Section 9.1: Diabetes Mellitus & Acute Complications
Key Takeaways
- Diagnostic criteria for diabetes mellitus require two abnormal tests: HbA1c >= 6.5%, Fasting Plasma Glucose >= 126 mg/dL, or 2-hour OGTT >= 200 mg/dL.
- Metformin is first-line for Type 2 Diabetes but is strictly contraindicated in patients with an eGFR < 30 mL/min/1.73m² due to lactic acidosis risk.
- SGLT2 inhibitors and GLP-1 agonists offer cardiorenal protection and weight loss benefits, but SGLT2 inhibitors carry a risk of euglycemic DKA.
- In DKA and HHS, aggressive fluid resuscitation is the first priority, and insulin must be withheld if the potassium level is below 3.3 mEq/L.
Diabetes Mellitus & Acute Complications
PANCE High-Yield Focus: Diabetes mellitus and its acute complications are major PANCE blueprint topics. Focus on the diagnostic thresholds for diabetes, distinguishing Type 1 vs. Type 2 pathophysiology, the mechanisms and contraindications of oral hypoglycemics (especially Metformin, SGLT2i, and GLP-1 agonists), and the step-by-step fluid, insulin, and potassium replacement protocols for DKA and HHS.
Pathophysiology and Presentation
Type 1 vs. Type 2 Diabetes Mellitus
Type 1 Diabetes Mellitus (T1DM) is an autoimmune disease where T-cell mediated destruction of pancreatic beta cells in the islets of Langerhans leads to absolute insulin deficiency. It is strongly linked to HLA-DR3 and HLA-DR4 genes. Common autoantibodies include glutamic acid decarboxylase (anti-GAD65), islet cell antibodies (ICA), and insulin autoantibodies (IAA).
Type 2 Diabetes Mellitus (T2DM) is characterized by peripheral insulin resistance (decreased tissue sensitivity to insulin) combined with a progressive decline in insulin secretion. It is heavily associated with obesity, visceral adiposity, physical inactivity, and metabolic syndrome.
Clinical Presentation
- Osmotic Symptoms: Both types present with polyuria, polydipsia, polyphagia, and blurred vision. Weight loss is common in T1DM due to catabolism.
- DKA: Rapid onset (under 24 hours), presenting with nausea, vomiting, diffuse abdominal pain, and lethargy. Physical signs include Kussmaul respirations (deep, rapid breathing), a fruity acetone breath odor, and signs of severe dehydration (tachycardia, hypotension).
- HHS: Insidious onset (days to weeks), presenting with severe dehydration, confusion, lethargy, focal neurological deficits, or coma. Acidosis is absent, but volume depletion is extreme.
Diagnostic Criteria and Screening
Screening and Diagnosis
The ADA recommends screening for asymptomatic adults beginning at age 35, or earlier in overweight patients (BMI >= 25 kg/m², or >= 23 kg/m² in Asian Americans) with risk factors.
A diagnosis of diabetes mellitus requires two abnormal tests from either the same sample or separate encounters. The criteria are:
- Fasting Plasma Glucose (FPG): >= 126 mg/dL (after >= 8 hours of fasting).
- Hemoglobin A1c (HbA1c): >= 6.5%.
- 2-hour Oral Glucose Tolerance Test (OGTT): >= 200 mg/dL (using 75g glucose load).
- Random Plasma Glucose: >= 200 mg/dL in a patient with classic symptoms of hyperglycemia.
Differentiating T1DM and T2DM Labs
To distinguish these conditions, obtain autoantibody panels (anti-GAD65) and a C-peptide level (a marker of endogenous insulin production):
- T1DM: Low or undetectable C-peptide levels.
- T2DM: Normal, elevated, or inappropriately normal C-peptide levels.
Pharmacological Management
Non-Insulin Antidiabetic Medications
- Metformin (Biguanide): First-line agent. It decreases hepatic gluconeogenesis and increases peripheral insulin sensitivity. It is weight-neutral and does not cause hypoglycemia. It is strictly contraindicated in patients with an eGFR < 30 mL/min/1.73 m² due to the risk of lactic acidosis. Hold for 48 hours after iodinated contrast.
- SGLT2 Inhibitors (e.g., Empagliflozin): Inhibits sodium-glucose cotransporter 2 in the proximal convoluted tubule, causing glucosuria. High-yield benefits: reduces heart failure hospitalizations and slows chronic kidney disease progression. Side effects include urinary tract infections, vulvovaginal candidiasis, and a risk of euglycemic DKA.
- GLP-1 Receptor Agonists (e.g., Semaglutide): Mimics incretin to stimulate glucose-dependent insulin secretion, suppress glucagon, and delay gastric emptying. It reduces cardiovascular events and promotes weight loss. It is contraindicated in patients with a history of medullary thyroid cancer or MEN 2.
Morning Hyperglycemia
To differentiate morning hyperglycemia, check a 3:00 AM blood glucose:
- Dawn Phenomenon: Physiological early-morning surge of growth hormone/cortisol. 3:00 AM glucose is normal or elevated. Treatment: Increase bedtime basal insulin.
- Somogyi Effect: Rebound hyperglycemia from nocturnal hypoglycemia. 3:00 AM glucose is low. Treatment: Decrease bedtime basal insulin or give a bedtime snack.
DKA vs. HHS Treatment Protocol
| Feature | DKA Criteria | HHS Criteria |
|---|---|---|
| Glucose | > 250 mg/dL | > 600 mg/dL |
| Arterial pH | < 7.30 | > 7.30 |
| Bicarbonate | < 18 mEq/L | > 18 mEq/L |
| Ketones | Positive | Absent or minimal |
| Osmolality | Variable | > 320 mOsm/kg |
Step-by-Step SIP Management
- S - Saline (IV Fluids): Resuscitate with 1–1.5 L of 0.9% Normal Saline in the first hour. When blood glucose drops to 200–250 mg/dL (in DKA) or 300 mg/dL (in HHS), add 5% Dextrose (D5 1/2NS) to the fluids to prevent rapid glucose drops and cerebral edema.
- I - Insulin Infusion: Give IV Regular insulin at 0.1 units/kg/hour. Continue until the anion gap is closed in DKA (pH > 7.3, Bicarb >= 15, AG < 12) or osmolality normalizes in HHS.
- P - Potassium Replacements: Insulin shifts potassium intracellularly, risking fatal arrhythmias. Check potassium before starting insulin:
- Potassium < 3.3 mEq/L: HOLD INSULIN. Give IV potassium (20–40 mEq/hr) until potassium is > 3.3 mEq/L.
- Potassium 3.3–5.2 mEq/L: Give insulin and add 20–30 mEq of potassium to each liter of IV fluid.
- Potassium > 5.2 mEq/L: Give insulin and monitor potassium closely without immediate replacement.
Classic PANCE Traps & Clinical Pearls
- The Potassium Trap: Initiating insulin in DKA when potassium is < 3.3 mEq/L will cause cardiovascular collapse. You must correct potassium first.
- Euglycemic DKA: SGLT2 inhibitors can cause DKA with normal or near-normal blood glucose. Check ketones in any patient on an SGLT2 inhibitor who presents with acidosis.
A 45-year-old female presents to the clinic for a routine check-up. She is overweight and has a family history of diabetes. Her fasting plasma glucose is 128 mg/dL. A repeat fasting plasma glucose performed the next week is 130 mg/dL. Which of the following is the most appropriate diagnosis for this patient?
A 62-year-old male with a history of Type 2 diabetes and chronic kidney disease stage 3b (estimated GFR of 28 mL/min/1.73m²) presents for a follow-up. He is currently taking Metformin 500 mg twice daily. His HbA1c is 7.4%. Which of the following is the most appropriate clinical action regarding his diabetes pharmacotherapy?
A 24-year-old female with Type 1 diabetes is admitted with diabetic ketoacidosis. Her initial laboratory results show a serum glucose of 450 mg/dL, arterial pH of 7.18, bicarbonate of 10 mEq/L, and a serum potassium of 3.0 mEq/L. Which of the following is the most appropriate initial step in the management of this patient?