Elisabetta Torlone - Academia.edu (original) (raw)
Papers by Elisabetta Torlone
Diabetes Research and Clinical Practice
Frontiers in Endocrinology
Pregnancy offers a window of opportunity to program the future health of both mothers and offspri... more Pregnancy offers a window of opportunity to program the future health of both mothers and offspring. During gestation, women experience a series of physical and metabolic modifications and adaptations, which aim to protect the fetus development and are closely related to both pre-gestational nutritional status and gestational weight gain. Moreover, pre-gestational obesity represents a challenge of treatment, and nowadays there are new evidence as regard its management, especially the adequate weight gain. Recent evidence has highlighted the determinant role of nutritional status and maternal diet on both pregnancy outcomes and long-term risk of chronic diseases, through a transgenerational flow, conceptualized by the Development Origin of Health and Diseases (Dohad) theory. In this review we will analyse the physiological and endocrine adaptation in pregnancy, and the metabolic complications, thus the focal points for nutritional and therapeutic strategies that we must early impleme...
Nutrition, Metabolism and Cardiovascular Diseases
Nutrition, Metabolism and Cardiovascular Diseases
Nutrition, Metabolism and Cardiovascular Diseases
Diabetes Research and Clinical Practice
Journal of Clinical Medicine
Fetal exposure to gestational diabetes mellitus (GDM) seems to stimulate a negative impact on the... more Fetal exposure to gestational diabetes mellitus (GDM) seems to stimulate a negative impact on the kidneys. Renal volumes and urinary biomarkers of renal function and tubular impairment and injury were evaluated in 30–40-day old newborns of GDM mothers (n = 139) who needed insulin therapy during pregnancy. We found that neonates of mothers who maintained strict control over normoglycemia (n = 65) during pregnancy and fulfilled the other criteria of the GDM management program showed no differences compared to control (n = 55). Conversely, those (n = 74), whose mothers did not maintain glycemic control and were not compliant to the management program, exhibited significantly lower levels of renal volumes and higher activity of N-acetyl-β-D-glucosaminidase and cathepsin B. Differences due to maternal pre-gestational and gestational body mass index (BMI) as well as to maternal weight gain were demonstrated. Our findings indicate that a multidisciplinary approach, which involves an approp...
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 1998
The recent introduction of recombinant DNA technology has made possible the manufacture of insuli... more The recent introduction of recombinant DNA technology has made possible the manufacture of insulin analogues with altered pharmacokinetic properties. Such analogues include insulins with single or multiple amino acid substitution(s) in the A or B chains of human insulin. The modification of the amino acid sequence results in a lower tendency towards aggregation of the insulin analogues when compared with human insulin. In particular, the subcutaneous injection of rapid-acting insulin analogues generates a peak that is superimposable on the peripheral plasma insulin profile of healthy individuals after a meal, without the need for a time interval between the injection and the meal. However, long term multicentre trials with rapid-acting insulin analogues have not shown an improvement in glycated haemoglobin (HbA(1c)) values despite an improvement in post-meal (2 hour) glycaemic control. This result is probably due to the shorter action of insulin analogues compared with human regular...
Contributions to nephrology, 1994
mnlpublimed.com
... Deficit nutrizionali materni sono più comunemente associati a parto pre-termine e basso peso ... more ... Deficit nutrizionali materni sono più comunemente associati a parto pre-termine e basso peso sia placentare che neonatale alla nascita, come confermato da recenti studi4; contro-versi invece sono quelli riguardanti il rischio di mor-te fetale e neonatale. ...
BioDrugs, 1998
ABSTRACT The recent introduction of recombinant DNA technology has made possible the manufacture ... more ABSTRACT The recent introduction of recombinant DNA technology has made possible the manufacture of insulin analogues with altered pharmacokinetic properties. Such analogues include insulins with single or multiple amino acid substitution(s) in the A or B chains of human insulin. The modification of the amino acid sequence results in a lower tendency towards aggregation of the insulin analogues when compared with human insulin. In particular, the subcutaneous injection of rapid-acting insulin analogues generates a peak that is superimposable on the peripheral plasma insulin profile of healthy individuals after a meal, without the need for a time interval between the injection and the meal. However, long term multicentre trials with rapid-acting insulin analogues have not shown an improvement in glycated haemoglobin (HbA1c) values despite an improvement in post-meal (2 hour) glycaemic control. This result is probably due to the shorter action of insulin analogues compared with human regular insulin, causing higher glycaemic values at 4 hours after insulin administration despite lower values at 2 hours. Thus, the simple substitution of rapid-acting analogues for regular insulin can lead to a potential deterioration of metabolic control, causing hyperketonaemia in patients without residual C-peptide secretion. Such patients should receive supplemental intermediate insulin at bedtime and also, at low dosages and on the basis of glucose values, at any time the interval between meals is longer than 4 hours.
New England Journal of Medicine, 1988
To assess the effect of asymptomatic nocturnal hypoglycemia on glycemic control in insulin-depend... more To assess the effect of asymptomatic nocturnal hypoglycemia on glycemic control in insulin-dependent diabetes mellitus, we studied, on three nights, 10 patients receiving their usual regimens of continuous subcutaneous insulin infusion. During a control night, the patients' mean (+/- SE) plasma glucose level reached a nadir of 4.5 +/- 0.2 mmol per liter at 3 a.m.; the fasting glucose level was 5.9 +/- 0.3 mmol per liter at 7:30 a.m., and a peak glucose level of 8.6 +/- 0.3 mmol per liter was reached at 10 a.m., after breakfast. During nights two and three, supplemental insulin was infused intravenously from 10 p.m. to 2 a.m. to simulate a clinical overdose of insulin. On these nights, either hypoglycemia (2.4 +/- 0.2 mmol per liter) was permitted to occur or a nearly normal glucose level (5.5 mmol per liter) was maintained by infusion of glucose. The subjects were asymptomatic on all three nights. Despite comparable plasma free insulin levels from 4 to 11 a.m., both fasting (7.3 +/- 0.2 mmol per liter) and postbreakfast (12.5 +/- 0.4 mmol per liter) plasma glucose levels were significantly higher after hypoglycemia than when hypoglycemia was prevented (6.2 +/- 0.2 mmol per liter and 8.7 +/- 0.4 mmol per liter, respectively; P less than 0.001 in both cases). Fasting levels of plasma glucose correlated directly with overnight plasma levels of epinephrine (r = 0.78, P less than 0.001), growth hormone (r = 0.57, P less than 0.009), and cortisol (r = 0.52, P less than 0.02) but correlated inversely with the overnight nadir of plasma glucose (r = -0.62, P less than 0.005). We conclude that asymptomatic nocturnal hypoglycemia can cause clinically important deterioration in glycemic control (the Somogyi phenomenon) in patients receiving intensive insulin therapy, and should therefore be considered in the differential diagnosis of unexplained morning hyperglycemia.
The American journal of physiology
To test the hypothesis that cortisol secretion plays a counterregulatory role in hypoglycemia in ... more To test the hypothesis that cortisol secretion plays a counterregulatory role in hypoglycemia in humans, four studies were performed in eight normal subjects. In all studies, insulin (15 mU.m-2.min-1) was infused subcutaneously (plasma insulin 27 +/- 1 microU/ml). In study 1, plasma glucose concentration and glucose fluxes [( 3-3H]glucose), substrate, and counterregulatory hormone concentrations were simply monitored, and plasma glucose decreased from 89 +/- 2 to 52 +/- 2 mg/dl for 12 h. In study 2, (pituitary-adrenal-pancreatic clamp), insulin and counterregulatory hormone secretion (except for catecholamines) was prevented by somatostatin (0.5 mg/h, iv) and metyrapone (0.5 g/4 h, per os), and glucagon, cortisol, and growth hormone were infused to reproduce the concentrations of study 1. In study 3 (lack of cortisol increase), the pituitary-adrenal-pancreatic clamp was performed with maintenance of plasma cortisol at basal levels, and glucose was infused, whenever needed, to reprod...
The American journal of physiology
To test the hypothesis that growth hormone secretion plays a counterregulatory role in prolonged ... more To test the hypothesis that growth hormone secretion plays a counterregulatory role in prolonged hypoglycemia in humans, four studies were performed in nine normal subjects. Insulin (15 mU.M-2.min-1) was infused subcutaneously (plasma insulin 27 +/- 2 microU/ml), and plasma glucose decreased from 88 +/- 2 to 53 +/- 1 mg/dl for 12 h. In study 1, plasma glucose, glucose fluxes (D-[3-3H]glucose), substrate, and counterregulatory hormone concentrations were simply monitored. In study 2 (pituitary-adrenal-pancreatic clamp), insulin and counterregulatory hormone secretions (except for catecholamines) were prevented by somatostatin (0.5 mg/h iv) and metyrapone (0.5 g/4 h po), and glucagon, cortisol, and growth hormone were reinfused to reproduce the concentrations of study 1. In study 3 (lack of growth hormone increase), the pituitary-adrenal-pancreatic clamp was performed with maintenance of plasma growth hormone at basal levels, and glucose was infused whenever needed to reproduce plasma...
Diabète & métabolisme
To assess the short-term metabolic effects a long-acting non-sulphydryl ACE-inhibitor benazepril ... more To assess the short-term metabolic effects a long-acting non-sulphydryl ACE-inhibitor benazepril on glycaemic control in Type 2 diabetes mellitus and arterial hypertension, 10 hypertensive diabetic patients treated with glibenclamide were studied in a double-blind, crossover fashion over two 10-day periods in which either benazepril (10 mg/day) or placebo was given. At the end of the 10 day treatment, both blood pressure and plasma glucose concentrations were lower after benazepril versus placebo (benazepril, blood pressure: 143 +/- 11/83 +/- 5 mmHg, plasma glucose: 7.1 +/- 1.2 mmol/l; placebo: blood pressure: 157 +/- 10/99 +/- 2 mmHg, plasma glucose: 8.2 +/- 1 mmol/l, p < 0.05). In response to an oral glucose tolerance test combined with 1 mg intravenous glibenclamide, plasma glucose levels were lower after benazepril versus placebo (0-460 min: 8.4 +/- 0.8 versus 10.5 +/- 0.9 mmol/l, p < 0.05), whereas plasma insulin, C-peptide and glibenclamide concentrations were not differ...
The American journal of physiology
To assess the role of adrenergic mechanisms during prolonged hypoglycemia, eight normal subjects ... more To assess the role of adrenergic mechanisms during prolonged hypoglycemia, eight normal subjects were studied on six occasions. In study 1, insulin was infused subcutaneously (15 mU.m-2.min-1 for 12 h), and plasma glucose concentration (PG) decreased from 89 +/- 2 to 50 +/- 1 mg/dl. In study 2 (insulin as in study 1 + propranolol and phentolamine + variable glucose to maintain PG as in study 1), the rate of hepatic glucose production (HGO, [3-3H]glucose) was approximately 30% lower after 1.5 h, and the rate of peripheral glucose utilization (GU) was approximately 15% greater after 5 h. To quantitate the effects of adrenergic mechanisms on glucose counterregulation, in a control study (study 3), glucoregulatory hormone secretion was blocked, and the hormones were reinfused to reproduce study 1. When alpha- and beta-blockade plus variable glucose were superimposed to study 3 (study 4), HGO was approximately 25% lower (after 2 h), and GU was approximately 10% greater (after 6 h) vs. st...
Diabetes Research and Clinical Practice
Frontiers in Endocrinology
Pregnancy offers a window of opportunity to program the future health of both mothers and offspri... more Pregnancy offers a window of opportunity to program the future health of both mothers and offspring. During gestation, women experience a series of physical and metabolic modifications and adaptations, which aim to protect the fetus development and are closely related to both pre-gestational nutritional status and gestational weight gain. Moreover, pre-gestational obesity represents a challenge of treatment, and nowadays there are new evidence as regard its management, especially the adequate weight gain. Recent evidence has highlighted the determinant role of nutritional status and maternal diet on both pregnancy outcomes and long-term risk of chronic diseases, through a transgenerational flow, conceptualized by the Development Origin of Health and Diseases (Dohad) theory. In this review we will analyse the physiological and endocrine adaptation in pregnancy, and the metabolic complications, thus the focal points for nutritional and therapeutic strategies that we must early impleme...
Nutrition, Metabolism and Cardiovascular Diseases
Nutrition, Metabolism and Cardiovascular Diseases
Nutrition, Metabolism and Cardiovascular Diseases
Diabetes Research and Clinical Practice
Journal of Clinical Medicine
Fetal exposure to gestational diabetes mellitus (GDM) seems to stimulate a negative impact on the... more Fetal exposure to gestational diabetes mellitus (GDM) seems to stimulate a negative impact on the kidneys. Renal volumes and urinary biomarkers of renal function and tubular impairment and injury were evaluated in 30–40-day old newborns of GDM mothers (n = 139) who needed insulin therapy during pregnancy. We found that neonates of mothers who maintained strict control over normoglycemia (n = 65) during pregnancy and fulfilled the other criteria of the GDM management program showed no differences compared to control (n = 55). Conversely, those (n = 74), whose mothers did not maintain glycemic control and were not compliant to the management program, exhibited significantly lower levels of renal volumes and higher activity of N-acetyl-β-D-glucosaminidase and cathepsin B. Differences due to maternal pre-gestational and gestational body mass index (BMI) as well as to maternal weight gain were demonstrated. Our findings indicate that a multidisciplinary approach, which involves an approp...
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 1998
The recent introduction of recombinant DNA technology has made possible the manufacture of insuli... more The recent introduction of recombinant DNA technology has made possible the manufacture of insulin analogues with altered pharmacokinetic properties. Such analogues include insulins with single or multiple amino acid substitution(s) in the A or B chains of human insulin. The modification of the amino acid sequence results in a lower tendency towards aggregation of the insulin analogues when compared with human insulin. In particular, the subcutaneous injection of rapid-acting insulin analogues generates a peak that is superimposable on the peripheral plasma insulin profile of healthy individuals after a meal, without the need for a time interval between the injection and the meal. However, long term multicentre trials with rapid-acting insulin analogues have not shown an improvement in glycated haemoglobin (HbA(1c)) values despite an improvement in post-meal (2 hour) glycaemic control. This result is probably due to the shorter action of insulin analogues compared with human regular...
Contributions to nephrology, 1994
mnlpublimed.com
... Deficit nutrizionali materni sono più comunemente associati a parto pre-termine e basso peso ... more ... Deficit nutrizionali materni sono più comunemente associati a parto pre-termine e basso peso sia placentare che neonatale alla nascita, come confermato da recenti studi4; contro-versi invece sono quelli riguardanti il rischio di mor-te fetale e neonatale. ...
BioDrugs, 1998
ABSTRACT The recent introduction of recombinant DNA technology has made possible the manufacture ... more ABSTRACT The recent introduction of recombinant DNA technology has made possible the manufacture of insulin analogues with altered pharmacokinetic properties. Such analogues include insulins with single or multiple amino acid substitution(s) in the A or B chains of human insulin. The modification of the amino acid sequence results in a lower tendency towards aggregation of the insulin analogues when compared with human insulin. In particular, the subcutaneous injection of rapid-acting insulin analogues generates a peak that is superimposable on the peripheral plasma insulin profile of healthy individuals after a meal, without the need for a time interval between the injection and the meal. However, long term multicentre trials with rapid-acting insulin analogues have not shown an improvement in glycated haemoglobin (HbA1c) values despite an improvement in post-meal (2 hour) glycaemic control. This result is probably due to the shorter action of insulin analogues compared with human regular insulin, causing higher glycaemic values at 4 hours after insulin administration despite lower values at 2 hours. Thus, the simple substitution of rapid-acting analogues for regular insulin can lead to a potential deterioration of metabolic control, causing hyperketonaemia in patients without residual C-peptide secretion. Such patients should receive supplemental intermediate insulin at bedtime and also, at low dosages and on the basis of glucose values, at any time the interval between meals is longer than 4 hours.
New England Journal of Medicine, 1988
To assess the effect of asymptomatic nocturnal hypoglycemia on glycemic control in insulin-depend... more To assess the effect of asymptomatic nocturnal hypoglycemia on glycemic control in insulin-dependent diabetes mellitus, we studied, on three nights, 10 patients receiving their usual regimens of continuous subcutaneous insulin infusion. During a control night, the patients' mean (+/- SE) plasma glucose level reached a nadir of 4.5 +/- 0.2 mmol per liter at 3 a.m.; the fasting glucose level was 5.9 +/- 0.3 mmol per liter at 7:30 a.m., and a peak glucose level of 8.6 +/- 0.3 mmol per liter was reached at 10 a.m., after breakfast. During nights two and three, supplemental insulin was infused intravenously from 10 p.m. to 2 a.m. to simulate a clinical overdose of insulin. On these nights, either hypoglycemia (2.4 +/- 0.2 mmol per liter) was permitted to occur or a nearly normal glucose level (5.5 mmol per liter) was maintained by infusion of glucose. The subjects were asymptomatic on all three nights. Despite comparable plasma free insulin levels from 4 to 11 a.m., both fasting (7.3 +/- 0.2 mmol per liter) and postbreakfast (12.5 +/- 0.4 mmol per liter) plasma glucose levels were significantly higher after hypoglycemia than when hypoglycemia was prevented (6.2 +/- 0.2 mmol per liter and 8.7 +/- 0.4 mmol per liter, respectively; P less than 0.001 in both cases). Fasting levels of plasma glucose correlated directly with overnight plasma levels of epinephrine (r = 0.78, P less than 0.001), growth hormone (r = 0.57, P less than 0.009), and cortisol (r = 0.52, P less than 0.02) but correlated inversely with the overnight nadir of plasma glucose (r = -0.62, P less than 0.005). We conclude that asymptomatic nocturnal hypoglycemia can cause clinically important deterioration in glycemic control (the Somogyi phenomenon) in patients receiving intensive insulin therapy, and should therefore be considered in the differential diagnosis of unexplained morning hyperglycemia.
The American journal of physiology
To test the hypothesis that cortisol secretion plays a counterregulatory role in hypoglycemia in ... more To test the hypothesis that cortisol secretion plays a counterregulatory role in hypoglycemia in humans, four studies were performed in eight normal subjects. In all studies, insulin (15 mU.m-2.min-1) was infused subcutaneously (plasma insulin 27 +/- 1 microU/ml). In study 1, plasma glucose concentration and glucose fluxes [( 3-3H]glucose), substrate, and counterregulatory hormone concentrations were simply monitored, and plasma glucose decreased from 89 +/- 2 to 52 +/- 2 mg/dl for 12 h. In study 2, (pituitary-adrenal-pancreatic clamp), insulin and counterregulatory hormone secretion (except for catecholamines) was prevented by somatostatin (0.5 mg/h, iv) and metyrapone (0.5 g/4 h, per os), and glucagon, cortisol, and growth hormone were infused to reproduce the concentrations of study 1. In study 3 (lack of cortisol increase), the pituitary-adrenal-pancreatic clamp was performed with maintenance of plasma cortisol at basal levels, and glucose was infused, whenever needed, to reprod...
The American journal of physiology
To test the hypothesis that growth hormone secretion plays a counterregulatory role in prolonged ... more To test the hypothesis that growth hormone secretion plays a counterregulatory role in prolonged hypoglycemia in humans, four studies were performed in nine normal subjects. Insulin (15 mU.M-2.min-1) was infused subcutaneously (plasma insulin 27 +/- 2 microU/ml), and plasma glucose decreased from 88 +/- 2 to 53 +/- 1 mg/dl for 12 h. In study 1, plasma glucose, glucose fluxes (D-[3-3H]glucose), substrate, and counterregulatory hormone concentrations were simply monitored. In study 2 (pituitary-adrenal-pancreatic clamp), insulin and counterregulatory hormone secretions (except for catecholamines) were prevented by somatostatin (0.5 mg/h iv) and metyrapone (0.5 g/4 h po), and glucagon, cortisol, and growth hormone were reinfused to reproduce the concentrations of study 1. In study 3 (lack of growth hormone increase), the pituitary-adrenal-pancreatic clamp was performed with maintenance of plasma growth hormone at basal levels, and glucose was infused whenever needed to reproduce plasma...
Diabète & métabolisme
To assess the short-term metabolic effects a long-acting non-sulphydryl ACE-inhibitor benazepril ... more To assess the short-term metabolic effects a long-acting non-sulphydryl ACE-inhibitor benazepril on glycaemic control in Type 2 diabetes mellitus and arterial hypertension, 10 hypertensive diabetic patients treated with glibenclamide were studied in a double-blind, crossover fashion over two 10-day periods in which either benazepril (10 mg/day) or placebo was given. At the end of the 10 day treatment, both blood pressure and plasma glucose concentrations were lower after benazepril versus placebo (benazepril, blood pressure: 143 +/- 11/83 +/- 5 mmHg, plasma glucose: 7.1 +/- 1.2 mmol/l; placebo: blood pressure: 157 +/- 10/99 +/- 2 mmHg, plasma glucose: 8.2 +/- 1 mmol/l, p < 0.05). In response to an oral glucose tolerance test combined with 1 mg intravenous glibenclamide, plasma glucose levels were lower after benazepril versus placebo (0-460 min: 8.4 +/- 0.8 versus 10.5 +/- 0.9 mmol/l, p < 0.05), whereas plasma insulin, C-peptide and glibenclamide concentrations were not differ...
The American journal of physiology
To assess the role of adrenergic mechanisms during prolonged hypoglycemia, eight normal subjects ... more To assess the role of adrenergic mechanisms during prolonged hypoglycemia, eight normal subjects were studied on six occasions. In study 1, insulin was infused subcutaneously (15 mU.m-2.min-1 for 12 h), and plasma glucose concentration (PG) decreased from 89 +/- 2 to 50 +/- 1 mg/dl. In study 2 (insulin as in study 1 + propranolol and phentolamine + variable glucose to maintain PG as in study 1), the rate of hepatic glucose production (HGO, [3-3H]glucose) was approximately 30% lower after 1.5 h, and the rate of peripheral glucose utilization (GU) was approximately 15% greater after 5 h. To quantitate the effects of adrenergic mechanisms on glucose counterregulation, in a control study (study 3), glucoregulatory hormone secretion was blocked, and the hormones were reinfused to reproduce study 1. When alpha- and beta-blockade plus variable glucose were superimposed to study 3 (study 4), HGO was approximately 25% lower (after 2 h), and GU was approximately 10% greater (after 6 h) vs. st...