Search Results

You are looking at 1 - 2 of 2 items for

  • Author: Joao Pedro Ferreira x
  • All content x
Clear All Modify Search
Restricted access

Joao Pedro Ferreira, Ana Cristina Oliveira, Francisca A. Saraiva, Francisco Vasques-Nóvoa, and Adelino Leite-Moreira

Background: Patients with insulin-treated type 2 diabetes (T2D) have a high risk of major adverse cardiovascular events. Sodium-glucose cotransporter inhibitors (SGLTi) improve outcomes without hypoglycemic risk.

Aims: To study the effect of SGLTi in patients with T2D with and without background insulin-treatment in outcome-driven RCTs.

Methods: Random effects models.

Results: A total of 54,374 patients with T2D were included in the analysis, of which 26,551 (48.8%) were treated with insulin. For 3P-MACE in patients without insulin treatment, the HR (95%CI) for the effect of SGLTi vs. placebo was 0.93 (0.81-1.05), with moderate heterogeneity (I2 =49.2%, Q statistic P =0.11). In insulin-treated patients, the HR (95%CI) was 0.88 (0.82-0.95), without evidence of heterogeneity (I2 =0.0%, Q statistic P =0.91). The pooled effect evidenced a 10% reduction of 3P-MACE with SGLTi (HR 0.90, 95%CI 0.85-0.96), without SGLTi-by-insulin interactionP=0.53. For the composite outcome of HF hospitalisation or cardiovascular death in patients without insulin treatment, the HR (95%CI) for the effect of SGLTi vs. placebo was 0.77 (0.61-0.92), with marked heterogeneity (I2 =66.8%, Q statistic P =0.02). In insulin-treated patients, the HR (95%CI) was 0.77 (0.68-0.86), without significant heterogeneity (I2 =31.7%, Q statistic P =0.25). The pooled effect evidenced a 23% reduction of HF hospitalisations or cardiovascular death with SGLTi (HR 0.77, 95%CI 0.68-0.85), without SGLTi -by-insulin interactionP=0.98.

Conclusion:SGLTi reduce cardiovascular events regardless of insulin use. However, the treatment effect is more homogeneous among insulin-treated patients, supporting the use of SGLTi for the treatment of patients with T2D requiring insulin for glycemic control.

Restricted access

João Pedro Ferreira, Zohra Lamiral, Constance Xhaard, Kévin Duarte, Emmanuel Bresso, Marie-Dominique Devignes, Edith Le Floch, Claire Dandine Roulland, Jean-François Deleuze, Sandra Wagner, Bruno Guerci, Nicolas Girerd, Faiez Zannad, Jean-Marc Boivin, and Patrick Rossignol

Objective:

Determining the factors associated with new-onset pre-diabetes and type 2 diabetes mellitus (T2D) is important for improving the current prevention strategies and for a better understanding of the disease.

Design:

To study the factors (clinical, circulating protein and genetic) associated with new onset pre-diabetes and T2D in an initially healthy (without diabetes) populational familial cohort with a long follow-up (STANISLAS cohort).

Methods:

A total of 1506 participants attended both the visit 1 and visit 4, separated by ≈20 years. Over 400 proteins, GWAS and genetic associations were studied using models adjusted for potential confounders. Both prospective (V1 to V4) and cross-sectional (V4) analyses were performed.

Results:

People who developed pre-diabetes (n = 555) and/or T2D (n = 73) were older, had higher BMI, blood pressure, glucose, LDL cholesterol, and lower eGFR. After multivariable selection, PAPP-A (pappalysin-1) was the only circulating protein associated with the onset of both pre-diabetes and T2D with associations persisting at visit 4 (i.e. ≈20 years later). FGF-21 (fibroblast growth factor 21) was a strong prognosticator for incident T2D in the longitudinal analysis, but not in the cross-sectional analysis. The heritability of the circulating PAPP-A was estimated at 44%. In GWAS analysis, the SNP rs634737 was associated with PAPP-A both at V1 and V4. External replication also showed lower levels of PAPP-A in patients with T2D.

Conclusions:

The risk of developing pre-diabetes and T2D increases with age and with features of the metabolic syndrome. Circulating PAPP-A, which has an important genetic component, was associated with both the development and presence of pre-diabetes and T2D.