Obesity. In Cecil-Loeb Textbook of Medicine.
Albrick M. 1971; Thirteenth Edition:1448-58.
Weight loss increases and fat loss decreases all-cause mortality rate: results from two independent cohort studies. Allison DB, Zannolli R, Faith MS, et al. Int J Obes Relat Metab Disord. 1999 Jun; 23(6):603-11. OBJECTIVE: In epidemiological studies, weight loss is usually associated with increased mortality rate. Contrarily, among obese people, weight loss reduces other risk factors for disease and death. We hypothesised that this paradox could exist because weight is used as an implicit adiposity index. No study has considered the independent effects of weight loss and fat loss on mortality rate. We studied mortality rate as a function of weight loss and fat loss. DESIGN: Analysis of 'time to death' in two prospective population-based cohort studies, the Tecumseh Community Health Study (1890 subjects; 321 deaths within 16y of follow-up) and the Framingham Heart Study (2731 subjects; 507 deaths within 8y of follow-up), in which weight and fat (via skinfolds) loss were assessable. RESULTS: In both studies, regardless of the statistical approach, weight loss was associated with an increased, and fat loss with a decreased, mortality rate (P or = 34) obese individuals is unclear. CONCLUSIONS: Among individuals that are not severely obese, weight loss is associated with increased mortality rate and fat loss with decreased mortality rate
Weight loss and delayed gastric emptying following a South American herbal preparation in overweight patients. Andersen T, Fogh J. J Hum Nutr Diet. 2001 Jun; 14(3):243-50. BACKGROUND: Obesity and overweight may soon affect more than half of the population in some regions of the world and are associated with diabetes, hypertension and other diseases that cause morbidity, mortality and high health-care expenditure. No one approach, whether dietetic management, medication, or commercial weight loss programme, can alone solve the problem--all potential treatments need to be investigated and exploited. Among the herbal preparations known to non-western cultures are materials which may have applications in modulating physiological processes which influence gut motility, food intake and energy balance. One such mixed herbal preparation is 'YGD' containing Yerbe Mate (leaves of Ilex paraguayenis), Guarana (seeds of Paullinia cupana) and Damiana (leaves of Turnera diffusa var. aphrodisiaca). AIMS: This study had two distinct aims: to determine the effect of a herbal preparation 'YGD' containing Yerbe Mate, Guarana and Damiana on gastric emptying; to determine the effect of the same preparation on weight loss over 10 days and 45 days and weight maintenance over 12 months. METHODS: Gastric emptying was observed using ultrasound scanning in seven healthy volunteers following YGD and placebo capsules taken with 420 mL apple juice. Body weight was observed before and after 10 days of treatment with three YGD capsules or three placebo capsules before each meal for 10 days in 44 healthy overweight patients attending a primary health care centre. Forty-seven healthy overweight patients entered a double-blind placebo-controlled parallel trial of three capsules of YGD capsules before each main meal for 45 days compared with three placebo capsules on body weight. Body weight was monitored in 22 patients who continued active (YGD capsules) treatment for 12 months. RESULTS: The herb preparation YGD was followed by a prolonged gastric emptying time of 58 +/- 15 min compared to 38 +/- 7.6 min after placebo (P = 0.025). Body weight reductions were 0.8 +/- 0.05 kg after YGD capsules compared to 0.3 +/- 0.03 kg after placebo capsules over 10 days, and 5.1 +/- 0.5 kg after PGD capsules compared to 0.3 +/- 0.08 kg after placebo over 45 days. Active treatment with YGD capsules resulted in weight maintenance of the group (73 kg at the beginning and 72.5 kg at the end of 12 months). CONCLUSIONS: The herbal preparation, YGD capsules, significantly delayed gastric emptying, reduced the time to perceived gastric fullness and induced significant weight loss over 45 days in overweight patients treated in a primary health care context. Maintenance treatment given in an uncontrolled context resulted in no further weight loss, nor weight regain in the group as a whole. The herbal preparation is thus shown to be one that significantly modulates gastric emptying. Further clinical studies with dietetic monitoring of energy intake, dietary quality, satiety ratings, body weight and body composition are now indicated, and examination of the active principles contained in the three herbal components may prove rewarding
The role of dietary fat in the prevention and treatment of obesity. Efficacy and safety of low-fat diets. Astrup A. Int J Obes Relat Metab Disord. 2001 May; 25 Suppl 1:S46-S50. BACKGROUND: Does dietary fat play a central role in weight gain and development of obesity? Do low-fat diets have adverse effects on blood lipids? OBJECTIVE AND DESIGN: To answer these questions we have reviewed the evidence linking the dietary fat content to energy balance and obesity, and examined the efficacy and safety of ad libitum low fat, high carbohydrate/protein diets in the prevention and management of obesity. RESULTS: Physiological studies have provided insight into the mechanisms by which the macronutrients differ in their effect on energy balance: (1) energy from fat is less satiating than energy from carbohydrate, and a high fat/carbohydrate ratio in the diet promotes passive overconsumption, a positive energy balance and weight gain in susceptible individuals; (2) fat is more readily absorbed from the intestine and fecal energy loss is much lower with a high dietary fat/carbohydrate ratio; (3) carbohydrate is more thermogenic than fat and energy expenditure is lower during positive energy balance produced by a diet with a high fat/carbohydrate ratio than during positive energy balance produced by a diet with a low fat/carbohydrate ratio. Randomized intervention studies comparing low fat diets to normal fat diets show that low fat diets prevent weight gain in normal weight subjects and produce weight loss in overweight individuals. In our meta-analysis of ad libitum low fat interventions we included 16 trials involving 1728 individuals. The difference in weight loss between intervention and control groups was 2.5 kg (95% CI, 1.5-3.5; P<0.0001). Weight loss was positively related to pre-treatment body weight (r="0.52," P<0.05) and to reduction in percentage energy as fat (0.37 kg/%, P<0.005). Extrapolated to a body mass index (BMI) approximately 30 kg/m(2), and assuming a 10% reduction in dietary fat, the predicted weight loss would be 4.4 kg (95% CI, 2.0-6.8 kg), which has been confirmed in subsequent studies. Newer studies have shown that replacing some carbohydrate with protein may enhance weight loss. CONCLUSION: The American Paradox, the observation that obesity prevalence is increasing despite a slight decrease in population dietary fat consumption, is easily explained by the concomitantly decreasing physical activity, which reduces fat requirements and counteracts the beneficial effect of a slight reduction in dietary fat. Low fat diets with a high content of complex carbohydrates and protein do not produce any adverse effect on cardiovascular risk factors when weight loss is allowed to occur, and they have been shown to decrease mortality among high risk subjects
Low-fat diets and energy balance: how does the evidence stand in 2002? Astrup A, Astrup A, Buemann B, et al. Proc Nutr Soc. 2002 May; 61(2):299-309. The role of high-fat diets in weight gain and obesity is assessed by evidence-based principles. Four meta-analyses of weight change occurring on ad libitum low-fat diets in intervention trials consistently demonstrate a highly significant weight loss of 3-4 kg in normal-weight and overweight subjects (P < 0.001). The analyses also find a dose-response relationship, i.e. the reduction in percentage energy as fat is positively associated with weight loss. Weight loss is also positively related to initial weight; a 10 % reduction in dietary fat is predicted to produce a 4-5 kg weight loss in an individual with a BMI of 30 kg/m2. The non-fat macronutrient composition of the diet is also important. Whereas the glycaemic index of the carbohydrate may play a role for cardiovascular risk factors, there is so far no evidence that low-glycaemic index foods facilitate weight control. In contrast, intervention studies show that sugar in drinks is more likely to produce weight gain than solid sugar in foods. Although the evidence is weak, alcoholic beverages promote a positive energy balance, and wine may be more obesity-promoting than beer. Protein is more satiating and thermogenic than carbohydrates, and one intervention study has shown that an ad libitum low-fat diet where carbohydrate was replaced by protein produced more weight loss after 6 months (8.1 v. 5.9 kg). The evidence linking particular fatty acids to body fatness is weak. If anything, monounsaturated fat may be more fattening than polyunsaturated and saturated fats, and no ad libitum dietary intervention study has shown that a normal-fat high-monounsaturated fatty acid diet is equivalent or superior to a low-fat diet in the prevention of weight gain and obesity. The evidence strongly supports the low-fat diet as the optimal choice for the prevention of weight gain and obesity, while the use of a normal-fat high-monounsaturated fatty acid diet is unsubstantiated
Effect of dietary composition on fasting-induced changes in serum thyroid hormones and thyrotropin. Azizi F. Metabolism. 1978 Aug; 27(8):935-42.
[Effect of chromium yeast and chromium picolinate on body composition of obese, non-diabetic patients during and after a formula diet]. Bahadori B, Wallner S, Schneider H, et al. Acta Med Austriaca. 1997; 24(5):185-7. The objective of this study was to assess the effects of chromium yeast and chromium picolinate on lean body mass during and after weight reduction with a very-low-calorie diet. 36 obese (BMI 33.7 +/- 5.4 kg/m2), non-diabetic patients aged 45 +/- 6 years undergoing a 8-week very-low-calorie diet followed by a 18-week maintenance period. During the whole 26 week treatment period subjects received either placebo or chromium yeast (200 micrograms/d) or chromium-picolinate (200 micrograms/d) in a double-blind manner. Body weight was measured as BMI and body composition after calculation from skinfold thickness. As a result all three groups showed comparable weight loss after 8 and 26 weeks. Lean body mass was reduced in all groups after 8 weeks. However, after 26 weeks chromium picolinate supplemented subjects showed increased lean body mass (p < 0.029) whereas the other treatment groups still had reduced lean body mass. Chromium picolinate, but not chromium yeast, is able to increase lean body mass in obese patients in the maintenance period after a very-low-calorie diet without counteracting the weight loss achieved
Obesity and insurance risk: the insurance industry's viewpoint. Baird IM. Pharmacoeconomics. 1994; 5(Suppl 1):62-5. Obesity is regarded by insurance companies as a substantial risk for both life and disability policies. This risk increases proportionally with the degree of obesity. Mortality statistics for life insurance were the earliest indicator that the cost of obesity to the individual was a decreased life span and increased illness, particularly that affecting the cardiovascular and musculoskeletal systems. The prevalence of coronary heart disease rises with increases in the body mass index in both men and women. Cigarette smoking greatly augments these risks in both sexes. Hypertension and diabetes are very common in obese persons and add further to the risks of vascular disease. Abdominal obesity (when the abdominal girth measured round the umbilicus exceeds the maximum measurement round the hips) is correlated with the risk of cardiac disease and stroke, independently of bodyweight. Insurance companies consider abdominal obesity as unfavourable and rate it accordingly. Obesity (even that of moderate degree) greatly increases the chances of disability due to cardiovascular disease or musculoskeletal illness. In one study of 51 522 adult Finns, 25% of disability pensions in women were found to result directly from obesity. Obesity causes increased health expenditure, decreased life span and productivity, and premature retirement. Insurance companies are compelled to build these risks into their policies. However, because the excess mortality occurs late in mild to moderate obesity, some companies may minimise this risk for life policies that mature early
Decrease in linoleic acid metabolites as a potential mechanism in cancer risk reduction by conjugated linoleic acid. Banni S, Angioni E, Casu V, et al. Carcinogenesis. 1999 Jun; 20(6):1019-24. Previous research suggested that conjugated linoleic acid (CLA) feeding during the period of pubescent mammary gland development in the rat resulted in diminished mammary epithelial branching which might account for the reduction in mammary cancer risk. Terminal end buds (TEB) are the primary sites for the chemical induction of mammary carcinomas in rodents. One of the objectives of the present study was to investigate the modulation of TEB density by increasing levels of dietary CLA and to determine how this might affect the risk of methylnitrosourea-induced mammary carcinogenesis. The data show a graded and parallel reduction in TEB density and mammary tumor yield produced by 0.5 and 1% CLA. No further decrease in either parameter was observed when CLA in the diet was raised to 1.5 or 2%. Thus, optimal CLA nutrition during pubescence could conceivably control the population of cancer-sensitive target sites in the mammary gland. Since both CLA and linoleic acid are likely to share the same enzyme system for chain desaturation and elongation, it is possible that increased CLA intake may interfere with the further metabolism of linoleic acid. Fatty acid analysis of total lipid showed that CLA and CLA metabolites continued to accumulate in mammary tissue in a dose-dependent manner over the range 0.5-2% CLA. There was no perturbation in tissue linoleic acid, however, linoleic acid metabolites (including 18:3, 20:3 and 20:4) were consistently depressed by up to 1% CLA. Of particular interest was the significant drop in 20:4 (arachidonic acid), which is the substrate for the cyclooxygenase and lipoxygenase pathways of eicosanoid biosynthesis. Thus the CLA dose-response effect on arachidonic acid suppression corresponded closely with the CLA dose-response effect on cancer protection in the mammary gland. This information is critical in providing new insights regarding the biochemical action of CLA
The effect of a 72-h fast on plasma levels of pituitary, adrenal, thyroid, pancreatic and gastrointestinal hormones in healthy men and women. Beer SF, Bircham PM, Bloom SR, et al. J Endocrinol. 1989 Feb; 120(2):337-50. Seventeen human subjects fasted without electrolyte replacement for 3 days and hormone levels were measured before, during and after the fast. Immediate consequences of the fasting state in healthy human subjects include a marked increase in plasma cortisol. ACTH, beta-endorphin, beta-lipotrophic hormone, adrenaline, noradrenaline and dopamine. Levels of all these hormones were much greater on the first morning of the fast than in the post-prandial state, even though the plasma glucose level was no lower than that observed on the morning before the fast began. A clear fall in TSH and tri-iodothyronine (T3) levels was observed, but thyroxine levels did not change significantly. Insulin levels fell whereas proinsulin levels did not fall during the fast, though they did rise markedly upon re-feeding. An increase in GH levels was particularly apparent in male subjects, but was also seen in females when evening samples were compared. Pancreatic glucagon showed a modest rise during the fast, but fell again on refeeding; total glucagon also rose as the fast proceeded, but increased markedly upon re-feeding. Levels of gastrin and peptide YY remained low during the fast. Plasma electrolyte levels were unchanged. The following were closely correlated: cortisol with ACTH, T3 with log10 TSH, dopamine with noradrenaline, and (negatively, during the fast) pancreatic glucagon with glucose
Cecil-Loeb Textbook of Medicine. Beeson P. 1968; Twelfth Edition
Cecil-Loeb Textbook of Medicine. Beeson P. 1971; Thirteenth Edition
Thyroid disease in the elderly. Part 1. Prevalence of undiagnosed hypothyroidism. Bemben DA, Winn P, Hamm RM, et al. J Fam Pract. 1994 Jun; 38(6):577-82. BACKGROUND. The purpose of this study was to examine the prevalence of previously unrecognized hypothyroidism in elderly patients. METHODS. The study was conducted in a primary care geriatrics clinic. Three hundred seventy elderly patients (287 women, 83 men) between 60 and 97 years of age were included in the study. Medical records of patients were reviewed retrospectively. Serum thyroid-stimulating hormone (TSH), free thyroxine (T4), height, weight, demographic variables, clinical signs and symptoms of hypothyroidism, history of thyroid diseases and treatment with thyroid medications, comorbidities, and current medications were obtained from the medical records. Patients who had both elevated TSH levels (5.0 to 14.9 microU/mL) and normal free T4 levels (0.7 to 2.0 ng/dL) met the criteria for "subclinical hypothyroidism." The criteria for "overt hypothyroidism" were TSH levels > or = 15 microU/mL and low free T4 levels (< 0.7 ng/dL). RESULTS. At the initial visit to the clinic, 18.1% of the patients (62 female and 5 male) had an established history of past or current thyroid disease. Another 20 women (5.4%) had a history of thyroid surgery. Of the remaining 283 patients with no history of thyroid disease, 14.6% of the women and 15.4% of the men had subclinical hypothyroidism. Overt hypothyroidism was discovered and subsequently treated in two female patients and one male patient (1.0% and 1.3%, respectively). Thyroid status was not significantly related to age group (60 to 64 years; 65 to 74; 75 to 84; 85 and older). Comorbidities typically associated with hypothyroidism were no more prevalent in hypothyroid patients than in euthyroid patients. CONCLUSIONS. We found a high prevalence of newly diagnosed subclinical hypothyroidism in both elderly male and female patients. Thyroid status was not related to age or to coexisting diseases. The clinical significance of treating subclinical hypothyroidism merits investigation
Induction of obesity by psychotropic drugs. Bernstein JG. Ann N Y Acad Sci. 1987; 499:203-15. Evidence from published studies and clinical experience indicates that neuroleptic drugs, tricyclic and heterocyclic antidepressants, monoamine oxidase inhibitor antidepressants, and lithium all possess varying abilities to increase appetite, stimulate carbohydrate craving, and cause weight gain over prolonged periods of administration. Sedatives and benzodiazepine-type antianxiety drugs fail to stimulate appetite or induce weight gain, and it is unlikely that the sedative or calming effects of other psychotropic drugs contribute significantly to changes in appetite or weight. Studies of the endocrine and metabolic aspects of psychotropic drugs suggest that these mechanisms do not contribute significantly to explaining the observed effects on appetite or weight. Numerous studies indicate that a wide variety of compounds, including the serotonin precursor, tryptophan, the serotonin receptor stimulant, fenfluramine, and the serotonin reuptake inhibitor, fluoxetine, are all capable of decreasing carbohydrate hunger, reducing consumption of carbohydrate-rich foods, and inhibiting weight gain in humans and animals. Widely divergent psychotropic drugs produce antagonistic effects at serotonin receptor sites, and it is likely that this action contributes to their ability to stimulate appetite, carbohydrate craving, and weight gain. Those psychotropic drugs that inhibit serotonin reuptake mechanisms, increasing serotonin activity within the central nervous system, either fail to stimulate carbohydrate hunger and weight gain or are actually capable of decreasing carbohydrate craving and facilitating weight loss. Because many antidepressants, including trazodone and amitriptyline, the neuroleptic, chlorpromazine, and the mood stabilizer, lithium, may all, under some circumstances, inhibit serotonin reuptake mechanisms and may simultaneously block serotonin receptor sites, their effects on appetite and weight gain may represent a balance between serotonergic and antiserotonin activities. Monoamine oxidase inhibitors, which slow the metabolic degradation of monoamines, including serotonin and norepinephrine, allow for increased levels of these neurotransmitters within the brain. It is conceivable that the relative noradrenergic effect related to an amphetamine-like structure of tranylcypromine may explain its lesser ability to stimulate appetite and weight gain than the appetite and weight effects observed with phenelzine. Furthermore, the production of dry mouth and thirst by psychotropic drugs appears to contribute to weight gain, secondary to consumption of high-calorie beverages.(ABSTRACT TRUNCATED AT 400 WORDS)
Long-term effect of fibre supplement and reduced energy intake on body weight and blood lipids in overweight subjects. Birketvedt GS, Aaseth J, Florholmen JR, et al. Acta Medica (Hradec Kralove). 2000; 43(4):129-32. A weight-reducing potential has been ascribed to high dietary fibre intake. To investigate the practical reliability of this hypothesis, fifty-three moderately overweight females (BMI > 27.5 kg/m2) on reduced energy intake (1200 kcal/day) were treated for 24 weeks with a fibre supplement on a randomly, double-blind, placebo-controlled basis. The fibre was administered as an initial dose of 6 g and a maintenance dose of 4 g. Body weight and blood pressure were recorded weekly during the first 3 months and thereafter every second week. Blood samples were drawn at start and at end of the study. Initial body weights were 75.6 +/- 1.6 kg in the fibre group versus 75.5 +/- 1.6 kg in the placebo group. After treatment, mean weight loss in the fibre group was 8.0 kg versus 5.8 kg in the placebo group (p < 0.05). Systolic and diastolic blood pressures were significantly reduced in both groups without differences between the groups. Serum concentrations of cholesterol, triglycerides and uric acid were significantly reduced in the group with reduced energy intake, whereas no additional effect was observed when fibre was supplemented. Serum concentrations of potassium and sodium did not change significantly. The results suggest that a dietary fibre supplement in combination with a hypocaloric diet is of value as an adjunct in the management of overweight
The regulation of adipose tissue distribution in humans. Bjorntorp P. Int J Obes Relat Metab Disord. 1996 Apr; 20(4):291-302. The regulation of adipose tissue distribution is an important problem in view of the close epidemiological and metabolic associations between centralized fat accumulation and disease. With visceral fat accumulation multiple endocrine perturbations are found, including elevated cortisol and androgens in women, as well as low growth hormone (GH) and, in men, testosterone (T) secretion. These abnormalities probably derive from a hypersensitive hypothalamo-pituitary-adrenal axis, with hyperinsulinemia related to a marked insulin resistance as a consequence. These hormonal changes exert profound effects on adipose tissue metabolism and distribution. At the adipocyte level cortisol and insulin promote lipid accumulation by expressing lipoprotein lipase activity, while T, GH and probably estrogens exert opposite effects. The consequences will most likely be more expressed in visceral than subcutaneous adipose tissues because of a higher cellularity, innervation and blood flow. Furthermore, the density of cortisol and androgen receptors seems to be higher in this than other adipose tissue regions. The endocrine perturbations found in visceral obesity with an abundance of the lipid accumulating hormones cortisol and insulin, and a relatively low secretion of the lipid mobilizing sex steroid hormones and GH would therefore be expected to be followed by visceral fat accumulation. The potential significance of local synthesis of steroid hormones in adipose tissue requires more attention. Although studies in vitro are informative when elucidating detailed mechanisms of hormonal interactions, they might not give a true picture of the regional integrated regulation of adipose tissue lipid storage and mobilization. Such information can be obtained by regional measurements of lipid mobilization by free fatty acid turnover or by microdialysis techniques, both showing lower rates of mobilization in leg than in upper body adipose tissues. More detailed information can be obtained by physiological oral administration of triglycerides, labelled with a small amount of oleic acid, followed by measurements of the regional uptake and turn-over of adipose tissue triglycerides. Such studies show lipid uptake in the order omental = retroperitoneal > subcutaneous abdominal > subcutaneous femoral adipose tissues in men, with a similar rank order for half-life of the triglyceride, indicating also a turn-over of triglycerides in that order. T amplifies these differences in men. In premenopausal women subcutaneous abdominal has a higher turnover than femoral adipose tissue. Results of studies in vitro indicate that this difference is diminished at the menopause, and restored by estrogen substitution, suggesting that the functional effects of estrogens in women are similar to those of T in men. The mechanisms are, however, probably indirect because of the apparent absence of specific estrogen and progesterone receptors in human adipose tissue. This interpretation from the studies referred to above fits well with physiological, and clinical conditions with increased visceral fat mass, where the balance between the lipid accumulating hormone couple (cortisol and insulin) and the hormones which prevent lipid accumulation and instead activate lipid mobilization pathways (sex steroid hormones and GH) is shifted to the advantage of the former. Such conditions include Cushing's syndrome, the polycystic ovary syndrome, menopause, aging, GH-deficiency, depression, smoking and excess alcohol intake. With appropriate interventions against hypercortisolemia and substitution of deficient sex steroids and GH, visceral fat mass is decreasing. Based on this evidence from physiological, clinical, interventional observations and detailed studies of mechanisms at cellular and molecular levels it is suggested that the combined endocrine abnormalities in the syndrome of visceral obesity direct storage fat to visceral adipose depots. Therefore, measurements of visceral fat accumulat
Conjugated linoleic acid reduces body fat mass in overweight and obese humans. Blankson H, Stakkestad JA, Fagertun H, et al. J Nutr. 2000 Dec; 130(12):2943-8. Conjugated linoleic acid (CLA) has been shown to reduce body fat mass (BFM) in animals. To investigate the dose-response relationships of conjugated linoleic acid with regard to BFM in humans, a randomized, double-blind study including 60 overweight or obese volunteers (body mass index 25-35 kg/m(2)) was performed. The subjects were divided into five groups receiving placebo (9 g olive oil), 1.7, 3.4, 5.1 or 6.8 g conjugated linoleic acid per day for 12 wk, respectively. Dual-energy X-ray absorptiometry was used to measure body composition [measurements at wk 0 (baseline), 6 and 12]. Of the 60 subjects, 47 completed the study. Eight subjects withdrew from the study due to adverse events; however, no differences among treatment groups were found regarding adverse events. Repeated-measures analysis showed that a significantly higher reduction in BFM was found in the conjugated linoleic acid groups compared with the placebo group (P: = 0.03). The reduction of body fat within the groups was significant for the 3.4 and 6.8 g CLA groups (P: = 0.05 and P: = 0.02, respectively). No significant differences among the groups were observed in lean body mass, body mass index, blood safety variables or blood lipids. The data suggest that conjugated linoleic acid may reduce BFM in humans and that no additional effect on BFM is achieved with doses > 3.4 g CLA/d
Severe sexual impairment produced by morbid obesity. Report of a case. Blum I, Marilus R, Barasch E, et al. Int J Obes. 1988; 12(3):185-9. A 45-year-old man, was admitted for investigation of severe sexual impairment. During 20 years of marriage, he had had no normal sexual intercourse and the couple was childless. Physical examination disclosed a severely obese man (weight 300 kg, height 1.75 m), with a relatively small and invaginated penis and small (5 ml) soft testes. Laboratory examinations disclosed the following: low serum testosterone (1 ng/ml), with a reduced response to HCG (3.8 ng/ml). Sex hormone binding globulin was at the lower limit of normal (0.38 microgram/dl), serum free testosterone was low (0.98% of total testosterone) as well as non-SHBG bound testosterone (22% of total testosterone). Daily total urinary estrogen excretion was increased (107 micrograms), the plasma estrone (78 pg/ml) and estradiol (74 pg/ml) were elevated. The gonadotropins were normal and responded adequately to LRH. Plasma growth hormone was decreased, prolactin, T4 and adrenal steroids were normal and responded normally to stimuli and inhibitors. Chromosomal constitution was 46XY. Thus, in this man the marked obesity produced a significant increase in estrogens which subsequently induced a severe decrease in testosterone and its free counterpart in excessive impairment of sexual function
The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids. Borkman M, Storlien LH, Pan DA, et al. N Engl J Med. 1993 Jan 28; 328(4):238-44. BACKGROUND. Insulin resistance and hyperinsulinemia are features of obesity, non-insulin-dependent diabetes mellitus, and other disorders. Skeletal muscle is a major site of insulin action, and insulin sensitivity may be related to the fatty-acid composition of the phospholipids within the muscle membranes involved in the action of insulin. METHODS. We determined the relation between the fatty-acid composition of skeletal-muscle phospholipids and insulin sensitivity in two groups of subjects. In one study, we obtained samples of the rectus abdominis muscle from 27 patients undergoing coronary artery surgery; fasting serum insulin levels provided an index of insulin sensitivity. In the second study, a biopsy of the vastus lateralis muscle was performed in 13 normal men, and insulin sensitivity was assessed by euglycemic-clamp studies. RESULTS. In the patients undergoing surgery, the fasting serum insulin concentration (a measure of insulin resistance) was negatively correlated with the percentage of individual long-chain polyunsaturated fatty acids in the phospholipid fraction of muscle, particularly arachidonic acid (r = -0.63, P < 0.001); the total percentage of C20-22 polyunsaturated fatty acids (r = "-0.68," P < 0.001); the average degree of fatty-acid unsaturation (r = "-0.61," P < 0.001); and the ratio of the percentage of C20:4 n-6 fatty acids to the percentage of C20:3 n-6 fatty acids (r = "-0.55," P < 0.01), an index of fatty-acid desaturase activity. In the normal men, insulin sensitivity was positively correlated with the percentage of arachidonic acid in muscle (r = "0.76," P < 0.01), the total percentage of C20-22 polyunsaturated fatty acids (r = "0.76," P < 0.01), the average degree of fatty-acid unsaturation (r = "0.62," P < 0.05), and the ratio of C20:4 n-6 to C20:3 n-6 (rho = "0.76," P = "0.007)." CONCLUSIONS. Decreased insulin sensitivity is associated with decreased concentrations of polyunsaturated fatty acids in skeletal-muscle phospholipids, raising the possibility that changes in the fatty-acid composition of muscles modulate the action of insulin
French's Index of Differential Diagnosis. Bouchier IAEDH. 1997;
Glycemic index and obesity. Brand-Miller JC, Holt SH, Pawlak DB, et al. Am J Clin Nutr. 2002 Jul; 76(1):281S-5S. Although weight loss can be achieved by any means of energy restriction, current dietary guidelines have not prevented weight regain or population-level increases in obesity and overweight. Many high-carbohydrate, low-fat diets may be counterproductive to weight control because they markedly increase postprandial hyperglycemia and hyperinsulinemia. Many high-carbohydrate foods common to Western diets produce a high glycemic response [high-glycemic-index (GI) foods], promoting postprandial carbohydrate oxidation at the expense of fat oxidation, thus altering fuel partitioning in a way that may be conducive to body fat gain. In contrast, diets based on low-fat foods that produce a low glycemic response (low-GI foods) may enhance weight control because they promote satiety, minimize postprandial insulin secretion, and maintain insulin sensitivity. This hypothesis is supported by several intervention studies in humans in which energy-restricted diets based on low-GI foods produced greater weight loss than did equivalent diets based on high-GI foods. Long-term studies in animal models have also shown that diets based on high-GI starches promote weight gain, visceral adiposity, and higher concentrations of lipogenic enzymes than do isoenergetic, macronutrientcontrolled, low-GI-starch diets. In a study of healthy pregnant women, a high-GI diet was associated with greater weight at term than was a nutrient-balanced, low-GI diet. In a study of diet and complications of type 1 diabetes, the GI of the overall diet was an independent predictor of waist circumference in men. These findings provide the scientific rationale to justify randomized, controlled, multicenter intervention studies comparing the effects of conventional and low-GI diets on weight control
In Werner and Ingbar's The Thyroid. Braverman E. 1996; Seventh Edition(Chapters 6 and 7)
Effect of diet and triiodothyronine on the activity of sn-glycerol-3-phosphate dehydrogenase and on the metabolism of glucose and pyruvate by adipose tissue of obese patients. Bray GA. J Clin Invest. 1969 Aug; 48(8):1413-22.
An aqueous extract of guarana (Paullinia cupana) decreases platelet thromboxane synthesis. Bydlowski SP, D'Amico EA, Chamone DA. Braz J Med Biol Res. 1991; 24(4):421-4. The effects of an aqueous extract of guarana (Paullinia cupana) on rabbit platelet aggregation and thromboxane synthesis were examined. The guarana extract (100 mg/ml) and fractions separated by TLC (origin and xanthines) decreased platelet aggregation (37, 27 and 31% of control values, respectively) and platelet thromboxane formation from [14C]-arachidonic acid (78, 70 and 50% of control values, respectively). The decreased thromboxane synthesis could be responsible, at least in part, for the antiaggregatory action of guarana
Alterations in basal and TRH-stimulated serum levels of thyrotropin, prolactin, and thyroid hormones in starved obese men. Carlson HE, Drenick EJ, Chopra IJ, et al. J Clin Endocrinol Metab. 1977 Oct; 45(4):707-13. To investigate further the alterations in pituitary-thyroid function seen during starvation, we have measured basal and TRH-stimulated serum levels of thyrotropin (TSH), prolactin (PRL), growth hormone, thyroxine (T4), triiodothyronine (T3), free T4, free T3, and reverse T3 during prolonged fasting in seven obese men. Fasting was associated with a significant decrease in serum (4, (3, and free T3, while there was an increase in serum reverse T3; these values tended to return toward pre-fast levels as the fast continued beyond 3 weeks. No significant changes were seen in basal serum TSH, PRL, growth hormone, or free T4. Although the TSH response to TRH was diminished during fasting, PRL, T4, and T3 responses were unchanged. In addition to transient alterations in the peripheral metabolism of T4, these findings suggest that alterations in the thyroid hormone binding capacity of serum carrier proteins may occur during fasting. The blunted TSH response to TRH despite reduction of serum T3 concentration suggests that subtle alterations in hypothalamic-pituitary function may also occur
Outcomes of pharmacological and surgical treatment for obesity. Cerulli J, Malone M. Pharmacoeconomics. 1998 Sep; 14(3):269-83. The purpose of this article is to review the data from pharmacotherapeutic and surgical intervention studies for the management of obesity. Clinical outcomes assessed include weight changes over time and the effects of weight loss on blood pressure, serum lipid profiles and blood glucose control. Quality of life and economic data have been incorporated where available. Double-blind, randomised controlled trials were used preferentially over shorter term open studies. The literature evaluation was based on a Medline search of published data between January 1990 and January 1998. Obesity affects 65 million adults in the US. Estimates based on 1990 data suggest that obesity and comorbid illness contributed to $US46 billion in direct costs and $US23 billion in indirect costs in the US. Obesity is a chronic condition which requires long term management. The risk of developing cardiovascular disease, hypertension, type 2 (non-insulin-dependent) diabetes mellitus, osteoarthritis, Pickwickian syndrome and cancer is increased in the obese population, resulting in excess morbidity and mortality. There are no long term prospective studies that have demonstrated that weight reduction in obese patients improves survival. However, on the basis of epidemiological data using the prevalence of disease and associated body mass index, it is generally accepted that weight reduction of 5 to 10% in obese patients is associated with significant health benefits. Current treatment modalities include diet and behaviour modification, exercise and, where indicated, pharmacological intervention. Surgical intervention is reserved for the clinically severe obese patient [body mass index (BMI) > 40 kg/m2]. Many studies have demonstrated weight loss and improved metabolic fitness over 6 to 12 months. Few studies have been conducted over a longer period. Limited data are available regarding reduced morbidity and mortality, improved quality of life and functional or employment status and even fewer have incorporated any economic assessments of the impact of medical or surgical intervention. Although prospective data have demonstrated reduced morbidity following surgical intervention, only retrospective data have demonstrated reduced mortality. Studies of new drugs and interventions under development should demonstrate long term safety and efficacy in terms of sustained weight loss and subsequent weight maintenance. Future studies should incorporate assessment of patient perceived satisfaction with weight loss, health status and quality-of-life evaluations and pharmacoeconomic data to aid clinicians in the decision-making process in terms of weight management of their obese patients
Opposite effects of linoleic acid and conjugated linoleic acid on human prostatic cancer in SCID mice. Cesano A, Visonneau S, Scimeca JA, et al. Anticancer Res. 1998 May; 18(3A):1429-34. The relationship between dietary fat intake (level and type) and cancer development is a matter of concern in Western society. The purpose of this study was to determine the effect of three different diets on the local growth and metastatic properties of DU-145 human prostatic carcinoma cells in severe combined immunodeficient (SCID) mice. Animals were fed a standard diet or diets supplemented with 1% LA or 1% CLA for 2 weeks prior to subcutaneous (s.c.) inoculation of DU-145 cells and throughout the study (total of 14 weeks). Mice receiving LA-supplemented diet displayed significantly higher body weight, lower food intake and increased local tumor load as compared to the other two groups of mice. Mice fed the CLA-supplemented diet displayed not only smaller local tumors than the regular diet-fed group, but also a drastic reduction in lung metastases. These results support the view that dietary polyunsaturated fatty acids may influence the prognosis of prostatic cancer patients, thus opening the possibility of new therapeutic options
Economic costs of obesity and inactivity. Colditz GA. Med Sci Sports Exerc. 1999 Nov; 31(11 Suppl):S663-S667. PURPOSE: The purpose of this paper is to assess the economic costs of inactivity (including those attributable to obesity). These costs represent one summary of the public health impact of increasingly sedentary populations in countries with established market economies. Components of the costs of illness include direct costs resulting from treatment of morbidity and indirect costs caused by lost productivity (work days lost) and forgone earnings caused by premature mortality. METHODS: We searched the Medline database for studies reporting the economic costs of obesity or inactivity, or cost of illness. From the identified references those relating to obesity or conditions attributable to obesity were reviewed. Chronic conditions related to inactivity include coronary heart disease (CHD), hypertension, Type II diabetes, colon cancer, depression and anxiety, osteoporotic hip fractures, and also obesity. Increasing adiposity, or obesity, is itself a direct cause of Type II diabetes, hypertension, CHD, gallbladder disease, osteoarthritis and cancer of the breast, colon, and endometrium. The most up-to-date estimates were extracted. To estimate the proportion of disease that could be prevented by eliminating inactivity or obesity we calculated the population-attributable risk percent. Prevalence based cost of illness for the U.S. is in 1995 dollars. RESULTS: The direct costs of lack of physical activity, defined conservatively as absence of leisure-time physical activity, are approximately 24 billion dollars or 2.4% of the U.S. health care expenditures. Direct costs for obesity defined as body mass index greater than 30, in 1995 dollars, total 70 billion dollars. These costs are independent of those resulting from lack of activity. CONCLUSION: Overall, the direct costs of inactivity and obesity account for some 9.4% of the national health care expenditures in the United States. Inactivity, with its wide range of health consequences, represents a major avoidable contribution to the costs of illness in the United States and other countries with modern lifestyles that have replaced physical labor with sedentary occupations and motorized transportation
Differential Diagnosis in Primary Care. Collins DR. 1981;
Genotoxic and mutagenic effects of guarana (Paullinia cupana) in prokaryotic organisms. da Fonseca CA, Leal J, Costa SS, et al. Mutat Res. 1994 May; 321(3):165-73. Aqueous extracts of Paullinia cupana (guarana), a species that belongs to the Sapindaceae family, were analyzed for the presence of genotoxic activities in bacterial cells. The extracts of guarana were genotoxic as assessed by lysogenic induction in Escherichia coli and they were also able to induce mutagenesis in Salmonella typhimurium. Addition of S9 microsomal fraction, catalase, superoxide dismutase or thiourea counteracted the genotoxic activity of guarana, suggesting that oxygen reactive species play an essential role in the genotoxicity of aqueous guarana extracts. The genotoxic activity in the extracts was related to the presence of a molecular complex formed by caffeine and a flavonoid (catechin or epicatechin) in the presence of potassium
Fat tissue: a steroid reservoir and site of steroid metabolism. Deslypere JP, Verdonck L, Vermeulen A. J Clin Endocrinol Metab. 1985 Sep; 61(3):564-70. Sex steroid concentrations and 17 beta-hydroxy-steroid dehydrogenase and aromatase activities were determined in fat tissue removed at surgery or, in order to allow comparisons in different sites, postmortem. Except for dehydroepiandrosterone (DHEA) sulfate (DHEAS), there existed a positive tissue/plasma gradient for all steroids studied (testosterone, androstenedione, DHEA, androstenediol, estrone, and estradiol), suggesting androgen uptake and estrogen synthesis in situ. Androgen concentrations did not vary according to site of origin of fat tissue, except that the DHEAS concentration was significantly lower in abdominal sc and omental fat than in breast, pericardial, or sc pubic fat. Tissue androgen concentrations were positively correlated with their plasma concentrations, but tissue and plasma estrogen concentrations were not correlated. All tissue steroid concentrations, with the exception of estradiol in men, decreased with age. Aromatase activity [androstenedione----estrone; mean maximum velocity, 7.4 +/- 3.7 (+/- SD) fmol estrone/mg protein . h] did not vary between sexes or with site of origin of fat tissue. 17 beta-Hydroxysteroid dehydrogenase activity (estradiol----estrone, mean maximum velocity 9.8 +/- 5.4 pmol/mg protein . h) was higher in fat from women than in that from men, higher in premenopausal than in postmenopausal women, and higher in omental than in sc fat. Its activity was noncompetitively inhibited in vitro by DHEA and DHEAS in near-physiological concentrations, and the enzyme activity was inversely correlated (P less than 0.001) with the tissue DHEA and DHEAS concentrations. We conclude that fat tissue is an important steroid hormone reservoir, that it is the site of active aromatase and 17 beta-hydroxysteroid dehydrogenase, and that tissue DHEA(S) may have a modulating effect on tissue estrogen production
Hyperinsulinemia as an independent risk factor for ischemic heart disease. Despres JP, Lamarche B, Mauriege P, et al. N Engl J Med. 1996 Apr 11; 334(15):952-7. BACKGROUND. Prospective studies suggest that hyperinsulinemia may be an important risk factor for ischemic heart disease. However, it has not been determined whether plasma insulin levels are independently related to ischemic heart disease after adjustment for other risk factors, including plasma lipoprotein levels. METHODS. In 1985 we collected blood samples from 2103 men from suburbs of Quebec City, Canada, who were 45 to 76 years of age and who did not have ischemic heart disease. A first ischemic event (angina pectoris, acute myocardial infarction or death from coronary heart disease) occurred in 114 men (case patients) between 1985 and 1990. Each case patient was matched for age, body-mass index, smoking habits, and alcohol consumption with a control selected from among the 1989 men who remained free of ischemic heart disease during follow-up. After excluding men with diabetes, we compared fasting plasma insulin and lipoprotein concentrations at base line in 91 case patients and 105 controls. RESULTS. Fasting insulin concentrations at base line were 18 percent higher in the case patients than in the controls (P<0.001). Logistic-regression analysis showed that the insulin concentration remained associated with ischemic heart disease (odds ratio for ischemic heart disease with each increase of 1 SD in the insulin concentration, 1.7; 95 percent confidence interval, 1.3 to 2.4) after adjustment for systolic blood pressure, use of medications, and family history of ischemic heart disease. Further adjustment by multivariate analysis for plasma triglyceride, apolipoprotein B, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol concentrations did not significantly diminish the association between the insulin concentration and the risk of ischemic heart disease (odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.3). CONCLUSIONS. High fasting insulin concentrations appear to be an independent predictor of ischemic heart disease in men
Treatment of obesity with a low protein calorically unrestricted diet. DOLE VP, SCHWARTZ IL, THAYSEN JH, et al. Am J Clin Nutr. 1954 Nov; 2(6):381-91.
Pharmacological activity of Guarana (Paullinia cupana Mart.) in laboratory animals. Espinola EB, Dias RF, Mattei R, et al. J Ethnopharmacol. 1997 Feb; 55(3):223-9. Mice that ingested a suspension of guarana (Paullinia cupana, Sapindaceae) in a dose of 0.3 mg/ml showed a significant increase in physical capacity when subjected to a stressful situation such as forced swimming after 100 and 200 days of treatment. Such an effect, however, was not obtained with a concentration of 3.0 mg/ml, nor with the ingestion of a suspension of ginseng 5.0 mg/ml, nor of a solution of caffeine 0.1 mg/ml. Guarana, both after a single (3.0 and 30 mg/kg) or chronic administrations (0.3 mg/ml), was able to partially reverse the amnesic effect of scopolamine as measured through a passive avoidance test in mice and rats, indicating a positive effect on memory acquisition. However, no effect was observed when an active avoidance task was used in rats, even after 20 days of guarana administration. There was also a tendency of rats treated with 0.3 mg/ml of guarana to better maintain the memory of a Lashley III maze path. The animals had the same average lifespan, indicating a low toxicity of guarana, even after 23 months of treatment
Experimental Biology Meeting. FASEB (Federation of American Societies for Experimental Biology). 2002;2002 Mar; 16(5):1. Abstr. 301.8
The Facts About Weight Loss Products and Programs 1992. FDA. 1992 DHHS Publ. No. 92-1189
Plasma amino acid levels and insulin secretion in obesity. Felig P, Marliss E, Cahill GF, Jr. N Engl J Med. 1969 Oct 9; 281(15):811-6.
A Manual of Laboratory and Diagnostic Tests. Fischbach F. 1996;
Overweight and obesity in the United States: prevalence and trends, 1960-1994. Flegal KM, Carroll MD, Kuczmarski RJ, et al. Int J Obes Relat Metab Disord. 1998 Jan; 22(1):39-47. OBJECTIVE: To describe the prevalence of, and trends in, overweight and obesity in the US population using standardized international definitions. DESIGN: Successive cross-sectional nationally representative surveys, including the National Health Examination Survey (NHES I; 1960-62) and the National Health and Nutrition Examination Surveys (NHANES I: 1971-1974; NHANES II: 1976-1980; NHANES III: 1988-94). Body mass index (BMI:kg/m2) was calculated from measured weight and height. Overweight and obesity were defined as follows: Overweight (BMI > or = 25.0); pre-obese (BMI 25.0-29.9), class I obesity (BMI 30.0-34.9), class II obesity (BMI 35.0-39.9), and class III obesity (BMI > or = 40.0). RESULTS: For men and women aged 20-74 y, the age-adjusted prevalence of BMI 25.0-29.9 showed little or no increase over time (NHES I: 30.5%, NHANES I: 32.0%, NHANES II: 31.5% and NHANES III: 32.0%) but the prevalence of obesity (BMI > or = 30.0) showed a large increase between NHANES II and NHANES III (NHES I: 12.8%; NHANES I, 14.1%; NHANES II, 14.5% and NHANES III, 22.5%). Trends were generally similar for all age, gender and race-ethnic groups. The crude prevalence of overweight and obesity (BMI >> 25.0) for age > or = 20 y was 59.4% for men, 50.7% for women and 54.9% overall. The prevalence of class III obesity (BMI > or = 40.0) exceeded 10% for non-Hispanic black women aged 40-59 y. CONCLUSIONS: Between 1976-80 and 1988-94, the prevalence of obesity (BMI > or= 30.0) increased markedly in the US. These findings are in agreement with trends seen elsewhere in the world. Use of standardized definitions facilitates international comparisons
Ultrastructure of B-cells of Langerhans islets in rats after the administration of L-leucine. Galabova R, Petkov P. Endocrinol Exp. 1976; 10(3):217-23. The results of studies with electron microscope supported the earlier biochemical findings on the stimulation of insulin secretion with the aid of L-leucine. The changes of the cell organelles of B-cells showed that both the synthesis and the release of insulin were activated, while the secretion by specific granules was unchanged. The stimulation of B-cells was accompanied by numerous membrane-like structures ("myelin-like figures") which were presumably formed from the endoplasmic reticulum
The effects of long-term administration of guarana on the cognition of normal, elderly volunteers. Galduroz JC, Carlini EA. Rev Paul Med. 1996 Jan; 114(1):1073-8. Paulinia cupana (guarana) is a Brazilian plant given great prestige in popular medicine, for example as being a potent stimulator of brain functions. The authors assessed the effects of the long-term administration of guarana on the cognition of normal, elderly volunteers. Forty-five volunteers were studied, with a random distribution in three experimental groups: placebo (n = 15), caffeine (n = 15), and guarana (n = 15), in a double-blind study. There were no significant cognitive alterations in these volunteers
Decreased pancreatic islet response to L-leucine in the spontaneously diabetic GK rat: enzymatic, metabolic and secretory data. Giroix MH, Saulnier C, Portha B. Diabetologia. 1999 Aug; 42(8):965-77. AIMS/HYPOTHESIS: Pancreatic islets from hereditarily non-insulin-dependent diabetic Goto-Kakizaki (GK) rats have a deficient insulin response not only to D-glucose but also to L-leucine. Our aim was to explain the cellular mechanism(s) underlying the beta-cell unresponsiveness to this amino acid. METHODS: Freshly collagenase isolated islets from GK rats and healthy Wistar control rats matched with them for sex and age were compared. Leucine uptake, metabolic fluxes and insulin secretory capacity were investigated on batch incubated-islets. Enzymatic activities were measured on sonicated islets. RESULTS: In GK rat islets, neither leucine transport nor leucine transaminase activity was disturbed. By contrast, 14CO2 production from either L-[U-14C]leucine or L-[1-14C]leucine was decreased. The L-[U-14C]leucine oxidation: L-[1-14C]leucine decarboxylation ratio was unaffected, indicating that the acetyl-CoA generated from leucine undergoes normal oxidation in the Krebs cycle. The leucine non-metabolizable analogue 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid induced insulin release and enhanced the secretory response to leucine as in controls, whereas leucine failed to amplify the response to the leucine analogue. Moreover, the potentiating action of L-glutamine on leucine-mediated insulin release was preserved. This coincided with normal glutamate dehydrogenase activity and L-[U-14C]glutamine oxidation. Finally, the secretory response to the leucine deamination product 2-ketoisocaproate was decreased, as was the 2-keto[1-14C]isocaproate oxidation. CONCLUSION/INTERPRETATION: In islet beta cells from GK rats, the defective secretory response to leucine cannot be ascribed to a deteriorated leucine-stimulated glutamate metabolism but rather to an impaired leucine catabolism. A reduced generation of acetyl-CoA from 2-ketoisocaproate, due to the defective oxidative decarboxylation of this keto-acid by the mitochondrial branched-chain 2-ketoacid dehydrogenase, is incriminated
Incidence of type II diabetes in Mexican Americans predicted by fasting insulin and glucose levels, obesity, and body-fat distribution. Haffner SM, Stern MP, Mitchell BD, et al. Diabetes. 1990 Mar; 39(3):283-8. Few data exist on predictors of non-insulin-dependent (type II) diabetes mellitus. We examined body mass index (BMI), ratio of subscapular-to-triceps skin fold (centrality index), and fasting glucose and insulin concentrations as predictors of decompensation to type II diabetes in Mexican Americans, a population at high risk for this disorder. Twenty-eight of 474 initially nondiabetic Mexican Americans developed type II diabetes after 8 yr of follow-up. Converters to diabetes were older and had higher BMIs, centrality indices, and fasting glucose and insulin concentrations than nonconverters. Subjects in the highest quartile of the insulin distribution had 6.6 times the risk of developing type II diabetes as subjects in the remaining three quartiles combined (95% confidence interval [CI] = 3.14-13.7). In multivariate analysis, fasting glucose (odds ratio [OR] = 5.80, 95% CI = 2.57-13.1) and insulin (OR = 3.12, 95% CI = 1.36-7.14) remained significantly related to conversion to diabetes. However, BMI and centrality index, which were significantly related to conversion in the univariate analysis, were no longer significant in the multivariate analysis once glucose and insulin concentrations were taken into consideration, suggesting that the effect of these variables may be mediated by insulin resistance. Nearly half of the incident cases developed in a subset of the population who were simultaneously in the highest quartile of both fasting insulin and glucose concentrations (population-attributable risk 44.2%). Our results support the insulin resistance/pancreatic exhaustion theory of type II diabetes
A twin study of weight loss and metabolic efficiency. Hainer V, Stunkard A, Kunesova M, et al. Int J Obes Relat Metab Disord. 2001 Apr; 25(4):533-7. OBJECTIVE: To assess the genetic contribution to determinants of therapeutic weight loss in obese female identical twins. DESIGN: Subjects were studied for 40 days on an inpatient unit in three phases: 7 baseline days; 28 days of weight reduction by a very low calorie diet (1.6 MJ per day); and 5 days after weight reduction. SUBJECTS: Fourteen pairs of premenopausal obese female identical twins (age: 39.0+/-1.7 y; body weight (BW): 93.9+/-21.2 kg; body mass index (BMI): 34.2+/-7.8 kg/m2). MEASUREMENTS:: Body composition by hydrodensitometry and resting metabolic rate by indirect calorimetry were assessed before and after weight loss. RESULTS:: There was great variability among pairs in loss of weight (5.9-12.4 kg) and body fat (3.1-12.4 kg). By contrast, the intraclass correlation (ICC) within twin pairs was 0.85, P<0.001 for weight and 0.88, P<0.001 for body fat. A measure of metabolic efficiency, calculated as the difference between 'estimated' and 'measured' energy deficit showed high intrapair correlation (ICC="0.77;" P<0.001). CONCLUSIONS: The high correlation in metabolic efficiency within twin pairs in response to therapeutic weight loss suggests a strong genetic contribution
Common Medical Diagnosis: An Algorithmic Approach. Healey PM. 1994;
Divergent trends in obesity and fat intake patterns: the American paradox. Heini AF, Weinsier RL. Am J Med. 1997 Mar; 102(3):259-64. PURPOSE: To compare recent changes in diet and physical activity with trends in body weight and obesity prevalence, using large survey studies representative of the US population. MATERIALS AND METHODS: Secular-trends survey studies were made from databases of NHANES II and III, USDA Nationwide Food Consumption Survey, Behavioral Risk Factor Survey System, and Calorie Control Council Report providing data on obesity prevalence, body mass index, calorie and fat intake, exercise-related physical activity, and consumption of low-calorie food extracted from surveys for the adult US population and specific subgroups. RESULTS: In the adult US population the prevalence of overweight rose from 25.4% from 1976 to 1980 to 33.3% from 1988 to 1991, a 31% increase. During the same period, average fat intake, adjusted for total calories, dropped from 41.0% to 36.6%, an 11% decrease. Average total daily calorie intake also tended to decrease, from 1,854 kcal to 1,785 kcal (-4%). Men and women had similar trends. Concurrently, there was a dramatic rise in the percentage of the US population consuming low-calorie products, from 19% of the population in 1978 to 76% in 1991. From 1986 to 1991 the prevalence of sedentary lifestyle represented almost 60% of the US population, with no change over time. CONCLUSIONS: Reduced fat and calorie intake and frequent use of low-calorie food products have been associated with a paradoxical increase in the prevalence of obesity. These diverging trends suggest that there has been a dramatic decrease in total physical activity related energy expenditure. Efforts to increase the average American's total exercise- and nonexercise-related physical activities may be essential for the prevention of obesity
Hyperinsulinemic obesity and carbohydrate addiction: the missing link is the carbohydrate frequency factor. Heller RF, Heller RF. Med Hypotheses. 1994 May; 42(5):307-12. It is proposed that chronic hyperinsulinemia is largely responsible for hunger, cravings and weight gain observed in many obese. This form of obesity can be treated by decreasing frequency of daily intake of carbohydrates to one well-balance meal each day and allowing for additional meals that are low in fat, low carbohydrates and high fiber. Animal experimentation and epidemiological evidence support the role of chronic hyperinsulinemia as a major factor in obesity and accounts for the frequent failures of diet and behavioral modification programs. Chronic hyperinsulinemia upsets metabolic balances and favors anabolic metabolism; fosters carbohydrate cravings; promotes insulin resistance which further promotes anabolic metabolism; and insulin resistance in turn exacerbates chronic hyperinsulinemia. This vicious cycle maintains excess weight and defeats diet and behavioral modification attempts to treat obesity. An eating program focused on reduction of chronic hyperinsulinemia coupled with appropriate exercise and behavior modification can successfully and permanently bring down cravings, hunger and body weight
EFFECTS OF PROLONGED FASTING ON SUBSEQUENT FOOD INTAKE IN OBESE HUMANS. HOLLIFIELD G, OWEN JA, Jr., LINDSAY RW, et al. South Med J. 1964 Sep; 57:1012-6.
Dietary fiber and weight regulation. Howarth NC, Saltzman E, Roberts SB. Nutr Rev. 2001 May; 59(5):129-39. The influence of dietary fiber on energy regulation remains controversial. This review summarizes published studies on the effects of dietary fiber on hunger, satiety, energy intake, and body composition in healthy individuals. Under conditions of fixed energy intake, the majority of studies indicate that an increase in either soluble or insoluble fiber intake increases postmeal satiety and decreases subsequent hunger. When energy intake is ad libitum, mean values for published studies indicate that consumption of an additional 14 g/day fiber for >2 days is associated with a 10% decrease in energy intake and body weight loss of 1.9 kg over 3.8 months. Furthermore, obese individuals may exhibit a greater suppression of energy intake and body weight loss (mean energy intake in all studies was reduced to 82% by higher fiber intake in overweight/obese people versus 94% in lean people; body weight loss was 2.4 kg versus 0.8 kg). These amounts are very similar to the mean changes in energy intake and body weight changes observed when dietary fat content is lowered from 38% to 24% of energy intake in controlled studies of nonobese and obese subjects. The observed changes in energy intake and body weight occur both when the fiber is from naturally high-fiber foods and when it is from a fiber supplement. In view of the fact that mean dietary fiber intake in the United States is currently only 15 g/day (i.e., approximately half the American Heart Association recommendation of 25-30 g/day), efforts to increase dietary fiber in individuals consuming <25 g/day may help to decrease the currently high national prevalence of obesity
Conjugated linoleic acid-enriched butter fat alters mammary gland morphogenesis and reduces cancer risk in rats. Ip C, Banni S, Angioni E, et al. J Nutr. 1999 Dec; 129(12):2135-42. Conjugated linoleic acid (CLA) is a potent cancer preventive agent in animal models. To date, all of the in vivo work with CLA has been done with a commercial free fatty acid preparation containing a mixture of c9,t11-, t10,c12- and c11,t13-isomers, although CLA in food is predominantly (80-90%) the c9,t11-isomer present in triacylglycerols. The objective of this study was to determine whether a high CLA butter fat has biological activities similar to those of the mixture of free fatty acid CLA isomers. The following four different endpoints were evaluated in rat mammary gland: 1) digitized image analysis of epithelial mass in mammary whole mount; 2) terminal end bud (TEB) density; 3) proliferative activity of TEB cells as determined by proliferating cell nuclear antigen immunohistochemistry; and 4) mammary cancer prevention bioassay in the methylnitrosourea model. It should be noted that TEB cells are the target cells for mammary chemical carcinogenesis. Feeding butter fat CLA to rats during the time of pubescent mammary gland development reduced mammary epithelial mass by 22%, decreased the size of the TEB population by 30%, suppressed the proliferation of TEB cells by 30% and inhibited mammary tumor yield by 53% (P < 0.05). Furthermore, all of the above variables responded with the same magnitude of change to both butter fat CLA and the mixture of CLA isomers at the level of CLA (0.8%) present in the diet. Interestingly, there appeared to be some selectivity in the uptake or incorporation of c9,t11-CLA over t10,c12-CLA in the tissues of rats given the mixture of CLA isomers. Rats consuming the CLA-enriched butter fat also consistently accumulated more total CLA in the mammary gland and other tissues (four- to sixfold increases) compared with those consuming free fatty acid CLA (threefold increases) at the same dietary level of intake. We hypothesize that the availability of vaccenic acid (t11-18:1) in butter fat may serve as the precursor for the endogenous synthesis of CLA via the Delta9-desaturase reaction. Further studies will be conducted to investigate other attributes of this novel dairy product
Conjugated linoleic acid inhibits proliferation and induces apoptosis of normal rat mammary epithelial cells in primary culture. Ip MM, Masso-Welch PA, Shoemaker SF, et al. Exp Cell Res. 1999 Jul 10; 250(1):22-34. The trace fatty acid conjugated linoleic acid (CLA) inhibits rat mammary carcinogenesis when fed prior to carcinogen during pubertal mammary gland development or during the promotion phase of carcinogenesis. The following studies were done to investigate possible mechanisms of these effects. Using a physiological model for growth and differentiation of normal rat mammary epithelial cell organoids (MEO) in primary culture, we found that CLA, but not linoleic acid (LA), inhibited growth of MEO and that this growth inhibition was mediated both by a reduction in DNA synthesis and a stimulation of apoptosis. The effects of CLA did not appear to be mediated by changes in epithelial protein kinase C (PKC) since neither total activity nor expression nor localization of PKC isoenzymes alpha, beta II, delta, epsilon, eta, or zeta were altered in the epithelium of CLA-fed rats. In contrast, PKCs delta, epsilon, and eta were specifically upregulated and associated with a lipid-like, but acetone-insoluble, fibrillar material found exclusively in adipocytes from CLA-fed rats. Taken together, these observations demonstrate that CLA can act directly to inhibit growth and induce apoptosis of normal MEO and may thus prevent breast cancer by its ability to reduce mammary epithelial density and to inhibit the outgrowth of initiated MEO. Moreover, the changes in mammary adipocyte PKC expression and lipid composition suggest that the adipose stroma may play an important in vivo role in mediating the ability of CLA to inhibit mammary carcinogenesis
Trial of mannoheptulose in man. Johnson BF, Wolff FW. Metabolism. 1970 May; 19(5):354-62.
Hyperinsulinemia cluster predicts the development of type 2 diabetes independently of family history of diabetes. Kekalainen P, Sarlund H, Pyorala K, et al. Diabetes Care. 1999 Jan; 22(1):86-92. OBJECTIVE: The aim of this prospective study was to determine risk factor clusters predicting type 2 diabetes in subjects with and without family history of diabetes by applying factor analyses. RESEARCH DESIGN AND METHODS: The study population consisted of 309 siblings of diabetic (DM+) or nondiabetic (DM-) probands. Risk factors, including lipids, lipoproteins, blood pressure, and glucose tolerance status, were measured at the baseline study and 8 years later. RESULTS: Siblings in the DM+ group had a significantly higher risk of diabetes (odds ratio [OR] = 3.25; P = 0.002) than siblings in the DM- group. Altogether, factor analyses revealed four significant factors in both the DM+ and DM- groups (the percentage of cumulative variance explained 62-66%). Of these, factor 1 (percentage of variance, 27-29%) was characterized by high loadings for BMI, hypertension, glucose area, insulin area (the highest loading), and triglycerides in both the DM+ and DM- groups; therefore, factor 1 can be interpreted as a hyperinsulinemia factor. Also, other factors were essentially similar in both groups. Hyperinsulinemia factor was similarly associated with the risk of developing diabetes in the DM+ group (OR = 4.33, 95% CI 2.29-8.19; P < 0.001) and the DM- group (OR = "4.22," 95% CI 2.02-8.81; P < 0.001) in logistic regression analyses. CONCLUSIONS: Our results indicate that a cluster of cardiovascular risk factors around hyperinsulinemia is an important predictor of diabetes in 8-year follow-up independent of family history of diabetes
Lower endogenous androgens predict central adiposity in men. Khaw KT, Barrett-Connor E. Ann Epidemiol. 1992 Sep; 2(5):675-82. Central adiposity, sometimes described as male pattern fat distribution, is adversely related to cardiovascular risk and mortality independent of other measures of obesity. In a cohort of 511 men aged 30 to 79 years in 1972 to 1974, levels of androstenedione, testosterone, and sex hormone-binding globulin measured at baseline were inversely related to subsequent central adiposity, estimated 12 years later using the waist-hip circumference ratio. The observed differences in waist-hip ratio between top and bottom tertiles of these hormones and sex hormone-binding globulin were similar to mean waist-hip ratio differences between men with stroke or ischemic heart disease and those without in another prospective study. These findings, consistent with studies suggesting that testosterone seems to mobilize the abdominal depot on males, suggest that "male pattern" fat distribution may be a misleading description for central adiposity, at least, in men. Degree of maleness as indicated by total androgen levels is, in fact, negatively associated with central adiposity. However, the role of sex hormone-binding globulin in regulating androgenic activity warrants further investigation
The relationship between aromatase activity and body fat distribution. Killinger DW, Perel E, Daniilescu D, et al. Steroids. 1987 Jul; 50(1-3):61-72. The metabolism of androstenedione (A) to estrone (E1) and 5 alpha-reduced androgens was studied in stromal cells derived from human adipose tissue from different body sites. The tissue was obtained from non-obese patients undergoing cosmetic liposuction or at the time of surgery for reduction mammoplasty. The conversion of A to E1 per 1x 10(6) cells was between 6- and 30-fold greater in the upper thigh, buttock, and flank than in the abdomen. These differences were present in primary culture and persisted to at least the third subculture. Estrogen formation in breast adipose tissue was similar to that found in cells from abdominal fat. The formation of 5 alpha-reduced metabolites (5 alpha-androstenedione, androsterone, and dihydrotestosterone) varied from patient to patient but was similar in cells from different body sites. These studies show that the regional distribution of fat may influence the metabolism of androgens in adipose tissue, with upper body fat tending to form a lower ratio of estrogens to 5 alpha-reduced androgens than lower body fat
Modulation of insulin signaling in human skeletal muscle in response to exercise. Kirwan JP, Jing M. Exerc Sport Sci Rev. 2002 Apr; 30(2):85-90. Exercise is widely recommended for the treatment of obesity, insulin resistance, and type II diabetes mellitus. Recent discoveries in the molecular and cellular regulation of insulin-mediated glucose metabolism in skeletal muscle have provided a deeper understanding of how exercise modulates insulin action
Enhanced conversion of androstenedione to estrogens in obese males. Kley HK, Deselaers T, Peerenboom H, et al. J Clin Endocrinol Metab. 1980 Nov; 51(5):1128-32. In normal and obese young males [90--120% and > 160% of ideal body weight (IBW); IBW = 100%], plasma concentrations of testosterone, androstenedione, estrone, and estradiol were measured. Metabolic clearance and production rates of androstenedione and the conversion ratios of androstenedione to testosterone, estrone, and estradiol were determined using the constant infusion technique. In the obese subjects, IBW was inversely correlated (P < 0.001) with plasma concentrations of androstenedione (r = "0.81)" and testosterone (r = "0.87)," while the levels of estrone (r = "0.92)" and estradiol (r = "0.95)" increased with IBW (P < 0.001). Thus, when normal and obese subjects were compared as groups, plasma androstenedione decreased form 1.24 +/- 0.13 to 0.93 +/- 0.15 ng/ml (mean +/- SD) and plasma testosterone decreased from 5.89 +/- 0.82 to 3.29 +/- 0.92 ng/ml (P < 0.001), while estrone increased from 28.2 +/- 3.4 to 60.0 +/- 9.4 pg/ml, and estradiol increased from 21.7 +/- 3.5 to 43.9 +/- 5.3 pg/ml. The testosterone to androstenedione and the estradiol to estrone ratios were not different in obesity, but changes in IBW were positively correlated (P < 0.001) with differences in the estrone to androstenedione (r = "0.93)" and estradiol to testosterone ratios (r = "0.93)," indicating that fat tissue may aromatize androgens, whereas reduction of 17-oxo-steroid appears to be of minor importance. As the MCR of androstenedione increased with IBW (from 2156 to 2636 liters/day P < 0.05) while plasma levels decreased, the apparent production rate of androstenedione was not influenced by the degree of obesity. The conversion of androstenedione to estrone (r = "0.89)" and of androstenedione to estradiol (r = "0.82)" was enhanced in obese subjects (P < 0.001). We suggest that enhanced aromatization of androstenedione due to an increased adipose tissue mass may account for the high plasma estrogen levels observed in obese men
Relationship of plasma sex hormones to different parameters of obesity in male subjects. Kley HK, Edelmann P, Kruskemper HL. Metabolism. 1980 Oct; 29(11):1041-5. Relationships between plasma sex hormones and different parameters of obesity (weight, ideal body weight [IBW], overweight, fat mass, and body surface) were investigated in 70 healthy nonobese and obese males, 20-40 yr of age and with a body weight of 85%-245% of IBW. Plasma sex hormones remained unaffected by weight up to approximately 160% of the IBW. Only in the massively obese subjects was plasma testosterone decreased to 40% of controls (from 6.2 to 2.5 ng/ml), whereas free testosterone remained almost constant. On the other hand, plasma estrone and estradiol exhibited significant increases in obese subjects, ranging from 31.5 +/- 52.3 +/- 5.8 pg/ml for estrone, and 25.4 +/- 5.4 increasing to 44.7 +/0 5.0 pg/ml for estradiol. Similarly, free estradiol was shown to significantly increase with obesity in men from 505 +/- 118 to 991 +/- 123 fg/ml (p < 0.001). The ratios of testosterone/androstenedione, as well as of estradiol/estrone, were not affected by obesity, suggesting that reduction of the 17-oxo-group of the steroids is not influenced by the amount of fat tissue. A significant (p < 0.001) correlation was found between IBW and estrone (r = "0.80)" and estradiol (r = "0.75)," as well as the ratios of estrone/androstenedione (r = "0.62)" and estradiol/testosterone (r = "0.86)." This is consistent in its evidence indicating that fat tissue may be able to aromatize androgens. In the obese subjects, there were significant correlations between plasma sex hormones (testosterone, estrone, estradiol, and free estradiol) and the parameters of obesity used. Among these, correlations were best with IBW, overweight, and fat mass (r = "0.74-0.89;" p < 0.001); body weight and body surface were less favorable
A genetic analysis of weight and overweight in 4-year-old twin pairs. Koeppen-Schomerus G, Wardle J, Plomin R. Int J Obes Relat Metab Disord. 2001 Jun; 25(6):838-44. OBJECTIVE: Although many twin and adoption studies document genetic influence on individual differences in weight, much less is known about genetic influences on overweight, about the genetic links between weight and overweight, or about the origins of weight and overweight in childhood, an age that might provide a good target for prevention of obesity. We tested the hypothesis that, in early childhood, overweight is as heritable as weight and that weight and overweight are linked genetically. DESIGN: Model-fitting analyses were used to compare monozygotic (MZ) and dizygotic (DZ) twins (same-sex and opposite-sex) for weight and overweight. SUBJECTS: The sample included 3636 4-y-old twins born in the UK in 1994. MEASUREMENTS: Heights and weights reported by parents were used to assess weight corrected for height, which yields results similar to body mass index (BMI) but corrects more completely for genetic effects on height. RESULTS: At 4 y of age, genetic factors contributed substantially both to individual differences in weight throughout the distribution and to the mean weight difference between overweight children and the rest of the population. Unlike results later in life, weight and overweight in 4-y-olds also suggest substantial shared family environmental influence. Results are similar for boys and girls. CONCLUSIONS: Overweight is the quantitative extreme of genetic and environmental factors responsible for normal variation in weight in childhood. Genes associated with overweight are likely to be associated with variation in weight throughout the distribution, as assumed by quantitative trait locus (QTL) theory. These findings linking weight and overweight in childhood have far-reaching implications for molecular genetic attempts to identify specific genes responsible for genetic influence, for investigating pathways between genes and behaviour, and for intervention and prevention
Mechanisms of insulin resistance in human obesity: evidence for receptor and postreceptor defects. Kolterman OG, Insel J, Saekow M, et al. J Clin Invest. 1980 Jun; 65(6):1272-84. To assess the mechanisms of the insulin resistance in human obesity, we have determined, using a modification of the euglycemic glucose clamp technique, the shape of the in vivo insulin-glucose disposal dose-response curves in 7 control and 13 obese human subjects. Each subject had at least three euglycemic studies performed at insulin infusion rates of 15, 40, 120, 240, or 1,200 mU/M2/min. The glucose disposal rate was decreased in all obese subjects compared with controls (101 +/- 16 vs. 186 +/- 16 mg/M2/min) during the 40 mU/M2/min insulin infusion. The mean dose-response curve for the obese subjects was displaced to the right, i.e., the half-maximally effective insulin concentration was 270 +/- 27 microU/ml for the obese compared with 130 +/- 10 microU/ml for controls. In nine of the obese subjects, the dose-response curves were shifted to the right, and maximal glucose disposal rates (at a maximally effective insulin concentration) were markedly decreased, indicating both a receptor and a postreceptor defect. On the other hand, four obese patients had right-shifted dose-response curves but reached normal maximal glucose disposal rates, consistent with decreased insulin receptors as the only abnormality. When the individual data were analyzed, it was found that the lease hyperinsulinemic, least insulin-resistant patients displayed only the receptor defect, whereas those with the greatest hyperinsulinemia exhibited the largest post-receptor defect, suggesting a continuous spectrum of defects as one advances from mild to severe insulin resistance. When insulin's ability to suppress hepatic glucose output was assessed, hyperinsulinemia produced total suppresssion in all subjects. The dose-response curve for the obese subjects was shifted to the right, indicating a defect in insulin receptors. Insulin binding to isolated adipocytes obtained from the obese subjects was decreased, and a highly significant inverse linear relationship was demonstrated between insulin binding and the serum insulin concentration required for halfmaximal stimulation of glucose disposal. In conclusion: (a) decreased cellular insulin receptors contribute to the insulin resistance associated with human obesity in all subjects; (b) in the least hyperinsulinemic, insulin-resistant patients, decreased insulin receptors are the sole defect, whereas in the more hyperinsulinemic, insulin-resistant patients, the insulin resistance is the result of a combination of receptor and postreceptor abnormalities; (c) all obese patients were insensitive to insulin's suppressive effects on hepatic glucose output; this was entirely the result of decreased insulin receptors; no postreceptor defect in this insulin effect was demonstrated
Obesity as a medical problem. Kopelman PG. Nature. 2000 Apr 6; 404(6778):635-43. Obesity is now so common within the world's population that it is beginning to replace undernutrition and infectious diseases as the most significant contributor to ill health. In particular, obesity is associated with diabetes mellitus, coronary heart disease, certain forms of cancer, and sleep-breathing disorders. Obesity is defined by a body-mass index (weight divided by square of the height) of 30 kg m(-2) or greater, but this does not take into account the morbidity and mortality associated with more modest degrees of overweight, nor the detrimental effect of intra-abdominal fat. The global epidemic of obesity results from a combination of genetic susceptibility, increased availability of high-energy foods and decreased requirement for physical activity in modern society. Obesity should no longer be regarded simply as a cosmetic problem affecting certain individuals, but an epidemic that threatens global well being
Insulin sensitivity and sodium excretion in normotensive offspring and hypertensive patients. Kopf D, Muhlen I, Kroning G, et al. Metabolism. 2001 Aug; 50(8):929-35. Insulin resistance and hyperinsulinemia have been suggested to precede and promote hypertension, possibly by impairing sodium balance. We examined insulin sensitivity and the influence of acute hyperinsulinemia on sodium excretion after acute sodium loading in hypertension-prone individuals. Insulin sensitivity and sodium excretion in response to a 1,000-mL isotonic saline bolus were examined in 24 strictly normotensive offspring of at least 1 hypertensive parent, 19 controls without a family history of hypertension, and 8 untreated, young hypertensive patients. After the saline bolus, urinary sodium excretion was measured at baseline and during a 2-hour euglycemic, hyperinsulinemic clamp, and insulin sensitivity was determined. Insulin, pressor hormones, and atrial natriuretic peptide (ANP), were measured by radioimmunoassay (RIA) or high-performance liquid chromatography (HPLC). Results are given as means +/- SEM. Offspring and controls were well matched in age (23.7 +/- 0.5; 24.6 +/- 0.5 years, respectively), blood pressure (113.0 +/- 2.9/68.5 +/- 1.9; 110.6 +/- 2.5/71.7 +/- 2.2 mm Hg, respectively), bone mass index (BMI), plasma glucose, and lipid parameters. Insulin sensitivity index did not significantly differ between offspring and controls (0.102 +/- 0.012; 0.112 +/- 0.018 micromol/min/kg/body weight [BW]/pmol, respectively), but was markedly reduced in hypertensives (0.045 +/- 0.006, P <.001). In response to sodium loading, natriuresis increased significantly (P <.05) in both offspring and controls to a similar extent, despite the presence of hyperinsulinemia, but failed to increase in hypertensives. In normotensive offspring of hypertensive patients who have not yet developed any features of the metabolic syndrome, insulin sensitivity is not impaired. Acute hyperinsulinemia impairs the ability to excrete an acute sodium load in hypertensive patients, but not in offspring of hypertensives with normal insulin sensitivity
Assessment of dietary and genetic factors influencing serum and adipose fatty acid composition in obese female identical twins. Kunesova M, Hainer V, Tvrzicka E, et al. Lipids. 2002 Jan; 37(1):27-32. Fourteen pairs of obese female monozygotic twins were recruited for a study of genetic influences on serum and adipose fatty acid (FA) composition. Following 1 wk of inpatient stabilization, fasting serum and adipose tissue obtained by surgical excision were analyzed by thin-layer and gas chromatography. Intrapair resemblances (IPR) for individual FA were assessed by Spearman rank correlation and by analysis of variance and were found in serum cholesteryl esters (CF), triglycerides (TG), and adipose TG. With two exceptions (CE linoleate and adipose eicosapentaenoate), these IPR were limited to the nonessential FA. Palmitate had significant IPR in four lipid fractions; in serum CE and adipose TG palmitate was strongly correlated with multiple measures of adiposity. In contrast to other lipid fractions, serum phosphatidylcholine (PC) FA had 12 [PR, of which 6 were essential FA including arachidonate (r = 0.76, P < 0.0005), eicosapentaenoate (r = "0.78," P < 0.0005), and docosahexaenoate (r = "0.86," P< 0.0001). The PC [PR could not be explained by analysis of preadmission 7-d food records. After dividing the pairs into two groups differing and nondiffering according to fat intake of individuals in the pair, there was no evidence of a gene-environment interaction between fat intake and FA composition. The IPR for nonessential FA indicate that there is active genetic control of either food choices or postabsorptive metabolic processing. The high level of IPR in the PC fraction in contrast to the other lipid fractions suggests strong genetic influence over selection of specific FA for this membrane fraction independent of diet
The responses of serum and adipose Fatty acids to a one-year weight reduction regimen in female obese monozygotic twins. Kunesova M, Phinney S, Hainer V, et al. Ann N Y Acad Sci. 2002 Jun; 967:311-23. We have reported strong intrapair resemblances (IPRs) in serum phosphatidylcholine (PC) fatty acid composition within adult monozygotic twins living apart. This study assessed the contribution of genetic factors to changes in serum and adipose tissue fatty acids resulting from weight loss and followed by a subsequent year of weight maintenance. Eleven pairs of female obese monozygotic twins (age: 38.9 +/- 1.8; BMI: 32.5 +/- 0.9) were recruited for the study. Fasting serum and adipose tissue were obtained after 1 week of inpatient stabilization, after 1 month of inpatient very-low-calorie diet (VLCD), and again after 1 year of outpatient weight maintenance. Fatty acids in serum lipid fractions and adipose tissue were quantitated by gas chromatography. Using multiple regression adjusted for age and initial value, IPRs were determined for the changes induced by VLCD and by the year of weight maintenance. There were few IPRs in nonessential fatty acids. By contrast, there were numerous IPRs for essential fatty acids (EFA), especially in the n-3 family across the VLCD. Following the maintenance year, however, frequent IPRs for nonessential fatty acids were seen, particularly in serum PC, and strong IPRs were seen for 18:3 n-3 and 20:5 n-3 across multiple fractions. These results infer the existence of strong genetic factors determining both the nonessential and EFA compositions of tissue lipids in humans independent of diet. Of particular note were the consistent IPRs for n-3 fatty acids despite dietary stress, indicating that the conservation and distribution of this EFA family are subject to considerable genetic variance in humans
D-Mannoketoheptose, a new sugar from the avocado. La Forge FB. J Biol Chem. 1916;(28):511-27.
Use of primary cultures of rat hepatocytes for the study of ageing and caloric restriction. Lambert AJ, Merry BJ. Exp Gerontol. 2000 Aug; 35(5):583-94. Primary cultures of hepatocytes are widely used to investigate liver function, but this technology has not been exploited fully in the study of ageing and caloric restriction (CR). Hepatocytes were isolated from adult and aged, fully fed, and calorie restricted male Sprague-Dawley rats and their viability and biochemical status assessed over 48h in primary culture. The in vivo differences in cellular protein and DNA content due to age and CR were maintained over the 48h experimental period. The results of this study confirm earlier reports that protein synthesis and degradation rates decline with age in liver tissue, and this decline is retarded by CR. Rates of protein synthesis and degradation in the first year of life were depressed in response to CR feeding and were only significantly higher than recorded for control animals during the second year of life. Cells from rats of both ages and diets maintained linear rates of extracellular protein synthesis, intracellular protein synthesis, protein degradation and albumin secretion between 24 and 48h in culture. These findings indicate that hepatocytes from CR rats did not respond adversely to the relatively rich culture medium and cells from CR animals did not immediately revert to the fully fed phenotype
Changes in food intake and meal patterns following injection of D-mannoheptulose in rats. Langhans W, Scharrer E. Behav Neural Biol. 1983 Jul; 38(2):269-86. Behavioral and metabolic effects of intraperitoneal D-mannoheptulose (MH) injections were investigated in rats fed a high carbohydrate (HC) or a high fat (HF) diet. Injection of 125 or 250 mg/kg body weight (body wt) MH did not affect food intake in HC rats. Injection of 400 mg/kg body wt MH inhibited feeding in HC rats by primarily reducing meal size. In contrast, none of the MH doses tested (125, 250, 400, 800 mg/kg body wt) affected food intake or meal patterns in HF rats. The hyperglycemia following MH injection (400 mg/kg body wt) was more pronounced in HC compared to HF rats. MH injection (400 mg/kg body wt) induced a strong taste aversion in HC rats, but had only weak aversive consequences in HF rats. The data throw some doubt on the hypothetical role of insulin in the production of satiety. In addition, the results suggest that a hedonic shift takes place following MH injection in HC rats. The strong dislike for the HC diet after MH injection might be triggered by the severe disturbance of glucose homeostasis and might contribute to the transient hypophagia in HC rats by primarily reducing meal size
Caloric restriction prevents age-associated accrual of oxidative damage to mouse skeletal muscle mitochondria. Lass A, Sohal BH, Weindruch R, et al. Free Radic Biol Med. 1998 Dec; 25(9):1089-97. The purpose of this study was to understand the nature of the causes underlying the senescence-related decline in skeletal muscle mass and performance. Protein and lipid oxidative damage to upper hindlimb skeletal muscle mitochondria was compared between mice fed ad libitum and those restricted to 40% fewer calories--a regimen that increases life span by approximately 30-40% and attenuates the senescence-associated decrement in skeletal muscle mass and function. Oxidative damage to mitochondrial proteins, measured as amounts of protein carbonyls and loss of protein sulfhydryl content, and to mitochondrial lipids, determined as concentration of thiobarbituric acid reactive substances, significantly increased with age in the ad libitum-fed (AL) C57BL/6 mice. The rate of superoxide anion radical generation by submitochondrial particles increased whereas the activities of antioxidative enzymes superoxide dismutase, catalase, and glutathione peroxidase in muscle homogenates remained unaltered with age in the AL group. In calorically-restricted (CR) mice there was no age-associated increase in mitochondrial protein or lipid oxidative damage, or in superoxide anion radical generation. Crossover studies, involving the transfer of 18- to 22-month-old mice fed on the AL regimen to the CR regimen, and vice versa, indicated that the mitochondrial oxidative damage could not be reversed by CR or induced by AL feeding within a time frame of 6 weeks. Results of this study indicate that mitochondria in skeletal muscles accumulate significant amounts of oxidative damage during aging. Although such damage is largely irreversible, it can be prevented by restriction of caloric intake
Gene expression profile of aging and its retardation by caloric restriction. Lee CK, Klopp RG, Weindruch R, et al. Science. 1999 Aug 27; 285(5432):1390-3. The gene expression profile of the aging process was analyzed in skeletal muscle of mice. Use of high-density oligonucleotide arrays representing 6347 genes revealed that aging resulted in a differential gene expression pattern indicative of a marked stress response and lower expression of metabolic and biosynthetic genes. Most alterations were either completely or partially prevented by caloric restriction, the only intervention known to retard aging in mammals. Transcriptional patterns of calorie-restricted animals suggest that caloric restriction retards the aging process by causing a metabolic shift toward increased protein turnover and decreased macromolecular damage
[Magnesium and glucose metabolism]. Lefebvre PJ, Paolisso G, Scheen AJ. Therapie. 1994 Jan; 49(1):1-7. The interrelationships between magnesium and carbohydrate metabolism have regained considerable interest over the last few years. Insulin secretion requires magnesium: magnesium deficiency results in impaired insulin secretion while magnesium replacement restores insulin secretion. Furthermore, experimental magnesium deficiency reduces the tissues sensitivity to insulin. Subclinical magnesium deficiency is common in diabetes. It results from both insufficient magnesium intakes and increase magnesium losses, particularly in the urine. In type 2, or non-insulin-dependent, diabetes mellitus, magnesium deficiency seems to be associated with insulin resistance. Furthermore, it may participate in the pathogenesis of diabetes complications and may contribute to the increased risk of sudden death associated with diabetes. Some studies suggest that magnesium deficiency may play a role in spontaneous abortion of diabetic women, in fetal malformations and in the pathogenesis of neonatal hypocalcemia of the infants of diabetic mothers. Administration of magnesium salts to patients with type 2 diabetes tend to reduce insulin resistance. Long-term studies are needed before recommending systematic magnesium supplementation to type 2 diabetic patients with subclinical magnesium deficiency
Effect of intravenous infusion of D-mannoheptulose on blood glucose and insulin levels in man. Lev-Ran A, Laor J, Vins M, et al. J Endocrinol. 1970 May; 47(1):137-8.
Absorption and subjective effects of caffeine from coffee, cola and capsules. Liguori A, Hughes JR, Grass JA. Pharmacol Biochem Behav. 1997 Nov; 58(3):721-6. Coffee is often perceived as producing greater pharmacological effects than cola. The present study compared the magnitude and rapidity of peak caffeine levels and subjective effects between coffee and cola. Thirteen users of both coffee and cola (mean daily caffeine consumption = 456 mg) ingested 400 mg caffeine via 12 oz unsweetened coffee, 24 oz sugar-free cola or 2 capsules in a random, double-blind, placebo-controlled, within-subjects design. Subjects provided a saliva sample and completed subjective effect scales 15 min before and 30, 60, 90, 120, 180 and 240 min after ingestion. Mean peak saliva caffeine levels did not differ between coffee (9.7 +/- 1.2 micrograms/ml) and cola (9.8 +/- 0.9 micrograms/ml) and appeared to be greater with these beverages than with the capsule (7.8 +/- 0.6 micrograms/ml; p = NS). Saliva caffeine levels peaked at similar times for coffee (42 +/- 5 min) and cola (39 +/- 5 min) but later for capsule (67 +/- 7 min; p = 0.004). There was no main effect of vehicle or interaction of vehicle and drug on magnitude of peak effect or time to peak increase on self-report scales. In summary, peak caffeine absorption, time to peak absorption, and subjective effects do not appear to be influenced by cola vs. coffee vehicle. Perceived differences in the effects of coffee vs. cola may be due to differences in dose, time of day, added sweetener, environmental setting or contingencies
The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. Ludwig DS. JAMA. 2002 May 8; 287(18):2414-23. The glycemic index was proposed in 1981 as an alternative system for classifying carbohydrate-containing food. Since then, several hundred scientific articles and numerous popular diet books have been published on the topic. However, the clinical significance of the glycemic index remains the subject of debate. The purpose of this review is to examine the physiological effects of the glycemic index and the relevance of these effects in preventing and treating obesity, diabetes, and cardiovascular disease
The stimulus-secretion coupling of amino acid-induced insulin release metabolic interaction of L-asparagine and L-leucine in pancreatic islets. Malaisse WJ, Malaisse-Lagae F, Sener A. Biochim Biophys Acta. 1984 Feb 14; 797(2):194-202. Because L-asparagine augments insulin release evoked by L-leucine, the metabolism of these two amino acids was investigated in rat pancreatic islets. L-Leucine inhibited the uptake and deamidation of L-asparagine, but failed to exert any obvious primary effect upon the further catabolism of aspartate derived from exogenous asparagine. L-Asparagine augmented the oxidation of L-leucine, an effect possibly attributable to activation of 2-ketoisocaproate dehydrogenase. The association of L-asparagine and L-leucine exerted a sparing action on the utilization of endogenous amino acids, so that the integrated rate of nutrients oxidation was virtually identical in the sole presence of L-leucine and simultaneous presence of L-asparagine and L-leucine, respectively. It is proposed that the enhancing action of L-asparagine upon insulin release evoked by L-leucine is attributable to an increased generation rate of cytosolic NADPH rather than any increase in nutrients oxidation
Androgen treatment of middle-aged, obese men: effects on metabolism, muscle and adipose tissues. Marin P, Krotkiewski M, Bjorntorp P. Eur J Med. 1992 Oct; 1(6):329-36. OBJECTIVES: This pilot investigation was conducted to explore the relationship between androgens and glucose tolerance in obese men and to select an optimal mode for androgen treatment. METHODS: For exploratory purposes, testosterone (T) or dihydrotestosterone (DHT) were given in different doses and preparations for different periods of time to obese, middle-aged men. The administration forms were selected in order to by-pass the liver. In the first two studies T was given as a single intramuscular injection of 250 or 500 mg and the results evaluated after 1 week. In two subsequent studies testosterone was administered in moderate doses either as oral T undecanoate or a T and DHT in preparations applied on the skin for transdermal absorption for 6 weeks and 3 months respectively. Before and after treatment the following examinations were performed: glucose tolerance tests with insulin determinations or euglycemic clamps at submaximal insulin levels. Anthropometric measurements including the waist/hip circumference ratio and estimations of body fat and lean body mass (from measurements of whole body potassium content) were performed. Plasma triglyceride and cholesterol concentrations, liver function tests and blood pressure were followed. Physical examination including the prostate was performed before and after study. Muscle function, glycogen synthase and morphology were examined in the 3-month study. RESULTS: Administration of T was followed by moderate increases of circulating T concentrations in all studies, except after injection of 500 mg, where large increases were seen. Follicle stimulating hormone and luteinizing hormone levels decreased consistently. Injection of 500 mg T resulted in a decreased glucose tolerance. In the other treatment groups, plasma insulin decreased or glucose disappearance rate increased in clamp measurements, suggesting improved insulin sensitivity. This was most pronounced in men with relative hypogonadism from the outset. In the study of 3 months duration, a decrease in the waist/hip ratio, without a change in body fat mass, was also seen. Plasma lipids, liver function tests and blood pressure did not change. Muscle strength, the fractional velocity of glycogen synthase as well as the percentage and diameter of type IIB fibres increased after T treatment. No adverse effects were seen. 17 -beta oestradiol concentrations were unaltered and DHT administration was less effective than T, suggesting that T rather than derivatives of this hormone was mainly responsible for the effects observed. CONCLUSION: The results suggest that T administration to middle-aged, obese man may have beneficial effects
Androgens and abdominal obesity. Marin P, Arver S. Baillieres Clin Endocrinol Metab. 1998 Oct; 12(3):441-51. Central or visceral obesity is recognized as a main risk factor for cardiovascular disease and type 2 diabetes mellitus. The co-existence of visceral obesity, increased blood lipid levels, hypertension and impaired glucose tolerance defines the metabolic syndrome that today is widely recognized as one of the prime factors behind cardiovascular morbidity and mortality. Endocrine disorders such as insulinoma, hypothyroidism and hypercortisolism are known to cause obesity. However, it is only hypercortisolism that is associated with increased abdominal fat accumulation. Recently, new findings have shed light on subtle endocrinopathies that are prevalent in individuals presenting with the metabolic syndrome. Such derangements are of borderline character and often fall within the normal reference range. Intervention studies demonstrate that correction of relative hypogonadism in men with visceral obesity and other manifestations of the metabolic syndrome seem to decrease the abdominal fat mass and reverse the glucose intolerance, as well as lipoprotein abnormalities in the serum. Further analysis of the underlying mechanism has also disclosed a regulatory role for testosterone in counteracting visceral fat accumulation. Longitudinal epidemiological data demonstrates that relatively low testosterone levels are a risk factor for development of visceral obesity. The primary event that triggers the initial development of visceral obesity is not known, but it seems plausible that increased activity in the hypothalamus-pituitary-adrenal axis can be of major importance
Guarana (Paullinia cupana): toxic behavioral effects in laboratory animals and antioxidants activity in vitro. Mattei R, Dias RF, Espinola EB, et al. J Ethnopharmacol. 1998 Mar; 60(2):111-6. The effects on toxic and behavioral levels of guarana (Paullinia cupana) were assessed in rats and mice subsequent to acute and chronic administrations and were compared to those produced by Ginseng (Panax ginseng). Experimental parameters included tests for antioxidant capacity in vitro and measured in vivo, toxicological screening, progress in weight, motor activity, death rate, and histopathological examination of the viscera. Guarana showed an antioxidant effect because, even at low concentrations (1.2 microg/ml), it inhibited the process of lipid peroxidation. In high doses of 1000-2000 mg/kg (i.p. and p.o.) it did not induce significant alterations in parameters for toxicological screening. No effects on motor activity were observed, neither did guarana alter the hypnotic effect of pentobarbital. Ginseng (250-1000 mg/kg i.p.), however, elicited reductions in motor activity, eyelid ptosis and bristling fur. Consumption of liquids containing guarana or ginseng and progress in weight of the animals remained at levels similar to the controls, even after prolonged administration. The percentage mortality was equivalent in control and in treated groups. The |