Ace the Case: A 70-Year-Old Woman With a 25-Year History of Type 2 Diabetes Mellitus and an Elevated A1C

Case Presentation

Chief Complaint: High blood sugar

History of Presenting Illness: The patient is a 70-year-old woman with a 25-year history of type 2 diabetes mellitus (T2DM) and is taking a combination of 2 oral agents and a glucagon-like peptide 1 (GLP-1) receptor agonist. She checks her blood sugar twice per day and reports a steady increase in fasting blood sugar over the past 4 to 6 months. She has no significant burden of hypoglycemia. She reports adherence to her current diabetes program. She has been walking on her treadmill “most days of the week.”

Past Medical History: T2DM complicated by polyneuropathy in her lower extremities, hypertension dyslipidemia, cataracts, depression

Medications: Metformin 1000 mg twice per day; empagliflozin 10 mg once daily; liraglutide 1.8 mg subcutaneously daily; atorvastatin 40 mg daily; lisinopril 10 mg daily; amlodipine 10 mg daily; aspirin 81 mg daily

Physical Examination: 
General appearance: patient is in no acute distress; blood pressure: 132/84 mm Hg bilaterally; heart rate: 82 beats/minute; weight: 101 kg (222 lbs); HEENT: nondilated, funduscopic examination showed no obvious abnormalities; mouth: dentition is in good repair; neck: no carotid bruit or jugular venous distention; respiratory: lungs are clear to auscultation bilaterally; cardiovascular: heart is regular without murmur, rub, or gallop; gastrointestinal: abdomen is obese, but nontender; extremities: no clubbing, cyanosis, or edema; foot examination: mild onychomycosis bilaterally; no cracks, fissures, or ulcerations; normal sensation to monofilament and vibratory testing; psych: alert and oriented X 3

Labs: A1C: 8.8% (increased from 8.0% 3 months prior)

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Question
Which of the following basal insulins has the longest duration of action?
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Correct answer: D

Rationale: Degludec insulin, a di-hexamer in the presence of zinc and phenol, has one single amino acid deleted in comparison to human insulin and is conjugated to hexadecanedioic acid via gamma-L-glutamyl spacer at the amino acid lysine at position B29.1 Following subcutaneous injection, there is a rapid loss of phenol in the subcutis, which changes the configuration of degludec into soluble multi-hexamer chains.1 The zinc then slowly diffuses from this complex, with the multi-hexamer chains breaking down into dimers and monomers before entering the systemic circulation.1 The microprecipitation of the multi-hexamer in the subcutaneous tissue results in delayed absorption, which is the predominant mechanism underlying its prolonged duration of action profile.1 This property confers a long duration of action (greater than 40 hours) and reduces variability and plasma concentration with once-daily dosing.

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