Factors Associated with Beta-Cell Dysfunction in Type 2 Diabetes: The BETADECLINE Study

<div><p>Aims</p><p>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.</p><p>Materials and Methods</p><p>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).</p><p>Results</p><p>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 (HbA_1c), 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).</p><p>Conclusions</p><p>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.</p></div

Significant univariate correlations (Pearson's test) of proinsulin/insulin (PI/I) ratio with study variables according to sex.

<p>Significant univariate correlations (Pearson's test) of proinsulin/insulin (PI/I) ratio with study variables according to sex.</p

Baseline clinical characteristics of BetaDecline study participants.

<p>Baseline clinical characteristics of BetaDecline study participants.</p

Type 2 diabetic subjects with HbA1c≥7.0% or <7.0% according to the degree of beta-cell dysfunction.

<p>Type 2 diabetic subjects with HbA1c≥7.0% or <7.0% according to the degree of beta-cell dysfunction.</p

Patients characteristics according to gender.

<p>Patients characteristics according to gender.</p

Quality indicators of diabetes care according to gender.

<p>The first three columns show the likelihood (odds ratios and their 95% confidence intervals) of women as compared to men (reference class) to be monitored for specific clinical parameters, to reach specific clinical outcomes and to be treated with specific classes of drugs. Odds ratios are crude, adjusted for patient characteristics only (age, diabetes duration, BMI, and smoking), and for patient characteristics and clustering effect. Statistically significant differences are in bold. The fourth column shows intra-class correlation coefficients (ICC). The higher the ICC, the greater the influence of the center level on the quality of care indicator. The fifth column shows the results of the multilevel analyses additionally adjusted for process indicators (i.e. monitoring and appropriateness indicators associated with each outcome).</p