Dietary carbohydrates and insulin action in humans

The metabolic syndrome represents a vicious cycle whereby insulin resistance leads to compensatory hyperinsulinaemia, which maintains normal plasma glucose but may exacerbate insulin resistance. Excess insulin secretion may eventually reduce beta-cell function due to amyloid deposition, leading to raised blood glucose and further deterioration of beta-cell function and insulin sensitivity via glucose toxicity. Reducing postprandial glucose and insulin responses may be a way to interrupt this process, but there is disagreement about the dietary approach to achieve this. Glucose and insulin responses are determined primarily by the amount of carbohydrate consumed and its rate of absorption. Slowly absorbed, low glycaemic-index (GI) foods are associated with increased HDL cholesterol and reduced risk of type 2 diabetes. There is some evidence that low-GI foods improve insulin sensitivity in humans, although studies using established techniques (glucose clamp or frequently sampled intravenous glucose tolerance test) have not been done. Low carbohydrate diets have been suggested to be beneficial in the treatment of the metabolic syndrome because of reduced postprandial insulin. However, they may increase fasting glucose and impair oral glucose tolerance--effects which define carbohydrate intolerance. The effects of low carbohydrate diets on insulin sensitivity depend on what is used to replace the dietary carbohydrate, and the nature of the subjects studied. Dietary carbohydrates may affect insulin action, at least in part, via alterations in plasma free fatty acids. In normal subjects a high-carbohydrate/low-GI breakfast meal reduced free fatty acids by reducing the undershoot of plasma glucose, whereas low-carbohydrate breakfasts increased postprandial free fatty acids. It is unknown if these effects occur in insulin-resistant or diabetic subjects. Thus further work needs to be done before a firm conclusion can be drawn as to the optimal amount and type of dietary carbohydrate for the treatment of the metabolic syndrome.     

Dietary fat, insulin sensitivity and the metabolic syndrome

Insulin resistance is the pathogenetic link underlying the different metabolic abnormalities clustering in the metabolic syndrome. It can be induced by different environmental factors, including dietary habits. Consumption of energy-dense/high fat diets is strongly and positively associated with overweight that, in turn, deteriorates insulin sensitivity, particularly when the excess of body fat is located in abdominal region. Nevertheless the link between fat intake and overweight is not limited to the high-energy content of fatty foods; the ability to oxidize dietary fat is impaired in some individuals genetically predisposed to obesity. Insulin sensitivity is also affected by the quality of dietary fat, independently of its effects on body weight. Epidemiological evidence and intervention studies clearly show that in humans saturated fat significantly worsen insulin-resistance, while monounsaturated and polyunsaturated fatty acids improve it through modifications in the composition of cell membranes which reflect at least in part dietary fat composition. A recent multicenter study (KANWU) has shown that shifting from a diet rich in saturated fatty acids to one rich in monounsaturated fat improves insulin sensitivity in healthy people while a moderate alpha-3 fatty acids supplementation does not affect insulin sensitivity. There are also other features of the metabolic syndrome that are influenced by different types of fat, particularly blood pressure and plasma lipid levels. Most studies show that alpha-3 fatty acids reduce blood pressure in hypertensive but not in normotensive subjects while shifting from saturated to monounsaturated fat intake reduces diastolic blood pressure. In relation to lipid abnormalities alpha-3 fatty acids reduce plasma triglyceride levels but in parallel, increase LDL cholesterol. Substitution of unsaturated fat for saturated fat not only reduces LDL cholesterol but contributes also to reduce plasma triglycerides in insulin resistant individuals. In conclusion, there is evidence available in humans indicating that dietary fat quality influences insulin sensitivity and associated metabolic abnormalities. Therefore, prevention of the metabolic syndrome has to be targeted: (1) to correct overweight by reducing the energy density of the habitual diet (i.e., fat intake) and (2) to improve insulin sensitivity and associated metabolic abnormalities through a reduction of dietary saturated fat, partially replaced, when appropriate, by monounsaturated and polyunsaturated fats.     

Dietary fat intake and insulin resistance in black and white children

OBJECTIVE: The purpose of this study was to determine whether dietary fat intake above current Acceptable Macronutrient Distribution Range (AMDR) guidelines was associated with greater insulin resistance in black and white children. RESEARCH METHODS AND PROCEDURES: We studied 142 healthy children (n = 81 whites, n = 61 blacks), 6.5 to 14 years old. Dietary composition was determined by repeated 24-hour dietary recall, body composition by DXA, visceral fat by computed tomography, and insulin sensitivity (SI) and acute insulin response to glucose (AIRg) by frequently sampled intravenous glucose tolerance test. Subjects were categorized by ethnicity (white/black) and dietary fat intake (above-AMDR/within-AMDR guidelines), and differences were analyzed by 2 x 2 analysis of covariance, adjusting for covariates. RESULTS: After adjusting for total body fat, gender, and Tanner stage, subjects consuming dietary fat above AMDR intake guidelines had lower SI and higher AIRg. This effect was specific to black children (32% lower SI and 62% higher AIRg in above-AMDR compared with within-AMDR blacks) and was not seen in whites. DISCUSSION: In black, but not white, children, those with dietary fat intake above current AMDR guidelines had lower SI and higher AIRg than those who met AMDR guidelines. These findings support current AMDR guidelines for dietary fat in black children and adolescents. The mechanism(s) underlying the ethnic differences in the relationship between dietary fat intake and SI in children require further investigation.     

Dietary fat saturation affects hepatocyte insulin binding and glucose metabolism in BHE rats

The influence of feeding 6% hydrogenated coconut oil, corn oil or menhaden oil on hepatocyte insulin binding, receptor number and glucose use was studied. Hepatocytes isolated from rats fed menhaden oil had a significantly greater affinity for insulin than hepatocytes from rats fed hydrogenated coconut oil. Glucose use was not influenced by diet; uniformly labeled glucose was metabolized to CO2 or to lipid similarly in cells isolated from rats fed the three oils. Thus, dietary fat type in a low fat diet influenced events at the plasma membrane without influencing intracellular events.     

Dietary fat

For the past two decades, epidemiologists have observed lower risks of lung, breast, prostate, colon, and other cancers in populations that frequently consume fruits and vegetables. Numerous phytoestrogens have been shown to be anticarcinogenic under experimental conditions and may account for at least part of the cancer‐prevention effects of fruit and vegetable consumption. These plant constituents include isoflavonoids, coumestans, lignans, phytosterols, and flavonoids. DietSys, the nutrient analysis program associated with the National Cancer Institute Health Habits and History Questionnaire (HHHQ), and other nationally available nutrient analysis databases do not fully assess these constituents. Therefore, we modified DietSys to include these components in foods on the basis of published values. In addition, as part of an epidemiological study of prostate cancer, we modified the food‐frequency component of the HHHQ to include the main foods contributing to phytoestrogen intake. Although there are limitations to the consistency and quality of many of the values because they were gathered from a variety of sources, our approach should provide a useful first tool for assessing the epidemiological association between phytoestrogen consumption and cancer risk. Furthermore, this work has already facilitated the identification of the major dietary contributors with phytoestrogen activity and prioritized future laboratory analyses of specific foods toward the development of a more complete and accurate database.     

Dietary fat and menstrual-cycle effects on the erythrocyte ghost insulin receptor in premenopausal women

The effect of high- and low-fat diets with different levels of fatty acid unsaturation on insulin receptors of erythrocyte ghosts was studied during different phases of the menstrual cycle in 31 healthy premenopausal women. Subjects were divided into two groups and consumed controlled diets containing 39% fat with a ratio of polyunsaturated to saturated fatty acids (P:S) of either 0.30 or 1.00 for four menstrual cycles. They were switched to 19% fat at the same P:S for another four cycles. Fasting blood samples were collected during the follicular and luteal phases. Insulin receptors were measured from right-side-out ghosts. Insulin binding was significantly lower due to fewer receptors when subjects were fed the low-fat, high-carbohydrate diet compared with the high-fat, low-carbohydrate diet. There was no significant effect of level of unsaturation or time of menstrual cycle on insulin binding. Thus, insulin receptors on erythrocytes respond to dietary lipids.     

Dietary guar gum effects on postprandial blood glucose, insulin and hydroxyproline in humans

Meals (425 kcal) containing various doses of guar gum (0, 2.5, 7.5 or 12.5 g) were ingested by nine healthy male subjects after a 12-h fast. The rise in blood glucose was higher after the control meal without guar gum than after the guar gum-containing meals, which all gave a similar rise in glucose. In contrast, increased doses of guar gum led to a greater reduction in the postprandial rise in insulin. The postprandial increase in serum hydroxyproline, an amino acid added to all meals, was decreased in a similar manner by all of the guar gum doses. Gastric emptying was measured after the control meal without guar gum and the meal containing 12.5 g of guar gum by monitoring 51Cr, which was added to the meals. Guar gum was found to reduce the variation between individuals, as well as the initial rate of gastric emptying, which correlated with changes in both serum hydroxyproline (rs = 0.93, P less than 0.01) and blood glucose (rs = 0.83, P less than 0.01). The effectiveness of guar gum in reducing postprandial response was lost after heating and homogenization for canning. A threshold in the reduction in rise of glucose or hydroxyproline was reached with the lowest dose (2.5 g) of viscous guar gum; larger doses had no additional effects. The reduced absorption seems to be an effect of a slower gastric emptying rate.     

Dietary fat and mammary carcinogenesis

Evidence that dietary fat has an influence on carcinogenesis comes from both epidemiological data and experiments with animals. The experimental studies have indicated that dietary fat acts primarily as a promoter of carcinogenesis and that the effect depends on the type as well as the amount of fat in the diet. Vegetable oils containing polyunsaturated fatty acids of the linoleic acid family (n‐6) have been shown to enhance mammary tumorigenesis, but a fish oil containing polyunsaturated fatty acids of the linolenic acid family (n‐3) had an inhibitory effect at higher levels of intake. These and other findings suggest that the effect may be related to prostaglandins or other biologically active products of polyunsaturated fatty acids. Epidemiological data show a positive correlation between dietary fat and mortality from cancer at various sites, and this is supported by results of animal experiments in the case of colon cancer and pancreatic cancer as well as breast cancer. In the epidemiological data, cancer mortality shows strong positive correlations with total dietary fat and with animal fat, but not with fat derived from plants. Fats and oils used as spreads, cooking fats, and salad oils are the main source of fat in the American diet. Other major sources are meats and dairy products. Fat intake could probably be reduced substantially without serious deleterious effects, and this might help to decrease the risk of developing certain types of cancer.

(Nutr Cancer 6, 254–259, 1985)     

Dietary fat and tumor metastasis

Evidence from several types of studies indicates a relationship between fat intake and occurrence of malignant tumors at specific sites. When rodents are fed high-fat diets, the incidence of mammary tumors sharply increases and latency of tumor appearance is greatly diminished, as compared with the same parameters in animals fed low levels of fat. Despite advances in surgical technique and the development of aggressive therapies for the treatment of primary cancers, most deaths in humans with cancer are caused by metastasis. Accordingly, we have reviewed the process of metastasis and have focused on the question of whether dietary fat can play a role. Metastasis is a complex, multistep, progressive process, and dietary fats may affect specific events such as implantation, survival, and proliferation of tumors. Finally, we discuss possible mechanisms by which dietary fat can modulate metastasis. Available data lead us to stress the importance of assessment of metastasis in studies of the effects of dietary fat on tumorigenesis.     

Dietary fat and natural-killer-cell activity

An intervention trial designed to lower the amount of fat in the diet was conducted to test the effect of reduced fat consumption (LF diet) on activity of natural killer (NK) cells in humans. Of 26 men enrolled initially, 17 successfully completed the intervention and lowered their fat intake to less than 30% of calories as fat. Data were analyzed in two ways. The paired t test showed a marked increase in NK-cell activity from baseline to the end of the LF-diet intervention (t = 4.77, p = 0.0002). Results of a general linear model showed an effect of lowering total dietary fat on increased NK-cell activity (approximately 0.53% increase for each absolute percent of calories as fat, p = 0.14) for all men and a highly significant effect in a subset of men who ate greater than 25% of calories as fat at baseline (approximately 1.22% increase, p = 0.009). These results were obtained after changes in total caloric intake, weight, exercise, and other fat-related covariates were accounted for.     

Dietary fat and mammary carcinogenesis

Evidence that dietary fat has an influence on carcinogenesis comes from both epidemiological data and experiments with animals. The experimental studies have indicated that dietary fat acts primarily as a promoter of carcinogenesis and that the effect depends on the type as well as the amount of fat in the diet. Vegetable oils containing polyunsaturated fatty acids of the linoleic acid family (n-6) have been shown to enhance mammary tumorigenesis, but a fish oil containing polyunsaturated fatty acids of the linolenic acid family (n-3) had an inhibitory effect at higher levels of intake. These and other findings suggest that the effect may be related to prostaglandins or other biologically active products of polyunsaturated fatty acids. Epidemiological data show a positive correlation between dietary fat and mortality from cancer at various sites, and this is supported by results of animal experiments in the case of colon cancer and pancreatic cancer as well as breast cancer. In the epidemiological data, cancer mortality shows strong positive correlations with total dietary fat and with animal fat, but not with fat derived from plants. Fats and oils used as spreads, cooking fats, and salad oils are the main source of fat in the American diet. Other major sources are meats and dairy products. Fat intake could probably be reduced substantially without serious deleterious effects, and this might help to decrease the risk of developing certain types of cancer.     

Dietary fat and physical performance

Although the relationship between dietary carbohydrate and physical performance is well described, there is much controversy about the relationship between dietary fat and physical performance. Recently, several studies have tried to clarify this relationship. Here the effects of acute fat on metabolism and performance will be discussed, as well as the effects of short-term and long-term high-fat diets.     

Dietary fat and N-nitrosation in the rat

1. Groups of four conventional (CV) rats ate natural or purified diets either with or without 100 g fat/kg and drank 0.235 M-sodium nitrate. The fats tested were butterfat, coconut oil, olive oil, maize oil and safflower oil. 2. Decreased urinary excretion of N-nitrosoproline (NPRO) was observed in rats fed on fat-supplemented diets compared with those fed on low-fat diets, with butterfat having the greatest effect of the fats tested. 3. Reduced excretion of NPRO was not the result of inhibition of the intragastric N-nitrosation reaction or absorption of nitrosamine from the gastrointestinal tract. 4. The availability of nitrite in aqueous solution was decreased by the fat diets but the effect was similar in all the fats tested. 5. Nitrate reductase activity was present in the forestomach contents of CV rats at pH greater than 4 and was apparently inhibited by feeding a fat diet. No nitrate reductase activity was detected in stomach contents of germ-free rats. 6. Nitrate reductase activity in stomach and small intestinal tissue was not altered by feeding a fat diet. 7. It was concluded that nitrate reductase activity in stomach contents was of microbial origin and the decreased urinary excretion of NPRO on feeding the fat diets was mainly due to the inhibition of nitrate reductase activity in stomach contents.     

Dietary saturated fat intake is inversely associated with bone density in humans: analysis of NHANES III

Mounting evidence indicates that the amount and type of fat in the diet can have important effects on bone health. Most of this evidence is derived from animal studies. Of the few human studies that have been conducted, relatively small numbers of subjects and/or primarily female subjects were included. The present study assessed the relation of dietary fat to hip bone mineral density (BMD) in men and women using NHANES III data (n = 14,850). Multivariate models using SAS-callable SUDAAN were used to adjust for the sampling scheme. Models were adjusted for age, sex, weight, height, race, total energy and calcium intakes, smoking, and weight-bearing exercise. Data from women were further adjusted for use of hormone replacement therapy. Including dietary protein, vitamin C, and beta-carotene in the model did not influence the outcome. Analysis of covariance was used to generate mean BMD by quintile of total and saturated fat intake for 4 sex/age groups. Saturated fat intake was negatively associated with BMD at several hip sites. The greatest effects were seen among men < 50 y old (linear trend P = 0.004 for the femoral neck). For the femoral neck, adjusted mean BMD was 4.3% less among men with the highest compared with the lowest quintile of saturated fat intake (BMD, 95% CI: highest quintile: 0.922 g/cm2, 0.909-0.935; lowest quintile: 0.963 g/cm2, 95% CI: 0.950-0.976). These data indicate that BMD is negatively associated with saturated fat intake, and that men may be particularly vulnerable to these effects.