Acquired Generalized Lipodystrophy Presenting As Severe Insulin Resistance

Saturday, May 14, 2022

12:10 PM – 12:25 PM

Location: Station 5, Sapphire West Foyer

Submitter(s)

BS
Baani Singh, MD
Resident Physician
Advocate Christ Medical Center
Burr Ridge, Illinois, United States

Co-Author(s)

TY
Tahira Yasmeen

Primary Author(s)

BS
Baani Singh, MD
Resident Physician
Advocate Christ Medical Center
Burr Ridge, Illinois, United States

Introduction : Roughly 100-150 cases are reported in the literature of acquired generalized lipodystrophy (AGL). This rare disorder is characterized by leptin deficiency resulting from low adipose mass and metabolic derangements such as hypertriglyceridemia and severe insulin resistance. These metabolic derangements lead to increased risk for pancreatitis, nonalcoholic fatty liver disease, and adverse cardiovascular events. The most common progression of AGL is onset of symptoms in childhood or adolescence with progression of complications into adulthood. Very few cases of this rare disease have been reported as adult-onset presenting with severe insulin resistance.

Case Description : A 62-year-old female presented with severe, progressive insulin resistance, persistent hyperglycemia, thin extremities and unintentional weight loss for 6 months. She denied polydipsia, neuropathy, abdominal symptoms, or any vision abnormality. History was remarkable for type 2 diabetes, hypertension and severe dyslipidemia. Vital signs stable. The patient was taking three oral anti-diabetic agents including metformin, dapaglaflozin and dulaglutide. In addition to triple therapy, this patient was on 60 units of short-acting insulin total for mealtime coverage and 45 units twice a day of long acting insulin. On exam, she was thin appearing and in no distress. Labs revealed C-Peptide 4.58 ng/mL and insulin 1.5 uIU/mL. P</span>atient had a HgA1c 18.5 %, GAD antibody negative, anti islet cell antibody negative, and TSH 1.414 uIu/ml. Although the patient was initially being labelled as noncompliant, they repeatedly endorsed taking all medications as prescribed without improvement of objective labs. Due to escalating insulin requirements and progressive metabolic derangement, AGL was suspected as the underlying disease due to physical exam findings and persistently escalating insulin requirements. In order to confirm the diagnosis, leptin level ordered with result of 2.2 ng/mL, which is low. In the absence of antibody positivity, the likely diagnosis was idiopathic AGL. After trial of lifestyle modifications, patient followed up with AGL specialist for metreleptin initiation, which is a recombinant human leptin analog. Subcutaneous administration of this in AGL patients with hypoleptinemia has been shown to improve blood glucose levels, triglycerides, and complications such as steatosis and coronary artery disease.

Discussion : This case represents an exceedingly rare diagnosis of AGL associated with severe insulin resistance in an adult. In this case, hypoleptinemia confirmed the clinical findings of AGL. Although there are few cases diagnosed each year, it is important to consider this diagnosis where clinical findings such as thin extremities and lipodystrophic fat distribution correlate with severe insulin resistance. If further workup was not performed for this patient, they would be labelled as noncompliant and not receive the necessary treatment for their disease. Research is still required on the efficacy of metreleptin in reducing morbidity and mortality in the adult population due to the exceedingly rare diagnosis in adulthood.