Podcast
Questions and Answers
What is the average lifespan of red blood cells (RBCs) correlating with hemoglobin A1c levels?
What is the average lifespan of red blood cells (RBCs) correlating with hemoglobin A1c levels?
Which of the following is a necessary preparation for an oral glucose tolerance test?
Which of the following is a necessary preparation for an oral glucose tolerance test?
Why are hemoglobin A1c tests not suitable for populations with high prevalence of hemoglobinopathies?
Why are hemoglobin A1c tests not suitable for populations with high prevalence of hemoglobinopathies?
What consequence does a higher hemoglobin A1c level predict?
What consequence does a higher hemoglobin A1c level predict?
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What must be done to confirm a diagnosis without unequivocal symptomatic hyperglycemia?
What must be done to confirm a diagnosis without unequivocal symptomatic hyperglycemia?
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What is the most common gastrointestinal manifestation of autonomic neuropathy?
What is the most common gastrointestinal manifestation of autonomic neuropathy?
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Which of the following symptoms is associated with cardiovascular autonomic neuropathy?
Which of the following symptoms is associated with cardiovascular autonomic neuropathy?
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What is a potential outcome of gastroparesis in autonomic neuropathy?
What is a potential outcome of gastroparesis in autonomic neuropathy?
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What characterizes a Hyperglycemic Hyperosmolar State?
What characterizes a Hyperglycemic Hyperosmolar State?
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In patients with Hyperglycemic Hyperosmolar State, which of the following symptoms may present?
In patients with Hyperglycemic Hyperosmolar State, which of the following symptoms may present?
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Which of the following is NOT a common sign of Hyperglycemic Hyperosmolar State?
Which of the following is NOT a common sign of Hyperglycemic Hyperosmolar State?
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What is a common renal manifestation of autonomic neuropathy?
What is a common renal manifestation of autonomic neuropathy?
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Which medication may improve gastroparesis symptoms associated with autonomic neuropathy?
Which medication may improve gastroparesis symptoms associated with autonomic neuropathy?
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What is the initial pharmacotherapy recommended for patients with hypertension whose blood pressure is greater than 140/90?
What is the initial pharmacotherapy recommended for patients with hypertension whose blood pressure is greater than 140/90?
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Which lifestyle modification is NOT recommended for patients with hypertension?
Which lifestyle modification is NOT recommended for patients with hypertension?
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In patients with diabetes mellitus over the age of 40, what is the recommended therapy regarding cholesterol management?
In patients with diabetes mellitus over the age of 40, what is the recommended therapy regarding cholesterol management?
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What dietary approach is recommended as part of lifestyle therapy for managing hypertension?
What dietary approach is recommended as part of lifestyle therapy for managing hypertension?
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When managing hypertension, what is typically required for effective treatment?
When managing hypertension, what is typically required for effective treatment?
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What is the target blood glucose level for adequate response to treatment?
What is the target blood glucose level for adequate response to treatment?
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What does Self Monitoring of Blood Glucose (SMBG) typically involve?
What does Self Monitoring of Blood Glucose (SMBG) typically involve?
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How often should blood glucose be monitored for adequate management in patients?
How often should blood glucose be monitored for adequate management in patients?
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What is the primary purpose of Continuous Glucose Monitoring (CGM)?
What is the primary purpose of Continuous Glucose Monitoring (CGM)?
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What feature distinguishes the continuous subcutaneous insulin infusion pump in managing diabetes?
What feature distinguishes the continuous subcutaneous insulin infusion pump in managing diabetes?
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Which brand is NOT associated with Continuous Glucose Monitoring systems?
Which brand is NOT associated with Continuous Glucose Monitoring systems?
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What potential misconception might patients have regarding insulin shots?
What potential misconception might patients have regarding insulin shots?
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How frequently should CGM sensors be replaced?
How frequently should CGM sensors be replaced?
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What is a common characteristic of Type 2 Diabetes Mellitus (T2DM) regarding insulin production?
What is a common characteristic of Type 2 Diabetes Mellitus (T2DM) regarding insulin production?
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Which of the following symptoms is NOT commonly associated with T2DM?
Which of the following symptoms is NOT commonly associated with T2DM?
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What is one reason for screening individuals for T2DM?
What is one reason for screening individuals for T2DM?
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Which of the following is a diagnostic criterion for diabetes in a nonpregnant patient?
Which of the following is a diagnostic criterion for diabetes in a nonpregnant patient?
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What phenomenon is associated with significant insulin resistance in T2DM?
What phenomenon is associated with significant insulin resistance in T2DM?
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Which measurement can help diagnose impaired glucose homeostasis?
Which measurement can help diagnose impaired glucose homeostasis?
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Which screening category indicates normal glucose homeostasis?
Which screening category indicates normal glucose homeostasis?
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What is a primary risk factor for developing chronic conditions associated with T2DM?
What is a primary risk factor for developing chronic conditions associated with T2DM?
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What is a typical characteristic of symptoms in Type 2 Diabetes Mellitus (T2DM)?
What is a typical characteristic of symptoms in Type 2 Diabetes Mellitus (T2DM)?
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Which condition is most commonly associated with significant insulin resistance in T2DM?
Which condition is most commonly associated with significant insulin resistance in T2DM?
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Which diagnostic measure can be used to identify diabetes mellitus in a nonpregnant patient?
Which diagnostic measure can be used to identify diabetes mellitus in a nonpregnant patient?
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What type of fat distribution is typically seen in individuals with T2DM?
What type of fat distribution is typically seen in individuals with T2DM?
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What is a primary reason for screening individuals for Type 2 Diabetes Mellitus?
What is a primary reason for screening individuals for Type 2 Diabetes Mellitus?
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What is the benefit of diagnosing prediabetes at an early stage?
What is the benefit of diagnosing prediabetes at an early stage?
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Which diagnostic test measures the average blood glucose control over the preceding months?
Which diagnostic test measures the average blood glucose control over the preceding months?
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What complication is most closely associated with prolonged undetected Type 2 Diabetes Mellitus?
What complication is most closely associated with prolonged undetected Type 2 Diabetes Mellitus?
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What plasma glucose level is typically indicative of a nonketotic hyperosmolar state?
What plasma glucose level is typically indicative of a nonketotic hyperosmolar state?
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What is the primary cause of Type 2 Diabetes Mellitus?
What is the primary cause of Type 2 Diabetes Mellitus?
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What is a significant characteristic of the serum osmolality in nonketotic hyperosmolar state?
What is a significant characteristic of the serum osmolality in nonketotic hyperosmolar state?
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What percentage of all diabetes cases does Type 2 Diabetes Mellitus represent in the US?
What percentage of all diabetes cases does Type 2 Diabetes Mellitus represent in the US?
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Which of the following is NOT typically present in a nonketotic hyperosmolar state?
Which of the following is NOT typically present in a nonketotic hyperosmolar state?
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What treatment is essential for managing nonketotic hyperosmolar state?
What treatment is essential for managing nonketotic hyperosmolar state?
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Which laboratory diagnostic test is primarily used to monitor long-term glucose levels in individuals with diabetes?
Which laboratory diagnostic test is primarily used to monitor long-term glucose levels in individuals with diabetes?
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What lifestyle change is considered the gold standard in the treatment of Type 2 Diabetes Mellitus?
What lifestyle change is considered the gold standard in the treatment of Type 2 Diabetes Mellitus?
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What component is crucial for every patient with Type 2 Diabetes Mellitus (T2DM)?
What component is crucial for every patient with Type 2 Diabetes Mellitus (T2DM)?
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What common complication arises from untreated Type 2 Diabetes Mellitus?
What common complication arises from untreated Type 2 Diabetes Mellitus?
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Which factor is identified as a primary risk for developing Type 2 Diabetes Mellitus?
Which factor is identified as a primary risk for developing Type 2 Diabetes Mellitus?
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How does insulin function in regulating blood glucose levels?
How does insulin function in regulating blood glucose levels?
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What is a common characteristic of Type 2 Diabetes Mellitus regarding insulin levels?
What is a common characteristic of Type 2 Diabetes Mellitus regarding insulin levels?
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What is the primary gastrointestinal manifestation of autonomic neuropathy?
What is the primary gastrointestinal manifestation of autonomic neuropathy?
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Which symptom is least likely to present in a patient with Hyperglycemic Hyperosmolar State?
Which symptom is least likely to present in a patient with Hyperglycemic Hyperosmolar State?
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What characteristic distinguishes Hyperglycemic Hyperosmolar State from diabetic ketoacidosis?
What characteristic distinguishes Hyperglycemic Hyperosmolar State from diabetic ketoacidosis?
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Which of the following is NOT a symptom of autonomic neuropathy?
Which of the following is NOT a symptom of autonomic neuropathy?
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What is a common treatment for alleviating symptoms of gastroparesis?
What is a common treatment for alleviating symptoms of gastroparesis?
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Which of the following symptoms may indicate poor glucose control due to gastroparesis?
Which of the following symptoms may indicate poor glucose control due to gastroparesis?
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What is a significant risk factor for developing a Hyperglycemic Hyperosmolar State?
What is a significant risk factor for developing a Hyperglycemic Hyperosmolar State?
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Which of the following complications can arise from bladder neuropathy in autonomic neuropathy?
Which of the following complications can arise from bladder neuropathy in autonomic neuropathy?
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What is the preferred dietary approach for patients managing type 2 diabetes?
What is the preferred dietary approach for patients managing type 2 diabetes?
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Which medication acts as an insulin secretagogue stimulating the release of insulin from pancreatic cells?
Which medication acts as an insulin secretagogue stimulating the release of insulin from pancreatic cells?
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What is a primary side effect associated with thiazolidinediones?
What is a primary side effect associated with thiazolidinediones?
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Which class of medication is primarily used to inhibit renal glucose reabsorption?
Which class of medication is primarily used to inhibit renal glucose reabsorption?
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What should be the starting approach for newly diagnosed type 2 diabetes patients with elevated symptoms?
What should be the starting approach for newly diagnosed type 2 diabetes patients with elevated symptoms?
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In managing type 2 diabetes, which recommendation is emphasized for exercise?
In managing type 2 diabetes, which recommendation is emphasized for exercise?
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What is a critical consideration when prescribing metformin?
What is a critical consideration when prescribing metformin?
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Which of the following medications has the lowest risk of causing hypoglycemia?
Which of the following medications has the lowest risk of causing hypoglycemia?
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What is a common side effect of the injectable GLP-1 receptor agonists?
What is a common side effect of the injectable GLP-1 receptor agonists?
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Which medication is NOT typically indicated for type 2 diabetes management due to its modest effect on glucose control?
Which medication is NOT typically indicated for type 2 diabetes management due to its modest effect on glucose control?
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What is a main drawback of using meglitinides in diabetes management?
What is a main drawback of using meglitinides in diabetes management?
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Which is a potential barrier to treatment in managing diabetes?
Which is a potential barrier to treatment in managing diabetes?
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Which type of medication would NOT typically be used for type 1 diabetes management?
Which type of medication would NOT typically be used for type 1 diabetes management?
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What is the primary mechanism of action for DPP-4 inhibitors?
What is the primary mechanism of action for DPP-4 inhibitors?
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What is the primary cause of vision loss in patients with nonproliferative diabetic retinopathy?
What is the primary cause of vision loss in patients with nonproliferative diabetic retinopathy?
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Which symptom is the earliest clinical sign of retinopathy that can be viewed through a fundoscopic exam?
Which symptom is the earliest clinical sign of retinopathy that can be viewed through a fundoscopic exam?
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What is the recommended frequency for T1D patients to undergo fundoscopic exams?
What is the recommended frequency for T1D patients to undergo fundoscopic exams?
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What is the main complication associated with diabetic retinopathy in terms of its impact on vision?
What is the main complication associated with diabetic retinopathy in terms of its impact on vision?
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Which preventative measure has been shown to contribute significantly to the management of retinopathy?
Which preventative measure has been shown to contribute significantly to the management of retinopathy?
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What primarily characterizes the pathophysiology of Type 2 Diabetes Mellitus?
What primarily characterizes the pathophysiology of Type 2 Diabetes Mellitus?
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Which of the following best describes the etiology of Type 2 Diabetes Mellitus?
Which of the following best describes the etiology of Type 2 Diabetes Mellitus?
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What is the most common laboratory diagnostic measure used to assess long-term glucose control in individuals with diabetes?
What is the most common laboratory diagnostic measure used to assess long-term glucose control in individuals with diabetes?
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Which factor is NOT associated with the prevalence of Type 2 Diabetes Mellitus in the US population?
Which factor is NOT associated with the prevalence of Type 2 Diabetes Mellitus in the US population?
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What essential treatment approach is recognized as the 'Gold Standard' for managing Type 2 Diabetes Mellitus?
What essential treatment approach is recognized as the 'Gold Standard' for managing Type 2 Diabetes Mellitus?
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Which of the following complications is most closely associated with long-term undetected Type 2 Diabetes Mellitus?
Which of the following complications is most closely associated with long-term undetected Type 2 Diabetes Mellitus?
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Which characteristic regarding insulin production is typical in individuals with Type 2 Diabetes Mellitus?
Which characteristic regarding insulin production is typical in individuals with Type 2 Diabetes Mellitus?
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What is a common statistical figure reflecting the economic impact of diabetes in the US as of 2017?
What is a common statistical figure reflecting the economic impact of diabetes in the US as of 2017?
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Which monitoring method provides unlimited glucose datapoints to define a time in a glycemic range?
Which monitoring method provides unlimited glucose datapoints to define a time in a glycemic range?
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What is the primary purpose of using a glucose monitoring method?
What is the primary purpose of using a glucose monitoring method?
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Why might patients be hesitant to take insulin despite its benefits?
Why might patients be hesitant to take insulin despite its benefits?
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Which statement about Self Monitoring of Blood Glucose (SMBG) is true?
Which statement about Self Monitoring of Blood Glucose (SMBG) is true?
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What is one of the primary advantages of using Continuous Glucose Monitoring over traditional methods?
What is one of the primary advantages of using Continuous Glucose Monitoring over traditional methods?
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What is the recommended target blood glucose level to consider treatment adequate?
What is the recommended target blood glucose level to consider treatment adequate?
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How often should Continuous Glucose Monitoring sensors be replaced?
How often should Continuous Glucose Monitoring sensors be replaced?
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Which of the following brands is associated with Self Monitoring of Blood Glucose (SMBG)?
Which of the following brands is associated with Self Monitoring of Blood Glucose (SMBG)?
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What best describes the presentation of Type 2 Diabetes Mellitus (T2DM)?
What best describes the presentation of Type 2 Diabetes Mellitus (T2DM)?
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Which symptom is commonly associated with long-term undetected Type 2 Diabetes Mellitus?
Which symptom is commonly associated with long-term undetected Type 2 Diabetes Mellitus?
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Which diagnostic criterion is NOT used for diagnosing diabetes in a nonpregnant patient?
Which diagnostic criterion is NOT used for diagnosing diabetes in a nonpregnant patient?
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What is a significant characteristic of the fat distribution commonly seen in individuals with Type 2 Diabetes Mellitus?
What is a significant characteristic of the fat distribution commonly seen in individuals with Type 2 Diabetes Mellitus?
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Which of the following best describes the role of screening for Type 2 Diabetes Mellitus?
Which of the following best describes the role of screening for Type 2 Diabetes Mellitus?
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What condition is specifically associated with significant insulin resistance?
What condition is specifically associated with significant insulin resistance?
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What is one of the primary benefits of diagnosing prediabetes early?
What is one of the primary benefits of diagnosing prediabetes early?
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Which category does a patient with normalized glucose homeostasis fall under?
Which category does a patient with normalized glucose homeostasis fall under?
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What is the primary mechanism of action of Metformin in treating type 2 diabetes?
What is the primary mechanism of action of Metformin in treating type 2 diabetes?
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Which of the following medications is known to potentially cause weight gain as a side effect?
Which of the following medications is known to potentially cause weight gain as a side effect?
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Which class of drug acts as an insulin secretagogue stimulating release from pancreatic beta cells?
Which class of drug acts as an insulin secretagogue stimulating release from pancreatic beta cells?
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What is a significant contraindication for the use of Thiazolidinediones?
What is a significant contraindication for the use of Thiazolidinediones?
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Which of the following is a contrasting characteristic of DPP4-Inhibitors compared to other diabetes medications?
Which of the following is a contrasting characteristic of DPP4-Inhibitors compared to other diabetes medications?
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What is the general A1C reduction effective range expected from SGLT2 Inhibitors?
What is the general A1C reduction effective range expected from SGLT2 Inhibitors?
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In which scenario might insulin therapy be considered from the outset for a patient with type 2 diabetes?
In which scenario might insulin therapy be considered from the outset for a patient with type 2 diabetes?
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Which of the following glucose-lowering medications is contraindicated in patients with a history of pancreatitis?
Which of the following glucose-lowering medications is contraindicated in patients with a history of pancreatitis?
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How does the mechanism of action of Alpha-glucosidase inhibitors primarily work?
How does the mechanism of action of Alpha-glucosidase inhibitors primarily work?
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Which of the following side effects is commonly associated with amylin analogs?
Which of the following side effects is commonly associated with amylin analogs?
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What dietary change is most often recommended for patients aiming to manage their diabetes effectively?
What dietary change is most often recommended for patients aiming to manage their diabetes effectively?
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What is a recognized barrier to treatment in patients with diabetes?
What is a recognized barrier to treatment in patients with diabetes?
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What is the desired weight loss percentage associated with improved cardiac risk factors in type 2 diabetes management?
What is the desired weight loss percentage associated with improved cardiac risk factors in type 2 diabetes management?
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What is the typical first line pharmacologic therapy recommended for type 2 diabetes management?
What is the typical first line pharmacologic therapy recommended for type 2 diabetes management?
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Study Notes
Autonomic Neuropathy
- Autonomic neuropathy can affect various systems, including the cardiovascular, gastrointestinal, genitourinary, and sudomotor system
- Gastrointestinal: Constipation is the most common GI manifestation
- Cardiovascular: Persistent sinus tachycardia and orthostasis are common findings
- Genitourinary: Bladder neuropathy can lead to poor urinary stream, straining, feeling of incomplete emptying, recurrent UTIs, and incontinence
- Sudomotor: Heavy sweating of the upper body and anhidrosis of the lower body are possible manifestations
Hyperglycemia Hyperosmolar State (HHS)
- HHS is the second most common form of hyperglycemic coma, a serious acute complication of diabetes
- Characterized by severe hyperglycemia without significant ketosis, leading to hyperosmolality and dehydration, resulting in altered mental status (AMS)
- Etiology: Primarily seen in type 2 diabetes (T2DM) patients with a concurrent illness or inadequate fluid intake
- Pathophysiology: Despite some insulin production in T2DM, the body cannot produce enough insulin to prevent hyperglycemia in these circumstances
- Signs and Symptoms: Develops gradually over days to weeks, presenting with polyuria, polydipsia, weight loss, weakness, tachycardia, hypotension, and dry skin and mucous membranes. Unlike diabetic ketoacidosis (DKA), there are no Kussmaul respirations.
Type 1 vs Type 2 Diabetes
- Type 1 Diabetes: Autoimmune destruction of beta cells leads to absolute insulin deficiency
- Type 2 Diabetes: Characterized by insulin resistance with hyperinsulinemia, but ultimately leading to relative insulin deficiency
T2DM Presentation
-
Signs and Symptoms:
- Often asymptomatic, leading to an insidious onset of the disease
- Overweight or obese individuals are more likely to be affected
- Increased urination and thirst are occasional symptoms
- Neurological or cardiovascular abnormalities may be present if the disease progresses without detection or treatment
-
Signs:
- Chronic skin infections due to immune system dysfunction
- Chronic yeast infections: Vulvovaginitis in women and inflammation of the foreskin and glans penis in men
- Increased centripetal fat distribution: Men with a waist circumference > 40 inches and women with a waist circumference > 35 inches
-
Clinical Manifestations:
- Acanthosis nigricans is associated with significant insulin resistance
- Eruptive xanthomas are indicative of hyperchylomicronemia (elevated triglycerides)
Screening and Diagnostics
-
Rationale for Screening:
- A significant proportion of individuals with T2DM are asymptomatic and unaware of their condition
- Early detection is crucial to prevent complications, which may already be present at diagnosis
- Prevent worsening or progression of the disease: Early treatment can favorably alter the natural course of T2DM and lead to better outcomes
- Early identification of prediabetes encourages efforts to prevent diabetes
- Cost-effectiveness of preventative measures
Who Needs Screening?
- Individuals at increased risk of developing T2DM should be screened
- Those with a family history of diabetes, ethnicity (African American, Hispanic, American Indian, Asian American), age (over 35 years), obesity, physical inactivity, and hypertension are considered high-risk
Diagnostic Evaluation
-
Glucose Tolerance Categories:
- Normal Glucose Homeostasis: Normal blood glucose levels
- Impaired Glucose Homeostasis: Blood glucose levels are higher than normal but not high enough for a diabetes diagnosis
- Diabetes Mellitus: Defined by persistently elevated blood glucose levels
-
Diagnostic Criteria:
- Elevated Fasting Plasma Glucose (FPG or FBG): ≥ 126 mg/dL on two separate occasions
- Random Elevated Glucose with Symptoms: ≥ 200 mg/dL with symptoms of diabetes (increased thirst, urination, hunger, fatigue, blurred vision)
- Elevated Hemoglobin A1C (HbA1c): ≥ 6.5%
- Abnormal Oral Glucose Tolerance Test (OGTT): ≥ 200 mg/dL, 2 hours after ingesting 75 grams of glucose
Diagnostic Evaluation: Specific Tests
- Plasma or Serum Glucose: Preferred over whole blood glucose due to less interference from red blood cell (RBC) concentration
- Glycosylated Hemoglobin (HbA1c): Reflects average blood glucose levels over the previous 6-12 weeks, providing a long-term measure of glycemic control. Elevated HbA1c increases the risk of microvascular complications.
- Oral Glucose Tolerance Test (OGTT): Performed to evaluate the body's ability to process glucose after a meal.
Correlation of A1C with Estimated Average Glucose Values
- HbA1c (%) | Mean Plasma Glucose (mg/dL)
- 5 | 97
- 6 | 126
- 7 | 154
- 8 | 183
- 9 | 212
- 10 | 240
- 11 | 269
- 12 | 298
Diagnostic Evaluation: Confirmation
- Confirmation of the diabetes diagnosis requires repeating the same test on a subsequent day or performing an insulin tolerance test, especially in the absence of unequivocal symptomatic hyperglycemia
Glucose Monitoring: Self-Monitoring of Blood Glucose (SMBG)
- SMBG involves using a finger prick to obtain a small blood sample for testing serum glucose levels
- Helps determine if treatment is effective and monitor blood glucose levels
- Target blood glucose range is 80-120 mg/dL
- Frequency: 1 to 2 times daily, or more frequently depending on individual needs
- Brands: One Touch, Freestyle, Contour, Accu-Check
Glucose Monitoring: Continuous Glucose Monitoring (CGM)
- Uses a sensor or electrode placed subcutaneously to continuously monitor interstitial glucose levels
- Provides real-time data on glucose trends and fluctuations
- Can help predict and prevent hyperglycemia and hypoglycemia
- Brands: Freestyle Libre, Dexcom G6 or G7, the Guardian, Eversense
Hypertension
-
Management:
- All patients with blood pressure (BP) ≥ 140/90 mm Hg should receive pharmacotherapy in addition to lifestyle modifications
-
Lifestyle Therapy:
- Weight loss if needed
- DASH diet (low sodium, high potassium)
- Moderate alcohol consumption
- Increased physical activity
-
Pharmacotherapy:
- Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) are recommended as first-line agents
- Multiple drug therapy is often necessary to achieve target BP
Cholesterol
-
Statin Therapy:
- Statins are recommended for all patients with T2DM over the age of 40, regardless of the presence or absence of cardiovascular disease (CVD) risk factors
- One of the four “Statin Benefit Groups” includes individuals with diabetes aged 40-75 years.
Autonomic Neuropathy
- A common complication of diabetes
- Can affect multiple systems including the GI, cardiovascular, and genitourinary systems
- Gastrointestinal: Constipation is the most common GI manifestation
- Cardiovascular: Persistent sinus tachycardia and orthostasis are common
- Genitourinary: Bladder neuropathy, poor urinary stream, incontinence, and erectile dysfunction can occur
Hyperglycemia Hyperosmolar State
- Characterized by severe hyperglycemia, hyperosmolality, and dehydration
- More common in type 2 diabetes
- Usually develops over days to weeks
- Can lead to altered mental status
Type 2 Diabetes
- Most common form of diabetes
- Caused by insulin resistance and pancreatic exhaustion
- Insulin produced but not utilized effectively by the body
- Genetics and environmental factors contribute to its development
Pathophysiology of Type 2 Diabetes
- Insulin is crucial for regulating blood glucose levels
- It facilitates glucose movement from blood into cells for energy
- Also transports glucose to liver and muscles for energy use
- Type 2 diabetics produce insulin, but not enough to meet the body's needs
Treatment of Type 2 Diabetes
- Management usually involves a stepwise approach
- Lifestyle modifications, including diet and exercise, are essential
- Metformin is the first-line pharmacologic treatment
- Other medications, such as sulfonylureas, thiazolidinediones, DPP4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors, are available for adjunctive therapy
- Insulin may be required if glycemic control cannot be achieved with other treatments
Metformin
- First-line treatment for type 2 diabetes
- Works by decreasing hepatic glucose production and increasing insulin sensitivity
- Can reduce HbA1c by 1-2%
- Can cause GI upset; contraindicated in patients with alcohol use, liver disease, unstable CHF, and severe renal impairment
Sulfonylureas
- Insulin secretagogues that stimulate insulin release from pancreatic beta cells
- Can cause hypoglycemia, particularly in elderly patients
- Contraindicated in patients with renal and liver insufficiency
Thiazolidinediones
- Reduce insulin resistance in the periphery
- Can cause weight gain, fluid retention, and heart failure; avoid in cardiac patients
DPP4 Inhibitors
- Prolong the action of endogenous GLP-1
- Can cause angioedema and immune-mediated dermatologic effects; reduce dose in patients with renal insufficiency
GLP-1 Receptor Agonists
- Mimic the action of GLP-1, stimulating glucose-dependent insulin release
- Reduce glucagon and slow gastric emptying
- Low risk of hypoglycemia
- Can cause GI side effects and weight loss
SGLT2 Inhibitors
- Inhibit glucose reabsorption in the kidneys, increasing renal glucose excretion
- Low risk of hypoglycemia
- Can cause hypotension, acute kidney injury, and DKA in patients with type 1 diabetes; avoid in these patients
Barriers to Treatment of Type 2 Diabetes
- Compliance
- Patient disbelief
- Lack of perceived need for treatment
- Cost of medications and devices
- Delivery system
- Psychosocial factors such as depression, anxiety, and eating disorders
Nonketotic Hyperosmolar State (HHNS)
- A serious complication of diabetes
- Characterized by severe hyperglycemia, hyperosmolality, and profound dehydration
- No significant acidosis
- Requires aggressive fluid resuscitation and insulin therapy
Management of T2DM
- Requires a multidisciplinary team approach
- A written plan should be developed, including medications, diet and exercise guidelines, and goal setting
- Blood glucose monitoring is essential
- Psychosocial counseling is important to address depression, anxiety, and other psychosocial issues
- Regular follow-up visits are necessary to monitor complications.
Diabetes Mellitus Overview
- Characterized by hyperglycemia
- Type 1A: 95% of cases, autoimmune destruction of beta cells leading to absolute insulin deficiency
- Type 1B: 5% of cases, idiopathic cause
- Type 2: Progressive loss of beta cell insulin secretion with variable degrees of tissue insulin resistance
- Gestational diabetes mellitus (GDM): Diagnosed during the 2nd or 3rd trimester of pregnancy without prior evidence of diabetes
- Maturity-onset diabetes of the young (MODY): Genetic defects in pancreatic beta cell function
- Latent autoimmune diabetes in adults (LADA): Slowly developing type 1 diabetes in adults. Initially have no insulin dependence and ketoacidosis, but over time beta cells diminish, leading to insulin dependence.
Type 2 Diabetes Mellitus: Pathophysiology and Epidemiology
- Insulin resistance is a key factor in the pathogenesis of type 2 diabetes.
- Etiology encompasses a combination of genetic predisposition and pancreatic exhaustion.
- Affects 37 million Americans, representing approximately 10.5% of the US population.
- Over 90-95% of all diabetes cases are type 2.
- 1.5 million new cases are diagnosed each year.
- Cost of diabetes in the US was estimated to be $327 billion in 2017.
Insulin's Role in Glucose Regulation
- Insulin facilitates the movement of glucose from the blood into cells for energy use.
- It transports glucose to the liver and muscles for energy utilization.
- Insulin also stores glucose in fat tissue.
- In type 2 diabetes, individuals often produce insulin but not enough to meet the body's needs and may struggle to utilize the produced insulin efficiently.
Relationship of Obesity and Diabetes
- Obesity significantly increases an individual's risk of developing type 2 diabetes.
- The prevalence of both obesity and type 2 diabetes has increased dramatically from 2004 to 2019.
Type 1 vs Type 2 Diabetes
- Type 1 diabetes involves autoimmune destruction of beta cells leading to absolute insulin deficiency.
- Type 2 diabetes features insulin resistance with hyperinsulinemia but ultimately results in relative insulin deficiency.
Clinical Manifestations of Type 2 Diabetes
- Often asymptomatic, leading to an insidious onset of the disease.
- Individuals are often overweight or obese.
- Increased urination and thirst may occur but are not always present.
- Neurological or cardiovascular abnormalities are possible in cases of prolonged undetected or untreated disease.
Physical Signs in Type 2 Diabetes
- Chronic skin infections are indicative of immune system dysfunction.
- Chronic yeast infections can affect women (vulvovaginitis) and men (inflammation of the foreskin and glans penis).
- Centralized fat distribution is a common finding, with a waist circumference greater than 40 inches in men and 35 inches in women.
Acanthosis Nigricans and Eruptive Xanthomas
- Acanthosis nigricans is a skin condition associated with significant insulin resistance.
- Eruptive xanthomas are a sign of hyperchylomicronemia, representing elevated triglyceride levels.
Screening and Diagnostics for Type 2 Diabetes
- A large percentage of individuals with the disorder remain asymptomatic and unaware of their condition.
- Screening is crucial to prevent complications such as retinopathy, nephropathy, and neuropathy, which can significantly affect long-term health.
- Early intervention can favorably alter the natural history of diabetes and improve outcomes.
Categories of Glucose Tolerance
- Normal glucose homeostasis: Normal blood sugar levels.
- Impaired glucose homeostasis: Blood sugar levels are higher than normal but not yet considered diabetic.
- Diabetes mellitus: Blood sugar levels are consistently high.
Diagnostic Criteria for Diabetes
- The diagnosis of diabetes in a non-pregnant adult can be established based on one of four abnormalities:
- Elevated fasting plasma glucose (FPG or FBG)
- Randomly elevated glucose with symptoms
- Elevated hemoglobin A1C
- Abnormal oral glucose tolerance test (OGTT)
Preferred Diagnostic Tests
- FPG (fasting plasma glucose)
- A1C (glycated hemoglobin)
Urine Glucose and Ketones
- Urine dipstick for glucose is sensitive to 100 mg/dL of glucose.
- Urine dipstick for ketones may not detect beta-hydroxybutyric acid, a significant ketone.
- Blood ketone evaluation is crucial to assess for all relevant ketones.
Treatment: A Stepwise Approach
- The initial step in managing type 2 diabetes is to implement lifestyle modifications including diet and exercise.
- Metformin is often prescribed as first-line pharmacologic therapy.
- A stepwise approach involves adding additional medications as needed to achieve target glycemic control.
Goals of Therapy for Type 2 Diabetes
- Eliminate symptoms related to hyperglycemia.
- Reduce or eliminate the long-term microvascular and macrovascular complications associated with diabetes.
- Enable patients to achieve as normal a lifestyle as possible.
Diet and Exercise Modifications
- Weight loss of 5-10% can significantly improve cardiac risk factors.
- Dietary recommendations include reducing carbohydrate intake to less than 45% and replacing it with monounsaturated fats.
- The American Diabetes Association recommends incorporating foods high in soluble fiber, such as oatmeal, cereals, and beans.
- Daily aerobic and resistance training is essential.
- Aim for 150 minutes per week of moderate aerobic activity, distributed over at least three days with no gaps longer than two days.
Metformin (Glucophage)
- Metformin is the first-line initial treatment for type 2 diabetes.
- It is a biguanide that acts as an antihyperglycemic agent by reducing hepatic glucose production, intestinal absorption of glucose, and increasing insulin sensitivity.
- Reduces HbA1C by 1-2%.
- Lowering triglycerides in obese patients and promoting weight loss.
- Low risk of hypoglycemia.
- Long-term use is associated with a decreased risk of microvascular and macrovascular complications.
- Typical dose: 2000 mg PO daily.
- Common side effect: GI upset.
- Contraindications:
- Alcohol
- Liver disease
- Unstable CHF (risk of lactic acidosis)
- CKD (eGFR < 30, elevated creatinine), DKA
Sulfonylureas
- Second-generation sulfonylureas: glyburide (Micronase, DiaBeta), glipizide (Glucotrol), glimepiride (Amaryl).
- MOA: Insulin secretagogues that stimulate the release of insulin from pancreatic beta cells.
- Reduces HbA1C by 1-2%.
- Adjunctive therapy to metformin for HbA1C and FPG/RPG reduction.
- Oral administration, with once-daily dosing for many patients.
- Side effects:
- Hypoglycemia, especially in elderly patients.
- Weight gain.
- Potential interactions with alcohol.
- Caution advised in individuals with renal or liver insufficiency.
Thiazolidinediones
- Pioglitazone (Actos), Rosiglitazone* (Avandia).
- MOA: Reduce insulin resistance in the periphery by enhancing muscle and fat sensitivity to insulin.
- Reduces HbA1C by 0.5-1.4%.
- Improves target-cell response to insulin without increasing insulin secretion.
- Lowers triglycerides.
- Adjunctive therapy to metformin for HbA1C and FPG/RPG reduction.
- Available in pill form.
- Side effects:
- Weight gain.
- Fluid retention and heart failure.
- Increased fracture risk in women.
- Possible increased risk of bladder cancer.
- Contraindications:
- Cardiac patients
- CHF
- Renal or liver insufficiency
DPP4 Inhibitors
- Sitagliptin (Januvia), Saxagliptin (Onglyza), Linagliptin (Tradjenta).
- MOA: Prolongs endogenous GLP-1 action, leading to increased insulin release, decreased glucagon, and reduced hyperglycemia.
- Reduces HbA1C by 0.5-0.8%.
- Adjunctive therapy to metformin for HbA1C and FPG/RPG reduction.
- Single daily oral dose.
- Side effects:
- Angioedema or urticarial.
- Immune-mediated dermatological effects.
- Dose reduction may be necessary in individuals with renal insufficiency.
- Contraindications:
- Pancreatic disease.
GLP-1 Receptor Agonists
- Semaglutide (Ozempic), Liraglutide (Victoza), Exenatide (Byetta).
- MOA: Mimics endogenous incretin GLP-1, stimulating glucose-dependent insulin release, reducing glucagon, and slowing gastric emptying, leading to early satiety.
- Low risk of hypoglycemia.
- Lowers cardiovascular risk.
- Reduces HbA1C by 0.5-1.0%.
- Adjunctive therapy to metformin, sulfonylureas, and thiazolidinediones for HbA1C and FPG/RPG reduction.
- Subcutaneous injection administered weekly or daily.
- Effective medication, but cost can be a barrier to therapy.
- Side effects:
- GI side effects.
- Weight loss.
- Pancreatitis.
- Contraindications:
- CKD.
- Pancreatitis.
- MEN 2.
- Medullary thyroid cancer.
SGLT2 Inhibitors
- Dapagliflozin (Farxiga), Empagliflozin (Jardiance), Sotagliflozin (Zynquista).
- MOA: Inhibits the reabsorption of glucose in the kidneys, increasing renal glucose excretion.
- Reduces HbA1C by 0.5-1.0%.
- Low risk of hypoglycemia.
- Promotes weight reduction and mild blood pressure reduction.
- Renal protective effects.
- Reduces cardiovascular events.
- Adjunctive therapy to metformin, sulfonylureas, and thiazolidinediones for HbA1C and FPG/RPG reduction.
- Single daily oral dose.
- Side effects:
- Hypotension.
- Acute kidney injury.
- DKA in type 1 diabetics (contraindication).
- Yeast infections.
- Acute pharyngitis.
- Changes in urinary habits.
Insulin in Type 2 Diabetes
- Consider initiating insulin in individuals newly diagnosed with type 2 diabetes who are symptomatic and have elevated glucose or HbA1C > 9%.
- Start with basal insulin initially and add bolus insulin if required.
- Start with a dose of 10 units or 0.1-0.2 units/kg and titrate every three days by 3 units.
- It can be challenging to discontinue insulin use once initiated.
- Prioritize maximizing the effectiveness of other antihyperglycemic medications before starting insulin.
Amylin
- Pramlintide (Symlin).
- MOA: Synthetic amylin, a hormone produced and secreted by pancreatic beta cells.
- Injectable pen device.
- Starting dose: 15 mcg with each meal containing at least 30g of carbohydrates or 250 calories, titratable to 120 mcg.
- Not widely used in the US, more common in Europe.
- The only medication besides insulin FDA approved for type 1 diabetes.
- Side effects:
- Severe hypoglycemia (consider adjusting mealtime insulin dosing).
- Nausea, vomiting, and stomach upset.
Alpha-Glucosidase Inhibitors
- Acarbose (Precose), Miglitol (Glyset).
- MOA: Prolongs carbohydrate absorption and helps prevent postprandial glucose surge.
- Reduces HbA1C by 0.5-0.8%.
- Minimal impact on glucose control.
- Oral administration, 1-3 pills per day.
- Limited use in the US, not routinely prescribed.
- Side effects:
- Flatulence.
- Monitoring of liver function tests (LFTs) is recommended.
Meglitinides
- Repaglinide (Prandin), Nateglinide (Starlix).
- MOA: Stimulates non-glucose-dependent insulin secretion, similar to sulfonylureas but weaker.
- Reduces HbA1C by 0.5-1.0%.
- Not routinely used in the US.
- Side effect: Hypoglycemia.
Barriers to Treatment
- Compliance
- Disbelief in the diagnosis.
- Apathy, stating "I don't feel that bad."
- Cost of medications.
- Delivery systems:
- Clearly differentiate non-insulin injectables vs. insulin.
- Address patient concerns about injection therapy, particularly if they have had negative experiences with insulin in the past.
Monitoring
- Regular monitoring of blood glucose, kidney function, blood pressure, and cholesterol levels is essential.
Glucose Monitoring
- Self-Monitoring of Blood Glucose (SMBG):
- Uses a small blood sample obtained via finger prick to test serum glucose levels.
- Determines the patient's response to treatment.
- Target range: 80-120 mg/dL.
- Frequency: 1-2 times daily, at least.
- Brands: OneTouch, Freestyle, Contour, Accu-Check.
Continuous Glucose Monitoring (CGM)
- Utilizes a sensor or electrode to detect interstitial glucose levels.
- Sensors are placed subcutaneously and typically replaced every 3-14 days.
- Provides continuous glucose data points, aiding in glycemic range definition.
- Enables monitoring of glucose changes and trends to prevent predicted hyper- or hypoglycemia.
- Brands: Freestyle Libre, Dexcom G6 or G7, the Guardian, Eversense.
Complications of Type 2 Diabetes
- Retinopathy: Vascular damage to the retina, the leading cause of blindness in individuals aged 20-74 in the US.
- Approximately 700,000 individuals in the US have proliferative diabetic retinopathy.
- Annual incidence: 65,000 cases.
- Early stages can be asymptomatic, but the earliest clinical signs are microaneurysms visible on fundoscopic examination.
- Later symptoms include floaters, distortion, and blurred vision.
- Macular edema is the most common cause of vision loss in individuals with nonproliferative diabetic retinopathy.
- Annual fundoscopic exams are recommended for all type 1 diabetics.
- Prevention: Strict glucose and HbA1C control.
- Key terms: Cotton wool spots.
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This quiz covers key aspects of autonomic neuropathy and Hyperglycemic Hyperosmolar State (HHS). Learn about the effects of autonomic neuropathy on various systems and understand the characteristics and etiology of HHS in type 2 diabetes. Test your knowledge on these important medical conditions.