Hi, Henry

There is definitely a strong familial tendency in Type 2 diabetes, and not all type 2 diabetics are obese.

Doing what you can to reduce the impact is the right approach for many reasons, but, if insulin resistance still develops, it doesn't necessarily mean you did anything "wrong".

hi sue what do you think actually causes insulin resistance, then? and what does a strong familial tendency mean, given that type 2 diabetes genes have piddling effects?

Robert, see the articles on this page;

http://artdevanyonline.com/1/category/diabetes/1.html

Particularly the fourth.

If you read and understand that (and the first article as well), you'll be ahead of most doctors and pretty much all the confidents one-cause know-alls.

Robert Peers - I can't tell if you're asking rhetorical questions or not.

For other readers, there is a difference between strict inheritance of diseases (such as haemophilia or thalassaemia) and diseases that tend to occur on families (like depression, atopy/asthma, and type 2 diabetes).

What do I think actually causes insulin resistance? It has nothing to do with what I think, but what the research shows (I am not an endocrinologist or researcher in endocrinology).

Studies of insulin resistance have been in the literature for decades. For example, "Diminished insulin sensitivity and increased insulin response in nonobese, nondiabetic Mexican Americans." Haffner et al, Metabolism, 1990. The AUstralian researcher and clinician, Stephen Lillioja, published in this area in the 1980's.

As I assume you know, not all type 2 diabetics have the full metabolic syndrome that includes truncal obesity. According to an article in Diabetologica 2010 "The molecular causes of insulin resistance, i.e. impaired insulin signalling through the phosphoinositol-3 kinase pathway with intact signalling through the mitogen-activated protein kinase pathway, are responsible for the impairment in insulin-stimulated glucose metabolism and contribute to the accelerated rate of CVD in type 2 diabetes patients."

Diabetologica 2011 has an article about lean type 2 diabetics - van Hoek et al "Association of an APOC3 promoter variant with type 2 diabetes risk and need for insulin treatment in lean persons."

Keith Thomas - what is your view of the papers I mentioned in relation to the causes of insulin resistance? You can find the full papers on-line in the journal Diabetologica.

(or do you prefer to ignore the endocrinology research and go for the populist paperbacks - to be "ahead of most doctors".)

Sue, I'm probably with you, not against you. I agree fully that insulin and other hormones, cell metabolism etc. are all part of this complex illness. I did not cite any "populist paperbacks" so I presume you are just wagging your finger at me metaphorically, and letting me know that medically and scientifically-qualified professionals who can comprehend and keep abreast with the formal medical literature are the only people who have an opinion worth listening to.

Diabetologica is, I openly admit, beyond me. But I am happy to rely on others who are well-equipped to keep up with the literature (Lustig, deVany, Taubes et al) and who take the time to distill and communicate the relevant science to lay people like me.

As I understand it, The Conversation serves a "populist paperback" role for me and I'm afraid you'll have to get used to people like me dominating the comments sections and dropping their opinions/perspectives/understandings here and seeing what the result is. I can tell you that I'd be wasting my time reading Diabetologica.

Taubes and others provide the academic references for their work, so professionals can follow them up. But they also add value by their science journalism.

hi sue see my reply to henry verberne...diseases that ted to run in families, like diabetes and depression, are western high-fat diseases, not seen in traditional societies like the kaluli in new guinea, or the older okinawans, or in japanese fishing villages...fatty diet in pregnancy exposes the foetal brain to maternal cortisol, which programmes lasting anxiety in 20-30% of westerners...if the anxious child or adult eats a fatty diet themselves, brain inflammation ensues, that converts anxiety to depression...as you know, depressed folks have high risk of also becoming diabetic, and of developing serious heart disease and hypertension...if they survive all that, parkinson's awaits them in later life, and maybe vascular dementia as well...so we don't need imaginary genes to explain these diseases...fatty maternal diet is the key to explaining anxiety, depression, diabetes, hypertension and heart disease...finally, reducing fat will relieve depression and some coronary risk, but the often-missed underlying anxiety requires specific treatment with inositol foods or [preferably] supplement, 5 gm/day: this centrally acting anti-anxiety nutraceutical reverses anxiety within days, resulting in reduced food craving, blood pressure and glucose reduction, easy weight loss, enhanced energy, better libido, major immune boosting, improved calmness and mental concentration, faster growth of head hair and nails, and activation of a host of anti-ageing genes [via inhibition of the insulin-like growth factor signalling pathway, as in caloric restriction]...voila!!!!

Robert peers - there is absolutely no evidence for your assertion that "diseases that ted to run in families, like diabetes and depression, are western high-fat diseases, not seen in traditional societies".

IN fact, a lot of research on insulin resistence was conducted in the 1980's by Stephen Lillioja in communities of Pima Indians (native americans).

There are many many familial illnesses - some with precise inheritance - like haemophilia, and some with familial tendency (like atopy/asthma).

There is also no evidence that depression develops in the manner you assert. Where are the results of your treatment of anxiety and depression available for review and verification?

Keith Thomas - why are you offended by the suggestion that someone who has studied and practised the clinical sciences might have a more informed (and valid) view of complex endocrine disorders than those who haven't?

hi sue i am afraid that i must remind you that are a medical, untrained in nutrition, and you also seem to be a stranger to epidemiology and the history of diseases

as a result, you ask many questions, but seem to have no answers

the pima indians, who were historically free of diabetes, are well known to have adopted a high fat white american diet many decades ago--especially cooking in highly diabetogenic hydrogenated crisco fat, supplied in tins

did you know that? crisco is not a traditional native american food

their mexican relatives, the tarahumara people, still eat a traditional diet of beans, corn, squash and vegetables, have no diabetes, and have incredible stamina from the high-inositol foods

in kenya, before ww2, there was a competition among british doctors, to find diabetes in a native kenyan; not one case was found

time for some epidemiology homework?--try professor sir harry himsworth's landmark 1930s studies, on the parallel rise of fat consumption and diabetes mortality in western nations, not seen in asia

as for depression, anxiety is well known to be the underlying predisposing factor in most cases, and the cause of this anxiety is well known, in animal studies, to be fatty maternal diet [t bilbo; e sullivan], which lets maternal cortisol programme anxiety in the foetal brain [m holmes, edinburgh neuroscientist]

depression, in turn, is linked to insulin resistance, glucose intolerance and increased diabetes risk; depression has been directly linked to fatty diet [f jacka], which causes the well known systemic and neural inflammation [b culver, 2005], that converts plain anxiety to depression

having only a medical qualification, but no training in nutrition or scientific discovery, makes it quite inappropriate for you to pontificate on these subjects

i suggest you would feel more relaxed, and enjoy better cognitive function, if you tried some inositol

Not at all. It's what I'd expect. The problem I have is that, in a forum like this, designed to enable interested lay people to learn from experts, some experts take the position that the best way to convince lay people who are wrong (in whatever way) is to refer them to academic specialist papers as if their responsibility has thereby been discharged.

This may work in a community of experts who have equal facility with the expert literature written for experts. Firing broadsides of academic papers is probably de rigueur in that rarified atmosphere.

But I expect experts who contribute to The Conversation to take a different approach. I expect them to draw out, using words and ideas accessible to lay people, the lessons for them. I instanced Robert Lustig, Gary Taubes and Art deVany - all have produced 'popular paperbacks' in this technical area that are not just accessible, but are even darned good reads.

Robert Lustig, for example, is a paediatric endocrinologist specializing in obesity who is on the Obesity Task Force of The Endocrine Society in the US. He doesn't tell his readers to go away and study the literature. On the contrary, he welcomes them to come along with him as he joyfully takes on the responsibility of outlining the field and then explaining his conclusions, striving all the time to keep his work accessible.

"depression, in turn, is linked to insulin resistance, glucose intolerance and increased diabetes risk; depression has been directly linked to fatty diet [f jacka], which causes the well known systemic and neural inflammation [b culver, 2005], that converts plain anxiety to depression"

Robert Peers - can you talk us through the research that supports your assertion, how it was done, and what it showed?

hi sue yeah it's a long story, how fatty diet [a proven cause of diabetes--himsworth, 1936] causes anxiety disorder prenatally, and also converts anxiety to depression

1. i routinely take diet histories, and put all patients on a preventive low-fat diet, and first noticed (about 1994-95) that depressed patients [especially young women willing to try my diet] soon lost their depression--but remained anxious

2. in 1990, i spotted a study by us researcher stephen koslow, that startled me: he found insulin resistance in both unipolar and bipolar depression--i had already collected studies showing that fatty diet [low ratio of polyunsaturated to saturated fatty acids] reduce "poly" content of cell membranes, which impairs insulin receptor function [m t clandinin], causing insulin resistance

3. polyunsaturate-depletion from dietary oil deprivation or fatty diet also affects mitochondrial membranes [p d klein, 1954; p divakaran], inhibiting respiratory Complex 1 and increasing superoxide free radical production

4. such oxidative stress activates inflammation, via pro-inflammatory oxidation-sensing transcription factors [NFkB and AP-1; I Rahman]; inflamed immune cells then release pro-inflammatory cytokines [IL-1beta, IL-6, TNFalpha] that directly induce sickness behaviour [depression symptoms], and also divert dietary tryptophan away from serotonin formation, in favour of neurotoxic tryptophan catabolites that impair cognition

5. these nasty inflammatory cytokines also hyper activate an already anxiety-activated pituitary-adrenal axis, meaning even more cortisol to impair frontal lobe function, to enhance tryptophan diversion toxicity, and to impair neurogenesis in the hippocampus

6. the brain inflammation from fatty diet may also drive the white matter pathology now described in depression

7. in 1916, dr charles mercer saw good responses to low fat diet in mental disorders [lancet: diet as a factor in the causation of mental diseases]

8. the first biochemical abnormality recorded in mental disorders was glucose intolerance [s a mann, 1925, j mental science]--which himsworth showed, in 1936, was caused by dietary fat

9. professor michael berk, in geelong, is working with diet-minded psychologist felice jacka, on diet and depression--they have shown a link with fatty diet, and hope to do a low-fat diet intervention trial

10. another common cause of depression in anxious folk is refined seed oil, which causes alzheimer's [very slowly]; the low vitamin e level oxidises neuronal and retinal membranes, causing irritable depression and glare sensitivity [photophobia]--so we have to remove such oils, as well as any sat fat, from the sufferer's diet

all this cortisol overactivity, insulin resistance and low-grade inflammation combine to create a perfect storm for diabetes development

Thanks for the theorising, Robert, but is there any evidence for what you propose?

Where is there evidence for "these nasty inflammatory cytokines also hyper activate an already anxiety-activated pituitary-adrenal axis, meaning even more cortisol to impair frontal lobe function, to enhance tryptophan diversion toxicity, and to impair neurogenesis in the hippocampus
and
6. the brain inflammation from fatty diet may also drive the white matter pathology now described in depression"?

There is evidence for monoamines, serotonin, noradrenaline and dopamine in the genesis of depression. I have not seen evidence of your "fatty diet" theory. Is it tested, or only theoretical?

hi again sue

naturally, i have detailed scientific references for all my claims about depression mechanisms, collected over 22 years

together, these refs, when grouped with my nutritional discoveries, are easy to integrate into an inductively strong simplifying hypothesis on the nutritional origins of anxiety and depression

i do not theorise--i collect and group a wide range of facts, in order to frame a robust scientific hypothesis--this is inductive reasoning, not karl popper's fanciful "guess then test" hypothetical-deductive reasoning, which is a poor substitute

technically, my hypothesis becomes a scientific theory when fully confirmed, and that is only a matter of time now

the serotonin/monoamine hypothesis was based on the accidental discovery that certain industrial chemicals had antidepressant properties--this was serendipity, not science-based, and the whole serotonin story is now under attack, from new theories based on neuroinflammation and neurodegeneration

e.g. see michael maes on pubmed--good mechanisms and descriptions [like medicine itself!] but totally lacking any aetiological explanation, which science demands

by the way, a fabulous description of how stress hormones take the frontal lobe "off-line" is on dr amy arnsten's yale lab webpage

i am lucky to be a very calm guy, but this is uncommon in medical graduates, who often enter medical studies with good iq, but saddled with obsessional anxiety--which is even worse in the law faculty

over the years, i have continually run into highly anxious, defensive medical researchers and practising doctors, who display remarkable dogmatism, scornful skepticism toward new ideas, and impaired executive function--unable to coolly assess and integrate new facts into a revised hypothesis, perhaps due to their higher intellectual functions being offline, in favour of a more primitive emotion-driven response based on stress-driven activation of the limbic structures lower in the brain

amy arnsten is a world expert on this cognitive inhibition, which may explain why medicals can learn dogma by rote, but cannot produce original breakthroughs or explanatory discoveries

perhaps we secretly like the diseases that keep us gainfully employed, and don't really want to know their simple and avoidable causes--preventing them would be like turkeys voting for thanksgiving day

needless to say, inositol quickly reverses all this anxiety, and restores cognitive flexibility, by relaxing the brain, letting creative imagination flow again

One must start with what is KNOWN to cause diabetes and work back from there ?
That is why as you have done above is try to describe how you try to understand WHY this happens to a human , try , NOT "this is what causes diabetes".
Logically you would go from what has been PROVEN to cause diabetes , especially if you have it , because you MUST 'figure it out' for your own sake.
So , logically , with all the evidence being considered you must START with the metal iron because simply it has been proven to cause diabetes when given , mistakenly , to people AND considering 'Bronze diabetes' in which the people load iron to the point they begin to shine like bronze.
There is a belief what the medical profession considers to be 'normal iron stores' is in fact , wrong.
Evidence based medicine has proven conclusively too much iron in a human causes diabetes and removal of this iron leads to recovery in diabetes.

"At NID, there was a 40%-55% improvement (P = 0.05-0.0001) of both fasting and glucose-stimulated plasma insulin concentrations"

"Repeated blood withdrawals from ferric-nitrilotriacetate-treated animals resulted in disappearance of hypergycmia, glycosuria,
ketonemia, and ketonuria; disappearance of iron from the liver
and pancreas; and restoration of islet beta granules to the
control level."

"Although the exact mechanism of iron-induced diabetes is uncertain, it is likely, as discussed below, to be mediated by three key mechanisms: 1) insulin deficiency, 2) insulin resistance, and 3) hepatic dysfunction. An understanding of the pathogenic pathways of iron-induced diabetes is derived mainly from studies on animal models of hemochromatosis."
http://care.diabetesjournals.org/content/30/7/1926.full

I wonder if as you claim type II diabetes is caused by some Fe imbalance, and mine was cured by fat loss that enabled me to get back to reasonable exercise, then could any Fe imbalance have also been cured. Chicken and egg situation?

As an analogy , you tell your doctor , it hurts when I raise my arm , and he tells you , "don't raise your arm" .
The same with diet , rather than try to understand why 'raising your arm hurts' / why you have diabetes , the medical profession tells you not to raise your arm / telling you to not eat sugar , not to eat fat and not eat carbohydrates all the things the increased iron CAUSES you not to be able to eat. So rather than being cured as you believe , you are merely controlling your diabetes with natural means , limiting sugar , fat and carbs because you cannot properly assimilate them / not raising your arm.
Which is why the NIH is conducting a clinical trial of iron depletion for type 2 and NAFLD , the accumulated evidence is so strong.

"Iron Depletion Therapy for Type 2 DM and NAFLD"
http://clinicaltrials.gov/ct2/show/NCT00230087

At one time they said it is IMPOSSIBLE for iron to be involved in diabetes because all diabetics are iron deficient , so it is simply IMPOSSIBLE for all diabetics to be iron overloaded , simply impossible.

Then , this study is produced.

"NTBI (non-transferrin-bound iron ) was commonly present in diabetes: 59% in newly diagnosed diabetes and 92%
in advanced diabetes"

So it goes from ALL are iron deficient to , voila , 92% have iron just floating around in the body , non-transferrin bound iron.
So , unless you don't know your odds , to go from IMPOSSIBLE to everyone of them has it , is kind of a long shot , if you know your odds.

Which is why atherosclerosis is found with diabetes.

"Can iron chelators influence the progression of atherosclerosis?"
http://www.ncbi.nlm.nih.gov/pubmed/18274990

"Fe depletion consistently enhanced glucose disposal"
http://www.ncbi.nlm.nih.gov/pubmed/11591239
"Transition metals redox: reviving an old plot for diabetic vascular disease"
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC199584/
"Insulin-Producing Cells, Iron, Oxidative Stress, and Lysosomal
Pathology"
"The decisive role of free lysosomal iron in oxidative stress is strongly supported by the following lines of evidence, provided by the present study (a) glucose- and amino acid-starvation promotes autophagic/crinophagic activity of the cells, resulting, in enrichment of intracellular (intralysosomal) desferrioxamine-available iron; (b) high-glucose conditions depress autophagic/crinophagic activity and, consequently, the occurrence of intralysosomal iron; (c) starvation-stimulated ferritin synthesis enhances lysosomal stability during oxidative stress by limiting lysosomal redox-active iron; (d) lysosomal destabilization and related apoptotic cell death are associated with the amounts of intralysosomal iron in redox-active form"
http://chaplin2.bibl.liu.se/liupubl/disp/disp99/Med599s.htm

This explains the problem with simple sugars and their seemingly straight to fat scenario.
The , "even in the absence of significant iron overload" , scenario where the medical profession doesn't believe there IS an iron problem.

http://www.medscape.com/viewarticle/439591_5
"Cross-Talk Between Iron Metabolism and Diabetes"
"It is increasingly recognized that iron influences glucose metabolism, even in the absence of significant iron overload'

Your preoccupation with the pathology of Fe borders on the obsessive. during my weight loss phase a couple of times my surgeon commented on blood test low-end Fe levels, and indicated this to be a normal indicator of success. They have been normal for two years now.

Whatever the general mechanism for diabetes type II control proves to be, the total avoidance of refined glucose from our food intake will help. The best use for sugar is production of drinking ethanol. It is certainly no economicsubstitute for petrol but try telling our government that.

Please cease attempting to detract from the original article which really tries to show diabetes sufferers hope.

"Please cease"

Actually the thread is .. what is diabetes .. you actually didn't include one cite , just your opinions , and I didn't tell you you are full of stupid ideas , did I ?
Afford me the same courtesy and in the meantime , don't read my posts.

"Researchers iron out the link between serum ferritin and diabetes"
"Reduction of serum ferritin levels in human patients increased insulin sensitivity and glucose tolerance"
http://medicalxpress.com/news/2012-09-iron-link-serum-ferritin-diabetes.html#jCp

This compilation gives a good idea how the medical profession gives iron to pregnant women causing them to manifest gestational diabetes and also deliver babies , if they manage , who have excess iron and diabetes , too.

"A new study conducted by researchers at Children's Hospital Oakland Research Institute (CHORI), in close collaboration with scientists at the National Institute of Perinatology in Mexico, is the first to show that the current iron supplement recommendation for pregnant women who are not anemic is too high and could lead to birth complications for
infants such as premature birth and low birth weight."
http://www.childrenshospitaloakland.org/about/press_releases/press_053106.asp

"Iron status in women with and without gestational diabetes mellitus."
"The role of iron excess in the pathogenesis of gestational diabetes mellitus needs to be examined."
http://www.ncbi.nlm.nih.gov/pubmed/18413178

"Gestational diabetes mellitus in the last trimester - a feature of maternal iron excess?"
"The role of iron excess in the pathogenesis of GDM needs to be examined."
http://www.ncbi.nlm.nih.gov/pubmed/11318843

"Iron supplementation and gestational diabetes in midpregnancy"
"Iron supplementation is associated with glucose impairment and hypertension in midpregnancy; its potential harmful effects might be carefully debated regarding its effectiveness."
http://www.ncbi.nlm.nih.gov/pubmed/19527900

"Iron supplements in pregnancy may not be without risks"
"Iron supplementation in pregnancy may have negative consequences"
http://journals.lww.com/ajnonline/fulltext/2009/11000/newscap__iron_supplements_in_pregnancy_may_not_be.13.aspx

"Impact of iron deficiency anemia on prevalence of gestational diabetes mellitus"
"The prevalence of GDM is reduced in iron deficiency anemia"
http://www.ncbi.nlm.nih.gov/pubmed/14988280

"Relative iron "overload" in offspring of patients with type 2 diabetes mellitus: a new component in the conundrum of insulin resistance syndrome?"
http://www.ncbi.nlm.nih.gov/pubmed/17003017

Apropos , this , just in.
"Ferritin levels and risk of type 2 diabetes mellitus: an updated systematic review and meta-analysis of prospective evidence"
"Elevated levels of ferritin may help identify individuals at high risk of T2DM, who are likely to benefit from lifestyle or therapeutic interventions"
http://www.ncbi.nlm.nih.gov/pubmed/23381919