There has been a burst of papers drawing further attention to the damage that glucose and insulin dysregulation does to the brain. A study just published in the journal Neurology investigates specifically…

“…the association between glucose tolerance status defined by a 75-g oral glucose tolerance test (OGTT) and the development of dementia.”

The authors subjected 1,017 community-dwelling dementia-free subjects 60 years and older to an oral glucose tolerance test, then followed them for 15 years. The outcome measure was clinically diagnosed dementia. What did their data show?

The age- and sex-adjusted incidence of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD) were significantly higher in subjects with diabetes than in those with normal glucose tolerance. These associations remained robust even after adjustment for confounding factors for all-cause dementia and AD, but not for VaD (all-cause dementia: adjusted hazard ratio [HR] = 1.74; AD: adjusted HR = 2.05; VaD: adjusted HR = 1.82). Moreover, the risks of developing all-cause dementia, AD, and VaD significantly increased with elevated 2-hour postload glucose (PG) levels even after adjustment for covariates, but no such associations were observed for fasting plasma glucose (FPG) levels: compared with those with 2-hour PG levels of <6.7 mmol/L [120.6 mg/dl], the multivariable-adjusted HRs of all-cause dementia and AD significantly increased in subjects with 2-hour PG levels of 7.8 to 11.0 mmol/L [140.4 to 198 mg/dl] or over, and the risk of VaD was significantly higher in subjects with levels of ≥11.1 mmol/L [199.8 mg/dl].”

This is striking. The risk of all-cause dementia doubled for those with diabetes, and there was a significant increase in the risk of all-cause dementia and Alzheimer’s disease with a 2 hour post-glucose load level of 140.4 mg/dl or more. Moreover, fasting glucose levels did not reveal the danger that was disclosed only by the functional OGTT. I always risk desensitizing my patients to the damage done to the brain by glucose and insulin dysregulation; better to let the authors’ conclusion do the talking:

“Our findings suggest that diabetes is a significant risk factor for all-cause dementia, AD, and probably VaD. Moreover, 2-hour PG levels, but not FPG levels, are closely associated with increased risk of all-cause dementia, AD, and VaD.”

Meanwhile, a time study just published in the journal Diabetic Medicine also examines the association of diabetes with Alzheimer’s disease. The authors’ intent was to determine…

“…whether diabetes mellitus influences functional status in patients with Alzheimer’s disease.”

They studied 608 community-dwelling patients with Alzheimer’s disease, assessing diabetes at the beginning. Functional status was examined twice yearly with the Activities of Daily Living scale. Each patient also had a baseline functional disability determined if their Activities of Daily Living score was less than 6. Decreases in these metrics over four years of follow-up exams was used to define worsening of functional disability due to AD. Their data also reveal the ruination of the brain by glucose intolerance:

“At baseline, diabetes was present in 63 participants (10.4%) and, compared with those without diabetes, was associated with functional impairment [age- and sex-adjusted OR = 2.73]. After controlling for confounders, the association remained significant [OR = 2.04]. Follow-up demonstrated a significant interaction between duration of Alzheimer’s disease and diabetes, which was associated with progression of functional impairment in patients who had been diagnosed with Alzheimer’s disease for less than 1 year, but not in those who had been diagnosed with Alzheimer’s disease for more than 1 year. Abnormal one-leg balance, polymedication and obesity seem to be important factors explaining the association between diabetes and functional status.”

Clinicians (non-neurologists), how often do you check one-leg balance? The authors’ data suggests that a year after a clear-cut Alzheimer’s diagnosis the damage is too extensive to discriminate the effect of diabetes, thus they conclude:

“At baseline, the presence of diabetes significantly increases the risk of functional disability in patients with Alzheimer’s disease; our longitudinal data confirm that in patients with a recent diagnosis of Alzheimer’s disease (but not in those who have had Alzheimer’s disease for longer than 1 year), diabetes continues to worsen functional status.”

Regarding mechanisms, an interesting paper just published in Current Diabetes Reviews examines recent findings illuminating the link between IGF-1 signaling and diabetes-associated dementia. The authors state:

“Patients with type 2 diabetes (T2DM) have a two- to three-fold increased risk for Alzheimer’s disease (AD), the most common form of dementia. Vascular complications might explain partially the increased incidence of neurodegeneration in patients with T2DM. Alternatively, neuronal resistance for insulin/insulin-like growth factor-1 (IGF-1) might represent a molecular link between T2DM and AD, characterizing AD as “brain-type diabetes”.”

They describe recent research findings that suggest decreased IGF-1 signaling (IIS) in the brain is a compensatory attempt to reduce the accumulation of toxic β-amyloid (Aβ):

“According to this hypothesis, brains from AD patients showed substantially downregulated expression of the Insulin receptor (IR), the IGF-1 receptor (IGF-1R), and the insulin receptor substrate (IRS) proteins…suggesting that decreased IIS [insulin/IGF-1 signaling] might be involved in the pathogenesis of both T2DM and AD. In contrast, type 2 diabetic patients suffering from AD accumulate less β-amyloid (Aβ) compared to non-diabetic AD patients raising the question, whether the changes in IIS are cause, consequence, or compensatory counterregulation to neurodegeneration. Recent data in C. elegans showed that reducing IIS decreases Aβ toxicity. This effect is accomplished via two transcription factors…suggesting that Insulin/IGF-1 transmitted signals influence Aβ proteotoxicity.”

This important point should not go unnoticed by those who are contemplating therapies that increase IGF-1—they may increase risk factors for Alzheimer’s disease and dementia.

And another paper recently published in Neurology highlights the damage done to the brain by advanced glycation end products due to poor glucose tolerance. The authors observe:

“Several studies report that diabetes increases risk of cognitive impairment; some have hypothesized that advanced glycation end products (AGEs) underlie this association. AGEs are cross-linked products that result from reactions between glucose and proteins. Little is known about the association between peripheral AGE concentration and cognitive aging.”

They studied 920 elders without dementia, 495 with diabetes and 425 with normal glucose, and examined baseline AGE concentration by urine pentosidine in association with performance on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and repeatedly over 9 years. What did the data show?

“On both tests, there was a more pronounced 9-year decline in those with high and mid pentosidine level [more AGEs] compared to those in the lowest tertile. Incident cognitive impairment was higher in those with high or mid pentosidine level than those in the lowest tertile.”

We are probably just beginning to understand the ways that glucose and insulin regulation, whose profound leverage on the physiology is evolutionarily preserved from relatively primitive organisms to humans, has on the brain. Regarding damage done by excessive glucose interaction with tissues, it is not necessary for glucose dysregulation to have progressed to diabetes as the authors conclude:

“High peripheral AGE level is associated with greater cognitive decline in older adults with and without diabetes.”

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Summary:

• The use of PSA as a screening tool for aggressive prostate cancer (PCa) is not supported by scientific studies of its effectiveness.
• Many men are subject to disabling, sometimes even fatal, interventions based on PSA tests when they would never have developed aggressive prostate cancer.
• The U.S. Preventive Services Task Force has prepared a draft recommendation to stop screening in those who have not been diagnosed with prostate cancer.
• There are many who, having benefited from PSA screening for PCa, feel strongly that this recommendation by the USPSTF is irresponsible.
• A broader understanding of the underlying causes of elevated PSA and PCa offers a ‘middle path’ of judicious PSA screening, with a meaningful action plan that doesn’t corner patients and doctors into risky invasive procedures or the anxiety of doing nothing. Factors such as insulin resistance and estrogen-testosterone balance are of vital importance for prostate and general health.

Anyone reading this is surely aware of the controversy swirling around the  draft recommendation statement of the U.S. Preventive Services Task Force (USPSTF) that…

“…recommends against prostate-specific antigen (PSA)-based screening for prostate cancer…This recommendation applies to men in the U.S. population that do not have symptoms that are highly suspicious for prostate cancer, regardless of age, race, or family history.”

The Task Force did not evaluate the use of the PSA test for men with highly suspicious symptoms or those with a diagnosis prostate cancer. This recommendation is based on a number of studies finding that PSA (including PSA velocity, the rate at which PSA goes up) is a poor predictor of prostate cancer in general and aggressive prostate cancer in particular, and the assertion that widespread screening has resulted in many unnecessarily invasive and debilitating procedures that themselves can be disabling and even fatal. Feelings are riding high as a large body of public health statistics is pitted against those who feel that a PSA test may have saved their life or the life of a patient. But practitioners and patients face more than a quandary—the debate as it’s currently framed is flawed by a glaring omission.

The PSA discussion is presently structured to assume that the response to a rising PSA can only be ignored (in favor of ‘watchful waiting’) or acted on with invasive biopsies that can seriously damage quality of life and aggressive therapies for what may in fact be indolent, slow growing tumors. That’s it, the clinical decision-making path would appear to fork into only those two roads. Here’s the problem: there is a surprising blind spot for the extensive body of science done on the underlying causes of prostate cancer that offer important opportunities to benefit.  Bear in mind that inflammation or enlargement of prostate tissue caused by various disrupting factors can elevate PSA. These can often be treated with lifestyle or wholesome, non-invasive measures that also reduce the risk of other conditions like diabetes and cardiovascular disease. You may wish to read earlier posts on this topic by typing ‘prostate’ in the search box above. For now consider a couple of the most glaring omissions:

To ignore the role of insulin resistance and metabolic syndrome in prostate disease is gigantic clinical error. Consider just one paper published recently in Nature Reviews Urology in which the authors state:

“The metabolic syndrome is common in countries with Western lifestyles. It comprises a number of disorders—including insulin resistance, hypertension and obesity—that all act as risk factors for cardiovascular diseases. Urological diseases have also been linked to the metabolic syndrome. Most established aspects of the metabolic syndrome are linked to benign prostatic hyperplasia (BPH) and prostate cancer. Fasting plasma insulin, in particular, has been linked to BPH and incident, aggressive and lethal prostate cancer.”

Moreover…

“Overall, the results of studies on urological aspects of the metabolic syndrome seem to indicate that BPH and prostate cancer could be regarded as two new aspects of the metabolic syndrome, and that an increased insulin level is a common underlying aberration that promotes both BPH and clinical prostate cancer.”

This is so important yet has been so ignored. Here it is again:

“Key points

• The metabolic syndrome is a cluster of disorders, including type 2 diabetes, atherosclerotic disease manifestations, hypertension, obesity and dyslipidemia, and is prevalent in countries with Western lifestyles
• The most important common underlying endocrine aberration of these disorders is an increased insulin level, which is also linked to benign prostatic hyperplasia (BPH) and prostate cancer
• Most aspects of the metabolic syndrome are risk factors for BPH and prostate cancer, which seems to suggest that these tumors are themselves aspects of the metabolic syndrome”

Insulin at high levels due to receptor resistance damages sensitive tissues and can act as a tumor promoter. The authors conclude:

“Urologists need to be aware of the effect that the metabolic syndrome has on urological disorders and should transfer this knowledge to their patients.”

Another of the most egregious omissions in prostate cancer management and prevention is attendance to the role played by estrogens in PCa development and progression. Consider a paper published in 2007 in the Journal of Cellular Biochemistry in which the authors observe:

“Prostate cancer is the commonest non-skin cancer in men. Incidence and mortality rates of this tumor vary strikingly throughout the world. Although several factors have been implicated to explain this remarkable variation, lifestyle and dietary factors may play a dominant role, with sex hormones behaving as intermediaries between exogenous factors and molecular targets in development and progression of prostate cancer.”

Furthermore…

“Human prostate cancer is generally considered a paradigm of androgen-dependent tumor; however, estrogen role in both normal and malignant prostate appears to be equally important. Aberrant aromatase expression and activity has been reported in prostate tumor tissues and cells, implying that androgen aromatization to estrogens may play a role in prostate carcinogenesis or tumor progression…In animal model systems estrogens, combined with androgens, appear to be required for the malignant transformation of prostate epithelial cells.”

After reviewing other aspects estrogen stimulation of prostate tissue including the opposing role of ERα and ERβ receptors, the authors conclude:

“In summary, although multiple consistent evidence suggests that estrogens are critical players in human prostate cancer, their role has been only recently reconsidered, being eclipsed for years by an androgen-dominated interest.”

The authors of a review published subsequently in European Urology recognized the dual role of estrogen receptors in prostate cancer when they set out to…

“…examine mechanisms of how oestrogens may affect prostate carcinogenesis and tumour progression.”

They report evidence for the effects of estrogenic stimulation of prostate tissue:

“The human prostate is equipped with a dual system of oestrogen receptors (oestrogen receptor alpha [ERα], oestrogen receptor beta [ERβ]) that undergoes profound remodelling during PCa development and tumour progression. In high-grade prostatic intraepithelial neoplasia (HGPIN), the ERα is upregulated and most likely mediates carcinogenic effects of estradiol as demonstrated in animal models…The partial loss of the ERβ in HGPIN indicates that the ERβ acts as a tumour suppressor…The progressive emergence of the ERα and the oestrogen-regulated progesterone receptor (PR) during PCa progression and hormone-refractory disease suggests that these tumours can use oestrogens and progestins for their growth.”

Moreover…

“The TMPRSS2-ERG gene fusion recently reported as a potentially aggressive molecular subtype of PCa is regulated by ER-dependent signalling.”

The authors also conclude:

“Oestrogens and their receptors are implicated in PCa development and tumour progression. There is significant potential for the use of ERα antagonists and ERβ agonists to prevent PCa and delay disease progression.”

A paper just published in the journal Endocrinology and Metabolism Clinics of North America echoes the theme:

“The mainstay targets for hormonal prostate cancer (PCa) therapies are based on negating androgen action. Recent epidemiologic and experimental data have pinpointed the key roles of estrogens in PCa development and progression. Racial and geographic differences, as well as age-associated changes, in estrogen synthesis and metabolism contribute significantly to the etiology.”

The authors go on to report on how estrogens and estrogen mimics contribute to development of PCa, and the roles of the different estrogen mediators in the process.

As is often the case, the principle of balance comes into play as examined in a fine paper published in The Journal of Steroid Biochemistry & Molecular Biology on the estrogen:androgen ratio in the prostate gland. The authors state:

“Although androgens and estrogens both play significant roles in the prostate, it is their combined action – and specifically their balance – that is critically important in maintaining prostate health and tissue homeostasis in adulthood. In men, serum testosterone levels drop by about 35% between the ages of 21 and 85 while estradiol levels remain constant or increase. This changing androgen:estrogen (T:E) ratio has been implicated in the development of benign and malignant prostate disease.”

They review the role of the aromatase enzyme in the production of estrogens from androgens, and the fact that its aberrant expression plays a critical role in the development of malignancy in a number of tissues. In the case of PCa, it leads to an altered T:E ratio that is associated with the development of disease. And since we do have for treatment purposes wholesome modulators of estrogen receptor function as well as aromatase enzyme inhibitors…

“The role of estrogen and the T:E balance in the prostate is further complicated by the differential actions of both estrogen receptors, α and β. Stimulation of ERα leads to aberrant proliferation, inflammation and pre-malignant pathology; whereas activation of ERβ appears to have beneficial effects regarding cellular proliferation and a putative protective role against carcinogenesis.”

Clinicians who manage, support patients with, or endeavor to prevent prostate cancer must bear their conclusion in mind:

“Overall, these data reveal that homeostasis in the normal prostate involves a finely tuned balance between androgens and estrogens. This has identified estrogen, in addition to androgens, as integral to maintaining normal prostate health, but also as an important mediator of prostate disease.”

A more comprehensive perspective on the use of PSA

There far more evidence for the application of these and other factors in prostate cancer development and expression that are equally important for conditions ranging from cardiovascular disease and diabetes to dementia than can be presented in this post. It is clear, however, that we must go beyond the fascination with the false promise of ‘silver bullet’ medications and lure of lucrative procedures to properly examine and treat the more complex web of underlying factors that support prostate cancer. In the judicious hands of a skilled clinician who has the knowledge and experience to evaluate the risk of prostate cancer in the context of the total health of their patient, observing an elevation of PSA offers more than a specter of indecision over the stark choices of invasive procedures or doing nothing. It is an opportunity to intervene in positive and wholesome ways that advance the overall, not just prostate, health of the patient in their care.

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Most readers of these posts, practitioner and layperson alike, have probably long been aware of the role of insulin resistance in cardiovascular disease, chronic inflammation and cancer as described in last week’s New York Times article. A fascinating study that adds to the mountain of scientific evidence was just published in the Public Library of Science (PLoS One) in which the authors show that higher insulin levels are associated with the unstable form of carotid artery plaque:

“The stability of atherosclerotic plaques determines the risk for rupture, which may lead to thrombus formation and potentially severe clinical complications such as myocardial infarction and stroke. Although the rate of plaque formation may be important for plaque stability, this process is not well understood. We took advantage of the atmospheric 14C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s) to determine the average biological age of carotid plaques.”

The authors dissected the cores of carotid plaques from 29 patients with carotid stenosis and analyzed them for 14C. Their findings are fascinating:

“The average plaque age (i.e. formation time) was 9.6±3.3 years. All but two plaques had formed within 5–15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels…plaques in the lowest tercile of plaque age (most recently formed) were characterized by further instability with a higher content of lipids and macrophages…Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation.”

As readers here know, a heart attack or stroke occurs when a vulnerable plaque ruptures and blocks a smaller vessel downstream. These investigators show that unstable plaque is associated with higher insulin levels. Intervening to reduce insulin resistance is one of the most important things that clinicians and patients can do for a host of conditions. The authors conclude:

“Our results show, for the first time, that plaque age, as judge[d] by relative incorporation of 14C, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age.”

Regarding laboratory testing to determine the presence of inflamed vulnerable plaque, see the earlier post on Lp-PLA2.

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Original research published recently in the Annals of Internal Medicine offers evidence that trans-palmitoleate, a fat present in milk, is responsible for metabolic benefits observed with dairy consumption. The authors set out to…

“…To investigate whether circulating trans-palmitoleate is independently related to lower metabolic risk and incident type 2 diabetes.”

They examined 3736 adults in the Cardiovascular Health Study for plasma phospholipid fatty acids, blood lipids, inflammatory markers, and glucose–insulin and dietary habits, taking into consideration relevant demographic, clinical, and lifestyle factors. They then determined how trans-palmitoleate related to major metabolic risk factors. Their data tell an interesting story of a helpful fat:

“In multivariate analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate levels. Higher trans-palmitoleate levels were associated with slightly lower adiposity and, independently, with higher high-density lipoprotein cholesterol levels, lower triglyceride levels, a lower total cholesterol–HDL cholesterol ratio, lower C-reactive protein levels, and lower insulin resistance. Trans-palmitoleate was also associated with a substantially lower incidence of diabetes…Protective associations with metabolic risk factors were confirmed in the validation cohort.”

Of course, this study does address the widespread problem of dairy allergy, nor does it discriminate between the widely varying qualities of dairy (organic from grass-fed free-range animals versus industrial dairy). But it does caution against the wholesale discrimination against fats in general and the dairy food group in particular. As always, clinical and lifestyle decisions depend on the needs of the individual which can be verified by objective outcome markers. Practitioners and health conscious individuals can consider the authors’ conclusion:

“Circulating trans-palmitoleate is associated with lower insulin resistance, presence of atherogenic dyslipidemia, and incident diabetes. Our findings may explain previously observed metabolic benefits of dairy consumption and support the need for detailed further experimental and clinical investigation.”

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A report just published in the Journal of the National Cancer Institute adds more evidence to the importance of insulin regulation in ER (estrogen receptor) negative breast cancer. The authors first note a conundrum in breast cancer epidemiology:

“Body mass index is inversely associated with risk of premenopausal breast cancer, but the underlying mechanisms for this association are poorly understood. Abdominal adiposity is associated with metabolic and hormonal changes, many of which have been associated with the risk of premenopausal breast cancer.”

They investigated the association between body fat distribution, hip circumference, and waist to hip ratio, and the incidence of premenopausal breast cancer in the Nurses’ Health Study II:

“During 426 164 person-years of follow-up from 1993 to 2005, 620 cases of breast cancer were diagnosed among 45 799 women. Hormone receptor status information was available for 84% of the breast cancers.”

When they looked at the group as a whole, no statistically significant associations were found. However…

“…each of the three body fat distribution measures was statistically significantly associated with greater incidence of estrogen receptor (ER)–negative breast cancer.”

The risk for ER-negative breast cancer was increased by 275% for waist circumference, 240% for hip circumference, and 195% for waist to hip ratio (comparing the highest to the lowest quintile). The authors state:

“These findings may suggest that an insulin-related pathway of abdominal adiposity is involved in the etiology of premenopausal breast cancer.“

The implication is that factors associated with increased abdominal adiposity influence the development of breast cancer through estrogen independent pathways, specifically the influence of excess levels of insulin on tumor growth that also promote the accumulation of fat around the waist. As experienced clinicians know, tumors often have mixed cell types. The role of insulin as a tumor promoter should never overlooked in case management, with careful attention to the regulation of blood sugar and insulin.

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An important study just published in the Annals of Oncology adds more evidence of the exceptional importance of  metabolic syndrome for prostate cancer. The authors state:

“Metabolic syndrome (MS) is a set of risk factors that includes obesity and insulin resistance and has been implicated in the development of prostate cancer.”

They proceeded to examine the impact of metabolic syndrome on prostate cancer patients treated with androgen deprivation therapy (ADT, blocking the production or signaling of male hormones). Comparing the data between patients with and without metabolic syndrome for the average time to PSA progression and overall survival (OS) yielded a stark contrast:

“Median time to PSA progression for patients with MS was 16 versus 36 months without MS. The median OS for patients with MS was 36.5 months after commencing ADT compared with 46.7 months for those patients without MS.”

The authors sum up their evidence in the usual understated fashion:

“This preliminary data suggest that MS is a risk factor for earlier development of castration-resistant prostate cancer and support the need for a prospective evaluation of this finding.”

It’s troubling to see how often clinicians fail to emphasize the great importance of blood sugar and insulin control when managing prostate cancer. Patients need to be aware that the lifestyle factors that address this are among the most important things they can do.

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A research article just published in PLoS (Public Library of Science) Medicine adds more evidence to the association between elevated blood sugar and cancer. The authors begin by stating:

“Prospective studies have indicated that elevated blood glucose levels may be linked with increased cancer risk…The aim of this study was to investigate the association between blood glucose and risk of incident and fatal cancer overall and at specific sites, as well as all-cause mortality, in a large study of six European cohorts including correction for random error in glucose levels..”

The Metabolic Syndrome and Cancer project (Me-Can) includes 274,126 men and 275,818 women from Norway, Austria and Sweden whose average age at the beginning of observation was 44.8 years. Over an average follow-up time of 10.4 years 18,621 men and 11,664 women were diagnosed with cancer, and 6,973 men and 3,088 women died of cancer. When the authors calculated the relative risk for glucose levels (adjusting for BMI and smoking), the data made a strong statement:

“Significant increases in risk among men were found for incident and fatal cancer of the liver, gallbladder, and respiratory tract, for incident thyroid cancer and multiple myeloma, and for fatal rectal cancer. In women, significant associations were found for incident and fatal cancer of the pancreas, for incident urinary bladder cancer, and for fatal cancer of the uterine corpus, cervix uteri, and stomach.”

The authors discuss the possible mechanisms:

“Insulin and bioavailable insulin-like growth factor-I (IGF-I) are possible links between glucose and cancer; hyperglycaemia induces elevation of these hormones that stimulate tumour growth. Glucose may also have a direct tumour-promoting effect as glucose is used as an energy substrate in tumour cells, particularly in fast-growing, highly proliferative tumour cells.”

They boil down their findings in this closing summary:

“In conclusion, abnormal glucose metabolism, independent of BMI, is associated with increases in risk of cancer and cancer death overall and at many specific sites. Furthermore, our data showed a linear and somewhat stronger association among women than among men, and the association was stronger for fatal compared to incident cancer.”

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An important paper was just published in the journal Cancer Epidemiology that provides further evidence of insulin as a tumor promoter in prostate cancer. The authors state:

“A higher insulin level has been linked to the risk of prostate cancer promotion…the insulin hypothesis was tested once more prospectively in men with a benign prostatic disorder.”

They proceeded by following 389 patients who had lower urinary tract symptoms without prostate cancer over 8-12 years. There were notable differences between the 44 who developed prostate cancer and the rest who didn’t:

“”Men with prostate cancer diagnosis had a higher systolic and diastolic blood pressure, were more obese as measured by BMI, waist and hip measurements than men who did not have prostate cancer diagnosis at follow-up. These men also had a higher uric acid level, and a higher fasting serum insulin level than men who did not have prostate cancer diagnosis at follow-up.”

All of these accessory factors—blood pressure, BMI, waist and hip circumference, uric acid—are directly related to elevated insulin. Considering the prevalence of both prostate cancer and metabolic syndrome (high insulin), it’s important for clinicians and the public alike to bear in mind the authors’ conclusion:

“Our data support the hypothesis that a higher insulin level is a promoter of prostate cancer. Moreover, our data suggest that the insulin level could be used as a marker of the risk of developing prostate cancer. The present findings also seem to confirm that prostate cancer is a component of the metabolic syndrome. Finally, our data generate the hypothesis that the metabolic syndrome conceals early prostate cancer.“

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This interesting paper recently published in the Journal of Clinical Endocrinology & Metabolism describes one of the reasons why support when undergoing a surgical procedure is so important (and links to the risks for delirium and accelerated dementia after surgery in the elderly). The authors set out to investigate the…

“…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.

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Surgeons are routinely surprised at the speed of recovery and reduction of complications and discomfort when they operate on our patients who have a surgical support program based on their individual needs. This interesting study published recently in the Journal of Clinical Endocrinology & Metabolism describes why supporting insulin function and regulation of the inflammatory response help so much.

“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.

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