Antonio Pezzarossa

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.

The control of blood glucose in the critical diabetic patient: a neuro-fuzzy method

Conventional algorithms for regulating insulin infusion rates in those critical diabetic patients submitted to parenteral glucose and insulin infusions do not allow to approach near normal blood glucose (BG) levels since traditional control systems are not fully effective in complex nonlinear systems as BG control is. Thus, we applied fuzzy logic principles and neural network techniques to modify intravenous insulin administration rates during glucose infusion. Forty critically ill, fasted diabetic subjects submitted to glucose and potassium infusion entered the study. They were randomly assigned to two treatment regimes: in group A, insulin infusion rates were adjusted, every 4 h at any step between -1.5 and +1.5 U/h, according to a neuro-fuzzy nomogram; in control group B, insulin infusion rates were modified according to a conventional algorithm. In group A, BG was lowered below 10 mmol/l faster than in group B (8.2+/-0.7 vs. 13+/-1.8 h, P<.02). Mean BG was 7.8+/-0.2 in group A and 10.6+/-0.3 mmol/l in group B (P<.00001). BG values below 4.4 mmol/l were: A=5.8% and B=10.2%. BG values lower than 2.5 mmol/l had never been observed. In conclusion, the neuro-fuzzy control system is effective in improving the BG control in critical diabetic patients without increasing either the number of BG determinations or the risk of hypoglycemia.

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.

Effects of maternal weight variations and gestational diabetes mellitus on neonatal birth weight

We evaluated the effects of gestational weight gain on neonatal birthweight women in whom gestational diabetes mellitus (GDM) was diagnosed after the 32nd week of gestation. The prevalence of macrosomia, the birthweight differences from 50th percentile value of a reference population, and the relationships among plasma glucose values during oral glucose tolerance test and neonatal birthweight were evaluated in 60 newborns from mothers with gestational diabetes mellitus divided according to pregravid body-mass index. Serving as controls were 132 newborns of mothers with normal glucose tolerance. The prevalence of macrosomia was higher in the GDM group; the neonatal birthweight difference above 50th percentile value was higher in newborns of mothers with GDM; and a strong relationship between maternal gestational weight gain and neonatal birth weight was present in all pregnant women. In conclusion, (1) the gestational weight gain is a good predictor of neonatal birth weight in all pregnant women; (2) GDM enhances the increase in neonatal size induced by excessive gestational weight gain alone, and (3) a weight gain of more than 9 kg makes the relative risk of macrosomia twofold higher in GDM than in control mothers.

Thyrotropin-releasing hormone-induced GH release after cocaine withdrawal in cocaine addicts

During cocaine addiction the hypothalamus-pituitary axis is widely affected and a blunted response of thyroid stimulating hormone (TSH) to thyroid releasing hormone (TRH) consistent with a hyperthyroid state has been observed. Since the thyroid status can affect the release of growth hormone (GH) the authors evaluated TSH and GH responses to TRH in cocaine addicts at the time of drug withdrawal and 30 days after. Twenty-six male cocaine addicts and 11 healthy male control subjects agreed to participate in the study. TRH and placebo tests were performed at random at 5 day intervals at the time of drug withdrawal and after 30 days. In drug addicts, at the time of the first test basal plasma levels of freeT3, freeT4 and TSH were normal, but the TSH response to TRH was impaired. After 30 days of cocaine abstinence basal freeT4 plasma levels were significantly lower, and TSH levels and the TSH response to TRH were higher than in the first test. At the first examination, basal GH concentrations were similar in cocaine addicts and in control subjects and GH did not respond to TRH. After 30 days of abstinence, basal GH plasma levels were unmodified, but the TRH became stimulatory of GH release in cocaine-deprived, but not in control subjects. In conclusion, in cocaine addicts, drug withdrawal is associated with a condition of subclinical hypothyroidism that makes the GH-releasing machinery sensitive to TRH.

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.

Lack of effect of nicardipine and dictiazem on gluoose-and aroinine-induced insulin release in obese subjects

SummaryThe metabolic effects of calcium channels blockers have already been studied hoth in normal and diabetic humans and results were quite controversial, depending on the drug used, the dose edministered, and the type of patient. Little information exists on the use of Ca2+ antagonists in obese people, even if these persons are a population risk group for devoloping diseases in which these drugs may be requested for treatment. Thus, we evaluated, in obese humans, the metabolic effects of two Ca2+ antagonist drugs recently made commercially available to treat diseases such as hypertension and ischemic heart diseaso: nicardipine and diltiasem. Sixtean chese subjects were submitted to an intravenous glucose talerance test (0.33 g/kg) (IVGTT) and an arginine test tolerance (30 g in 30 minutes) (ATT) before and after a week of oral treatment with nicardipine (60 mg/day) or diltiazem (360 mg/day). Plasma values of glucose, insulin, and C-peptide during IVGTT, and of glucose, insulin and glucagon during ATT did not show any modification during treatment with either drug. Thus the Ca2+ antagonists, nicardipine and diltiazem, at therapeutic doses in obese subjects do not significantly affect glucose tolerance or insulin and glucagon relense.

Glucose tolerance in chronic alcoholics after alcohol withdrawal: Effect of accompanying diet

The effect of alcoholism or acute alcohol ingestion on carbohydrate metabolism is not clear. The metabolic features of alcoholics cannot be easily achieved in normal men submitted to investigations concerning the effects of alcohol on glucose tolerance. Undernutrition and/or malnutrition characterize the eating behavior of alcoholics. It is also well-known that diet is an important determinant of carbohydrate tolerance. Thus, we studied the effects of a controlled diet on glucose tolerance and insulin release in a group of chronic alcoholics, with or without withdrawal from alcohol. Twenty-two subjects took part in the study; their mean caloric intake was 2,805 +/- 91 kcal/d, 58% of which was due to alcohol. In all subjects five days after an isocaloric diet and no alcohol, we performed an oral glucose tolerance test (OGTT). After that, the subjects were divided into three subgroups: group A, eight subjects with alcohol withdrawal and an 17.5 kcal/kg/d diet; group B, eight subjects with alcohol withdrawal and a 35 kcal/kg/d diet, and group C, six subjects with a 35 kcal/kg/d diet plus ethanol 200 g/d. After 3 weeks a second OGTT was performed. We found a significant improvement of the glucose tolerance and of the release of insulin in group B as well as group C; the alcohol withdrawal per se was irrelevant to the observed modifications of the glucose tolerance. Our data suggest that a poor diet would be a major cause of carbohydrate intolerance in alcoholics.

Effect of domperidone on the release of insulin after intravenous glucose load in man

To determine whether the blockade of the dopaminergic system is capable of modifying glucose-induced insulin release in man, the responses of insulin to an iv glucose load were measured at various domperidone infusion rates. The infusion of 5 μg/kg/min of domperidone increased significantly plasma insulin levels during the acute phase of glucose-induced insulin release and lowered plasma glucose values at 50 and 60 min; the k of glucose disappearance improved significantly. At lower domperidone infusion rates the acute increment of insulin after glucose load was indistinguishable from the response observed at 5 μg/kg/min until 0.5 μg/kg/min, while similar responses in control and experimental tests were observed at 0.25 μg/kg/min. A group of subjects was submitted to an arginine load in order to establish whether the effect observed with domperidone was specific for the glucose-induced insulin release; but, this time, we did not observe any significant effect during the domperidone-induced dopaminergic blockade. Furthermore, we also measured the plasma prolactin levels, to see whether the specific and well known effect of domperidone on prolactin release matches with the effect on β-cell function. As far as prolactin is concerned, we observed a dose response effect of domperidone infusion, with a detectable elevation of prolactin at infusion rate of 0.25 μg/kg/min. Since domperidone is a specific antagonist of dopamine D2-receptors, we propose that dopamine might exert a specific inhibiting effect on glucose-induced insulin release through this class of dopamine receptors.

Glucose tolerance and insulin release in adolescent female

The increase in insulin requirement at the onset of adolescence is compensated by an increase of insulin secretion. This metabolic pattern persists during adolescence but is no longer present in adults. It is supposed to depend on a decrease of insulin sensitivity of uncertain origin. We compared the metabolic pattern of late adolescent girls (13–16 year old) with young women (21–30 year old) with similar body mass indexes, testing subjects with iv glucose tolerance test (IVGTT) (glucose 0.33 g/kg) and arginine test (ATT) (arginine 30 g in 30 min). In late adolescent vs adult women we observed: i) IVTT: similar k of glucose tolerance and higher insulin and C-peptide responses; ii) ATT: unmodified plasma glucose, insulin and glucagon values, higher GH plasma levels; iii) in adolescent girls GH and CPR incremental areas significantly correlated (r = 0.755, p < 0.05). These data show that: i) the adolescent pattern of glucose metabolism persists after completion of sexual development and, ii) there is a positive correlation between GH response to arginine and beta-cell response to glucose. So GH should play a role in the impairment of glucose metabolism during adolescence.