Microvascular complications do not interact to raise mortality in type 1 diabetes
medwireNews: All-cause mortality risk in patients with type 1 diabetes and more than one microvascular complication does not exceed the combined risk estimates of each separate complication, Danish researchers report.
They used multi-state modelling to show that diabetic kidney disease and neuropathy are “strong and independent risk markers of mortality in type 1 diabetes,” but “mortality risk in individuals with more than one complication is simply the product of the risk estimates from each separate complication; no evidence was found of additional risk from having more than one complication,” they write.
Furthermore, the time spent with each of these complications had little effect on outcome.
The team, led by Lasse Bjerg from Aarhus University, examined how concurrent microvascular complication burden affects all-cause mortality over time in a cohort of 3828 individuals with type 1 diabetes attending the Steno Diabetes Center Copenhagen from 2001 to 2013.
At the time of study enrollment, 706 individuals had diabetic kidney disease, 663 had neuropathy, and 1875 had retinopathy, each with or without one of the other complications.
During 26,665 person–years of follow-up, these complications developed in 546, 523, and 723 patients, respectively, and 503 patients died.
Bjerg and co-investigators report in Diabetologia that individuals with diabetic kidney disease were more than twice as likely to die as those without, at a significant mortality rate ratio of 2.20, after adjustment for potential confounders such as age, sex, calendar time, diabetes duration, glycated hemoglobin, BMI, and cardiovascular disease status.
Of note, the association was slightly stronger immediately after diagnosis, at a mortality rate ratio of 2.80, but then stabilized to 2.20 after 3 years with the complication.
Individuals with neuropathy had a significant 1.72-fold higher risk for death than those without neuropathy, overall, but a slightly lower risk (approximately 1.6-fold) at the time of diagnosis which increased and then stabilized with time.
By contrast, the researchers found no association between mortality risk and retinopathy of any duration.
For individuals with more than one complication, mortality risk did not exceed the combined risk from each individual complication. For example, patients with all three microvascular complications had a significant adjusted mortality rate ratio of 3.86 (derived from 2.20 × 1.72 × 1.02 = 3.86).
Bjerg et al believe their study is unique because it “assessed both the separate risk and the combined mortality risk associated with all three microvascular complications, while taking duration since diagnosis of complications into account.”
“[T]his knowledge could facilitate implementation of better integrated risk models in daily clinical practice,” they write.
The authors also point out that while they “did not find evidence for a statistical interaction between the microvascular complications, this does not mean that a biological interaction does not exist.”
By Laura Cowen
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