November 02, 2025

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Microvascular Complications Have Synergistic Negative Effect On All Cause Mortality Among Diabetics

Italy: A recent study published in Cardiovascular Diabetology has shown the synergistic, long-term, and adverse effects of diabetic microvascular complications (MVC) on mortality in both type 1 diabetes (T1D) and type 2 diabetes (T2D) patients.
Diabetes-related MVC poses a significant burden on both patients and the healthcare systems. Chronic exposure to hyperglycemia in diabetes patients impairs microvascular functions, often leading to microvascular complications. The predictive value of common and frequently associated MVC, namely cardiac autonomic neuropathy (CAN), chronic kidney disease (CKD), retinopathy (DR), and peripheral neuropathy (DPN), is well established. However, there has yet to be a proper assessment of their different combinations on long-term mortality.

Against the above background, Luca Sacchetta and colleagues from Italy sought to assess the long-term prognostic role of diabetes-related MVC, alone or in combination, on all-cause mortality in both T1D and T2D.
For this purpose, the researchers retrospectively analyzed 21-year longitudinal data from 303 patients with long-standing diabetes (type 1 or type 2 diabetes), thoroughly characterized at baseline for MVC presence through extensive screening. The patients were aged between 18 and 75 years.
The CHAMP1ON study, CHronic diabetes complications and All-cause Mortality in Pisa from 1999 ONwards, is an observational, single-centre study involving 497 consecutive outpatients referred for dysglycemia in the University Hospital of Pisa between 1999 and 2000.
The study demonstrated the following findings:
· A total of 133 (43.9%) deaths occurred after a 5,244 person-years follow-up.
· The presence of CAN and CKD, irrespective of other MVC, raised the risk of adjusted all-cause mortality by 117% (HR 2.17) and 54% (HR 1.54), respectively.
· Concomitant CKD&CAN at baseline was associated with the highest mortality risk (HR 5.08), followed by CKD&DR (HR 2.95) and CAN&DR (HR 2.07).
· The mortality risk was numerically more significant in patients with any isolated MVC (HR 1.52) than in patients free from MVC. In contrast, in patients with two and three concomitant MVC, it increased by 203% (HR 3.03) and 692% (HR 7.92), respectively.
"Over a significantly long follow-up period of 21 years, CKD, DR, and CAN, but DPN, lowered life expectancy by 1.3 to 2.6 years, and CAN and CKD raised the adjusted all-cause mortality by 117% and 54%," the researchers concluded.
"The findings should encourage comprehensive screenings for microvascular complications in both T1D and T2D to improve treatment and risk stratification," they wrote.
Reference:
Sacchetta, L., Chiriacò, M., Nesti, L. et al. Synergistic effect of chronic kidney disease, neuropathy, and retinopathy on all-cause mortality in type 1 and type 2 diabetes: a 21-year longitudinal study. Cardiovasc Diabetol 21, 233 (2022). https://doi.org/10.1186/s12933-022-01675-6

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