Development Of Macrovascular Complications Research Articles

The role of glycemic control in the development of late complications of diabetes mellitus

The incidence of type 2 diabetes mellitus is constantly increasing throughout the world. It is known that type 2 diabetes is associated with the development of atherosclerotic cardiovascular diseases, chronic heart failure, and chronic kidney disease. Modern therapy for type 2 diabetes mellitus requires complex treatment and should be aimed not only at reducing glycemia, but also at managing the risks of cardiovascular and renal complications. The results of large scientific studies ADVANCE, ACCORD and VADT have clearly proven the role of glycemic control in the prevention of microvascular complications of diabetes. A number of studies have established that the parameters of glycemic variability are of independent importance in predicting diabetic retinopathy, nephropathy and cardiovascular complications. Hyperglycemia also plays an important role in the development of macrovascular complications. The modern approach to the management of diabetes as one of the most important methods of preventing micro-and macroangiopathies includes the need for mandatory self-monitoring of blood glucose. Self-monitoring of glycemia should be accurate, simple and convenient, allowing the patient to carry out effective and safe glucose-lowering therapy. One of the main aspects of self-monitoring of blood glucose is the choice of a glucometer. From the doctor’s point of view, the most important criterion for choosing a glucometer is compliance with accuracy standards, and from the patient’s point of view, convenience and ease of use. Thanks to the improvement of technology, the accuracy of blood glucose measurements increases, the procedure for self-monitoring of glycemia is simplified, which leads to increased adherence to treatment and the effectiveness of glucose-lowering therapy. Achieving and maintaining the target glycemic level, preventing micro-and macrovascular complications are impossible without the active full participation of the patient himself in the treatment of diabetes, self-monitoring of blood glucose using an accurate and patient-friendly glucometer, i.e., Contour Plus One.

The Contribution of Wnt Signaling to Vascular Complications in Type 2 Diabetes Mellitus.

Vascular complications are the leading cause of morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). These vascular abnormalities result in a chronic hyperglycemic state, which influences many signaling molecular pathways that initially lead to increased oxidative stress, increased inflammation, and endothelial dysfunction, leading to both microvascular and macrovascular complications. Endothelial dysfunction represents the initial stage in both types of vascular complications; it represents “mandatory damage” in the development of microvascular complications and only “introductory damage” in the development of macrovascular complications. Increasing scientific evidence has revealed an important role of the Wnt pathway in the pathophysiology of the vascular wall. It is well known that the Wnt pathway is altered in patients with T2DM. This review aims to be an update of the current literature related to the Wnt pathway molecules that are altered in patients with T2DM, which may also be the cause of damage to the vasculature. Both microvascular complications (retinopathy, nephropathy, and neuropathy) and macrovascular complications (coronary artery disease, cerebrovascular disease, and peripheral arterial disease) are analyzed. This review aims to concisely concentrate all the evidence to facilitate the view on the vascular involvement of the Wnt pathway and its components by highlighting the importance of exploring possible therapeutic strategy for patients with T2DM who develop vascular pathologies.

IDF21-0476 Macrovascular complications in type 1 diabetes mellitus patients with over 25 years of disease

Background: Macrovascular complications (MvC) are the most common cause of death in people with diabetes. Intensive glycemic control has proven to reduce its incidence in diabetes mellitus type 1 (T1DM). However, as for the general population, there are other factors influencing the development of cardiovascular disease. Aim: In a sample of T1DM patients with 25 years of disease: to evaluate the prevalence of MvC; to analyze the relationship between the development of MvC and several factors; to analyze the relationship between macrovascular and microvascular complications. Method: We performed a retrospective study based on the clinical files of T1DM patients with over 25 years of disease. Information was gathered regarding years of disease, average A1C per patient for each five year time period (A-A1C), types of treatment and complications. Statistical analysis was performed with SPSSv23, using: qui-square test for categorical variables, t-test (if normal distribution) or Mann-Whitney (if non-normal distribution) for continuous variables and Kaplan-Meier curves. The results were considered statistically significant if p<0,05. Results: The sample was constituted by 43 patients, 60,5% female, average age 52,6±1,5 years and average duration of T1DM 35,1±1,0 years. Arterial hypertension was present in 60,5% and dyslipidemia in 83,7%. The prevalence of MvC was 39,5% (average time for first MvC 29,4±2 years after diagnosis): 23,3% coronary heart disease; 20,9% heart failure; 20,9% peripheral artery disease and 9,3% cerebrovascular disease. All the patients were treated with intensive insulin therapy (median beginning time 1±7,5 years after diagnosis); 88,4% used functional insulin therapy (average start 19,5±2,0 years after diagnosis); 46,5% used subcutaneous continuous insulin perfusion (average start 21,7±1,5 years after diagnosis). A-A1C analysis was difficulted by several missing values, specially from the initial years of disease. However we observed that patients with MvC tended to have greater A-A1C values in most time periods, without statistical significance. The group with MvC had a longer course of disease (p=0,036) and predominance of the male gender (p=0,036). The patients with arterial hypertension had more (p=0,003) and more precocious (p=0,022) MvC. There were also more MvC in the patients with dyslipidemia (p=0,019). There was a tendency towards more prevalence of nephropathy, retinopathy and neuropathy in the group with MvC (p=0,068, 0,056 e 0,084, respectively). The group with MvC had more time of evolution of microvascular complications in average (p=0,019). Discussion: This work stands out the importance of dyslipidemia and arterial hypertension as contributors to MvC. There was a longer time of evolution of microvascular complications in the MvC group and a tendency towards a higher prevalence of each type of microvascular complications in this group. This data is likely explained by the importance of glycemic control in both types of complications. Although higher A-A1C values in the group with McV did not attain statistical significance, this is probably due to low sample size and several missing data.

Impact of micro- and macrovascular complications of type 2 diabetes on quality of life: Insights from the DISCOVER prospective cohort study.

BackgroundThe key goals of management in patients with type 2 diabetes (T2D) are to prolong life and improve quality of life. Micro‐ and macrovascular complications of T2D not only increase the risk of morbidity and mortality, but cross‐sectional studies indicate they may also worsen quality of life. We prospectively examined the association of complications that developed during the follow‐up with concurrent changes in quality of life.Materials and methodsDISCOVER is a multinational, prospective, observational cohort study of T2D patients enrolled at initiation of second‐line glucose‐lowering therapy. Quality of life was assessed with the SF‐36 Physical (PCS) and Mental Components Summary (MCS) scores at baseline, 6 months, and 1, 2 and 3 years. Hierarchical repeated measures regression models for PCS and MCS were constructed with complications included as time‐dependent covariates; first each complication was modelled alone and then second including all interval complications (to account for different complications occurring in the same patient).ResultsAmong 7830 patients with T2D from 30 countries (mean age 56.6 years, 47.6% women, mean duration of T2D 5.6 years), baseline mean SF‐36 PCS was 48.0 ± 7.8 and SF‐36 MCS was 45.5 ± 10.4. At baseline, 1422 (18.2%) patients had a known microvascular complication, and 966 (12.3%) had a macrovascular complication. Over the 3 years of the study, 641 (12.0%) developed a new microvascular complication (most commonly neuropathy) and 372 (5.8%) developed a new macrovascular complication (most commonly coronary disease). New diagnoses of coronary disease, peripheral artery disease, heart failure and neuropathy were each associated with subsequent moderate reductions in SF‐36 PCS (range 0.7 to 1.6 points) and new cerebrovascular disease was associated with a reduction in SF‐36 MCS (2.6 points). Results were consistent when all interval complications were considered in the same model.ConclusionIn a prospective, multinational study of patients with T2D, the development of macrovascular complications and neuropathy was associated with decreases in both physical and mental quality of life. Our results provide additional support for clinicians to focus on the prevention, detection and management of the complications of T2D.

PANCREATIC AND EXTRA PANCREATIC EFFECTS OF GLYMEPIRIDE

Insulin resistance (IR) and hyperinsulinemia (GI) play a leading role in the development of macrovascular complications in type 2 diabetes mellitus (DM), which are the main cause of mortality in these patients. Taking into account the decisive importance of gluco- and lipotoxicity in the development of microangiopathies, the main goal of antidiabetic pharmacological correction is to influence IR and dysfunction of β-cells of the pancreas

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.

Correlation between glycemic control, lipid profile and C-reactive protein in adults with type 2 diabetes mellitus done in a tertiary care hospital of Nellore, Andhra Pradesh, India

Background: Diabetes mellitus refers to a group of common metabolic disorders that shares the phenotype of hyperglycemia. Complications of diabetes mellitus involve many organ systems only to play an important role in morbidity and mortality. Poor glycemic control is significantly associated with the development of macrovascular complications. Earlier studies have indicated that C-reactive protein (CRP) is an important risk factor for cardiovascular disease as evident from its higher levels in people with diabetes mellitus compared to those without. Not much is known whether CRP is related to the level of glycemic control. The purpose of this study is, to determine the relation between HbA1C, Lipid profile and CRP in individuals with type 2 diabetes mellitus.Methods: Fifty patients with T2DM reporting to Narayana Medical College and Hospital were included in the study, in whom CRP levels were estimated by using commercially available kits and correlated with HbA1C and other risk factors of coronary artery disease. Follow-up was done on 20 patients who were not on statin therapy with repeat HbA1C and CRP.Results: This study showed that both HbA1C and CRP levels had reduced significantly in follow-up patients after putting them on treatment (p&lt;0.05). It was also found that lower the HbA1C, lower was the CRP. A positive correlation was found between HbA1C and CRP (p&lt;0.05).Conclusions: In this study of 50 patients with T2DM, it was found that CRP is significantly correlated with HbA1C level. A positive correlation was found between serum CRP and HbA1C in the initial group and in the follow-up patients, showing that CRP levels lowers with better glycemic control and correlates with dyslipidaemia profile.

High levels of endothelial and platelet microvesicles in patients with type 1 diabetes irrespective of microvascular complications

IntroductionPatients with type 1 diabetes have high risk of developing microvascular complications, and microangiopathy contributes to premature cardiovascular disease in this population. The role that microvesicles (MVs) may play in the development of microangiopathy in type 1 diabetes remains unclear. Materials and methodsPlasma levels of endothelial MVs (EMVs) and platelet MVs (PMVs) in 130 patients with type 1 diabetes without microangiopathy, 106 patients with microangiopathy and 100 matched healthy controls were analyzed using flow cytometry. MV expression of procoagulant phosphatidylserine (PS) and proinflammatory high mobility group box-1 protein (HMGB1) was also assessed. ResultsPatients with type 1 diabetes had markedly elevated levels of EMVs and PS+ EMVs as well as PMVs and PS+ PMVs compared to healthy controls (p < .001 for all). Furthermore, HMGB1+ EMVs and HMGB1+ PMVs were significantly increased in patients (p < .001 for all). After adjusting for potential confounders, there were no clear differences between patients with or without microvascular complications for any of the MV parameters. ConclusionType 1 diabetes is a prothrombotic and proinflammatory disease state that, regardless of the presence of clinical microangiopathy, is associated with elevated levels of plasma MVs, in particular those of an endothelial origin. We have for the first time demonstrated that patients with type 1 diabetes have higher levels of HMGB1+ MVs. HMGB1 is an alarmin with potent proinflammatory effects that drive endothelial dysfunction, and it would therefore be of interest to further study the role of HMGB1+ MVs in the development of macrovascular complications in type 1 diabetes.

Cardiovascular risk in type 2 diabetes patients

Cardiovascular diseases remain leading cause of high mortality in diabetes patients. The article is focused on the influence of diabetes on cardiovascular risks. The prevalence presented, as the significance of the main and additional risk factors of cardiovascular diseases in the development of macrovascular complications in diabetes. In the context of influence on cardiovascular risks, modern glucose lowering drugs are considered, the safety and efficacy properties. Advantages of dapagliflozin underscored, the novel oral drug of new generation, with safe and prominent antidiabetic effect and ability to correct the main factors of cardiovascular risk (obesity, hypertension).

Double diabetes: the cardiovascular implications of combining type 1 with type 2 diabetes

Double diabetes: the cardiovascular implications of combining type 1 with type 2 diabetes

The impact of smoking on the development of diabetes and its complications

Diabetes is one of the most common metabolic disorders and emerges secondary to an interaction between genetic, environmental and lifestyle factors. This work provides an overview of the impact of smoking on the development of vascular complications in this condition and also provides an overview of the potential role of smoking in predisposition to diabetes. There are many studies documenting the impact of smoking on health (not focused on patients with diabetes), suggesting that the health exposure in these individuals is at least comparable to that observed in the general population. Distinct studies of smoking in patients with diabetes have unambiguously confirmed an increased prevalence and a higher risk of early death associated with the development of macrovascular complications. Smoking is also associated with premature development of microvascular complications and may contribute to the pathogenesis of type 2 diabetes. It has been shown that smoking is a predictor of the progression of glucose intolerance at both the transition from normoglycaemia to impaired glucose tolerance status and the increased risk of developing diabetes. The mechanisms explaining the relationship between smoking and the development of diabetes are not fully understood, although a number of hypotheses have been put forward. Current evidence indicates that smoking cessation is not only important to prevent macrovascular complications in diabetes, but also has a role in limiting microvascular disease and may also facilitate glycaemic management in this condition.

Macrovascular Complications in Patients with Diabetes and Prediabetes.

Diabetes is a significant health problem worldwide, and its association with cardiovascular disease (CVD) was reported in several studies. Hyperglycemia and insulin resistance seen in diabetes and prediabetes lead to an increase in reactive oxygen species, which triggers intracellular molecular signaling. The resulting prothrombotic state and increase in inflammatory mediators expedite atherosclerotic changes and the development of macrovascular complications. Individuals with diabetes or prediabetes have a higher risk of developing myocardial infarction, stroke, and peripheral artery disease. However, no significant difference in cardiovascular morbidity has been observed with tight glycemic control despite a reduction in some CVD outcomes, and the risk of adverse outcomes such as hypoglycemia was increased. Recently, some GLP-1 receptor agonists and SGLT-2 inhibitors have been shown to reduce cardiovascular events and mortality. In this review we give an overview of the risk and pathogenesis of cardiovascular disease among diabetic and prediabetic patients, as well as the implication of recent changes in diabetes management.

Control of cardiovascular risk in patients with diabetes

Prevalence of diabetes mellitus (DM) is a version of pandemic, in Russia as well, nowadays. Mortality of patients suffering from DM is associated with the development of macrovascular complications and successful prevention of these complications depends on the complex approach to identify and to correct all modifiable risk factors, included in risk indexes. According to many experts’ point of view, key moments in reducing the risk of cardiovascular complications in patients with DM are to achieve target blood pressure and target levels of lipid metabolism, including the application of non-drug therapies. However, the appearance of new data concerning the possibility of antihyperglycemic therapy, no doubt, will change our point of view on managing cardiovascular risk in patients with DM, in particular empagliflozin, which can influence on cardiovascular outcomes.

Pulsatile Hyperglycaemia Induces Vascular Oxidative Stress and GLUT 1 Expression More Potently than Sustained Hyperglycaemia in Rats on High Fat Diet.

IntroductionPulsatile hyperglycaemia resulting in oxidative stress may play an important role in the development of macrovascular complications. We investigated the effects of sustained vs. pulsatile hyperglycaemia in insulin resistant rats on markers of oxidative stress, enzyme expression and glucose metabolism in liver and aorta. We hypothesized that liver’s ability to regulate the glucose homeostasis under varying states of hyperglycaemia may indirectly affect oxidative stress status in aorta despite the amount of glucose challenged with.MethodsAnimals were infused with sustained high (SHG), low (SLG), pulsatile (PLG) glucose or saline (VEH) for 96 h. Oxidative stress status and key regulators of glucose metabolism in liver and aorta were investigated.ResultsSimilar response in plasma lipid oxidation was observed in PLG as in SHG. Likewise, in aorta, PLG and SHG displayed increased expression of glucose transporter 1 (GLUT1), gp-91PHOX and super oxide dismutase (SOD), while only the PLG group showed increased accumulation of oxidative stress and oxidised low density lipoprotein (oxLDL) in aorta.ConclusionPulsatile hyperglycaemia induced relatively higher levels of oxidative stress systemically and in aorta in particular than overt sustained hyperglycaemia thus supporting the clinical observations that pulsatile hyperglycaemia is an independent risk factor for diabetes related macrovascular complications.

Управление сердечно-сосудистыми рисками у больных сахарным диабетом

Prevalence of diabetes mellitus (DM) is a version of pandemic, in Russia as well, nowadays. Mortality of patients suffering from DM is associated with the development of macrovascular complications and successful prevention of these complications depends on the complex approach to identify and to correct all modifiable risk factors, included in risk indexes. According to many experts’ point of view, key moments in reducing the risk of cardiovascular complications in patients with DM are to achieve target blood pressure and target levels of lipid metabolism, including the application of non-drug therapies. However, the appearance of new data concerning the possibility of antihyperglycemic therapy, no doubt, will change our point of view on managing cardiovascular risk in patients with DM, in particular empagliflozin, which can influence on cardiovascular outcomes.

Sleep Apnea–Hypopnea Syndrome and Type 2 Diabetes. A Reciprocal Relationship?

Epidemiological data suggest that sleep apnea–hypopnea syndrome (SAHS) is independently associated with the development of insulin resistance and glucose intolerance. Moreover, despite significant methodological limitations, some studies report a high prevalence of SAHS in patients with type 2 diabetes mellitus (DM2). A recent meta-analysis shows that moderate–severe SAHS is associated with an increased risk of DM2 (relative risk=1.63 [09–2.45]), compared to the absence of apneas and hypopneas.Common alterations in various pathogenic pathways add biological plausibility to this relationship. Intermittent hypoxia and sleep fragmentation, caused by successive apnea–hypopnea episodes, induce several intermediate disorders, such as activation of the sympathetic nervous system, oxidative stress, systemic inflammation, alterations in appetite-regulating hormones and activation of the hypothalamic–pituitary–adrenal axis which, in turn, favor the development of insulin resistance, its progression to glucose intolerance and, ultimately, to DM2.Concomitant SAHS seems to increase DM2 severity, since it worsens glycemic control and enhances the effects of atherosclerosis on the development of macrovascular complications. Furthermore, SAHS may be associated with the development of microvascular complications: retinopathy, nephropathy or diabetic neuropathy in particular. Data are still scant, but it seems that DM2 may also worsen SAHS progression, by increasing the collapsibility of the upper airway and the development of central apneas and hypopneas.

Síndrome de apneas-hipopneas del sueño y diabetes tipo 2. ¿Una relación de ida y vuelta?

Epidemiological data suggest that sleep apnea-hypopnea syndrome (SAHS) is independently associated with the development of insulin resistance and glucose intolerance. Moreover, despite significant methodological limitations, some studies report a high prevalence of SAHS in patients with type 2 diabetes mellitus (DM2). A recent meta-analysis shows that moderate-severe SAHS is associated with an increased risk of DM2 (relative risk=1.63 [1.09 to 2.45]), compared to the absence of apneas and hypopneas.Common alterations in various pathogenic pathways add biological plausibility to this relationship. Intermittent hypoxia and sleep fragmentation, caused by successive apnea-hypopnea episodes, induce several intermediate disorders, such as activation of the sympathetic nervous system, oxidative stress, systemic inflammation, alterations in appetite-regulating hormones and activation of the hypothalamic-pituitary-adrenal axis which, in turn, favor the development of insulin resistance, its progression to glucose intolerance and, ultimately, to DM2.Concomitant SAHS seems to increase DM2 severity, since it worsens glycemic control and enhances the effects of atherosclerosis on the development of macrovascular complications. Furthermore, SAHS may be associated with the development of microvascular complications: retinopathy, nephropathy or diabetic neuropathy in particular. Data are still scant, but it seems that DM2 may also worsen SAHS progression, by increasing the collapsibility of the upper airway and the development of central apneas and hypopneas.

Association of RAGE gene polymorphism with vascular complications in Indian type 2 diabetes mellitus patients

AimsThe study was designed to evaluate the association of −374T/A and −429T/C polymorphism in the promoter region and Gly82Ser polymorphism in exon 3 region of RAGE gene with diabetic vascular complications in Indian population. MethodsWe screened 603 subjects which includes 176 healthy controls, 140 type 2 diabetes mellitus (T2DM) subjects without any vascular complications (DM), 152 T2DM subjects with microvascular complications (DM-micro) and 135 T2DM subjects with macrovascular complications (DM-macro) for −374T/A, −429T/C and Gly82Ser polymorphisms of RAGE gene. DNA isolated from the enrolled subjects were genotyped by PCR-RFLP. Logistic regression analysis was used to evaluate the association of single nucleotide polymorphisms (SNPs). ResultsThe −429 T/C and Gly82Ser RAGE polymorphisms were found to be significantly associated with the development of macrovascular and microvascular complications, respectively, in T2DM subjects while −374A allele showed reduced risk towards the development of macrovascular complications. Further, −429T/C, −374T/A and Gly82Ser haplotype analysis revealed association of CTG haplotype with development of macrovascular complications while haplotype TAG was observed to be significantly protective towards development of macrovascular complications in T2DM subjects (OR=0.617, p=0.0202). ConclusionsOur data indicates significant association of RAGE SNPs and haplotypes with vascular complications in North Indian T2DM subjects.

Association of RAGE gene polymorphism with circulating AGEs level and paraoxonase activity in relation to macro-vascular complications in Indian type 2 diabetes mellitus patients

Background and aimsSustained interaction of advanced glycation end products (AGEs) with their receptor RAGE and subsequent signaling plays an important role in the development of diabetic complications. Genetic variation of RAGE gene may be associated with the development of vascular complications in type 2 diabetes mellitus (T2DM). ObjectivesThe present study aimed to explore the possible association of RAGE gene polymorphisms namely −374T/A, −429T/C and G82S with serum level of AGEs, paraoxonase (PON1) activity and macro-vascular complications (MVC) in Indian type 2 diabetes mellitus patients (T2DM). MethodsA total of 265 diabetic patients, including DM without any complications (n=135), DM-MVC (n=130) and 171 healthy individuals were enrolled. Genotyping of RAGE variants were assessed by polymerase chain reaction-restriction fragment length polymorphism. Serum AGEs were estimated by ELISA and fluorometrically. and PON1 activity was assessed spectrophotometrically. ResultsOf the three examined SNPs, association of −429T/C polymorphism with MVC in T2DM was observed (OR=3.001, p=0.001) in the dominant model. Allele ‘A’ of −374T/A polymorphism seems to confer better cardiac outcome in T2DM. Patients carrying C allele (−429T/C) and S allele (G82S) had significantly higher AGEs levels. −429T/C polymorphism was also found to be associated with low PON1 activity. Interaction analysis revealed that the risk of development of MVC was higher in T2DM patients carrying both a CC genotype of −429T/C polymorphism and a higher level of AGEs (OR=1.343, p=0.040). ConclusionRAGE gene polymorphism has a significant effect on AGEs level and PON1 activity in diabetic subjects compared to healthy individuals. Diabetic patients with a CC genotype of −429T/C are prone to develop MVC, more so if AGEs levels are high and PON1 activity is low.

Pivotal Role of Timely Basal Insulin Replacement After Metformin Failure in Sustaining Long-Term Blood Glucose Control at a Target in Type 2 Diabetes

Type 2 diabetes over time associates with the development of vascular complications (1). The causative role of long-term elevation of blood glucose is well established, at least for microvascular complications, since intervention strategies directed at reducing hyperglycemia lower onset and/or progression of microangiopathy (1,2). The role of hyperglycemia and its treatment in the development of macrovascular complications is less well established. In fact, it takes a longer time to observe a positive effect of better blood glucose control (in addition to reducing the multiple risk factors often associated with type 2 diabetes such as hypertension, visceral obesity, and hyperdyslipidemia) on macroangiopathy compared with microangiopathy (1,3,4). Today’s understanding of the complex relationship between hyperglycemia and complications in type 2 diabetes predicates that only an early and aggressive blood glucose–lowering intervention (in addition to reduction of the above mentioned risk factors), successfully sustained over time, will translate into benefits on macrovascular complications several years later (likely 10–15 years) (1,3–5). Thus, the present recommendation is to intensively treat people with type 2 diabetes from the clinical onset of the disease, particularly subjects with short diabetes duration who likely have not yet developed vascular complications and who presumably have a long life-expectancy (6). At present, the question is not whether to intensively treat people with type 2 diabetes at onset of the disease to prevent long-term complications. The question rather is how to intensively treat type 2 diabetes over the many years and decades of the progression of the disease to consistently keep A1C levels <7.0% over the entire cycle of type 2 diabetes. At present, this question is difficult to answer, primarily because of the lack of evidence of long-term effects of one specific intervention, compared with several other possible intervention strategies …