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Hospitalisation from seasonal influenza
among persons with type 1 diabetes: a
cohort study from the Swedish National
Diabetes Register
Elin Allansson Kjölhede ,1,2 Hanne Krage Carlsen,3 Oliver Martyn,4
Lena Svensson, 5 Magnus Gisslén,6,7 Björn Eliasson,1,3 Katarina Eeg-Olofsson
STRENGTHS AND LIMITATIONS OF THIS STUDY
⇒ A nationwide cohort of persons with type 1 diabetes
and a control group of persons match for age, sex
and county of residence from the general population.
⇒ National identification numbers were used to cross-
link nationwide databases with information about
hospital diagnoses for previous comorbidities and
outcomes, as well as information about socioeco-
nomic factors.
ABSTRACT
Objectives
The aim of this study was to investigate the
risk of severe influenza resulting in hospitalisation among
adults with type 1 diabetes (T1D).
Design
Nationwide cohort study using register data.
Settings
Data from the National Diabetes Register (NDR)
linked to the Swedish Patient Register, Statistics Sweden
and the Swedish Population Register.
Participants
Persons with T1D in the Swedish NDR
n=35 596 and control persons from the Swedish Population
Register matched on age, sex and county of residence,
n=155 590.
Primary and secondary outcomes
Hospitalisation from
seasonal influenza from October 2013 to December 2019.
Season-wise incidence and HRs were analysed in the T1D
group compared with controls. Secondary outcomes were
associations between clinical variables and hospitalisation
due to seasonal influenza for persons with T1D.
Results
There were 347 (1.0%) influenza admissions in
persons with T1D and 332 (0.2%) in the control group. The
overall incidence rate was 16.9/10 000 person-years in
the T1D group and 3.6/10 000 person-years for the control
group.
Persons with T1D had an unadjusted HR 4.7 (95%
CI 4.0 to 5.5) for risk of hospitalisation from influenza
during the study period and HR 3.4 (95% CI 2.9 to 4.0)
when adjusted for age, sex, socioeconomic factors and
chronic medical conditions at baseline.
Within the T1D
cohort, individuals hospitalised due to influenza were older,
were more often smokers, had lower glomerular filtration
rate and more often had a previous history of ischaemic
heart disease and stroke.
Conclusions
To our knowledge, this is the first large
study to highlight that persons with T1D have a threefold
higher risk of hospitalisation due to seasonal influenza
compared with matched controls from the general
population.
It is important for healthcare professionals to
acknowledge this excess risk, particularly in older persons
with T1D, who have cardiovascular risk factors and
reduced kidney function.
Prepublication history
and additional supplemental
material for this paper are
available online. To view these
files, please visit the journal
online
https://doi.org/10.1136/
bmjopen-2024-084165
From Discussion
Our study demonstrates that persons with type 1 diabetes
face a threefold higher risk of hospitalisation due to
seasonal influenza compared with age-matched and sex-
matched controls from the general population.
Further-
more, we observed that persons with type 1 diabetes who
were hospitalised for influenza were older, had longer
diabetes duration and had lower kidney function. Also,
they were more often smokers and more often had a
history of cardiovascular disease than those not hospital-
ised for influenza.
Although the absolute risk of hospi-
talisation from influenza was low, the high relative risk
compared with controls remained after adjusting for
socioeconomic factors and comorbidities. The study
results also showed elevated incidence rates in persons
with type 1 diabetes considered to be in high influenza
risk groups due to age and comorbidities.
The results of our study are consistent with previous
findings reported by Muller et al20 with higher risk of
lower respiratory tract infection in type 1 diabetes. The
threefold risk of influenza-related hospitalisation found
in our study is in also line with the findings by Chaudhry
et al21 demonstrating a threefold excess risk (incidence
rate ratio 2.9) for lower respiratory infection. Carey et
al3 found an almost fourfold increased risk for infection-
related hospitalisation in type 1 diabetes compared with
the general population (incidence rate ratio 3.7). Benfield
et al22 have shown that both diabetes and hyperglycaemia
were associated with risk of hospitalisation from infec-
tions, including pneumonia. The increased risk of hospi-
talisation from influenza in type 1 diabetes might be due
to both increased vulnerability to the infection and risk
of acute complications due to the underlying diabetes
illness, for example, difficulty to adapt to changes in
insulin dosage during the infection.
Investigated metabolic variables within the group with
type 1 diabetes showed that
• lower eGFR,
• higher HbA1c, as
• well as higher triglycerides and
• low HDL,
were associated
with increased risk of hospitalisation from influenza.
This
is in accordance with findings seen in persons afflicted by
severe SARS- CoV-223 24 suggesting that lipid metabolism
may have an impact on the body’s response to infections
or that lipid elevations reflect comorbidities that increase
the risk of severe infections. Further investigation into the
clinical significance and mechanisms is warranted. Our
data did not show a linear association between levels of
HbA1c and risk of hospitalisation from seasonal influ-
enza although there was significantly higher risk among
those with the highest HbA1c. The same pattern was
seen among persons with type 1 diabetes in the recently
published study by Hopkins et al.25 In the study by Breit-
ling,26 the same pattern in HbA1c was observed but that
study did not separate between type 1 and type 2 diabetes.
It is worth noting that other studies, such as Hulme et al,27
Marshall et al28 and Papachristoforou et al29 have indicated
that it might be glucose variability that affects the suscep-
tibility to severe infections rather than a high HbA1c as
such. Unfortunately, our study does not contain informa-
tion regarding glucose variability in our diabetes cohort,
as this was not yet reported to the Swedish NDR during
the studied period.
Our study benefits from a large nationwide cohort, and
the ability to, via national identification numbers, cross-
link several nationwide databases with information about
all diagnoses on admission and discharge from Swedish
hospitals as well as information about socioeconomic
factors. In addition, we have detailed diabetes-related
information on most persons living with type 1 diabetes
in Sweden from the Swedish NDR.
A weakness of our study is the fact that information on
discharge diagnoses is based on reported diagnoses from
hospital records and we do not have access to the actual
hospital records and cannot verify the diagnoses. The
absolute number of hospitalised persons with influenza
is low in our study, this might be due to missed diagnoses
on discharge from the hospitals, however, the potentially
missed diagnoses ought to equally common in persons
with diabetes and their controls. Though there were
missing data on clinical variables that might influence
the result of risk factor analyses, we refrain from using
imputation methods as we are not confident that analysis
of imputed data will improve the quality of the results.
Another important limitation is the lack of information
on vaccination status in both persons with diabetes and
controls. At a national level, vaccination records were not
yet digitalised during the study period, and therefore,
not included in the study. However, this could be an area
for future research due to improvements in vaccination
status registration in Swedish regions following the SARS-
CoV-2 pandemic.
The findings in this study with increased risk of hospi-
talisation from influenza in type 1 diabetes support the
current vaccination recommendations from WHO,30
European Centre for Disease Prevention and Control31
and the Centers for Disease Control and Prevention 32 in
the USA and the Public Health Agency of Sweden.14
To conclude, to our knowledge, this is the first large
study to focus on persons with type 1 diabetes and risk of
hospitalisation from seasonal influenza.
The study shows
a threefold higher risk of hospitalisation due to seasonal
influenza in persons with type 1 diabetes compared with
matched controls from the general population. Although
we did not include vaccines in our study, the increased
risk observed underlines the importance of adherence to
evidence-based risk reduction measures such as vaccina-
tions, particularly in older persons with type 1 diabetes,
who have cardiovascular risk factors and reduced kidney
function.
_______________________________
Mer
T1DM och T2DM och sjukhusvård för Covid-19 Magnus Gisslen m fl. NDR data
Lancet Reg Health
Läs artikeln free pdf
https://pubmed.ncbi.nlm.nih.gov/33969336/
Severe COVID-19 in people with type 1 and type 2 diabetes in Sweden: A nationwide retrospective cohort study
Aidin Rawshani 1 2 3 , Elin Allansson Kjölhede 1 3 , Araz Rawshani 1 2 3 , Naveed Sattar 4 , Katarina Eeg-Olofsson 1 3 , Martin Adiels 1 2 3 , Johnny Ludvigsson 5 , Marcus Lindh 1 , Magnus Gisslén 3 6 , Eva Hagberg 1 3 , Georgios Lappas 1 , Björn Eliasson 1 3 , Annika Rosengren 1 2 3
Abstract
Background: Whether infection with SARS-CoV-2 leads to excess risk of requiring hospitalization or intensive care in persons with diabetes has not been reported, nor have risk factors in diabetes associated with increased risk for these outcomes.
Methods:
We included 44,639 and 411,976 adult patients with type 1 and type 2 diabetes alive on Jan 1, 2020, and compared them to controls matched for age, sex, and county of residence (n=204,919 and 1,948,900). Age- and sex-standardized rates for COVID-19 related hospitalizations, admissions to intensive care and death, were estimated and hazard ratios were calculated using Cox regression analyses.
Findings:
There were 10,486 hospitalizations and 1,416 admissions into intensive care. A total of 1,175 patients with diabetes and 1,820 matched controls died from COVID-19, of these 53•2% had been hospitalized and 10•7% had been in intensive care. Patients with type 2 diabetes, compared to controls, displayed an age- and sex-adjusted hazard ratio (HR) of 2•22, 95%CI 2•13-2•32) of being hospitalized for COVID-19, which decreased to HR 1•40, 95%CI 1•34-1•47) after further adjustment for sociodemographic factors, pharmacological treatment and comorbidities, had higher risk for admission to ICU due to COVID-19 (age- and sex-adjusted HR 2•49, 95%CI 2•22-2•79, decreasing to 1•42, 95%CI 1•25-1•62 after adjustment, and increased risk for death due to COVID-19 (age- and sex-adjusted HR 2•19, 95%CI 2•03-2•36, complete adjustment 1•50, 95%CI 1•39-1•63). Age- and sex-adjusted HR for COVID-19 hospitalization for type 1 diabetes was 2•10, 95%CI 1•72-2•57), decreasing to 1•25, 95%CI 0•3097-1•62) after adjustment• Patients with diabetes type 1 were twice as likely to require intensive care for COVID-19, however, not after adjustment (HR 1•49, 95%CI 0•75-2•92), and more likely to die (HR 2•90, 95% CI 1•6554-5•47) from COVID-19, but not independently of other factors (HR 1•38, 95% CI 0•64-2•99). Among patients with diabetes, elevated glycated hemoglobin levels were associated with higher risk for most outcomes.
Interpretation:
In this nationwide study, type 2 diabetes was independently associated with increased risk of hospitalization, admission to intensive care and death for COVID-19. There were few admissions into intensive care and deaths in type 1 diabetes, and although hazards were significantly raised for all three outcomes, there was no independent risk persisting after adjustment for confounding factors.
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T1DM HbA1c and CGM data
Diabetes Ther
https://pubmed.ncbi.nlm.nih.gov/38598054/
. 2024 Jun;15(6):1301-1312.
doi: 10.1007/s13300-024-01572-z. Epub 2024 Apr 10.
Associations Between HbA1c and Glucose Time in Range Using Continuous Glucose Monitoring in Type 1 Diabetes: Cross-Sectional Population-Based Study
Björn Eliasson 1 2 , Elin Allansson Kjölhede 3 4 , Sofia Salö 5 , Nick Fabrin Nielsen 6 , Katarina Eeg-Olofsson 3 7 4
Abstract
Introduction:
Continuous glucose monitoring (CGM) introduces novel indicators of glycemic control.
Methods:
This cross-sectional study, based on the Swedish National Diabetes Register, examines 27,980 adults with type 1 diabetes. It explores the relationships between HbA1c (glycated hemoglobin) and various CGM-derived metrics, including TIR (time in range, representing the percentage of time within the range of 4-10 mmol/l for 2 weeks), TAR (time above range), TBR (time below range), mean glucose, standard deviation (SD), and coefficient of variation (CV). Pearson correlation coefficients and linear regression models were utilized for estimation.
Results:
The analysis included 46% women, 30% on insulin pump, 7% with previous coronary heart disease and 64% with retinopathy. Mean ± SD values were age 48 ± 18 years, diabetes duration 25 ± 16 years, HbA1c 58.8 ± 12.8 mmol/mol, TIR 58.8 ± 19.0%, TAR 36.3 ± 20.0%, TBR 4.7 ± 5.4%, mean sensor glucose 9.2 ± 2.0 mmol/l, SD 3.3 ± 1.0 mmol/l, and CV 36 ± 7%. The overall association between HbA1c and TIR was – 0.71 (Pearson’s r), with R2 0.51 in crude linear regression and 0.57 in an adjusted model. R2 values between HbA1c and CGM mean glucose were 0.605 (unadjusted) 0.619 (adjusted) and TAR (unadjusted 0.554 and fully adjusted 0.568, respectively), while fully adjusted R2 values were 0.458, 0.175 and 0.101 between HbA1c and CGM SD, CGM CV and TBR, respectively.
Conclusions:
This descriptive study demonstrates that the degree of association between HbA1c and new and readily available CGM-derived metrics, i.e., time in range (TIR), time above range (TAR), and CGM mean glucose, is robust in assessing the management of individuals with type 1 diabetes in clinical settings. Metrics from CGM that pertain to variability and hypoglycemia exhibit only weak correlations with HbA1c.
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