“…determine the association of systolic BP control achieved and adverse cardiovascular outcomes in a cohort of patients with diabetes and CAD (coronary artery disease).”

They analyzed data for 6400 subjects from 862 sites in 14 countries for more than ten years.

“Patients received first-line treatment of either a calcium antagonist or β-blocker followed by angiotensin-converting enzyme inhibitor, a diuretic, or both to achieve systolic BP of less than 130 and diastolic BP of less than 85 mm Hg. Patients were categorized as having tight control if they could maintain their systolic BP at less than 130 mm Hg; usual control if it ranged from 130 mm Hg to less than 140 mm Hg; and uncontrolled if it was 140 mm Hg or higher.”

The data they accumulated painted this picture:

“…little difference existed between those with usual control and those with tight control…The all-cause mortality rate was 11.0% in the tight-control group vs 10.2% in the usual-control group; however, when extended follow-up was included, risk of all-cause mortality was 22.8% in the tight control vs 21.8% in the usual control group.”

Note that the tight control group had a slightly higher risk of all-cause mortality over the longer time period. Besides the greater likelihood of adverse effects with higher doses of medication, lower blood pressure means diminished delivery of oxygen to tissues (the pressure acts to overcome the increased resistance of less a healthy circulatory system).

Their conclusion clearly states the lack of benefit with suppression to less than 130 mm Hg:

“Tight control of systolic BP among patients with diabetes and CAD was not associated with improved cardiovascular outcomes compared with usual control.”

See another recent study that proves the same point.

“…study the effects of metformin on the incidence of vitamin B-12 deficiency (<150 pmol/l), low concentrations of vitamin B-12 (150-220 pmol/l), and folate and homocysteine concentrations in patients with type 2 diabetes receiving treatment with insulin.”

Incidentally, this reference for vitamin B-12 is extremely low and far from optimal. After following 390 patients with type 2 diabetes who were treated with 850 mg metformin or placebo three times a day for 4.3 years, what did they conclude from their data?

“Long term treatment with metformin increases the risk of vitamin B-12 deficiency, which results in raised homocysteine concentrations. Vitamin B-12 deficiency is preventable; therefore, our findings suggest that regular measurement of vitamin B-12 concentrations during long term metformin treatment should be strongly considered.”

Do remember that serum B12 is not a reliable indicator. To ascertain that your genetic and circumstantial needs for this critical cofactor are actually being methylmalonic acid, measured in serum or urine, is much more reliable.

“…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.

“This study examines the risk of acute myocardial infarction (MI) conferred by the metabolic syndrome (MS) and its individual factors in multiple ethnic populations.”

The authors evaluated data from 26,903 subjects in 52 countries according to the World Health Organization (WHO) and International Diabetes Federation (IDF) criteria for MS, and correlated them with the occurrence of heart attack to calculate the odds. Crunching the numbers produced these results:

“Using the WHO definition, the association with MI by the MS is similar to that of diabetes mellitus and hypertension and significantly stronger than that of the other component risk factors…The IDF definition showed similar results.”

The practical conclusion to be drawn from this evidence is that the evaluation and treatment of metabolic syndrome in general and insulin resistance in particular is mandatory for realistic heart attack risk assessment and prevention.

“The mechanisms behind postoperative insulin resistance and impaired glucose utilization are not fully understood…In this study, we aimed to specifically evaluate the transcription profile of genes in the insulin and adipokine signaling pathways…after surgical injury.”

Adipokines are cytokines such as IL-6 and TNFα secreted by fat cells. The authors measured changes in the messenger RNA (mRNA) levels that code for insulin signaling and inflammatory cytokines to define how genes alter their expression in response to a surgical trauma. Their data showed a signficant effect:

“After surgery…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.”

Their conclusion is important for surgeons and their patients:

“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, such as insulin resistance and hyperglycemia.”

If you are anticipating an elective procedure and your surgeon is not trained to design a supportive protocol based on an evaluation using the appropriate tests, you may wish to seek out a practitioner experienced in the functional approach.

“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.

“According to 2007 estimates, 27% of all patients with diabetes use some form of insulin therapy. The increasing utilization of insulin has become a cause for concern because findings from several observational trials have suggested an association with an increased risk of developing cancer.”

The authors undertook a review of scientific studies that assessed the carcinogenic or mitogenic effects of insulin therapy [mitogenic = stimulating mitosis, thus increasing the rate of existing tumor growth]. Here’s how the evidence weighed in:

“Data from our review suggest that insulin analogs…may play more of a mitogenic than a carcinogenic role in association with different types of cancer, suggesting an amplified rate of existing tumor growth in the presence of insulin analogs. Evidence for insulin-induced mitogenicity appears to be most prevalent in prostate, breast, pancreatic, and colorectal cancers.”

I don’t think I can emphasize enough the importance of healthy insulin regulation in cancer prevention and treatment. As the authors state in their conclusion:

“…clinicians must be diligent in both screening for new cancers in patients receiving insulin and in monitoring for tumor growth or maintenance of remission in patients with existing cancers.”

“Epidemiological surveys have demonstrated that habitual coffee consumption reduces the risk of type 2 diabetes. The aim of this work was to study the antidiabetic effect of coffee and caffeine in spontaneously diabetic KK-Ay mice.”

The mice were not taken to Starbucks for mini espresso shots, but were…

“…given regular drinking water (controls) or 2-fold diluted coffee for 5 weeks.”

The results were pretty amazing:

“Coffee ingestion ameliorated the development of hyperglycemia and improved insulin sensitivity. White adipose tissue mRNA levels of inflammatory cytokines (MCP-1, IL-6, and TNFα), adipose tissue MCP-1 concentration, and serum IL-6 concentration in the coffee group were lower than the control group. Moreover, coffee ingestion improved the fatty liver.”

The authors summed up their findings by stating:

“…coffee exerts a suppressive effect on hyperglycemia by improving insulin sensitivity, partly due to reducing inflammatory cytokine expression and improving fatty liver. Moreover, caffeine may be one of the effective antidiabetic compounds in coffee.”

“The ability of nuts to improve the blood lipid profile and reduce the risk of CHD (coronary heart disease) is now well established. The interest that health effects of nuts have gained recently has brought the possible benefits of consuming nuts, such as improvement in the conditions of the metabolic syndrome, and their potential to prevent and control diabetes into focus.”

They report an important observation:

“Acute feeding studies indicate that nuts have minimal effects on rising postprandial blood glucose levels when eaten alone, and diminish the postprandial glycaemic response when consumed with high-glycaemic index carbohydrate foods in both normoglycaemic and type 2 diabetic individuals.”

This means that whether your blood sugar is still OK or has already gone too high, if you consume nuts with a meal or snack—even if it is, at least to a degree, more glycemic than desirable—the nuts will prevent your blood sugar from spiking too high and overstimulating the release of insulin. And eating nuts alone has a trivial effect on raising blood sugar.

The authors further note…

“Nuts have a healthy nutritional profile, high in MUFA (monounsaturated fatty acids) and PUFA (polyunsaturated fatty acids), are a good source of vegetable protein and are rich in fibre, vitamins and minerals….early data indicate that the inclusion of nuts in the diets of individuals with diabetes and the metabolic syndrome is warranted, in view of their potential to reduce CHD risk.”

However, don’t forget that tree nuts are among the more common food allergens.

“As obesity’s ties to multiple cancers strengthen, a new study suggests that inflammation may be the primary culprit in at least one malignancy: liver cancer.”

The study itself was recently published in the journal Cell. The report that…

“We now demonstrate that either dietary or genetic obesity is a potent bona fide liver tumor promoter in mice…Obesity-promoted HCC (hepatocellular carcinoma = liver cancer) development was dependent on enhanced production of the tumor-promoting cytokines IL-6 and TNF, which cause hepatic inflammation and activation of the oncogenic transcription factor STAT3.”

Readers here will not be surprised that they also assert…

“The chronic inflammatory response caused by obesity and enhanced production of IL-6 and TNF may also increase the risk of other cancers.”

Three important points: (1) nothing increases the storage of fat in the liver like the high levels of insulin associated with insulin resistance (remember the link between insulin and fatty liver disease). (2) Chronic inflammation, whatever the cause, is a component of most chronic degenerative diseases. (3) Those of us who are health care professionals should be using the available laboratory tests for inflammatory cytokines in the care of our patients when appropriate; readers who are patients should be asking about them.