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Am Stat ; 45 1 : 54— Google Scholar. Download references. KHA received grants from The Danish Diabetes Association and the Novo Nordisk Foundation. We thank the NUGENOB project steering committee, especially Arne Astrup as the main responsible for the dietary intervention, as well as all participants and employees involved in collecting the data from the 8 NUGENOB study centers.

We also thank Tina Hvidtfeldt Lorentzen for extraction of the DNA and Jette Bork-Jensen and Vincent Appel for bioinformatic assistance.

Section of Metabolic Genetics, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Department of Clinical Epidemiology, Bispebjerg and Frederiksberg Hospitals, Frederiksberg, Denmark. No statistically significant changes in fat cell size were observed in pioglitazone-treated volunteers. Pioglitazone treatment also improves insulin sensitivity and lowers WHR, but this is due to a selective increase in lower body fat.

This confirms a site-specific responsiveness of adipose tissue to TZD and suggests that improvements in insulin sensitivity by pioglitazone are achieved independent of changes in intra-abdominal fat.

Body fat distribution is an important variable in the relationship between overweight and insulin resistance. Intra-abdominal or visceral fat accumulation is more strongly associated with insulin resistance, and insulin resistance can be improved by decreasing this fat depot via diet, exercise, or surgery 1 , 2.

Thiazolidinediones TZDs are also known to improve insulin sensitivity despite paradoxically increasing total fat mass 3 — 5. It has been suggested that redistribution of body fat may contribute to their insulin-sensitizing qualities. Indeed, regional variability in TZD responsiveness has been demonstrated; preadipocytes from subcutaneous fat differentiate more in response to TZD in vitro than visceral adipose tissue 6.

If the same phenomenon occurs in vivo, one would expect selective adipocyte proliferation and thus body fat redistribution.

However, studies of animals and diabetic humans have reported increasing, decreasing, and unchanged visceral and subcutaneous fat depots after TZD administration despite improved insulin sensitivity 3 — 5 , 7 , 8. This suggests that TZD effects on visceral adiposity, if present in vivo, might not contribute to their insulin sensitization.

We assessed the effects of pioglitazone on fat distribution, fat cell size, and the relationship between fat distribution and insulin sensitivity in upper body obesity, a known insulin-resistant state.

Comparison of the effects of pioglitazone with diet and exercise, a standard intervention to improve insulin sensitivity, was performed to place the results in context. Written informed consent was obtained from 68 healthy upper body obese men and premenopausal women. Subjects were nondiabetic, sedentary, and weight stable up to at least 6 months before entering the research program.

If WHR exceeded 0. Exclusion criteria were a history of coronary heart disease, atherosclerosis, known systemic illness, renal or liver failure, clinically diagnosed type 2 diabetes, hypertension requiring medication that could not be safely stopped 2 weeks before the study, smoking, pregnancy, and breast-feeding.

Thirteen volunteers were excluded on the basis of screening laboratory results, 10 volunteers withdrew before starting the program and 6 dropped out for a variety of reasons.

One volunteer was excluded for noncompliance with the diet and exercise program. The remaining 39 volunteers underwent blood testing complete blood count, chemistry panel, and lipid profile , an insulin-modified intravenous glucose tolerance test, CT measures of visceral fat area L 2—3 level 9 , and dual-energy X-ray absorptiometry DEXA DPX-IQ; Lunar Radiation, Madison, WI for body composition assessment before and after the intervention.

Adipose tissue biopsies were taken from femoral and abdominal subcutaneous areas. Oxygen consumption V˙ o 2peak and maximum heart rate were determined by a graded exercise test performed on a Quinton Seattle, WA motor-driven treadmill using a modified Bruce protocol Heart rate and rhythms were monitored continuously via a lead electrocardiogram.

The difference between resting and maximal heart rate defined the heart rate reserve, which was used to determine exercise intensity goals for those in the diet and exercise program see below. After the baseline measurements, the volunteers were randomized to receive 30 mg pioglitazone daily or a diet and exercise program for 18—20 weeks.

The pioglitazone treated volunteers were monitored every 4 weeks for weight, liver function tests, and pill counts. In addition, the diet and exercise group participated in a behavior modification modified LEARN program biweekly and worked with a general clinical research center dietitian every 4 weeks.

After 18—20 weeks, all tests and biopsies were repeated. The CT images were analyzed to distinguish compartmental fat volumes, as previously described 9. Results were combined with data from DEXA 9 to calculate the following fat compartments: total body fat, lower body fat, upper body nonvisceral fat, and visceral intra-abdominal fat Fig.

Subcutaneous fat was aspirated from femoral and abdominal depots under sterile conditions using local anesthesia. Adipocytes were isolated centrifuge and stained with methylene blue to visualize the nuclei.

Histograms were graphically and numerically displayed. Cell volumes were calculated using the Goldrick formula Adipocellular lipid content was calculated as fat cell volume times 0.

The following assays were used: glucose: Hitachi Chemistry Analyzer using the hexokinase reagent Boehringer Mannheim, Indianapolis, IN or the Beckman Glucose Analyzer Beckman Instruments, Fullerton, CA ; insulin: chemiluminiscence method with Access Ultrasensitive Immunoenzymatic Assay system Beckman, Chaska, MN ; C-peptide: direct, double antibody sequential radioimmunoassay Linco Research, St.

Louis, MO ; triglycerides: Hitachi chemistry analyzer using Technicon triglyceride reagent Bayer, Tarrytown, NY. An intravenous injection of 0. Values are expressed as means ± SE. Statistical comparisons of the two groups pioglitazone versus diet and exercise and the responses of the groups to the interventions were done using repeated-measures ANOVA, followed by t tests paired or nonpaired if needed.

Nineteen volunteers 10 men and 9 women completed the diet and exercise intervention and 20 volunteers 10 men and 10 women completed the pioglitazone intervention. The two groups were well matched for age, BMI, WHR, insulin sensitivity parameters, and body composition Tables 1 — 3. C-peptide was significantly correlated with these parameters as well as with BMI 0.

The diet and exercise program induced a weight loss of Proportionately more abdominal than femoral and more visceral than subcutaneous abdominal fat was lost, as evidenced by the changes in WHR, the ratio of visceral fat to subcutaneous abdominal fat area, and the various fat compartments measured by DEXA Tables 1 and 3.

In the pioglitazone group, the average weight gain of 2. There was no change in abdominal fat compartments visceral or upper body nonvisceral. Consistent with the DEXA and CT data, WHR decreased due to increased hip, but not waist, circumference.

The average adipocyte lipid content after the pioglitazone treatment was less in both the femoral and abdominal sites but the difference from baseline was not statistically significant decrease by 0. Decreases in fasting plasma glucose and C-peptide concentrations were similar in both groups.

The changes in serum lipid concentrations were more marked in the diet and exercise group; the only significant between-group difference, however, was for serum total cholesterol Table 2. The greater decrease in insulin in the pioglitazone group is confounded by higher baseline concentrations.

Overnight postabsorptive plasma free fatty acid concentrations were not different between the two groups before or after treatment. Changes in S i were not significantly correlated with changes in body composition in either group results not shown.

In addition, changes in glucose, C-peptide, or S i did not correlate with changes in femoral or abdominal fat cell size in either group. We compared the effects of two insulin-sensitizing regimens, pioglitazone versus diet and exercise, on body composition, body fat distribution, and insulin sensitivity.

Nondiabetic upper body obese adults were studied because of the high prevalence of insulin resistance in this population. The anticipated improvement in S i occurred with each treatment, and the change in body fat compartments in response to diet and exercise was consistent with previous reports.

We unexpectedly found that pioglitazone resulted in the preferential accumulation of lower body fat rather than loss of visceral fat.

Thus, both diet and exercise and pioglitazone resulted in a reduced WHR but the mechanism was quite different. The shift toward a lower body fat distribution by pioglitazone via gain of leg fat, not loss of visceral fat, is consistent with adipose depot-specific responses, but not of the type previously reported.

The lack of change in intra-abdominal adipose tissue area with pioglitazone is consistent with some, but not all, previous findings. Some results apparently contradict each other from a biological point of view. This highlights the marker-value of reported food intake, indicating the presence of unknown or inadequately measured causative factors that are disregarded by converting reported intake of foods into estimated nutrient intake.

Only few of the underlying associations reached statistical significance reflecting the fact that reported frequency of food intake is a weak predictor of waist- and hip circumference compared to covariates such as BMI and age.

The lower number of items on the food frequency questionnaire in might have introduced a bias in the estimated associations between reported intake and circumferences.

However, adjustment for survey year should remove systematic errors. Moreover, when comparing level-specific associations between survey-years we did not find more differences than expected by chance.

A mechanistic interpretation of our results would suggest an association between fat intake and abdominal obesity. Increased use of convenience foods hamburgers, French fried potatoes , generally considered as markers of a diet high in fatty acids, was associated with an increase in WC.

The latter findings are in accordance with reports that highlight the importance of fat quality rather than total amount of dietary fat, although the question of the role of fat intake in the causation of obesity, diabetes and cardiovascular disease is still unresolved [ 36 — 42 ].

Further, our results support evidence suggesting that a diet high in low-fat dairy products and low in fast food and soft drinks is associated with smaller gains in BMI and waist circumference [ 17 , 43 , 44 ]. Previous findings of a negative association between intake of potatoes and WC [ 45 ] could not be confirmed in our population.

In this study, reported food intake is interpreted as marker for a general lifestyle. Any intervention targeted at individuals defined as high risk by the findings in this study, would therefore have to simultaneously aim at these lifestyle factors, rather than only try to modify consumption of a selected food item.

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Halkjaer J, Sorensen TI, Tjonneland A, Togo P, Holst C, Heitmann BL: Food and drinking patterns as predictors of 6-year BMI-adjusted changes in waist circumference. Download references. We are indebted to a previous anonymous reviewer for valuable suggestions.

This study was supported by the Joint Committee of the local county councils of Jämtland, Norrbotten, Västernorrland, Västerbotten "Visare Norr" and a grant by Norrbottensakademin.

The Northern Sweden MONICA Project has been supported by grants from Norrbotten and Västerbotten counties, by the Joint Committee of Northern Sweden Health Care Region, the Swedish Public Health, the Swedish Medical Research Council MFR , the Heart and Chest Foundation, the Stroke Fund, King Gustaf V's and Queen Victoria's foundation, Vårdalstiftelsen, the Social Sciences Research Council.

None of the above-mentioned funding bodies had any influence on study design, data collection, analysis or interpretation; writing or decision to submit the manuscript for publication. Department of Medicine, Kalix Hospital, Kalix, Sweden.

Behavioural Medicine, Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. Department of Medicine, Sunderby Hospital, Luleå, Sweden. Medicine, Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.

Epidemiology and Public Health Sciences, Umeå University, Umeå, Sweden. Odontology, Cariology, Umeå University, Umeå, Sweden. Nutrition Research, Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.

You can also search for this author in PubMed Google Scholar. Correspondence to Benno Krachler. BK was responsible for the design of the study, performed the statistical analysis and drafted the manuscript. ME contributed in its design and contributed to the manuscript. HS contributed to design and statistical analysis.

IJ participated in data collection and validation. GH participated in data collection and validation and contributed to the manuscript.

A priori-defined diet quality indices, biomarkers and risk for type 2 diabetes in five ethnic groups: the Multiethnic Cohort. Download references. We thank the Multiethnic Cohort Study participants who generously donated their time and effort and we acknowledge the excellence performance of the study staff.

Funding was provided by the grants from the US National Institutes of Health P01CA, U01CA, P30CA, UL1TR University of Hawaii Cancer Center, Honolulu, HI, USA. Gertraud Maskarinec, Lisa A. Namatame, Minji Kang, Steven D.

Buchthal, John A. Shepherd, Lynne R. Wilkens, Carol J. University of Southern California, Los Angeles, CA, USA. You can also search for this author in PubMed Google Scholar. LLM, UL, and LRW designed the overall research project; CJB developed nutritional support and the diet scores; SDB, TE, and JAS provided essential services in imaging and adiposity measures; LAN, MK, and GM analyzed the data and drafted the paper; LRW provided statistical advice; all authors contributed to data interpretation and critical revisions.

GM had primary responsibility for the final content. Correspondence to Gertraud Maskarinec. Reprints and permissions. Maskarinec, G. et al. Differences in the association of diet quality with body fat distribution between men and women.

Eur J Clin Nutr 74 , — Download citation. Received : 10 October Revised : 06 January Accepted : 14 January Published : 24 January Issue Date : October Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content Thank you for visiting nature. nature european journal of clinical nutrition articles article. Subjects Biomarkers Risk factors. Results Mean HEI scores were higher for women than men at cohort entry Conclusions The inverse association of diet quality with adiposity was similar in both sexes, but diet quality appeared to have a stronger influence on VAT in women than men.

Access through your institution. Buy or subscribe. Change institution. Learn more. References Lee H, Pak YK, Yeo E-J, Kim YS, Paik HY, Lee SK.

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Article CAS Google Scholar Nazare JA, Smith JD, Borel AL, Haffner SM, Balkau B, Ross R, et al. Article CAS Google Scholar Ellen W, Demerath SSS, Rogers Nikki, Lee Miryoung, Reed Derek, Choh AudreyC, et al. Only in overweight women was physical inactivity associated with metabolic syndrome independent of all regional depots.

Thus, adjusting results for smoking and physical activity did not appear to confound associations between regional fat depots and metabolic syndrome. The overall prevalence of the metabolic syndrome in this older cohort was similar to that reported for older adults in the United States 4 and nearly double that reported for middle-aged adults.

With an oversampling of blacks, we were able to determine that, although the overall prevalence of metabolic syndrome was not different between blacks and whites, there were racial differences in the prevalence of specific criteria that define metabolic syndrome.

Specifically, blacks had higher rates of hypertension and abnormal glucose metabolism, whereas whites had higher rates of dysregulated lipid metabolism. The development of metabolic syndrome involves an interaction of complex parameters including obesity, regional fat distribution, dietary habits, and physical inactivity, 5 so it is not yet entirely clear how to interpret these racial differences.

Nevertheless, this suggests that the cause of metabolic syndrome is different in blacks and whites. The prevalence of metabolic syndrome, not surprisingly, was much higher among the obese.

However, differences in generalized obesity by BMI or total body fat criteria in those with metabolic syndrome were at best modest. Obese women with the metabolic syndrome actually had a lower proportion of body fat than obese women without metabolic syndrome.

Regional fat distribution, particularly visceral abdominal AT and intermuscular AT, clearly discriminated those with the metabolic syndrome, particularly among the nonobese.

This implies that older men and women can have normal body weight, and even have relatively lower total body fat, but still have metabolic syndrome, due to the amount of AT located intra-abdominally or interspersed within the musculature. What makes this observation more remarkable is that these associations were much less robust or even nonexistent for subcutaneous AT.

More subcutaneous AT in the thighs of obese men and women was actually associated with a lower prevalence of metabolic syndrome. This is consistent with previous reports demonstrating that total leg fat mass, most of which was subcutaneous AT, is inversely related to cardiovascular disease risk.

Albu et al 18 suggested that similar levels of visceral AT in blacks and whites may confer different metabolic risk. Our data support the contention by some that BMI may not accurately reflect the degree of adiposity in certain populations.

The current results parallel our previous observation in the Health ABC cohort that visceral and intermuscular AT strongly predict insulin resistance and type 2 diabetes. These associations between regional fat deposition and metabolic dysregulation are also consistent with other previous findings in both middle-aged and older adults.

Although we included in the analysis physical activity as a potential confounder to our associations, it is possible that the self-reported estimates for physical activity were not sensitive enough to detect significant associations with metabolic syndrome demonstrated in previous studies.

However, predictors of the incidence of metabolic syndrome can be examined when data become available in this longitudinal study. There are several possible explanations for the observed association between excess visceral fat accumulation and the metabolic syndrome. Visceral fat is thought to release fatty acids into the portal circulation, where they may cause insulin resistance in the liver and subsequently in muscle.

A parallel hypothesis is that adipose tissue is an endocrine organ that secretes a variety of endocrine hormones such as leptin, interleukin 6, angiotensin II, adiponectin, and resistin, which may have potent effects on the metabolism of peripheral tissues.

In conclusion, excess accumulation of either visceral abdominal or muscle AT is associated with a higher prevalence of metabolic syndrome in older adults, particularly in those who are of normal body weight.

This suggests that practitioners should not discount the risk of metabolic syndrome in their older patients entirely on the basis of body weight or BMI. Indeed, generalized body composition, in terms of both BMI and the proportion of body fat, does not clearly distinguish older subjects with the metabolic syndrome.

Moreover, racial differences in the various components of the metabolic syndrome provide strong evidence that the cause of the syndrome likely varies in blacks and whites. Thus, the development of a treatment for the metabolic syndrome as a unifying disorder is likely to be complex.

Correspondence: Bret H. Goodpaster, PhD, Department of Medicine, North MUH, University of Pittsburgh Medical Center, Pittsburgh, PA bgood pitt.

Dr Goodpaster was supported by grant KAG from the National Institute on Aging, National Institutes of Health. full text icon Full Text.

Download PDF Top of Article Abstract Methods Results Comment Article Information References. Figure 1. View Large Download. Table 1. Characteristics of Men and Women With and Without Metabolic Syndrome. Regional Fat Distribution According to Metabolic Syndrome Status. Abdominal AT in Men and Women With and Without Metabolic Syndrome According to a Revised Definition Omitting Waist Circumference.

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A unified approach to mixed linear models. Am Stat ; 45 1 : 54— Google Scholar. Download references. KHA received grants from The Danish Diabetes Association and the Novo Nordisk Foundation.

We thank the NUGENOB project steering committee, especially Arne Astrup as the main responsible for the dietary intervention, as well as all participants and employees involved in collecting the data from the 8 NUGENOB study centers.

We also thank Tina Hvidtfeldt Lorentzen for extraction of the DNA and Jette Bork-Jensen and Vincent Appel for bioinformatic assistance. Section of Metabolic Genetics, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Department of Clinical Epidemiology, Bispebjerg and Frederiksberg Hospitals, Frederiksberg, Denmark. Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark. You can also search for this author in PubMed Google Scholar. Correspondence to M Svendstrup. Supplementary Information accompanies this paper on International Journal of Obesity website. Reprints and permissions.

Svendstrup, M. et al. Genetic risk scores for body fat distribution attenuate weight loss in women during dietary intervention.

Int J Obes 42 , — Download citation. Received : 11 July Revised : 08 September Accepted : 12 October Published : 16 November Issue Date : March Anyone you share the following link with will be able to read this content:.

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Subjects Genetic variation Genetics Obesity Risk factors Weight management. Abstract Objective: The well-established link between body fat distribution and metabolic health has been suggested to act through an impact on the remodeling capacity of the adipose tissue.

Design: We included participants women and men from the NUGENOB multi-center week diet intervention study with weekly weight measurements.

Results: The GRS total and GRS women attenuated weight loss in women. Conclusion: Our findings suggest that genetic variants influencing body fat distribution attenuate weight loss in women independently on the effect on WHR.

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