title: Preserved proinsulin production in homozygous protein tyrosine phosphatase nonreceptor type 22 C1858T variant type 1 diabetes: a possible explanation for absence of overt ketoacidosis despite omission of exogenous insulin.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  History, physical examination, laboratory testing, and genotyping were performed. We also review the medical literature pertinent to this patient's phenotype and genotype.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center, Boston University School of Medicine, Boston, MA 02118 , USA.
authors: Devin W
authors: DW
authors: Steenkamp
authors: Jeff M
authors: JM
authors: Milunsky
authors: Elliot
authors: E
authors: Sternthal
mesh_terms: D000328:Adult; D002096:C-Peptide / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D007662:Ketosis / Q000175:diagnosis*; D011384:Proinsulin / Q000378:metabolism*; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics / Q000378:metabolism*
chemical_list: D002096:C-Peptide; D007328:Insulin; D011384:Proinsulin; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22