Both fasting and glucose-stimulated proinsulin levels predict hyperglycemia and incident type 2 diabetes: a population-based study of 9,396 Finnish men

PLoS One. 2015 Apr 8;10(4):e0124028. doi: 10.1371/journal.pone.0124028. eCollection 2015.


Background: Hyperproinsulinemia is an indicator of β-cell dysfunction, and fasting proinsulin levels are elevated in patients with hyperglycemia. It is not known whether proinsulin levels after a glucose load are better predictors of hyperglycemia and type 2 diabetes than fasting proinsulin.

Methods: Participants were 9,396 Finnish men (mean±SD, age 57.3±7.1 years, BMI 27.0±4.0 kg/m2) of the population-based METabolic Syndrome In Men Study who were non-diabetic at the recruitment, and who participated in a 6-year follow-up study. Proinsulin and insulin levels were measured in the fasting state and 30 and 120 min after an oral glucose load. Area under the curve (AUC) and proinsulin to insulin ratios were calculated.

Results: Fasting proinsulin, proinsulin at 30 min and proinsulin AUC during the first 30 min of an oral glucose tolerance test significantly predicted both the worsening of hyperglycemia and type 2 diabetes after adjustment for confounding factors. Further adjustment for insulin sensitivity (Matsuda index) or insulin secretion (Disposition index) weakened these associations. Insulin sensitivity had a major impact on these associations.

Conclusion: Our results suggest that proinsulin in the fasting state and after an oral glucose load similarly predict the worsening of hyperglycemia and conversion to type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Area Under Curve
  • Biomarkers / blood
  • Blood Glucose / metabolism*
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / diagnosis*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Fasting
  • Finland
  • Follow-Up Studies
  • Glucose Tolerance Test
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / diagnosis*
  • Insulin / blood*
  • Insulin Resistance
  • Male
  • Middle Aged
  • Prognosis
  • Proinsulin / blood*


  • Biomarkers
  • Blood Glucose
  • Insulin
  • Proinsulin

Supplementary concepts

  • Hyperproinsulinemia

Grant support

This work has been supported by the grants from the Academy of Finland, the Finnish Diabetes Research Foundation, the Finnish Cardiovascular Research Foundation, the Strategic Research Funding from the University of eastern Finland, Kuopio, Finland, and EVO Grant 5263 from the Kuopio University Hospital to ML. The funding bodies named above had no role in the design and conduct of the study; collection management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.