Substituting dietary saturated fat with polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity

Aims/hypothesis: British dietary recommendations are to decrease total fat intake to less than 30 % of daily energy intake and saturated fat to less than 10 %. In practice, it is difficult for people to make these changes. It may be easier to encourage people to switch from a diet rich in saturated fatty acids to one rich in polyunsaturated fatty acids. Methods: A total of 17 subjects – six people with Type II (non-insulin-dependent) diabetes mellitus, six non-obese and five obese people without diabetes – were randomised to spend two 5-week periods on a diet rich in saturated or in polyunsaturated fatty acids, in a crossover design. At the start of the study and after each dietary period, we assessed abdominal fat distribution using magnetic resonance imaging, insulin sensitivity using hyperinsulinaemic-euglycaemic clamps and fasting lipid parameters. Results: Dietary compliance, assessed by weekly 3-day dietary records and measurement of biochemical markers, was good. Energy and fat intake appeared to be reduced on the diet rich in polyunsaturated fatty acids although body weights did not change. Insulin sensitivity and plasma low density lipoprotein cholesterol concentrations improved with the diet rich in polyunsaturated fatty acids compared with the diet rich in saturated fatty acids. There was also a decrease in abdominal subcutaneous fat area. Conclusion/interpretation: If this result is confirmed in longer-term studies, this dietary manipulation would be more readily achieved by the general population than the current recommendations and could result in considerable improvement in insulin sensitivity, reducing the risk of developing Type II diabetes. [Diabetologia (2002) 45: 369–377] Received: 3 August 2001 and in revised form: 26 November 2001     

The influence of dietary fat on insulin resistance

Dietary fat has been implicated in the development of insulin resistance in both animals and humans. Most, although not all, studies suggest that higher levels of total fat in the diet result in greater whole-body insulin resistance. Although, in practice, obesity may complicate the relationship between fat intake and insulin resistance, clinical trials demonstrate that high levels of dietary fat can impair insulin sensitivity independent of body weight changes. In addition, it appears that different types of fat have different effects on insulin action. Saturated and certain monounsaturated fats have been implicated in causing insulin resistance, whereas polyunsaturated and omega-3 fatty acids largely do not appear to have adverse effects on insulin action. Given the importance of insulin resistance in the development of diabetes and heart disease, establishing appropriate levels of fat in the diet is an important clinical goal.     

Polyunsaturated fatty acids may impair blood glucose control in type 2 diabetic patients.

Fifteen patients with Type 2 diabetes were given two diets rich in either saturated fat or polyunsaturated fat in alternate order over two consecutive 3-week periods on a metabolic ward. Both diets contained the same amount of fat, protein, carbohydrates, dietary fibre, and cholesterol. The proportions of saturated, monounsaturated and polyunsaturated fatty acids in the saturated fat diet were 16, 10, and 5%-energy and in the polyunsaturated fat diet (PUFA) 9, 10, and 12%-energy. The PUFA diet contained a high proportion of n-3 fatty acids. Metabolic control improved significantly in both dietary periods, due to both qualitative dietary changes and a negative energy balance. The serum lipoprotein concentrations decreased on both diets but the serum lipids were significantly lower after the PUFA diet (serum triglycerides -20%, p = 0.001; serum cholesterol -5%, p = 0.03; VLDL-triglycerides -29%, p less than 0.001; and VLDL-cholesterol -31%, p = 0.001) than after the saturated fat diet. Average blood glucose concentrations during the third week were significantly higher fasting (+15%, p less than 0.01), and during the day at 1100 h (+18%, p less than 0.001) and 1500 h (+17%, p = 0.002) on PUFA than on the saturated fat diet. Significantly higher blood glucose levels were also recorded with a standard breakfast, while the sum of the insulin values was lower (-19%, p = 0.01). HbA1c did not differ significantly between the two dietary periods.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dietary fatty acids and insulin resistance

High-fat diets have been associated with insulin resistance, a risk factor for both Type II diabetes and heart disease. The effect of dietary fat on insulin varies depending on the type of fatty acid consumed. Saturated fatty acids have been consistently associated with insulin resistance. On the other hand, medium and long-chain fatty acid intakes are associated with insulin sensitivity, as are high intakes of ϕ3 fatty acids. Trans fatty acids appear to potentiate insulin secretion, at least in the short-term, to a greater degree than cis fatty acids. This may reflect chronic alterations in insulin sensitivity, although this remains to be tested. In summary, although it must be emphasized that all diets high in fat cause insulin resistance relative to high-carbohydrate diets, it appears that dietary saturated, short-chain and ϕ6 fatty acids have the most deleterious effects on insulin action.     

Adults with type 1 diabetes eat a high-fat atherogenic diet that is associated with coronary artery calcium

Aims/hypothesis  Coronary heart disease is the leading cause of mortality among people with type 1 diabetes. Diet is an important lifestyle factor that relates to risk of CHD. The aim of this study was to examine how diet and adherence to dietary guidelines differ between adults with and without type 1 diabetes, and their correlation with CHD risk factors and coronary artery calcium (CAC). Methods  The study involved 571 people with type 1 diabetes and 696 controls, aged 19 to 56 years, who were asymptomatic for CHD. CAC was measured by electron-beam computed tomography. Results  Compared with the controls, adults with type 1 diabetes reported a diet higher in fat, saturated fat and protein but lower in carbohydrates. Fewer than half of those with type 1 diabetes met dietary guidelines for fat and carbohydrate intake, and only 16% restricted saturated fat to less than 10% of daily energy intake. Adults with type 1 diabetes were significantly less likely to meet dietary guidelines than controls. Fat and saturated fat intakes were positively correlated, but carbohydrate intake was negatively correlated with CHD risk factors and HbA_1c. A high-fat diet and higher intake of protein were associated with greater odds of CAC, while higher carbohydrate intake was associated with reduced odds of CAC. Conclusions/interpretation  Adults with type 1 diabetes reported consuming higher than recommended levels of fat and saturated fat. High fat intake was associated with increased CHD risk factors, worse glycaemic control and CAC. An atherogenic diet may contribute to the risk of CHD in adults with type 1 diabetes.     

Diet and syndrome X

Syndrome X is a cluster of abnormalities, associated with resistance to insulin-mediated glucose uptake, that increases risk of coronary heart disease. Increased carbohydrate intake (with reciprocal decreased fat intake) within the boundaries of menus that can be followed in the free-living state have not been shown to decrease insulin resistance directly, by enhancing insulin sensitivity, or indirectly, by producing and maintaining weight loss. Moreover, such diets accentuate the metabolic abnormalities that constitute Syndrome X. Substitution of monounsaturated fat, polyunsaturated fat, or both for saturated fat results in the same reduction in low-density lipoprotein-cholesterol concentration as seen in diets low in fat and high in carbohydrates but without any untoward effects on the various manifestations of Syndrome X. Consequently, substituting unsaturated fat for saturated fat, without increasing intake of dietary protein or carbohydrate, may be useful for patients with hypercholesterolemia, Syndrome X, or both.     

Dietary fat and heart failure: moving from lipotoxicity to lipoprotection

There is growing evidence suggesting that dietary fat intake affects the development and progression of heart failure. Studies in rodents show that in the absence of obesity, replacing refined carbohydrate with fat can attenuate or prevent ventricular expansion and contractile dysfunction in response to hypertension, infarction, or genetic cardiomyopathy. Relatively low intake of n-3 polyunsaturated fatty acids from marine sources alters cardiac membrane phospholipid fatty acid composition, decreases the onset of new heart failure, and slows the progression of established heart failure. This effect is associated with decreased inflammation and improved resistance to mitochondrial permeability transition. High intake of saturated, monounsaturated, or n-6 polyunsaturated fatty acids has also shown beneficial effects in rodent studies. The underlying mechanisms are complex, and a more thorough understanding is needed of the effects on cardiac phospholipids, lipid metabolites, and metabolic flux in the normal and failing heart. In summary, manipulation of dietary fat intake shows promise in the prevention and treatment of heart failure. Clinical studies generally support high intake of n-3 polyunsaturated fatty acids from marine sources to prevent and treat heart failure. Additional clinical and animals studies are needed to determine the optimal diet in terms of saturated, monounsaturated, and n-6 polyunsaturated fatty acids intake for this vulnerable patient population.     

Evidence-based guideline of the German Nutrition Society: carbohydrate intake and prevention of nutrition-related diseases

The relative contribution of nutrition-related chronic diseases to the total disease burden of the society and the health care costs has risen continuously over the last decades. Thus, there is an urgent necessity to better exploit the potential of dietary prevention of diseases. Carbohydrates play a major role in human nutrition - next to fat, carbohydrates are the second biggest group of energy-yielding nutrients. Obesity, type 2 diabetes mellitus, dyslipoproteinaemia, hypertension, metabolic syndrome, coronary heart disease and cancer are wide-spread diseases, in which carbohydrates could have a pathophysiologic relevance. Correspondingly, modification of carbohydrate intake could have a preventive potential. In the present evidence-based guideline of the German Nutrition Society, the potential role of carbohydrates in the primary prevention of the named diseases was judged systematically. The major findings were: a high carbohydrate intake at the expense of total fat and saturated fatty acids reduces the concentrations of total, LDL and HDL cholesterol. A high carbohydrate consumption at the expense of polyunsaturated fatty acids increases total and LDL cholesterol, but reduces HDL cholesterol. Regardless of the type of fat being replaced, a high carbohydrate intake promotes an increase in the triglyceride concentration. Furthermore, a high consumption of sugar-sweetened beverages increases the risk of obesity and type 2 diabetes mellitus, whereas a high dietary fibre intake, mainly from whole-grain products, reduces the risk of obesity, type 2 diabetes mellitus, dyslipoproteinaemia, cardiovascular disease and colorectal cancer at varying evidence levels. The practical consequences for current dietary recommendations are presented.     

The effect of dietary fat content and composition on adipocyte lipids in normal and diabetic states

Cellular insulin resistance is a common feature of the diabetic and obese state. To determine the effect of dietary fat and the insulin resistant state of diabetes on adipose tissue composition, control and streptozotocin-induced diabetic rats were fed four diets differing in fat content (10 percent w/w or 20% w/w) and polyunsaturated to saturated fatty acid (P/S) ratios (0.2 or 2.0) for 6 weeks. At 3 weeks diabetes was induced in half the animals in each diet group. Increasing the fat content and P/S ratio of the diet increased the content of polyunsaturated fatty acids and decreased the contents of monounsaturated and omega-3 fatty acids. The higher level of C-18:2(6) and the lower levels of C20:4(6) and monounsaturated fatty acids observed in diabetic animals is consistent with altered desaturase enzyme activity. Diet and diabetes induced compositional changes in essential and non-essential fatty acids in the adipose tissue may alter the total body pools of available fatty acids for the synthesis of other lipids such as phospholipids.     

膳食营养与慢性肾脏病

膳食结构是影响慢性非传染性疾病的重要危险因素之一。慢性肾脏病(CKD)是心血管疾病、住院及死亡事件的独立危险因素,发病率进行性增加。不同的膳食营养成分摄入及膳食模式对CKD产生不同程度的影响。多数研究表明,摄食较多的盐、动物性蛋白质、高能量但营养价值低的碳水化合物、饱和脂肪酸、含糖饮料等与CKD发生及进展风险增加相关,而植物性蛋白质、含较多谷物纤维的碳水化合物、多不饱和脂肪酸、膳食纤维、水果和蔬菜等与CKD发生及进展风险降低相关。此外,坚持得舒食、地中海饮食或素食与CKD发生及进展风险降低相关,而西方饮食和中国传统南方饮食模式与CKD发生及进展风险增加相关。因此,如何更好的选择膳食营养成分摄入及膳食模式,促进肾脏健康、预防CKD的发生及发展,有待进一步提高认识。     

Dietary influence on the insulin function in the epididymal fat cell of the Wistar rat. I. Effect of type of fat

For at least 3-4 weeks, young male Wistar rats were fed semisynthetic diets containing sunflowerseed oil, palm oil, olive oil, linseed oil, cocoa butter and coconut oil as dietary fat. The type of dietary fat had little effect on body weight, epididymal fat pad weight and on the diameter of fat cells isolated from the epididymal fat pads, but the rats fed the linseed oil-containing diet had a lower epididymal fat pad weight. The fatty acid composition of the triacylglycerol fractions of the fat pads correlated well with those of the dietary fats. The correlations with the fatty acid composition of the phospholipids of the fat pads were less pronounced. High responses to insulin in the epididymal fat cells were obtained with sunflowerseed oil, linseed oil and olive oil, whereas low responses were found for cocoa butter, palm oil or coconut oil. Rather than the amount of polyunsaturated fatty acids or the ratio of polyunsaturated to saturated fatty acids, the amount of saturated fatty acids with 12, 14 or 16 carbon atoms appeared to be the most important parameter in determining the maximal insulin response. A negative correlation was found between the amount of saturated fatty acids in the diet and the extent of insulin response. The modulating effects of the dietary type of fat on the response to insulin cannot be fully explained by changes in the number of insulin receptors on the fat cell surface as determined by insulin binding but must, at least partially, be ascribed to postreceptor effects.     

Dietary fats and diabetes mellitus: is there a good fat?

As knowledge of the fatty acid functions has increased, so has the complexity of making dietary fat recommendations to people with type 2 diabetes. Oleic acid seems to offer a slight advantage over linoleic acid in reducing plasma glucose, insulin levels, total cholesterol, low-density lipoproteins (LDL_s), and triglycerides, but may also have atherogenic properties through another mechanism. A diet containing a higher proportion of polyunsaturated fatty acids (PUFA_s) may require a concomitant increase in antioxidant intake because PUFA_s oxidize easily and are then converted to oxidized LDL, which is more atherogenic. In addition to raising total and LDL cholesterol, long chain saturated free fatty acids may interact with plasma glucose to increase insulin secretion. Omega-3 fatty acids decrease triglycerides and reduce the risk of fatal cardiac arrhythmias. Glycemic control does not appear to be adversely affected by omega-3 fatty acids at amounts of up to 3 g/d.     

Ernährungstherapie des Typ-2-Diabetes

During the last decade dietary treatment of type 2 diabetes has become more important than ever before because there has been a further increase in the mean body mass index of patients suffering from this disease. In addition to the classical low fat diet, novel diets have been established for dietary treatment of type 2 diabetes, such as carbohydrate-reduced diets or the traditional Mediterranean diet. However, the scientific evidence supporting very low carbohydrate diets is still limited with respect to long-term effects and is not sufficient to replace the current recommendation for a low fat diet. At present, patients with type 2 diabetes have various options for dietary treatment which are equally improving metabolic control. Common components of these diets include moderate energy restriction, high fibre intake, low glycemic index (GI) and modification of fat intake including a reduction of saturated fats and trans-fatty acids. Patients with nephropathy should restrict and modify protein intake.     

Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU study

Aims/hypothesis. The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders. Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans. Methods. The KANWU study included 162 healthy subjects chosen at random to receive a controlled, isoenergetic diet for 3 months containing either a high proportion of saturated (SAFA diet) or monounsaturated (MUFA diet) fatty acids. Within each group there was a second assignment at random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo. Results. Insulin sensitivity was significantly impaired on the saturated fatty acid diet (-10 %, p = 0.03) but did not change on the monounsaturated fatty acid diet ( + 2 %, NS) (p = 0.05 for difference between diets). Insulin secretion was not affected. The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion. The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median (37E %). Here, insulin sensitivity was 12.5 % lower and 8.8 % higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively (p = 0.03). Low density lipoprotein cholesterol (LDL) increased on the saturated fatty acid diet ( + 4.1 %, p < 0.01) but decreased on the monounsaturated fatty acid diet (MUFA) (–5.2, p < 0.001), whereas lipoprotein (a) [Lp(a)] increased on a monounsaturated fatty acid diet by 12 % (p < 0.001). Conclusions/interpretation. A change of the proportions of dietary fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty acid, improves insulin sensitivity but has no effect on insulin secretion. A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake ( > 37E %). [Diabetologia (2001) 44: 312–319] Received: 21 August 2000 and in revised form: 8 November 2000     

The -514 C/T polymorphism in the hepatic lipase gene promoter is associated with insulin sensitivity in a healthy young population

Impaired insulin action has been associated with diabetes, dyslipidemia and atherosclerotic vascular disease. The expression of insulin resistance results from the interaction of environmental and genetic factors. Human hepatic lipase (HL) is a lipolytic enzyme that plays a role in the metabolism of several lipoproteins, while insulin up-regulates the activity of HL via insulin-responsive elements in the HL promoter. We have examined the influence of -514 C/T polymorphism in the hepatic lipase gene promoter on insulin sensitivity in 59 healthy young subjects (30 males and 29 females). The volunteers were subjected to three dietary periods, each lasting four weeks. During the first period all subjects consumed a saturated fat (SFA)-enriched diet with 38% as fat (20% SFA, 12% monounsaturated fatty acids (MUFA) and 6% polyunsaturated fatty acids (PUFA)). In the second and third dietary periods, a randomized crossover design was used, consisting of a low fat, high carbohydrate diet (CHO diet) (< 10% SFA, 12% MUFA and 6% PUFA) and a high-MUFA, or Mediterranean diet, with < 10% SFA, 22% MUFA and 6% PUFA. We determined the in vivo insulin resistance using the insulin suppression test with somatostatin. Steady-state plasma glucose (SSPG) concentrations (a measure of insulin sensitivity) were significantly higher in men carriers of the -514T allele after the consumption of the SFA diet than after the CHO diet and the Mediterranean diet. This effect was not observed in women. Moreover, there were no significant differences in insulin sensitivity after the three diets in men and women with the CC genotype. In summary, our results show an improvement in insulin sensitivity in men with the -514T allele of the HL promoter polymorphism, when MUFA and carbohydrates are consumed instead of SFA fat.     

UKPDS 18: Estimated Dietary Intake in Type 2 Diabetic Patients Randomly Allocated to Diet,Sulphonylurea or Insulin Therapy

Self-reported dietary intake was estimated from 3-day prospective food diaries completed by Type 2 diabetic patients in the UK Prospective Diabetes Study. All patients had received individual dietary advice and had been randomly allocated to diet, sulphonylurea or insulin therapy 3 months after diagnosis. A total of 132 patients (120 white Caucasian, 12 Asian) stratified for gender, obesity and allocated therapy with mean age 55 years (SD 8), body mass index 28 kg m⁻² (SD 4), and with a diabetes duration of 3 to 6 years were selected at random from 5 of 23 clinical centres. Patients reported a similar proportion of their energy intake as carbohydrate (43 %) to the general population and had not increased to the recommended 50–55 %. Their protein intake (21 %) was higher than the advised 10–15 %. Estimated energy intake from fat (37 %) was close to that recommended for diabetic patients (30–35%) and was lower than that reported for the UK population (40 %). The estimated polyunsaturated/saturated fat intake ratio (0.48) was higher than that reported for the UK population (0.35) compared with the recommended 1.0. Mean fibre intake at 22 g day⁻¹ was less than the recommended 30 g day⁻¹. The 8 male Asian patients took a higher proportion of their dietary intake as fat (46 % vs 37 %) and lower as protein (14 % vs 21 %) than the male white Caucasian patients. No significant differences were seen in estimated nutrient constituents between patients allocated to diet, sulphonylurea or insulin therapy as part of the UK Prospective Diabetes Study and followed for mean 4.2 years (SD1.6). This suggests that dietary factors will not confound UK Prospective Diabetes Study treatment related analyses.     

Effects of High Monounsaturated and Polyunsaturated Fat Diets on Plasma Lipoproteins and Lipid Peroxidation in Type 2 Diabetes Mellitus

Increased free radical peroxidation of lipoproteins may contribute to the excess atherosclerosis in Type 2 diabetes mellitus and may be aggravated by increasing polyunsaturate intake. Increasing intake of monounsaturates might have similar hypolipidaemic effects while avoiding this problem. Therefore the effects of high monounsaturated and polyunsaturated fat diets on plasma lipoproteins and lipid peroxidation were compared, against each other and a relatively high saturated fat baseline diet, in 13 men with Type 2 diabetes and 12 healthy controls, randomized in crossover fashion to each diet. There were no differences in plasma lipoproteins between the monounsaturated and polyunsaturated fat diets in the diabetic and control groups separately, but when both groups were combined, high density lipoprotein cholesterol was higher on the monounsaturated fat diet (p = 0.04). Plasma lipid peroxidation was similar on the monounsaturated and polyunsaturated fat diets in both groups, but all indices of plasma lipid peroxidation in the diabetic group and lipid peroxides in the controls were significantly lower on these diets compared to the baseline diet. Both high monounsaturated and polyunsaturated fat diets increase hepatic metabolism of low density lipoprotein and shorten its circulating half-life and both may reduce lipid peroxidation, compared to high saturated fat diets, by this mechanism. On high polyunsaturated fat diets, this effect may offset any increased susceptibility of polyunsaturate enriched low density lipoprotein to peroxidation.     

What dietary modification best improves insulin sensitivity and why?

Insulin resistance (IR) has been proposed as the strongest single predictor for incident type 2 diabetes and is mainly caused by adiposity as a result of chronic excessive energy intake. Loss of body weight and fat mass improve insulin sensitivity. However, independent of energy intake and changes in body weight/composition, dietary content and specific metabolic effects of certain nutrients may play significant additional roles in influencing IR. These effects are mainly relatively modest, with modulation of IR and diabetes risk within the range of 10–30%, but could be of major relevance on a population level. Examples include dietary concepts and patterns such as the traditional Mediterranean diet; the isoenergetic modulation of the composition of types of fatty acids in the diet; low‐carbohydrate–high‐protein diets; the quality of carbohydrate‐rich foods, which includes the concepts of glycaemic index (GI) and glycaemic load; and, not necessarily related to the GI concept, specific metabolic effects of high‐fibre diets, with relevant differences between the type of fibre consumed. Effects of further selected foods (e.g. coffee, tea and nuts) and micronutrients (e.g. magnesium, selenium and zinc) on the modulation of IR have been reviewed elsewhere. This study focuses on changes in IR by isoenergetic modulation of the main macronutrients (fat, carbohydrates including dietary fibre, and dietary protein), with discussion of novel concepts and the potential interplay of food components in the current dietary concepts.     

Limited impact of lifestyle education in patients with Type 2 diabetes mellitus and microalbuminuria: results from a randomized intervention study.

AIMS: To assess the effect of intensified education on lifestyle (diet, exercise and smoking) as part of an intensified multifactorial intervention over a 4-year period in patients with Type 2 diabetes mellitus with microalbuminuria. METHODS: Patients, aged 45-65 years, were randomly assigned either to an intensive group focusing on change of behaviour as well as polypharmacological treatment (n = 80) or to a control group receiving conventional treatment (n = 80). Diet intervention focused on dietary fat and carbohydrate. Food intake was estimated by dietary history interviews and nutrients were calculated from food tables. Exercise and smoking habits were evaluated by interviews. RESULTS: Mean follow-up was 3.8 (SD 0.3) years. The decrease in total fat intake (% of energy intake) was larger in the intensive group as compared to the control group (41.2 (6.2) to 34.2 (6.0) vs. 41.9 (6.5) to 38.3 (6.4)%, P = 0,0001). The decrease in saturated fatty acids (% of total fat intake) was from 47 (4) to 44 (6)% with intensive therapy vs. 45 (5) to 46 (5)%, P = 0.001 and the increase in polyunsaturated fatty acids was from 14 (4) to 18 (6) vs. 16 (5) to 14 (4)%, P < 0.0001. Also the increase in carbohydrate was larger with intensive therapy. However, changes in exercise and smoking habits did not differ between groups. CONCLUSION: Despite the many resources invested in behaviour modification in this study, only modest changes were obtained in nutrient intake. Further studies are required to determine the best method of inducing long-lasting changes in behaviour in Type 2 diabetic patients.     

A Mediterranean and a high-carbohydrate diet improve glucose metabolism in healthy young persons

Aims/hypothesis: Insulin resistance usually precedes the diagnosis of Type II (non-insulin-dependent) diabetes mellitus. However, in most patients, the clinical expression of the disease could be prevented by dietary and lifestyle changes. We investigated the effects of a diet enriched in monounsaturated fatty acids (Mediterranean diet) and a low fat, high-carbohydrate diet on in vivo and in vitro glucose metabolism in 59 young subjects (30 men and 29 women). Methods: We carried out an intervention dietary study with a saturated fat phase and two randomized-crossover dietary periods: a high-carbohydrate diet and a Mediterranean diet for 28 days each. We analysed the plasma lipoproteins fractions, free fatty acids, insulin sensitivity and glucose uptake in isolated monocytes at the end of the three dietary periods. Results: In comparison to the saturated fat diet, the CHO and Mediterranean diets induced a decrease of LDL-cholesterol (p < 0.001) and HDL-cholesterol (p < 0.001). Steady-state plasma glucose decreased (p = 0.023) and basal and insulin-stimulated 2-deoxiglucose uptake in peripheral monocytes increased in both diets (CHO and Mediterranean), (p = 0.007) indicating an improvement in insulin sensitivity. Fasting free fatty acids plasma values were correlated positively with steady state plasma glucose (r = 0.45; p < 0.0001). In addition, there was an inverse correlation between the mean glucose of the steady state plasma glucose period and logarithmic values of basal (r = –0.34; p = 0.003) and insulin stimulated glucose uptake in monocytes (r = –0.32; p = 0.006). Conclusion/interpretation: Isocaloric substitution of carbohydrates and monounsaturated fatty acids for saturated fatty acids improved insulin sensitivity in vivo and in vitro, with an increase in glucose disposal. Both diets are an adequate alternatives for improving glucose metabolism in healthy young men and women. [Diabetologia (2001) 44: 2038–2043] Received: 19 February 2001 and in revised form: 9 July 2001