What is the clinical evidence from this study?

Study design: Cohort. Population: Type 1 and Type 2 diabetes (n=303). Intervention: Three concomitant microvascular complications vs. No microvascular complications. Primary outcome: All-cause mortality (HR 7.92, 95% CI 2.93-21.37).

November 5, 2022Cardiovascular Diabetology38 citationsOpen Access

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

LSLuca SacchettaUniversity of Pisa MCMartina ChiriacòUniversity of Pisa LNLorenzo NestiUniversity of Pisa

Key Result

The presence of three concomitant microvascular complications increased the risk of all-cause mortality by 692% (HR 7.92) compared with patients free from complications.

Study Design

Type

Cohort (n=303)

Multicenter

Structured PICO

Does the presence of single or combined diabetic microvascular complications increase all-cause mortality in patients with type 1 and type 2 diabetes?

Population

303 patients aged 18-75 with long-standing type 1 or type 2 diabetes were screened for microvascular complications and followed for a median of 21 years to assess all-cause mortality.

Exposure

Presence of single or combined diabetic microvascular complications (chronic kidney disease, cardiac autonomic neuropathy, diabetic peripheral neuropathy, diabetic retinopathy)

Comparator

Patients without the respective microvascular complications

Outcome

All-cause mortalityhard clinical

The presence of multiple concomitant diabetic microvascular complications, particularly chronic kidney disease and cardiac autonomic neuropathy, synergistically increases the long-term risk of all-cause mortality in patients with diabetes.

Main Result

Hazard Ratio: 7.92 (95% CI 2.93–21.37)

Limitations

Retrospective design
Could not retrieve reliable information on incident CVD events or the cause of death
Could not evaluate the time course of microvascular complications, clinical parameters, or treatment changes after enrollment
Limited number of subjects and events in some analyses, especially for the Type 1 diabetes subgroup
Diagnosis of diabetic retinopathy relied on a single operator-dependent assessment

Abstract

BACKGROUND: The prognostic value of common and frequently associated diabetic microvascular complications (MVC), namely chronic kidney disease (CKD), cardiac autonomic neuropathy (CAN), peripheral neuropathy (DPN), and retinopathy (DR), is well established. However, the impact of their different combinations on long-term mortality has not been adequately assessed. METHODS: Tc-DTPA dynamic renal scintigraphy, overnight urine collection, cardiovascular autonomic tests, monofilament testing, and dilated fundus oculi examination. RESULTS: After a 5,244 person-years follow-up, a total of 133 (43.9%) deaths occurred. The presence of CKD and CAN, regardless of other MVC, increased the adjusted all-cause mortality risk by 117% (HR 2.17 1.45-3.26) and 54% (HR 1.54 1.01-2.36), respectively. Concomitant CKD&CAN at baseline were associated with the highest mortality risk (HR 5.08 2.52-10.26), followed by CKD&DR (HR 2.95 1.63-5.32), and CAN&DR (HR 2.07 1.11-3.85). Compared with patients free from MVC, the mortality risk was only numerically higher in those with any isolated MVC (HR 1.52 0.87-2.67), while increased by 203% (HR 3.03 1.62-5.68) and 692% (HR 7.92 2.93-21.37) in patients with two and three concomitant MVC, respectively. CONCLUSIONS: Our study demonstrates the long-term, synergistic, negative effects of single and concomitant diabetic MVC on all-cause mortality, which should encourage comprehensive screenings for MCV in both T1D and T2D to improve risk stratification and treatment.

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