Regular readers will know that obesity is the major driver of the world-wide diabetes epidemic. But not everyone who is overweight will ultimately get diabetes.

So why do some people with excess fat become diabetic while others don’t?

Since the discovery that some people show marked signs of inflammation in their fat depots, researchers have suggested that this chronic inflammation may cause fat cells to produce molecules that promote diabetes and other metabolic complications (this has been referred to as metainflammation).

A new study by John Wentworth and colleagues from the Walter and Eliza Hall Institute of Medical Research, Victoria, Australia, published in last month’s edition of DIABETES, shows that pro-inflammatory cells found in adipose tissue may promote insulin resistance and thereby increase the risk for diabetes.

The researchers examined white blood cells (macrophages) isolated from adipose tissue samples obtained from lean and obese women undergoing bariatric surgery.

In obese women, the density of activated CD11c(+) macrophages was greater in subcutaneous than omental adipose tissue and correlated with markers of insulin resistance.

Furthermore, the researchers showed that these CD11c(+) macrophages not only metabolize lipids and may initiate immune responses but also secrete substances that impair insulin-stimulated glucose uptake by human adipocytes.

The authors conclude that these pro-inflammatory CD11c(+) macrophages in adipose tissue may serve as of insulin resistance and may explain why some people may develop diabetes in response to obesity.

Obviously, the paper does not answer the question why some people are more likely to accumulate these pro-inflammatory cells in their fat tissues. For one thing, it is clearly not simply related to the amount of fat, as some people with substantial amounts of excess fat can go their entire lives without ever developing diabetes.

On the other hand, some people appear to be particularly prone to showing signs of inflammation with weight gain and for them the difference of a few pounds of extra fat can mean the difference between having and not having diabetes.

Perhaps, one day, targeting the inflammation in adipose tissue may prove a novel way to prevent and treat diabetes associated with excess weight.

AMS
Edmonton, Alberta

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Wentworth JM, Naselli G, Brown WA, Doyle L, Phipson B, Smyth GK, Wabitsch M, O’Brien PE, & Harrison LC (2010). Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes, 59 (7), 1648-56 PMID: 20357360

As blogged before, overweight and obese patients frequently present with fibromyalgia, characterized by chronic pain, fatigue and depressed mood.

A paper by Akiko Okifuji from the University of Utah, Salt Lake City, just published in the Journal of Pain, examines the relationship between fibromyalgia and obesity in pain, function, mood, and sleep.

The study examines the impact of obesity on hyperalgesia, symptoms, physical abilities, and sleep in 215 fibromyalgia patients, who also underwent tender point examination, physical performance testing, and 7-day home sleep assessment.

Almost 50% of participants were obese and an additional 30% were overweight.

Obesity was positively related to greater tender point sensitivity, reduced physical strength and lower-body flexibility, shorter sleep duration, and greater restlessness during sleep.

The results confirmed that obesity is a prevalent comorbidity of fibromyalgia and the authors suggest that weight management may need to be incorporated into treatments.

In the paper, Okifuji and colleagues also discuss several potential mechanisms linking obesity to fibromyalgia including alterations in the endogenous opioid system, the endocrine system, and systemic inflammation, whereby adipose-tissue derived cytokines may enhance central sensitization.

Clinicians should be aware of the relationship between excess weight and fibromyalgia, which can often pose an important contributor to weight gain and a major barrier to weight management.

AMS
Edmonton, Alberta

Okifuji A, Donaldson GW, Barck L, & Fine PG (2010). Relationship Between Fibromyalgia and Obesity in Pain, Function, Mood, and Sleep. The journal of pain : official journal of the American Pain Society PMID: 20542742

Today, I am attending the 8th World Congress on Trauma, Shock, Inflammation and Sepsis in Munich, Germany.

Interestingly, this conference features a whole series of seminars on the interdisciplinary management of obesity (under the rather unfortunate title ‘Fat Man – We Will Help You’ [sic]).

I have been invited to chair and speak at the session on medical therapy, but there are also sessions on adipose tissue biology, perioperative management, bariatric surgical procedures, and the emergency management of bariatric patients.

As I often say in my presentations to colleagues: it does not matter what discipline in medicine you practice – you will be seeing an increasing number of heavier patients with their own issues and complications.

The fact that a world conference on trauma should devote this much time to sessions on obesity assessment and management is clearly to be commended in the light of the global obesity epidemic.

The more all health professionals learn and understand the complexities and problems posed by heavier patients, the better we can serve this particularly vulnerable patient population.

AMS
Munich, Germany

Obesity is often described as a state of low grade inflammation. Activated macrophages (white blood cells) in adipose tissue play an important role in this inflammatory response by secreting a number of pro-inflammatory molecules (cytokines) that can promote the development of insulin resistance and other complications of obesity.

Previous studies have shown that the “glitazone” class of antidiabetic agents can suppress inflammatory macrophage activation and can also increase the expression of an DGAT1 (triacylglycerol (TG) synthesis enzyme acyl CoA:diacylglycerol acyltransferase 1), an enzyme that makes it easier for fat cells and macrophages to store excess fat.

Now a paper by Suneil Koliwad and colleagues from the Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA, published in this weeks’ issue of the Journal of Clinical Investigation, provides further evidence that increasing activity of DGAT1 in adipocytes and macrophages may protect animals from the pro-inflammatory effects of obesity.

The researchers found that although mice overexpressing DGAT1 in both macrophages and adipocytes were more prone to weight gain, they did not show signs of the inflammatory response commonly seen with diet-induced obesity.

Through a series of experiments, the researchers were able to establish that DGAT1 is indeed necessary to protect against this inflammatory response, thereby raising the question of wether stimulation of this enzyme may also protect against the complications of obesity in humans.

Thus, although this research may not lead to new ways of preventing or reducing obesity, it may open new avenues for attenuating some of the health consequences related to excess weight.

AMS
Copenhagen, Denmark

To anyone regularly dealing with overweight and obese patients, the frequent association between excess weight and chronic musculoskeletal pain is no secret.

This association is particularly true for the rather enigmatic syndrome of fibromyalgia, characterised by the presence of generalized pain in muscle and joints, often associated with fatigue, poor sleep, and depression. Patients typically present with exquisite tenderness over discrete anatomical points, commonly referred to as tender points.  While there is still much debate around the exact etiology or even the exact diagnostic criteria (e.g. number of tender points) for fibromyalgia, there is no doubt that the presence of this syndrome can prove a major barrier to weight management.

Indeed, it is not at all clear whether there may in fact be an etiological link between fibromyalgia and obesity. As outlined in a paper by Akiko Okifuji and colleagues from Salt Lake City, UT, published last year in Clinical Rheumatology, 70% of fibromyalgia patients in their study were overweight or obese and presented with elevated levels of IL-6, catecholamines, cortisol, and CRP, all of which are common findings in obese patients. Furthermore, the patients with fibromyalgia, as do obese patients, presented with reduced sleep duration and efficiency. Based on these commonalities, Okifuji and colleagues concluded that excess weight and obesity may well play a role in fibromyalgia and related dysfunction. 

Interestingly, in 2008, Alan Saber and colleagues published an article in Obesity Surgery describing a significant improvement in pain score and points of tenderness in patients with fibromyalgia who underwent laparoscopic Roux-en-Y gastric bypass surgery. Based on these findings, the authors suggested that weight loss may be an important treatment modality for severely obese patients with this syndrome.

Whether or not less drastic approaches to weight management can provide benefits remains to be seen. Nevertheless, there have been reports of limited response to education, exercise, and psychological interventions. Thus, currently accepted non-pharmacological treatments for fibromyalgia remain rather limited.

Recently, a Cochrane review concluded that duloxetine is efficacious for treating pain in fibromyalgia and another systematic review found evidence that gabapentin and pregabalin can also reduce pain in these patients. 

Nevertheless, fibromyalgia continues to be a common but largely undertreated problem in overweight and obese patients and can often pose a significant barrier to increasing physical activity or modifying ingestive behaviour. 

As blogged before, assessment for muskuloskeletal pain should be a regular and essential feature of any assessment for overweight and obesity. 

I very much look forward to comments from any readers struggling with fibromyalgia or from colleagues on how they manage this debilitating syndrome.

AMS
Edmonton, Alberta