Alterations in the Levels of Circulating and Endothelial Progenitor Cells Levels in Young Adults with Type 1 Diabetes: A 2-Year Follow-Up from the Observational METRO Study

Q: What are the key findings of this study?

Intensive insulin therapy over 2 years significantly increased circulating EPCs in young adults with type 1 diabetes, independently predicted by MAGE reduction (β = -0.316, P = 0.004 for CD34+KDR+).

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Type 1 diabetes (n=204). Intervention: Continuous subcutaneous insulin infusion (CSII) and glucose variability reduction vs. Multiple daily insulin injections (MDI). Primary outcome: Change in circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs) levels over 2 years, and association with glucose variability (MAGE) (p=0.004).

Q: What does this research mean for the field?

Intensive insulin therapy over two years increases circulating endothelial progenitor cell levels in young adults with type 1 diabetes, with the increase independently predicted by reductions in glucose variability. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Miriam Longo; Lorenzo Scappaticcio; Giuseppe Bellastella; Vlenia Pernice; Paolo Cirillo; Antonietta Maio; Filomena Castaldo; Dario Giugliano; Katherine Esposito; Maria Ida Maiorino

doi:10.2147/dmso.s238588

March 1, 2020Diabetes Metabolic Syndrome and ObesityOpen Access

Alterations in the Levels of Circulating and Endothelial Progenitor Cells Levels in Young Adults with Type 1 Diabetes: A 2-Year Follow-Up from the Observational METRO Study

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Key result

Intensive insulin therapy increases circulating EPCs in young T1D adults, linked to reduced glycemic variability.

P=0.004
n=204

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Why the study?

Type 1 diabetes carries a high CVD risk, and reduced CPC and EPC levels indicate risk for adverse cardiovascular outcomes and death. The study evaluated changes in CPC and EPC levels over 2 years in young type 1 diabetes patients treated with intensive insulin.

Does intensive insulin therapy (CSII vs MDI) and improvement in glucose variability increase circulating and endothelial progenitor cell levels over 2 years in young adults with type 1 diabetes?

Key Points

To evaluate changes in circulating progenitor cells and endothelial progenitor cells over two years in young adults with type 1 diabetes receiving intensive insulin therapy.
Followed 204 young adults with type 1 diabetes (mean age 24.5 years, mean duration 13.6 years), including 84 using continuous subcutaneous insulin infusion (CSII) and 120 using multiple daily injections (MDI), over a 2-year period.
Quantified circulating progenitor cell (CPC) and endothelial progenitor cell (EPC) phenotypes via flow cytometry alongside clinical measures of glycemic control and glucose variability.
At 2 years, HbA1c significantly declined (-0.3%, P <0.001), with reductions in MAGE (-0.5 mmol/L, P <0.001), CONGA (-0.2 mmol/L, P = 0.006), and blood glucose standard deviation (-0.2 mmol/L, P <0.001).
Circulating EPC phenotypes increased significantly across the cohort, with larger increases observed in the CSII group, whereas overall CPC count did not significantly rise.
Decreased MAGE emerged as an independent predictor for increases in both CD34+ (β = -0.322, P = 0.020) and CD34+KDR+ cells (β = -0.316, P = 0.004) in multivariable regression.

Study Design

Type

Cohort (n=204)

Blinding

Blinded Dexcom G4 CGM system for 14 days at basal evaluation and after 24 months

Multicenter

No

Structured PICO

Does intensive insulin therapy (CSII vs MDI) and improvement in glucose variability increase circulating and endothelial progenitor cell levels over 2 years in young adults with type 1 diabetes?

P

Population

204 young adults with type 1 diabetes (mean age 24.5 years, 48.5% female) and persistent poor glycemic control (HbA1c ≥7.5%) treated with CSII or MDI at a single center in Italy, followed for 2 years.

E

Exposure

Intensive insulin regimen via continuous subcutaneous insulin infusion (CSII, insulin pump, n=84) over 2 years of follow-up

C

Comparator

Intensive insulin regimen via multiple daily insulin injections (MDI, n=120) over 2 years of follow-up

O

Outcome

Change in circulating progenitor cells (CPCs: CD34+, CD133+, CD34+CD133+) and endothelial progenitor cells (EPCs: CD34+KDR+, CD133+KDR+, CD34+KDR+CD133+) levels assessed by direct flow cytometry on peripheral blood mononuclear cells at baseline and after 2 yearssurrogate

Main Result

Absolute Event Rate: 50% vs 40%

p-value: p=0.004

Limitations

Short follow-up period (2 years) prevents predicting whether increased EPCs number results in a reduced risk of microvascular and macrovascular complications
Observational nature of the study prevents making inference regarding cause and effect
Potential for residual confounding by uncontrolled covariates
Short follow-up period (2 years) precludes predicting whether increased EPC numbers result in a reduced risk of microvascular and macrovascular complications
Observational nature of the study precludes causal inference

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Implication

Reducing glucose variability in young adults with type 1 diabetes is independently associated with a 2-year increase in circulating and endothelial progenitor cells, particularly among insulin pump users, suggesting a potential mechanism for improved endothelial homeostasis and vascular repair.

Abstract

PURPOSE: Type 1 diabetes is associated with high risk of cardiovascular disease (CVD). Reduced levels of circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs) have been indicated as a risk factor for adverse cardiovascular outcomes and death in people at high cardiovascular risk. The aim of the present study was to evaluate the change in CPCs and EPCs levels in a population of young type 1 diabetic patients treated with intensive insulin regimen over a period of 2 years. PATIENTS AND METHODS: A total of 204 type 1 diabetic patients, of whom 84 treated with insulin pump (CSII) and 120 with multiple daily insulin injections (MDI), completed a 2-year follow-up. Clinical measurements, including the indices of glycemic control and glucose variability, were collected at baseline and after 2 years. Both CPC and EPC cell count were assessed by flow cytometry. RESULTS: Mean age of participants was 24.5 years and mean diabetes duration was 13.6 years. After 2 years, we found a significant reduction of HbA1c (-0.3% versus baseline, P <0.001), associated with decrease in mean amplitude of glucose excursion (MAGE) (-0.5 mmol/L versus baseline, P<0.001), continuous overall net glycemic action (CONGA) (-0.2 mmol/L versus baseline, P=0.006), and blood glucose standard deviation (BGSD) (-0.2 mmol/L versus baseline, P<0.001). The number of all EPCs phenotypes, but not CPC cell count, significantly raised up in the entire population, with higher increase in CSII group. MAGE resulted as an independent predictor for increased levels of both CD34+ (P = 0.020) and CD34+KDR+ (P = 0.004) cell count in the whole population. CONCLUSION: Over a 2-year follow-up, young type 1 diabetic patients showed an increase in circulating EPCs levels, which was higher in patients with CSII. Glucose variability resulted as an independent predictor of the raised levels of EPCs in this selected population.

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Cite This Study

Longo et al. (2020) conducted a cohort in Type 1 diabetes (n=204). Continuous subcutaneous insulin infusion (CSII) and glucose variability reduction vs. Multiple daily insulin injections (MDI) was evaluated on Change in circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs) levels over 2 years, and association with glucose variability (MAGE) (p=0.004). Intensive insulin therapy over 2 years significantly increased circulating EPCs in young adults with type 1 diabetes, independently predicted by MAGE reduction (β = -0.316, P = 0.004 for CD34+KDR+).

synapsesocial.com/papers/6a7c96908a7077a9e43f6abf https://doi.org/10.2147/dmso.s238588

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Alterations in the Levels of Circulating and Endothelial Progenitor Cells Levels in Young Adults with Type 1 Diabetes: A 2-Year Follow-Up from the Observational METRO Study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Alterations in the Levels of Circulating and Endothelial Progenitor Cells Levels in Young Adults with Type 1 Diabetes: A 2-Year Follow-Up from the Observational METRO Study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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