PubMed Health⌕ Search

Biomedical subjects

G Paolisso

Publications and source records attributed to G Paolisso.

At least 55 records · Page 3Linked to original sources
PubMed2000

Plasma leptin concentrations and cardiac autonomic nervous system in healthy subjects with different body weights.

Previous studies have shown that leptin stimulates sympathetic nervous system; heart rate variability (HRV) is a widely used technique for assessing the sympathovagal balance at the cardiac level. The aim of our study was to investigate a possible relationship between plasma leptin levels and the autonomic regulation using spectral analysis of HRV. In 120 healthy nonobese subjects the plasma leptin concentration was determined, and HRV was recorded at baseline and during tilt. All subjects were categorized in quartiles of plasma leptin concentration. Analysis of data showed a significant increase in body mass index, body fat, fasting plasma insulin, triglyceride concentration, and homeostatic model assessment values throughout the different quartiles of plasma leptin concentration. Concerning cardiovascular parameters, heart rate, arterial blood pressures, and RR intervals were not significantly different among the quartiles. Total power and high frequency (HF) in normalized units were significantly decreased, whereas low frequency (LF) normalized units was progressively increased from the first to the fourth quartile. Thus, the LF/HF ratio rose gradually and significantly from the lowest to the highest quartile. Such results were independent of the body fat estimate (P < 0.03 for the trend). The change in the LF/HF ratio was significantly enhanced during tilt (P < 0.001 vs. rest values for all quartiles); the effect was stronger in subjects in the fourth quartile of plasma leptin concentration (P < 0.005 for the trend). The latter parameter was also independent of body fat content and distribution (P < 0.01). Our study shows that increasing fasting plasma leptin concentrations are associated with a shift of the sympathovagal balance toward a progressive increase in sympathetic activation and an increased response to orthostatic stimulus in nonobese subjects with different body fat contents.

Adipose Tissue↗
PubMed2000

Hemodynamic effects of acute hyperglycemia in type 2 diabetic patients.

OBJECTIVE: The aim of the present study was to evaluate the hemodynamic effects of acute hyperglycemia in type 2 diabetic patients and to see whether these effects are related to changes in nitric oxide (NO) availability. RESEARCH DESIGN AND METHODS: Twenty newly diagnosed complication-free diet-treated type 2 diabetic patients participated in the study. All patients underwent 3 hyperglycemic glucose clamps in random order: 1) the control study was performed with plasma glucose clamped at 18 mmol/l for 2 h; 2) the octreotide study with plasma insulin blocked at basal levels during the clamp; and 3) the L-arginine study with L-arginine (1 g/min) infused during the last 30 min of the clamp. A group of 8 patients also underwent a glutathione infusion (600 mg as an intravenous bolus followed by 5 mg/min infusion) during the clamp. RESULTS: During hyperglycemia, there were significant increments of systolic (sBP) (from 115.5 +/- 9.1 to 120.3 +/- 8.2 mmHg, P < 0.01) and diastolic (dBP) (from 70.3 +/- 7.8 to 79.7 +/- 5.3 mmHg, P < 0.01) blood pressure, as well as heart rate (from 75.2 +/- 7.8 to 80.8 +/- 5.4 beats/min, P < 0.01) and plasma catecholamines (P < 0.05). Squatting ratios, a measure of the baroreflex activity, significantly deteriorated after hyperglycemia (P < 0.01). The infusion of octreotide, used to avoid the possible confounding influence of insulin, did not change the hemodynamic effects of hyperglycemia. Glutathione, a free radical scavenger, completely prevented the vascular effects of hyperglycemia. L-Arginine produced a fall in sBP and dBP to baseline values and normalized squatting ratios. CONCLUSIONS: Acute hyperglycemia in newly diagnosed type 2 diabetic patients causes significant hemodynamic changes that are independent of endogenous insulin and are prevented by glutatione and reversed by L-arginine, suggesting an interference with endogenous NO availability. These observations could help explain the adverse cardiovascular effects of hyperglycemic spikes.

Adult↗
PubMed1999

Prognostic importance of insulin-mediated glucose uptake in aged patients with congestive heart failure secondary to mitral and/or aortic valve disease.

Previous studies have demonstrated that insulin resistance is a common feature of congestive heart failure (CHF), but the clinical significance of such insulin resistance is still debated. We tested the hypothesis that insulin-mediated glucose uptake (IMGU) is a prognostic factor in CHF in aged patients. For this purpose 174 aged patients with CHF participated in a cross-sectional and a longitudinal study of 24 months' duration. In this latter study survival analysis was calculated comparing subjects at the first and second tertile of IMGU with those at third tertile. All subjects underwent anthropometric (body mass index, waist/hip ratio), cardiovascular (arterial blood pressure, 24-hour Holter monitoring, peak VO2, left ventricular ejection fraction, echocardiography), and metabolic (determination of fasting plasma glucose, insulin, catecholamine, free fatty acids, tumor necrosis factor-alpha concentrations, and assessment of IMGU by euglycemic hyperinsulinemic glucose clamp) investigations. In the cross-sectional study, IMGU correlated with age (r = -0.33, p <0.001), body mass index (r = -0.46 p <0.001), ventricular premature complexes (r = -0.78, p <0.001), left ventricular ejection fraction (r = -0.15, p <0.05), fasting plasma norepinephrine (r = -0.75, p <0.001), tumor necrosis factor-alpha (r = -0.45, p <0.001), free fatty acids (r = -0.54, p <0.001), and peak VO2 (r = 0.67, p <0.001). In the longitudinal study patients at the first and second tertile of IMGU had a lower probability of survival than patients at the third tertile (p <0.03). Cox regression analysis showed IMGU to be a prognostic factor independent of fasting plasma norepinephrine, tumor necrosis factor-alpha, free fatty acid concentration, New York Heart Association class, peak VO2, and left ventricle ejection fraction (relative risk 1.1, 95% confidence intervals 1.0 to 2.1). In conclusion, our study demonstrates that insulin resistance is a common feature of CHF most likely due to elevated plasma norepinephrine and tumor necrosis factor-alpha concentrations, and that IMGU is an independent prognostic factor in CHF.

Aged↗
PubMed1999

Intralipid infusion combined with propranolol administration has favorable metabolic effects in elderly malnourished cancer patients.

Previous studies have shown that an elevated basal metabolic rate (BMR) is present in elderly malnourished cancer patients. A possible dysfunction of the autonomic nervous system needs to be demonstrated. In aged weight-losing cancer patients (n = 40), aged non-weight-losing cancer patients (n = 30), and aged weight-losing noncancer patients (n = 18), the baseline BMR and heart rate variability were studied. Aged weight-losing cancer patients (n = 40) underwent bioimpedance analysis, ambulatory electrocardiographic monitoring with analysis of heart rate variability, and determination of the BMR. Then, the patients received infusion of Intralipid (Pharmacia, Uppsala, Sweden) without and with propranolol (6 days of 40 mg twice daily) administration. At baseline, a simple correlation between the BMR and the low-frequency component (LF) (r = .42, P < .006) and LF to high-frequency (HF) ratio (r = .51, P < .001) was found. After propranolol administration, the percent decline in the BMR was significantly correlated with the percent decline in the LF (r = .39, P < .01) and LF/HF ratio (r = .53, P < .001). The percent decline in the BMR was not correlated with the HF (r = .13, P < .34) or the plasma noradrenaline concentration (r = .21, P < .20) at any time. With regard to the BMR and substrate oxidation, 6-day propranolol administration plus Intralipid infusion produced the strongest decline in the BMR. This study demonstrates that autonomic nervous system dysfunction occurs and is responsible for the elevated BMR in elderly cancer patients, propranolol administration rectifies the autonomic dysfunction, and Intralipid infusion combined with propranolol administration is useful for enhancing the daily caloric intake without a strong increase in energy expenditure.

Adrenergic beta-Antagonists↗
PubMed1999

Effects of different insulin infusion rates on heart rate variability in lean and obese subjects.

The low-frequency to high-frequency ratio (LF/HF ratio) is an index of cardiac sympathovagal balance. We hypothesized that insulin might also stimulate the LF/HF ratio. Thus, 15 lean and 15 obese subjects were studied. Each subject underwent sequential hyperinsulinemic clamps (insulin infusion rate 0.50, 1, and 2 mU/kg x min) while the heart rate was recorded by the Holter technique continuously. Indirect calorimetry allowed determination of the respiratory quotient (Rq) and substrate oxidation. The leg blood flow (LBF), leg vascular resistance (LVR), and plasma norepinephrine concentration were also measured. In seven lean subjects, hyperinsulinemic clamps were repeated along with propranolol infusion (0.1 mg x kg(-1) as an intravenous bolus dose followed by continuous intravenous infusion of 0.5 mg x kg(-1) x min(-1) throughout the study). Lean subjects had better insulin action than obese subjects. Insulin infusion was associated with an increase of the deltaLF/HF ratio in both lean (P < .001 for time-dependent changes) and obese (P < .02 for time-dependent changes) subjects; however, the extent of insulin-mediated stimulation of the LF/HF ratio was greater in lean versus obese subjects. Insulin infusion did not significantly affect HF values in both groups. Independently of gender, body fat, changes in the plasma norepinephrine concentration, LBF, and LVR, the deltaLF/HF ratio at the end of the fastest insulin infusion (0.8 +/- 0.2 v 0.3 +/- 0.2, P < .04) was still greater in lean versus obese subjects. The deltaLF/HF ratio was also more stimulated during insulin versus insulin + propranolol infusion in lean subjects. In conclusion, insulin stimulates the LF/HF ratio in both lean and obese subjects and thus produces a shift in the cardiac autonomic nervous system activity toward sympathetic predominance.

Adrenergic beta-Antagonists↗
PubMed1999

Lack of association between changes in plasma leptin concentration and in food intake during the menstrual cycle.

BACKGROUND: Changes in plasma leptin concentration and food intake occur during the menstrual cycle; because leptin regulates food intake, one could hypothesize that changes in plasma leptin concentration and in food intake are associated throughout the menstrual cycle. However, no data have ever been provided to support such a relationship. The aim of our study was to investigate, during the different phases of the menstrual cycle, (a) the changes in plasma leptin concentration and, if such changes were demonstrated, (b) the potential relationship between the changes in plasma leptin concentration and food intake. DESIGN: The study was designed as an observational study. The plasma leptin concentration was determined in 16 healthy, young women during different phases of the menstrual cycle. At the same time, the basal metabolic rate (BMR), respiratory quotient (RQ) and food intake (FI) were also determined. RESULTS: The plasma leptin concentration increased throughout the menstrual cycle (P < 0.01 for trend) and was significantly correlated with plasma progesterone concentration (r = 0.55, P < 0.007, for follicular phase, r = 0.58, P < 0.02, for the periovulatory period and r = 0.57, P < 0.02, for the luteal phase). No significant differences in BMR and fasting RQ throughout the different phases of the menstrual cycle were found. In contrast, FI significantly declined in the periovulatory phase. No significant correlations between BMR, RQ and FI values and fasting plasma leptin concentration at all menstrual phases were found. CONCLUSION: Changes in plasma leptin concentration and in food intake were found at different phases of the menstrual cycle. Nevertheless, no correlation among those parameters at any phase of the menstrual cycle was observed.

Adult↗
PubMed1999

Advancing age and insulin resistance: new facts about an ancient history.

The relationship between advancing age and insulin resistance is widely known, but the cause(s) of such association are less well understood. Age-related changes in anthropometric characteristics and environmental factors (changes in diet habits and decline in physical activity) have been hypothesized as being among the main causes. More recently, the role of plasma insulin-like growth factor I (IGF-I), dehydroepiandrosterone sulphate (DHEAS) and tumour necrosis factor alpha (TNF-alpha) concentrations as well as the degree of oxidative stress have also been evaluated. As far as the anthropometric changes are concerned, a decline in fat-free mass and a relative or absolute increase in fat mass are common findings in aged subjects. Such changes are combined with a decline in plasma DHEAS and IGF-I concentration and a rise in plasma TNF-alpha concentrations and oxidative stress, which, in turn, may interact with the anthropometric changes determining the worsening in insulin-mediated glucose uptake. Finally, age-related environmental factors (changes in diet quality and decline in the degree of physical activity) might be a common factor allowing anthropometric factors and age-related remodelling to accelerate their negative impact on insulin action.

Aging↗
PubMed1999

Mean arterial blood pressure and serum levels of the molar ratio of insulin-like growth factor-1 to its binding protein-3 in healthy centenarians.

OBJECTIVE: Healthy centenarians have a greater molar ratio of plasma insulin-like growth factor-1 to insulin-like growth factor binding protein-3 than that of aged subjects. We investigated the question of whether differences in mean arterial pressure and in this plasma ratio were related in healthy centenarians. SUBJECTS AND METHODS: We studied 52 subjects in total, 30 aged subjects (70-99 years) and 22 healthy centenarians (> 100 years) to determine differences in mean arterial pressure, endothelial function and intracellular cation levels. RESULTS: In the healthy centenarians, the molar ratio of fasting plasma insulin-like growth factor-1 to its binding protein-3 was significantly correlated with mean arterial pressure (r = -0.66, P < 0.001). Baseline (19.3 +/- 1.5 versus 27.6 +/- 2.2 mumol/l, P < 0.05) and L-arginine-stimulated percentage increases in the plasma total nitrate: nitrite ratio (67 +/- 3.4 versus 48 +/- 4.5%, P < 0.03) were greater in the healthy centenarians than in the aged subjects. An L-arginine bolus elicited an increase in forearm blood flow which was correlated with the percentage increase in the plasma total nitrate: nitrite ratio (r = 0.79, P < 0.001) and with the fasting erythrocyte magnesium concentration (r = 0.80, P < 0.001) in healthy centenarians. Both correlations remained significant (P < 0.01) after adjustment for sex, body mass index and the waist: hip ratio. Moreover, the fasting plasma molar ratio of insulin-like growth factor-1 to its binding protein-3 was correlated with the percentage increase in forearm blood flow (r = 0.59, P < 0.005) and with the percentage increase in the plasma total nitrate: nitrite ratio (r = 0.54, P < 0.009) in healthy centenarians. The centenarians had higher baseline total erythrocyte magnesium and lower calcium concentrations than the aged subjects. The addition of insulin growth factor-1 to the incubation medium increased the total intracellular erythrocyte magnesium content and decreased the calcium content in both groups of subjects. Nevertheless, the percentage increase in total erythrocyte magnesium (33 +/- 3.8 versus 12 +/- 3.4%, P < 0.03) and decline in intracellular calcium (17 +/- 2.8 versus 8 +/- 3.1%, P < 0.02) concentrations were greater in the healthy centenarians than the aged subjects. CONCLUSION: In healthy centenarians, insulin-like growth factor-1 may preserve endothelial function and modulate the intracellular cation content, thus contributing to a lower mean arterial pressure than that in aged subjects.

Aged↗
PubMed1999

Low plasma insulin-like growth factor-1 concentrations predict worsening of insulin-mediated glucose uptake in older people.

OBJECTIVE: The relationship among insulin action, advancing age, and insulin like growth factor-1 (IGF-1) is poorly understood. To gain further insight, the predictive role that low plasma IGF-1 concentration may have on insulin- mediated glucose uptake in older persons was investigated. DESIGN: The study was designed as a longitudinal, observational trial. PARTICIPANTS: Fifty-eight healthy aged (73.1+/-9.4 years) subjects (31 males/27 females) were followed up for 12 months. MEASUREMENTS: At baseline and at the end of the follow-up, insulin-mediated glucose uptake was assessed by euglycemic glucose clamp and plasma total IGF-1 and IGF-binding protein 3 (IGF-BP-3) in each subject, and concentrations were determined. RESULTS: At baseline, plasma IGF-1 concentrations correlated with whole body glucose uptake (WBGD) (r = 0.39, P < .003), insulin-stimulated glucose oxidation (GOX) (r = 0.35, P < .009), and non-oxidative glucose metabolism (r = 0.37, P < .007). Such correlations were also independent of age, sex, body fat, and waist/hip ratio. Fasting plasma total IGF-1 concentrations (84+/-56 vs 63+/-44 microg/L, P < .040), plasma IGF-1/IGF-BP3 molar ratio (0.13+/-0.05 vs 0.10+/-0.03 P < .050), and WBGD (34.8+/-5.0 vs 23.1+/-4.6 micromol/kg x min, P < .010) were more elevated at baseline than at the end of the follow-up. Low baseline fasting plasma IGF-1 concentration (RR = 1.5, 95%CI = 1.3-1.7) and plasma IGF-1/IGFBP-3 molar ratio (RR = 1.4, 95% CI = 1.3-1.8) predicted a decline in WBGD. The predictive role of plasma IGF-1 on age-related decline in WBGD was independent of age, sex, body fat, waist/hip ratio, and degree of physical activity (model 1), or of fasting plasma free fatty acid and triglyceride concentrations, LDL/HDL ratio, and basal adjusted respiratory quotient (model 2). Finally, low plasma IGF-1 concentration predicts a decline in WBGD independent of body fat, free fatty acids, waist/hip ratio, and basal adjusted respiratory quotient (model 3). CONCLUSION: Our study demonstrates that fasting plasma IGF-1 concentration may have a modulatory role on insulin action in older people. This finding might prompt an evaluation of the direct effect of IGF-1 administration on insulin sensitivity in older adults.

Adipose Tissue↗
PubMed1999

Effects of glutathione on red blood cell intracellular magnesium: relation to glucose metabolism.

Recent evidence suggests that the endogenous antioxidant glutathione may play a protective role in cardiovascular disease. To directly investigate the role of glutathione in the regulation of glucose metabolism in hypertension, we studied the acute effects of in vivo infusions of this antioxidant (alone or in combination with insulin) on whole body glucose disposal (WBGD) using euglycemic glucose clamp and the effects on total red blood cell intracellular magnesium (RBC-Mg) in hypertensive (n=20) and normotensive (n=30) subjects. The relationships among WBGD, circulating reduced/oxidized glutathione (GSH/GSSG) levels, and RBC-Mg in both groups were evaluated. The in vitro effects of glutathione (100 micromol/L) on RBC free cytosolic magnesium (Mg(i)) were also studied. In vivo infusions of glutathione (15 mg/minx120 minutes) increased RBC-Mg in both normotensives and hypertensives (1.99+/-0.02 to 2.13+/-0.03 mmol/L, P<0.01, and 1.69+/-0.03 to 1.81+/-0.03 mmol/L, P<0.01, respectively). In vitro GSH but not GSSG increased Mg(i) (179+/-3 to 214+/-5 micromol/L, P<0.01). In basal conditions, RBC-Mg values were related to GSH/GSSG ratios (r=0.84, P<0.0001), and WBGD was directly, significantly, and independently related to both GSH/GSSG ratios (r=0.79, P<0.0001) and RBC-Mg (r=0.89, P<0.0001). This was also true when hypertensive and control groups were analyzed separately. On multivariate analysis, basal RBC-Mg (t=6.81, P<0.001), GSH/GSSG (t=3. 67, P<0.02), and blood pressure (t=2.89, P<0.05) were each independent determinants of WBGD, with RBC-Mg explaining 31% of the variability of WBGD. These data demonstrate a direct action of glutathione both in vivo and in vitro to enhance intracellular magnesium and a clinical linkage between cellular magnesium, GSH/GSSG ratios, and tissue glucose metabolism.

Adult↗
PubMed1999

Effects of vitamin E and glutathione on glucose metabolism: role of magnesium.

Vitamin E is an antioxidant that has been demonstrated to improve insulin action. Glutathione, another natural antioxidant, may also be important in blood pressure and glucose homeostasis, consistent with the involvement of free radicals in both essential hypertension and diabetes mellitus. Our group has recently suggested that the effects of reduced glutathione on glucose metabolism may be mediated, at least in part, by intracellular magnesium levels (Mg([i])). Recent evidence suggests that vitamin E enhances glutathione levels and may play a protective role in magnesium deficiency-induced cardiac lesions. To directly investigate the effects of vitamin E supplementation on insulin sensitivity in hypertension, in relation to the effects on circulating levels of reduced (GSH) and oxidized (GSSG) glutathione and on Mg([i]), we performed a 4-week, double-blind, randomized study of vitamin E administration (600 mg/d) versus placebo in 24 hypertensive patients and measured whole-body glucose disposal (WBGD) by euglycemic glucose clamp, GSH/GSSG ratios, and Mg([i]) before and after intervention. The relationships among WBGD, GSH/GSSG, and Mg([i]) in both groups were evaluated. In hypertensive subjects, vitamin E administration significantly increased WBGD (25.56+/-0.61 to 31.75+/-0.53 micromol/kg of fat-free mass per minute; P<0.01), GSH/GSSG ratio (1.10+/-0.07 to 1.65+/-0.11; P<0.01), and Mg([i]) (1.71+/-0.042 to 1.99+/-0.049 mmol/L; P<0.01). In basal conditions, WBGD was significantly related to both GSH/GSSG ratios (r=0.58, P=0.047) and Mg([i]) (r=0.78, P=0.003). These data show a clinical link between vitamin E administration, cellular magnesium, GSH/GSSG ratio, and tissue glucose metabolism. Further studies are needed to explore the cellular mechanism(s) of this association.

Double-Blind Method↗
PubMed1999

Plasma leptin level is associated with myocardial wall thickness in hypertensive insulin-resistant men.

Leptin, the product of the ob gene, has been shown to increase heart rate and blood pressure through a stimulation of cardiac sympathetic nervous system activity, a phenomenon also involved in the pathogenesis of left ventricular hypertrophy in hypertensives. Thus, we hypothesize that plasma leptin concentration is associated with left ventricular hypertrophy. Forty hypertensive males and 15 healthy male subjects underwent anthropometric and echocardiographic evaluations, assessment of insulin sensitivity through euglycemic glucose clamp combined with indirect calorimetry, and determination of fasting plasma leptin concentration. Fasting plasma leptin levels were higher in hypertensives than in controls (6.48+/-2.9 versus 4. 62+/-1.5 ng/mL, P<0.05); these results were unchanged after adjustment for body mass index (P<0.05). In the whole group of patients (n=55), fasting plasma leptin concentration was correlated with body mass index (r=0.46, P<0.001) and waist/hip ratio (r=0.50, P<0.001); independent of body mass index and waist/hip ratio, fasting plasma leptin concentration was correlated (n=55) with whole-body glucose disposal (r=-0.27, P<0.04), interventricular septum thickness (r=0.34, P<0.001), posterior wall thickness (r=0.38, P<0.003), and the sum of wall thicknesses (r=0.68, P<0.001). In a multivariate analysis (n=55), age, body mass index, fasting plasma leptin concentration, plasma Na(+) concentration, whole-body glucose disposal, and diastolic blood pressure explained 68% of the variability of the sum of wall thicknesses with fasting plasma leptin concentration (P<0.03), whole body glucose disposal (P<0.002), and diastolic blood pressure (P<0.001), which were significantly and independently associated with the sum of wall thicknesses. In conclusion, our study demonstrates that fasting plasma leptin levels are associated with increased myocardial wall thickness independent of body composition and blood pressure levels in hypertensives.

Adult↗
PubMed1999

Baseline heart rate variability in healthy centenarians: differences compared with aged subjects (>75 years old).

Healthy centenarians have better anthropometric, endocrine, metabolic and immunological parameters than aged subjects (>75 years old). Heart rate variability (HRV) has been demonstrated to be a good index of the cardiac autonomic nervous system. It is not known whether there are any differences in cardiac autonomic nervous system activity between aged subjects and healthy centenarians. It is possible that differences in cardiac autonomic nervous system activity could represent one of a cluster of factors explaining the extreme survival of centenarians. Thus we aimed to answer the following question: is there any difference in baseline HRV parameters between aged subjects and healthy centenarians? Therefore power spectral analysis of HRV at baseline was investigated in 25 aged subjects (age > or = 75 years) and 30 healthy centenarians (age > or = 0 years). Anthropometric measurements were made in all subjects, fasting blood samples were drawn for metabolite determinations, and HRV was determined. Independent of age, gender, body mass index and fasting plasma noradrenaline and free 3,3',5-tri-iodothyronine concentrations, healthy centenarians had lower basal values for total power (1318+/-546 compared with 1918+/-818 ms(2); P<0.01) and the low-frequency component (33+/-21 compared with 50+/-11 normalized units; P<0.03) and a higher value for the high-frequency component (77+/-15 compared with 61+/-18 normalized units; P<0.05) than aged subjects. Consequently, the low-frequency/high-frequency ratio (0.43+/-0.07 compared with 0.91+/-0.05; P<0.02) was also lower in the healthy centenarians than in the aged subjects. Our study demonstrates that the basal low-frequency/high-frequency ratio, an indirect index of cardiac sympathovagal balance, is lower in healthy centenarians than in aged subjects.

Aged↗
PubMed1999

Primary and secondary prevention of atherosclerosis: is there a role for antioxidants?

Elevated plasma free radical concentration (expression of enhanced oxidative stress) is related to different pathophysiological conditions such as ageing, cancer and diabetes. Nevertheless, even in healthy subjects a rise in plasma free radicals is due to hyperglycaemia, elevated free fatty acids and hyperinsulinaemia. Once elevated oxidative stress occurs, accelerated atherosclerosis may be present. Thus, antioxidants might potentially be useful in preventing or delaying the development of atherosclerosis. Several epidemiological studies have provided conflicting results, whereas interventional studies have demonstrated that antioxidant administration at pharmacological doses is useful for secondary prevention of atherosclerosis. The role of antioxidants in diabetic patients is still debatable, and it is too early to suggest this means for the prevention of atherosclerosis. Concerning trace elements, several studies have indicated that iron, copper, zinc and selenium may play a role in the pathogenesis of atherosclerosis. Nevertheless, only future longitudinal studies can provide a final response. In conclusion, the whole body of studies to date clearly demonstrates that antioxidants may be useful for secondary prevention of coronary heart disease.

Antioxidants↗
PubMed1998

Role of non-esterified fatty acids in the pathogenesis of type 2 diabetes mellitus.

Over 30 years after the original description of Randle's cycle, the mechanisms by which elevated circulating non-esterified fatty acids might be causally related to glucose intolerance in Type 2 diabetes mellitus remain uncertain. This review examines the evidence that elevated plasma NEFA can inhibit glucose-stimulated insulin secretion by pancreatic beta-cells and impair glucose- and insulin-stimulated glucose disposal by peripheral tissues. Experimental evidence beginning to examine the mechanisms of these phenomena is discussed.

Blood Glucose↗
PubMed1998

Lowering fatty acids potentiates acute insulin response in first degree relatives of people with type II diabetes.

Studies have shown that a high plasma non-esterified fatty acid concentration may inhibit glucose induced insulin secretion in vitro and in vivo. The effect of lowering the fatty acid concentration on the acute insulin response was investigated in first degree relatives of people with Type II diabetes in a double-blind, randomised, placebo-controlled trial. Fifty first degree relatives of people with Type II diabetes volunteered for the study. Twenty five were given acipimox (250 mg/day, four times daily) and 25 placebo. The group treated with acipimox had a lower 2-h plasma glucose concentration (6.1 +/- 0.2 vs 7.7 +/- 0.3 vs mmol/l, p < 0.01); better insulin-mediated glucose uptake (35.4 +/- 0.5 vs 28.3 +/- 0.4 mumol/kg fat free mass per min, p < 0.01), acute insulin response (68 +/- 4.4 vs 46 +/- 7.3 mU/l, p < 0.01) and respiratory quotient (0.81 +/- 0.02 vs 0.77 +/- 0.03, p < 0.05); and a rise in the plasma glucagon (164 +/- 63 vs 134 +/- 72 ng/1, p < 0.05), growth hormone (1.31 +/- 0.13 vs 0.97 +/- 0.21 microgram/l, p < 0.03) and cortisol (325 +/- 41 vs 284 +/- 139 nmol/l, p < 0.05) concentrations. The difference in the acute insulin response persisted, even after adjustment for the 2-h plasma glucose concentration, insulin-mediated glucose uptake, the fasting plasma glucagon concentration and the growth hormone concentration (p < 0.05). In a subgroup of eight patients acipimox was compared with acipimox plus intralipid. The acute insulin response (44 +/- 5.1 vs 71 +/- 5.3 mU/l, p < 0.01) and the insulin-mediated glucose uptake (27.4 +/- 0.4 vs 36.7 +/- 0.5 mumol/kg fat free mass per min, p < 0.003) were lower with acipimox plus intralipid treatment than with acipimox alone. It is concluded that long term acipimox treatment lowers the plasma fasting free fatty acid concentration and improves the acute insulin response and the insulin mediated glucose uptake.

Adult↗