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Abstract
To report a postulated mechanism for resistance to overt ketoacidosis due to prolonged insulin omission in a severely hyperglycemic woman with a 14-year history of autoimmune type 1 diabetes (T1D). History, physical examination, laboratory testing, and genotyping were performed. We also review the medical literature pertinent to this patient's phenotype and genotype. Proinsulin levels remained within the normal range (suppressed with hypoglycemia) despite simultaneous almost unmeasurable C-peptide levels during hyperglycemia. We confirmed a homozygous (TT) variant of protein tyrosine phosphatase nonreceptor type 22 (PTPN22) 1858T, a T1D susceptibility gene associated with higher proinsulin levels. The extraordinarily preserved proinsulin biological activity may explain the unusual resistance to overt ketoacidosis despite omission of exogenous insulin administration for extended periods of time. The role of the associated PTPN22 1858TT variant remains speculative.
Published Version
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