Endocrinology Flashcards

Question

Which lipid abnormality is commonly observed in Type 2 Diabetes Mellitus due to insulin resistance in adipose tissue? a) Increased high-density lipoprotein (HDL) b) Increased free fatty acid release and VLDL-triglyceride production c) Decreased low-density lipoprotein (LDL) d) Decreased lipolysis in adipose tissue

Answer 1

Answer: b) Increased free fatty acid release and VLDL-triglyceride production Explanation In Type 2 Diabetes Mellitus (T2DM), insulin resistance in adipose tissue leads to increased lipolysis and the release of free fatty acids (FFAs) into the circulation. The liver takes up these excess FFAs and converts them into very low-density lipoprotein (VLDL) particles, which carry triglycerides. This process contributes to the characteristic dyslipidemia seen in T2DM, marked by elevated triglycerides and often reduced HDL levels. • (a) Increased HDL is not typical in T2DM; HDL is usually low. • (c) Decreased LDL is also not a hallmark of T2DM dyslipidemia; LDL levels may be normal or mildly elevated, but often LDL particles are smaller and denser, which is more atherogenic. • (d) Decreased lipolysis would be the opposite of what typically occurs in insulin-resistant adipose tissue. Hence, the excess FFA flux from adipose tissue to the liver and the subsequent increased VLDL production are key features of dyslipidemia in T2DM.

Answer 2

Answer: b) Adipokines and free fatty acids from excess adipose tissue exacerbate insulin resistance Explanation Obesity, particularly when associated with excess visceral adipose tissue, leads to increased secretion of adipokines (such as TNF-α, IL-6) and a higher release of free fatty acids. These factors contribute to the development of insulin resistance in peripheral tissues like muscle and liver. This insulin resistance is a central component in the pathogenesis of Type 2 Diabetes Mellitus (T2DM). • Option a is incorrect because obesity is directly related to insulin resistance in these tissues. • Option c is incorrect because while lean individuals are less likely to develop T2DM, they can still be affected, albeit less commonly. • Option d is incorrect because even subcutaneous fat can influence insulin sensitivity, though visceral fat has a stronger association with insulin resistance. Thus, the best description is that the increased adipokines and free fatty acids in obesity worsen insulin resistance, thereby playing a key role in T2DM pathogenesis.

Answer 3

Answer: b) Insulin secretion is initially increased but inappropriate for the degree of insulin resistance. Explanation In the early stages of Type 2 Diabetes Mellitus (T2DM), the body’s tissues—especially skeletal muscle and adipose tissue—develop insulin resistance. In response to this decreased sensitivity, the pancreatic beta cells compensate by increasing insulin secretion. This compensatory mechanism leads to hyperinsulinemia. However, even though insulin levels are elevated, they are still insufficient to overcome the high level of insulin resistance, resulting in hyperglycemia. Over time, chronic metabolic stress (including glucotoxicity and lipotoxicity) can impair beta-cell function further, leading to a decline in insulin secretion. But at the onset of T2DM, the primary characteristic is an inappropriately high insulin secretion relative to the degree of insulin resistance. Why the Other Options Are Incorrect Option a) Insulin secretion is completely absent due to beta-cell destruction. • Incorrect: This describes the pathophysiology of Type 1 Diabetes Mellitus, where autoimmune destruction of beta cells leads to an absolute insulin deficiency. In T2DM, especially early on, beta cells are still functional and actually overproduce insulin in response to insulin resistance. Complete absence of insulin secretion does not occur until very late stages, if at all. Option c) Insulin secretion is normal and remains unchanged throughout the disease. • Incorrect: While insulin secretion may initially be elevated as a compensatory mechanism, it is not normal relative to the degree of insulin resistance. Over time, beta-cell function declines due to chronic metabolic stress. Therefore, insulin secretion does not remain unchanged throughout the disease; it typically deteriorates with disease progression. Option d) Insulin secretion is rapidly depleted due to mitochondrial dysfunction. • Incorrect: Although mitochondrial dysfunction in beta cells can contribute to impaired insulin secretion in T2DM, this process is gradual rather than rapid. In early T2DM, beta cells are compensating by increasing insulin output despite some degree of metabolic stress. The term “rapidly depleted” implies an acute loss of insulin secretion, which is more characteristic of conditions with acute beta-cell failure (e.g., Type 1 Diabetes) rather than the progressive decline seen in T2DM.

Answer 4

a. ADA, recommends that all women of childbearing age be counseled about the importance of tight glycemic control (Hba1C <6%) prior to conception Hba1C <6.5% not 6.0 Harrison’s 21st Ed pg 3103

Answer 5

The correct answer is: Harrison 21st Ed pg 3103 d. May have associated conditions such as insulin resistance, hypertension, CVD, dyslipidemia, or PCOS. Explanation: Alvin’s presentation (polydipsia, polyuria, polyphagia) and positivity for GAD and ZnT8 antibodies strongly suggest Type 1 Diabetes Mellitus (T1DM) or Latent Autoimmune Diabetes in Adults (LADA) rather than Type 2 DM. a. Lean body habitus → CORRECT • T1DM and LADA are typically associated with lean or normal BMI, unlike Type 2 DM, which is often linked to obesity. b. Requirement of insulin as the initial therapy → CORRECT • T1DM and LADA are autoimmune diseases leading to β-cell destruction, causing absolute insulin deficiency that requires insulin therapy from the start. c. Propensity to develop ketoacidosis → CORRECT • Individuals with T1DM or LADA are at risk for diabetic ketoacidosis (DKA) due to insulin deficiency. d. May have associated conditions such as insulin resistance, hypertension, CVD, dyslipidemia, or PCOS → INCORRECT (ANSWER) • These conditions are more characteristic of Type 2 DM (T2DM), which is linked to insulin resistance and metabolic syndrome. • While some overlap can exist, autoimmune diabetes (T1DM/LADA) is not primarily associated with these comorbidities.

Answer 6

C. C-peptide level are able to distinguish type 1 from type 2 DM C-peptide level are UNABLE to distinguish type 1 from type 2 DM as many individuals with type 1 retain some C-peptide production Harrison’s 21st pg 3103

Answer 7

C. High glucose uptake in insulin-sensitive tissues Harrison’s 21st pg 3097-3098 Explanation: During the fasting state, the body maintains glucose homeostasis by: A. Low insulin levels, High glucagon → CORRECT • Insulin decreases (since there’s no food intake), while glucagon increases to promote glucose production. B. Promote hepatic gluconeogenesis and glycogenolysis → CORRECT • The liver breaks down glycogen (glycogenolysis) and synthesizes glucose from non-carbohydrate sources (gluconeogenesis) to maintain blood sugar levels. C. High glucose uptake in insulin-sensitive tissues → INCORRECT (ANSWER) • Insulin-sensitive tissues (e.g., muscle and adipose tissue) require insulin for glucose uptake via GLUT4 transporters. • In fasting, low insulin levels lead to reduced glucose uptake in these tissues, preserving glucose for essential organs like the brain (which uses insulin-independent GLUT1 and GLUT3 transporters). D. Increase mobilization of gluconeogenic precursors (amino acids and free fatty acids) → CORRECT • Proteins break down into amino acids, and fat stores release free fatty acids, providing substrates for gluconeogenesis and ketogenesis.

Answer 8

Correct Answer: c) <7.0% Harrison’s 21st pg 3104 Explanation: According to the American Diabetes Association (ADA), the recommended HbA1c target for most non-pregnant adults with diabetes is <7.0% to reduce the risk of microvascular and macrovascular complications. • <8.0% for older adults, those with limited life expectancy, or those at high risk of severe hypoglycemia.

Answer 9

Correct Answer: c) It reduces hepatic glucose production and improves insulin sensitivity Explanation: Harrison’s 21st edition pg 3110 Metformin is a first-line therapy for Type 2 Diabetes that primarily: • Reduces hepatic glucose production (decreasing gluconeogenesis). • Increases insulin sensitivity in peripheral tissues (muscle and liver). • Does not stimulate insulin secretion, reducing the risk of hypoglycemia. Why the other options are incorrect: a) It primarily increases insulin secretion from pancreatic beta cells → FALSE • Metformin does not stimulate insulin secretion (unlike sulfonylureas). b) It should be discontinued immediately after a diabetes diagnosis → FALSE • Metformin is first-line therapy unless contraindicated. d) It is contraindicated in all patients with any level of kidney disease → FALSE • Metformin is contraindicated in severe renal impairment (eGFR <30 mL/min/1.73 m²), but it can be used cautiously in mild to moderate kidney disease with dose adjustments.

Answer 10

Answer C. Pioglitazone Harrison’s 21st pg 3112 Concerns about increased cardiovascular risk associated with rosiglitazone led to considerable restrictions on its use and to the FDA issuing a black box warning in 2007. However, based on new informa-tion, the FDA has revised its guidelines and categorizes rosiglitazone similar to other drugs for type 2 DM. According to an FDA review, pioglitazone may be associated with an increased risk of bladder cancer. In one study, pioglitazone lowered the risk for recurrent stroke or myocardial infarction in insulin-resistant individuals without diabetes who had a prior stroke or transient ischemic attack.

Answer 11

Correct Answer: C. MODY 3 Explanation: Harrison’s pg 3102 MODY 3 is caused by mutations in the HNF-1α gene. This form of monogenic diabetes typically shows a progressive decline in glycemic control due to gradually worsening β-cell function. However, patients with MODY 3 are known to be highly sensitive to sulfonylureas, which can effectively lower blood glucose levels by stimulating insulin secretion. MODY 1 (HNF-4α mutation) may share some clinical features but is less common and has a slightly different clinical course. MODY 2 (Glucokinase mutation) usually presents with mild to moderate , stable hyperglycemia that is often non-progressive and typically does not require treatment with sulfonylureas. MODY 4 is a less common variant and is not characterized by a strong response to sulfonylureas.

Answer 12

A. Lipid profile testing every 6 months Explanation: Harrison’s 21st page 3104 Guidelines for ongoing, Comprehensive Medical Care for Individuals with Diabetes Lipids (1-2 times/year) Urine albumin (annual) or screening of albuminuria should commence 5years after the onset of Type 1 DM and at the time of diagnosis of type 2 DM Blood pressure should assess 2-4 times/year Foot examination (1-2 times/year by provider, daily by patient)

Answer 13

The correct answer is: b. Continuous glucose monitoring (CGM) Explanation: HPIM Ch 404 p. 3105 The patient’s symptoms—awakening at midnight with diaphoresis and tremors—are suggestive of nocturnal hypoglycemia, which is common in type 1 diabetes mellitus (T1DM) due to insulin therapy. To minimize the occurrence of this condition, it is crucial to monitor glucose levels, especially at night, to detect trends and adjust insulin or dietary intake accordingly. Why CGM is the Best Option? • Continuous glucose monitoring (CGM) provides real-time glucose readings throughout the day and night. • It detects hypoglycemic episodes during sleep, which can be missed with routine fingerstick monitoring. • CGM helps identify trends (e.g., dropping glucose at night) and allows for better insulin adjustments. Why Not the Other Options? • 1,5-Anhydroglucitol (1,5-AG) – Reflects postprandial glucose control but is not useful for detecting nocturnal hypoglycemia. • Fructosamine – Reflects 2–3 weeks of average glucose levels but does not show daily fluctuations or nocturnal hypoglycemia. • HbA1c – Provides a 3-month average of glucose levels but does not reveal hypoglycemic episodes or glucose variability. Thus, CGM is the most useful tool for assessing and minimizing nocturnal hypoglycemia in this patient.

Answer 14

The correct answer is: a. Degludec Explanation: HPIM Ch 404 p. 3107-3109 The patient has nocturnal hypoglycemia, which is often associated with basal insulin peaking at night or having an inconsistent duration of action. To reduce nocturnal hypoglycemia, we need a basal insulin with a longer and more stable duration of action. Why Insulin Degludec? • Ultra-long-acting insulin with a duration of over 42 hours. • Provides a steady and peakless insulin release, reducing the risk of nocturnal hypoglycemia. • Studies show lower nocturnal hypoglycemia rates compared to insulin glargine and detemir. Why Not the Other Options? • Insulin Detemir – Long-acting, but has a shorter half-life than degludec and may require twice-daily dosing in some patients. • Insulin Glargine (U-100) – Long-acting, but peaks slightly and has a shorter duration (~24 hours), increasing the risk of nocturnal hypoglycemia. • Neutral Protamine Hagedorn (NPH) – Intermediate-acting, has a pronounced peak, and is associated with the highest risk of nocturnal hypoglycemia. Final Recommendation: Switching the patient to insulin degludec (Tresiba) will provide the longest duration of action and the lowest risk of nocturnal hypoglycemia.

Answer 15

Answer: D D. Learn glucose response to different types of exercise Explanation: Harrison’s 21st page 3105 To avoid exercise-related hyper- or hypoglycemia, individuals with type 1 DM should (1) monitor blood glucose before, during, and after exercise; (2) delay exercise if blood glucose is >14 mmol/L (250 mg/ dL) and ketones are present; (3) if the blood glucose is <5.0 mmol/L (90 mg/dL), ingest carbohydrate before exercising; (4) monitor glucose during exercise and ingest carbohydrate as needed to prevent hypo-glycemia; (5) decrease insulin doses (based on previous experience) before and after exercise and inject insulin into a nonexercising area; and (6) learn individual glucose responses to different types of exercise. In individuals with type 2 DM, exercise-related hypoglycemia is less common but can occur in individuals taking either insulin or insulin secretagogues.

Answer 16

d. They have linked to single gene defects like MODY Explanation: The condition described is Atypical Diabetes or Ketosis-Prone Diabetes (KPD), a non-autoimmune form of diabetes that has characteristics of both Type 1 and Type 2 diabetes but is not caused by single-gene defects like MODY. a. Development of a type 2 diabetes phenotype before puberty → TRUE Some patients with KPD or other forms of atypical diabetes may develop insulin resistance (a hallmark of Type 2 diabetes) early in life. b. Type 2 diabetes phenotype in very lean individuals → TRUE Some individuals with KPD or atypical diabetes exhibit insulin resistance despite having a low BMI, which is usually associated with Type 1 diabetes. c. Ketosis-prone diabetes where individuals present with ketoacidosis, but do not require long-term exogenous insulin therapy → TRUE A defining feature of Ketosis-Prone Diabetes (KPD) is that patients may present with diabetic ketoacidosis (DKA) initially but later regain beta-cell function and can sometimes be managed without insulin. d. They have linked to single gene defects like MODY → FALSE Maturity-Onset Diabetes of the Young (MODY) is a monogenic form of diabetes caused by specific single-gene mutations affecting beta-cell function. It does not typically present with ketosis or DKA and does not have the same characteristics as KPD.

Answer 17

a. Dulaglutide Explanation: The best treatment option for this patient is to add dulaglutide (Option A). At the time of diagnosis, metformin was initiated, which is first-line pharmacologic therapy for the management of type 2 diabetes mellitus. Although she has made some progress with hemoglobin A1c reduction and weight loss, her glycemic target is still not at goal. In young, otherwise healthy patients, the American Diabetes Association recommends a hemoglobin A target of less than 7% in most nonpregnant adults, suggesting that an even more stringent target, less than 6.5%, may be appropriate for some patients if it can be achieved without significant hypoglycemia or adverse effects. Patients should be re-evaluated at 3-month intervals and treatment escalated with additional agents if the hemoglobin Ac remains above goal. In patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors for ASCVD, a glucagon-like peptide 1 receptor agonist (GLP-1 RA) or sodium-glucose cotransporter 2 (SGLT2) inhibitor with demonstrated cardiovascular benefit is recommended to reduce the risk for major adverse cardiovascular events, independent of hemoglobin Alc lowering. This patient has multiple risk factors for ASCVD (hypertension, dyslipidemia, obesity). In addition, GLP-1 RAs are associated with weight loss, which would be beneficial for this patient with obesity. Dulaglutide is a GLP-1 RA with proven cardiovascular benefit. Glipizide (Option B) is a sulfonylurea and stimulates insulin secretion. It is associated with weight gain and has no ASCVD benefits. In most patients who need the greater glucose-lowering effect of an injectable medication, GLP-1 RAs are preferred to insulin (Option C). Insulin administration is not associated with the ASCVD benefits of a GLP-1 RA and may also cause weight gain. Pioglitazone (Option D), a thiazolidinedione, increases peripheral uptake of glucose. Although pioglitazone can possibly decrease cardiovascular disease events, it is associated with weight gain, which is undesirable in this patient with obesity.

Answer 18

a. Empagliflozin Explanation: The most appropriate treatment is empagliflozin (Option A). This drug has proven benefit for patients with type 2 diabetes mellitus who have atherosclerotic cardiovascular disease (ASCVD), which is a major cause of morbidity and mortality in this population. The American Diabetes Association recommends dual antiplatelet therapy with low-dose aspirin and a P2Y12 inhibitor (clopidogrel, ticagrelor) for 1 year after an acute coronary syndrome not treated with percutaneous coronary intervention. Patients should also receive high-intensity statin therapy (atorvastatin, rosuvastatin), an ACE inhibitor or angiotensin receptor blocker, and a ß-blocker (metoprolol, carvedilol). For patients with type 2 diabetes who have established ASCVD or established kidney disease, a sodium-glucose cotransporter 2 (SGLT2) inhibitor or glucagon-like peptide 1 receptor agonist (GLP-1 RA) with demonstrated cardiovascular disease benefit is recommended as part of the glucose-lowering regimen. SGLT2 inhibitors with established cardiovascular disease benefit include empagliflozin, canagliflozin, and dapagliflozin; corresponding GLP-1 RAs include albiglutide, dulaglutide, lira-glutide, and injectable semaglutide. The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients demonstrated a reduction in the primary composite outcome (cardiovascular-related death, nonfatal myocardial infarction, nonfatal stroke) and all-cause mortality when empagliflozin was added to standard care versus placebo. SGLT2 inhibitors should be used with caution in patients with previous amputation, severe peripheral neuropathy, severe peripheral vascular disease, or active diabetic foot ulcers or soft tissue infections. Patients should be monitored for genital fungal infection, urinary tract infection, euglycemic diabetic acidosis, and lower limb ulcerations and soft tissue infections. The presence of any of these conditions should prompt consideration of an alternative drug to reduce cardiovascular complications. Based on randomized controlled trials, the risk for cardiovascular events does not appear to be increased with second-generation sulfonylureas such as glipizide (Option B). Also, no evidence shows that second-generation sulfonylureas reduce cardiovascular events in patients at high risk, such as this patient. In patients with ASCVD or multiple ASCVD risk factors, an SGLT2 inhibitor or GLP-1 RA is preferred to sulfonylureas. Pramlintide (Option C) is an amylin mimetic that slows gastric emptying, suppresses glucagon secretion, and increases satiety. No long-term studies have shown a decrease in adverse cardiovascular outcomes with pramlitide use. Sitagliptin (Option D), a dipeptidyl peptidase-4 inhibitor, may improve the patient's glycemic control; however, this drug class has no proven ASCVD benefit.

Answer 19

a. Empagliflozin Explanation: This patient would be best treated with empagliflozin (Option A). This sodium-glucose cotransporter 2 (SGLT2) inhibitor blocks renal glucose reabsorption and promotes the excretion of glucose and sodium via glycosuria, thus lowering blood glucose levels. The FDA approved empagliflozin for reduction of cardiovascular death in adults with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Also, the American Diabetes Association suggests that in patients with type 2 diabetes and established heart failure, an SGLT2 inhibitor may be considered to reduce the risk for heart failure-related hospitalization. Because empagliflozin is renally cleared, considerations for renal dose adjustment are required. The marked benefit in cardiac and renal protection of this drug class must be balanced against the risks of euglycemic diabetic ketoacidosis, increased urinary tract infections, genital fungal infections, and increased rate of lower limb infection, ulceration, and amputations. Glipizide (Option B) is a sulfonylurea. This drug class stimulates B-cell insulin secretion from the pancreas. Although the sulfonylureas initially are effective and inexpensive, they lose their efficacy as a result of gradual B-cell loss. They also cause weight gain, potentially contributing to further insulin resistance. Liraglutide (Option C) is a glucagon-like peptide 1 receptor agonist (GLP-1 RA) that acts through several mechanisms, including increased insulin secretion in response to hyperglycemia, reduction of gastric emptying, and reduction of glucagon secretion. Similar to SGLT2 inhibitors, this drug class has also demonstrated significant risk reductions in atherosclerotic cardiovascular disease and diabetic kidney disease. However, based on postmarketing reports of acute pancreatitis in association with GLP-1 RAs, they are not recommended for patients with a history of pancreatitis. Liraglutide has not been shown to reduce the risk for heart failure-related hospitalization. Pioglitazone (Option D) is part of the thiazolidinedione class and is an insulin sensitizer. Pioglitazone may reduce cardiovascular disease and triglyceride levels; however, it may cause weight gain because of volume retention and an increase in fat mass. In addition, these agents are contraindicated in heart failure, making it a poor choice in this patient.

Answer 20

Answer: C Liraglutide Explanation: Adding liraglutide (Option C) a glucagon-like peptide 1 receptor agonist (GLP-1 RA), would provide the most benefit to this patient. Because her hemoglobin A1c is not at goal with metformin alone, the addition of a second agent is warranted. The American Diabetes Association recommends a goal hemoglobin A1c of less than 7% in most nonpregnant adults. Individualized goals may vary based on patient factors such as disease duration, established vascular complications, hypoglycemia risk, and life expectancy. A patient-centered approach should be used to guide the choice of pharmacologic agents. Physicians should consider cardiovascular comorbidities, hypoglycemia risk, impact on weight, cost, risk for adverse effects, and patient preferences. This patient with diabetes mellitus has a BMI of 35 despite lifestyle modifications: therefore, a diabetes medication associated with weight loss would be beneficial Diabetes medications associated with weight loss include GLP-1 RAs, sodium-glucose cotransporter 2 (SGLT2) inhibitors, a-glucosidase inhibitors, and amylin mimetics. The GLP-1 RAs increase glucose-stimulated insulin secretion, inhibit glucagon, slow gastric emptying, and increase satiety; they can lower hemoglobin A1c by 1% to 1.5%. Their additional ability to promote weight loss makes them an excellent choice for this patient. Although the SGLT2 inhibitors, such as dapagliflozin (Option A), are also associated with improvement in hemoglobin A1c and weight loss, they carry a risk for increased genitourinary tract infections. This patient has a history of recurrent urinary tract infections; therefore, dapagliflozin is not the most appropriate treatment option. a-Glucosidase inhibitors and amylin mimetics are also associated with weight loss, but the optimal roles of these agents in the treatment of diabetes are unclear. Insulin secretagogues, including sulfonylureas, thiazolidinediones. and insulin, often cause weight gain. Although the sulfonylurea glimepiride (Option B) decreases hemoglobin A1c by 1% to 1.5%, weight gain is not desired in this patient. Metformin is typically a weight-neutral medication, although some studies show a modest weight loss. Increasing the metformin dosage (Option D) is unlikely to significantly improve hemoglobin A1c or contribute to substantial weight loss. Dipeptidyl peptidase-4 inhibitors also are weight neutral.

Answer 21

b. Insulin; glucose target 140 to 180 mg/dL (7.8-10.0 mmol/L) Explanation: The most appropriate management of diabetes mellitus is to initiate insulin to achieve blood glucose values of 140 to 180 mg/dL (7.8-10.0 mmol/L) (Option B). Inpatient hyperglycemia, defined as consistently elevated glucose values greater than 140 mg/dL (7.8 mmol/L), is associated with poor outcomes, but attempts to achieve blood glucose targets less than 140 mg/dL (7.8 mmol/L) is associated with hypoglycemia. The American Diabetes Association recommends that insulin therapy should be initiated for treatment of persistent hyperglyceria starting at a threshold of 180 mg/dL (10.0 mmol/L). After insulin therapy is started, a target glucose range of 140 to 180 mg/dL (7.8-10.0 mmol/L) is recommended for most critically ill and non-critically ill patients. This recommendation is based on the findings from the NICE-SUGAR randomized clinical trial and is supported by several meta-analyses, some of which suggest that tight glycemic control (80-110 mg/dL [4.4-6.1 mmol/L]) increases mortality compared with more moderate glycemic targets and generally causes higher rates of hypoglycemia. Intravenous insulin therapy is recommended for critically ill inpatients with a history of type 1 or type 2 diabetes. Subcutaneous insulin is appropriate for non-critically ill inpatients. Tighter glycemic control (80-110 mg/dL [4.4-6.1 mmol/LI) has been studied in critically ill patients and has not consistently been associated with improved outcomes and may increase mortality. Therefore, a goal of 80 to 110 mg/dL (4.4-6.1 mmol/L) (Option A) is inappropriate in this patient. Inpatient hyperglycemia, defined as consistently elevated glucose values greater than 140 mg/dL (7.8 mmol/L), is associated with poor outcomes. Therefore, it is inappropriate to target higher blood glucose values (180-200 mg/dL 110.0-11.1 mmol/L) (Option C). Likewise, it is inappropriate to choose no intervention (Option D), allowing this patient's glucose levels to be greater than 180 mg/dL (10.0 mmol/L). Insulin is the preferred treatment for hyperglycemia in hospitalized patients, particularly critically ill patients in the ICU. The safety of oral antihyperglycemic agents for critically ill patients has not been established, and frequent clinical status changes may increase the risk for adverse events associated with noninsulin therapies.

Answer 22

b. Screen now; if negative, rescreen at 24 to 28 weeks gestation Explanation: This patient should be screened now for preexisting diabetes mellitus and again at 24 to 28 weeks gestation (Option B) for gestational diabetes if the first test is neg-ative. Gestational diabetes is defined as hyperglycemia during the second or third trimester in women without a prepregnancy diagnosis of type 1 or type 2 diabetes. Undiagnosed preexisting diabetes in patients who are pregnant is often first noticed during pregnancy; however, this diagnosis is not gestational diabetes. It is reasonable to test women with risk factors for diabetes at the time of a positive pregnancy test using standard diagnostic criteria, which includes measurement of hemoglobin Alc and fasting blood glucose or an oral glucose tolerance test (OGTT). Hyperglycemia identified during the first trimester is classified as type 2 diabetes rather than gestational diabetes. Women who do not meet diagnostic criteria for diabetes on the original assessment should be re-screened between 24 and 28 weeks gestation using an OGTT (either one-step or two-step strategy). This patient has several risk factors, including overweight and family history of diabetes, and thus should be screened now in addition to the standard screening between 24 and 28 weeks' gestation if the original screening is negative. It is important to diagnose and manage diabetes in pregnancy because adverse maternal and neonatal outcomes related to diabetes increase with worsening hyperglycemia. Complications include macrosomia, labor and delivery complications, preeclampsia, fetal defects, neonatal hypoglycemia, spontaneous abortion, and intrauterine fetal demise. Performing standard screening for gestational diabetes with the OGTT only at 24 to 28 weeks' gestation (Option A) would miss the opportunity to diagnose preexisting diabetes. Screening now and only once (Option C) would miss the opportunity to diagnose gestational diabetes if this screening test is negative. Self-monitoring of blood glucose (Option D) does not have a role in the diagnosis of diabetes. This patient does not have known diabetes, either preexisting or gestational, and should be screened with the standard methods.

Answer 23

c. Metformin Explanation: This patient has ketosis-prone diabetes mellitus and should be transitioned from insulin to metformin (Option C). The term "ketosis-prone diabetes" incorporates several glycemic syndromes and is also known as ketosis-prone type 2 diabetes mellitus, "Flatbush diabetes," idiopathic type 1 diabetes, type 1B diabetes, and atypical diabetes. These syndromes present with episodic diabetic ketoacidosis (DKA) resulting from insulin deficiency but have variable periods of insulin dependence and independence. For individuals with ketosis-prone diabetes, insulin therapy for DKA is required until DKA has resolved and the B cells are no longer impaired by glucose toxicity and can produce sufficient amounts of insulin to suppress lipolysis. Assessment of B-cell reserve with a fasting C-peptide level should be performed weeks to months after the episode of DKA; B-cell function is indicated by a C-peptide concentration of at least 1 ng/mL. (0.33 nmo-1/L). Patients should also be evaluated for type 1 diabetes with fasting C-peptide measurement or a glutamic acid decarboxy-lase antibodies test. This patient has the clinical characteristics of type 2 diabetes (insulin production, obesity, strong family history), intact B-cell function, negative antibodies, and is on relatively low doses of insulin for her body weight. The insulin may be discontinued, and she can start metformin. No clinical evidence supports that sodium-glucose cotransporter 2 inhibitors such as empagliflozin (Option A) are effective treatment in ketosis-prone diabetes. Moreover, this class of medications carries a higher risk for euglycemic DKA and thus would not be the best option in a patient with ketosis-prone diabetes. Glimepiride (Option B) is a sulfonylurea and is associated with weight gain. It is not the best option for this patient with obesity, who would benefit more from an insulin sensitizer like metformin. The American Diabetes Association recommends that all patients with type 2 diabetes should be treated with metformin as an initial agent, along with aggressive lifestyle modifications. Given the previous episode of DKA, lifestyle changes alone with no additional treatment (Option D) are insufficient to manage diabetes in this patient.

Answer 24

b. Intensive lifestyle modifications Explanation: This patient has prediabetes, and intensive lifestyle modifications (Option B) should be implemented to delay or prevent the development of type 2 diabetes mellitus. Prediabetes is defined as a hemoglobin Ac level between 5.7% and 6.4%, fasting glucose between 101 mg/dL (5.6 mmol/L) and 125 mg/dL (6.9 mmol/L), or impaired glucose tolerance test with 2-hour glucose between 140 mg/dL (7.7 mmol/L) and 199 mg/dL (11.0 mmol/L) after a 75-g oral glucose load. This patient had three laboratory test results consistent with prediabetes in the past 6 months. The development of type 2 diabetes in persons at high risk can be delayed or prevented with modifications to lifestyle (diet, exer-cise), pharmacologic intervention, or metabolic surgery. The initial step in management of prediabetes should be intensive lifestyle management. Lifestyle modifications have been shown to reduce the incidence of type 2 diabetes by 58% in persons with prediabetes. The American Diabetes Association recommends a program for intensive lifestyle behavioral changes that includes at least a 7% weight loss over 6 months and at least 150 minutes per week of moderate-intensity exercise. Patients with prediabetes should be retested yearly to monitor for the development of type 2 diabetes. Although some pharmacologic agents, including a-glucosidase inhibitors, glucagon-like peptide 1 receptor agonists, and thiazolidinediones have been shown to reduce the incidence of diabetes in some trials, none are FDA approved for diabetes prevention. Glipizide (Option A), a sulfonylurea, is not indicated as a treatment for diabetes prevention. In addition, glipizide is associated with weight gain. In contrast, metformin (Option C) has demonstrated efficacy in diabetes risk reduction. In the Diabetes Prevention Program, metformin was not as effective as lifestyle modification but reduced the incidence of diabetes by 31% compared with placebo and by 18% at 10-year follow-up. Metformin may be considered for prevention of type 2 diabetes in patients with prediabetes unresponsive to lifestyle modifications, particularly in patients with BMl greater than 35, age younger than 60 years, or a history of gestational dia-betes. If this patient fails to lose weight, metformin would be a reasonable addition. Although weight neutral, sitagliptin (Option D), a dipeptidyl peptidase-4 inhibitor, is not indicated as a treatment for diabetes prevention.

Answer 25

A. 56/M with type 2 DM, BMI 35 kg/m2, HbA1c 10% despite insulin regimen Explanation: Harrison’s 21st page 3114 According to the American Diabetes Association (ADA) Standards of Care, metabolic surgery (bariatric surgery) is recommended for patients with type 2 diabetes mellitus (T2DM) who meet the following criteria: • BMI ≥ 40 kg/m², regardless of glycemic control • BMI 35–39.9 kg/m², if hyperglycemia is inadequately controlled despite optimal medical therapy • BMI 30–34.9 kg/m², if hyperglycemia remains uncontrolled despite medical therapy (considered in select cases) Why the other choices are incorrect: • B. 56/M with type 1 DM, BMI 35 kg/m², HbA1c 10% despite insulin regimen → Metabolic surgery is NOT recommended for type 1 DM, as it does not address the underlying autoimmune process. (Incorrect) • C. 56/M with type 1 DM, BMI 30 kg/m², HbA1c 10% despite insulin regimen → Again, metabolic surgery is not recommended for type 1 DM. (Incorrect) • D. 56/M with type 2 DM, BMI 30 kg/m², HbA1c 10% despite insulin regimen → Metabolic surgery may be considered for BMI 30–34.9 kg/m², but it is not a primary recommendation. (Less optimal choice compared to A)