Difference between revisions of "Blood Sugar"

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It is critical for overall health to keep blood sugar levels under control, especially for the brain.  The higher your blood sugar levels, the higher your brain sugar.  Sixty percent of blood sugar is brain sugar. So for example, if a blood glucose level is 100, brain glucose is 60.  
It is critical for overall health to keep blood sugar levels under control, especially for the brain.  The higher your blood sugar levels, the higher your brain sugar.  Sixty percent of blood sugar is brain sugar. So for example, if a blood glucose level is 100, brain glucose is 60.  
It should be noted that while blood glucose typically becomes elevated from foods that are considered high glycemic, there are other non-food factors that can elevate blood glucose as well (discussed below).
It should be noted that while blood glucose typically becomes elevated from foods that are considered high glycemic, there are other non-food factors that can elevate blood glucose as well (discussed below).


=== Hemoglobin A1c ===  
=== Hemoglobin A1c ===  
This test, conducted by a lab, reflects the average level of blood sugar over the past 2 to 3 months. It's also called HbA1c, or sometimes just A1c.  According to the American Diabetes Association:  A1c less than 5.7% is “normal”, A1c 5.7 to 6.4 is prediabetes, A1c 6.5 or higher is diabetes
[[File:A1c to average blood sugar.jpg|thumbnail|How to convert an HbA1c reading into average blood glucose levels]]
 
This test, conducted by a lab, reflects the average level of blood sugar over the past 2 to 3 months. It's also called HbA1c, or sometimes just A1c.  According to the American Diabetes Association:  A1c less than 5.7% is “normal”, A1c 5.7 to 6.4 is prediabetes, A1c 6.5 or higher is diabetes.
 
However, Dr Bredesen's protocol recommends an A1c of less than 5.6, see [[Fasting insulin less than 5; HgbA1c less than 5.6]]
 
Our [https://www.apoe4.info/forums/viewtopic.php?f=33&t=1418 PRIMER: An introduction to ApoE4, biochemistry, and possible prevention strategies] recommends keeping A1c to 5.5 or under (37 mmol/mol), preferably closer to 5% (32 mmol/mol). 
 
There are those who say down to 5.2 there’s an increased risk for brain shrinkage.  Studies that have additionally determined that HbA1c levels considered "normal", especially at the higher end of normal, are associated with increased risk for cardiovascular disease, and lowered mortality, see studies cited in the Deeper Dive section of [[Insulin Resistance]]
 
=== Fasting blood glucose (FBG)  ===
 
This is determined from a blood sample after fasting (no food or caloric drinks) for at least 8 hours.  Blood can be tested by a lab or at home with a glucose meter.  Blood sugar that is higher than 130 mg/dl (milligrams per deciliter) is conventionally considered hyperglycemia (high blood glucose), but it can easily be argued that standard is too lenient. 
 
Our [https://www.apoe4.info/forums/viewtopic.php?f=33&t=1418 PRIMER: An introduction to ApoE4, biochemistry, and possible prevention strategies] recommends a fasting glucose of under 99 mg/dl (5.5 mmol/l) to start, with aiming for 90mg/dl or less (5mmol/l) as one gets better at managing their diet and insulin resistance.


== Why it is important for ApoE4s ==
== Why it is important for ApoE4s ==

Revision as of 12:28, 3 March 2019

Introduction

Blood sugar is also known as (aka) blood glucose (BG), the two terms are used interchangeably.

The body, in particular the brain needs glucose. The brain needs glucose constantly, 24 hours a day, the brain can’t burn fatty acids like other cells in the body. The brain can use ketones as a source of fuel, it’s cleaner and more efficient than glucose, which is why metabolic flexibility (the ability to easily switch from burning glucose to ketones) or ketosis (when the body is almost completely fueled by fat/ketones) is often recommended for ApoE4s, see Ketosis and Ketogenic Diet. But the brain has special cells, glutaminergic cells, that can only burn glucose. So the brain cannot run on ketones alone. Under the best of circumstances, ketones can only provide about 2/3rds of what the brain needs to work properly.

While the brain does indeed need glucose, it doesn’t want too much of it. A person doesn’t need to eat sugar to provide glucose to the brain. Such foods are known as high glycemic, they are typically carbohydrates and sugar. But even people who follow a zero carb/zero sugar diet (a type of ketogenic diet not advocated for ApoE4s) are able to maintain acute mental clarity, this is because the body, primarily the liver, can make its own glucose, a process called gluconeogenesis. So eating glucose isn’t necessary to provide fuel the brain, in fact too much glucose is detrimental to the brain (discussed below).

I eat sugar and carbohydrates and my blood sugar levels are fine, so why worry?

As shown by the blue line, Blood Glucose levels can remain relatively normal while demand for insulin rises to keep glucose under control rise. If insulin resistant, blood glucose levels rise slowly over many years because the body is able to produce enough insulin, but at some point the pancreas can no longer produce sufficient insulin, blood glucose levels rise significantly and that’s Type 2 diabetes. This slow glucose ramp-up period is stressful for the body, health concerns are developing despite the “normal” blood glucose levels, even if Type 2 Diabetes never results. Graph source: Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study, (Tabák, A, et al, 2009 Figure 1, https://www.sciencedirect.com/science/article/pii/S014067360960619X

It’s hard to discuss blood glucose without including insulin.

The body wants blood glucose levels to be just right (metabolic homeostasis). Insulin is the hormone that works to keep blood sugar levels steady, neither too high (hyperglycemia) nor too low (hypoglycemia). But when insulin has been overworked, being asked to keep blood glucose levels under control for too long (a period of many years), insulin eventually “gives up,” blood glucose levels subsequently raise dramatically and that, very simplistically, is Type II Diabetes.

That insulin “breaking point” (when the blue line goes from a slow upward progression to a rapid upward trajectory) comes from overloading the body with glucose, so while the overall glucose numbers may look “good” (and the conventional wisdom of what is considered “good” is discussed below), glucose spikes from high glycemic foods are overworking the body. Add snacks to three meals a day or follow the faulty advice of consuming six small meals a day to “reduce glucose spikes” and this just asks the pancreas to constantly produce insulin, something it was not “designed” to do, it needs rest time.

These practices result in a person becoming insulin resistant. During this phase, when insulin is “overworked” and blood glucose numbers are “normal” but slowly rising, insulin receptors are getting damaged, they’re becoming numb (desensitized) to insulin, and they’re “downregulating” i.e. becoming fewer in number, the fat cells are expanding to a point where they can’t get any bigger, these overstuffed fat cells can’t get enough oxygen and inflammation results, the fatty acids look for other storage places, areas where fat were never meant to go: the abdominal cavity (visceral fat), other organs (liver, pancreas, kidneys), and muscle. So while blood glucose levels can be “normal” and a person can feel fine, inside the body can be insulin resistant and very, very unhappy.

Comparing glucose spikes of a standard diet to a ketogenic diet. The flatter the line, the happier the body. Incorporating intermittent fasting (eliminating one or two meals) in addition to a ketogenic diet will flatten those upticks even more. Source: Slide taken from presentation by Miriam Kalamian, EdM, MS, CNS, at Low Carb USA in San Diego, July 2017.

Insulin resistance doesn’t need to progress to Type 2 diabetes to damage the body and manifest in the form of a chronic disease, such as Alzheimer’s. See Insulin Resistance.

This is also one of the justifications for ApoEε4s to follow a ketogenic diet, in addition to providing ketones for fuel to an insulin resistant energy starved brain, a ketogenic diet flattens glucose spikes, placing less demand on insulin thus facilitating the reversal of insulin resistance. See Ketosis and Ketogenic Diet and Insulin Resistance in the brain.

High blood glucose, hyperglycemia, turns blood from a life sustaining fluid into a slow, silent, destructive force. According to WebMD High Blood Sugar and Diabetes (accessed Feb 27, 2019) ongoing high blood sugar may cause:

  • Vaginal and skin infections
  • Slow-healing cuts and sores
  • Worse vision
  • Nerve damage causing painful cold or insensitive feet, loss of hair on the lower extremities, or erectile dysfunction
  • Stomach and intestinal problems such as chronic constipation or diarrhea
  • Damage to your eyes, blood vessels, or kidneys
Too much blood glucose is neurotoxic

High blood glucose is also damaging to the brain, it istoxic to neurons in a variety of different ways. Glucose Neurotoxicity (DR Tomlinson and NJ Gardiner, 2008)

  • Depletes natural antioxidant reserves, glutathione, the body’s own antioxidant
  • Promotes damaging free radical formation, these are violent molecules that create collateral damage, wrecking havoc with your DNA and more
  • Generates Advanced Glycation End Products (AGEs), sticky dysfunctional proteins
  • Slows nerve cell conduction speed
  • Reduces growth factor activity, growth factor keeps cells healthy and robust and thriving

Low Blood Sugar

What is low blood sugar? The American Diabetes Association says anything below 70 is low blood sugar, hypoglycemia. But if not diabetic, and especially if maintaining a ketogenic diet, don’t freak out if the glucose meter reflects something below 70. We have ketogenic ApoEε4 members who have undertaken multi-day fasts and experienced blood glucose levels in the 30s yet felt fine: no feelings of energy deprivation, full mental clarity, and they maintained normal daily routines including muscle-demanding workouts. This is because they met the necessary energy demands with ketone production. Ketones rose significantly in the initial first days of the multi-day fast in reciprocal relationship to the blood glucose level which went down. Later in the fast, the body turned to gluconeogenesis to meet its glucose needs. It should be noted electrolyte supplementation was included with the fast, lackluster energy can be the result of low electrolytes, not necessarily low blood sugar.

Can blood sugar be too low for the brain? Because of the brain’s constant demand for energy, a healthy body does everything it can to provide enough glucose for the brain. During periods of extended severe caloric restriction, like how our ancestors experienced in the wintertime or during droughts, the human body will even breakdown its own muscles in order to produce glucose for the brain and will compensate for the rest of the brain’s energy needs by producing ketones. So it’s very hard to have blood sugar so low that the brain can’t function.

However, the brain can experience slow glucose processing known as cerebral glucose hypometabolism. The brain can be surrounded by plenty of glucose yet not be able to use it as a result of insulin resistance. This is found universally in Alzheimer’s patients, which is why Alzheimer’s is often referred to colloquially as Type 3 Diabetes. This situation is like the Samuel Taylor Coleridge quote, “Water, water everywhere but not a drop to drink” only we’re talking glucose being everywhere and not only is the brain unable to use it, but the excess glucose is damaging the brain. See Insulin Resistance in the brain

Blood Sugar Measurement - common tests including “new normals”

It is critical for overall health to keep blood sugar levels under control, especially for the brain. The higher your blood sugar levels, the higher your brain sugar. Sixty percent of blood sugar is brain sugar. So for example, if a blood glucose level is 100, brain glucose is 60.

It should be noted that while blood glucose typically becomes elevated from foods that are considered high glycemic, there are other non-food factors that can elevate blood glucose as well (discussed below).

Hemoglobin A1c

How to convert an HbA1c reading into average blood glucose levels

This test, conducted by a lab, reflects the average level of blood sugar over the past 2 to 3 months. It's also called HbA1c, or sometimes just A1c. According to the American Diabetes Association: A1c less than 5.7% is “normal”, A1c 5.7 to 6.4 is prediabetes, A1c 6.5 or higher is diabetes.

However, Dr Bredesen's protocol recommends an A1c of less than 5.6, see Fasting insulin less than 5; HgbA1c less than 5.6

Our PRIMER: An introduction to ApoE4, biochemistry, and possible prevention strategies recommends keeping A1c to 5.5 or under (37 mmol/mol), preferably closer to 5% (32 mmol/mol).

There are those who say down to 5.2 there’s an increased risk for brain shrinkage. Studies that have additionally determined that HbA1c levels considered "normal", especially at the higher end of normal, are associated with increased risk for cardiovascular disease, and lowered mortality, see studies cited in the Deeper Dive section of Insulin Resistance

Fasting blood glucose (FBG)

This is determined from a blood sample after fasting (no food or caloric drinks) for at least 8 hours. Blood can be tested by a lab or at home with a glucose meter. Blood sugar that is higher than 130 mg/dl (milligrams per deciliter) is conventionally considered hyperglycemia (high blood glucose), but it can easily be argued that standard is too lenient.

Our PRIMER: An introduction to ApoE4, biochemistry, and possible prevention strategies recommends a fasting glucose of under 99 mg/dl (5.5 mmol/l) to start, with aiming for 90mg/dl or less (5mmol/l) as one gets better at managing their diet and insulin resistance.

Why it is important for ApoE4s

1) "Individuals with both type 2 diabetes and the APOE epsilon4 allele had an RR of 5.5 (CI 2.2-13.7) for AD compared with those with neither risk factor. Participants with type 2 diabetes and the epsilon4 allele had a higher number of hippocampal neuritic plaques (IRR 3.0 [CI 1.2-7.3]) and neurofibrillary tangles in the cortex (IRR 3.5 [1.6-7.5]) and hippocampus (IRR 2.5 [1.5-3.7]), and they had a higher risk of cerebral amyloid angiopathy (RR 6.6, 1.5-29.6)." [1]

2) In contrast, the Kungsholmen project ([2]) reported no interaction between diabetes and the APOE ε4 genotype, as described in [3]. These authors stated that “These differences could be due to chance or differences in ethnicity and sex distribution in the populations.”

3) “Unexpectedly, memory-impaired epsilon4+ subjects showed poorer recall following insulin administration on one test of memory.” [4]. However, a 2013 study showed that the response might be dose related. [5]

4) "Among AD individuals with DM2, those who are ApoE ε4 carriers had significantly greater neuropathology than those who do not carry an ApoE ε4 allele. Positive DM2 status appears to exacerbate AD neuropathology in the presence of ApoE ε4." [6]


Strategies for controlling blood sugar

Doctors tend to overlook testing for blood glucose levels in Alzheimer's patients. When recruiting people for a resveratrol study to study glucose effects in patients with Alzheimer’s, a Georgetown neurologist was “shocked” by how many had pre-diabetes. [7]

For strategies, check out the Insulin Resistance page.


The Science

- Epidemiological studies.

1) Glucose levels and risk of dementia. (2013) PubMed ID:23924004

2) Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. (2004, full text) PubMed ID:15148141

3) Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. (2002, full text) PubMed ID:11916953

4) Risk of Dementia among Persons with Diabetes Mellitus: A Population-based Cohort Study (1997, full text) PubMed ID:9329716

5) Increased Alzheimer's disease neuropathology is associated with type 2 diabetes and ApoE ε.4 carrier status. (2013) PubMed ID:23627755


- Other studies.

1) Intranasal Insulin as a Treatment for Alzheimer’s Disease: A Review of Basic Research and Clinical Evidence (2013, full text) PubMed ID:23719722


- Animal studies.

1) Increased Susceptibility to Amyloid-β Toxicity in Rat Brain Microvascular Endothelial Cells under Hyperglycemic Conditions. (2013) PubMed ID:23948922

2) Amyloid-β and tau pathology of Alzheimer's disease induced by diabetes in a rabbit animal model. (2012) PubMed ID:22785400

3) Epigenetic mechanisms linking diabetes and synaptic impairments. (2013) PubMed ID:24154559


Proposed mechanism(s)

1) Insulin plays an important role in the formation of memories. Abnormal insulin and insulin receptor levels and activities are seen in Alzheimer's dementia, whereas administration of insulin significantly improves the cognitive performance of these patients. ([8]) Increased blood glucose increases amyloid beta “oligomer” assemblies in the brain, which bind to hippocampal neurons and cause insulin receptors to be eliminated from the surface membranes, contributing to insulin resistance in the brain. ([9])

2) Diabetes may induce epigenetic modifications in the brain. Elevation of HDAC IIa in the brains of diabetics coincide with altered expression of synaptic proteins. [10]


Related SNPs

SNPs associated with Type II Diabetes: List

SNPs associated with HbA1c levels : Article