“…mechanisms behind postoperative insulin resistance and impaired glucose utilization…”

They shrewdly analyzed the expression of 21 target genes in abdominal adipose (fat) tissue from samples taken at the beginning and end of patients undergoing abdominal surgery. What did the data show?

“After surgery, both sc [subcutaneous] and omental adipose tissue mRNA levels of genes involved in the IL6 and nicotinamide phosphoribosyltransferase pathways were increased, whereas mRNA levels of insulin receptor substrate 1 and adiponectin were reduced. TNF pathway genes were differently regulated between sc and omental adipose tissue, and glucose transporter 4 mRNA levels were decreased only in omental adipose tissue.”

In other words, surgery elicits a shift in genetic expression that favors insulin resistance and inflammation. The authors conclude:

“The transcriptional output of pivotal inflammatory and insulin signaling pathway genes is altered after surgery…This could be of importance for the metabolic aberrations associated to postsurgical complications…”

This helps to understand why patients who are lucky enough to receive adjunctive support for the insulin and inflammatory signaling pathways and receptors recover faster and with less complications.

“Current diagnostic tests, such as glycemic indicators, have limitations in the early detection of insulin resistant individuals. We searched for novel biomarkers identifying these at-risk subjects.”

The authors use of ‘random forest statistical analysis’ of 399 nondiabetic subjects (representing a broad spectrum of insulin sensitivity and glucose tolerance) selected α-hydroxybutyrate (α–HB) as the most accurate biochemical for detecting insulin resistance.

“α–HB also separated subjects with normal glucose tolerance from those with impaired fasting glycemia or impaired glucose tolerance independently of, and in an additive fashion to, insulin resistance. These associations were also independent of sex, age and BMI.”

Thus the authors conclude:

“α–hydroxybutyrate is an early marker for both insulin resistance and impaired glucose regulation.“

I have been testing α–HB for years as part of an organic acids panel because it is also an indicator of toxin-stimulated upregulation of detoxification pathways and glutathione demand. So it makes sense that the authors would also add:

“The underlying biochemical mechanisms may involve increased lipid oxidation and oxidative stress.”

I’m looking at an organic acids report from the file of a patient with other signs of insulin resistance plus a recurrence of breast cancer and, sure enough, α–hydroxybutyrate is abnormally elevated.

“Abdominal obesity and type 2 diabetes mellitus are associated with erectile and urinary dysfunction in men.”

The investigators set out to determine the extent to which weight loss would impact overall sexual function and lower urinary tract symptoms by measuring the effects of an 8 week low-calorie diet using meal replacements* on insulin sensitivity, testosterone, erectile function, sexual desire, prostate symptoms, abdominal obesity and waist circumference. What did their data show?

“Weight loss of ~10% was significantly associated with increased insulin sensitivity, plasma testosterone levels, IIEF-5 (erectile function) and SDI (sexual desire) scores, as well as reduced WC (waist circumference) and IPSS (prostate) scores, in diabetic as well as nondiabetic men.”

They further observed that…

“The degree of weight loss was significantly associated with improvements in plasma testosterone levels, erectile function and LUTS. Reduction in LUTS was significantly associated with increased plasma testosterone, erectile function and sexual desire.”

Hence their clear-cut conclusion:

“Diet-induced weight loss significantly and rapidly improves sexual function, and reduces LUTS, in obese middle-aged men with or without diabetes.”

This is a compelling illustration of the link between insulin resistance and male sexual function.

* Although effective in this study (at 800 calories per day) there are better meal replacement products available for weight loss than this one loaded with fructose, milk protein, and low grade minerals and fish oil.

Insulin resistance

“Epidemiological evidence from our prospective study, the Japan Public Health Center-based Prospective (JPHC) study, and systematic literature reviews generally support the idea that factors related to diabetes or insulin resistance are associated with an increased risk of colon (mostly in men), liver, and pancreatic cancers… The suggested mechanism of these effects is that insulin resistance and the resulting chronic hyperinsulinemia and increase in bioavailable insulin-like growth factor 1 (IGF1) stimulate tumor growth.”

The data from the Japan Public Health Center-based Prospective (JPHC) study support this conclusion:

“…there is substantial evidence to show that cancers of the colon, liver, and pancreas are associated with insulin resistance, and that these cancers can be prevented by increasing physical activity, and possibly coffee consumption.”

That’s right, coffee consumption—see the numerous posts documenting the benefits of coffee. Past and forthcoming posts report on studies that describe the association of insulin resistance and other cancers. The ‘take home’ message is that it’s important to maintain insulin at a healthy level long before the onset of type 2 diabetes by lifestyle factors (good eating and exercise) and evidence-based supplementation appropriate to your genetic and circumstantial needs.

“The benefits of coffee on abnormal liver biochemistry, cirrhosis and hepatocellular carcinoma have been reported…this study aims to investigate if coffee use has any relationship with bright liver, measured by ultrasound bright liver score (BLS), in patients with non-alcoholic fatty liver disease (NAFLD), and which relationship, if any, is present with BMI and insulin resistance.”

‘Bright liver’ refers to the appearance of a fatty liver on ultrasound imaging, and a higher BLS measurement means more fat deposits in the liver. What did they find?

“Less fatty liver involvement is present in coffee vs. non-coffee drinkers. Odds ratios show that obesity, higher insulin resistance, lower HDL cholesterol, older age and arterial hypertension are associated with a greater risk of more severe BLS; to the contrary, coffee drinking is associated with less severe BLS…Coffee use is inversely associated with the degree of bright liver, along with insulin resistance and obesity…”

Their conclusion is similar to numerous other studies:

“A possible opposite, if not antagonistic, role of coffee with regard to overweightness and insulin resistance, similar to that reported in hepatocarcinoma and cirrhosis, is envisaged in the natural history of NAFLD.”

“Insulin resistance is associated with metabolic syndrome and type 2 diabetes, representing a risk factor for cardiovascular disease.”

They set out to investigate a link between insulin resistance and low testosterone, even in the absence of overweight. What did their data show?

“In older men, lower total testosterone is associated with insulin resistance independently of measures of central obesity. This association is seen with testosterone levels in the low to normal range.”

Do you see the connections between erectile dysfunction, cardiovascular disease, insulin resistance and low testosterone that are emerging here?

1. Insulin resistance and cognitive impairment in Archives of Neurology
2. Hyperinsulinemia and risk of Alzheimer’s disease in Neurology
3. Insulin resistance and executive dysfunction in the Journal of the American Geriatrics Society
4. Hyperinsulinemia and Alzheimer’s disease in the journal Age and Ageing
5. Body mass index, cardiovascular risk factors, and dementia in Archives of Internal Medicine

Testing your levels of hemoglobin A1C,  glucose, insulin and triglycerides along with measuring your waist-to-hip ratio are among the ways we can see how you’re doing.

1. Fat accumulation around organs is linked to decreased heart function
2. Body mass index (BMI) is not a reliable predictor of fat accumulation
3. Fat in the liver was associated with insulin resistance and triglycerides.

I have seen numerous individuals who do not appear overweight and whose BMI was normal, but bioelectric impedance analysis (an objective measurement of body fat percentage) revealed that they were ‘metabolically obese’—there was excess fat around their organs. Insulin resistance was a factor in each case.