Acquired generalized lipodystrophy complicated by fulminant type 1 diabetes mellitus: a case report with review of literature and immunological insights.

Acquired generalized lipodystrophy (AGL) is a rare disorder characterized by progressive loss of subcutaneous and visceral adipose tissue and severe metabolic disturbances, including diabetes mellitus (DM). Although AGL is typically associated with type 2 DM, clinical experience with patients affected by both AGL and Fulminant type 1 DM (FT1DM) remains limited. We report a case of a 50-year-old man with long-standing (4-year) FT1DM who developed AGL, with histopathological and immunological evaluation and long-term follow-up after metreleptin therapy. The patient presented with rapid deterioration of glycemic control and extreme insulin resistance, requiring a marked increase in insulin dose. Imaging studies revealed generalized loss of subcutaneous and visceral adipose tissue, and skin biopsy demonstrated marked adipose tissue atrophy with infiltration of CD3+ (cluster of differentiation 3) and CD8+ T lymphocytes. Notably, soluble interleukin-2 receptor (sIL-2R) levels remained persistently elevated for more than 12 months, suggesting sustained systemic T-cell activation. Although metreleptin therapy resulted in partial improvement in glycemic control, hemoglobin A1c (HbA1c) did not return to the pre-AGL level during follow-up. This case raises the possibility that persistent immune activation may contribute to insulin resistance beyond leptin deficiency in some patients with AGL.