A. Bertoli

Lipid profile, BMI, body fat distribution, and aerobic fitness in men with metabolic syndrome

Abstract.Obesity, impaired glucose tolerance, type 2 diabetes, hyperlipidemia, hypertension, and insulin resistance are wellknown components of metabolic syndrome and are associated to increased cardiovascular morbidity. The present study aimed to evaluate the relationships between cardiorespiratory fitness, body fat distribution, and selected coronary heart disease risk factors. A total of 22 untrained subjects affected by one or more features of metabolic syndrome and without clinical history of cardiovascular disease were studied. Nondiabetic subjects underwent an oral glucose tolerance test for glucose and insulin measurement; fasting glucose and insulin were measured in diabetic patients. Complete lipid profile, thyroid hormones, and thyroid-stimulating hormone were measured in all subjects. Basal energy expenditure and cardiorespiratory fitness were measured using a K4 analyzer. Cardiorespiratory fitness (VO2max/kg) was assessed using a treadmill graded exercise test. Peak aerobic capacity (VO2max/kg) was predicted by body fat distribution, insulin sensitivity index, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol (p<0.001). A significant relationship was found between cardiorespiratory fitness (VO2max/kg) and body mass index (BMI), insulin sensitivity index, and LDL cholesterol (r=0.60, p<0.05; r=0.66, p<0.01 and r=0.54, p<0.05, respectively). Data demonstrated that aerobic fitness is related to metabolic parameters and to body fat distribution, and suggest that its modification may improve well-known predictors of coronary artery disease.

Dose-Dependent Effect of Octreotide on Insulin Secretion after OGTT in Obesity

Objective: The present study aimed at evaluating the acute effect of increasing doses of octreotide (OCT), a long-acting somatostatin analogue, on glucose tolerance and insulin secretion. Methods: A standard and two other oral glucose tolerance tests 30 min after subcutaneous administration of OCT were performed in randomized order in each subject. Obese subjects received 10, 25, or 50 µg of OCT; control subjects received only 10 and 25 µg. Fifteen obese and 10 control subjects were studied; all of them had a normal glucose tolerance. Plasma glucose and insulin levels were measured at times –30, 0, 30, 60, 90, 120, 150, and 180 min after the glucose tolerance test. Results: The results demonstrated that, following OCT administration, both control and obese subjects developed a reduced glucose tolerance, a delayed glycemic peak, and an increase of late plasma glucose values. Fasting as well as stimulated insulin secretions were higher in obese subjects as compared with controls, and insulin secretion was inhibited in a dose-dependent manner by OCT. Conclusions: These data indicate that the action of OCT might be due to at least two different cooperative mechanisms: (1) a delayed glucose absorption, as suggested by the delay of glycemic peak, and (2) a direct or vagal-mediated effect on β-cells, as suggested by the reduction of the area under the curve values in spite of the elevated late glycemic levels. It is noteworthy that doses of OCT as low as 10 and 25 µg are sufficient to inhibit insulin secretion both in normal and obese subjects.

Morbid obesity: evaluation of metabolic indexes after adjustable silicone gastric banding

Abstract.Morbid obesity is frequently associated with other characteristics of metabolic syndrome and is related to an increased risk of cardiovascular disease. This study aimed at evaluating time–course changes in body weight, body mass index (BMI), insulin sensitivity indexes and lipid profile in severely obese patients who underwent adjustable silicone gastric banding. We studied 19 obese subjects before and 6–36 months after surgery. An oral glucose tolerance test was performed in all non-diabetic patients. All subjects were evaluated using insulin sensitivity indexes (ISI-HOMA and QUICKI), lipid profile, and anthropometric parameters (WHR, WC, BMI), and body composition was assessed with bioelectrical impedance analysis (BIA). Most of the weight reduction occurred within the first 6–12 months, followed by near stabilisation or even weight regain. We found a significant decrease in fasting insulin, improvement in waist–hip ratio, reduction in BMI and fat mass percent. We observed an improvement in insulin sensitivity evaluated by means of ISI-HOMA and QUICKI. Bariatric surgery was an effective therapeutic approach for these obese patients because it reduced both weight and insulin resistance, along with improving metabolic parameters. Improvement in metabolic parameters appears to precede body weight reduction.

Ketoalkalosis as a result of triple derangement of acid-base equilibrium in a diabetic patient

SummaryA diabetic patient presented with weight loss, ketosis, and hyperventilation, thus mimicking the clinical picture of diabetic ketoacidosis. Laboratory investigations revealed alkalemia and a pattern consistent with a triple derangement of acid-base equilibrium: respiratory alkalosis, metabolic acidosis and metabolic alkalosis. High cortisol level suggested a genesis of ketosis different from diabetes mellitus. The patient died suddenly from acute gastrointestinal bleeding. Autopsy showed a carcinoma of the head of the pancreas with secondary portal hypertension and rupture of varices. Pulmonary micrometastases were demonstrated. It is suggested that stress hormones were the main cause of the ‘ketoalkalotic’ pattern observed.

Decreased insulin binding to red blood cells in liver cirrhosis

SummaryEleven male cirrhotic subjects, all with impaired glucose tolerance (IGT), were studied. Insulin binding to circulating erythrocytes was evaluated. The specific bound fraction was decreased compared to normals (5.95 ± 0.76vs 7.08 ± 0.84%; p<0.005). A negative correlation was found between fasting insulin and bound fraction (r=−0.68; p<0.05). We suggest that serum insulin may be chronically augmented as a consequence of liver damage. This induces a down-regulation of insulin receptors that is responsible for insulin resistance and at least in part for the impairment of glucose tolerance.

Response of insulin receptors to oral glucose in normal subjects

Insulin binding to circulating monocytes was studied in ten male volunteers before and 1, 2, and 5 hours after the oral intake of 100 g of glucose. Results indicate an increase in the specific cell binding fraction with a change in receptor affinity 5 hours after glucose. Since the same changes appear 3 hours after food intake they are probably not directly induced by insulinemia.

The effect of physical activities of various intensities on the energy expenditure of type 2 diabetic men.

Abstract.Interventions that focus on changing lifestyles through the combined use of dietary management, weight reduction, and increased physical activity are essential for managing type 2 diabetes mellitus (T2DM). The objective of the present study was to examine mildly obese T2DM patients [n=10; mean age (±SD), 51.29±6.80 years; body mass index (BMI), 30.26±6.19 kg/m2; and glycosylated haemoglobin (HbA1c), 8.16±1.16%)] and to compare them with normoglycaemic persons (n=10; age, 53.00±9.48 years; BMI, 27.63±3.33 kg/m2, and HbA1c, 5.85±0.56%) in terms of energy expenditure while performing physical activities of various intensities (i. e. light, moderate, and heavy). The resting metabolic rate for T2DM patients was significantly higher than that for healthy controls (2,200±354 kcal/day vs. 1,628±176 kcal/day, respectively; p<0.0001). The values of energy expenditure at all three levels of physical activity were comparable between the two groups. Physical activity seems to have various beneficial effects on mildly obese T2DM patients because it increases the plasma glucose consumption, resulting in similar energy expenditure in comparison with normoglycaemic individuals.

Evidence that human and porcine insulin differently affect the human insulin receptor : studies with monoclonal anti-insulin receptor antibodies

Binding studies have been carried out with radioiodinated monoclonal antibodies directed to various epitopes of the insulin receptor in order to detect differences between human and porcine insulin in the interaction with the human insulin receptor. Human insulin was more effective that porcine insulin at inhibiting the binding of 125I-MA-5 to IM-9 cells, Hep-2 human larynx cells and human placenta membranes. On the contrary, human and porcine insulin showed similar inhibitory effect on the binding of two other labeled anti-insulin receptor monoclonal antibodies, thus ruling out the possibility that results were due to experimental artifacts. Although several interpretations are possible, data reported suggest that human insulin and porcine insulin might differently affect the insulin receptor, even if, the biological significance of these findings remains unknown.

Inhibition of basal insulin secretion induces insulin resistance in normal man: evidence for a tonic effect of insulin on carbohydrate metabolism

Insulin resistance has been demonstrated both in insulin deficiency and insulin excess in man and in animals. This study was carried out in normal man to evaluate the role of insulinopenia in the pathogenesis of insulin resistance. Insulin suppression was obtained by 4 h somatostatin (SRIF) infusion. Insulin receptors on circulating monocytes were evaluated before and after SRIF infusion; an insulin tolerance test (ITT) was performed after SRIF, saline or SRIF and replacing basal insulin secretion. Insulin binding to circulating monocytes did not change after 4 h insulinopenia (2.19 +/- 0.30 vs. 2.35 +/- 0.80%), while insulin sensitivity appeared decreased after SRIF (KITT = 0.97 +/- 0.13) as compared with saline (KITT = 3.30 +/- 0.42), and this effect was prevented by insulin (KITT = 2.46 +/- 0.38). A relationship was detected between KITT and plasma insulin concentration before ITT (r = 0.85, p less than 0.01), suggesting that insulin deficiency is the main cause of the phenomenon observed. The present data suggest that basal insulin concentration plays an essential role in the control of insulin sensitivity. If insulin binding on monocytes mimics the behavior of major insulin target tissues, it is possible that the impaired insulin action after 4 h of insulin deficiency is related to a post binding effect.

Thromboxane production in diabetes mellitus

SummaryA correlation between increased platelet adhesiveness and aggregation and the development of angiopathy in diabetes mellitus can be made. Thromboxane produced by platelets represents a potent platelet aggregation factor. We studied the platelet TXB2 production during blood coagulation in carefully selected patients with type II diabetes mellitus in good metabolic control and the results were correlated with the presence or absence of microangiopathy, fasting blood glucose levels, type of therapy, age, duration of diabetes and the most important hematochemical parameters. No statistically significant differences were found between serum TXB2 concentrations in diabetic patients and control subjects, in diabetics with or without microangiopathy and in diabetics on insulin therapy or on oral hypoglycemic agents. We did not observe any correlation between TXB2 production and age, duration of diabetes, sex, basal blood glucose levels, total and HDL-cholesterol, triglycerides, blood creatinine and blood electrolytes. The thromboxane production may be a not important factor for determining the increased platelet aggregation which is at the origin of the angiopathy in diabetes mellitus.