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Reeves 2010 (biomedical research!?) CFS associated with Metabolic Syndrome


Tom Kindlon posted this to co-cure Feb 9 2010

[Tom: This study used the "empiric criteria" (Reeves, 2005) for CFS]

(if: Am I missing something? Is this Reeves doing biomedical research? Is there something wrong here? What, if any, are the implications?)

Chronic fatigue syndrome is associated with metabolic syndrome: results from
a case-control study in Georgia

Maloney EM, Boneva RS, Lin JM, Reeves WC.

Metabolism. 2010 Jan 25. [Epub ahead of print]

Centers for Disease Control and Prevention, Chronic Viral Diseases Branch,
National Center for Zoonotic, Vector-borne and Enteric Diseases, MS-A15,
1600 Clifton Rd, Atlanta, GA 30333, USA.

We hypothesized that persons with chronic fatigue syndrome (CFS) would have
a higher prevalence of metabolic syndrome compared with well controls, and
that unwell persons with insufficient symptoms or fatigue for CFS (termed
ISF) would have a prevalence of metabolic syndrome intermediate between
those with CFS and the controls.

We also sought to examine the relationship
between metabolic syndrome and measures of functional impairment, fatigue,
and other symptoms.

Our analysis was based on a population-based
case-control study conducted in metropolitan, urban, and rural areas of
Georgia, United States, between September 2004 and July 2005. There were 111
persons with CFS, 259 with ISF, and 123 controls.

Metabolic syndrome was
determined based on having at least 3 of 5 standard risk components
(abdominal obesity, high triglycerides, high blood pressure, elevated
fasting glucose, and decreased high-density lipids) according to the
National Cholesterol Education Program Adult Treatment Panel III definition.

Persons with CFS were 2-fold as likely to have metabolic syndrome (odds
ratio = 2.12, confidence interval = 1.06, 4.23) compared with the controls.
There was a significant graded relationship between the number of metabolic
syndrome factors and CFS; each additional factor was associated with a 37%
increase in likelihood of having CFS. The association of ISF with metabolic
syndrome was weaker (odds ratio = 1.72, confidence interval = 0.94-3.16).

Among persons with CFS, the number of metabolic syndrome factors was
significantly correlated with worse fatigue
on a standardized summary
measure of fatigue (r = 0.20, P = .04).

In conclusion, CFS was associated
with metabolic syndrome, which further exacerbated fatigue

Published by Elsevier Inc.

PMID: 20102774 [PubMed - as supplied by publisher]

From Wiki:
Metabolic syndrome is a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes.[1] It affects one in five people, and prevalence increases with age. Some studies estimate the prevalence in the USA to be up to 25% of the population.[2]

Metabolic syndrome is also known as metabolic syndrome X, syndrome X, insulin resistance syndrome, Reaven's syndrome, and CHAOS (Australia)[3]. A similar condition in overweight horses is referred to as equine metabolic syndrome; it is unknown if they have the same etiology.


I'd be interested in people who are more informed of the research, and Reeve's, history than I am. I think I might have just found part of the answer here:
CFS, Reeves, and the CDC: Rich History but Poor Past
from Craig Maupin's cfidsreport

Myth 2. For years, sufferers have accused Reeves "of thinking ME/CFS was a psychological disorder but his open-ended attempt to merge gene expression, gene polymorphism and laboratory and clinical data suggested he was open, at least at that point, to various interpretations of the disease."

This statement is based on a belief that biological research and genetic research belong to biomedical fields, not psychiatry. While this belief is understandable from a layman's perspective, it is not accurate. Current models of psychiatric disorders are multidimensional: stress trigger, genetic predisposition, lead to biological effects and behavioral perpetuation. Today, depression, stress disorders, and anxiety disorders are researched with an emphasis on genetics, behavioral interventions, neuroendocrine imbalances, and mild immune alterations. (2).


Senior Member
REEVES SUPPORTS RETROVIRUS/CFS LINK (inadvertently). Check out Lipodystrophy and HIV!

Islandfinn, thanks for your sharp eyes, and for this great post on Reeves, CFS, and Metabolic Syndrome. The great thing is that this thread could also be called Reeves, XMRV and other Retroviruses, and Lipodystrophy!:Retro smile:
Persons with CFS were 2-fold as likely to have metabolic syndrome...Among persons with CFS, the number of metabolic syndrome factors was significantly correlated with worse fatigue
True to form, Reeves blames this metabolic complication on us:
In conclusion, CFS was associated with metabolic syndrome, which further exacerbated fatigue.
In other words, if we'd just comply with CBT and GET, we wouldn't be such a drain on the health care system and our beleaguered health care workers.

There is another way to look at Metabolic Syndrome and CFS - which is cause for hilarity!...
And that's through the lens of the abundant research on the retrovirus HIV,
Lipodystrophy, and Metabolic Syndrome!

Cause for hilarity: Reeves is s inadvertently supporting a CFS/Retrovirus/Lipodystrophy hypothesis!
A bit of background on a well-known phenomenon with another retrovirus and metabolic complications: Lipodystrophy and HIV. (A simple definition of Lipodystrophy = "disturbance of fat metabolism"). Do we know yet whether XMRV causes ME/CFS and lipodystrophy? Not YET. But it certainly is plausible, given the familiar linkage between HIV lipodystrophy, abnormal cytokines, involvement of endocrine systems, etc. Firstly, it is important to recognize that a well known cause of HIV lipodystrophy is from antiretroviral therapy itself, specifically from protease-inhibitors and nucleoside reverse-transcriptase inhibitors. Thanks to the psycholobby though, we don't have to worry about iatrogenic medication-induced lipodystrophy yet.:Retro wink:

Clear and abundant linkages between Retroviral infection and Lipodystrophy & Metabolic Syndrome
There remain, however, clear linkages between HIV infection itself, and lipodystrophy. In other words, even in the absence of antiretroviral treatment, if XMRV proves to be linked with ME/CFS, we are very possibly at risk for metabolic complications and lipodystrophy.

From: http://www.thefreelibrary.com/HIV-a...me:+an+accelerated+form+of+the...-a0155400372
On the basis of kinetic metabolic studies in the fasting and fed states in patients with HIV-associated lipodystrophy, Sekhar et al (20,21) identified basic defects in adipocyte function that result in a marked acceleration of lipolysis or hydrolysis of stored triglycerides leading to a net release of free fatty acids into the circulation... As to the mechanisms underlying adipocyte dysfunction, they are likely complex and multifactorial, and probably include one or more HAART agents, increased proinflammatory cytokine activity, (22) or proteins expressed by HIV itself.
From: http://www.tufts.edu/med/nutrition-infection/hiv/health_lipo.html
Lipodystrophy, also called fat redistribution syndrome, is a condition that often occurs in HIV-positive people and is characterized by changes in body shape and metabolism. Body shape changes may include the accumulation and/or loss of fat, which can affect appearance. Metabolic changes may include increased resistance to insulin and abnormally high levels of blood cholesterol and triglycerides....Health experts are not sure why HIV-positive people develop lipodystrophy, but they think it may be related to antiretroviral medications they take to control their disease. In addition to medications, factors including a persons age, gender, weight, genetic predisposition, length of time he or she has been HIV-positive, and severity of the disease may be linked to the development of lipodystrophy.

The most visible signs of lipodystrophy and the ones that people may notice first are deposits of fat at various sites on their bodies. The two places where fat generally accumulates are the back of the neck (called buffalo hump) and around the abdomen (truncal obesity)...

What metabolic changes can occur with lipodystrophy? Insulin resistance may be related to some of the antiretroviral medications used to treat HIV, and/or to a genetic predisposition in the individual...Dyslipidemia, or higher than normal amounts of lipids (cholesterol and/or triglycerides) in the blood, is another metabolic change which often occurs in HIV-positive people with lipodystrophy. It also may be related to some of the antiretroviral medications used to treat the disease, and/or to genetic predisposition.
From: http://www.thebody.com/content/art1885.html
The causes of lipodystrophy are not well understood. Multiple studies have shown strong association with the severity or duration of HIV disease (Look back to Reeves' linkage: the greater the fatigue, the greater the Metabolic Syndrome in CFS patients!); with persons with longer period of untreated infection or lowest-ever CD4 cell counts at greatest risk. Additional host (or patient) risk factors include age, gender (men at greater risk) and race (Caucasians at greater risk)... Even before the era of antiretroviral medications, it was observed that HIV-positive persons had marked elevations in triglyceride levels.
From: http://emedicine.medscape.com/article/1082199-overview
Lipohypertrophy in this syndrome is characterized by the presence of an enlarged dorsocervical fat pad, circumferential expansion of the neck, breast enlargement, and abdominal visceral fat accumulationOther features of HIV lipodystrophy syndrome include hyperlipidemia, insulin resistance, hyperinsulinemia, and hyperglycemia. Patients with HIV lipodystrophy syndrome are at increased risk for the development of atherosclerosis and diabetes mellitus.

HIV-1 may cause dyslipidemia and lipodystrophy in the absence of HAART therapy, via impaired cholesterol efflux from macrophages and increased tumor necrosis factor-alpha, which modulates free fatty acid metabolism and lipid oxidation and attenuates insulin-mediated suppression of lipolysis.1
From: http://www.ncbi.nlm.nih.gov/pubmed/20001516
The relationship of adipocytokine with the development of HIV-related lipodystrophy was investigated in a case-control study... Most of the patients (96.3%) developed HIV-LD after month 12. ...The adiponectin level had a correlation with serum triglycerides (r = -0.616, p < 0.0001), serum insulin concentration (r = -0.494, p = 0.001), and HDL-C (r = 0.673, p < 0.0001). The lower baseline concentration of adiponectin and the greater change rate at month 18 were independent risk factors of HIV-LD. The adiponectin level had a correlation with serum triglycerides, serum insulin concentration, and HDL-C, suggesting that adiponectin may link the metabolic abnormalities and HIV-LD.
From: http://www.ncbi.nlm.nih.gov/pubmed/19954415
IL-18 is a pleiotropic and multifunctional proinflammatory cytokine that is often produced in response to a viral infection. The cytokine plays an important role in both innate and adaptive antiviral immune responses. Depending upon the context, it can promote TH1, TH2 and TH17 responses. Increased serum concentrations of IL-18 and concomitantly decreased concentrations of its natural antagonist have been described in HIV-infected persons as compared to HIV-seronegative healthy subjects. We discuss in this review article how increased biological activities of IL-18 contribute towards immunopathogenesis of AIDS, HIV-associated lipodystrophy syndrome and related metabolic disturbances.
From: http://www.ncbi.nlm.nih.gov/pubmed/19662737
Many reports have described endocrine and metabolic disorders in the human immunodeficiency virus (HIV) infection... Endocrine and metabolic disturbances occur in the course of HIV infection. Pathogenesis includes direct infection of endocrine glands by HIV or opportunistic organisms, infiltration by neoplasms and side effects of drugs. Adrenal insufficiency is the commonest HIV endocrinopathy with cytomegalovirus adrenalitis occurring in 40-88% of cases. Thyroid dysfunction may occur as euthyroid sick syndrome or sub-clinical hypothyroidism....

CONCLUSION: Virtually every endocrine organ is involved in the course of HIV infection. Detailed endocrinological and metabolic evaluation and appropriate treatment is necessary in the optimal management of patients with HIV infection in our environment.
From: http://www.ncbi.nlm.nih.gov/pubmed/19654854
Body fat disorders are a common and relevant problem in HIV-1-infected patients that can be associated with metabolic alterations. Many controversies in their definition, pathogenesis, measurement, and management remain unclear. Several factors including HIV-1 infection itself and antiretroviral therapy have been associated with the development of these alterations.
From: http://www.ncbi.nlm.nih.gov/pubmed/19654853
Interleukin-18 is a proinflammatory, proapoptotic, and proatherogenic cytokine belonging to the interleukin-1 family of cytokines. The cytokine may play a major role in the development and pathogenesis of AIDS in HIV-infected persons. Insufficient/lack of interleukin-12 and related cytokines may compromise the ability of interleukin-18 to induce interferon-gamma production from natural killer and T-cells.... The cytokine is also likely to be involved in the higher incidence of atherosclerotic plaques and systemic insulin resistance in these patients. Finally, increased production of the cytokine in the brain may lead to motor and cognitive dysfunctions, leading to the development of HIV-associated dementia. In conclusion, increased interleukin-18 concentrations in HIV-infected persons are likely to play an important role in the development and progression of the infection toward AIDS and associated clinical conditions.
From: http://www.ncbi.nlm.nih.gov/pubmed/20167996
We evaluated endothelial dysfunction, an early event in the development of atherosclerosis, and pro-atherosclerotic plasma biomarkers in HIV-infected patients with lipodystrophy... Lipodystrophy was associated with significantly higher plasma levels of interleukin 6 (IL-6) and plasminogen activator inhibitor 1 (PAI-1) and lower levels of adiponectin; severe lipodystrophy was associated with higher concentrations of vascular cell adhesion molecule 1 (sVCAM-1). There was an inverse correlation between FMD and IL-6... the only independent predictor of endothelial dysfunction was lipodystrophy... CONCLUSIONS: Lipodystrophy is associated with endothelial dysfunction, independently of the presence of traditional cardiovascular risk factors. This finding and the accompanying profile of pro-atherosclerotic biomarkers support an increased cardiovascular risk in HIV-infected patients with lipodystrophy.
(I think this was tomk?)Is this Reeves doing biomedical research? What, if any, are the implications?
The hilarious implications of Reeves' latest work are that he is
pointing to retroviral involvement in ME/CFS!
:Sign Good one:


Senior Member
[Tom: This study used the "empiric criteria" (Reeves, 2005) for CFS]
The "empiric criteria" (Reeves, 2005) for CFS are so rubbish I don't count it as CFS research to be honest.

The CDC research has been a bit different from the UK research funded by the government; in the latter, they generally do little biological testing unless it is on the HPA-axis (so they can associate it with stress). The CDC have done a broader range of research. But if you have lots of people who just "don't get much done"/have "reduced activity", but don't really have to have what even looks like CFS, lots of these people are just going to be underactive people who have unhealthy lifestyles.
This paper might have been in Elsevier's pipeline before Reeves got "booted." In any event, my first psychiatrist was way ahead of him. When I kept losing weight on his anti-depressants, he squawked "metabolic problem."

I have borderline hypertension, and not only low HDL, but low total cholesterol (90-100). In fact, I had the latter for at least 5 years before "onset." In the first couple in 12 years of illness I dropped ten pounds from 150, both subcutaneous fat and muscle, noticeable it seemed only to me. Few except a GWI and the HIV doctor I wound up with put significance to it and said I had lipodystrophy or lipoatrophy and wasting.

The last two summers since I moved from SoCal have seen me drop another 10, fat and muscle. This Xmas, my family finally noticed. While "stress" can drastically affect someone's weight either way, it's hard for me to get three good meals in a shortened day, and a lot harder in the summer humidity. As it is, I seem to have a body that just torches fuel while sitting still - perhaps revved up against something. I've gone to protein shakes and am seeing a new ID doc this week.

My former AIDS doc is very intrigued by XMRV, partly because of the lipo' and cholesterol similarities he often sees in ME/CFS. Unfortunately, we're 25 years into HIV and no one knows any more about how to stop or reverse lipodystrophy/atrophy than 10 years ago. Dr. Klimas couldn't have been more correct in noting we "are delicate creatures," that retrovirals are not a simple solution. True, a lot of HIVers are "hale and hearty." A lot of them are getting plastic surgery on their face and buttocks, too. HIV may not be as fatal in the West, but it is not exactly easily managed, either.
"Metabolic syndrome was
determined based on having at least 3 of 5 standard risk components
(abdominal obesity, high triglycerides, high blood pressure, elevated
fasting glucose, and decreased high-density lipids) according to the
National Cholesterol Education Program Adult Treatment Panel III definition."

I'm skinny, eat loads, and have really low blood pressure!

I just looked at wikipedia, and one of the key factors mentioned as leading to metabolic syndrome is a 'sedentary lifestyle'.

Are you kidding me? Can we stop spending money of studies to see if suffering from CFS means that you more at risk to conditions where a sedentary lifestyle is a significant contributing factor? I think that could be taken as a given at this point, unless they think we're all just lying, and sneaking out for a spot of tennis whenever their backs are turned. Maybe it would be worthwhile comparing CFS patients to those whose activity level is comparably low but do not have fatigue problems (MMORPG fans?) - comparing CFS patients to the general population - of course we're more likely to lead a sedentry lifestyle and have the health problems related to that. (One of my problems with some other biological research into CFS is that it fails to try to account for this, and I think this is one of the reasons many choose to ignore it).

edit - Just to be clear: I realise I know almost nothing about metabloic syndrome, and have no idea of the potential significance of high-density lipids etc, but I really don't see the point of this research. What could it have led on to? It seems completely pointless.


Phoenix Rising Founder
I think this article illustrates how poorly the CDC research program was faring - I'll bet it was stuff like this that got Reeves canned. After 10 years Reeves demonstrated that a portion of CFS patients have a general inflammatory condition; it may or may not be true - alot of people think there is an inflammatory element in CFS - but that won't win you many awards. Its pitiful how that program ended up.


Senior Member
NYC (& RI)
Low, not high, blood pressure is common in ME/CFIDS. Don't know about the other risk factors. I have heard speculation in some of the literature that there's probably a high incidence of hypoglycemia and diabetes in ME..