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Alexander Tenenbaum

Publications and source records attributed to Alexander Tenenbaum.

At least 37 records · Page 2Linked to original sources
PubMed2004

Which is the best lipid-modifying strategy in metabolic syndrome and diabetes: fibrates, statins or both?

Although less clinical intervention studies have been performed with fibrates than with statins, there are evidences indicating that fibrates may reduce risk of cardiovascular events. The potential clinical benefit of the fenofibrate will be specified by the ongoing Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, which rationale, methods and aims have been just published. Controlled clinical trials show similar or even greater cardiovascular benefits from statins-based therapy in patient subgroups with diabetes compared with overall study populations. Therefore, statins are the drug of first choice for aggressive lipid lowering actions and reducing risk of coronary artery disease in these patients. However, current therapeutic use of statins as monotherapy is still leaving many patients with mixed atherogenic dyslipidemia at high risk for coronary events. A combination statin/fibrate therapy may be often necessary to control all lipid abnormalities in patients with metabolic syndrome and diabetes adequately, since fibrates provide additional important benefits, particularly on triglyceride and HDL-cholesterol levels. Thus, this combined therapy concentrates on all the components of the mixed dyslipidemia that often occurs in persons with diabetes or metabolic syndrome, and may be expected to reduce cardiovascular morbidity and mortality. Safety concerns about some fibrates such as gemfibrozil may lead to exaggerate precautions regarding fibrate administration and therefore diminish the use of the seagents. However, other fibrates, such as bezafibrate and fenofibrate appear to be safer and better tolerated. We believe that a proper co-administration of statins and fibrates, selected on basis of their safety, could be more effective in achieving a comprehensive lipid control as compared with monotherapy.

Editorial↗
PubMed2004

Peroxisome proliferator-activated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease.

BACKGROUND: Recent studies have shown that type 2 diabetes is preventable by both lifestyle interventions and medications that influence primary glucose metabolism. Whether pharmacological interventions that influence primary lipid metabolism can also delay development of type 2 diabetes is unknown. The goal of this study was to evaluate the effect of the peroxisome proliferator-activated receptor ligand bezafibrate on the progression of impaired fasting glucose phase to type 2 diabetes in patients with coronary artery disease over a 6.2-year follow-up period. METHODS AND RESULTS: The study sample comprised 303 nondiabetic patients 42 to 74 years of age with a fasting blood glucose level of 110 to 125 mg/dL (6.1 to 6.9 mmol/L). The patients received either 400 mg bezafibrate retard (156 patients) or placebo (147 patients) once a day. No patients were using statins, and use of ACE inhibitors, which also reduce diabetes incidence, was relatively low. During follow-up, development of new-onset diabetes was recorded in 146 patients: in 80 (54.4%) from the placebo group and 66 (42.3%) from the bezafibrate group (P=0.04). The mean time until onset of new diabetes was significantly delayed in patients on bezafibrate compared with patients on placebo: 4.6+/-2.3 versus 3.8+/-2.6 years (P=0.004). Multivariate analysis identified bezafibrate treatment as an independent predictor of reduced risk of new diabetes development (hazard ratio, 0.70; 95% CI, 0.49 to 0.99). Other significant variables associated with future overt type 2 diabetes in patients with impaired fasting glucose were total cholesterol level (hazard ratio, 1.22; 95% CI 1.0 to 1.51) and body mass index (hazard ratio, 1.10; 95% CI, 1.05 to 1.16). CONCLUSIONS: Bezafibrate reduces the incidence and delays the onset of type 2 diabetes in patients with impaired fasting glucose. Whether the combination of bezafibrate with other recommended drugs for secondary prevention (statins and ACE inhibitors) would be as efficacious as suggested by our results remains to be determined.

Aged↗
PubMed2004

Oral antidiabetic therapy in patients with heart disease. A cardiologic standpoint.

Five types of oral antihyperglycemic drugs are currently approved for the treatment of diabetes: biguanides, sulfonylureas, meglitinides, glitazones, and alpha-glucosidase inhibitors. The cardiovascular effects of the most commonly used antidiabetic drugs in these groups are briefly reported, in an attempt to improve knowledge and awareness regarding their influences and potential risks when treating patients with coronary artery disease (CAD). Regarding biguanides, gastrointestinal disturbances such as diarrhea are frequent, and the intestinal absorption of group B vitamins and especially folate is impaired during chronic therapy. This deficiency may lead to increased plasma homocysteine levels which, in turn, accelerate the progression of vascular disease due to adverse effects on platelets, clotting factors, and endothelium. The existence of a graded association between homocysteine levels and overall mortality in patients with CAD is well established. In addition, metformin may lead to lethal lactic acidosis, especially in patients with clinical conditions that predispose to this complication, such as heart failure or recent myocardial infarction. Sulfonylureas avoid ischemic preconditioning. During myocardial ischemia, they may prevent the opening of the ATP-dependent potassium channels, impeding the necessary hyperpolarization that protects the cell by blocking calcium influx. Meglitinides may exert similar effects, due to their analogous mechanism of action. During treatment with glitazones, edema has been reported in 5% of patients, and these drugs are contraindicated in diabetics with NYHA class III or IV cardiac status. The long-term effects of alpha-glucosidase inhibitors on morbidity and mortality rates and on diabetic micro- and macrovascular complications are yet unknown. The combined sulfonylurea/metformin therapy reveals additive effects on mortality. It is concluded that(1) four of the five oral antidiabetic drug groups present proven or potential cardiac hazards;(2) these hazards are not mere "side effects", but are deeply rooted in the drugs' mechanism of action;(3) current data indicate that the combined glibenclamide/metformin therapy seems to present special risk and should be avoided in the long-term management of type 2 diabetics with proven CAD; and(4) customized antihyperglycemic pharmacological approaches should be investigated for optimal treatment of diabetic patients with heart disease.

Administration, Oral↗
PubMed2004

Spiral computed tomography evidence of close correlation between coronary and thoracic aorta calcifications.

UNLABELLED: Coronary calcium (CC) is invariably associated with coronary atherosclerosis and can be diagnosed noninvasively by fast spiral computed tomography (dual slice mode) (CT). Calcium is often deposited in the aorta as well, but the pathogenesis, correlates and clinical implications of calcification of the aorta are not yet elucidated. A possible association between the presence of CC and thoracic aorta calcification, as detected by spiral CT, has not been investigated yet. The goal of the present work was to examine by spiral CT whether an association exists between the presence of CC and thoracic aorta calcification in patients with high risk for atherosclerotic development. Four hundred and five patients with at least two risk factors for atherosclerosis were included (212 men and 193 women, age ranged 52-79 years). All underwent chest CT for CC and aortic calcification scoring. Calcifications' thickness of > or =5 mm was considered advanced. CC was documented in 294 patients (170 men, 124 women; mean age 66 +/- 6 years, range 55-78 years). The non-CC group (control) included 111 patients (42 men, 69 women; mean age 64 +/- 6 years, range 52-79 years). Significant differences were found between CC group and control for the presence of ascending aorta calcification (69% versus 36%, P < 0.001), and advanced calcification of > or =5mm (17% versus 4%, P < 0.001). Significant differences were also found between groups regarding the presence of descending aorta calcification (60% versus 38%, P < 0.001), and number of consecutive slices with calcification (18.8 +/- 12.4 versus 10.7 +/- 8.7, P < 0.01). We identified age (in decades) (OR 1.9, 95% CI 1. 2-3.0, P < 0.001), gender (female) (OR 0.4, 95% CI 0.2-0.6, P < 0.001), and thoracic aorta calcification (OR 2.9, 95% CI 1.7-5.0, P < 0.001) as the independent variables significantly associated with CC. Only age [odds ratio (OR) 3.05, 95% confidence interval (CI) 1.86-5.01, P < 0.001] and CC (OR 2.53, 95% CI 1.26-5.08, P = 0.006) were identified as independent variables for the prediction of thoracic aorta calcification. CONCLUSIONS: Our study demonstrated a strong association of CC and calcification of the thoracic aorta on spiral CT.

Aged↗
PubMed2004

Aortic valve calcification in hypertensive patients: prevalence, risk factors and association with transvalvular flow velocity.

BACKGROUND: The important role of the "nonobstructive" aortic valve calcification (AVC) in cardiovascular morbidity and mortality has recently been emphasized. The present work had two goals: (1) to analyze the prevalence and factors determining the extent of AVC in hypertensive patients; (2) to investigate a possible association between the extent of AVC and flow velocity across the aortic valve. METHODS: This was a prospective study performed in a university hospital. The sample included 263 consecutive patients (139 men and 124 women), mean age 65+/-6, who underwent echo-Doppler. The upper quartile of peak flow velocity across the aortic valve (>130 mm/s in our population) was defined as augmented flow velocity. RESULTS: There were 31 (12%) patients in the advanced AVC group and 122 (46%) without any calcified deposits (the no AVC group). The remaining 110 (42%), who did not meet criteria for advanced AVC, comprised the trivial AVC group. Peak flow velocity was significantly higher in patients with advanced vs. trivial AVC and no AVC groups: 135+/-45, 116+/-23 and 113+/-23 cm/s, respectively; p=0.0002. Prevalence of augmented transvalvular aortic flow was significantly higher (p=0.01) among patients with advanced AVC (41.9%) vs. trivial (20.9%) and no AVC (20.5%). Multivariate analyses identified age as the only independent variable associated with advanced AVC [OR 1.6 (CI 1.2-2.3), 5 years increment]. Advanced AVC and female gender were identified as independent variables for augmented transvalvular aortic flow with OR 2.9 (CI 1.3-6.4) and 2.5 (CI 1.4-4.6), respectively. CONCLUSIONS: Prevalence of AVC among hypertensive patients is high and clearly age-related. Female gender and advanced (but not trivial) AVC are associated with augmented aortic transvalvular peak flow. Our results stress the role of protruding calcium deposits in augmentation of rest flow velocity across the aortic valve regardless of visible restriction of leaflet opening.

Age Factors↗
PubMed2004

Macrovascular complications of metabolic syndrome: an early intervention is imperative.

The metabolic syndrome is a widespread clinical condition and an important cluster of atherothrombotic disease risk factors. The inclusion of this syndrome in the recently published Adult Treatment Panel III (ATP III) guidelines focused the attention of the physicians on this entity. Abdominal obesity, PPAR modulation, insulin resistance (with or without glucose intolerance), atherogenic dyslipidemia, elevated blood pressure, prothrombotic and proinflammatory states are the principal factors of this multifaceted syndrome. There are two major pathways of metabolic syndrome progress: (1) With preserved pancreatic beta cells function and insulin hypersecretion, which can recompense for insulin resistance. This pathway leads mostly to the macrovascular complications of metabolic syndrome. (2) With substantial injure of pancreatic beta cells leading to gradually reduced insulin secretion and to hyperglycemia (e.g. overt type 2 diabetes). This pathway leads to both microvascular and macrovascular complications. Because macrovascular complications of insulin resistance state precede the onset of hyperglycemia, early intervention in patients with metabolic syndrome is particularly important. Since central obesity (accompanied by insulin resistance even in the absence of hyperglycemia) is the key factor leading to development of metabolic syndrome and its future macrovascular complications, we assume that next logical step is the recognition of central obesity itself as a major risk factor for cardiovascular diseases.

Adult↗
PubMed2004

Ischemic preconditioning: nearly two decades of research. A comprehensive review.

The phenomenon of "ischemic preconditioning" has been recognized for almost two decades. In experimental animals and humans, a brief period of ischemia has been shown to protect the heart from more prolonged episodes of ischemia, and reduce the degree of impaired ventricular function or subsequent damage. Ischemic preconditioning is classified into two distinct components: the classic early preconditioning and the delayed or late preconditioning, each with its own biologic mechanism of adaptation. A comprehensive understanding of these mechanisms and application to clinical scenarios has the promise of providing unique opportunities, particularly regarding the development of preconditioning mimetic agents. Administration of these mimetic drugs or procedures could potentially advance the use of preconditioning as a therapeutic tool and/or preventive factor for cardiovascular disease.

Animals↗
PubMed2004

Coronary calcium by spiral computed tomography predicts cardiovascular events in high-risk hypertensive patients.

OBJECTIVE: The ability of coronary artery calcium (CAC) to predict coronary events has been shown in several studies. We aimed to investigate the hypothesis that CAC as assessed by dual slice spiral computed tomography (DSCT), is an independent risk factor for cardiovascular events in hypertensive patients. METHODS: We followed 446 participants of INSIGHT (International Nifedipine Study Intervention as Goal for Hypertension Therapy) calcification study, for the incidence of cardiovascular events as a function of CAC and other factors. All were hypertensive, without coronary artery disease (CAD), ages > 55 years and with at least one more major cardiovascular risk factor. All underwent a baseline DSCT and were followed for a mean period of 3.8 +/- 0.4 years. All events were documented while the scheduled visits and confirmed by the INSIGHT critical event committee. RESULTS: Follow-up was conducted on all participants. 294 patients (66%) had CAC at baseline. Forty-seven patients experienced a first cardiovascular event: acute myocardial infarction (MI), 16; sudden cardiac death, two; unstable angina resulting in revascularization, 14; stroke, 15. The incidence of first cardiovascular events was 3.7 times higher among those who had CAC at baseline than among those who had no CAC (14.5% (41 of 294) versus 3.9% (6 of 152)). Patients who experienced an event were more likely to be males, had had higher prevalence of peripheral vascular disease, longer duration of hypertension, and had higher levels of systolic blood pressure (SBP), glucose, creatinine and uric acid. Adjusting for these covariates, CAC (total coronary calcium score (TCS) > 0) independently predicted cardiovascular events with an odds ratio (OR) of 2.76 [95% confidence interval (CI) 1.09-6.99, P = 0.032]. CONCLUSION: The presence of CAC predicts cardiovascular events in high-risk asymptomatic hypertensive patients.

Aged↗
PubMed2004

Is hypoglycaemia a marker for increased long-term mortality risk in patients with coronary artery disease? An 8-year follow-up.

BACKGROUND: No information is available regarding the association between low plasma glucose levels and cause-specific and all-cause mortality in patients with coronary artery disease (CAD). We aimed to investigate the relationship between hypoglycaemia and all-cause, cardiovascular and cancer mortality in a large population of patients with CAD. DESIGN: Patients were recruited from the BIP (Bezafibrate Infarction Prevention) registry, a secondary prevention prospective multicentre randomized, placebo-controlled, double-blind trial aimed to assess the efficacy of bezafibrate in reduction of coronary events. METHODS: The study included 14,670 CAD patients aged 45-74, divided into six groups: (1) hypoglycaemic (up to 69 mg/dl); (2) low normal (70-79 mg/dl); (3) euglycaemic (80-109 mg/dl); (4) impaired fasting glucose (IFG) (110-125 mg/dl); (5) borderline diabetics (126-139 mg/dl); (6) diabetics (> or 140 mg/dl). RESULTS: Patients comprised 131 with hypoglycaemia (0.9%), 731 with low normal glucose (5%), 9308 euglycaemic (63.4%), 1577 with IFG (10.7%), 617 borderline diabetics (4.2%) and 2306 diabetics (15.7%). Over a mean 8-year follow-up, crude all-cause mortality was higher in both diabetic (31.8%) and hypoglycaemic groups (25.2%) as compared with euglycaemics (14.9%; P<0.0001); CAD mortality was higher in diabetic and borderline groups (17.8 and 13.3%, respectively, versus 7.9% in euglycaemics; P<0.0001). The highest prevalence of cancer mortality was documented in the hypoglycaemic group (6.1 versus 2.9% in euglycaemics; P<0.02). Actuarial survival curves showed the lowest mortality in euglycaemic and low normal groups; the highest was seen in diabetic and hypoglycaemic patients. Intermediate values were found in borderline and IFG patients. After adjustment for variables, a significantly higher mortality rate was seen in hypoglycaemics when compared with euglycaemics (P<0.0001). Hypoglycaemia was identified as a predictor of increased all-cause and cancer mortality with a hazard ratio (HR) of 1.84 [95% confidence interval (CI) 1.29-2.61] and 2.26 (95% CI 1.12-4.57), respectively, but not of increased CAD mortality, with HR 1.30 (95% CI 0.73-2.29). CONCLUSIONS: Over a mean 8-year follow-up, hypoglycaemia emerges as a marker for substantially increased all-cause and cancer mortality among patients with CAD presenting with low fasting glucose levels.

Aged↗
PubMed2004

Impaired glucose metabolism in patients with heart failure: pathophysiology and possible treatment strategies.

The firm association of diabetes mellitus with congestive heart failure (CHF) has been undoubtedly established. Recent reports support the presence of the reciprocal interrelationships between CHF and glucose abnormalities. The present review provides an overview of some aspects of the multifactorial interrelationships between heart failure and diabetes mellitus. Patients with heart failure are generally at higher risk of developing type 2 diabetes mellitus. Several factors may be involved, such as a lack of physical activity, hypermetabolic state, intracellular metabolic defects, poor muscle perfusion, and poor nutrition. Serum levels of inflammatory cytokines and leptin are elevated in patients with heart failure. Activation of the sympathetic system in CHF not only increases insulin resistance but also decreases the release of insulin from the pancreatic beta cells, increases hepatic glucose production by stimulating both gluconeogenesis and glycogenolysis, and increases glucagon production and lipolysis. People who develop type 2 diabetes mellitus usually pass through the phases of nuclear peroxisome proliferator-activated receptor modulation, insulin resistance, hyperinsulinemia, pancreatic beta-cell stress and damage leading to progressively decreasing insulin secretion, and impaired fasting and postprandial blood glucose levels. Once hyperglycemia ensues, the risk of metabolic and cardiovascular complications also increases. It is possible that the cornerstone of diabetes mellitus prevention in patients with CHF could be controlled by increased physical activity in a cardiac rehabilitation framework. Pharmacologic interventions by some medications (metformin, orlistat, ramipril and acarbose) can also effectively delay progression to type 2 diabetes mellitus in general high risk populations, but the magnitude of the benefit in patients with CHF is unknown. In patients with CHF and overt diabetes mellitus, ACE inhibitors may provide a special advantage and should be the first-line agent. Recent reports have suggested that angiotensin receptor antagonists (angiotensin receptor blockers), similar to ACE inhibitors, provide beneficial effects in patients with diabetes mellitus and should be the second-line agent if ACE inhibitors are contraindicated. Treatment with HMG-CoA reductase inhibitors should probably now be considered routinely for all diabetic patients with CHF, irrespective of their initial serum cholesterol levels, unless there is a contraindication.

Blood Glucose↗
PubMed2003

Increased prevalence of left ventricular hypertrophy in hypertensive women with type 2 diabetes mellitus.

BACKGROUND: Left ventricular hypertrophy (LVH) is a powerful independent risk factor for cardiovascular morbidity and mortality among hypertensive patients. Data regarding relationships between diabetes and LVH are controversial and inconclusive, whereas possible gender differences were not specifically investigated. The goal of this work was to investigate whether gender differences in left heart structure and mass are present in hypertensive patients with type 2 diabetes. METHODS: Five hundred fifty hypertensive patients with at least one additional cardiovascular risk factor (314 men and 246 women, age 52 to 81, mean 66 +/- 6 years), were enrolled in the present analysis. In 200 (36%) of them--108 men and 92 women--type 2 diabetes mellitus was found upon enrollment. End-diastolic measurements of interventricular septal thickness (IVS), LV internal diameter, and posterior wall thickness were performed employing two-dimensionally guided M-mode echocardiograms. LVH was diagnosed when LV mass index (LVMI) was > 134 g/m2 in men and > 110 g/m2 in women. RESULTS: Mean LVMI was significantly higher among diabetic vs. nondiabetic women (112.5 +/- 29 vs. 105.6 +/- 24, p = 0.03). In addition, diabetic women presented a significantly higher prevalence of increased IVS thickness, LVMI and left atrial diameter on intra-gender comparisons. The age adjusted relative risk for increased LVMI in diabetics vs. nondiabetics was 1.47 (95% CI: 1.0-2.2) in females and only 0.8 (0.5-1.3) in males. CONCLUSION: Type 2 diabetes mellitus was associated with a significantly higher prevalence of LVH and left atrial enlargement in hypertensive women.

Journal Article↗
PubMed2003

Quantumlike short-time behavior of a classical crystal.

We have performed a molecular-dynamics simulation of a face-centered-cubic Lennard-Jones crystal, and studied its relaxation toward equilibrium and its microcanonical equilibrium dynamics through the computation of the normal modes. At low temperature, the weak interaction among normal modes yields a very slow relaxation of the fluctuation of the kinetic energy; this requires a new formulation of the measure of the microcanonical specific heat at constant volume. This specific heat turns out to depend on the time of observation; for times of the order of 20 ps, its values are much nearer to the quantum ones than to the value 3R predicted by the classical Dulong and Petit law. For longer observation times, the classical specific heat progressively approaches 3R over most of the temperature range of the solid crystal, with the exception of the lowest temperature range, where it still drops to values close to zero. The time dependence of the specific heat of the crystal is similar to the behavior found in a supercooled liquid near the glass transition.

Journal Article↗
PubMed2003

Current smoking, smoking cessation, and the risk of sudden cardiac death in patients with coronary artery disease.

BACKGROUND: Cigarette smoking is a known risk factor for sudden cardiac death (SCD). However, the effect of continued cigarette smoking and smoking cessation on SCD risk in patients with established coronary artery disease (CAD) is subject to controversy. We, therefore, evaluated the effect of cigarette smoking on SCD risk in a large cohort of patients with established CAD. METHODS: The study population was composed of 3122 patients with a previous myocardial infarction or stable angina who participated in the Bezafibrate Infarction Prevention Trial. Patients were prospectively followed up for a mean of 8.2 years. The primary end point was the incidence of SCD according to smoking status. RESULTS: Among the 370 patients who were current smokers, 30 (8.1%) experienced SCD; 83 (4.6%) of the 1821 patients who had quit smoking and 43 (4.6%) of the 931 patients who had never smoked experienced SCD (P =.01). In multivariate analyses, current smoking was associated with a significant increase in the risk of SCD (hazard ratio, 2.47; 95% confidence interval, 1.46-4.19). Patients who had stopped smoking had no significant increase in the risk of SCD compared with patients who had never smoked (hazard ratio, 1.06; 95% confidence interval, 0.70-1.62). CONCLUSIONS: Current cigarette smoking is a powerful independent predictor of SCD risk in patients with CAD. Patients who quit smoking experienced a significant reduction in SCD risk. Thus, efforts to reduce mortality from SCD in patients with CAD should include vigorous smoking cessation strategies.

Aged↗
PubMed2003

Cardiovascular diabetology in the core of a novel interleukins classification: the bad, the good and the aloof.

BACKGROUND: The impressive correlation between cardiovascular disease and glucose metabolism alterations has raised the likelihood that atherosclerosis and type 2 diabetes may share common antecedents. Inflammation is emerging as a conceivable etiologic mechanism for both. Interleukins are regulatory proteins with ability to accelerate or inhibit inflammatory processes. PRESENTATION OF THE HYPOTHESIS: A novel interleukins classification is described, based on their role in diabetes and atherosclerosis, hypothesizing that each interleukin (IL) acts on both diseases in the same direction--regardless if harmful, favorable or neutral. TESTING THE HYPOTHESIS: The 29 known interleukins were clustered into three groups: noxious (the "bad", 8 members), comprising IL-1, IL-2, IL-6, IL-7, IL-8, IL-15, IL-17 and IL-18; protective (the "good", 5 members), comprising IL-4, IL-10, IL-11, IL-12 and IL-13; and "aloof", comprising IL-5, IL-9, IL-14, IL-16 and IL-19 through IL-29 (15 members). Each group presented converging effects on both diseases. IL-3 was reluctant to clustering. IMPLICATIONS: These observations imply that 1) favorable effects of a given IL on either diabetes or atherosclerosis predicts similar effects on the other; 2) equally, harmful IL effects on one disease can be extrapolated to the other; and 3) absence of influence of a given IL on one of these diseases forecasts lack of effects on the other. These facts further support the unifying etiologic theory of both ailments, emphasizing the importance of a cardiovascular diabetologic approach to interleukins for future research. Pharmacologic targeting of these cytokines might provide an effective means to simultaneously control both atherosclerosis and diabetes.

Journal Article↗
PubMed2003

Metabolic syndrome and type 2 diabetes mellitus: focus on peroxisome proliferator activated receptors (PPAR).

The metabolic syndrome is a highly prevalent clinical entity. The recent Adult Treatment Panel (ATP III) guidelines have called specific attention to the importance of targeting the cardiovascular risk factors of the metabolic syndrome as a method of risk reduction therapy. The main factors characteristic of this syndrome are abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, insulin resistance (with or without glucose intolerance), prothrombotic and proinflammatory states. An insulin resistance following nuclear peroxisome proliferator activated receptors (PPAR) deactivation (mainly obesity-related) is the key phase of metabolic syndrome initiation. Afterwards, there are 2 principal pathways of metabolic syndrome development: 1) with preserved pancreatic beta cells function and insulin hypersecretion which can compensate for insulin resistance. This pathway leads mainly to the macrovascular complications of metabolic syndrome; 2) with massive damage of pancreatic beta cells leading to progressively decrease of insulin secretion and to hyperglycemia (e.g. overt type 2 diabetes). This pathway leads to both microvascular and macrovascular complications. We suggest that a PPAR-based appraisal of metabolic syndrome and type 2 diabetes may improve our understanding of these diseases and set a basis for a comprehensive approach in their treatment.

Journal Article↗
PubMed2003

Functional class in patients with heart failure is associated with the development of diabetes.

PURPOSE: Recent reports suggest that decreased functional capacity in patients with heart failure may be associated with abnormalities in glucose metabolism. We followed patients with coronary artery disease who participated in the Bezafibrate Infarction Prevention study to determine the incidence of diabetes by baseline functional status during a 7.7-year follow-up. METHODS: The sample comprised 2616 nondiabetic patients aged 45 to 74 years with a fasting blood glucose level <7 mmol/L (126 mg/dL). They were divided into three groups by New York Heart Association (NYHA) criteria: class I (n = 1986 patients), class II (n = 518), and class III (n = 112). The detection of a fasting blood glucose level > or =7 mmol/L during follow-up was defined as the criterion for the development of diabetes. RESULTS: The study groups had similar demographic and clinical characteristics, except that patients with symptomatic heart failure (NYHA class II or III) were more likely to have angina. During follow-up, diabetes developed in 259 patients (13%) in NYHA class I, 76 (15%) in class II, and 22 (20%) in class III (P for trend = 0.05). At the last visit, patients in NYHA class III were twice as likely (17% [n = 19]) to have fasting blood glucose levels > or =7 mmol/L as those in NYHA class I (7.8% [n = 154]) or class II (8.7% [n = 45]) (P = 0.005). In a multivariate analysis, NYHA class III was associated with a 1.7-fold (95% confidence interval [CI]: 1.1 to 2.6) increase in the rate of development of diabetes, but NYHA class II was not (hazard ratio = 1.0; 95% CI: 0.8 to 1.3). CONCLUSION: Among patients with coronary artery disease, advanced heart failure (NYHA class III) is associated with a significantly increased risk of developing diabetes during a 6- to 9-year follow-up.

Age Distribution↗