Search

Aims: To estimate the incidence rates of genital warts (GWs) in women and men with type 1 diabetes compared to persons without diabetes. Methods: In this nationwide registry-based cohort study, we included the entire population aged 15 to 49 years living in Denmark between 1996 and 2016. From national registries, we retrieved individual level information on diabetes status, diagnoses and treatment of GWs, and potential confounding variables. We used Poisson regression to model sex- and age-specific incidence rates of GWs in persons with type 1 diabetes and persons without diabetes. Based on the models, we computed sex-specific incidence rate ratios (IRRs) of GWs in persons with type 1 diabetes compared to persons without diabetes, overall and according to age. Results: The analysis included 3,514,824 persons without type 2 diabetes and no GW diagnoses before baseline. The incidence rate of GWs in persons with type 1 diabetes was higher than in those without diabetes, both among women (IRR = 1.59; 95% CI, 1.42–1.78) and men (IRR = 1.36; 95% CI, 1.25–1.48). The pattern of increased incidence rates of GWs in persons with type 1 diabetes was seen at all ages. Conclusions: Persons with type 1 diabetes have higher incidence rates of GWs than persons without diabetes. This supports the importance of HPV vaccination of young girls and boys with type 1 diabetes.

Summary Background Diabetes prevalence is increasing in most places in the world, but prevalence is affected by both risk of developing diabetes and survival of those with diabetes. Diabetes incidence is a better metric to understand the trends in population risk of diabetes. Using a multicountry analysis, we aimed to ascertain whether the incidence of clinically diagnosed diabetes has changed over time. Methods In this multicountry data analysis, we assembled aggregated data describing trends in diagnosed total or type 2 diabetes incidence from 24 population-based data sources in 21 countries or jurisdictions. Data were from administrative sources, health insurance records, registries, and a health survey. We modelled incidence rates with Poisson regression, using age and calendar time (1995–2018) as variables, describing the effects with restricted cubic splines with six knots for age and calendar time. Findings Our data included about 22 million diabetes diagnoses from 5 billion person-years of follow-up. Data were from 19 high-income and two middle-income countries or jurisdictions. 23 data sources had data from 2010 onwards, among which 19 had a downward or stable trend, with an annual estimated change in incidence ranging from −1·1% to −10·8%. Among the four data sources with an increasing trend from 2010 onwards, the annual estimated change ranged from 0·9% to 5·6%. The findings were robust to sensitivity analyses excluding data sources in which the data quality was lower and were consistent in analyses stratified by different diabetes definitions. Interpretation The incidence of diagnosed diabetes is stabilising or declining in many high-income countries. The reasons for the declines in the incidence of diagnosed diabetes warrant further investigation with appropriate data sources. Funding US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

OBJECTIVE Experiencing adversities in childhood may increase the risk of type 1 diabetes through hyperactivation of the stress response system, but the empirical evidence is conflicting. We aim to describe the age-specific incidence of type 1 diabetes for males and females separately in five predefined groups covering the most common trajectories of adversity among Danish children. RESEARCH DESIGN AND METHODS We included all 1,081,993 children without parental type 1 diabetes born in Denmark from 1980 to 1998. We used register data to estimate age-specific incidence rates of type 1 diabetes in five trajectory groups of adversity characterized by 1) low adversity, 2) early life material deprivation, 3) persistent material deprivation, 4) loss or threat of loss in the family, and 5) cumulative high adversity. All analyses were stratified by sex. RESULTS In total, 5,619 people developed type 1 diabetes before 2016. We found only minor differences when comparing the incidence rates of type 1 diabetes between the trajectory groups. The only clear exceptions were in the high versus low adversity group, in which males had a higher incidence of type 1 diabetes in childhood ( CONCLUSIONS Childhood adversities were generally not associated with age-specific incidence of type 1 diabetes except among those exposed to a very high and increasing annual rate of childhood adversities. Differences between highly exposed males and females seem to depend on age at onset of type 1 diabetes.

Background People with type 1 diabetes often live for many years with different combinations of diabetes-related complications. We aimed to quantify how complication duration and total complication burden affect mortality, using data from national registers. Methods This study included 33 396 individuals with type 1 diabetes, registered in the Swedish National Diabetes Register at any time between 2001 and 2012. Each individual was followed and classified according to their time-updated diabetes-related complication status. The main outcomes were all-cause mortality, cardiovascular (CV) mortality and non-CV mortality. Poisson models were used to estimate the rate of these outcomes as a function of the time-updated complication duration. Results Overall, 1748 of the 33 396 individuals died during 198 872 person-years of follow-up. Overall, the time-updated all-cause mortality rate ratio (MRR) was 2.25 [95% confidence interval (CI): 1.99–2.54] for patients with diabetic kidney disease, 0.98 (0.82–1.18) for patients with retinopathy and 4.00 (3.56–4.50) for patients with cardiovascular disease relative to individuals without complications. The excess rate was highest in the first period after a diagnosis of CVD, with an 8-fold higher mortality rate, and stabilized after some 5 years. After diagnosis of diabetic kidney disease, we observed an increase in all-cause mortality with an MRR of around 2 compared with individuals without diabetic kidney disease, which stabilized after few years. Conclusions In this cohort we show that duration of diabetes-related complications is an important determinant of mortality in type 1 diabetes, for example the MRR associated with CVD is highest in the first period after diagnosis of CVD. A stronger focus on time-updated information and thorough consideration of complication duration may improve risk stratification in routine clinical practice.

BackgroundPrevious studies have indicated an association between childhood adversities and type 1 diabetes but have been underpowered and limited by selection. We aim to quantify the effect of accumulation of childhood adversities on type 1 diabetes risk, and to assess whether the effect differs between males and females in a large and unselected population sample.MethodsWe used register-based data covering all children born in Denmark between 1980 and 2015, totalling >2 million children. We specified a multi-state model to quantify the effect of accumulation of childhood adversities on type 1 diabetes risk. The effects of specific childhood adversities on type 1 diabetes were estimated using proportional hazards models.ResultsAccumulation of childhood adversities had a quantitatively small effect on type 1 diabetes risk among females [adjusted hazard ratio (HR) per adversity increase: 1.07; 95% confidence interval (CI): 1.02–1.11], but not among males (adjusted HR per adversity increase: 0.99; 95% CI: 0.97–1.03). Females exposed to extreme numbers (7+) of adversities had two times higher risk of type 1 diabetes compared with unexposed females (adjusted HR: 2.06; 95% CI: 1.10–3.86).ConclusionsIn an unselected total population sample, we generally find no or negligible effects of childhood adversities on type 1 diabetes risk, which may be reassuring to persons with type 1 diabetes who are concerned that personal trauma contributed to their disease. There is a very small group of females exposed to a high degree of adversity who may have a higher risk of type 1 diabetes and this group needs further attention.

Background: Cardiovascular outcome trials have shown cardiovascular benefit with sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors have not shown an effect. We aimed to address knowledge gaps regarding the comparative effectiveness of SGLT2 inhibitor use in clinical practice (with DPP-4 inhibitor use as an active comparator) across a range of cardiovascular risks and in diverse geographical settings. Methods: In this comparative cohort study, we used data from clinical practice from 13 countries in the Asia-Pacific, Middle East, European, and North American regions to assess the risk of cardiovascular events and death in adult patients with type 2 diabetes newly initiated on SGLT2 inhibitors compared with those newly initiated on DPP-4 inhibitors. De-identified health records were used to select patients who were initiated on these drug classes between Dec 1, 2012, and May 1, 2016, with follow-up until Dec 31, 2014, to Nov 30, 2017 (full range; dates varied by country). Non-parsimonious propensity scores for SGLT2 inhibitor initiation were developed for each country and patients who were initiated on an SGLT2 inhibitor were matched with those who were initiated on a DPP-4 inhibitor in a 1:1 ratio. Outcomes assessed were hospitalisation for heart failure, all-cause death, myocardial infarction, and stroke. Hazard ratios (HRs) were estimated by country and then pooled in a weighted meta-analysis. Findings: Following propensity score matching, 193 124 new users of SGLT2 inhibitors and 193 124 new users of DPP-4 inhibitors were included in the study population. Participants had a mean age of 58 years (SD 12·2), 170 335 (44·1%) of 386 248 were women, and 111 933 (30·1%) of 372 262 had established cardiovascular disease. Initiation of an SGLT2 inhibitor versus a DPP-4 inhibitor was associated with substantially lower risks of hospitalisation for heart failure (HR 0·69, 95% CI 0·61–0·77; p

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.

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.

Discontinuation of diabetes medication in the last years of life has been suggested to improve quality of life while deemed safe to implement. However, the extent, patterns, and secular changes in discontinuation of glucose-lowering medication in older people with type 2 diabetes have been scarcely described. We therefore aimed to describe the trends in the use of glucose-lowering medication during the last 10 years of life of older people and explore how key clinical and socioeconomic covariates are associated with these patterns.In this register-based cohort study, all individuals with type 2 diabetes who died aged 80 years or older between Jan 1, 2006, and Dec 31, 2018, were identified through the Danish Diabetes Register and linked to the Danish National Prescription Registry. We followed the population backwards in time from death to date of last medication intake. To estimate the cumulative proportion of people on glucose-lowering medication, a Poisson regression model for the rate of medication as a function of time before death (0 to 10 years before death) and calendar year of death (2006-18) was fitted. Both single-substance and combination glucose-lowering medications were included and categorised as insulins, sulfonylureas, metformin, DPP-4 inhibitors, GLP-1 analogues, SGLT2 inhibitors, acarbose, and thiazolidinediones. Insulin was further subdivided into four groups: fast-acting, intermediate-acting, long-acting, and mixed insulin. To identify which covariates were associated with discontinuation, estimates were adjusted for sex, age at death, diabetes duration at time of death, the total number of diabetes complications at time of death (from no complications to four or more), level of education, immigrant status, and income quartile.52 523 individuals (28 746 [54·7%] females and 23 777 [45·3%] males) were identified, with a mean age at type 2 diabetes diagnosis of 77 years (SD 8), median age at death of 86 years (IQR 83-90), and median diabetes duration at death of 9 years (IQR 5-14). We found a considerable discontinuation of glucose-lowering medication during the last 10 years of life, with the proportion of people on glucose-lowering medication starting at between 89% (95% CI 87-91) in 2006 and 87% (86-88) in 2018 at 10 years before death and decreasing to between 52% (50-54) in 2006 and 38% (37-39) in 2018 at the time of death. Specifically, we found that the proportion of people on sulfonylureas, at any time before death, decreased substantially from 2006 to 2018, whereas the proportion on metformin and DPP-4 inhibitors increased with calendar year of death. Changes were less pronounced for the remaining medications. The overall discontinuation patterns changed with increasing calendar year of death, such that discontinuation rates increased and occurred earlier (further away from time of death) with increasing calendar year. Discontinuations were generally more pronounced during the last year of life. Proportions of people on medication and patterns of discontinuation, as well as the association with covariates, varied with medication class. Covariates most frequently associated with changes in discontinuation rates were sex, age at death, type 2 diabetes duration at death, and number of complications. For example, females were less likely to receive metformin than males at all years before death (rate ratio 0·91 (95% CI 0·89-0·94, p0·0001), and there was a negative association between the proportion of individuals on metformin and increasing age at death (rate ratio per year increase 0·96 [0·96-0·96], p0·0001) and type 2 diabetes duration (0·95 per year increase [0·94-0·95], p0·0001).Our results suggest that increased focus on and implementation of discontinuation of glucose-lowering medication in recent years might have had an effect on discontinuation patterns, particularly during the last year of life.None.

IntroductionLifetime risk and lifetime lost to diabetes are measures of current diabetes burden in a population. We aimed at quantifying these measures in the Danish population.Research design and methodsWe modeled incidence and mortality of type 1 diabetes (T1D) and type 2 diabetes (T2D) and non-diabetes mortality based on complete follow-up of the entire population of Denmark in 1996–2016. A multistate model with these transition rates was used to assess the lifetime risk of diabetes, as well as the difference in expected lifetime between persons with type 1 and T2D and persons without.ResultsIn 2016, the lifetime risk of T1D was 1.1% and that for T2D 24%, the latter a 50% increase from 1996. For 50-year-old persons, the lifetime lost was 6.6 years for T1D and 4.8 years for T2D. These figures have been declining over the study period.At 2016, the total foreseeable lives lost in Denmark among patients with T1D were 182 000 years, and those among patients with T2D were 766 000 years, corresponding to 6.6 and 3.0 years per person, respectively.ConclusionAt the individual level, improvements in the disease burden for both T1D and T2D have occurred. At the population level, the increasing number of patients with T2D has contributed to a large increase in the total loss of lifetime.

Diabetes is a major cause of end stage renal disease (ESRD), yet the natural history of diabetic kidney disease is not well understood. We aimed to identify patterns of estimated GFR (eGFR) trajectory and to determine the clinical and genetic factors and their associations of these different patterns with all-cause mortality in patients with type 2 diabetes. Among 6330 patients with baseline eGFR >60 ml/min per 1.73 m2 in the Hong Kong Diabetes Register, a total of 456 patients (7.2%) developed Stage 5 chronic kidney disease or ESRD over a median follow-up of 13 years (incidence rate 5.6 per 1000 person-years). Joint latent class modeling was used to identify different patterns of eGFR trajectory. Four distinct and non-linear trajectories of eGFR were identified: slow decline (84.3% of patients), curvilinear decline (6.5%), progressive decline (6.1%) and accelerated decline (3.1%). Microalbuminuria and retinopathy were associated with accelerated eGFR decline, which was itself associated with all-cause mortality (odds ratio [OR] 6.9; 95% confidence interval [CI]: 5.6–8.4 for comparison with slow eGFR decline). Of 68 candidate genetic loci evaluated, the inclusion of five loci (rs11803049, rs911119, rs1933182, rs11123170, and rs889472) improved the prediction of eGFR trajectories (net reclassification improvement 0.232; 95% CI: 0.057-–0.406). Our study highlights substantial heterogeneity in the patterns of eGFR decline among patients with diabetic kidney disease, and identifies associated clinical and genetic factors that may help to identify those who are more likely to experience an accelerated decline in kidney function.

Some studies have suggested a declining mortality in type 1 diabetes, but it is unclear if the pattern of mortality trends differs by country and age group, and how mortality trends in type 1 diabetes relate to trends in the general population mortality. We assembled aggregated data on all-cause mortality in people with type 1 diabetes by 5-year age group and sex between 2000 and 2016 from an international diabetes consortium database, GLOBODIAB. Data were from administrative sources, health insurance records and registries. We used joinpoint regression analysis to examine trends in annual mortality rates (standardized to the 2010 European Union population) and mortality rate ratios (MRRs) (relative to the mortality in people without diabetes) in all age groups, and stratified by age ( In conclusion, all-cause mortality in type 1 diabetes has declined in recent years in the majority of data sources, but remains considerably higher than in the nondiabetic population. These data highlight that there is still scope to improve mortality in type 1 diabetes and reduce inequalities within and between populations. Disclosure P. Lopez-doriga ruiz: None. G. A. Nichols: Research Support; Self; Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, National Institute of Diabetes and Digestive and Kidney Diseases. S. Pildava: None. S. H. Read: Employee; Self; Certara. S. Wild: Advisory Panel; Self; Gilead Sciences, Inc., Other Relationship; Self; Novo Nordisk. J. E. Shaw: Advisory Panel; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp., Pfizer Inc., Research Support; Self; AstraZeneca, Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk. D. J. Magliano: None. L. Chen: None. J. I. Morton: None. A. Salim: None. B. Carstensen: Stock/Shareholder; Self; Novo Nordisk. E. W. Gregg: None. M. E. Pavkov: None. M. Mata-cases: Consultant; Self; Mundipharma International, Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., MSD Corporation, Novo Nordisk. D. Mauricio: None. Funding Centers for Disease Control and Prevention

In the elderly population with type 2 diabetes (T2D), decisions about discontinuation of medication is important, as it may lead to improved outcomes and reduced polypharmacy-associated adverse events. However, the extent, patterns and secular changes of discontinuation of cardioprotective medication during the last years of life have been scarcely described. All individuals with T2D that died at age ≥ 80, between 2006-2018 were identified through the Danish Diabetes Register and linked to the Register of Medicinal Products Statistics. The population was followed backward in time, from death to date of last intake of cardioprotective medication. To estimate the cumulative proportion on different medication classes, we fitted a crude Poisson regression model for the rate of medication with time before death. A total of 52,523 persons (55% female) were identified, with a mean (SD) age at T2D diagnosis of 77 (8) years, a median (Q1-Q3) age at death of 86 (83-90) years and a median (Q1-Q3) diabetes duration at death of 9 (5-14) years. From year of death in 2006 to 2018, we found an increased utilization of antihypertensive and lipid-lowering medication, during the last 10 years of life, while the opposite was true for aspirin (ASA) (Figure 1). We also found a simultaneous increase in discontinuation rates during the last years of life, which was particularly pronounced during the last year of life. Disclosure V. Kosjerina: None. B. Carstensen: Stock/Shareholder; Self; Novo Nordisk. M. E. Jorgensen: Research Support; Self; Boehringer Ingelheim International GmbH, Sanofi-Aventis, Stock/Shareholder; Self; Novo Nordisk A/S. B. Brock: None. H. Christensen: None. J. Rungby: None. G. S. Andersen: Stock/Shareholder; Self; Novo Nordisk A/S.

Background: Severe mental illness (SMI) is linked with a higher incidence of type 2 diabetes (T2D); however, it is unclear whether persons with SMI and T2D have a higher incidence of diabetes complications compared to persons with T2D only. We calculated incidence rate ratios (IRR) and incidence rates (IR) of micro- and macrovascular diabetes complications among persons with T2D and SMI compared to those with T2D only. Methods: We used Danish nationwide registers to follow all persons with T2D from 1996 to 2018. IRR and age-specific IR of first event of each diabetes complication was estimated using Poisson regression models with risk time as offset comparing persons with T2D with and without SMI, while adjusting for sex, age, diabetes duration, calendar year, substance abuse and Charlson’s Comorbidity Index. Results: A total of 371,625 persons with T2D were on average followed for 6.9 - 7.6 year depending on the complication outcome. Persons with T2D and SMI (n=29,249) were younger at T2D diagnosis than persons with T2D only (mean [SD], 59 [15] vs. 63 [14] year). In total, 73,598 (27%) developed cardiovascular disease (CVD), 25,846 (7%) developed retinopathy, 20,191 (5%) developed nephropathy, and 6,796 (2%) underwent an amputation during follow-up. Persons with T2D and SMI had an increased risk of CVD (IRR: 1.14 (95% CI: 1.11-1.18)) and nephropathy (IRR: 1.11 (95% CI: 1.03-1.16)), and a decreased risk of retinopathy (IRR: 0.83 (95% CI: 0.78-0.86)) compared to persons with T2D only when adjusting for confounders. The risk for amputations were similar in persons with T2D with and without SMI (IRR: 1.00 (95% CI: 0.90-1.12)). The increased risk of CVD and nephropathy in persons with SMI were persistent in all ages except for the ages 80-95 year. Conclusion: Persons with T2D and SMI have a slightly higher risk of CVD and nephropathy and a lower risk of retinopathy compared to persons with T2D only. Disclosure S. H. Scheuer: None. V. Kosjerina: None. N. Lindekilde: None. F. Pouwer: None. B. Carstensen: Stock/Shareholder; Self; Novo Nordisk. M. E. Jørgensen: Research Support; Self; Boehringer Ingelheim International GmbH, Sanofi-Aventis, Stock/Shareholder; Self; Novo Nordisk A/S. M. E. Benros: None. G. S. Andersen: Stock/Shareholder; Self; Novo Nordisk A/S.

In this register-based cohort study, we estimated the incidence of human papillomavirus (HPV)-related anogenital precancer and cancer in women with diabetes compared with women without diabetes. We followed all women living in Denmark born 1916 to 2001 (n = 2 508 321) for individual-level information on diabetes (Type 1 or 2 [T1D or T2D]), diagnoses of cervical, vaginal, vulvar and anal intraepithelial neoplasia Grade 2 or 3 (IN2/3) and cancer and other covariates from nationwide registries. We used Poisson regression to model the incidence rates of anogenital IN2/3 and cancer as a function of diabetes status, age, HPV vaccination, education, calendar year, and cervical cancer screening status. Incidence rate ratios (IRRs) were estimated for diabetes overall, and separately for T1D and T2D, compared with women without diabetes. Women with diabetes had higher rates of vulvar IN2/3 (IRR = 1.63; 95% confidence interval [CI]: 1.41-1.88), vulvar cancer (IRR = 1.61; 95% CI: 1.36-1.91) and vaginal cancer (IRR = 1.79; 95% CI: 1.27-1.91) than women without diabetes. Similar patterns were observed for anal IN2/3, anal cancer and cervical cancer, although not statistically significant. In contrast, women with diabetes had lower rates of cervical IN2/3 (IRR = 0.74; 95% CI: 0.69-0.79) than women without diabetes. Patterns were generally similar in women with T1D and T2D, although cancer rates were higher in women with T2D. In conclusion, the incidence of most anogenital precancers and cancers were increased in women with diabetes. However, women with diabetes had lower incidence of cervical precancer. Our findings could be explained by biological mechanisms and/or behavioral factors, such as smoking and less frequent cervical screening participation.

This chapter addresses Case-control and case-cohort studies. In a Case-control study, one samples persons based on their disease outcome, so the fraction of diseased persons in a Case-control study is usually known (at least approximately) before data collection. In a cohort (follow-up) study, the relationship between some exposure and disease incidence is investigated by following the entire cohort and measuring the rate of occurrence of new cases in the different exposure groups. The follow-up records all persons who develop the disease during the study period. Implicit in this is that the relevant exposure information is available at all times for all persons under follow-up. The chapter then looks at the statistical model for the odds ratio, before differentiating between odds ratio and rate ratio. It also considers confounding and stratified sampling; individually matched studies; and nested Case-control studies.

This chapter provides a brief introduction to some of the most common measures of disease occurrence used in epidemiology, both the empirical and theoretical versions of the measures. It begins with the prevalence of a disease in a population, which is the fraction of the population that has the disease at a given date. The chapter then considers mortality rate, incidence rate, standardized mortality ratio (SMR), and survival. Mortality is typically reported as a number of people that have died in a population of a certain size. Incidence rates are defined exactly as mortality rates, where one just counts incident cases, that is, newly diagnosed cases of a particular disease. Meanwhile, the SMR is a measure of the mortality in a group of persons as compared to the general population. Finally, the survival after diagnosis of a disease is defined as the fraction of diagnosed individuals alive at a given time after diagnosis.

This chapter explores the problems caused by categorizing quantitative variables (here termed continuous variables). Optimum decisions are made by applying a utility function to a predicted value. At the decision point, one can solve for the personalized cutpoint for predicted risk that optimizes the decision. Dichotomization on independent variables is completely at odds with making optimal decisions. To make an optimal decision, the cutpoint for a predictor would necessarily be a function of the continuous values of all the other predictors. Moreover, categorization assumes that the relationship between the predictor and the response is flat within intervals; this assumption is far less reasonable than a linearity assumption in most cases. Categorization of continuous variables using percentiles is particularly hazardous. To make a continuous predictor be more accurately modelled when categorization is used, multiple intervals are required.

ObjectivesAbdominal fat has been identified as a risk marker of cardiometabolic disease independent of overall adiposity. However, it is not clear whether there are ethnic disparities in this risk. We investigated the associations of visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) with cardiometabolic risk factors in three ethnic diverse populations of Inuit, Africans and Europeans.DesignCross-sectional pooled study.SettingGreenland, Kenya and Denmark.MethodsA total of 5113 participants (2933 Inuit, 1397 Africans and 783 Europeans) from three studies in Greenland, Kenya and Denmark were included. Measurements included abdominal fat distribution assessed by ultrasound, oral glucose tolerance test, hepatic insulin resistance, blood pressure and lipids. The associations were analysed using multiple linear regressions.ResultsAcross ethnic group and gender, an increase in VAT of 1 SD was associated with higher levels of hepatic insulin resistance (ranging from 14% to 28%), triglycerides (8% to 16%) and lower high-density lipoprotein cholesterol (HDL-C, −1.0 to −0.05 mmol/L) independent of body mass index. VAT showed positive associations with most of the other cardiometabolic risk factors in Inuit and Europeans, but not in Africans. In contrast, SAT was mainly associated with the outcomes in Inuit and Africans. Of notice was that higher SAT was associated with higher HDL-C in African men (0.11 mmol/L, 95% CI: 0.03 to 0.18) and with lower HDL-C in Inuit (−0.07 mmol/L, 95% CI: -0.12 to –0.02), but not in European men (−0.02 mmol/L, 95% CI: −0.09 to 0.05). Generally weaker associations were observed for women. Furthermore, the absolute levels of several of the cardiometabolic outcomes differed between the ethnic groups.ConclusionsVAT and SAT were associated with several of the cardiometabolic risk factors beyond overall adiposity. Some of these associations were specific to ethnicity, suggesting that ethnicity plays a role in the pathway from abdominal fat to selected cardiometabolic risk factors.

Background and aim: Both micro- and macro vascular complications represent major problems for diabetes patients and monitoring of the extent of these among diabetes patients is essential. Several studies have reported decreasing complications rates. We describe the burden and trend in 18 groups of complications in persons with diabetes in Denmark 1996-2016. Methods: We compiled a diabetes register for the entire Danish population, including reliable classification of type of diabetes. From the National Patient Register we extracted dates of recorded complications in 18 classes. Binomial regression was used to describe the prevalence of complications at diagnosis and change in these over time. Rate models based on Poisson likelihood were used to describe the incidence rates and changes in these. Analyses were conducted separately for T1D and T2D, and controlled for sex, age, duration of diabetes and including a linear term to describe the calendar time effect (date of diagnosis). Results: The prevalence at diagnosis of previous CVD was 10% in T1D and 37% in T2D, with annual relative changes of 3% in T1D and 5% in T2D. Retinopathy prevalence at diagnosis was 4.3% in T1D and 1.7% in T2D with no change in T1D, but a relative decrease of 6% in T2D. We found similar decreases in rates of complications in T1D and T2D; decrease of 2%/year in rates of CVD, 5%/year in amputations, while there were no changes in the incidence rates of retinopathy and renal disease over the period 1996-2016. For most complications we found a very high incidence during the first year after diagnosis, most likely reflecting a diagnostic catch-up and not any biological phenomenon. Conclusions: A steady decrease in incidence rates of most complications was seen, but not for microvascular complications. The pattern of complications at diagnosis was more mixed, influenced by fluctuations in diagnostic activity over the period. In general an encouraging trend in complication occurrence was seen in Denmark in the period 1996-2016. Disclosure B. Carstensen: Stock/Shareholder; Self; Novo Nordisk A/S. H. Amadid: None. M.E. Jørgensen: Research Support; Self; Amgen, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S.

Background: Lipid-lowering treatment is crucial in preventing cardiovascular disease in type 2 diabetes subjects. It is unknown how well treatment guidelines translate into clinical practice. We examined measured lipid levels in relation to use of lipid-lowering drugs among type 2 diabetes subjects in Denmark from 2010 to 2017. Methods: The study population consisted of 404,389 subjects with type 2 diabetes living in Denmark between 1996 and 2017 identified using the Danish Diabetes Register. Redemptions of prescribed lipid-lowering drugs were ascertained from the nationwide Register of Medicinal Products Statistics. Data on lipid levels was sourced from the National Laboratory Database containing detailed information on laboratory measurements at major clinical laboratories since 2010. A drug-exposure function was developed and applied to examine follow-up of lipid-lowering drug coverage at any given time based on the redeemed amount and dose of lipid-lowering drugs. Annual mean lipid levels were obtained by calculating the mean lipid measurement value per subject, per calendar year, and per lipid type. Proportions of subjects within LDL thresholds were calculated according to thresholds defined by 2019 European Society of Cardiology dyslipidemia guidelines. Results: In total, 64% of subjects redeemed at least two prescriptions of lipid-lowering drugs during the study period. A decline in levels of total-cholesterol and LDL was observed in the years from 2010 to 2017 in users and non-users of lipid-lowering drugs. Annual mean LDL levels were lower among lipid-lowering drug users compared with non-users (in 2017: 1.84 and 2.57 mmol/L, respectively). A greater fraction of lipid-lowering drug users achieved the LDL goal of Conclusions: Lipid-lowering drug use and LDL levels are far from optimal in the Danish type 2 diabetes population and constitute a large potential for improvement. Disclosure H. Amadid: None. M. Bekker-Nielsen Dunbar: None. P.F. Rønn: Research Support; Self; Amgen, Danish Diabetes Academy. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. J.S. Knudsen: None. B. Carstensen: Stock/Shareholder; Self; Novo Nordisk A/S. F. Persson: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Research Support; Self; Amgen, AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S. M.E. Jørgensen: Research Support; Self; Amgen, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S. Funding Amgen Inc.

Background: Non-western (non-w) migrants in Europe are at increased risk of type 2 diabetes (T2D) but it is not known if this translates into increased risk of atherosclerotic cardiovascular disease (ASCVD). We calculated age- and sex-specific incidence rates (IR) of ASCVD following T2D among 1st generation migrants in Denmark compared with Danish-born citizens. Methods: Data were obtained from nationwide registers. A total of 346,947 people diagnosed with T2D between 1997-2016 were followed for a median (IQR) of 6.7 (8.8) yr, and classified as Danish-born citizens, western- or non-w migrants according to country of birth. IR of first ASCVD event and death from other causes were estimated separately using Poisson regression with risk time as offset, adjusting for T2D duration and education. Results: Non-w migrants (n=27,693) were younger at T2D diagnosis than Danish-born (mean [SD], 50.8 [11.8] vs. 61.6 [13.5] yr). In total, 104,286 persons (30.1%) developed ASCVD. In adjusted models, ASCVD rates were higher for non-w migrant women at 40-60 yr but lower for both genders at 60-80 yr, compared to western migrants and Danish-born (Figure 1A-B). Non-ASCVD related mortality was also lower among non-w migrants (Figure 1C). Conclusion: Non-w migrants had lower risk of developing ASCVD at 60-80 yr and lower mortality from other causes. This may reflect a ’healthy migrant effect’ or differences in lifestyle or medication. Disclosure G.S. Andersen: Stock/Shareholder; Self; Novo Nordisk A/S. S. Byberg: None. A.D. Bjørkman: None. A.A. Isaksen: Research Support; Self; Novo Nordisk Foundation. H. Amadid: None. B. Carstensen: Stock/Shareholder; Self; Novo Nordisk A/S. M.E. Jørgensen: Research Support; Self; Amgen, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S.

IntroductionThe objective of this study was to give an overview of prevalence, incidence and mortality of type 1 (T1D) and type 2 diabetes (T2D) in Denmark, and their temporal trends.Research design and methodsWe constructed a diabetes register from existing population-based healthcare registers, including a classification of patients as T1D or T2D, with coverage from 1996 to 2016. Using complete population records for Denmark, we derived prevalence, incidence, mortality and standardized mortality ratio (SMR).ResultsThe overall prevalence of diabetes at 2016 was 0.5% for T1D and 4.4% for T2D, with annual increases since 1996 of 0.5% for T1D and 5.5% for T2D. Incidence rates of T1D decreased by 3.5% per year, with increase for persons under 25 years of age and a decrease for older persons. T2D incidence increased 2.5% per year until 2011, decreased until 2014 and increased after that, similar in all ages. The annual decrease in mortality was 0.3% for T1D and 2.9% for T2D. The mortality rate ratio between T1D and T2D was 1.9 for men and 1.6 for women. SMR decreased annually 2% for T1D and 0.5% for T2D.ConclusionsIncidence and prevalence of diabetes is increasing, but mortality among patients with diabetes in Denmark is decreasing faster than the mortality among persons without diabetes. T1D carries a 70% higher mortality than T2D.

Background Metformin has been shown to have both neuroprotective and neurodegenerative effects. The aim of this study was to investigate the effect of metformin in combination with insulin on cardiovascular autonomic neuropathy (CAN) and distal peripheral neuropathy (DPN) in individuals with type 2 diabetes (T2DM). Methods The study is a sub-study of the CIMT trial, a randomized placebo-controlled trial with a 2 × 3 factorial design, where 412 patients with T2DM were randomized to 18 months of metformin or placebo in addition to open-labelled insulin. Outcomes were measures of CAN: Changes in heart rate response to deep breathing (beat-to-beat), orthostatic blood pressure (OBP) and heart rate and vibration detection threshold (VDT) as a marker DPN. Serum levels of vitamin B12 and methyl malonic acid (MMA) were analysed. Results After 18 months early drop in OBP (30 s after standing) was increased in the metformin group compared to placebo: systolic blood pressure drop increased by 3.4 mmHg (95% CI 0.6; 6.2, p = 0.02) and diastolic blood pressure drop increased by 1.3 mmHg (95% CI 0.3; 2.6, p = 0.045) compared to placebo. Beat-to-beat variation decreased in the metformin group by 1.1 beats per minute (95% CI − 2.4; 0.2, p = 0.10). Metformin treatment did not affect VDT group difference − 0.33 V (95% CI − 1.99; 1.33, p = 0.39) or other outcomes. Changes in B12, MMA and HbA1c did not confound the associations. Conclusions Eighteen months of metformin treatment in combination with insulin compared with insulin alone increased early drop in OBP indicating an adverse effect of metformin on CAN independent of vitamin B12, MMA HbA1c. Trial registration The protocol was approved by the Regional Committee on Biomedical Research Ethics (H–D-2007-112), the Danish Medicines Agency and registered with ClinicalTrials.gov (NCT00657943).

Aims To examine the incidence rates of any and referable diabetic retinopathy (DR) among migrants in Denmark. Methods Nationwide clinical data on diabetes patients followed since 2005 were analysed. Patients were classified according to country of origin into six groups: Denmark, other Europe, Sub Saharan Africa, Middle East/North Africa, Asia, and America/Oceania. A total of 93,780 or 110,897 patients without any (including unspecific diagnoses) or referable (proliferative) DR at baseline were analyzed. We estimated event rates and hazard ratios (HRs) for incidence of any and referable DR according to country of origin. Results After an average follow-up of 3.59 years 6727 had incident any DR and 4747 patients had referable DR. Compared to people of Danish origin, migrants from the Middle East/North Africa and Asia had a higher risk of any and referable DR after adjustment for age, sex, body mass index, smoking status, types and duration of diabetes, clinic type (general practice vs outpatient clinic), HbA1c, blood pressure and lipid levels. The associations remained significant after further adjustment for frequency of eye screening. Conclusions Migrants from the Middle East/North Africa and Asia were at increased risk of developing any and referable DR compared to native Danes, and these differences were not fully explained by differences in underlying clinical, diabetic and cardiometabolic risk factors.

Background Randomized trials demonstrated a lower risk of cardiovascular (CV) events with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in patients with type 2 diabetes (T2D) at high...

Background Prior studies found patients treated with sodium-glucose co-transporter-2 inhibitors (SGLT-2i) had lower rates of death and heart failure (HF). Whether the benefits of SGLT-2i vary based upon the presence of cardiovascular disease (CVD) is unknown. Objectives This study sought to determine the association between initiation of SGLT-2i therapy and HF or death in patients with and without CVD. Methods The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study was a multinational, observational study in which adults with type 2 diabetes were identified. Patients prescribed an SGLT-2i or other glucose-lowering drugs (GLDs) were matched based on a propensity score for initiation of an SGLT-2i. Hazard ratios (HRs) for the risk of death, HF, and HF or death in patients with and without established CVD were estimated for each country and pooled. Results After propensity score matching, 153,078 patients were included in each group. At baseline, 13% had established CVD. Compared with therapy using other GLDs, initiation of an SGLT-2i was associated with lower risk of death in patients with and without CVD (HR: 0.56; 95% confidence interval [CI]: 0.44 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.63, respectively). There were also associations between SGLT-2i and lower risk of HF (HR: 0.72; 95% CI: 0.63 to 0.82; and HR: 0.61; 95% CI: 0.48 to 0.78, respectively) and the composite of HF or death (HR: 0.63; 95% CI: 0.57 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.62, respectively) observed in patients with and without established CVD. Conclusions In this large, multinational, observational study, initiation of SGLT-2i was associated with lower risk of death and HF regardless of pre-existing CVD. Ongoing clinical trials will provide further evidence regarding the benefit of SGLT-2i in patients without established CVD. (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors [CVD-REAL]; NCT02993614)

Current evidence suggests that type 2 diabetes may have a greater impact on those with earlier diagnosis (longer duration of disease), but data are limited. We examined the effect of age at diagnosis of type 2 diabetes on the risk of all-cause and cause-specific mortality over 15 years. The data of 743,709 Australians with type 2 diabetes who were registered on the National Diabetes Services Scheme (NDSS) between 1997 and 2011 were examined. Mortality data were derived by linking the NDSS to the National Death Index. All-cause mortality and mortality due to cardiovascular disease (CVD), cancer and all other causes were identified. Poisson regression was used to model mortality rates by sex, current age, age at diagnosis, diabetes duration and calendar time. The median age at registration on the NDSS was 60.2 years (interquartile range [IQR] 50.9–69.5) and the median follow-up was 7.2 years (IQR 3.4–11.3). The median age at diagnosis was 58.6 years (IQR 49.4–67.9). A total of 115,363 deaths occurred during 7.20 million person-years of follow-up. During the first 1.8 years after diabetes diagnosis, rates of all-cause and cancer mortality declined and CVD mortality was constant. All mortality rates increased exponentially with age. An earlier diagnosis of type 2 diabetes (longer duration of disease) was associated with a higher risk of all-cause mortality, primarily driven by CVD mortality. A 10 year earlier diagnosis (equivalent to 10 years’ longer duration of diabetes) was associated with a 1.2–1.3 times increased risk of all-cause mortality and about 1.6 times increased risk of CVD mortality. The effects were similar in men and women. For mortality due to cancer (all cancers and colorectal and lung cancers), we found that earlier diagnosis of type 2 diabetes was associated with lower mortality compared with diagnosis at an older age. Our findings suggest that younger-onset type 2 diabetes increases mortality risk, and that this is mainly through earlier CVD mortality. Efforts to delay the onset of type 2 diabetes might, therefore, reduce mortality.

Aims To compare the sodium-glucose-cotransporter-2 (SGLT-2) inhibitor dapagliflozin with dipeptidyl peptidase-4 (DPP-4) inhibitors with regard to risk associations with major adverse cardiovascular ...

AIMS/HYPOTHESIS: We assessed whether the risk of developing type 2 diabetes and the age of onset varied with the age at diabetes diagnosis of affected family members.METHODS: We performed a national register-based open cohort study of individuals living in Denmark between 1995 and 2012. The population under study consisted of all individuals aged 30 years or older without diagnosed diabetes at the start date of the cohort (1 January 1995) and who had information about their parents' identity. Individuals who turned 30 years of age during the observation period and had available parental identity information were also added to the cohort from that date (open cohort design). These criteria restricted the study population mostly to people born between 1960 and 1982. Multivariable Poisson regression models adjusted for current age and highest educational attainment were used to estimate incidence rate ratios (IRRs) of type 2 diabetes.RESULTS: We followed 2,000,552 individuals for a median of 14 years (24,034,059 person-years) and observed 76,633 new cases of type 2 diabetes. Compared with individuals of the same age and sex who did not have a parent or full sibling with diabetes, the highest risk of developing type 2 diabetes was observed in individuals with family members diagnosed at an early age. The IRR was progressively lower with a higher age at diabetes diagnosis in family members: 3.9 vs 1.4 for those with a parental age at diagnosis of 50 or 80 years, respectively; and 3.3 vs 2.0 for those with a full sibling's age at diagnosis of 30 or 60 years, respectively.CONCLUSIONS/INTERPRETATION: People with a family member diagnosed with diabetes at an earlier age are more likely to develop diabetes and also to develop it at an earlier age than those with a family member diagnosed in later life. This finding highlights the importance of expanding our understanding of the interplay between genetic diabetes determinants and the social, behavioural and environmental diabetes determinants that track in families across generations. Accurate registration of age at diagnosis should form an integral part of recording a diabetes family history, as it provides easily obtainable and highly relevant detail that may improve identification of individuals at increased risk of younger onset of type 2 diabetes. In particular, these individuals may benefit from closer risk factor assessment and follow-up, as well as prevention strategies that may involve the family.

Background: We assessed the effect of parental and sibling age at diabetes diagnosis on index individuals’ risk of developing diabetes. Methods: We carried out a register-based closed cohort analysis of 869,489 initially diabetes-free index individuals living in Denmark between 1995 and 2012. We assessed the effect of parents’ and full siblings’ age at diabetes diagnosis on the incidence of diabetes in the index individual, beyond the general effect of a positive family history. We calculated incidence rate ratios (IRR) in sex-stratified Poisson regression models. Results: A total of 58,339 index individuals developed diabetes during 14 million person-years of follow-up. Diabetes risk was highest when parents had a diabetes diagnosis at a younger age. Men and women with a mother diagnosed with diabetes at age 50 had an IRR of 3.62 (95% CI: 2.86 to 4.57) and 5.03 (95% CI: 3.90 to 6.49) respectively compared to people of the same age and sex without a mother with diabetes. At a maternal diagnosis age of 70, the IRRs were 1.56 (95% CI: 1.46 to 1.57) and 1.67 (95% CI: 1.53 to 1.82) for men and women respectively. Conclusions: Diabetes early detection strategies might consider that younger parental age at diabetes diagnosis may reflect more severe forms of diabetes, conferring a higher risk of developing the disease. Disclosure J. Silverman Retana: Other Relationship; Self; Danish Diabetes Academy, Steno Diabetes Center Aarhus. A. Hulman: None. J. NIelsen: None. B. Carstensen: Consultant; Self; Leo Pharma. Speaker's Bureau; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk Inc. R.K. Simmons: None. L. Bjerg: None. L. Johnston: None. D.R. Witte: None. Funding Danish Diabetes Academy (to J.O.S.R.); Novo Nordisk Foundation; Steno Diabetes Center Aarhus

Several studies have suggested a fall or stabilisation of diabetes incidence rates in the last decade. We therefore conducted a multi-country analysis of trends in diabetes incidence over time. Data from 16 countries comprising 17 administrative sources and one set of annual surveys were analysed according to a standard protocol mainly from the period 1995-2015. We modelled incidence rates using age and calendar time as quantitative variables (scored as the midpoint of each interval), and using restricted cubic splines with 6 knots for age and one knot per 4 years of observation for calendar time. The estimated rates from the models were presented as age- and sex-standardized rates (standardized to the 2010 EU population) for each centre to provide an overview of general trends. To formally assess temporal changes in incidence rates, we also fitted joinpoint models with joinpoints at one of the dates 2009, 2010, 2011, and 2012, estimating the average trend before and after the joinpoint. Among the 18 populations we assembled, 4 of the studies were from predominantly non-Europid populations (Taiwan, Korea, Singapore, Hong Kong) and only 2 of the studies were from middle-income countries (Ukraine and Latvia). In general, from 2000 (or when data were available) until 2010 we saw increasing trends in incidence rates in populations from the U.S., Canada, Australia, Denmark, UK, Spain, Scotland and Latvia, while we saw decreasing incidence rates in Israel, Italy, UK, Hong Kong, Taiwan and Korea. In contrast, after 2010, incidence rates appeared stable or decreasing in 14/18 centres, with U.S. (Kaiser Permanente Healthcare), Ukraine, Singapore, and Taiwan showing increasing trend of diabetes incidence. In conclusion, incidence rates of diabetes have shown a tendency to stabilise or even fall across some high-income populations in Europe, Asia, Canada and Australia. Patterns in low to middle income countries may be different, but little information is currently available from these. Disclosure D.J. Magliano: None. R.M. Islam: None. L. Chen: None. B. Carstensen: Consultant; Self; Leo Pharma. Speaker's Bureau; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk Inc. M.E. Pavkov: None. E.W. Gregg: None. M. Tabesh: None. D. Koye: None. J.L. Harding: None. J.E. Shaw: Advisory Panel; Self; Abbott, Merck Sharp & Dohme Corp. Speaker's Bureau; Self; AstraZeneca, Mylan, Roche Diabetes Care, Sanofi-Aventis. Funding Centers for Disease Control and Prevention

Background: Lipid-lowering drug (LLD) treatment is important for cardiovascular risk reduction in type 2 diabetes. Statins are first choice of treatment but increasing public concern of side effects may have changed the prescription patterns of LLDs. We mapped trends in LLD usage among type 2 diabetes patients in Denmark from 1997 to 2017. Methods: The study population was defined as all persons registered with type 2 diabetes in the national registers in the period 1997 through 2017. All redeemed LLDs (ATC-codes: C10) were extracted from the Register of Medicinal Product Statistics. Medication coverage at any given day was calculated based on amount purchased and doses prescribed if recorded; otherwise on Defined Daily Dose. Results: A total of 420,751 persons living in Denmark with type 2 diabetes was included. Out of these, 266,385 (63%) individuals redeemed at least two LLD prescriptions in the period. The proportion covered by LLDs increased from 24% in 1997 to 58% in 2013, where after it declined (Figure 1). By 2017, 35% of the population was on simvastatin, 15% on atorvastatin, 4% on rosuvastatin, 2% on ezetemibe and 1% on other drugs. Conclusion: Changing guidelines has had a clear impact on the actual use of LLDs among type 2 diabetes patients, but the declining tendency emphasize that there is still room for improvement. There was, however, not a noteworthy shift from statins to other drugs. Figure 1. Disclosure P.F. Rønn: Research Support; Self; Amgen AB. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. B. Carstensen: Consultant; Self; Leo Pharma. Speaker's Bureau; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk Inc. J.S. Knudsen: None. F. Persson: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. M.E. Jørgensen: Research Support; Self; Amgen Inc., AstraZeneca, Danish Diabetes Association, Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S. Funding Amgen AB

We read with interest the article from Laiteerapong et al. (1) about the effect of early glycemic control on micro- and macrovascular complications and mortality in individuals with newly diagnosed type 2 diabetes. However, we have major concerns regarding their study. First, we are concerned about the use of conditioning on the future when selecting the study sample, i.e., those still alive 10 years after diagnosis, while including this period in the follow-up time. The authors cautiously mentioned this as a limitation (lack of generalizability); however, we think that conditioning on the future makes the mortality figures erroneous and the interpretation of the complication results problematic with substantially limited clinical utility. The authors fitted a …

Objective Studies of diabetes in migrant populations have shown a higher prevalence compared to their respective countries of origin and to people natively born in the host country, but there is little population-based data on diabetes incidence and mortality in migrant populations. The aim of the current study was (1) to describe the incidence rates and prevalence of diabetes among first generation migrants in Denmark compared to the Danish background population, and (2) to compare standardised mortality rates (SMRs) for individuals with and without diabetes according to country of origin. Research design and methods Information was obtained from linkage of the National Diabetes Register with mortality statistics and information from the Central Personal Register on country of origin. Age- and sex-specific estimates of prevalence, incidence rates, mortality rates and SMRs relative to the part of the population without diabetes were calculated based on follow up of the entire Danish population. Results Compared with native born Danes, the incidence of diabetes was about 2.5 times higher among migrants from Africa, Asia, and the Middle East, and these migrant groups also showed significantly higher prevalence. The standardised mortality rates (SMR) were higher particularly above 50 years of age among most migrant groups compared with native born Danes, and with a higher annual increase. Conclusions The highest diabetes incidence rates and prevalence estimates were observed among migrants from Africa, Asia, and the Middle East, and the annual increase in SMRs was higher in these groups compared to native born Danes. © 2016 Elsevier Ireland Ltd

Background: Up-to-date information on undiagnosed type 2 diabetes and prediabetes based on current diagnostic criteria is lacking. The study aimed to model the total numbers of people with undiagnosed type 2 diabetes and prediabetes in Denmark based on existing population-based surveys. Methods: Two population-based Danish studies with information on HbA1c, date of examination, gender, age and known type 2 diabetes were identified: the Danish General Suburban Population Study, n = 21,205, and the Danish Health Examination Survey, n = 18,065. The prevalence of known, undiagnosed and pre-diabetes were estimated in the Danish General Suburban Population Study, and population-level age-specific prevalence of known type 2 diabetes was estimated from national registers. The Danish Health Examination Survey was included for sensitivity analysis. Combining estimates of the survey participation rate among known type 2 diabetes patients with known overall participation rates from the studies allowed for the correction of survey prevalence to plausible population-level estimates of age- and gender-specific prevalence. Results: The prevalence of known, undiagnosed and pre-diabetes was highest among men, increasing with age with a peak at age 70. Applying the survey-based prevalence to the entire Danish population, the estimated number (May 2011) with undiagnosed type 2 diabetes was 60,681, corresponding to 24% of all type 2 diabetes cases, and 292,715 had prediabetes, about 50% more than the total type 2 diabetes population. Conclusions: Estimates of undiagnosed type 2 diabetes and prediabetes are dramatically lower than reported in previous studies (60,681 vs 200,000 and 292,715 vs 750,000); however, whether this reflects a true decrease in incidence or the change to HbA1c-based diagnostic criteria is not clear.

AIMS/HYPOTHESIS: The role of burden and duration of multiple microvascular complications on mortality rate has not been explored in detail in type 1 diabetes. Taking complication burden and time-updated duration into account we aimed to quantify mortality rate in individuals with and without microvascular complications.METHODS: This observational clinical cohort included 3828 individuals with type 1 diabetes attending the Steno Diabetes Center Copenhagen in 2001-2013. We used information on mortality and detailed clinical measures of microvascular complications from electronic patient records. Poisson models were used to model mortality rates according to complication burden.RESULTS: During 26,665 person-years of follow-up, 503 deaths occurred. Compared with individuals without microvascular complications, the mortality rate ratio was 2.20 (95% CI 1.79, 2.69) for individuals with diabetic kidney disease, 1.72 (95% CI 1.39, 2.12) for individuals with neuropathy and 1.02 (95% CI 0.77, 1.37) for individuals with retinopathy, all adjusted for calendar time (year/month/day), age, duration of diabetes, sex, HbA1c, LDL-cholesterol, BMI, smoking status, systolic blood pressure, use of antihypertensive and lipid-lowering medication, and cardiovascular disease status. In individuals with two complications or more, the risk of mortality did not exceed the combined risk from each individual complication. Mortality rate ratios increased immediately after diagnosis of neuropathy and diabetic kidney disease. Mortality rate ratios were independent of the duration of neuropathy and retinopathy, while the mortality rate associated with diabetic kidney disease reached a stable level after approximately 3 years.CONCLUSIONS/INTERPRETATION: Neuropathy and diabetic kidney disease are strong and independent risk markers of mortality in type 1 diabetes, whereas no evidence of higher mortality rate was found for retinopathy. We found no indication that the mortality risk with multiple complications exceeds the risk conferred by each complication separately. The duration spent with microvascular complications had only a marginal effect on mortality.

OBJECTIVE Type 1 diabetes is a complex disease, and development of multiple complications over time can be analyzed only with advanced statistical methods. This study describes the development of microvascular complications and explores the effect of complication burden and important concurrent risk factors by applying a multistate model. RESEARCH DESIGN AND METHODS We used a clinical cohort at the Steno Diabetes Center Copenhagen to study the development of diabetic kidney disease, retinopathy, and neuropathy. We extracted information from electronic patient records and estimated incidence rates of complications by concurrent complication burden. We explored the extent to which concurrent complications modify the effect of selected risk factors on the development of microvascular complications. RESULTS We included 3,586 individuals. Incidence rate ratios in individuals with two previous complications were 3.2 (95% CI 2.3–4.5) for diabetic kidney disease, 2.1 (1.5–3.1) for retinopathy, and 1.7 (1.2–2.4) for neuropathy compared with individuals without complications. The models included diabetes duration; calendar time and age as timescales; and sex, HbA1c, lipid-lowering and antihypertensive treatment, systolic blood pressure, BMI, estimated glomerular filtration rate (eGFR), cardiovascular disease (CVD), LDL cholesterol, insulin dose (units/kg/day), and smoking status as covariates. Effects of HbA1c, diabetes duration, systolic blood pressure, BMI, eGFR, and LDL cholesterol where not modified by concurrent complication burden, whereas the effect of sex and CVD were. CONCLUSIONS The risk of microvascular complications highly depends on the concurrent complication burden and risk factor profile in individuals with type 1 diabetes. The results emphasize attention to risk factors, regardless of existing number of complications, to prevent development of further microvascular complications.

ObjectivesTo investigate the impact of a multifactorial treatment programme in a real-life setting on clinical outcomes and estimated cardiovascular disease (CVD) risk.DesignA retrospective observational cohort study, using data from the electronic medical records and national registers.SettingTertiary diabetes centre in Denmark.ParticipantsPatients with type 2 diabetes (n=4299) referred to a programme with focus on treatment of hyperglycaemia, hypertension and dyslipidaemia between 1 January 2001 and 1 April 2016.OutcomesPrimary outcomes were changes in haemoglobin A1c (HbA1c), blood pressure (BP) and low-density lipoprotein (LDL) cholesterol as well as proportion reaching treatment targets. Our secondary outcome was to investigate changes in antidiabetic, antihypertensive and lipid-lowering treatment, together with the impact on estimated CVD risk. Linear mixed model for repeated measurements were used for continuous variables and logistic regression for dichotomous variables.ResultsThe patients achieved a mean±SD decrease in HbA1c, systolic and diastolic BP and LDL cholesterol of 1.0%±0.04% (10.6±0.4 mmol/mol), 6.3±0.4 mm Hg, 2.7±0.2 mm Hg and 0.32±0.02 mmol/L, respectively (p1c(ConclusionsOur data support that short-term multifactorial treatment of patients with glycaemic dysregulation in a specialist outpatient setting is both achievable and effective, and associated with a clinically meaningful improvement in CVD risk.

Background In patients with type 2 diabetes and a high cardiovascular risk profile, the sodium-glucose co-transporter-2 (SGLT2) inhibitors empagliflozin and canagliflozin have been shown to lower cardiovascular morbidity and mortality. Using real-world data from clinical practice, we aimed to compare cardiovascular mortality and morbidity in new users of SGLT2 inhibitors versus new users of other glucose-lowering drugs, in a population with a broad cardiovascular risk profile. Methods CVD-REAL Nordic was an observational analysis of individual patient-level data from the Prescribed Drug Registers, Cause of Death Registers, and National Patient Registers in Denmark, Norway, and Sweden. All patients who filled a prescription for glucose-lowering drugs between 2012 and 2015 were included and followed up until Dec 31, 2015. Patients were divided into new users of SGLT2 inhibitors and new users of other glucose-lowering drugs. Each SGLT2 inhibitor user was matched with three users of other glucose-lowering drugs by use of propensity scores. Hazard ratios (HRs) were estimated by country (Cox survival model) and weighted averages were calculated. Cardiovascular outcomes investigated were cardiovascular mortality, major adverse cardiovascular events (cardiovascular mortality, myocardial infarction, and ischaemic or haemorrhagic stroke), hospital events for heart failure (inpatient or outpatient visit with a primary diagnosis of heart failure), non-fatal myocardial infarction, non-fatal stroke, and atrial fibrillation. We also assessed incidence of severe hypoglycaemia. Findings Matched SGLT2 inhibitor (n=22 830) and other glucose-lowering drug (n=68 490) groups were well balanced at baseline, with a mean follow-up of 0·9 (SD 4·1) years (80 669 patient-years) and mean age of 61 (12·0) years; 40% (36 362 of 91 320) were women and prevalence of cardiovascular disease was 25% (22 686 of 91 320). 94% of the total SGLT2 inhibitor exposure time was for use of dapagliflozin, with 5% for empagliflozin, and 1% for canagliflozin. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with decreased risk of cardiovascular mortality (HR 0·53 [95% CI 0·40–0·71]), major adverse cardiovascular events (0·78 [0·69–0·87]), and hospital events for heart failure (0·70 [0·61–0·81]; p

OBJECTIVE This study aimed to examine nationwide incidence trends and predictors of hospitalization for hypoglycemia (HH) in the adult population with type 1 diabetes in Denmark. RESEARCH DESIGN AND METHODS All 17,230 patients with type 1 diabetes aged 16 years and above registered in the Danish Adult Diabetes Database (DADD) from 2006 were followed to 2012 by linkage of registers. Incidence rates of HH were modeled by Poisson regression by calendar time, taking sex, age, diabetes duration, clinical variables, and previous HH into account. RESULTS A total of 2,369 events of HH occurred among 1,735 patients with type 1 diabetes of HH during 70,002 patient-years (mean follow-up 3.7 years). A decrease in incidence rate was observed with calendar time with an 8.4% (4.9–11.7%) annual decrease. Predictors of HH included previous HH, age, diabetes duration, albuminuria, and HbA1c. CONCLUSIONS This study revealed a decreasing trend in incidence of HH in patients with type 1 diabetes. Previous HH, longer diabetes duration, macroalbuminuria, and HbA1c were associated with increased risk of HH in type 1 diabetes, and attention to those factors is warranted in both clinical and public health aspects.

BACKGROUND: Ethnic variation in abdominal fat distribution may explain differences in cardiometabolic risk between populations. However, the ability of anthropometric measures to quantify abdominal fat is not clearly understood across ethnic groups. The aim of this study was to investigate the associations between anthropometric measures and visceral (VAT) and subcutaneous abdominal adipose tissue (SAT) in Inuit, Africans and Europeans.METHODS: We combined cross-sectional data from 3 studies conducted in Greenland, Kenya and Denmark using similar methodology. A total of 5275 individuals (3083 Inuit, 1397 Africans and 795 Europeans) aged 17-95 years with measures of anthropometry and ultrasonography of abdominal fat were included in the study. Multiple regression models with fractional polynomials were used to analyse VAT and SAT as functions of body mass index (BMI), waist circumference, waist-to-hip ratio, waist-to-height ratio and body fat percentage.RESULTS: The associations between conventional anthropometric measures and abdominal fat distribution varied by ethnicity in almost all models. Europeans had the highest levels of VAT in adjusted analyses and Africans the lowest with ethnic differences most apparent at higher levels of the anthropometric measures. Similar ethnic differences were seen in the associations with SAT for a given anthropometric measure.CONCLUSIONS: Conventional anthropometric measures like BMI and waist circumference do not reflect the same amount of VAT and SAT across ethnic groups. Thus, the obesity level at which Inuit and Africans are at increased cardiometabolic risk is likely to differ from that of Europeans.

BACKGROUND AND AIMS: Inuit populations have lower levels of cardiometabolic risk factors for the same level of body mass index (BMI) or waist circumference (WC) compared to Europeans in cross-sectional studies. We aimed to compare the longitudinal associations of anthropometric measures with cardiovascular disease (CVD) and all-cause mortality in Inuit and Europeans.METHODS: Using pooled data from three population-based studies in Canada, Greenland and Denmark, we conducted a cohort study of 10,033 adult participants (765 Nunavik Inuit, 2960 Greenlandic Inuit and 6308 Europeans). Anthropometric measures collected at baseline included: BMI, WC, waist-to-hip-ratio (WHR), waist-to-height-ratio (WHtR) and a body shape index (ABSI). Information on CVD and death was retrieved from national registers or medical files. Poisson regression analyses were used to calculate incidence rates for CVD and all-cause mortality.RESULTS: During a median follow-up of 10.5 years, there were 642 CVD events and 594 deaths. Slightly higher absolute incidence rates of CVD for a given anthropometric measure were found in Nunavik Inuit compared with Greenlandic Inuit and the Europeans; however, no cohort interactions were observed. For all-cause mortality, all anthropometric measures were positively associated in the Europeans, but only ABSI in the two Inuit populations. In contrast, BMI and WC were inversely associated with mortality in the two Inuit populations.CONCLUSIONS: Inuit and Europeans have different absolute incidences of CVD and all-cause mortality, but the trends in the associations with the anthropometric measures only differ for all-cause mortality. Previous findings of a lower obesity-associated cardiometabolic risk among Inuit were not confirmed.

Aims/hypothesis The prognostic role of different diabetes treatment types has not been studied in detail. We compared mortality rates among cancer patients with and without diabetes, accounting for diabetes treatment and diabetes duration.

Background Vitamin D, certain single nucleotide polymorphisms (SNPs) in the vitamin D-receptor (VDR) gene and vitamin D metabolism genes have been associated with type 1 diabetes (T1D). Objective We wanted to examine if the most widely studied SNPs in genes important for production, transport, and action of vitamin D were associated with T1D or to circulating levels of vitamin D 25-hydroxyvitamin D [25(OH)D] in a juvenile Danish population. Methods We genotyped eight SNPs in five vitamin D metabolism genes in 1467 trios. 25(OH)D status were analyzed in 1803 children (907 patients and 896 siblings). Results We did not demonstrate association with T1D for SNPs in the following genes: CYP27B1, VDR, GC, CYP2R1, DHCR7, and CYP24A1. Though, variants in the GC gene were significantly associated with 25(OH)D levels in the joint model. Conclusion Some of the most examined SNPs in vitamin D metabolism genes were not confirmed to be associated with T1D, though 25(OH) levels were associated with variants in the GC gene.

OBJECTIVE Regular physical activity (PA) reduces the risk of developing type 2 diabetes, and different subtypes of dysglycemia have shown different associations with PA. To better understand the associations of PA and glucose homeostasis, we examined the association of objectively measured PA energy expenditure (PAEE) with detailed measures of glucose homeostasis. RESEARCH DESIGN AND METHODS In 1,531 men and women, with low to high risk of developing type 2 diabetes, we measured 7 days of PAEE using a combined accelerometry and heart rate monitor (ActiHeart). Measures and indices of glucose homeostasis were derived from a 3-point oral glucose tolerance test in addition to measures of long-term glycemia (glycated hemoglobin A1c and advanced glycation end products). Associations of PAEE with glucose homeostasis markers were examined using linear regression models. RESULTS Median age (IQR) was 66.6 years (62.1–71.6) (54% men) with a median ActiHeart wear time of 6.9 days (6.0–7.1) and PAEE level of 33.0 kJ/kg/day (23.5–46.1). In fully adjusted models, we found higher levels of PAEE to be positively associated with insulin sensitivity and negatively with insulin 2 h after glucose load (P < 0.05). CONCLUSIONS Even in an elderly population with low levels of PA, we found higher objectively measured PAEE levels to be associated with a more beneficial glucose metabolic profile. Although our findings are cross-sectional, they indicate that even without high-intensity exercise, increasing the overall level of PAEE slightly in an entire population at risk for developing type 2 diabetes may be a realistic and worthwhile goal to reach in order to achieve beneficial effect in terms of glucose metabolism.