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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.

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

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.

We evaluated the associations of age and duration of type 2 diabetes with major diabetes-related complications.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.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.Duration of diabetes is a stronger risk factor for ESKD and LEA than it is for cardiovascular disease or mortality.

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)

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

The incidence of type 1 diabetes (T1D) is increasing, either because of environmental factors accelerating onset of the disease or because of inducement of autoimmune diabetes in children who previously were at lower risk. High levels of immunoglobulin (Ig), specifically, IgM and IgA, and a low level of IgG were reported in adult patients; however no studies have analyzed the increasing incidence in relation to Ig levels. Our aim was to describe Ig in children newly diagnosed with diabetes and in their healthy siblings. Children with T1D expressed significantly lower IgG (p0.01) and higher IgA levels (p = 0.045), whereas no differences in IgE or IgM (p0.5) levels were found. Age-specific levels were unchanged over a 9-year period. In patients and siblings IgG, IgA and IgE increased by age (p0.001); which was in contrast to IgM (p0.05). The continued increase in IgG levels by age indicates that adult levels are reached later than in previously studied cohorts, thereby indicating a slower maturation of the immune system.

We evaluated variations in glucose measurements and the reproducibility of glucose tolerance classification in a high-risk screening setting in general practice. Screening for diabetes was performed in persons aged 40-69 years. Based on capillary fasting (FBG) and 2-h blood glucose (2 hBG) individuals with impaired fasting glycaemia (IFG), impaired glucose tolerance (IGT) and diabetes had a second test done after 14 days. Intra-individual coefficients of variation (CV) were estimated in each glucose tolerance class using the approximation CV(2)(x)=var(ln(x)). Bland-Altman plots with limits of agreement were made. In the total population, the CV(intra) was 7.9% and 13.8% for FBG and 2 hBG, respectively. Limits of agreement ranged from -1.15 to 1.67 mmol/l for FBG and from - 2.62 to 3.27 mmol/l for 2 hBG. One individual with IFG and 22.5% with IGT had diabetes at the second test, 76.1% with diabetes had this diagnosis confirmed, and about 30% with IFG and IGT had normal glucose tolerance at the second test. The expected values of repeated capillary blood glucose measurements were about+/-1 and+/-3 mmol/l for FBG and 2 hBG, respectively. Yet, 70% of high-risk prediabetic individuals were persistently classified with abnormal glucose regulation; diabetes was confirmed in 76% of the cases.

Purpose To examine the age- and gender-specific prevalence and describe the common phenotype of early age-related maculopathy (ARM) and late-stage age-related macular degeneration (AMD) among the Inuit in Greenland. Design Population-based cross-sectional study. Participants All ≥60-year-olds born in Greenland and living in the communities of Nuuk and Sisimiut, Greenland. Methods The presence and form of early (ARM) and late age-related macular disease (AMD) were determined by grading color fundus photographs using the international classification and grading system for ARM and AMD. Main Outcome Measures Prevalences of ARM and AMD were assessed by masked grading of fundus photographs. Results Overall, 695 persons were included in the study (response rate, 74.8%). Prevalence of any ARM was 52.3%. Age-related maculopathy was present in the worse eye in 50.0%, 58.8%, and 44.7% of age groups 60 to 69, 70 to 79, and ≥80, respectively. Prevalence of any AMD was 9.5%. Any AMD was present in the worse eye in 3.9%, 14.6%, and 43.2% of age groups 60 to 69, 70 to 79, and ≥80. Prevalences of pure geographic atrophy (GA) in one or both eyes, exudative degeneration in one or both eyes, and GA in one eye and exudative degeneration in the other eye were 2.3%, 6.1%, and 1.1%, respectively. Conclusions The prevalence of ARM is higher than in most other populations studied, and the prevalence of AMD in the oldest age group is higher than in most other populations studied. The prevalence of exudative degeneration is higher than the prevalence of GA, in contrast to findings in some of the Nordic countries—particularly Iceland—and earlier observations in Greenland.