Macrovascular Complications In Diabetic Patients Research Articles

Improvement of time in range and glucose management indicator in Type 1 and Type 2 Diabetes Mellitus patients after introduction of continuous Glucose monitoring in internal medicine residency clinic

Continuous glucose monitoring (CGM)-derived time in range (TIR) correlates with Glucose management indicator(GMI) which correlates with hemoglobin A1c (HbA1c) among patients with type 1 and type 2 diabetes mellitus. Compare to HbA1c it has better correlation with glucose control, because HbA1c can be influenced by conditions like anemia, Chronic kidney disease, Cirrhosis of the liver etc. With our current project we wanted to introduce CGM not in specialized endocrine clinic, but in Internal medicine Residency clinic. The CGM team had 12 Internal Medicine and Transitional year Residents who were functioning under the supervision of Board Certified Endocrinologist who was a member of the clinic also. Twenty Five patients -85% with type 2 DM and 15% with type 1 DM on multiple injections of Insulin per day-3-4, self-monitored their blood Glucose(SMBG). They were given CGM- Dexcom G6 in the clinic. In the first 2- weeks after the switch the TIR of the blood glucose of the patients-70-180 mg/dl was 18%. Their average blood glucose was 286 mg/dl, GMI was 11.21%. During then first 2- weeks after initiation of CGM the patients were educated in length by our CGM team about their diet, physical activity, how to adjust their Insulin based on their blood glucose levels as well as how to treat the hypoglycemia. Members of the CGM team were contacting the patients twice a week to adjust patients treatment with Insulin and other per oral antidiabetic medications and or injectable – GLP1-RAG if needed after consultation with the Endocrinologist in the clinic based on the shared information between the clinic and the patients. Once a month the patients were seen in the clinic by member of the CGM team as well. The patients were followed for 2- years. After 3- months on CGM and followed for the 2 years thereafter the patients TIR improved from 18 % to 74%, GMI decreased from 11.21% to 7.04% and the average blood glucose decreased from 286 mg/dl to 158 mg/dl. There was also significant reduction of the hypoglycemia. Twenty percent of the patients were able to discontinue their Insulin and be treated only with oral antidiabetic medications plus/minus GLP1-RAG and have GMI less than 7%. We have showed that targeted TIR – above 70% which has been associated recently with diabetic micro and macrovascular complications in diabetic patients can be achieved not only in specialized endocrine clinics , but in Internal Medicine residency clinic and can be adopted by other Internal Medicine Residency programs in USA.

Efficacy of acupuncture on cardiovascular complications in patients with diabetes mellitus in Korea: A nationwide retrospective cohort

ObjectiveThe main aim of this study is to investigate whether acupuncture could be an effective complementary treatment for reducing the risk of macrovascular complications in diabetic patients currently taking antidiabetic medications using a nationwide population-based database. MethodsWe conducted a retrospective cohort study to assess the efficacy of acupuncture on cardiovascular complications in diabetic patients using data from patients between 40 and 79 years of age, newly diagnosed with diabetes between 2003 and 2006, found in the National Health Insurance Service-National Sample Cohort (NHIS-NSC) in Korea. From the data, we identified 21,232 diabetic patients who were taking antidiabetic medication between 2003 and 2006. The selected patients were divided into two groups—those who received acupuncture at least three times and those who received no acupuncture (non-acupuncture) in the year following their diagnosis of diabetes. After 1:1 propensity score matching (PSM), each group had 3350 patients, and the observation ceased at the occurrence of a major adverse cardiovascular event (MACE), which was defined as either myocardial infarction, stroke, or death due to cardiovascular cause. ResultsAfter PSM, the acupuncture group had a lower incidence of MACE (hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.81–0.94; P = 0.0003) and all-cause mortality (HR: 0.77; 95% CI: 0.70–0.84; P < 0.0001) than the non-acupuncture group; the HRs for stroke-related mortality (HR: 0.75; 95% CI: 0.56–1.00; P = 0.0485), ischemic heart disease mortality (HR: 0.53; 95% CI: 0.34–0.84; P = 0.006) and circulatory system disease mortality (HR: 0.67; 95% CI: 0.55–0.82; P < 0.0001) were lower in the acupuncture group than in the non-acupuncture group in the secondary analysis. ConclusionOur results indicate that diabetic patients receiving acupuncture treatment might have a lower risk of MACE, all-cause mortality and cardiovascular mortality. This population-based retrospective study suggests beneficial effects of acupuncture in preventing macrovascular complications associated with diabetes. These findings call for further prospective cohort or experimental studies on acupuncture treatment for cardiovascular complications of diabetes.Please cite this article as: Jung H, Won T, Kim GY, Jang J, Yeo S, Lim S. Efficacy of acupuncture on cardiovascular complications in patients with diabetes mellitus in Korea: A nationwide retrospective cohort. J Integr Med. 2023; 21(2): 176–183.

Association of cardiovascular factors in diabetic patients with non-alcoholic fatty liver disease.

To evaluate the association between severity of hepatic steatosis/fibrosis with clinical, laboratory, and echocardiographic characteristics, including visceral obesity and type 2 diabetes mellitus (T2DM)-related micro- and macrovascular complications in diabetic patients with non-alcoholic fatty liver disease (NAFLD). We studied 60 consecutive NAFLD outpatients with T2DM, recording several demographic and clinical characteristics, trunk and visceral fat, cardiac ultrasound, and micro- and macrovascular complications of diabetes mellitus including microalbuminuria, diabetic peripheral neuropathy, peripheral vascular disease, and cardiac autonomic function. Severity of steatosis and fibrosis was evaluated with abdominal ultrasound and liver stiffness measurements, respectively. Twenty-three (41%) of the patients had grade 1 steatosis and mean liver stiffness was 7.5 ± 3kPa. After applying Bonferroni correction for multiple comparisons, ferritin concentration was the only factor significantly different between patients with mild (grade 1) compared to those with moderate/severe (grade 2/3) steatosis and showed good discriminative ability for the presence of moderate/severe steatosis (AUC: 0.74, sensitivity 88%, specificity 48%, PPV 74%, and NPV 72%). In addition, waist circumference was the only factor associated with the presence of significant fibrosis (≥ F2) with very good discriminative ability (AUC: 0.77, sensitivity 89%, specificity 45%, PPV 75%, and NPV 70%). Specific clinical and laboratory characteristics, which may be determined via widely accessible and noninvasivetechniques, were associated withseverity of diabetics NAFLD, taking into account echocardiographic characteristics, visceral obesity, and T2DM-related systemic complications.

Prevalence of micro and macro vascular complications and their risk factors in type 2 diabetes in Saudi Arabian population: an analysis from SHIS.

Diabetes mellitus is a non-communicable disease (NCD) with metabolic dysfunction that has attained epidemic proportions worldwide. Vascular complications account for the mortality and morbidity associated with diabetes. Hence, the study aimed to estimate the prevalence and risk factors for vascular complications in patients with type 2 diabetes mellitus (T2DM). A cross-sectional national multistage survey, the Saudi Health Interview Survey (SHIS), was used in this study, which surveyed individuals aged 15 years or older. After inclusion and exclusion criteria, 1240 diabetic patients' data were analyzed for sociodemographic data, risk factors, and prevalence of micro and macrovascular complications. Binary logistic regression with stepwise backward elimination was performed to build the optimal model to assess the determinants of macrovascular complications in diabetic patients. The strength of the associations was examined by estimating adjusted odds ratios (aOR) with their 95% CI. p-value < 0.05 was considered statistically significant. R Studio Version 1.2.1093 was used for statistical analysis RESULTS: Prevalence of micro and macrovascular complications in the diabetic patients was 6.05%, in which 3.5% had myocardial infarction, 1.2% had stroke and 1.9% had renal failure. The optimal model showed that for each year increase in age (aOR=1.05, 95%CI 1.02-1.07; p-value=0.000), smoking history (aOR=4.02, 95%CI 2.23-7.26; p-value=0.000), hypertensive patients (aOR=2.71, 95%CI 1.47-4.99; p-value=0.001), patients with low physical activity (aOR=4.32, 95%CI 1.26-14.82; p-value=0.001) were more likely to develop macro and microvascular complications in diabetic patients. The high prevalence of microvascular and macrovascular complications in diabetic patients poses a serious threat to public health in Saudi Arabia. A multisectoral approach needs to be undertaken to properly control and modify common risk factors at the community level.

Makrovasküler Komplikasyon Gelişen Diyabetik Hastalarda Risk Faktörlerinin Değerlendirilmesi

Amaç: Biz çalışmamızda 2015-2018 yılları arasında hastanemize diyabetes mellitusun makrovasküler komplikasyonlarından olan akut miyokard infarktüsü veya serebrovasküler olay tanısı konulan hastaların risk faktörleri açısından araştırılmasını planladık. Gereç ve Yöntemler: Retrospektif olarak yapılan çalışmaya 48 diyabetes mellitus tanılı makrovasküler komplikasyon gelişen hasta alınmış iken kontrol grubu olarak da polikliniğimizden takipli makrovasküler komplikasyon gelişmemiş olan 97 diyabetik hasta çalışmaya dahil edilmiştir. Komplikasyon gelişen hastaların ve kontrol grubu hastaların son 6 ayındaki polikliniğimize olan başvurusunda laboratuar sonuçları incelenerek yaş, BMİ, açlık kan şekeri, Hba1C, MPV, RDW, PLT ve kreatinin parametrelerine göre risk faktörleri belirlenmeye çalışıldı. İstatistiksel analizler SPSS versiyon 17.0 programı ile gerçekleştirilmiştir. Değişkenlerin normal dağılıma uygunluğu histogram grafikleri ve Kolmogorov-Smirnov testi ile normal dağılım gösteren (parametrik) değişkenlerin gruplar arasında değerlendirilirken; bağımsız gruplarda T Testi, normal dağılım göstermeyenler (non parametrik) gruplar arasında değerlendirilirken Mann Whitney U Testi kullanılmıştır. Bulgular: Yaptığımız çalışma sonucunda diyabetik hastalarda makrovasküler komplikasyon gelişimi ile yaştaki artışın, HbA1c düzeyindeki progresyonun, MPV değerinin &amp;gt;11,9 ve kreatinin düzeylerinin 1.2 mg/dl dğerinin üzerinde olması durumuyla istatistiksel olarak anlamlı bir ilişki saptadık fakat cinsiyet, BMI, açlık kan şekeri, RDW ve platelet değerleri her iki grupta benzer olarak bulundu. Sonuç: Elde edilen veriler doğrultusunda diyabetik hastaların takiplerinde ileri yaş, MPV,kreatinin, Hba1c değerlerinin yakın takibinin yapılması ve bu parametrelerdeki bozulmaların makrovasküler komplikasyon gelişimi açısından bize yol gösterebileceğini düşünmekteyiz.

From Endothelial Dysfunction to Arterial Stiffness in Diabetes Mellitus.

Prevalence of diabetes mellitus has increased drastically over time, especially in more populous countries such as the United States, India, and China. Patients with diabetes have an increased risk of major cardiovascular events such as acute myocardial infarction, cerebrovascular disease, and peripheral vascular disease. Arterial stiffness is a process related to aging and vascular, metabolic, cellular and physiological deterioration. In recent years, it has been described as an independent predictor of cardiovascular mortality and coronary artery disease. Additionally, it plays an important role in the measurement of chronic disease progression. Recent studies have suggested a strong relationship between diabetes mellitus and arterial stiffness since they share a similar pathophysiology involving endothelial dysfunction. The literature has shown that microvascular and macrovascular complications in diabetic patients could be screened and measured with arterial stiffness. Additionally, new evidence proposes that there is a relationship between blood glucose levels, microalbuminuria, and arterial stiffness. Moreover, arterial stiffness predicts cardiovascular risk and is independently associated with mortality in diabetic patients. Abnormal arterial stiffness values in diabetic patients should alert the clinician to the presence of vascular disease, which merits early study and treatment. We await more studies to determine if arterial stiffness could be considered a routine useful non-invasive tool in the evaluation of diabetic patients. There is enough evidence to conclude that arterial stiffness is related to the progression of diabetes mellitus.

Prevalence of Macrovascular complications in Diabetic Patients in Sohag Governorate: Sex Differences

Background: Atherosclerotic cardiovascular disease (ASCVD) is the major cause of death and disability in patients with type 2 diabetes. Objective: The aim of the research was to study the differences between male and female diabetic patients as regard the prevalence of macrovascular complications in Sohag Governorate, Upper Egypt. Methods: This Study was a cross sectional study on diabetes mellitus in Upper Egypt. The study included 500 diabetic patients randomly selected from rural and urban areas of Sohag Governorate. all patients were subjected to: history taking, clinical examination, blood pressure and pulse evaluation, ECG, echocardiography and laboratory investigations including blood glucose and HbA1c estimation. Results: 500 diabetics patients included in this study, 44.2% of them were males while 55.8% were females. one third of males were smokers and body mass index was statistically higher in females than males. No difference between male and female diabetics as regard control of diabetes or lipogram. The prevalence of hypertension, heart failure with reduced ejection fraction (HFrEF), and diastolic dysfunction were higher in males with significant difference. Peripheral arterial disease was higher in females while stroke was higher in males but with no significant difference. Conclusion: Macrovascular complications are prevalent among male and female diabetic patients. Hypertension, HFrEF and diastolic dysfunction were higher in males than females with significant difference.

May C-peptide index be a new marker to predict proteinuria in anemic patients with type 2 diabetes mellitus?

C-peptide is a reliable marker of beta cell reserve and is associated with diabetic complications. Furthermore, HbA1c level is associated with micro- and macro-vascular complications in diabetic patients. HbA1c measurement of diabetic patients with anemia may be misleading because HbA1c is calculated in percent by taking reference to hemoglobin measurements. We hypothesized that there may be a relationship between C-peptide index (CPI) and proteinuria in anemic patients with type 2 diabetes mellitus (T2DM). Therefore, the aim of the present study was to investigate the association between C-peptide levels and CPI in anemic patients with T2DM and proteinuria. The patients over 18 years of age with T2DM whose C-peptide levels were analyzed in Endocrinology and Internal medicine clinics between 2014 and 2018 with normal kidney functions (GFR>60 ml/min) and who do not use any insulin secretagogue oral antidiabetic agent (i.e. sulfonylurea) were enrolled into the study. Hemoglobin levels were present in 342 patients with T2DM. Among these 342 cases, 258 (75.4%) were non-anemic whereas 84 (24.6%) were anemic. The median DM duration of the anemic group was statistically significantly higher in T2DM (p=0.003). There was no statistically significant difference found in proteinuria prevalence between non-anemic and anemic patient groups (p=0.690 and p=0.748, respectively). Anemic T2DM cases were corrected according to the age, gender, and duration of DM. C-peptide and CPI levels were not statistically significant to predict proteinuria (p=0.449 and p=0.465, respectively). The present study sheds light to the association between C-peptide, CPI, and anemic diabetic nephropathy in T2DM patients and indicates that further prospective studies are needed to clarify this issue.

Screening for macrovascular complications in diabetic patients in Korca, Albania

Screening for macrovascular complications in diabetic patients in Korca, Albania

Haemoglobin A1c as a marker predicting extent and severity of coronary artery disease in non-diabetic patients

Objective Lowering haemoglobin A1c (HbA1c) was shown to be associated with reduction of microvascular, neuropathic and possibly macrovascular complications in diabetic patients. However, in non-diabetic patients, few reports have examined the relation between HbA1c and extent of coronary artery disease. The aim of this study was to examine the relationship between HbA1c level and severity of coronary artery disease (CAD) in non-diabetic patients scheduled for elective coronary angiography.Methods We prospectively studied 408 consecutive non-diabetic patients with or without history of previous myocardial infarction who were scheduled for conventional coronary angiography. HbA1c was measured in all patients at the time of admission. Severity of CAD was assessed by the Gensini score. Gensini score > 30 was considered severe coronary atherosclerosis. Patients were divided into two groups: the high-risk group (HbA1c, 5.7-6.4%) and the low-risk group (HbA1c, < 5.7%).Results Patients in the high-risk group had a higher Gensini score (45.1 ± 36.7 vs 26.8 ± 26.0, P< 0.001). Patients with a Gensini score > 30 had higher values of HbA1c (6.0 ± 0.48 vs 5.75 ± 0.54, P< 0.001). HbA1c showed a positive correlation with the Gensini score. HbA1c value of 5.85% showed a sensitivity and specificity of 70 and 50%, respectively, for prediction of severe coronary atherosclerosis.Conclusion HbA1c is significantly associated with severe coronary atherosclerosis in non-diabetic patients.

Bilirubin as a New Biomarker of Diabetes and its Microvascular Complications

Hyperglycemia is the hallmark of diabetes mellitus [DM]; it activates certain biochemical pathways leading to micro- and macrovascular complications in diabetic patients. Moreover, hyperglycemia generates oxidative stress and causes free radicalmediated lipid peroxidation. In turn, the oxidative stress causes endothelial dysfunction, and has been suggested as one of the important mechanisms underlying the onset and progression of diabetic vascular complications.

Biomarkers of progression in diabetic nephropathy: The past, present and future.

More than 380 million people are currently suffering from diabetes. The International Diabetes Federation estimated that this would rise to 592 million within a generation. Despite this relentless increase in the prevalence of type 2 diabetes worldwide, with the advent of potent statins, there has been a gradual decline in mortality from macrovascular complications, such as stroke and coronary heart disease. However, this is not the situation in diabetic nephropathy, which remains a leading cause of end-stage renal disease (ESRD) globally, with its incidence being still on a rising trend. Notably, once nephropathy develops, approximately 20–40% of patients inevitably progress to ESRD. Therefore, we need biomarkers that would enable early risk stratification in diabetic nephropathy (Figure​(Figure1),1), so that those at higher risk of progression to ESRD are identified at early stages of nephropathy development. Long-term follow up of interventional studies, such as STENO-2, have clearly shown that, even at the stage of microalbuminuria, intensive multifactorial management targeting blood pressure (particularly with blockade of the renin–angiotensin system), glucose, cholesterol and lifestyle issues could reduce the progression to ESRD as well as the associated cardiovascular mortality. The availability of sensitive and well-validated biomarkers for nephropathy progression would allow targeted intensive management to be provided to those who would derive the most cost-effective benefits from such intervention.

High tissue glucose alters intersomitic blood vessels in zebrafish via methylglyoxal targeting the VEGF receptor signaling cascade.

Hyperglycemia causes micro- and macrovascular complications in diabetic patients. Elevated glucose concentrations lead to increased formation of the highly reactive dicarbonyl methylglyoxal (MG), yet the early consequences of MG for development of vascular complications in vivo are poorly understood. In this study, zebrafish were used as a model organism to analyze early vascular effects and mechanisms of MG in vivo. High tissue glucose increased MG concentrations in tg(fli:EGFP) zebrafish embryos and rapidly induced several additional malformed and uncoordinated blood vessel structures that originated out of existing intersomitic blood vessels (ISVs). However, larger blood vessels, including the dorsal aorta and common cardinal vein, were not affected. Expression silencing of MG-degrading enzyme glyoxalase (glo) 1 elevated MG concentrations and induced a similar vascular hyperbranching phenotype in zebrafish. MG enhanced phosphorylation of vascular endothelial growth factor (VEGF) receptor 2 and its downstream target Akt/protein kinase B (PKB). Pharmacological inhibitors for VEGF receptor 2 and Akt/PKB as well as MG scavenger aminoguanidine and glo1 activation prevented MG-induced hyperbranching of ISVs. Taken together, MG acts on smaller blood vessels in zebrafish via the VEGF receptor signaling cascade, thereby describing a new mechanism that can explain vascular complications under hyperglycemia and elevated MG concentrations.

Glycosylated hemoglobin as a predictor for the occurrence of macroangiopathic complications in diabetic patients from bihor county

Abstract Background and Aims: Prospective studies showed that long-term hemoglobin A1c (HbA1c) levels correlate directly with the risk of developing and progression of diabetic complications. The aim of the study was to evaluate the correlation between metabolic control and HbA1c variability with macrovascular complications and assess the role of HbA1c as an independent predictive factor for the occurrence of macrovascular complications in diabetic patients from Bihor County, Romania. Material and method: The study was conducted for a 5 years period (2007-2011) and included 321 diabetic patients with no evidence of macroangipathic complications. During the follow-up all the major vascular events were recorded. Results: At the end of the study a total of 85 chronic macrovascular complications were reported. Distribution plots show significantly higher incidence of vascular complications in patients in the group with poor glycemic control. Multivariate analysis showed that HbA1c can be considered an independent predictor of atherosclerotic complications as well as atherosclerotic complications risk score. The variability of HbA1C was not an independent predictor for macroangiopathic complications (p=0.78). Conclusions: Overall glycemic control was the most important factor in the progression of atherosclerosis but we could not rule out that glycemic variability might play a role in the development of complications in type 2 diabetes mellitus (T2DM) patients.

Visfatin and adiponectin as early markers of atherosclerosis in type 2 diabetes mellitus

Abstract Introduction As cardiovascular disease is the leading cause of mortality in type 2 diabetes mellitus, new markers for early detection and risk stratification of diabetic macroangiopathy and microangiopathy are highly desired. Adipocytokines were considered to lead to an increased risk of vascular complications in patients with type 2 diabetes by modulating vascular function and affecting the inflammatory process, thus enhancing atherosclerosis. Two of these were of particular interest, namely, visfatin and adiponectin. Aim The aim of this study was to evaluate serum visfatin, serum, and urinary adiponectin as early, sensitive surrogate markers of vascular atherosclerosis. We also correlated the levels of these markers to the degree of carotid intimal medial thickness (reflecting the atherosclerotic burden) in type 2 diabetic patients. Results Sixty diabetic patients were subdivided into two groups: group I (30 patients with carotid atherosclerosis as assessed by carotid Doppler) and group II (30 patients without carotid atherosclerosis). Twenty healthy volunteers participated as controls. Serum visfatin as well as serum and urinary adiponectin were assessed in all the study groups. We found significantly higher levels of serum visfatin among diabetics compared with the control group. Visfatin was also significantly higher in group I diabetics with atherosclerosis than those without (P&lt;0.05). Similarly, urinary adiponectin was significantly higher in group I than in group II and in diabetics than in the control group. Serum adiponectin was higher in the control group than both the study groups. Using a regression model, visfatin proved to be the only significant predictor in the model (ß = 0.03, P&lt;0.001). In fact, visfatin alone proved significant, explaining 63% of the variability in carotid intima-media thickness (P&lt;0.001). Conclusion Serum visfatin is highly correlated with macrovascular complications in diabetic patients. Serum visfatin may emerge as a valuable and cheaper surrogate marker for the prediction of prevalent macrovascular complications in a type 2 diabetic population. It is a novel and easy-to-obtain method for the clinical assessment of vascular stress and cardiovascular disease risk in type 2 diabetes. Future prospective studies are needed to confirm our results.

Diabetes Mellitus Reveals Its Micro-Signature

See related article, pages 810–817 With 285 millions individuals affected worldwide in 2010 and more than 400 millions expected in 2030, diabetes mellitus is a major public health concern and a huge economic burden. This disease, characterized by chronic elevation of blood glucose levels, is frequently associated with micro- and macrovascular complications, putting diabetic patients at risk for heart and renal failure, stroke, lower limb amputations, and blindness.1 In view of the dramatic impact of diabetes on public health, the definition of new methods predicting the manifestation of the disease and the occurrence of its debilitating complications deserves the highest priority. In this issue of Circulation Research , Zampetaki et al report that a group of circulating RNA molecules belonging to the microRNA family is considerably less abundant in the blood of diabetes patients compared to normoglycemic individuals.2 Interestingly, a reduction in the level of these microRNAs is already detectable years before the appearance of the disease and is correlated with subclinical and manifest peripheral artery disease. These findings suggest that plasma microRNA levels may become valuable tools to assess the probability of diabetes manifestation in high-risk individuals displaying impaired fasting glucose and could assist in predicting the occurrence of micro- and macrovascular complications in diabetic patients. MicroRNAs are small noncoding RNA molecules discovered in 1993 in Caenorhabditis elegans. Later on, they were identified in many other eukaryotes and it became clear that all mammalian cells contain hundreds of them.3 Many microRNAs are ubiquitously expressed, but some of them are restricted to a limited number of tissues where they play specific roles. Since their discovery, microRNAs have been the focus of intense investigations and have rapidly turned out to form a complementary RNA–directed regulatory network acting in concert with transcription factors to tune gene expression. In …

Activation of Protein Kinase C Isoforms and Its Impact on Diabetic Complications

Both cardio- and microvascular complications adversely affect the life quality of patients with diabetes and have been the leading cause of mortality and morbidity in this population. Cardiovascular pathologies of diabetes have an effect on microvenules, arteries, and myocardium. It is believed that hyperglycemia is one of the most important metabolic factors in the development of both micro- and macrovascular complications in diabetic patients. Several prominent hypotheses exist to explain the adverse effect of hyperglycemia. One of them is the chronic activation by hyperglycemia of protein kinase (PK)C, a family of enzymes that are involved in controlling the function of other proteins. PKC has been associated with vascular alterations such as increases in permeability, contractility, extracellular matrix synthesis, cell growth and apoptosis, angiogenesis, leukocyte adhesion, and cytokine activation and inhibition. These perturbations in vascular cell homeostasis caused by different PKC isoforms (PKC-alpha, -beta1/2, and PKC-delta) are linked to the development of pathologies affecting large vessel (atherosclerosis, cardiomyopathy) and small vessel (retinopathy, nephropathy and neuropathy) complications. Clinical trials using a PKC-beta isoform inhibitor have been conducted, with some positive results for diabetic nonproliferative retinopathy, nephropathy, and endothelial dysfunction. This article reviews present understanding of how PKC isoforms cause vascular dysfunctions and pathologies in diabetes.

The Parodox of Glycemic Control and Cardiovascular Complications: Sorting Out the Data

The results of three recent trials, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, the Action in Diabetes and Vascular Disease (ADVANCE) trial, and the Veterans Affairs Diabetes Trial (VADT), indicate that lower blood glucose levels are not always better. The major aim of all three randomized controlled trials was to determine whether lowering the blood glucose (hemoglobin A [A1C]) to normal or near-normal would 1c reduce the occurrence of cardiovascular events. In the ACCORD trial, unexpected deaths in the intensive therapy (IT) group, over and above the number of deaths in the conventional therapy (CT) group, resulted in the early discontinuation of the trial.1 There were no findings of increased mortality related to IT in the ADVANCE trial; however, preliminary analyses have found no reduction in rates of macrovascular events in the IT group.2 The VADT also found no difference in macrovascular event rates between IT and CT groups.3 Taken together, data from all three of these trials suggest there is no benefit of aggressive glycemic control on macrovascular complications in diabetic patients. These outcomes leave many of us questioning what we thought we knew. Glycemic control as close to the normal range as possible purportedly simulates the nondiabetic state. It is well established that tight glycemic control reduces rates of microvascular complications in diabetic patients; why wouldn't the same hold true for macrovascular events and cardiovascular mortality? A closer look at these important clinical trials may clarify some points but may also leave us with further questions. All three trials shared the aim of determining the relationship between glycemic control and macrovascular events (myocardial infarction and stroke); however, the study designs, populations, and outcomes were somewhat different. ACCORD randomized 10,251 patients with type 2 diabetes (mean age 62 years) and a baseline median …

Effect of Valsartan on Blood Pressure and Urinary Albumin Excretion in Hypertensive Type 2 Diabetic Patients: An Open-Label, Multicenter Study

Background: Activation of renin-angiotensin system (RAS) has been an important mechanism of microvascular and macrovascular complications in diabetic patients. It has been reported that RAS blockades reduce the development and progression of diabetic nephropathy. The aim of this study was to evaluate whether valsartan, an angiotensin II receptor blocker (ARB), reduced blood pressure and urinary albumin excretion rate (UAER) in hypertensive type 2 diabetic patients. Method: Three hundred forty-seven hypertensive type 2 diabetic patients who had not taken angiotensin converting enzyme inhibitors or ARB for 6 months prior to this study were enrolled. We measured blood pressure and UAER before and after 24 weeks of valsartan treatment. Result: Baseline mean systolic and diastolic blood pressure was 143 ± 15 and 87 ± 11 mmHg, respectively and the median albumin excretion rate was 27 ug/mg. Reduction i n systolic and diastolic blood pressure was 16 mmHg/10 mmHg and the median UAER was 19.3 ug/mg after 24 weeks (P < 0.01, respectively). When we divided the subjects into three groups according to the UAER (normoalbuminuria, microalbuminuria and macroalbuminuria), significant changes were reported in the microalbuminuria and the macroalbuminuria groups. Thirty-eight (42%) patients with microalbuminuria improved to

Complicações cardiovasculares na diabetes

Introduction: Diabetes is a disease with a high prevalence and macrovascular complications of diabetes are among the most feared consequences of diabetes, with high costs. Constant evolution of knowledge in this area justifies a new review of the literature on this topic. Objectives: To define the goals of primary and secondary prevention of macrovascular complications in diabetic patients, based on the best available scientific knowledge. Methods: A review of guidelines, recommendations, randomized controlled trials and meta-analyses of prevention of macrovascular complications of diabetes was performed. Results: In diabetic patients it is necessary to manage all risk factors of vascular disease. For primary prevention, lifestyle modifications are of great importance. Diet should be modified to reduce fat, salt and caloric intake, and regular exercise should be promoted. Smokers should be encouraged to quit. Glycemic levels should be controlled to achieve a HbA1C