I spent an interesting day last Saturday at a USC post-graduate course on “premalignant lesions of the GI react.”
Part of the session discussed the question of obesity and diet. “Fatty liver” is a condition related to obesity and metabolic syndrome.
The Wikipedia definition includes.
1. abdominal (central) obesity,
2. elevated blood pressure,
3. elevated fasting plasma glucose,
4. high serum triglycerides, and
5. low high-density lipoprotein (HDL) levels
Central obesity is not the same as subcutaneous obesity, which is what we all think of. Titters out there is a racial factor with blacks more likely to have subcutaneous obesity without the central obesity involving the liver and internal organs.
Metabolic syndrome and prediabetes appear to be the same disorder, with insulin resistance as a major factor.
Other signs of metabolic syndrome include high blood pressure, decreased fasting serum HDL cholesterol, elevated fasting serum triglyceride level (VLDL triglyceride), impaired fasting glucose, insulin resistance, or prediabetes.
Associated conditions include:
1. hyperuricemia,
2. fatty liver (especially in concurrent obesity) progressing to
3. nonalcoholic fatty liver disease,a.so called NAFL
4. polycystic ovarian syndrome (in women),
5. erectile dysfunction (in men), and
6. acanthosis nigricans.
It is generally accepted that the current food environment contributes to the development of metabolic syndrome: our diet is mismatched with our biochemistry. Weight gain is associated with metabolic syndrome. Rather than total adiposity, the core clinical component of the syndrome is visceral and/or ectopic fat (i.e., fat in organs not designed for fat storage) whereas the principal metabolic abnormality is insulin resistance.
A lot of this seems to point to insulin resistance which I first heard of about 25 years ago when it was a new subject. I remember the new chief of the Diabetes service at USC discussing this new discovery and showing slides of insulin levels in patients who were not diabetic. His work suggested that high levels of serum insulin preceded type II diabetes by years but seemed to be associated.
Here is a study in the journal Circulation from 11 years ago.
The common pathway seemed to be insulin resistance.
A second category of causation is insulin resistance. Many investigators place a greater priority on insulin resistance than on obesity in pathogenesis.2,3 They argue that insulin resistance, or its accomplice, hyperinsulinemia, directly causes other metabolic risk factors. Identifying a unique role for insulin resistance is complicated by the fact that it is linked to obesity. Insulin resistance generally rises with increasing body fat content, yet a broad range of insulin sensitivities exists at any given level of body fat.4 Most people with categorical obesity (body mass index [BMI] ?30 kg/m2) have postprandial hyperinsulinemia and relatively low insulin sensitivity,5 but variation in insulin sensitivities exists even within the obese population.4
Is this due to fat in the diet ? For a long time this was suspected and low fat diets have been advocated for decades.
When the risk for new-onset diabetes was examined for the Framingham cohort, in both men and women, the presence of metabolic syndrome was highly predictive of new-onset diabetes. Almost half of the population-attributable risk for diabetes could be explained by the presence of ATP III metabolic syndrome.
Is this still the theory of causation ? A lot of this work is in animal models and the early research involving rabbits fed meat set the medical world off on the wrong track for 50 years. We ended with high carbohydrate diets and, it is my belief, that this led to the obesity epidemic all over the world.
Recent work suggests a more important role for inflammation and immunity.
The interplay between immune cells and adipose tissue is a key event for the development of insulin resistance that precedes type 2 diabetes. CD40, a well-documented costimulatory receptor, is required for efficient systemic adaptive immune responses. However, we and other groups recently showed that CD40 unexpectedly ameliorates inflammation in VAT and accordingly attenuates obesity-induced insulin resistance. Specifically, although CD40 is typically considered to play its principal immune roles on B lymphocytes and myeloid cells, we found that CD40(+)CD8(+) T lymphocytes were major contributors to the protective effect.
That is interesting but early in the game. The American Diabetes Association suggests a low carb, high protein diet may be helpful in diabetics.
Thus, a LoBAG diet [a low-biologically-available-glucose (LoBAG) diet.] ingested for 5 weeks dramatically reduced the circulating glucose concentration in people with untreated type 2 diabetes. Potentially, this could be a patient-empowering way to ameliorate hyperglycemia without pharmacological intervention. The long-term effects of such a diet remain to be determined.
George Lundberg, a former AMA Journal editor has a different opinion and recommends a high carb diet.
Very recent work suggests that bile salts could reverse insulin resistance.
Adipose tissue secretes adipokines that regulate insulin sensitivity in adipocytes and other peripheral tissues critical to glucose metabolism. Insulin resistance is associated with severe alterations in adipokines characterized by release of increased pro-inflammatory cytokines and decreased anti-inflammatory cytokines from adipose tissue. The role of Farnesoid X receptor (FXR) activation on adipokines in relation to adipose tissue inflammation and insulin resistance is not completely explored. For the first time, we have evaluated the ability of Chenodeoxycholic acid (CDCA), an endogenous FXR ligand, in restoring the disturbance in adipokine secretion and insulin resistance in palmitate treated 3T3-L1 cells and adipose tissues of High fat diet (HFD) rats.
We are getting into the weeds here but this rat study suggests that the inflammatory reaction may be more important than diet alone. Chenodeoxycholic acid, a bile salt, seems to help. Why ?
Here is more work on inflammation in metabolic syndrome.
It now appears that, in most obese patients, obesity is associated with a low-grade inflammation of white adipose tissue (WAT) resulting from chronic activation of the innate immune system and which can subsequently lead to insulin resistance, impaired glucose tolerance and even diabetes. WAT is the physiological site of energy storage as lipids.
What about gut bacteria ? It may play a role and probiotics may be helpful. Is there anything bacteria don’t do ?
The best advice is don;t get fat. The best way to avoid that is to eat less. What is the role of carbohydrates in obesity ? The results are slow in coming. Some studies suggest low glucose load, including carbohydrates is associated with less obesity but this is not definitive.
Where information is available, the associations between risk factors and GL are either similar or stronger in the overweight or obese, as judged by BMI, and apply to both body weight and blood risk factors. The implications tend to favour a long-term benefit of reducing GL, for which further study is necessary to eliminate any possibility of publication bias and to establish results in clinical trials with overweight and obese patients.
Where information is available, the associations between risk factors and GL are either similar or stronger in the overweight or obese, as judged by BMI, and apply to both body weight and blood risk factors. The implications tend to favour a long-term benefit of reducing GL, for which further study is necessary to eliminate any possibility of publication bias and to establish results in clinical trials with overweight and obese patients.
I still favor the Atkins diet.