Implications of all the available evidence
Excess mortality remains in people with Type 1 diabetes, but prognosis needs to be individualized and diversified since large groups without cardiorenal complications show low mortality rates and cardiovascular incidences.
To reduce the overall gap in mortality for persons with Type 1 diabetes, improved secondary prevention in patients with cardiorenal complications is urgently needed.
From the artcile
Discussion
In this population-based study of persons with T1D over
two decades, mortality rates and incidences of AMI, HF,
and stroke decreased over time. However, the gap
between T1D persons and controls did not converge due
to improvements in prognosis in the general popula-
tion. By contrast, people with T1D ≥45 years of age with-
out previous cardiovascular or renal complications
(constituting approximately 50% of this group over
time) had mortality rates similar to persons ≥45 years
without diabetes, as well as low risks of AMI, HF, and
stroke.
Previous studies have evaluated excess risks of mor-
tality and CVD over time for persons with diabetes in
different geographic regions showing excess risks on a
group level but only a few studies have distinguished
patients by cardiorenal complications or other risk fac-
tors.15−18,21−23 Whether diabetes is a cardiovascular risk
equivalent has been debated, i.e., whether persons with
diabetes free from coronary artery disease have similar
risk of myocardial infarction as persons in the general
population with established coronary disease.24 This
has primarily been evaluated in persons with type 2 dia-
betes (T2D) and has been an important basis for
whether they should receive more aggressive primary
preventive treatment. We found T1D to be a cardiovas-
cular risk equivalent with respect to AMI highlighting
he need for aggressive CVD prevention in this patient
group. For HF, the impact of renal complications was
even stronger than when AMI was evaluated.
Renal complications
Renal complications are a marker of past elevated glucose
levels and a key explanatory variable for excess mortality in
persons with T1D.1,15−18 The gap in mortality between per-
sons with T1D and the general population would likely con-
verge if mortality and cardiovascular risk could be reduced
in patients with renal complications. In the current study,
renal complications had a marked impact on mortality,
implying that aggressive prevention is needed at early
stages of renal complications.
Lower blood pressure and treatment with RAAS-
inhibitors are recommended for patients with renal
complications to reduce further renal progression.
Moreover, persons at high risk of AMI, stroke, and HF
likely benefit from very strict blood pressure control,
although this has been debated among people with
T2D.25 Lower blood lipid targets than the overall targets
of LDL 2.5 mmol/l (97 mg/dl) may be warranted for
individuals with T1D and renal complications who are
not yet on dialysis.
SGLT2-inhibitors have shown a preventive effect
regarding advanced renal complications, HF, and cardio-
vascular mortality not only in patients with T2D but also
in people without diabetes.26−30 Similar preventive
effects, not acting via the glucose-lowering effect, but
among other mechanisms via reduction of intraglomeru-
lar pressure are likewise beneficial for patients with
T1D.31 Future studies are needed to evaluate the effect of
SGLT-2 inhibitors in T1D persons with cardiovascular
and cardiorenal disease. As in T2D guidelines, clinicians
ought to characterize T1D patients as at high- or low-risk
to a greater extent.32 Moreover, other cardiorenal preven-
tive treatments need further investigation, including
finerenone which has shown beneficial effects in persons
with T2D and renal complications.33,34
Risk factors and cardiorenal complications
Persons with T1D free from cardiovascular and renal
complications showed slightly increased risk of AMI
compared with persons without diabetes. Hence, some
patients seem to convert from low-risk to high-risk via
AMI. When exploring traditional risk factors the stron-
gest association existed with glucose control. Patients
with historical mean HbA1c ≤7.5% (58 mmol/mol)
without cardiorenal complications had no excess risk of
AMI. The strong association between AMI and HbA1c
may be explained by other risk factors (hypertension
and LDL cholesterol levels) that were well-treated overall
whereas HbA1c 60−65 mmol/mol were nearly double
compared to levels in the general population in Sweden
with mean HbA1c 34 mmol/mol.
The importance of glucose control to prevent a
patient from converting to a high-risk profile is
supported by the fact that hyperglycemia is a prerequi-
site for diabetic nephropathy.3 Continuous glucose
monitoring (CGM) and advanced insulin pumps con-
necting CGM with an insulin pump for adjusting insu-
lin delivery may reduce cardiorenal complications by
improving glucose control. In a recent study including
patients from four countries, renal complications were
still common in patients with diabetes onset over the
last 20 years, and the majority of patients had glucose
levels above target.36 Hence, improved prevention in
people with T1D and cardiorenal complications should
be the focus of attention in clinical practice and research
to reduce the gap in mortality over time.
Strengths and limitations
A strength of the current study is the population-based
design comprising nearly all persons with T1D in Swe-
den over 2 decades including information on diabetes
complications and risk factors. This study has several
limitations. First, due to the registry-based study design,
it is inevitable that some data are missing, for example
information on renal complications was less compre-
hensive during the first 3 years of follow-up. Moreover,
coverage of the NDR in the first time periods was lower
but improved over time to include almost all persons
with T1D during the last decade. It should also be
acknowledged that the NDR does not contain data
regarding race and ethnicity, so these variables were not
accounted for in the analyses. Second, information on
CVD in age- and sex-matched controls was available but
levels of blood pressure, blood lipids, BMI, and smoking
were not. Third, information about renal complications
was not available in controls, although renal complica-
tions are known to be relatively rare in persons without
diabetes. Fourth, information on use of medication to
prevent and treat renal complications and hyperlipid-
emia were not considered in the analysis. This may be
of interest in future analyses, especially in high risk
patients. Finally, in real-life evaluations as the current,
data registration depends on when examinations are
performed in clinical practice and not evaluated at spe-
cific predefined time points.
Conclusions
Mortality and cardiovascular disease prognosis is
improving in persons with T1D but clear excess risks
remain overall compared with individuals without dia-
betes. With respect to mortality, the prognosis of per-
sons with T1D and without cardiorenal complications is
similar to persons without diabetes. Increased focus on
prevention in patients with renal complications, and
improved glucose control in the T1D population overall,
are likely key factors to reducing the overall gap in mor-
tality for persons with T1D compared with the general
population. Accordingly, a differentiated treatment
focus is needed in future care of T1D patients.
