Tag Archives: Insulin Resistance

Cholesterol Buzz

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To a great degree, the battle of dietary recommendations for cholesterol and other fats have hinged on the belief that serum cholesterol levels are a direct predictor of cardiovascular disease. Despite the broad awareness and even larger acceptance of this theory, science still struggles to authenticate this claim. Dietary cholesterol and saturated fats do, indeed, influence serum cholesterol levels, but is that truly a good predictor of cardiovascular risk? If history has any say in the matter, decades of fat-free marketing, food products, and diet plans haven’t seemed to curtail the mortality rate, and cardiovascular disease still remains the number one cause of death in this country. Dietary guidelines continue to push for an increase in omega-3 and omega-6 polyunsaturated fatty acids in place of saturated fats, but again, this advice is rooted in the so-called improvement in serum cholesterol ratios, resulting from this shift in dietary fat, even in the absence of cardiovascular improvements. We have even explored the effects of replacing saturated fats with carbohydrates on cardiovascular risk factors, and not surprisingly, that has not yielded positive results either. In fact, replacing saturated fats with carbohydrates has worsened cardiovascular risks by increasing small, dense low-density lipoprotein particles, which are more indicative of cardiovascular events than large LDL particles, which are produced by dietary saturated fats.Slowly, studies are emerging with fresh ideas pointing to oxidative stress, inflammation, and endothelial dysfunction – not hyperlipidemia – as major risk factors in cardiovascular disease. These same factors are associated with insulin resistance and type-2 diabetes, making an obvious connection between the epidemic of deranged blood sugar levels and cardiovascular dysfunction – a.k.a. the phenomenon of metabolic syndrome. So why doesn’t the mainstream mindset focus on restricting inflammatory foods and processed foodstuffs that increase oxidative stress, in favor of antioxidant-rich produce and fiber-filled legumes? Why has the focus persistently been upon cholesterol?

As alternative health care practitioners already know, it is high time that the U.S. Department of Health and Human Services stop demonizing eggs and begin targeting some of the commodity crops for the cardiovascular mortality rates in this country. When 1032 participants were studied for 5 years in the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study, it was found that “egg or cholesterol intakes were not associated with increased CAD risk, even in ApoE4 carriers (i.e., in highly susceptible individuals)” and yet, recommendations to limit these items have been central to American dietary guidelines for decades. At the same time, evidence points to dietary sugars as being a more influential factor on cardiometabolic risks, independent of obesity. The OmniCarb study, one of the largest studies “to test effects of high- versus low-GI diets in the context of moderate- and low-CHO diets” showed that higher total carbohydrate consumption, rather than glycemic index, contributed more negatively to cardiovascular risks. In an era and nation where carbohydrate and sugar consumption has extended beyond the ceiling level, why isn’t the focus shifting to these food groups? Studies on the effects of carbohydrates on cardiovascular disease have been strangely stifled, but to the keen observer, this should not come as a surprise. After all, grains and sugar are commodity foodstuffs heavily subsidized by the government, so who would fund studies that would link these foodstuffs to America’s top cause of mortality?

While we can be thankful that the U.S. Department of Health and Human Services has finally taken the long overdue step of acknowledging that cholesterol and eggs are not a health trap, and changing dietary guidelines accordingly, it will take years to remove long held beliefs regarding cholesterol and cardiovascular disease. Nevertheless, the next time a patient proudly exclaims that their doctor has given them a “clean bill of health” based on a standard lipid profile, a prime opportunity stands waiting for you to re-educate, one patient at a time.

Alzheimer’s Disease: Type 3 Diabetes?

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Alzheimer’s Disease: Type 3 Diabetes?

It is no coincidence that we are witnessing a skyrocketing increase in the incidence of Alzheimer’s disease (AD), which parallels those of metabolic syndrome, type 2 diabetes, and obesity. All of these are, in part, outcomes related to carbohydrate intolerance and the mismatch between our biological makeup and our modern diet and lifestyle. In fact, the connections between glucose, insulin dysregulation and Alzheimer’s disease are so strong that many researchers now commonly refer to AD as “type 3 diabetes

The blood-brain-barrier is a powerful border that carefully regulates the entry of fuel substrates and nutrients from the periphery. However, it is not capable of protecting the brain from the deleterious effects of an onslaught of refined carbohydrates, oxidized vegetable oils, and nutritionally empty processed foods. The brain is an intensely energy-hungry organ, and anything that impedes its use of glucose—such as peripheral and/or central insulin resistance—will have disastrous consequences for cognitive function. Alzheimer’s disease is the end stage manifestation after a significant number of neurons have “starved to death” due to a loss of their ability to metabolize glucose.

Although the outward manifestations of AD—such as memory loss, confusion, and disturbing behavioral changes—are easy to observe, there are also physiological factors that can be measured and quantified. One of the earliest and most profound observable biochemical changes in the AD brain is a reduction in the rate at which the brain uses glucose, called the cerebral metabolic rate of glucose (CMRglu). This can be measured in vivo, with AD patients showing upwards of 45% reduction in CMRglu compared to healthy, age-matched controls. Some researchers see this decline in glucose usage by the brain as the predominant abnormality in AD

Interestingly, the decline in CMRglu can be observed in people at risk for AD (based on family history or genotype) as early as in their 30s or 40s, long before overt signs of AD have manifested. Thus, the decreased CMRglu can be seen as a kind of “canary in the coal mine”—an early warning sign that something is going awry in the brain. The extent of the reduction in CMRglu is tied to AD severity. A longitudinal study using PET scan to measure CMRglu.  in people age 50-80 showed that reduced hippocampal CMRglu at baseline predicted progression from normal cognitive function to AD, with the greatest reductions at baseline correlating with the quickest development of full-blown AD.

At baseline, hippocampal glucose metabolism in people who progressed from healthy to AD was 26% below that of people who did not develop AD, and the annual rate of decline averaged 4.4%. In people who progressed from normal to mild cognitive impairment (a precursor to AD), CMRglu was 15% reduced at baseline, with an annual rate of decline at 2.4%. The rate of decline for people who had normal CMRglu at baseline and did not develop AD was just 0.8%. Assuming the rates of decline were somewhat constant, extrapolating backward indicates that the decline may have started as early as 20 years before overt signs of AD were present. At baseline, despite the already decreased CMRglu in some subjects, all subjects were cognitively normal. This suggests that a starting point of reduced glucose usage in the brain and a stronger rate of continued decline might be one of the first triggering events in AD. The brain may be able to compensate for years before damage is so widespread that overt symptoms are observable. The normal forgetfulness and foibles we associate with “just getting older”—Where did I leave my keys? Don’t I have an appointment somewhere this week?—might be the earliest indicators that the brain is struggling to fuel itself.

An interesting potential contributor to the reduced CMRglu is peripheral and/or central insulin resistance. Plasma concentration of insulin is positively correlated with AD severity.  When neurons become insulin resistant, they are afflicted by the same pathology that occurs in the periphery—an inability to properly metabolize glucose, causing glucose to accumulate in extracellular spaces for an extended period of time. This results in rampant glycation and the formation of advanced glycation end products (AGEs). These AGEs add insult to injury by forming cross-linkages with each other that may alter the shape of neuronal synapses and impede cellular communication and nerve impulse transmission in the brain, with cognitive abnormalities being an obvious consequence. With hyperinsulinemia affecting 40% of people over age 80, it’s no surprise to find a link between insulin dysregulation and a condition that preferentially strikes older individuals. Moreover, hyperinsulinemia has been found to be and independent risk factor for AD.

The beta-amyloid (Aβ) plaques often implicated as a cause of AD may, in fact, be a result of peripheral hyperinsulinemia. In addition to the reduced CMRglu, the presence of insoluble Aβ plaques is one of the defining signatures of AD pathology. However, Aβ is a normal product of protein degradation, and there is no evidence that AD patients overproduce Aβ. Rather, the problem seems to be that Aβ isn’t cleared away as it should be, which results in these small, otherwise soluble peptide fragments aggregating into insoluble plaques. (These plaques are then subject to glycation and blocking synapses, adding yet another obstruction to neuronal communication.)

A fascinating thing to note is that what is responsible for clearing away Aβ in a timely manner—before it dwells long enough to form plaques—is insulin degrading enzyme (IDE), the same enzyme that clears away insulin. However, the affinity of IDE for insulin is so high that even small amounts of insulin completely the degradation of AB. One study demonstrated that peripheral infusion of insulin in older subjects increased the level of AB in cerebrospinal fluid within 120 minutes, and this also correlated to decreased memory function. Thus, the formation of Aβ plaques is facilitated by hyperinsulinemia. Adding yet another piece of evidence to the theory that Aβ plaques are an effect of AD pathology, rather than its cause, is the fact that the decline in CMRglu precedes the formation of the plaques. Therefore, the presence of Aβ plaques is not likely the triggering factor. (They may exacerbate disease severity, but they are not the initial event in its initiation.)

Considering the connections between impaired glucose metabolism, chronically elevated insulin, and Alzheimer’s disease, the phrase “type 3 diabetes” is viable.