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

Vangipurapu J, Stančáková A, Kuulasmaa T, Kuusisto J, Laakso M - PLoS ONE (2015)

Bottom Line: 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.Insulin sensitivity had a major impact on these associations.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.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Health Sciences, Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Proinsulin levels across the categories of fasting and 2 hour glucose in the METSIM cross-sectional study.Mean values of proinsulin levels (pmol/l) and their 95% confidence intervals are shown. Overall P values based on ANOVA across the categories of fasting and 2 hour glucose were significant (P<0.001) for all traits. All mean values were significantly (P<0.001) different from mean values of the reference group (FPG ≤5 mM and 2hr glucose ≤5 mM) except for those marked with ‘x’.
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pone.0124028.g001: Proinsulin levels across the categories of fasting and 2 hour glucose in the METSIM cross-sectional study.Mean values of proinsulin levels (pmol/l) and their 95% confidence intervals are shown. Overall P values based on ANOVA across the categories of fasting and 2 hour glucose were significant (P<0.001) for all traits. All mean values were significantly (P<0.001) different from mean values of the reference group (FPG ≤5 mM and 2hr glucose ≤5 mM) except for those marked with ‘x’.

Mentions: Statistical analyses were conducted using IBM SPSS version 19 (IBM SPSS, Chicago, IL). All traits except for age were log-transformed to correct for their skewed distributions. All variables were standardized (based on their respective SD’s) to obtain comparable Hazard’s ratios (HR). A linear regression model was used to evaluate the proinsulin measures as predictors for Glucose AUC at the follow-up study, wherein previously diagnosed diabetes subjects were excluded from analyses. Standardized effect size (β) was estimated by linear regression analysis. To investigate the association of proinsulin measures with incident type 2 diabetes, the follow-up time was calculated (in months) and Cox regression analysis was applied. Adjustments were primarily done for age, BMI, smoking, physical activity and follow-up time where applicable. Additional adjustments were done for Matsuda ISI and Disposition index. After Bonferroni correction for multiple testing (for 14 tests given the 7 proinsulin variables and 2 glycemic traits), P<0.0036 was considered as statistically significant.


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

Vangipurapu J, Stančáková A, Kuulasmaa T, Kuusisto J, Laakso M - PLoS ONE (2015)

Proinsulin levels across the categories of fasting and 2 hour glucose in the METSIM cross-sectional study.Mean values of proinsulin levels (pmol/l) and their 95% confidence intervals are shown. Overall P values based on ANOVA across the categories of fasting and 2 hour glucose were significant (P<0.001) for all traits. All mean values were significantly (P<0.001) different from mean values of the reference group (FPG ≤5 mM and 2hr glucose ≤5 mM) except for those marked with ‘x’.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390238&req=5

pone.0124028.g001: Proinsulin levels across the categories of fasting and 2 hour glucose in the METSIM cross-sectional study.Mean values of proinsulin levels (pmol/l) and their 95% confidence intervals are shown. Overall P values based on ANOVA across the categories of fasting and 2 hour glucose were significant (P<0.001) for all traits. All mean values were significantly (P<0.001) different from mean values of the reference group (FPG ≤5 mM and 2hr glucose ≤5 mM) except for those marked with ‘x’.
Mentions: Statistical analyses were conducted using IBM SPSS version 19 (IBM SPSS, Chicago, IL). All traits except for age were log-transformed to correct for their skewed distributions. All variables were standardized (based on their respective SD’s) to obtain comparable Hazard’s ratios (HR). A linear regression model was used to evaluate the proinsulin measures as predictors for Glucose AUC at the follow-up study, wherein previously diagnosed diabetes subjects were excluded from analyses. Standardized effect size (β) was estimated by linear regression analysis. To investigate the association of proinsulin measures with incident type 2 diabetes, the follow-up time was calculated (in months) and Cox regression analysis was applied. Adjustments were primarily done for age, BMI, smoking, physical activity and follow-up time where applicable. Additional adjustments were done for Matsuda ISI and Disposition index. After Bonferroni correction for multiple testing (for 14 tests given the 7 proinsulin variables and 2 glycemic traits), P<0.0036 was considered as statistically significant.

Bottom Line: 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.Insulin sensitivity had a major impact on these associations.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.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Health Sciences, Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus