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Elevated Intact Proinsulin Levels During an Oral Glucose Challenge Indicate Progressive β-Cell Dysfunction and May Be Predictive for Development of Type 2 Diabetes.
J Diabetes Sci Technol 2015; 9(6):1307-12JD

Abstract

BACKGROUND

Elevated fasting intact proinsulin is a biomarker of late-stage β-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 β-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+Show Affiliations

Pfützner Science & Health Institute, Diabetes Center and Practice, Mainz, Germany Andreas.pfuetzner@pfuetzner-mainz.com.University Hospital Mainz, Center of Thrombosis and Homeostasis, Mainz, Germany.Pfützner Science & Health Institute, Diabetes Center and Practice, Mainz, Germany.Pfützner Science & Health Institute, Diabetes Center and Practice, Mainz, Germany.Sciema UG, Mainz, Germany.Universitäty Hospital, Department of Endocrinology & Diabetes, Marburg, Germany.University-Hospital, Department of Endocrinology & Diabetes, Mainz, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26420624

Citation

Pfützner, Andreas, et al. "Elevated Intact Proinsulin Levels During an Oral Glucose Challenge Indicate Progressive β-Cell Dysfunction and May Be Predictive for Development of Type 2 Diabetes." Journal of Diabetes Science and Technology, vol. 9, no. 6, 2015, pp. 1307-12.
Pfützner A, Hermanns I, Ramljak S, et al. Elevated Intact Proinsulin Levels During an Oral Glucose Challenge Indicate Progressive β-Cell Dysfunction and May Be Predictive for Development of Type 2 Diabetes. J Diabetes Sci Technol. 2015;9(6):1307-12.
Pfützner, A., Hermanns, I., Ramljak, S., Demircik, F., Pfützner, A. H., Kann, P. H., & Weber, M. M. (2015). Elevated Intact Proinsulin Levels During an Oral Glucose Challenge Indicate Progressive β-Cell Dysfunction and May Be Predictive for Development of Type 2 Diabetes. Journal of Diabetes Science and Technology, 9(6), pp. 1307-12. doi:10.1177/1932296815607862.
Pfützner A, et al. Elevated Intact Proinsulin Levels During an Oral Glucose Challenge Indicate Progressive β-Cell Dysfunction and May Be Predictive for Development of Type 2 Diabetes. J Diabetes Sci Technol. 2015 Sep 29;9(6):1307-12. PubMed PMID: 26420624.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Elevated Intact Proinsulin Levels During an Oral Glucose Challenge Indicate Progressive β-Cell Dysfunction and May Be Predictive for Development of Type 2 Diabetes. AU - Pfützner,Andreas, AU - Hermanns,Iris, AU - Ramljak,Sanja, AU - Demircik,Filiz, AU - Pfützner,Anke H, AU - Kann,Peter H, AU - Weber,Matthias M, Y1 - 2015/09/29/ PY - 2015/10/1/entrez PY - 2015/10/1/pubmed PY - 2016/8/25/medline KW - diabetes prediction KW - insulin resistance KW - intact proinsulin KW - oral glucose challenge KW - β-cell dysfunction SP - 1307 EP - 12 JF - Journal of diabetes science and technology JO - J Diabetes Sci Technol VL - 9 IS - 6 N2 - BACKGROUND: Elevated fasting intact proinsulin is a biomarker of late-stage β-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 β-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. SN - 1932-2968 UR - https://www.unboundmedicine.com/medline/citation/26420624/Elevated_Intact_Proinsulin_Levels_During_an_Oral_Glucose_Challenge_Indicate_Progressive_β_Cell_Dysfunction_and_May_Be_Predictive_for_Development_of_Type_2_Diabetes_ L2 - http://journals.sagepub.com/doi/full/10.1177/1932296815607862?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -