Empagliflozin Use Is Associated With Lower Risk of All-Cause Mortality, Hospitalization for Heart Failure, and End-Stage Renal Disease Compared to DPP-4i in Nordic Type 2 Diabetes Patients: Results From the EMPRISE (Empagliflozin Comparative Effectiveness and Safety) Study.

Objective: To evaluate the effectiveness of empagliflozin in reducing all-cause mortality (ACM), hospitalization for heart failure (HHF), myocardial infarction (MI), stroke, cardiovascular mortality (CVM), and end-stage renal disease (ESRD) in routine clinical practice in the Nordic countries of the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) study. Methods: This noninterventional, multicountry cohort study used secondary data from four Nordic countries (Denmark, Sweden, Finland, and Norway). Propensity score (PS) matched (1:1) adults with type 2 diabetes (T2D) initiating empagliflozin (a sodium-glucose cotransporter-2 inhibitor) during 2014-2018 who were compared to those initiating a dipeptidyl peptidase-4 inhibitor (DPP-4i). Cox proportional hazards regression modelling was used to assess the risk for ACM, HHF, MI, stroke, CVM, and ESRD. Meta-analyses were conducted and hazard ratios (HRs) with 95% confidence intervals (CIs) from random-effects models were calculated. Results: A total of 43,695 pairs of PS-matched patients were identified. Patients initiating empagliflozin exhibited a 49% significantly lower risk of ACM (HR: 0.51, 95% CI 0.40-0.64) compared to DPP-4i. Additionally, empagliflozin was associated with a 36% significantly lower risk of HHF (HR: 0.64, 95% CI 0.46-0.89), a 52% significantly lower risk of CVM (HR: 0.48, 95% CI 0.37-0.63), and a 66% significantly lower risk of ESRD (HR: 0.34, 95% CI 0.15-0.77) compared to DPP-4i. No significant differences were observed in the risk of stroke and MI between patients initiating empagliflozin compared with those initiating a DPP-4i. Results were generally consistent for subgroups (with/without pre-existing CV disease or congestive heart failure) and in sensitivity analyses. Conclusion: Empagliflozin initiation was associated with a significantly reduced risk of ACM, HHF, CVM, and ESRD compared with initiation of DPP-4i in patients with T2D when examining routine clinical practice data from Nordic countries.

Impact of type 2 diabetes and its duration on incidence rates of dementia death and medication prescription in the Australian population during 2003-2016.

AIMS: To quantify rates of dementia treatment and death among Australians with type 2 diabetes relative to those without diabetes using linked national registries of Australia. METHODS: The study included 891,418 people with type 2 diabetes registered on the National Diabetes Services Scheme and a randomly sampled, population-based comparison group (n = 1,131,369). Outcomes included dementia death (all-cause dementia, Alzheimer's disease (AD) or vascular dementia), and first prescription of cholinesterase inhibitors or memantine. RESULTS: Excess dementia risk was observed in the diabetes group for the composite outcome of all-cause dementia death or dementia medication prescription but varied with age at diabetes diagnosis and its duration. At age 70, the rate of dementia death/medication prescription was ∼1.3 (95% CI 1.2, 1.3) and 1.1 (95% CI 1.1, 1.2) times higher in people with ten and five years of diabetes duration, respectively. Individual outcomes showed that diabetes was associated with a higher incidence of vascular dementia death, whereas an increased risk of AD death was only observed beyond âˆ¼10 years of diabetes duration. Further, the incidence of dementia medication prescription was lower among people with diabetes. CONCLUSIONS: A higher incidence of AD death in the setting of 10+ years of diabetes duration coupled with a lower incidence of AD treatment suggests an under-recognition of this dementia phenotype among people with type 2 diabetes.

Evaluating the incidence of complications among people with diabetes according to age of onset: Findings from the UK Biobank.

AIMS: To examine the impact of current age, age at diagnosis, and duration of diabetes on the incidence rate of complications among people with type 2 diabetes. METHODS: Baseline data from 19,327 individuals with type 2 diabetes in the UK Biobank were analysed. Poisson regression was used to model incidence rates by current age, age at diagnosis, and duration of diabetes for the following outcomes: myocardial infarction (MI), heart failure (HF), stroke, end-stage kidney diseases (ESKD), chronic kidney diseases (CKD), liver diseases, depression, and anxiety. RESULTS: The mean age at baseline was 60.2 years, and median follow-up was 13.9 years. Diabetes duration was significantly longer among those with younger-onset type 2 diabetes (diagnosed at <40 years) compared to later-onset type 2 diabetes (diagnosed at ≥40 years), 16.2 and 5.3 years, respectively. Incidence rates of MI, HF, stroke, and CKD had strong positive associations with age and duration of diabetes, whereas incidence rates of ESKD liver diseases, and anxiety mainly depended on duration of diabetes. The incidence rates of depression showed minor variation by age and duration of diabetes and were highest among those diagnosed at earlier ages. No clear evidence of an effect of age of onset of diabetes on risk of complications was apparent after accounting for current age and duration of diabetes. CONCLUSIONS: Our study indicates age at diagnosis of diabetes does not significantly impact the incidence of complications, independently of the duration of diabetes. Instead, complications are primarily influenced by current age and diabetes duration.

Trends in Incidence of Hospitalization for Hypoglycemia and Diabetic Ketoacidosis in Individuals With Type 1 or Type 2 Diabetes With and Without Severe Mental Illness in Denmark From 1996 to 2020: A Nationwide Study.

OBJECTIVE: To examine trends in incidence of acute diabetes complications in individuals with type 1 or type 2 diabetes with and without severe mental illness (SMI) in Denmark by age and calendar year. RESEARCH DESIGN AND METHODS: We conducted a cohort study using nationwide registers from 1996 to 2020 to identify individuals with diabetes, ascertain SMI status (namely, schizophrenia, bipolar disorder, or major depression) and identify the outcomes: hospitalization for hypoglycemia and diabetic ketoacidosis (DKA). We used Poisson regression to estimate incidence rates (IRs) and incidence rate ratios (IRRs) of recurrent hypoglycemia and DKA events by SMI, age, and calendar year, accounting for sex, diabetes duration, education, and country of origin. RESULTS: Among 433,609 individuals with diabetes, 8% had SMI. Risk of (first and subsequent) hypoglycemia events was higher for individuals with SMI than for those without SMI (for first hypoglycemia event, IRR: type 1 diabetes, 1.77 [95% CI 1.56-2.00]; type 2 diabetes, 1.64 [95% CI 1.55-1.74]). Individuals with schizophrenia were particularly at risk for recurrent hypoglycemia events. The risk of first DKA event was higher in individuals with SMI (for first DKA event, IRR: type 1 diabetes, 1.78 [95% CI 1.50-2.11]; type 2 diabetes, 1.85 [95% CI 1.64-2.09]). Except for DKA in the type 2 diabetes group, IR differences between individuals with and without SMI were highest in younger individuals (<50 years old) but stable across the calendar year. CONCLUSIONS: SMI is an important risk factor for acute diabetes complication and effective prevention is needed in this population, especially among the younger population and those with schizophrenia.

Statistical models for assessing agreement for quantitative data with heterogeneous random raters and replicate measurements.

Agreement between methods for quantitative measurements are typically assessed by computing limits of agreement between pairs of methods and/or by illustration through Bland-Altman plots. We consider the situation where the observed measurement methods are considered a random sample from a population of possible methods, and discuss how the underlying linear mixed effects model can be extended to this situation. This is relevant when, for example, the methods represent raters/judges that are used to score specific individuals or items. In the case of random methods, we are not interested in estimates pertaining to the specific methods, but are instead interested in quantifying the variation between the methods actually involved making measurements, and accommodating this as an extra source of variation when generalizing to the clinical performance of a method. In the model we allow raters to have individual precision/skill and permit linked replicates (i.e., when the numbering, labeling or ordering of the replicates within items is important). Applications involving estimation of the limits of agreement for two datasets are shown: A dataset of spatial perception among a group of students as well as a dataset on consumer preference of French chocolate. The models are implemented in the MethComp package for R [Carstensen B, Gurrin L, Ekstrøm CT, Figurski M. MethComp: functions for analysis of agreement in method comparison studies; 2013. R package version 1.22, R Core Team. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2012].

Christmas article: Snacking preferences at the office during the Christmas season ­ a secret intervention study among diabetes researchers.

Introduction To quantify the effect of Christmas vs. New Year's resolutions season on snacking preferences by measuring intake of four different snacks. Methods Prospective ad libitum intervention snacking study with four combinations of sweet/savory and fatty/non-fatty snacks: cookies, candy, TUC crackers, and rye crackers. A snacking buffet, continuously refilled by a secret Santa, was provided during the Christmas season and New Year's Resolutions season by the secret Santas of the office. Participants were diabetes researchers and were not informed about the study before the end of data collection. The main outcome was daily intake (g) of the four snacks. Results In general, the intake of candy was high compared to the other snacks. The average intake of cookies was significantly higher during the Christmas season compared to New Year's resolution season (8 g/day/participant, p = 0.03), but decreased when approaching Christmas and increased again as time passed by after Christmas (although not significantly). The strongest correlation between the intake of snacks was found between the two sweet snacks, i.e., candy and cookies. Conclusion Researchers have a high preference for sweet foods, especially candy. Irrespective of the type of snack, the preference for cookies was high during the Christmas season but seemed to decrease with decreasing proximity to Christmas, hence, canceling Christmas will unlikely improve diet quality. In fact, we encourage further research to consider whether having Christmas all year could be a potential prevention strategy in the combat of the obesity pandemic. Funding none. Trial registration none.

Glucose Monitoring Metrics in Individuals With Type 1 Diabetes Using Different Treatment Modalities: A Real-World Observational Study.

OBJECTIVE: This study aimed to investigate the association between continuous glucose monitoring (CGM)-derived glycemic metrics and different insulin treatment modalities using real-world data. RESEARCH DESIGN AND METHODS: A cross-sectional study at Steno Diabetes Center Copenhagen, Denmark, included individuals with type 1 diabetes using CGM. Data from September 2021 to August 2022 were analyzed if CGM was used for at least 20% of a 4-week period. Individuals were divided into four groups: multiple daily injection (MDI) therapy, insulin pumps with unintegrated CGM (SUP), sensor-augmented pumps with low glucose management (SAP), and automated insulin delivery (AID). The MDI and SUP groups were further subdivided based on CGM alarm features. The primary outcome was percentage of time in range (TIR: 3.9-10.0 mmol/L) for each treatment group. Secondary outcomes included other glucose metrics and HbA1c. RESULTS: Out of 6,314 attendees, 3,184 CGM users were included in the analysis. Among them, 1,622 used MDI, 504 used SUP, 354 used SAP, and 561 used AID. Median TIR was 54.0% for MDI, 54.9% for SUP, 62,9% for SAP, and 72,1% for AID users. The proportion of individuals achieving all recommended glycemic targets (TIR >70%, time above range <25%, and time below range <4%) was significantly higher in SAP (odds ratio [OR] 2.4 [95% CI 1.6-3.5]) and AID (OR 9.4 [95% CI 6.7-13.0]) compared with MDI without alarm features. CONCLUSIONS: AID appears superior to other insulin treatment modalities with CGM. Although bias may be present because of indications, AID should be considered the preferred choice for insulin pump therapy.

Empagliflozin is associated with lower cardiovascular risk compared with dipeptidyl peptidase-4 inhibitors in adults with and without cardiovascular disease: EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study results from Europe and Asia.

BACKGROUND: Studies that have reported lower risk for cardiovascular outcomes in users of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) are limited by residual cofounding and lack of information on prior cardiovascular disease (CVD). This study compared risk of cardiovascular events in patients within routine care settings in Europe and Asia with type 2 diabetes (T2D) initiating empagliflozin compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) stratified by pre-existing CVD and history of heart failure (HF). METHODS AND RESULTS: Adults initiating empagliflozin and DPP-4i in 2014-2018/19 from 11 countries in Europe and Asia were compared using propensity score matching and Cox proportional hazards regression to assess differences in rates of primary outcomes: hospitalisation for heart failure (HHF), myocardial infarction (MI), stroke; and secondary outcomes: cardiovascular mortality (CVM), coronary revascularisation procedure, composite outcome including HHF or CVM, and 3-point major adverse cardiovascular events (MACE: MI, stroke and CVM). Country-specific results were meta-analysed and pooled hazard ratios (HR) with 95% confidence intervals (CI) from random-effects models are presented. In total, 85,244 empagliflozin/DPP4i PS-matched patient pairs were included with overall mean follow-up of 0.7 years. Among those with pre-existing CVD, lower risk was observed for HHF (HR 0.74; 95% CI 0.64-0.86), CVM (HR 0.55; 95% CI 0.38-0.80), HHF or CVM (HR 0.57; 95% CI 0.48-0.67) and stroke (HR 0.79; 95% CI 0.67-0.94) in patients initiating empagliflozin vs DPP-4i. Similar patterns were observed among patients without pre-existing CVD and those with and without pre-existing HF. CONCLUSION: These results from diverse patient populations in routine care settings across Europe and Asia demonstrate that initiation of empagliflozin compared to DPP-4i results in favourable cardioprotective effects regardless of pre-existing CVD or HF status.

Time Trends in the Incidence of Diabetic Ketoacidosis Leading to Hospital Admission Among Adults With Type 1 Diabetes: A Nationwide Danish Register Study.

OBJECTIVE: Diabetic ketoacidosis (DKA) is a life-threatening but preventable complication in people with type 1 diabetes. We aimed to quantify the incidence of DKA according to age and describe the time trend of DKA among adults with type 1 diabetes in Denmark. RESEARCH DESIGN AND METHODS: Individuals aged ≥18 years with type 1 diabetes were identified from a nationwide Danish diabetes register. Hospital admissions due to DKA were ascertained from the National Patient Register. The follow-up period was from 1996 to 2020. RESULTS: The cohort consisted of 24,718 adults with type 1 diabetes. The incidence rate of DKA per 100 person-years (PY) decreased with increasing age for both men and women. From 20 to 80 years of age, the DKA incidence rate decreased from 3.27 to 0.38 per 100 PY. From 1996 to 2008, the incidence rate of DKA increased for all age-groups, with a subsequent minor decrease in incidence rate until 2020. From 1996 to 2008, the incidence rates increased from 1.91 to 3.77 per 100 PY for a 20-year-old individual and from 0.22 to 0.44 per 100 PY for an 80-year-old individual living with type 1 diabetes. From 2008 to 2020 the incidence rates decreased from 3.77 to 3.27 and from 0.44 to 0.38 per 100 PY, respectively. CONCLUSIONS: The incidence rates of DKA are declining for all ages, with an overall decline from 2008 for both men and women. This likely reflects improved diabetes management for individuals with type 1 diabetes in Denmark.

Glycaemic control, risk of hypoglycaemia and all-cause mortality in new users of second-generation basal insulin with type 2 diabetes and chronic kidney disease: a nationwide register-based cohort study.

AIMS/HYPOTHESIS: The aim of this study was to compare the performance of the second-generation basal insulins, insulin degludec 100 U/ml (Deg-100) and insulin glargine 300 U/ml (Gla-300), in terms of change in HbA1c, hospitalisation for hypoglycaemia and all-cause mortality among individuals with type 2 diabetes and concurrent chronic kidney disease. METHODS: This register-based cohort study, based on the entire Danish diabetes population, included 6519 new users of Deg-100 and Gla-300 with type 2 diabetes and moderate to end-stage chronic kidney disease. HbA1c trajectories, from initiation of either Deg-100 (2013) or Gla-300 (2015) to end of follow-up (2020), were modelled with mixed-effect models while rates of hospitalisation for hypoglycaemia and all-cause mortality were modelled in separate models using Poisson likelihood. RESULTS: Of the 6519 (44% women) individuals included in the study, 3747 were exposed to Deg-100 and 2772 to Gla-300. Both mean (SD) type 2 diabetes duration (14.4 [6.6] years vs 15.2 [6.7] years) and median (IQR) chronic kidney disease duration (2.3 [1.3, 3.9] years vs 2.8 [1.6, 4.6] years) were significantly shorter in the Gla-300 group. The median (IQR) follow-up time was similar between groups: 1.0 (0.5-1.6) year for Gla-300 and 1.0 (0.3-1.5) year for Deg-100. In both groups mean HbA1c levels were reduced by 13-14 mmol/mol (1.2-1.3%) from initiation to end of follow-up, with the largest reduction (of 8-9 mmol/mol [0.7-0.8%]) occurring during the first year. There was no significant difference in HbA1c reduction between Deg-100 and Gla-300. Both the rate of hospitalisation for hypoglycaemia (rate ratio 1.02 [95% CI 0.70, 1.49], Deg-100 vs Gla-300) and the rate of all-cause mortality (rate ratio 0.98 [95% CI 0.84, 1.15], Deg-100 vs Gla-300) were similar between the groups. CONCLUSIONS/INTERPRETATION: We found no difference in HbA1c reduction, hospitalisation for hypoglycaemia or all-cause mortality between Gla-300 and Deg-100 in a real-world population of new users with type 2 diabetes and moderate to end-stage chronic kidney disease. Therefore, we conclude that these two treatment options are equally effective and safe in this vulnerable population.

Trends in the Incidence of End-Stage Kidney Disease in Type 1 and Type 2 Diabetes in Australia, 2010-2019.

RATIONALE & OBJECTIVE: Trends in end-stage kidney disease (ESKD) among people with diabetes may inform clinical management and public health strategies. We estimated trends in the incidence of ESKD among people with type 1 and type 2 diabetes in Australia from 2010-2019 and evaluated their associated factors. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 71,700 people with type 1 and 1,112,690 people with type 2 diabetes registered on the Australian National Diabetes Services Scheme (NDSS). We estimated the incidence of kidney replacement therapy (KRT) via linkage to the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) and the incidence of KRT or death from ESKD by linking the NDSS to the ANZDATA and the National Death Index for Australia. PREDICTORS: Calendar time, sex, age, and duration of diabetes. OUTCOME: Incidence of KRT and KRT or death from ESKD. ANALYTICAL APPROACH: Incidence of ESKD, trends over time, and associations with factors related to these trends were modeled using Poisson regression stratified by diabetes type and sex. RESULTS: The median duration of diabetes increased from 15.3 to 16.8 years in type 1 diabetes, and from 7.6 to 10.2 years in type 2 diabetes between 2010 and 2019. The incidence of KRT and KRT or death from ESKD did not significantly change over this time interval among people with type 1 diabetes. Conversely, the age-adjusted incidence of KRT and KRT or death from ESKD increased among males with type 2 diabetes (annual percent changes [APCs]: 2.52% [95% CI, 1.54 to -3.52] and 1.27% [95% CI, 0.53 2.03], respectively), with no significant change among females (0.67% [95% CI, -0.68 to 2.04] and 0.07% [95% CI, -0.81 to 0.96], respectively). After further adjustment for duration of diabetes, the incidence of ESKD fell between 2010 and 2019, with APCs of-0.09% (95% CI, -1.06 to 0.89) and-2.63% (95% CI, -3.96 to-1.27) for KRT and-0.97% (95% CI, -1.71 to-0.23) and-2.75% (95% CI, -3.62 to-1.87) for KRT or death from ESKD among males and females, respectively. LIMITATIONS: NDSS only captures 80%-90% of people with diabetes; lack of clinical covariates limits understanding of trends. CONCLUSIONS: While the age-adjusted incidence of ESKD increased for males and was stable for females over the last decade, after adjusting for increases in duration of diabetes the risk of developing ESKD has decreased for both males and females. PLAIN-LANGUAGE SUMMARY: Previous studies showed an increase in new cases of kidney failure among people with type 2 diabetes, but more recent data have not been available. Here, we report trends in the rate of kidney failure for people with type 2 diabetes from 2010 to 2019 and showed that while more people with type 2 diabetes are developing kidney failure, accounting for the fact that they are also surviving longer (and therefore have a higher chance of kidney failure) the growth in this population is not caused by a higher risk of kidney failure. Nevertheless, more people are getting kidney failure than before, which will impact health care systems for years to come.

Empagliflozin cardiovascular and renal effectiveness and safety compared to dipeptidyl peptidase-4 inhibitors across 11 countries in Europe and Asia: Results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study.

BACKGROUND: Continued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with type 2 diabetes compared to similar therapies. METHODS: The EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014-2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors. Primary endpoints included hospitalization for heart failure, all-cause mortality, myocardial infarction and stroke. Other cardiovascular, renal, and safety outcomes were examined. FINDINGS: Among 83,946 matched patient pairs, (0·7 years overall mean follow-up time), initiation of empagliflozin was associated with lower risk of hospitalization for heart failure compared to dipeptidyl peptidase-4 inhibitors (Hazard Ratio 0·70; 95% CI 0.60 to 0.83). Risks of all-cause mortality (0·55; 0·48 to 0·63), stroke (0·82; 0·71 to 0·96), and end-stage renal disease (0·43; 0·30 to 0·63) were lower and risk for myocardial infarction, bone fracture, severe hypoglycemia, and lower-limb amputation were similar between initiators of empagliflozin and dipeptidyl peptidase-4 inhibitors. Initiation of empagliflozin was associated with higher risk for diabetic ketoacidosis (1·97; 1·28 to 3·03) compared to dipeptidyl peptidase-4 inhibitors. Results were consistent across continents and regions. INTERPRETATION: Results from this EMPRISE Europe and Asia study complements previous clinical trials and real-world studies by providing further evidence of the beneficial cardiorenal effects and overall safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors.

Lifetime risk, life expectancy, and years of life lost to type 2 diabetes in 23 high-income jurisdictions: a multinational, population-based study.

BACKGROUND: Diabetes is a major public health issue. Because lifetime risk, life expectancy, and years of life lost are meaningful metrics for clinical decision making, we aimed to estimate these measures for type 2 diabetes in the high-income setting. METHODS: For this multinational, population-based study, we sourced data from 24 databases for 23 jurisdictions (either whole countries or regions of a country): Australia; Austria; Canada; Denmark; Finland; France; Germany; Hong Kong; Hungary; Israel; Italy; Japan; Latvia; Lithuania; the Netherlands; Norway; Scotland; Singapore; South Korea; Spain; Taiwan; the UK; and the USA. Our main outcomes were lifetime risk of type 2 diabetes, life expectancy in people with and without type 2 diabetes, and years of life lost to type 2 diabetes. We modelled the incidence and mortality of type 2 diabetes in people with and without type 2 diabetes in sex-stratified, age-adjusted, and calendar year-adjusted Poisson models for each jurisdiction. Using incidence and mortality, we constructed life tables for people of both sexes aged 20-100 years for each jurisdiction and at two timepoints 5 years apart in the period 2005-19 where possible. Life expectancy from a given age was computed as the area under the survival curves and lifetime lost was calculated as the difference between the expected lifetime of people with versus without type 2 diabetes at a given age. Lifetime risk was calculated as the proportion of each cohort who developed type 2 diabetes between the ages of 20 years and 100 years. We estimated 95% CIs using parametric bootstrapping. FINDINGS: Across all study cohorts from the 23 jurisdictions (total person-years 1 577 234 194), there were 5 119 585 incident cases of type 2 diabetes, 4 007 064 deaths in those with type 2 diabetes, and 11 854 043 deaths in those without type 2 diabetes. The lifetime risk of type 2 diabetes ranged from 16·3% (95% CI 15·6-17·0) for Scottish women to 59·6% (58·5-60·8) for Singaporean men. Lifetime risk declined with time in 11 of the 15 jurisdictions for which two timepoints were studied. Among people with type 2 diabetes, the highest life expectancies were found for both sexes in Japan in 2017-18, where life expectancy at age 20 years was 59·2 years (95% CI 59·2-59·3) for men and 64·1 years (64·0-64·2) for women. The lowest life expectancy at age 20 years with type 2 diabetes was observed in 2013-14 in Lithuania (43·7 years [42·7-44·6]) for men and in 2010-11 in Latvia (54·2 years [53·4-54·9]) for women. Life expectancy in people with type 2 diabetes increased with time for both sexes in all jurisdictions, except for Spain and Scotland. The life expectancy gap between those with and without type 2 diabetes declined substantially in Latvia from 2010-11 to 2015-16 and in the USA from 2009-10 to 2014-15. Years of life lost to type 2 diabetes ranged from 2·5 years (Latvia; 2015-16) to 12·9 years (Israel Clalit Health Services; 2015-16) for 20-year-old men and from 3·1 years (Finland; 2011-12) to 11·2 years (Israel Clalit Health Services; 2010-11 and 2015-16) for 20-year-old women. With time, the expected number of years of life lost to type 2 diabetes decreased in some jurisdictions and increased in others. The greatest decrease in years of life lost to type 2 diabetes occurred in the USA between 2009-10 and 2014-15 for 20-year-old men (a decrease of 2·7 years). INTERPRETATION: Despite declining lifetime risk and improvements in life expectancy for those with type 2 diabetes in many high-income jurisdictions, the burden of type 2 diabetes remains substantial. Public health strategies might benefit from tailored approaches to continue to improve health outcomes for people with diabetes. FUNDING: US Centers for Disease Control and Prevention and Diabetes Australia.

The association of attained age, age at diagnosis, and duration of type 2 diabetes with the long-term risk for major diabetes-related complications.

AIM: We evaluated the associations of age and duration of type 2 diabetes with major diabetes-related complications. METHODS: We included 1.1 million people with type 2 diabetes from the Australian diabetes registry, followed from 2010 to 2019. We estimated the incidence of hospitalization or death from myocardial infarction (MI), stroke, and heart failure (HF), and hospitalisation for lower extremity amputation (LEA); end-stage kidney disease (ESKD; kidney replacement therapy or death from ESKD); and all-cause mortality. Poisson regression was used to model incidence by attained age, age at diabetes diagnosis, and duration of diabetes. RESULTS: Risk for complications increased exponentially with diabetes duration. Effects of attained age differed for each complication: age was a strong risk factor for MI, stroke, HF, and mortality, while diabetes duration, not age, was the predominant determinant of LEA and ESKD. At a given age, a 10-year longer diabetes duration was associated with a 1.1-1.5-fold increased risk of stroke and mortality, a 1.5-2.0-fold increased risk of MI and HF, and a 2-4-fold increased risk of LEA and ESKD. CONCLUSIONS: Duration of diabetes is a stronger risk factor for ESKD and LEA than it is for cardiovascular disease or mortality.

Severe Mental Illness and the Risk of Diabetes Complications: A Nationwide, Register-based Cohort Study.

CONTEXT: Individuals with severe mental illness (SMI) are at increased risk of developing type 2 diabetes. OBJECTIVE: This work explores whether individuals with diabetes and SMI are also at increased risk of diabetes complications and the potential age-specific differences in development of these. METHODS: Using nationwide registry data, we followed the entire Danish population with type 2 diabetes from January 1, 1996 to December 31, 2018. Exposure was SMI (schizophrenia, bipolar, or depression disorders). Outcome was diabetes complications (nephropathy, retinopathy, lower limp amputations, and cardiovascular disease). We applied Poisson regression models to estimate overall incidence rate ratios (IRRs) and age-specific incidence rates (IRs) and IRRs of the first event of each complication in individuals with SMI compared to individuals without SMI. The models were adjusted for sex, age, diabetes duration, calendar year, education, and migration status. RESULTS: We followed 371 625 individuals with type 2 diabetes, of whom 30 102 had coexisting diagnosed SMI. Individuals with SMI had a higher IR of nephropathy (IRR: 1.15; 95% CI, 1.12-1.18), amputations (IRR: 1.15; 95% CI, 1.04-1.28), and cardiovascular disease (men: IRR: 1.10; 95% CI, 1.05-1.15, women: IRR: 1.18; 95% CI, 1.13-1.22) but a lower IR of retinopathy (IRR: 0.75; 95% CI, 0.70-0.81) when compared to individuals without SMI, after adjustment for confounders. For all complications except amputations, the difference in IR was highest in the younger age groups. CONCLUSION: Individuals with type 2 diabetes and SMI had a higher risk and an earlier onset of several diabetes complications diagnoses, emphasizing focusing on improving diabetes management in younger age groups with SMI.

Mortality trends in type 1 diabetes: a multicountry analysis of six population-based cohorts.

AIMS/HYPOTHESIS: Mortality has declined in people with type 1 diabetes in recent decades. We examined how the pattern of decline differs by country, age and sex, and how mortality trends in type 1 diabetes relate to trends in general population mortality. METHODS: We assembled aggregate data on all-cause mortality during the period 2000-2016 in people with type 1 diabetes aged 0-79 years from Australia, Denmark, Latvia, Scotland, Spain (Catalonia) and the USA (Kaiser Permanente Northwest). Data were obtained from administrative sources, health insurance records and registries. All-cause mortality rates in people with type 1 diabetes, and standardised mortality ratios (SMRs) comparing type 1 diabetes with the non-diabetic population, were modelled using Poisson regression, with age and calendar time as quantitative variables, describing the effects using restricted cubic splines with six knots for age and calendar time. Mortality rates were standardised to the age distribution of the aggregate population with type 1 diabetes. RESULTS: All six data sources showed a decline in age- and sex-standardised all-cause mortality rates in people with type 1 diabetes from 2000 to 2016 (or a subset thereof), with annual changes in mortality rates ranging from -2.1% (95% CI -2.8%, -1.3%) to -5.8% (95% CI -6.5%, -5.1%). All-cause mortality was higher for male individuals and for older individuals, but the rate of decline in mortality was generally unaffected by sex or age. SMR was higher in female individuals than male individuals, and appeared to peak at ages 40-70 years. SMR declined over time in Denmark, Scotland and Spain, while remaining stable in the other three data sources. CONCLUSIONS/INTERPRETATION: All-cause mortality in people with type 1 diabetes has declined in recent years in most included populations, but improvements in mortality relative to the non-diabetic population are less consistent.

Trends in all-cause mortality among people with diagnosed diabetes in high-income settings: a multicountry analysis of aggregate data.

BACKGROUND: Population-level trends in mortality among people with diabetes are inadequately described. We aimed to examine the magnitude and trends in excess all-cause mortality in people with diabetes. METHODS: In this retrospective, multicountry analysis, we collected aggregate data from 19 data sources in 16 high-income countries or jurisdictions (in six data sources in Asia, eight in Europe, one from Australia, and four from North America) for the period from Jan 1, 1995, to Dec 31, 2016, (or a subset of this period) on all-cause mortality in people with diagnosed total or type 2 diabetes. We collected data from administrative sources, health insurance records, registries, and a health survey. We estimated excess mortality using the standardised mortality ratio (SMR). FINDINGS: In our dataset, there were approximately 21 million deaths during 0·5 billion person-years of follow-up among people with diagnosed diabetes. 17 of 19 data sources showed decreases in the age-standardised and sex-standardised mortality in people with diabetes, among which the annual percentage change in mortality ranged from -0·5% (95% CI -0·7 to -0·3) in Hungary to -4·2% (-4·3 to -4·1) in Hong Kong. The largest decreases in mortality were observed in east and southeast Asia, with a change of -4·2% (95% CI -4·3 to -4·1) in Hong Kong, -4·0% (-4·8 to -3·2) in South Korea, -3·5% (-4·0 to -3·0) in Taiwan, and -3·6% (-4·2 to -2·9) in Singapore. The annual estimated change in SMR between people with and without diabetes ranged from -3·0% (95% CI -3·0 to -2·9; US Medicare) to 1·6% (1·4 to 1·7; Lombardy, Italy). Among the 17 data sources with decreasing mortality among people with diabetes, we found a significant SMR increase in five data sources, no significant SMR change in four data sources, and a significant SMR decrease in eight data sources. INTERPRETATION: All-cause mortality in diabetes has decreased in most of the high-income countries we assessed. In eight of 19 data sources analysed, mortality decreased more rapidly in people with diabetes than in those without diabetes. Further longevity gains will require continued improvement in prevention and management of diabetes. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

A large remaining potential in lipid-lowering drug treatment in the type 2 diabetes population: A Danish nationwide cohort study.

AIM: To assess lipid-lowering drug (LLD) use patterns during 1996-2017 and examine lipid levels in relation to the use of LLDs and prevalent atherosclerotic cardiovascular disease (ASCVD). METHODS: Using a nationwide diabetes register, 404 389 individuals with type 2 diabetes living in Denmark during 1996-2017 were identified. Individuals were followed from 1 January 1996 or date of type 2 diabetes diagnosis until date of emigration, death or 1 January 2017. Redemptions of prescribed LLDs were ascertained from the nationwide Register of Medicinal Products Statistics. Data on lipid levels were sourced from the National Laboratory Database since 2010. LLD coverage was calculated at any given time based on the redeemed amount and dose. Trends in lipid levels were estimated using an additive mixed-effect model. Low-density lipoprotein cholesterol (LDL-C) goal attainment was assessed based on recommended targets by the 2011, 2016 and 2019 guidelines for management of dyslipidaemias. RESULTS: LLD use has decreased since 2012 and only 55% of those with type 2 diabetes were LLD users in 2017. A decline in levels of total cholesterol and LDL-C, and an increase in triglycerides, was observed during 2010-2017. Annual mean levels of LDL-C were lower among LLD users compared with non-users (in 2017: 1.84 vs. 2.57 mmol/L). A greater fraction of LLD users achieved the LDL-C goal of less than 1.8 mmol/L compared with non-users (in 2017: 51.7% and 19%, respectively). Among LLD users with prevalent ASCVD, 26.9% and 55% had, as recommended by current 2019 European guidelines, an LDL-C level of less than 1.4 mmol/L and less than 1.8 mmol/L, respectively, in 2017. CONCLUSIONS: LLD use and LDL-C levels are far from optimal in the Danish type 2 diabetes population and improvement in LLD use could reduce ASCVD events.

Incidence of HPV-related Anogenital Intraepithelial Neoplasia and Cancer in Men With Diabetes Compared With the General Population.

BACKGROUND: Diabetes may increase risk of human papillomavirus (HPV)-related precancer and cancer. We estimated incidence of penile and anal high-grade intraepithelial neoplasia (hgPeIN, hgAIN) and squamous cell carcinoma (SCC) in men with diabetes compared with the entire Danish male population without diabetes. METHODS: In this registry-based cohort study, we included all men born 1916-2001 and residing in Denmark (n = 2,528,756). From nationwide registries, we retrieved individual-level information on diabetes, educational level, and diagnoses of hgPeIN, hgAIN, penile SCC, and anal SCC. We used Poisson regression models to estimate incidence of hgPeIN, hgAIN, penile SCC, and anal SCC as a function of diabetes status, attained age, calendar period, and education. We estimated incidence rate ratios (IRRs) of each outcome in men with diabetes compared with nondiabetic men, both for diabetes overall and separately for type 1 (T1D) and type 2 diabetes (T2D). RESULTS: Men with diabetes had increased incidence rate of penile SCC compared with nondiabetic men (IRR = 1.5, 95% CI = 1.2, 1.9). We saw similar trends for anal SCC, hgPeIN, and hgAIN. The combined incidence rate of penile and anal SCC was increased in men with T2D (IRR = 1.5, 95% CI = 1.3, 1.8), but not with T1D (IRR = 0.53, 95% CI = 0.20, 1.4) compared with men without diabetes. CONCLUSION: The incidence of penile and anal high-grade intraepithelial neoplasia and SCC in men with diabetes was increased compared with men without diabetes. For penile and anal SCCs, this was primarily due to an increased risk in men with T2D.