Showing papers by "Giuseppe Paolisso published in 1997"

Serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function.

Abstract: It has been demonstrated that healthy centenarians have more favorable anthropometric characteristics and insulin-mediated glucose uptake than aged subjects. The plasma insulin-like-growth factor I (IGF-I) concentration may account for such differences. Three groups of subjects were studied: 1) adults ( 100 yr; n = 19). In all subjects, fasting plasma IGF-I, IGF-binding protein-3 (IGFBP-3), leptin, and lipid concentrations were determined; body composition was assessed by bioimpedance analysis; and insulin-mediated glucose up-take was evaluated by euglycemic hyperinsulinemic glucose clamp. IGF-I declined with advancing age, but no differences between aged subjects and centenarians were found. IGFBP-3 showed a trend similar to IGF-I, but lower values were present in centenarians than in aged subjects. Nevertheless, centenarians had a plasma IGF-I/IGFBP-3 molar ratio greater than that in aged subjects. Centenarians had also a whole body glucose disposal (WBGD) greater than that in aged subjects, but similar to that in adults. Mini Mental State Examination (27 +/- 2.1 vs. 18.3 +/- 3.1; P < 0.02) and Instrumental Activities Daily Living (26 +/- 2.6 vs. 8.4 +/- 4.1; P < 0.001) scores were significantly different in aged subjects and centenarians, respectively. In centenarians, the plasma IGF-I/IGFBP-3 molar ratio correlated with the body mass index (r = -0.55; P < 0.009); the amount of body fat (r = -0.62; P < 0.003); fat-free mass (r = 0.56; P < 0.008); fasting plasma leptin (r = -0.63; P < 0.004), triglycerides (r = -0.58; P < 0.01), free fatty acid (r = -0.64; P < 0.005), and low density lipoprotein cholesterol (r = -0.59; P < 0.009) concentrations; Mini Mental State Examination (r = 0.53; P < 0.0.03); and WBGD (r = 0.64; P < 0.005). All correlations were independent of daily fat and carbohydrate intake and WBGD (P < 0.05 for all). No significant correlations between the plasma IGF-I/IGFBP-3 molar ratio and plasma total (r = 0.31; P = NS) and high density lipoprotein cholesterol (r = 0.34; P = NS) concentrations were present. The correlation between the plasma IGF-I/IGFBP-3 molar ratio and WBGD persisted after adjustment for body fat, fasting plasma insulin concentration, daily carbohydrate and fat intake, and daily physical activity (r = 0.55; P < 0.009), but not after further adjustment for plasma free fatty acid concentration (r = 0.30; P = 0.17). In conclusion, healthy centenarians have plasma IGF-I/IGFBP-3 molar ratio greater than aged subjects. A more elevated plasma IGF-I/IGFBP-3 molar ratio might improve insulin action and plasma lipid concentration in centenarians.

The role of blood pressure in cognitive impairment in an elderly population

Abstract: OBJECTIVE The aim of this study was to investigate the cross-sectional relationship between arterial blood pressure and cognitive impairment in a group of elderly subjects, controlling for such confounding variables as age, education, depression, drug use and antihypertensive treatment. DESIGN AND SETTING A cross-sectional survey in Campania, a region in southern Italy. SUBJECTS AND METHODS A random sample of 1339 elderly subjects aged 65-95 years (mean 73.9 +/- 6.2 years) selected from the electoral rolls was interviewed by trained physicians. Sociodemographic characteristics, results of Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), blood pressure and whether antihypertensive treatment was being administered were recorded. When subjects with neurological diseases and those under psychotropic therapy were excluded from the analyses, the population numbered 1106. RESULTS The MMSE score was less than 24 for 27.9% of the subjects and the mean GDS score was 10.8 +/- 6.3. The mean systolic blood pressure (SBP) was 145.3 +/- 19.0 mmHg and the mean diastolic blood pressure (DBP) was 82.0 +/- 9.2 mmHg. Logistic regression analysis showed that female sex, age, GDS score and DBP but not SBP were predictive of cognitive impairment. Educational level and antihypertensive treatment, on the contrary, play a protective role. DBP was associated with cognitive impairment in subjects aged 75 years (odds ratio 1.62, 95% confidence interval 1.16-2.25) and over (odds ratio 5.16, 95% confidence interval 1.50-17.71) but not in those aged 65-74 years. CONCLUSION DBP but not SBP is predictive of cognitive impairment in subjects aged 75 years and over without neurological disorders independently from sex, age, education, GDS and antihypertensive treatment

Losartan mediated improvement in insulin action is mainly due to an increase in non-oxidative glucose metabolism and blood flow in insulin-resistant hypertensive patients

Abstract: We investigated the possible role of losartan on insulin-mediated glucose uptake, substrate oxidation and blood flow in insulin-resistant hypertensive patients. Sixteen newly diagnosed patients with mild-to-moderate hypertension were studied. The study design was a single-blind, randomised, placebo-controlled trial. After a 1 week run-in period, each patient was randomly assigned to placebo (n = 7) and losartan (n = 9). Both treatment periods lasted 4 weeks. At baseline, and at the end of the placebo and losartan treatment periods, euglycaemic hyperinsulinaemic glucose clamp and indirect calorimetry were performed. Before and along each glucose clamp, blood flow was also determined in the femoral artery by image-directed duplex ultrasonography combining B-mode imaging and pulse Doppler beams. Losartan vs placebo lowered systolic blood pressure by 163 +/- 3.5 and 147 +/- 4.1 mm Hg (P < 0.001), and diastolic blood pressure by 95 +/- 3.2 and 85 +/- 3.2 mm Hg (P < 0.001). Losartan enhanced glucose metabolic clearance rate by 5.1 +/- 0.3 and 6.3 +/- 0.4 mg/kg x min (P < 0.05), and whole body glucose disposal (WBGD) by 29.2 +/- 0.5 and 38.1 +/- 0.4 mumol/kg free fatty mass (FFM) x min (P < 0.01) but did not affect heart rate. Insulin-mediated change in blood flow was greater after losartan than placebo administration (111 +/- 4 vs 84 +/- 3%, P < 0.01). Per cent change in insulin-mediated stimulation of blood flow and WBGD were also correlated (r = 0.76, P < 0.01). Analysis of substrate oxidation revealed that losartan administration improved insulin action and non-oxidative glucose metabolism (NOGM) (30.8 +/- 2.2 vs 22.8 +/- 2.8 mumol/kg FFM x min, P < 0.05). In conclusion losartan improves insulin-mediated glucose uptake through an increase in NOGM and blood flow in hypertensive patients.

Is insulin action a determinant of left ventricular relaxation in uncomplicated essential hypertension

Abstract: ObjectiveTo examine the relation of insulin action and left ventricular diastolic function in uncomplicated essential hypertension.MethodsDoppler echocardiography and glucose clamping combined with indirect calorimetry were performed in 29, newly diagnosed, hypertensive men, free from cardiac and me

Glucose ingestion affects cardiac ANS in healthy subjects with different amounts of body fat.

Abstract: Low-to-high frequency ratio (LF/HF) is an indirect index of sympathovagal balance derived by heart rate spectral analysis. We investigated the effect of glucose ingestion on LF/HF in 17 healthy, no...

Association of fasting plasma free fatty acid concentration and frequency of ventricular premature complexes in nonischemic non-insulin-dependent diabetic patients.

Abstract: We investigated the association between free fatty acid (FFA) concentration and ventricular premature complexes (VPCs) in nonischemic patients with non-insulin-dependent diabetes mellitus using 3 approaches: cross-sectional analysis (n = 142), intervention including induction of elevated FFA levels with Intralipid heparin (n = 15), and reduction in FFA levels with Acipimox (n = 34) and a longitudinal follow-up study (n = 59). Patients at the third tertile of fasting plasma FFA concentration had the strongest increase in VPCs. Independently of age, sex, body mass index (BMI), waist/hip ratio, left ventricular mass index, glycated hemoglobin, fasting plasma insulin and triglyceride concentration, and daily physical activity, FFA concentration and VPCs were significantly correlated (r = 0.21 p <0.01). At multiple logistic regression analysis independently of age, sex, BMI, waist/hip ratio, left ventricular mass index, mean arterial blood pressure, glycated hemoglobin, fasting plasma insulin, triglycerides and potassium concentration, fasting plasma low-density lipoprotein/high-density lipoprotein cholesterol ratio, and daily physical activity, plasma FFA concentration was a significant determinant of VPCs (odds ratio 1.2, 95% confidence interval 1.0 to 2.3). Intralipid infusion (10% in 24 hours) (n = 15) and acipimox administration (250 mg, 4 times/day) (n = 34) increased, and decreased fasting plasma FFA concentration, respectively. In those studies, change in VPCs paralleled the effects on plasma FFA. In the longitudinal study (n = 59), plasma FFA concentration predicted the development of VPCs (RR 1.4 95% confidence interval 1.0 to 1.9) independently of age, sex, BMI, waist/hip ratio, left ventricular mass index, mean arterial blood pressure, fasting plasma triglyceride concentration, fasting plasma low-density lipoprotein/high-density lipoprotein cholesterol ratio, and daily physical activity. In conclusion, in nonischemic patients with non-insulin-dependent diabetes mellitus, plasma FFA concentration is associated with the frequency of ventricular premature complexes.

l-arginine but not d-arginine stimulates insulin-mediated glucose uptake

Abstract: Our study aims at investigating a possible role for l -arginine and d -arginine in insulin-mediated glucose uptake. Twelve lean healthy subjects volunteered for the study and were submitted to three euglycemic-hyperinsulinemic glucose clamps to investigate the effect of l -arginine (0.5 g/min in the last 60 minutes of the clamp), d -arginine (0.5 g/min in the last 60 minutes of the clamp), and saline 0.9% NaCl on insulin-mediated glucose uptake. All tests were made in random order. In study 1, l -arginine versus saline infusion was associated with a significant increase in blood flow (131% ± 7% v 87% ± 5%, P l -arginine delivery. After adjustment for the change in blood flow, WBGD was still greater after l -arginine than after saline infusion. Along with l -arginine infusion and independently of the change in blood flow, the percent change in WBGD correlated with the percent change in plasma cGMP (r = .56, P d -Arginine infusion did not affect insulin-mediated glucose uptake. In particular, WBGD (42.1 ± 3.4 v 41.3 ± 3.5 μmol/kg FFM · min, P = NS) was similar in both experimental conditions. Basal levels (2.8 ± 0.2 v 2.7 ± 0.3 nmol/L, P = NS) and the insulin-mediated increase (43% ± 5% v 39% ± 4%, P = NS) in plasma cGMP were also superimposable along with insulin plus d -arginine and insulin alone, respectively. Finally, blood flow (224 ± 29 v 230 ± 35 mL/min, P = NS) was not different at baseline and was similarly stimulated (84% ± 4% v 87% ± 5%, P = NS) by insulin infusion. In conclusion, l -arginine but not d -arginine stimulates insulin-mediated glucose uptake. Nitric oxide (NO), the metabolic mediator for l -arginine, potentiates insulin-mediated glucose uptake through the increase in blood flow. Nevertheless, an independent effect of intracellular cGMP on WBGD cannot be ruled out.

Insulin resistance and advancing age: what role for dehydroepiandrosterone sulfate?

Abstract: The relationship between insulin resistance and aging is still debated. This study aims to investigate the role that age-related differences in plasma dehydroepiandrosterone sulfate (DHEAS) concentration may have on insulin action. For this reason, 75 subjects (42 men and 33 women) with a wide age range (21 to 106 years) were studies. In all subjects, plasma DHEAS and total testosterone concentrations were measured and a euglycemic clamp was used, but substrate oxidation was not determined in centenarians (n = 15). Plasma DHEAS correlated with age (r = −.77, P

Preserved Antilipolytic Insulin Action Is Associated with a Less Atherogenic Plasma Lipid Profile in Healthy Centenarians

Abstract: OBJECTIVE: Recent studies have demonstrated that centenarians have a preserved glucose tolerance and insulin action and a more favorable body composition and fat distribution than aged subjects. The strong relationship among glucose tolerance, insulin action, plasma lipid concentration, and lipoprotein metabolism would lead to the hypothesis that healthy centenarians may also have a less atherogenic profile than aged subjects less than 100 years old. DESIGN: Investigation of the relationship between insulin action and lipid metabolism in healthy centenarians. PARTICIPANTS: Fifty-six subjects were categorized into three groups: Adults (≤ 50 years old; n = 20); Aged (≥ 75 years old; n = 22); Centenarians (≥100 years old; n = 14). The latter represented a select group of individuals free of major age-related diseases. MEASUREMENTS: Anthropometric measurements were made in all subjects, fasting blood samples were drawn for metabolite determinations, and an euglycemic glucose clamp was performed. RESULTS: Compared with aged subjects, healthy centenarians appeared to have a less atherogenic plasma lipid profile. Fasting plasma LDL cholesterol (2.4 ± 0.6 vs 3.7 ± .6 mmol/L P < .010) was significantly higher in aged subjects than in centenarians, whereas fasting plasma HDL cholesterol (1.0 ± 0.4 vs 1.7 ± .4 mmol/L P < .005) had an opposite trend. In centenarians, insulin-mediated glucose uptake was greater (34.6 ± 0.5 vs 23.3 ± .05 μmol/Kg FFM × min P < .010) than in aged subjects and correlated with fasting plasma triglycerides, FFA, LDL, and HDL cholesterol, Apo B, and Apo A1 concentrations. Finally, insulin infusion suppressed plasma FFA concentration in similar ways in adults and centenarians. CONCLUSION: Our study demonstrates that centenarians have a less atherogenic plasma lipid and lipoprotein profile than aged subjects J Am Geriatr Soc 45:1504–1509, 1997.