Diabetes MM

Diabetes Overview

• Date: 11.19 - First of three lectures on diabetes

• Participant engagement: Asking audience about personal connections to diabetes (friends/family)

• Structure: The lecture will cover background info, assessment, prevention of diabetes, treatment goals, non-pharmacologic strategies, first-line medications.

Part 1: Background Information

Epidemiology of Diabetes

• Statistics: 38 million people in the U.S. have diabetes, approximately 11% of the population.

• Higher prevalence in older adults: nearly 30% of those over 65 years.

• Consequences of Diabetes:

  • Leading cause of kidney failure, amputation, and new blindness cases.

  • 8th leading cause of death in the U.S.

Definition of Diabetes Mellitus

• Diabetes Mellitus: A disorder characterized by impaired insulin secretion and/or insulin resistance leading to hyperglycemia (elevated blood sugar).

• Terminology: Blood sugar is often used interchangeably with blood glucose (technically blood glucose is a type of sugar).

Insulin Function

• Insulin as a Key: Analogy of insulin as a key that allows glucose into muscle cells for energy.

• Type 1 vs. Type 2 Diabetes:

  • Type 1 Diabetes: No insulin production, leading to glucose floating in the blood.

  • Type 2 Diabetes: Insulin resistance at the receptor level, leading to overproduction of insulin, eventually resulting in diabetes.

Part 2: Types of Diabetes

Type 1 Diabetes

• Frequency: 5-10% of all diabetes cases.

• Nature: Autoimmune disease with rapid onset (days to weeks); typical onset at ages 12-14.

• Symptoms: Rapid symptoms can include weight loss because the body breaks down fat when glucose cannot enter cells, leading to ketone production.

• LADA: Latent Autoimmune Diabetes in Adults is now considered a subtype of Type 1.

• Symptoms at Diagnosis: Weight loss, ketones present.

Type 2 Diabetes

• Prevalence: Most common type, accounting for about 90% of cases.

• Nature: Primarily driven by insulin resistance, often correlating with obesity.

• Emerging Trends: Increasing incidence in youth due to rising obesity.

Gestational Diabetes

• Definition: A temporary condition during pregnancy with normal blood sugar levels prior to pregnancy.

• Risks: Can lead to large babies (macrosomia) and complications like C-sections and stillbirths.

• Post-Pregnancy: Strong risk factor for developing Type 2 diabetes later in life (about 40% chance).

Part 3: Risk Factors and Screening

• BMI: A BMI greater than or equal to 25 classifies an individual as overweight; greater than 30 as obese.

• Other Screening Criteria:

  • Family history of diabetes (first-degree relatives).

  • Certain ethnic groups potentially at increased risk.

  • Physical inactivity, history of hypertension, dyslipidemia, PCOS, and prediabetes.

  • HIV adds a risk factor due to inflammatory conditions.

Part 4: Measuring Blood Glucose Control

Hemoglobin A1c (A1C)

• Description: Monitors average blood sugar levels over the past 2-3 months.

• Normal Range: 4 to 5.6%.

• Prediabetes: A1C between 5.7% and 6.4%.

• Diabetes Diagnosis: A1C greater than or equal to 6.5%; fasting glucose ≥ 126 mg/dL or 2-hour glucose ≥ 200 mg/dL.

Symptoms of Hyperglycemia

• Classic Symptoms:

  • Polyuria (frequent urination)

  • Polydipsia (increased thirst)

  • Polyphagia (increased hunger)

  • Weight loss (in Type 1 diabetes)

• Other Symptoms: Brain fog, lethargy, headaches, blurry vision.

Part 5: Management and Treatment Goals

Non-Pharmacologic Treatment

• Goals: Achieve and maintain optimal blood sugar levels, weight management.

• Physical Activity: 150 minutes of exercise weekly, encourage lifestyle changes.

• Dietary changes: Limit carbohydrate intake (45-60 grams per meal).

• Smoking cessation: Highly recommended.

Pharmacologic Treatment Overview

• First-line Medications:

  • Metformin is the preferred first-line treatment for Type 2 diabetes.

  • SGLT2 inhibitors and GLP-1 receptor agonists can be used based on comorbid conditions and patient preferences.

  • Sulfonylureas as adjunctive therapy but potential for weight gain and hypoglycemia.

Treatment Goals According to ADA Guidelines

• A1C Target: <7% for most individuals; may vary based on patient characteristics and preferences.

• Fasting Glucose: Target range of 80-130 mg/dL.

• Postprandial Glucose: <180 mg/dL.

Part 6: Complications of Diabetes

Macrovascular and Microvascular Complications

• Macrovascular Disease: Increased risk for coronary artery disease, strokes, heart attacks. Statins and blood pressure control are key management strategies.

• Microvascular Disease: A1C control lowers risk for retinopathy, nephropathy, and neuropathy.

New Complication Terminology

• MASLD: Metabolic Dysfunction-associated Steatotic Liver Disease (formerly known as fatty liver disease).

Part 7: Insulin Management in Type 1 vs. Type 2 Diabetes

Insulin Initiation in Type 2 Diabetes

• First Steps: Consider starting basal insulin (10 units/day or 0.1-0.2 units/kg).

• Titration Protocol: Adjust doses based on blood glucose patterns.

Insulin for Type 1 Diabetes

• Initial Calculation: Total daily dose of insulin should be based on body weight (0.5 units/kg).

• Basal and Bolus Administration: 50% of total daily insulin as basal and divided up between meals.

• Inhaled Insulin: Afrezza is an option, but not commonly used due to safety concerns.

Part 8: Conclusion and Practical Considerations

• Patient Education: Discuss signs of hypoglycemia and how to manage it (15 grams of fast-acting carbohydrate).

• Injection Techniques: Rotate injection sites to prevent lipodystrophy and ensure proper insulin absorption.

• Individualized Approaches: Patient backgrounds, preferences, and comorbidities should guide treatment regimens and goals. Engage in frequent follow-ups for monitoring and adjustment.

DETAILED

Diabetes Overview

• Date: 11.19 - First of three lectures on diabetes, setting the foundation for understanding this chronic condition.

• Participant engagement: Initiated by asking the audience about personal connections to diabetes (friends/family) to foster relevance and encourage active participation.

• Structure: The lecture series will comprehensively cover background information, detailed assessment methods, strategies for diabetes prevention, specific treatment goals, a range of non-pharmacologic intervention strategies, and an in-depth look at first-line pharmacologic medications.

Part 1: Background Information

Epidemiology of Diabetes

• Statistics: A significant public health concern, approximately 38 million people in the U.S. have diabetes, representing about 11% of the total population. This number continues to rise, posing a substantial healthcare burden.

• Higher prevalence in older adults: The risk significantly increases with age, with nearly 30% of individuals over 65 years old diagnosed with diabetes.

• Consequences of Diabetes: If poorly managed, diabetes is a leading cause of severe complications:

  • The primary cause of new cases of kidney failure, often leading to dialysis or kidney transplantation.

  • A major contributor to lower-limb amputations, typically stemming from neuropathy and poor circulation.

  • The most common cause of new cases of blindness (retinopathy) in working-aged adults.

  • Ranked as the 8th leading cause of death in the U.S., primarily due to cardiovascular complications.

Definition of Diabetes Mellitus

• Diabetes Mellitus: A complex metabolic disorder fundamentally characterized by the body's impaired ability to produce or use insulin effectively. This dysregulation leads to chronic hyperglycemia (persistently elevated blood sugar levels). The term "mellitus" is Latin for "honey-sweet," referring to the sweet taste of urine from excess sugar.

• Terminology: While used interchangeably, it's important to note that blood sugar is a general term, whereas blood glucose specifically refers to the primary sugar found in the blood that provides energy to the body's cells.

Insulin Function

• Insulin as a Key: Insulin, a hormone produced by the pancreas, acts like a key that unlocks specialized receptors on cell membranes, primarily on muscle, fat, and liver cells. This allows glucose (sugar) from the bloodstream to enter these cells for energy production or storage.

• Type 1 vs. Type 2 Diabetes:

  • Type 1 Diabetes: An autoimmune condition where the body's immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. This results in little to no insulin production, meaning glucose cannot enter cells and thus accumulates in the bloodstream.

  • Type 2 Diabetes: Characterized by insulin resistance, where cells do not respond effectively to insulin, causing the pancreas to overproduce insulin initially. Over time, the pancreas becomes exhausted and unable to produce sufficient insulin, leading to chronically elevated blood glucose levels.

Part 2: Types of Diabetes

Type 1 Diabetes

• Frequency: Accounts for a smaller proportion, approximately 5-10% of all diagnosed diabetes cases. Its incidence appears to be slowly increasing globally.

• Nature: An autoimmune disease, meaning the body's immune system attacks its own cells. It typically has a rapid onset, manifesting over days to weeks, often triggered by a combination of genetic predisposition and environmental factors. The typical age of onset is often during childhood or adolescence, specifically at ages 12-14, but it can occur at any age.

• Symptoms: Due to the body's inability to utilize glucose for energy, it begins to break down fat for fuel. This process leads to the production of ketones, which can accumulate and cause diabetic ketoacidosis (DKA), a life-threatening condition. Rapid weight loss is a common symptom because the body is catabolizing its own tissues.

• LADA: Latent Autoimmune Diabetes in Adults is a slower-progressing form of autoimmune diabetes that shares characteristics with Type 1 but often presents later in adulthood, sometimes initially misdiagnosed as Type 2 diabetes.

• Symptoms at Diagnosis: Patients typically present with significant weight loss, the presence of ketones in urine or blood, and classic hyperglycemia symptoms.

Type 2 Diabetes

• Prevalence: The most common type, accounting for about 90% of all diabetes cases, making it a widespread public health issue.

• Nature: Primarily driven by insulin resistance, which is often strongly correlated with obesity, sedentary lifestyles, and genetic predispositions. It develops gradually over many years, often without noticeable symptoms in its early stages.

• Emerging Trends: There is a concerning increase in the incidence of Type 2 diabetes in youth, largely attributed to the rising rates of childhood obesity and related lifestyle factors.

Gestational Diabetes

• Definition: A temporary condition where women develop high blood sugar levels during pregnancy. Crucially, their blood sugar levels were normal prior to conception, meaning they were not previously diabetic.

• Risks: Uncontrolled gestational diabetes poses significant risks to both the mother and the developing fetus. It can lead to macrosomia (excessively large babies, defined as birth weight > $4000 ext{ g}$ or > $8 ext{ SD}$ above mean), which increases the likelihood of complications during birth, such as C-sections, shoulder dystocia, and, in severe cases, stillbirths or neonatal hypoglycemia.

• Post-Pregnancy: Women who experience gestational diabetes have a strong and elevated risk of developing Type 2 diabetes later in life, with about a 40% chance within 5-10 years post-delivery. Regular screening after pregnancy is essential.

Part 3: Risk Factors and Screening

• BMI: Body Mass Index is a key indicator. A BMI greater than or equal to $25 ext{ kg/m}^2$ classifies an individual as overweight, while a BMI greater than $30 ext{ kg/m}^2$ classifies them as obese. Both are significant risk factors for Type 2 diabetes.

• Other Screening Criteria: Screening for diabetes should be considered for individuals displaying any of the following:

  • Family history of diabetes in a first-degree relative (parent, sibling, child), indicating a genetic predisposition.

  • Membership in certain ethnic groups (e.g., African Americans, Hispanic/Latino Americans, American Indians, Asian Americans, Pacific Islanders) who have a genetically increased risk.

  • Physical inactivity and sedentary lifestyles, which contribute to insulin resistance.

  • History of hypertension (high blood pressure) or dyslipidemia (abnormal cholesterol/triglyceride levels), as these conditions often coexist with insulin resistance.

  • Polycystic Ovary Syndrome (PCOS) in women, which is linked to insulin resistance.

  • A previous diagnosis of prediabetes, indicating impaired glucose tolerance.

  • HIV infection adds a risk factor due to certain antiretroviral medications and chronic inflammatory conditions associated with the virus.

Part 4: Measuring Blood Glucose Control

Hemoglobin A1c (A1C)

• Description: The Hemoglobin A1c (HbA1c or A1C) test provides an average measure of a person's blood sugar levels over the preceding 2-3 months. It works by measuring the percentage of hemoglobin in red blood cells that is coated with sugar (glycated). Since red blood cells have a lifespan of about 3 months, it offers a long-term glucose snapshot.

• Normal Range: A healthy A1C level is typically between 4% and 5.6%.

• Prediabetes: An A1C result between 5.7% and 6.4% indicates prediabetes, a stage where blood sugar levels are higher than normal but not yet high enough to be classified as diabetes. This is a critical window for intervention.

• Diabetes Diagnosis: Diabetes is diagnosed with an A1C greater than or equal to 6.5%. Other diagnostic criteria include a fasting plasma glucose (FPG) level $ext{greater than or equal to } 126 ext{ mg/dL} ext{ (no caloric intake for at least 8 hours)}$ or a 2-hour plasma glucose level $ext{greater than or equal to } 200 ext{ mg/dL}$ during an oral glucose tolerance test ($ext{after a 75-gram glucose load)}$. A random plasma glucose $ext{greater than or equal to } 200 ext{ mg/dL}$ in a person with classic symptoms of hyperglycemia or hyperglycemic crisis is also diagnostic.

Symptoms of Hyperglycemia

• Classic Symptoms: These usually appear when blood glucose levels are significantly elevated:

  • Polyuria (frequent urination): High blood glucose overwhelms the kidneys' ability to reabsorb sugar, leading to glucose spilling into the urine, which pulls water along with it (osmotic diuresis).

  • Polydipsia (increased thirst): Excessive urination leads to dehydration, triggering intense thirst.

  • Polyphagia (increased hunger): Despite high glucose in the blood, cells are starved of energy (due to lack of insulin or insulin resistance), prompting a sensation of hunger.

  • Weight loss (particularly prominent in Type 1 diabetes): The body breaks down fat and muscle for energy, leading to unintentional weight loss.

• Other Symptoms: Patients may also experience cognitive impairment (brain fog), generalized lethargy and fatigue, headaches, and blurry vision due to osmolality changes affecting the eye lens.

Part 5: Management and Treatment Goals

Non-Pharmacologic Treatment

• Goals: The primary aims are to achieve and maintain optimal blood sugar levels, manage weight, and improve overall health to prevent or delay complications. Emphasis is placed on sustainable lifestyle modifications.

• Physical Activity: Adults should aim for at least 150 minutes of moderate-intensity aerobic exercise weekly (e.g., brisk walking, swimming), spread over at least 3 days, with no more than 2 consecutive days without activity. Resistance training 2-3 times per week is also beneficial. Encourage lifestyle changes that integrate more movement into daily routines.

• Dietary Changes: A key component is limiting carbohydrate intake (e.g., 45-60 grams per meal, though individualized based on patient needs and dietary preferences) and focusing on nutrient-dense foods, lean proteins, and healthy fats. Dietitians can provide tailored meal plans.

• Smoking Cessation: Highly recommended for all individuals with diabetes, as smoking significantly exacerbates cardiovascular risks and other complications.

Pharmacologic Treatment Overview

• First-line Medications: The choice of medication is individualized based on patient characteristics, comorbidities, and preferences:

  • Metformin is widely preferred as the first-line treatment for Type 2 diabetes, primarily due to its efficacy in reducing hepatic glucose production, improving insulin sensitivity, and its relatively low cost and favorable safety profile.

  • SGLT2 inhibitors (Sodium-Glucose Cotransporter-2 inhibitors) and GLP-1 receptor agonists (Glucagon-like Peptide-1 receptor agonists) are increasingly recommended early in treatment, especially for patients with atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, due to their proven cardiovascular and renal benefits, independent of their glucose-lowering effects.

  • Sulfonylureas may be used as adjunctive therapy when other agents are insufficient. However, they carry a higher potential for weight gain and hypoglycemia (low blood sugar), which limits their use as first-line options.

Treatment Goals According to ADA Guidelines

• A1C Target: For most non-pregnant adults, the American Diabetes Association (ADA) recommends an individualized A1C target of <7%. This goal may be less stringent (<8%) for older adults, individuals with a history of severe hypoglycemia, or those with significant comorbidities, to minimize treatment burden and risk of adverse events.

• Fasting Glucose: The target range for fasting plasma glucose is typically 80-130 mg/dL.

• Postprandial Glucose: Postprandial (2 hours after a meal) glucose levels should ideally be <180 mg/dL.

Part 6: Complications of Diabetes

Macrovascular and Microvascular Complications

• Macrovascular Disease: High blood glucose contributes to atherosclerosis (hardening and narrowing of arteries), significantly increasing the risk for major cardiovascular events such as coronary artery disease (leading to angina, heart attacks), strokes (cerebrovascular disease), and peripheral artery disease. Aggressive management of blood pressure and dyslipidemia with medications like statins is crucial to mitigate these risks.

• Microvascular Disease: Poor A1C control is directly linked to damage to small blood vessels, leading to:

  • Retinopathy: Damage to the blood vessels in the retina, potentially leading to vision impairment or blindness.

  • Nephropathy: Kidney damage, which can progress to chronic kidney disease and end-stage renal disease, requiring dialysis or transplantation.

  • Neuropathy: Nerve damage, which can manifest as peripheral neuropathy (numbness, tingling, pain in extremities, leading to increased risk of foot ulcers and amputations), autonomic neuropathy (affecting digestion, heart rate, sexual function), or focal neuropathies.

New Complication Terminology

• MASLD: Metabolic Dysfunction-associated Steatotic Liver Disease (formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD)). This condition is strongly associated with Type 2 diabetes and metabolic syndrome, characterized by fat accumulation in the liver, which can lead to inflammation, fibrosis, and advanced liver disease.

Part 7: Insulin Management in Type 1 vs. Type 2 Diabetes

Insulin Initiation in Type 2 Diabetes

• First Steps: For Type 2 diabetes patients requiring insulin, basal insulin (long-acting insulin) is typically the initial choice. A common starting dose is 10 units/day or 0.1-0.2 units/kg once daily, usually at bedtime or in the morning.

• Titration Protocol: Doses are gradually adjusted or

Part 7: Insulin Management in Type 1 vs. Type 2 Diabetes

Insulin Initiation in Type 2 Diabetes

• First Steps: For Type 2 diabetes patients who require insulin, basal insulin (long-acting insulin) is typically the initial choice when oral medications are no longer sufficient or contraindications exist. A common starting dose is 10 units/day or 0.1−0.2extunits/kg0.1−0.2extunits/kg administered once daily, often at bedtime to mimic physiological basal insulin secretion, or in the morning. The goal is to control fasting and pre-meal blood glucose levels.

• Titration Protocol: Doses are gradually adjusted based on self-monitored blood glucose (SMBG) patterns, aiming for specific fasting glucose targets (e.g., 80−130extmg/dL80−130extmg/dL). A common approach involves increasing the dose by 2 units every 2-3 days until the target fasting glucose is consistently achieved, provided no hypoglycemia occurs. Patients are educated on how to adjust their insulin based on these readings, often in consultation with a healthcare provider. Frequent follow-ups are crucial to optimize the regimen and prevent adverse events.

Insulin for Type 1 Diabetes

• Initial Calculation: For individuals with Type 1 diabetes, the total daily dose (TDD) of insulin is typically based on body weight, with an initial estimate often around 0.5extunits/kg/day0.5extunits/kg/day. This starting dose is a general guideline and may vary based on factors such as age, residual beta-cell function, physical activity level, and pubertal status. The TDD may need to be adjusted during periods of illness, stress, or significant changes in diet or exercise.

• Basal and Bolus Administration: The TDD is typically divided between basal (background) and bolus (mealtime/correction) insulin. Approximately 50% of the total daily insulin is given as basal insulin to provide continuous coverage and prevent ketosis, while the remaining 50% is divided and administered as bolus insulin before meals (mealtime insulin) and to correct high blood glucose levels (correction insulin).

  • Basal Insulin: Long-acting insulin delivered once or twice daily, or continuously via an insulin pump.

  • Bolus Insulin: Rapid-acting insulin administered pre-meal based on carbohydrate intake (using an insulin-to-carbohydrate ratio) and to correct hyperglycemia (using a correction factor or insulin sensitivity factor). Patients learn to calculate their bolus doses based on food intake and current blood glucose levels.

• Inhaled Insulin: Afrezza is a rapid-acting inhaled insulin option approved for use in adults with Type 1 or Type 2 diabetes. It is administered at the beginning of a meal and works quickly, with a short duration of action. However, it is not commonly used due to specific contraindications (e.g., chronic lung disease like asthma, COPD), potential side effects (e.g., cough, throat pain), safety concerns related to lung function monitoring (required spirometry at baseline and periodically), and its higher cost compared to injectable insulins. It is typically used in combination with long-acting insulin for Type 1 diabetes.

1. What type of diabetes mellitus does HL have – type 1, type 2 or gestational diabetes? How can you tell?
   HL has Type 2 Diabetes Mellitus.

   • She has a history of being "chubby" (current BMI of ~$27.5 ext{ kg/m}^2$, classifying her as overweight), which often correlates with insulin resistance in Type 2 Diabetes.

   • She has a long history of diabetes (5 years) and associated comorbidities such as hypertension (8 years) and dyslipidemia (6 years), which are commonly seen with Type 2 Diabetes.

   • Her family history is significant, with her mother and two brothers all having Type 2 Diabetes, indicating a strong genetic predisposition.

   • She had gestational diabetes during her second pregnancy, requiring insulin. Gestational diabetes is a strong risk factor for developing Type 2 Diabetes later in life.

   • Her current symptoms (exhaustion, blurry vision, polyphagia, polyuria) are classic signs of hyperglycemia, consistent with uncontrolled diabetes.

   • She does not exhibit rapid onset or weight loss typically seen in Type 1 Diabetes, nor presence of ketones (her UA is negative for ketones).

2. Does she have any signs or symptoms of microvascular complications like retinopathy, neuropathy or nephropathy?
   Yes, HL shows signs and symptoms of all three microvascular complications:

   • Retinopathy: She complains of "intermittent blurry vision," which is a common symptom of diabetic retinopathy due to osmolality changes affecting the eye lens.

   • Neuropathy: Her physical exam reveals "loss of protective sensation at the base of the right 1st metatarsal joint" using the 10g monofilament test, a definitive sign of peripheral neuropathy.

   • Nephropathy: Her Urine Albumin-to-Creatinine Ratio (UACR) is $64 ext{ mg/g}$. A UACR between $30 ext{ mg/g}$ and $299 ext{ mg/g}$ indicates microalbuminuria, which is an early sign of diabetic nephropathy.

3. What are her risk factors for diabetes?
   HL has several risk factors for diabetes:

   • Overweight/Obesity: Her BMI is approximately $27.5 ext{ kg/m}^2$, classifying her as overweight (a BMI $ext{greater than or equal to } 25 ext{ kg/m}^2$).

   • Family History: Her mother and two brothers have Type 2 Diabetes (first-degree relatives).

   • History of Gestational Diabetes: She took insulin during her second pregnancy, indicating a prior diagnosis of gestational diabetes, which is a strong risk factor for developing Type 2 Diabetes later.

   • Hypertension and Dyslipidemia: She has a medical history of both HTN x 8 years and Dyslipidemia x 6 years; these conditions frequently coexist with insulin resistance and increase diabetes risk.

   • Physical Inactivity: She reports attending Zoom dance class only once a week and no other exercise due to fatigue, indicating insufficient physical activity.

   • Age: At 52 years old, her risk for Type 2 Diabetes is elevated, as prevalence increases with age.

4. What are the diagnostic thresholds for DM based on A1c, FBG and random BG?
   According to ADA guidelines, diabetes is diagnosed by:

   • Hemoglobin A1c (A1C): A1C greater than or equal to $6.5\%$ .

   • Fasting Plasma Glucose (FBG): FBG greater than or equal to $126 ext{ mg/dL}$ (no caloric intake for at least 8 hours).

   • 2-hour Plasma Glucose (Oral Glucose Tolerance Test): 2-hour plasma glucose greater than or equal to $200 ext{ mg/dL}$ during an oral glucose tolerance test (after a 75-gram glucose load).

   • Random Plasma Glucose: Random plasma glucose greater than or equal to $200 ext{ mg/dL}$ in a patient with classic symptoms of hyperglycemia (e.g., polyuria, polydipsia, unexplained weight loss) or hyperglycemic crisis.

5. What are HL’s fasting blood sugar, 2 hr post-prandial blood sugar and A1c goals per the ADA guidelines?
   For HL, given her age (52) and existing comorbidities with no history of severe hypoglycemia, the ADA treatment goals are:

   • A1C Target: <7%

   • Fasting Glucose: Target range of $80-130 ext{ mg/dL}$

   • Postprandial Glucose (2 hours after a meal): <$180 ext{ mg/dL}$

6. What is HL’s blood pressure goal per the ACC/AHA 2025 guidelines?
   The notes emphasize that blood pressure control is a key management strategy for macrovascular disease. Based on ACC/AHA guidelines for an adult patient with diabetes and hypertension like HL, the blood pressure goal is generally <$130/80 ext{ mmHg}$.

7. Evaluate HL’s lipid lowering medication regimen. Is it appropriate based on the ADA guidelines? Why or why not?
   HL is currently on simvastatin 10 mg PO daily. Based on ADA guidelines, this regimen is likely not appropriate:

   • HL is 52 years old with Type 2 Diabetes, hypertension, dyslipidemia, and a calculated 10-year ASCVD risk score of $6.2\%$ (which is in the moderate risk range, but diabetes itself is a significant risk enhancer). She also has microvascular complications (neuropathy, nephropathy), signifying established diabetes complications.

   • ADA guidelines recommend statin therapy for most adults with diabetes.

   • For adults aged 40-75 years with diabetes, a moderate-intensity statin is recommended, and for those with multiple ASCVD risk factors or established ASCVD, a high-intensity statin may be considered. Simvastatin 10 mg is a low-intensity statin.

   • Her current LDL-C of $130 ext{ mg/dL}$ is still elevated and her triglycerides are also high ($229 ext{ mg/dL}$), indicating that the current low-intensity statin dose is insufficient to meet lipid management goals and adequately reduce her ASCVD risk.

   • Therefore, HL should likely be on at least a moderate-intensity statin, and potentially a high-intensity statin, to achieve better lipid control and reduce her high cardiovascular risk.

8. Which one of the following non-pharmacologic treatment recommendations is MOST appropriate to recommend to HL?
   B. Increase exercise to 150 minutes per week

   • The notes highlight that 150 minutes of exercise weekly is a key non-pharmacologic goal. HL currently only attends a Zoom dance class once a week and feels too tired for other exercise. Increasing her physical activity is a direct, evidence-based recommendation from the note's guidelines to improve blood sugar control and overall health.

   • A. Bariatric surgery is generally considered for BMI > $35 ext{ kg/m}^2$ with comorbidities or > $40 ext{ kg/m}^2$ without, which HL's BMI of ~$27.5 ext{ kg/m}^2$ does not meet.

   • C. Eliminating carbohydrates from the diet is an extreme and often unsustainable dietary approach. The notes recommend limiting carbohydrate intake (45-60 grams per meal), not elimination.

   • D. Discontinuing drinking alcohol: While reducing alcohol intake can be beneficial, 7 glasses/week is within moderate limits for women, and addressing physical inactivity is a more pressing non-pharmacologic intervention directly aligned with her diabetes management goals.

9. HL is on the most common first treatment for T2DM already. How should this medication be initiated in treatment naïve patients? (Include generic name, dose, route, frequency and titration). What is the maximum dose?
   HL is currently taking Glucophage (Metformin).

   • Generic Name: Metformin

   • Initiation in treatment-naïve patients:

     • Dose: Typically started at Metformin (immediate release) $500 ext{ mg}$

     • Route: Oral (PO)

     • Frequency: Once daily (usually with the largest meal of the day) or twice daily.

     • Titration: To minimize gastrointestinal side effects, the dose should be gradually increased by $500 ext{ mg}$ per week or every two weeks as tolerated. A common titration might be $500 ext{ mg}$ daily for 1-2 weeks, then $500 ext{ mg}$ twice daily for 1-2 weeks, then $1000 ext{ mg}$ in the morning and $500 ext{ mg}$ in the evening, eventually reaching $1000 ext{ mg}$ twice daily.

   • Maximum Dose:

     • Immediate-release (IR) formulations: Generally up to $2550 ext{ mg/day}$ (divided doses).

     • Extended-release (ER) formulations: Generally up to $2000 ext{ mg/day}$ (once daily).

10. What are the common side effects associated with the treatment for diabetes that HL is currently taking? How can the side effects be minimized?
    HL is taking Metformin.

    • Common Side Effects: Gastrointestinal (GI) disturbances are the most common, including diarrhea, nausea, vomiting, abdominal discomfort/cramping, and a metallic taste in the mouth. Less common but serious is lactic acidosis. Long-term use can also be associated with Vitamin B12 deficiency.

    • Minimizing Side Effects:

      • Slow Titration: Gradually increasing the dose over several weeks (as described in Q9) allows the body to adjust.

      • Take with Food: Administering metformin with meals (or immediately after) can significantly reduce GI upset.

      • Extended-Release (ER) Formulation: Switching to an ER formulation of metformin can often improve GI tolerability compared to the IR formulation.

11. When is this medication contraindicated?
    Metformin is contraindicated in:

    • Severe renal impairment (eGFR less than $30 ext{ mL/min/1.73m}^2$).

    • Acute or chronic metabolic acidosis, including diabetic ketoacidosis (DKA).

    • Acute conditions with potential for altered renal function (e.g., dehydration, sepsis, shock).

    • Hypersensitivity to metformin.

12. HL’s blood sugars are not controlled and she needs an additional medication. What are the advantages and disadvantages of each of the following medications in HL? (Consider efficacy, cost, hypoglycemia risk, her BMI and DM complications). Circle the medication below that you think is the best option for HL (Assume that her insurance will pay for all of the options).
    HL's A1C is $9.2\%$ while on Metformin, indicating uncontrolled diabetes. She is overweight, has HTN, dyslipidemia, and early microvascular complications (neuropathy, microalbuminuria).

    • Glipizide (Glucotrol) - Sulfonylurea

      • Advantages: High efficacy in A1C reduction, relatively inexpensive (if generic).

      • Disadvantages: High risk of hypoglycemia (especially when HL's current regimen is escalated or meals are skipped/delayed), causes weight gain (undesirable for overweight HL), no cardiovascular or renal protective benefits.

    • Semaglutide subcut (Ozempic) - GLP-1 Receptor Agonist

      • Advantages: High efficacy in A1C reduction, significant weight loss (beneficial for overweight HL), proven cardiovascular benefits (reduces ASCVD events, relevant for HL's HTN, dyslipidemia, and ASCVD risk factors), low risk of hypoglycemia (when not combined with insulin/sulfonylureas), improves blood pressure.

      • Disadvantages: Injectable (subcutaneous), common gastrointestinal side effects (nausea, vomiting, diarrhea/constipation), higher cost (though not a factor here per prompt).

    • Sitagliptin (Januvia) - DPP-4 Inhibitor

      • Advantages: Oral, generally well-tolerated, weight-neutral, low risk of hypoglycemia (when not combined with insulin/sulfonylureas), moderate A1C efficacy.

      • Disadvantages: Moderate A1C reduction (less potent than GLP-1 RAs or SGLT2 inhibitors), no significant weight loss, generally no proven cardiovascular or renal protection, higher cost than sulfonylureas.

    • Empagliflozin (Jardiance) - SGLT2 Inhibitor

      • Advantages: High efficacy in A1C reduction, causes weight loss, proven cardiovascular benefits (reduces heart failure hospitalizations and CV death), significant renal benefits (slows progression of kidney disease, very relevant for HL's microalbuminuria/early nephropathy), low risk of hypoglycemia, helps lower blood pressure, oral once daily.

      • Disadvantages: Risk of genital mycotic infections and UTIs, increased urination, potential for volume depletion (leading to hypotension/dizziness), rare risk of euglycemic DKA, higher cost.

    • Pioglitazone (Actos) - Thiazolidinedione (TZD)

      • Advantages: Durable A1C reduction, improves insulin sensitivity, low risk of hypoglycemia.

      • Disadvantages: Causes weight gain (undesirable for overweight HL), notorious for fluid retention (can worsen or cause heart failure, a concern for a patient with HTN), risk of bone fractures, potential bladder cancer risk (long-term), slow onset of action.

    Best Option for HL:
    Empagliflozin (Jardiance)

    Rationale for choice: HL has multiple cardiovascular risk factors (HTN, dyslipidemia) and has already developed microvascular complications, including mild nephropathy (UACR $64 ext{ mg/g}$). Empagliflozin, as an SGLT2 inhibitor, offers compelling evidence for both cardiovascular and renal protective benefits, which directly address HL's specific comorbidity profile and progressive disease. It also promotes weight loss and has a low risk of hypoglycemia, making it an excellent choice for a patient like HL who is overweight and needs aggressive A1C improvement while protecting her organs.

13. What are selected adverse drug reactions (ADRs), warnings, precautions and contraindications for each of the following medications? What to focus on is specified under each medication.

    • Sulfonylureas (e.g., Glipizide)

      • Beers Criteria Warning: Sulfonylureas, particularly older/first-generation agents but also some second-generation (like glipizide), are listed on the Beers Criteria as potentially inappropriate medications for older adults due to a high risk of severe, prolonged hypoglycemia. This risk is especially pronounced in patients with impaired renal function, irregular eating habits, or those on multiple glucose-lowering agents, leading to potential falls, fractures, and other adverse events.

    • Semaglutide subcut (Ozempic)

      • BBW (Black Box Warning): Risk of thyroid C-cell tumors (medullary thyroid carcinoma - MTC) based on rodent studies; it is unknown whether it causes MTC in humans. It is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

      • Warnings: Acute pancreatitis, diabetic retinopathy complications (particularly in patients with pre-existing retinopathy who experience rapid glucose lowering), acute kidney injury (due to dehydration), gallbladder disease (cholelithiasis), increased heart rate.

    • Sitagliptin (Januvia)

      • 4 Rare ADRs: Acute pancreatitis, severe and disabling arthralgia (joint pain), bullous pemphigoid (a severe blistering skin condition), and hypersensitivity reactions (e.g., anaphylaxis, angioedema, Stevens-Johnson Syndrome).

      • Warning same as GLP-1 RAs: Acute pancreatitis.

    • Empagliflozin (Jardiance)

      • ADRs: Genital mycotic infections (vulvovaginal candidiasis, balanitis), urinary tract infections (UTIs), increased urination (polyuria), volume depletion (e.g., hypotension, dizziness, particularly in elderly or those on diuretics), increased LDL-C, rare but serious risk of euglycemic diabetic ketoacidosis (DKA), necrotizing fasciitis of the perineum (Fournier's gangrene) which is a rare but life-threatening infection.

    • Pioglitazone (Actos)

      • BBW (Black Box Warning): May cause or exacerbate congestive heart failure. Do not use in patients with symptomatic heart failure or established New York Heart Association (NYHA) Class III or IV heart failure. Monitor patients for signs and symptoms of heart failure (e.g., rapid weight gain, dyspnea, edema).

14. When would you check an A1c after adding a medication for T2DM?
    An A1C test should be checked approximately 3 months after adding a new medication for Type 2 Diabetes. This timeframe allows for sufficient red blood cell turnover for the A1C level to reflect the average blood glucose control impacted by the new treatment regimen.

15. HL’s primary care provider would like you to make a recommendation regarding initiating insulin in HL. Design a complete pharmacotherapeutic plan to improve HL’s glycemic control including drug (brand and generic name), dose, route, and frequency. Include your rationale of why you selected this regimen.

Pharmacotherapeutic Plan to Improve Glycemic Control for HL

HL has significantly uncontrolled Type 2 Diabetes, evidenced by an A1C of $10.1\%$, an average fasting blood glucose (FBG) of $216\text{ mg/dL}$, and average 2-hour post-dinner readings of $310\text{ mg/dL}$. She is experiencing symptoms of hyperglycemia and worsening neuropathy, despite being on a regimen of metformin, tirzepatide (Mounjaro), empagliflozin (Jardiance), and glipizide (Glucotrol).

1. Discontinue:

• Glipizide (Glucotrol) $10\text{ mg PO BID}$

  • Rationale: Sulfonylureas increase insulin secretion and carry a high risk of hypoglycemia, particularly when combined with exogenous insulin. Discontinuing glipizide will significantly lower the risk of severe hypoglycemia upon insulin initiation.

2. Initiate Basal Insulin:

• Drug: Insulin Glargine U-100 (Lantus, Basaglar, Toujeo)

• Dose: $10\text{ units}$

• Route: Subcutaneously (subcut)

• Frequency: Once daily (e.g., at bedtime or consistent time daily)

• Titration Protocol: Instruct HL to increase the dose by $2\text{ units}$ every $2-3\text{ days}$ based on her fasting blood glucose (FBG) readings, targeting an FBG between $80-130\text{ mg/dL}$. She should monitor her FBG daily and be educated on recognizing and managing hypoglycemia (e.g., consuming $15\text{ grams}$ of fast-acting carbohydrates).

3. Continue & Monitor Existing Medications:

• Metformin (Glucophage) $1000\text{ mg PO BID}$

  • Note: HL's eGFR is $49\text{ mL/min/1.73m}^2$. While metformin can generally be continued at this eGFR, close monitoring for renal function decline and potential for metformin accumulation is essential. If eGFR falls below $45\text{ mL/min/1.73m}^2$, dose reduction (e.g., to $1000\text{ mg/day}$ or $1500\text{ mg/day}$) should be considered, and it is contraindicated below $30\text{ mL/min/1.73m}^2$.

• Tirzepatide (Mounjaro) $15\text{ mg subcut every Friday}$

  • Rationale: Tirzepatide, a dual GIP/GLP-1 receptor agonist, offers significant A1C reduction, supports weight loss (beneficial for HL's BMI of $30.6\text{ kg/m}^2$), and has cardiovascular benefits. It can safely be continued with basal insulin, as the risk of hypoglycemia is low when not combined with sulfonylureas.

• Empagliflozin (Jardiance) $25\text{ mg PO daily}$

  • Rationale: Empagliflozin, an SGLT2 inhibitor, provides proven cardiovascular and renal protective benefits, which are crucial for HL given her comorbidities (hypertension, dyslipidemia) and complications (neuropathy, declining eGFR). It also contributes to A1C reduction and weight loss. Monitoring for volume depletion, urinary tract infections, and genital mycotic infections is important.

Justification for the Regimen:
HL's markedly elevated A1C of $10.1\%$ and persistent hyperglycemia despite a maximal regimen of non-insulin agents underscore the need for insulin therapy. Basal insulin is the initial treatment of choice for Type 2 diabetes patients who are inadequately controlled on multiple oral and/or injectable non-insulin therapies, or when A1C is significantly above target (>10%). Insulin directly addresses the body's impaired insulin secretion, which is a component of Type 2 diabetes progression. The chosen basal insulin regimen is tailored for simplicity (once daily dosing) and effectiveness in targeting fasting hyperglycemia, with subsequent titration to achieve individualized glucose goals. By discontinuing glipizide and continuing Mounjaro and Jardiance, this plan maximizes glycemic control while leveraging the cardioprotective and renoprotective benefits of these newer agents, and minimizing the risk of adverse effects like severe hypoglycemia and further weight gain. Close monitoring and patient education are vital for successful implementation and safety.

• CASE #2

  ND is a 23-year old trans man who presents to clinic complaining of fatigue, increased urination, feeling thirsty (leading to drinking 2 cartons/day of orange juice), feeling aches in legs, and weight loss.
  He is diagnosed with T1DM. ND weighs 118 lbs and is 5’6”.

  16. Which one of the following regimens is the MOST appropriate to initiate in ND?

      • D. Novolog 4 units subcut pre-meals tid and Basaglar 12 units subcut q am

      Rationale: ND has Type 1 Diabetes, which requires both basal and bolus insulin. To calculate the initial total daily dose (TDD), use 0.5 \text{ units/kg}.NDweighs118lbs(approximately.NDweighs118lbs(approximately53.6 \text{ kg}).TDD=).TDD=0.5 \text{ units/kg} \times 53.6 \text{ kg} = 26.8 \text{ units}(roundto27units).DividetheTDDinto50Basalinsulin:(roundto27units).DividetheTDDinto50Basalinsulin:50\% \text{ of } 27 \text{ units} = 13.5 \text{ units}.Bolusinsulin:.Bolusinsulin:50\% \text{ of } 27 \text{ units} = 13.5 \text{ units}(dividedbeforemeals).OptionDprovidesBasaglar(basalinsulin)12unitssubcutqam,andNovolog(rapid−actingbolusinsulin)4unitssubcutpre−mealstid((dividedbeforemeals).OptionDprovidesBasaglar(basalinsulin)12unitssubcutqam,andNovolog(rapid−actingbolusinsulin)4unitssubcutpre−mealstid(4 \text{ units} \times 3 \text{ meals} = 12 \text{ units}).Thetotaldailydoseis).Thetotaldailydoseis12 \text{ (basal)} + 12 \text{ (bolus)} = 24 \text{ units}.Thisregimenoffersbothbasalandbolusinsulin,inaclinicallyappropriateratioandtotalamountforinitialT1DMmanagement.OptionA(Lantusonly)providesonlybasalinsulin,whichisinsufficientforT1DM.OptionB(Victoza)isaGLP−1receptoragonist,notinsulin,andistypicallyforT2DM.OptionC(Humalogpre−breakfastandTresiba)providesbasalandsomebolus,butbolusonlyforonemealisinadequateforT1DM.2monthslater,NDpresentstoclinicforfollow−up.Hiscontinuousglucosemeterresultsfromthepast2weeksareasfollows:CGMuse–80TAR(>250)=2TAR(>180−250)=34TIR(70−180)=64TBR(<70)=0FBS–range96−132,avg110Pre−lunch–range180−257,avg222Pre−dinner–range94−120,avg115Bedtime–range134−157,avg142HeistakingBasaglar10unitssubcutatqamandApidra3unitssubcuttidpre−meals.Whatchangeswouldyourecommendbasedonhisglucosemeterreadings?Recommendation:BasedonND′scontinuousglucosemonitoring(CGM)resultsandspecificbloodglucosereadings,themostcriticaladjustmentistoincreasehisrapid−acting(Apidra)insulindosebeforebreakfast.Rationale:TimeinRange(TIR):ND′sTIR(70−180mg/dL)is64FastingBloodSugar(FBS):HisaverageFBS(110mg/dL)iswithinthetargetrangeof.Thisregimenoffersbothbasalandbolusinsulin,inaclinicallyappropriateratioandtotalamountforinitialT1DMmanagement.OptionA(Lantusonly)providesonlybasalinsulin,whichisinsufficientforT1DM.OptionB(Victoza)isaGLP−1receptoragonist,notinsulin,andistypicallyforT2DM.OptionC(Humalogpre−breakfastandTresiba)providesbasalandsomebolus,butbolusonlyforonemealisinadequateforT1DM.2monthslater,NDpresentstoclinicforfollow−up.Hiscontinuousglucosemeterresultsfromthepast2weeksareasfollows:CGMuse–80TAR(>250)=2TAR(>180−250)=34TIR(70−180)=64TBR(<70)=0FBS–range96−132,avg110Pre−lunch–range180−257,avg222Pre−dinner–range94−120,avg115Bedtime–range134−157,avg142HeistakingBasaglar10unitssubcutatqamandApidra3unitssubcuttidpre−meals.Whatchangeswouldyourecommendbasedonhisglucosemeterreadings?Recommendation:BasedonND′scontinuousglucosemonitoring(CGM)resultsandspecificbloodglucosereadings,themostcriticaladjustmentistoincreasehisrapid−acting(Apidra)insulindosebeforebreakfast.Rationale:TimeinRange(TIR):ND′sTIR(70−180mg/dL)is64FastingBloodSugar(FBS):HisaverageFBS(110mg/dL)iswithinthetargetrangeof80-130 \text{ mg/dL}.Thissuggeststhathiscurrentbasalinsulindose(Basaglar10unitsqam)islargelyeffectivefornocturnalandfastingcontrol.Pre−lunchGlucose:Hisaveragepre−lunchglucoseis.Thissuggeststhathiscurrentbasalinsulindose(Basaglar10unitsqam)islargelyeffectivefornocturnalandfastingcontrol.Pre−lunchGlucose:Hisaveragepre−lunchglucoseis222 \text{ mg/dL}(range180−257).Thisissignificantlyabovethepostprandialtargetof<(range180−257).Thisissignificantlyabovethepostprandialtargetof<180 \text{ mg/dL}andindicatesthattheApidra3unitstakenbeforebreakfastisinsufficienttocoverhiscarbohydrateintakeforthatmeal.Pre−dinnerGlucose:Hisaveragepre−dinnerglucoseisandindicatesthattheApidra3unitstakenbeforebreakfastisinsufficienttocoverhiscarbohydrateintakeforthatmeal.Pre−dinnerGlucose:Hisaveragepre−dinnerglucoseis115 \text{ mg/dL}(range94−120),whichiswithintarget.ThissuggeststheApidra3unitstakenbeforelunchiscurrentlyadequate.BedtimeGlucose:Hisaveragebedtimeglucoseis(range94−120),whichiswithintarget.ThissuggeststheApidra3unitstakenbeforelunchiscurrentlyadequate.BedtimeGlucose:Hisaveragebedtimeglucoseis142 \text{ mg/dL}$$ (range 134-157), which is slightly elevated but relatively stable. This might suggest a minor adjustment needed for dinner bolus, but the pre-lunch hyperglycemia is more pronounced.

  17. No Hypoglycemia: ND has 0% time below range (TBR <70 mg/dL), indicating there is no risk of hypoglycemia at his current doses and thus room for insulin dose increases.

Specific Changes:

• Increase Apidra (rapid-acting insulin) dose before breakfast: Increase the Apidra dose from 3 units to, for example, 4 or 5 units before breakfast. This adjustment directly addresses the consistently high pre-lunch glucose readings. Further titration can be done based on continued glucose monitoring.

• Consider educating on carbohydrate co