Case Report: Rapid loss of endogenous insulin secretion and reversible subcutaneous insulin resistance following exogenous insulin exposure in a patient initially diagnosed with type 2 diabetes.

BACKGROUND

Subcutaneous insulin resistance (SIR) is a rare condition characterized by impaired responsiveness to subcutaneous insulin despite preserved intravenous insulin efficacy. The coexistence of SIR with rapid loss of endogenous insulin secretion following exogenous insulin exposure has rarely been reported.

CASE PRESENTATION: A 47-year-old Chinese man initially classified as having type 2 diabetes (T2D) had preserved endogenous insulin secretion (random C-peptide, 4.59 ng/mL) and negative insulin autoantibody (IAA), glutamic acid decarboxylase antibody, and insulinoma-associated protein 2 antibody at diagnosis. Shortly after initiation of subcutaneous insulin therapy, he developed pruritic, erythematous, and indurated injection-site lesions with progressive hyperglycemia and subsequently presented with diabetic ketoacidosis. C-peptide became undetectable, whereas IAA increased to >175 IU/mL. Intravenous insulin consistently restored glycemic control, while several subcutaneous insulin preparations were initially ineffective, indicating a marked route-dependent difference in insulin responsiveness. Subcutaneous insulin responsiveness later recovered, first with biphasic protamine human insulin 40/60 and subsequently with insulin analogues, despite persistent IAA positivity. At recent follow-up, 14-day continuous glucose monitoring showed a mean glucose of 7.6 mmol/L, time in range of 80%, and time below range of 3%. A heterozygous WFS1 variant (NM_006005.3:c.2147C>G, p.Ala716Gly) was identified as an exploratory finding of uncertain clinical significance.

CONCLUSION

This case highlights the coexistence of rapid loss of endogenous insulin secretion and severe but reversible SIR following exogenous insulin exposure. Preserved intravenous insulin responsiveness and recovery of subcutaneous insulin efficacy despite persistent IAA positivity underscore the dynamic and route-specific nature of this phenotype. The underlying mechanism remains uncertain, and no causal relationship with the WFS1 variant can be inferred. Recognition of this pattern may facilitate appropriate insulin delivery and longitudinal monitoring.