The association between variability of risk factors and complications in type 2 diabetes mellitus: a retrospective study.

The variability in diabetes risk factors, such as uric acid and lipids, may influence the development of complications. This study aimed to investigate the influence of such variability on the occurrence of diabetic complications. A retrospective analysis of electronic medical records was conducted with type 2 diabetic patients who received treatment at a tertiary care hospital in Chengdu, Sichuan Province, between 2013 and 2022. The risk factor variability is presented as the standard deviation (SD). The associations between the variability and complications were examined using a binary logistic regression model. The study included 369 patients with type 2 diabetes. The findings revealed that outpatient special disease management served as a protective factor against the development of complications [OR = 0.53, 95% confidence interval (CI) (0.29-0.10)], particularly for the prevention of diabetic peripheral neuropathy [OR = 0.51, 95% CI (0.30-0.86)]. Variability in total cholesterol (TC-SD) was found to be a risk factor for the development of complications [OR = 2.42, 95% CI (1.18-4.97)] and acted as a risk factor for diabetic peripheral vasculopathy [OR = 2.50, 95% CI (1.25-5.02)]. TC-SD is a risk factor for the occurrence of diabetic peripheral neuropathy and diabetic peripheral vasculopathy, whereas outpatient special disease management functions as a protective factor against complications and diabetic peripheral neuropathy. Thus, in addition to glycaemic control, the regulation of lipid levels should be emphasized, particularly among patients without outpatient special disease management, to delay the onset of complications.

Walking pace and microvascular complications among individuals with type 2 diabetes: A cohort study from the UK Biobank.

INTRODUCTION: Walking pace is associated with various health-related outcomes. The aim of this study was to investigate the association between self-reported walking pace and the incidences of diabetic microvascular complications among participants with type 2 diabetes (T2D). METHODS: Self-reported walking pace was classified as brisk, average, or slow. The outcomes were the incidences of diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. COX proportional hazards models adjusted for sociodemographic, lifestyle, and health-related factors were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: A total of 14 518 participants with T2D in the UK Biobank (mean age 59.7 ± 7.0 years, 5028 [34.6%] women) were included. During a median follow-up of 12.5 (interquartile range: 11.6-13.4) years, 2980 participants developed diabetic microvascular complications. After adjusting for confounding factors, and compared with brisk walkers, slow walkers had a multivariable-adjusted HR of 1.98 (95% CI 1.58, 2.47) for composite diabetic microvascular complications, 1.54 (95% CI 1.11, 2.14) for diabetic retinopathy, 3.26 (95% CI 2.08, 5.11) for diabetic neuropathy, and 2.32 (95% CI 1.91, 2.82) for diabetic nephropathy. Average walking pace was associated with a higher risk for diabetic nephropathy (HR 1.51, 95 CI% 1.27-1.79) compared with brisk walking. Additionally, ≥1 diabetic microvascular complication occurred in 447 (14.7%) of participants with brisk walking pace, 1702 (19.5%) with average walking pace, and 831 (30.4%) with slow walking pace. Time from study recruitment to first diagnosis was shorter in participants who reported a slow walking pace, compared with brisk or average walkers. Among participants who had diabetic nephropathy as their first diagnosis, slow walking pace was associated with subsequent risk of a second diabetic microvascular complication (HR 3.88, 95 CI% 2.27-6.60). CONCLUSIONS: Self-reported slow walking pace is associated with a higher risk of diabetic microvascular complications among participants with T2D in this population-based cohort study.

Vascular complications of diabetes: A narrative review.

Diabetes mellitus is a complex chronic metabolic disease characterized by hyperglycemia and various complications. According to the different pathophysiological mechanisms, these complications can be classified as microvascular or macrovascular complications, which have long-term negative effects on vital organs such as the eyes, kidneys, heart, and brain, and lead to increased patient mortality. Diabetes mellitus is a major global health issue, and its incidence and prevalence have increased significantly in recent years. Moreover, the incidence is expected to continue to rise as more people adopt a Western lifestyle and diet. Thus, it is essential to understand the epidemiology, pathogenesis, risk factors, and treatment of vascular complications to aid patients in managing the disease effectively. This paper provides a comprehensive review of the literature to clarify the above content. Furthermore, this paper also delves into the correlation between novel risk factors, such as long noncoding RNAs, gut microbiota, and nonalcoholic fatty liver disease, with diabetic vascular complications.

Changes in smoking status, amount of smoking and their relation to the risk of microvascular complications in men with diabetes mellitus.

BACKGROUND: Smoking is a definite risk factor for macrovascular complications in diabetes mellitus (DM). However, the effect of smoking on microvascular complications is inconclusive. METHOD: Study participants were 26,673 diabetic men who received health check-up both in 2003-2004 and 2009, excluding women. Assessing smoking status (never, quitting and current) at 2003-2004 and 2009, changes in smoking status were categorised into 7 groups (never - never, never - quitting, never - current, quitting-quitting, quitting-current, current-quitting and current-current). Smoking amount was categorised into never, light (0-10 pack years), moderate (10-20 pack years), and heavy smoking (>20 pack years) based on 2009 data. They were followed-up until 2013 to identify incident microvascular complications. We calculated the adjusted hazard ratios (HR) and 95% confidence interval (CI) (adjusted HR [95% CI]) for incident microvascular complications according to changes in smoking status and smoking amount. RESULTS: Current-quitting (1.271 [1.050-1.538]), current-current (1.243 [1.070-1.444]) and heavy smoking (1.238 [1.078-1.422]) were associated with an increased risk of overall microvascular complications. The risk of nephropathy increased in current-current smoking (1.429 [1.098-1.860]) and heavy smoking (1.357 [1.061-1.734]). An increased risk of neuropathy was observed in current-quitting smoking (1.360 [1.076-1.719]), current-current smoking (1.237 [1.025-1.492]) and heavy smoking (1.246 [1.048-1.481]). However, we couldn't see the interpretable findings for the association between smoking and retinopathy. CONCLUSIONS: Lasting and heavy smoking increases the risk of microvascular complications, including nephropathy and neuropathy. Quitting smoking and reducing smoking amount are imperative in preventing microvascular complications in DM patients.

Serum albumin and risk of incident diabetes and diabetic microvascular complications in the UK Biobank cohort.

AIM: To examine the associations between serum albumin and the incidences of diabetes and diabetic microvascular complications in participants of the UK Biobank cohort. METHODS: There were 398,146 participants without diabetes and 30,952 patients with diabetes from the UK Biobank cohort included in this study. Multivariate-adjusted Cox proportional hazard models were used to analyze the association of albumin with the incidences of diabetes and diabetic microvascular complications. Mendelian randomization (MR) analysis was used to determine the genetic relationships between serum albumin and diabetes. RESULTS: After a median 12.90 years follow-up, 14,710 participants developed incident diabetes (58.83 ± 7.52 years, 56.10% male). After multivariate adjustment, serum albumin was inversely associated with incident diabetes: hazard ratio (HR) [95% confidence interval] per 10 g/l increase 0.88 [0.82;0.94]. MR analyses suggested a potential genetic influence of serum albumin on diabetes in both the UK Biobank and the FinnGen consortium: odds ratios (ORs) [95% confidence interval per 1 g/l increase 0.99 [0.98;1.00] and 0.78 [0.67;0.92], respectively. In patients with diabetes, higher serum albumin levels were significantly associated with lower risk for diabetic microvascular complications. Specifically, per 10 g/l increase in serum albumin, the HRs for diabetic nephropathy, ophthalmopathy, and neuropathy were 0.42 [0.30;0.58], 0.61 [0.52;0.72], and 0.67 [0.51;0.88], respectively. CONCLUSION: In this large prospective study, serum levels of albumin were inversely associated with the incidences of diabetes and diabetic microvascular complications. These findings underscore the importance of maintaining optimal nutrient status in reducing the risk of diabetes and its complications.

Role of ADMA in the pathogenesis of microvascular complications in type 2 diabetes mellitus.

Diabetic microangiopathy is a typical and severe problem in diabetics, including diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, and diabetic cardiomyopathy. Patients with type 2 diabetes and diabetic microvascular complications have significantly elevated levels of Asymmetric dimethylarginine (ADMA), which is an endogenous inhibitor of nitric oxide synthase (NOS). ADMA facilitates the occurrence and progression of microvascular complications in type 2 diabetes through its effects on endothelial cell function, oxidative stress damage, inflammation, and fibrosis. This paper reviews the association between ADMA and microvascular complications of diabetes and elucidates the underlying mechanisms by which ADMA contributes to these complications. It provides a new idea and method for the prevention and treatment of microvascular complications in type 2 diabetes.

Prevalence of diabetes, epidemiological characteristics and vascular complications.

OBJECTIVE: To estimate prevalence of diabetes in outpatient care and to describe its epidemiological characteristics, comorbidities, and related vascular complications. METHODS: Observational cross-sectional study which included all adults affiliated from a private insurance health plan on March 2019, at Hospital Italiano de Buenos Aires, from Argentina. RESULTS: The global prevalence of diabetes resulted in 8.5% with 95% CI 8.3-8.6 (12,832 out of a total of 150,725 affiliates). The age stratum with the highest prevalence was the group between 65 and 80 years old with 15.7% (95% CI 15.3-16.1). People with diabetes had a mean age of 70 years (SD 14), 52% were women, and the most frequently associated cardiovascular risk factors were: dyslipidaemia (88%), arterial hypertension (74%) and obesity (55%). In relation to metabolic control, 60% had at least one glycosylated hemoglobin measured in the last year, 70% of which were less than 7%. Almost 80% have LDL measured at least once in the last 2 years, 55% of them had an LDL value equal to or less than 100 mg/dl. The macrovascular complications present in order of frequency were: acute myocardial infarction (11%), cerebrovascular accident (8%) and peripheral vascular disease (4%); while the microvascular complications were found to be diabetic neuropathy (4%) and retinopathy (2%). 7% had diabetic foot, with less than 1% amputations. CONCLUSION: Diabetes represents a prevalent problem, even in elderly patients. This population continues to present a high cardiovascular risk, with little compliance with therapeutic goals.

OBJETIVO: Estimar la prevalencia de diabetes en atención ambulatoria y describir sus características epidemiológicas, comorbilidades y complicaciones vasculares relacionadas. MÉTODO: Corte transversal que incluyó la totalidad de adultos afiliados a la prepaga del Hospital Italiano de Buenos Aires en marzo de 2019, Argentina. RESULTADOS: La prevalencia global de diabetes resultó del 8.5% con intervalo de confianza del 95% (IC95%): 8.3-8.6 (12,832 de un total de 150,725 afiliados). El estrato etario con mayor prevalencia fue el grupo entre 65 y 80 años, con un 15.7% (IC95%: 15.3-16.1). Las personas con diabetes presentaban una media de edad de 70 años (desviación estándar: 14), el 52% eran mujeres, y los factores de riesgo cardiovasculares más frecuentemente asociados fueron: dislipidemia (88%), hipertensión arterial (74%) y obesidad (55%). En relación con el control metabólico, el 60% tenía al menos una hemoglobina glucosilada medida en el último año, siendo el 70% de estas menores al 7%. Casi el 80% tiene medido el colesterol vinculado a lipoproteínas de baja densidad (c-LDL) al menos una vez en los últimos dos años, de ellos el 55% presentaba un valor de c-LDL igual o menor a 100 mg/dl. Las complicaciones macrovasculares presentes en orden de frecuencia fueron: infarto agudo de miocardio (11%), accidente cerebrovascular (8%) y enfermedad vascular periférica (4%); mientras que las complicaciones microvasculares resultaron ser neuropatía diabética (4%) y retinopatía (2%). El 7% tuvo pie diabético, con menos del 1% de amputaciones. CONCLUSIONES: La diabetes representa un problema prevalente, incluso en pacientes ancianos. Esta población sigue presentando un elevado riesgo cardiovascular, con escaso cumplimiento de objetivos terapéuticos.

Diabetic microvascular complications are associated with left atrial structural alterations in asymptomatic type 2 diabetes patients: A cross-sectional study.

AIMS: We used 4D-Auto LAQ to quantitatively evaluate the morphological and functional changes of left atrium in patients with asymptomatic type 2 diabetes mellitus (T2DM), and explored its correlations with diabetic microvascular complications (MICRO). METHODS: This study included 319 patients with asymptomatic T2DM. According to the occurrence of MICRO, these patients were divided into 3 groups: patients with no complication, 1 complication, and 2-3 complications. 4D-Auto LAQ was used to evaluate left atrial volume (LAVImin, LAVImax, LAVIpre) and calculate the left atrial function (DEI, PEI, AEI) in different phases. Multiple linear regression was used to analyze the correlation between changes in left atrial volume and function and the number of MICROs in DM patients. RESULTS: A total of 279 patients with asymptomatic T2DM were included in this study. (1) The ultrasound data of the three T2DM groups showed that there was no significant difference in left ventricular size and function among the three groups; (2) with the increase of MICRO number, the left atrial volume (LAVImin, LAVImax, LAVIpre) progressively increased, the left atrial storage function index (DEI) gradually decreased, and the differences were significant (P < 0.05). (3) Multiple linear regression analysis showed that: with the increase of MICRO number (no complication→1 complication→2-3 complications), the left atrial volume (LAVImin, LAVIpre) showed an increasing trend (both P < 0.05). CONCLUSION: In asymptomatic T2DM patients, MICRO number showed a significant positive correlation with LAVImin and LAVIpre (P < 0.05). Therefore, the increase in left atrial volume can dynamically reflect the severity of microvascular lesions in patients with asymptomatic T2DM.

Revascularizations and limb outcomes of hospitalized patients with diabetic peripheral arterial disease in the contemporary era.

BACKGROUND: Concomitant diabetes mellitus and peripheral artery disease (PAD) is a complex disease process. This retrospective analysis of the National Inpatient Sample sought to understand trends in limb outcomes of this unique and prevalent cohort of patients. METHODS: The National Inpatient Sample was queried between 2003 and 2017 for hospitalizations of patients with both type 2 diabetes mellitus and PAD. Trends in hospitalizations, limb outcomes, vascular interventions, and costs were analyzed. RESULTS: There were 10,303,673 hospitalizations of patients with concomitant diabetes mellitus and PAD that were identified between 2003 and 2017. The prevalence of hospitalizations associated with this disease process increased from 1644 to 3228 per 100,000 hospitalizations, a 96.4% increase. This included an increase of 288 to 587 per 100,000 hospitalizations of patients aged 18 to 49 years old, which was accompanied by a 10.8% increase in minor amputations. Nontraumatic lower extremity amputations decreased overall. Black and Hispanic ethnicity were associated with an increased risk for amputation, along with Medicaid insurance and lower income quartile. Inpatient endovascular revascularization has increased over time with an associated decrease in open revascularization procedures. Amputation-related hospital costs significantly increased from $6.6 billion in 2003 to $14.8 billion in 2017. CONCLUSIONS: An alarming increase of disease prevalence, negative in-hospital limb outcomes, and costs are seen in the current era in this analysis of patients with concurrent diabetes and PAD.

A multi-centre investigation of macrovascular and non-ocular microvascular complications in children and adolescents with diabetes mellitus in southern Ghana.

Objectives: To investigate the prevalence of macrovascular and non-ocular microvascular complications and the associated factors among children and adolescents with diabetes mellitus in selected hospitals in southern Ghana. Design: A cross-sectional study. Setting: The out-patient clinics of the Departments of Child Health, Medicine and Therapeutics, Family Medicine, Ophthalmology, and the National Diabetes Management and Research Centre, all at the Korle Bu Teaching Hospital, Accra, as well as from Cape-Coast Teaching Hospital in the Central Region of Ghana. Participants: Fifty-eight children and adolescents aged 4-19 years who had been diagnosed with diabetes mellitus. Main outcome measures: Macrovascular (peripheral artery disease and coronary heart disease) and non-ocular microvascular complications (neuropathy and nephropathy). Results: Data from 58 children and adolescents with diabetes were analysed. The mean age of participants was 14.6±2.6 years, and a female preponderance was observed (45, 77.6%). The prevalence of macrovascular and non-ocular microvascular complications was 27.6% and 8.6%, respectively. Long duration of diabetes diagnosis (p=0.044) and low triglycerides (p=0.009) were associated with microvascular complications, while high triglycerides (p=0.032), lower HDL cholesterol (p=0.046), and abnormal body mass index (p=0.020) were associated with macrovascular complications. Conclusions: Macrovascular and non-ocular microvascular complications are common among children and adolescents with diabetes in southern Ghana and are associated with a long duration of diabetes diagnosis, abnormal body mass index, low HDL cholesterol, and triglyceride levels. Therefore, the early institution of regular screening for diabetes-related complications to allow early detection and appropriate management is recommended. Funding: University of Ghana Research Fund.

Sjögren syndrome is a hidden contributor of macrovascular and microvascular complications in patients with type 2 diabetes.

OBJECTIVE: To investigate cardiovascular risk among diabetic patients with Sjögren syndrome. METHODS: This study was a nationwide population-based case-control study from 1997 to 2013, in which the association between autoimmune diseases and diabetes was investigated. The study population consisted of individuals with newly diagnosed type 2 diabetes with macrovascular or microvascular complications with at least two outpatient visits or one hospitalization as the outcome variables, and the exposure variables included traditional risk factors, medications, and autoimmune diseases. The odds ratio of cardiovascular events among each prevalent autoimmune disease and hydroxychloroquine's effect on cardiovascular risk were analyzed. RESULTS: The study included a total of 7026 individuals with diabetes with microvascular and macrovascular complications and the same number of patients in the control group. Sjögren syndrome was significantly higher in the diabetes complication group than in the non-complication group (0.8% vs 0.5%, P = 0.036). By using multivariate analysis, we found hypertension, hyperlipidemia, and Sjögren syndrome to be three independent risk factors for diabetes vascular complications (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.82-2.10; OR 1.53, 95% CI 1.42-1.64; and OR 1.67, 95% CI 1.06-2.65; respectively, all P < 0.05). Treatment with traditional statins and aspirin might be able to overcome the increased risk of developing cardiovascular events while comparing between diabetes patients with and without Sjögren syndrome. CONCLUSION: Sjögren syndrome is an unrecognized independent risk factor for cardiovascular events among diabetes patients, which indicates that patients with diabetes combined with Sjögren syndrome require closer follow up regarding cardiovascular complications in clinical settings. Treatment with hydroxychloroquine might not be enough to lower the cardiovascular risk significantly in diabetes patients with Sjögren syndrome.

Fetuin-A and risk of diabetes-related vascular complications: a prospective study.

BACKGROUND: Fetuin-A is a hepatokine which has the capacity to prevent vascular calcification. Moreover, it is linked to the induction of metabolic dysfunction, insulin resistance and associated with increased risk of diabetes. It has not been clarified whether fetuin-A associates with risk of vascular, specifically microvascular, complications in patients with diabetes. We aimed to investigate whether pre-diagnostic plasma fetuin-A is associated with risk of complications once diabetes develops. METHODS: Participants with incident type 2 diabetes and free of micro- and macrovascular disease from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (n = 587) were followed for microvascular and macrovascular complications (n = 203 and n = 60, respectively, median follow-up: 13 years). Plasma fetuin-A was measured approximately 4 years prior to diabetes diagnosis. Prospective associations between baseline fetuin-A and risk of complications were assessed with Cox regression. RESULTS: In multivariable models, fetuin-A was linearly inversely associated with incident total and microvascular complications, hazard ratio (HR, 95% CI) per standard deviation (SD) increase: 0.86 (0.74; 0.99) for total, 0.84 (0.71; 0.98) for microvascular and 0.92 (0.68; 1.24) for macrovascular complications. After additional adjustment for cardiometabolic plasma biomarkers, including triglycerides and high-density lipoprotein, the associations were slightly attenuated: 0.88 (0.75; 1.02) for total, 0.85 (0.72; 1.01) for microvascular and 0.95 (0.67; 1.34) for macrovascular complications. No interaction by sex could be observed (p > 0.10 for all endpoints). CONCLUSIONS: Our data show that lower plasma fetuin-A levels measured prior to the diagnosis of diabetes may be etiologically implicated in the development of diabetes-associated microvascular disease.

Consultation rates in people with type 2 diabetes with and without vascular complications: a retrospective analysis of 141,328 adults in England.

OBJECTIVE: To assess trends in primary and specialist care consultation rates and average length of consultation by cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), or cardiometabolic multimorbidity exposure status. METHODS: Observational, retrospective cohort study used linked Clinical Practice Research Datalink primary care data from 01/01/2000 to 31/12/2018 to assess consultation rates in 141,328 adults with newly diagnosed T2DM, with or without CVD. Patients who entered the study with either a diagnosis of T2DM or CVD and later developed the second condition during the study are classified as the cardiometabolic multimorbidity group. Face to face primary and specialist care consultations, with either a nurse or general practitioner, were assessed over time in subjects with T2DM, CVD, or cardiometabolic multimorbidity. Changes in the average length of consultation in each group were investigated. RESULTS: 696,255 (mean 4.9 years [95% CI, 2.02-7.66]) person years of follow up time, there were 10,221,798 primary and specialist care consultations. The crude rate of primary and specialist care consultations in patients with cardiometabolic multimorbidity (N = 11,881) was 18.5 (95% CI, 18.47-18.55) per person years, 13.5 (13.50, 13.52) in patients with T2DM only (N = 83,094) and 13.2 (13.18, 13.21) in those with CVD (N = 57,974). Patients with cardiometabolic multimorbidity had 28% (IRR 1.28; 95% CI: 1.27, 1.31) more consultations than those with only T2DM. Patients with cardiometabolic multimorbidity had primary care consultation rates decrease by 50.1% compared to a 45.0% decrease in consultations for those with T2DM from 2000 to 2018. Specialist care consultation rates in both groups increased from 2003 to 2018 by 33.3% and 54.4% in patients with cardiometabolic multimorbidity and T2DM, respectively. For patients with T2DM the average consultation duration increased by 36.0%, in patients with CVD it increased by 74.3%, and in those with cardiometabolic multimorbidity it increased by 37.3%. CONCLUSIONS: Annual primary care consultation rates for individuals with T2DM, CVD, or cardiometabolic multimorbidity have fallen since 2000, while specialist care consultations and average consultation length have both increased. Individuals with cardiometabolic multimorbidity have significantly more consultations than individuals with T2DM or CVD alone. Service redesign of health care delivery needs to be considered for people with cardiometabolic multimorbidity to reduce the burden and health care costs.

Cardiovascular Effects of Incretin-Based Therapies: Integrating Mechanisms With Cardiovascular Outcome Trials.

As the worldwide prevalence of diabetes and obesity continues to rise, so does the risk of debilitating cardiovascular complications. Given the significant association between diabetes and cardiovascular risk, the actions of glucose-lowering therapies within the cardiovascular system must be clearly defined. Incretin hormones, including GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic polypeptide), are gut hormones secreted in response to nutrient intake that maintain glycemic control by regulating insulin and glucagon release. GLP-1 receptor agonists (GLP-1Ras) and dipeptidyl peptidase 4 inhibitors (DPP-4is) represent two drug classes used for the treatment of type 2 diabetes mellitus (T2DM) that improve glucose regulation through stimulating the actions of gut-derived incretin hormones or inhibiting their degradation, respectively. Despite both classes acting to potentiate the incretin response, the potential cardioprotective benefits afforded by GLP-1Ras have not been recapitulated in cardiovascular outcome trials (CVOTs) evaluating DPP-4is. This review provides insights through discussion of clinical and preclinical studies to illuminate the physiological mechanisms that may underlie and reconcile observations from GLP-1Ra and DPP-4i CVOTs. Furthermore, critical knowledge gaps and areas for further investigation will be emphasized to guide future studies and, ultimately, facilitate improved clinical management of cardiovascular disease in T2DM.

One year into the clash of pandemics of diabetes and COVID-19: Lessons learnt and future perspectives.

There is a bidirectional relationship between coronavirus disease 2019 (COVID-19) and diabetes. Furthermore, the COVID-19 pandemic has catalyzed the use of technology in diabetes care. Future research is required to assess the impact of COVID-19 on new-onset diabetes and the influence of diabetes on responses to COVID-19 vaccines.

Do diabetic complications influence cancer-related events in people with type 2 diabetes? A cohort approach.

AIM: To investigate whether diabetic micro- and macrovascular complications (mMVC) influence cancer-related events in people with type 2 diabetes. METHODS: People with type 2 diabetes from the SURDIAGENE cohort were characterized (duration of diabetes, HbA1c, mMVC, history of cancer) and prospectively followed-up for death and cancer-related events (occurrence, dissemination and cancer-related death). RESULTS: Between 2002 and 2012, 1468 participants (58% men, mean age 64.8 ± 10.7 years, mean duration of diabetes 14.5 ± 9.9 years at baseline) were enrolled. At baseline, 119 (8%) had a personal history of cancer. Incident cancer occurred in 207 (14%) patients during a mean follow-up of 7.3 ± 3.7 years and was associated with older age, smoking status and personal history of cancer. mMVC were not associated with cancer-related events, considering cancer occurrence, node/metastasis dissemination and cancer-specific death. Risk of all-cause mortality was increased in diabetic patients cumulating cancer history and mMVC (HR 1.73, 95%CI 1.25-2.38) compared to those with neither cancer nor mMVC. In our cohort, cancer-related death was not associated with mMVC (HR 1.05, 95%CI 0.67-1.64), but conversely history of cancer was significantly associated with cardiovascular-related death (HR 2.41, 95%CI 1.36-4.26). CONCLUSION: In our cohort, mMVC were not associated with cancer-related events, while history of cancer was significantly associated with cardiovascular death.

Predictors of outcome in diabetic patients undergoing infrapopliteal endovascular revascularization for chronic limb-threatening ischemia.

OBJECTIVE: The incidence of chronic limb-threatening ischemia in diabetic patients is increasing. The factors influencing outcome after infrapopliteal revascularization in these patients are largely unknown. Therefore, this study aims to identify the impact of perioperative glucose control on the long-term outcomes in this patient cohort, and furthermore to identify other factors independently associated with outcome. METHODS: Consecutive diabetic patients undergoing infrapopliteal endovascular revascularization for chronic limb-threatening ischemia were identified. Patients' demographics, procedural details, daily capillary blood glucose, and hemoglobin A1C levels were collected and analyzed against the study end points using Kaplan-Meier and Cox regression analysis. RESULTS: A total of 437 infrapopliteal target vessels were successfully crossed in 203 patients. Amputation-free survival by Kaplan-Meier (estimate (standard error)%) was 74 (3.3)% and 63 (3.7)%, primary patency was 61 (4.2)% and 50 (4.9)%, assisted primary patency was 69 (5.2)% and 55 (6.1)%, and secondary patency was 71 (3.8)% and 59 (4.1)% at 1 year and 2 years, respectively. Cox regression analysis showed high perioperative capillary blood glucose levels to be an independent predictor of binary restenosis (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.31-1.1.78; P = .015). Postprocedural dual-antiplatelet therapy was found to be an independent predictor of amputation-free survival (HR, 1.69; 95% CI, 1.04-2.75; P = .033), and freedom from major adverse limb events (HR: 1.96; 95% CI, 1.16-3.27; P = .023) and baseline estimated glomerular filtration rate was significantly associated with better amputation-free survival (HR, 0.52; 95% CI, 0.31-0.87; P = .014). CONCLUSIONS: Poor perioperative glycemic control is associated with a higher incidence of restenosis after infrapopliteal revascularization in diabetic patients. Dual antiplatelet therapy is associated with better outcomes in this group.

Ankle-Brachial Index Is Independently Associated With Cardiovascular Outcomes and Foot Ulcers in Asian Patients With Type 2 Diabetes Mellitus.

Background and Aims: The ankle-brachial index (ABI) is an efficient tool for objectively documenting the presence of lower-extremity peripheral arterial disease (PAD). The predictive factors of cardiovascular events and diabetic foot ulcer were not clear from the ABI examination in Taiwanese patients with type 2 diabetes mellitus (DM). Methods: We enrolled 482 patients with type 2 DM who regularly visited the outpatient department of Chang Gung Memorial Hospital and received ABI as well as brachial-ankle pulse wave velocity (ba-PWV) examinations from 2010 to 2017. Age, gender, PAD symptoms, comorbidities, family history of chronic diseases, lifestyle (smoking, alcohol consumption, and exercise), height, weight, waist circumference, monofilament testing and foot ulcer status were studied. Results: There were 104 (22%) patients (mean age, 67.8 years) with the ABI <1.0. These patients with low ABI (ABI<1.0) had a significantly older age (p=0.001), higher delta PWV (p<0.001), higher rates of stroke (p=0.007), myocardial infarction (p=0.016), and foot ulcer (p=0.039). In a multivariable analysis model, the adjusted odds ratio (aOR) for myocardial infarction, stroke, and foot ulcers associated with low ABI were 1.219 (0.397-3.743, p=0.729), 1.204 (0.556-2.610, p=0.638), and 2.712 (1.199-6.133, p=0.017), respectively. The patients with low PWV (PWV<1400 cm/s) were significantly younger (p<0.001) and had a lower rate of hypertension (p<0.001), and higher percentages of stroke (p=0.027) and dialysis (p=0.041) family history. Conclusions: Low ABI was associated with cardiovascular events and diabetic foot ulcer independently in patients with type 2 DM.

Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks.

Hypoglycemia has been recognized as a risk factor for diabetic vascular complications and cognitive decline, but the molecular mechanisms of the effect of hypoglycemia on target organs are not fully understood. In this work, gene networks of hypoglycemia and cardiovascular disease, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, cognitive decline, and Alzheimer's disease were reconstructed using ANDSystem, a text-mining-based tool. The gene network of hypoglycemia included 141 genes and 2467 interactions. Enrichment analysis of Gene Ontology (GO) biological processes showed that the regulation of insulin secretion, glucose homeostasis, apoptosis, nitric oxide biosynthesis, and cell signaling are significantly enriched for hypoglycemia. Among the network hubs, INS, IL6, LEP, TNF, IL1B, EGFR, and FOS had the highest betweenness centrality, while GPR142, MBOAT4, SLC5A4, IGFBP6, PPY, G6PC1, SLC2A2, GYS2, GCGR, and AQP7 demonstrated the highest cross-talk specificity. Hypoglycemia-related genes were overrepresented in the gene networks of diabetic complications and comorbidity; moreover, 14 genes were mutual for all studied disorders. Eleven GO biological processes (glucose homeostasis, nitric oxide biosynthesis, smooth muscle cell proliferation, ERK1 and ERK2 cascade, etc.) were overrepresented in all reconstructed networks. The obtained results expand our understanding of the molecular mechanisms underlying the deteriorating effects of hypoglycemia in diabetes-associated vascular disease and cognitive dysfunction.