A 54-year-old woman presents for follow-up care for her type 2 diabetes mellitus. She was diagnosed approximately 2 years ago and was treated with dietary modifications, an exercise regimen, metformin, and glipizide. She reports that her increased thirst and urinary frequency has not improved with her current treatment regimen. Her hemoglobin A1c is 8.5% at this visit. She is started on a medication that will result in weight loss but places her at increased risk of developing urinary tract infections and vulvovaginal candidiasis. Which of the following is the mechanism of action of the prescribed medication?

Sodium-glucose co-transporter-2 inhibitor

Peroxisome proliferator-activated receptor activator

Glucagon-like protein-1 receptor agonist

Dipeptidyl peptidase-4 inhibitor

A 65-year-old woman comes to the emergency department because of blurry vision for 10 hours. She has also had urinary urgency and discomfort while urinating for the past 4 days. She has been feeling increasingly weak and nauseous since yesterday. She has a history of type 2 diabetes mellitus and arterial hypertension. One year ago she was treated for an infection of her eyes. She drinks 2–3 glasses of wine weekly. Current medications include captopril, metoprolol, metformin, and insulin. Her temperature is 37.5°C (99.5°F), pulse is 107/min, and blood pressure is 95/70 mm Hg. Visual acuity is decreased in both eyes. The pupils are equal and reactive to light. The corneal reflexes are brisk. The mucous membranes of the mouth are dry. The abdomen is soft and not distended. Cardiopulmonary examination shows no abnormalities. Which of the following is the most likely diagnosis?

Hyperosmolar hyperglycemic state

A 53-year-old woman with type 2 diabetes mellitus is admitted for evaluation of recurrent episodes of nausea, tremors, and excessive sweating. She works as a nurse and reports self-measured blood glucose levels below 50 mg/dL on several occasions. Her family history is positive for borderline personality disorder. The only medication listed in her history is metformin. Which of the following is the most appropriate next step in management?

Ask the patient if she is taking any medications other than metformin

Measure serum C-peptide concentration

Search the patient's belongings for insulin

Measure glycated hemoglobin concentration

Report the patient to her employer

A 50-year-old Caucasian man presents for a routine checkup. He does not have any current complaint. He is healthy and takes no medications. He has smoked 10–15 cigarettes per day for the past 10 years. His family history is negative for gastrointestinal disorders. Which of the following screening tests is recommended for this patient according to the United States Preventive Services Task Force (USPSTF)?

Colonoscopy for colorectal cancer

Abdominal ultrasonography for abdominal aortic aneurysm

Carcinoembryonic antigen for colorectal cancer

Low-dose computerized tomography for lung cancer

Prostate-specific antigen for prostate cancer

A 51-year-old man presents to his physician with increased thirst, frequent urination, and fatigue. These symptoms have increased gradually over the past 3 years. He has no past medical history or current medications. Also, he has no family history of endocrinological or cardiovascular diseases. The blood pressure is 140/90 mm Hg, and the heart rate is 71/min. The patient is afebrile. The BMI is 35.4 kg/m2. On physical examination, there is an increased adipose tissue over the back of the neck, and hyperpigmentation of the axilla and inguinal folds. Which of the following laboratory results is diagnostic of this patient’s most likely condition?

Plasma glucose of 209 mg/dL 2 hours after the oral glucose load

Random plasma glucose 167 mg/dL

Serum insulin level of 10 μU/mL

Fasting plasma glucose 123 mg/dL

A 26-year-old primigravida woman comes to her primary care physician for the second prenatal visit. She is 10 weeks pregnant. She has no current complaint except for occasional nausea. She does not have any chronic health problems. She denies smoking or alcohol intake. Her family history is positive for paternal colon cancer at the age of 55. Vital signs include a temperature of 37.1°C (98.8°F), blood pressure of 120/60 mm Hg, and pulse of 90/min. Physical examination discloses no abnormalities. According to the United States Preventive Services Task Force (USPSTF), which of the following screening tests is recommended for this patient?

Urine culture for asymptomatic bacteriuria

Colonoscopy for colorectal cancer at the age of 40

HbA1C for type 2 diabetes mellitus

Colonoscopy for colorectal cancer at the age of 50

Glucose tolerance test for gestational diabetes mellitus

A 40-year-old man presents to the physician for a scheduled checkup. He was diagnosed with type 2 diabetes mellitus 5 years ago and has been taking his prescribed metformin daily, as prescribed. He also started exercising and has improved his diet. He has no particular complaints at the time. The patient has no other medical concerns and takes no medications. There is no family history of cardiovascular disease or diabetes. He does not smoke tobacco, drink alcohol, or use illicit drugs. Vitals are normal. There are no physical findings. His laboratory tests show: Serum glucose (fasting) 149 mg/dL Hemoglobin A1c 7.7 % Serum electrolytes Sodium 142 mEq/L Potassium 3.9 mEq/L Chloride 101 mEq/L Serum creatinine 0.8 mg/dL Blood urea nitrogen 9 mg/dL Urinalysis Glucose Negative Ketones Negative Leucocytes Negative Nitrite Negative Red blood cells (RBC) Negative Casts Negative Which of the following lipid profile abnormalities is most likely to be seen?

Elevated triglycerides, low HDL

Normal triglycerides, elevated LDL

A 75-year-old man presents to his primary care physician for foot pain. The patient states that he has had chronic foot pain, which has finally caused him to come and see the doctor. The patient's past medical history is unknown and he has not seen a doctor in over 50 years. The patient states he has led a healthy lifestyle, consumes a plant-based diet, exercised regularly, and avoided smoking, thus his lack of checkups with a physician. The patient lives alone as his wife died recently. His temperature is 98.1°F (36.7°C), blood pressure is 128/64 mmHg, pulse is 80/min, respirations are 13/min, and oxygen saturation is 98% on room air. The patient's BMI is 19 kg/m^2 and he appears healthy. Physical exam demonstrates a right foot that is diffusely swollen, mildly tender, and deformed. The patient's gait is abnormal. Which of the following is associated with the underlying cause of this patient's presentation?

Hyperfiltration damage of the kidney

Methicillin-resistant bacterial agent

Type 2 diabetes mellitus for USMLE Step 2 CK: High-Yield Internal Medicine Lessons

Pathophysiology - The Sugar Struggle

Insulin Resistance: The primary defect. Peripheral tissues (muscle, adipose) and liver fail to respond to insulin, leading to hyperglycemia.
- Liver: ↑ Hepatic glucose production.
- Muscle: ↓ Glucose uptake.
- Adipose: ↑ Lipolysis, releasing free fatty acids (FFAs) which worsen resistance.
Beta-Cell Dysfunction: Pancreatic β-cells initially compensate with hyperinsulinemia, but eventually fail, leading to relative insulin deficiency.
Risk Factors: Central obesity, family history, sedentary lifestyle, ethnicity (Black, Hispanic, Native American).

⭐ Exam Favorite: Initially, T2DM is characterized by high insulin levels (hyperinsulinemia) as the body tries to overcome resistance. Over time, beta-cells exhaust, leading to lower insulin levels (hypoinsulinemia).

Cellular mechanisms of insulin resistance in type 2 diabetes

Diagnosis & Screening - The Numbers Game

Screening (USPSTF): Recommended for adults aged 35-70 years with a BMI ≥25. This strategy aims for early detection in at-risk populations to mitigate long-term complications. Re-screen at least every 3 years if results are normal.
Diagnosis & Prediabetes Thresholds: Diagnosis is established if any one of the primary criteria are met. Prediabetes values signify an elevated risk and a critical window for intervention.

⭐ For an asymptomatic patient, diagnosis requires two abnormal test results (e.g., two tests from one blood draw or two separate occasions).

Pharmacotherapy - The Drug Lineup

First Line: Metformin
- MOA: ↓ hepatic gluconeogenesis, ↑ insulin sensitivity.
- SE: GI upset, B12 deficiency, lactic acidosis (rare).
- CI: eGFR < 30 mL/min.
Second Line (if ASCVD/HF/CKD):
- GLP-1 Agonists (-tide): CV benefit, promote weight loss.
- SGLT2 Inhibitors (-flozin): CV & renal benefit, promote weight loss.
Other Options (based on patient needs):
- Sulfonylureas (e.g., glipizide): ↑ insulin secretion. ⚠️ High risk of hypoglycemia.
- TZDs (-glitazone): ↑ insulin sensitivity. ⚠️ Can cause weight gain, edema, worsen HF.

⭐ SGLT2 inhibitors are notable for reducing the risk of hospitalization for heart failure in patients with and without established ASCVD.

Complications - The Long Haul

Microvascular
- Retinopathy: Annual screen.
- Nephropathy: Annual screen with urine albumin/creatinine ratio.
- Neuropathy: Annual foot exam.
Macrovascular
- Coronary Artery Disease (CAD), Peripheral Artery Disease (PAD), Stroke.
- 📌 Manage ABCs: A1c, Blood pressure, Cholesterol.
Acute
- Hyperosmolar Hyperglycemic State (HHS): Severe hyperglycemia (>600 mg/dL), profound dehydration, high serum osmolality, no significant ketoacidosis.

Normal vs. Diabetic Retinopathy

⭐ In HHS, serum osmolality is often >320 mOsm/kg, and the profound dehydration is a key feature distinguishing it from DKA.

High‑Yield Points - ⚡ Biggest Takeaways

Type 2 Diabetes Mellitus is primarily a disease of insulin resistance with eventual β-cell dysfunction.

Obesity and family history are the strongest risk factors.

First-line treatment is lifestyle modification (diet, exercise) and metformin.

Diagnostic criteria include an HbA1c ≥ 6.5% or a fasting glucose ≥ 126 mg/dL.

Long-term complications are macrovascular (CAD, stroke) and microvascular (retinopathy, nephropathy).

C-peptide levels are detectable, distinguishing it from Type 1 DM.

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