Impact of Retinopathy and Systemic Vascular Comorbidities on All-Cause Mortality.

Purpose: To assess the impact of retinopathy and systemic vascular comorbidities on the all-cause mortality in a representative U.S. sample. Methods: A total of 5703 participants (≥40 years old) from the 2005-2008 National Health and Nutrition Examination Survey. The Early Treatment Diabetic Retinopathy Study grading scale was used to evaluate the retinopathy status. Systemic vascular comorbidities included diabetes mellitus (DM), high blood pressure (HBP), chronic kidney disease (CKD) and cardiovascular disease (CVD). Time to death was calculated as the time from baseline to either the date of death or censoring (December 31st, 2015), whichever came first. Risks of mortality were estimated using Cox proportional hazards models after adjusting for confounders and vascular comorbidities. Results: After a median follow-up of 8.33 years (IQR: 7.50-9.67 years), there were 949 (11.8%) deaths from all causes. After adjusting for confounders, the presence of retinopathy predicted higher all-cause mortality (hazard ratio (HR), 1.41; 95% confidence interval (CI), 1.08-1.83). The all-cause mortality among participants with both retinopathy and systemic vascular comorbidities including DM (HR, 1.72; 95% CI, 1.21-2.43), HBP (HR, 1.47; 95% CI, 1.03-2.10), CKD (HR, 1.73; 95% CI, 1.26-2.39) and CVD (HR, 1.92; 95% CI, 1.21-3.04) was significantly higher than that among those without either condition. When stratified by diabetic or hypertension status, the co-occurrence of retinopathy and CKD or CVD further increased the all-cause mortality compared to those without either condition. Conclusions: The co-occurrence of retinopathy and systemic vascular conditions predicted a further increase in the risk of mortality. More extensive vascular risk factor assessment and management are needed to detect the burden of vascular pathologies and improve long-term survival in individuals with retinopathy.

Evaluation of the prognostic ability of serum uric acid for elderly acute coronary syndrome patients with diabetes mellitus: a prospective cohort study.

OBJECTIVES: This study evaluated the prognostic power of serum uric acid (UA) in predicting adverse events in elderly acute coronary syndrome (ACS) patients with diabetes mellitus (DM). METHODS: The analysis involved 718 ACS patients |>80 years old whose general clinical data and baseline blood biochemical indicators were collected prospectively from January 2006 to December 2012. These patients were classified into two groups based on DM status, and then followed up after discharge. The Kaplan-Meier method was used for major adverse cardiac event (MACE) rates and all-cause mortality. Multivariate Cox regression was performed to analyze the relationship between UA level and long-term clinical prognosis. Receiver operating characteristic (ROC) curves were analyzed to predict the cutoff value of UA in elderly ACS patients with DM. There were 242 and 476 patients in the DM and non-DM (NDM) groups, respectively, and the follow-up time after discharge was 40‒120 months (median, 63 months; interquartile range, 51‒74 months). RESULTS: The all-cause mortality, cardiac mortality, and MACE rates in both DM and NDM patients were higher than those in the control group (P=0.001). All-cause mortalities, cardiac mortalities, and MACE rates in DM patients with moderate and high UA levels were significantly higher than those in the NDM group (P=0.001). Long-term survival rates decreased significantly with increased UA levels in the ACS groups (P=0.001). UA (odds ratio (OR)=2.106, 95% confidence interval (CI)=1.244‒3.568, P=0.006) was found to be an independent risk factor for all-cause mortality and MACE in elderly ACS patients with DM. The cutoff value of UA was 353.6 µmol/L (sensitivity, 67.4%; specificity, 65.7%). CONCLUSIONS: Serum UA level is a strong independent predictor of long-term all-cause death and MACE in elderly ACS patients with DM.

Importance of hematological parameters for micro- and macrovascular outcomes in patients with type 2 diabetes: the Rio de Janeiro type 2 diabetes cohort study.

BACKGROUND: The prognostic importance of several hematological parameters has been scarcely investigated in type 2 diabetes. So, we aimed to evaluate their prognostic importance for development of complications in a cohort of type 2 diabetes. METHODS: In a prospective study, 689 individuals with type 2 diabetes had blood red cell, platelet and leukocyte parameters obtained at baseline. Multivariate Cox analyses examined the associations between several hematological parameters (including neutrophyl-to-lymphocyte, lymphocyte-to-monocyte, platelet-to-lymphocyte, and monocyte-to-HDL ratios) and the occurrence of microvascular (retina, renal and peripheral neuropathy) and cardiovascular complications (total cardiovascular events [CVEs], and major adverse CVEs [MACEs]), and all-cause and cardiovascular mortality. Improvements in risk discrimination were assessed by C-statistics and Integrated Discrimination Improvement (IDI) index. RESULTS: During a median follow-up of 10.5 years, 212 patients had a CVE (174 MACEs), 264 patients died (131 cardiovascular deaths); 206 had a renal, 161 a retinopathy and 179 patients had a neuropathy outcome. In multivariate-adjusted analyses, the lymphocytes count and lymphocyte-to-monocyte ratio were protective (hazard ratios [HRs]: 0.77 and 0.72, respectively), whereas the neutrophyl-to-lymphocyte and platelet-to-lymphocyte ratios were associated with increased risks (HRs: 1.19 and 1.17) for all-cause mortality. For cardiovascular mortality, the monocytes count, the neutrophyl-to-lymphocyte and monocyte-to-HDL ratios were associated with increased risks and the lymphocyte-to-monocyte ratio was protective. Higher lymphocyte-to-monocyte ratio was protective for renal failure outcome. However, none of them improved risk discrimination. CONCLUSIONS: Low lymphocytes count and leukocyte ratios that mainly included lymphocytes were predictors of macrovascular complications and mortality in individuals with type 2 diabetes. However, they did not improve risk prediction over traditional risk factors.

Up and down waves of glycemic control and lower-extremity amputation in diabetes.

Lower extremity amputations (LEA) are associated with a high mortality and medical expenditure. Diabetes accounts for 45% to 70% of LEA and is one of the most potent risk factors for peripheral artery diseases (PAD). The existence of a link between the recent relaxation of glycemic targets and the resurgence of LEA is suggested from the analysis of adult participants in the National Health and Nutrition Examination Survey (NHANES) between 2010 and 2015, when diabetes-related LEA increased by more than 25% associated with a decline in glycemic control. Indeed, in "the perfect wave" of NHANES, including the years 2007-2010, there was the highest number of diabetic people with hemoglobin A1c (HbA1c), non-high-density lipoprotein (HDL) cholesterol and blood pressure levels at their respective targets, associated with the lowest number of LEA. Until now, the ACCORD study, testing the role of aggressive vs conventional glucose control, and the LEADER trial, evaluating the effects of liraglutide versus placebo, have shown a reduced incidence of LEA in people with type 2 diabetes. The results of ongoing clinical trials involving glucagon-like peptide-1 receptor agonists (GLP-1RA, liraglutide or semaglutide) hopefully will tell us whether the wider use of these drugs may provide additional vascular benefits for diabetic people affected by PAD to decrease their risk of LEA.

Microvascular Disease and Risk of Cardiovascular Events and Death From Intensive Treatment in Type 2 Diabetes: The ACCORDION Study.

OBJECTIVE: To assess whether the presence of microvascular complications modifies the effect of intensive glucose reduction on long-term outcomes in patients with type 2 diabetes. PATIENTS AND METHODS: Using ACCORD and ACCORDION study data, we investigated the risk of the primary outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) or death in relation to the prerandomization type and extent of microvascular complications. Interaction terms were fitted in survival models to estimate the risk of both outcomes across levels of an overall microvascular disease score (range 0 to 100) and its individual components: diabetic nephropathy, retinopathy, and neuropathy. RESULTS: During a mean follow-up of 7.7 years, 1685 primary outcomes and 1806 deaths occurred in 9405 participants. The outcome-specific microvascular score was ≤30 in 97.9% of subjects for the primary outcome and in 98.5% for death. For participants with scores of 0 and 30, respectively, the 10-year absolute risk difference between intensive glucose control and standard treatment ranged from -0.8% (95% CI, -2.6, 1.1) to -3.0% -7.1, 1.1) for the primary outcome and from -0.5% (-2.1, 1.1) to 0.7% (-4.2, 5.6) for mortality. Retinopathy was associated with the largest effects, with a 10-year absolute risk difference of -6.5% (-11.1 to -2.0) for the primary outcome and -3.9% (-7.8 to 0.1) for mortality. CONCLUSION: This hypothesis-generating study identifies diabetic retinopathy as predictor of the beneficial effect of intensive glucose control on the risk of cardiovascular disease and possibly death. Further long-term studies are required to confirm these findings.

Evaluation of Clinical Outcomes Following Minor Amputations in Australia - An Important Consideration for Timing of Revascularisation.

BACKGROUND: Vascular patients with tissue loss requiring minor amputations could be an early sign of a terminal event. The long-term outcomes and timing of revascularisation for these patients are not well-studied. The aim of this study was to determine the clinical outcomes following minor amputations. Primary outcomes were functional status, limb loss, and mortality. Secondary outcomes compared immediate and delayed revascularisation. METHODS: A retrospective analysis of 200 vascular patients who required minor amputations at Austin Hospital, Melbourne was performed over 5 years. Demographics, details of revascularisation, functional status, and clinical outcomes such as recurrent tissue loss, limb loss and death were recorded. RESULTS: Of the entire cohort requiring minor amputations, 118 (59%) patients underwent revascularisation. 111 (94%) revascularisation procedures were performed within 90 days of minor amputation. Over all 5-year limb preservation was 89.9%. Patients who required revascularisation were not statistically significantly more at risk for limb loss at 5 years [13.6% vs. 6.6%; P=0.08]. Limb salvage at 1 year was not different between groups revascularized before and after amputation [89.5% vs. 90.9%; P=0.70]. Over all 5-year mortality rate was 50%. In the diabetic subset, those who had revascularisation after minor amputation had a greater 5-year mortality [67.9% vs. 50%; P=0.03]. A scoring system based on risk factors was developed but was not reliable based on the study data. CONCLUSIONS: The data from this study suggest that patients with diabetes who undergo revascularisation after minor amputation have worse outcomes than those revascularised prior to minor amputation. A predictive model applied at presentation could help detect high-risk patients but requires further work.

Endovascular Treatment for Critical Limb Ischemia in Type II Diabetes Mellitus Involving Femoropopliteal and Infrapopliteal Segments: Revascularization Strategy.

PURPOSE: To determine if further endovascular infrapopliteal angioplasty in combination with femoropopliteal revascularization improves the clinical outcomes regarding major amputation rate, rate of secondary interventions, and mortality in diabetic type-II patients presented with critical lower limb ischemia (CLI). PATIENTS AND METHODS: This is a retrospective study in which all type-II diabetic patients with CLI at King Abdullah University Hospital between October 2015 and September 2019 were identified. Patients with concomitant femoropopliteal and infrapopliteal vessels atherosclerotic lesions (total occlusion or more than 50% stenosis) who received successful endovascular treatment were included. Patients were divided into 2 groups. Group-I included patients treated for femoropopliteal segment alone, while Group-II included patients treated for both femoropopliteal and infrapopliteal segments. The outcomes of the two groups were compared regarding major amputation rate, rate of secondary interventions, and mortality. In addition, demographic data, atherosclerotic lesions distributions and cardiovascular risk factors were also collected and analyzed. RESULTS: In all, 90 patients (65 males and 25 females) with a mean age of 67.5±12 years were included. In Group-I; 44 patients (48.9%) were included (36 males and 8 females) with a mean age of 67±12 years. In group-II; 46 patients (51.1%) were included (29 males and 17 females) with a mean age of 68±13 years. The major amputation rate was higher and statistically significant in Group-I (38.6% vs 17.4%, p-value = 0.034). However, the secondary interventions and the mortality rates showed no statistically significant differences (56.8% vs 39.1%, p-value = 0.139) and (22.7% vs 28.3%, p-value = 0.632), respectively. CONCLUSION: Endovascular infrapopliteal angioplasty in combination with femoropopliteal revascularization in diabetic type-II patients with CLI improves the clinical outcome regarding major amputation rate. However, there were no significant differences regarding the rate of secondary interventions and the mortality rate.

Cause-specific mortality rates in patients with diabetes according to comorbid macro- and microvascular complications: BioBank Japan Cohort.

Objective: This study aimed to compare cause-specific mortality rates in patients with type 2 diabetes with and without various vascular complications. Methods: In Japanese hospitals, we followed up 30 834 patients with a mean age of 64.4 (standard deviation [SD]: 11.1) years. Patients were followed up from 2003 to 2007 for a median of 7.5 (interquartile range: 6.1-9.7) years. We calculated cause-specific mortality rates (number of deaths/1000 person-years) and confounder-adjusted hazard ratios in patients with macrovascular disease and in those with diabetic nephropathy, neuropathy and retinopathy, allowing for overlap of complications. Results: All-cause mortality rate was highest (51.4) in the nephropathy group, followed by the macrovascular disease group (45.2), the neuropathy group (39.5), the retinopathy group (38.7) and the nonvascular complication group (18.1). In the nephropathy group, morality rates of ischaemic heart, cerebrovascular, and infectious diseases and cancer were also highest among the groups. However, the cancer mortality rate was similar among the vascular complication groups. Relative to the nonvascular complication group, covariate-adjusted hazard ratios for ischaemic heart and cerebrovascular disease mortality were triple to quadruple in the macro- and microvascular complication groups. All-cause mortality rates rose exponentially according to age. Conclusion: Highest risks of all-cause, cancer, and ischaemic heart, infectious, and cerebrovascular disease mortality were determined in Japanese patients with diabetic nephropathy. Although cancer is the primary cause of death in Japanese patients with diabetes, cancer mortality rates are similar among those with and without vascular complications.

Serum glycated albumin predicts all-cause mortality in dialysis patients with diabetes mellitus: meta-analysis and systematic review of a predictive biomarker.

BACKGROUND AND AIM: HbA1c, the traditional and current gold standard biomarker guiding diabetic management, has been scrutinized for low predictive value for patients with chronic kidney disease due to variables affecting erythrocyte number and turnover. Glycated albumin, the precursor to advanced glycation end products, reflects glycemic status over the preceding 2-3 week period and already outperforms HbA1c for glycemic monitoring. Our aim was to establish whether serum GA can be further used to predict mortality risk in dialysis patients with diabetes mellitus (DM) METHODS: We did systematic review of the literature in PubMed/Medline, Web of Science, Embase (Elsevier) and the Cochrane Central Register of Controlled Trials (Wiley) up to and including February 2020. RESULTS: This meta-analysis included 25,932 dialysis patients across 12 studies with maximum follow-up of 11 years. Higher GA levels were associated with the risk of all-cause mortality in dialysis patients with DM (HR 1.02, 95% CI 1.01 to 1.03, P < 0.001) irrespective of the type of dialysis, whereas higher GA was not associated with cardiovascular mortality (HR 1.03, 95% CI 0.99 to 1.06, P = 0.15) and cardiovascular events (both fatal and non-fatal) (HR 1.03, 95% CI 0.97 to 1.09, P = 0.31) in dialysis patients with DM. CONCLUSION: Serum glycated albumin predicts all-cause mortality risk in dialysis patients with DM. The endpoints of cardiovascular mortality and cardiovascular events trended similarly, but did not reach significance at the current sample size.

Improving outcome prediction in individuals with colorectal cancer and diabetes by accurate assessment of vascular complications: Implications for clinical practice.

BACKGROUND: Diabetes is considered a risk factor for mortality following a diagnosis of cancer. We hypothesised that the risk will vary due to the heterogeneous nature of the population and accurate classification of vascular complications will improve prediction of clinical outcomes. METHODS: The COloRECTal cancer data Repository (CORECT-R) was used to identify individuals with primary colorectal cancer, who underwent surgical resection in England (2005-2016). Diabetes was recorded using ICD10 codes (E10-E14) during inpatient hospital admission in the six years preceding cancer diagnosis, complication status was determined using the adapted Diabetes Complications Severity Index (aDCSI). Survival and post-operative outcomes were compared between groups. RESULTS: Of 232,367 individuals, 28,642 (12.3%) were recorded as having diabetes, 49.2% of whom had complications according to the aDCSI. Patients with diabetes complications had increased incidence of adverse post-operative outcomes (90-day post-operative mortality (6.6% versus 3.2%) and death during the surgical episode (7.9% versus 3.6%)), compared to those without diabetes. Those without complications had rates comparable to the population without diabetes. The odds of death within a year of diagnosis were higher for those with complicated diabetes compared to those without diabetes [OR 1.58 (95%CI 1.51-1.66) p < 0.01], but no difference was observed between those with uncomplicated diabetes and those without diabetes [OR 1.05 (95%CI 0.99-1.11) p = 0.10]. CONCLUSIONS: Prediction of outcome following surgery in colorectal cancer patients with diabetes relies on the accurate assessment of complications. This study suggests that the poor post-operative outcomes in diabetes patients may be associated with diabetes complication rather than diabetes itself.

Global trend of diabetes mortality attributed to vascular complications, 2000-2016.

BACKGROUND: The global epidemic of diabetes mellitus continues to grow and affects developed and developing countries alike. Intensive glycemic control is thought to modify the risks for vascular complications, hence the risks for diabetes-related death. We investigated the trend of diabetic vascular complication-related deaths between 2000 and 2016 in the global diabetes landscape. METHODS: We collected 17 years of death certificates data from 108 countries in the World Health Organization mortality database between 2000 and 2016, with coding for diabetic complications. Crude and age-standardized proportions and rates were calculated. Trend analysis was done with annual average percentage change (AAPC) of rates computed by joinpoint regression. RESULTS: From 2000 through 2016, 7,108,145 deaths of diabetes were reported in the 108 countries. Among them, 26.8% (1,904,787 cases) were attributed to vascular complications in damaged organs, including the kidneys (1,355,085 cases, 71.1%), peripheral circulatory (515,293 cases, 27.1%), nerves (28,697 cases, 1.5%) and eyes (5751 cases, 0.3%). Overall, the age-standardized proportion of vascular complication-related mortality was 267.8 [95% confidence interval (95% CI), 267.5-268.1] cases per 1000 deaths and the rate was 53.6 (95% CI 53.5-53.7) cases per 100,000 person-years. Throughout the 17-year period, the overall age-standardized proportions of deaths attributable to vascular complications had increased 37.9%, while the overall age-standardized mortality rates related to vascular complications had increased 30.8% (AAPC = 1.9% [1.4-2.4%, p < 0.05]). These increases were predominantly driven by a 159.8% increase in the rate (AAPC = 2.7% [1.2-4.3%, p < 0.05]) from renal complications. Trends in the rates and AAPC of deaths varied by type of diabetes and of complications, as well as by countries, regions and domestic income. CONCLUSION: Diabetic vascular complication-related deaths had increased substantially during 2000-2016, mainly driven by the increased mortality of renal complications.

An Early-Onset Subgroup of Type 2 Diabetes: A Multigenerational, Prospective Analysis in the Framingham Heart Study.

OBJECTIVE: To assess the relation of type 2 diabetes occurring earlier (age <55 years) versus later in life to the risk of cardiovascular death and to diabetes in offspring. RESEARCH DESIGN AND METHODS: In the Framingham Heart Study, a community-based prospective cohort study, glycemic status was ascertained at serial examinations over six decades among 5,571 first- and second-generation participants with mortality data and 2,123 second-generation participants who initially did not have diabetes with data on parental diabetes status. We assessed cause of death in a case (cardiovascular death)-control (noncardiovascular death) design and incident diabetes in offspring in relation to parental early-onset diabetes. RESULTS: Among the participants in two generations (N = 5,571), there were 1,822 cardiovascular deaths (including 961 coronary deaths). The odds of cardiovascular versus noncardiovascular death increased with decreasing age of diabetes onset (P < 0.001 trend). Compared with never developing diabetes, early-onset diabetes conferred a 1.81-fold odds (95% CI 1.10-2.97, P = 0.02) of cardiovascular death and 1.75-fold odds (0.96-3.21, P = 0.07) of coronary death, whereas later-onset diabetes was not associated with greater risk for either (P = 0.09 for cardiovascular death; P = 0.51 for coronary death). In second-generation participants, having a parent with early-onset diabetes increased diabetes risk by 3.24-fold (1.73-6.07), whereas having one or both parents with late-onset diabetes increased diabetes risk by 2.19-fold (1.50-3.19). CONCLUSIONS: Our findings provide evidence for a diabetes subgroup with an early onset, a stronger association with cardiovascular death, and higher transgenerational transmission.

Sex Differences in Coronary Artery Calcium and Mortality From Coronary Heart Disease, Cardiovascular Disease, and All Causes in Adults With Diabetes: The Coronary Calcium Consortium.

OBJECTIVE: While diabetes has been previously noted to be a stronger risk factor for cardiovascular disease (CVD) in women compared with men, whether this is still the case is not clear. Coronary artery calcium (CAC) predicts coronary heart disease (CHD) and CVD in people with diabetes; however, its sex-specific impact is less defined. We compared the relation of CAC in women versus men with diabetes for total, CVD, and CHD mortality. RESEARCH DESIGN AND METHODS: We studied adults with diabetes from a large registry of patients with CAC scanning with mortality follow-up over 11.5 years. Cox regression examined the relation of CAC with mortality end points. RESULTS: Among 4,503 adults with diabetes (32.5% women) aged 21-93 years, 61.2% of women and 80.4% of men had CAC >0. Total, CVD, and CHD mortality rates were directly related to CAC; women had higher total and CVD death rates than men when CAC >100. Age- and risk factor-adjusted hazard ratios (HRs) per log unit CAC were higher among women versus men for total mortality (1.28 vs. 1.18) (interaction P = 0.01) and CVD mortality (1.47 vs. 1.27) (interaction P = 0.04) but were similar for CHD mortality (1.48 and 1.48). For CVD mortality, HRs with CAC scores of 101-400 and >400 were 3.67 and 6.27, respectively, for women and 1.63 and 3.48, respectively, for men (interaction P = 0.04). For total mortality, HRs were 2.56 and 4.05 for women, respectively, and 1.88 and 2.66 for men, respectively (interaction P = 0.01). CONCLUSIONS: CAC predicts CHD, CVD, and all-cause mortality in patients with diabetes; however, greater CAC predicts CVD and total mortality more strongly in women.

Predictors of intra-hospital mortality in patients with diabetic foot ulcers in Nigeria: data from the MEDFUN study.

BACKGROUND: Diabetic foot ulcers (DFU) are associated with high morbidity and mortality globally. Mortality in patients hospitalized for DFU in Nigeria is unacceptably high. This study was undertaken to determine factors that predict mortality in patients hospitalized for DFU in Nigeria. METHODS: The current study was part of Multi-centre Evaluation of Diabetic Foot Ulcer in Nigeria (MEDFUN), an observational study conducted in six tertiary healthcare institutions across the 6 geopolitical zones of Nigeria. Consecutive type 1 or 2 diabetic patients hospitalized for DFU who consented to participate were recruited and subjected to relevant clinical, biochemical, and radiological assessments and multidisciplinary care until discharge or death. Data for type 1 diabetes mellitus (DM) patients were expunged from current mortality analysis due to their small number. RESULTS: Three hundred and twenty-three type 2 DM subjects with mean age and mean duration of DM of 57.2 ± 11.4 years and 8.7 ± 5.8 years respectively participated in this study. The median duration of ulcers was 39 days with a range of 28 to 54 days and the majority (79.9%) presented with advanced ulcers of at least Wagner grade 3. Mortality of 21.4% was recorded in the study, with the highest mortality observed among subjects with Wagner grade 5. Variables significantly associated with mortality with their respective p values were DM duration more than 120 months (p 0.005), ulcer duration > 1 month (p 0.020), ulcer severity of Wagner grade 3 and above (p 0.001), peripheral arterial disease (p 0.005), proteinuria (p < 0.001), positive blood cultures (p < 0.001), low HDL (p < 0.001), shock at presentation (p < 0.001), cardiac failure (p 0.027), and renal impairment (p < 0.001). On Multivariate regression analysis, presence of bacteraemia (OR 5.053; 95% CI 2.572-9.428) and renal impairment (OR 2.838; 95% CI 1.349-5.971) were significantly predictive of mortality independent of other variables. CONCLUSIONS: This study showed high intra-hospital mortality among patients with DFU, with the majority of deaths occurring among those with advanced ulcers, bacteraemia, cardiac failure, and renal impairment. Prompt attention to these factors might help improve survival from DFU in Nigeria.

Arterial Stiffness Predicts Mortality in Individuals With Type 1 Diabetes.

OBJECTIVE: Type 1 diabetes is accompanied by a significant burden of cardiovascular disease (CVD), which is poorly explained by traditional risk factors. We therefore aimed to explore whether arterial stiffness estimated by the augmentation index (AIx) predicts mortality in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: After baseline examination comprising pulse wave analysis by applanation tonometry alongside assessment of traditional cardiovascular risk factors, 906 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study were followed up for a median of 8.2 years (interquartile range 5.7-9.7). Associations between baseline hemodynamics, including AIx, and all-cause mortality as well as a composite of cardiovascular and/or diabetes-related mortality were investigated using multivariable Cox regression models. RESULTS: The 67 individuals who died during follow-up had higher baseline AIx (median 28% [interquartile range 21-33] vs. 19% [9-27]; P < 0.001) compared with those alive. This association was independent of conventional risk factors (age, sex, BMI, HbA1c, estimated glomerular filtration rate [eGFR], and previous CVD event) in Cox regression analysis (standardized hazard ratio 1.71 [95% CI 1.10-2.65]; P = 0.017) and sustained in a subanalysis of individuals with chronic kidney disease. Similarly, higher AIx was associated with the composite secondary end point of cardiovascular and diabetes-related death (N = 53) after adjustments for sex, BMI, eGFR, previous CVD event, and height (standardized hazard ratio 2.30 [1.38-3.83]; P = 0.001). CONCLUSIONS: AIx predicts all-cause mortality as well as a composite cardiovascular and/or diabetes-related cause of death in individuals with type 1 diabetes, independent of established cardiovascular risk factors.

Influenza Vaccination Is Associated With Reduced Cardiovascular Mortality in Adults With Diabetes: A Nationwide Cohort Study.

OBJECTIVE: Recent influenza infection is associated with an increased risk of atherothrombotic events, including acute myocardial infarction (AMI) and stroke. Little is known about the association between influenza vaccination and cardiovascular outcomes in patients with diabetes. RESEARCH DESIGN AND METHODS: We used nationwide register data to identify patients with diabetes in Denmark during nine consecutive influenza seasons in the period 2007-2016. Diabetes was defined as use of glucose-lowering medication. Patients who were not 18-100 years old or had ischemic heart disease, heart failure, chronic obstructive lung disease, cancer, or cerebrovascular disease were excluded. Patient exposure to influenza vaccination was assessed before each influenza season. We considered the outcomes of death from all causes, death from cardiovascular causes, and death from AMI or stroke. For each season, patients were monitored from December 1 until April 1 the next year. RESULTS: A total of 241,551 patients were monitored for a median of four seasons (interquartile range two to eight seasons) for a total follow-up of 425,318 person-years. The vaccine coverage during study seasons ranged from 24% to 36%. During follow-up, 8,207 patients died of all causes (3.4%), 4,127 patients died of cardiovascular causes (1.7%), and 1,439 patients died of AMI/stroke (0.6%). After adjustment for confounders, vaccination was significantly associated with reduced risks of all-cause death (hazard ratio [HR] 0.83, P < 0.001), cardiovascular death (HR 0.84, P < 0.001), and death from AMI or stroke (HR 0.85, P = 0.028) and a reduced risk of being admitted to hospital with acute complications associated with diabetes (diabetic ketoacidosis, hypoglycemia, or coma) (HR 0.89, P = 0.006). CONCLUSIONS: In patients with diabetes, influenza vaccination was associated with a reduced risk of all-cause death, cardiovascular death, and death from AMI or stroke. Influenza vaccination may improve outcome in patients with diabetes.

Temporal Trend in Young-Onset Type 2 Diabetes-Macrovascular and Mortality Risk: Study of U.K. Primary Care Electronic Medical Records.

OBJECTIVE: To evaluate temporal prevalence trend, cardiometabolic risk factors, and the risk of atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality (ACM) in incident young- and usual-onset type 2 diabetes. RESEARCH DESIGN AND METHODS: From the U.K. primary care database, 370,854 people with a new diagnosis of type 2 diabetes from 2000 to 2017 were identified. Analyses were conducted by age-group (18-39, 40-49, 50-59, 60-69, 70-79 years) and high-/low-risk status without history of ASCVD at diagnosis, with subjects with two or more of current smoking, high systolic blood pressure, high LDL cholesterol (LDL-C), or chronic kidney disease classified as high risk. RESULTS: The proportion of people aged <50 years at diagnosis increased during 2000-2010 and then stabilized. The incidence rates of ASCVD and ACM declined in people aged ≥50 years but did not decrease in people <50 years. Compared with people aged ≥50 years, those aged 18-39 years at diagnosis had a higher proportion of obesity (71% obese) and higher HbA1c (8.6%), and 71% had high LDL-C, while only 18% were on cardioprotective therapy. Although 2% in this age-group had ASCVD at diagnosis, 23% were identified as high risk. In the 18-39-year age-group, the adjusted average years to ASCVD/ACM in high-risk individuals (9.1 years [95% CI 8.2-10.0]/9.3 years [8.1-10.4]) were similar to the years in those with low risk (10.0 years [9.5-10.5]/10.5 years [9.7-11.2]). However, individuals aged ≥50 years with high risk were likely to experience an ASCVD event 1.5-2 years earlier and death 1.1-1.5 years earlier compared with low-risk groups (P < 0.01). CONCLUSIONS: Unlike usual-onset, young-onset type 2 diabetes has similar cardiovascular and mortality risk irrespective of cardiometabolic risk factor status at diagnosis. The guidelines on the management of young-onset type 2 diabetes for intensive risk factor management and cardioprotective therapies need to be urgently reevaluated through prospective studies.

Mannose-Binding Lectin and Risk of Cardiovascular Events and Mortality in Type 2 Diabetes: A Danish Cohort Study.

OBJECTIVE: Mannose-binding lectin (MBL) is linked to risk of cardiovascular disease (CVD) in diabetes, but the nature of the association is unclear. We investigated the association between MBL and the risk of cardiovascular events (CVE) and all-cause mortality in type 2 diabetes. RESEARCH DESIGN AND METHODS: In a cohort study of 7,588 patients with type 2 diabetes, we measured serum MBL in 7,305 patients and performed MBL expression genotyping in 3,043 patients. We grouped serum MBL and MBL expression genotypes into three categories: low, intermediate, and high. Outcomes were CVE (myocardial infarction, stroke, coronary revascularization, unstable angina, or cardiovascular death) and all-cause mortality. The association with outcomes was examined by spline and Cox regression analyses. RESULTS: Serum MBL and CVE showed a U-shaped association. Compared with the intermediate serum MBL category, the adjusted hazard ratio (HR) for CVE was 1.82 (95% CI 1.34-2.46) for the low-MBL category and 1.48 (95% CI 1.14-1.92) for the high-MBL category. We found a similar U-shaped association for all-cause mortality, but with lower risk estimates. Compared with the intermediate MBL expression genotype, the adjusted HR for CVE was 1.40 (95% CI 0.87-2.25) for the low-expression genotype and 1.44 (95% CI 1.01-2.06) for the high-expression genotype. MBL expression genotype was not associated with all-cause mortality. CONCLUSIONS: Both serum MBL and MBL expression genotype showed a U-shaped association with CVE risk in individuals with type 2 diabetes. Our findings suggest that serum MBL is a risk factor for CVD in this population.

Body Weight Variability and the Risk of Cardiovascular Outcomes and Mortality in Patients With Type 2 Diabetes: A Nationwide Cohort Study.

OBJECTIVE: Obesity and type 2 diabetes are risk factors for cardiovascular diseases and mortality, and they commonly result in weight variabilities. We aimed to investigate the association between body weight variability and risk of major cardiovascular outcomes and mortality in individuals with type 2 diabetes using large-scale, nationwide cohort data on the Korean population. RESEARCH DESIGN AND METHODS: We enrolled 624,237 individuals with type 2 diabetes who underwent health examinations provided by the Korean National Health Insurance System between 2009 and 2010, with three or more body weight measurements within 5 years since enrollment and followed up until the end of 2017. We assessed body weight variability using four indices, including variability independent of the mean (VIM). A multivariate-adjusted Cox proportional hazards regression analysis was performed. RESULTS: During the follow-up, 15,832, 25,038, and 44,716 cases of myocardial infarction (MI), stroke, and all-cause mortality, respectively, were recorded. Body weight variability was associated with increased risks of major cardiovascular outcomes after adjusting for confounding variables. Compared with the hazard ratios (HRs) of the lowest quartile group, the HRs (95% CIs) of the highest quartile group of VIM for body weight were 1.15 (1.10-1.20), 1.22 (1.18-1.26), and 1.58 (1.53-1.62) for MI, stroke, and all-cause mortality, respectively. CONCLUSIONS: Body weight variability was associated with increased risks of MI, stroke, and all-cause mortality in patients with type 2 diabetes and may be a predictor of cardiovascular outcomes in such patients. Appropriate interventions to maintain stable weight could positively influence health outcomes in patients with type 2 diabetes.