Mechanisms of postprandial hyperglycemia in liver transplant recipients: comparison of liver transplant patients with kidney transplant patients and healthy controls.

Impaired glucose tolerance or diabetes mellitus are frequent complications after organ transplantation, and are usually attributed to glucocorticoid and immunosuppressive treatments. Liver transplantation results in total hepatic denervation which may also affect glucoregulation. We therefore evaluated postprandial glucose metabolism in a group of patients with liver cirrhosis before and after orthotopic liver transplantation. Seven patients with liver cirrhosis of various etiologies, 6 patients having received a kidney transplant, and 6 healthy subjects were studied. Their glucose metabolism was evaluated in the basal state and over 4 hours after ingestion of a glucose load with 6.6 (2) H glucose dilution analysis. The patients with liver cirrhosis were studied before, and again 4 weeks (range 2-6) and 38 weeks (range 20-76, n=6) after orthotopic liver transplantation. Basal glucose metabolism was similar in liver and kidney transplant recipients. Impaired glucose tolerance was present in both groups, but postprandial hyperglycemia was exaggerated and lasted longer in liver transplant patients. Postprandial insulinemia was lower in liver transplant recipients, while C-peptide concentrations were comparable to those of kidney transplant recipients, indicating increased insulin clearance. Glucose turnover was not altered in both groups of patients during the initial 3 hours after glucose ingestion, but was higher in liver transplant early after transplantation during the fourth hour. Postprandial hyperglycemia remained unchanged in liver transplant recipients 38 weeks after liver transplantation, despite substantial reduction of immunosuppressive and glucocorticoid doses. We conclude that liver transplant recipients have severe postprandial hyperglycemia which can be attributed to insulinopenia (secondary, at least in part, to increased insulin clearance) and a late increased glucose turnover. These changes may be secondary to hepatic denervation.

Effects of gastric bypass and gastric banding on glucose kinetics and gut hormone release.

BACKGROUND: Bariatric surgery markedly improves glucose homeostasis in patients with type 2 diabetes even before any significant weight loss is achieved. Procedures that involve bypassing the proximal small bowel, such as Roux-en-Y gastric bypass (RYGBP), are more efficient than gastric restriction procedures such as gastric banding (GB). OBJECTIVE: To evaluate the effects of RYGBP and GB on postprandial glucose kinetics and gastro-intestinal hormone secretion after an oral glucose load. METHODS AND PROCEDURES: This study was a cross-sectional comparison among non-diabetic, weight-stable women who had undergone RYGBP (n = 8) between 9 and 48 months earlier or GB (n = 6) from 25 to 85 months earlier, and weight- and age-matched control subjects (n = 8). The women were studied over 4 h following ingestion of an oral glucose load. Total glucose and meal glucose kinetics were assessed using glucose tracers and plasma insulin, and gut hormone concentrations were simultaneously monitored. RESULTS: Patients who had undergone RYGBP showed a a more rapid appearance of exogenous glucose in the systemic circulation and a shorter duration of postprandial hyperglycemia than patients who had undergone GB and C. The response in RYGBP patients was characterized by early and accentuated insulin response, enhanced postprandial levels of glucagon-like peptide-1 (GLP-1) and polypeptide YY (PYY), and greater postprandial suppression of ghrelin. DISCUSSION: These findings indicate that RYGBP is associated with alterations in glucose kinetics and glucoregulatory hormone secretion. These alterations are probably secondary to the anatomic rearrangement of the foregut, given the fact that they are not observed after GB. Increased PYY and GLP-1 concentrations and enhanced ghrelin suppression are compatible with reduced food intake after RYGBP.

Effects of regular insulin or insulin LISPRO on glucose metabolism after an oral glucose load in patients with type 2 diabetes mellitus.

Seven obese Type 2 diabetic patients were studied for two 4-h periods after ingestion of a glucose load to determine the effects of preprandial subcutaneous injection of Insulin Lispro (5 min before the meal) or regular insulin (20 min before the meal) on glucose metabolism. Glucose production and utilisation were measured using a dual isotope method. After Lispro, the mean postprandial increase in plasma glucose was 29% lower and the increase in insulin concentration 25% higher than after regular insulin (p < 0.05). Suppression of endogenous glucose production was similar with both types of insulin. Thus, preprandial injection of Lispro reduced postprandial glucose increments in Type 2 diabetic patients as compared to regular insulin. This effect is best explained by the increased postprandial bioavailability of Lispro.

Inhibition of renal glucose reabsorption as a novel treatment for diabetes patients

The importance of the kidney in glucose homeostasis has been recognized for many years. Recent observations indicating a greater role of renal glucose metabolism in various physiologic and pathologic conditions have rekindled the interest in renal glucose handling as a potential target for the treatment of diabetes. The enormous capacity of the proximal tubular cells to reabsorb the filtered glucose load entirely, utilizing the sodium-glucose co-transporter system (primarily SGLT-2), became the focus of attention. Original studies conducted in experimental animals with the nonspecific SGLT inhibitor phlorizin showed that hyperglycemia after pancreatectomy decreased as a result of forced glycosuria. Subsequently, several compounds with more selective SGLT-2 inhibition properties (“second-generation”) were developed. Some agents made it into pre-clinical and clinical trials and a few have already been approved for commercial use in the treatment of type 2 diabetes. In general, a 6-month period of therapy with SGLT-2 inhibitors is followed by a mean urinary glucose excretion rate of ~80 g/day accompanied by a decline in fasting and postprandial glucose with average decreases in HgA1C ~1.0%. Concomitant body weight loss and a mild but consistent drop in blood pressure also have been reported. In contrast, transient polyuria, thirst with dehydration and occasional hypotension have been described early in the treatment. In addition, a significant increase in the occurrence of uro-genital infections, particularly in women has been documented with the use of SGLT-2 inhibitors. Conclusion: Although long-term cardiovascular, renal and bone/mineral effects are unknown SGLT-2 inhibitors, if used with caution and in the proper patient provide a unique insulin-independent therapeutic option in the management of obese type 2 diabetes patients.

Impact of postprandial glycaemia on health and prevention of disease

Postprandial glucose, together with related hyperinsulinemia and lipidaemia, has been implicated in the development of chronic metabolic diseases like obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). In this review, available evidence is discussed on postprandial glucose in relation to body weight control, the development of oxidative stress, T2DM, and CVD and in maintaining optimal exercise and cognitive performance. There is mechanistic evidence linking postprandial glycaemia or glycaemic variability to the development of these conditions or in the impairment in cognitive and exercise performance. Nevertheless, postprandial glycaemia is interrelated with many other (risk) factors as well as to fasting glucose. In many studies, meal-related glycaemic response is not sufficiently characterized, or the methodology with respect to the description of food or meal composition, or the duration of the measurement of postprandial glycaemia is limited. It is evident that more randomized controlled dietary intervention trials using effective low vs. high glucose response diets are necessary in order to draw more definite conclusions on the role of postprandial glycaemia in relation to health and disease. Also of importance is the evaluation of the potential role of the time course of postprandial glycaemia.

Influence of lower cutoff values for 100-g oral glucose tolerance test and glycemic profile for identification of pregnant women at excessive fetal growth risk

Objective: To evaluate data from patients with normal oral glucose tolerance test (OGTT) results and a normal or impaired glycemic profile (GP) to determine whether lower cutoff values for the OGTT and GP (alone or combined) could identify pregnant women at risk for excessive fetal growth. Methods: We classified 701 pregnant women with positive screening for gestational diabetes mellitus (GDM) into 2 categories - (1) normal 100-g OGTT and normal GP and (2) normal 100-g OGTT and impaired GP - to evaluate the influence of lower cutoff points in a 100-g OGTT and GP (alone or in combination) for identification of pregnant women at excessive fetal growth risk. The OGTT is considered impaired if 2 or more values are above the normal range, and the GP is impaired if the fasting glucose level or at least 1 postprandial glucose value is above the normal range. To establish the criteria for the OGTT (for fasting and 1, 2, and 3 hours after an oral glucose load, respectively), we considered the mean (75 mg/dL, 120 mg/dL, 113 mg/dL, and 97 mg/dL), mean plus 1 SD (85 mg/dL, 151 mg/dL, 133 mg/dL, and 118 mg/dL), and mean plus 2 SD (95 mg/dL, 182 mg/dL, 153 mg/dL, and 139 mg/dL); and for the GP, we considered the mean and mean plus 1 SD (78 mg/dL and 92 mg/dL for fasting glucose levels and 90 mg/dL and 130 mg/dL for 1- or 2-hour postprandial glucose levels, respectively). Results: Subsequently, the women were reclassified according to the new cutoff points for both tests (OGTT and GP). Consideration of values, in isolation or combination, yielded 6 new diagnostic criteria. Excessive fetal growth was the response variable for analysis of the new cutoff points. Odds ratios and their respective confidence intervals were estimated, as were the sensitivity and specificity related to diagnosis of excessive fetal growth for each criterion. The new cutoff points for the tests, when used independently rather than collectively, did not help to predict excessive fetal growth in the presence of mild hyperglycemia. Conclusion: Decreasing the cutoff point for the 100-g OGTT (for fasting and 1, 2, and 3 hours) to the mean (75 mg/dL, 120 mg/dL, 113 mg/dL, and 97 mg/dL) in association with the GP (mean or mean plus 1 SD-78 mg/dL and 92 mg/dL for the fasting state and 90 mg/dL and 130 mg/dL for 1- or 2-hour postprandial values-increased the sensitivity and specificity, and both criteria had statistically significant predictive power for detection of excessive fetal growth. © 2008 AACE.

Effect of Growth Hormone (GH) on Fasting and Postprandial Metabolism in GH Deficiency

Hypopituitarism with adult-onset growth hormone deficiency (GHD) is associated with increased cardiovascular morbidity and mortality due to premature and progressive atherosclerosis. An underlying cause of atherosclerosis is increased insulin resistance. Elevated fasting and postprandial glucose and lipid levels may contribute to premature atherosclerosis. We studied effects of growth hormone replacement (GHRT) on fasting and postprandial metabolic parameters as well as on insulin sensitivity in patients with adult-onset GHD.

Influence of time point of calibration on accuracy of continuous glucose monitoring in individuals with type 1 diabetes

Abstract Background and Aims: Data on the influence of calibration on accuracy of continuous glucose monitoring (CGM) are scarce. The aim of the present study was to investigate whether the time point of calibration has an influence on sensor accuracy and whether this effect differs according to glycemic level. Subjects and Methods: Two CGM sensors were inserted simultaneously in the abdomen on either side of 20 individuals with type 1 diabetes. One sensor was calibrated predominantly using preprandial glucose (calibration(PRE)). The other sensor was calibrated predominantly using postprandial glucose (calibration(POST)). At minimum three additional glucose values per day were obtained for analysis of accuracy. Sensor readings were divided into four categories according to the glycemic range of the reference values (low, ≤4 mmol/L; euglycemic, 4.1-7 mmol/L; hyperglycemic I, 7.1-14 mmol/L; and hyperglycemic II, >14 mmol/L). Results: The overall mean±SEM absolute relative difference (MARD) between capillary reference values and sensor readings was 18.3±0.8% for calibration(PRE) and 21.9±1.2% for calibration(POST) (P<0.001). MARD according to glycemic range was 47.4±6.5% (low), 17.4±1.3% (euglycemic), 15.0±0.8% (hyperglycemic I), and 17.7±1.9% (hyperglycemic II) for calibration(PRE) and 67.5±9.5% (low), 24.2±1.8% (euglycemic), 15.5±0.9% (hyperglycemic I), and 15.3±1.9% (hyperglycemic II) for calibration(POST). In the low and euglycemic ranges MARD was significantly lower in calibration(PRE) compared with calibration(POST) (P=0.007 and P<0.001, respectively). Conclusions: Sensor calibration predominantly based on preprandial glucose resulted in a significantly higher overall sensor accuracy compared with a predominantly postprandial calibration. The difference was most pronounced in the hypo- and euglycemic reference range, whereas both calibration patterns were comparable in the hyperglycemic range.

Consistent reduction of postprandial glucagon and insulin by lixisenatide in the GetGoal clinical trial programme

Background and aims: Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in subjects with type 2 diabetes mellitus. We evaluated 2-hour glucose, glucagon and insulin changes following a standardized mixed-meal tolerance test before and after 24 weeks of treatment with the once-daily prandial GLP-1 receptor agonist lixisenatide (approved for a therapeutic dose of 20 μg once daily) in six randomized, placebo-controlled studies within the lixisenatide Phase III GetGoal programme. In the studies, the mixed-meal test was conducted before and after: (1) lixisenatide treatment in patients insufficiently controlled despite diet and exercise (GetGoal-Mono), (2) lixisenatide treatment in combination with oral antidiabetic drugs (OADs) (GetGoal-M and GetGoal-S), or (3) lixisenatide treatment in combination with basal insulin ± OAD (GetGoal-Duo 1, GetGoal-L and GetGoal-L-Asia).Materials and methods: A meta-analysis was performed (lixisenatide n=1124 vs placebo n=707) combining ANCOVA least squares (LS) mean values using an inverse variance weighted analysis. Results: Lixisenatide significantly reduced 2-hour postprandial glucose from baseline (LS mean difference vs placebo: -4.9 mmol/L, p<0.0001, Figure) and glucose excursions (LS mean difference vs placebo: -4.5 mmol/L, p<0.0001). As measured in two studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs placebo: -19.0 ng/L, p<0.0001) and insulin (LS mean difference vs placebo: -64.8 pmol/L, p<0.0001), although the glucagon/insulin ratio was increased (LS mean difference vs placebo: 0.15, p=0.02) compared with placebo. Conclusion: The results show that lixisenatide potently reduces the glucose excursion after meal ingestion in subjects with type 2 diabetes, in association with marked reductions in glucagon and insulin levels. It is suggested that diminished glucagon secretion and slower gastric emptying contribute to reduced hepatic glucose production and delayed glucose absorption, enabling postprandial glycaemia to be controlled with less demand on beta-cell insulin secretion. Clinical Trial Registration Number: NCT00688701; NCT00712673; NCT00713830; NCT00975286; NCT00715624; NCT00866658 Supported by: Sanofi

Estimating cardiovascular risk in patients with type 2 diabetes: a national multicenter study in Brazil

According to Brazilian National Data Survey diabetes is the fifth cause for hospitalization and is one of the ten major causes of mortality in this country. Aims to stratify the estimated cardiovascular risk (eCVR) in a population of type 2 diabetics (T2DM) according to the Framingham prediction equations as well as to determine the association between eCVR with metabolic and clinical control of the disease. Methods From 2000 to 2001 a cross-sectional multicenter study was conducted in 13 public out-patients diabetes/endocrinology clinics from 8 Brazilian cities. The 10-year risk of developing coronary heart disease (CHD) was estimated by the prediction equations described by Wilson et al (Circulation 1998). LDL equations were preferably used; when patients missed LDL data we used total cholesterol equations instead. Results Data from 1382 patients (59.0% female) were analyzed. Median and inter-quartile range (IQ) of age and duration of diabetes were 57.4 (51-65) and 8.8 (3-13) years, respectively without differences according to the gender. Forty-two percent of these patients were overweight and 35.4% were obese (the prevalence of higher BMI and obesity in this T2DM group was significantly higher in women than in men; p < 0.001). The overall estimated eCVR in T2DM patients was 21.4 (13.5-31.3). The eCVR was high (> 20%) in 738 (53.4%), intermediate in 202 (14.6%) and low in 442 (32%) patients. Men [25.1(15.4-37.3)] showed a higher eCVR than women [18.8 (12.4-27.9) p < 0.001]. The most common risk factor was high LDL-cholesterol (80.8%), most frequently found in women than in men (p = 0.01). The median of risk factors present was three (2-4) without gender differences. Overall we observed that 60 (4.3%) of our patients had none, 154(11.1%) one, 310 (22.4%) two, 385 (27.9%) three, 300 (21.7%) four, 149 (10.5%) five and six, (2%) six risk factors. A higher eCVR was noted in overweight or obese patients (p = 0.01 for both groups). No association was found between eCVR with age or a specific type of diabetes treatment. A correlation was found between eCVR and duration of diabetes (p < 0.001), BMI (p < 0.001), creatinine (p < 0.001) and triglycerides levels (p < 0.001) but it was not found with HbA1c, fasting blood glucose and postprandial glucose. A higher eCVR was observed in patients with retinopathy (p < 0.001) and a tendency in patients with microalbuminuria (p = 0.06). Conclusion: our study showed that in this group of Brazilian T2DM the eCVR was correlated with the lipid profile and it was higher in patients with microvascular chronic complications. No correlation was found with glycemic control parameters. These data could explain the failure of intensive glycemic control programs aiming to reduce cardiovascular events observed in some studies.

Placental growth hormone (GH), GH-binding protein, and insulin-like growth factor axis in normal, growth-retarded, and diabetic pregnancies: Correlations with fetal growth

We previously described significant changes in GH-binding protein (GHBP) in pathological human pregnancy. There was a substantial elevation of GHBP in cases of noninsulin-dependent diabetes mellitus and a reduction in insulin-dependent diabetes mellitus. GHBP has the potential to modulate the proportion of free placental GH (PGH) and hence the impact on the maternal GH/insulin-like growth factor I (IGF-I) axis, fetal growth, and maternal glycemic status. The present study was undertaken to investigate the relationship among glycemia, GHBP, and PGH during pregnancy and to assess the impact of GHBP on the concentration of free PGH. We have extended the analysis of specimens to include measurements of GHBP, PGH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), IGFSP-2, and IGFBP-3 and have related these to maternal characteristics, fetal growth, and glycemia. The simultaneous measurement of GHBP and PGH has for the first time allowed calculation of the free component of PGH and correlation of the free component to indexes of fetal growth and other endocrine markers. PGH, free PGH, IGF-I, and IGF-II were substantially decreased in IUGR at 28-30 weeks gestation (K28) and 36-38 weeks gestation (K36). The mean concentration (+/-SEM) of total PGH increased significantly from K28 to K36 (30.0 +/- 2.2 to 50.7 +/- 6.2 ng/mL; n = 40), as did the concentration of free PGH (23.4 +/- 2.3 to 43.7 +/- 6.0 ng/mL; n = 38). The mean percentage of free PGH was significantly less in IUGR than in normal subjects (67% vs. 79%; P < 0.01). Macrosomia was associated with an increase in these parameters that did not reach statistical significance. Multiple regression analysis revealed that PGH/IGF-I and IGFBP-5 account for 40% of the variance in birth weight. IGFBP-3 showed a significant correlation with IGF-I, IGF-II, and free and total PGK at K28 and K36. Noninsulin-dependent diabetes mellitus patients had a lower mean percentage of free PGH (65%; P < 0.01), and insulin-dependent diabetics had a higher mean percentage of free PGH (87%; P < 0.01) than normal subjects. Mean postprandial glucose at K28 correlated positively with PGH and free PGH (consistent with the hyperglycemic action of GH). GHBP correlated negatively with both postprandial and fasting glucose. Although GHBP correlated negatively with PGH (r = -0.52; P

Tube feeding with a diabetes-specific feed for 12 weeks improves glycaemic control in type 2 diabetes patients

Background and aims: Assess longer-term (12 weeks) effects of a diabetes-specific feed on postprandial glucose response, glycaemic control (HbA1c), lipid profile, (pre)-albumin, clinical course and tolerance in diabetic patients. Methods: In this randomized, controlled, double-blind, parallel group study 25 type 2 diabetic patients on tube feeding were included. Patients received a soy-protein based, multi-fibre diabetes-specific feed or isocaloric, fibre-containing standard feed for 12 weeks, while continuing on their anti-diabetic medication. At the beginning, after 6 and 12 weeks, several (glycaemic) parameters were assessed. Results: The postprandial glucose response (iAUC) to the diabetes-specific feed was lower at the 1st assessment compared with the standard feed (p = 0.008) and this difference did not change over time. HbA1c decreased over time in the diabetes-specific and not in the standard feed group (treatment*time:p = 0.034): 6.9 +/- 0.3% (mean +/- SEM) at baseline vs. 6.2 +/- 0.4% at 12 weeks in the diabetes-specific group compared to 7.9 +/- 0.3% to 8.7 +/- 0.4% in the standard feed group. No significant treatment*time effect was found for fasting glucose, insulin, (pre-) albumin or lipid profile, except for increase of HDL in the diabetes-specific group. Conclusions: The diabetes-specific feed studied significantly improved longer-term glycaemic control in diabetic patients. This was achieved in addition to on-going anti-diabetic medication and may affect clinical outcome. (C) 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.

Female alcoholics: electrocardiographic changes and associated metabolic and electrolytic disorders

OBJECTIVE: To identify the electrocardiographic changes and their associations with metabolic and electrolytic changes in female alcoholics. METHODS: The study comprised 44 female alcoholics with no apparent physical disorder. They underwent the following examinations: conventional electrocardiography; serologic tests for syphilis, Chagas' disease, and hepatitis B and C viruses; urinary pregnancy testing; hematimetric analysis; biochemical measurements of albumin, fibrinogen, fasting and postprandial glycemias, lipids, hepatic enzymes, and markers for tissue necrosis and inflammation. RESULTS: Some type of electrocardiographic change was identified in 33 (75%) patients. In 17 (38.6%) patients, more than one of the following changes were present: prolonged QTc interval in 24 (54.5%), change in ventricular repolarization in 11(25%), left ventricular hypertrophy in 6 (13.6%), sinus bradycardia in 4 (9.1%), sinus tachycardia in 3 (6.8%), and conduction disorder in 3 (6.8%). The patients had elevated mean serum levels of creatine phosphokinase, aspartate aminotransferases, and gamma glutamyl transferase, as well as hypocalcemia and low levels of total cholesterol and LDL-cholesterol. The patients with altered electrocardiograms had a more elevated age, a lower alcohol consumption, hypopotassemia, and significantly elevated levels of triglycerides, postprandial glucose, sodium and gamma glutamyl transferase than those with normal electrocardiograms. The opposite occurred with fasting glycemia, magnesium, and alanine aminotransferase. CONCLUSION: The electrocardiographic changes found were prolonged QTc interval, change in ventricular repolarization, and left ventricular hypertrophy. Patients with normal and abnormal electrocardiograms had different metabolic and electrolytic changes.

Glucagon-like peptide-1 and control of insulin secretion.

Although glucose is the major regulator of insulin secretion by pancreatic beta cells, its action is modulated by several neural and hormonal stimuli. In particular, hormones secreted by intestinal endocrine cells stimulate glucose-induced insulin secretion very potently after nutrient absorption. These hormones, called gluco-incretins or insulinotropic hormones, are major regulators of postprandial glucose homeostasis. The main gluco-incretins are GIP (gastric inhibitory polypeptide or glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like polypeptide-1). The secretion of GIP, a 42 amino acid polypeptide secreted by duodenal K cells, is triggered by fat and glucose. GIP stimulation of insulin secretion depends on the presence of specific beta-cell receptors and requires glucose at a concentration at least equal to or higher than the normoglycaemic level of approximately 5 mM. GIP accounts for about 50% of incretin activity, and the rest may be due to GLP-1 which is produced by proteolytic processing of the preproglucagon molecule in intestinal L cells. GLP-1 is the most potent gluco-incretin characterized so far. As with GIP, its stimulatory action requires a specific membrane receptor and normal or elevated glucose concentrations. Contrary to GIP, the incretin effect of GLP-1 is maintained in non-insulin-dependent diabetic patients. This peptide or agonists of its beta-cell receptor could provide new therapeutic tools for the treatment of Type II diabetic hyperglycaemia.

Improving interMediAte Risk management. MARK study

Background: Cardiovascular risk functions fail to identify more than 50% of patients who develop cardiovascular disease. This is especially evident in the intermediate-risk patients in which clinical management becomes difficult. Our purpose is to analyze if ankle-brachial index (ABI), measures of arterial stiffness, postprandial glucose, glycosylated hemoglobin, self-measured blood pressure and presence of comorbidity are independently associated to incidence of vascular events and whether they can improve the predictive capacity of current risk equations in the intermediate-risk population. Methods/Design: This project involves 3 groups belonging to REDIAPP (RETICS RD06/0018) from 3 Spanish regions. We will recruit a multicenter cohort of 2688 patients at intermediate risk (coronary risk between 5 and 15% or vascular death risk between 3-5% over 10 years) and no history of atherosclerotic disease, selected at random. We will record socio-demographic data, information on diet, physical activity, comorbidity and intermittent claudication. We will measure ABI, pulse wave velocity and cardio ankle vascular index at rest and after a light intensity exercise. Blood pressure and anthropometric data will be also recorded. We will also quantify lipids, glucose and glycosylated hemoglobin in a fasting blood sample and postprandial capillary glucose. Eighteen months after the recruitment, patients will be followed up to determine the incidence of vascular events (later follow-ups are planned at 5 and 10 years). We will analyze whether the new proposed risk factors contribute to improve the risk functions based on classic risk factors. Discussion: Primary prevention of cardiovascular diseases is a priority in public health policy of developed and developing countries. The fundamental strategy consists in identifying people in a high risk situation in which preventive measures are effective and efficient. Improvement of these predictions in our country will have an immediate, clinical and welfare impact and a short term public health effect