PANCE Blueprint Endocrinology (6%)

A 53 y/o with weakness, polydipsia, and polyuria

Patient will present as → a 35-year-old Mexican American male complaining of increased thirst, frequent urination, hunger, fatigue, and blurred vision. A random finger stick blood glucose is 225.

Diabetes mellitus medications

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Know Your Medication - Side Effects and Functions

• Metformin (Glucophage, Glumetza, Fortamet, Riomet):
  • Mechanism: Reduces hepatic glucose production, increases peripheral glucose uptake (improves insulin sensitivity), and decreases intestinal glucose absorption. These actions contribute to weight neutrality or weight loss and are effective in lowering blood glucose without increasing insulin levels.
  • Side Effects: Risk of lactic acidosis, particularly in renal impairment. Requires discontinuation 24 hours before contrast studies and resumption 48 hours after, with monitoring of creatinine. Discontinue if creatinine is >1.5 mg/dL.
• Sulfonylureas - Glyburide (Diabeta, Glynase), Glipizide (Glucotrol, Glucotrol XL), Glimepiride (Amaryl):
  • Mechanism: Stimulates insulin release from pancreatic beta cells (insulin secretagogue), increasing insulin levels regardless of glucose levels.
  • Side Effects: Significant risk of hypoglycemia and weight gain. Particularly risky in elderly or those with renal impairment.
• Thiazolidinediones - Pioglitazone (Actos), Rosiglitazone (Avandia):
  • Mechanism: Increases insulin sensitivity by activating peroxisome proliferator-activated receptor-gamma (PPAR-γ) in adipose tissue, muscle, and liver, enhancing glucose uptake without increasing insulin secretion.
  • Side Effects: Fluid retention, leading to edema and worsening heart failure. Rosiglitazone is associated with increased cardiovascular events (MI), while Pioglitazone has a possible link to bladder cancer.
• α-Glucosidase Inhibitors - Acarbose (Precose), Miglitol (Glyset):
  • Mechanism: Inhibits α-glucosidase enzymes in the intestinal brush border, delaying the breakdown of carbohydrates and slowing glucose absorption, reducing postprandial hyperglycemia.
  • Side Effects: GI-related symptoms such as flatulence, diarrhea, and abdominal discomfort. May increase liver enzymes (LFTs) and in rare cases cause hepatitis.
• Meglitinides - Repaglinide (Prandin), Nateglinide (Starlix):
  • Mechanism: Short-acting insulin secretagogues that stimulate insulin release from the pancreas in response to meals, providing flexible postprandial glucose control.
  • Side Effects: Hypoglycemia, though less severe than with sulfonylureas due to the shorter action. Weight gain is also common.
• GLP-1 Receptor Agonists - Exenatide (Byetta, Bydureon), Liraglutide (Victoza, Saxenda), Dulaglutide (Trulicity), Semaglutide (Ozempic, Rybelsus):
  • Mechanism: Mimics the action of the incretin hormone GLP-1, stimulating insulin secretion in a glucose-dependent manner, reducing glucagon secretion, and slowing gastric emptying, leading to improved glycemic control and weight loss.
  • Side Effects: Common GI side effects such as nausea and vomiting due to delayed gastric emptying. Risk of hypoglycemia when combined with insulin or sulfonylureas. Caution in patients with gastroparesis.
• DPP-4 Inhibitors - Sitagliptin (Januvia), Saxagliptin (Onglyza), Linagliptin (Tradjenta), Alogliptin (Nesina):
  • Mechanism: Inhibits dipeptidyl peptidase-4 (DPP-4), which degrades incretin hormones such as GLP-1, leading to prolonged action of endogenous incretins, enhancing glucose-dependent insulin release and suppressing glucagon secretion.
  • Side Effects: May cause pancreatitis and joint pain. Potential risk of renal dysfunction, particularly in patients with pre-existing renal disease. Saxagliptin has been associated with an increased risk of heart failure.
• SGLT2 Inhibitors - Canagliflozin (Invokana), Dapagliflozin (Farxiga), Empagliflozin (Jardiance), Ertugliflozin (Steglatro):
  • Mechanism: Inhibits sodium-glucose co-transporter-2 (SGLT2) in the proximal renal tubules, preventing glucose reabsorption and increasing glucose excretion in urine, leading to decreased blood glucose levels and weight loss.
  • Side Effects: Increased risk of genital mycotic infections, urinary tract infections, and dehydration. May also cause euglycemic diabetic ketoacidosis (DKA) and an increased risk of lower limb amputations (especially with Canagliflozin).

Summary of Mechanisms and Key Side Effects:

• Metformin: Reduces hepatic glucose production; risk of lactic acidosis
• Sulfonylureas: Stimulates insulin release; risk of hypoglycemia, weight gain
• Thiazolidinediones: Increases insulin sensitivity; risk of fluid retention, cardiovascular issues
• α-Glucosidase Inhibitors: Delays glucose absorption; GI side effects.
• Meglitinides: Stimulates meal-time insulin release; risk of hypoglycemia, weight gain
• GLP-1 Agonists: Mimics incretin, promotes insulin release; GI side effects, hypoglycemia with other agents
• DPP-4 Inhibitors: Prolongs incretin activity; risk of pancreatitis, joint pain, heart failure
• SGLT2 Inhibitors: Increases glucose excretion via urine; risk of UTIs, ketoacidosis, amputations

Normal fasting glucose is between 70 and 100

A C-peptide test is often used to help tell the difference between type 1 and type 2 diabetes

• C-peptide is a substance made in the pancreas, along with insulin. C-peptide and insulin are released from the pancreas at the same time and in about equal amounts. So a C-peptide test can show how much insulin your body is making
  • With type 1 diabetes, your pancreas makes little to no insulin, and little or no C-peptide = ↓ C-peptide
  • With type 2 diabetes, the body makes insulin but doesn't use it well. This can cause ↑ C-peptide

Diet and exercise with lifestyle changes are first-line - carbs 50-60% and protein 15-20%

• Studies demonstrate that just 150 minutes (2.5 hours) per week of moderate to vigorous exercise significantly reduces microvascular complications, including retinopathy, in patients with T2D

Glucose goals and management

• A1C < 7.0 % check every 3 months if not controlled or if therapy has changed/requires adjustment and 2 x per year if controlled
• Preprandial glucose 80-130 mg/dL (60-90 if pregnant)
• Peak postprandial (1 to 2 hours after the beginning of the meal) blood glucose < 180 mg/dL
• Annual dilated eye exams, ACEI if microalbuminuria, annual foot examination

Insulins
Image by A. Peters, M. Komorniczak. License: CC BY 3.0
Insulin effect	Type of Insulin	Onset of action	Peak of action	Duration of action
Fast acting	Lispro	15–30 minutes	1–3 hours	4–6 hours
	Aspart
	Glulisine
Short-acting	Regular	30 minutes	1.5–3.5 hours	8 hours
Intermediate-acting	NPH	1–2 hours	4–6 hours	> 12 hours
Long-acting	Detemir	1–2 hours	3–9 hours	14–24 hours
	Glargine	3–4 hours	No peak	Approximately 24 hours
	Degludec	Approximately 1 hour	No peak	> 40 hours
Example of insulin regimen:  Breakfast: Rapid-acting → Lunch: Rapid-acting → Dinner: Rapid-acting → Bedtime: Long-acting

Blood pressure

• JNC 8 treatment targets: Reduce BP to < 140/90 mm Hg for everyone < 60, including those with a kidney disorder or diabetes
• ADA recommends treating BP of <140 and <90 mmHg.  Lower treatment targets, i.e., 130/80 mmHg, may be appropriate for individuals at high risk of CVD, if they can be achieved without undue treatment burden.
• ACC/AHA blood pressure targets - target for patients with comorbidities: < 130/80

From ADA Standards - Section 10, CV Disease  **Thiazide-like diuretics; long-acting agents shown to reduce cardiovascular events, such as chlorthalidone and indapamide, are preferred. ***Dihydropyridine calcium channel blocker (CCB).

Cholesterol

• New statin guidelines recommend statins in all persons with diabetes mellitus who are 40 to 75 years of age with LDL-C levels of 70 to 189 mg per dL but without clinical ASCVD (see guidelines)

Aspirin

• Aspirin (75 to 162 mg/day) is recommended for secondary prevention in diabetic patients with a history of MI, vascular bypass, stroke or transient ischemic attack, peripheral vascular disease, claudication, or angina
• For the primary prevention of ASCVD in patients with diabetes at increased cardiovascular risk (10-year risk >10 percent), we suggest aspirin (75 to 162 mg daily)
• Prevention of ASCVD in adults with diabetes at low risk (10-year ASCVD risk <10 percent) is not routinely recommended

Vaccination

• Influenza vaccination yearly, with adults 65 years of age and older administered the high-dose vaccine
• Pneumococcal vaccination with one pneumococcal conjugate vaccine (PCV13) in adults ≥65 years and pneumococcal polysaccharide vaccine (PPSV23) once before and once after age 65. Once the patient is ≥65 years (and ≥1 year after PPSV23), give PCV13.
• Hepatitis B vaccination for unvaccinated adults younger than 60 years of age without evidence of prior infection
• Tetanus and diphtheria vaccinations, based on CDC guidelines
• Herpes zoster, recombinant vaccine, based on CDC guidelines

Monitoring in patients with diabetes mellitus (summary table)