Cardiovascular Complications In Diabetic Patients Research Articles

Effect of L-Carnitine Supplementation on Apelin and Apelin Receptor (Apj) Expression in Cardiac Muscle of Obese Diabetic Rats.

Objective L-carnitine (LC) has been shown to protect cardiac metabolism in diabetes patients with cardiovascular diseases (CVDs). Apelin, a newly discovered adipocytokines, is an important regulator of cardiac muscle function; however, the role of the level of expression of Apelin axis in improvement of cardiac function by LC in diabetic patients, is not clear. In the present study, obese insulin-resistant rats were used to determine the effect of LC, when given orally with a high-calorie diet, on Apelin and Apelin receptor (Apj) expression in cardiac muscle. Materials and Methods In this experimental study, rats were fed with high-fat/high-carbohydrate diet for five weeks and subsequently were injected with streptozotocin 30 mg/kg for induction of obesity and insulin resistance. After confirming the induction of diabetes (serum glucose above 7.5 mmol/L), the animals received LC 300 mg/kg in drinking water for 28 days. On days 0, 14 and 28 after treatment, cardiac Apelin and Apj gene expression was evaluated by real time polymerase chain reaction (PCR) analysis. Serum levels of insulin, Apelin, glucose, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and the homeostasis model assessment of insulin resistance (HOMA-IR) were also measured using commercial kits. Results Cardiac Apelin and Apj expression and serum Apelin were increased in obese rats, while LC supplementation decreased the serum levels of Apelin and down-regulated Apelin and Apj expression in cardiac muscle. These changes were associated with reduced insulin resistance markers and serum inflammatory factors and improved lipid profile. ConclusionWe concluded that LC supplementation could attenuate the over-expression of Apelin axis in heart of diabetic rats, a novel mechanism by which LC improves cardiovascular complications in diabetic patients.

Comparison of microalbuminuria and heart rate variability in prediction of cardiovascular complications in diabetic population: a pilot study

Background: Microalbuminuria is considered as an early marker and strongly associated with risk of cardiovascular complications in diabetic patients. Autonomic imbalance due to micro vascular damage to parasympathetic and sympathetic fibers results in reduced heart rate variability; also predicts increased risk for cardiovascular events in diabetics. Hence it is necessary to identify an early and effective predictor of diabetic micro vascular complications. Objective of the study was to compare heart rate variability of controls with type 2 diabetes with and without microalbuminuria.Methods: This comparative study was conducted among individuals without diabetes, hypertension and dyslipidemia (controls) and Type II diabetics with and without microalbuminuria (cases). Cases and controls were subjected to general clinical examination; microalbuminuria and HbA1C were noted. heart rate variability was assessed using digital physiograph. Frequency (HF, LF, LF/HF ratio) domain readings were noted.Results: Mann Whitney U test was employed to analyze nonparametric data. Diabetics with microalbuminuria when compared with controls showed statistically significant (p-value=0.015) reduction in vagal activity. When compared with diabetics without microalbuminuria (180.4±151.7) they showed reduction in HF with no statistical significance. When diabetic group without microalbuminuria (0.56±0.31) was compared with controls they showed alternation in LF/HF ratio which has no statistical significance. Diabetics with microalbuminuria when compared with controls showed a statistically significant (p-value=0.009) alternation in LF /HF ratio implying an autonomic imbalance.Conclusions: This study shows there is significant vagal inhibition and autonomic imbalance in diabetic patients with microalbuminuria compared to controls. To ascertain the role of HRV as an early predictor of cardiovascular complications we propose to conduct study with a larger sample size in future.

Effect of Saxagliptin on Circulating Endothelial Progenitor Cells and Endothelial Function in Newly Diagnosed Type 2 Diabetic Patients.

Endothelial dysfunction is associated with the risk of cardiovascular complications in diabetic patients. Endothelial progenitor cells (EPCs) and flow-mediated dilation (FMD) are common markers of endothelial function. In this study, we aim to investigate whether the DPP-4 inhibitor saxagliptin modulate EPCs number and FMD in newly diagnosed, treatment-naive type 2 diabetic patients. This was a controlled, randomized, open-label clinical trial. Saxagliptin group and metformin group consumed either saxagliptin 5 mg per day or metformin 1 500 mg per day respectively for 12 weeks. Changes of FMD and EPCs number after 12-week intervention were the primary endpoints. 31 patients were initially enrolled and randomized to saxagliptin group (n=16) and metformin group (n=15). 27 patients completed the trial (saxagliptin group n=14 and metformin group n=13), and 4 patients dropped out during the study. FMD and EPCs number increased significantly in both saxagliptin group and metformin group, and there was no significant difference between groups. 2-h postprandial plasma glucose, HbA1c and diastolic blood pressure improved significantly in both groups, and there was no significant difference between groups. Saxagliptin and metformin had comparable beneficial effects on endothelial function.

MRNA-miRNA integrative analysis of diabetes-induced cardiomyopathy in rats.

An integrative analysis of miRNA and mRNA expression profiles in left ventricle (LV) of diabetes-induced rats was performed to elucidate the role of miRNAs and their mRNAs target in diabetic cardiomyopathy (DCM). mRNA (GSE4745) and miRNA (GSE44179) datasets were downloaded from Gene Expression Omnibus 2R (GEO2R) and differentially expressed mRNAs and miRNAs were selected. Cardiotoxicity-related mRNAs (n=7) were analyzed by Ingenuity Pathway Analyses 6 (IPA) and regulatory miRNAs (n=639) were identified using TargetScan 7.1. web dataset. The integrative analysis was performed between miRNAs differentially expressed in GSE44179 and regulatory TargetScan-detected miRNAs of mRNAs differentially expressed in GSE4745. Pla2g2a and Hk2 mRNAs were up-and-down regulated, respectively, in GSE4745 on days 3 and 42 after diabetes-induction. The Pla2g2a regulatory miRNAs, rno-miR-877, rno-miR-320 and rno-miR-214, were down-regulated, and Hk2 regulatory miRNAs, rno-miR-17, rno-miR-187, rno-miR-34a, rno-miR-322, rno-miR-188, rno-miR-532 and rno-miR-21, were up-regulated in GSE44179 dataset. These results are suggestive that Pla2g2a and Hk2 mRNAs and their regulatory miRNAs play a role in DCM pathogenesis and they may be potential circulating biomarkers to detect early cardiovascular complications in diabetic patients.

Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release.

Thrombosis and its complications are the leading cause of death in patients with diabetes. Metformin, a first-line therapy for type 2 diabetes, is the only drug demonstrated to reduce cardiovascular complications in diabetic patients. However, whether metformin can effectively prevent thrombosis and its potential mechanism of action is unknown. Here we show, metformin prevents both venous and arterial thrombosis with no significant prolonged bleeding time by inhibiting platelet activation and extracellular mitochondrial DNA (mtDNA) release. Specifically, metformin inhibits mitochondrial complex I and thereby protects mitochondrial function, reduces activated platelet-induced mitochondrial hyperpolarization, reactive oxygen species overload and associated membrane damage. In mitochondrial function assays designed to detect amounts of extracellular mtDNA, we found that metformin prevents mtDNA release. This study also demonstrated that mtDNA induces platelet activation through a DC-SIGN dependent pathway. Metformin exemplifies a promising new class of antiplatelet agents that are highly effective at inhibiting platelet activation by decreasing the release of free mtDNA, which induces platelet activation in a DC-SIGN-dependent manner. This study has established a novel therapeutic strategy and molecular target for thrombotic diseases, especially for thrombotic complications of diabetes mellitus.

Diabetes-linked transcription factor HNF4α regulates metabolism of endogenous methylarginines and β-aminoisobutyric acid by controlling expression of alanine-glyoxylate aminotransferase 2.

Elevated levels of circulating asymmetric and symmetric dimethylarginines (ADMA and SDMA) predict and potentially contribute to end organ damage in cardiovascular diseases. Alanine-glyoxylate aminotransferase 2 (AGXT2) regulates systemic levels of ADMA and SDMA, and also of beta-aminoisobutyric acid (BAIB)-a modulator of lipid metabolism. We identified a putative binding site for hepatic nuclear factor 4 α (HNF4α) in AGXT2 promoter sequence. In a luciferase reporter assay we found a 75% decrease in activity of Agxt2 core promoter after disruption of the HNF4α binding site. Direct binding of HNF4α to Agxt2 promoter was confirmed by chromatin immunoprecipitation assay. siRNA-mediated knockdown of Hnf4a led to an almost 50% reduction in Agxt2 mRNA levels in Hepa 1–6 cells. Liver-specific Hnf4a knockout mice exhibited a 90% decrease in liver Agxt2 expression and activity, and elevated plasma levels of ADMA, SDMA and BAIB, compared to wild-type littermates. Thus we identified HNF4α as a major regulator of Agxt2 expression. Considering a strong association between human HNF4A polymorphisms and increased risk of type 2 diabetes our current findings suggest that downregulation of AGXT2 and subsequent impairment in metabolism of dimethylarginines and BAIB caused by HNF4α deficiency might contribute to development of cardiovascular complications in diabetic patients.

Betaine Down Regulates Apelin Gene Expression in Cardiac and Adipose Tissues of Insulin Resistant Diabetic Rats Fed by High-Calorie Diet

Apelin is a newly discovered peptide that its serum level increases in diabetic patients with cardiovascular dysfunction. Recent studies indicate the beneficial actions of betaine in reducing the cardiovascular and metabolic complications, however data related to its effect on adipocytokine expression is limited. The aim of this study was to evaluate the effect of betaine supplementation on Apelin gene expression in cardiac muscle and adipose tissue of insulin resistance, diabetic rats fed by a high calorie diet. To induce insulin resistance rats were fed with high fat/high carbohydrate diet for five weeks and then 30 mg/kg STZ was injected intraperitoneally. After confirming of diabetes incidence (serum glucose above 7.5 mmol/l) the animals were treated with 1 % betaine in drinking water for 28 days. At days 14 and 28 after treatment, animals were euthanized and Apelin gene expression was evaluated by real time PCR and western blot in heart and adipose tissues. Serum levels of insulin, Apelin and glucose and HOMA–IR were also measured. Our results showed that feeding of rats by a high calorie diets caused insulin resistance, which was manifested by elevated plasma insulin, glucose and Apelin levels and also HOMA–IR. Apelin gene expression in heart and adipose tissues were significantly increased simultaneously with the progression of diabetes. Betaine supplementation decreased serum Apelin and down regulated Apelin expression in adipose tissue and cardiac muscle, particularly at day 28 of treatment. We concluded that betaine might improve metabolic and cardiovascular complications in diabetic patients by regulation of Apelin expression and secretion.

Dipeptidyl peptidase- IV inhibitor alogliptin improves stress-induced insulin resistance and prothrombotic state in a murine model

BackgroundStress evokes lipolytic release of free fatty acid (FFA) and low-grade inflammation in visceral adipose tissue, mediated by increased adipokine secretion, and contributes to glucose metabolism disorder and prothrombotic state. We tested the hypothesis that alogliptin, a dipeptidyl peptidase-4 inhibitor, can ameliorate the biological effects of chronic stress in mice. Method and resultsC57BL/6J mice were subjected to 2-week intermittent restraint stress and orally treated with vehicle or alogliptin (dose: 15 or 45mg/kg/day). Plasma levels of lipids, proinflammatory cytokines (monocyte chemoattractant protein-1, tumor necrosis factor-α, and interleukin-6), and 8-hydroxydeoxyguanosine were measured with enzyme-linked immunosorbent assay. Monocyte/macrophage accumulation in inguinal white adipose tissue (WAT) was examined by CD11b-positive cell count and mRNA expression of CD68 and F4/80 was examined by immunohistochemistry and RT-PCR, respectively. The mRNA levels of the above-mentioned proinflammatory cytokines, NADPH oxidase 4, adiponectin, and coagulation factors (plasminogen activation inhibitor-1 and tissue factor) in WAT were also assessed with RT-PCR. Glucose metabolism was assessed by glucose and insulin tolerance tests, plasma levels of DPP-4 activity, glucagon-like peptide-1, expression of DPP-4, insulin receptor substrate-1 and glucose transporter 4 in WAT and skeletal muscle. Alogliptin administration suppressed stress-induced FFA release, oxidative stress, adipose tissue inflammation, DPP-4 activation, and prothrombotic state in a dose-dependent manner, and improved insulin sensitivity in stressed mice. ConclusionsThe results indicate that alogliptin improves stress-induced prothrombotic state and insulin resistance; suggesting that alogliptin could have beneficial therapeutic effects against cardiovascular complications in diabetic patients under stress.

Riscos para complicações cardiovasculares em portadores de diabetes mellitus

Objetivo: estratificar o risco para complicações cardiovasculares em pacientes diabéticos cadastrados em uma Estratégia de Saúde da Família do município de Primavera do Leste/Mato Grosso. Método: Pesquisa descritiva de abordagem quantitativa, de campo e de análise secundária, realizado com pacientes diabéticos cadastrados no Programa HIPERDIA. Resultados: participaram 52 pacientes, com predomínio do sexo feminino, faixa etária entre 50 e 60 anos, escolaridade inferior a sete anos de estudo. Dentre os participantes, 48 pacientes apresentava diabetes tipo II (92,3%), 45 (86,5%) faziam uso de hipoglicemiante oral e 38 (73%) apresentava hipertensão arterial sistêmica associada. Ambos os sexos mantinham uma dieta inadequada. Quanto à percepção do tratamento, todos consideravam importante o controle da patologia. O sexo masculino apresentou alto risco para doença cardiovascular e as mulheres, em sua maioria, risco intermediário. Conclusão: reeducação alimentar e educação em saúde são importantes no controle da doença e redução de possíveis complicações.

Glycated Albumin is Independently Associated With Arterial Stiffness in Non-Diabetic Chronic Kidney Disease Patients.

Glycated albumin (GA) exhibits atherogenic effects and increased serum GA levels are associated with the development of cardiovascular complications in diabetic patients. GA production also increases with aging, oxidative stress, and renal dysfunction. We performed this study to further ascertain the association between GA and arterial stiffness in nondiabetic chronic kidney disease (CKD) patients. We enrolled 129 nondiabetic CKD patients. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV) using a volume plethysmographic instrument along with simultaneous measurements of GA. Insulin resistance was determined with the homeostatic model assessment. The estimated glomerular filtration rate was calculated using serum creatinine and cystatin C according to the CKD-EPI Creatinine-Cystatin C equation adjusted for age, sex, and race (eGFRcr-cys). Nondiabetic CKD patients with arterial stiffness (baPWV ≥1400 cm/s) showed higher GA levels than those without arterial stiffness (14.2 [8.7-20.2]% vs 13.0 [8.8-18.9]%, P = 0.004). In the subgroup analysis, the patients who had both a higher GA level and a lower eGFRcr-cys, showed the highest baPWV compared with patients with a higher GA or a lower GFR alone. By Spearman's correlation analysis, GA correlated significantly with baPWV (r = +0.291, P = 0.001) and fasting serum glucose level (r = +0.191, P = 0.030), whereas The homeostatic model assessment of insulin resistance did not show any significant correlation with baPWV. Systolic blood pressure (r = +0.401 P < 0.001), age (r = +0.574, P < 0.001), high-density lipoprotein (HDL)-cholesterol level (r = -0.317, P < 0.001), and eGFRcr-cys (r = -0.285, P = 0.002) had a significant correlation with baPWV. According to multivariable logistic regression analysis, higher GA and systolic blood pressure were the independent risk factors affecting arterial stiffness. Our results suggest that serum GA is a potential risk factor of arterial stiffness in nondiabetic CKD patients.

Telmisartan attenuates hyperglycemia-exacerbated VCAM-1 expression and monocytes adhesion in TNFα-stimulated endothelial cells by inhibiting IKKβ expression

Uncontrolled hyperglycemia accelerates endothelial damage and vascular inflammation caused by proinflammatory cytokines including tumor necrosis factor α (TNFα), which leads to arteriosclerotic cardiovascular diseases such as myocardial infarction. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), is prescribed for treatment of hypertensive patients with concurrent diabetes mellitus (DM). Although a few clinical trials have suggested that telmisartan decreases cardiovascular complications in diabetic patients, the molecular mechanism for the beneficial effects remains elusive. Here, we investigated a molecular mechanism and effects of telmisartan on the expression of vascular cell adhesion molecule-1 (VCAM-1) and attachment of monocytes onto endothelial cells induced by TNFα in hyperglycemia-treated bovine aortic endothelial cells (BAEC). Telmisartan dose-dependently decreased hyperglycemia-aggravated IκB kinase β (IKKβ) expression and nuclear factor-κB (NF-κB) p65-Ser536 phosphorylation, which accompanied a decrease in VCAM-1 expression and THP-1 monocytes adhesion. Among ARBs, including losartan and fimasartan, only telmisartan showed the inhibitory effects on expression of VCAM-1 and IKKβ, and phosphorylation of NF-κB p65-Ser536. The telmisartan's beneficial effects were not changed by pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor γ (PPARγ) antagonist, although GW9662 clearly inhibited rosiglitazone-induced CD36 expression. Finally, ectopic expression of wild type (WT)-IKKβ significantly restored telmisartan-attenuated VCAM-1 expression, NF-κB p65-Ser536 phosphorylation, and THP-1 monocytes adhesion. Taken together, our findings demonstrate that telmisartan ameliorates hyperglycemia-exacerbated vascular inflammation, at least in part, by decreasing expression of IKKβ and VCAM-1 independently of PPARγ. Telmisartan may be useful for the treatment of DM-associated vascular inflammation and cardiovascular diseases.

Accelerated onset of senescence of endothelial progenitor cells in patients with type 2 diabetes mellitus: Role of dimethylarginine dimethylaminohydrolase 2 and asymmetric dimethylarginine

The risk of cardiovascular complications in diabetic patients is mainly associated with endothelial dysfunction. Reduced number of EPCs and impaired function of EPCs in diabetes result in imbalance of endothelial homeostasis and dysfunction of vessels. In patients with diabetes mellitus, plasma levels of asymmetric dimethylarginine (ADMA) were elevated, while the expression and activity of dimethylarginine dimethylaminohydrolase (DDAH) were reduced. In the present study, we investigated the role of the DDAH2/ADMA pathway in the senescence of EPCs in type 2 diabetic patients and cultured EPCs treated with high glucose. The results showed that the percentage of senescent EPCs increased while the expression of DDAH2 decreased concomitantly with an increase in the plasma levels of ADMA in patients with type 2 diabetes mellitus (T2DM). Similar results were seen in cultured EPCs treated with high glucose. Exogenous application of ADMA accelerated the senescence of EPCs in a dose-dependent manner, and overexpression of DDAH2 inhibited high glucose-induced EPCs senescence. In addition, it has also been reported that DDAH/ADMA pathway is regulated by silent information regulator 1 (SIRT1) in endothelial cell. In the present study, we found decreased expression of SIRT1 both in T2DM patients and EPCs pretreated with high glucose. And resveratrol (activating SIRT1) inhibited high glucose-induced EPCs senescence by upregulating the expression of DDAH2 and decreasing the levels of ADMA. Taken together, we concluded that DDAH2/ADMA is involved in the accelerated senescence of EPCs in diabetes, which is associated with the activation of SIRT1.

Mangiferin inhibits endoplasmic reticulum stress-associated thioredoxin-interacting protein/NLRP3 inflammasome activation with regulation of AMPK in endothelial cells

BackgroundEndothelial dysfunction is tightly associated with cardiovascular complications in diabetic patients. This study aims to investigate the effects of mangiferin on the regulation of endothelial homeostasis under endoplasmic reticulum stress (ER stress) conditions. ResultsHigh glucose (25mmol/L) exposure induced ER stress and promoted ROS production in endothelial cells. Mangiferin effectively inhibited ER stress-associated oxidative stress by attenuating IRE1α phosphorylation and reducing ROS production. In response to ER stress, thioredoxin-interacting protein (TXNIP) expression increased, followed by NLRP3 inflammasome activation and increased IL-1β secretion. Mangiferin treatment attenuated the expressions of TXNIP and NLRP3 and reduced IL-1β and IL-6 production, demonstrating its inhibitory effects on TXNIP/NLRP3 inflammasome activation. NLRP3 inflammasome activation is responsible for mitochondrial cell death. Mangiferin restored the loss of the mitochondrial membrane potential (Δψm) and inhibited caspase-3 activity, and thereby protected cells from high glucose-induced apoptosis. Moreover, mangiferin inhibited ET-1 secretion and restored the loss of NO production when cells were exposed to high glucose. Mangiferin enhanced AMPK phosphorylation and AMPK inhibitor compound C diminished its beneficial effects, indicating the potential role of AMPK in its action. ConclusionOur work showed the beneficial effects of mangiferin on the improvement of endothelial homeostasis and elucidated the molecular pathway through which mangiferin ameliorated endothelial dysfunction by inhibition of ER stress-associated TXNIP/NLRP3 inflammasome activation in endothelial cells. SignificanceThese findings demonstrated the beneficial effects of mangiferin on the regulation of endothelial homeostasis and indicated its potential application in the management of diabetic cardiovascular complications.

Cardiovascular Complications in Diabetic Patients Undergoing Regular Hemodialysis

We aimed to study the vascular outcomes in hemodialysis (HD) patients based on their diabetic status. A cohort observational study was conducted among patients undergoing regular HD with a 5-year follow-up. Of the 252 consecutive HD patients, 60% were diabetic. Compared with nondiabetics, diabetics were 11 years older, 4 years lesser on HD, and more likely to have prior cerebrovascular and coronary artery disease (CAD). Overall 5-year follow-up showed that diabetic patients had higher rates of HD vascular accesses (57% vs 41%, P = .01), CAD (64% vs 33%, P = .001), major amputations (8.6% vs 0%, P = .003), and mortality (66% vs 23%, P = .001). On multivariate analysis, independent predictors of mortality included number of vascular accesses in nondiabetics and HD duration, CAD, and peripheral artery disease in diabetic patients. Diabetes mellitus is associated with a significant vascular burden and mortality among HD patients. Moreover, our finding highlights the vascular impact of renal failure and HD.

Increased peripheral proinflammatory T helper subsets contribute to cardiovascular complications in diabetic patients.

Background. Coronary atherosclerotic heart disease (CHD) is one of the major concerns in type 2 diabetes (T2D). The systemic chronic inflammation has been postulated to bridge the increased risk of cardiovascular disease and T2D. We formulated that increased peripheral proinflammatory T helper subsets contributed to the development of cardiovascular complications in diabetic patients. Methods. The frequencies of peripheral total CD4+ T helper cells, proinflammatory Th1, Th17, and Th22 subsets were determined by flow cytometry in diabetic patients with or without CHD (n = 42 and 67, resp.). Results. Both peripheral frequencies and total numbers of Th1, Th17, and Th22 cells were further increased in diabetic patients with CHD. Logistic regression and categorical cross-table analysis further confirmed that increased proinflammatory Th subsets, especially Th22, were independent risk factors of cardiovascular complication in diabetes. Elevated Th subsets also correlated with increased CRP levels and the atherogenic index of plasma. Moreover, Th1 frequency and Th22 numbers demonstrated remarkable potential in predicting CHD in diabetes. Conclusions. Increased peripheral proinflammatory T helper subsets act in concert and contribute to the increased prevalence of diabetic cardiovasculopathy. The recently identified Th22 cells might play an independent role in CHD and represent a novel proxy for cardiovascular risks in diabetes.

Type 1 Diabetes, Cardiovascular Complications and Sesame (芝麻 Zhī Má)

Diabetes is a major concern among medical practitioners, with the annual mortality rate increasing up to 26.9% in a person aged 65 years or older and 11.3% in the adult. There are many serious complications associated with diabetes, particularly cardiovascular complications due to microvascular diseases. A prerequisite to reduce the risk of microvascular and neurologic complications of type 1 diabetes is normoglycemia. Insulin therapy is the most common treatment used nowadays in type 1 diabetes. However, this method still has many disadvantages such as increased episode of severe hypoglycemia, hypoglycemia unawareness, increased weight gain, transient exacerbation of pre-existing retinopathy, etc. Using insulin pump (the insulin pump is a medical device used for continuous subcutaneous insulin infusion to manage the insulin level in the treatment of diabetes mellitus), is associated with known disadvantages including increased ketoacidosis, infection at the infusion site, and the treatment being less suitable in young children (less than 7 years of age). Therefore, alternative treatment for diabetes is still in great demand. We took the approach of traditional Chinese medicine to discuss this matter. Sesame (芝麻 Zhī Má), a herb, has been used medicinally for thousands of years in almost all the countries in the world. The beneficial effects of sesame in remediating diabetes, such as hypoglycemic effects, antioxidant, anti-inflammatory, and hypolipidemic effects, improving fat metabolism, and reducing cholesterol, have been demonstrated in many studies,. However, reports on the effects of sesame in remediating cardiovascular complications in diabetic patients are limited, which necessitates further studies on the effects of sesame on cardiovascular complications.

High glucose condition induces autophagy in endothelial progenitor cells contributing to angiogenic impairment.

Cardiovascular complications are the major causes of death in patients with diabetes mellitus. Several studies have demonstrated that endothelial progenitor cells (EPCs), adult stem cells contributing to the regeneration of vascular endothelium, are dysfunctional under diabetic condition resulting in impaired peripheral circulation and delayed wound healing. In this study, we investigated the cellular alteration of EPCs under high glucose condition, to elucidate the mechanisms underlying diabetes-associated EPC dysfunction. EPCs were isolated from bone marrow and cultured in normal glucose (5.5 mM)- or high glucose (HG; 30 mM)-containing medium. High glucose treated-EPCs showed decreased ability to form tubule-like networks in Matrigel compared to EPCs under normal glucose, which matched well to the clinical observation of diabetic EPC dysfunction. Conversion of LC3-I to LC3-II was increased in EPCs under HG condition, showing that HG induced autophagy in EPCs. Flow cytometric analysis revealed generation of oxidative stress and disruption of mitochondrial permeability in HG exposed EPCs. Increased mitochondrial oxidative stress was also observed by mitochondria-specific superoxide indicator, MitoSOX(TM). Taken together, we demonstrated that autophagy and mitochondrial impairment were induced in EPCs under high glucose condition, giving a new insight into the mechanism underlying dysfunction of diabetic EPCs. We hope that our finding can contribute to the development of a new treatment option for cardiovascular complications in diabetic patients.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

Haptoglobin genotype is a consistent marker of coronary heart disease risk among individuals with elevated glycosylated hemoglobin.

This study sought to investigate into the biologically plausible interaction between the common haptoglobin (Hp) polymorphism rs#72294371 and glycosylated hemoglobin (HbA(1c)) on risk of coronary heart disease (CHD). Studies of the association between the Hp polymorphism and CHD report inconsistent results. Individuals with the Hp2-2 genotype produce Hp proteins with an impaired ability to prevent oxidative injury caused by elevated HbA(1c). HbA(1c) concentration and Hp genotype were determined for 407 CHD cases matched 1:1 to controls (from the NHS [Nurses' Health Study]) and in a replication cohort of 2,070 individuals who served as the nontreatment group in the ICARE (Prevention of Cardiovascular Complications in Diabetic Patients With Vitamin E Treatment) study, with 29 CHD events during follow-up. Multivariate models were adjusted for lifestyle and CHD risk factors as appropriate. A pooled analysis was conducted of NHS, ICARE, and the 1 previously published analysis (a cardiovascular disease case-control sample from the Strong Heart Study). In the NHS, Hp2-2 genotype (39% frequency) was strongly related to CHD risk only among individuals with elevated HbA(1c) (≥ 6.5%), an association that was similar in the ICARE trial and the Strong Heart Study. In a pooled analysis, participants with both the Hp2-2 genotype and elevated HbA(1c) had a relative risk of 7.90 (95% confidence interval: 4.43 to 14.10) for CHD compared with participants with both an Hp1 allele and HbA(1c) <6.5% (p for interaction = 0.004), whereas the Hp2-2 genotype with HbA(1c) <6.5% was not associated with risk (relative risk: 1.34 [95% confidence interval: 0.73 to 2.46]). Hp genotype was a significant predictor of CHD among individuals with elevated HbA(1c).

Insulin Resistance among Adults with Type 1 Diabetes Mellitus at the Philippine General Hospital

Background: Insulin resistance has been proven to increase the risks for cardiovascular complications in type 2 diabetes mellitus. Recently, insulin resistance has also been shown to play a bigger role in the natural history of type 1 diabetes mellitus (T1DM) disease process than is commonly recognized. Limitations and difficulties in assessing insulin resistance in patients with T1DM have been addressed by the creation of clinical scoring known as estimated glucose disposal rate (eGDR). Given the clear association of insulin resistance and cardiovascular complications in diabetic patients, detecting the prevalence of insulin resistance in T1DM population, will probably clarify the welldocumented gaps in the management of this type of diabetes. Objectives: The main objective of this study is to determine the prevalence of insulin resistance among Filipino adults with established type 1 diabetes mellitus at the Philippine General Hospital. The secondary objective is to describe the clinical features of type 1 diabetic patients with insulin resistance compared to patients without insulin resistance. Study Design and methods: This cross-sectional analytic study recruited 104 adult subjects, 19 years old and above, with established type 1 diabetes mellitus in Philippine General Hospital. Mixed meal stimulated C-peptide level was done to confirm the diagnosis of type 1 diabetes mellitus. The main outcome measure, insulin resistance, was determined using the validated clinical scoring, Estimated Glucose Disposal Rate (eGDR) with the following formula: eGDR=24.31 – (12.22 × Waist-to-hip ratio) – (3.29 × 1 if with hypertension or on anti-hypertensive or x 0 if no hypertension) – (0.57 × HbA1c). Patients with eGDR of ≤ 7.5 mg/kg/min were considered to have insulin resistance. Results: The prevalence rate of insulin resistance was found to be 53% among adults with established type 1 diabetes mellitus.T1DM patients with insulin resistance were significantly older (mean=29.49 ± 8.14 yr vs 25.63 ± 6.32 yr, p=0.008), had higher waist-to-hip ratio (mean=0.95 ± 0.03 vs 0.92 ± 0.04, p=0.000),had higher systolic and diastolic blood pressure (mean=111.1 ± 13.39 vs 105.76 ± 10.83, p=0.028; mean=71.82 ± 7.76 vs 68.98 ± 6.55, p=0.048, respectively), and had poorer glycemic control (mean HbA1c=8.31 ± 1.73 vs 7.67 ± 0.90, p=0.017) compare to those T1DM without insulin resistance. There were also more T1DM with insulin resistance among subjects with duration of illness of more than 5 years (59.2% vs 40.8%, p=0.033), and among those who were either overweight or obese (52.6% vs 47.4% and 76.2% vs 23.8%, p=0.023, respectively). T1DM with insulin resistance group had higher insulin requirement per day than those without insulin resistance but the difference were not statistically significant (p>0.5). Both groups had high prevalence of dyslipidemia and family history of diabetes mellitus. Conclusion: The result of this study showed a high prevalence rate of insulin resistance among Filipino adults with established type 1 diabetes mellitus. Old age, high waist-to-hip ratio, hypertension, poor glycemic control, long duration of diabetes and overweight/obesity are the features more common among type 1 diabetic patients with insulin resistance than those without insulin resistance.