title: Elevated Intact Proinsulin Levels During an Oral Glucose Challenge Indicate Progressive ß-Cell Dysfunction and May Be Predictive for Development of Type 2 Diabetes.
abstract: BACKGROUND
  Elevated fasting intact proinsulin is a biomarker of late-stage ß-cell-dysfunction associated with clinically relevant insulin resistance. In this pilot investigation, we explored the potential value of measuring intact proinsulin as a functional predictor of ß-cell exhaustion during an oral glucose tolerance test (OGTT).
  
  
  METHODS
  The study was performed with 31 participants, 11 of whom were healthy subjects (7 female, age: 59 ± 20 years), 10 had impaired glucose tolerance (IGT, 6 female, 62 ± 10 years), and 10 had known type 2 diabetes (T2DM, 5 female, 53 ± 11 years, HbA1c: 7.0 ± 0.6%, disease duration: 8 ± 5 years). During OGTT, blood was drawn after 0 hours, 1 hour, and 2 hours for determination of glucose and intact proinsulin. Five years later, patients were again contacted to assess their diabetes status and the association to the previous OGTT results was analyzed.
  
  
  RESULTS
  The OGTT (0 hours/1 hour/2 hours) results were as follows: healthy subjects: glucose: 94 ± 8 mg/dL/140 ± 29 mg/dL/90 ± 24 mg/dL, intact proinsulin: 3 ± 2 pmol/L/10 ± 7 pmol/L/10 ± 5 pmol/L); IGT: glucose: 102 ± 9 mg/dL/158 ± 57 mg/dL/149 ± 34 mg/dL, intact proinsulin: 7 ± 4 pmol/L/23 ± 8 pmol/L/28 ± 6 pmol/L; T2DM: glucose: 121 ± 20 mg/dL/230 ± 51 mg/dL/213 ± 34 mg/dL; intact proinsulin: 7 ± 7 pmol/L/26 ± 9 pmol/L/27 ± 10 pmol/L). Five years later, all of the IGT and 2 of the healthy subjects had developed T2DM and one had devloped IGT. All of them had elevated 2-hour proinsulin values in the initial OGTT, while patients with normal intact proinsulin results did not develop diabetes.
  
  
  CONCLUSIONS
  Elevated 2-hour intact proinsulin levels during OGTT were predictive for later type 2 diabetes development. Further studies need to confirm our findings in larger populations.
authors.affiliation: Pfützner Science & Health Institute, Diabetes Center and Practice, Mainz, Germany Andreas.pfuetzner@pfuetzner-mainz.com.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pfützner
authors.affiliation: University Hospital Mainz, Center of Thrombosis and Homeostasis, Mainz, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Hermanns
authors.affiliation: Pfützner Science & Health Institute, Diabetes Center and Practice, Mainz, Germany.
authors.forename: Sanja
authors.initials: S
authors.lastname: Ramljak
authors.affiliation: Pfützner Science & Health Institute, Diabetes Center and Practice, Mainz, Germany.
authors.forename: Filiz
authors.initials: F
authors.lastname: Demircik
authors.affiliation: Sciema UG, Mainz, Germany.
authors.forename: Anke H
authors.initials: AH
authors.lastname: Pfützner
authors.affiliation: Universitäty Hospital, Department of Endocrinology & Diabetes, Marburg, Germany.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Kann
authors.affiliation: University-Hospital, Department of Endocrinology & Diabetes, Mainz, Germany.
authors.forename: Matthias M
authors.initials: MM
authors.lastname: Weber
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D044882:Glucose Metabolism Disorders / Q000097:blood / Q000175:diagnosis*; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011384:Proinsulin / Q000097:blood*; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; D011384:Proinsulin; C517652:hemoglobin A1c protein, human
keywords: diabetes prediction; insulin resistance; intact proinsulin; oral glucose challenge; ß-cell dysfunction