Factors associated with beta-cell dysfunction in type 2 diabetes: the BETADECLINE study

PLoS One. 2014 Oct 27;9(10):e109702. doi: 10.1371/journal.pone.0109702. eCollection 2014.


Aims: Beta-cell dysfunction is an early event in the natural history of type 2 diabetes. However, its progression is variable and potentially influenced by several clinical factors. We report the baseline data of the BetaDecline study, an Italian prospective multicenter study on clinical predictors of beta-cell dysfunction in type 2 diabetes.

Materials and methods: Clinical, lifestyle, and laboratory data, including circulating levels of inflammatory markers and non-esterified fatty acids, were collected in 507 type 2 diabetic outpatients on stable treatment with oral hypoglycemic drugs or diet for more than 1 year. Beta-cell dysfunction was evaluated by calculating the proinsulin/insulin ratio (P/I).

Results: At baseline, the subjects in the upper PI/I ratio quartile were more likely to be men and receiving secretagogue drugs; they also showed a borderline longer diabetes duration (P = 0.06) and higher serum levels of glycated hemoglobin (HbA1c), fasting blood glucose, and triglycerides. An inverse trend across all PI/I quartiles was noted for BMI and serum levels of total cholesterol (T-C), LDL-C, HDL-C and C reactive protein (CRP), and with homeostatic model assessment (HOMA-B) and HOMA of insulin resistance (HOMA-IR) values (P<0.05 for all). At multivariate analysis, the risk of having a P/I ratio in the upper quartile was higher in the subjects on secretagogue drugs (odds ratio [OR] 4.2; 95% confidence interval [CI], 2.6-6.9) and in the males (OR 1.8; 95% CI, 1.1-2.9).

Conclusions: In the BetaDecline study population, baseline higher PI/I values, a marker of beta-cell dysfunction, were more frequent in men and in patients on secretagogues drugs. Follow-up of this cohort will allow the identification of clinical predictors of beta-cell failure in type 2 diabetic outpatients.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Diabetes Mellitus, Type 2 / etiology*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin Resistance
  • Insulin-Secreting Cells / metabolism*
  • Male
  • Middle Aged
  • Proinsulin / metabolism
  • Prospective Studies
  • Risk Factors


  • Glycated Hemoglobin A
  • Insulin
  • Proinsulin

Grants and funding

This study was organized by AMD Foundation Rome, and was in part funded by Merck Sharp & Dohme Corp. The funds are used for the costs of laboratory and data monitoring. There is no one outside of the author SC who is employed or has relationships with Merck Sharp & Dohme. SC's contribution is in data analysis and interpretation. No additional funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.