Prevención cardiovascular en la diabetes mellitus. ¿Es adecuado hablar de riesgo moderado o intermedio? / Cardiovascular prevention in diabetes mellitus. Is it appropriate to speak of moderate or intermediate risk?

La diabetes, especialmente la tipo 2, está considerada como una situación de riesgo de enfermedad cardiovascular aterosclerosa (ECVA). Los sujetos con diabetes tipo 2 tienen una mortalidad por ECVA 3 veces superior a la de la población general, atribuida a la hiperglucemia y a la frecuente asociación de otros factores de riesgo cardiovascular, como la dislipidemia aterogénica. Numerosas sociedades científicas han establecido una clasificación de riesgo de ECVA en la diabetes basada en 3 grados (moderado, alto y muy alto). Los objetivos del control de la dislipidemia están claramente definidos y aceptados, y varían dependiendo del riesgo cardiovascular previamente establecido. En el riesgo moderado o intermedio, las guías proponen una intervención menos intensiva, manteniendo cifras de c-LDL<100mg/dL y de c-no-HDL<130mg/dL, y esperar 10 años hasta alcanzar la categoría de alto riesgo para iniciar un tratamiento más intensivo. Sin embargo, durante la década de seguimiento preconizada en las guías, el depósito de colesterol en la pared arterial va aumentando, facilitando el desarrollo de una placa de ateroma inestable e inflamatoria, y el desarrollo de ECVA. Alternativamente, se podría considerar desde el inicio que la diabetes conlleva una situación de alto riesgo y el objetivo debería ser c-LDL<70mg/dL. Además, mantener cifras de c-LDL<70mg/dL contribuye a reducir y estabilizar la placa de ateroma, evitando o disminuyendo episodios de mortalidad por ECVA durante esos años de evolución de la diabetes. ¿Deberíamos mantener los objetivos propuestos en los sujetos con diabetes y riesgo moderado durante una década hasta alcanzar la fase de alto riesgo cardiovascular o, por el contrario, adoptar desde el inicio una postura más intensiva buscando reducir el riesgo cardiovascular en la mayoría de los pacientes con diabetes? ¿Es mejor esperar o prevenir con medidas terapéuticas efectivas desde el primer momento? (AU)

Diabetes, especially type 2, is considered a risk situation for atherosclerotic cardiovascular disease (ASCVD). Subjects with diabetes type 2 have a mortality rate due to ASCVD 3 times higher than that found in the general population, attributed to hyperglycemia and the frequent association of other cardiovascular risk factors, such as atherogenic dyslipidemia. Numerous scientific societies have established a risk classification for ASCVD in diabetes based on 3 degrees (moderate, high and very high). The objectives of dyslipidemia control are clearly defined and accepted, and vary depending on the previously established cardiovascular risk. In moderate or intermediate risk, the guidelines propose a less intensive intervention, maintaining LDL-C levels<100mg/dL and NO-HDL-C levels<130mg/dL, and waiting 10 years until reaching the high-risk category to initiate more intensive treatment. However, during the decade of follow-up recommended in the guidelines, cholesterol deposition in the arterial wall increases, facilitating the development of an unstable and inflammatory atheromatous plaque, and the development of ASCVD. Alternatively, diabetes could be considered from the outset to be a high-risk situation and the goal should be LDL-C<70mg/dL. Furthermore, maintaining LDL-C levels<70mg/dL contributes to reducing and stabilizing atheromatous plaque, avoiding or reducing mortality episodes due to ASCVD during those years of diabetes evolution. Should we maintain the proposed objectives in subjects with diabetes and moderate risk for a decade until reaching the high cardiovascular risk phase or, on the contrary, should we adopt a more intensive stance from the beginning seeking to reduce cardiovascular risk in the majority of patients with diabetes? Is it better to wait or prevent with effective therapeutic measures from the first moment? (AU)

Unfavorable social determinants of health and risk of mortality in adults with diabetes: findings from the National Health Interview Survey.

INTRODUCTION: Understanding the role of social determinants of health as predictors of mortality in adults with diabetes may help improve health outcomes in this high-risk population. Using population-based, nationally representative data, this study investigated the cumulative effect of unfavorable social determinants on all-cause mortality in adults with diabetes. RESEARCH DESIGN AND METHODS: We used data from the 2013-2018 National Health Interview Survey, linked to the National Death Index through 2019, for mortality ascertainment. A total of 47 individual social determinants of health were used to categorize participants in quartiles denoting increasing levels of social disadvantage. Poisson regression was used to report age-adjusted mortality rates across increasing social burden. Multivariable Cox proportional hazards models were used to assess the association between cumulative social disadvantage and all-cause mortality in adults with diabetes, adjusting for traditional risk factors. RESULTS: The final sample comprised 182 445 adults, of whom 20 079 had diabetes. In the diabetes population, mortality rate increased from 1052.7 per 100 000 person-years in the first quartile (Q1) to 2073.1 in the fourth quartile (Q4). In multivariable models, individuals in Q4 experienced up to twofold higher mortality risk relative to those in Q1. This effect was observed similarly across gender and racial/ethnic subgroups, although with a relatively stronger association for non-Hispanic white participants compared with non-Hispanic black and Hispanic subpopulations. CONCLUSIONS: Cumulative social disadvantage in individuals with diabetes is associated with over twofold higher risk of mortality, independent of established risk factors. Our findings call for action to screen for unfavorable social determinants and design novel interventions to mitigate the risk of mortality in this high-risk population.

Effects of inappropriate cause-of-death certification on mortality from cardiovascular disease and diabetes mellitus in Tonga.

BACKGROUND: Cardiovascular disease (CVD) and diabetes mellitus are major health issues in Tonga and other Pacific countries, although mortality levels and trends are unclear. We assess the impacts of cause-of-death certification on coding of CVD and diabetes as underlying causes of death (UCoD). METHODS: Tongan records containing cause-of-death data (2001-2018), including medical certificates of cause-of-death (MCCD), had UCoD assigned according to International Classification of Diseases 10th revision (ICD-10) coding rules. Deaths without recorded cause were included to ascertain total mortality. Diabetes and hypertension causes were reallocated from Part 1 of the MCCD (direct cause) to Part 2 (contributory cause) if potentially fatal complications were not recorded, and an alternative UCoD was assigned. Proportional mortality by cause based on the alternative UCoD were applied to total deaths then mortality rates calculated by age and sex using census/intercensal population estimates. CVD and diabetes mortality rates for unaltered and alternative UCoD were compared using Poisson regression. RESULTS: Over 2001-18, in ages 35-59 years, alternative CVD mortality was higher than unaltered CVD mortality in men (p = 0.043) and women (p = 0.15); for 2010-18, alternative versus unaltered measures in men were 3.3/103 (95%CI: 3.0-3.7/103) versus 2.9/103 (95%CI: 2.6-3.2/103), and in women were 1.1/103 (95%CI: 0.9-1.3/103) versus 0.9/103 (95%CI: 0.8-1.1/103). Conversely, alternative diabetes mortality rates were significantly lower than the unaltered rates over 2001-18 in men (p < 0.0001) and women (p = 0.013); for 2010-18, these measures in men were 1.3/103 (95%CI: 1.1-1.5/103) versus 1.9/103 (95%CI: 1.6-2.2/103), and in women were 1.4/103 (95%CI: 1.2-1.7/103) versus 1.7/103 (95%CI: 1.5-2.0/103). Diabetes mortality rates increased significantly over 2001-18 in men (unaltered: p < 0.0001; alternative: p = 0.0007) and increased overall in women (unaltered: p = 0.0015; alternative: p = 0.014). CONCLUSIONS: Diabetes reporting in Part 1 of the MCCD, without potentially fatal diabetes complications, has led to over-estimation of diabetes, and under-estimation of CVD, as UCoD in Tonga. This indicates the importance of controlling various modifiable risks for atherosclerotic CVD (including stroke) including hypertension, tobacco use, and saturated fat intake, besides obesity and diabetes. Accurate certification of diabetes as a direct cause of death (Part 1) or contributory factor (Part 2) is needed to ensure that valid UCoD are assigned. Examination of multiple cause-of-death data can improve understanding of the underlying causes of premature mortality to better inform health planning.

Relación entre indicadores de desarrollo social y mortalidad por Diabetes Mellitus en Brasil: análisis espacial y temporal / Relationship between social development indicators and mortality due to Diabetes Mellitus in Brazil: a space-time analysis / Relação indicadores de desenvolvimento social e mortalidade por diabetes mellitus no Brasil: análise espacial e temporal

Objetivo: identificar el patrón espacial y temporal de la mortalidad por Diabetes Mellitus en Brasil y su relación con los indicadores de desarrollo social. Método: estudio ecológico y de series temporales, a nivel nacional, con base en datos secundarios del Departamento de Informática del Sistema Único de Salud, con análisis espacial y temporal e inserción de indicadores en modelos de regresión no espacial y espacial. Se realizaron: cálculo de la tasa de mortalidad general; caracterización del perfil sociodemográfico y regional de las muertes mediante análisis descriptivo y temporal; y elaboración de mapas temáticos. Resultados: en Brasil se registraron 601.521 muertes relacionadas con la Diabetes Mellitus, lo que representa una mortalidad media de 29,5/100.000 habitantes. Los estados de Rio Grande do Norte, Paraíba, Pernambuco, Alagoas y Sergipe, Río de Janeiro, Paraná y Rio Grande do Sul presentaron conglomerados alto-alto. Mediante el uso de modelos de regresión, se comprobó que el índice de Gini (β=11,7) y la cobertura de la Estrategia Salud de la Familia (β=3,9) fueron los indicadores que más influyeron en la mortalidad por Diabetes Mellitus en Brasil. Conclusión: la mortalidad por diabetes en Brasil tiene una tendencia general alcista, está fuertemente asociada a los lugares con peores indicadores sociales.

Objective: to identify the space-time pattern of mortality due to Diabetes Mellitus in Brazil, as well as its relationship with social development indicators. Method: an ecological and time series nationwide study based on secondary data from the Unified Health System Informatics Department, with space-time analysis and inclusion of indicators in non-spatial and spatial regression models. The following was performed: overall mortality rate calculation; characterization of the sociodemographic and regional profiles of the death cases by means of descriptive and time analysis; and elaboration of thematic maps. Results: a total of 601,521 deaths related to Diabetes Mellitus were recorded in Brazil, representing a mean mortality rate of 29.5/100,000 inhabitants. The states of Rio Grande do Norte, Paraíba, Pernambuco, Alagoas and Sergipe, Rio de Janeiro, Paraná and Rio Grande do Sul presented high-high clusters. By using regression models, it was verified that the Gini index (β=11.7) and the Family Health Strategy coverage (β=3.9) were the indicators that most influenced mortality due to Diabetes Mellitus in Brazil. Conclusion: in Brazil, mortality due to Diabetes presents an overall increasing trend, revealing itself as strongly associated with places that have worse social indicators.

Objetivo: identificar o padrão espacial e temporal da mortalidade por diabetes mellitus, no Brasil, e sua relação com indicadores de desenvolvimento social. Método: estudo ecológico e de séries temporais, de abrangência nacional, com base em dados secundários do Departamento de Informática do Sistema Único de Saúde, com análise espacial e temporal e inserção de indicadores em modelos de regressão não espacial e espacial. Realizaram-se: cálculo da taxa de mortalidade geral; caracterização do perfil sociodemográfico e regional dos óbitos mediante análise descritiva e temporal; e construção de mapas temáticos. Resultados: foram registrados 601.521 óbitos relacionados ao diabetes mellitus no Brasil, representando mortalidade média de 29,5/100.000 habitantes. Os estados do Rio Grande do Norte, Paraíba, Pernambuco, Alagoas e Sergipe, Rio de Janeiro, Paraná e Rio Grande do Sul apresentaram aglomerados alto-alto. Por meio do uso de modelos de regressão, verificou-se que o índice Gini (β=11,7) e a cobertura da Estratégia de Saúde da Família (β=3,9) foram os indicadores que mais influenciaram a mortalidade por diabetes mellitus no Brasil. Conclusão: a mortalidade por diabetes, no Brasil, exibe tendência geral ascendente, revelando-se fortemente associada a locais com piores indicadores sociais.

Trends in all causes and cause specific mortality attributable to ambient particulate matter pollution in China from 1990 to 2019: A secondary data analysis study.

BACKGROUND: Particularly fine particulate matter (PM2.5) has become a significant public health concern in China due to its harmful effects on human health. This study aimed to examine the trends in all causes and cause specific morality burden attributable to PM2.5 pollution in China. METHODS: We extracted data on all causes and cause specific mortality data attributable to PM2.5 exposure for the period 1990-2019 in China from the Global Burden of Disease 2019. The average annual percent change (AAPC) in age-standardized mortality rates (ASMR) and years of life lost (YLLs) due to PM2.5 exposure were calculated using the Joinpoint Regression Program. Using Pearson's correlation, we estimated association between burden trends, urban green space area, and higher education proportions. RESULTS: During the period 1990-1999, there were increases in mortality rates for All causes (1.6%, 95% CI: 1.5% to 1.8%), Diabetes mellitus (5.2%, 95% CI: 4.9% to 5.5%), Encephalitis (3.1%, 95% CI: 2.6% to 3.5%), Ischemic heart disease (3.3%, 95% CI: 3% to 3.6%), and Tracheal, bronchus and lung cancer (5%, 95% CI: 4.7% to 5.2%). In the period 2010-2019, Diabetes mellitus still showed an increase in mortality rates, but at a lower rate with an AAPC of 1.2% (95% CI: 1% to 1.4%). Tracheal bronchus and lung cancer showed a smaller increase in this period, with an AAPC of 0.5% (95% CI: 0.3% to 0.6%). In terms of YLLs, the trends appear to be similar. CONCLUSION: Our findings highlight increasing trends in disease burden attributable to PM2.5 in China, particularly for diabetes mellitus, tracheal, bronchus, and lung cancer.

Relationship between social development indicators and mortality due to Diabetes Mellitus in Brazil: a space-time analysis. / Relación entre indicadores de desarrollo social y mortalidad por Diabetes Mellitus en Brasil: análisis espacial y temporal.

OBJECTIVE: to identify the space-time pattern of mortality due to Diabetes Mellitus in Brazil, as well as its relationship with social development indicators. METHOD: an ecological and time series nationwide study based on secondary data from the Unified Health System Informatics Department, with space-time analysis and inclusion of indicators in non-spatial and spatial regression models. The following was performed: overall mortality rate calculation; characterization of the sociodemographic and regional profiles of the death cases by means of descriptive and time analysis; and elaboration of thematic maps. RESULTS: a total of 601,521 deaths related to Diabetes Mellitus were recorded in Brazil, representing a mean mortality rate of 29.5/100,000 inhabitants. The states of Rio Grande do Norte, Paraíba, Pernambuco, Alagoas and Sergipe, Rio de Janeiro, Paraná and Rio Grande do Sul presented high-high clusters. By using regression models, it was verified that the Gini index (ß=11.7) and the Family Health Strategy coverage (ß=3.9) were the indicators that most influenced mortality due to Diabetes Mellitus in Brazil. CONCLUSION: in Brazil, mortality due to Diabetes presents an overall increasing trend, revealing itself as strongly associated with places that have worse social indicators. HIGHLIGHTS: (1) The time-space pattern of mortality due to Diabetes presents an increasing trend. (2) The Northeast and South regions present high rates of mortality due to Diabetes. (3) Mortality due to Diabetes is associated with worse sociodemographic indicators. (4) A relationship is observed between income, access to health and mortality due to Diabetes.

Machine learning-based models to predict one-year mortality among Chinese older patients with coronary artery disease combined with impaired glucose tolerance or diabetes mellitus.

PURPOSE: An accurate prediction of survival prognosis is beneficial to guide clinical decision-making. This prospective study aimed to develop a model to predict one-year mortality among older patients with coronary artery disease (CAD) combined with impaired glucose tolerance (IGT) or diabetes mellitus (DM) using machine learning techniques. METHODS: A total of 451 patients with CAD combined with IGT and DM were finally enrolled, and those patients randomly split 70:30 into training cohort (n = 308) and validation cohort (n = 143). RESULTS: The one-year mortality was 26.83%. The least absolute shrinkage and selection operator (LASSO) method and ten-fold cross-validation identified that seven characteristics were significantly associated with one-year mortality with creatine, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and chronic heart failure being risk factors and hemoglobin, high density lipoprotein cholesterol, albumin, and statins being protective factors. The gradient boosting machine model outperformed other models in terms of Brier score (0.114) and area under the curve (0.836). The gradient boosting machine model also showed favorable calibration and clinical usefulness based on calibration curve and clinical decision curve. The Shapley Additive exPlanations (SHAP) found that the top three features associated with one-year mortality were NT-proBNP, albumin, and statins. The web-based application could be available at https://starxueshu-online-application1-year-mortality-main-49cye8.streamlitapp.com/ . CONCLUSIONS: This study proposes an accurate model to stratify patients with a high risk of one-year mortality. The gradient boosting machine model demonstrates promising prediction performance. Some interventions to affect NT-proBNP and albumin levels, and statins, are beneficial to improve survival outcome among patients with CAD combined with IGT or DM.

Association between glucose tolerance and mortality among Japanese community-dwelling older adults aged over 75 years: 12-year observation of the Tosa Longitudinal Aging Study.

AIM: Although the relationship between impaired glucose tolerance (IGT) and mortality has been investigated in diverse populations, few studies have focused on older populations. This study aimed to investigate the relationship between glucose tolerance and overall mortality among populations aged ≥75 years. METHODS: Data were obtained from the Tosa Longitudinal Aging Study, a community-based cohort survey conducted in Kochi, Japan. According to the results of a 75-g oral glucose tolerance test conducted in 2006, the participants were classified into four categories: normal glucose tolerance (NGT), impaired fasting glucose (IFG)/IGT, newly diagnosed diabetes mellitus (NDM), and known diabetes mellitus (KDM). The primary endpoint was overall mortality. Differences in overall mortality among the four categories were evaluated using the Cox proportional hazards model. RESULTS: During a median of 11.5 years of observation, 125 deaths of the 260 enrolled participants were recorded. The cumulative overall survival rate was 0.52, and the survival rates of NGT, IFG/IGT, NDM, and KDM were 0.48, 0.49, 0.49, and 0.25, respectively (log-rank test, P = 0.139). Adjusted hazard ratios (HRs) for mortality in the IFG/IGT and NDM groups compared with the NGT group were 1.02 (95% confidence interval [CI], 0.66-1.58) and 1.11 (95% CI, 0.56-2.22), while mortality in the KDM group was significantly higher than that in the NGT group (HR, 2.43; 95% CI, 1.35-4.37). CONCLUSION: Mortality did not differ significantly between the IFG/IGT, NDM, and NGT groups, but was higher in the KDM group than in the NGT group. Geriatr Gerontol Int 2023; 23: 341-347.

Research Note: COVID-19 Is Not an Independent Cause of Death.

The COVID-19 pandemic has had overwhelming global impacts with deleterious social, economic, and health consequences. To assess the COVID-19 death toll, researchers have estimated declines in 2020 life expectancy at birth (e0). When data are available only for COVID-19 deaths, but not for deaths from other causes, the risks of dying from COVID-19 are typically assumed to be independent of those from other causes. In this research note, we explore the soundness of this assumption using data from the United States and Brazil, the countries with the largest number of reported COVID-19 deaths. We use three methods: one estimates the difference between 2019 and 2020 life tables and therefore does not require the assumption of independence, and the other two assume independence to simulate scenarios in which COVID-19 mortality is added to 2019 death rates or is eliminated from 2020 rates. Our results reveal that COVID-19 is not independent of other causes of death. The assumption of independence can lead to either an overestimate (Brazil) or an underestimate (United States) of the decline in e0, depending on how the number of other reported causes of death changed in 2020.

Trends and all-cause mortality associated with multimorbidity of non-communicable diseases among adults in the United States, 1999-2018: a retrospective cohort study.

OBJECTIVES: Multimorbidity of non-communicable diseases (NCDs) has brought enormous challenges to public health, becoming a major medical burden. However, the patterns, temporal trends, and all-cause mortality associated with NCD multimorbidity over time have not been well described in the United States. METHODS: All adult participants were sourced from nationally representative data from the National Health and Nutrition Examination Survey. In total, 55,081 participants were included in trend analysis, and 38,977 participants were included in Cox regression. RESULTS: The 5 NCDs with the largest increases over the study period were diabetes, osteoporosis, obesity, liver conditions, and cancer. The estimated prevalence of multimorbidity increased with age, especially for middle-aged participants with 5 or more NCDs; in general, the prevalence of NCD multimorbidity was higher among females than males. Participants with 5 or more NCDs were at 4.49 times the risk of all-cause mortality of participants without any diseases. Significant interactions were found between multimorbidity and age group (p for interaction <0.001), race/ethnicity (p for interaction<0.001), and educational attainment (p for interaction=0.010). CONCLUSIONS: The prevalence of multiple NCDs significantly increased from 1999 to 2018. Those with 5 or more NCDs had the highest risk of all-cause mortality, especially among the young population. The data reported by this study could serve as a reference for additional NCD research.

Años de vida saludable perdidos por diabetes mellitus en Cuba / Years of Healthy Life Lost Due to Diabetes Mellitus in Cuba

Introducción: El reciente incremento de la prevalencia de la diabetes mellitus en Cuba sucedió con mayor celeridad, y las políticas encaminadas a su control requieren de su cuantificación sistemática. Objetivo: Identificar las diferencias en Cuba, según provincia y sexo, de los años de vida saludable perdidos por la diabetes mellitus en el 2015. Métodos: En el estudio de extensión nacional se obtuvieron los años de vida saludable perdidos como resultado de la suma de los años perdidos de vida potencial por mortalidad prematura y los años de vida perdidos por morbilidad y otros indicadores para identificar la mortalidad temprana en el año 2015. Resultados: En todas las provincias los índices de años de vida saludable perdidos por morbilidad superaron los de mortalidad prematura con predominio del sexo femenino, mientras en la mayoría de las provincias, las edades de las defunciones fueron más tempranas en el masculino. Las diferencias halladas permitieron agrupar a Artemisa, La Habana, Mayabeque, Matanzas, Villa Clara, Cienfuegos, Santi Spíritus y Camagüey, con los mayores promedios de años perdidos por morbilidad y fallecimientos más tardíos, y al resto de las provincias cubanas, con los menores años perdidos por morbilidad, pero con defunciones en edades más tempranas. Conclusiones: Las pérdidas de años de vida saludable difieren según el sexo y la provincia. Este conocimiento permite la identificación de diferentes patrones de morbimortalidad útiles para orientar las acciones de prevención y control de la enfermedad para cada territorio(AU)

Introduction: The recent increase in the prevalence of diabetes mellitus in Cuba occurred more rapidly, and policies aimed at its control require systematic quantification. Objective: To identify the differences in Cuba, according to province and sex, of the years of healthy life lost due to diabetes mellitus in 2015. Methods: The national extension study collected data on the healthy years of life lost as a result of the sum of years lost from potential life due to premature mortality and years of life lost due to morbidity and other indicators to identify early mortality in 2015. Results: In all provinces, the rates of years of healthy life lost due to morbidity exceeded those of premature mortality with a predominance of women, while in most provinces, the ages of death were earlier in the male sex. The differences found allowed to group Artemisa, Havana, Mayabeque, Matanzas, Villa Clara, Cienfuegos, Santi Spíritus and Camagüey provincesn with the highest averages of years lost due to morbidity and later deaths, and the rest of the Cuban provinces, with the lowest years lost due to morbidity, but with deaths at younger ages. Conclusions: Losses of years of healthy life differ by sex and province. This knowledge allows the identification of different patterns of morbidity and mortality useful to guide the prevention and control actions of the disease for each territory(AU)

Diabetes acts on mortality in hemodialysis patients predicted by asymmetric dimethylarginine and inflammation.

BACKGROUND: The mortality rate of diabetic patients on dialysis is higher than that of non-diabetic patients. Asymmetric dimethylarginine and inflammation are strong predictors of death in hemodialysis. This study aimed to evaluate asymmetric dimethylarginine and C-reactive protein interaction in predicting mortality in hemodialysis according to the presence or absence of diabetes. METHODS: Asymmetric dimethylarginine and C-reactive protein were measured in 202 patients in maintenance hemodialysis assembled from 2011 to 2012 and followed for four years. Effect modification of C-reactive protein on the relationship between asymmetric dimethylarginine and all-cause mortality was investigated dividing the population into four categories according to the median of asymmetric dimethylarginine and C-reactive protein. RESULTS: Asymmetric dimethylarginine and C-reactive protein levels were similar between diabetics and non-diabetics. Asymmetric dimethylarginine - median IQR µM - (1.95 1.75-2.54 versus 1.03 0.81-1.55 P=0.000) differed in non-diabetics with or without evolution to death (HR 2379 CI 1.36-3.68 P=0.000) and was similar in diabetics without or with evolution to death. Among non-diabetics, the category with higher asymmetric dimethylarginine and C-reactive protein levels exhibited the highest mortality (69.0% P=0.000). No differences in mortality were seen in diabetics. A joint effect was found between asymmetric dimethylarginine and C-reactive protein, explaining all-cause mortality (HR 15.21 CI 3.50-66.12 P=0.000). CONCLUSIONS: Asymmetric dimethylarginine is an independent predictor of all-cause mortality in non-diabetic patients in hemodialysis. Other risk factors may overlap asymmetric dimethylarginine in people with diabetes. Inflammation dramatically increases the risk of death associated with high plasma asymmetric dimethylarginine in hemodialysis.

Predictive value of a novel sub-item mortality risk score derived from the Norfolk Quality of Life in Diabetic Neuropathy questionnaire in Romanian participants with diabetes mellitus.

AIMS: To evaluate whether the Norfolk Quality of Life in Diabetic Neuropathy (QOL-DN) questionnaire and the novel Norfolk Mortality Risk Score (NMRS), comprising Norfolk QOL-DN items, can identify 4-year mortality risk in individuals with diabetes. METHODS: Of 21,756 adults completing Norfolk QOL-DN in 2012, two groups of surviving and deceased patients were identified in 2016: Group 1, from a county capital and Group 2, from six small cities. NMRS was calculated in Group 1 using the 2012 scores of Norfolk QOL-DN items that discriminate between deceased and surviving participants (p < 0.05) and was subsequently applied to Group 2. RESULTS: 763 participants were included (Group 1: 481 [450 surviving, 31 deceased]; Group 2: 282 [218 surviving, 64 deceased]). Total Norfolk QOL-DN score was significantly higher (worse) in deceased participants than in survivors in both groups (p ≤ 0.008). Optimal cut-off for the 25-item NMRS was 11.5 in Group 1. Individuals in Groups 1 and 2 with NMRS≥ 11.5 in 2012 had a 4-year mortality risk ratio of 4.24 (95 % confidence interval [CI]: 1.65-10.84) and 2.33 (95 % CI: 1.33-4.07), respectively, corresponding to 8 and 16 additional deaths/100 persons/4 years (p = 0.001). CONCLUSION: Norfolk QOL-DN and NMRS can identify individuals with diabetes at risk of 4-year mortality.

Age and sex-specific associations of visit-to-visit variability of glycated hemoglobin A1c with all-cause mortality in patients with diabetes.

BACKGROUND: Visit-to-visit variability (VVV) of glycated hemoglobin (HbA1c) levels have been found to be associated with prognosis of diabetes. However, little is known about whether or to what extent sex and age may modify the effects of VVV. METHODS: To investigate age- and sex-specific rates of mortality from all causes and relative hazards of mortality in association with VVV of HbA1c levels, 47,145 patients with diabetes and prescription of any antidiabetic agents >6 months were identified from outpatient visits of a tertiary medical center in northern Taiwan during 2003-2018. VVV of HbA1c was measured by quartiles of standard deviation (SD), coefficient of variation (CV), and average real variability (ARV), respectively. The study subjects were linked to Taiwan's National Death Registry to identify all-cause mortality. The person-year approach with the Poisson assumption was used to assess the all-cause mortality rates, and Cox proportional hazard regression model was used to evaluate the relative hazards of all-cause mortality concerning various levels of VVV of HbA1c. RESULTS: The lowest all-cause mortality rate was found in either the first or second quartile of various measures for VVV of HbA1c, but the highest mortality rate was consistently observed in the fourth quartile of VVV, regardless of SD, CV, or ARV across ages and sexes. Increased hazards of overall all-cause mortality were noticed from the second to fourth quartile of VVV of HbA1c. In detailed age- and sex-stratified analyses, elevated risk of mortality was seen in the fourth quartile of those aged <50 years while in those aged >69 years, increased risk of mortality was noticed in the third and fourth quartiles of any VVV of HbA1c irrespective of sex. In those aged 50-69 years, incremental increased hazards of mortality were consistently observed in the second to fourth quartiles of VVV of HbA1c. CONCLUSION: HbA1c variability whether it was SD, CV, or ARV could strongly predict the risks of all-cause mortality. The extent of the relationship between VVV of HbA1c and all-cause mortality in different age groups was comparable between both sexes. Given the importance of long-term glucose fluctuation, the inclusion of HbA1c variability calculated from the standardized method should be considered by clinical guideline policymakers as part of the biochemical panel in daily diabetes management.

Trends in lifetime risk and years of potential life lost from diabetes in the United States, 1997-2018.

BACKGROUND: Both incidence and mortality of diagnosed diabetes have decreased over the past decade. However, the impact of these changes on key metrics of diabetes burden-lifetime risk (LR), years of potential life lost (YPLL), and years spent with diabetes-is unknown. METHODS: We used data from 653,811 adults aged ≥18 years from the National Health Interview Survey, a cross-sectional sample of the civilian non-institutionalized population in the United States. LR, YPLL, and years spent with diabetes were estimated from age 18 to 84 by survey period (1997-1999, 2000-2004, 2005-2009, 2010-2014, 2015-2018). The age-specific incidence of diagnosed diabetes and mortality were estimated using Poisson regression. A multistate difference equation accounting for competing risks was used to model each metric. RESULTS: LR and years spent with diabetes initially increased then decreased over the most recent time periods. LR for adults at age 20 increased from 31.7% (95% CI: 31.2-32.1%) in 1997-1999 to 40.7% (40.2-41.1%) in 2005-2009, then decreased to 32.8% (32.4-33.2%) in 2015-2018. Both LR and years spent with diabetes were markedly higher among adults of non-Hispanic Black, Hispanic, and other races compared to non-Hispanic Whites. YPLL significantly decreased over the study period, with the estimated YPLL due to diabetes for an adult aged 20 decreasing from 8.9 (8.7-9.1) in 1997-1999 to 6.2 (6.1-6.4) in 2015-2018 (p = 0.02). CONCLUSION: In the United States, diabetes burden is declining, but disparities by race/ethnicity remain. LR remains high with approximately one-third of adults estimated to develop diabetes during their lifetime.

Relation of Hemoglobin A1C Levels to Risk of Ischemic Stroke and Mortality in Patients With Diabetes Mellitus and Atrial Fibrillation.

Diabetes mellitus (DM) is associated with an increased risk of complications in atrial fibrillation (AF). This study aimed to assess the incidence and risks of ischemic stroke and mortality according to baseline HbA1c levels in patients with DM and AF. We conducted a cohort study using Clalit Health Services electronic medical records. The study population included all Clalit Health Services members aged ≥25 years, with the first diagnosis of AF between January 1, 2010, and December 31, 2016, who had a diagnosis of DM. The risk of stroke and all-cause death were compared according to HbA1c levels at the time of AF diagnosis: <7.0%, between 7% and 9%, and ≥9%. A total of 44,451 patients with DM and AF were identified. The median age was 75 years (interquartile 65 to 83), and 52.5% were women. During a mean follow-up of 38 months, higher levels of HbA1c were associated with an increased risk of stroke with a dose-dependent response when compared with patients with HbA1c <7% (Adjusted hazard ratio [aHR] =1.30 [95% confidence interval 1.10 to 2.05] for levels between 7% and 9% and 1.60 (95% confidence interval 1.25 to 2.03) for HbA1c >9%, even after adjusting for CHA2DS2-Vasc risk factors and use of oral anticoagulants. The risk for overall mortality was significantly higher in the HBA1C >9% group (aHR = 1.17 [1.07 to 1.28]). In conclusion, in this cohort of patients with AF and DM, HbA1c levels were associated with the risk of stroke in a dose-dependent manner even after accounting for other recognized risk factors for stroke.

Excess years of life lost to COVID-19 and other causes of death by sex, neighbourhood deprivation, and region in England and Wales during 2020: A registry-based study.

BACKGROUND: Deaths in the first year of the Coronavirus Disease 2019 (COVID-19) pandemic in England and Wales were unevenly distributed socioeconomically and geographically. However, the full scale of inequalities may have been underestimated to date, as most measures of excess mortality do not adequately account for varying age profiles of deaths between social groups. We measured years of life lost (YLL) attributable to the pandemic, directly or indirectly, comparing mortality across geographic and socioeconomic groups. METHODS AND FINDINGS: We used national mortality registers in England and Wales, from 27 December 2014 until 25 December 2020, covering 3,265,937 deaths. YLLs (main outcome) were calculated using 2019 single year sex-specific life tables for England and Wales. Interrupted time-series analyses, with panel time-series models, were used to estimate expected YLL by sex, geographical region, and deprivation quintile between 7 March 2020 and 25 December 2020 by cause: direct deaths (COVID-19 and other respiratory diseases), cardiovascular disease and diabetes, cancer, and other indirect deaths (all other causes). Excess YLL during the pandemic period were calculated by subtracting observed from expected values. Additional analyses focused on excess deaths for region and deprivation strata, by age-group. Between 7 March 2020 and 25 December 2020, there were an estimated 763,550 (95% CI: 696,826 to 830,273) excess YLL in England and Wales, equivalent to a 15% (95% CI: 14 to 16) increase in YLL compared to the equivalent time period in 2019. There was a strong deprivation gradient in all-cause excess YLL, with rates per 100,000 population ranging from 916 (95% CI: 820 to 1,012) for the least deprived quintile to 1,645 (95% CI: 1,472 to 1,819) for the most deprived. The differences in excess YLL between deprivation quintiles were greatest in younger age groups; for all-cause deaths, a mean of 9.1 years per death (95% CI: 8.2 to 10.0) were lost in the least deprived quintile, compared to 10.8 (95% CI: 10.0 to 11.6) in the most deprived; for COVID-19 and other respiratory deaths, a mean of 8.9 years per death (95% CI: 8.7 to 9.1) were lost in the least deprived quintile, compared to 11.2 (95% CI: 11.0 to 11.5) in the most deprived. For all-cause mortality, estimated deaths in the most deprived compared to the most affluent areas were much higher in younger age groups, but similar for those aged 85 or over. There was marked variability in both all-cause and direct excess YLL by region, with the highest rates in the North West. Limitations include the quasi-experimental nature of the research design and the requirement for accurate and timely recording. CONCLUSIONS: In this study, we observed strong socioeconomic and geographical health inequalities in YLL, during the first calendar year of the COVID-19 pandemic. These were in line with long-standing existing inequalities in England and Wales, with the most deprived areas reporting the largest numbers in potential YLL.

Long-term exposure to objective and perceived residential greenness and diabetes mortality: A census-based cohort study.

BACKGROUND: Residing close to green spaces might reduce diabetes mellitus (DM) risk; however, evidence for diabetes mortality is limited. Moreover, individual and neighbourhood social factors may determine DM risk. Exposure to green spaces may also depend on socioeconomic position (SEP). This study examined the associations between residential greenness and diabetes-related mortality, and the role of the social environment in these associations. METHODS: We used the 2001 Belgian census linked to mortality register data for the period 2001-2014. We included individuals aged 40-79 years old and residing in the five largest Belgian urban areas at baseline. Exposure to residential greenness was assessed with surrounding greenness using the Normalized Difference Vegetation Index (NDVI) within 500-m of residence (objective indicator), and perceived neighbourhood greenness (subjective indicator). We conducted mixed-effects Cox proportional hazards models to obtain hazard ratios (HR) for diabetes-related mortality per interquartile range (IQR) increments of residential greenness. We assessed effect modification by social factors through stratification. RESULTS: From 2,309,236 individuals included at baseline, 1.2% died from DM during follow-up. Both residential greenness indicators were inversely associated with diabetes-related mortality after adjustment for individual social factors. After controlling for neighbourhood SEP, the beneficial association with surrounding greenness disappeared [HR 1.02 (95%CI:0.99,1.06)], but persisted with perceived neighbourhood greenness [HR 0.93 (95%CI:0.91,0.95)]. After stratification the inverse associations with perceived neighbourhood greenness were strongest for women, the lowest educated, and individuals residing in least deprived neighbourhoods. CONCLUSIONS: Our findings suggest that an overall positive perception of neighbourhood green spaces reduces independently the risk of diabetes-related mortality, regardless of the neighbourhood social environment. Nevertheless, neighbourhood SEP may be a strong confounder in the associations between diabetes-related mortality and greenness indicators derived from satellite images. Perception factors not captured by objective measurements of green spaces are potentially relevant in the association with DM, especially among disadvantaged groups.

Resolving the equation between mucormycosis and COVID-19 disease.

The COVID-19 patients, both infected and recovered are rapidly contracting mucormycetes infections due to the 'Mucorales' order, under Zygomycetes class of fungi. The mucorales fungi commonly known to exist in our natural surroundings including soil, but the frequency of incidences was never rampant. This sudden spike in infections, is locally known as 'black fungus,' and is affecting various organs, including- eyes, sinuses, nose, brain, skin, intestine, lungs, etc. The severity of situation is ascertainable from the fact that, in certain cases surgical eye/jaws removal persists as the only viable option to avert mortality, as therapeutic interventions are limited. This epidemic situation intrigued experts to investigate the probable reason behind this unpredicted escalation in reported cases, including in recuperated COVID-19 patients, as person-to-person spread of infection is not common. The comparison of physiological parameters in healthy and COVID-19 afflicted patients highlights that the underlying conditions including diabetes mellitus, steroidal therapy, lymphopenia (decreased CD4+ and CD8+ lymphocytes), deregulated cytokine release storm, elevated free iron levels (hemosiderosis) in blood and insulin insensitivity are playing major roles in deteriorating conditions in rarely pathogenic fungal infections. This review is an attempt to explain the rationalities that makes people vulnerable to mucormycetes infection.

Long-term glycemic variability and the risk of mortality in diabetic patients receiving peritoneal dialysis.

BACKGROUND: The large amount of glucose in the dialysate used in peritoneal dialysis (PD) likely affects the glycemic control. The aim of this study was to investigate the association between HbA1c variability, as a measure of long-term glycemic variability, and the risk of all-cause mortality in diabetic patients with PD. METHODS: 325 patients with diabetes and ESRD were followed (2008-2018) in the Swedish Renal Registry. Patients were separated in seven groups according to level of HbA1c variability. The group with the lowest variability was denoted the reference. The ratio of the standard deviation (SD) to the mean of HbA1c, HbA1c (SD)/HbA1c (mean), i.e. the coefficient of variation (CV), was defined as HbA1c variability. Hazard ratios (HR) and 95% confidence intervals (CI) were examined using Cox regression analyses. RESULTS: During follow-up, 170 (52%) deaths occurred. The highest mortality was among patients with the second highest HbA1c variability, CV≥2.83 [n = 44 of which 68% patients died]. In the multivariate analyses where lowest HbA1c variability (CV≤0.51) was used as the reference group, HbA1c CV 2.83-4.60 (HR 3.15, 95% CI 1.78-5.55; p<0.001) and CV> 4.6 (HR 2.48, 95% CI 1.21-5.11; p = 0.014) were associated with increased risk of death. CONCLUSION: The high risk of all-cause mortality in patients with diabetes and PD increased significantly with elevated HbA1c variability, as measure of long-term glycemic control. This indicates that stable glycemia is associated with an improvement of survival; whereas more severe glycemic fluctuations, possibly caused by radical changes in dialysis regimes or peritonitis, are associated with a higher risk of mortality in diabetic patients with PD.