[fgummett]

Lifestyle choices to blame for insulin resistance more than genes: study

Lifestyle choices, such as diet and exercise, may have more influence on the development of insulin resistance than heredity, suggests new research.

Insulin resistance occurs when the body produces too little of the hormone insulin and fails to effectively regulate the metabolism of fats, proteins and sugars. The condition can lead to diabetes.

The study, published online Wednesday in the American Journal of Physiology Endocrinology and Metabolism, was conducted by researchers at the Helsinki University Central Hospital and the University of Helsinki.

They studied identical twins born between 1975 and 1979 to determine the impact of lifestyle choices on their genes.

Fourteen pairs of the twins had radically differing body weights, with one twin obese and the other a normal weight.

All were measured for body insulin sensitivity, body composition and heart fitness levels. The obese twins had lower insulin sensitivity and poorer fitness levels than their leaner siblings.

Researchers also found that the expression of genes that help cells in the body produce energy were impaired in those who did not exercise regularly and were obese. This condition in turn made it more difficult to lose weight, leading to additional weight gain.

"The study shows that independent of genetic factors, obesity is associated with poor fitness, low insulin sensitivity and decreased transcript levels of genes involved in mitochondrial oxidative phosphoration," the process by which gene expression is altered, write the authors.

The authors do not rule out the role of genetic factors in altering gene expression. They say that more study is needed.

"Fourteen pairs of twins" = only 28 test subjects... more study is needed.

This appears to based on the assumption that poor choices caused the obesity in the first place... perhaps it was BS dysregulation that lead to overeating that lead to the obesity that lead to the insulin resistance? Do we know the root cause of Type 2 D?

Researchers also found that the expression of genes that help cells in the body produce energy were impaired in those who did not exercise regularly and were obese.

Again.. chicken and egg... what if the impaired expression of genes that produce energy lead to less exercise and resultant weight gain?

[fgummett]

I found a web-site for the American Journal of Physiology Endocrinology and Metabolism... but I am so far unable to find this article in the recent publications. Anyone?

But I did find this one from 1997:

Negative energy balance with exercise in identical twins: plasma glucose and insulin responses

J. M. Oppert, A. Nadeau, A. Tremblay, J. P. Despres, G. Theriault and C. Bouchard
Nutrition Department, Hotel-Dieu Hospital, Paris, France.

The effects of long-term (93 days) negative energy balance on plasma glucose and insulin were investigated by means of exercise with constant energy intake in seven pairs of young sedentary male identical twins. Results showed a significant decrease in fasting (-24%, P < 0.02) and postprandial insulin (-16%, P < 0.05). Fasting and postprandial plasma glucose and glucagon were not modified. Mean glucose disposal rate measured during a euglycemic-hyperinsulinemic clamp performed in five twin pairs was increased by 34% (P = 0.13). No significant intrapair similarity was found for the responses of fasting and postprandial insulin levels and of glucose disposal rate. Changes in glucose disposal rate were significantly greater in high compared with low losers for computerized tomography-measured abdominal visceral fat (3.0 +/- 1.1 vs. 0.3 +/- 0.5 mg x kg(-1) x min(-1), P < 0.05) despite similar losses in total body fat. We conclude that 1) a long-term negative energy balance generated by exercise training significantly reduces plasma insulin levels, whereas insulin sensitivity tends to be improved; 2) training-induced changes in insulin sensitivity are associated with changes in abdominal visceral fat; and 3) data from this experiment conducted with a small number of twin pairs suggest that the genotype does not seem to be a major determinant of the changes in insulin levels and sensitivity brought about by negative energy balance with exercise.

If I read this correctly is suggests (also with a small sample group) that identical twins do not react the same with exercise..?

[volleyball]

This is the article

Am J Physiol Endocrinol Metab (May 6, 2008). doi:10.1152/ajpendo.00580.2007
This Article
Accepted on April 22, 2008
Acquired obesity and poor physical fitness impair expression of genes of mitochondrial oxidative phosphorylation in monozygotic twins discordant for obesity
Linda Mustelin1*, Kirsi H Pietilainen2, Aila Rissanen3, Anssi Raimo Sovijarvi4, Paivi Piirila5, Jussi Naukkarinen6, Leena Peltonen7, Jaakko Kaprio8, and Hannele Yki-Jarvinen9

1 Department of Public Health, Twin Research Unit, University of Helsinki, Mannerheimintie 172, Helsinki, 00014, Finland; Department of Laboratory Medicine, Division of Clinical Physiology and Nuclear Medicine, Helsinki University Central Hospital, Helsinki, Finland
2 Department of Public Health, Twin Research Unit, University of Helsinki, Mannerheimintie 172, Helsinki, 00014, Finland; Obesity Research Unit, Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland; Department of Medicine, Division of Diabetes, Helsinki University Central Hospital, Helsinki, Finland
3 Obesity Research Unit, Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland
4 Department of Laboratory Medicine, Division of Clinical Physiology and Nuclear Medicine, Helsinki University Central Hospital, Helsinki, Finland
5 Department of Laboratory Medicine, Division of Clinical Physiology and Nuclear Medicine, Helsinki University Central Hospital, Helsinki, Finland; Helsinki, Finland
6 Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
7 Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland; Department of Medical Genetics and Research Program of Molecular Medicine, University of Helsinki, United States
8 Finnish Twin Cohort Study, Department of Public Health, University of Helsinki, Helsinki, Finland; Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland
9 Department of Medicine/Division of Diabetes, University of Helsinki, Haartmaninkatu 4, FIN-00290 Helsinki, Finland; Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland

* To whom correspondence should be addressed. E-mail: linda.mustelin@helsinki.fi.

Defects in expression of genes of oxidative phosphorylation in mitochondria have been suggested to be a key pathophysiological feature in familial insulin resistance. We examined whether such defect can arise from lifestyle-related factors alone. Fourteen obesity-discordant (BMI difference 5.2 ± 1.8 kg/m2) and 10 concordant (1.0 ± 0.7 kg/m2) MZ twin pairs aged 24-27 yr were identified among 658 MZ pairs in the population-based FinnTwin16 study. Whole body insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp technique. Transcript profiles of mitochondrial genes were compared using microarray data of fat biopsies from discordant twins. Body composition of twins was determined using DEXA and maximal oxygen uptake (VO2max) and working capacity (Wmax) using a bicycle ergometer exercise test with gas exchange analysis. The obese co-twins had lower insulin sensitivity than their non-obese counterparts (M-value 6.1 ± 2.0 mg/kgLBM·min vs. 9.2 ± 3.2 mg/kgLBM·min, P<0.01). Transcript levels of genes involved in the oxidative phophorylation pathway (GO:0006119) in adipose tissue were lower (P<0.05) in the obese as compared to the non-obese co-twins. The obese co-twins were also less fit, as measured by VO2max (50.6 ± 6.5 ml/kgLBM·min vs. 54.2 ± 6.4 ml/kgLBM·min, for obese vs. non-obese, P<0.05), Wmax (3.9 ± 0.5 W/kgLBM vs. 4.4 ± 0.7 W/kgLBM, P<0.01) and also less active, by the Baecke leisure-time physical activity index (2.8 ± 0.5 vs. 3.3 ± 0.6, P<0.01). This would imply that acquired poor physical fitness is associated with defective expression of the oxidative pathway components in adipose tissue mitochondria.

link is Acquired obesity and poor physical fitness impair expression of genes of mitochondrial oxidative phosphorylation in monozygotic twins discordant for obesity -- Mustelin et al., 10.1152/ajpendo.00580.2007 -- AJP - Endocrinology and Metabolism

[fgummett]

Good find... Thanks

[Scrabblechick]

Hmmm... And what about identical twins who develop T2 within 1 year of each other? Here are the stats: each twin is 6'0, and weighs between 190-210 pounds. Both are basketball coaches and are very active. How did it happen there?

That's my dad and his identical twin.

IMHO: A sedentary lifestyle certainly does not HELP insulin resistance. It does not improve it. However, does a sedentary lifestyle or obesity CAUSE insulin resistance and T2? No way. There are too many fat folks around who have perfectly normal BG. And, there are too many normal weight people who have T2, who have never been obese. Like my dad and my uncle.

Again, I'm reminded of the DirectTV commercial: "90 percent of all statistics can be made to say whatever you want them to say-- 50 percent of the time." That's quite a pearl of wisdom from a commercial! LOL.

I think the reason the numbers were interpreted this way is because this is the prevailing attitude and the scientists make more money going with the trend than bucking it. Studies that buck the trends don't get funded.

[volleyball]

The reporter not only doesn't know anything about the story, they must have sat on it for a month. I figured lazy reporter, go back a month and read and there it was.

The study was not very good. results are the obese twin had less endurance and less control than the healthy weight one.
Big surprise. Now if they follow them for the next 40 years to see if either/both get diabetes and when

[RobiJo]

This study is seriously lacking...

However, my height has not changed in the last 10 years. My weight (up) and activity levels (down) have changed a lot. My insulin needs have at least doubled. I don't think it'd take a huge study to figure out why.

[BlueSky]

Originally Posted by Scrabblechick

... A sedentary lifestyle certainly does not HELP insulin resistance. It does not improve it. However, does a sedentary lifestyle or obesity CAUSE insulin resistance and T2? No way. There are too many fat folks around who have perfectly normal BG. .....

All this could simply mean that, because of their genetic makeup, many people people don't become insulin resistant in spite of their lifestyles. The incidence of insulin resistance and T2 diabetes has increased too quickly over the last 30 years for for the explanation to be defective genes. The finding of the study in question makes pretty good sense to me.

[Hammer]

Originally Posted by Scrabblechick

Again, I'm reminded of the DirectTV commercial: "90 percent of all statistics can be made to say whatever you want them to say-- 50 percent of the time." That's quite a pearl of wisdom from a commercial! LOL.

Yeah, reminds me of a newspaper article I read some years ago. It said that rabies infections in humans has increased by 300% over the last year in a certain county. I thought that was a serious increase until I read more about it. The previous year there was 1 case of rabies....the next year there were three. So yes, there was a 300% increase but it was still only 3 cases.

[fgummett]

Originally Posted by BlueSky

All this could simply mean that, because of their genetic makeup, many people people don't become insulin resistant in spite of their lifestyles. The incidence of insulin resistance and T2 diabetes has increased too quickly over the last 30 years for for the explanation to be defective genes. The finding of the study in question makes pretty good sense to me.

I'm still not going with the default argument that a huge segment of the population have just chosen to become fat and lazy... let's not discount what else has changed over the past 30 years or so:
* widespread use of plastics in food preparation and storage,
* reduced nutritional value of fruits and vegetables due to farming methods... pesticides, burned-out soil, fecal contamination etc...,
* increased use of antibiotics, growth hormones and feeding (herbivorous) animals the remains of other animals!
* increased pollution of our air and water,
* increased UV rays reaching the surface pf the planet,
* massively increased portion sizes and easy access to fast foods with multi-billion dollar advertising including marketing to children,
* increased use of trans-fats and HFCS in just about every processed food product,
* government subsidies to corn farmers so that HFCS is even cheaper and more widespread... especially in cheaper processed foods which tend to be bought by lower income families who tend to be the ones gaining weight,
* social and urban planning seems to have left sidewalks and parks out of the equation when building new sub-divisions... encouraging a car-culture
...

I'm not looking for excuses, or someone else to blame for my excess pounds but I am sick of people suggesting that, "it's easy... just exercise more and eat less". I am trying to make sense of why I, and so many others have gone down this road. I certainly question which came first in me... the weight gain or the BS dysregulation

[volleyball]

Originally Posted by BlueSky

All this could simply mean that, because of their genetic makeup, many people people don't become insulin resistant in spite of their lifestyles. The incidence of insulin resistance and T2 diabetes has increased too quickly over the last 30 years for for the explanation to be defective genes. The finding of the study in question makes pretty good sense to me.

Why not? How can you dismiss defective genes? Until there is a stressor on that gene, how would it manifest itself? And could the medical community identify it? I laugh at cops shows where they run a test on something and come up with some unique compound that is maybe specific to a small locality. Most test are run for specific things, not what is in it. Unless they suspected certain things, they never would have tested for them.
That could be the way it is for us. Our gene pool may all originate from one person a million year ago who gene went askew and passed it all down to us. It turned out that the offspring were prolific producers and whenever 2 "cousins" met up over the centuries, it became part of the our makeup, Thousands of years of dying from other things, made it hard to identify.
The current makeup of our world means we are living with the stressor that helps the manifestation. Plus medicine allows us to live long enough to reproduce, carrying the genes forward.
While different mutations may make us succeptable to type 1 or 2, the theory is still plausible. The industrial revolution a century ago may have been the trigger, it just takes longer in humans to exhibit symptoms because of our slow reproduction rate

[Evermont]

If the study is correct then this is great news!

The genes are in the outer circle, like weather and job security. Lifestyle is in the inner circle. R U with me?

[REDLAN]

what this study and press release illustrate is that you need to read the actual study rather than the press release to understand what the study actually showed

here is the press release headline

Lifestyle choices to blame for insulin resistance more than genes: study

and here is the study headline

Acquired obesity and poor physical fitness impair expression of genes of mitochondrial oxidative phosphorylation in monozygotic twins discordant for obesity

the study is testing the hypothesis that impaired expression of genes for mitochondrial oxidative phosphorylation is the primary mechanism that causes insulin resistance. The authors suspect (or know) that insulin resistance is higher in obese individuals.

(you don't need to know or care what oxidative phosphorylation is to understand the results of the study)

so they pick out all the twins that have big disparities in BMI - notice the language - obesity discordant BMI's - I'm not sure what this means, but I believe it just means a big difference in BMI, rather than saying that any of the pairs are actually fat.
Now notice the average difference - 5.2, and compare this to the quote from the press release

with one twin obese and the other a normal weight.

What ith an average difference of 5.2 in BMI? I rather think not.

now to the study and what it showed

1) twins with lower BMI, were fitter as measured by Vo2max, and Vmax, and more active.

2) the fitter twins had lower insulin resistance than the unfitter twin.

3) the less active twin had lower expression of the mitochondrial gene - supporting the authors hypothesis (it's a very lonq way from proving the hypothesis)

If you read the title for the study again, you'll find that this is what the title says only in more complicated language.

To anyone with type 2, these results are completely unsurprising...

taking exercise improves insulin resistance, and helps to lower weight.

other bits of note...

the age of the participants is 24-27 - it is impossible to say whether the differences in insulin resistance at this age will have any influence on the progression or development of type 2 diabetes.

insulin resistance - the press headline says "Lifestyle choices to blame for insulin resistance", while the study shows that those who have higher BMI's/are less fit have higher insulin resistance than those who are thinner/exercise more. This quite clearly is not the same thing.

there is something odd about the study population - most identical twins are very close to each other in weight (genes are responsible for around 70% of your body weight) regardless of lifestyle - these 14 pairs are not which suggests there is something genetically different about them, hence the author comment

The authors do not rule out the role of genetic factors in altering gene expression.

So to sum up...

this study basically supports the current treatment regime for people with type 2 - exercise and lowering body weight helps with insulin sensitivity.

The study also weakly supports the hypothesis that insulin resistance is caused by altered gene expression in mitochondria.

[fgummett]

A couple of other things to consider...

firstly an addition to my list (above) of things that have changed in the last 30 or so years: post WWII there was still food rationing (into the 1950's in the UK at least). That certainly reinforced the attitude of my parents and older siblings to not waste any food. I was never as a child allowed to leave food on a plate. That is proving a hard habit to break. I know I am not alone in that experience.

secondly Peptic Ulcers...: not too many years ago the Health Care/Scientific Community were convinced that these resulted from lifestyle choices... rushed food, poor diet, smoking, too much coffee, stress etc... a very clear causality link existed. Naturally, treatments focused on changing these lifestyle choices. Then, even less time ago someone discovered that at least 80% of Peptic Ulcers result from a bacterial infection! Overnight, treatment changed to a course of antibiotics!

I'm not saying that an infection is, or is not, the cause of our current epidemic of obesity and Type 2 D... but it is something to consider; if for no other reason than to realise that what we know today as "fact" may be proven wrong in the future.

[Alice]

I like the way it was discussed on Larry King last week (cardiologists on the show)...they basically said "genetics is the gun...but lifestyle pulls the trigger." They were discussing the case of Tim Russert and lack of prevention in the U.S. The drugs are there for control...but prevention isn't happening.