HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) All Versions of this Article: R600015-JLR200v1 47/8/1668    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McAuley, K. Articles by Mann, J. Search for Related Content PubMed PubMed Citation Articles by McAuley, K. Articles by Mann, J. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 47, 1668-1676, August 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Thematic Review

Thematic review series: Patient-Oriented Research. Nutritional determinants of insulin resistance

Kirsten McAuley^* and Jim Mann^1,*,

^* Edgar National Centre for Diabetes Research, University of Otago, Dunedin, New Zealand
Department of Human Nutrition, University of Otago, Dunedin, New Zealand

Published, JLR Papers in Press, May 23, 2006.

¹ To whom correspondence should be addressed. e-mail: jim.mann{at}stonebow.otago.ac.nz

	ABSTRACT

TOP ABSTRACT INTRODUCTION EXCESS ADIPOSITY DIETARY FAT CARBOHYDRATE, FIBER, AND... DIETARY PATTERNS SUMMARY REFERENCES

 
Interpreting the literature relating to the nutritional determinants of insulin resistance is complicated by the wide range of methods used to determine insulin sensitivity. Excess adiposity is unquestionably the most important determinant of insulin resistance, although the effect may be tempered by a relatively high proportion of lean body mass. Weight loss is associated with improved insulin sensitivity. Thus, diet-related factors that promote excessive energy intake may be regarded as promoters of insulin resistance. In the context of energy balance, diets characterized by high intakes of saturated fat and low intakes of dietary fiber are associated with reduced insulin sensitivity. Total fat intakes greater than the usually consumed range appear to promote insulin resistance, although the relative proportions of total fat and carbohydrate within the usual range appear unimportant. Monounsaturated fatty acids with a cis configuration and fiber-rich carbohydrate foods appear to be appropriate substitutes for saturated fatty acids and rapidly digested glycemic carbohydrates. In animal studies, n-3 unsaturated fatty acids have been shown to enhance insulin sensitivity and fructose and sucrose to increase insulin resistance. However, human data are limited. Large prospective studies currently being conducted should confirm the most appropriate macronutrient composition of diets for preventing and treating insulin resistance as well as establishing whether a range of candidate genes explains the variation in response to dietary change.

Supplementary key words adiposity • dietary fat • carbohydrate

	INTRODUCTION

TOP ABSTRACT INTRODUCTION EXCESS ADIPOSITY DIETARY FAT CARBOHYDRATE, FIBER, AND... DIETARY PATTERNS SUMMARY REFERENCES

 
Insulin resistance and its associated metabolic abnormalities are considered to be important determinants of coronary heart disease (1). This review summarizes the nutritional determinants of insulin resistance that may be translated into nonpharmacological interventions aimed at contributing to coronary heart disease risk reduction.

Insulin resistance was first described in the 1970s, and in 1988, Reaven (2) suggested that it was the underlying cause of a syndrome characterized by hyperinsulinemia, hypertension, increased triglyceride, reduced HDL cholesterol, hyperglycemia, and an increased risk of coronary heart disease. Several additional abnormalities have been identified, and the cluster of clinical and metabolic features is now known as the insulin resistance or metabolic syndrome (3). Despite the widespread use of the term, there are several different sets of diagnostic criteria (4–6), and some have questioned whether the cluster of abnormalities should be described as a syndrome (7, 8). It has not been established whether resistance to the action of insulin is a cause of the other abnormalities or merely another associated variable. A wide variety of methods exist for the measurement of insulin sensitivity (9, 10). Even the gold standard measures, the hyperinsulinemic, euglycemic insulin clamp and the intravenous glucose tolerance test, have been performed using different protocols in different studies. Surrogate measures of insulin sensitivity, usually based around a fasting insulin measurement, are also not standardized, and individuals with hyperinsulinemia may not have insulin resistance determined using an insulin clamp (11). Regardless of the method used, values for insulin sensitivity vary widely in healthy populations, and there is no agreed-upon cutoff for the definition of insulin-sensitive or insulin-resistant individuals. The fact that different researchers have used varying techniques to measure insulin sensitivity has greatly complicated the study of the nutritional determinants of insulin resistance. Some studies have described the effects of lifestyle-related variables on the metabolic syndrome, which has then been regarded as a surrogate measure of insulin resistance. Nevertheless, some general conclusions are possible.

	EXCESS ADIPOSITY

TOP ABSTRACT INTRODUCTION EXCESS ADIPOSITY DIETARY FAT CARBOHYDRATE, FIBER, AND... DIETARY PATTERNS SUMMARY REFERENCES

 
Obese individuals are much more likely to be insulin-resistant than normal weight individuals, and increasing adiposity, however measured, is associated with reduced insulin sensitivity (12, 13). Conversely, weight loss is almost always associated with improved insulin sensitivity (14). However, not all overweight or obese individuals are insulin-resistant. Brochu and colleagues (15) identified a greater lean body mass as an important distinguishing characteristic of obese individuals who are not insulin-resistant compared with those who are. A higher lean body mass is associated with enhanced glucose disposal. Physical activity contributes to increased lean body mass and enhanced insulin sensitivity and favorably influences many of the other metabolic abnormalities associated with obesity and the metabolic syndrome (16, 17). Thus, physical activity may reduce the risk of insulin resistance associated with obesity directly and via enhanced lean body mass.

The importance of regional adiposity in determining insulin action has been widely assumed, but the findings have not been entirely consistent. Abdominal or truncal adiposity has been implicated as having a key role in the pathogenesis of insulin resistance (18–20). This has largely been based on cross-sectional and longitudinal epidemiological studies in which waist circumference has been used to assess abdominal obesity and surrogate measures (e.g., fasting insulin) have been used to determine insulin sensitivity (18, 21–23). An intervention study by Markovic and colleagues (24) confirmed that reduced abdominal fat was associated with increased insulin sensitivity and improved indicators of both glucose metabolism and other measures of the metabolic syndrome, changes not seen with alteration of fat stores in other sites. Interestingly, Klein et al. (25) have recently shown that reducing subcutaneous abdominal tissue alone (by liposuction) did not improve insulin sensitivity. Decreasing adipose tissue alone does not achieve the same benefit as weight loss. It has been suggested that increased visceral adiposity in particular may cause insulin resistance as a result of its high levels of metabolic activity, particularly lipolytic activity (26).

However, this hypothesis has been questioned on the basis of studies using a euglycemic insulin clamp to measure insulin action and computed tomography or MRI to measure regional adiposity. In seven of nine such studies, it appeared that visceral fat does not have a unique effect on insulin sensitivity; rather, subcutaneous abdominal fat is a better predictor of insulin resistance than visceral fat, intraperitoneal fat, or peripheral subcutaneous fat (23). Liver fat, whether associated with obesity or not, is associated with insulin resistance, which may explain why even lean individuals may be insulin-resistant (27). Fat deposition in skeletal muscle (as estimated by muscle attenuation on computed tomography) has been shown to be a better marker of insulin sensitivity than total or abdominal fat (28). State-of-the-art techniques for investigating the distribution of body fat, insulin sensitivity, and adipocyte-derived hormones are likely to clarify the importance of regional adiposity and to explain the mechanisms by which adipocytes in certain sites are especially likely to promote insulin resistance. However, in the context of the current global epidemic of obesity and the central role of excess adiposity in determining insulin resistance, it may be appropriate to consider nutritional determinants of obesity as determinants of insulin resistance, regardless of whether or not they have been linked to a reliable measure of insulin sensitivity. Conversely, dietary attributes that reduce the risk of obesity may be regarded as protective against insulin resistance. Thus, frequent consumption of large portions of energy-dense foods and sugary drinks may be regarded as promotive and high intake of fiber-rich whole-grain cereals and intact fruits and vegetables may be regarded as protective (29). The role of individual nutrients is considered below.

	DIETARY FAT

TOP ABSTRACT INTRODUCTION EXCESS ADIPOSITY DIETARY FAT CARBOHYDRATE, FIBER, AND... DIETARY PATTERNS SUMMARY REFERENCES

 
Diets high in total fat are energy-dense. They may be less satiating than carbohydrates, at least in some individuals (30, 31). As a result, they tend to promote excess energy intake and are associated with an increased risk of obesity and insulin resistance (30). A meta-analysis suggests that among overweight individuals, a total fat intake of <30% total energy facilitates weight loss (32). Thus, high-fat diets may promote insulin resistance via their obesogenic potential. The contribution of fat to total energy intake, and whether the nature of dietary fat influences insulin resistance and other features of the metabolic syndrome in the context of energy balance, are less clearly established. These are important practical considerations because most overweight individuals will fairly rapidly achieve their maximum weight loss, and the appropriate dietary advice will be that which facilitates weight maintenance and ensures the greatest degree of insulin sensitivity.

At least 11 studies (33–43) have compared the effects on insulin sensitivity of isoenergetic diets high (typically, 40–50% of total energy) and low (typically, 15–25% of total energy) in total fat intake (Table 1 ). The comparisons were made under isoenergetic conditions, with the bulk of the remaining energy provided by varying carbohydrate, protein remaining fairly constant, and insulin sensitivity assessed by means of a clamp or frequent-sampling intravenous glucose tolerance test. In 6 of the 11 studies (34, 35, 39–42), there were no appreciable differences in insulin sensitivity on the high- and low-fat diets. Four studies suggested reduced sensitivity on the high-fat diets, but in these the percentage of energy from fat was extreme, as was the intake of saturated fat (33, 36, 37, 43). In one study, insulin sensitivity appeared to be slightly enhanced on the high-fat diet compared with the high-carbohydrate diet, but that study was carried out in people with diabetes in whom the sudden substantial increase in carbohydrate may have resulted in a deterioration in glycemic control (38). Although statistically significant results have been reported, power calculations have usually not been presented, and most of the studies appear to be underpowered. In addition, the majority of studies are of short duration.

Definitive evidence of an association between the nature of dietary fat and insulin sensitivity can only be determined by intervention studies (Table 2 ). Several relatively underpowered studies (54–59) compared the effects of saturated and unsaturated fatty acids on insulin sensitivity in healthy individuals and those with type 2 diabetes. Perhaps not surprisingly, the results were inconclusive. However, a relatively recent study known as KANWU (signifying the collaborating centers in five countries) was sufficiently powered to obtain a convincing outcome (60). A large group (162) of healthy individuals was randomized to receive high-saturated-fat or high-monounsaturated-fat diets. A randomly selected subsample within each group was given fish oil supplements or placebo. Insulin sensitivity, measured by the intravenous glucose tolerance test, was reduced by 10% on the diet high in saturated fatty acids. Interestingly, when the subjects were divided into those consuming above and below the median total fat intake for the group as a whole (37% of total energy as fat), a difference between saturated and monounsaturated fatty acids was apparent only in those with a total fat intake below the median. Indeed, among them, the difference in insulin sensitivity was twice that (20.3%) seen in the group as a whole. All of those with the higher fat intake showed a reduction in insulin sensitivity. This finding suggests that total fat may indeed adversely affect insulin sensitivity when intakes are particularly high and that this may not have been apparent in all of the studies mentioned above because intakes on the high-fat diet were not high enough. A study by Pérez-Jiménez et al. (61) examining the effects of a high-MUFA Mediterranean diet also suggests an improvement in insulin sensitivity compared with a diet richer in saturated fatty acids. Changing from a saturated to a monounsaturated fat diet may be a particularly important means of improving insulin sensitivity in the context of more moderate intakes of total fat.

The mechanism by which the nature of dietary fat might influence insulin sensitivity is not clearly understood. It is possible that a change in the fatty acid composition of cell membranes, which can be achieved by dietary modification, influences insulin receptor binding or activity as well as ion permeability and cell signaling (53).

Overwhelmingly, the most important messages with regard to fat modification in the treatment of insulin resistance are the avoidance of excessive intakes and reduction of saturated fatty acids and replacement by monounsaturated fatty acids and some polyunsaturated fatty acids with a cis configuration. Two recent reviews describing the effects of dietary conjugated linoleic acid on the regulation of adiposity and insulin sensitivity suggest that more subtle effects of fatty acids may also be relevant (68, 69). It appears that specific isomers of conjugated linoleic acid may reduce adiposity, especially abdominal fat, but insulin sensitivity is also reduced. Thus, the last word on the effects of the nature of dietary fat on insulin has yet to be written.

	CARBOHYDRATE, FIBER, AND GLYCEMIC INDEX

TOP ABSTRACT INTRODUCTION EXCESS ADIPOSITY DIETARY FAT CARBOHYDRATE, FIBER, AND... DIETARY PATTERNS SUMMARY REFERENCES

 
Diets rich in low-energy-dense foods, including whole-grain cereals and cereal products and other foods rich in dietary fiber, promote satiety and may, as a consequence, facilitate appropriate energy intake (29). Thus, by reducing the risk of obesity, such foods may be regarded as reducing the risk of insulin resistance. In the context of energy balance and weight maintenance, there is evidence that the type of carbohydrate may influence insulin sensitivity and associated metabolic features. The findings in some studies that increasing the proportions of carbohydrate in relation to fat in the range of usually consumed quantities will influence insulin resistance and other metabolic abnormalities may be explained more by the type of carbohydrate than the amount.

Insulin resistance and its associated dyslipidemia (high triglyceride, low HDL) have been shown to be more marked on a high-carbohydrate diet compared with a diet rich in monounsaturated fatty acids (38, 39, 70–77). In individuals with diabetes, glycemic control may also be adversely influenced and plasminogen activator inhibitor type 1 levels are increased, suggesting an increased thrombogenic tendency (77). However, studies that have examined this issue have generally failed to consider the importance of the nature of the carbohydrate. Several dietary intervention studies have shown that many, if not all, of these untoward effects can be avoided if the carbohydrate is rich in dietary fiber, especially the soluble forms, and if most of the carbohydrate-containing foods have a low glycemic index (i.e., are associated with a relatively low postprandial glucose excursion as a result of slow digestion and absorption) (78–80). Whether the beneficial effects are attributable to the fiber content, the fact that the plant cell walls remain intact and encapsulate the carbohydrate, or simply that the foods have a low glycemic index for whatever reason has not been fully resolved. Most carbohydrate-containing, fiber-rich foods also have a low glycemic index. A single carefully conducted intervention study in people with type 2 diabetes (81) showed that insulin and plasminogen activator inhibitor type 1 levels were reduced when the overall glycemic index of the diet was reduced, even though dietary fiber content remained consistent. Glycemic index was modified by altering food structure (e.g., fiber-rich cooked dried beans were eaten either whole or finely ground).

Two large cross-sectional studies using validated food frequency questionnaires to assess nutrient intakes and either the frequent-sampling intravenous glucose tolerance test or homeostasis model assessment for insulin resistance found that intake of dietary fiber was inversely associated with the probability of having insulin resistance (82, 83). In the Insulin Resistance Atherosclerosis Study (83), it was possible to demonstrate that fiber increased insulin sensitivity even after adjustment for body mass index. However, neither study found any relationship between insulin sensitivity and glycemic index or glycemic load. Although cross-sectional studies do have limitations, these findings, considered in conjunction with the favorable effects of dietary fiber on other metabolic derangements associated with insulin resistance, provide a relatively strong case for including a recommendation regarding dietary fiber in nutritional guidelines aimed at increasing insulin sensitivity. It is less certain that particular foods should be recommended on the basis of their glycemic index.

There has been considerable interest in the potential role of sugars as determinants of insulin resistance. Free sugars (principally comprising sucrose or high fructose corn syrup added to foods or drinks by manufacturer, cook, or consumer, plus concentrated sugars in honey, syrups, and fruit juices) may contribute to excessive weight gain and so to a reduction in insulin sensitivity (29, 84). Such foods are energy-dense, and sugary drinks, although not energy-dense, appear not to be satiating. Analysis of a subgroup of individuals in the CARMEN study who were diagnosed with the metabolic syndrome showed that the reduction in body weight and improved metabolic indices seen when simple carbohydrates (sugars) were replaced with complex ones were more striking in people with this disorder than in the general population (85). The fact that fructose, compared with glucose, is preferentially metabolized to lipid in the liver and that fructose consumption induces insulin resistance, impaired glucose tolerance, hyperinsulinemia, hypertriglyceridemia, and hypertension in animal models have led to the suggestion that fructose, sucrose, or high fructose corn syrup may have uniquely untoward effects compared with other carbohydrates in humans in the context of energy balance. However, the existing evidence is limited and conflicting, and no conclusions can be drawn (86, 87).

Thus, international guidelines for the nutritional management and prevention of type 2 diabetes mellitus (88), which may be regarded as also being appropriate for reducing insulin resistance, emphasize that carbohydrate intake may range between 45% and 60% of total energy (Table 3 ). Although vegetables, legumes, intact fruits, and whole-grain cereals are always the preferred source of carbohydrates, it is particularly important to emphasize foods that are rich in dietary fiber when carbohydrate intake is at the upper end of the recommended range. Similarly, when carbohydrate intake is at the lower end of this range, or perhaps even as low as 40% in the context of a relatively high-protein diet, it is essential to ensure that the nature of dietary fat is appropriate (i.e., predominantly monounsaturated fatty acids with modest intakes of n-6 polyunsaturated fatty acids, with the diet also providing at least some n-3 fatty acids). Restriction of free sugars to 10% or less of total energy is justified on the grounds of reducing the obesogenic potential of the diet.

	DIETARY PATTERNS

TOP ABSTRACT INTRODUCTION EXCESS ADIPOSITY DIETARY FAT CARBOHYDRATE, FIBER, AND... DIETARY PATTERNS SUMMARY REFERENCES

Although the prudent diet is comparable to that recommended for high-risk individuals and populations by authorities in many countries, and indeed is similar to traditional dietary patterns in many parts of the world, a new range of dietary patterns has now emerged and several are being widely recommended and adapted for weight loss and cardiovascular risk reduction. Among the best known of these are the high-fat/low-carbohydrate diets (e.g., Atkins) and the high-protein dietary approach (e.g., Zone, South Beach diet).

There is no doubt that such alternative dietary approaches can facilitate weight loss, decrease insulin levels, and improve many of the metabolic derangements associated with insulin resistance in the short term (42, 43, 91–95). However, long-term data are limited. Two 12 month randomized trials suggest that any initial benefit achieved by the high-fat Atkins approach compared with the high-carbohydrate/high-fiber/low-fat approach (the prudent diet) is lost after 1 year (42, 96). A study by McAuley et al. (97, 98) comparing, in the same study, the high-fat, high-protein, and high-carbohydrate/high-fiber approaches in insulin-resistant women provided some useful additional information. In that study, the early benefits of the high-fat diet compared with the high-carbohydrate diet in terms of weight loss, fasting insulin, and triglyceride were not significant after 1 year. The high-protein approach, on the other hand, appeared to be associated during the first 6 months with an impressive improvement in metabolic and clinical measurements, which were sustained over a 1 year follow-up period. The more modest changes seen on the high-carbohydrate/high-fiber prudent diet were also sustained. The improvements in the metabolic variables appear to be proportional to the reduction in fat mass. The greater improvement in the high-protein compared with the high-carbohydrate diet may be attributable to the lesser degree of compliance with the high-carbohydrate diet in terms of consumption of the appropriate fiber-rich cereals, vegetables, and fruit as well as in the quantity of carbohydrate. The high-fat approach appears not to be sustainable in the long term, and even in the short term it may be associated with both atherogenic and thrombogenic effects, despite the potentially beneficial effects on insulin sensitivity and associated metabolic variables. These observations suggest that weight loss (reduction in fat mass) rather than nutrient distribution may be responsible for improvement in insulin sensitivity and that a range of dietary patterns, although not a very-high-fat diet, may be equally acceptable approaches to enhance insulin sensitivity and to treat the abnormalities of the metabolic syndrome.

	SUMMARY

TOP ABSTRACT INTRODUCTION EXCESS ADIPOSITY DIETARY FAT CARBOHYDRATE, FIBER, AND... DIETARY PATTERNS SUMMARY REFERENCES

 
Despite the difficulty of interpreting the literature relating to the nutritional determinants of insulin resistance, there are several nutritional interventions that can significantly improve insulin sensitivity. Excess adiposity, especially when centrally distributed, is clearly the most important nutrition-related factor determining insulin resistance. Although it is generally assumed that visceral abdominal obesity is especially relevant, further research involving more direct measurements of both insulin sensitivity and the localization of excessive adipose tissue are required to confirm the importance of regional adiposity. Reducing adiposity by dietary modification and increased physical activity improves insulin sensitivity and the range of abnormalities associated with insulin resistance. High-carbohydrate/high-fiber/low-glycemic index/low-fat diets are the tried and tested means of treating overweight and obesity and reversing the associated clinical and metabolic abnormalities, including insulin resistance. On the other hand, more moderate intakes of carbohydrate (40% of total energy) with higher intakes of protein and appropriate fat appear to be more acceptable to some people. This alternative dietary approach has been shown to achieve comparable or greater weight reduction and improvement in insulin sensitivity and clinical and biochemical variables associated with insulin resistance. Importantly, these benefits appear to be sustained. For successful weight maintenance, a wide range of carbohydrate intakes is acceptable, the generally accepted range being between 45% and 60% of total energy. Vegetables, legumes, intact fruits, and whole-grain cereals are the preferred sources of carbohydrate, and when carbohydrate intake is at the upper end of the recommended range, it is particularly important to emphasize foods rich in dietary fiber and with a low glycemic index. Ideally, dietary fiber intake should be at least 40 g/day (or 20 g/1,000 kcal/day), approximately half of which should be soluble, but beneficial effects are also obtained with lower, and for some, more acceptable amounts. As diets high in fructose, sucrose, and possibly other free sugars, such as high fructose corn syrup, may promote obesity and thus insulin resistance and other metabolic abnormalities, total free sugars should not exceed 10% of total energy. In diets of more moderate carbohydrate intakes, it is imperative that cis unsaturated fatty acids, especially monounsaturated fatty acids, should predominate. In both moderate- and high-carbohydrate diets, saturated fatty acids should be substantially restricted, trans unsaturated fatty acids should be eliminated as much as possible, and n-6 and n-3 unsaturated fatty acids should be consumed in moderation. Although n-3 fatty acids are essential fatty acids, there are no proven beneficial effects on insulin sensitivity in humans. Prospective studies under way at present should confirm the distribution of macronutrients most likely to achieve maximum insulin sensitivity as well as determine whether a range of candidate genes explain variation in response to diet.

Manuscript received May 3, 2006 and in revised form May 23, 2006.

	REFERENCES

TOP ABSTRACT INTRODUCTION EXCESS ADIPOSITY DIETARY FAT CARBOHYDRATE, FIBER, AND... DIETARY PATTERNS SUMMARY REFERENCES

1. Mann, J. 2000. Stemming the tide of diabetes mellitus. Lancet. 356: 1454–1455.[CrossRef][Medline]

2. Reaven, G. M. 1988. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 37: 1595–1607.[Abstract]

3. Byrne, C. D., and S. H. Wild, editors. 2005. The Metabolic Syndrome. John Wiley & Sons, London.

4. World Health Organisation. 1999. Definition, Diagnosis, and Classification of Diabetes Mellitus and Its Complications. Report of a WHO Consultation. World Health Organisation, Geneva.

5. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. 2001. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). J. Am. Med. Assoc. 285: 2486–2497.

6. International Diabetes Federation. The IDF Consensus Worldwide Definition of the Metabolic Syndrome. Available at http://www.idf.org/webdata/docs/MetSyndrome_FINAL.pdf. Accessed May 2, 2006.

7. Kahn, R., J. Buse, E. Ferrannini, and M. Stern. 2005. The metabolic syndrome: time for a critical appraisal. Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 48: 1684–1699.[CrossRef][Medline]

8. Gale, E. A. 2005. The myth of the metabolic syndrome. Diabetologia. 48: 1679–1683.[CrossRef][Medline]

9. Ferrannini, E., and A. Mari. 1998. How to measure insulin sensitivity. J. Hypertens. 16: 895–906.[CrossRef][Medline]

10. Monzillo, L. U., and O. Hamdy. 2003. Evaluation of insulin sensitivity in clinical practice and in research settings. Nutr. Rev. 61: 397–412.[CrossRef][Medline]

11. Ferrannini, E., and B. Balkau. 2002. Insulin: in search of a syndrome. Diabet. Med. 19: 724–729.[CrossRef][Medline]

12. Ferrannini, E., A. Natali, P. Bell, P. Cavallo-Perin, N. Lalic, and G. Mingrone. 1997. Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR). J. Clin. Invest. 100: 1166–1173.[Medline]

13. Karter, A. J., R. B. D'Agostino, E. J. Mayer-Davis, L. E. Wagenknecht, A. J. Hanley, R. F. Hamman, R. Bergman, M. F. Saad, S. M. Haffner, and IRAS investigators. 2005. Abdominal obesity predicts declining insulin sensitivity in non-obese normoglycaemics: the Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Obes. Metab. 7: 230–238.[CrossRef][Medline]

14. Weyer, C., K. Hanson, C. Bogardus, and R. E. Pratley. 2000. Long-term changes in insulin action and insulin secretion associated with gain, loss, regain and maintenance of body weight. Diabetologia. 43: 36–46.[CrossRef][Medline]

15. Brochu, M., A. Tchernof, I. J. Dionne, C. K. Sites, G. H. Eltabbakh, E. A. Sims, and E. T. Poehlman. 2001. What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women? J. Clin. Endocrinol. Metab. 86: 1020–1025.[Abstract/Free Full Text]

16. DeFronzo, R. A., R. S. Sherwin, and N. Kraemer. 1987. Effect of physical training on insulin action in obesity. Diabetes. 36: 1379–1385.[Abstract]

17. Laaksonen, D. E., H. M. Lakka, J. T. Salonen, L. K. Niskanen, R. Rauramaa, and T. A. Lakka. 2002. Low levels of leisure-time physical activity and cardiorespiratory fitness predict development of the metabolic syndrome. Diabetes Care. 25: 1612–1618.[Abstract/Free Full Text]

18. Kissebah, A. H., N. Vydelingum, R. Murray, D. J. Evans, A. J. Hartz, R. K. Kalkhoff, and P. W. Adams. 1982. Relation of body fat distribution to metabolic complications of obesity. J. Clin. Endocrinol. Metab. 54: 254–260.[Abstract/Free Full Text]

19. Bjorntorp, P. 1988. Abdominal obesity and the development of noninsulin-dependent diabetes mellitus. Diabetes Metab. Rev. 4: 615–622.[Medline]

20. Carey, D. G., A. B. Jenkins, L. V. Campbell, J. Freund, and D. J. Chisholm. 1996. Abdominal fat and insulin resistance in normal and overweight women: direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM. Diabetes. 45: 633–638.[Abstract]

21. Fujioka, S., Y. Matsuzawa, K. Tokunaga, and S. Tarui. 1987. Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity. Metabolism. 36: 54–59.[CrossRef][Medline]

22. Peiris, A. N., M. F. Struve, R. A. Mueller, M. B. Lee, and A. H. Kissebah. 1988. Glucose metabolism in obesity: influence of body fat distribution. J. Clin. Endocrinol. Metab. 67: 760–767.[Abstract/Free Full Text]

23. Peiris, A. N., M. I. Hennes, D. J. Evans, C. R. Wilson, M. B. Lee, and A. H. Kissebah. 1988. Relationship of anthropometric measurements of body fat distribution to metabolic profile in premenopausal women. Acta Med. Scand. Suppl. 723: 179–188.[Medline]

24. Markovic, T. P., A. B. Jenkins, L. V. Campbell, S. M. Furler, E. W. Kraegen, and D. J. Chisholm. 1998. The determinants of glycemic responses to diet restriction and weight loss in obesity and NIDDM. Diabetes Care. 21: 687–694.[Abstract]

25. Klein, S., L. Fontana, V. L. Young, A. R. Coggan, C. Kilo, B. W. Patterson, and B. S. Mohammed. 2004. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N. Engl. J. Med. 350: 2549–2557.[Abstract/Free Full Text]

26. Garg, A. 2004. Regional adiposity and insulin resistance. J. Clin. Endocrinol. Metab. 89: 4206–4210.[Free Full Text]

27. Yki-Jarvinen, H. 2005. Fat in the liver and insulin resistance. Ann. Med. 37: 347–356.[CrossRef][Medline]

28. Goodpaster, B. H., F. L. Thaete, J. A. Simoneau, and D. E. Kelley. 1997. Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat. Diabetes. 46: 1579–1585.[Abstract]

29. World Health Organisation. 2003. Diet, nutrition and the prevention of chronic diseases. World Health Organ. Tech. Rep. Ser. 916: i–viii, 1–149.

30. Golay, A., and E. Bobbioni. 1997. The role of dietary fat in obesity. Int. J. Obes. Relat. Metab. Disord. 21 (Suppl. 3): 2–11.

31. Rolls, B. J., and D. J. Shide. 1992. The influence of dietary fat on food intake and body weight. Nutr. Rev. 50: 283–290.[Medline]

32. Astrup, A., G. K. Grunwald, E. L. Melanson, W. H. Saris, and J. O. Hill. 2000. The role of low-fat diets in body weight control: a meta-analysis of ad libitum dietary intervention studies. Int. J. Obes. Relat. Metab. Disord. 24: 1545–1552.[CrossRef][Medline]

33. Chen, M., R. N. Bergman, and D. Porte. 1988. Insulin resistance and beta-cell dysfunction in aging: the importance of dietary carbohydrate. J. Clin. Endocrinol. Metab. 67: 951–957.[Abstract/Free Full Text]

34. Swinburn, B. A., V. L. Boyce, R. N. Bergman, B. V. Howard, and C. Bogardus. 1991. Deterioration in carbohydrate metabolism and lipoprotein changes induced by modern, high fat diet in Pima Indians and Caucasians. J. Clin. Endocrinol. Metab. 73: 156–165.[Abstract/Free Full Text]

35. Borkman, M., L. V. Campbell, D. J. Chisholm, and L. H. Storlien. 1991. Comparison of the effects on insulin sensitivity of high carbohydrate and high fat diets in normal subjects. J. Clin. Endocrinol. Metab. 72: 432–437.[Abstract/Free Full Text]

36. Lovejoy, J. C., M. M. Windhauser, J. C. Rood, and J. A. de la Bretonne. 1998. Effect of a controlled high-fat versus low-fat diet on insulin sensitivity and leptin levels in African-American and Caucasian women. Metabolism. 47: 1520–1524.[CrossRef][Medline]

37. Bisschop, P. H., J. de Metz, M. T. Ackermans, E. Endert, H. Pijl, F. Kuipers, A. J. Meijer, H. P. Sauerwein, and J. A. Romijn. 2001. Dietary fat content alters insulin-mediated glucose metabolism in healthy men. Am. J. Clin. Nutr. 73: 554–559.[Abstract/Free Full Text]

38. Parillo, M., A. A. Rivellese, A. V. Ciardullo, B. Capaldo, A. Giacco, S. Genovese, and G. Riccardi. 1992. A high-monounsaturated-fat/low-carbohydrate diet improves peripheral insulin sensitivity in non-insulin-dependent diabetic patients. Metabolism. 41: 1373–1378.[CrossRef][Medline]

39. Garg, A., S. M. Grundy, and R. H. Unger. 1992. Comparison of effects of high and low carbohydrate diets on plasma lipoproteins and insulin sensitivity in patients with mild NIDDM. Diabetes. 41: 1278–1285.[Abstract]

40. Sarkkinen, E., U. Schwab, L. Niskanen, M. Hannuksela, M. Savolainen, K. Kervinen, A. Kesaniemi, and M. Uusitupa. 1996. The effects of monounsaturated-fat enriched diet and polyunsaturated-fat enriched diet on lipid and glucose metabolism in subjects with impaired glucose tolerance. Eur. J. Clin. Nutr. 50: 592–598.[Medline]

41. Thomsen, C., O. Rasmussen, C. Christiansen, E. Pedersen, M. Vesterlund, H. Storm, J. Ingerslev, and K. Hermansen. 1999. Comparison of the effects of a monounsaturated fat diet and a high carbohydrate diet on cardiovascular risk factors in first degree relatives to type-2 diabetic subjects. Eur. J. Clin. Nutr. 53: 818–823.[CrossRef][Medline]

42. Foster, G. D., H. R. Wyatt, J. O. Hill, B. G. McGuckin, C. Brill, B. S. Mohammed, P. Szapary, D. J. Rader, J. S. Edman, and S. Klein. 2003. A randomized trial of a low-carbohydrate diet for obesity. N. Engl. J. Med. 348: 2082–2090.[Abstract/Free Full Text]

43. Samaha, F. F., N. Iqbal, P. Seshadri, K. L. Chicano, D. A. Daily, J. McGrory, T. Williams, M. Williams, E. J. Gracely, and L. Stern. 2003. A low-carbohydrate as compared with a low-fat diet in severe obesity. N. Engl. J. Med. 348: 2074–2081.[Abstract/Free Full Text]

44. Storlien, L. H., A. B. Jenkins, D. J. Chisholm, W. S. Pascoe, S. Khouri, and E. W. Kraegen. 1991. Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and omega-3 fatty acids in muscle phospholipid. Diabetes. 40: 280–289.[Abstract]

45. Maron, D. J., J. M. Fair, and W. L. Haskell. 1991. Saturated fat intake and insulin resistance in men with coronary artery disease. The Stanford Coronary Risk Intervention Project investigators and staff. Circulation. 84: 2020–2027.[Abstract/Free Full Text]

46. Parker, D. R., S. T. Weiss, R. Troisi, P. A. Cassano, P. S. Vokonas, and L. Landsberg. 1993. Relationship of dietary saturated fatty acids and body habitus to serum insulin concentrations: the Normative Aging Study. Am. J. Clin. Nutr. 58: 129–136.[Abstract/Free Full Text]

47. Mayer, E. J., B. Newman, C. P. Quesenberry, and J. V. Selby. 1993. Usual dietary fat intake and insulin concentrations in healthy women twins. Diabetes Care. 16: 1459–1469.[Abstract]

48. Feskens, E. J., J. G. Loeber, and D. Kromhout. 1994. Diet and physical activity as determinants of hyperinsulinemia: the Zutphen Elderly Study. Am. J. Epidemiol. 140: 350–360.[Abstract/Free Full Text]

49. Marshall, J. A., D. H. Bessesen, and R. F. Hamman. 1997. High saturated fat and low starch and fibre are associated with hyperinsulinaemia in a non-diabetic population: the San Luis Valley Diabetes Study. Diabetologia. 40: 430–438.[CrossRef][Medline]

50. Brunner, E. J., H. Wunsch, and M. G. Marmot. 2001. What is an optimal diet? Relationship of macronutrient intake to obesity, glucose tolerance, lipoprotein cholesterol levels and the metabolic syndrome in the Whitehall II study. Int. J. Obes. 25: 45–53.[CrossRef][Medline]

51. Pelikanova, T., M. Kohout, J. Valek, J. Base, and L. Kazdova. 1989. Insulin secretion and insulin action related to the serum phospholipid fatty acid pattern in healthy men. Metabolism. 38: 188–192.[CrossRef][Medline]

52. Vessby, B., S. Tengblad, and H. Lithell. 1994. Insulin sensitivity is related to the fatty acid composition of serum lipids and skeletal muscle phospholipids in 70-year-old men. Diabetologia. 37: 1044–1050.[Medline]

53. Pan, D. A., S. Lillioja, M. R. Milner, A. D. Kriketos, L. A. Baur, C. Bogardus, and L. Storlien. 1995. Skeletal muscle membrane lipid composition is related to adiposity and insulin action. J. Clin. Invest. 96: 2802–2808.[Medline]

54. Heine, R. J., C. Mulder, C. Popp-Snijders, J. van der Meer, and E. A. van der Veen. 1989. Linoleic-acid-enriched diet: long-term effects on serum lipoprotein and apolipoprotein concentrations and insulin sensitivity in noninsulin-dependent diabetic patients. Am. J. Clin. Nutr. 49: 448–456.[Abstract/Free Full Text]

55. Uusitupa, M., U. Schwab, S. Makimattila, P. Karhapaa, E. Sarkkinen, H. Maliranta, J. Agren, and I. Penttila. 1994. Effects of two high-fat diets with different fatty acid compositions on glucose and lipid metabolism in healthy young women. Am. J. Clin. Nutr. 59: 1310–1316.[Abstract/Free Full Text]

56. Schwab, U. S., L. K. Niskanen, H. M. Maliranta, M. J. Savolainen, Y. A. Kesaniemi, and M. I. Uusitupa. 1995. Lauric and palmitic acid-enriched diets have minimal impact on serum lipid and lipoprotein concentrations and glucose metabolism in healthy young women. J. Nutr. 125: 466–473.[Abstract/Free Full Text]

57. Fasching, P., K. Ratheiser, B. Schneeweiss, M. Rohac, P. Nowotny, and W. Waldhausl. 1996. No effect of short-term dietary supplementation of saturated and poly- and monounsaturated fatty acids on insulin secretion and sensitivity in healthy men. Ann. Nutr. Metab. 40: 116–122.[CrossRef][Medline]

58. Summers, L. K., B. A. Fielding, H. A. Bradshaw, V. Ilic, C. Beysen, M. L. Clark, N. R. Moore, and K. N. Frayn. 2002. Substituting dietary saturated fat with polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity. Diabetologia. 45: 369–377.[CrossRef][Medline]

59. Lovejoy, J. C., S. R. Smith, C. M. Champagne, M. M. Most, M. Lefevre, J. P. DeLany, Y. M. Denkins, J. C. Rood, J. Veldhuis, and G. A. Bray. 2002. Effects of diets enriched in saturated (palmitic), monounsaturated (oleic), or trans (elaidic) fatty acids on insulin sensitivity and substrate oxidation in healthy adults. Diabetes Care. 25: 1283–1288.[Abstract/Free Full Text]

60. Vessby, B., M. Uusitupa, K. Hermansen, G. Riccardi, A. A. Rivellese, L. C. Tapsell, C. Nalsen, L. Berglund, A. Louheranta, B. M. Rasmussen, et al. 2001. Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: the KANWU Study. Diabetologia. 44: 312–319.[CrossRef][Medline]

61. Pérez-Jiménez, F., J. López-Miranda, M. D. Pinillos, P. Gómez, E. Paz-Rojas, P. Montilla, C. Marín, M. J. Velasco, A. Blanco-Molina, J. A. Jiménez Perepérez, et al. 2001. A Mediterranean and a high-carbohydrate diet improve glucose metabolism in healthy young persons. Diabetologia. 44: 2038–2043.[CrossRef][Medline]

62. Borkman, M., D. J. Chisholm, S. M. Furler, L. H. Storlien, E. W. Kraegen, L. A. Simons, and C. N. Chesterman. 1989. Effects of fish oil supplementation on glucose and lipid metabolism in NIDDM. Diabetes. 38: 1314–1319.[Abstract]

63. Annuzzi, G., A. Rivellese, B. Capaldo, L. Di Marino, C. Iovine, G. Marotta, and G. Riccardi. 1991. A controlled study on the effects of n-3 fatty acids on lipid and glucose metabolism in non-insulin-dependent diabetic patients. Atherosclerosis. 87: 65–73.[CrossRef][Medline]

64. Boberg, M., T. Pollare, A. Siegbahn, and B. Vessby. 1992. Supplementation with n-3 fatty acids reduces triglycerides but increases PAI-1 in non-insulin-dependent diabetes mellitus. Eur. J. Clin. Invest. 22: 645–650.[Medline]

65. McManus, R. M., J. Jumpson, D. T. Finegood, M. T. Clandinin, and E. A. Ryan. 1996. A comparison of the effects of n-3 fatty acids from linseed oil and fish oil in well-controlled type II diabetes. Diabetes Care. 19: 463–467.[Abstract]

66. Rivellese, A. A., A. Maffettone, C. Iovine, L. Di Marino, G. Annuzzi, M. Mancini, and G. Riccardi. 1996. Long-term effects of fish oil on insulin resistance and plasma lipoproteins in NIDDM patients with hypertriglyceridemia. Diabetes Care. 19: 1207–1213.[Abstract]

67. Luo, J., S. W. Rizkalla, H. Vidal, J. M. Oppert, C. Colas, A. Boussairi, M. Guerre-Millo, A. S. Chapuis, A. Chevalier, G. Durand, et al. 1998. Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on glucose metabolism and could ameliorate the lipid profile in type 2 diabetic men. Results of a controlled study. Diabetes Care. 21: 717–724.[Abstract]

68. Brown, J. M., and M. K. McIntosh. 2003. Conjugated linoleic acid in humans: regulation of adiposity and insulin sensitivity. J. Nutr. 133: 3041–3046.[Abstract/Free Full Text]

69. Larsen, T. M., S. Toubro, and A. Astrup. 2003. Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies. J. Lipid Res. 44: 2234–2241.[Abstract/Free Full Text]

70. Garg, A., A. Bonanome, S. M. Grundy, Z. J. Zhang, and R. H. Unger. 1988. Comparison of a high-carbohydrate diet with a high-monounsaturated-fat diet in patients with non-insulin-dependent diabetes mellitus. N. Engl. J. Med. 319: 829–834.[Abstract]

71. Garg, A. 1998. High-monounsaturated-fat diets for patients with diabetes mellitus: a meta-analysis. Am. J. Clin. Nutr. 67 (Suppl.): 577–582.

72. Rivellese, A. A., R. Giacco, S. Genovese, L. Patti, G. Marotta, D. Pacioni, G. Annuzzi, and G. Riccardi. 1990. Effects of changing amount of carbohydrate in diet on plasma lipoproteins and apolipoproteins in type II diabetic patients. Diabetes Care. 13: 446–448.[Abstract]

73. Campbell, L. V., P. E. Marmot, J. A. Dyer, M. Borkman, and L. H. Storlien. 1994. The high-monounsaturated fat diet as a practical alternative for NIDDM. Diabetes Care. 17: 177–182.[Abstract]

74. Garg, A., J. P. Bantle, R. R. Henry, A. M. Coulston, K. A. Griver, S. K. Raatz, L. Brinkley, Y. D. Chen, S. M. Grundy, and B. A. Huet. 1994. Effects of varying carbohydrate content of diet in patients with non-insulin-dependent diabetes mellitus. J. Am. Med. Assoc. 271: 1421–1428.[Abstract/Free Full Text]

75. Lerman-Garber, I., S. Ichazo-Cerro, J. Zamora-Gonzalez, G. Cardoso-Saldana, and C. Posadas-Romero. 1994. Effect of a high-monounsaturated fat diet enriched with avocado in NIDDM patients. Diabetes Care. 17: 311–315.[Abstract]

76. Parillo, M., R. Giacco, A. V. Ciardullo, A. A. Rivellese, and G. Riccardi. 1996. Does a high-carbohydrate diet have different effects in NIDDM patients treated with diet alone or hypoglycemic drugs? Diabetes Care. 19: 498–500.[Abstract]

77. Lopez-Segura, F., F. Velasco, J. Lopez-Miranda, P. Castro, R. Lopez-Pedrera, A. Blanco, J. Jimenez-Pereperez, A. Torres, J. Trujillo, J. M. Ordovas, et al. 1996. Monounsaturated fatty acid-enriched diet decreases plasma plasminogen activator inhibitor type 1. Arterioscler. Thromb. Vasc. Biol. 16: 82–88.[Abstract/Free Full Text]

78. Riccardi, G., and A. A. Rivellese. 1991. Effects of dietary fiber and carbohydrate on glucose and lipoprotein metabolism in diabetic patients. Diabetes Care. 14: 1115–1125.[Abstract]

79. Rivellese, A. A., P. Auletta, G. Marotta, G. Saldalamacchia, A. Giacco, V. Mastrilli, O. Vaccaro, and G. Riccardi. 1994. Long term metabolic effects of two dietary methods of treating hyperlipidaemia. BMJ. 308: 227–231.[Abstract/Free Full Text]

80. Mann, J. 2001. Dietary fibre and diabetes revisited. Eur. J. Clin. Nutr. 55: 919–921.[CrossRef][Medline]

81. Jarvi, A. E., B. E. Karlstrom, Y. E. Granfeldt, I. E. Bjorck, N. G. Asp, and B. O. Vessby. 1999. Improved glycemic control and lipid profile and normalized fibrinolytic activity on a low-glycemic index diet in type 2 diabetic patients. Diabetes Care. 22: 10–18.[Abstract/Free Full Text]

82. Lau, C., K. Faerch, C. Glumer, I. Tetens, O. Pedersen, B. Carstensen, T. Jorgensen and K. Borch-Johnsen. 2005. Dietary glycemic index, glycemic load, fiber, simple sugars, and insulin resistance: the Inter99 Study. Diabetes Care. 28: 1397–1403.[Abstract/Free Full Text]

83. Liese, A. D., M. Schulz, F. Fang, T. M. Wolever, R. B. D'Agostino, K. C. Sparks, and E. J. Mayer-Davis. 2005. Dietary glycemic index and glycemic load, carbohydrate and fiber intake, and measures of insulin sensitivity, secretion, and adiposity in the Insulin Resistance Atherosclerosis Study. Diabetes Care. 28: 2832–2838.[Abstract/Free Full Text]

84. Mann, J. 2004. Free sugars and human health: sufficient evidence for action? Lancet. 363: 1068–1070.[CrossRef][Medline]

85. Poppitt, S. D., G. F. Keogh, A. M. Prentice, D. E. Williams, H. M. Sonnemans, E. E. Valk, E. Robinson, and N. J. Wareham. 2002. Long-term effects of ad libitum low-fat, high-carbohydrate diets on body weight and serum lipids in overweight subjects with metabolic syndrome. Am. J. Clin. Nutr. 75: 11–20.[Abstract/Free Full Text]

86. Elliott, S. S., N. L. Keim, J. S. Stern, K. Teff, and P. J. Havel. 2002. Fructose, weight gain, and the insulin resistance syndrome. Am. J. Clin. Nutr. 76: 911–922.[Abstract/Free Full Text]

87. Daly, M. 2003. Sugars, insulin sensitivity, and the postprandial state. Am. J. Clin. Nutr. 78 (Suppl.): 865–872.

88. Mann, J. I., I. De Leeuw, K. Hermansen, B. Karamanos, B. Karlstrom, N. Katsilambros, G. Riccardi, A. A. Rivellese, S. Rizkalla, G. Slama, et al. for the Diabetes and Nutrition Study Group (DNSG) of the European Association. 2004. Evidence-based nutritional approaches to the treatment and prevention of diabetes mellitus. Nutr. Metab. Cardiovasc. Dis. 14: 373–394.[CrossRef][Medline]

89. Esposito, K., R. Marfella, M. Ciotola, C. Di Palo, F. Giugliano, G. Giugliano, M. D'Armiento, F. D'Andrea, and D. Giugliano. 2004. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. J. Am. Med. Assoc. 292: 1440–1446.[Abstract/Free Full Text]

90. McAuley, K. A., S. M. Williams, J. I. Mann, A. Goulding, A. Chisholm, N. Wilson, G. Story, R. T. McLay, M. J. Harper, and I. E. Jones. 2002. Intensive lifestyle changes are necessary to improve insulin sensitivity: a randomized controlled trial. Diabetes Care. 25: 445–452.[Abstract/Free Full Text]

91. Landers, P., M. M. Wolfe, S. Glore, R. Guild, and L. Phillips. 2002. Effect of weight loss plans on body composition and diet duration. J. Okla. State Med. Assoc. 95: 329–331.[Medline]

92. Brehm, B. J., R. J. Seeley, S. R. Daniels, and D. A. D'Alessio. 2003. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J. Clin. Endocrinol. Metab. 88: 1617–1623.[Abstract/Free Full Text]

93. Parker, B., M. Noakes, N. Luscombe, and P. Clifton. 2002. Effect of a high-protein, high-monounsaturated fat weight loss diet on glycemic control and lipid levels in type 2 diabetes. Diabetes Care. 25: 425–430.[Abstract/Free Full Text]

94. Dumesnil, J. G., J. Turgeon, A. Tremblay, P. Poirier, M. Gilbert, L. Gagnon, S. St-Pierre, C. Garneau, I. Lemieux, A. Pascot, et al. 2001. Effect of a low-glycaemic index-low-fat-high protein diet on the atherogenic metabolic risk profile of abdominally obese men. Br. J. Nutr. 86: 557–568.[Medline]

95. Skov, A. R., S. Toubro, B. Ronn, L. Holm, and A. Astrup. 1999. Randomized trial on protein vs carbohydrate in ad libitum fat reduced diet for the treatment of obesity. Int. J. Obes. Relat. Metab. Disord. 23: 528–536.[CrossRef][Medline]

96. Stern, L., N. Iqbal, P. Seshadri, K. L. Chicano, D. A. Daily, J. McGrory, M. Williams, E. J. Gracely, and F. F. Samaha. 2004. The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial. Ann. Intern. Med. 140: 778–786.[Abstract/Free Full Text]

97. McAuley, K. A., C. M. Hopkins, K. J. Smith, R. T. McLay, S. M. Williams, R. W. Taylor, and J. I. Mann. 2005. Comparison of high-fat and high-protein diets with a high-carbohydrate diet in insulin-resistant obese women. Diabetologia. 48: 8–16.[CrossRef][Medline]

98. McAuley, K. A., K. J. Smith, R. W. Taylor, R. T. McLay, S. M. Williams, and J. I. Mann. 2006. Long-term effects of popular dietary approaches on weight loss and features of insulin resistance. Int. J. Obes. 30: 342–349.[CrossRef][Medline]

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				E. J. Schaefer, J. A. Gleason, and M. L. Dansinger Dietary Fructose and Glucose Differentially Affect Lipid and Glucose Homeostasis J. Nutr., June 1, 2009; 139(6): 1257S - 1262S. [Abstract] [Full Text] [PDF]

				E. Ferrannini and G. Mingrone Impact of Different Bariatric Surgical Procedures on Insulin Action and {beta}-Cell Function in Type 2 Diabetes Diabetes Care, March 1, 2009; 32(3): 514 - 520. [Full Text] [PDF]

				A. M Hodge, D. R English, K. O'Dea, A. J Sinclair, M. Makrides, R. A Gibson, and G. G Giles Plasma phospholipid and dietary fatty acids as predictors of type 2 diabetes: interpreting the role of linoleic acid Am. J. Clinical Nutrition, July 1, 2007; 86(1): 189 - 197. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) All Versions of this Article: R600015-JLR200v1 47/8/1668    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McAuley, K. Articles by Mann, J. Search for Related Content PubMed PubMed Citation Articles by McAuley, K. Articles by Mann, J. Social Bookmarking                      What's this?