Enzo Bonora

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

SummaryIn 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.

Combined sulphonylurea-biguanide therapy for non-insulin dependent diabetics. Metabolic effects of glibenclamide and metformin or phenformin in newly diagnosed obese patients

SummaryFasting, pre-prandial and post-prandial blood glucose levels and blood lactate, blood pyruvate, serum cholesterol, serum triglycerides and body weight were measured in 30 obese, newly diagnosed, non-insulin-dependent diabetics at the end of 4 subsequent periods of different regimens, each lasting for 5 days. In the first period, patients remained on free diet; in the second period, a hypocaloric diet (20 kcal/kg IBW) was followed; in the third period, glibenclamide (2.5u2009mg 3-times daily) was added to hypocaloric diet. During the last period, the patients were divided into two groups: Group A (15 patients) received, in addition to diet and glibenclamide, phenformin (25u2009mg 3-times daily) and Group B (15 patients) received, in addition to diet and glibenclamide, metformin (500u2009mg 3-times daily). Five similar patients served as controls and, at the end of the free-diet period, were put on hypocaloric diet and continued this regimen throughout the study period. The results showed that biguanides allowed...

Possible roles of insulin, glucagon, growth hormone and free fatty acids in the pathogenesis of insulin resistance of subjects with chronic liver diseases

SummaryIn the present investigation, insulin sensitivity and fasting levels of insulin, C-peptide, glucagon, growth hormone and free fatty acids were estimated and correlated in a population of individuals suffering from liver cirrhosis or chronic hepatitis. Insulin sensitivity, assessed by glucose disappearance rate after intravenous bolus injection of insulin, was reduced but not significantly different from controls in subjects with chronic persistent hepatitis, while it was significantly reduced in individuals suffering from chronic active hepatitis or liver cirrhosis. Insulin, glucagon, growth hormone, and free fatty acid fasting levels were higher than in healthy subjects in individuals with liver cirrhosis or chronic active hepatitis but not in subjects with chronic persistent hepatitis. C-peptide concentrations did not differ from controls in subjects with liver disease. Significant negative correlations occurred between coefficients of insulin sensitivity and fasting concentrations of insulin, glucagon, growth hormone and free fatty acids, but not with fasting levels of C-peptide. Positive relationships were present between fasting levels of free fatty acids and both glucagon and growth hormone concentrations. These results show that, unlike subjects with liver cirrhosis and chronic active hepatitis, individuals suffering from chronic persistent hepatitis do not differ from healthy subjects in insulin sensitivity and fasting levels of insulin, glucagon, growth hormone, and free fatty acids. Moreover, they suggest that both hyperinsulinemia and high concentrations of counterregulatory substances might play a role in the pathogenesis of insulin resistance in subjects suffering from chronic liver disease.

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 < 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 < 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.

Evidence for Unimpaired Pancreatic Secretion and Hepatic Removal of Insulin in Healthy Offspring of Type 2 (Noninsulin-Dependent) Diabetic Couples

The aim of the present study was to investigate the secretion and the hepatic removal of insulin in a group of 14 unaffected offspring of 14 type 2 (noninsulin-dependent) diabetic couples compared to 14 healthy subjects without family history of diabetes mellitus. The two groups, each consisting of 5 obese and 9 nonobese subjects, were carefully matched for sex, age, and body weight. We examined glucose, insulin, and C-peptide levels, as well as C-peptide to insulin ratios and relations during the oral glucose tolerance test. Glucose concentrations and incremental areas were similar in the two groups, as well as insulin and C-peptide levels and areas. C-peptide to insulin molar ratios, both in fasting state and after glucose load, as well as relations between C-peptide and insulin incremental areas were not different. Our results suggest that the healthy offspring of type 2 diabetic couples have a normal response of beta-cell to oral glucose as well as a normal removal of insulin by the liver.

Insulin Metabolism Is a Major Factor Responsible for High or Low Peripheral Insulin Levels in Response to Oral Glucose Loading in the Healthy Man

In the present study we evaluated C-peptide peripheral levels after an oral glucose load in 30 healthy subjects (18 females, 12 males, aged from 15 to 55) with high or low insulin response to glucose challenge in order to clarify whether or not their beta-cell secretion rate keeps pace with peripheral insulin levels. Moreover, by the study of the relations between C-peptide and insulin in peripheral blood, we had an insight into the extent of insulin metabolism. On the basis of an insulin incremental area higher or lower than the mean +/- 1 SD after a 100-gram oral glucose load, 6 subjects were classified as high insulin responders and 6 other subjects as low insulin responders. Their insulin incremental area after glucose averaged 0.25 +/- 0.01 nmol X 1-1 X min and 0.078 +/- 0.005 nmol X 1-1 X min, respectively (p less than 0.001). The two groups were matched for sex, age and body weight. The glycemic profile after oral glucose load was higher in low insulin responders than in high insulin responders. C-peptide concentrations after glucose load were similar in the two groups, as well as C-peptide incremental areas (0.92 +/- 0.12 vs. 0.74 +/- 0.08 nmol X l-1 X min in high insulin responders and low insulin responders, respectively). The molar ratios of C-peptide to insulin after oral glucose load, as well as the relations between the incremental areas of the two peptides, were significantly lower in high insulin responders than in low insulin responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Secretion and Hepatic Removal of Insulin in Female Obese Subjects with Reactive Hypoglycemia

In the present study insulin and C-peptide responses to oral glucose as well as C-peptide to insulin ratios and relations were evaluated in 10 nondiabetic obese female subjects with reactive hypoglycemia and in 10 age- and weight-matched controls. Insulin levels and incremental areas did not differ significantly in the two groups, whereas C-peptide concentrations and incremental areas were significantly higher in the obese group with reactive hypoglycemia. C-peptide to insulin molar ratio increments after glucose load as well as relations between incremental areas of the two peptides were significantly higher in obese subjects with reactive hypoglycemia than in controls. Our results suggest that B-cell response to oral glucose as well as insulin uptake by the liver in obese subjects with reactive hypoglycemia are greater than in controls.

Evidence that basal beta cell activity may play a role in determining insulin sensitivity in healthy man.

Aim of this investigation was to correlate basal beta cell function and insulin sensitivity in healthy man. A group of 10 healthy subjects with normal body weight and glucose tolerance was studied. Insulin sensitivity was assessed by glucose disappearance rate after insulin injection (0.1 IU/kg body weight). Beta cell secretion rate was estimated by the evaluating of fasting C peptide circulating levels. A positive and significant relationship was observed between fasting C peptide concentrations and coefficients of insulin sensitivity (r = 0.694, p less than 0.05). We conclude that in healthy man basal beta cell secretion rate plays an important role in determining the peripheral sensitivity to insulin. In particular, hormone sensitivity is directly proportional to pancreatic hormone production in basal condition.

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 • min, respectively (p < 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 • min (p < 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 • min (p < 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. Also the relation between C-peptide and insulin incremental areas after oral glucose did not differ in the two conditions under study (0.63 ± 0.05 vs. 0.67 ± 0.05). These results suggest that insulin extraction by the liver after oral glucose load is independent of the amount of insulin secreted in response to stimulus, and of the amount of ingested glucose.