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Obesity, diabetes, and insulin resistance: implications from molecular biology, epidemiology, and experimental studies in humans and animals. Synopsis of the American Diabetes Association's 29th Research Symposium and Satellite Conference of the 7th International Congress on Obesity, Boston, Massachusetts.

The number of genetic features potentially contributing to the development of obesity and of NIDDM continues to expand, even while evidence from epidemiological studies and prospective longitudinal evaluations of risk factors continue to argue strongly for nongenetic factors in the expression of these disorders. Even as the intensive search goes on for the diabesity gene(s), it is imminently clear that treatment initiatives can and must be oriented to reducing the well-established risk factors, most likely through multiple simultaneous interventions and alterations. Clearly restriction of calories is the most immediately effective of the various tools currently available. The recent results of long-term minimal restriction suggest extraordinary benefits to health can result for those predisposed to the diabesity or insulin resistance syndrome. Changes in diet composition may facilitate maintenance of a lower calorie intake, but in themselves they are not likely to significantly alter the risks of the syndrome, with the exception of lower cholesterol diets for reducing elevated cholesterol levels. Exercise and increased general physical activity must be seen as potentially beneficial; however, because of the magnitude of the physical training activities likely to be effective in lowering insulin resistance on a chronic basis, the expected outcomes from the usual types of relatively limited exercise regimen are less likely to have powerful preventive effects. Nevertheless, the combination of exercise and moderate alterations in caloric intake is likely to have a synergistic beneficial effect. Pharmacological interventions in the insulin resistance syndrome are in their early developmental phases, and we look forward to new developments in this area. Effective anti-obesity agents are greatly needed, and new understanding of the excess risk carried by obesity for many features of the diabesity or insulin resistance syndrome suggest the urgency of greater investment in research toward new modes of therapy. We look forward with great anticipation to the next Obesity, Diabetes, and Insulin Resistance Conference, where new progress in prediction, new understanding of pathogenesis, new genetic markers and modifiers, and new treatment candidates are sure to be forthcoming.

Animals↗

Collinear nutrients and the risk of colon cancer.

The relationship between colon cancer risk and the relative contributions of fat and caloric intake are assessed. A lack of consensus exists regarding the role of each of these dietary factors in the development of colon cancer. This lack of agreement originates from the high correlations between the nutrients, as well as the manner in which researchers treat these dietary variables in their analyses. Four proposed methods are evaluated which attempt to address the collinearity problem in nutritional epidemiology: (1) exclude one or more collinear variables, (2) use the proportion of calories consumed attributable to each dietary component, (3) use a regression-adjustment approach to purge the collinearity correlated nutrients, and (4) ridge regression. Diagnostic tests are reported which assess the degree of collinearity on data collected for a case-control study of colon cancer conducted in Utah between 1979 and 1983. Using logistic regression analyses, we apply each of these methods to case-control data. We find that the risks associated with fat and caloric consumption are extremely sensitive to a priori analytic decisions made by epidemiologist about the underlying collinearity problem.

Case-Control Studies↗

Relationship between protein and energy in the feeding of preterm infants during the first month of life.

Energy and protein quantity and quality in the diet are factors regulating the rate of growth in the preterm infant. In the present study twenty infants 31-36 weeks of gestational age were fed with identical test formulas which varied only in the content of energy. One formula (F-81) contained 3.1 g protein (60 bovine whey: 40 bovine caseins) and 81 kcal per dl. The second formula (F-94) contained the same amount of protein but 94 kcal per dl. At an intake of 150 ml/kg/d the infants received 4.6 g protein/kg/d and either 121 or 141 kcal/kg/d. The infants on F-94 had a significantly higher rate of weight gain, but growth of length and head circumference was equal in the two groups. Significant differences were found in the plasma concentrations of glutamine and alanine between the two feeding groups. The other plasma amino acids were not statistically different in the two groups of infants. Urine excretion of threonine, serine, glycine, alanine, histidine, tyrosine, glutamine and cystathionine was significantly increased in the high caloric, F-94-group. The results indicate that increasing the caloric intake above 120 kcal/kg/d in preterm infants on a relatively high protein intake does not increase linear growth but does produce increased weight gain. The biochemical results provide indirect evidence that this weight increase is the result of increased fat accretion.

Acid-Base Equilibrium↗

[Dietary evaluation of pregnant adolescents during first, second and third trimester].

In order to identify risk of inadequate intake of calories and nutrients during pregnancy, 75 pregnant adolescents (14 to 18 years old) apparently healthy, from low socioeconomic level, in their first prenatal control (12 weeks) were studied by two 24 hour recalls and a food frequency questionnaire at each trimester. Nutritional status was assessed by body mass index (pregestation weight/height) and classified according to American Medicine Institute reference. Paired t-test, frequency distribution and ANOVA were used for statistical analysis. Low weight was found in 34.6% of adolescent at the first visit and 5.3% were overweight. Even though, caloric intake was below recommendation, significant increases were observed between first and second trimester for energy, carbohydrates, niacin and zinc (p < 0.001) and for fat, proteins, riboflavin, thiamin, vitamin C, calcium and iron (p < 0.05). From second to third trimester, differences (p < 0.05) were significant only for vitamin A. Between first and third trimester, differences were significant (p < 0.05) for energy, proteins, carbohydrates, niacin, riboflavin, zinc and for thiamin, vitamin A and calcium (p < 0.05). A high proportion of pregnant adolescent did not reach recommendations for energy, folate, calcium and zinc. Food intake pattern did not change significantly among trimesters. Mean total weight gain was 9.2 kg and 0.412 +/- 0.4 g/week. Newborn's mean weight was 3.221 +/- 418 grams. It is concluded that adolescents are at high nutritional risk and deficiency of dietary intake should be followed. Attention should be addressed from the preconceptional period to postpartum in order to improve maternal and fetal conditions.

Adolescent↗

Energy intake and body weight in ovo-lacto vegetarians.

Vegetarians have a lower body weight than omnivores. In this study the relationship between the weight/height ratio and food consumption was evaluated in 92 ovo-lacto vegetarians and 113 omnivores in Israel. The average weight of the vegetarians was significantly lower than that of the omnivores (60.8 kg vs. 69.1 kg), even though the vegetarian diet supplied a significantly higher amount of calories than the nonvegetarian diet (3,030.5 cal/day vs. 2,626.8 cal/day). Consumption of fat was similar in both groups. Carbohydrate consumption was higher in the vegetarians while protein consumption was lower. The prevalence of obesity was significantly lower in the vegetarian group (5.4%) as compared to 19.5% among the omnivores. The lower body weight of vegetarians despite a higher caloric intake is of considerable interest.

Adult↗

Factors influencing energy expenditure in patients with burns.

Twenty-three consecutive patients with a mean burn size of 39% of total body surface area (%TBSA) were studied prospectively. Expected basal energy expenditure (EBEE) calculated by the Harris-Benedict formula, initial and twice weekly measurements of energy expenditure (MEE) by indirect calorimetry, and simultaneous estimation of nutrient intake were obtained. In the whole cohort the EBEE was 1,715 +/- 24 kcal/day and the MEE was 2,218 +/- 59 kcal/day. The degree of hypermetabolism was 29.0 +/- 2.8%. A subgroup of 16 patients had metabolic rates measured in both the fed and unfed states. The degree of hypermetabolism was only 6.5 +/- 4.5% in the unfed, but increased to 34.1 +/- 3.2% when the same patients were fed (p less than 0.001). The factors affecting MEE were then evaluated by stepwise multiple regression analysis which showed that MEE = -4343 + (10.5 X %TBSA) + (0.23 X Caloric intake [CI]) + (0.84 X EBEE) + (114 X Temp [C]) - (4.5 X Postburn days), r = 0.82, p less than .001. We conclude that 25% of the CI is used to increase the MEE, which suggests that these measurements done in the fasting state cannot be used to predict requirements.

Adult↗

Fuel sensing and the central nervous system (CNS): implications for the regulation of energy balance and the treatment for obesity.

This review describes the product of the 3-day International Association for the Study of Obesity (IASO) Stock Conference held in March 2004 and sponsored by Abbott Laboratories. The conference was focused on how the mechanisms by which individual cells sense their own fuel status might influence the energy balance of the entire organism. Whether you are a single-celled organism or a sophisticated mammal with a large cerebral cortex, it is critical that cellular activity be matched to the available fuel necessary for that activity. Rapid progress has been made in the last decade in our understanding of the critical metabolic events that cells monitor to accomplish this critical task. More recent developments have begun to apply this understanding to how critical populations of neurones may monitor similar events to control both food intake and energy expenditure. The picture that emerges is that numerous peripheral fuel sensors communicate to the central nervous system (CNS) via neural and humoral routes. Moreover, it has been known for decades that specific populations of neurones sense changes in ambient glucose levels and adjust their firing rate in response and changes in neuronal glucose metabolism can influence energy balance. The CNS, however, does not just sense glucose but rather appears to be sensitive to a wide range of metabolic perturbations associated with fuel availability. This information is used to adjust both caloric intake and the disposition of fuels in the periphery. Increased understanding of these CNS fuel-sensing mechanisms may lead to novel therapeutic targets for obesity.

Central Nervous System↗

Effects of body weight and food intake on pleasantness ratings for a sweet stimulus.

A physiological role for pleasure has been suggested from observations that glucose loads reduced pleasantness ratings for sweet stimuli in normal weight but not in weight-reduced subjects. This hypothesis was reexamined in fasting and food-loaded, lean and obese subjects. Magnitude estimates of sweetness and pleasantness were obtained for seven sucrose concentrations. Indices of obesity including percent overweight, percent body fat, and body mass index were calculated. Pleasantness ratings of fasting subjects either increased up to a moderate concentration and then declined (type I hedonic response) or increased monotonically with concentration (type II hedonic response). Both types of response were found in lean and obese subjects. Within each weight group there appeared a negative correlation between pleasantness response and indices of obesity. Caloric loads reduced hedonic ratings of type II lean and obese subjects, but did not affect pleasantness response of type I lean and obese subjects. These findings indicate the presence of an hedonic monitor biased by body weight and caloric intake. The data suggest a physiological role for pleasure in regulating body weight at different set points in lean and obese subjects.

Adult↗

Effect of a high-fat diet on food intake and hypothalamic neuropeptide gene expression in streptozotocin diabetes.

Insulin-deficient diabetic rats are markedly hyperphagic when fed a high-carbohydrate (HC) diet, but normophagic when fed a high-fat (HF) diet. When maintained on a HC diet, diabetic rats also exhibit increased gene expression of the orexigenic peptide neuropeptide Y (NPY) in the hypothalamic arcuate nucleus, and reduced expression of the anorectic peptide corticotropin-releasing hormone (CRH) in the paraventricular nucleus, and these changes are hypothesized to contribute to diabetic hyperphagia. In this experiment we assessed whether the normophagia displayed by HF-fed diabetic rats is associated with the opposite profile of NPY and CRH expression. Our results show that relative to diabetic rats on the HC diet, the diabetic rats on the HF diet exhibited significantly reduced caloric intake (-40%), NPY expression in the arcuate nucleus (-27%), and elevated CRH expression in the paraventricular nucleus (+37%). Insulin and corticosterone, which are known to affect hypothalamic NPY and CRH expression, were not different between these two groups, making it unlikely that they can account for the differences in either feeding behavior or hypothalamic peptide expression. There was a small but significant increase in plasma leptin levels in the diabetic animals maintained on the HF, and large differences in parameters associated with elevated fat oxidation. These observations support the hypothesis that the normalization of food intake observed in diabetic rats consuming a HF diet may in part be mediated by reductions in NPY expression and elevations in CRH expression.

Animals↗

Energy intake and physical activity during short-term smoking cessation in postmenopausal women.

This study assessed the effect of short-term (2-week) smoking abstinence on weight gain, energy intake, and physical activity in 60 postmenopausal women. Participants were stratified by their use of hormone replacement therapy (HRT; currently taking/not taking) and then randomized to abstinence or continued smoking for 2 weeks. The 30 abstainers gained a mean of 1.28 kg, compared with a 0.54 kg loss for the 30 continued smokers (P=.002). The abstainers also reported a significantly greater increase than did the smokers in total kilocalorie and in carbohydrate consumption for both weeks. There were no changes in physical activity and HRT effect. These are the first published findings on caloric intake and weight gain during smoking abstinence in postmenopausal women-an understudied population in the smoking cessation literature.

Adult↗

Enteral nutritional support and wound excision and closure do not prevent postburn hypermetabolism as measured by continuous metabolic monitoring.

BACKGROUND: Estimation of nutritional needs in burn patients is difficult. In 24 severely burned patients, we measured CO2 production and O2 consumption continuously during their period of mechanical ventilation. METHODS: Patients with extensive burns were placed on a continuous metabolic monitor (CMM) (Puritan Bennett Co., Kingwood, TX), and metabolic expenditure was recorded each 24 hours. High protein enteral feedings were started within several hours of admission, and administration rates were adjusted to meet daily caloric demands as determined by the CMM. Full-thickness wounds were excised as early as patient condition permitted, and wounds were closed with autograft, allograft, or TransCyte (Advanced Tissue Sciences Inc., La Jolla, CA). Daily 24-hour caloric needs as measured by CMM were compared with baseline caloric needs predicted by the Harris-Benedict equation and also compared with actual daily caloric intake. Patients were removed from study when they were off continuous mechanical ventilation. RESULTS: A total of 24 patients were studied, with a mean age of 46 years and a 44% total body burn size (partial- and full-thickness). All full-thickness burns were completely excised by a mean of 6.5 days postburn. Mean daily energy expenditures remained elevated through the duration of the study period (42 days), with a mean elevation of 184.9% of baseline as predicted by Harris-Benedict equation. Patients received enteral feedings, which met 99.4% of actual caloric needs as predicted by CMM during the study period. CONCLUSION: Continuous metabolic monitoring demonstrates that early wound excision and wound closure, coupled with aggressive enteral nutritional support with high protein formulas, do not prevent the marked hypermetabolism that accompanies thermal injury.

Burns↗

[Evaluation of nutritional status in a group of patients undergoing CAPD].

The onset of a protein-energy malnutrition represents a real risk for patients on CAPD. In order to verify the nutritional status and the effectiveness of the dietetic surveillance in preventing this complication, dietary intake, anthropometric measurements and biochemical parameters were monitored in 46 patients (27 males, 19 females, mean age: 58.7 +/- 14.8 years), suffering from ESRF and treated with CAPD, for a total observation period of 1731.67 months (mean: 37.64 +/- 25.17 months). The mean glucose concentration in the dialysate was 2.00 +/- 0.36 g/dl, the glucose reabsorption from dialysate per kg of ideal body weight (kg-IBW) was equivalent to 5.1 kcal, the mean dialysate protein loss was 13.08 +/- 5.52 g/day and the incidence of peritonitis episodes was 1 every 30.38 months-patient. The daily total caloric intake (by mouth and dialysate) was 30.8 kcal/kg-IBW with a normal subdivision for each diet component: there were not statistically significant differences in distribution according to age, sex and in the follow-up. The mean daily value of protein intake (PI) evaluated by dietary interviews was 0.99 g/kg-IBW, with a significant increase 1 year since the beginning of CAPD; the PI evaluated from urea nitrogen appearance was 1.22 g/kg-IBW. The PI remained stable later in the follow-up and in patients that made use of dietetic supplements, the mean daily increase by this way was 0.47 g/kg-IBW. Anthropometric measurements showed a statistically significant increase of %RBW after 1 year and of TS and % body fat after 3 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Six-month overnight intraperitoneal amino-acid infusion in continuous ambulatory peritoneal dialysis (CAPD) patients--no effect on nutritional status.

The long-term effect of an AA solution based on Travasol, a solution for total parenteral nutrition, given intraperitoneally over a 6-month period was studied in 5 patients 22 to 75 years old, having been on continuous ambulatory peritoneal dialysis (CAPD) for 3 to 57 months. A low oral protein intake (less than 0.8 g/kg bw/day) and/or a low serum albumin (less than 35 g/L) were used as inclusion criteria. Two liters of 1% AA solution were infused overnight, while a glucose Dianeal was used for the other exchanges. During the study, BUN increased from 22.04 mM/L to 28.06 mM/L the first month and remained at these levels, indicating the increased protein intake. However, average oral total energy and protein intake, body weight (bw), serum creatinine, cholesterol, triglycerides, total proteins, albumin, transferrin, skinfold thickness, total body potassium, and plasma AA levels remained basically unchanged. The average total body nitrogen decreased from 1.746 to 1.554 Kg, but this decrease did not reach statistical significance (p greater than 0.05). We conclude that intraperitoneal overnight administration of 2 L of 1% AA based on Travasol over 6 months did not improve the nutritional status of CAPD patients. This ineffectiveness might be due to the AA composition of the solution, the timing of administration, or to a low caloric intake and/or that our patients were not severely malnourished.

Amino Acids↗

The effects of rate and route of nutrient intake on protein metabolism.

Isotopic measurements of protein kinetics are useful for the investigation of metabolic protein disorders during surgical illness. The effects of rate and route (oral vs parenteral) of nutritional substrate intake have not been well defined. Fischer 344 rats were infused with a total parenteral nutrition (TPN) solution at either 25, 100, or 175% of their normal substrate intake or were fed an oral diet ad libitum. After 4 days, [15N]glycine was infused at 0.138 mg 15N/hr for 24 hr. Whole-body protein turnover (WPT), synthesis, and catabolism were determined by 15N urea enrichment. Fractional synthesis rates (FSR) of liver and muscle protein were calculated by analyzing 15N tissue enrichment. WPT (r = 0.93, P less than 0.001) and liver FSR (r = 0.57, P less than 0.01) increased linearly with TPN infusion rates. All rats had protein synthesis rates greater than catabolism rates except for the rats infused with 25% TPN. Although caloric intake was the same in rats fed orally and those infused with 100% TPN, the orally fed rats had faster WPT (P less than 0.001), synthesis (P less than 0.05), catabolism (P less than 0.001), and liver FSR (P less than 0.05) than the TPN rats. Muscle FSR was not significantly affected by either the route of feeding or the TPN infusion rate. In this study, rate and route of substrate intake affected protein kinetics in the whole animal and liver, but not in muscle. Rate and route of nutrient intake need to be carefully specified and controlled during isotopic studies of protein kinetics.

Animal Nutritional Physiological Phenomena↗

Resting energy expenditure, weight loss, and altered body composition in HIV infection.

Failure to downregulate resting energy expenditure (REE) as an adaption to anorexia or malabsorption is often stated as the major cause of weight loss in individuals with AIDS. In a prospective study, REE was compared with weight changes in HIV-infected patients. The impact of altered body composition on REE was reassessed by critical review of the literature. Patients were 65 male HIV-infected patients, 28 with recent weight loss (WL), and 37 who were weight stable (WS); 50/65 patients had AIDS, and 29/65 had acute infections; 29 male healthy persons served as controls. Indirect calorimetry, prospective intake protocol, and bioelectrical impedance analysis were performed. Absolute REE was lower in WL patients than in controls (1459 +/- 309 versus 1711 +/- 151 kcal/d, p < 0.001) and in WS patients (1625 +/- 402 kcal/d, p < 0.05). REE/kg body cell mass (BCM) was higher in WL and WS than in controls (both p < 0.01) due to lower BCM in both patient groups (p < 0.001). REE (%Harris-Benedict) was not different among the three groups. Weight changes around the measurement were not correlated to REE (r2 = 0.0008, p = 0.82). REE was independent of diarrhea, acute infection, fever, or caloric intake. REE had a stronger correlation to body weight and to Harris-Benedict's prediction than to fat-free mass or BCM. REE explains < 1% of weight changes. Many patients can downregulate REE as an adaption to anorexia and/or malabsorption. Higher REE/kg BCM does not signify hypermetabolism at the cellular level but can be explained by the maintenance of energy-consuming visceral tissue within the BCM during BCM loss.

Acquired Immunodeficiency Syndrome↗

Effect of diazoxide on brain capillary insulin receptor binding and food intake in hyperphagic obese Zucker rats.

Insulin is believed to act as a central adiposity signal by binding to hypothalamic and other brain insulin receptors. Entry of circulating insulin into the brain is accomplished by a saturable receptor-mediated transendothelial transport system and is believed to be impaired in hyperinsulinemic, insulin-resistant, and hyperphagic obese Zucker rats. Theoretically, if hyperinsulinemia is decreased simultaneously while brain capillary insulin binding is increased, uptake of insulin into the brain can be enhanced leading to reduced food intake. To test this hypothesis, we administered diazoxide (DZ, 150 mg/kg/day), an inhibitor of glucose-mediated insulin secretion, or vehicle (control) to 7-week-old female obese and lean Zucker rats for 4 weeks (n = 24-28/subgroup-strain). Animals were assigned to either fasted (FD) or free-fed (FF) protocol for determination of plasma and cerebrospinal fluid (CSF) insulin and brain capillary insulin binding at the end of 4 weeks. DZ obese consumed fewer calories (P<0.01) and gained less weight than control obese (P<0.01), whereas DZ lean had similar amounts of caloric intake and weight gain compared with lean controls. DZ obese had lower fasting and random plasma glucose than control obese (P<0.05). FD and FF DZ-treated obese and lean rats had lower plasma insulin than their respective obese (P<0.01) and lean (P<0.01) controls. FD and FF DZ-treated obese rats demonstrated higher CSF insulin (P<0.05) and CSF/ plasma insulin ratio (P<0.01) than their controls, while only FF DZ lean animals showed higher CSF/plasma insulin ratio (P<0.01) than their controls (P<0.05). This was associated with enhanced brain capillary insulin binding in FD and FF DZ-treated obese (P<0.01) and lean (P<0.05) animals compared with their respective controls. It was concluded that DZ treatment in obese Zucker rats caused a decrease in insulin secretion and partially reversed impaired insulin binding to brain capillaries, leading to enhanced brain insulin uptake, and resulted in reduced food intake and weight gain observed in these animals.

Animals↗

Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea.

The development of functional hypothalamic amenorrhea (FHA) in weight-stable, nonathletic women has long been thought to be psychogenic in origin. This study was designed to gain insight into the possibility that nutritional deficits and compensatory endocrine-metabolic adaptations contribute to the development and maintenance of FHA of the psychogenic type. Nutritional intake, insulin sensitivity, and 24-h dynamics of insulin/glucose, cortisol, leptin, somatotropic, and LH axes were simultaneously assessed in eight women with FHA not associated with exercise or weight loss and in eight age- and body mass index-matched regular cycling controls (NC). The percent fat body mass was lower and lean body mass was higher in FHA than in NC (P < 0.05). The FHA subjects scored higher (P < 0.05) on two Eating Disorder Inventory subscales and had a higher (P < 0.05) Beck depression rating than NC, although all were in the subclinical range. Although daily caloric intake did not differ, FHA consumed 50% less (P < 0.001) fat, twice (P < 0.05) as much fiber, and more carbohydrate (P < 0.05) compared to NC. During the feeding phase of the day, FHA exhibited lower glucose (P < 0.05) and insulin (P < 0.01) levels than NC, and the degree of hypoinsulinemia was directly related to relative dietary fat (r = 0.73). Although 24-h mean GH levels did not differ, the pattern of GH release in FHA was distinctly altered from that in NC. GH pulse amplitude was blunted, pulse frequency was accelerated 40% (P < 0.01), and interpulse GH concentrations were elevated 2-fold (P < 0.01) throughout the day for FHA compared to NC. This distorted pattern of GH pulses was associated with a 40% decrease (P < 0.01) in GH-binding protein levels. Levels of the insulin-dependent insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) were elevated (P < 0.001) during the feeding portion of the day in FHA and were inversely related to insulin (r = -0.50) and directly related to cortisol (r = 0.64) levels for FHA and NC groups together. Although levels of IGF-I and IGFBP-3 did not differ, the elevation of IGFBP-1 levels in FHA resulted in a reduced (P < 0.01) ratio of IGF-I/IGFBP-1, which may decrease the bioactivity and hypoglycemic effect of IGF-I. Twenty-four-hour mean leptin levels and the diurnal excursion of leptin in FHA did not differ from those in NC. LH pulse frequency was slowed 50% (P < 0.001) in FHA, with unaltered pulse amplitude, resulting in 45% lower (P < 0.01) 24-h mean LH levels for FHA compared to NC. LH pulse frequency for the two groups was related positively to insulin (r = 0.80) levels and the ratio of IGF-I/IGFBP-1 (r = 0.70) and negatively with cortisol (r = -0.61) and IGFBP-1 (r = -0.72) concentrations. In summary, we found evidence of subclinical eating disorders in weight-stable, nonathletic women with FHA accompanied by a severe restriction of dietary fat intake. Unbalanced nutrient intake in psychogenic FHA was associated with multiple endocrine-metabolic alterations. Among these, reduced levels of plasma glucose and serum GHBP, a decrease in the ratio of IGF-I/IGFBP-1, accelerated GH pulse frequency, and elevated interpulse GH levels are indicative of a hypometabolic state. In addition, the magnitude of glucoregulatory responses (increased cortisol secretion and decreased insulin/IGF-I action) were directly related to the degree of suppression of GnRH/LH pulse frequency. These results are remarkably similar to those seen in highly trained athletes with FHA(1). Thus, nutritional deficits may represent a common contributing factor to the development and maintenance of multiple neuroendocrine-metabolic aberrations underlying both psychogenic and exercise-related FHA.

Adult↗

[Toxicological effects induced by the chronic intake of brominated vegetable oils].

Several biochemical parameters of male Wistar rats fed during 15 weeks with standard laboratory chow, supplemented with 0.1 g of brominated vegetable oil (olive, sunflower) per 100 g of diet, were compared to those of a control group fed a normal diet during the same period of time. The former group showed a significant increase of triglyceride content in both heart and soleus muscle, as well as of total and sterified cholesterol in heart muscle. This increase was accompanied by decreased plasma levels of total and HDL-cholesterol. Some of these abnormalities were similar to those observed in rats fed the same standard laboratory chow, supplemented with 0.5 g of brominated oil per 100 g of diet. The hepatic levels of triglycerides, total proteins and glycogen, as well as the weight gain and caloric intake of the animals which were fed 0.1 g of brominated oil per 100 g diet, were similar to those of the control group. In summary, the toxicologic effects observed during the chronic intake of diets supplemented with relatively low doses of brominated oils, suggest the need to undertake wider and deeper biochemical studies. The authors consider that these are necessary in order to ascertain the maximum tolerance levels for the use of these compounds, to minimize the risk of inducing important biological alterations.

Animals↗