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I Zavaroni

Publications and source records attributed to I Zavaroni.

At least 37 records · Page 2Linked to original sources

Abnormalities of insulin and lipid metabolism in Milan hypertensive rats.

Plasma glucose, insulin, triglyceride, and cholesterol concentrations were measured in male rats of the Milan hypertensive strain (MHS) and compared to the Milan normotensive strain (MNS) of the same body weight. Both blood pressure (P less than .001) and left ventricular weight (P less than .005) were higher in rats of the MHS. Although plasma glucose concentrations were similar in both groups, mean (+/- SEM) plasma insulin concentration were significantly higher (P less than .01) in MHS as compared to MNS rats (30 +/- 4 v. 13 +/- 5 microU/mL). In addition mean (+/- SEM) plasma triglyceride concentrations were higher (P less than .01) in MHS rats (112 +/- 9 mg/dL) than in MNS rats (81 +/- 6 mg/dL), as were plasma cholesterol concentrations (114 +/- 3 v 100 +/- 2 mg/dL, P less than .001). These data demonstrate the presence of hyperinsulinemia and hypertriglyceridemia in another genetic model of rat hypertension.

Animals↗

Insulin-resistance and associated risk factors for coronary heart disease as seen in families.

Recent reports have shown that resistance to insulin-stimulated glucose uptake, increased plasma glucose and insulin response to oral glucose, and hypertriglyceridemia can be seen in first degree relatives of patients with type 2 diabetes. We have recently shown that very similar metabolic changes can be seen in hyperinsulinemic individuals who have either normal or impaired glucose tolerance (IGT). Given these data, we thought it would be of interest to compare the plasma glucose and insulin response to an oral glucose challenge, plasma lipid concentrations, and blood pressure in offspring of parents with IGT as compared to offspring of parents with normal glucose tolerance. Parents with IGT had higher plasma insulin and triglyceride levels and blood pressure than those with normal glucose tolerance. The two groups of offspring were young, non-obese and similar in terms of age, gender distribution and body mass index. Statistically significant increases in plasma insulin response to oral glucose and in systolic and diastolic blood pressure were present in the offspring of parents with IGT. Demonstration of similar abnormalities in plasma insulin response to glucose and blood pressure regulation in patients with IGT and in their offspring is consistent with the view that individual differences in insulin metabolism and blood pressure are modulated by genetic factors and that both may be related to variations in insulin-stimulated glucose uptake and/or plasma insulin concentration.

Blood Glucose↗

High plasma insulin and triglyceride concentrations and blood pressure in offspring of people with impaired glucose tolerance.

The plasma glucose and insulin response to an oral glucose challenge, fasting plasma lipid concentration, and blood pressure were compared in 13 offspring of parents previously diagnosed as having impaired glucose tolerance (IGT) and 13 offspring of parents previously shown to have normal glucose tolerance. The parents with IGT had higher plasma glucose, insulin and triglyceride concentration, and blood pressure than parents with normal glucose tolerance. The two groups of offspring were young and non-obese, and similar in terms of age, gender distribution, and body mass index. However, the total integrated plasma insulin response during a 75 g oral glucose tolerance test was significantly higher (p less than 0.05, Student's t-test) in offspring of parents with IGT (718 +/- 71 pmol l-1 h) than in the subjects whose parents had normal glucose tolerance (524 +/- 47 pmol l-1 h). In addition, serum triglyceride concentration was somewhat higher in offspring of parents with IGT (1.17 +/- 0.11 vs 0.92 +/- 0.08 mmol l-1, 0.10 greater than p greater than 0.05), as were both systolic (132 +/- 5 vs 118 +/- 3 mmHg, p less than 0.05) and diastolic (79 +/- 3 vs 70 +/- 2 mmHg, p less than 0.05) blood pressure. Demonstration of similar abnormalities in plasma insulin response to glucose and blood pressure regulation in patients with IGT and in their offspring is consistent with the view that these changes have a genetic component.

Adult↗

Risk factors for coronary artery disease in healthy persons with hyperinsulinemia and normal glucose tolerance.

We studied the relation of serum insulin levels to plasma lipid levels and blood pressure in two groups drawn from among 247 healthy, normotensive nonobese subjects with normal glucose tolerance. One group of 32 subjects was defined as having hyperinsulinemia (serum insulin, greater than 2 SD above the mean) and then compared with 32 normoinsulinemic subjects (serum insulin within 1 SD of the mean) matched for age (mean, 39 years), sex (22 men and 10 women), and body-mass index (24.7). The two groups had similar patterns of smoking, drinking, and physical exercise. Plasma glucose levels after an oral glucose challenge were significantly higher (P less than 0.05) in the hyperinsulinemic group. In addition, the mean (+/- SEM) fasting plasma triglyceride levels in subjects with hyperinsulinemia were significantly higher (1.73 +/- 0.2 vs. 1.24 +/- 0.1 mmol per liter) and the plasma high-density lipoprotein cholesterol concentrations were lower (1.21 +/- 0.06 vs. 1.43 +/- 0.06 mmol per liter) than in subjects with normoinsulinemia. Both systolic (126 vs. 119 mm Hg; P less than 0.05) and diastolic (85 vs. 78 mm Hg; P less than 0.01) blood pressures were significantly elevated in the group with hyperinsulinemia. We conclude that healthy persons with hyperinsulinemia and normal glucose tolerance have an increase in risk factors for coronary artery disease, as compared with a well-matched group of healthy subjects with normal insulin levels.

Adult↗

Habitual leisure-time physical activity is associated with differences in various risk factors for coronary artery disease.

Various risk factors for coronary artery disease (CAD) were compared in 100 healthy, male factory workers, divided into two groups of 50 each on the basis of their leisure-time activity. The two groups, designated as sedentary and physically active, were similar in terms of age and body mass index, but the physically active group had a significantly slower pulse rate. In addition, the plasma glucose and insulin responses to an oral glucose load were significantly lower in physically active individuals. Furthermore, fasting plasma triglyceride concentration was significantly lower and the high-density lipoprotein-cholesterol concentration was higher in the physically active individuals. Thus, substantial benefits in terms of CAD risk were associated with increased leisure-time physical activity.

Adult↗

Relationship between blood pressure and plasma insulin in non-obese and obese non-diabetic subjects.

In this study, we have measured plasma insulin at fasting and following an oral glucose load and blood pressure after glucose load in 367 (247 non-obese, 120 obese) normotensive and untreated mildly hypertensive subjects. Overall, there was no independent association between fasting plasma insulin levels and blood pressure values. After controlling for age and body weight, a significant relationship between postglucose plasma insulin levels and diastolic blood pressure was found. When non-obese and obese subjects were examined separately, significant relationships were identified between postglucose plasma insulin levels and both systolic and diastolic blood pressure values in the former but not in the latter. A comparison of sex-, age-, and weight-matched hyperinsulinaemic vs normoinsulinaemic subjects showed that the former had significantly higher values of blood pressure only if not obese. These results demonstrate that the plasma insulin response to glucose is independently correlated with blood pressure.

Adult↗

Fractional hepatic extraction of insulin in man: is it constant?

The present study was designed to compare insulin extraction by the liver following oral glucose administrations of different size, in order to evaluate insulin removal by the liver in relation to the insulin exposure, and to the amount of ingested glucose. Insulin secretion by the pancreas was estimated by the measurement of peripheral C-peptide levels, and insulin extraction by the liver by the analysis of peripheral C-peptide to insulin ratios and relations. Ten healthy subjects (5 males and 5 females), aged 16 to 66 yr, with normal bw, and without family history of diabetes mellitus were investigated by means of the administration, on alternate days, of 50 and 150 g oral glucose loads. After the 150 g oral glucose load plasma glucose levels were significantly higher than after the 50 g oral glucose administration: glucose incremental areas of 1.45 +/- 0.12 vs. 0.55 +/- 0.04 mmol/l X min, respectively (p less than 0.001). Similarly, insulin concentrations were significantly higher following 150 g than after 50 g glucose ingestion: insulin incremental areas of 0.52 +/- 0.09 vs. 0.20 +/- 0.04 nmol/l X min (p less than 0.001). Also C-peptide levels were higher after 150 vs. 50 g oral glucose load: C-peptide incremental areas of 1.85 +/- 0.41 vs. 0.64 +/- 0.13 nmol/l X min (p less than 0.01). C-peptide to insulin molar ratios were similar during the two glucose challenge, and averaged 5.25 +/- 0.42 vs. 5.08 +/- 0.50 after 50 and 150 g oral glucose loads, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Evidence that multiple risk factors for coronary artery disease exist in persons with abnormal glucose tolerance.

Multiple risk factors for coronary artery disease were determined in 50 healthy, non-diabetic persons with an oral glucose tolerance test result that could not be classified as normal by current criteria and 50 sex-, age-, and weight-matched persons with normal oral glucose tolerance. The results indicated that persons with abnormal oral glucose tolerance were hyperinsulinemic, as well as hypercholesterolemic and hypertriglyceridemic. In addition, patients with abnormal results in glucose tolerance tests had significantly elevated systolic blood pressure and heart rates. These data suggest that a cluster of risk factors for coronary artery disease exists in non-diabetic persons with abnormal oral glucose tolerance.

Adult↗

Influence of the menstrual cycle on glucose tolerance and insulin secretion.

To evaluate the impact of the menstrual cycle on glucose tolerance and insulin secretion, in the present study we have measured the plasma concentrations of glucose, insulin, and C-peptide during a 2-hour oral glucose tolerance test in 110 healthy, nonobese, regularly menstruating women. Fifty-five women were in the follicular phase, and 55 were in the luteal phase of the cycle. The two groups were well matched for age and body weight. Plasma concentrations of glucose, insulin, and C-peptide either in the fasting state or after the oral glucose load did not differ in the two groups. These results suggest that in nondiabetic women the menstrual cycle has no major effect on glucose tolerance and insulin secretion and that the phase of the menstrual cycle should not be considered in programming and interpreting an oral glucose tolerance test.

Adult↗

Renal metabolism of C-peptide in man.

Renal metabolism of C-peptide was studied in nine nondiabetic nonobese patients with normal renal function by the arterial-venous difference technique before and after the oral administration of an amino acid mixture simulating an animal protein meal. In the basal state, the kidney removed 25.7 +/- 7.5% (+/- SD) of the arterial plasma C-peptide. Renal uptake was approximately 7-fold greater than urinary excretion, and thus, more than 85% of the amount extracted was metabolized by the kidney. Renal C-peptide clearance was very high and approximated the glomerular filtration rate, whereas urinary C-peptide clearance was only 14% of its renal clearance. Shortly after amino acid ingestion, arterial C-peptide levels increased by 107%, and C-peptide renal fractional extraction, uptake, and net metabolism also increased markedly (67%, 278%, and 328%, respectively); urinary clearance and excretion did not change. Renal clearance became 2-fold greater than the glomerular filtration rate, indicating that in this phase the kidney removed substantial amounts of C-peptide from peritubular blood as well as by filtration. Both renal uptake and urinary excretion of C-peptide were related to its arterial levels (P less than 0.001 and P less than 0.05, respectively), but renal uptake increased much more than urinary excretion for each increment in arterial C-peptide levels. These results indicate that renal C-peptide metabolism is considerable in the postabsorptive state and is even more marked during the postprandial period. The kidney, therefore, plays a key role in both the regulation of circulating plasma levels and the metabolic clearance of C-peptide.

Adult↗

Relationships between insulin secretion, insulin metabolism and insulin resistance in mild glucose intolerance.

The aim of this study was to evaluate whether the correlation between insulin resistance and peripheral hyperinsulinaemia existing in mild glucose intolerance corresponds to a relationship between insulin resistance and insulin overproduction by the pancreas. In addition, the possibility that insulin resistance is related to insulin metabolism was examined. Twenty five subjects with fasting normoglycaemia and an abnormal glucose response to the oral glucose tolerance test (OGTT) were studied. Insulin secretion by the pancreas was estimated by means of fasting C-peptide levels in peripheral blood. Insulin resistance was estimated by the rate of glucose disappearance from plasma after i.v. insulin injection. Insulin metabolism was estimated indirectly by the C-peptide: insulin molar ratio. A negative correlation was found between the glucose disappearance rate from plasma after i.v. insulin injection and fasting insulin levels (r = -0.677, p less than 0.001), but not fasting C-peptide concentrations (r = -0.164, p = NS). Glucose disappearance rate from plasma correlated positively with the C-peptide: insulin molar ratio (r = 0.626, p less than 0.001). These results suggest that in mild glucose intolerance insulin resistance and insulin secretion by the pancreas are not related phenomena, and that the defect responsible for insulin resistance might also be implicated in the impaired insulin metabolism.

Adult↗

Further evidence that insulin metabolism is a major determinant of peripheral insulin response to oral glucose in subjects with mild glucose intolerance.

In mild glucose intolerance plasma concentration of C-peptide seems to give an estimate of pancreatic B cell secretion more reliable than plasma insulin itself. In the present study we measured the plasma levels of insulin and C-peptide after oral glucose load in 100 mildly glucose intolerant subjects, focusing our attention on high and low insulin responders. According to an insulin incremental area after oral glucose higher or lower than the mean +/- SD of the mean, 16 subjects were classified as "high insulin responders", and 17 as "low insulin responders". The two groups were similar for sex, age and bw. Mean insulin incremental area was almost 9-fold greater in high insulin responders than in low insulin responders (0.88 +/- 0.03 vs 0.10 +/- 0.01 pmol/ml min, p less than 0.001). Also mean C-peptide incremental area was significantly greater in high insulin responders than in low insulin responders, but the differences between the two groups were smaller. Indeed, mean C-peptide area was approximately 2.5-fold greater in high insulin responders than in low insulin responders (1.58 +/- 0.12 vs 0.66 +/- 0.07 pmol/ml min, p less than 0.001). These results give further support to the concept that in mild glucose intolerance insulin metabolism is a major determinant of peripheral insulin response to oral glucose load.

Adult↗

Pathogenetic mechanisms of the endogenous hypertriglyceridemia in a nonobese rat model.

Male Sprague-Dawley IVA-SIV rats were compared to male Sprague-Dawley Charles River rats of the same age, body weight, and daily food intake. The IVA-SIV rats demonstrated hypertriglyceridemia (182 +/- 9.4 v 131 +/- 9.4 mg/dL, P less than 0.001), associated with increased fasting plasma glucose (115 +/- 3 v 84 +/- 2 mg/dL, P less than 0.001), and plasma insulin (35 +/- 5 v 19 +/- 2 microU/mL, P less than 0.001) levels. Furthermore, IVA-SIV rats responded to an oral glucose load with higher plasma glucose and insulin levels. Very-low-density lipoprotein (VLDL)-triglyceride (TG) turnover studies were performed, documenting a higher TG production rate, which correlated with the plasma TG concentrations, (r = 0.58, P less than 0.01) in the IVA-SIV rats. Since lipoprotein lipase activity in both adipose tissue and muscle was not significantly different in the two groups of rats, it appears that the hypertriglyceridemia in IVA-SIV rats is due to increased VLDL-TG secretion, associated with hyperglycemia, hyperinsulinemia, and increased plasma FFA levels. The IVA-SIV rats provide a model of endogenous hypertriglyceridemia, independent of obesity.

Adipose Tissue↗

Endogenous hypertriglyceridemia in a nonobese rat model: plasma lipoproteins and dietary sensitivity.

Sprague-Dawley male rats from the Ivanovas-Sieve colony (IVA-SIV) show higher plasma triglyceride levels compared to the standard Charles River (CR) rats. The triglyceride enrichment occurs primarily in the very-low-density lipoproteins (VLDL), otherwise of a normal % composition, suggesting that the number of particles is increased, rather than their triglyceride (TG) content. High-density lipoprotein (HDL) particles, corresponding to HDL1, appear to be increased in the IVA-SIV rats, as confirmed by rate-zonal ultracentrifugation. The apoprotein composition of isolated lipoproteins (apo B content and isoelectric focusing pattern), does not differ in the two strains. The IVA-SIV rats are remarkably more TG inducible, compared to the standard CR. This can be shown with fructose loading and with a cholesterol-cholic acid diet. The plasma TG increase, after Triton administration, indicative of the VLDL-TG production, is fourfold higher in the IVA-SIV, compared to the CR rats. These findings provide evidence for some similarities between the IVA-SIV rat and human endogenous hypertriglyceridemia, and suggest an increased TG biosynthesis in this model.

Animals↗

Effect of age and environmental factors on glucose tolerance and insulin secretion in a worker population.

The effect of age on glucose tolerance, as differentiated from the effects of obesity, work and leisure physical activity, family history of diabetes, and the use of drugs known to adversely affect glucose tolerance and/or insulin secretion, has been analyzed in 732 factory workers aged 22 to 73 years. Glucose tolerance, as evaluated by the plasma glucose response to 75 g of oral glucose deteriorated with age, associated with an increase in plasma insulin levels. However, the age-related decrease in glucose tolerance also correlated significantly with degree of obesity, leisure-time physical activity, and the use of potential diabetogenic drugs. Partial correlation coefficients were calculated to define the effect of age per se on glucose tolerance, controlling for the presence of these other age-related variables. When this was done, the degree of correlation between age and glucose tolerance was reduced, particularly in women, to where it became of marginal statistical significance. The effect of age on insulin response was affected to a greater degree by age-related variables, and was no longer statistically significant when these other factors were taken into consideration. These data suggest that the elevation in plasma glucose and insulin levels associated with age are to a certain extent due to age-related environmental factors, and the deterioration in glucose tolerance with age is relatively modest in magnitude in a generally healthy population.

Adult↗

Insulin and C-peptide responses to 75 g oral glucose load in the healthy man.

Plasma insulin and C-peptide levels in the fasting state and after a 2-h 75 g oral glucose tolerance test (OGTT) in a large number of healthy subjects are reported. 247 volunteers (134 males, 113 females), aged 13-69 years, who had a negative history of diabetes, no history of significant disease, normal physical examination, normal body weight, normal glucose tolerance, normal blood tests, and who were taking no drugs were studied. Results, mean +/- SEM (range): fasting glucose concentration = 4.64 +/- 0.03 mmol/l (3.10 - 6.10), 1-h glucose concentration = 5.23 +/- 0.10 mmol/l (2.20 - 9.90), 2-h glucose concentration = 4.11 +/- 0.06 mmol/l (2.00 - 6.80); fasting insulin level = 0.088 +/- 0.002 nmol/l (0.03 - 0.28), 1-h insulin level = 0.45 +/- 0.01 nmol/l (0.06 - 1.63), 2-h insulin level = 0.24 +/- 0.01 nmol/l (0.05 - 1.12); fasting C-peptide concentration = 0.60 +/- 0.01 nmol/l (0.14 - 1.34), 1-h C-peptide concentration = 2.17 +/- 0.05 (0.63 - 8.56), 2-h C-peptide concentration = 1.77 +/- 0.04 nmol/(0.35 - 5.74). Fasting insulin and fasting C-peptide concentrations correlated to post-glucose insulin and C-peptide concentrations, respectively. At each sampling-point insulin concentration correlated to C-peptide concentration. After glucose ingestion, both insulin and C-peptide plasma levels correlated significantly with the corresponding glucose levels. During fasting, C-peptide but no insulin level correlated to glucose level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Evidence for an independent relationship between plasma insulin and concentration of high density lipoprotein cholesterol and triglyceride.

Increased plasma insulin and triglycerides and decreased high density lipoprotein concentrations are primary risk factors in the development of coronary artery disease. The aim of the present study was to verify whether there was an independent relationship between plasma insulin levels and both HDL cholesterol and triglyceride in a worker population of 607 subjects, 389 men and 218 women, aged 23-73 years. An oral glucose tolerance test (75 g) was performed. Plasma glucose, insulin, triglyceride and HDL cholesterol were measured at fasting, plasma glucose and insulin were determined also 1 h and 2 h after glucose load. The results, examined separately in men and women documented a significant negative relationship between plasma insulin and HDL cholesterol level, as well as pointing out that both HDL cholesterol and insulin are significantly correlated to degree of hypertriglyceridemia, degree of obesity and level of glucose tolerance. The partial correlation coefficients between HDL cholesterol and plasma insulin levels at fasting in men and post-glucose load in women, demonstrated an independent relationship between increased plasma insulin and decreased plasma HDL concentration. However, the strongest relationship, revealed by partial correlation coefficient analysis, was between the degree of hyperinsulinemia and hypertriglyceridemia.

Adult↗