Diabetes and Insulin Resistance

Diabetes is a chronic metabolic disorder in which the body doesn't produce or properly use insulin, a hormone that is made in the pancreas and is essential for the healthy functioning of all cells in the body. After a meal, the digestive system breaks most food down into glucose, a form of sugar that travels in the bloodstream throughout the body and powers cellular activity. In the blood and in the brain, insulin helps glucose enter cells. As glucose levels rise in the blood after a meal, the pancreas releases insulin to help cells take in and use the glucose. Insulin released by the pancreas after a meal and throughout the day is transported into the brain, where it has important effects on brain function.

About 5-10 percent of people with diabetes have type 1 diabetes, an autoimmune disease that attacks the pancreas so that it can no longer make insulin. By far, the more common form of diabetes is type 2, a condition in which the pancreas makes enough insulin, but the cells do not respond properly to it—a condition called insulin resistance.

In insulin resistance, the pancreas works overtime to make more insulin to help glucose enter cells, so insulin levels rise in the blood. No matter how much insulin the pancreas produces, it can't control glucose levels, and glucose builds up in the blood, creating high blood glucose levels. Many people with insulin resistance have high levels of both glucose and insulin in their blood. When a certain threshold is crossed, a person will be diagnosed with type 2 diabetes.

Risk factors for insulin resistance and type 2 diabetes are obesity (particularly excess fat at the waist), lack of exercise, increased age, and genetic factors. Many people with type 2 diabetes have no symptoms at first. When symptoms begin to emerge, they can include infections, vision problems, nerve damage, extreme thirst, and fatigue. Over time, diabetes damages the heart, blood vessels, eyes, kidneys, and nerves. These complications can be reduced by managing blood glucose levels through weight control, diet, exercise, medications and, sometimes, the administration of insulin injections.

Type 2 diabetes affects almost one fifth of Americans over sixty. More than twenty-three million Americans have diabetes, including nearly six million who don't know they have it. Millions of others have insulin resistance. "With the increase in obesity, the lack of physical activity, and changes in our diet," Dr. Craft told us, "this is a rapidly growing condition."

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Excerpted from THE ALZHEIMER'S PROJECT: MOMENTUM IN SCIENCE, published by Public Affairs, www.publicaffairsbooks.com.

Alzheimer's Disease (AD)

A progressive degenerative disease of the brain that causes impairment of memory and other cognitive abilities.

Amyloid Precursor Protein (APP)

The larger protein from which beta-amyloid is formed.

ApoE Gene

A gene that codes for a protein that carries cholesterol to and within cells; different forms of the ApoE gene are associated with differing risks for late-onset Alzheimer's disease. This gene may be referred to as a risk factor gene or a "susceptibility gene" because one form of the gene, called APOE4, is associated with the risk of developing late onset AD.

Beta-Amyloid

Derived from the amyloid precursor protein and found in plaques, the insoluble deposits outside neurons. May also be called A-beta.

Beta-Amyloid Plaque

A largely insoluble deposit found in the space between nerve cells in the brain. The plaques in Alzheimer's disease are made of beta-amyloid and other molecules, surrounded by non-nerve cells (glia) and damaged axons and dendrites from nearby neurons.

Cognitive Reserve

The brain's ability to operate effectively even when some damage to cells or brain cell communications has occurred.

Dementia

A broad term referring to a decline in cognitive function that interferes with daily life and activities. Alzheimer's disease is one form of dementia.

Functional MRI (fMRI)

An adaptation of an MRI (see magnetic resonance imaging) technique that measures brain activity during a mental task, such as one involving memory, language, or attention.

Hippocampal Formation

A structure in the brain that plays a major role in learning and memory and is involved in converting short-term to long-term memory. Also called the hippocampus.

Inflammation

The process by which the body responds to cellular injury by attempting to eliminate foreign matter and damaged tissue.

Insulin Resistance

A condition in which the pancreas makes enough insulin, but the cells do not respond properly to it; characterizes and precedes type 2 diabetes.

Magnetic Resonance Imaging (MRI)

A diagnostic and research technique that uses magnetic fields to generate a computer image of internal structures in the body.

Mild Cognitive Impairment (MCI)

A condition in which a person has cognitive problems greater than those expected for his or her age. Amnestic MCI includes memory problems, but not the personality or other cognitive problems that characterize AD.

Neurodegenerative Disease

A disease characterized by a progressive decline in the structure and function of brain tissue. These diseases include AD, Parkinson's disease, frontotemporal lobar degeneration, and dementia with Lewy bodies. They are usually more common in older people.

Oligomers

Clusters of a small number of beta-amyloid peptides.

Oxidative Damage

Damage that can occur to cells when they are exposed to too many free radicals.

Pittsburgh Compound B (PiB)

The radioactive tracer compound used during a PET (see Positron Emission Tomography) scan of the brain to show beta-amyloid deposits.

Pittsburgh Compound B (PiB)

The radioactive tracer compound used during a PET (see Positron Emission Tomography) scan of the brain to show beta-amyloid deposits.

Synapse

The tiny gap between nerve cells across which neurotransmitters and nerve signals pass.

Tau

A protein that helps to maintain the structure of microtubules in normal nerve cells. Abnormal tau is a principal component of the paired helical filaments in neurofibrillary tangles.

Tangles

A protein that helps to maintain the structure of microtubules in normal nerve cells. Abnormal tau is a principal component of the paired helical filaments in neurofibrillary tangles.

Memory

Normal Aging

Genetic Risk Factor

Dominant and Recessive Genes

Genes and Proteins

Protein-Misfolding Disease

Cholesterol

Biomarkers

Disease-Modifying Drug

Transgenic Mice

An animal that has had a gene (such as the human APP gene) inserted into its chromosomes for the purpose of research. Mice carrying a mutated human APP gene often develop plaques in their brains as they age.

Pathology

Microglia

Insulin & Insulin Resistance

Susceptibility Gene

A variant in a cell's DNA that does not cause a disease by itself but may increase the chance that a person will develop a disease.

Susceptibility Genes

A variant in a cell's DNA that does not cause a disease by itself but may increase the chance that a person will develop a disease.

Genome-Wide Association Study

Vascular Disease

Genetics

Genetics

Normal Aging