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The Link Between Alzheimer's and Diabetes Explained

September 19, 2022 8 min read

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:

  • Diabetes raises the risk of heart disease and stroke, which hurt the heart and blood vessels. Damaged blood vessels in the brain may potentially contribute to cognitive decline.
  • Too much insulin may cause an imbalance of chemicals in the brain. Some of these changes may help trigger cognitive decline.
  • Inflammation is caused by high blood sugar which may damage brain cells and cause dementia to develop.

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.

What is Type 3 Diabetes?

Diabetes mellitus refers to a health condition where your body has difficulty converting sugar to energy. Typically, we think of three kinds of diabetes:
Type 1 diabetes is a chronic health condition in which your body’s endocrine part of the pancreas doesn’t produce enough of the hormone insulin, and your blood sugar (glucose) level becomes too high.

Type 2 diabetes is a chronic condition in which your body develops resistance to insulin, and your blood sugar level becomes too high as a result.
Gestational diabetes occurs during a pregnancy, and the blood sugar level is too high during this time.

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.

Evidence That Type 2 Diabetes is Linked to Alzheimer's Disease

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 and Neurodegeneration

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].

Underlying Causes of Brain Insulin Resistance

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:

  1. The rates and characteristics of aging vary widely among individuals;
  2. The nature of and target organs diseased by insulin resistance are different; and
  3. There is no clear reason why aging per se should result in chronic inflammation, insulin and IGF resistance, or growth hormone deficiency.

Lifestyles Promoting Systemic Insulin Resistance

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, starch-, sugar- 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 nonalcoholic 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.

Preventing Type 3 Diabetes

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:

  • Try to exercise four times per week for 30 minutes per day.  
  • Resistance training is absolutely fundamental to include in your exercise regimen and building skeletal muscle should be the cornerstone of your exercise program. Skeletal muscle is the biggest organ for glucose disposal in our bodies and can greatly increase insulin sensitivity.
  • Try to eat healthy foods low in saturated fat, rich in protein, and high in fiber. Include plenty of fruit and vegetables.  High quality protein should be a priority of your nutrition program. High quality protein which comprises all the essential amino acids, including the branched-chain amino acids is absolutely necessary to stimulate protein synthesis.
  • Carefully monitor your blood sugar according to your healthcare provider’s recommendations.
  • Take prescribed medications on schedule and with regularity as directed by your healthcare physician.
  • Manage your weight and aim to reduce bodyfat as much as possible.


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!

References:
1.    Hoyer, S., Glucose metabolism and insulin receptor signal transduction in Alzheimer disease. Eur J Pharmacol, 2004. 490(1-3): p. 115-25.
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.
4.    Talbot, K., et al., Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J Clin Invest, 2012. 122(4): p. 1316-38.
5.    Frolich, L., et al., Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease. J Neural Transm (Vienna), 1998. 105(4-5): p. 423-38.
6.    Sato, N., et al., Role of insulin signaling in the interaction between Alzheimer disease and diabetes mellitus: a missing link to therapeutic potential. Curr Aging Sci, 2011. 4(2): p. 118-27.
7.    Zemva, J., et al., Neuronal overexpression of insulin receptor substrate 2 leads to increased fat mass, insulin resistance, and glucose intolerance during aging. Age (Dordr), 2013. 35(5): p. 1881-97.
8.    Horrillo, D., et al., Age-associated development of inflammation in Wistar rats: Effects of caloric restriction. Arch Physiol Biochem, 2011. 117(3): p. 140-50.
9.    Chiang, D.J., M.T. Pritchard, and L.E. Nagy, Obesity, diabetes mellitus, and liver fibrosis. Am J Physiol Gastrointest Liver Physiol, 2011. 300(5): p. G697-702.
10.    Williamson, R., A. McNeilly, and C. Sutherland, Insulin resistance in the brain: an old-age or new-age problem? Biochem Pharmacol, 2012. 84(6): p. 737-45.
11.    Lokken, K.L., et al., Evidence of executive dysfunction in extremely obese adolescents: a pilot study. Surg Obes Relat Dis, 2009. 5(5): p. 547-52.
12.    Yaffe, K., Metabolic syndrome and cognitive decline. Curr Alzheimer Res, 2007. 4(2): p. 123-6.
13.    Whitmer, R.A., Type 2 diabetes and risk of cognitive impairment and dementia. Curr Neurol Neurosci Rep, 2007. 7(5): p. 373-80.
14.    Whitmer, R.A., et al., Body mass index in midlife and risk of Alzheimer disease and vascular dementia. Curr Alzheimer Res, 2007. 4(2): p. 103-9.
15.    Perry, W., R.C. Hilsabeck, and T.I. Hassanein, Cognitive dysfunction in chronic hepatitis C: a review. Dig Dis Sci, 2008. 53(2): p. 307-21.
16.    de la Monte, S.M. and M. Tong, Brain metabolic dysfunction at the core of Alzheimer's disease. Biochem Pharmacol, 2014. 88(4): p. 548-59.
17.    Kassi, E., et al., Metabolic syndrome: definitions and controversies. BMC Med, 2011. 9: p. 48.
18.    Burns, J.M., et al., Insulin is differentially related to cognitive decline and atrophy in Alzheimer's disease and aging. Biochim Biophys Acta, 2012. 1822(3): p. 333-9.

Dr. Paul Henning

About Dr. Paul

I'm currently an Army officer on active duty with over 15 years of experience and also run my own health and wellness business. The majority of my career in the military has focused on enhancing Warfighter health and performance. I am passionate about helping people enhance all aspects of their lives through health and wellness. Learn more about me