A new and convenient biomarker for early insulin resistance

Posted on June 16, 2010 by Dr. Jonathan

PLoS One Elevated levels of insulin due to insulin resistance can do so much damage throughout the body long before the onset of type 2 diabetes that better tools for making the diagnosis early enough for lifestyle changes to have their maximum benefit are always welcome. This research article just published in PLoS One (Public Library of Science) validates the use of an ‘old friend’, α-hydroxybutyrate (α–HB, α = alpha), as a valuable warning sign in the non-diabetic population. The authors first note that…

“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.

Another reminder about insulin and cancer

Posted on June 15, 2010 by Dr. Jonathan

A paper published in the most recent issue of Postgraduate Medicine brings to mind the importance of insulin regulation in cancer prevention and treatment. The authors studied the interplay between the use of insulin therapy in diabetes and cancer.

“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.”

Sugars raise bad fats in the blood

Posted on May 4, 2010 by Dr. Jonathan

JAMA Readers and patients here know how higher levels of insulin from a high glycemic diet can result in an increase in the harmful kinds of fat in the blood. It will come as no surprise that a paper just published in the Journal of the American Medical Association adds more evidence to the association. The the objective of the authors was to…

“…assess the association between consumption of added sugars and blood lipid levels in US adults.”

They analyzed the data for 6,113 adults collected over seven years for sugars in the diet and levels of HDL and LDL cholesterol and triglycerides. A clear correlation between higher levels of sugars and lower HDL (“good” cholesterol), higher LDL (“bad” cholesterol) and higher triglycerides emerged. There was strong evidence for maintaining a low glycemic diet to regulate cholesterol:

“Among higher consumers (≥10% added sugars) the odds of low HDL-C levels were 50% to more than 300% greater compared with the reference group (<5% added sugars).”

Their conclusion was mildly stated:

“In this study, there was a statistically significant correlation between dietary added sugars and blood lipid levels among US adults.”

Have you been trying but not succeeding in getting cholesterol and/or triglycerides down with a low fat diet? There has been so much science done on the correlation between insulin sensitivity and cholesterol levels; it’s surprising this wasn’t noted by the authors. Just one example is a fresh paper in the Journal of Lipid Research that begins with the well-known fact:

“Cholesterol synthesis is upregulated and absorption downregulated in insulin resistance and in type 2 diabetes.”

Interestingly, the authors wanted to see if any level of insulin resistance would have an effect on cholesterol synthesis:

“We investigated whether alterations in cholesterol metabolism are observed across the glucose tolerance status, from normoglycemia through impaired glucose tolerance to type 2 diabetes…”

What conclusions did they draw from their data?

“In conclusion, cholesterol metabolism was altered already in subjects with impaired fasting glucose. Upregulated cholesterol synthesis was associated with peripheral insulin resistance independent of obesity.”

How to eat healthy fat and oil is another topic, but if cholesterol and triglycerides are the issue—pay attention to sugars and insulin.

Kidney damage can occur before diabetes sets in

Posted on April 26, 2010 by Dr. Jonathan

Clinical Journal of the Amer Soc of Nephro An important study just published in the Clinical Journal of the American Society of Nephrology that offers powerful evidence for the need to maintain healthy insulin and glucose levels well before that system fails and blood sugar crosses the line into the type 2 diabetes territory. High levels of insulin do nasty mischief throughout the body and the kidneys are especially sensitive. The authors set out with this objective:

“Prevalence of chronic kidney disease (CKD) in people with diagnosed diabetes is known to be high, but little is known about the prevalence of CKD in those with undiagnosed diabetes or prediabetes. We aimed to estimate and compare the community prevalence of CKD among people with diagnosed diabetes, undiagnosed diabetes, prediabetes, or no diabetes.”

Their data paints a worrisome picture:

“Fully 39.6% of people with diagnosed and 41.7% with undiagnosed diabetes had CKD…Among those with CKD, 39.1% had undiagnosed or prediabetes.”

Remember dear reader that chronic kidney disease means that there has been an irretrievable loss of kidney tissue; this is beyond normal age-related changes. This is yet another important reason to confirm that your strategy for maintaining healthy insulin function is suiting your needs. This is not difficult to determine with the right test assessment. The authors conclude:

“CKD prevalence is high among people with undiagnosed diabetes and prediabetes. These individuals might benefit from interventions aimed at preventing development and/or progression of both CKD and diabetes.”

Limit insulin use as much as possible for type 2 diabetes

Posted on April 3, 2010 by Dr. Jonathan

Diabetes, Obesity and Metabolism Metabolic syndrome crosses the line to type 2 diabetes when insulin resistance worsens to the point that the pancreas can no longer increase insulin production to yet higher levels. By then the elevated insulin ‘in the background’ has already been doing damage throughout the body for years. If blood sugar can no longer be controlled with natural agents that re-sensitize insulin receptors and support blood sugar metabolism or other oral anti-diabetic agents, then exogenous (from the outside) insulin is used. But if higher levels of native insulin contribute to a variety of diseases, are higher therapeutic levels a concern? This study published in the journal Diabetes, Obesity and Metabolism investigates just that:

“Aim: To compare population-based rates of all-cause and cardiovascular (CV) mortality in newly treated patients with type 2 diabetes according to levels of insulin exposure.”

The authors collected data for 12,272 individuals on cumulative insulin exposure and its correlation with death from cardiovascular diseases and death from any disease. What did the data show?

“The highest mortality rates were in the high exposure group…we observed a graded risk of mortality associated with increasing exposure to insulin… Analyses restricted to CV-related and non-vascular mortality showed virtually identical results.”

Here’s how they summed up their findings:

“We observed a significant and graded association between mortality risk and insulin exposure level in an inception cohort of patients with type 2 diabetes that persisted despite multivariable adjustment.”

Wouldn’t you think this is one reason why other studies have shown that too aggressive pharmaceutical blood sugar control results in worse outcomes? There are a number of evidence-based natural agents that support insulin receptor sensitivity and other functional aspects of type 2 diabetes. The more these can be used to minimize the dependence on increasing insulin the better.

Fructose even worse than glucose for fat and insulin

Posted on January 12, 2010 by Dr. Jonathan

This is why the ubiquitous high-fructose corn syrup is such a disaster for public health. The authors of this study published in The Journal of Clinical Investigation note that “Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance.” When they examined the effect in humans they found that all the following were increased markedly in the subjects on fructose but not glucose: visceral adiposity (fat around the organs), plasma triglycerides, fat in the liver, small dense LDL, oxidized LDL, fasting glucose and fasting insulin. At the same time insulin sensitivity decreased in the subjects consuming fructose but not glucose. The authors conclude: “These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults.” [DNL = de novo lipogenesis which means making fat from scratch in the liver.] An accompanying commentary in the same journal states: “In the event that any readers harbor some remaining skepticism, an unprecedented thorough analysis in close to 900,000 participants from almost 60 prospective studies was very recently published, proving beyond any possible doubt that progressive excess mortality is caused by increased body adiposity…Stanhope and colleagues provide major scientific progress by demonstrating marked differences in the metabolic effects of these two major sugars with respect to their ability to promote intraabdominal lipid deposition and hepatic lipid production, while shifting cholesterol metabolism in an unfavorable manner and diminishing insulin sensitivity in humans.” Public health is groaning under a burden of overweight/obesity; how much disease could we prevent just by cutting out most of the sweet drinks (including most fruit juices) for children and adults?

Insulin and cognitive disorders

Posted on December 23, 2009 by Dr. Jonathan

Insulin receptors are found throughout the central nervous system. Fascinating fact: “insulin affects distinct cognitive processes, e.g. by triggering the formation of psychological memory contents.” As the authors of this paper published recently in the journal Diabetologia state: “metabolic and cognitive disorders such as obesity, type 2 diabetes mellitus and Alzheimer’s disease are associated with resistance of central nervous structures to the effects of insulin…” They go on to conclude: “Enhancement of central nervous insulin signalling…has yielded encouraging results that bode well for the successful translation of these effects into future clinical practice.” Targeted tests are available to determine how you can best take care of your brain by managing blood sugar and insulin.

Moderate-intensity exercise more effective than vigorous intensity for cardiovascular risk

Posted on December 4, 2009 by Dr. Jonathan

A surprising paper of great practical significance was just published in the journal Obesity that documents a significantly greater improvement in cardiovascular risk-related variables (triglycerides, insulin, metabolic syndrome score) with moderate-intensity exercise than with vigorous exercise. The authors offer this life-style pearl: “That all three of these strong, independent, cardiovascular risk factors were significantly affected by moderate-intensity exercise suggests that regular walking exercise might be as effective, if not more so, than more vigorous exercise in favorably modifying cardiovascular risk.” Further research will have to validate my expectation that the adrenocortical stress response plays a role here. Don’t forget the importance of interval training (see earlier posts), but at least get out for a walk.

Sugar shortens life span

Posted on November 25, 2009 by Dr. Jonathan

You are probably aware of earlier studies that demonstrated increase in life span of experimental animals by the effect of caloric restriction on insulin regulating pathways. This interesting study recently published in the journal Cell Metabolism elucidates the flip side: “We found that adding a small amount of glucose to the medium (2%) shortened the life span of C. elegans by inhibiting the activities of life span-extending transcription factors that are also inhibited by insulin signaling…” The authors conclude: “Together, these findings raise the possibility that a low-sugar diet might have beneficial effects on life span in higher organisms.”

Serum insulin, not glucose, linked to prostate cancer

Posted on November 19, 2009 by Dr. Jonathan

Here we have another study linking insulin resistance and higher serum insulin to prostate cancer. This recently published article in the Journal of the National Cancer Institute concludes: “Elevated fasting levels of serum insulin (but not glucose) within the normal range appear to be associated with a higher risk of prostate cancer.” Gentlemen, it is important to know that insulin levels rise in the background while glucose appears normal for years before type 2 diabetes is diagnosed. Make sure you know how to keep insulin receptors healthy.