The Genetic Variants -717T>C (rs2794521), 1444G>A (rs1130864), and 1846 C > T (rs1205) of CRP Gene, Their Haplotypes, and Their Association with Serum CRP Levels, Acute Coronary Syndrome, and Diabetes in Patients from Western Mexico.

Background: C-reactive protein (CRP) is involved in inflammatory pathways that are associated with the onset and progression of type 2 diabetes mellitus (T2DM) as well as an increased risk of an acute coronary syndrome (ACS). This research aimed to evaluate the potential association of the genetic variants -717T>C, 1444G>A, and 1846 C > T of CRP gene on CRP levels, ACS, and T2DM in participants from Western Mexico. Methods: Six hundred three participants were studied: (1) control group (CG); (2) ACS participants classified as unstable angina (UA), myocardial infarction without ST-segment elevation (NSTEMI), and myocardial infarction with ST-segment elevation (STEMI); (3) T2DM Participants; and (4) ACS plus T2DM participants (ACS+T2DM). Genetic variants were genotyped using allelic discrimination with TaqMan® probes, and high-sensitivity CRP (hs-CRP) was measured by Turbidimetry. Results: TAC haplotype frequency was significantly higher in ACS+T2DM versus CG and versus ACS participants (odds ratio [OR] = 2.774, P = 0.017 and OR = 3.479, P = 0.020, respectively). hs-CRP levels were especially higher for ACS and for ACS+T2DM participants with respect to CG and T2DM (with P < 0.0001). We observed higher hs-CRP levels in NSTEMI and STEMI versus UA in ACS scenario (P = 0.001, P = 0.027, respectively) and for ACS+T2DM scenario (P = 0.0001, P = 0.002, respectively). Conclusion: hs-CRP level fluctuations are related to the presence of T2DM and the presence and severity of ACS. Very high levels (>10 mg/L) are a risk marker of cardiovascular complications. Our results demonstrate a possible relationship between TAC haplotype and an increased risk for T2DM and ACS.

ApoB/ApoA1 ratio and non-HDL-cholesterol/HDL-cholesterol ratio are associated to metabolic syndrome in patients with type 2 diabetes mellitus subjects and to ischemic cardiomyopathy in diabetic women.

BACKGROUND AND AIM: Presence of metabolic syndrome (MS) in patients with type 2 diabetes mellitus (T2DM) involves an increased risk of cardiovascular disease and death. Markers such as ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios have been used to predict this risk with conflicting results. The study objective was to establish the relationship between the apoB/apoA1 and non-HDL-cholesterol/HDL-cholesterol ratios and MS in T2DM patients from a Madrid (Spain) district. PATIENTS AND METHODS: One hundred patients with T2DM who attended University Hospital Infanta Leonor (Vallecas, Madrid, Spain) between January 2014 and June 2017 were enrolled. A blood sample was taken every 6 months from all patients to measure the different lipid parameters and to calculate ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios. A Mann-Whitney's U test to compare means and a Spearman's correlation test for correlations between variables were used, and a multivariate regression analysis was performed to determine the association between MS and the ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios. Values of p<0.05 were considered significant. RESULTS: Associations were found between MS and ApoA1 (R2=0.164, p=0.028), ApoB/ApoA1 (R2=0.187, p=0.001), and non-HDL-cholesterol/HDL-cholesterol (R2= 0.269, p=0.0001) ratios and, in women with MS, between ApoB/ApoA1 ratio and ischemic cardiomyopathy (IC) (R2=0.160, p=0.032). Associations remained after adjusting for comorbidities and risk factors. CONCLUSIONS: In the T2DM patients studied, MS was independently associated to ApoA1 and the ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios. Both ratios were better predictors of MS in T2DM subjects that its components alone. The ApoB/ApoA1 ratio could be used as a cardiovascular risk marker in women with MS.

Update on the treatment of type 2 diabetes mellitus.

To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases risk of macrovascular and microvascular complications. At present there are different treatments, both oral and injectable, available for the treatment of type 2 diabetes mellitus (T2DM). Treatment algorithms designed to reduce the development or progression of the complications of diabetes emphasizes the need for good glycaemic control. The aim of this review is to perform an update on the benefits and limitations of different drugs, both current and future, for the treatment of T2DM. Initial intervention should focus on lifestyle changes. Moreover, changes in lifestyle have proven to be beneficial, but for many patients is a complication keep long term. Physicians should be familiar with the different types of existing drugs for the treatment of diabetes and select the most effective, safe and better tolerated by patients. Metformin remains the first choice of treatment for most patients. Other alternative or second-line treatment options should be individualized depending on the characteristics of each patient. This article reviews the treatments available for patients with T2DM, with an emphasis on agents introduced within the last decade.

Management of hospitalized type 2 diabetes mellitus patients.

Both hyperglycemia and hypoglycemia in hospitalized patients are associated with adverse outcomes including increased rates of infection, longer hospital length of stay, and even death. Clinical trials in patients with type 2 diabetes mellitus proved that by improving glycemic control, we can reduce all of them. Insulin is the preferred treatment for glycemic control in most cases, but alternative treatment options that can normalize blood glucose levels without hypoglycemia are being sought. Moreover, hospitalized patients are particularly vulnerable to severe, prolonged hypoglycemia since they may be unable to sense or respond to the early warning signs and symptoms of low blood glucose. Finally, nutritional support, corticosteroid therapy, and surgery increase the risk of hyperglycemia that leads to an increased risk of morbidity and mortality. We review the management of type 2 diabetes mellitus patients who are admitted to the general medical wards of the hospital for a procedure of intercurrent illness.

Mechanisms of hypoglycemia unawareness and implications in diabetic patients.

Hypoglycemia unawareness (HU) is defined at the onset of neuroglycopenia before the appearance of autonomic warning symptoms. It is a major limitation to achieving tight diabetes and reduced quality of life. HU occurs in approximately 40% of people with type 1 diabetes mellitus (T1DM) and with less frequency in T2DM. Though the aetiology of HU is multifactorial, possible mechanisms include chronic exposure to low blood glucose, antecedent hypoglycaemia, recurrent severe hypoglycaemia and the failure of counter-regulatory hormones. Clinically it manifests as the inability to recognise impeding hypoglycaemia by symptoms, but the mechanisms and mediators remain largely unknown. Prevention and management of HU is complex, and can only be achieved by a multifactorial intervention of clinical care and structured patient education by the diabetes team. Less know regarding the impact of medications on the development or recognition of this condition in patients with diabetes. Several medications are thought to worsen or promote HU, whereas others may have an attenuating effect on the problem. This article reviews recent advances in how the brain senses and responds to hypoglycaemia, novel mechanisms by which people with insulin-treated diabetes develop HU and impaired counter-regulatory responses. The consequences that HU has on the person with diabetes and their family are also described. Finally, it examines the evidence for prevention and treatment of HU, and summarizes the effects of medications that may influence it.

[Current status of continuous subcutaneous insulin infusion and continuous glucose monitoring systems in the Community of Madrid]. / Estado actual de los sistemas de infusión subcutánea continua de insulina y monitorización continua de glucosa en la Comunidad de Madrid.

OBJECTIVE: To analyze the available information about continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems in the public health care system of the Community of Madrid. MATERIAL AND METHODS: A survey consisting of 31 items was sent to the 28 endocrinology department of the Madrid public hospitals. Items focused on CSII and CGM and included patients' registrations, as well as data regarding healthcare, administrative, and logistic aspects. Responses from a total of 20 hospitals where these procedures are used were received from March 2013 to May 2014. Data about pediatric patients were obtained from adult endocrinology departments, except for two hospitals which directly reported the information. RESULTS: A total of 1256 CSII pumps were recorded in the Madrid region, of which 1089 were used by adults, and the remaining 167 by pediatric patients. During 2013, 151 new CSII systems were implanted (12% of the total), while 14 pumps were withdrawn. Availability of human resources (medical assistance) and the number of staff practitioners experienced in management of these systems widely varied between hospitals. Eighty-five percent of hospitals used retrospective CGM systems, and 40% routinely placed them before starting an insulin pump. Thirteen hospitals (65%) used long-term, real-time CGM systems in selected cases (a total of 67 patients). CONCLUSIONS: Use of these technologies in diabetes is unequal between public health care hospitals in Madrid, and is still significantly lower as compared to other countries with similar incomes. However, there appears to be a trend to an increase in their use.

Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?

Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin. Compared with individuals without diabetes, patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality, and are disproportionately affected by cardiovascular disease. Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension, dyslipidaemia and obesity in these patients. However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors. Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus. Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events. Many of these risk factors could be common history for both diabetes mellitus and cardiovascular disease, reinforcing the postulate that both disorders come independently from "common soil". The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients.

Microvascular complications and risk factors in patients with type 2 diabetes

Realizar un estudio prospectivo en sujetos con diabetes mellitus tipo 2 (DM2) sin complicaciones microvasculares, analizando la asociación entre varios factores de riesgo al inicio y el desarrollo de complicaciones microvasculares durante el seguimiento. Métodos Estudio prospectivo, observacional en 376 sujetos con DM2 incluidos en 2004. El objetivo clínico final fue la excreción urinaria de albúmina (EUA) > 30mg/24h y/o presencia de retinopatía al final del seguimiento en 2007. Basalmente las variables fueron: edad, sexo, duración de la diabetes, glucosa plasmática en ayunas, hemoglobina glucada (HbA1c), presión arterial sistólica y diastólica, peso, talla, índice de masa corporal, circunferencia de la cintura, colesterol total, triglicéridos, colesterol unido a lipoproteína de alta densidad (c-HDL), colesterol unido a lipoproteína de baja densidad (c-LDL), proteína C reactiva de alta sensibilidad (PCR-as), fibrinógeno, EUA, creatinina, tabaquismo, ejercicio, consumo de alcohol, utilización de medicación hipoglucemiante, hipolipemiante e hipotensora, y otros datos relacionados con los antecedentes familiares de diabetes y factores de riesgo. Resultados Al final del seguimiento 95 sujetos (25,2%) desarrollaron una complicación microvascular. En el análisis de regresión logística, los principales factores de riesgo independientes fueron la EUA > 12mg/24h (odds ratio [OR]: 6,12; p=0,000), la PCR-as > 3mg/l (OR: 3,00; p=0,004) y la hipertensión (OR: 2,43; p=0,023). Conclusiones Los niveles de EUA superiores a 12mg/24h, la PCR-as > 3mg/l y la presencia de hipertensión fueron factores de riesgo independientes para el desarrollo de complicaciones microvasculares en los sujetos con DM2 estudiados (AU)

To conduct a prospective study in patients with type 2 diabetes mellitus (T2DM) with no microvascular complications, analyzing the association between various baseline risk factors and development of microvascular complications at follow-up.MethodsA prospective, observational study in 376 patients with T2DM enrolled in 2004. The clinical end-point was urinary albumin excretion (UAE) > 30mg/24h and/or presence of retinopathy at follow-up in 2007. Baseline variables included age, gender, duration of T2DM, fasting plasma glucose, glycated hemoglobin (HbA1c), systolic and diastolic blood pressure, body weight, height, body mass index, waist circumference, total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), high sensitive C-reactive protein (hs-CRP), fibrinogen, UAE, creatinine, smoking status, exercise, alcohol consumption, use of hypoglycemic and lipid-lowering drugs, antihypertensive medications, and other data related to family history of diabetes and risk factors.Results Ninety-five subjects (25.2%) developed a microvascular complication at the end of the follow-up period. In logistic regression analyses, the main independent risk factors were UAE >12mg/24h (odds ratio [OR]: 6.12; P=.000), hs-CRP> 3mg/L (OR: 3.00; P=.004), and hypertension (OR: 2.43; P=.023).ConclusionsUAE levels higher than 12mg/24h, hs-CRP >3mg/L, and presence of hypertension were all independent risk factors for development of microvascular complications in patients with T2DM studied (AU)

Microvascular complications and risk factors in patients with type 2 diabetes.

AIM: To conduct a prospective study in patients with type 2 diabetes mellitus (T2DM) with no microvascular complications, analyzing the association between various baseline risk factors and development of microvascular complications at follow-up. METHODS: A prospective, observational study in 376 patients with T2DM enrolled in 2004. The clinical end-point was urinary albumin excretion (UAE) > 30mg/24h and/or presence of retinopathy at follow-up in 2007. Baseline variables included age, gender, duration of T2DM, fasting plasma glucose, glycated hemoglobin (HbA(1c)), systolic and diastolic blood pressure, body weight, height, body mass index, waist circumference, total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), high sensitive C-reactive protein (hs-CRP), fibrinogen, UAE, creatinine, smoking status, exercise, alcohol consumption, use of hypoglycemic and lipid-lowering drugs, antihypertensive medications, and other data related to family history of diabetes and risk factors. RESULTS: Ninety-five subjects (25.2%) developed a microvascular complication at the end of the follow-up period. In logistic regression analyses, the main independent risk factors were UAE >12mg/24h (odds ratio [OR]: 6.12; P=.000), hs-CRP> 3mg/L (OR: 3.00; P=.004), and hypertension (OR: 2.43; P=.023). CONCLUSIONS: UAE levels higher than 12mg/24h, hs-CRP >3mg/L, and presence of hypertension were all independent risk factors for development of microvascular complications in patients with T2DM studied.

Strict control of modifiable cardiovascular risk factors in patients with type 2 diabetes mellitus.

BACKGROUND AND OBJECTIVE: To assess the effect of a strict control of modifiable cardiovascular risk factors on coronary risk (CR) in patients with type 2 diabetes mellitus (T2DM) in clinical practice. PATIENTS AND METHOD: Longitudinal, open and observational study in 530 patients with T2DM. Fasting plasma glucose (FPG), glycated haemoglobin (HbA 1C), postprandial capillary glucose (PCG), total cholesterol, high-density lipoprotein-cholesterol, triglycerides, systolic (SBP) and diastolic (DBP) blood pressure were measured; low-density lipoprotein-cholesterol and body mass index were calculated; and 10 years CR was predicted before and after 6 months of therapy implementation. The percentage of patients who reached the targets, according to published guidelines, and the use of insulin and various cardioprotective medications were compared before and after therapy implementation. RESULTS: There was a significant decrease in mean HbA 1C, FPG, PCG, total cholesterol, triglycerides, SBP, DBP, and CR after intervention. The percentage of patients who reached the HbA 1C, FPG, PCG, total cholesterol, triglycerides, SBP, DPB, and CR targets, and the number of subjects taking insulin and cardioprotective drugs increased significantly after intervention. CONCLUSIONS: This study shows that a strict control of modifiable cardiovascular risk factors in patients with T2DM in clinical practice has a beneficial effect over predicted CR.

Control estricto de los factores de riesgo cardiovascular modificables en pacientes con diabetes mellitus tipo 2 / Strict control of modifiable cardiovascular risk factors in patients with type 2 diabetes mellitus

Fundamento y objetivo: Valorar en la práctica clínica qué efecto tiene, en pacientes con diabetes mellitus tipo 2 (DM2), el control estricto de los factores de riesgo cardiovascular modificables sobre el riesgo coronario (RC). Pacientes y método: Se ha realizado un estudio longitudinal, abierto y observacional. En 530 pacientes con DM2 se midieron la glucosa plasmática en ayunas (GPA), hemoglobina glucosilada (HbA1C), glucosa capilar posprandial (GCP), colesterol total, colesterol unido a lipoproteínas de alta densidad, triglicéridos, presión arterial sistólica (PAS) y diastólica (PAD); además se calcularon el colesterol unido a lipoproteínas de baja densidad, el índice de masa corporal y el RC a 10 años, antes y 6 meses después de intensificar el tratamiento. Se compararon el porcentaje de pacientes que alcanzaron los objetivos, de acuerdo con las guías publicadas, y la utilización de insulina y de medicaciones cardioprotectoras antes y 6 meses después de la intervención. Resultados: Después de la intervención se observó una disminución significativa de los valores de HbA1C, GPA, GCP, colesterol total, triglicéridos, PAS, PAD y RC, así como un incremento significativo del porcentaje de pacientes que alcanzaron los objetivos de HbA1C, GPA, GCP, colesterol total, triglicéridos, PAS, PAD y RC, y del número de sujetos en tratamiento con insulina y medicamentos cardioprotectores. Conclusiones: Este estudio de práctica clínica muestra que el control estricto de los factores de riesgo cardiovascular modificables en pacientes con DM2 se traduce en efectos beneficiosos sobre el RC

Background and objective: To assess the effect of a strict control of modifiable cardiovascular risk factors on coronary risk (CR) in patients with type 2 diabetes mellitus (T2DM) in clinical practice. Patients and method: Longitudinal, open and observational study in 530 patients with T2DM. Fasting plasma glucose (FPG), glycated haemoglobin (HbA1C), postprandial capillary glucose (PCG), total cholesterol, high-density lipoprotein-cholesterol, triglycerides, systolic (SBP) and diastolic (DBP) blood pressure were measured; low-density lipoprotein-cholesterol and body mass index were calculated; and 10 years CR was predicted before and after 6 months of therapy implementation. The percentage of patients who reached the targets, according to published guidelines, and the use of insulin and various cardioprotective medications were compared before and after therapy implementation. Results: There was a significant decrease in mean HbA1C, FPG, PCG, total cholesterol, triglycerides, SBP, DBP, and CR after intervention. The percentage of patients who reached the HbA1C, FPG, PCG, total cholesterol, triglycerides, SBP, DPB, and CR targets, and the number of subjects taking insulin and cardioprotective drugs increased significantly after intervention. Conclusions: This study shows that a strict control of modifiable cardiovascular risk factors in patients with T2DM in clinical practice has a beneficial effect over predicted CR

Cardiovascular risk factors in patients with type 2 diabetes. Do we follow the guidelines?

OBJECTIVE: To assess the degree of control of modifiable cardiovascular risk factors (CRFs) in type 2 diabetic patients. STUDY DESIGN AND METHODS: Cross-sectional study in 501 patients with type 2 diabetes mellitus. The following parameters were used to define optimal control: glycated haemoglobin (HbA(1C)) <7.0%, fasting plasma glucose (FPG) <7.2 mmol/l, postprandial capillary glucose (PCG) <10.0 mmol/l, high-density lipoprotein cholesterol (HDL-C) >1.1 mmol/l, low-density lipoprotein cholesterol (LDL-C) <2.6 mmol/l, triglyceride levels (TG) <1.7 mmol/l, systolic blood pressure (SBP) <130 mmHg, diastolic blood pressure (DBP) <80 mmHg, body mass index (BMI) <25 kg/m2, waist circumference (WC) <88 cm in women and <102 cm in men, and current non-smoking status. The use of various cardioprotective medications was also evaluated. RESULTS: Mean (+/-S.D.) age was 65.4 +/- 11.9 years, 218 (44%) were male. Ninety-six (19%) met coronary artery disease (CAD). Two hundred seven patients (41%) had an HbA(1C) <7.0%, 134 (27%) a FPG <7.2 mmol/l and 231 of 353 (65%) a PCG <10.0 mmol/l. Only 206 (41%) achieved an LDL-C <2.6 mmol/l, but 370 (74%) and 308 (62%) reached an HDL-C >1.1 mmol/l and a TG levels <1.7 mmol/l, respectively. In 359 (72%) patients DBP was <80 mmHg, but in only 136 (27%) was SBP <130 mmHg. Sixty four (13%) achieved a BMI <25 kg/m2, and 420 (84%) were non-smokers. Forty three (15%) women and 104 (48%) men had a WC <88 or <102 cm, respectively. None of the patients had optimal control of all CRFs. CONCLUSIONS: These data demonstrate poor control of modifiable CRFs in the population studied, and support the need for great effort to achieve the recommended goals.