Risk of cancer in young and middle-aged adults with childhood-onset type 1 diabetes in Sweden-A prospective cohort study.

AIMS/HYPOTHESIS: In persons with type 1 diabetes, the risk of cancer remains controversial. We wanted to examine the excess risk of cancer in a large population-based cohort diagnosed with type 1 diabetes before 15 years of age. STUDY POPULATION AND METHODS: From 1 July 1977 to 31 December 2013, we prospectively and on a national scale included 18,724 persons (53% men) with childhood-onset type 1 diabetes. For each person with type 1 diabetes, we selected four referents, matched for the date at birth and municipality of living at the time when the case developed diabetes. Cases and referents were linked to national registers of cancer and of the cause of death. RESULTS: A total of 125 persons (61% women) with diabetes had 135 different cancers, all diagnosed after the diabetes diagnosis. The median duration from diabetes diagnosis to first cancer diagnosis was 19 years (interquartile range 10-26). The median age at cancer diagnosis in the diabetes group was 28 years (interquartile range 20-35). The overall standardized incidence ratio (95%), using the Swedish general population as referents for women with diabetes was 1.28 (1.02, 1.58) and when comparing women with diabetes with matched referents, we found a hazard ratio of 1.42 (1.10, 1.85). No elevated risk was seen for men. Cancers of the breast and testis were the most common types in women and men respectively. CONCLUSIONS: Women with childhood-onset type 1 diabetes had a small but significantly elevated risk of cancer. No such tendency was seen for men. The reason behind this is unclear.

Development of a life expectancy table for individuals with type 1 diabetes.

AIMS/HYPOTHESIS: Tables reporting life expectancies by common risk factors are available for individuals with type 2 diabetes; however, there is currently no published equivalent for individuals with type 1 diabetes. We aimed to develop a life expectancy table using a recently published simulation model for individuals with type 1 diabetes. METHODS: The simulation model was developed using data from a real-world population of patients with type 1 diabetes selected from the Swedish National Diabetes Register. The following six important risk factors were included in the life table: sex; age; current smoking status; BMI; eGFR; and HbA1c. For each of 1024 cells in the life expectancy table, a synthetic cohort containing 1000 individuals was created, with other risk factors assigned values representative of the real-world population. The simulations were executed for all synthetic cohorts and life expectancy for each cell was calculated as mean survival time of the individuals in the respective cohort. RESULTS: There was a substantial variation in life expectancy across patients with different risk factor levels. Life expectancy of 20-year-old men varied from 29.3 years to 50.6 years, constituting a gap of 21.3 years between those with worst and best risk factor levels. In 20-year-old women, this gap was 18.9 years (life expectancy range 35.0-53.9 years). The variation in life expectancy was a function of the combination of risk factor values, with HbA1c and eGFR consistently showing a negative and positive correlation, respectively, with life expectancy at any level combination of other risk factors. Individuals with the lowest level (20 kg/m2) and highest level of BMI (35 kg/m2) had a lower life expectancy compared with those with a BMI of 25 kg/m2. Non-smokers and women had a higher life expectancy than smokers and men, respectively, with the difference in life expectancy ranging from 0.4 years to 2.7 years between non-smokers and smokers, and from 1.9 years to 5.9 years between women and men, depending on levels of other risk factors. CONCLUSIONS/INTERPRETATION: The life expectancy table generated in this study shows a substantial variation in life expectancy across individuals with different modifiable risk factors. The table allows for rapid communications of risk in an easily understood format between healthcare professionals, health economists, researchers, policy makers and patients. Particularly, it supports clinicians in their discussion with patients about the benefits of improving risk factors.

The pattern-recognition molecule H-ficolin in relation to diabetic kidney disease, mortality, and cardiovascular events in type 1 diabetes.

H-ficolin recognizes patterns on microorganisms and stressed cells and can activate the lectin pathway of the complement system. We aimed to assess H-ficolin in relation to the progression of diabetic kidney disease (DKD), all-cause mortality, diabetes-related mortality, and cardiovascular events. Event rates per 10-unit H-ficolin-increase were compared in an observational follow-up of 2,410 individuals with type 1 diabetes from the FinnDiane Study. DKD progression occurred in 400 individuals. The unadjusted hazard ratio (HR) for progression was 1.29 (1.18-1.40) and 1.16 (1.05-1.29) after adjustment for diabetes duration, sex, HbA1c, systolic blood pressure, and smoking status. After adding triglycerides to the model, the HR decreased to 1.07 (0.97-1.18). In all, 486 individuals died, including 268 deaths of cardiovascular causes and 192 deaths of complications to diabetes. HRs for all-cause mortality and cardiovascular mortality were 1.13 (1.04-1.22) and 1.05 (0.93-1.17), respectively, in unadjusted analyses. These estimates lost statistical significance in adjusted models. However, the unadjusted HR for diabetes-related mortality was 1.19 (1.05-1.35) and 1.18 (1.02-1.37) with the most stringent adjustment level. Our results, therefore, indicate that H-ficolin predicts diabetes-related mortality, but neither all-cause mortality nor fatal/non-fatal cardiovascular events. Furthermore, H-ficolin is associated with DKD progression, however, not independently of the fully adjusted model.

Risk of cause-specific death, its sex and age differences, and life expectancy in post-pancreatitis diabetes mellitus.

AIMS: The aim was to investigate sex- and age-stratified risks of cause-specific death and life expectancy in individuals with post-pancreatitis diabetes mellitus (PPDM). METHODS: Nationwide data on mortality in New Zealand were obtained. For two head-to-head comparisons (PPDM versus type 2 diabetes mellitus [T2DM]; PPDM versus type 1 diabetes mellitus [T1DM]), the groups were matched on age, sex, and calendar year of diabetes diagnosis. Multivariable Cox regression analyses were conducted to estimate risks of vascular, cancer, and non-vascular non-cancer mortality. Remaining life expectancy at age of diabetes diagnosis was estimated using the Chiang II method. RESULTS: A total of 15,848 individuals (1,132 PPDM, 3,396 T1DM, and 11,320 T2DM) were included. The risks of vascular mortality and non-vascular non-cancer mortality did not differ significantly between PPDM and T2DM or T1DM. PPDM was associated with a significantly higher risk of cancer mortality compared with T2DM (adjusted hazard ratio, 1.32; 95% confidence interval, 1.08-1.63) or T1DM (adjusted hazard ratio, 1.65; 95% confidence interval, 1.27-2.13). The risk of cancer mortality associated with PPDM (versus T2DM) was significantly higher in women than in men (p for interaction = 0.003). This sex difference in cancer mortality risk was also significant in the comparison between PPDM and T1DM (p for interaction = 0.006). Adults of both sexes with PPDM had the lowest remaining life expectancy (in comparison with T2DM or T1DM) up to 64 years of age. CONCLUSIONS: People with PPDM have a higher risk of cancer mortality compared with those with T2DM or T1DM. This is especially pronounced in women. Young and middle-aged adults with PPDM have a lower life expectancy compared with their counterparts with T2DM or T1DM.

Overall and Cause-Specific Mortality in Patients With Type 1 Diabetes Mellitus: A Population-Based Cohort Study in Taiwan From 1998 Through 2014.

BACKGROUND: To investigate all-cause and cause-specific mortality in Taiwanese patients with type 1 diabetes. METHODS: A cohort of 17,203 patients with type 1 diabetes were identified from Taiwan's National Health Insurance claims in the period of 1998-2014. Person-years were accumulated for each individual from date of type 1 diabetes registration to date of death or the last day of 2014. Age, sex, and calendar year standardized mortality ratios (SMRs) were calculated with reference to the general population. RESULTS: In up to 17 years of follow-up, 4,916 patients died from 182,523 person-years. Diabetes (30.15%), cancer (20.48%), circulatory diseases (13.14%), and renal diseases (11.45%) were the leading underlying causes of death. Mortality rate (26.93 per 1,000 person-years) from type 1 diabetes in Taiwan was high, the cause of death with the highest mortality rate was diabetes (8.12 per 1,000 person-years), followed by cancer (5.52 per 1,000 person-years), and circulatory diseases (3.54 per 1,000 person-years). The all-cause SMR was significantly elevated at 4.16 (95% confidence interval, 4.04-4.28), with a greater all-cause SMR noted in females than in males (4.62 vs 3.79). The cause-specific SMR was highly elevated for diabetes (SMR, 16.45), followed by renal disease (SMR, 14.48), chronic hepatitis and liver cirrhosis (SMR, 4.91) and infection (SMR, 4.59). All-cause SMRs were also significantly increased for all ages, with the greatest figure noted for 15-24 years (SMR, 8.46). CONCLUSIONS: Type 1 diabetes in both genders and all ages was associated with significantly elevated SMRs for all-cause and mostly for diabetes per se and renal disease.

Carotid-Femoral Pulse Wave Velocity as a Risk Marker for Development of Complications in Type 1 Diabetes Mellitus.

Background The value of carotid-femoral pulse wave velocity (cfPWV) as risk factor for development of complications in type 1 diabetes mellitus remains to be determined. We investigated associations between cfPWV and renal outcomes, cardiovascular events, and all-cause mortality in people with type 1 diabetes mellitus. Methods and Results cfPWV was measured with SphygmoCor in 633 people with type 1 diabetes mellitus. Median (interquartile range) follow-up was 6.2 (5.8-6.7) years. End points included progression in albuminuria group, decline in estimated glomerular filtration rate (eGFR) ≥30%, end-stage kidney disease, cardiovascular event, mortality, and a composite renal end point. Hazard ratios (HRs) were calculated per 1-SD increase in cfPWV. Adjustments included age, sex, hemoglobin A1c, mean arterial pressure, body mass index, low-density lipoprotein cholesterol, smoking, urine albumin excretion rate, and eGFR. The cohort included 45% women, mean (SD) age was 54 (13) years, mean (SD) eGFR was 83.2 (27.9) mL/min per 1.73 m2, and mean (SD) cfPWV was 10.4 (3.3) m/s. Median (interquartile range) albumin excretion rate was 17 (17-63) mg/24 h. After adjustment, higher cfPWV was associated with increased hazard of progression in albuminuria (HR, 1.59; 95% CI, 1.10-2.32); decline in eGFR ≥30% (HR, 1.38; 95% CI, 1.06-1.79); cardiovascular event (HR, 1.31; 95% CI, 1.01-1.70); mortality (HR, 1.36; 95% CI, 1.00-1.85); and the composite renal end point (HR, 1.30; 95% CI, 1.04-1.63), but not with end-stage kidney disease (HR, 1.18; 95% CI, 0.62-2.26). Higher cfPWV was associated with steeper yearly increase in albumin excretion and steeper yearly decline in eGFR after adjustment (P=0.002 and P=0.01, respectively). Conclusions cfPWV was associated with increased hazard of renal outcomes, cardiovascular event, and mortality. cfPWV may be suited for risk stratification in type 1 diabetes mellitus.

Global, regional, and national burden and trend of diabetes in 195 countries and territories: an analysis from 1990 to 2025.

Diabetes mellitus is a leading cause of mortality and reduced life expectancy. We aim to estimate the burden of diabetes by type, year, regions, and socioeconomic status in 195 countries and territories over the past 28 years, which provide information to achieve the goal of World Health Organization Global Action Plan for the Prevention and Control of Noncommunicable Diseases in 2025. Data were obtained from the Global Burden of Disease Study 2017. Overall, the global burden of diabetes had increased significantly since 1990. Both the trend and magnitude of diabetes related diseases burden varied substantially across regions and countries. In 2017, global incidence, prevalence, death, and disability-adjusted life-years (DALYs) associated with diabetes were 22.9 million, 476.0 million, 1.37 million, and 67.9 million, with a projection to 26.6 million, 570.9 million, 1.59 million, and 79.3 million in 2025, respectively. The trend of global type 2 diabetes burden was similar to that of total diabetes (including type 1 diabetes and type 2 diabetes), while global age-standardized rate of mortality and DALYs for type 1 diabetes declined. Globally, metabolic risks (high BMI) and behavioral factors (inappropriate diet, smoking, and low physical activity) contributed the most attributable death and DALYs of diabetes. These estimations could be useful in policy-making, priority setting, and resource allocation in diabetes prevention and treatment.

Are the Different Diabetes Subgroups Correlated With All-Cause, Cancer-Related, and Cardiovascular-Related Mortality?

CONTEXT: Numerous studies have shown that cardiovascular disease (CVD) represents the most important cause of mortality among people with diabetes mellitus (DM). However, no studies have evaluated the risk of CVD-related mortality among different DM subgroups. OBJECTIVE: We aimed to examine all-cause, CVD-related, and cancer-related mortality for different DM subgroups. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: We included participants (age ≥ 20 years) from the National Health and Nutrition Examination Survey III (NHANES III) data set. We evaluated the risks of all-cause and cause-specific (CVD and cancer) mortality among 5 previously defined diabetes subgroups: severe autoimmune diabetes (SAID), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). PRIMARY OUTCOME MEASURE: The hazard ratios (HRs) for all-cause and cause-specific (CVD and cancer) mortality were measured for each of the 5 DM subgroups. We also evaluated the odds ratios (ORs) for retinopathy and nephropathy in each subgroup. RESULTS: A total of 712 adults were enrolled and the median follow-up time was 12.71 years (range, 0.25-18.08 years). The number of deaths in the 5 subgroups (SAID, SIDD, SIRD, MOD, and MARD) were 50, 75, 64, 7, and 18, respectively, and the number of CVD-related deaths in the 5 subgroups was 29, 30, 26, 2, and 11, respectively. Compared to the MOD subgroup, the adjusted HRs and 95% CIs of CVD-related mortality for the SAID, SIDD, SIRD, and MARD subgroups were 3.23 (95% CI, 0.77-13.61), 2.87 (95% CI, 0.68-12.06), 2.23 (95% CI, 0.53-9.50), and 4.75 (95% CI, 1.05-21.59), respectively (the HR for the MARD subgroup had a P value of .04). In addition, compared to the MARD subgroup, the adjusted ORs and 95% CIs for retinopathy in the SAID and SIDD groups were 2.38 (95% CI, 1.13-5.01, P = .02) and 3.34 (95% CI, 1.17-6.88, P = .001), respectively. The ORs for nephropathy were nonsignificant. CONCLUSIONS: Our study of patients from the NHANES III data set indicated that among the different DM subgroups, the MARD subgroup tended to have a higher CVD-related mortality than the MOD subgroup. The all-cause and cancer-related mortality rates were similar across the different diabetes subgroups. In addition, compared to the MARD subgroup, the SAID and SIDD subgroups had a higher retinopathy risk, but there was no difference in nephropathy among the subgroups.

Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study.

BACKGROUND: Diabetes has been associated with increased COVID-19-related mortality, but the association between modifiable risk factors, including hyperglycaemia and obesity, and COVID-19-related mortality among people with diabetes is unclear. We assessed associations between risk factors and COVID-19-related mortality in people with type 1 and type 2 diabetes. METHODS: We did a population-based cohort study of people with diagnosed diabetes who were registered with a general practice in England. National population data on people with type 1 and type 2 diabetes collated by the National Diabetes Audit were linked to mortality records collated by the Office for National Statistics from Jan 2, 2017, to May 11, 2020. We identified the weekly number of deaths in people with type 1 and type 2 diabetes during the first 19 weeks of 2020 and calculated the percentage change from the mean number of deaths for the corresponding weeks in 2017, 2018, and 2019. The associations between risk factors (including sex, age, ethnicity, socioeconomic deprivation, HbA1c, renal impairment [from estimated glomerular filtration rate (eGFR)], BMI, tobacco smoking status, and cardiovascular comorbidities) and COVID-19-related mortality (defined as International Classification of Diseases, version 10, code U07.1 or U07.2 as a primary or secondary cause of death) between Feb 16 and May 11, 2020, were investigated by use of Cox proportional hazards models. FINDINGS: Weekly death registrations in the first 19 weeks of 2020 exceeded the corresponding 3-year weekly averages for 2017-19 by 672 (50·9%) in people with type 1 diabetes and 16 071 (64·3%) in people with type 2 diabetes. Between Feb 16 and May 11, 2020, among 264 390 people with type 1 diabetes and 2 874 020 people with type 2 diabetes, 1604 people with type 1 diabetes and 36 291 people with type 2 diabetes died from all causes. Of these total deaths, 464 in people with type 1 diabetes and 10 525 in people with type 2 diabetes were defined as COVID-19 related, of which 289 (62·3%) and 5833 (55·4%), respectively, occurred in people with a history of cardiovascular disease or with renal impairment (eGFR <60 mL/min per 1·73 m2). Male sex, older age, renal impairment, non-white ethnicity, socioeconomic deprivation, and previous stroke and heart failure were associated with increased COVID-19-related mortality in both type 1 and type 2 diabetes. Compared with people with an HbA1c of 48-53 mmol/mol (6·5-7·0%), people with an HbA1c of 86 mmol/mol (10·0%) or higher had increased COVID-19-related mortality (hazard ratio [HR] 2·23 [95% CI 1·50-3·30, p<0·0001] in type 1 diabetes and 1·61 [1·47-1·77, p<0·0001] in type 2 diabetes). In addition, in people with type 2 diabetes, COVID-19-related mortality was significantly higher in those with an HbA1c of 59 mmol/mol (7·6%) or higher than in those with an HbA1c of 48-53 mmol/mol (HR 1·22 [95% CI 1·15-1·30, p<0·0001] for 59-74 mmol/mol [7·6-8·9%] and 1·36 [1·24-1·50, p<0·0001] for 75-85 mmol/mol [9·0-9·9%]). The association between BMI and COVID-19-related mortality was U-shaped: in type 1 diabetes, compared with a BMI of 25·0-29·9 kg/m2, a BMI of less than 20·0 kg/m2 had an HR of 2·45 (95% CI 1·60-3·75, p<0·0001) and a BMI of 40·0 kg/m2 or higher had an HR of 2·33 (1·53-3·56, p<0·0001); the corresponding HRs for type 2 diabetes were 2·33 (2·11-2·56, p<0·0001) and 1·60 (1·47-1·75, p<0·0001). INTERPRETATION: Deaths in people with type 1 and type 2 diabetes rose sharply during the initial COVID-19 pandemic in England. Increased COVID-19-related mortality was associated not only with cardiovascular and renal complications of diabetes but, independently, also with glycaemic control and BMI. FUNDING: None.

A performance score of the quality of inpatient diabetes care is a marker of clinical outcomes and suggests a cause-effect relationship between hypoglycaemia and the risk of in-hospital mortality.

AIMS: To build a tool to assess the management of inpatients with diabetes mellitus and to investigate its relationship, if any, with clinical outcomes. MATERIALS AND METHODS: A total of 678 patients from different settings, Internal Medicine (IMU, n = 255), General Surgery (GSU, n = 230) and Intensive Care (ICU, n = 193) Units, were enrolled. A work-flow of clinical care of diabetes was created according to guidelines. The workflow was divided into five different domains: (a) initial assessment; (b) glucose monitoring; (c) medical therapy; (d) consultancies; (e) discharge. Each domain was assessed by a performance score (PS), computed as the sum of the scores achieved in a set of indicators of clinical appropriateness, management and patient empowerment. Appropriate glucose goals were included as intermediate phenotypes. Clinical outcomes included: hypoglycaemia, survival rate and clinical conditions at discharge. RESULTS: The total PS and those of initial assessment and glucose monitoring were significantly lower in GSU with respect to IMU and ICU (P < .0001). The glucose monitoring PS was associated with lower risk of hypoglycaemia (OR = 0.55; P < .0001), whereas both the PSs of glucose monitoring and medical therapy resulted associated with higher in-hospital survival only in the IMU ward (OR = 6.67 P = .001 and OR = 2.38 P = .03, respectively). Instrumental variable analysis with the aid of PS of glucose monitoring showed that hypoglycaemia may play a causal role in in-hospital mortality (P = .04). CONCLUSIONS: The quality of in-hospital care of diabetes may affect patient outcomes, including glucose control and the risk of hypoglycaemia, and through the latter it may influence the risk of in-hospital mortality.

Periodontal disease, smoking, cardiovascular complications and mortality in type 1 diabetes.

AIM: To assess the role of periodontal disease (PD) as a predictor of coronary artery disease (CAD) and mortality in a prospective type 1 diabetes (T1D) cohort and to evaluate the role of smoking in this relationship. METHODS: Data were based on 320 participants of the Pittsburgh Epidemiology of Diabetes Complications study of T1D who, during 1992-94, received a partial mouth periodontal exam, and who were followed for up to 19 years to ascertain complication incidence. PD was defined as clinical attachment loss of ≥4 mm for at least 10% of the examined sites. Predictors of all-cause mortality; Hard CAD (CAD death, myocardial infarction or revascularization), and Total CAD (Hard CAD, angina, ischemic ECG) were assessed using Cox models. RESULTS: During 19 years of follow-up, 33.7% (97/288) developed CAD, 27.3% (83/304) developed Hard CAD, and 16.9% (54/320) died. Among current smokers, 46.4% (26/56) developed CAD, 42.7% (24/56) developed Hard CAD and 29.5% (18/61) died. PD was not associated with all-cause mortality, although it was a significant predictor of both CAD (HR = 1.12, CI = 1.01-1.23) and Hard CAD (HR = 1.30, CI = 1.11-1.51). As smoking modified the PD-CAD and PD-Hard CAD associations, analyses were stratified by smoking status. PD was associated with an increased risk of CAD (HR = 1.25, CI = 1.03-1.50) and Hard CAD (HR = 1.85, CI = 1.17-2.93) only among smokers. CONCLUSION: PD was a significant predictor of CAD and Hard CAD among current smokers with T1D.

Young adult patients with type 1 diabetes have a higher risk of mortality than those of similar age with type 2 diabetes: A nationwide analysis in Hungary.

BACKGROUND: There are few papers comparing complications of type 1 diabetes with those of a similarly young age with type 2 diabetes. The aim of our nationwide study was to compare the risks of mortality and morbidities between the two types of diabetes (age ≤ 40). METHODS: We identified all young adult patients with type 1 diabetes who were recorded in the database of the Hungarian National Health Insurance Fund between 2001 and 2014 (n = 11 863) and compared them with a population of similar age with young adult type 2 diabetes (n = 47 931). The incidence of all-cause mortality, myocardial infarction, stroke, any type of cancer, diabetic ketoacidosis, and hypoglycemia was followed from the onset of diabetes to the date of death or end of study period. RESULTS: The risks of all-cause mortality were significantly higher in patients with type 1 compared with patients with type 2 diabetes (hazard ratio, 95%CI; 2.17, 1.95-2.41; P < .0001). The risks of myocardial infarction (0.90, 0.71-1.13; P = 0.36) and stroke (1.06, 0.87-1.29; P = .582) were not significantly different in type 1 compared with type 2. In contrast, the risk of cancer (1.35, 1.15-1.59; P = .0003), dialysis (2.20, 1.76-2.75; P < .0001), hypoglycemia (7.70, 6.45-9.18; P < .0001), and ketoacidosis (22.12, 19.60-25.00; P < .0001) was higher among patients with type 1 compared with those with type 2 diabetes. CONCLUSIONS: A comparatively higher incidence of diabetic ketoacidosis and hypoglycemia and higher risk of cancer and dialysis in patients with type 1 diabetes than in those with type 2 may play a role in the higher risk of mortality.

Insulin Dependence Is Associated With Increased Medical Complications and Mortality After Shoulder Arthroscopy.

PURPOSE: To compare complications after shoulder arthroscopy in patients with insulin-dependent diabetes mellitus (IDDM), patients with non-insulin-dependent diabetes mellitus (NIDDM), and nondiabetic patients. METHODS: A retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program database for the years 2005 to 2016 was conducted. Logistic regression analyses were used to assess the relation between diabetic status (nondiabetic patients, n = 50,626; NIDDM patients, n = 5,332; and IDDM patients, n = 2,484) and outcomes. Multivariate models were established to adjust for age, sex, body mass index, hypertension, congestive heart failure, chronic obstructive pulmonary disease, smoking status, American Society of Anesthesiologists classification, and functional status. RESULTS: Patients with IDDM were at a higher risk of medical complications, with an adjusted odds ratio (AOR) of 1.524 (95% confidence interval [CI], 1.082-2.147), including pulmonary complications (AOR, 2.078; 95% CI, 1.089-3.964) and urinary tract infections (AOR, 2.129; 95% CI, 1.027-4.415). Patients with IDDM also had a higher risk of 30-day hospital admission (AOR, 1.581; 95% CI, 1.153-2.169) and 30-day mortality (AOR, 3.821; 95% CI, 1.243-11.750). Conversely, patients with NIDDM had comparable risks of medical and surgical complications, unplanned hospital admission, and death to nondiabetic patients. CONCLUSIONS: Medical complications, 30-day hospital admission, and death after shoulder arthroscopy were more likely in patients with IDDM. These risks diminished among patients with NIDDM, with their risks being comparable with those of nondiabetic patients. LEVEL OF EVIDENCE: Level III, retrospective comparison study.

Fas/FasL-mediated cell death in rat's diabetic hearts involves activation of calcineurin/NFAT4 and is potentiated by a high-fat diet rich in corn oil.

This study investigated if calcineurin/nuclear factor of activated T cells (NFAT) axis mediates the cardiac apoptosis in rats with type 1 diabetes mellitus (T1DM)-induced rats or administered chronically high-fat diet rich in corn oil (CO-HFD). Also, it investigated the impact of chronic administration of CO-HFD on Fas/Fas ligand (Fas/FasL)-induced apoptosis in the hearts of T1DM-induced rats. Adult male Wistar rats (140-160 g) were classified as control: (10% fat) CO-HFD: (40% fat), T1DM, and T1DM + CO-HFD (n=20/each). In vitro, cardiomyocytes were cultured in either low glucose (LG) or high glucose (HG) media in the presence or absence of linoleic acid (LA) and other inhibitors. Compared to the control, increased reactive oxygen species (ROS), protein levels of cytochrome C, cleaved caspase-8 and caspase-3, myocardial damage and impeded left ventricular (LV) function were observed in the hearts of all treated groups and maximally in T1DM + CO-HFD-treated rats. mRNA of all NFAT members (NFAT1-4) were not affected by any treatment. CO-HFD or LA significantly up-regulated Fas levels in both LVs and cultured cardiomyocytes in a ROS dependent mechanism and independent of modulating intracellular Ca2+ levels or calcineurin activity. T1DM or hyperglycemia significant up-regulated mRNA and protein levels of Fas and FasL by activating Ca2+/calcineurin/NFAT-4 axis. Furthermore, Fas/FasL cell death induced by recombinant FasL (rFasL) or HG media was enhanced by pre-incubating the cells with LA. In conclusion, activation of the Ca2+/calcineurin/NFAT4 axis is indispensable for hyperglycemia-induced Fas/FasL cell death in the cardiomyocytes and CO-HFD sensitizes this by up-regulation of Fas.

Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet.

The burden of diabetic cardiovascular autonomic neuropathy (CAN) is expected to increase due to the diabetes epidemic and its early and widespread appearance. CAN has a definite prognostic role for mortality and cardiovascular morbidity. Putative mechanisms for this are tachycardia, QT interval prolongation, orthostatic hypotension, reverse dipping, and impaired heart rate variability, while emerging mechanisms like inflammation support the pervasiveness of autonomic dysfunction. Efforts to overcome CAN under-diagnosis are on the table: by promoting screening for symptoms and signs; by simplifying cardiovascular reflex tests; and by selecting the candidates for screening. CAN assessment allows for treatment of its manifestations, cardiovascular risk stratification, and tailoring therapeutic targets. Risk factors for CAN are mainly glycaemic control in type 1 diabetes mellitus (T1DM) and, in addition, hypertension, dyslipidaemia, and obesity in type 2 diabetes mellitus (T2DM), while preliminary data regard glycaemic variability, vitamin B12 and D changes, oxidative stress, inflammation, and genetic biomarkers. Glycaemic control prevents CAN in T1DM, whereas multifactorial intervention might be effective in T2DM. Lifestyle intervention improves autonomic function mostly in pre-diabetes. While there is no conclusive evidence for a disease-modifying therapy, treatment of CAN manifestations is available. The modulation of autonomic function by SGLT2i represents a promising research field with possible clinical relevance.

Risk of insulin-dependent diabetes mellitus in patients undergoing carotid endarterectomy.

OBJECTIVE: There is conflicting evidence regarding the association of diabetes mellitus (DM) and insulin use with outcomes after carotid endarterectomy (CEA). Therefore, we sought to evaluate the risk of insulin-dependent DM (IDDM) and noninsulin-dependent DM (NIDDM) on 30-day outcomes after CEA. METHODS: We identified patients undergoing CEA from the Targeted Vascular module of the National Surgical Quality Improvement Program (2011-2015) and stratified patients on the basis of their preprocedural symptom status. We compared 30-day outcomes between nondiabetics and patients with NIDDM or IDDM, with 30-day stroke/death as the primary end point. RESULTS: Of 16,739 CEA patients, 9784 (58%) were asymptomatic, of whom 6720 (69%) had no diagnosis of DM, 1109 (11%) had IDDM, and 1955 (20%) had NIDDM. Of the 6955 symptomatic patients, 4982 (72%) had no diagnosis of DM, 810 (12%) had IDDM, and 1163 (17%) had NIDDM. Among asymptomatic patients, patients with IDDM experienced higher rates of 30-day stroke/death compared with those without DM (3.4% vs 1.5%; P < .001), whereas those with NIDDM experienced rates similar to those of patients without DM (2.1% vs 1.5%; P = .1). Moreover, asymptomatic patients with IDDM and an anatomic high-risk criterion experienced a 30-day stroke/death rate of 6.6%. After adjustment, IDDM was associated with 30-day stroke/death in asymptomatic patients compared with patients without DM (odds ratio, 2.3; 95% confidence interval, 1.5-3.4; P < .001), but NIDDM was not (odds ratio, 1.4; 95% confidence interval, 1.0-2.1; P = .1). In comparison, among symptomatic patients, those with IDDM and NIDDM experienced similar rates of 30-day stroke/death as patients without DM (4.9% vs 3.6% and 4.0% vs 3.6%; both P > .1). After adjustment, neither IDDM nor NIDDM was associated with 30-day stroke/death in symptomatic patients compared with symptomatic patients without DM. CONCLUSIONS: Rates of 30-day stroke/death after CEA in asymptomatic patients with IDDM exceed international vascular societies' guideline thresholds for acceptable outcomes in asymptomatic patients, especially those with anatomic high-risk criteria. Thus, asymptomatic patients with IDDM may not benefit from CEA, although more data are needed about the natural history of carotid disease in this population.

Effect of duration and burden of microvascular complications on mortality rate in type 1 diabetes: an observational clinical cohort study.

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.

Variations in Risk of End-Stage Renal Disease and Risk of Mortality in an International Study of Patients With Type 1 Diabetes and Advanced Nephropathy.

OBJECTIVE: Patients with type 1 diabetes and diabetic nephropathy are targets for intervention to reduce high risk of end-stage renal disease (ESRD) and deaths. This study compares risks of these outcomes in four international cohorts. RESEARCH DESIGN AND METHODS: In the 1990s and early 2000s, Caucasian patients with type 1 diabetes with persistent macroalbuminuria in chronic kidney disease stages 1-3 were identified in the Joslin Clinic (U.S., 432), Finnish Diabetic Nephropathy Study (FinnDiane) (Finland, 486), Steno Diabetes Center Copenhagen (Denmark, 368), and INSERM (France, 232) and were followed for 3-18 years with annual creatinine measurements to ascertain ESRD and deaths unrelated to ESRD. RESULTS: During 15,685 patient-years, 505 ESRD cases (rate 32/1,000 patient-years) and 228 deaths unrelated to ESRD (rate 14/1,000 patient-years) occurred. Risk of ESRD was associated with male sex; younger age; lower estimated glomerular filtration rate (eGFR); higher albumin/creatinine ratio, HbA1c, and systolic blood pressure; and smoking. Risk of death unrelated to ESRD was associated with older age, smoking, and higher baseline eGFR. In adjusted analysis, ESRD risk was highest in Joslin versus reference FinnDiane (hazard ratio [HR] 1.44, P = 0.003) and lowest in Steno (HR 0.54, P < 0.001). Differences in eGFR slopes paralleled risk of ESRD. Mortality unrelated to ESRD was lowest in Joslin (HR 0.68, P = 0.003 vs. the other cohorts). Competing risk did not explain international differences in the outcomes. CONCLUSIONS: Despite almost universal renoprotective treatment, progression to ESRD and mortality in patients with type 1 diabetes with advanced nephropathy are still very high and differ among countries. Finding causes of these differences may help reduce risk of these outcomes.

Hospitalization and mortality by diabetes mellitus in children: analysis of temporal series / Interna y mortalidad por diabetes mellitus en la infancia: análisis de series temporais / Internação e mortalidade por diabetes mellitus na infância: análise de séries temporais

ABSTRACT Objective: to analyze the trend of hospitalization rates and mortality due to Diabetes Mellitus in children and adolescents in Brazil. Method: temporal series study, hospitalization rates and diabetes mortality in children and adolescents. Data were obtained from the Hospital Information System and Mortality Information System, from 2005-2015, with analysis performed by polynomial regression modeling. Results: 87,100 hospitalizations and 1,120 deaths from diabetes were analyzed. Hospitalizations rates increased for both genders and all age groups, with an increase for adolescents aged 10-14 years. The mortality rate declined, except for the 15-19-year age group. In the overall mortality trend in Brazil, the South and Southeast showed a decrease, whereas for hospitalizations only the Center-West remained constant, while the others increased. Conclusion: however, there was a decrease in infant mortality and increase in hospitalizations.

RESUMEN Objetivo: analizar la tendencia de las tasas de internación y mortalidad por diabetes mellitus en niños y adolescentes en Brasil. Método: estudio de series temporales, de las tasas de internación y mortalidad por diabetes en niños y adolescentes. Los datos fueron obtenidos del Sistema de Informaciones Hospitalarias y del Sistema de Información sobre Mortalidad, de 2005-2015, con análisis realizado por el modelado de regresión polinomial. Resultados: se analizaron 87.100 internaciones y 1.120 muertes por diabetes. Las tasas de internaciones presentaron aumento para ambos sexos y todas las franjas etarias, con incremento para adolescentes entre 10-14 años. La tasa de mortalidad presentó caída, excepto para el grupo de edad de 15-19 años. A la tendencia de la mortalidad general en Brasil, las regiones Sur y Sudeste presentaron descenso, mientras que para las internaciones, sólo la región Centro-Oeste permaneció constante, mientras que las demás aumentaron. Conclusión: ocurrió decrecimiento de la mortalidad en la infancia, sin embargo, con aumento de las internaciones.

RESUMO Objetivo: analisar a tendência das taxas de internação e mortalidade por Diabetes Mellitus em crianças e adolescentes no Brasil. Método: estudo de séries temporais, das taxas de internação e mortalidade por diabetes em crianças e adolescentes. Os dados foram obtidos do Sistema de Informações Hospitalares e do Sistema de Informações sobre Mortalidade, de 2005-2015, com análise realizada pela modelagem de regressão polinomial. Resultados: foram analisadas 87.100 internações e 1.120 óbitos por diabetes. As taxas de internações apresentaram aumento para ambos os sexos e todas as faixas etárias, com incremento para adolescentes entre 10-14 anos. A taxa de mortalidade apresentou queda, exceto para o grupo etário de 15-19 anos. À tendência da mortalidade geral no Brasil, as regiões Sul e Sudeste apresentaram decréscimo, enquanto que para as internações, apenas a região Centro-Oeste permaneceu constante, enquanto as demais aumentaram. Conclusão: ocorreu decréscimo da mortalidade na infância, porém, com aumento das internações.

Mortality risk remains higher in individuals with type 1 diabetes: A population-based cohort study (the Ayrshire diabetes follow-up cohort [ADOC]).

AIMS: Type 1 diabetes is associated with an increased risk of cardiovascular disease and all-cause mortality. Numerous studies have demonstrated that outcomes for diabetes are improved by intensive glycaemic control, blood pressure control, and treatment of dyslipidaemia in addition to cessation of smoking. The aim of this study was to compare mortalities in individuals with type 1 diabetes with that in non-diabetic individuals, and to investigate the effects of age, gender, glycaemic control, socio-economic status, hypertension, ischaemic heart disease (IHD), smoking status, body mass index (BMI) and dyslipidaemia. METHODS: A population-based analysis in Ayrshire and Arran, Scotland included 253 304 non-diabetic individuals and 1324 individuals with type 1 diabetes who were tracked from 2009 to 2014. RESULTS: Patients with type 1 diabetes had higher mortality rates than non-diabetic individuals (HR, 3.20; P < .01), with relative mortality in female individuals with type 1 diabetes being higher than that in males (OR, 2.38 vs 1.52; P < .01). Increasing age (HR, 2.37), smoking (HR, 1.85), IHD (HR, 1.62) and hypertension (HR, 1.21) (all P < .01) increased mortality risk. A hypertensive female with type 1 diabetes and IHD who smoked had an HR of 11.6 compared with a non-smoking, normotensive non-diabetic female without IHD. For a hypertensive male with type 1 diabetes and IHD who smoked, HR was 6.96. BMI > 30 kg/m2 was associated with reduced mortality risk in both non-diabetic (HR, 0.61) and diabetic subjects (HR, 0.40). CONCLUSIONS: This study confirmed that the risk of mortality in individuals with type 1 diabetes remains elevated. Further studies are required to understand how gender affects the disparity in mortality and why obesity appears to be protective.