Tuesday, February 21, 2012, Cleveland: With 1 in 5 overweight Americans suffering from chronic kidney disease, Cleveland Clinic researchers analyzed the nutritional and lifestyle habits of overweight adults, finding that their methods included diets and diet pills that may cause further kidney damage.

The study findings, published online this month in the International Journal of Obesity, came from an analysis of food choices and lifestyle habits of 10,971 overweight adults taken from the National Health and Nutrition Examination Survey (NHANES), a federally-administered assessment of the overall health and nutritional status of Americans.

Of the overweight and obese patients with kidney disease included in the survey, 50 percent reported that they had attempted to lose weight in the past year. The survey showed that, on average, obese Americans with kidney disease consume protein in amounts that are above the recommended levels prescribed by the National Kidney Foundation for chronic kidney disease patients.

The typical American diet each day includes approximately 1.2g of protein per kilogram of body weight. Patients with CKD are advised to consume 0.6g to 0.75g protein per kilogram of body weight each day and popular high-protein diets may call for up to 1.9g per kilogram of body weight.

“People who are overweight or obese are at higher risk for chronic kidney disease and there is a great need to define what the appropriate lifestyle changes and weight loss modalities are for protecting kidney function,” said Sankar Navaneethan, M.D., a nephrologist in the Glickman Urological and Kidney Institute at Cleveland Clinic and lead author of the study. “Rather than using fad diets or diet pills, overweight and obese people with kidney disease may adopt a weight loss plan that incorporates a low-protein, low-calorie diet, regular physical activity and close follow-up by their physicians.”

The survey asked patients whether they participated in regimens that included diet or exercise or both, but the specific program, such as a high-protein diet or low-protein diet, was not named. The survey also found that eight percent of weight loss seekers with CKD used medications as part of their weight loss regimen. Certain weight loss methods, especially high-protein diets and weight loss medications are not recommended in people with kidney disease as they may lead to further kidney damage.

The authors recommend further studies designed to identify safe treatment strategies for weight loss with regards to protecting kidney function.

According to the Centers for Disease Control and Prevention, more than 10 percent of adults aged 20 or older in the U.S., or more than 20 million people, have chronic kidney disease (CKD), a condition that describes the progressive worsening of kidney function. It is often found in patients who have diabetes or hypertension, and can exist without symptoms until it progresses to severe levels. When CKD progresses to end-stage renal disease, patients typically require treatment through dialysis or transplantation. The prevalence of the disease is rapidly growing as is the cost burden. Medicare costs in the U.S. for the care of patients with end-stage renal disease has risen from $12.2 billion in 2000 to $20.8 billion in 2007.

Source: Eurekalert

More on Weight Control from WeightControl.com

Author Interview: Frédéric Fumeron, PhD

UFR de Médecine Université Paris Diderot – Paris

What are the main findings of the study?

The Peroxysome proliferator activity receptor gamma (PPARg) is involved in adipose tissue and lipid metabolisms. There is a common genetic variation modifying the protein, Pro12Ala.

In a large cohort study, with a 9-year follow-up, DESIR, a high fat consumption (the highest tertile in percentage of energy intake) is associated with an increase in type 2 diabetes risk in people carrying the common genotype ProPro only, but not in those carrying Ala.

However those carrying the Ala Ala genotype had a higher Body Mass Index when consuming a high fat diet.

Were any of the findings unexpected?

The main results of our study might seem paradoxical. A high fat intake increases BMI in AlaAla individuals but increases T2D risk in ProPro homozygotes.

This may be in line with the effects of the PPARg agonists, the glitazones which are drugs for treatment of diabetes that increase body weight.

Also another genetic variant highly linked to Pro12Ala has paradoxically an opposite effect on BMI, for unknown reason.

What should clinicians and patients take away from this study?

1) the effects of dietary intake might be different among individuals, depending on the genetic background. But it is too early to make prescriptions according to the genotype yet.

2) in some people, a high fat diet may increase the BMI without increasing their type 2 diabetes risk.

What recommendations do you have for future research as a result of your study?

Future research is needed for understanding the mechanisms of these interactions. The emphasis should be put on the specific fatty acid composition of the diet too.

Reference:

Dietary fat intake and polymorphisms at the PPARG locus modulate BMI and type 2 diabetes risk in the D.E.S.I.R. prospective study.

Lamri A, Abi Khalil C, Jaziri R, Velho G, Lantieri O, Vol S, Froguel P, Balkau B, Marre M, Fumeron F.
Int J Obes (Lond). 2012 Feb;36(2):218-24. doi: 10.1038/ijo.2011.91. Epub 2011 May 3.

Author Interview: Professor P Buono
Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali
Università degli Studi di Napoli ‘Parthenope’, Via Medina 40
Naples 80133, Italy

What are the main findings of the study?

Recently, UCP3 gene as been  proposed as a candidate gene for the human obesity.

We found four novel mutation in UCP3 gene associated to severe obesity
in a cohort of 200 children.

Our data support the notion that protein UCP3 is
involved in long-chain fatty acid metabolism in mitochondria and in
the prevention of cytosolic triglyceride storage. We also provide
evidence that telmisartan positively affected HbA1c, total and
low-density lipoprotein cholesterol and hypertension in type 2
diabetes patients, improves palmitate oxidation in cells expressing
wt or mutant UCP3 proteins.

Were any of the findings unexpected?

The findings were not unexpected, but our study provide for the first time a functional analyses of wt and mutant UCP3 proteins in in-vitro.

Furthermore, we provides evidences that telmisartan improves palmitate oxidation also in cells expressing the dominant-negative UCP3 mutant proteins.

What should clinicians and patients take away from this study?

Our in-vitro data suggests that telmisartan may be useful in subjects in
whom fatty acid metabolism is severely impaired.

What recommendations do you have for future research as a result of
your study?

Our future aim is to enlarge our cohort study and to
investigate if the activity of mutant-negative UCP3 proteins is
correlated with dietary fat intake and/or with the degree of daily
physical activity.

Reference:

Four novel UCP3 gene variants associated with childhood obesity: effect on fatty acid oxidation and on prevention of triglyceride storage.

Musa CV, Mancini A, Alfieri A, Labruna G, Valerio G, Franzese A, Pasanisi F, Licenziati MR, Sacchetti L, Buono P.
Int J Obes (Lond). 2012 Feb;36(2):207-17. doi: 10.1038/ijo.2011.81. Epub 2011 Apr 19.

Professor J-H Nam,
Department of Biotechnology
The Catholic University of Korea
43-1 Yeokgok-dong, Wonmi-gu
Bucheon, 420-743, Korea

What are the main findings of the study?

We found that Adenovirus 36 (Ad36) which can induce human obesity was associated with some novel pathways, including the PPAR gamma, inflammation, and mitochondria, raising the possibility that these pathways may be key regulators of Ad36 induced adipogenesis.
Moreover, human mesenchymal stem cells (hMSCs) could be good model system to research Ad36.

Were any of the findings unexpected?

It is surprising for us that mitochondria pathway may be activated in Ad36 induced obesity.
The induction of mitochondria function may be related with the improvement of hyperglycemia.

What should clinicians and patients take away from this study?

Ad36 is considered as obesity agent for human. However, Ad36 infection seems to be a double-edged sword because Ad36 infection can trigger the obesity, whereas it can improve the glycemic control due to several reasons including induction of mitochondria activity.

What recommendations do you have for future research as a result of your study?

We will focus on the role of mitochondria in Ad36 infection for further study.

Reference:

Novel genes and cellular pathways related to infection with adenovirus-36 as an obesity agent in human mesenchymal stem cells.

Na HN, Kim H, Nam JH.

Department of Biotechnology, The Catholic University of Korea, Bucheon, Korea.
Int J Obes (Lond). 2012 Feb;36(2):195-200. doi: 10.1038/ijo.2011.89. Epub 2011 May 3.

Effectiveness of interventions for reducing diabetes and cardiovascular disease risk in people with metabolic syndrome: systematic review and mixed treatment comparison meta-analysis 

Author Interview  Dr. Laura Gray, BSc (Hons), MSc, PhD.

Lecturer of Population and Public Health Sciences
University of Leicester

What are the main findings of the study?

All three anti-obesity drugs gave modest weight and BMI reductions, with rimonabant and sibutramine (which are both now unlicensed in the UK) giving the greatest reductions.

Lifestyle advice also reduced weight at 6 and 12 months compared to placebo but not to the same extent as the pharmacological interventions.

Were any of the findings unexpected?

These finding were not unexpected, but this is the first time all the evidence for the 3 anti-obesity drugs have been synthesized in a single analysis.

What should clinicians and patients take away from this study?

Orlistat is the only drug currently approved worldwide for the long-term treatment of obesity. In clinical practice, Orlistat should be considered to aid weight reduction with lifestyle interventions in those individuals who have not been successful in reducing their weight with lifestyle alone.

What recommendations do you have for future research as a result of your study?

The effectiveness of the withdrawn interventions – sibutramine and rimonabant – suggests that more effective drugs may be available in the future if the side effect risk can be alleviated.

Reference:

Effectiveness of interventions foe reducing diabetes and cardiovascular disease risk in people with metabolic syndrome: systematic review and mixed treatment comparison meta-analysis.

Dunkley AJ, Charles K, Gray LJ, Camosso-Stefinovic J, Davies MJ, Khunti K.
Diabetes Obes Metab. 2012 Jan 27. doi: 10.1111/j.1463-1326.2012.01571.x.

Author Interview: Charmaine S. Tam, PhD
6400 Perkins Road, Baton Rouge, Louisiana

What are the main findings of the study?

It is well-established that obesity is a state of low-grade inflammation. Fat tissue, especially in obese people, secretes inflammatory mediators into the circulation which may have an influence on developing future diabetes. We examined whether muscle tissue in obese people with type 2 diabetes or elderly subjects also have increased inflammation.

Our study found low levels of inflammation in muscle tissue in obese people with type 2 diabetes, which were unchanged after a 9-month exercise program. We also found little evidence of inflammation in young compared to elderly people.

Were any of the findings unexpected?

Yes, there have been a few studies in animal models and 1 study in humans which have shown increased inflammation in muscle tissue in obese people.

In contrast, our study using the same methods, found low levels of inflammation in muscle tissue from obese people.

What should clinicians and patients take away from this study?

This research is still preliminary and is only the second study in humans to examine inflammation in muscle tissue.

What recommendations do you have for future research as a result of your study?

Further studies need to replicate this study to examine whether muscle tissue is a significant source of inflammation in obese people.

Overall, fat tissue still remains the main source of inflammatory mediators in obese people. Decreasing fat mass, and therefore inflammation, will help reduce metabolic and cardiovascular risk in obese people.

Reference:

Low macrophage accumulation in skeletal muscle of obese type 2 diabetics and elderly subjects.

Tam CS, Sparks LM, Johannsen DL, Covington JD, Church TS, Ravussin E.
Obesity (Silver Spring). 2012 Feb 8. doi: 10.1038/oby.2012.24. [Epub ahead of print]

Author Interview: Mengmeng Du, MSc

Doctoral candidate
Department of Epidemiology
Harvard School of Public Health
677 Huntington Avenue Boston, MA 02115

What are the main findings of the study?

We examined associations among physical activity, sedentary behavior, and leukocyte telomere length in 7,813 women aged 43-70 years. Independent of body mass, greater total and moderate- or vigorous-intensity activities were associated with longer telomeres. Moreover, 2-4 hours per week of moderate or vigorous activities appeared beneficial, with the difference in telomere length corresponding to 4.4 years of aging when comparing active with inactive women. More sedentary participants had telomere length similar to that of their less sedentary counterparts.

Were any of the findings unexpected?

We hypothesized that increasing activity would associate with longer telomeres, but were surprised to observe that moderate amounts of activity conferred similar benefits as the highest. There was no additional increase in telomere length for the most active compared with moderately active women. We hypothesized that this may be because moderate amounts of regular activity induce adaptive increases in antioxidant defenses in the body, while too much activity may generate excess levels of oxidative stress, which in turn accelerates telomere attrition.

What should clinicians and patients take away from this study?

Leukocyte telomere length is a potential indicator of cellular aging and studies show links between telomere length and the development of many chronic diseases. Thus, it is important to identify modifiable lifestyle factors that influence telomere dynamics. Our findings provide insight into the understanding of how regular moderate exercise corresponding to current US guidelines (2.5-5 hours/week) may influence health in a population of middle-aged and older women. If our findings are confirmed, this knowledge provides clinicians with an important message for the promotion of regular physical activity to their patients: Exercise – even in moderate amounts – may benefit health on the cellular level.

What recommendations do you have for future research as a result of your study?

The cross-sectional design of our study precludes us from establishing whether longer telomeres are a cause or consequence of increased activity.  In addition, we assessed telomere length using a single measure at one time point, which prevented us from directly examining telomere attrition. Our findings warrant further investigation in large prospective studies with detailed activity and sedentary behavior assessment and repeated measurements of telomere length over time. This will help establish whether regular activity can reduce the rate of telomere shortening over time, which has important biological and public health implications.

Reference:

Physical Activity, Sedentary Behavior, and Leukocyte Telomere Length in Women.

Du M, Prescott J, Kraft P, Han J, Giovannucci E, Hankinson SE, De Vivo I.
Am J Epidemiol. 2012 Feb 1. [Epub ahead of print]

Author Interview: Charmaine S. Tam, PhD
6400 Perkins Road, Baton Rouge, Louisiana 70808

What are the main findings of the study?

Collagen, long touted for preserving healthy, wrinkle-free skin, might also correlate significantly with lower body mass index (BMI). Previous studies in adults with obesity and rodent models reveal increased fibrosis, ie. excess collagen deposition in fat tissue. Using biopsies collected from 65 healthy weight and overweight children, our study shows distinct differences in collagen deposition in fat tissue between adults and children. Indeed, in children the more collagen you have in your fat tissue, the lower your BMI.

These preliminary findings suggest that in children, the presence of collagen in fat tissue acts to inhibit fat tissue expansion, whereas its absence allows for fat tissue growth.

What should clinicians and patients take away from this study?

Unlike in obese adults where excess collagen deposition in fat tissue is a pathological response, collagen in fat tissue in children is part of a normal physiological process associated with fat tissue growth.

What recommendations do you have for future research as a result of your study?

The results from the current study may provoke future studies examining collagen and extracellular matrix remodeling in fat tissue children. We would like to utilize a more thorough investigation of body composition, measure additional markers of fat tissue remodeling and perform investigations in more obese children.

Reference:

Adipose Tissue Remodeling in Children: The Link between Collagen Deposition and Age-Related Adipocyte Growth.

Charmaine S. Tam, Joan Tordjman, Adeline Divoux, Louise A. Baur, and Karine Clément
JCEM jc.2011-2806; doi:10.1210/jc.2011-2806

Author Interview: Stamatis Efstathiou, MD, MSc, PhD
Senior Consultant in Internal Medicine & Hypertension
Center for Cardiovascular Disease Prevention
Hygeias Melathron Infirmary
Athens, Greece

What are the main findings of the study?

The prevalence of metabolic syndrome in adolescence has gradually increased to approximately 10% in the United States and Western Europe. Because it is strongly associated with adult metabolic syndrome, subclinical atherosclerosis, and type 2 diabetes mellitus, the early detection of children at high risk may have potential clinical impact.

After assessment of an overall urban population of 2361 white children and adolescents over a 10-year period, the present study showed the coexistence of low birth weight (< 10th percentile) and small birth head circumference (< 10th percentile) together with parental (in at least 1 parent) overweight or obesity to predict metabolic syndrome in adolescence with a sensitivity of 91% and a specificity of 98%.

Were any of the findings unexpected?

A rather unexpected finding was that birth weight/head circumference and parental overweight/obesity appeared more influential for risk of metabolic syndrome than children’s weight at age 6-8 in the population studied.

In particular, while a greater proportion of overweight/obese children already existed at age 6-8 among participants who developed metabolic syndrome (36%) than among those who did not (20%), the prevalence of overweight/obesity increased in the time interval between 6-8 and 12-15 years to 90% in the former as compared to 25% in the latter group.

Thus, it may be argued that the period between childhood and adolescence was the most critical for the increase in the weight of children who developed metabolic syndrome in adolescence.

What should clinicians and patients take away from this study?

The proposed score identifies a high-risk group, whereas the finding that 75% of children who met the International Diabetes Federation provisional definition of metabolic syndrome at age 6-8 finally developed metabolic syndrome in adolescence reveals an important target for individual intervention that applies to a small group of younger children.

However, although weight at 6-8 years did not track well enough in the Greek children studied to identify future weight, the increase in obesity was critical for the remainder of the cohort. In this respect, the complementary importance of both population-based and individual prevention strategies should be taken into account when designing health policies.

Prevention and management metabolic syndrome in adolescence could not be specific to the syndrome per se, but rather should be focused on the underlying central disorder of overweight and abdominal obesity and considered as a matter that involves the entire family. With regard to intervention, the prevention of excess weight gain in preadolescence (i.e., between early childhood and adolescence) may be recommended on the basis of the above data.

What recommendations do you have for future research as a result of your study?

Our findings should be replicated in other settings with varying dietary habits, physical activity, and socioeconomic and cultural patterns, as well as with pretest probabilities different from those of our derivation cohort, in which approximately one third of parents were overweight/obese.

Likewise, since our analysis did not include potentially crucial factors that could influence offspring’s metabolic profile (e.g., attending schools of lower academic grading, parental education level and socioeconomic status, or second-hand smoke exposure at home), large-scale validation addressing such issues is needed before routine application of the score.

Moreover, specially designed research is required to identify with appropriate methodology the critical period for subsequent development of metabolic syndrome, because this may be more important than having a predictive risk score.

Reference:

Metabolic Syndrome in Adolescence: Can it be Predicted from Natal and Parental Profile? The Prediction of Metabolic Syndrome in Adolescence (PREMA) Study

Stamatis P. Efstathiou, Irini I. Skeva, Evi Zorbala, Evangelos Georgiou, andTheodore D. Mountokalakis
Circulation. 2012;CIRCULATIONAHA.111.034546
published online before printJanuary 12 2012,
doi:10.1161/CIRCULATIONAHA.111.034546

Author Interview: Inga Peter, PhD

Associate Professor
Department of Genetics & Genomic Sciences
Mount Sinai School of Medicine
1425 Madison Avenue, Box 1498
New York, NY 10029

What are the main findings of the study?

The main findings of the study are that overweight or obese individuals with type 2 diabetes who participated in the Look AHEAD clinical trial of intensive lifestyle intervention , involving caloric restriction and physical activity, carried a heavier load of genetic risk variants associated with diabetes than persons without  diabetes or obesity. Also, we showed that at baseline, individuals who carry one or two copies of the diabetes-risk TCF7L2 gene have lower body mass index compared to their non-carrier counterparts. In addition, we detected only a small association of genetic variants that increase risk of type 2 diabetes with the success of 1-year weight loss.

Were any of the findings unexpected?

Yes, we hypothesized that genetic variants that predispose to type 2 diabetes would make it harder for the carriers to lose weight during caloric restriction in a setting of type 2 diabetes, but it was not the case.

What should clinicians and patients take away from this study?

Clinicians and patients should learn that intensive lifestyle intervention is very effective for weight reduction independent of genetic burden associated with diabetes risk and that carriers of these risks can benefit from a weight loss intervention almost as much as non-carriers.

What recommendations do you have for future research as a result of your study?

Given a significant variation in the weight loss among individuals receiving a standardized intensive lifestyle intervention, our results suggest the existence of novel genomic regions that may be distinct from the diabetes-susceptibility genes but that enhance or mitigate weight loss during caloric restriction in individuals with type 2 diabetes. These variants should be explored through unbiased genome-wide screening studies.

Reference:

Association of Type 2 Diabetes Susceptibility Loci with One-Year Weight Loss in the Look AHEAD Clinical Trial

I. Peter, J.M. McCaffery, A. Kelley-Hedgepeth, H. Hakonarson, S. Reis, L.E. Wagenknecht, A.S. Kopin and G.S. Huggins for the Genetics Subgroup of the Look AHEAD Study

Obesity doi:10.1038/oby.2012.11; accepted article preview online February 6, 2012