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Biomedical subjects

E Ferrannini

Publications and source records attributed to E Ferrannini.

At least 109 records · Page 6Linked to original sources
PubMed1997

Metabolic and cardiovascular assessment in moderate obesity: effect of weight loss.

Metabolic and hemodynamic abnormalities have been separately described in obesity, and weight reduction is known to lead to some improvement in each. Our aim was to simultaneously assess metabolic and cardiovascular function in normotensive, normotolerant patients with moderate obesity (body mass index = 32.6 +/- 1.1 kg/m2) before and after weight loss. The obese were insulin resistant [37.4 +/- 4.8 mumol/min.kg FFM; P < 0.02 vs. 12 lean controls (50.6 +/- 2.6), on a euglycemic insulin clamp], secreted more insulin both in the fasting state and after oral glucose (70 +/- 10 vs. 48 +/- 6 nmol/mmol.L plasma glucose; P < 0.05), and had higher resting energy expenditure (4.62 +/- 0.18 vs. 4.00 +/- 0.23 kJ/min), systolic and mean blood pressure, stroke volume (87 +/- 8 vs. 67 +/- 4 mL/min; P = 0.05), and cardiac output. There was, however, no relationship between the metabolic and hemodynamic abnormalities. After a weight loss of 11 +/- 1 kg (approximately 15%), insulin sensitivity improved in proportion to the weight reduction, whereas insulin hypersecretion and high energy expenditure persisted. In contrast, all hemodynamic changes reverted to normal. We conclude that in moderate obesity, the metabolic and cardiovascular abnormalities are largely independent of one another; accordingly, weight loss affects them differentially. Partial weight normalization may provide sufficient cardiovascular protection.

Adult↗
PubMed1997

Effect of insulin on systemic and renal handling of albumin in nondiabetic and NIDDM subjects.

Insulin resistance and hyperinsulinemia cluster with microalbuminuria in both diabetic and nondiabetic subjects, but the mechanism underlying this association is unknown. To test the hypothesis that insulin influences protein permeability, we measured the albumin transcapillary escape rate (TER) by the (131)I-labeled albumin technique in 12 healthy volunteers and 12 normoalbuminuric NIDDM patients (fasting plasma glucose, 10.9 +/- 1.3 mmol/l) during 4 h of isoglycemia with high (1.1 mU x min(-1) x kg(-1)) or, on a different day, low (0.1 mU x min(-1) x kg(-1)) insulin infusion. In both patients and control subjects, high insulin was associated with a 7% decrease in blood volume (P = 0.006) and a 6% decrease in diastolic blood pressure (P < 0.02), these two changes being related to one another (r = 0.56, P < 0.01). Basal albumin TER was similar in patients (8.4 +/- 0.5% x h(-1)) and control subjects (7.7 +/- 0.7% x h(-1)) and was not significantly changed by high insulin in either group (patients vs. control subjects, 7.3 +/- 0.9 vs. 6.2 +/- 0.4% x h(-1); NS vs. low insulin). In contrast, high insulin increased renal albumin excretion (from 3.6 +/- 0.8 to 5.4 +/- 1.1 microg/min, P < 0.01) and clearance rate (0.09 +/- 0.02 to 0.13 +/- 0.03 microl/min, P < 0.001) in patients but not in control subjects. To localize the effect of insulin along the nephron, we measured the urinary excretion of N-acetyl-beta-D-glucosaminidase (beta-NAG), released by the proximal tubule; retinol-binding protein (RBP), reabsorbed by the proximal tubule; and Tamm-Horsfall protein (THP) and epidermal growth factor (EGF), both secreted by the distal tubule. For both beta-NAG and RBP, but not EGF or THP, insulin enhanced urinary excretion (diabetics vs. controls: beta-NAG, 0.48 vs. -0.15 microU/min [P = 0.03]; RBP, 78 vs. -32 ng/min [P = 0.05]). In conclusion, physiological hyperinsulinemia does not affect systemic albumin permeability in healthy subjects or normoalbuminuric NIDDM patients. In contrast, in NIDDM patients, but not in healthy subjects, insulin increases the urinary excretion of albumin and protein markers of proximal tubular function. The significance of this finding for the pathogenesis of diabetic nephropathy remains to be established.

Adult↗
PubMed1996

Cardiac and skeletal muscle insulin resistance in patients with coronary heart disease. A study with positron emission tomography.

Patients with coronary artery disease or heart failure have been shown to be insulin resistant. Whether in these patients heart muscle participates in the insulin resistance, and whether reduced blood flow is a mechanism for such resistance is not known. We measured heart and skeletal muscle blood flow and glucose uptake during euglycemic hyperinsulinemia (insulin clamp) in 15 male patients with angiographically proven coronary artery disease and chronic regional wall motion abnormalities. Six age- and weight-matched healthy subjects served as controls. Regional glucose uptake was measured by positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose (FDG), blood flow was measured by the H2(15)O method. Myocardial glucose utilization was measured in regions with normal perfusion and wall motion as assessed by radionuclide ventriculography. Whole-body glucose uptake was 37+/-4 micromol x min(-1) x kg(-1) in controls and 14+/-2 mciromol x min(-1) x kg(-1) in patients (P = 0.001). Myocardial blood flow (1.09+/-0.06 vs. 0.97+/-0.04 ml x min(-1) x g(-1), controls vs. patients) and skeletal muscle (arm) blood flow (0.046+/-0.012 vs. 0.043+/-0.006 ml x min(-1) x g(-1)) were similar in the two groups (P = NS for both). In contrast, in patients both myocardial (0.38+/-0.03 vs. 0.70+/-0.03 micromol x min(-1) x g(-1), P = 0.0005) and muscle glucose uptake (0.026+/-0.004 vs. 0.056+/-0.006 micromol x min(-1) x g(-1), P = 0.005) were markedly reduced in comparison with controls. In the whole dataset, a direct relationship existed between insulin-stimulated glucose uptake in heart and skeletal muscle. Patients with a history of myocardial infarction and a low ejection fraction are insulin resistant. This insulin resistance affects both the myocardium and skeletal muscle and is independent of blood flow.

Adult↗
PubMed1996

Hyperinsulinemia in glucose-tolerant women with preeclampsia. A controlled study.

Essential hypertension is associated with insulin resistance and hyperinsulinemia. To assess whether hyperinsulinemia is also present in hypertensive disease induced by pregnancy, we studied the plasma glucose and insulin responses to 50 g of oral glucose in 10 women with definite, severe preeclampsia but normal glucose tolerance, and compared them with the responses observed in a well-matched control group of healthy pregnant women. Fasting plasma glucose concentrations were similar in healthy and preeclamptic pregnant mothers (4.1 +/- 0.4 mmol/L v 4.5 +/- 0.4 mmol/L, respectively, P = NS). Similar plasma glucose levels were also observed after glucose ingestion (5.5 +/- 0.3 mmol/L v 6.2 +/- 0.3 mmol/L in healthy and preeclamptic women, respectively P = NS). In contrast, fasting plasma insulin concentrations in the preeclamptic women were significantly higher than in normal pregnant mothers (175 +/- 29 pmol/L v 101 +/- 11 pmol/L, P < .05). Postload plasma insulin concentrations were nearly fourfold higher in the preeclamptic group as compared with the control group (1162 +/- 70 pmol/L v 366 +/- 39 pmol/L, P < .01). We conclude that preeclampsia is associated with marked hyperinsulinemia both in the fasting state and after oral glucose ingestion, suggesting that insulin resistance may play a role in pregnancy-induced hypertension.

Adult↗
PubMed1996

Effect of insulin on renal sodium and uric acid handling in essential hypertension.

In normal subjects, insulin decreases the urinary excretion of sodium, potassium, and uric acid. We tested whether these renal effects of insulin are altered in insulin resistant hypertension. In 37 patients with essential hypertension, we measured the changes in urinary excretion of sodium, potassium, and uric acid in response to physiological euglycemic hyperinsulinemia (by using the insulin clamp technique at an insulin infusion rate of 6 pmol/min/kg). Glucose disposal rate averaged 26.6 +/- 1.5 mumol/min/kg, i.e., 20% lower than in normotensive controls (33.1 +/- 2.1 mumol/min/kg, P = .015) In the basal state, fasting plasma uric acid concentrations were higher in men than women (P < .001), were positively related to body mass index (r = 0.38, P = .02), waist/hip ratio (r = 0.35, P < .05), and serum triglyceride levels (r = 0.59, P = .0001), and negatively related to HDL cholesterol concentrations (r = -0.59, P = .0001) and glucose disposal rate (r = 0.42, P < .01). Uric acid clearance, on the other hand, was inversely related to body mass index (r = 0.41, P = .01), plasma uric acid (r = 0.65, P < .0001) and triglyceride concentrations (r = 0.39, P < .02), and directly related to HDL cholesterol levels (r = 0.52, P < .001). During insulin infusion, blood pressure, plasma uric acid and sodium concentration, and creatinine clearance did not change. In contrast, hyperinsulinemia caused a significant decrease in the urinary excretion of uric acid (2.67 +/- 0.12 to 1.86 +/- .14 mumol/min/1.73 m2, P = .0001), sodium (184 +/- 12 to 137 +/- 14 mumol/min/1.73 m2, P = .0001), and potassium (81 +/- 7 to 48 +/- 4 mumol/ min/1.73 m2, P = .0001). Both in absolute terms (clearance and fractional excretion rates) and percentagewise, these changes were similar to those found in normotensive subjects. Insulin-induced changes in urate excretion were coupled (r = 0.55, P < .0001) to the respective changes in sodium excretion. In hypertensive patients, higher uric acid levels and lower renal urate clearance rates cluster with insulin resistance and dyslipidemia. Despite insulin resistance of glucose metabolism, acute physiological hyperinsulinemia causes normal antinatriuresis, antikaliuresis, and antiuricosuria in these patients.

Adult↗
PubMed1996

In vivo effect of insulin on intracellular calcium concentrations: relation to insulin resistance.

Elevated intracellular calcium concentrations ([Ca2+]i) have been described in essential hypertension and other insulin-resistant states. Our aim was to explore the relationship between insulin resistance and abnormal Ca2+ metabolism. In 50 nondiabetic subjects, half of whom had untreated essential hypertension, we simultaneously measured the in vivo effect of insulin on glucose metabolism (by the insulin clamp technique) and on platelet [Ca2+]i (by the Fura-2 method). In each subject, [Ca2+]i measurements (both in Ca(2+)-free medium and, sequentially, following in vitro Ca2+ loading) were obtained in the fasting state and after 2 hours of euglycemic hyperinsulinemia. In the fasting state, no association was found between any measure of [Ca2+]i and gender, age, body mass index (BMI), blood pressure, or insulin sensitivity. In contrast, following in vivo insulin, platelet [Ca2+]i increased significantly (from 23 +/- 1 to 28 +/- 1 nmol/L in Ca(2+)-free medium, P < .01) in the whole group, and an insulin-induced increase in [Ca2+]i was associated with insulin resistance (r = .35, P = .01) but not with hypertension (r = .2, P = .17) and with impaired glucose storage (as determined by indirect calorimetry, r = .39, P = .01) but not with glucose oxidation. Thus, the 12 most insulin-resistant subjects were characterized by a cluster of abnormalities (mild overweight, higher blood pressure and prevalence of hypertension, higher serum triglycerides and insulin response to oral glucose, and reduced glucose storage) that included an insulin-induced increase in [Ca2+]i (9 +/- 2 nmol/L, P < .001 v basal). We conclude that insulin resistance, rather than hypertension, is associated with an abnormal in vivo effect of insulin on platelet [Ca2+]i.

Adult↗
PubMed1996

Insulin decreases circulating vitamin E levels in humans.

Both hyperinsulinemia and free oxygen radicals have been implicated in the pathogenesis of atherosclerosis, but the relationship between insulin levels or insulin action and the oxidant/antioxidant balance has not been explored. We measured the effect of physiologic hyperinsulinemia on plasma concentrations of vitamin E, a major free radical scavenger molecule. Isoglycemic clamps (at an insulin infusion rate of 6 pmol . min-1 . kg-1) were performed in four groups of subjects: (1) 12 non-insulin-dependent diabetic (NIDDM) patients, (2) eight patients with essential hypertension, (3) 11 nondiabetic obese individuals, and (4) 12 healthy subjects. In 10 healthy volunteers, a time-control experiment was performed by replacing the insulin infusion with normal saline. Vitamin E and plasma lipid levels were determined at baseline and after 2 hours of insulin/saline infusion. Insulin sensitivity was reduced in diabetic, obese, and hypertensive groups in comparison to healthy controls, but fasting plasma vitamin E concentrations were similar in all groups. A consistent decrement in plasma vitamin E concentrations (averaging 12% of baseline, P < .0001) was observed in all subjects receiving insulin regardless of the level of insulin sensitivity, whereas no significant changes in plasma vitamin E were seen in subjects receiving saline infusion (P < .001 v insulin infusion groups). The insulin-induced decrement persisted in all study groups when plasma vitamin E concentrations were corrected for total serum cholesterol levels (-8.9% +/- 1.2% v -0.4 +/- 2.3% of saline controls, P = .0004) or serum low-density lipoprotein (LDL(-10.0% +/- 1.2% v -0.4% +/- 2.2%, P = .0002). We conclude that insulin infusion acutely depletes vitamin E in circulating lipids regardless of insulin resistance. This effect may represent a physiologic means of transferring vitamin E into cell membranes; alternatively, it might reflect a pro-oxidant action of insulin in vivo.

Adult↗
PubMed1996

Renovascular hypertension and insulin sensitivity.

We tested the hypothesis that the status of the renin-angiotensin-aldosterone system affects insulin sensitivity. Insulin sensitivity (by the euglycaemic insulin clamp technique) was measured in eight patients with angiographically proven renovascular hypertension and in eight normotensive subjects matched for age, gender, body mass index and glucose tolerance. In the patients, insulin sensitivity was measured both at baseline and following 7 days of ACE inhibition. Following glucose ingestion, patients and controls showed similar insulin and glucose responses. Insulin infusion (7 pmol min-1 kg-1) promoted similar glucose utilization in the hypertensives and normotensives: 24.8 +/- 2.3 vs. 26.0 +/- 3.0 mumol min-1 kg-1 respectively. One week of ACE inhibition caused a 20 +/- 4 mmHg decrease in mean blood pressure and a 20 +/- 6% decrease in peripheral vascular resistance. Plasma angiotensin II concentrations dropped from 24.6 +/- 6.3 to 13.5 +/-5.0 pg mL-1 (P < 0.05) and plasma aldosterone from 17 +/- 4 to 9 +/- 2 ng dL-1 (P < 0.05), and plasma renin activity doubled (from 1.6 +/- 0.3 to 3.4 +/- 1.7 ng mL-1 h-1, P < 0.02). Nevertheless, insulin sensitivity was unchanged (before, 24.8 +/- 2.3; after 25.8 +/- 2.2 mumol min-1 kg-1, P = Ns). During insulin infusion, forearm blood flow did not change from baseline in either set of studies. Also, the antinatriuretic (before, -26 +/- 18; after, -22 +/- 14%) and antikaliuretic (before: -36 +/- 13%, after -39 +/- 11%) action of the hormone was unaffected by the therapy. In conclusion, renovascular hypertension is not associated with insulin resistance. Furthermore, a selective, drastic reduction of the renin-angiotensin-aldosterone system activity and vascular tone does not alter insulin action on glucose and electrolyte metabolism.

Adult↗
PubMed1996

Insulin sensitivity in cardiological syndrome X.

OBJECTIVES: To test whether cardiological syndrome X is an insulin-resistant state. SETTING, DESIGN AND SUBJECTS: The coronary care unit of a referral centre for angina pectoris in Pisa, Italy. A case-control study, involving 10 patients with unequivocal (angiographycally proven) cardiological syndrome X, but normal glucose tolerance, blood pressure and lipid levels, and 13 matched healthy subjects. MAIN OUTCOME MEASURES: Insulin sensitivity and pattern of substrate oxidation (assessed by the euglycaemic insulin clamp technique in combination with indirect calorimetry). RESULTS: Fasting plasma glucose and insulin levels were 5.05 +/- 0.11 versus 4.88 +/- 0.11 mmol l-1 and 68 +/- 10 versus 56 +/- 6 pmol l-1, respectively (controls versus patients, ns). During the insulin clamp, glucose disposal rate was nearly identical in patients and controls (25.9 +/- 1.8 and 27.2 +/- 1.8 mumol kg-1 min-1, respectively. P = 0.88). Non-oxidative glucose disposal accounted for similar proportions of total glucose uptake (59 versus 53%, patients versus controls, ns). Resting energy expenditure (13.7 +/- 0.6 versus 13.8 +/- 0.8 cal kg-1 min-1, ns) and insulin-induced thermogenesis were similar in the two groups. Fasting plasma NEFA concentrations (0.64 +/- 0.09 and 0.64 +/- 0.06 mmol l-1, patients and controls, ns) fell in a similar time-course and to virtually identical nadirs (0.13 +/- 0.02 and 0.14 +/- 0.02 mmol l-1) after insulin infusion. Fasting plasma potassium was similar in patients and controls (3.99 +/- 0.10 and 4.16 +/- 0.04 mmol l-1, ns), and insulin induced equivalent hypokalaemia (-14 versus -19%). CONCLUSIONS: None of the in vivo actions of insulin were impaired in patients with 'pure' syndrome X when compared to matched controls. Therefore, we conclude that cardiological syndrome X is not an insulin resistant state per se, and that any decrease in insulin sensitivity found in this condition is likely to be secondary.

Blood Glucose↗
PubMed1996

Effect of a reduced-fat diet with or without pravastatin on glucose tolerance and insulin sensitivity in patients with primary hypercholesterolemia.

Pharmacological treatment of hyperlipidemia may be associated with deterioration of glucose tolerance. We randomized 20 nonobese patients with primary familial hypercholesterolemia (serum total cholesterol 7.8 +/- 0.4 mM, triglycerides 1.4 +/- 0.2 mM) to an isocaloric, reduced fat (< 30%) low-cholesterol (200 mg/day) diet with placebo or pravastatin (40 mg/day). Oral glucose tolerance, endogenous insulin response to glucose, insulin sensitivity (determined by the euglycemic insulin clamp technique), hepatic glucose production (by the tritiated glucose technique), and substrate utilization (by indirect calorimetry) were measured at baseline and after 8 weeks of treatment. Ten normocholesterolemic healthy subjects, matched to the patients by age, sex, and body weight, served as the control group. Diet alone (with no change in body weight) was associated with a significant 15% decrease in both serum low density lipoprotein (LDL)-cholesterol and triglycerides (p < 0.001 for both), and a slight decrease in high density lipoprotein (HDL)-cholesterol concentrations, paralleled by reductions in Apo B, C2, C3, and E levels (p < 0.05 or less). The addition of pravastatin led to a significantly larger reduction in LDL-cholesterol (30%, p < 0.05) and an 8% increase (p < 0.02) in total HDL-cholesterol concentrations. Accordingly, the ratio of LDL:HDL cholesterol (which was 60% higher than in controls at baseline) remained unchanged in the placebo-diet group whereas it was restored to normal in the pravastatin-diet group. Glucose tolerance, insulin response, insulin-induced inhibition of hepatic glucose production and lipolysis, and insulin-mediated glucose uptake and oxidation were all slightly but not significantly improved after treatment, with no significant differences between pravastatin and placebo. In nonobese patients with primary hypercholesterolemia, pravastatin treatment in combination with an isocaloric, reduced-fat diet leads to a marked reduction in LDL-cholesterol and triglycerides levels and a normalization of the LDL:HDL ratio without affecting glucose tolerance or insulin sensitivity.

Adult↗
PubMed1996

Acute insulin administration does not affect plasma leptin levels in lean or obese subjects.

Whether leptin levels are related to insulin sensitivity or subject to acute regulation by insulin is not known. In 12 obese [body mass index (BMI) = 34.0 +/- 1.5 kg m-2] and 12 lean (BMI = 22.2 +/- 0.6 kg m-2) non-diabetic subjects, plasma leptin concentrations were measured in the fasting state and during 2 hours of euglycaemic hyperinsulinaemia (approximately 600 pmol L-1). Fasting plasma leptin was significantly higher in obese (26.6 +/- 3.2) than in lean subjects (6.4 +/- 1.2 ng mL-1, P = 0.0001), and in women (21.1 +/- 3.3) than in men (7.3 +/- 2.3 ng mL-1, P = 0.01). In univariate analysis, fasting plasma leptin was strongly related to all anthropometric measures (body weight, fat mass, percent fat mass, waist and hip circumferences). In multiple regression, per cent adiposity, hip circumference and duration of obesity explained 90% of the variability in fasting leptin concentrations. Fasting and stimulated (OGTT) insulin levels, insulin sensitivity (22.6 +/- 1.9 vs 36.7 +/- 2.0 mumol min-1 kg-1 in lean and obese subjects, respectively, P < 0.0001), glucose area, and serum triglycerides were positively related to fasting plasma leptin concentrations; none of these associations, however, was statistically significant after adjusting for BMI. During the clamp, plasma leptin concentrations remained constant in both lean and obese subjects. We conclude that neither insulin levels nor sensitivity relate to leptin levels independently of fat mass, and that leptin is not subject to acute (2 hours) regulation by insulin in lean or obese humans.

Adult↗
PubMed1996

Roles of glucose transport and glucose phosphorylation in muscle insulin resistance of NIDDM.

Insulin resistance for glucose metabolism in skeletal muscle is a key feature in NIDDM. The quantitative role of the cellular effectors of glucose metabolism in determining this insulin resistance is still imperfectly known. We assessed transmembrane glucose transport and intracellular glucose phosphorylation in vivo in skeletal muscle in nonobese NIDDM patients. We performed euglycemic insulin clamp studies in combination with the forearm balance technique (brachial artery and deep forearm vein catheterization) in five nonobese NIDDM patients and seven age- and weight-matched control subjects (study 1). D-Mannitol (a nontransportable molecule), 3-O-[14C]methyl-D-glucose (transportable, but not metabolizable) and D[3-3H]glucose (transportable and metabolizable) were simultaneously injected into the brachial artery, and the washout curves were measured in the deep venous effluent blood. In vivo rates of transmembrane transport and intracellular phosphorylation of D-glucose in forearm muscle were determined by analyzing the washout curves with the aid of a multicompartmental model of glucose kinetics in forearm tissues. At similar steady-state concentrations of plasma insulin (approximately 500 pmol/l) and glucose (approximately 5.0 mmol/l), the rates of transmembrane influx (34.3 +/- 9.1 vs. 58.5 +/- 6.5 micromol x min(-1) x kg(-1), P < 0.05) and intracellular phosphorylation (5.4 +/- 1.6 vs. 38.8 +/- 5.1 micromol x min(-1) x kg(-1), P < 0.01) in skeletal muscle were markedly lower in the NIDDM patients than in the control subjects. In the NIDDM patients (study 2), the insulin clamp was repeated at hyperglycemia, (approximately 13 mmol/l) trying to match the rates of transmembrane glucose influx measured during the clamp in the controls. The rate of transmembrane glucose influx (62 +/- 15 micromol x min(-1) x kg(-1)) in the NIDDM patients was similar to the control subjects, but the rate of intracellular glucose phosphorylation (16.6 +/- 7.5 micromol x min(-1) x kg(-1)), although threefold higher than in the patients during study 1 (P < 0.05), was still approximately 60% lower than in the control subjects (P < 0.05). These data suggest that when assessed in vivo, both transmembrane transport and intracellular phosphorylation of glucose are refractory to insulin action and add to each other in determining insulin resistance in skeletal muscle of NIDDM patients. It will be of interest to compare the present results with the in vivo quantitation of the initial rate of muscle glucose transport when methodology to perform this measurement becomes available.

3-O-Methylglucose↗
PubMed1996

Insulin action and age. European Group for the Study of Insulin Resistance (EGIR).

Evidence that age is associated with insulin resistance is discordant. We analyzed euglycemic insulin clamp (1 mU x min(-1) x kg(-1)) data collected at 20 centers throughout Europe from 1,146 men and women with normal glucose tolerance, ranging in age from 18 to 85 years. In the whole group, insulin action (as the M value) declined slightly with age (at a rate of 0.9 micromol x min(-1)-kg(-1) per decade of life, 95% CI = 0.4-1.3, P = 0.0002). When adjusted for BMI, this relationship was no longer statistically significant. The same result was obtained whether insulin action was expressed per kilogram of body weight or per kilogram of fat-free mass, expressed as the M:I ratio, or estimated from fasting plasma insulin concentrations. Subgroup analysis showed that a significant BMI-adjusted decrease in insulin action with age was present only in lean (BMI <25 kg/m2) women (a rate of 1.6 micromol x min(-1) x kg(-1) per decade, 95% CI = 0.6-2.5, P = 0.001), in whom percentage fat mass also increased with age (by 0.38% body weight per decade, P = 0.0007). Insulin action was positively associated with insulin suppression of circulating free fatty acids (FFAs) (+1.5 micromol x min(-1) x kg(-1) for each 10% increase in FFA suppression, P < 0.0001) in a multivariate model accounting for sex, BMI, age, and fasting FFA levels. Furthermore, insulin suppression of FFAs improved with age in men (2% per decade, P < 0.0001) but not in women. In the subgroup of lean women in whom insulin action declined with age, adding FFA suppression to a multiple regression equation canceled the association between age and insulin action. Thus, the small effect of age on insulin action could be adequately explained on the basis of age-related changes in body composition and substrate competition. We conclude that in healthy Europeans, age per se is not a significant cause of insulin resistance of glucose metabolism or lipolysis.

Adult↗
PubMed1996

Differential impact of insulin and obesity on cardiovascular risk factors in non-diabetic subjects.

OBJECTIVE: To assess the differential impact of obesity and hyperinsulinaemia on cardiovascular risk factors in non-diabetic, normotensive subjects. DESIGN: Cross-sectional (n = 1897) and 8-year follow-up data (n = 1047) from non-diabetic, normotensive, normolipidaemic men and women (screened in the San Antonio Heart Study) with a body mass index [BMI] in the range 15.2-58.5 kg/m2. RESULTS: 183 of 849 obese subjects (BMI > or = 27 kg/m2 in men, > or = 26 in women) had fasting and post-glucose plasma insulin concentrations superimposable on those of the normoinsulinaemic segment of the non-obese subgroup. Yet, waist/hip ratio (WHR), systolic and diastolic blood pressure, fasting plasma glucose and triglyceride levels were significantly higher, and serum HDL-cholesterol concentrations lower, in the obese than in the non-obese. In the whole sample (n = 1897), both obesity and hyperinsulinaemia were independently associated with higher WHR, arterial blood pressure, fasting and post-load plasma glucose and triglyceride concentrations, and lower HDL-cholesterol levels. This pattern of associations was essentially unaltered after adjustment by WHR. In the subjects re-tested 8 years following the initial screening, the 8-year changes in the level of cardiovascular risk factors were significantly associated with the corresponding changes in both fasting plasma insulin and BMI, independently of one another. CONCLUSIONS: Although plasma insulin and body weight are closely inter-related variables, they have a separate impact on the cardiovascular risk profile in normal subjects.

Adult↗
PubMed1996

Delta-aminolevulinic acid dehydratase and zinc protoporphyrin in very low lead-exposed pets: a community study.

Markers of lead intoxication have been developed based on their capacity to identify lead intoxication at the preclinical, ie biochemical stage of manifestation. However, little information on these markers is available under conditions of low lead exposure. This prompted us to conduct a community-based study to determine the usefulness of theta-aminolevulinic acid dehydratase (ALAD) and zinc protoporphyrin (ZnPP) in conditions of low lead environmental exposure by studying the relationships between low blood lead levels, ALAD and ZnPP in a large group of healthy dogs living in an Italian urban area. The study population consisted of 79 dogs. Each sample was tested for ALAD, lead and ZnPP and for complete blood count, hemoglobin, AST, ALT, and urea values. A weak inverse relationship between ALAD and ZnPP was found. An inverse relationship between ALAD and lead concentrations was found in the whole group (p < 0.0005). This relationship remained significant when selecting the values falling between 2 standard deviations of the mean blood lead concentrations of the population below the "concerned lead levels" (< 10 mg/dl; p = 0.0005). There was no relationship between whole blood ZnPP concentrations and whole blood lead levels. The sensitivity and specificity of ALAD measurements, calculated by using the 2 x 2 contingency table with respect to blood lead concentrations, were of poor predictive diagnostic value.

Animals↗
PubMed1995

Effect of insulin on acetylcholine-induced vasodilation in normotensive subjects and patients with essential hypertension.

BACKGROUND: The present study was designed to directly test the vasodilation action of insulin and its relation to endothelium-dependent mechanisms. METHODS AND RESULTS: In 18 normotensive subjects and 27 patients with untreated mild to moderate essential hypertension, we studied the effect of intrabrachial insulin on the changes in forearm blood flow (strain-gauge plethysmography) induced by intrabrachial acetylcholine (at doses of 0.15, 0.45, 1.5, 4.5, and 15 micrograms.min-1.dL-1), an endothelium-dependent vasodilator, or sodium nitroprusside (at doses of 1, 2, and 4 micrograms.min-1.dL-1), and endothelium-independent vasodilator. Local hyperinsulinemia (deep venous plasma insulin, 48 +/- 6 and 51 +/- 5 microU/mL in control subjects and hypertensive patients, respectively) did not affect basal forearm blood flow and stimulated forearm glucose extraction (control subjects, 3 +/- 1% to 11 +/- 2%, P < .001; hypertensive patients, 3 +/- 1% to 6 +/- 1%, P < .001; P < .01 for the between-group difference). In both normotensive and hypertensive subjects, insulin significantly potentiated acetylcholine-induced vasodilation, whereas it did not alter the vasodilatory response to sodium nitroprusside. NG-monomethyl-L-arginine, an inhibitor of endothelial nitric oxide synthesis, blunted insulin-induced facilitation of acetylcholine vasodilation in normotensive but not in hypertensive subjects. In contrast, in hypertensive patients but not in normotensive control subjects, the potentiation of the vascular response to acetylcholine induced by local hyperinsulinemia was abolished by intrabrachial ouabain, an inhibitor of Na(+)-K+ pump. CONCLUSIONS: In healthy humans and essential hypertensive patients alike, local physiological hyperinsulinemia per se does not increase forearm blood flow but potentiates the vasodilation induced by acetylcholine regardless of metabolic insulin resistance. This effect is endothelium-dependent because it is not seen with nitroprusside and is related to the L-arginine-nitric oxide pathway in normotensive subjects and to smooth muscle cell hyperpolarization in essential hypertensive patients.

Acetylcholine↗