The cortisol burden in elderly subjects with metabolic syndrome and its association with low-grade inflammation.

BACKGROUND: Elderly people are exposed to an increased load of stressful events and neuro-hormonal stimulation is a key finding in metabolic syndrome and its related disorders. AIMS: To determine the role of cortisol in elderly subjects, with or without metabolic syndrome (MetS), by means of a national multicentre observational study, AGICO (AGIng and Cortisol). METHODS: From 2012 to 2017, the AGICO study enrolled n.339 subjects (aged > 65), after obtaining their informed consent. The investigators assessed a cardio-metabolic panel (including electrocardiogram, carotid ultrasonography and echocardiography), the presence of MetS (on Adult Treatment Panel III criteria), a neurological examination (including brain imaging), and cortisol activity (using a consecutive collection of diurnal and nocturnal urine). RESULTS: In the patients presenting with MetS, the standardized diurnal and nocturnal cortisol excretion rates were 210.7 ± 145.5 and 173.7 ± 118.1 (mean ± standard deviation) µg/g creatinine/12 h; in those without MetS, the standardized diurnal and nocturnal cortisol excretion rates were 188.7 ± 92.7 and 144.1 ± 82.3 µg/g creatinine/12 h, respectively (nocturnal urinary cortisol in patients with MetS versus those without MetS p = 0.05, female patients with MetS vs female patients without MetS, p < 0.025). A significant positive correlation was found between the CRP levels and both the diurnal and nocturnal urinary cortisol levels with r = 0.187 (p < 0.025) and r = 0.411 (p < 0.00000001), respectively. DISCUSSION: The elderly patients with MetS showed a trend towards increased standardized nocturnal cortisol excretions, with particular regard to the female subjects. CONCLUSION: The positive correlation between cortisol excretion and low-grade inflammation suggests a common mechanism driving both hormonal and inflammatory changes.

Similar prediction of total mortality, diabetes incidence and cardiovascular events using relative- and absolute-component Mediterranean diet score: the SUN cohort.

BACKGROUND AND AIM: Accumulated evidence supports the effectiveness of Mediterranean-type diets (MeDiet) in reducing mortality and preventing several chronic diseases. Widely used scores to assess adherence to MeDiet are based on specific sample characteristics; alternatively, they might be built according to absolute/normative cut-off points for the consumption of specific food groups (pre-defined servings/day or/week). The aim of this study was to compare sample-specific MeDiet adherence scores (MDS) versus absolute-normative scores (Mediterranean Diet Adherence Screener - MEDAS) on their association with macronutrient intake, total mortality and incidence of chronic diseases. DESIGN: SUN (Seguimiento Universidad de Navarra) dynamic prospective cohort study (60.5% women; mean age 38.4 years). METHODS AND RESULTS: In cross-sectional analyses (n=20,155) we evaluated macronutrient distribution according to MDS (based on 136-item FFQ), MEDAS (based on 13 questions), and variants of both. In prospective analyses (n=9109; mean follow-up: 6.2 years), we evaluated disease incidence or mortality. Adherence to MeDiet increased with age and, as expected, was associated with higher fiber intake, lower total fat intake but higher monounsaturated/saturated fat ratio, using all scores. Among subjects initially free of cancer, diabetes, and cardiovascular disease (CVD), adherence to MeDiet appraised with an absolute-normative score (MEDAS) similarly predicted macronutrient distribution and disease incidence or mortality (diabetes incidence, CVD or all-cause mortality), when compared to a sample-specific score based on 136-item FFQ (MDS). CONCLUSIONS: Adherence to MeDiet was associated with a decreased incidence of a composite outcome including diabetes incidence, cardiovascular events incidence or all-cause mortality.

Senile anorexia in different geriatric settings in Italy.

OBJECTIVES: Anorexia is the most frequent modification of eating habits in old age, which may lead to malnutrition and consequent morbidity and mortality in older adults. We aimed to estimate the prevalence and factors associated to anorexia in a sample of Italian older persons living in different settings. Our secondary aim was to evaluate the impact of senile anorexia on nutritional status and on eating habits, as well as on functional status. DESIGN AND SETTING: Observational study in nursing homes, in rehabilitation and acute geriatric wards, and in the community in four Italian regions (Lazio, Sicily, Emilia-Romagna, and Veneto). PARTICIPANTS: 526 over 65 years old participants were recruited; 218 free-living subjects, 213 from nursing homes, and 96 patients from rehabilitation and acute geriatric wards in the context of a National Research Project (PRIN) from the Italian Ministry of Instruction, University and Research (2005-067913 "Cause e Prevalenza dell'Anoressia senile"). MEASUREMENTS: Anthropometric and nutritional evaluation, olfactory, chewing, and swallowing capacity, food preferences, cognitive function, functional status, depression, quality of life, social aspects, prescribed drugs, and evaluation of gastrointestinal symptoms and pain. Laboratory parameters included prealbumin, albumin, transferrin, C-reactive protein, mucoprotein, lymphocyte count, as well as neurotransmitters leptin, and ghrelin. Anorexia was considered as ≥50% reduction in food intake vs. a standard meal (using 3-day "Club Francophone de Gériatrie et Nutrition" form), in absence of oral disorders preventing mastication. RESULTS: The overall prevalence of anorexia was 21.2% with higher values among hospitalized patients (34.1% women and 27.2% men in long-term facilities; 33.3% women and 26.7% men in rehabilitation and geriatric wards; 3.3% women and 11.3% men living in the community) and in the oldest persons. Anorexic subjects were significantly less self-sufficient and presented more often a compromised nutritional and cognitive status. Diet composition analyses of anorexic older adults revealed a lower intake of all food groups and a general tendency to a monotonous diet. CONCLUSION: Anorexia is a frequent condition in older Italians, particularly those hospitalized, with important consequences in the nutritional and functional status. The analysis of dietary components and its quality along with the frequency of intake of single food groups may be useful to plan intervention strategies aiming to improve the nutritional and health status of older adults with anorexia. An early detection of anorexia followed by an adequate intervention in older hospitalized patients to avoid further worsening of clinical and functional status is warranted.

Magnesium and anabolic hormones in older men.

Optimal nutritional and hormonal statuses are determinants of successful ageing. The age associated decline in anabolic hormones such as testosterone and insulin-like growth factor 1 (IGF-1) is a strong predictor of metabolic syndrome, diabetes and mortality in older men. Studies have shown that magnesium intake affects the secretion of total IGF-1 and increase testosterone bioactivity. This observation suggests that magnesium can be a modulator of the anabolic/catabolic equilibrium disrupted in the elderly people. However, the relationship between magnesium and anabolic hormones in men has not been investigated. We evaluated 399 ≥65-year-old men of CHIANTI in a study population representative of two municipalities of Tuscany (Italy) with complete data on testosterone, total IGF-1, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS) and serum magnesium levels. Linear regression models were used to test the relationship between magnesium and testosterone and IGF-1. Mean age of the population was 74.18 ± 6.43 (years ± SD, age range 65.2-92.4). After adjusting for age, magnesium was positively associated with total testosterone (ß ± SE, 34.9 ± 10.3; p = 0.001) and with total IGF-1 (ß ± SE, 15.9 ± 4.8; p = 0.001). After further adjustment for body mass index (BMI), log (IL-6), log (DHEAS), log (SHBG), log (insulin), total IGF-1, grip strength, Parkinson's disease and chronic heart failure, the relationship between magnesium and total testosterone remained strong and highly significant (ß ± SE, 48.72 ± 12.61; p = 0.001). In the multivariate analysis adjusted for age, BMI, log (IL-6), liver function, energy intake, log (insulin), log (DHEAS), selenium, magnesium levels were also still significantly associated with IGF-1 (ß ± SE, 16.43 ± 4.90; p = 0.001) and remained significant after adjusting for total testosterone (ß ± SE, 14.4 ± 4.9; p = 0.01). In a cohort of older men, magnesium levels are strongly and independently associated with the anabolic hormones testosterone and IGF-1.

Magnesium and aging.

Over the past decades, the clinical relevance and biological significance of magnesium (Mg) have been documented. Deficiency in Mg, aside from having a negative impact on the energy production pathway required by mitochondria to generate ATP, also reduces the threshold antioxidant capacity of the aging organism and its resistance to free-radical damage. Mg also acts as an antioxidant against free radical damage of the mitochondria. Chronic inflammation and oxidative stress have both been identified as pathogenic factors in aging and in several age-related diseases. Chronic Mg deficiency results in excessive production of oxygen-derived free radicals and low grade inflammation. Aging is very often associated with Mg inadequacy and with increased incidence of many chronic diseases, with muscle loss and sarcopenia, altered immune responses, and vascular and metabolic conditions, such as atherosclerosis, diabetes and the cardiometabolic syndrome. The most common cause of Mg deficit in the elderly population is dietary Mg deficiency, although secondary Mg deficit in aging may also results from many different mechanisms. The aim of the present manuscript is to discuss the mechanisms and consequences of the modifications of Mg metabolism with age, the difficulties in the measurement of Mg status, and to review the current evidences suggesting that age-related chronic Mg deficits may be proposed as one of the physiopathological links that may help to explain the interactions between inflammation, oxidative stress with the aging process and many age-related diseases.

Test-and-treat strategy for Helicobacter pylori (HP) infection in older patients.

UNLABELLED: Despite Helicobacter pylori (HP) infection is highly prevalent in older populations, low rates of HP diagnosis and eradication are reported in older persons, even in geriatric wards. We aim to evaluate the results of a HP-eradicating program in a sample of older patients in relation to dyspeptic symptoms and to endoscopic findings. A pool of 140 subjects (female/ale=86/54, mean age 68.6±5.4 years) with positive C(13)-urea breath test were recruited, clinically evaluated to investigate the presence and characteristics of dyspepsia and abdominal pain, and underwent gastric endoscopic examination. HP-eradication was obtained in 87.9% of subjects with first-line triple therapy, regardless of endoscopic findings. Sixty-eight (48.6%) patients were symptomatic and 72 (51.4%) were asymptomatic. HP-related organic disease in endoscopic examination was frequent (present in 53.6% of the patients) but the distribution of different pathologies were similar in patients with and without symptoms (p=0.86). CONCLUSIONS: even if diagnosis and treatment of HP infection in older patients is underestimated, this population should be a priority for HP-eradication since the infection is more frequent, peptic disease and gastric cancer are frequent, and eradication is effective.

Induction of vascular endothelial growth factor release by transcutaneous frequency modulated neural stimulation in diabetic polyneuropathy.

BACKGROUND: Pharmacological treatment for diabetic polyneuropathy (DP) has shown limited benefit; frequency-modulated electrical stimulation (FREMS) has shown positive results in pain control and nerve conduction velocity in DP. OBJECTIVE: To investigate the effects of FREMS vs transcutaneous electrical nerve stimulation (TENS) on the release of vascular endothelial growth factor (VEGF) in Type 2 diabetic and in non-diabetic subjects. METHODS: 10 non-diabetic [mean age 37+/-5 yr; females (F)/males (M): 6/4] and 10 Type 2 diabetic subjects (mean age 52+/-6 yr; F/M: 5/5) with DP underwent TENS (for 10 min) followed by 30 min interval without electrical stimulation, and then FREMS (for 10 min) over the forearm volar surface. Blood samples for VEGF measurements were obtained from the contra-lateral arm every 2 min during TENS/FREMS application and every 10 min during the intervals. RESULTS: We observed a significant rise in plasma VEGF during FREMS in both non-diabetic and diabetic subjects (maximal response 89.4+/-80.3 pg/ml and 48.5+/-18.3 pg/ml, respectively; p<0.01 vs basal) with a lower, but still significant response in diabetics. No changes in VEGF were observed during TENS application. CONCLUSION: VEGF release during FREMS may help explain the positive effects on nerve conduction velocity in DP, possibly mediated by favorable effects on vasa nervorum microangiopathy.

Ageing, lifestyle modifications, and cardiovascular disease in developing countries.

Developing countries face the double menace of still prevalent infectious diseases and increasing cardiovascular disease (CVD) with epidemic proportions in the near future, linked to demographic changes (expansion and ageing), and to urbanisation and lifestyle modifications. It is estimated that the elderly population will increase globally (over 80% during the next 25 years), with a large share of this rise in the developing world because of expanding populations. Increasing longevity prolongs the time exposure to risk factors, resulting in a greater probability of CVD. As a paradox, increased longevity due to improved social and economical conditions associated with lifestyle changes in the direction of a rich diet and sedentary habits in the last century, is one of the main contributors to the incremental trend in CVD. The variable increase rate of CVD in different nations may reflect different stages of "epidemiological transition" and it is probable that the relatively slow changes seen in developing populations through the epidemiological transition may occur at an accelerated pace in individuals migrating from nations in need to affluent societies (i.e. Hispanics to the USA, Africans to Europe). Because of restrained economic conditions in the developing world, the greatest gains in controlling the CVD epidemic lies in its prevention. Healthy foods should be widely available and affordable, and healthy dietary practices such as increased consumption of fresh fruits and vegetables, reduced consumption of saturated fat, salt, and simple sugars, may be promoted in all populations. Specific strategies for smoking and overweight control may be regulation of marketed tobacco and unhealthy fast food and promotion of an active lifestyle. Greater longevity and economic progress are accompanied by an increasing burden of CVD and other chronic diseases with an important decrease in quality of life, which should question the benefit of these additional years without quality.

Bisphosphonates and atherosclerosis: why?

The increasing knowledge on bone calcification processes has revealed some similarities with vascular tissue, where calcifications of arteries and cardiac valves contribute to several cardiovascular problems, such as heart failure, systolic hypertension, and myocardial and peripheral ischemic disease. Bisphosphonates have been used extensively for over two decades for the treatment of diseases associated with excessive bone resorption, i.e., osteoporosis, osteolytic bone metastasis, hypercalcemia and Paget's disease, by blocking osteoclastic function. Etidronate, pamidronate and clodronate has been shown to inhibit the development of experimental atherosclerosis, and proposed mechanisms for this action include inhibition of arterial calcification and lipid accumulation, degradation of atherogenic LDL-cholesterol and reduced foam cell formation. Bisphosphonates inhibit various enzymes involved in cholesterol biosynthesis and suppress macrophages in atheromatous lesions. The possibility of pharmacological agents that effectively treat both osteoporosis and atherosclerosis is attractive, however, current evidence is not conclusive and further research is necessary to confirm these actions in the clinical setting.

[Osteoporosis and diabetes]. / Osteoporosi e diabete mellito.

Diabetes mellitus and osteoporosis are chronic diseases with an elevated and growing incidence in the elderly. Recent epidemiological studies have demonstrated an elevated risk of hip, humerus and foot fractures in elder diabetic subjects. While type 1 diabetes is generally associated with a mild reduction in bone mineral density (BMD), type 2 diabetes, more prevalent in old subjects, is frequently linked to a normal or high BMD. Studies on experimental models of diabetes have suggested an altered bone structure that may help to explain the elevated risk of fractures observed in these animals and may as well help to explain the paradox of an incremented risk of fractures in type 2 diabetic elderly in the presence of normal or elevated BMD. In addition, diabetic elderly have an increased risk of falls, consequent at least in part to a poor vision, peripheral neuropathy, and weaken muscular performance. Diabetes may affect bone tissue by different mechanisms including obesity, hyperinsulinemia, deposit of advanced glycosilation end products in collagen fibre, reduced circulating levels of IGF-1, hypercalciuria, renal function impairment, microangiopathy and chronic inflammation. A better understanding of these mechanisms may help implement the prevention of fractures in the growing population of mature diabetics.

[The discovery of insulin: what really happened 80 years ago]. / La scoperta dell'insulina: quello che è realmente accaduto ottanta anni fa.

The Nobel Prize in Physiology and Medicine in 1923 for the discovery of insulin in 1921 was awarded to Frederick G. Banting and John J.R. MacLeod. This choice was highly debated: Banting decided to share his part of the prize with his younger co-worker Charles H. Best, and MacLeod, too, decided to share his part with biochemist James B. Collip. Although previous investigators such as Nicolas C. Paulesco, had obtained some positive results isolating "the internal secretion" of the pancreas, only the group in Toronto succeeded in proving consistently the efficacy of their insulin extracts. Banting had the idea of isolating insulin after reading an article in a medical journal. He received support for his proposed research at the University of Toronto, under the direction of John J.R. MacLeod and was assisted by Charles H. Best, a medical student. Banting's and Best's initial experiments were not definitive, but their apparently favorable results encouraged greater efforts that, with the important contribution of biochemist James B. Collip who has hardly ever been associated with this event, culminated in the discovery of insulin.

Altered cellular magnesium responsiveness to hyperglycemia in hypertensive subjects.

Previous studies by our group have identified ionic aspects of insulin resistance in hypertension, in which cellular responses to insulin were influenced by the basal intracellular ionic environment-the lower the cytosolic free magnesium (Mg(i)), the less Mg(i) increased following insulin stimulation. To investigate whether this ionic insulin resistance represents a more general abnormality of cellular responsiveness in hypertension, we studied Mg(i) responses to nonhormonal signals such as hyperglycemia (15 mmol/L) and used (31)P-nuclear magnetic resonance (NMR) spectroscopy to measure Mg(i) in erythrocytes from normal (NL, n=14) and hypertensive (HTN, n=12) subjects before and 30, 60, 120, and 180 minutes after in vitro glucose incubations. Basal Mg(i) levels were significantly lower in HTN subjects than in NL subjects (169+/-10 versus 205+/-8 micromol.L(-1), P<0.01). In NL cells, hyperglycemia significantly lowered Mg(i), from 205+/-8 micromol.L(-1) (basal, T=0) to 181+/-8, 162+/-6, 152+/-7, and 175+/-9 micromol.L(-1) (T=30, 60, 120, and 180, respectively; P<0.005 versus T=0 at all times). In HTN cells, maximal Mg(i) responses to hyperglycemia were blunted, from 169+/-10 micromol.L(-1) (basal, T=0) to 170+/-11, 179+/-12, 181+/-14, and 173+/-15 micromol.L(-1) (T=30, 60, 120, and 180, respectively; P=NS versus T=0 at all times). For all subjects, Mg(i) responses to hyperglycemia were closely related to basal Mg(i) levels: the higher the Mg(i), the greater the response (n=26, r=0.620, P<0.001). Thus, (1) erythrocytes from hypertensive vis-à-vis normotensive subjects are resistant to the ionic effects of extracellular hyperglycemia on Mg(i) levels, and (2) cellular ionic responses to glucose depend on the basal Mg(i) environment. Altogether, these data support a role for altered extracellular glucose levels in regulating cellular magnesium metabolism and also suggest the importance of ionic factors in determining cellular responsiveness to nonhormonal as well as hormonal signals.

Insulin-mimetic action of vanadate: role of intracellular magnesium.

The insulin-mimetic effect of vanadate is well established, and vanadate has been shown to improve insulin sensitivity in diabetic rats and humans. Although the exact mechanism(s) remain undefined, we have previously demonstrated a direct relation of intracellular free magnesium (Mg(i)) levels to glucose disposal, to insulinemic responses following glucose loading, and to insulin-induced ionic effects. To investigate whether the insulin-mimetic effects of vanadate could similarly be mediated by Mg(i), we utilized (31)P-nuclear magnetic resonance spectroscopy to measure Mg(i) in erythrocytes from normal (NL, n=10) and hypertensive (HTN, n=12) subjects, before and after incubation with insulin and with different doses of sodium vanadate. In NL, vanadate elevated Mg(i) levels, with maximum efficacy at 50 7 micromol/L (186+/-6 to 222+/-6 7micromol/L, P>0.01), as did physiologically maximal doses of insulin, 200 7microU/mL (185+/-6 to 222+/-8 7micromol/L, P<0.01). In HTN, only vanadate, but not insulin, increased Mg(i) (insulin: 173+/-7 to 180+/-9 7micromol/L, P=NS; vanadate: 170+/-7 to 208+/-10 7micromol/L, P<0.01). Mg(i) responses to insulin (r=0.637, P<0.001), but not to vanadate (r=0.15, P=NS), were closely and directly related to basal Mg(i) levels. We conclude that (1) both vanadate and insulin stimulate erythrocyte Mg(i) levels; (2) cellular Mg(i) responses to insulin, but not to vanadate, depend on basal Mg(i) content-the lower the basal Mg(i), the less the Mg(i) response to insulin. As such, (3) Mg(i) responses to vanadate were equivalent among HTN and NL, whereas HTN cells exhibited blunted Mg(i) responses to insulin, and (4) the ability of vanadate to improve insulin sensitivity clinically may be mediated, at least in part, by its ability to increase Mg(i) levels, which in turn, helps to determine cellular insulin action.

Relation of cellular potassium to other mineral ions in hypertension and diabetes.

To investigate the role of intracellular potassium (K(i))and other ions in hypertension and diabetes, we utilized (39)K-, (23)Na-, (31)P-, and (19)F-nuclear magnetic resonance (NMR) spectroscopy to measure K(i), intracellular sodium (Na(i)), intracellular free magnesium (Mg(i)), and cytosolic free calcium (Ca(i)), respectively, in red blood cells of fasting normotensive nondiabetic control subjects (n=10), untreated (n=13) and treated (n=14) essential hypertensive subjects, and diabetic subjects (n=5). In 12 subjects (6 hypertensive and 6 normotensive controls), ions were also measured before and after the acute infusion of 1 L of normal saline. Compared with those in controls (K(i)=148+/-2.0 mmol/L), K(i) levels were significantly lower in hypertensive (132.2+/-2.9 mmol/L, sig=0.05) and in type 2 diabetic subjects (121.2+/-6.8 mmol/L, sig=0.05). K(i) was higher in treated hypertensives than in untreated hypertensives (139+/-3.1 mmol/L, sig=0.05) but was still lower than in normals. Although no significant relation was observed between basal K(i) and Na(i) values, saline infusion elevated Na(i) (P<0.01) and reciprocally suppressed K(i) levels (142+/-2.4 to 131+/-2.2 mmol/L, P<0.01). K(i) was strongly and inversely related to Ca(i) (r=-0.846, P<0.001), and was directly related to Mg(i) (r=0.664, P<0.001). We conclude that (1) K(i) depletion is a common feature of essential hypertension and type 2 diabetes, (2) treatment of hypertension at least partially restores K(i) levels toward normal, and (3) fasting steady-state K(i) levels are closely linked to Ca(i) and Mg(i) homeostasis. Altogether, these results emphasize the similar and coordinate nature of ionic defects in diabetes and hypertension and suggest that their interpretation requires an understanding of their interaction.

Effects of drug therapy on cardiac arrhythmias and ischemia in hypertensives with LVH.

Left ventricular hypertrophy (LVH) in hypertensive subjects is associated with an increased prevalence of ventricular arrhythmias. To evaluate the effect of antihypertensive treatment on cardiac arrhythmias (CA) and transient episodes of myocardial ischemia (TEMI), we studied 46 hypertensive patients with LVH, divided into four groups randomly treated with enalapril, hydrochlorothiazide (HCTZ), atenolol, or verapamil (SR-V) for 6 months. Office blood pressure and office heart rate values were recorded, in basal conditions, after 1 and 6 months of treatment, and all patients underwent echocardiography, electrocardiographic Holter monitoring, and stress testing. All drugs significantly lowered blood pressure, whereas left ventricular mass index was reduced by atenolol, enalapril, and SR-V, but not by HCTZ. Treatment induced a significant reduction in the number of patients with supraventricular arrhythmias (35 v 15, P < .034, and 28 v 8, excluding patients treated with HCTZ, P < .008). The number of patients with ventricular arrhythmias was also reduced (32 v 16 considering all groups, P < .08, and 24 v 9, excluding patients treated with HCTZ, P < .04). The number of TEMI during Holter monitoring significantly decreased from 47 to 23 (P = .043) in all patients, and from 39 to 14 (P = .013) excluding patients treated with HCTZ. In all groups, irrespective of treatment, a reduction of blood pressure, heart rate, and systolic blood pressure/heart rate product measured by exercise stress test was observed. The present study shows that in hypertensive patients with LVH, antihypertensive treatment with atenolol, enalapril and SR-V reduces LVH and decreases the prevalence of CA and TEMI. Treatment with HCTZ during the 6-month study did not alter LVH and did not appear to reduce CA and TEMI.

Cellular ionic alterations with age: relation to hypertension and diabetes.

BACKGROUND: Cytosolic free calcium (Cai) and magnesium (Mgi) are vital to cellular homeostasis and function. OBJECTIVE: To evaluate cellular divalent cations in normal subjects at different ages and their relationship to ion levels in essential hypertension and diabetes. DESIGN: A cross-sectional study. SETTING: A university hospital in New York. PARTICIPANTS: A total of 103 subjects (32 older, 71.1 +/- 1.2 y/o, and 71 young/middle aged subjects, 51.1 +/- 2.3 y/o). INTERVENTION: Oral glucose tolerance test. MEASUREMENTS: 19F and 31P NMR spectroscopy were used to measure Cai and Mgi levels in erythrocytes from normal (>65 y/o, n = 11; <65 y/o, n = 26), hypertensive (EH) (>65 y/o, n = 9; <65 y/o, n = 30), and type 2 diabetic (DM) (>65 y/o, n = 12; <65 y/o, n = 15) subjects; these levels were also compared with glucose and insulin levels before and after oral glucose loading. RESULTS: Fasting Mgi levels were lower (207 +/- 7.8 vs 236 +/- 7.5 microM; P < .05) and Cai higher (32.2 +/- 3.0 vs 20.3 +/- 1.8 nM; P < .05) in older than in younger normal subjects. For all normal subjects, the greater the age, the higher the Cai (r = 0.622, P = .004) and the lower the Mgi (r = -0.423; P = .011). However, no significant (P = NS) differences in Mgi or Cai levels were observed between older normal and young/middle-aged subjects with EH (Mgi = 189.7 +/- 5.9 vs 182.6 +/- 9.8 microM; Cai = 33.8 +/- 4.9 vs 35.6 +/- 4.0 nM) or DM (Mgi = 182.8 +/- 10.9 vs 180.8 +/- 8.1 microM; Cai = 33.6 +/- 4.3 vs 39.7 +/- 5.9 nM). Significant relationships were also found between cellular ion content, blood pressure, and glycemic indices. CONCLUSIONS: Aging is associated with the onset of altered Cai and Mgi levels, indistinguishable from those observed in hypertension and diabetes, independent of age. We suggest that these ionic changes may be clinically significant, underlying the predisposition of older subjects to cardiovascular and metabolic diseases.

Trends of congestive heart failure epidemiology: contrast with clinical trial results.

Congestive heart failure (CHF) is an important and growing public health problem and the cause of substantial morbidity and mortality. Its increasing incidence and prevalence may be in part explained by the progressive aging of the world population. The improvement in coronary artery disease and hypertension treatment allows the individuals to lie longer and develop CHF. Indeed, the most common etiology of CHF is coronary artery disease, the leading cause of cardiovascular morbidity and mortality worldwide, and the second cause of CHF is hypertension which is still markedly increasing in developing countries. Estimates of prevalence of CHF are 0.4 to 2% of the general population. The number of hospital admissions for CHF has also been steadily increasing. Half of the patients carrying a diagnosis of CHF will die within 4 years and patients with severe CHF will die within 1 year. At present, there is no evidence that the prognosis of heart failure in the community has changed despite the advances in therapy over the past decades, such as the demonstration that angiotensin-converting enzyme inhibitors and other vasodilators improve the clinical signs and symptoms of patients with CHF, reduce mortality and slow the progression of myocardial dysfunction. Nevertheless, the overall mortality from this condition remains very high. It is possible that the results of the trials have not yet been evidenced in the majority of patients with CHF because the ideal conditions, treatment and follow-up in the trials are not yet widely achieved in the population.

Effects of insulin and metformin on glucose metabolism in rat vascular smooth muscle.

Glucose metabolism in vascular smooth muscle cells (VSMCs) is characterized by substantial lactate production even in fully oxygenated conditions. Insulin and metformin, an insulin-sensitizing agent, have direct effects on the vascular tissue metabolism. We investigated whether insulin or metformin can induce a switch in VSMC glucose metabolism from lactate production to pyruvate oxidation, by measuring lactate oxidation as determined by the conversion of [1-14C]-D,L-lactate to [1-14C]-pyruvate and subsequent oxidation to acetyl coenzyme A and 14CO2 by pyruvate dehydrogenase (PDH). Lactate oxidation was measured in control rat aortic cultured VSMCs incubated for 30 minutes in media with and without additional glucose compared with VSMCs cultured in the presence of insulin or metformin. The addition of glucose to VSMCs decreased lactate oxidation (4.6+/-1.7 v 9.6+/-2.4 pmol/cell/min, P < .001). In the absence of additional glucose, metformin decreased lactate oxidation in VSMCs compared with controls (4.9+/-1.4 v 9.6+/-2.4 pmol/cell/min, P < .01). Metformin in the presence of glucose caused the greatest decline in lactate oxidation (2.5+/-0.4 pmol/cell/min, P < .001). In contrast to the effects of metformin, insulin increased lactate oxidation both with (12.9+/-1.5 pmol/cell/min, P < .001) and without (17.9+/-4.4, P < .01) additional glucose. This suggests that insulin facilitates VSMC utilization of lactate as a source of pyruvate and energy production even during noncontractile periods.

Cardiovascular risk factors in South America and the Caribbean.

Facing the conclusion of the twentieth century, cardiovascular disease (CVD) remains a major cause of morbidity and a leading contributor to mortality worldwide. Developing countries, including those in South America and the Caribbean, contribute substantially to the global burden of CVD. Indeed, 8 to 9 million deaths attributable to CVD (63% of world total) occurred in developing countries in 1990, compared to 5.3 million deaths in developed nations. Over the next 25 years, it is projected that there will be a rise in CVD mortality rates in the developing countries, linked not only to demographic changes (expansion and aging of the population), but also to progressive urbanization and lifestyle modifications. As such, the ratio of deaths from CVD to deaths from infectious disease is likely to triple during the next 20 years in South America and the Caribbean. The identification of major risk factors and the implementation of control strategies (eg, community education and target of high risk individuals) have contributed to the fall in CVD mortality rates observed in industrialized nations. Most countries of South America and the Caribbean lack an efficient health care system, and the medical and socio-economic consequences of the projected rise in CVD will further strain financial resources. Therefore, appropriate strategies based on knowledge extrapolated from research among other populations should be initiated. The agenda of any lifestyle-related disease control program should include the promotion of healthy diet, exercise, and should encourage decreasing tobacco and alcohol usage.