Hypoglycemia Abrogates the Vascular Endothelial Protective Effect of Exenatide in Type 2 Diabetes Mellitus.
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SUBMITTER: Torimoto K
PROVIDER: S-EPMC6531533 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Endothelial glycocalyx perturbation contributes to increased vascular permeability. In the present study we set out to evaluate whether: (1) glycocalyx is perturbed in individuals with type 2 diabetes mellitus, and (2) oral glycocalyx precursor treatment improves glycocalyx properties.Male participants with type 2 diabetes (n = 10) and controls (n = 10) were evaluated before and after 2 months of sulodexide administration (200 mg/day). The glycocalyx dimension was estimated in two different vascular beds using sidestream dark field imaging and combined fluorescein/indocyanine green angiography for sublingual and retinal vessels, respectively. Transcapillary escape rate of albumin (TER(alb)) and hyaluronan catabolism were assessed as measures of vascular permeability.Both sublingual dimensions (0.64 [0.57-0.75] ?m vs 0.78 [0.71-0.85] ?m, p < 0.05, medians [interquartile range]) and retinal glycocalyx dimensions (5.38 [4.88-6.59] ?m vs 8.89 [4.74-11.84] ?m, p < 0.05) were reduced in the type 2 diabetes group compared with the controls whereas TER(alb) was increased (5.6 ± 2.3% vs 3.7 ± 1.7% in the controls, p < 0.05). In line with these findings, markers of hyaluronan catabolism were increased with diabetes (hyaluronan 137 ± 29 vs 81 ± 8 ng/ml and hyaluronidase 78 ± 4 vs 67 ± 2 U/ml, both p < 0.05). Sulodexide increased both the sublingual and retinal glycocalyx dimensions in participants with diabetes (to 0.93 [0.83-0.99] ?m and to 5.88 [5.33-6.26] ?m, respectively, p < 0.05). In line, a trend towards TER(alb) normalisation (to 4.0 ± 2.3%) and decreases in plasma hyaluronidase (to 72 ± 2 U/ml, p < 0.05) were observed in the diabetes group.Type 2 diabetes is associated with glycocalyx perturbation and increased vascular permeability, which are partially restored following sulodexide administration. Further studies are warranted to determine whether long-term treatment with sulodexide has a beneficial effect on cardiovascular risk.www.trialregister.nl NTR780/ http://isrctn.org ISRCTN82695186An unrestricted Novartis Foundation for Cardiovascular Excellence grant (2006) to M. Nieuwdorp/E. S. G. Stroes, Dutch Heart Foundation (grant number 2005T037).
| S-EPMC2974920 | biostudies-other
Project description:BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1 RAs) demonstrated good glycemic efficacy in patients with type 2 diabetes mellitus (T2DM) recent years, whereas studies on GLP-1 RAs' biliary effects were limited. Therefore, we aimed to assess the effect of exenatide on bile acids (BAs) and investigate the role of BAs in the glycemic control effect of exenatide.MethodsThirty-eight newly diagnosed T2DM participants without glucose-lowering drugs intake were recruited. Plasma total bile acids in fasting state (FTBAs) and other parameters were tested at baseline. Then exenatide were applied to the T2DM participants for 12 weeks. FTBAs and glycemic parameters were measured again after exenatide treatment, and correlation analysis between changes of FTBAs and glycemic parameters were conducted to investigate the role of BAs in the glycemic control effect of exenatide.ResultsThe baseline FTBAs level of T2DM patients had no significance (3.84 ± 2.06 vs. 3.87 ± 2.89, P = 0.954) compared with healthy subjects. After 12-week exenatide treatment for the T2DM patients, FTBAs were decreased from 3.84 ± 2.06 μmol/L to 3.06 ± 1.27 μmol/L (P < 0.01). The correlation analysis showed that changes of FTBAs was positively correlated with changes of FPG (r = 0.355, P < 0.05).ConclusionsOur results demonstrated a decreased FTBAs level after exenatide treatment for 12 weeks, without the interference of metformin and other glucose-lowering drugs. The reduction of FTBAs might not exert a positive role in the glycemic control effect of exenatide.Trial registrationTrial registration number: NCT04303819. Registered in March 11, 2020 - Retrospectively registered.
| S-EPMC7296654 | biostudies-literature
Project description:BackgroundThe fear of hypoglycemia in type 2 diabetes mellitus (T2DM) patients with hypoglycemia has seriously affected their quality of life. They are always afraid of hypoglycemia and often take excessive action to avoid it. Yet, researchers have investigated the relationship between hypoglycemia worries and excessive avoiding hypoglycemia behavior using total scores on self-report measures. However, network analysis studies of hypoglycemia worries and excessive avoiding hypoglycemia behavior in T2DM patients with hypoglycemia are lacking.PurposeThe present study investigated the network structure of hypoglycemia worries and avoiding hypoglycemia behavior in T2DM patients with hypoglycemia and aimed to identify bridge items to help them correctly treat hypoglycemia and properly deal with hypoglycemia fear.MethodsA total of 283 T2DM patients with hypoglycemia were enrolled in our study. Hypoglycemia worries and avoiding hypoglycemia behavior were evaluated with the Hypoglycemia Fear Scale. Network analyses were used for the statistical analysis.ResultsB9 "Had to stay at home for fear of hypoglycemia" and W12 "I am worried that hypoglycemia will affect my judgment" have the highest expected influences in the present network. In the community of hypoglycemia worries, W17 "I worry about hypoglycemia during sleep" has the highest bridge expected influence. And in the community of avoiding hypoglycemia behavior, B9 "Had to stay at home for fear of hypoglycemia" has the highest bridge expected influence.ConclusionComplex patterns of associations existed in the relationship between hypoglycemia worries and avoiding hypoglycemia behavior in T2DM patients with hypoglycemia. From the perspective of network analysis, B9 "Had to stay at home for fear of hypoglycemia" and W12 "I am worried that hypoglycemia will affect my judgment" have the highest expected influence, indicating their highest importance in the network. W17 "I worry about hypoglycemia during sleep" aspect of hypoglycemia worries and B9 "Had to stay at home for fear of hypoglycemia" aspect of avoiding hypoglycemia behavior have the highest bridge expected influence, indicating they have the strongest connections with each community. These results have important implications for clinical practice, which provided potential targets for interventions to reduce hypoglycemia fear and improve the quality of life in T2DM patients with hypoglycemia.
| S-EPMC10053460 | biostudies-literature
Project description:BACKGROUND:Hypoglycemia is a very serious complication in patients with type 2 diabetes mellitus (T2DM) and affects the economic burden of treatment. This study aims to create models of the cost of treating hypoglycemia in patients with T2DM based upon physician estimates of medical resource usage. METHODS:Using a literature review and personal advice from endocrinologists and emergency physicians, we developed several models for managing patients with hypoglycemia. The final model was approved by the consulting experts. We also developed 3 unique surveys to allow endocrinologists, emergency room (ER) physicians, and primary care physicians to evaluate the resource usage of patients with hypoglycemia. Medical costs were calculated by multiplying the estimated medical resource usage by the corresponding health insurance medical care costs reported in 2014. RESULTS:In total, 40 endocrinologists, 20 ER physicians, and 30 primary care physicians completed the survey. We identified 12 types of standard medical models for secondary or tertiary hospitals and 4 for primary care clinics based on the use of ER, general ward, or intensive care unit (ICU) and patients' status of consciousness and self-respiration. Estimated medical costs per person per hypoglycemic event ranged from $17.28 to $1,857.09 for secondary and tertiary hospitals. These costs were higher for patients who were unconscious and for those requiring ICU admission. CONCLUSION:Hypoglycemia has a substantial impact on the medical costs and its prevention will result in economic benefits for T2DM patients and society.
| S-EPMC4790854 | biostudies-literature
Project description:BackgroundThe prevalence of type 2 diabetes (DM) has been increasing globally, particularly among older adults who are more susceptible to DM-related complications. Elderly individuals with diabetes are at higher risk of developing hypoglycemia compared with younger diabetes patients. Hypoglycemia in elderly patients can result in serious consequences such as cognitive changes, increased risk of falls, heart and other vascular problems, and even high mortality rate.ObjectiveTo assess prevalence, and factors associated with hypoglycemia events among geriatric outpatients with type 2 diabetes mellitus.MethodsThe study was conducted at King Abdullah University Hospital (KAUH) at the outpatient diabetes clinic from October 1st, 2022 to August 1st, 2023. Variables such as socio-demographics, medication history, and comorbidities were obtained using electronic medical records. The prevalence of hypoglycemia was determined through patient interviews during their clinic visit. Patients were prospectively monitored for hospital admissions, emergency department visits, and mortality using electronic medical records over a three-month follow-up period. Logistic regression models were conducted to identify factors associated with hypoglycemia and hospital admissions/ emergency visits. Ethical Approval (Reference # 53/151/2022) was obtained on 19/9/2022.ResultsElectronic medical charts of 640 patients who have type 2 diabetes mellitus and age ≥ 60 years were evaluated. The mean age ± SD was 67.19 (± 5.69) years. Hypoglycemia incidents with different severity levels were prevalent in 21.7% (n = 139) of the patients. Insulin administration was significantly associated with more hypoglycemic events compared to other antidiabetic medication. Patients with liver diseases had a significantly higher risk of hypoglycemia, with odds 7.43 times higher than patients without liver diseases. Patients with dyslipidemia also had a higher risk of hypoglycemia (odd ratio = 1.87). Regression analysis revealed that hypoglycemia and educational level were significant predictors for hospital admission and emergency department (ER) visits. Hypoglycemia was a positive predictor, meaning it increased the odds of these outcomes, while having a college degree or higher was associated with reduced odds of hospital admission and ER visits.ConclusionCurrent study identified a considerable prevalence of hypoglycemia among older patients with type 2 diabetes, particularly, among those with concurrent liver diseases and dyslipidemia. Furthermore, hypoglycemia was associated with an increased rate of emergency department visits and hospital admissions by 2 folds in this population.
| S-EPMC11361436 | biostudies-literature
Project description:ObjectiveThe 10-year intensive lifestyle intervention (ILI) of the Look AHEAD study left a legacy of relative deficits in cognitive function among participants who entered the clinical trial with obesity or a history of cardiovascular disease. We hypothesized that altered levels of two weight-sensitive proangiogenic cytokines, leptin and vascular endothelial growth factor (VEGF), accounted for this concerning finding.MethodsSerum leptin and VEGF concentrations were determined in 1,279 Look AHEAD participants at baseline, proximal to cessation of the interventions (Epoch 1), and an average of 4 years later (Epoch 2). Up to four standardized assessments of attention, executive function, and memory were collected during follow-up. Mixed effects models were used to assess relative differences in leptin and VEGF concentrations between intervention groups and whether these accounted for changes in cognitive composite scores.ResultsILI and diabetes support and education differences in VEGF, but not leptin, concentrations varied depending on baseline history of cardiovascular disease and obesity, but neither leptin nor VEGF concentrations accounted for the relative decrements in cognitive function in participants assigned to ILI.ConclusionsAlterations in two weight-sensitive proangiogenic cytokines did not account for the long-term adverse effects of ILI on cognitive function among adults with diabetes and either obesity or cardiovascular disease.
| S-EPMC9420754 | biostudies-literature
Project description:Aims. Dipeptidyl-peptidase IV inhibitors (DPP-4i) are among the most popular oral antidiabetic agents. However, the effects of DPP-4i on diabetic nephropathy are not well-established. The aim of this study was to determine the renoprotective effects of DPP-4i, using albuminuria and glomerular filtration rate (GFR) as indicators, in type 2 diabetes mellitus (T2DM) patients. Methods. This retrospective observational cohort study used the clinical database of a tertiary hospital. The changes of urine albumin/creatinine ratio (UACR), estimated GFR (eGFR), and metabolic parameters after treatment were compared with the changes of those parameters before treatment using paired Student's t-test. Results. The mean UACR in the entire study population decreased to approximately 45 mg/g 1 year after DPP-4i treatment, while it was increased approximately 39 mg/g 1 year before DPP-4i treatment (p < 0.05). Patients with macroalbuminuria showed a significant reduction in albumin levels after DPP-4i treatment (p < 0.05); however, patients with microalbuminuria and normoalbuminuria did not show improvements in albuminuria levels after treatment. Although eGFR was not changed 1 year after DPP-4i treatment, reductions in eGFR were slowed in patients with microalbuminuria and reversed in the macroalbuminuria or normoalbuminuria groups, 4 years after treatment. Conclusions. Administration of DPP-4i reduces urine albumin excretion and mitigates reduction of eGFR in T2DM patients.
| S-EPMC5228170 | biostudies-literature
Project description:BackgroundStudies have found conflicting evidence regarding the association of hypoglycemia with dementia. We evaluated an association of hypoglycemia with subsequent dementia in patients with type 2 diabetes.MethodsThis retrospective longitudinal cohort study used the Clinical Practice Research Datalink, an electronic medical records data from the United Kingdom, from 2003 to 2012. We included patients aged >65 years diagnosed with type 2 diabetes, with no prior diagnosis of dementia. Dementia was defined using diagnosis codes from medical records. All patients were followed from the date of initial diabetes diagnosis. To account for competing risk of death, we used Fine and Gray's competing risk model to determine the association of hypoglycemia with dementia while adjusting for potential confounders. Hypoglycemia was modeled as a time-dependent covariate.ResultsOf 53,055 patients, 5.7% (n = 3,018) had at least one hypoglycemia episodes. The overall incidence rate of dementia was 12.7 per 1,000 person-years. In the fully adjusted model that controlled for all confounders, the occurrence of at least one hypoglycemia episode was associated with 27% higher odds of subsequent dementia (hazard ratio = 1.27; 95% confidence interval = 1.06-1.51). The risk increased with the number of hypoglycemia episodes: one episode (hazard ratio = 1.26; 95% confidence interval = 1.03-1.54); two or more episodes (hazard ratio = 1.50; 95% confidence interval = 1.09-2.08).ConclusionsHypoglycemia is associated with a higher risk of dementia and may be responsible in part for the higher risk of dementia in patients with diabetes. Alternatively, hypoglycemia may be a marker for undiagnosed cognitive impairment, and we cannot rule out the possibility of reverse causation between hypoglycemia and dementia.
| S-EPMC5861972 | biostudies-literature
Project description:To assess the impact of continuous glucose monitoring on hypoglycemia in people with type 1 diabetes.In this randomized, controlled, multicenter study, 120 children and adults on intensive therapy for type 1 diabetes and a screening level of glycated hemoglobin A(1c) (HbA(1c)) <7.5% were randomly assigned to a control group performing conventional home monitoring with a blood glucose meter and wearing a masked continuous glucose monitor every second week for five days or to a group with real-time continuous glucose monitoring. The primary outcome was the time spent in hypoglycemia (interstitial glucose concentration <63 mg/dL) over a period of 26 weeks. Analysis was by intention to treat for all randomized patients.The time per day spent in hypoglycemia was significantly shorter in the continuous monitoring group than in the control group (mean ± SD 0.48 ± 0.57 and 0.97 ± 1.55 h/day, respectively; ratio of means 0.49; 95% CI 0.26-0.76; P = 0.03). HbA(1c) at 26 weeks was lower in the continuous monitoring group than in the control group (difference -0.27%; 95% CI -0.47 to -0.07; P = 0.008). Time spent in 70 to 180 mg/dL normoglycemia was significantly longer in the continuous glucose monitoring group compared with the control group (mean hours per day, 17.6 vs. 16.0, P = 0.009).Continuous glucose monitoring was associated with reduced time spent in hypoglycemia and a concomitant decrease in HbA(1c) in children and adults with type 1 diabetes.
| S-EPMC3064030 | biostudies-literature
Project description:BackgroundGlucagon-like peptide 1 (GLP-1) stimulates insulin secretion and reduces blood glucose in type 2 diabetes mellitus (T2DM). TCF7L2 rs7903146 polymorphism has been associated with decreased insulin secretion, reduced GLP-1 action, and possible impaired peripheral insulin sensitivity.ObjectivesTo evaluate the postprandial pancreatic hormone response in patients with T2DM carriers of the TCF7L2 variant rs7903146 (CT/TT) compared with noncarriers of this variant (CC) after treatment with the GLP-1 agonist exenatide.MethodsIntervention study. Patients with T2DM (n = 162) were genotyped for the TCF7L2 rs7903146 single nucleotide polymorphism (SNP). Individuals with CT/TT and CC genotypes were compared regarding basal serum levels of glucose, glycosylated hemoglobin A1C (HbA1c), HDL, uric acid, insulin, and C-peptide. A subset of 56 individuals was evaluated during a 500-calorie mixed-meal test with measurements of glucose, insulin, proinsulin, C-peptide and glucagon before and after treatment with exenatide for 8 weeks.ResultsPatients with genotypes CC and CT/TT presented similar glucose area under the curve (AUC) 0-180 min before treatment and a similar decrease after treatment (p < 0.001). Before exenatide, insulin levels at 30-120 min were higher in CT/TT versus CC subjects (p < 0.05). After treatment with exenatide, only CT/TT individuals demonstrated insulin reduction at 30-180 min during the meal test (p < 0.05). Patients with the CC genotype presented no differences in insulin concentrations before and after treatment. The areas under the glucagon curve between 0 and 180 min were similar before treatment and reduced after treatment in both groups (p < 0.001).ConclusionsThe presence of the TCF7L2 rs7903146 T allele in patients with T2DM was associated with increased secretion of insulin response to a mixed-meal test. Furthermore, after treatment with exenatide, only the carriers of the T allele showed significantly decreased postprandial plasma insulin peak levels comparing with non carriers.
| S-EPMC6347826 | biostudies-literature