More than 34 million Americans are living with diabetes. According to the American Diabetes Association, 25% of people age 65 and older in the United States have diabetes (diagnosed and undiagnosed), and about half have prediabetes.
Physicians don’t yet understand exactly how cognitive decline and diabetes are connected, but they do know that high blood sugar or insulin can harm the brain in several ways:
Most people with diabetes have Type 2, which is linked to lack of exercise and being overweight. When diabetes is not controlled, too much sugar remains in the blood.
Over time, this can damage organs, including the brain.
Scientists are finding more evidence that could link Type 2 diabetes with Alzheimer’s disease, which is the most common cause of dementia.
Diabetes mellitus refers to a health condition where your body has difficulty converting sugar to energy.
Typically, we think of three kinds of diabetes:
There is some evidence that Alzheimer’s disease should also be classified as a type of diabetes, called type 3 diabetes.
Type 3 diabetes describes the hypothesis that Alzheimer’s disease, which is a major cause of dementia, is triggered by a type of insulin resistance and insulin-like growth factor dysfunction that occurs specifically in the brain.
The classification of type 3 diabetes is highly controversial, and it’s not widely accepted by the medical community as a clinical diagnosis.
Intact insulin and insulin like growth factor (IGF) signaling have important roles in relation to brain structure and function, including myelin integrity and neuronal plasticity. Impairments in insulin and IGF signaling caused by receptor resistance or inadequate ligand disrupt energy balance and interacting networks that support vital functions such as cell survival.
Accumulating evidence supports the concept that cognitive impairment and neurodegeneration are associated with and probably are caused by insulin and IGF resistance.
In addition, the dramatic increase in rates of Alzheimer’s disease and other insulin resistance disease states, including obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, and metabolic syndrome within the past several decades point toward environmental or exposure factors mediating disease.
Since each of these disease processes can occur independently or overlap with one or more of the others, one idea is that their etiologies are shared but selective organ/tissue involvement is dictated by other variables such as genetics.
This article will focus on how peripheral insulin resistance contributes to cognitive impairment and neurodegeneration, and potential contributions of environmental and genetic factors in the pathogenesis of Alzheimer’s disease.
Insulin resistance is now a major public health problem because of its link to obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, metabolic syndrome, polycystic ovarian disease, age-related macular degeneration, and Alzheimer’s disease epidemics.
Growing evidence supports the concept that insulin resistance and metabolic dysfunction are mediators of Alzheimer’s disease [1], and therefore, Alzheimer’s disease could be regarded as a metabolic disease mediated by brain insulin and IGF resistance [2].
In fact, Alzheimer’s disease shares many features in common with systemic insulin resistance diseases including, reduced insulin-stimulated growth and survival signaling, increased oxidative stress, pro-inflammatory cytokine activation, mitochondrial dysfunction, and impaired energy metabolism [3].
Early stages of Alzheimer’s disease is marked by deficits in cerebral glucose utilization, and as the disease ensues, brain metabolic derangements with impairments in insulin signaling, insulin-responsive gene expression, glucose utilization, and metabolism deteriorate [4].
Human postmortem studies showed that brain insulin resistance with reduced insulin receptor expression and insulin receptor binding were consistently present in Alzheimer’s disease brains and get worse as the disease progresses [4].
What’s extremely interesting is that the pathways strongly affected in Alzheimer’s disease are the ones needed to maintain neuronal viability, energy production, gene expression, and plasticity [5].
Aging: Insulin and IGF resistance increase with aging, while longevity is associated with preservation of insulin/IGF responsiveness [6].
The cumulative challenges and stresses over a lifespan can damage cells and tissues due to excessive signaling through insulin/IGF-1 receptors [7].
Hence, chronic overuse of insulin/IGF signaling networks, which occurs as a consequence of hyper-insulinemia and insulin resistance, may be harmful and accelerate aging.
It is doubtful that insulin resistance, cognitive impairment, and Alzheimer’s disease are just inevitable consequences of aging since one of the key factors in the equation is that the chronic low-grade inflammation, which accompanies aging, drives insulin resistance [8].
Evidence suggests that underlying, potentially genetic factors may dictate consequences of aging because:
Insulin resistance diseases, including Alzheimer’s disease, obesity, Type 2 Diabetes Mellitus, non-alcoholic steatohepatitis, and metabolic syndrome are now pandemic [9] and the major cause of sky-rocketing healthcare costs, disability rates, and premature death.
The causes are directly linked to increased consumption of highly processed sugar, starch, and fat-laden, calorically dense foods that are rendered “tasty” by commercial enterprises.
Within the past 40–50 years, initially the United States and now the world has witnessed rapid increases in insulin resistance-related disease prevalence among young and middle-aged individuals, including adolescents and children.
Type 2 diabetes, non-alcoholic fatty liver disease, metabolic syndrome, cognitive impairment, and cardiovascular diseases are epidemic and are occurring at an earlier age than in prior years [10].
These trends are linked to the increased prevalence of obesity and sedentary lifestyles.
Since the nature and consequences of insulin resistance diseases in younger groups are nearly the same as in older individuals, it could be argued that certain lifestyles, habits, and behaviors cause disease by accelerating aging.
The corollary is that lifestyle modifications should slow aging and prevent aging-associated insulin resistance diseases.
Obesity: With regard to the brain, both epidemiological and clinical research indicate that glucose intolerance, deficits in insulin secretion, and insulin resistance diseases (type 2 diabetes mellitus, obesity/dyslipidemic disorders, or non-alcoholic steatohepatitis) all increase risk for developing mild cognitive impairment or Alzheimer’s disease-type dementia [3].
In addition, obese individuals have higher rates of executive function impairment [11], and have at least double the risk of developing Alzheimer’s disease than the general population [12].
Type 2 diabetes mellitus: The molecular and biochemical abnormalities in Alzheimer’s disease brains mimic the effects of type 2 diabetes mellitus or non-alcoholic steatohepatitis on skeletal muscle, adipose tissue, and liver, further indicating that Alzheimer’s disease is a brain insulin resistance-related disease.
Insulin resistance diseases often overlap within the same individuals.
In support of this notion, longitudinal research demonstrates that type 2 diabetes mellitus and obesity/dyslipidemic disorders correlate with subsequent development of mild cognitive impairment, dementia, or Alzheimer’s disease [13].
Non-alcoholic fatty liver disease: The fact that obesity by itself, is not an independent risk factor for mild cognitive impairment and neurodegeneration suggests that factors associated with obese states govern these tendencies [14].
Independent research demonstrates that cognitive impairment and neuropsychiatric dysfunction occur with steatohepatitis (i.e. an advanced stage of non-alcoholic fatty liver disease) and hepatic insulin resistance of various etiologies, including obesity, alcohol abuse, chronic Hepatitis C virus infection and Reyes syndrome [15].
Nonalcoholic fatty liver disease with type 2 diabetes mellitus and visceral obesity is associated with brain atrophy, neurodegeneration, and cognitive impairment [16].
Metabolic syndrome: Metabolic syndrome is a collection of disease processes centered around insulin resistance, visceral obesity, hypertension, and dyslipidemia [17].
Studies have linked peripheral insulin resistance, visceral obesity, and metabolic syndrome to brain atrophy, cognitive impairment, and impaired executive function [18].
Comprehensive findings in humans and experimental models suggest that peripheral/systemic insulin resistance disease states serve as cofactors in the pathogenesis and progression of neurodegeneration.
If you already have type 2 diabetes, there are ways that you can better manage it and lower your risk for developing type 3 diabetes.
Here are some of the proven methods for managing type 2 diabetes and minimizing organ damage:
Like most diseases humans face today, lifestyle factors contribute a large amount in determining your risk.
This is why it is so important to ensure that you are sleeping well, eating well, hydrating with water, exercising daily, and maintaining a healthy weight, and it is also why STEEL drills these points home as much as possible.
After all, many of these 'lifestyle' diseases can largely be prevented by just focusing on the basics!
If you'd like to learn more about how exercise can protect your brain's health, you can learn more
here.
And if you'd like to help your body's ability to maximize your anabolic state and force-feed muscle tissue by more efficiently shuttling carbohydrates and nutrients into your muscles faster for better pumps, muscle endurance and expedited recovery times, add this to your daily routine.
References:
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2. Steen, E., et al., Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease--is this type 3 diabetes? J Alzheimers Dis, 2005. 7(1): p. 63-80.
3. de la Monte, S.M., et al., Insulin resistance and neurodegeneration: roles of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis. Curr Opin Investig Drugs, 2009. 10(10): p. 1049-60.
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17. Kassi, E., et al., Metabolic syndrome: definitions and controversies. BMC Med, 2011. 9: p. 48.
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