To compare the validity and robustness of five methods for handling missing characteristics when using cardiovascular disease risk prediction models for individual patients in a real-world clinical ...setting.
The performance of the missing data methods was assessed using data from the Swedish National Diabetes Registry (n = 419,533) with external validation using the Scottish Care Information ˗ diabetes database (n = 226,953). Five methods for handling missing data were compared. Two methods using submodels for each combination of available data, two imputation methods: conditional imputation and median imputation, and one alternative modeling method, called the naïve approach, based on hazard ratios and populations statistics of known risk factors only. The validity was compared using calibration plots and c-statistics.
C-statistics were similar across methods in both development and validation data sets, that is, 0.82 (95% CI 0.82–0.83) in the Swedish National Diabetes Registry and 0.74 (95% CI 0.74–0.75) in Scottish Care Information-diabetes database. Differences were only observed after random introduction of missing data in the most important predictor variable (i.e., age).
Validity and robustness of median imputation was not dissimilar to more complex methods for handling missing values, provided that the most important predictor variables, such as age, are not missing.
To estimate the number of deaths attributable to diabetes in 20–79-year-old adults in 2019.
The following were used to estimate the number of deaths attributable to diabetes: all-cause mortality ...estimates from the World Health Organization life table, country level age- and sex-specific estimates of diabetes prevalence in 2019 and relative risks of death in people with diabetes compared to people without diabetes.
An estimated 4.2 million deaths among 20–79-year-old adults are attributable to diabetes. Diabetes is estimated to contribute to 11.3% of deaths globally, ranging from 6.8% (lowest) in the Africa Region to 16.2% (highest) in the Middle East and North Africa. About half (46.2%) of the deaths attributable to diabetes occur in people under the age of 60 years. The Africa Region has the highest (73.1%) proportion of deaths attributable to diabetes in people under the age of 60 years, while the Europe Region has the lowest (31.4%).
Diabetes is estimated to contribute to one in nine deaths among adults aged 20–79 years. Prevention of diabetes and its complications is essential, particularly in middle-income countries, where the current impact is estimated to be the largest. Contemporary data from diverse populations are needed to validate these estimates.
Aims/hypothesis
The aim of this study was to investigate the risks of all-cause and cause-specific mortality among participants with neither, one or both of diabetes and depression in a large ...prospective cohort study in the UK.
Methods
Our study population included 499,830 UK Biobank participants without schizophrenia and bipolar disorder at baseline. Type 1 and type 2 diabetes and depression were identified using self-reported diagnoses, prescribed medication and hospital records. Mortality was identified from death records using the primary cause of death to define cause-specific mortality. We performed Cox proportional hazards models to estimate the risk of all-cause mortality and mortality from cancer, circulatory disease and causes of death other than circulatory disease or cancer among participants with either depression (
n
=41,791) or diabetes (
n
=22,677) alone and with comorbid diabetes and depression (
n
=3597) compared with the group with neither condition (
n
=431,765), adjusting for sociodemographic and lifestyle factors, comorbidities and history of CVD or cancer. We also investigated the interaction between diabetes and depression.
Results
During a median of 6.8 (IQR 6.1–7.5) years of follow-up, there were 13,724 deaths (cancer,
n
=7976; circulatory disease,
n
=2827; other causes,
n
=2921). Adjusted HRs of all-cause mortality and mortality from cancer, circulatory disease and other causes were highest among people with comorbid depression and diabetes (HRs 2.16 95% CI 1.94, 2.42; 1.62 95% CI 1.35, 1.93; 2.22 95% CI 1.80, 2.73; and 3.60 95% CI 2.93, 4.42, respectively). The risks of all-cause, cancer and other mortality among those with comorbid depression and diabetes exceeded the sum of the risks due to diabetes and depression alone.
Conclusions/interpretation
We confirmed that depression and diabetes individually are associated with an increased mortality risk and also identified that comorbid depression and diabetes have synergistic effects on the risk of all-cause mortality that are largely driven by deaths from cancer and causes other than circulatory disease and cancer.
Graphical abstract
Aims/hypothesis
Data on type 1 diabetes incidence and prevalence are limited, particularly for adults. This study aims to estimate global numbers of incident and prevalent cases of type 1 diabetes in ...2017 for all age groups, by country and areas defined by income and region.
Methods
Incidence rates of type 1 diabetes in children (available from 94 countries) from the IDF Atlas were used and extrapolated to countries without data. Age-specific incidence rates in adults (only known across full age range for fewer than ten countries) were obtained by applying scaling ratios for each adult age group relative to the incidence rate in children. Age-specific incidence rates were applied to population estimates to obtain incident case numbers. Duration of diabetes was estimated from available data and adjusted using differences in childhood mortality rate between countries from United Nations demographic data. Prevalent case numbers were derived by modelling the relationship between prevalence, incidence and disease duration. Sensitivity analyses were performed to quantify the impact of alternative assumptions and model inputs.
Results
Global numbers of incident and prevalent cases of type 1 diabetes were estimated to be 234,710 and 9,004,610, respectively, in 2017. High-income countries, with 17% of the global population, accounted for 49% of global incident cases and 52% of prevalent cases. Asia, which has the largest proportion of the world’s population (60%), had the largest number of incident (32%) and prevalent (31%) cases of type 1 diabetes. Globally, 6%, 35%, 43% and 16% of prevalent cases were in the age groups 0–14, 15–39, 40–64 and 65+ years, respectively. Based on sensitivity analyses, the estimates could deviate by ±15%.
Conclusions
/
interpretation
Globally, type 1 diabetes represents about 2% of the estimated total cases of diabetes, ranging from less than 1% in certain Pacific countries to more than 15% in Northern European populations in 2017. This study provides information for the development of healthcare and policy approaches to manage type 1 diabetes. The estimates need further validation due to limitations and assumptions related to data availability and estimation methods.
Graphical abstract
To provide global, regional, and country-level estimates of diabetes prevalence and health expenditures for 2021 and projections for 2045.
A total of 219 data sources meeting pre-established quality ...criteria reporting research conducted between 2005 and 2020 and representing 215 countries and territories were identified. For countries without data meeting quality criteria, estimates were extrapolated from countries with similar economies, ethnicity, geography and language. Logistic regression was used to generate smoothed age-specific diabetes prevalence estimates. Diabetes-related health expenditures were estimated using an attributable fraction method. The 2021 diabetes prevalence estimates were applied to population estimates for 2045 to project future prevalence.
The global diabetes prevalence in 20–79 year olds in 2021 was estimated to be 10.5% (536.6 million people), rising to 12.2% (783.2 million) in 2045. Diabetes prevalence was similar in men and women and was highest in those aged 75–79 years. Prevalence (in 2021) was estimated to be higher in urban (12.1%) than rural (8.3%) areas, and in high-income (11.1%) compared to low-income countries (5.5%). The greatest relative increase in the prevalence of diabetes between 2021 and 2045 is expected to occur in middle-income countries (21.1%) compared to high- (12.2%) and low-income (11.9%) countries. Global diabetes-related health expenditures were estimated at 966 billion USD in 2021, and are projected to reach 1,054 billion USD by 2045.
Just over half a billion people are living with diabetes worldwide which means that over 10.5% of the world’s adult population now have this condition.
Context:
Fatty liver is associated with an increased risk of type 2 diabetes, but whether an increased risk remains in people in whom fatty liver resolves over time is not known.
Objective:
The ...objective of the study was to assess the risk of incident diabetes at a 5-year follow-up in people in whom: 1) new fatty liver developed; 2) existing fatty liver resolved, and 3) fatty liver severity worsened over 5 years.
Design and Methods:
A total of 13 218 people without diabetes at baseline from a Korean occupational cohort were examined at baseline and after 5 years, using a retrospective study design. Fatty liver status was assessed at baseline and follow-up as absent, mild, or moderate/severe using standard ultrasound criteria. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for incident diabetes at follow-up were estimated after controlling for multiple potential confounders.
Results:
Two hundred thirty-four people developed incident diabetes. Over 5 years, fatty liver resolved in 828, developed in 1640, and progressed from mild to moderate/severe in 324 people. Resolution of fatty liver was not associated with a risk of incident diabetes aOR 0.95 (95% CIs 0.46, 1.96), P = .89. Development of new fatty liver was associated with incident diabetes aOR 2.49 (95% CI 1.49, 4.14), P < .001. In individuals in whom severity of fatty liver worsened over 5 years (from mild to moderate/severe), there was a marked increase in the risk of incident diabetes aOR 6.13 (2.56, 95% CI 14.68) P < .001 (compared with the risk in people with resolution of fatty liver).
Conclusion:
Change in fatty liver status over time is associated with markedly variable risks of incident diabetes.
Studies using claims databases reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection >30 days earlier was associated with an increase in the incidence of type 1 ...diabetes. Using exact dates of diabetes diagnosis from the national register in Scotland linked to virology laboratory data, we sought to replicate this finding.
A cohort of 1,849,411 individuals aged <35 years without diabetes, including all those in Scotland who subsequently tested positive for SARS-CoV-2, was followed from 1 March 2020 to 22 November 2021. Incident type 1 diabetes was ascertained from the national registry. Using Cox regression, we tested the association of time-updated infection with incident diabetes. Trends in incidence of type 1 diabetes in the population from 2015 through 2021 were also estimated in a generalized additive model.
There were 365,080 individuals who had at least one detected SARS-CoV-2 infection during follow-up and 1,074 who developed type 1 diabetes. The rate ratio for incident type 1 diabetes associated with first positive test for SARS-CoV-2 (reference category: no previous infection) was 0.86 (95% CI 0.62, 1.21) for infection >30 days earlier and 2.62 (95% CI 1.81, 3.78) for infection in the previous 30 days. However, negative and positive SARS-CoV-2 tests were more frequent in the days surrounding diabetes presentation. In those aged 0-14 years, incidence of type 1 diabetes during 2020-2021 was 20% higher than the 7-year average.
Type 1 diabetes incidence in children increased during the pandemic. However, the cohort analysis suggests that SARS-CoV-2 infection itself was not the cause of this increase.
Life expectancy is increasing in some countries and declining in others.1 Age-standardised cardiovascular disease incidence and mortality are declining in many populations, with more marked declines ...in more developed countries.2 However, more people die each year from cardiovascular disease than any other cause, with 31% of global deaths attributed to cardiovascular disease, partly as a consequence of increasing population size and ageing.3 Risk factor prevalence and the strength of associations between risk factors and cardiovascular disease and mortality are reasonably well described in high-income countries (HICs), but data for middle-income countries (MICs) and low-income countries (LICs) are more scarce. The WHO “STEPwise approach to surveillance” facilitates collection of comparable information on risk factor prevalence across countries but does not investigate associations with outcomes.4 The Global Burden of Disease Study provides national, regional, and global estimates of the burden of cardiovascular disease by modelling available data from heterogeneous sources over a wide time frame.1,2 It uses extensive extrapolation to cover countries for which data are not available, and most of these countries are LICs and MICs. The findings from the PURE study5 that indicate a large proportion of cardiovascular disease events and mortality can be attributed to a small number of modifiable risk factors are consistent with and extend the findings from several other large studies, including the Global Burden of Disease,2 INTERSTROKE,6 and INTERHEART studies.7 Taken together, the findings highlight the potential for further improvements in prevention of cardiovascular disease and premature mortality across the globe, through reductions in modifiable risk factors.
OBJECTIVE: There is dissociation between insulin resistance, overweight/obesity, and fatty liver as risk factors for type 2 diabetes, suggesting that different mechanisms are involved. Our aim was to ...1) quantify risk of incident diabetes at follow-up with different combinations of these risk factors at baseline and 2) determine whether each is an independent risk factor for diabetes. RESEARCH DESIGN AND METHODS: We examined 12,853 subjects without diabetes from a South Korean occupational cohort, and insulin resistance (IR) (homeostasis model assessment-IR ≥75th centile, ≥2.0), fatty liver (defined by standard ultrasound criteria), and overweight/obesity (BMI ≥25 kg/m2) identified at baseline. Odds ratios (ORs) and 95% confidence intervals (CIs) for incident diabetes at 5-year follow-up were estimated using logistic regression. RESULTS: We identified 223 incident cases of diabetes from which 26 subjects had none of the three risk factors, 37 had one, 56 had two, and 104 had three. In the fully adjusted model, the OR and CI for diabetes were 3.92 (2.86–5.37) for IR, 1.62 (1.17–2.24) for overweight/obesity, and 2.42 (1.74–3.36) for fatty liver. The OR for the presence of all three factors in a fully adjusted model was 14.13 (8.99–22.21). CONCLUSIONS: The clustering of IR, overweight/obesity, and fatty liver is common and markedly increases the odds of developing type 2 diabetes, but these factors also have effects independently of each other and of confounding factors. The data suggest that treatment for each factor is needed to decrease risk of type 2 diabetes.
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