulins over regular insulin?

    <p>To reduce the risk of hypoglycemia</p> Signup and view all the answers

    What is a disadvantage of NPH insulin?

    <p>It has a peak action that can cause hypoglycemia</p> Signup and view all the answers

    What is the primary benefit of using continuous subcutaneous insulin infusion (CSII) via an insulin pump?

    <p>It provides more consistent insulin delivery throughout the day</p> Signup and view all the answers

    What is a less expensive option for intensive insulin regimens?

    <p>Using two injections of intermediate-acting insulin and two injections of short-acting insulin</p> Signup and view all the answers

    What is a key feature of insulin pump therapy (CSII)?

    <p>It allows for both basal and bolus insulin administration.</p> Signup and view all the answers

    How is the total daily insulin dose typically distributed for patients on insulin pump therapy?

    <p>50% basal insulin and 50% prandial insulin.</p> Signup and view all the answers

    What is the role of carbohydrate counting in insulin pump therapy?

    <p>To adjust prandial insulin doses according to carbohydrate intake.</p> Signup and view all the answers

    For which type of patients is pramlintide indicated?

    <p>Patients with type 1 DM who are not meeting glycemic targets despite optimized mealtime insulin.</p> Signup and view all the answers

    How often should patients on intensive insulin therapy perform SMBG?

    <p>At least four times daily, before meals and at bedtime.</p> Signup and view all the answers

    What is recommended for patients with type 1 DM who are not meeting glycemic goals according to current guidelines?

    <p>Use of continuous glucose monitoring (CGM).</p> Signup and view all the answers

    Why should patients with hypoglycemia unawareness use continuous glucose monitoring (CGM)?

    <p>To better detect and prevent hypoglycemic events.</p> Signup and view all the answers

    When should patients with diabetes perform SMBG in addition to their regular schedule?

    <p>During intercurrent illness or stress.</p> Signup and view all the answers

    What is the purpose of the basal insulin rate in an insulin infusion device?

    <p>To provide a consistent background level of insulin</p> Signup and view all the answers

    What is the classification of hypoglycemia with a blood glucose level of ≤70 mg/dL?

    <p>Level 1: Hypoglycemia alert value</p> Signup and view all the answers

    What type of insulin is used in an insulin infusion device?

    <p>Rapid-acting insulin (aspart, lispro, or glulisine)</p> Signup and view all the answers

    What is the goal of adjusting the basal insulin rate in an insulin infusion device during the evening and morning?

    <p>To decrease hypoglycemia during the evening and increase it in the morning</p> Signup and view all the answers

    What is the purpose of using rapid-acting insulin (aspart, lispro, or glulisine) in a multiple-component insulin regimen?

    <p>To provide glycemic coverage for each meal</p> Signup and view all the answers

    What is the classification of hypoglycemia that requires treatment with a fast-acting carbohydrate and may need medication dose adjustment?

    <p>Level 1: Hypoglycemia alert value</p> Signup and view all the answers

    What is a common initial autonomic symptom of diabetes mellitus?

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

    What is often associated with neuroglycopenic symptoms?

    <p>Low blood glucose levels</p> Signup and view all the answers

    What is a characteristic of initial autonomic symptoms of diabetes mellitus?

    <p>Fast heart rate</p> Signup and view all the answers

    What is often experienced by individuals with diabetes mellitus?

    <p>Both A and B</p> Signup and view all the answers

    What is a common autonomic symptom of diabetes mellitus?

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

    What is the primary reason glucagon may be given in a hypoglycemic emergency?

    <p>To increase glycogenolysis in the liver</p> Signup and view all the answers

    Why should a glucagon kit be prescribed to patients on insulin?

    <p>To treat severe hypoglycemia quickly</p> Signup and view all the answers

    How should a patient be positioned if they are unconscious to avoid aspiration?

    <p>On their side with head tilted slightly downward</p> Signup and view all the answers

    What is the ADA's recommendation for patients with established ASCVD?

    <p>Low-dose aspirin therapy</p> Signup and view all the answers

    What action should clinicians take at every visit regarding hypoglycemia?

    <p>Monitor hypoglycemia</p> Signup and view all the answers

    What should be done for patients with frequent or severe hypoglycemia?

    <p>Reevaluate their treatment regimen</p> Signup and view all the answers

    When is it recommended to initiate drug therapy to reduce cardiovascular events in patients with high blood pressure?

    <p>For BP &gt;140/90 mm Hg</p> Signup and view all the answers

    What is the ADA's recommendation for patients with BP exceeding 120/80 mm Hg?

    <p>Dietary changes, physical activity, and weight loss</p> Signup and view all the answers

    For patients with diabetes and no preexisting ASCVD, what type of statin therapy is recommended?

    <p>Moderate-intensity statin therapy</p> Signup and view all the answers

    Which antidiabetic agents should be strongly considered for patients with established ASCVD?

    <p>GLP1-RA or SGLT-2 inhibitor</p> Signup and view all the answers

    When should a combination of two medications be used for managing high blood pressure in patients?

    <p>For BP &gt;160/100 mm Hg</p> Signup and view all the answers

    What is the recommended screening frequency for albuminuria in persons with type 2 diabetes?

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

    What type of medications can slow the progression of renal disease in patients with diabetes?

    <p>ACE inhibitors and ARBs</p> Signup and view all the answers

    What is the effect of SGLT2 inhibitors on kidney function in patients with chronic kidney disease?

    <p>They significantly reduce the decline in kidney function</p> Signup and view all the answers

    When should screening for albuminuria begin in patients with type 1 diabetes?

    <p>At puberty and after 5 years' disease duration</p> Signup and view all the answers

    What is the primary reason for using diuretics in patients with diabetes?

    <p>To treat volume expanded states</p> Signup and view all the answers

    What is the primary goal of routine eye examinations for patients with diabetes?

    <p>To fully evaluate the retina</p> Signup and view all the answers

    What is the primary treatment for peripheral neuropathy in patients with type 2 DM?

    <p>Improved glycemic control</p> Signup and view all the answers

    What is the primary benefit of laser photocoagulation in patients with diabetic retinopathy?

    <p>Sight preservation</p> Signup and view all the answers

    What is the characteristic of bevacizumab, ranibizumab, and aflibercept in the treatment of diabetic retinopathy?

    <p>Anti-vascular endothelial growth factor (VEGF) therapy</p> Signup and view all the answers

    What is the most common complication in patients with type 2 DM?

    <p>Peripheral neuropathy</p> Signup and view all the answers

    What is the primary goal of pharmacologic therapy in the treatment of peripheral neuropathy?

    <p>To alleviate symptoms</p> Signup and view all the answers

    Which medication may be used to help manage gastroparesis in diabetic patients?

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

    What is the initial therapy for managing erectile dysfunction in diabetic patients?

    <p>Phosphodiesterase-5 inhibitors</p> Signup and view all the answers

    What type of vaccine should be administered annually to diabetic patients?

    <p>Influenza vaccine</p> Signup and view all the answers

    Which test is used to monitor long-term glycemic control every 3-6 months?

    <p>A1C</p> Signup and view all the answers

    Which medication may be useful in cases of diabetic diarrhea that do not respond to antibiotics?

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

    Which of the following interventions may be necessary for managing orthostatic hypotension in diabetic patients?

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

    Which symptoms are typically associated with asthma?

    <p>Shortness of breath and chest tightness</p> Signup and view all the answers

    What causes the contraction of airway smooth muscle in asthma?

    <p>Proinflammatory mediators</p> Signup and view all the answers

    Which cell types are activated by inhaled allergens in allergic asthma patients?

    <p>Mast cells, neutrophils, and macrophages</p> Signup and view all the answers

    When do asthma symptoms often occur?

    <p>Frequently during exercise</p> Signup and view all the answers

    What is a defining characteristic of asthma in terms of airflow?

    <p>Variable expiratory airflow limitation</p> Signup and view all the answers

    Which of the following is not typically a symptom of chronic asthma?

    <p>Increased appetite</p> Signup and view all the answers

    What is the primary symptom of acute severe asthma?

    <p>Severe dyspnea and shortness of breath</p> Signup and view all the answers

    What is the characteristic of spirometry in patients with chronic asthma?

    <p>Decreased FEV1/FVC ratio</p> Signup and view all the answers

    What is the primary method for diagnosing chronic asthma?

    <p>Spirometry and lung function tests</p> Signup and view all the answers

    What is a common sign of acute severe asthma?

    <p>Tachycardia and tachypnea</p> Signup and view all the answers

    What is the characteristic of a patient's speech in acute severe asthma?

    <p>Speaking only a few words with each breath</p> Signup and view all the answers

    What is one of the primary goals of long-term asthma management?

    <p>Minimizing future risk of exacerbations</p> Signup and view all the answers

    Which nonpharmacologic therapy is specifically recommended for patients with severe asthma or poor symptom perception?

    <p>Routine PEF monitoring</p> Signup and view all the answers

    What is a crucial step in treating acute asthma exacerbations?

    <p>Initiate oxygen therapy</p> Signup and view all the answers

    What is the importance of patient education in asthma management?

    <p>It improves medication adherence and self-management skills</p> Signup and view all the answers

    What is a recommended nonpharmacologic therapy to improve asthma symptoms and reduce medication use?

    <p>Avoidance of known allergenic triggers</p> Signup and view all the answers

    What is the preferred treatment for adults and adolescents with asthma?

    <p>GINA track 1 with as-needed ICS-formoterol</p> Signup and view all the answers

    What should be considered when adding-on treatment for severe asthma?

    <p>Inflammatory phenotype and other clinical features</p> Signup and view all the answers

    When should low-dose maintenance oral corticosteroid (OCS) therapy be considered for asthma treatment?

    <p>As a last resort if no other options are available</p> Signup and view all the answers

    After achieving good asthma control, what should be considered?

    <p>Stepping down gradually to find the patient's lowest treatment</p> Signup and view all the answers

    What is typically administered concurrently to facilitate rapid improvement in acute asthma exacerbations?

    <p>Inhaled SABAs, systemic corticosteroids, inhaled ipratropium, IV magnesium sulfate, and oxygen</p> Signup and view all the answers

    What is the primary goal of asthma treatment?

    <p>To control both symptoms and exacerbations</p> Signup and view all the answers

    What is the primary indication for the use of SABAs like albuterol?

    <p>Acute severe asthma management</p> Signup and view all the answers

    What is an advantage of aerosol administration of β2-agonists?

    <p>Enhanced bronchoselectivity and rapid response</p> Signup and view all the answers

    What is the duration of bronchodilation provided by LABAs like formoterol and salmeterol?

    <p>12 hours or longer</p> Signup and view all the answers

    When can formoterol be dosed?

    <p>Daily and as needed</p> Signup and view all the answers

    What is the dosing frequency for LABAs like formoterol and salmeterol?

    <p>Twice daily</p> Signup and view all the answers

    What is the main advantage of inhaled corticosteroids (ICS) as a long-term control therapy for persistent asthma?

    <p>High potency and consistent effectiveness</p> Signup and view all the answers

    What is a potential systemic effect of high-dose inhaled corticosteroids (ICS)?

    <p>Adrenal insufficiency</p> Signup and view all the answers

    What is a local adverse effect of inhaled corticosteroids (ICS) that can be reduced by using a spacer device?

    <p>Oropharyngeal candidiasis</p> Signup and view all the answers

    When should systemic corticosteroids be administered in patients with acute severe asthma?

    <p>Within 1 hour of presentation</p> Signup and view all the answers

    What is the advantage of IV corticosteroid therapy over oral administration in patients with acute severe asthma?

    <p>No advantage, except in patients unable to take oral medications</p> Signup and view all the answers

    Which medication is useful as adjunctive therapy in acute severe asthma not completely responsive to SABA alone?

    <p>Ipratropium bromide</p> Signup and view all the answers

    What type of patients might be prescribed ipratropium for rescue inhaler use instead of short acting β2 agonists?

    <p>Patients intolerant to short acting β2 agonists</p> Signup and view all the answers

    What is the duration of action for tiotropium bromide in asthma treatment?

    <p>24 hours</p> Signup and view all the answers

    Which of these medications may be considered as add-on therapy for patients not well controlled with ICS and LABA combination therapy?

    <p>Tiotropium bromide</p> Signup and view all the answers

    Which therapeutic class directly reverses cholinergic mediated bronchoconstriction?

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

    What is the primary effect of leukotriene receptor antagonists on the body?

    <p>Reduce the proinflammatory and bronchoconstriction effects of leukotriene D4</p> Signup and view all the answers

    What is the primary limitation of using zafirlukast and montelukast compared to inhaled corticosteroids (ICS) and long-acting beta2 agonists (LABAs)?

    <p>They are less effective than ICS and LABAs</p> Signup and view all the answers

    What is a rare but serious adverse effect associated with the use of zafirlukast?

    <p>Fatal hepatic failure</p> Signup and view all the answers

    What is a common neuropsychiatric adverse effect associated with the use of montelukast and zafirlukast?

    <p>All of the above</p> Signup and view all the answers

    What is the mechanism of action of zileuton?

    <p>5-lipoxygenase inhibitor</p> Signup and view all the answers

    What is a potential interaction associated with the use of zileuton?

    <p>Inhibition of metabolism of drugs metabolized by CYP3A4</p> Signup and view all the answers

    Why are methylxanthines rarely used today?

    <p>High risk of severe life-threatening toxicity</p> Signup and view all the answers

    What is a required procedure when administering theophylline?

    <p>Monitoring of serum concentrations</p> Signup and view all the answers

    Which enzyme system is primarily involved in the metabolism of theophylline?

    <p>CYP P450 microsomal enzymes</p> Signup and view all the answers

    How frequently should inhalation technique be evaluated initially for patients on inhaled drugs?

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

    What is the expected time frame for maximum improvement after increasing anti-inflammatory therapy dosage?

    <p>4-8 weeks</p> Signup and view all the answers

    Which condition is characterized by abnormal, permanent enlargement of the airspaces distal to the terminal bronchioles?

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

    What is the most common cause of Chronic Obstructive Pulmonary Disease (COPD)?

    <p>Exposure to tobacco smoke</p> Signup and view all the answers

    Which of these is a primary symptom of Chronic Obstructive Pulmonary Disease (COPD)?

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

    How long must chronic bronchitis symptoms persist for a diagnosis to be made?

    <p>Most days for at least 3 months of the year for at least 2 consecutive years</p> Signup and view all the answers

    What cardiovascular condition can result from chronic hypoxemia and changes in pulmonary vasculature in COPD patients?

    <p>Cor pulmonale</p> Signup and view all the answers

    Which type of cell activity results in the chronic airflow limitation seen in COPD?

    <p>Inflammatory cell activation</p> Signup and view all the answers

    What is the primary characteristic of symptoms in patients with chronic obstructive lung disease?

    <p>They develop over several years</p> Signup and view all the answers

    What is the term used to describe the sensation of 'increased effort to breathe' or 'air hunger' in patients with chronic obstructive lung disease?

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

    What is the purpose of spirometry in the diagnosis of chronic obstructive lung disease?

    <p>To measure lung volumes and capacities</p> Signup and view all the answers

    What is the term used to classify the severity of airflow limitation in chronic obstructive lung disease?

    <p>GOLD classification</p> Signup and view all the answers

    What is a characteristic of patients with severe chronic obstructive lung disease?

    <p>Shallow breathing</p> Signup and view all the answers

    What is the term used to describe the 'barrel chest' appearance in patients with chronic obstructive lung disease?

    <p>Lung hyperinflation</p> Signup and view all the answers

    Which intervention is most crucial for preventing the development and progression of COPD?

    <p>Smoking cessation</p> Signup and view all the answers

    Which type of therapy is primarily used to relieve symptoms of dyspnea in COPD patients?

    <p>Short-acting inhaled bronchodilators</p> Signup and view all the answers

    What is included in pulmonary rehabilitation programs for COPD patients?

    <p>Exercise training, breathing exercises, and psychosocial support</p> Signup and view all the answers

    What kind of vaccine is recommended annually for COPD patients?

    <p>Influenza vaccine</p> Signup and view all the answers

    What aspect is crucial for determining the initial treatment according to GOLD guidelines?

    <p>Frequency of exacerbations in the previous 12 months</p> Signup and view all the answers

    Which class of drugs forms the mainstay of pharmacologic therapy for COPD?

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

    Study Notes

    Diabetes Mellitus (DM)

    • A group of metabolic disorders characterized by chronically elevated blood glucose and abnormal metabolism of carbohydrates, fats, and proteins.

    Acute Complications of DM

    • Diabetic ketoacidosis (DKA)
    • Hyperosmolar hyperglycemic syndrome (HHS)

    Chronic Complications of Hyperglycemia

    • Microvascular complications
    • Macrovascular complications
    • Neuropathic complications

    Pathophysiology of Type 1 DM

    • Results from autoimmune destruction of pancreatic β-cells
    • Leads to absolute deficiency of insulin due to islet cell antibody
    • Typically presents in children and adolescents, but can occur at any age

    Type 2 Diabetes Mellitus (T2DM)

    • Characterized by multiple defects, accounting for 90%–95% of DM cases
    • Impaired insulin secretion due to:
    • Reduced incretin effect
    • Incretin hormones affected: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)
    • Insulin resistance manifested by:
    • Excessive hepatic glucose production
    • Decreased skeletal muscle uptake of glucose
    • Increased lipolysis and free fatty acid production
    • Additional characteristics:
    • Excess glucagon secretion
    • Upregulation of sodium-glucose cotransporter-2 (SGLT-2) in the kidney, leading to increased glucose reabsorption and contributing to hyperglycemia

    Gestational Diabetes Mellitus (GDM)

    • A type of DM that occurs in women during pregnancy

    Diabetes Complications

    Microvascular Complications

    • Retinopathy
    • Neuropathy
    • Nephropathy

    Macrovascular Complications

    • Coronary heart disease (CHD)
    • Stroke
    • Peripheral vascular disease

    Clinical Presentation of Diabetes Mellitus

    Type 1 Diabetes Mellitus

    • Patients often exhibit symptoms in the days or weeks preceding diagnosis, including polyuria, polydipsia, polyphagia, weight loss, fatigue, and lethargy.
    • Individuals are often thin and prone to developing Diabetic Ketoacidosis (DKA) in the absence of adequate insulin supply, with many patients initially presenting with DKA.
    • Symptom onset can be triggered by infection, trauma, or psychological stress.

    Type 2 Diabetes Mellitus

    • Most patients are asymptomatic or experience mild fatigue at the time of diagnosis, with many cases incidentally discovered through routine laboratory testing (e.g., plasma glucose or A1C) or development of complications (e.g., myocardial infarction, stroke).
    • Mild hyperglycemia may exist for years prior to diagnosis, resulting in microvascular and macrovascular complications often being present at the time of diagnosis.
    • Most patients are overweight or obese.

    Diagnostic Criteria for Diabetes Mellitus (DM)

    • A1C ≥6.5% is a criterion for diagnosing DM
    • Fasting plasma glucose (FPG) ≥126 mg/dL is another criterion for diagnosing DM
    • Oral glucose tolerance test (OGTT) ≥200 mg/dL is also a criterion for diagnosing DM
    • Random plasma glucose ≥200 mg/dL with classic symptoms of hyperglycemia or hyperglycemic crisis is the fourth criterion for diagnosing DM

    Prediabetes

    • Prediabetes is a condition of abnormal blood glucose (BG) that is not high enough to meet DM diagnostic thresholds
    • Prediabetes often progresses to DM

    Screening for Diabetes

    • Screening for type 1 DM in asymptomatic individuals is not recommended due to low disease prevalence and acute onset of symptoms
    • Screening for type 2 DM is recommended for asymptomatic adults who are overweight (BMI ≥25 kg/m2) and have at least one other risk factor for developing type 2 DM
    • All adults should be screened every 3 years starting at 45 years old, regardless of risk factors
    • Children at risk for developing type 2 DM should undergo screening every 3 years starting at age 10 years

    Treatment of Diabetes

    • The primary goal of treatment is to prevent or delay the progression of long-term microvascular and macrovascular complications.

    Goals of Treatment

    • Alleviate symptoms of hyperglycemia
    • Minimize hypoglycemia and other adverse effects
    • Individualize glycemic targets, with more or less stringent goals depending on the patient

    Nonpharmacologic Therapy

    Medical Nutrition Therapy (MNT)

    • Implement a healthy meal plan that is:
      • Moderate in calories and carbohydrates
      • Low in saturated fat
      • Rich in essential vitamins and minerals
    • Target an initial weight loss goal of at least 5% in type 2 DM patients who are overweight or obese through calorie restriction

    Physical Activity

    • Aerobic exercise goals:
      • At least 150 minutes/week of moderate-intensity exercise
      • Spread over at least 3 days/week
      • No more than 2 days between activity
    • Resistance/strength training:
      • Recommended at least 2 times/week
      • Except for patients with proliferative diabetic retinopathy

    Patient Involvement and Education

    • Patients must be involved in decision-making and have strong knowledge of the disease and associated complications

    Insulin Therapy

    • Insulin has the advantage of individualized dosing based on glycemic levels, making it a more personalized treatment option.

    Advantages and Disadvantages

    • Disadvantages of insulin include the risk of hypoglycemia, need for injections, and weight gain.

    Administration of Insulin

    • Most insulin products are administered subcutaneously (SC) for chronic diabetes management.
    • Inhaled human insulin is an exception, which is a dry powder of regular insulin that is inhaled and absorbed through pulmonary tissue.

    Pharmacokinetics of Insulin

    • The pharmacokinetics of insulin products are characterized by their onset, peak, and duration of action.

    Basal Insulin

    • Basal insulin (or background insulin) refers to longer-acting insulins that regulate BG levels in between meals.
    • Options for basal insulin include:
      • NPH (not ideal due to distinct peak and twice daily dosing requirement)
      • Detemir (has a peak and often lasts)

    Insulin Options

    • Bolus insulin options include Aspart, lispro, and glulisine, which are rapid-onset, short-duration insulins
    • Other options include inhaled human insulin, fast-acting insulin aspart (Fiasp®), and insulin lispro (Lyumjev®), which are ultrarapid onset insulins

    Characteristics of Rapid-Acting Insulins

    • Offer a faster onset and shorter duration of action compared to regular insulin
    • Ultra-rapid acting insulins have an even faster onset, mimicking prandial endogenous insulin release more closely

    Insulin Types and Characteristics

    • Rapid-acting insulins have a lower risk of hypoglycemia compared to regular insulin.

    Premixed Insulin Products

    • Premixed insulin products contain both basal and prandial components.
    • These products are limited by fixed mixed formulations, making it challenging to tailor the dosing regimen.

    Insulin Dosage

    • The average daily insulin requirement for type 1 DM is 0.5–0.6 units/kg.
    • The daily insulin dose is typically divided into two components: 50% as basal insulin and 50% for meal coverage.

    Adverse Effects of Insulin Therapy

    • Hypoglycemia is the most common adverse effect of insulin therapy.
    • Insulin therapy also causes dose-dependent weight gain.

    Subcutaneous Insulin Administration

    • SC administration can result in lipoatrophy or lipohypertrophy.
    • Rotating injection sites can prevent lipoatrophy or lipohypertrophy.

    Metformin Mechanism of Action

    • Decreases hepatic glucose production and enhances insulin sensitivity in peripheral (muscle) tissues
    • Increases glucose uptake into muscle cells

    Metformin Recommendations

    • Recommended as first-line pharmacotherapy in patients with type 2 DM (unless a contraindication or intolerability exists)

    Effects on Body Weight and Glucose Regulation

    • Does not cause weight gain
    • May lead to a modest (2–3 kg) weight loss
    • Does not directly increase pancreatic insulin secretion, resulting in a low risk of hypoglycemia

    Effects on Lipid Profile

    • Decreases plasma triglycerides and low-density lipoprotein cholesterol (LDL-C)
    • Modestly increases high-density lipoprotein cholesterol (HDL-C)

    Adverse Effects

    • Frequently causes GI side effects (diarrhea, abdominal discomfort, stomach upset)
    • GI side effects are usually dose-dependent, transient, mild, and can be minimized with slow dose titration and taking metformin with or immediately after meals
    • May cause a metallic taste
    • May lower vitamin B12 concentrations, requiring annual measurement or supplementation if indicated

    Rare but Serious Adverse Effects

    • Lactic acidosis occurs rarely, usually in the setting of severe illness or acute kidney injury
    • Diagnosis must be confirmed by laboratory measurement of high lactic acid levels and acidosis

    Renal Considerations

    • Metformin is renally excreted and accumulates in renal insufficiency
    • Withhold metformin therapy starting the day of IV contrast dye procedure and resume it 2–3 days later if normal renal function has been documented

    Combination Therapy

    • Can be used in combination with any other antihyperglycemic therapy
    • Often continued when insulin therapy is initiated

    Mechanism of Action

    • SGLT-2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin) reduce plasma glucose by preventing the kidneys from reabsorbing glucose back into the bloodstream, leading to increased glucose excretion in the urine.

    Efficacy

    • SGLT-2 inhibitors lower both FPG (Fasting Plasma Glucose) and postprandial glucose (PPG).

    Indications and Contraindications

    • Can be added to metformin or other second-line agents.
    • Can be used as monotherapy in patients who cannot tolerate or take metformin.
    • Recommended for patients at high risk for or with established ASCVD (Atherosclerotic Cardiovascular Disease), heart failure, or CKD (Chronic Kidney Disease).

    Adverse Effects

    • Unlikely to cause hypoglycemia unless combined with medications such as sulfonylureas, meglitinides, or insulin.
    • Most common adverse effect is genital mycotic infections, more common in women and uncircumcised men.
    • Slightly increased risk of urinary tract infections.
    • May cause polyuria, dehydration, dizziness, or hypotension due to osmotic diuresis effects.

    Mechanism of Action

    • GLP1-RAs stimulate insulin secretion and suppress inappropriately high postprandial glucagon secretion, decreasing hepatic glucose output
    • They also slow gastric emptying, increase satiety, and cause weight loss (average 1–3 kg)

    Classification of GLP1-RAs

    • Short-acting agents: exenatide, lixisenatide (predominantly lower PPG levels)
    • Long-acting agents: dulaglutide, liraglutide, exenatide XR, semaglutide (lower both FPG and PPG, with larger effects on FPG)

    FDA Approval

    • Dulaglutide, liraglutide, and semaglutide are FDA approved to reduce the risk of major adverse CV events in adults with type 2 DM and established ASCVD

    Clinical Use

    • GLP1RAs can be used as monotherapy in patients who cannot tolerate or take first line therapy
    • Six GLP1RAs are administered SC (subcutaneously)
    • Semaglutide is available as SC and oral preparations

    DPP-4 Inhibitors Mechanism of Action

    • Prolong half-life of endogenously produced GLP-1 and GIP, increasing glucose-dependent insulin secretion from the pancreas.
    • Reduce inappropriate postprandial glucagon secretion, resulting in lower glucose levels.

    Effects on Body

    • Do not alter gastric emptying.
    • Do not cause weight gain or loss.

    Clinical Usage

    • Considered second- or third-line therapy.

    Advantages

    • Once-daily dosing.
    • Oral administration.
    • Weight neutrality.
    • Low risk of hypoglycemia.
    • Good tolerability.

    Mechanism of Action

    • TZDs bind to PPAR-γ receptors, primarily located on fat and vascular cells, to enhance insulin sensitivity in muscle, liver, and fat tissues.

    Efficacy

    • Maximum effects of TZDs may not be seen until 3-4 months of therapy.

    Clinical Use

    • TZDs are considered second- or third-line agents for type 2 DM.
    • They can be used in combination with metformin and other commonly prescribed medications.

    Adverse Effects

    • Fluid retention may occur, leading to peripheral edema, HF, hemodilution of hemoglobin and hematocrit, and weight gain.
    • Weight gain is dose-related and results from both fluid retention and fat accumulation.

    Contraindications

    • TZDs are contraindicated in patients with New York Heart Association Class III or IV HF.
    • They should be used with caution in patients with Class I or II HF.

    Mechanism of Action

    • Sulfonylureas enhance insulin secretion by binding to the sulfonylurea receptor SUR1 on pancreatic β-cells.

    Advantages and Limitations

    • Sulfonylureas have an extensive record of safety and effectiveness.
    • They are administered orally.
    • They are inexpensive.
    • However, they are discouraged or used with caution due to the risk of hypoglycemia and weight gain.
    • Tachyphylaxis to the insulin secretion effect occurs, leading to poor long-term durability of response in most patients.

    Side Effects

    • The most common side effect is hypoglycemia.
    • Weight gain is common, typically 1–2 kg.

    Allergy Concerns

    • Patients with sulfa allergy rarely experience cross-reactivity with sulfonylureas.

    α-Glucosidase Inhibitors

    • Acarbose and miglitol delay the breakdown of sucrose and complex carbohydrates in the small intestine, prolonging carbohydrate absorption.
    • Suitable for patients who are near target A1C levels with near-normal FPG but high PPG levels.
    • Common side effects include flatulence, abdominal pain, and diarrhea, which can be reduced by slow dosage titration.

    Meglitinides

    • Nateglinide and repaglinide stimulate insulin secretion from pancreatic β-cells by binding to a site adjacent to the sulfonylurea receptor.
    • They have a faster onset and shorter duration of action compared to sulfonylureas.
    • Main side effects are hypoglycemia and weight gain, similar to sulfonylureas.
    • Suitable for patients with erratic meal schedules, but may require multiple daily dosing, which can decrease adherence.
    • Must be taken by mouth with each meal.

    Bile Acid Sequestrants

    • Colesevelam's mechanism to lower plasma glucose levels is unknown.
    • Its role in therapy is unclear.

    Dopamine Agonists

    • 1-Bromocriptine mesylate is FDA-approved for treating type 2 diabetes mellitus (DM).
    • The mechanisms by which it improves glycemic control are unknown.
    • Its role in treating type 2 DM is unclear.

    Amylin Analogs

    • Pramlintide is a synthetic amylin analog that reduces glucagon secretion, slows gastric emptying, and increases satiety.
    • It was the first non-insulin agent approved for patients with type 1 diabetes mellitus (DM).
    • It is used primarily in type 1 DM as adjunctive therapy for patients who are not achieving postprandial glucose (PPG) goals despite maximizing mealtime insulin doses.
    • It can also decrease weight and may allow for lower mealtime insulin doses.

    Treatment of Type 2 Diabetes

    • Upon diagnosis, set a patient-specific A1C target and implement comprehensive lifestyle modifications.
    • Initial treatment typically begins with metformin, unless there is a comorbidity that requires a different agent.
    • Comorbidity-specific recommendations include:

      Cardiovascular Disease

      • Use of SGLT2 inhibitors or GLP1RA in high-risk or established ASCVD patients.

      Heart Failure

      • Use of SGLT2 inhibitors in Heart Failure patients, avoiding TZDs.

      Chronic Kidney Disease

      • Use of SGLT2 inhibitors in CKD patients, with or without ASCVD.
    • If the initial A1C is close to goal (≤7.5%), consider treating with lifestyle modifications alone if the patient is motivated.
    • Consider starting two medications (e.g., metformin plus a second agent) if the initial A1C is >1.5% higher than the target A1C.
    • Consider early introduction of basal insulin in patients with very high A1C levels (>10%) or symptoms of hyperglycemia.
    • Patients who are not meeting their goals should be seen at least every 3 months, and those meeting goals should be seen at least every 6 months, with additional therapy added if glucose targets have not been met.

    Managing Type 2 Diabetes Mellitus

    • Most patients with type 2 DM eventually require combination therapy.
    • If the A1C target is not achieved after 3 months of dual therapy or if the patient cannot tolerate the selected drug(s), triple therapy is recommended, adding a drug from another class.
    • Oral medications can often manage type 2 DM for years before injectable medications are needed.
    • Insulin is recommended for extreme (A1C >10%) or symptomatic hyperglycemia.
    • GLP-1 RAs are preferred over basal insulin due to equal or superior A1C lowering efficacy, weight loss, and low risk of hypoglycemia.
    • Basal insulin can be initiated if additional glucose lowering is needed after maximizing GLP-1 RA dose.
    • If A1C target is not reached by maximally titrating basal insulin, consider a GLP-1 RA or SGLT-2 inhibitor if the patient is not already taking one, as PPG levels are likely elevated.
    • Prandial insulin is also an option, with dose titration over time to achieve target PPG levels.

    Insulin Regimens for Type 1 Diabetes

    • All patients with type 1 diabetes require exogenous insulin.
    • Adequate glycemic control is achieved through intensive insulin regimens that mimic normal physiologic insulin secretion.

    Components of Insulin Regimens

    • Basal insulin: consistent secretion of insulin throughout the day to manage glucose levels overnight and in between meals.
    • Prandial insulin: bursts of insulin in response to glucose rises after ingestion of carbohydrates.

    Methods of Insulin Delivery

    • Multiple daily injections (MDI)
    • Continuous subcutaneous insulin infusion (CSII) via an insulin pump.

    Common Insulin Regimens

    • One injection of long-acting insulin (e.g., insulin glargine) for the basal component.
    • Three injections of rapid-acting insulin (e.g., insulin lispro) for the prandial component.
    • Alternative option: two injections of intermediate-acting insulin (e.g., NPH insulin) and two injections of short-acting insulin (e.g., regular insulin).

    Recommendations

    • The ADA Standards of Care recommend using rapid-acting insulins rather than regular insulin to reduce the risk of hypoglycemia.

    Insulin Pump Therapy (CSII)

    • Infuses rapid-acting insulin to cover both basal and prandial insulin needs
    • Provides a constant basal rate throughout the day
    • Allows for bolus doses based on current glucose levels, carbohydrate intake, and insulin on board

    Insulin Dosing

    • Total daily insulin dose is divided into 50% basal insulin and 50% prandial insulin
    • Prandial insulin is distributed across meals
    • Insulin doses are adjusted based on self-monitoring of blood glucose (SMBG) data

    Carbohydrate Counting and Bolus Doses

    • Patients should learn to count carbohydrates to match prandial insulin doses to their intake
    • Carbohydrate-to-insulin ratios (C:I ratios) and correction factors (CF) help individualize bolus insulin doses

    Pramlintide Therapy

    • Indicated as adjunctive treatment in patients with type 1 DM who are not achieving glycemic targets despite optimization of mealtime insulin

    Monitoring and Follow-up

    • Patients should SMBG before each meal or use continuous glucose monitoring (CGM) to evaluate the insulin regimen and make treatment decisions
    • Assess patients every 3 months if uncontrolled and every 6 months if controlled
    • Intensive insulin therapy patients should SMBG at least four times daily, before meals and at bedtime
    • SMBG is crucial during times of intercurrent illness or stresses for early detection and prevention of DKA

    Continuous Glucose Monitoring (CGM)

    • Recommended in patients with type 1 DM who are not meeting glycemic goals
    • Recommended in patients with hypoglycemia unawareness to better detect and prevent hypoglycemic events

    Insulin Regimens

    • Multiple-component insulin regimen consists of one injection of long-acting insulin (detemir, glargine, degludec) for basal glycemic coverage and three injections of rapid-acting insulin (aspart, lispro, glulisine) for glycemic coverage for each meal.
    • Alternative insulin regimen consists of two injections of intermediate-acting insulin (NPH) and rapid-acting insulin (aspart, lispro, glulisine), or short-acting regular insulin.

    Insulin Administration by Insulin Infusion Device

    • The basal insulin rate is decreased during the evening and increased slightly prior to the patient awakening in the morning.
    • Rapid-acting insulin (aspart, lispro, or glulisine) is used in the insulin pump.

    Hypoglycemia

    • Hypoglycemia is a common complication of some diabetes medications.
    • Hypoglycemia severity levels:
      • Level 1: Hypoglycemia alert value (≤70 mg/dL); may not cause symptoms, but treatment with fast-acting carbohydrate and medication dose adjustment may be necessary.
      • Level 2: Clinically significant hypoglycemia.

    Initial Autonomic Symptoms of Hypoglycemia

    • Tachycardia is a common initial autonomic symptom of hypoglycemia, characterized by a rapid heart rate.
    • Palpitations, a feeling of irregular heartbeat or fluttering, are also a typical initial autonomic symptom.
    • Sweating is a classic autonomic symptom of hypoglycemia, indicating the body's "fight or flight" response.
    • Tremors, or involuntary muscle tremors, are another initial autonomic symptom of hypoglycemia.
    • Hunger, or Shakiness, is a initial autonomic symptom of hypoglycemia, which may be accompanied by other symptoms.

    Neuroglycopenic Symptoms

    • Neuroglycopenic symptoms often occur when blood glucose (BG) levels are low.
    • These symptoms are related to the brain's response to low glucose levels.

    Management of Hypoglycemia

    • If the patient is unconscious, administer IV glucose or glucagon injection to increase glycogenolysis in the liver.
    • Glucagon kits should be prescribed and readily available to patients on insulin at risk of severe hypoglycemia.
    • It takes 10-15 minutes for glucose levels to rise after glucagon administration, and patients often experience vomiting.
    • Position the patient on their side with the head tilted downward to prevent aspiration.

    Monitoring and Prevention of Hypoglycemia

    • Clinicians should monitor hypoglycemia at every visit to minimize future episodes.
    • Reevaluate the treatment regimen of patients with frequent or severe hypoglycemia to prevent future episodes.

    Macrovascular Complications

    • Macrovascular complications, such as CHD and stroke, are the leading causes of death in people with diabetes.
    • The ADA recommends low-dose aspirin therapy (75-162 mg daily) for all patients with established ASCVD.
    • Clopidogrel may be used in patients allergic to aspirin as an alternative to aspirin therapy.

    Cardiovascular Prevention

    • The role of antiplatelet therapy for primary cardiovascular (CV) prevention is unclear due to the potential risk of bleeding, but may be recommended if the 10-year risk of a CV event is >20%.

    Management of Established ASCVD

    • In patients with established ASCVD, consider using a GLP1-RA (Glucagon-Like Peptide-1 Receptor Agonist) or an SGLT-2 inhibitor.

    Blood Pressure Management

    • For patients with BP > 120/80 mm Hg, recommend lifestyle changes, including:
      • Dietary changes
      • Physical activity
      • Weight loss in overweight or obese patients
    • For patients with BP > 140/90 mm Hg, start drug therapy using agents proven to reduce CV events.
    • For patients with BP > 160/100 mm Hg, use a combination of two medications.

    Statin Therapy

    • Initiate high-intensity statin therapy in all patients with:
      • Diabetes
      • Preexisting ASCVD
      • Regardless of baseline lipid levels
    • Prescribe moderate-intensity statin to all patients with:
      • Type 1 or type 2 DM
      • Over the age of 40
      • Without ASCVD

    Microvascular Complications

    • Improving glucose control reduces the risk of developing microvascular complications and slows their progression.

    Nephropathy

    • Albuminuria is a marker of renal damage.
    • Screening for albuminuria should begin: • At diagnosis and annually thereafter in persons with type 2 DM. • At puberty and after 5-years’ disease duration in persons with type 1 DM.
    • Glucose and BP control are crucial for preventing and slowing nephropathy progression.
    • SGLT2 inhibitors (empagliflozin, canagliflozin, and dapagliflozin) reduce the decline in kidney function in patients with CKD, with or without diabetes.
    • ACE inhibitors and ARBs slow the progression of renal disease in patients with diabetes.
    • Diuretics are often necessary due to volume expanded states and are recommended as second-line therapy.
    • The ADA recommends a BP goal (no specific value mentioned in the text).

    Retinopathy

    • Patients with diabetes require routine eye examinations to thoroughly evaluate the retina.
    • Early retinopathy can be reversed with improved glycemic control and optimal blood pressure control.
    • Advanced retinopathy will not fully regress with improved glycemic control.
    • Laser photocoagulation has significantly improved sight preservation.
    • Intravitreal antivascular endothelial growth factor (VEGF) therapy is highly effective for sight preservation.

    Anti-VEGF Medications

    • Bevacizumab (used off-label) is an anti-VEGF monoclonal antibody.
    • Ranibizumab is an anti-VEGF monoclonal antibody.
    • Aflibercept is a VEGF decoy receptor.

    Neuropathy

    • Peripheral neuropathy is the most common complication in patients with type 2 diabetes mellitus.
    • Predominant symptoms of peripheral neuropathy include paresthesias, numbness, and pain.
    • The feet are more commonly affected than the hands.
    • Improved glycemic control is the primary treatment for peripheral neuropathy and may alleviate some symptoms.
    • Pharmacologic therapy for peripheral neuropathy is symptomatic and includes:
      • Low-dose tricyclic antidepressants (nortriptyline or desipramine)
      • Duloxetine
      • Gabapentin
      • Pregabalin
      • Venlafaxine
      • Topical capsaicin
      • Tramadol

    Diabetic Complications and Management

    • Gastroparesis can be improved with good glycemic control and medication such as metoclopramide or low-dose erythromycin.
    • Diabetic diarrhea often occurs at night and can be treated with a 10-14 day course of antibiotics like doxycycline or metronidazole.
    • Octreotide may be used in cases of diarrhea that do not respond to antibiotics.
    • Orthostatic hypotension may be treated with mineralocorticoids like fludrocortisone or adrenergic agonists like midodrine.
    • Erectile dysfunction is a common complication, and initial treatment often involves a trial of oral phosphodiesterase-5 inhibitors like sildenafil, vardenafil, or tadalafil.

    Monitoring and Evaluation

    • Measure A1C every 3-6 months to monitor long-term glycemic control.
    • For patients with type 1 DM, SMBG should be performed 4-6 times a day, including before meals, physical activity, and at bedtime.
    • The optimal frequency of SMBG for patients with type 2 DM on oral agents is still unclear.
    • Healthcare providers should ask patients with type 1 DM about hypoglycemia frequency and severity at each visit.
    • Screen for complications, including:
      • Eye exams
      • Blood pressure assessment
      • Foot examination
      • Albuminuria screening
      • Fasting lipid panel check

    Preventive Care

    • Administer an annual influenza vaccine to patients with diabetes.
    • Assess for administration of pneumococcal and hepatitis B vaccine series.
    • Manage other cardiovascular risk factors, such as smoking.

    Definition and Characteristics of Asthma

    • Asthma is a heterogeneous disease characterized by chronic airway inflammation.
    • It is defined by a history of respiratory symptoms that vary over time and in intensity.
    • Symptoms include wheezing, shortness of breath, chest tightness, and cough.

    Pathophysiology of Asthma

    • The disease involves a variable degree of airflow obstruction.
    • In allergic patients, inhaled allergens activate inflammatory cells (mast cells, neutrophils, and macrophages).
    • These cells release proinflammatory mediators, such as histamine and eicosanoids, which induce:
      • Contraction of airway smooth muscle (bronchospasm)
      • Mucus secretion
      • Edema
      • Exudation of plasma in the airways

    Clinical Presentation of Asthma

    Chronic Asthma

    • Signs and symptoms include:
      • Episodes of shortness of breath
      • Chest tightness
      • Dry coughing (particularly at night)
      • Wheezing or a whistling sound when breathing
    • These symptoms can occur:
      • With exercise
      • Spontaneously
      • In association with known allergens

    Acute Severe Asthma

    • Uncontrolled asthma can progress to an acute state, characterized by anxiety, severe dyspnea, shortness of breath, chest tightness, or burning, and limited ability to speak.
    • Symptoms are unresponsive to usual measures, such as SABAs (short-acting beta2-agonists).

    Signs of Acute Severe Asthma

    • Dry, hacking cough
    • Tachypnea (rapid breathing rate)
    • Tachycardia (rapid heart rate)
    • Pallor or cyanosis (pale or blue-tinged skin)
    • Hyperinflated chest with intercostal and supraclavicular retractions (visible chest deformity)

    Diagnosis of Chronic Asthma

    • Diagnosis is primarily made through history and confirmatory spirometry.
    • Spirometry demonstrates obstruction, indicated by a low FEV1/FVC ratio (forced expiratory volume in 1 second / forced vital capacity).

    Goals of Asthma Treatment

    • Achieve good control of symptoms and maintain normal activity levels.
    • Minimize future risk of exacerbations and side effects.

    Nonpharmacologic Therapy

    Patient Education

    • Mandatory to improve medication adherence, self-management skills, and use of healthcare services.

    Monitoring and Triggers

    • Routine PEF monitoring is recommended for patients with severe asthma or poor symptom perception.
    • Avoidance of known allergenic triggers can improve symptoms and reduce medication use.

    Smoking and Dehydration

    • Smokers should be encouraged to quit.
    • Correct dehydration if present in acute asthma exacerbations.

    Oxygen Therapy

    • Initiate oxygen therapy in acute asthma exacerbations.

    Preferred Treatment for Adults and Adolescents

    • GINA track 1 with as-needed ICS-formoterol remains the preferred treatment for adults and adolescents.
    • ICS-formoterol reduces the risk of severe exacerbation compared to SABA reliever, with similar symptom control.

    Add-on Treatment for Severe Asthma

    • Add-on treatment for severe asthma includes long-acting muscarinic antagonist (LAMA), leukotriene receptor antagonists (LTRA), and biologic agents.
    • Choice of add-on treatment depends on inflammatory phenotype (e.g. allergic asthma, eosinophilic asthma) and other clinical features.

    Maintenance Oral Corticosteroid (OCS)

    • Low-dose maintenance oral corticosteroid (OCS) should be considered only as a last resort due to long-term side effects.

    Stepping Down Treatment

    • Once good asthma control is achieved and maintained for 2-3 months, consider stepping down treatment gradually to find the patient's lowest treatment that controls both symptoms and exacerbations.

    Primary Therapy for Acute Exacerbations

    • Inhaled SABAs and systemic corticosteroids are primary therapies for acute exacerbations.
    • Additional treatments may include inhaled ipratropium, intravenous (IV) magnesium sulfate, and oxygen.
    • Treatments are typically administered concurrently to facilitate rapid improvement.

    β2-Agonists

    • SABAs (e.g., albuterol) are the first-choice treatment for acute severe asthma management and intermittent episodes of bronchospasm (e.g., exercise-induced bronchospasm).
    • Aerosol administration of SABAs enhances bronchoselectivity and provides a more rapid response compared to systemic administration.

    Long-Acting β2-Agonists (LABAs)

    • Two LABAs, formoterol and salmeterol, provide bronchodilation for 12 hours or longer and are dosed twice daily.
    • When combined with an inhaled corticosteroid (ICS), formoterol can be dosed daily and as needed (more frequently than twice daily).

    Corticosteroids in Asthma Management

    • ICS are the preferred long-term control therapy for persistent asthma due to their potency and consistent effectiveness.
    • ICS are the only therapy shown to reduce the risk of mortality from asthma.
    • Response to ICS is delayed, requiring patience and consistent use.

    Systemic Toxicity of ICS

    • Systemic toxicity of ICS is minimal with low-to-moderate doses.
    • However, high doses of ICS increase the risk of systemic effects, including:
      • Growth suppression in children
      • Osteoporosis
      • Cataracts
      • Dermal thinning
      • Adrenal insufficiency

    Local Adverse Effects of ICS

    • Local adverse effects of ICS include:
      • Dose-dependent oropharyngeal candidiasis
      • Dysphonia
    • These effects can be reduced by using a spacer device.

    Systemic Corticosteroids in Acute Severe Asthma

    • Systemic corticosteroids are indicated in all patients with acute severe asthma not responding completely to initial inhaled β2-agonist administration.
    • Systemic corticosteroids should be administered within 1 hour of presentation.

    IV vs Oral Administration

    • IV therapy offers no advantage over oral administration except in patients unable to take oral medications.

    Anticholinergics in Asthma

    • Anticholinergics reverse cholinergic mediated bronchoconstriction and are effective bronchodilators in asthma.

    Ipratropium Bromide in Asthma

    • Ipratropium bromide is useful as adjunctive therapy in acute severe asthma not completely responsive to SABA alone.
    • Patients with persistent asthma who are intolerant to short-acting β2-agonists may be prescribed ipratropium for rescue inhaler use.

    Tiotropium Bromide in Asthma

    • Tiotropium bromide is a long-acting inhaled anticholinergics with a duration of 24 hours.
    • Tiotropium may be considered an add-on therapy in patients whose asthma is not well controlled with ICS and LABA combination therapy.

    Leukotriene Modifiers

    • Zafirlukast and montelukast are oral leukotriene receptor antagonists (LTRA) that reduce the proinflammatory and bronchoconstriction effects of leukotriene D4.
    • Less effective than Inhaled Corticosteroids (ICS) and Long-Acting Beta-Agonists (LABAs) when added to ICS.
    • Not used to treat acute exacerbations, must be taken regularly, even during symptom-free periods.

    Adverse Effects

    • Unusual adverse effects observed, including:
      • Irritability
      • Aggressiveness
      • Sleep disturbances
      • Rarely, suicidality
    • Monitor patients for signs of these effects, especially within a few weeks of starting therapy.

    Zileuton

    • 5-lipoxygenase inhibitor
    • Limited use due to:
      • Potential for elevated hepatic enzymes
      • Inhibition of metabolism of drugs metabolized by CYP3A4 (e.g., theophylline, warfarin)

    Safety Concerns

    • Fatal hepatic failure associated with zafirlukast reported.

    Methylxanthines

    • Rarely used today due to high risk of severe life-threatening toxicity, numerous drug interactions, and decreased efficacy compared to ICS, LABAs, and biologics.
    • Theophylline is available for oral and IV administration.

    Theophylline Dosing and Monitoring

    • Dosing requires monitoring of serum concentrations for both efficacy and toxicity.
    • Monitoring is necessary to prevent seizures and death.
    • Theophylline is metabolized primarily by the hepatic CYP P450 microsomal enzymes.

    Drug Interactions and Metabolism

    • Drug interactions affect theophylline metabolism, significantly impacting blood concentrations.
    • Hepatic CYP P450 microsomal enzymes play a crucial role in theophylline metabolism.

    Evaluating Therapeutic Outcomes

    • Inhalation technique should be evaluated monthly initially and then every 3–6 months for patients on inhaled drugs.
    • Most patients should experience decreased symptoms within 1–2 weeks and achieve maximum improvement within 4–8 weeks after initiation of anti-inflammatory therapy or dosage increase.

    Definition and Characteristics of COPD

    • COPD is a heterogeneous lung condition characterized by chronic respiratory symptoms, including dyspnea, cough, sputum production, and/or exacerbations.
    • These symptoms are caused by abnormalities of the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema) that lead to persistent, often progressive, airflow obstruction.

    Component Conditions of COPD

    • Chronic bronchitis: characterized by chronic or recurrent excess mucus secretion with cough that occurs on most days for at least 3 months of the year for at least 2 consecutive years.
    • Emphysema: characterized by abnormal, permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls, without fibrosis.

    Pathophysiology of COPD

    • The most common cause of COPD is exposure to tobacco smoke.
    • Inhalation of noxious particles and gases activates inflammatory cells to release inflammatory mediators.
    • Inflammatory cells and mediators lead to widespread destructive changes in airways, resulting in chronic airflow limitation.
    • Chronic hypoxemia and changes in pulmonary vasculature lead to increases in pulmonary pressures.
    • Sustained elevated pulmonary pressures can lead to right-sided heart failure (cor pulmonale) characterized by right ventricle hypertrophy in response to increased pulmonary vascular resistance.

    Clinical Presentation of COPD

    • Initial symptoms include chronic cough and sputum production, which may persist for several years before dyspnea develops.
    • Dyspnea is characterized as "increased effort to breathe" or "air hunger", worsens with exercise, and progresses over time, leading to decreased exercise tolerance or decline in physical activity.
    • Additional symptoms may include chest tightness, wheezing, shallow breathing, increased resting respiratory rate, "barrel chest" due to lung hyperinflation, pursed lips during expiration, use of accessory respiratory muscles, and cyanosis of mucosal membranes.

    Diagnosis of COPD

    • Diagnosis is based on patient symptoms, history of exposure to risk factors (e.g., tobacco smoke and occupational substances), and confirmation by pulmonary function testing (spirometry).
    • Spirometry assesses lung volumes and capacities, including Forced Vital Capacity (FVC) and Forced Expiratory Volume (FEV1).
    • The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines classify airflow limitation into four grades: mild (GOLD 1), moderate (GOLD 2), severe (GOLD 3), and very severe (GOLD 4).

    Goals of Treatment for COPD

    • Prevent or slow disease progression
    • Relieve symptoms
    • Improve exercise tolerance
    • Improve overall health status
    • Prevent and treat exacerbations
    • Prevent and treat complications
    • Reduce morbidity and mortality

    Nonpharmacologic Therapy for COPD

    • Smoking cessation is the most important intervention to prevent development and progression of COPD
    • Reducing exposure to occupational dust and fumes as well as other environmental toxins is crucial
    • Pulmonary rehabilitation programs include:
      • Exercise training
      • Breathing exercises
      • Psychosocial support
    • Annual influenza vaccination is recommended during each influenza season
    • Vaccination against pneumococcal infection is recommended for all adults with COPD
    • Long-term O2 therapy (by nasal cannula) is required for some patients with severe COPD

    Pharmacologic Therapy for COPD

    • Bronchodilators are the mainstay of drug therapy
    • Classes of bronchodilators include:
      • Short- and long-acting β2-agonists
      • Short- and long-acting muscarinic antagonists (anticholinergics)
      • Methylxanthines
    • Short-acting inhaled bronchodilators relieve symptoms (e.g., dyspnea)
    • Long-acting inhaled bronchodilators relieve symptoms and reduce exacerbation frequency

    Patient Assessment and Selection of Therapy

    • GOLD guidelines combine symptoms (by questionnaires) and frequency of exacerbations in the previous 12 months to determine patient risk group and recommend initial treatment

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