M. Oleggini

Insulin Resistance in Essential Hypertension

High blood pressure is prevalent in obesity and in diabetes, both conditions with insulin resistance. To test whether hypertension is associated with insulin resistance independently of obesity and glucose intolerance, we measured insulin sensitivity (using the euglycemic insulin-clamp technique), glucose turnover (using [3H]glucose isotope dilution), and whole-body glucose oxidation (using indirect calorimetry) in 13 young subjects (38 +/- 2 years [+/- SEM]) with untreated essential hypertension (165 +/- 6/112 +/- 3 mm Hg), normal body weight, and normal glucose tolerance. In the postabsorptive state, all measures of glucose metabolism were normal. During steady-state euglycemic hyperinsulinemia (about 60 microU per milliliter), hepatic glucose production and lipolysis were effectively suppressed, and glucose oxidation and potassium disposal were normally stimulated. However, total insulin-induced glucose uptake was markedly impaired (3.80 +/- 0.32 vs. 6.31 +/- 0.42 mg per minute per kilogram of body weight in 11 age- and weight-matched controls, P less than 0.001). Thus, reduced nonoxidative glucose disposal (glycogen synthesis and glycolysis) accounted for virtually all the defect in overall glucose uptake (1.19 +/- 0.24 vs. 3.34 +/- 0.44 mg per minute per kilogram, P less than 0.001). Total glucose uptake was inversely related to systolic or mean blood pressure (r = 0.76 for both, P less than 0.001). These results provide preliminary evidence that essential hypertension is an insulin-resistant state. We conclude that this insulin resistance involves glucose but not lipid or potassium metabolism, is located in peripheral tissues but not the liver, is limited to nonoxidative pathways of intracellular glucose disposal, and is directly correlated with the severity of hypertension.

Operation of Randle's Cycle in Patients With NIDDM

It has been suggested that the insulin resistance of non-insulin-dependent diabetes mellitus (NIDDM) may be caused by substrate competition between glucose and free fatty acids (FFAs) (Randles cycle). We measured substrate oxidation and energy metabolism in 10 nonobese untreated NIDDM patients with fasting glucose levels of 7–8 mM with indirect calorimetry in the basal state and during an isoglycemic-hyperinsulinemic (∼100 mU/L) clamp without (control) and with a concomitant infusion (∼0.35 mmol/min) of Intralipid, a triglyceride emulsion. In the control study, fasting rates of total glucose turnover ([3−3H]glucose) and glucose and lipid oxidation (9.4 ± 1.4, 7.3 ± 1.3, and 3.0 ± 0.4 μmol · kg−1 · min−1, respectively) were comparable with those of nondiabetic individuals. After insulin administration, lipid oxidation was normally suppressed (to 1.3 ± 0.3 μ · kg−1 · min−1 P < 0.01), as were the circulating levels of FFA, glycerol, and β-hydroxybutyrate, whereas glucose oxidation doubled (14.1 ± 1.8 μmol; · kg−1 · min−1 P <0.01). Because glycemia was clamped at 7.5 mM, endogenous glucose production (EGP) was completely suppressed, and total glucose disposal was stimulated (to 25.7 ± 5.2 μmol · kg−1 · min−1 P < 0.01 vs. baseline), but glucose clearance (3.6 ± 0.8 ml · kg−1 · min−1) was 30% reduced compared with normal. With concomitant lipid infusion, FFA, glycerol, and β-hydroxybutyrate all rose during the clamp; correspondingly, lipid oxidation was maintained at fasting rates (3.6 ± 0.2 μmol · kg−1 · min−1 P < 0.01 vs. control). As a consequence, the insulin-induced increase in glucose oxidation was abolished (7.9 ±1.3 μmol · kg−1 · min−1 P < 0.01 vs. control), and total glucose disposal was inhibited (21.8 ± 4.6 μmol · kg−1 · min−1 P < 0.05 vs. control) by an amount almost equal to the decrement in glucose oxidation. Lipid infusion did not detectably interfere with insulin-induced suppression of EGP. Energy expenditure failed to increase during the control insulin clamp but was significantly stimulated (∼10%, P < 0.01) by concomitant lipid administration (diet-induced thermogenesis). We conclude that in mildly hyperglycemic, nonobese NIDDM patients, excessive fatty substrate oxidation is unlikely to be responsible for the insulin resistance; increased lipid provision, however, enhances lipid oxidation and energy expenditure and inhibits glucose oxidation and total disposal. Thus, in this type of diabetes, Randles cycle does not appear to be spontaneously overactive but can be induced acutely, with metabolic and energetic consequences similar to those observed in nondiabetic subjects.

Energy metabolism of surgical patients in the early postoperative period: a reappraisal.

Energy metabolism was measured at the bedside in 22 uncomplicated surgical patients in the early (24 to 48 h) postoperative period with the use of continuous computerized indirect calorimetry with a canopy system. Energy production rates were higher than those predicted by the Harris-Benedict formula both in absolute value (1516 +/- 61 vs. 1387 +/- 49 kcal/day, p less than .05) and when normalized by body weight (BW; 23.5 +/- 0.5 vs. 21.7 +/- 0.5 kcal/day.kg BW, p less than .01) or by lean body mass (LBM; 32.8 +/- 0.8 vs. 30.2 +/- 0.9 kcal/day.kg LBM, p less than .01). Furthermore, surgical patients had higher energy production rates than those measured in 22 overnight fasted, resting healthy subjects matched for age, sex, and body size (23.5 +/- 0.5 vs. 21.8 +/- 0.6 kcal/day.kg BW, p less than .05). In both the patients and the control group, measured energy production bore a direct relation to LBM. We conclude that the early postoperative period of uncomplicated surgery is associated with a small (about 7%) but consistent increase in energy metabolism above the level observed in the overnight fasted, resting healthy individual. This increase appears to be an effect of surgery itself, and is not predicted by Harris-Benedict equations.

Inadvertent Catheterization of the Internal Thoracic Vein Mimicking Pulmonary Embolism: A Case Report

Although aberrant locations are typical complications of central venous catheterization, the right internal thoracic vein (mammary vein) is an exceptional one. A case of this unusual aberrant location occurring after right internal jugular venous cannulation for total parenteral nutrition, is described. This aberrant position caused signs and symptoms resembling pulmonary embolism. This is the first known description of the symptoms induced by the infusion of parenteral solution into the right internal thoracic vein.

The Relationships between Oxygen Delivery and Consumption and Continuous Mixed Venous Oximetry are Predictive Parameters in Septic Shock

Life is essentially a process of energy that consumes oxygen and produces carbon dioxide. The survival of all mammalian cells depends on a continuous supply of oxygen. To ensure this survival, oxygen is transported from the environment to the cells of the body via a complicated delivery system that is dependent on three organ systems: lungs (ventilation), blood (oxygen content) and cardiovascular system (cardiac output). Living organisms maintain their identity and integrity only by a continuing process of consumption of energy. Under normal conditions, this energy is captured by a mechanism that results in the formation of high energy posphate bonds, mostly as ATP. When the energy demand of all cells increases, there are adjustments in pulmonary oxygen exchange, cardiac output, oxygen binding of hemoglobin and capillary resistance that facilitate cellular availability of oxygen. Moreover, when one component of this system fails, adjustments in the remaining components satisfy systemic oxygen requirements until oxygen delivery falls below a critical level.

Measured and Predicted Values of Oxygen Consumption During Isoflurane Anesthesia in Man

Continuous oxygen consumption monitoring during inhalation anesthesia can be done by metabolic gas exchange measurements (indirect calorimetry). This method requires meticulous attention to technique, and many factors limit its usefulness in daily clinical practice. During inhalation anesthesia, the major limiting factor is the presence of exhaled anesthetic agents 1. Different systems and solutions have been proposed to obtain accurate and precise measurement of oxygen consumption during inhalation anesthesia 2. However, these systems are complex in use and dear (e.g., mass spectrometry) to be taken in account in daily clinical practice. With the recent progress in the development of closed circuit anesthesia systems, it has become possible to practice inhalation anesthesia together with on line registration of oxygen consumption 3. This measurement has been improving our ability to study various pathophysiological problems during anesthesia and operation 3. In a totally closed circuit system the rate of oxygen delivery is determined by the rate of oxygen consumption by the patient. The system measures the end-expiratory anesthetic circuit volume and oxygen concentration and adjusts the oxygen flow to maintain a constant circuit volume. According to a simple physical principle (conservation of mass), the rate of mass flowing into a system (patient) normally must equal the rate of mass flowing from the system