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Dietary and lifestyle interventions in the management of the metabolic syndrome: present status and future perspective


Objective: To review the mechanisms underlying the metabolic syndrome, or syndrome X, in humans, and to delineate dietary and environmental strategies for its prevention.

Design: Review of selected papers of the literature.

Results: Hyperinsulinemia and insulin resistance play a key role in the development of the metabolic syndrome. Strategies aimed at reducing insulin resistance may be effective in improving the metabolic syndrome. They include low saturated fat intake, consumption of low-glycemic-index foods, physical exercise and prevention of obesity.

Conclusions: Future research, in particular the genetic basis of the metabolic syndrome and the interorgan interactions responsible for insulin resistance, is needed to improve therapeutic strategies for the metabolic syndrome.


Impaired glucose tolerance or diabetes mellitus, dyslipidemia (high triglyceride levels, high LDL cholesterol, low HDL cholesterol), high blood pressure and overweight are often present in more than 50% of the US population. Together they constitute what has been called the syndrome X or metabolic syndrome (Reaven, 1991). Hyperuricemia, high blood fibrinogen levels and low plasminogen activator inhibitor 1 are additional features of this syndrome. It is highly prevalent in affluent societies, and confers a high risk of cardiovascular morbidity and mortality in affected individuals. It therefore constitutes a major public health issue.

Although the pathogenesis of this syndrome is not fully elucidated, there is strong evidence that insulin resistance and the ensuing hyperinsulinemia play a major role in several of its metabolic hallmarks (Reaven et al, 1996; Figure 1). Insulin resistance may obviously play a major role in the development of impaired glucose tolerance or diabetes mellitus (DeFronzo, 1988). Hyperinsulinemia may contribute to dyslipidemia by increasing hepatic free fatty acid reesterification and VLDL triglyceride secretion (Parks & Hellerstein, 2000). Hyperinsulinemia may simultaneously stimulate de novo formation and reesterification of fatty acids in the adipose tissue, thus increasing adipose tissue triglycerides, which constitute the major source of circulating fatty acids.

Figure 1

Relationship between insulin resistance and individual features of the metabolic syndrome.

Increased plasma free fatty acids are generally observed in dyslipidemic patients. Such plasma fatty acid levels have been widely documented as an important factor contributing to the development of insulin resistance. Potential mechanisms of fatty acids-induced insulin resistance will be briefly discussed below. Low HDL cholesterol concentrations are also associated with insulin resistance, although the mechanisms remain unknown.

Recent data indicate that insulin resistance differentially effects the hepatic glucose-producing pathways (gluconeogenesis) and glycerophosphate production (glyceroneogenesis), and lipogenic pathways (Shimomura et al, 2000). Thus, impaired suppression of glucose production concomitant with an increased hepatic glucose uptake and de novo lipogenesis may be a hallmark of insulin resistance. Moreover, there is also evidence that hyperinsulinemia contributes to increase blood pressure by stimulating kidney sodium reabsorption and by activating the sympathetic nervous system (DeFronzo, 1991; Figure 1).

Factors involved in the development of insulin resistance

Several conditions are clearly associated with a decrease in insulin sensitivity. There is a positive correlation between body fat mass and fasting or postprandial insulin concentrations, and whole body insulin sensitivity (defined as insulin-mediated glucose disposal) is significantly decreased in most obese individuals (Tappy et al, 1991). Abdominal obesity is more specifically associated with insulin resistance (Bjorntorp & Rosmond, 2000).

  • Low physical activity—there is ample evidence that insulin sensitivity increases in proportion with aerobic capacity and that individuals with a low level of physical activity have a lower insulin-mediated glucose disposal and a higher cardiovascular risk (Ravussin & Gautier, 1999). In healthy sedentary individuals, insulin actions are enhanced by physical training (Borghouts & Keizer, 2000).

  • Genetic factors—there is a considerable interindividual variation in insulin sensitivity amongst healthy individuals, even when body weight and the level of physical activity are taken into consideration. Some authors consider that approximately 25% of the ‘normal’ population has insulin resistance (Reaven, 1999). Genetic factors are likely to be involved since variations in insulin sensitivity represent a familial trait (Sakul et al, 1997).

  • Dietary factors—diets providing high amounts of simple carbohydrates and/or fructose (Hollenbeck, 1993) are associated with insulin resistance, and low plasma HDL cholesterol. In contrast, diets providing high amounts of complex carbohydrates and fiber are associated with increased insulin sensitivity (Riccardi & Rivellese, 1991, 2000). High-saturated-fat diets are also associated with insulin resistance in both human and animal models (Marshall et al, 1997; Vessby et al, 2001).

All three conditions are tightly linked with the development of obesity. Genetic factors are likely to account for a substantial portion of body fat mass. Low physical activity and diets containing a high proportion of energy as fat are clearly associated with excess body weight. In turn, obesity is a central feature of the metabolic syndrome and is significantly associated with insulin resistance.

Mechanisms of insulin resistance: the fatty acid hypothesis

Insulin transduction signals are highly complex mechanisms, which are only partly elucidated. Several molecular mechanisms have been shown to be potentially involved in the pathogenesis of insulin resistance. Complete discussion of such factors is, however, beyond the scope of this review, and they have been extensively discussed elsewhere (Shulman, 2000). There is a substantial amount of evidence that lipids are tightly involved in insulin resistance of obese individuals. High body fat mass is associated with increased whole body lipolysis and plasma free fatty acid concentrations (Felber et al, 1992). Several hypotheses link increased fatty acid concentrations with insulin-mediated glucose disposal in skeletal muscle, the major glucose-utilizing tissue (Figure 2). In the early sixties, Randle and collaborators raised the hypothesis that high fatty acid concentrations were responsible for increased lipid oxidation in skeletal muscle, and that this led to the secondary inhibition of several key steps in glucose oxidation, glycolysis and glucose transport (Randle et al, 1963). More recently, this hypothesis has been challenged on the basis of several experimental studies in vivo and in vitro. It has indeed been proposed that intracellular fatty acyl CoA may directly inhibit muscle glucose transport by impairing insulin signaling (Dresner et al, 1999). According to this scheme, impaired muscle lipid oxidation, possibly related to a low muscle oxidative capacity (as often observed in insulin resistant individuals; Kelley & Simoneau, 1997) would lead to accumulation of muscle fatty acyl CoA and insulin resistance (Ruderman et al, 1999).

Figure 2

Role of fatty acids in the pathogenesis of the metabolic syndrome.

Recent interest has focused on the potential role of intramyocellular lipids (ie lipids stored within the skeletal muscle fibers) in the pathogenesis of insulin resistance. There is a good correlation between intramyocellular lipid content of skeletal muscles and whole-body insulin resistance. Moreover, intramyocellular lipid evaluated by nuclear magnetic resonance and fatty acyl CoA content in muscle correlates with insulin sensitivity in humans (Krssak et al, 1999; Ellis et al, 2000). Intramyocellular lipids may hypothetically impair insulin's actions in skeletal muscle through increased muscle fatty acyl–CoA if the oxidation of muscle does not match intramuscular lipolysis. In support of this hypothesis, Dobbins and his colleagues have studied the effect of the inhibition of lipid oxidation by the carnitine palmitoyltransferase-1 inhibitor, etomoxir, on intramyocellular lipid content in rats (Dobbins et al, 2001). The intramyocellular lipids significantly increased with etomoxir under both low-fat diet and high-fat diet. Insulin-mediated glucose disposal measured during hyperinsulinemic–euglycemic clamps correlated with the intramyocellular lipid content when the different dietary groups were considered together (low-fat group, low- fat+etoxomir group, high-fat group and high-fat+ etoxomir group). These results suggest that intramyocellular lipid is increasingly formed from excess intramyocellular fatty acyl CoA because of low muscle lipid oxidation.

It has recently been observed that fatty acid may also reduce insulin-mediated glucose disposal through actions exerted at the level of blood vessels. Several conditions such as oral feeding, hyperinsulinemia or mental stress produce skeletal muscle vasodilation by stimulating the release of NO from endothelial cells (Baron, 1993). This vasodilation appears to enhance insulin actions by increasing the delivery of glucose and insulin itself to insulin-sensitive tissues. Infusion of lipids, which leads to elevation of plasma free fatty acid concentrations, impairs endothelial function and reduces insulin actions (Steinberg & Baron, 1997). It is of particular interest, that elevated free fatty acid concentrations also enhance blood pressure during mental stress, indicating that vascular effects of fatty acids may be involved in several features of the metabolic syndrome (Seematter et al, 2000; Battilana et al, 2001).

Prevention and management of the metabolic syndrome

Given the central role played by insulin resistance in the pathogenesis of the syndrome, all strategies which improve insulin sensitivity are thought to be effective in preventing or improving the metabolic syndrome. This corresponds to the control of the factors indicated in the previous section.

  • Prevention of excess body weight/reduction of obesity—in obese patients, moderate energy restriction and low-fat diets, or cognitive/behavioral approaches may be effective in reducing body weight. Appetite-suppressing drugs, or inhibitors of lipid digestion and absorption may assist in the loss of excess body weight. In more severe obesity, gastric reduction surgery or gastric by-pass may be an effective option (Anonymous, 2000). Altogether, all weight-reducing programs appear essentially ineffective. Every effort should therefore be made to prevent the occurrence of obesity. For this purpose, maintenance of a high level of physical activity (and/or, in children, limitation of sedentary activities such as TV watching; (Golan et al, 1998) may increase energy expenditure. There is also evidence that obese patients generally consume a diet in which fat represents an important proportion of energy consumed (Blundell et al, 1996). This may favor excess energy intake by increasing the energy density of nutritions as well as their palability. Consumption of a high-complex-carbohydrate, low-fat diet may help to reduce spontaneous food intake.

  • Promotion of physical activity—physical fitness is positively associated with insulin sensitivity. An acute bout of exercise stimulates skeletal muscle glucose uptake. This effect is attained by non-insulin-dependent translocation of GLUT 4 transporters to the plasmaleurmal membrane as a result of AMP-dependent protein kinase activation (Winder & Hardie, 1999) during muscle contraction. This may contribute to lower plasma glucose and insulin concentrations. Physical training is also associated with an increase in glucose utilizing muscle mass at the whole body level, and with a decreased body fat. It may also lead to an increased oxidative capacity of skeletal muscle, or to changes in the plasma membrane composition in fatty acids (Kelley & Simoneau, 1997; Andersson et al, 2000).

  • Dietary management—several approaches may improve insulin sensitivity and/or reduce hyperglycemia and hyperinsulinemia. There is evidence that plasma glucose and insulin concentrations are related to carbohydrate ingestion, and that diets providing high amounts of simple carbohydrates may impair glucose tolerance, reduce plasma HDL cholesterol, and increase plasma VLDL triglycerides (Reaven, 1997; Riccardi & Rivellese, 2000). Ingestion of food items containing essentially complex carbohydrates, associated with a high fiber content (and more particularly a high content of soluble fibers) appears to have different effects. The slower absorption of carbohydrate from such foods leads to lower postprandial plasma glucose (low glycemic index) and insulin excursion and to an improved glycemic control in insulin resistant individuals. Much of this effect appears to be directly secondary to a slower rate of systemic glucose delivery after ingestion of such foods (Battilana et al, 2001). It has, however, also been reported that feeding a diet rich in low glycemic index foods improve insulin-mediated glucose utilization in isolated muscle in vitro, through mechanisms which remain unexplained. There is, however, concern that high-carbohydrate diets, even under the form of low-glycemic-index foods, may adversely affect HDL cholesterol levels and the cardiovascular risk. An alternative approach consists in the administration of a low-carbohydrate high-monosaturated-fatty acid diet (Campbell et al, 1994; Riccardi & Rivellese, 2000). With such diets, carbohydrate intake can be effectively replaced by energy furnished by monounsaturated fats without decreasing insulin sensitivity.

  • Pharmacotherapy—Thiazolidinediones are novel therapeutic agents approved for the treatment of type 2 diabetic which act essentially by enhancing insulin sensitivity (Day, 1999). This effect appears to be mediated by activation of PPAR-γ, presumably in adipose tissue. The mechanisms by which action of thiazolidinediones on adipose cells improve whole body insulin sensitivity remain unknown (Kersten et al, 2000). Alterations of adipose TNFα or leptin synthesis, or of fatty acid release, have been suggested as possible links. Metformin is an antidiabetic agent which has been used as an antidiabetic agent for several decades in Europe. It is currently thought to lower plasma glucose concentrations by decreasing hepatic gluconeogenesis (Bailey & Turner, 1996). The place of these agents in the treatment of the metabolic syndrome in non-diabetic individuals remain to be evaluated.

Future perspectives

The dietary management of the metabolic syndrome is presently based on observational studies and is essentially empirical. There is strong evidence that genetic factors play a role in interindividual variations of insulin sensitivity. It is therefore highly likely that genetic alterations and gene–environment interactions play an important role in the development of this syndrome. It can be expected that elucidation of the modified genetic background of patients with the metabolic syndrome will improve our understanding of its pathogenesis. It may also allow a more accurate characterization of possible subtypes of the syndrome, and assist in developing specific dietary strategies.

The metabolic syndrome is not the consequence of a decrease in insulin actions in a single organ or tissue, but results of the interaction of metabolic dysregulations present in several organs. Alterations of insulin actions in skeletal muscle, dysregulation of adipocytes functions, impaired hepatic glucose metabolism and decreased insulin secretion from β cells, all contribute to the syndrome. Little, however, is known about the interorgan substrate and signal exchanges. Future research directed in the interorgan control of glucose and lipid metabolism will undoubtedly help to further delineate the pathogenesis of the syndrome. In particular, the possible role of metabolic/endocrine alterations in adipose cells and/or hepatocytes deserve further studies. The use of animal models with targeted/overexpression of selected genes has already pointed to interesting, although challenging, interrelationship between adipose tissue and liver metabolism and whole- body insulin sensitivity and their underlying molecular mechanisms. Two different transgenic models of mice with lipodystrophy (ie near complete absence of adipose tissue) have been produced. These mice develop severe generalized insulin resistance and impaired glucose tolerance (Reitman et al, 1999). Interestingly, normal glucose homeostasis was restored by grafting adequate amounts of adipose tissue. This important observation by itself indicates that the adipose tissue plays a major role in whole body glucose metabolism. Furthermore, thiazolidinediones, a new class of insulin sensitizers which are thought to act primarily as ligands for PPAR-γ on adipose cells, were ineffective in these animals unless adipose tissue was also transplanted. This supports the hypothesis that thiazolidinediones exert their antidaibetogenic effects through actions exerted on adipose tissue (possibly by activating the differntiation of small-size, insulin-sensitive adipocytes).

Heterozygous PPAR-γ deficient mice are lipodystrophic, but interestingly they are highly insulin sensitive. They are leaner than wild-type mice and protected from insulin resistance under a high-fat diet (Kubota et al, 1999). These mice are characterized by overexpression and hypersecretion of leptin despite of the smaller size of adipocytes and decreased fat mass. It is unknown whether the hypersecretion of leptin explains this protective effect.

Transgenic, lipodystrophic mice also have dyslipidemia. In contrast with their effect on glucose tolerance, thiazolidinediones improved their plasma lipids profiles even in the complete absence of adipose cells. This effect appears to be mediated by activation of PPAR-γ abnormally expressed in liver cells of insulin-resistant individuals, and is associated with hepatic lipid uptake and liver steatosis (Chao et al, 2000).

The study of transgenic animals have also pointed to a potential role of primary liver alterations in the pathogenesis of generalized insulin resistance. Targeted disruption of the insulin receptor gene in liver cells (but not in muscle, adipose tissue or pancreatic β cells) leads to the development of severe extrahepatic insulin resistance. Overexpression of the key enzyme responsible for hexosamine synthesis in liver cells leads to an initial increased insulin sensitivity with high glucose utilization in the liver; subsequently, however, the animals develop a fatty liver, dyslipidemia, and severe extrahepatic insulin resistance.

The results obtained with these transgenic animal models raise several questions, yet unanswered. However they clearly point to potential important roles of ‘metabolic cross-talks’ between adipose tissue and the liver on one hand, and skeletal muscle and pancreatic β cells on the other hand. Further studies are needed to better delineate the molecular mechanisms underlying such ‘cross-talks’, as well as how diet and/or exercise may be used to modulate them.

There is evidence that the effects on endothelial function differ according to the type of fatty acid considered. There is also evidence that intramyocellular lipid droplets may be tightly associated with insulin actions in skeletal muscle (Krssak et al, 1999). There is therefore an urgent need for studies aimed at assessing the effects of dietary fats in endothelial function, intracellular fatty acid profiles and intramyocellular lipids.


  1. Andersson A, Sjödin A, Hedman A, Olsson R, Vessby B . 2000 Fatty acid profile of skeletal muscle phospholipids in trained and untrained young men Am. J. Physiol. Endocrinol. Metab. 279: E744–E751

    CAS  Article  Google Scholar 

  2. Anonymous . 2000 Overweight, obesity, and health risk. National Task Force on the Prevention and Treatment of Obesity Arch. Intern Med. 160: 898–904

    Article  Google Scholar 

  3. Bailey CJ, Turner RC . 1996 Metformin New Engl. J. Med. 29: 574–579

    Article  Google Scholar 

  4. Baron AD . 1993 Cardiovascular actions of insulin in humans. Implications for insulin sensitivity and vascular tone Baillieres Clin. Endocrinol. Metab. 7: 961–987

    CAS  Article  Google Scholar 

  5. Battilana P, Seematter G, Schneiter TP, Jéquier E, Tappy L . 2001 Effects of free fatty acids on insulin sensitivity and haemodynamics during mental stress J. Clin. Endocrinol. Metab. 86: 124–128

    CAS  PubMed  Google Scholar 

  6. Battilana P, Ornstein K, Minehira K, Schwarz JM, Acheson K, Schneiter TP, Burri J, Jequier E, Tappy L . 2001 Mechanisms of action of beta-glucan in postprandial glucose metabolism in healthy men Eur. J. Clin. Nutr. 55: 327–333

    CAS  Article  Google Scholar 

  7. Bjorntorp P, Rosmond R . 2000 Neuroendocrine abnormalities in visceral obesity Int. J Obes. 24: (Suppl. 2): 80–85

    Article  Google Scholar 

  8. Blundell JE, Lawton CL, Cotton JR, Macdiarmid JI . 1996 Control of human appetite: implications for the intake of dietary rat A. Rev. Nutr. 16: 285–319

    CAS  Article  Google Scholar 

  9. Borghouts LB, Keizer HA . 2000 Exercise and insulin sensitivity: a review Int. J. Sport Med. 21: 1–12

    CAS  Article  Google Scholar 

  10. Campbell LV, Marmot PE, Dyer JA, Borkman M, Storlien LH . 1994 The high-monounsaturated rat diet as a practical alternative for-NIDDM Diabetes Care 17: 177–182

    CAS  Article  Google Scholar 

  11. Chao L, Marcus-Samuels B, Mason MM, Moitra J, Vinson C, Arioglu E, Gavrilova O, Reitman ML . 2000 Adipose tissue is required for the antidiabetic, but not for the hypolipidemic, effect of thiazolidinediones J. Clin. Invest. 106: 1221–1228

    CAS  Article  Google Scholar 

  12. Day C . 1999 Thiazolidinediones: a new class of antidiabetic drugs Diabetic Med. 16: 179–192

    CAS  Article  Google Scholar 

  13. DeFronzo RA . 1988 The triumvirate: β-cell, muscle, liver. A collusion responsible for NIDDM Diabetes 37: 667–687

    CAS  Article  Google Scholar 

  14. DeFronzo RA . 1991 Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease Diabetes Care 14: 173–194

    CAS  Article  Google Scholar 

  15. Dobbins RL, Szczepaniak LS, Bentley B, Esser V, Myhill J, McGarry JD . 2001 Prolonged inhibition of muscle carnitine palmitoyltransferase-1 promotes intramyocellular lipid accumulation and insulin resistance in rats Diabetes 50: 123–130

    CAS  Article  Google Scholar 

  16. Dresner A, Laurent D, Marcucci M, Griffin ME, Dufour S, Cline GW, Slezak LA, Andersen DK, Hundal RS, Rothman DL, Petersen KF, Shulman GI . 1999 Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity J. Clin. Invest. 103: 253–259

    CAS  Article  Google Scholar 

  17. Ellis BA, Poynten A, Lowry AJ, Furler SM, Chisholm DJ, Kraegen EW, Cooney GJ . 2000 Long-chain acyl-CoA esters as indicators of lipid metabolism and insulin sensitivity in rat and human muscle Am. J. Physiol. Endocrinol. Metab. 279: E554–E560

    CAS  Article  Google Scholar 

  18. Felber JP, Acheson KJ, Tappy L . 1992 From Obesity to Diabetes. Chichester: John Wiley

    Google Scholar 

  19. Golan M, Fainaru M, Weizman A . 1998 Role of behaviour modification in the treatment of childhood obesity with the parents as the exclusive agents of change Int. J. Obes. Relat. Metab. Disord. 22: 1217–1224

    CAS  Article  Google Scholar 

  20. Hollenbeck CB . 1993 Dietary fructose effects on lipoprotein metabolism and risk fu¨r coronary artery disease Am. J. Clin. Nutr. 58: (Suppl.): 800–809

    Article  Google Scholar 

  21. Kelley DE, Simoneau J-A . 1997 Mechanisms of insulin resistance in obesity In: Clinical Research in Diabetes and Obesity ed. B Draznin & R Rizza pp 57–72 Totawa, NY: Humana Press

    Chapter  Google Scholar 

  22. Kersten S, Desvergne B, Wahli W . 2000 Roles of PPARs in health and disease Nature 405: 421–424

    CAS  Article  Google Scholar 

  23. Krssak M, Falk Petersen K, Dresner A, DiPietro L, Vogel SM, Rothman DL, Roden M, Shulman GI . 1999 Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study Diabetologia 42: 113–116

    CAS  Article  Google Scholar 

  24. Kubota N, Terauchi Y, Miki H, Tamemoto H, Yamauchi T, Komeda K, Satoh S, Nakano R, Ishii C, Sugiyama T, Eto K, Tsubamoto Y, Okuno A, Murakami K, Sekihara H, Hasegawa G, Naito M, Toyoshima Y, Tanaka S, Shiota K, Kitamura T, Fujita T, Ezaki O, Aizawa S, Kadowaki T . 1999 PPAR gamma mediates high-rat diet-induced adipocyte hypertrophy and insulin resistance Mol. Cell 4: 597–609

    CAS  Article  Google Scholar 

  25. Marshall JA, Bessesen DH, Hamman RF . 1997 High saturated rat and low starch and fibre are associated with hyperinsulinaemia in a non-diabetic population: the San Luis Valley Diabetes Study Diabetologia 40: 430–438

    CAS  Article  Google Scholar 

  26. Parks EJ, Hellerstein MK . 2000 Carbohydrate-induced hypertriacylglycerolemia: historical perspective and review of biological mechanisms Am. J. Clin. Nutr. 71: 412–433

    CAS  Article  Google Scholar 

  27. Randle P, Garland P, Hales C, Newsholme E . 1963 The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus Lancet 1: 785–789

    CAS  Article  Google Scholar 

  28. Ravussin E, Gautier JF . 1999 Metabolic predictors of weight gain Int. J. Obes. Relat. Metab. Disord. 23(1): 47–41

    Google Scholar 

  29. Reaven GM . 1991 Insulin resistance, hyperinsulinemia, hypertriglyceridemia, and hypertension. Parallels between human disease and rodent models Diabetes Care 14: 195–202

    CAS  Article  Google Scholar 

  30. Reaven GM . 1997 Do high carbohydrate diets prevent the development or attenuate the manifestations (or both) of syndrome X? A viewpoint strongly against Curr. Opinion Lipidol. 8: 23–27

    CAS  Article  Google Scholar 

  31. Reaven GM . 1999 Insulin resistance: a chicken that has come to roost Ann. NY Acad. Sci. 892: 45–57

    CAS  Article  Google Scholar 

  32. Reaven GM, Lithell H, Landsberg L . 1996 Hypertension and associated metabolic abnormalities—the role of insulin resistance and the sympathoadrenal system New Engl. J. Med. 334: 374–381

    CAS  Article  Google Scholar 

  33. Reitman ML, Mason MM, Moitra J, Gavrilova O, Marcus-Samuels B, Eckhaus M, Vinson C . 1999 Transgenic mice lacking white fat: models for understanding human lipoatrophic diabetes Ann. NY Acad. Sci. 892: 289–296

    CAS  Article  Google Scholar 

  34. Riccardi G, Rivellese AA . 1991 Effects of dietary fiber and carbohydrate on glucose and lipoprotein metabolism in diabetic patients Diabetes Care 14: 1115–1125

    CAS  Article  Google Scholar 

  35. Riccardi G, Rivellese AA . 2000 Dietary treatment of the metabolic syndrome—the optimal diet Br. J. Nutr. 83(1): 143–148

    Google Scholar 

  36. Ruderman NB, Saha AK, Vavvas D, Witters LA . 1999 Malonyl–CoA, fuel sensing, and insulin resistance Am. J. Physiol. 276: E1–E18

    CAS  PubMed  Google Scholar 

  37. Sakul H, Pratley R, Cardon L, Ravussin E, Mott D, Bogardus C . 1997 Familiality of physical and metabolic characteristics that predict the development of non-insulin-dependent diabetes mellitus in Pima Indians Am. J. Hum. Genet. 60: 651–656

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Seematter G, Guenat E, Schneiter P, Cayeux C, Jéquier E, Tappy L . 2000 Effects of mental stress on insulin-mediated glucose metabolism and energy expenditure in lean and obese women Am. J. Physiol. 279: E799–E805

    CAS  Google Scholar 

  39. Shimomura L, Matsuda M, Hammer RE, Bashmakov Y, Brown MS, Goldstein JL . 2000 Decreased IRS-2 and increased SREBP-l c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice Mol. Cell 6: 77–86

    CAS  Article  Google Scholar 

  40. Shulman GI . 2000 Cellular mechanisms of insulin resistance J. Clin. Invest. 106: 171–176

    CAS  Article  Google Scholar 

  41. Steinberg HO, Baron A . 1997 Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation J. Clin. Invest. 100: 1230–1239

    CAS  Article  Google Scholar 

  42. Tappy L, Felber JP, Jéquier E . 1991 Energy and substrate metabolism in obesity and postobese state Diabetes Care 14: 1180–1188

    CAS  Article  Google Scholar 

  43. Vessby B, Uusitupa M, Hermansen K, Riccardi G, Rivellese AA, Tapseil LC, Nälsén C, Berglund L, Louheranta A, Rasmussen BM, Calvert GD, Maffetone A, Pedersen E, Gustafsson I-B, Storlien LH . 2001 Substituting dietary saturated fu¨r monounsaturated rat impairs insulin sensitivity in healthy men and women: the KANWU study Diabetologia 44: 312–319

    CAS  Article  Google Scholar 

  44. Winder WW, Hardie DG . 1999 AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes Am. J. Physiol. 277: E1–E10

    CAS  PubMed  Google Scholar 

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Minehira, K., Tappy, L. Dietary and lifestyle interventions in the management of the metabolic syndrome: present status and future perspective. Eur J Clin Nutr 56, 1264–1269 (2002).

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  • insulin resistance
  • fat intake
  • intramyocellular lipid
  • free fatty acid
  • exercise

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