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Type I Diabetes Mellitus Increases the Cardiovascular Complications of Influenza Virus Infection.

ABSTRACT: People with diabetes mellitus are susceptible to both cardiovascular disease and severe influenza A virus infection. We hypothesized that diabetes also increases risks of influenza-associated cardiac complications. A murine type 1 (streptozotocin-induced) diabetes model was employed to investigate influenza-induced cardiac distress. Lung histopathology and viral titres revealed no difference in respiratory severity between infected control and diabetic mice. However, compared with infected control mice, infected diabetic mice had increased serum cardiac troponin I and creatine-kinase MB, left ventricular structural changes and right ventricular functional alterations, providing the first experimental evidence of type I diabetes increasing risks of influenza-induced cardiovascular complications.

SUBMITTER: Sinclair JE

PROVIDER: S-EPMC8476859 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Type I Diabetes Mellitus Increases the Cardiovascular Complications of Influenza Virus Infection.

Sinclair Jane E JE Bloxham Conor J CJ Chiu Han H Chew Keng Yih KY Russell Jake J Yoshikawa Yusuke Y Bielefeldt-Ohmann Helle H Steele Lauren E LE Hulme Katina D KD Verzele Nathalie Aj NA Noye Ellesandra C EC Wu Melanie M Reichelt Melissa E ME Thomas Walter G WG Gallo Linda A LA Redd Meredith A MA Short Kirsty R KR

Frontiers in cellular and infection microbiology 20210914

People with diabetes mellitus are susceptible to both cardiovascular disease and severe influenza A virus infection. We hypothesized that diabetes also increases risks of influenza-associated cardiac complications. A murine type 1 (streptozotocin-induced) diabetes model was employed to investigate influenza-induced cardiac distress. Lung histopathology and viral titres revealed no difference in respiratory severity between infected control and diabetic mice. However, compared with infected contr ...[more]

PMID: 34595130

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Project description:Sphingolipid metabolism is dysregulated in type 2 diabetes mellitus (T2DM); however, the focus of previous studies was mostly limited to ceramide (Cer), and only few studies have investigated other metabolites, including sphingosine-1 phosphate (So1P). The present study aimed to examine the involvement of 8 major sphingolipid metabolites, including Cer, glucosyl ceramide (GluCer), lactosyl ceramide (LacCer), sphingomyelin (SM), sphinganine (Sa), So1P, sphingosine (So) and sphinganine-1-phosphate (Sa1P), during the progression of T2DM, and to evaluate the ability of serum sphingolipids to predict cases of diabetes with an elevated risk of cardiovascular complications. Blood samples were obtained from 245 participants who were divided into 3 groups: Healthy controls, pre-diabetes (pre-DM) and diagnosed diabetes. The 8 major sphingolipid metabolites were measured by high-performance liquid chromatography-tandem mass spectrometry and blood parameters were determined by routine laboratory assays for all subjects. Among the sphingolipid metabolites, So1P was associated with sex and lean mass index, but not with the body mass index. So1P was highest in healthy controls and gradually decreased when the disease proceeded to pre-DM and T2DM. GluCer, SM, Sa and So decreased in pre-DM and rose again in T2DM, graphically exhibiting a 'U' shape change during the progression of diabetes. So1P and Sa were identified to be significantly associated with cardiovascular complications by multivariate logistic regression analysis. Receiver operating characteristic curve analysis also suggested that So1P and Sa were able to indicate cardiovascular complications in diabetic patients. Pre-DM and diabetes were significantly associated with decreased So1P, SM, Sa and So, compared with the healthy controls. So1P was correlated with the progression of T2DM, and was a predictor of an elevated risk of cardiovascular complications among T2DM patients, along with Sa. The present study was registered with ClinicalTrials.gov (no. NCT02826759; April 2016).

Project description:BackgroundIntensive diabetes mellitus therapy of type 1 diabetes mellitus reduces diabetes mellitus complications but can be associated with excess weight gain, central obesity, and dyslipidemia. The purpose of this study was to determine whether excessive weight gain with diabetes mellitus therapy of type 1 diabetes mellitus is prospectively associated with atherosclerotic disease.Methods and resultsSubjects with type 1 diabetes mellitus (97% white, 45% female, mean age 35 years) randomly assigned to intensive or conventional diabetes mellitus treatment during the Diabetes Control and Complications Trial (DCCT) underwent intima-media thickness (n = 1015) and coronary artery calcium score (n = 925) measurements during follow-up in the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. Intensive treatment subjects were classified by quartile of body mass index change during the DCCT. Excess gainers (4th quartile, including conventional treatment subjects meeting this threshold) maintained greater body mass index and waist circumference, needed more insulin, had greater intima-media thickness (+5%, P < 0.001 EDIC year 1, P = 0.003 EDIC year 6), and trended toward greater coronary artery calcium scores (odds ratio, 1.55; confidence interval, 0.97 to 2.49; P = 0.07) than minimal gainers. DCCT subjects meeting metabolic syndrome criteria for waist circumference and blood pressure had greater intima-media thickness in both EDIC years (P = 0.02 to < 0.001); those meeting high-density lipoprotein criteria had greater coronary artery calcium scores (odds ratio, 1.6; confidence interval, 1.1 to 2.4; P = 0.01) during follow-up. Increasing frequency of a family history of diabetes mellitus, hypertension, and hyperlipidemia was associated with greater intima-media thickness with intensive but not conventional treatment.ConclusionsExcess weight gain in DCCT is associated with sustained increases in central obesity, insulin resistance, dyslipidemia and blood pressure, as well as more extensive atherosclerosis during EDIC.Clinical trial registrationURL for DCCT: http://clinicaltrials.gov; Unique identifier: NCT00360815. URL for EDIC: http://clinicaltrials.gov; Unique identifier: NCT00360893.

Project description:AimTo characterize clinically relevant subgroups of patients with type-2 diabetes mellitus (T2DM) based on adiposity, insulin secretion, and resistance indices.MethodsA cross-sectional study was conducted at Eastern Regional Hospital in Ghana from July to October 2021 to investigate long-term patients with T2DM. To select participants, a systematic random sampling method was employed. Demographic data was collected using a structured questionnaire and fasting blood samples were taken to measure glycemic and lipid levels. Blood pressure and adiposity indices were measured during recruitment. The risk of cardiovascular disease (CVD) was defined using Framingham scores and standard low-density lipoprotein thresholds. To analyze the data, k-means clustering algorithms and regression analysis were used.ResultsThe study identified three groups in female patients according to body mass index, relative fat mass, glycated hemoglobin, and triglyceride-glucose index. These groups included the obesity-related phenotype, the severe insulin resistance phenotype, and the normal weight phenotype with improved insulin resistance. Among male patients with T2DM, two groups were identified, including the obesity-related phenotype with severe insulin resistance and the normal weight phenotype with improved insulin sensitivity. The severe insulin resistance phenotype in female patients was associated with an increased risk of high CVD (OR = 5.34, 95%CI:2.11-13.55) and metabolic syndrome (OR = 7.07; 95%CI:3.24-15.42). Among male patients, the obesity-related phenotype with severe insulin resistance was associated with an increased intermediate (OR = 21.78, 95%CI:4.17-113.78) and a high-risk CVD (OR = 6.84, 95%CI:1.45-32.12).ConclusionsThe findings highlight significant cardiometabolic heterogeneity among T2DM patients. The subgroups of T2DM patients characterized by obesity and/or severe insulin resistance with or without poor glycemic control, have increased risk of CVD. This underscores the importance of considering differences in adiposity, insulin secretion, and sensitivity indices when making clinical decisions for patients with T2DM.

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Type I Diabetes Mellitus Increases the Cardiovascular Complications of Influenza Virus Infection.

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Type I Diabetes Mellitus Increases the Cardiovascular Complications of Influenza Virus Infection.

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