Short-term progression of cardiometabolic risk factors in relation to age at type 2 diabetes diagnosis: a longitudinal observational study of 100,606 individuals from the Swedish National Diabetes Register

Aims/hypothesis: The reasons underlying a greater association of premature mortality with early-onset type 2 diabetes relative to late-onset disease are unclear. We evaluated the clinical characteristics at type 2 diabetes diagnosis and the broad trajectories in cardiometabolic risk factors over the initial years following diagnosis in relation to age at diagnosis. Methods: Our cohort consisted of 100,606 individuals with newly diagnosed type 2 diabetes enrolled in the Swedish National Diabetes Register from 2002 to 2012. The average follow-up time was 2.8 years. Analyses were performed using a linear mixedeffects model for continuous risk factors and a mixed generalised linear model with a logistic link function for dichotomous risk factors. Results: The individuals diagnosed at the youngest age (18–44 years) were more often male and had the highest BMI (mean of 33.4 kg/m2 ) at diagnosis and during follow-up compared with all other groups (those diagnosed at 45–59 years, 60–74 years and ≥75 years; p < 0.05), being ~5 kg/m2 higher than the oldest group. Although HbA1c patterns were similar between all age groups, there was a difference of about 5 mmol/mol (0.45%) between the two groups at 8 years post-diagnosis (p < 0.05). Additionally, individuals diagnosed younger had ~0.7 mmol/l higher triacylglycerol, and ~0.2 mmol/l lower HDL-cholesterol levels at diagnosis relative to the oldest group. Such differences continued for several years post diagnosis. Yet, although more of these younger individuals were receiving oral glucose-lowering agents, other cardioprotective therapies were prescribed less often in this group. Differences in BMI, blood glucose and lipid levels remained with adjustment for potential confounders, including marital status, education and country of birth, and, where relevant, differential treatments by age, and in those with at least 5 years of follow-up. Conclusions/interpretation: Individuals who develop type 2 diabetes at a younger age are more frequently obese, display a more adverse lipid profile, have higher HbA1c and a faster deterioration in glycaemic control compared with individuals who develop diabetes later in life. These differences largely remain for several years after diagnosis and support the notion that early-onset type 2 diabetes may be a more pathogenic condition than late-onset disease

Health utilities of type 2 diabetes-related complications: a cross-sectional study in sweden.

This study estimates health utilities (HU) in Sweden for a range of type 2 diabetes-related complications using EQ-5D and two alternative tariffs (UK and Swedish) from 1757 patients with type 2 diabetes from the Swedish National Diabetes Register (NDR). Ordinary least squares were used for statistical analysis. Lower HU was found for female gender, younger age at diagnosis, higher BMI, and history of complications. Microvascular and macrovascular complications had the most negative effect on HU among women and men, respectively. The greatest decline in HU was associated with kidney disorders (-0.114) using the UK tariff and stroke (-0.059) using the Swedish tariff. Multiple stroke and non-acute ischaemic heart disease had higher negative effect than a single event. With the UK tariff, each year elapsed since the last microvascular/macrovascular complication was associated with 0.013 and 0.007 units higher HU, respectively. We found important heterogeneities in effects of complications on HU in terms of gender, multiple event, and time. The Swedish tariff gave smaller estimates and so may result in less cost-effective interventions than the UK tariff. These results suggest that incorporating subgroup-specific HU in cost-utility analyses might provide more insight for informed decision-making

A national observation study of cancer incidence and mortality risks in type 2 diabetes compared to the background population over time

We examined changing patterns in cancer incidence and deaths in diabetes compared to the background population. A total of 457,473 patients with type 2 diabetes, included between 1998 and 2014, were matched on age, sex, and county to five controls from the population. Incidence, trends in incidence and post-cancer mortality for cancer were estimated with Cox regression and standardised incidence rates. Causes of death were estimated using logistic regression. Relative importance of risk factors was estimated using Heller’s relative importance model. Type 2 diabetes had a higher risk for all cancer, HR 1.10 (95% CI 1.09–1.12), with highest HRs for liver (3.31), pancreas (2.19) and uterine cancer (1.78). There were lesser increases in risk for breast (1.05) and colorectal cancers (1.20). Type 2 diabetes patients experienced a higher HR 1.23 (1.21–1.25) of overall post-cancer mortality and mortality from prostate, breast, and colorectal cancers. By the year 2030 cancer could become the most common cause of death in type 2 diabetes. Persons with type 2 diabetes are at greater risk of developing cancer and lower chance of surviving it. Notably, hazards for specific cancers (e.g. liver, pancreas) in type 2 patients cannot be explained by obesity alone

Range of risk factor levels: control, mortality and cardiovascular outcomes in type 1 diabetes mellitus

Background—Individuals with type 1 diabetes have high risk of cardiovascular complications, but it is unknown to what extent fulfilling all cardiovascular treatment goals is associated with residual risk of mortality and cardiovascular outcomes in type 1 diabetes compared with the general population. Methods—We included all patients with type 1 diabetes aged >=18 years registered in the Swedish National Diabetes Register from January 1, 1998 - December 31, 2014, in all 33,333 patients, each matched for age and sex with 5 controls without diabetes randomly selected from the population. Patients with type 1 diabetes were categorized according to number of risk factors not at target: glycated hemoglobin, blood pressure, albuminuria, smoking and LDL cholesterol. Risk of all-cause mortality, acute myocardial infarction (AMI), heart failure hospitalization (HF) and stroke was examined in relation to the number of risk factors at target.Results—The mean follow-up was 10.4 years in the diabetes group. Overall, 2074 of 33,333 patients with diabetes and 4141 of 166,529 controls died. Risk for all outcomes increased stepwise for each additional risk factor not at target. Adjusted hazard ratios (HR) for patients achieving all risk factor targets compared with controls were 1.31 (95% CI 0.93-1.85) for all-cause mortality; 1.82 (95% CI 1.15-2.88) for AMI; 1.97 (95% CI 1.04-3.73) for HF; and 1.17 (95% CI 0.51-2.68) for stroke. HR for patients versus controls with none of the risk factors meeting target was 7.33 (95% CI 5.08-10.57) for all-cause mortality; 12.34 (95% CI 7.91-19.48) for AMI: 15.09 (95% CI 9.87-23.09) for HF; and 12.02 (95% CI 7.66-18.85) for stroke.Conclusions—A steep graded association exists between decreasing number of CV risk factors at target and major adverse CV outcomes among patients with T1DM. However, risks for all outcomes were numerically higher for T1DM patients compared with controls, even when all risk factors were at target, with risk for AMI and HF statistically significantly so

Use of sodium glucose cotransporter 2 inhibitors and risk of major cardiovascular events and heart failure:Scandinavian register based cohort study

Objective To investigate the cardiovascular effectiveness of sodium glucose cotransporter 2 (SGLT2) inhibitors in routine clinical practice. Design Cohort study using data from nationwide registers and an active-comparator new-user design. Setting Denmark, Norway, and Sweden, from April 2013 to December 2016. Participants 20 983 new users of SGLT2 inhibitors and 20 983 new users of dipeptidyl peptidase 4 (DPP4) inhibitors, aged 35-84, matched by age, sex, history of major cardiovascular disease, and propensity score. Main outcome measures Primary outcomes were major cardiovascular events (composite of myocardial infarction, stroke, and cardiovascular death) and heart failure (hospital admission for heart failure or death due to heart failure). Secondary outcomes were the individual components of the cardiovascular composite and any cause death. In the primary analyses, patients were defined as exposed from treatment start throughout follow-up (analogous to intention to treat); additional analyses were conducted with an as-treated exposure definition. Cox regression was used to estimate hazard ratios. Results Mean age of the study cohort was 61 years, 60% were men, and 19% had a history of major cardiovascular disease. Of the total 27 416 person years of follow-up in the SGLT2 inhibitor group, 22 627 (83%) was among patients who initiated dapagliflozin, 4521 (16%) among those who initiated empagliflozin, and 268 (1%) among those who initiated canagliflozin. During follow-up, 467 SGLT2 inhibitor users (incidence rate 17.0 events per 1000 person years) and 662 DPP4 inhibitor users (18.0) had a major cardiovascular event, whereas 130 (4.7) and 265 (7.1) had a heart failure event, respectively. Hazard ratios were 0.94 (95% confidence interval 0.84 to 1.06) for major cardiovascular events and 0.66 (0.53 to 0.81) for heart failure. Hazard ratios were consistent among subgroups of patients with and without history of major cardiovascular disease and with and without history of heart failure. Hazard ratios for secondary outcomes, comparing SGLT2 inhibitors with DPP4 inhibitors, were 0.99 (0.85 to 1.17) for myocardial infarction, 0.94 (0.77 to 1.15) for stroke, 0.84 (0.65 to 1.08) for cardiovascular death, and 0.80 (0.69 to 0.92) for any cause death. In the as-treated analyses, hazard ratios were 0.84 (0.72 to 0.98) for major cardiovascular events, 0.55 (0.42 to 0.73) for heart failure, 0.93 (0.76 to 1.14) for myocardial infarction, 0.83 (0.64 to 1.07) for stroke, 0.67 (0.49 to 0.93) for cardiovascular death, and 0.75 (0.61 to 0.91) for any cause death. Conclusions In this large Scandinavian cohort, SGLT2 inhibitor use compared with DPP4 inhibitor use was associated with reduced risk of heart failure and any cause death, but not with major cardiovascular events in the primary intention-to-treat analysis. In the additional as-treated analyses, the magnitude of the association with heart failure and any cause death became larger, and a reduced risk of major cardiovascular events that was largely driven by the cardiovascular death component was observed. These data help inform patients, practitioners, and authorities regarding the cardiovascular effectiveness of SGLT2 inhibitors in routine clinical practice

Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes

Background: Patients with diabetes are at higher risk for death and cardiovascular outcomes than the general population. We investigated whether the excess risk of death and cardiovascular events among patients with type 2 diabetes could be reduced or eliminated. Methods: In a cohort study, we included 271,174 patients with type 2 diabetes who were registered in the Swedish National Diabetes Register and matched them with 1,355,870 controls on the basis of age, sex, and county. We assessed patients with diabetes according to age categories and according to the presence of five risk factors (elevated glycated hemoglobin level, elevated low-density lipoprotein cholesterol level, albuminuria, smoking, and elevated blood pressure). Cox regression was used to study the excess risk of outcomes (death, acute myocardial infarction, stroke, and hospitalization for heart failure) associated with smoking and the number of variables outside target ranges. We also examined the relationship between various risk factors and cardiovascular outcomes. Results: The median follow-up among all the study participants was 5.7 years, during which 175,345 deaths occurred. Among patients with type 2 diabetes, the excess risk of outcomes decreased stepwise for each risk-factor variable within the target range. Among patients with diabetes who had all five variables within target ranges, the hazard ratio for death from any cause, as compared with controls, was 1.06 (95% confidence interval [CI], 1.00 to 1.12), the hazard ratio for acute myocardial infarction was 0.84 (95% CI, 0.75 to 0.93), and the hazard ratio for stroke was 0.95 (95% CI, 0.84 to 1.07). The risk of hospitalization for heart failure was consistently higher among patients with diabetes than among controls (hazard ratio, 1.45; 95% CI, 1.34 to 1.57). In patients with type 2 diabetes, a glycated hemoglobin level outside the target range was the strongest predictor of stroke and acute myocardial infarction; smoking was the strongest predictor of death. Conclusions: Patients with type 2 diabetes who had five risk-factor variables within the target ranges appeared to have little or no excess risk of death, myocardial infarction, or stroke, as compared with the general population. (Funded by the Swedish Association of Local Authorities and Regions and others.)