Enrollment in High-Deductible Health Plans and Incident Diabetes Complications.

Importance: Preventing diabetes complications requires monitoring and control of hyperglycemia and cardiovascular risk factors. Switching to high-deductible health plans (HDHPs) has been shown to hinder aspects of diabetes care; however, the association of HDHP enrollment with microvascular and macrovascular diabetes complications is unknown. Objective: To examine the association between an employer-required switch to an HDHP and incident complications of diabetes. Design, Setting, and Participants: This retrospective cohort study used deidentified administrative claims data for US adults with diabetes enrolled in employer-sponsored health plans between January 1, 2010, and December 31, 2019. Data analysis was performed from May 26, 2022, to January 2, 2024. Exposures: Adults with a baseline year of non-HDHP enrollment who had to switch to an HDHP because their employer offered no non-HDHP alternative in that year were compared with adults who were continuously enrolled in a non-HDHP. Main Outcomes and Measures: Mixed-effects logistic regression models examined the association between switching to an HDHP and, individually, the odds of myocardial infarction, stroke, hospitalization for heart failure, lower-extremity complication, end-stage kidney disease, proliferative retinopathy, treatment for retinopathy, and blindness. Models were adjusted for demographics, comorbidities, and medications, with inverse propensity score weighting used to account for potential selection bias. Results: The study included 42 326 adults who switched to an HDHP (mean [SD] age, 52 [10] years; 19 752 [46.7%] female) and 202 729 adults who did not switch (mean [SD] age, 53 [10] years; 89 828 [44.3%] female). Those who switched to an HDHP had greater odds of experiencing all diabetes complications (odds ratio [OR], 1.11; 95% CI, 1.06-1.16 for myocardial infarction; OR, 1.15; 95% CI, 1.09-1.21 for stroke; OR, 1.35; 95% CI, 1.30-1.41 for hospitalization for heart failure; OR, 2.53; 95% CI, 2.38-2.70 for end-stage kidney disease; OR, 2.23; 95% CI, 2.17-2.29 for lower-extremity complication; OR, 1.17; 95% CI, 1.13-1.21 for proliferative retinopathy; OR, 2.35; 95% CI, 2.18-2.54 for blindness; and OR, 2.28; 95% CI, 2.15-2.41 for retinopathy treatment). Conclusions and Relevance: This study found that an employer-driven switch to an HDHP was associated with increased odds of experiencing all diabetes complications. These findings reinforce the potential harm associated with HDHPs for people with diabetes and the importance of affordable and accessible chronic disease management, which is hindered by high out-of-pocket costs incurred by HDHPs.

Genetics and epigenetics of diabetes and its complications in India.

Diabetes mellitus (DM) has become a significant health concern with an increasing rate of morbidity and mortality worldwide. India ranks second in the number of diabetes cases in the world. The increasing burden of DM can be explained by genetic predisposition of Indians to type 2 diabetes mellitus (T2DM) coupled with rapid urbanization and socio-economic development in the last 3 decades leading to drastic changes in lifestyle. Environment and lifestyle changes contribute to T2DM development by altering epigenetic processes such as DNA methylation, histone post-translational modifications, and long non-coding RNAs, all of which regulate chromatin structure and gene expression. Although the genetic predisposition of Indians to T2DM is well established, how environmental and genetic factors interact and lead to T2DM is not well understood. In this review, we discuss the prevalence of diabetes and its complications across different states in India and how various risk factors contribute to its pathogenesis. The review also highlights the role of genetic predisposition among the Indian population and epigenetic factors involved in the etiology of diabetes. Lastly, we review current treatments and emphasize the knowledge gap with respect to genetic and epigenetic factors in the Indian context. Further understanding of the genetic and epigenetic determinants will help in risk prediction and prevention as well as therapeutic interventions, which will improve the clinical management of diabetes and associated macro- and micro-vascular complications.

Diabetic complications and risk of depression and anxiety among adults with type 2 diabetes.

AIMS: To investigate if diabetic complications increase the risk of depression and/or anxiety among adults with type 2 diabetes. METHODS: This register-based, prospective study included 265,799 adult individuals diagnosed with type 2 diabetes between 1997 and 2017 without a recent history of depression or anxiety. Diabetic complications included cardiovascular disease, amputation of lower extremities, neuropathy, nephropathy and retinopathy. Both diabetic complications and depression and anxiety were defined by hospital contacts and prescription-based medication. All individuals were followed from the date of type 2 diabetes diagnosis until the date of incident depression or anxiety, emigration, death or 31 December 2018, whichever occurred first. RESULTS: The total risk time was 1,915,390 person-years. The incidence rate of depression and/or anxiety was 3368 per 100,000 person-years among individuals with diabetic complications and 1929 per 100,000 person-years among those without. Having or developing any diabetic complication was associated with an increased risk of depression and/or anxiety (HR 1.77, 95% CI 1.73-1.80). The risk for depression and/or anxiety was increased for all types of diabetic complications. The strongest association was found for amputation of lower extremities (HR 2.16, 95% CI 2.01-2.31) and the weakest for retinopathy (HR 1.13, 95% CI 1.09-1.17). CONCLUSION: Individuals with type 2 diabetes and diabetic complications are at increased risk of depression and anxiety. This points towards the importance of an increased clinical focus on mental well-being among individuals with type 2 diabetes and complications.

Modeling multiple correlated end-organ disease trajectories: A tutorial for multistate and joint models with applications in diabetes complications.

State-of-the-art biostatistics methods allow for the simultaneous modeling of several correlated non-fatal disease processes over time, but there is no clear guidance on the optimal analysis in most settings. An example occurs in diabetes, where it is not known with certainty how microvascular complications of the eyes, kidneys, and nerves co-develop over time. In this article, we propose and contrast two general model frameworks for studying complications (sequential state and parallel trajectory frameworks) and review multivariate methods for their analysis, focusing on multistate and joint modeling. We illustrate these methods in a tutorial format using the long-term follow-up from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study public data repository. A formal comparison of prediction error and discrimination is included. Multistate models are particularly advantageous for determining the order and timing of complications, but require discretization of the longitudinal outcomes and possibly a very complex state space process. Intermittent observation of the states must be accounted for, and discretization is a probable disadvantage in this setting. In contrast, joint models can account for variations of continuous biomarkers over time and are particularly designed for modeling complex association structures between the complications and for performing dynamic predictions of an outcome of interest to inform clinical decisions (eg, a late-stage complication). We found that both models have helpful features that can better-inform our understanding of the complex trajectories that complications may take and can therefore help with decision making for patients presenting with diabetes complications.

Investigation of predictors of severity of diabetes complications among hospitalized patients with diabetes in Florida, 2016-2019.

BACKGROUND: Severe diabetes complications impact the quality of life of patients and may lead to premature deaths. However, these complications are preventable through proper glycemic control and management of risk factors. Understanding the risk factors of complications is important in guiding efforts to manage diabetes and reduce risks of its complications. Therefore, the objective of this study was to identify risk factors of severe diabetes complications among adult hospitalized patients with diabetes in Florida. METHODS: Hospital discharge data from 2016 to 2019 were obtained from the Florida Agency for Health Care Administration through a Data Use Agreement with the Florida Department of Health. Adapted Diabetes Complications Severity Index (aDCSI) scores were computed for 1,061,140 unique adult patients with a diagnosis of diabetes. Severe complications were defined as those with an aDCSI ≥ 4. Population average models, estimated using generalized estimating equations, were used to identify individual- and area-level predictors of severe diabetes complications. RESULTS: Non-Hispanic Black patients had the highest odds of severe diabetes complications compared to non-Hispanic White patients among both males (Odds Ratio [OR] = 1.20, 95% Confidence Interval [CI]: 1.17, 1.23) and females (OR = 1.27, 95% CI: 1.23, 1.31). Comorbidities associated with higher odds of severe complications included hypertension (OR = 2.30, 95% CI: 2.23, 2.37), hyperlipidemia (OR = 1.29, 95% CI: 1.27, 1.31), obesity (OR = 1.24, 95% CI: 1.21, 1.26) and depression (OR = 1.09, 95% CI: 1.07, 1.11), while the odds were lower for patients with a diagnosis of arthritis (OR = 0.81, 95% CI: 0.79, 0.82). Type of health insurance coverage was associated with the severity of diabetes complications, with significantly higher odds of severe complications among Medicare (OR = 1.85, 95% CI: 1.80, 1.90) and Medicaid (OR = 1.83, 95% CI: 1.77, 1.90) patients compared to those with private insurance. Residing within the least socioeconomically deprived ZIP code tabulation areas (ZCTAs) in the state had a protective effect compared to residing outside of these areas. CONCLUSIONS: Racial, ethnic, and socioeconomic disparities in the severity of diabetes complications exist among hospitalized patients in Florida. The observed disparities likely reflect challenges to maintaining glycemic control and managing cardiovascular risk factors, particularly for patients with multiple chronic conditions. Interventions to improve diabetes management should focus on populations with disproportionately high burdens of severe complications to improve quality of life and decrease premature mortality among adult patients with diabetes in Florida.

[Vascular complications of diabetes mellitus worldwide and in Russia: The path of 100 years. A review].

With the discovery and introduction of insulin, the "palette" of life-threatening conditions for patients with diabetes mellitus has changed dramatically: from diabetic coma of the "pre-insulin era" to severe vascular complications in the modern period. The key risk factors for diabetic angiopathies in diabetes mellitus are poor glycemic control in combination with a long course of the disease. Over the past 30 years, there has been a downward trend in the incidence of late vascular complications of diabetes both worldwide and in Russia. In particular, the frequency of cardiovascular events (myocardial infarctions, strokes, amputations) decreased, and the incidence of several other complications, such as diabetic retinopathy and neuropathy, stabilized. However, the incidence of chronic kidney disease and chronic heart failure is still increasing. The Joslin Medal, awarded to patients over 50, 75 and even 80 years of life with diabetes, reflects success in the fight against this disease.

Hypoglycemia unawareness among insulin-treated diabetic patients in Madinah, Saudi Arabia: prevalence and risk factors.

Background: Hypoglycemia unawareness (HU) is associated with significant risks. Screening for impaired awareness of hypoglycemia in patients with diabetes is important to minimize those risks. There are limited data on the prevalence of HU in patients with diabetes in Saudi Arabia (KSA). In the current study, we investigated the frequency of HU and its risk factors among insulin treated diabetic patients in Madinah, KSA. Methods: A cross-sectional study was conducted in a diabetes center and four primary healthcare centers at Madinha, KSA. Patients ≥14 years old with type 1 or type 2 diabetes treated with insulin for more than a year were included. HU was assessed by Clarke's and modified Pedersen-Bjergaard's scores. The risk factors for HU were determined. Results: Of the 413 included patients, 60.3% were women, and 60.8% were on insulin alone. One-third of the participants had T1DM, while 68.5% had T2DM, with median ages of 25 and 56 years, diabetes durations of 10 and 15 years, and durations of insulin use of 10 and 5 years, respectively. The prevalence of HU was 25.2% by Clarke's survey. The risk factors for HU were poor knowledge of the patient's latest HbA1c, type of insulin, and dose of insulin. Poor medical follow-up, previous stroke, and ischemic heart disease were the other risk factors for HU. When the modified Pedersen-Bjergaard method was used, the prevalence of HU was 48.9%. Conclusion: Despite the advances in diabetes management, HU continues to be prevalent among diabetic patients on insulin, and poor diabetes knowledge is a major risk factor. Diabetes education on self-management is of utmost importance to reduce hypoglycemia and HU.

[Complications due to diabetes mellitus in Brazil: 2019 nationwide study]. / Complicações por diabetes mellitus no Brasil: estudo de base nacional, 2019.

Inadequate management of diabetes mellitus (DM) can lead to complications that affect quality of life. The prevalence of DM and its complications is increasing, presenting an uneven distribution in the population. The objective was to estimate the prevalence of complications due to DM and to assess inequalities in the Brazilian population. It involved a cross-sectional study, with data from the 2019 National Health Survey (NHS). The complications evaluated were: diabetic coma, heart attack/cerebrovascular accident/stroke; kidney problem; vision problem and foot ulcer or amputation. The related factors were schooling and income. The prevalence of complications was calculated separately, combination in pairs, presence of any complications and number of complications. Inequality was estimated through adjusted analysis and the slope index (SII) and concentration index (CIX) indices. The sample consisted of 6,317 people with DM. More than a third (37.8%) reported having some complication. Vision problems (30.6%) and kidney problems (9.7%) were the most prevalent. The prevalence of having "one" and "two or more" complications were 25.4% and 12.4%, respectively. Inequalities were found with a higher prevalence of complications among the least educated and the poorest.

O manejo inadequado da diabetes mellitus (DM) pode levar a complicações que afetam a qualidade de vida. A prevalência da DM e suas complicações está aumentando, apresentando distribuição desigual na população. O objetivo foi estimar a prevalência de complicações devido à DM e avaliar as desigualdades na população brasileira. Estudo transversal, com dados da Pesquisa Nacional de Saúde (PNS), de 2019. As complicações avaliadas foram: coma diabético, infarto/Acidente Vascular Cerebral/derrame, problema nos rins, problema na visão e úlcera nos pés ou amputação. As exposições foram a escolaridade e renda. Foram calculadas as prevalências das complicações separadamente, combinação em duplas, presença de alguma complicação e número de complicações. A desigualdade foi estimada por meio de análise ajustada e dos índices: slope index (SII) e o concentration index (CIX). A amostra foi composta por 6.317 pessoas com DM. Mais de um terço (37,8%) referiu ter alguma complicação. O problema na visão (30,6%) e nos rins (9,7%) foram os mais prevalentes. As prevalências de ter "uma" e "duas ou mais" complicações foram 25,4% e 12,4%. Foram evidenciadas desigualdades com maior prevalência de complicações entre os menos escolarizados e mais pobres.

Prediction of clinical events by liver stiffness and chronic kidney disease by NAFLD in patients with type-2 diabetes / Predicción de eventos clínicos por elasticidad hepática y enfermedad renal crónica por EHMet en pacientes con diabetes tipo 2

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with poorer glycemic control and a higher risk of type-2 diabetes (T2D) complications, extrahepatic and cardiovascular disease (CVD). Our study aim was to evaluate the association between NAFLD, T2D complications, and the development of overall clinical events (OCE) (CV, liver-related, and mortality) in patients with T2D. Methods: Prospective single-center study comprising T2D subjects with no history of CVD and non-T2D matched controls. Patients were selected from the Outpatient Diabetes Clinic of Vall d’Hebron Hospital and related primary care centers. Results: 186 diabetics and 57 controls were included. Amongst T2D, 124/186 subjects had NAFLD (66.6%). T2D-NAFLD subjects showed a heavier metabolic burden and higher median liver stiffness (5.6kPa [4.5–7.3] vs 4.8 [4.2–5.8]; p=0.004) compared to non-NAFLD diabetics. During a median follow-up of 5.6 years, 33 (17.7%) T2D patients developed OCE vs 4 (7.0%) controls (p=0.049). No differences were found for OCE between NAFLD and non-NAFLD diabetics (16.9% vs 19.4%; p=0.68). CV was the most reported outcome and only one liver event occurred. NAFLD diabetics showed more often chronic kidney disease (CKD), whereas T2D complications and subclinical CVD rates were similar. A higher liver stiffness, older age, and male gender were independently associated with OCE amongst the entire T2D population and NAFLD diabetics. Conclusions: NAFLD and liver stiffness were associated with CKD and clinical outcomes in diabetics, respectively. A hepatic evaluation is recommended to identify high-risk T2D patients that would benefit from early referral to specialized care. (AU)

Antecedentes y objetivos: La esteatosis hepática metabólica (EHMet) se asocia con un peor control glucémico y un mayor riesgo de complicaciones de la diabetes tipo 2 (DM2), enfermedad extrahepática y cardiovascular (CV). El objetivo fue evaluar la asociación entre EHMet, complicaciones microvasculares y el desarrollo de eventos clínicos globales (ECG) (CV, hepáticos y mortalidad) en diabéticos. Métodos: Estudio unicéntrico prospectivo que incluye diabéticos sin historia de CV y controles sin DM2. Se seleccionaron pacientes de la consulta de Diabetes del Hospital Vall d’Hebron y centros de atención primaria asociados. Resultados: Se incluyeron 186 diabéticos y 57 controles. Entre los diabéticos, 124/186 presentaron EHMet (66,6%). Los pacientes DM2 con EHMet presentaron mayor carga metabólica y una elasticidad hepática superior (5,6kPa [4,5-7,3] vs. 4,8 [4,2-5,8]; p=0,004) a los diabéticos sin EHMet. Durante una mediana de seguimiento de 5,6 años, 33 (17,7%) diabéticos desarrollaron ECG vs. 4 (7,0%) controles (p=0,049). No hubo diferencias en ECG entre diabéticos con y sin EHMet (16,9% vs. 19,4%; p=0,68). El evento más reportado fue CV y solamente se produjo un evento hepático. La enfermedad renal crónica (ERC) fue más frecuente en diabéticos con EHMet, mientras que los ratios de complicaciones microvasculares y enfermedad CV silente fueron similares. El género masculino, una mayor edad y elasticidad hepática se asociaron de forma independiente a ECG para el total de diabéticos y para aquellos con EHMet. Conclusiones: La EHMet y la elasticidad hepática se asociaron a ERC y eventos clínicos en diabéticos. Se recomienda una evaluación hepática para identificar pacientes diabéticos de riesgo que se beneficiarían de una derivación precoz al especialista. (AU)

Distribution and Economic Burden of Diabetes-Related Microvascular Complications in Türkiye.

BACKGROUND: The aim of the study was to map microvascular complications associated with diabetes mellitus from personal health records and to guide chronic disease management by revealing the economic burden of the disease. METHOD: The data of patients with diabetes who developed microvascular complications were obtained from the e-Pulse database of the Ministry of Health, with the definitions of the disease. First, the distribution of patients by province and gender was determined and then patients with multiple complications were identified. Only direct costs and their distribution on the basis of complications were determined from the database according to the cost of illness methodology from the payer's perspective. Then, average annual per-patient costs were determined using a top-down costing approach. RESULTS: Between 2016 and 2020, a total of 7 656 700 patients with diabetes were reached. The number of patients with microvascular complications between 2016 and 2020 obtained from the e-Pulse database with the above definitions was 1 466 387. Regarding the complications, a total of 66 838 people developed nephropathy, 314 706 people developed retinopathy, and 1 084 843 people developed neuropathy. The total cost of patients with microvascular complications was $1 482 278 950.76 and the average annual cost per patient was $1010.84. The average annual cost of neuropathy is $659 862 971.96, retinopathy is $356 594 282.51 and nephropathy is $465 821 696.29, with per-patient costs of $701.82, $1495.24, and $10 516.11, respectively. CONCLUSION: Diabetes mellitus, with its microvascular complications, causes significant disease and economic burden. Türkiye's national health database system, e-Pulse, is an important database that provides patient follow-up at both individual and population levels and helps with the management of the disease and taking preventive measures before the development of the complications.

Early use of oral semaglutide in the UK: A cost-effectiveness analysis versus continuing metformin and SGLT-2 inhibitor therapy.

OBJECTIVES: Many people with type 2 diabetes experience clinical inertia, remaining in poor glycaemic control on oral glucose-lowering medications rather than intensifying treatment with a glucagon-like peptide-1 receptor agonist, despite an efficacious, orally administered option, oral semaglutide, being available. The present study evaluated the long-term cost-effectiveness of initiating oral semaglutide versus continuing metformin plus sodium-glucose cotransporter-2 (SGLT-2) inhibitor therapy in the UK. DESIGN: Outcomes were projected over patients' lifetimes using the IQVIA Core Diabetes Model (V.9.0). Clinical data were taken from the oral semaglutide and placebo arms of the patient subgroup receiving metformin plus an SGLT-2 inhibitor in PIONEER 4. Costs, expressed in 2021 Pounds sterling (GBP), were accounted from a healthcare payer perspective. INTERVENTIONS: Modelled patients received oral semaglutide immediately (in the first year of the analysis) or after a 2-year delay, after which all physiological parameters were brought to values observed in the immediate therapy arm. During the simulation, patients intensified with the addition of basal insulin and, subsequently, by switching to basal-bolus insulin. RESULTS: Immediate oral semaglutide therapy was associated with improvements in life expectancy of 0.17 (95% CIs 0.16 to 0.19) years, and quality-adjusted life expectancy of 0.15 (0.14 to 0.16) quality-adjusted life years (QALYs), versus a 2-year delay. Benefits were due to a reduced incidence of diabetes-related complications. Direct costs were estimated to be GBP 1423 (1349 to 1496) higher with immediate oral semaglutide therapy versus a 2-year delay, with higher treatment costs partially offset by cost savings from avoidance of diabetes-related complications. Immediate oral semaglutide therapy was therefore associated with an incremental cost-effectiveness ratio of GBP 9404 (8380 to 10 538) per QALY gained versus a 2-year delay. CONCLUSIONS: Immediate oral semaglutide is likely to represent a cost-effective treatment in people with type 2 diabetes with inadequate glycaemic control on metformin plus an SGLT-2 inhibitor in the UK. TRIAL REGISTRATION NUMBER: NCT02863419.

Predicting the onset of diabetes-related complications after a diabetes diagnosis with machine learning algorithms.

AIMS: Using machine learning algorithms and administrative data, we aimed to predict the risk of being diagnosed with several diabetes-related complications after one-, two- and three-year post-diabetes diagnosis. METHODS: We used longitudinal data from administrative registers of 610,019 individuals in Catalonia with a diagnosis of diabetes and checked the presence of several complications after diabetes onset from 2013 to 2017: hypertension, renal failure, myocardial infarction, cardiovascular disease, retinopathy, congestive heart failure, cerebrovascular disease, peripheral vascular disease and stroke. Four different machine learning (ML) algorithms (logistic regression (LR), Decision tree (DT), Random Forest (RF), and Extreme Gradient Boosting (XGB)) will be used to assess their prediction performance and to evaluate the prediction accuracy of complications changes over the period considered. RESULTS: 610,019 people with diabetes were included. After three years since diabetes diagnosis, the area under the curve values ranged from 60% (retinopathy) to 69% (congestive heart failure), whereas accuracy rates varied between 60% (retinopathy) to 75% (hypertension). RF was the most relevant technique for hypertension, myocardial and retinopathy, and LR for the rest of the comorbidities. The Shapley additive explanations values showed that age was associated with an elevated risk for all diabetes-related complications except retinopathy. Gender, other comorbidities, co-payment levels and age were the most relevant factors for comorbidity diagnosis prediction. CONCLUSIONS: Our ML models allow for the identification of individuals newly diagnosed with diabetes who are at increased risk of developing diabetes-related complications. The prediction performance varied across complications but within acceptable ranges as prediction tools.

Exploring diabetes status and social determinants of health influencing diabetes-related complications in a Northwestern community, Ontario, Canada: A mixed method study protocol.

Diabetes is a common chronic condition affecting the many spheres of individuals' lives. It can also lead to severe complications without continuous management. Accordingly, this paper describes a study protocol aimed at 1) determining the status and prevalence of diabetes complications in a Northwestern Ontario community; 2) exploring the internal (e.g., demographic and clinical variables) and external factors (e.g., access to services and resources) affecting diabetes outcomes (e.g., complications, emergency room visits, hospitalizations); 3) critically exploring how the social determinants of health affect self-management for individuals living with diabetes; and 4) identifying individuals' needs, concerns, and challenges to monitor and regulate diabetes. The study uses a cross-sectional design and a social constructivist approach based on qualitative data collection. The proposed study will include patients with type 1 and type 2 diabetes with or without diabetes complications who have been attending the Centre for Complex Diabetes Care (CCDC) in Thunder Bay, Ontario, Canada, since January 2019. Quantitative data related to diabetes complications and other outcomes, diabetes management, and demographic and clinical status will be retrieved from patients' charts using a data extraction form. Analyses of the quantitative data will include the prevalence of diabetes complications, rate of hospitalizations, and their associations with diabetes management, access to services, and social determinants of health. Additionally, interviews will occur with at least 10 participants with or without diabetes complications to understand their needs, concerns, and struggle to self-manage diabetes daily. The results of this study will generate evidence to support future research and policy on the development and implementation of an educational program to improve self-care management and outcomes for individuals living with diabetes and its complications in Northwestern Ontario.

Quantifying association and disparities between diabetes complications and COVID-19 outcomes: A retrospective study using electronic health records.

BACKGROUND: Despite established relationships between diabetic status and an increased risk for COVID-19 severe outcomes, there is a limited number of studies examining the relationships between diabetes complications and COVID-19-related risks. We use the Adapted Diabetes Complications Severity Index to define seven diabetes complications. We aim to understand the risk for COVID-19 infection, hospitalization, mortality, and longer length of stay of diabetes patients with complications. METHODS: We perform a retrospective case-control study using Electronic Health Records (EHRs) to measure differences in the risks for COVID-19 severe outcomes amongst those with diabetes complications. Using multiple logistic regression, we calculate adjusted odds ratios (OR) for COVID-19 infection, hospitalization, and in-hospital mortality of the case group (patients with diabetes complications) compared to a control group (patients without diabetes). We also calculate adjusted mean difference in length of stay between the case and control groups using multiple linear regression. RESULTS: Adjusting demographics and comorbidities, diabetes patients with renal complications have the highest odds for COVID-19 infection (OR = 1.85, 95% CI = [1.71, 1.99]) while those with metabolic complications have the highest odds for COVID-19 hospitalization (OR = 5.58, 95% CI = [3.54, 8.77]) and in-hospital mortality (OR = 2.41, 95% CI = [1.35, 4.31]). The adjusted mean difference (MD) of hospital length-of-stay for diabetes patients, especially those with cardiovascular (MD = 0.94, 95% CI = [0.17, 1.71]) or peripheral vascular (MD = 1.72, 95% CI = [0.84, 2.60]) complications, is significantly higher than non-diabetes patients. African American patients have higher odds for COVID-19 infection (OR = 1.79, 95% CI = [1.66, 1.92]) and hospitalization (OR = 1.62, 95% CI = [1.39, 1.90]) than White patients in the general diabetes population. However, White diabetes patients have higher odds for COVID-19 in-hospital mortality. Hispanic patients have higher odds for COVID-19 infection (OR = 2.86, 95% CI = [2.42, 3.38]) and shorter mean length of hospital stay than non-Hispanic patients in the general diabetes population. Although there is no significant difference in the odds for COVID-19 hospitalization and in-hospital mortality between Hispanic and non-Hispanic patients in the general diabetes population, Hispanic patients have higher odds for COVID-19 hospitalization (OR = 1.83, 95% CI = [1.16, 2.89]) and in-hospital mortality (OR = 3.69, 95% CI = [1.18, 11.50]) in the diabetes population with no complications. CONCLUSIONS: The presence of diabetes complications increases the risks of COVID-19 infection, hospitalization, and worse health outcomes with respect to in-hospital mortality and longer hospital length of stay. We show the presence of health disparities in COVID-19 outcomes across demographic groups in our diabetes population. One such disparity is that African American and Hispanic diabetes patients have higher odds of COVID-19 infection than White and Non-Hispanic diabetes patients, respectively. Furthermore, Hispanic patients might have less access to the hospital care compared to non-Hispanic patients when longer hospitalizations are needed due to their diabetes complications. Finally, diabetes complications, which are generally associated with worse COVID-19 outcomes, might be predominantly determining the COVID-19 severity in those infected patients resulting in less demographic differences in COVID-19 hospitalization and in-hospital mortality.

Long-term effects of coronavirus disease 2019 on diabetes complications and mortality in people with diabetes: Two cohorts in the UK and Hong Kong.

AIM: To evaluate the long-term associations between coronavirus disease 2019 (COVID-19) and diabetes complications and mortality, in patients with diabetes. MATERIALS AND METHODS: People with diabetes diagnosed with COVID-19 infection (exposed group), from 16 March 2020 to 31 May 2021 from the UK Biobank (UKB cohort; n = 2456), and from 1 April 2020 to 31 May 2022 from the electronic health records in Hong Kong (HK cohort; n = 80 546), were recruited. Each patient was randomly matched with participants with diabetes but without COVID-19 (unexposed group), based on age and sex (UKB, n = 41 801; HK, n = 391 849). Patients were followed for up to 18 months until 31 August 2021 for UKB, and up to 28 months until 15 August 2022 for HK. Characteristics between cohorts were further adjusted with Inverse Probability Treatment Weighting. Long-term association of COVID-19 with multi-organ disease complications and all-cause mortality after 21 days of diagnosis was evaluated by Cox regression. RESULTS: Compared with uninfected participants, patients with COVID-19 infection with diabetes were consistently associated with higher risks of cardiovascular diseases (coronary heart disease [CHD]: hazard ratio [HR] [UKB]: 1.6 [95% confidence interval {CI}: 1.0, 2.4], HR [HK]: 1.2 [95% CI: 1.0, 1.5]; and stroke: HR [UKB]: 2.0 [95% CI: 1.1, 3.6], HR [HK]: 1.5 [95% CI: 1.3, 1.8]), microvascular disease (end stage renal disease: HR [UKB]: 2.1 [95% CI: 1.1, 4.0], HR [HK]: 1.2 [95% CI: 1.1, 1.4]) and all-cause mortality (HR [UKB]: 4.6 [95% CI: 3.8, 5.5], HR [HK]: 2.6 [95% CI: 2.5, 2.8]), in both cohorts. CONCLUSIONS: COVID-19 infection is associated with long-term increased risks of diabetes complications (especially cardiovascular complications, and mortality) in people with diabetes. Monitoring for signs/symptoms of developing these long-term complications post-COVID-19 infection in the infected patient population of people with diabetes may be beneficial in minimizing their morbidity and mortality.

Factors associated with glycemic control and diabetes complications in a group of Saudi patients with type 2 diabetes.

Poor glycemic control is a risk factor for micro and macrovascular complications of diabetes. The aim of this study was to assess the prevalence and factors related to suboptimal glycemic control and diabetes complications in a group of patients with type 2 diabetes mellitus (T2DM). This cross-sectional descriptive study conducted in Al Qassim region, Saudi Arabia. Two hundred patients with T2DM were enrolled. Demographic, social, and self-care behavior data were collected. A thorough clinical evaluation was done. Glycated hemoglobin, lipid, and kidney profile results were recorded. Mann-Whitney test was used to compare different groups. For comparing categorical data, Chi-square (χ2) test was performed. Multivariate logistic regression analyses used to detect predictors of poor glycemic control and macrovascular and microvascular complications. The median age of patients was 58 years, and 62% of them were males. Only 22.5% of patients had glycated hemoglobin <7%. Forty-four patients (22%) had evidence of macrovascular complications. Retinopathy, neuropathy, and nephropathy were found in 42.5%, 32.5%, and 12%, respectively. Longer diabetes duration was significantly associated with poor glycemic control (OR = 1.006, P < .005). The age of the patients was independently associated with macrovascular complications (OR = 1.050, P = .029). Hyperlipidemia was significantly associated with neuropathy (OR = 0.229, P = .043) and retinopathy (OR = 12.887, P = .003). Although physical activity was lower in patients with suboptimal glycemic levels (P = .024), cardiovascular disease (P = .030), neuropathy (P < .001), retinopathy (P < .001), and nephropathy (P = .019), multivariate analysis showed that it was only independently associated with neuropathy (OR = 0.614, P = .001). The prevalence of suboptimal glycemic control is high in the studied population. Effective health measures are urgently needed to stop diabetes complications, especially retinopathy and neuropathy. Elderly people with long durations of diabetes, and lower physical activity should be the focus of the interventions. Tailored exercise programs are particularly needed for better diabetes control and for the prevention of complications in patients with T2DM.

DNA methylation and 28-year cardiovascular disease risk in type 1 diabetes: the Epidemiology of Diabetes Complications (EDC) cohort study.

BACKGROUND: The potential for DNA methylation (DNAm) as an early marker for cardiovascular disease (CVD) and how such an association might differ by glycemic exposure has not been examined in type 1 diabetes, a population at increased CVD risk. We thus performed a prospective epigenome-wide association study of blood leukocyte DNAm (EPIC array) and time to CVD incidence over 28 years in a childhood-onset (< 17 years) type 1 diabetes cohort, the Pittsburgh Epidemiology of Diabetes Complications (EDC) study (n = 368 with DNA and no CVD at baseline), both overall and separately by glycemic exposure, as measured by HbA1c at baseline (split at the median: < 8.9% and ≥ 8.9%). We also assessed whether DNAm-CVD associations were independent of established cardiometabolic risk factors, including body mass index, estimated glucose disposal rate, cholesterol, triglycerides, blood pressure, pulse rate, albumin excretion rate, and estimated glomerular filtration rate. RESULTS: CVD (first instance of CVD death, myocardial infarction, coronary revascularization, ischemic ECG, angina, or stroke) developed in 172 participants (46.7%) over 28 years. Overall, in Cox regression models for time to CVD, none of the 683,597 CpGs examined reached significance at a false discovery rate (FDR) ≤ 0.05. In participants with HbA1c < 8.9% (n = 180), again none reached FDR ≤ 0.05, but three were associated at the a priori nominal significance level FDR ≤ 0.10: cg07147033 in MIB2, cg12324048 (intergenic, chromosome 3), and cg15883830 (intergenic, chromosome 1). In participants with HbA1c ≥ 8.9% (n = 188), two CpGs in loci involved in calcium channel activity were significantly associated with CVD (FDR ≤ 0.05): cg21823999 in GPM6A and cg23621817 in CHRNA9; four additional CpGs were nominally associated (FDR ≤ 0.10). In participants with HbA1c ≥ 8.9%, DNAm-CVD associations were only modestly attenuated after cardiometabolic risk factor adjustment, while attenuation was greater in those with HbA1c < 8.9%. No pathways were enriched in those with HbA1c < 8.9%, while pathways for calcium channel activity and integral component of synaptic membrane were significantly enriched in those with HbA1c ≥ 8.9%. CONCLUSIONS: These results provide novel evidence that DNAm at loci involved in calcium channel activity and development may contribute to long-term CVD risk beyond known risk factors in type 1 diabetes, particularly in individuals with greater glycemic exposure, warranting further study.

The magnitude of chronic diabetes complications and its associated factors among diabetic patients attending the general hospitals in Tigray region, Northern Ethiopia.

BACKGROUND: Diabetes is a severe challenge to global public health since it is a leading cause of morbidity, mortality, and rising healthcare costs. 3.0 million Ethiopians, or 4.7% of the population, had diabetes in 2021. Studies on the chronic complications of diabetes in Ethiopia have not been conducted in lower-level healthcare facilities, so the findings from tertiary hospitals do not accurately reflect the issues with chronic diabetes in general hospitals. In addition, there is a lack of information and little research on the complications of chronic diabetes in Ethiopia. The objective of this study was to assess the degree of chronic diabetes complications and associated factors among diabetic patients presenting to general hospitals in the Tigray area in northern Ethiopia. METHODS: As part of a multi-centre cross-sectional study, 1,158 type 2 diabetes (T2D) patients from 10 general hospitals in the Tigray region were randomly chosen. An interviewer-administered questionnaire, a record review, and an SPSS version 20 analysis were used to collect the data. All continuous data were presented as mean standard deviation (SD), while categorical data were identified by frequencies. Using a multivariable logistic regression model, the factors associated with chronic diabetes complications among T2D diabetic patients were found, and linked factors were declared at p 0.05. RESULTS: Fifty-four of people with diabetes have chronic problems. Hypertension (27%) eye illness, renal disease (19.1%), and hypertension (27%) eye disease were the most common long-term effects of diabetes. Patients with chronic diabetes complications were more likely to be older than 60, taking insulin and an OHGA (Oral Hyperglycemic Agent) (AOR = 3.00; 95% CI 1.73, 5.26), having diabetes for more than five years, taking more than four tablets per day (AOR = 1.63; 95% CI 1.23,2.15), and having high systolic and diastolic blood pressure. Patients with government employment (AOR = 0.48; 95% CI 0.26, 0.90), antiplatelet drug use (AOR = 0.29; 95% CI 0.16, 0.52), and medication for treating dyslipidemia (AOR = 0.54; 95% CI 0.35, 0.84), all had a decreased chance of developing a chronic diabetes problem. CONCLUSION: At least one chronic diabetic complication was present in more than half of the patients in this study. Chronic diabetes problems were related to patients' characteristics like age, occupation, diabetes treatment plan, anti-platelet, anti-dyslipidemia medicine, duration of diabetes, high Systolic BP, high Diastolic BP, and pill burden. To avoid complications from occurring, diabetes care professionals and stakeholders must collaborate to establish appropriate methods, especially for individuals who are more likely to experience diabetic complications.

The impact of the incidence of diabetic complications on mortality in colorectal cancer patients with diabetes: A nationwide study.

PURPOSE: The prevalence of diabetes is higher in patients with colorectal cancer, which is important because diabetes is recognized as a risk factor for increased mortality. This study investigated the impact of incident diabetes-related complications on all-cause five-year mortality in older aged colorectal cancer patients with diabetes. METHODS: The 2008 to 2019 National Health Insurance Service data on the elderly were used to identify patients with colorectal cancer aged 60 years or above diagnosed with type 2 diabetes mellitus. The outcome measure was all-cause five-year mortality. The main independent variable was incident status of diabetes-related complications using the Diabetes Complications Severity Index (DCSI). Survival analyses were performed using the Cox proportional hazards model, in addition to the calculation of risk differences. Subgroup analysis was conducted based on the type of complication and DCSI scores. RESULTS: Among 1,312 individuals, 319 (24.3%) died within five years after one year of a cancer diagnosis. The risk of mortality was higher in patients with diabetes and cancer having incident diabetes-related complications (Hazard Ratio 1.29, 95% Confidence Interval 1.03-1.63). These tendencies were generally maintained regardless of the type of complication and DCSI scores. CONCLUSION: The incidence of diabetes-related complications after cancer diagnosis was associated with an increased risk of all-cause five-year mortality in older patients with colorectal cancer and preexisting diabetes.

The LongitudinAl Nationwide stuDy on Management And Real-world outComes of diabetes in India over 3 years (LANDMARC trial).

INTRODUCTION: LANDMARC (CTRI/2017/05/008452), a prospective, observational real-world study, evaluated the occurrence of diabetes complications, glycemic control and treatment patterns in people with type 2 diabetes mellitus (T2DM) from pan-India regions over a period of 3 years. METHODS: Participants with T2DM (≥25 to ≤60 years old at diagnosis, diabetes duration ≥2 years at the time of enrollment, with/without glycemic control and on ≥2 antidiabetic therapies) were included. The proportion of participants with macrovascular and microvascular complications, glycemic control and time to treatment adaptation over 36 months were assessed. RESULTS: Of the 6234 participants enrolled, 5273 completed 3 years follow-up. At the end of 3-years, 205 (3.3%) and 1121 (18.0%) participants reported macrovascular and microvascular complications, respectively. Nonfatal myocardial infarction (40.0%) and neuropathy (82.0%) were the most common complications. At baseline and 3-years, 25.1% (1119/4466) and 36.6% (1356/3700) of participants had HbA1c <7%, respectively. At 3-years, population with macrovascular and microvascular complications had higher proportion of participants with uncontrolled glycemia (78.2% [79/101] and 70.3% [463/659], respectively) than those without complications (61.6% [1839/2985]). Over 3-years, majority (67.7%-73.9%) of the participants were taking only OADs (biguanides [92.2%], sulfonylureas [77.2%] and DPP-IV inhibitors [62.4%]). Addition of insulin was preferred in participants who were only on OADs at baseline, and insulin use gradually increased from 25.5% to 36.7% at the end of 3 years. CONCLUSION: These 3-year trends highlight the burden of uncontrolled glycemia and cumulative diabetes-related complications, emphasizing the importance of optimizing diabetes management in India.