IRIS II study: intact proinsulin is confirmed as a highly specific indicator for insulin resistance in a large cross-sectional study design.
BACKGROUND
The cross-sectional IRIS-II study tried to assess the prevalence of insulin resistance and macrovascular disease in orally treated patients with Type 2 diabetes.


METHODS
In total, 4,270 patients were enrolled into the study (2,146 male, 2,124 female; mean +/- SD age 63.9 +/- 11.1 years; body mass index 30.1 +/- 5.5 kg/m2; duration of disease 5.4 +/- 5.6 years; hemoglobin A1c 6.8 +/- 1.3%). The study consisted of a single morning visit with completion of a standardized questionnaire and collection of a fasting blood sample.


RESULTS
The mean intact proinsulin value was 11.4 +/- 12.4 pmol/L (normal range < 10 pmol/L). Homeostasis model assessment resulted in 1,147 insulin-sensitive patients (26.9%) and 3,123 patients (73.1%) with insulin resistance. Of the latter patients 1,465 (34.3% of all patients) had also elevated intact proinsulin values, while 1,658 (38.8%) had no proinsulin elevation. In contrast, 1,042 (24.4%) of the insulin-sensitive patients had normal intact proinsulin, and only 105 (2.4%) had elevated intact proinsulin concentrations (chi2 test P < 0.0001). A specificity of 93.2% (sensitivity 46.9%) was calculated for elevated intact proinsulin as an indirect marker for insulin resistance. Of the 1,451 patients treated with sulfonylurea 52% had elevated intact proinsulin values and increased prevalence of cardiovascular complications (odds ratio 1.45).


CONCLUSIONS
Type 2 patients with elevated fasting intact proinsulin values can be regarded as being insulin resistant. The results confirm that fasting intact proinsulin is a suitable measure for beta-cell dysfunction and insulin resistance in type 2 diabetes and may be used to support therapeutic decisions.
Pfützner
Andreas
A
University of Applied Sciences, Rheinbach, Germany. AndreasP@ikfe.de
Standl
Eberhard
E
Hohberg
Cloth
C
Konrad
Thomas
T
Strotmann
Hermann-Josef
HJ
Lübben
Georg
G
Langenfeld
Matthias R
MR
Schulze
Jan
J
Forst
Thomas
T
D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006304:Health Status; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D011384:Proinsulin / Q000097:blood*; D011795:Surveys and Questionnaires; D014652:Vascular Diseases / Q000453:epidemiology*
D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D011384:Proinsulin