Stanford Blood Sugar Study Findings Known for More Than 45 Years

This week Stanford University published a study which substantiates the huge glucose spikes that “healthy” people with normal blood sugar levels experience and that Dr. Joseph Kraft began documenting 45 years ago [2,3,4] — until just before his death in 2017 [5].  To those of us that are familiar with the research of Dr. Kraft, this is a bit like the 1969 Apollo 11 lunar astronauts ‘discovering’ the existence of craters and mountains on the moon that were documented by Galileo in 1609.

Kraft called these abnormal glucose spikes along with the corresponding abnormal spikes of insulin ‘occult diabetes‘ or ‘diabetes in situ‘ [4] and used the term ‘occult diabetes’ to describe it since ‘occult’ in this context means “not accompanied by readily discernible signs or symptoms“.  It is these ‘covert’ glucose spikes that Stanford university researchers reported this week.

The Stanford Study

Stanford researchers gave 57 healthy subjects without prior diagnosis of diabetes continuous glucose monitors (CGM) that recorded their blood sugar fluctuations in their normal environment for two weeks. There were 32 women, 25 men — ranging in age from 25 to 76, with an average age of 51 years [1].

Subject’s Blood Sugar Upon Screening

Upon screening for the study, 5 of the subjects were discovered to have met criteria for having type 2 diabetes, as defined as HbA1c ≥6.5%, fasting blood glucose ≥ 126 mg/dL (7.0 mmol/L), or 2-hour glucose during 75 gram Oral Glucose Tolerance Test (OGTT) ≥ 200 mg/dL (11.1 mmol/L); 14 subjects were found to meet the criteria for prediabetes, defined as HbA1c > 5.7% and < 6.5%, fasting blood glucose 100–125 mg/dL (5.5 mmol/l-6.9 mmol/L) , or 2-hour glucose during OGTT 140–199 mg/dL (7.8-11.0 mmol/L). The remaining 38 subjects had normal blood glucose defined as fasting and 2-hour OGTT plasma glucose and HbA1c below the diagnostic thresholds for prediabetes and diabetes. Average fasting glucose was 93 mg/dL (5.2 mmol/L), 2-hour glucose 125 mg/dL (6.9 mmol/L) and HbA1c 5.4%[1].

Huge Variations in Blood Sugar Response

Researchers found that there was huge inter-individual (between individuals) and intra-individual (in the same individual at different times) variation in blood sugar response which is exactly what a 2015 study that fitted 800 people with CGMs reported [6]. In light of only the glucose part of Kraft’s findings as well as the data from the Israeli study with a study population more than 10x the size, the Stanford findings are not ‘new’.

Using mathematical techniques including spectral clustering and dynamic time warping, researchers defined 3 clusters of glucose patterns which were said to capture 73% of the variation [1]. Based on the amount of variability in glucose levels in each cluster, researchers classified the 3 patterns as low, moderate and severe variability.

Some People had lots of Abnormal Glucose “Spikes”

The researchers found that each of the 3 patterns showed a progressive increase in both the severity and magnitude of the blood sugar fluctuations. As well, some subjects mainly stayed in the low variability range, whereas others were mostly in the moderate to severe variability range. These are basically rankings of blood sugar “spike” intensity [7].

Of significance, blood sugar in the individuals that were considered healthy fluctuated a lot more than what is normally picked up by standard ‘finger-prick’ methods of blood sugar testing and these fluctuations come in the form of “spikes’; which are rapid increases in the amount of glucose (sugar) in the blood, especially after eating specific foods — most commonly carbohydrate [7].

Dr. Michael Snyder, professor and chair of genetics at Stanford and senior author of the study said;

“There are lots of folks running around with their glucose levels spiking, and they don’t even know it. The covert spikes are a problem because high blood sugar levels, especially when prolonged can contribute to cardiovascular disease risk and a person’s tendencies to develop insulin resistance, which is a common precursor to diabetes.”

“We saw that some folks who think they’re healthy actually are misregulating glucose—sometimes at the same severity of people with diabetes—and they have no idea [7].”
~ Dr. Michael Snyder

Stanford researchers documented that abnormal glucose responses were more common than they previously thought [7], but these results come as no surprise to those of us familiar with Kraft’s research [2-5] and the findings of the 2015 study from Israel [6].

You can read more about the significance of these covert glucose and corresponding insulin spikes in this article titled When Normal Fasting Blood Glucose Results Aren’t Necessarily “Fine”.

Cornflakes For Breakfast?

The Stanford researchers conducted a sub-study in 30 subjects whose prior blood sugar tests indicated that they were “healthy” (i.e. not prediabetic or diabetic). They were fitted with continuous glucose monitors (CGMs) and alternated between 3 breakfasts; (1) a bowl of cornflakes with milk, (2) a peanut butter sandwich and (3) a protein bar.

Significantly, more than half of the “healthy” group had blood sugar spikes at the same high levels as those who were diagnosed as prediabetic or diabetic [1,7].

Dr. Michael Snyder, professor and senior author of the study said;

“We saw that 80% of our participants spiked after eating a bowl of cornflakes and milk. Make of that what you will, but my own personal belief is it’s probably not such a great thing for everyone to be eating[7].”

Ordinary Blood Tests Available to Detect These Abnormal “Spikes”

Different people respond to carbohydrate based foods differently and even the same individual can respond to the same carbohydrate-based food differently — depending on part on the degree of processing it has undergone, or whether it is eaten alone or after eating protein-containing foods (see two articles on the Perils of Food Processing for more information).

As elaborated on in a previous article titled “Are You Pushing Your Pancreas Too Hard, abnormalities in insulin, including insulin resistance and/or hyperinsulinemia begin to occur as much as 20 years before a diagnosis of Type 2 Diabetes [8]; while blood sugar results are still normal and the results of this new Stanford study underscores the need to diagnose these abnormalities by capturing the blood glucose and insulin spikes well in advance of that!

The problem is, if we only monitor people’s fasting blood glucose and glycated hemoglobin (HbA1C) as a screening tool, we can miss that someone’s pancreas is overworking by constantly producing too much insulin.

Even if a standard 2 hour Oral Glucose Tolerance Test (OGTT) is run, if a person’s blood glucose results are normal at fasting and normal at 2 hours (such as was the case in the Stanford study!), we will miss the “spike” that occurs 30 minutes to 1 hour after the glucose is consumed in those with covert glucose spikes. The way to capture those “spikes” is to run a 2 hour Oral Glucose Tolerance Test with simultaneous glucose and insulin and do the two measurements at baseline (fasting), 30 minutes / 1 hour, and at 2 hours. When we detect these “spikes”, we can implement dietary changes to avoid further β-cell damage or β-cell death whose end-result is type 2 diabetes.

The Cost of Documenting These “Spikes” – penny wise and pound foolish

For less than $130 (cost in British Columbia, Canada), a physician can order a 2-hour OGTT with both glucose and insulin measured at (a) fasting, (b) 1 hour and (2) 2 hours which will capture abnormal glucose spikes at 1 hour, as well as the underlying hyperinsulinemia.

When there are clinical reasons to suspect that a person may be insulin resistant and/or hyperinsulinemic, a blood test that assesses simultaneous glucose and insulin response to a glucose challenge can provide sufficient motivation for individuals to implement dietary changes that can prevent progression to Type 2 Diabetes.

is such a test that costs <$130 to the public healthcare system not good value when the cost per person per year of having Type 2 Diabetes in Canada ranges from $1611 to $3427 ( more about that here)?

In British Columbia, the cost of a standard 2 hour Oral Glucose Tolerance Test is $11.82 before tax and $13.36 with HST.

Each additional glucose assessment is $3.48 before tax and $3.93 after tax.

Each insulin assessment costs $32.82 before tax and $37.09 after tax, so a 2 hour Oral Glucose Tolerance Test with additional glucose assessor at 1 hour and 3 insulin assessors at fasting, 1 hour and 2 hour costs as follows;

2 hour Oral Glucose Tolerance (fasting, 2 hours)           = $  13.36  with GST
additional glucose at 1 hour                                                       = $   3.93   with GST
3 insulin assessors at fasting, 1 hour, 2 hours                   = $111.27  with GST
TOTAL                                                                                                   = $128.56 with GST

The reason often given by physicians for NOT requisition the above tests is that it is “saving healthcare system dollars”, but in those with clear risk indicators, how is it wise to ignore what can’t be detected with standard screening tests?

More Info?

If you would like more information about determining how you respond to carbohydrate containing foods and whether you are at risk for prediabetes type 2 diabetes especially if your blood sugar values appear normal on standard screening tests, I can help.

You can learn more about my services under the Services tab or in the Shop.

If you have questions, please feel free to send me a note using the Contact Me form above and I will reply as soon as I can.

To your good health!

Joy

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Copyright ©2019 BetterByDesign Nutrition Ltd.

LEGAL NOTICE: The contents of this blog, including text, images and cited statistics as well as all other material contained here (the “content”) are for information purposes only.  The content is not intended to be a substitute for professional advice, medical diagnosis and/or treatment and is not suitable for self-administration without the knowledge of your physician and regular monitoring by your physician. Do not disregard medical advice and always consult your physician with any questions you may have regarding a medical condition or before implementing anything  you have read or heard in our content.

References

  1. Hall H, Perelman D, Breschi A, et al, 2018, Glucotypes reveal new patterns of glucose dysregulation. PLOS Biology 16(7). https://doi.org/10.1371/journal.pbio.2005143
  2. Kraft JR, Glucose Insulin Tolerance. A routine Clinical Laboratory Tool Enhancing Diabetes Detection. In O.B. Hunter. Jr. (ed): Radio assay: Clinical Concepts. Skokie, IL. Professional Education Dept. G.D. Searie & Co., 1974. Pp 91-106.
  3. Kraft JR, The Glucose Tolerance Examination: An Obsolete Procedure. read at the Symposium on Radioimmunioassay in Diagnostic Medicine.” Annual Convention, American Medical Association, Chicago, IL. June 26, 1974
  4. Kraft JR, Detection of Diabetes Mellitus In Situ (Occult Diabetes), Laboratory Medicine, Volume 6, Issue 2, 1 February 1975, Pages 10–22, https://doi.org/10.1093/labmed/6.2.10
  5. Crofts C, Schofield G, Zinn C, Wheldon M, Kraft J., Identifying hyperinsulinaemia in the absence of impaired glucose tolerance: An examination of the Kraft database. Diabetes Res Clin Pract, 2016. 118: p. 50-7.
  6. Zeevi D, Korem T, Zmora N, et al. Personalized Nutrition by Prediction of Glycemic Responses. Cell. 2015 Nov 19;163(5):1079-1094.
  7. Medical Press, July 24, 2019, Diabetic-level glucose spikes seen in healthy people, study finds, https://medicalxpress.com/news/2018-07-diabetic-level-glucose-spikes-healthy-people
  8. Sagesaka H, S.Y., Someya Y, et al, Type 2 Diabetes: When Does It Start? Journal of the Endocrine Society, 2018. 2(5): p. 476-484.

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Part 1: What is Insulin Resistance?

The hormone insulin plays a number of roles, one of which is to help move the glucose that is produced from the digestion of food – from the blood and into the cells for energy. Insulin resistance is where the body isn’t responding to insulin’s signals to take up glucose, so blood glucose remains high, despite normal or high levels of insulin.

Type 2 Diabetes (T2D) is essentially a state of very high insulin resistance.

Insulin normally goes up when we eat foods that contain carbohydrate (breads, pasta, rice, fruit, milk products, etc.) and acts on the liver to help store the incoming food energy – first as glycogen and when liver and muscle glycogen stores are “full”, it acts to store the excess energy as fat (de novo lipogenesis).

When we haven’t eaten for a while or are sleeping, the hormone glucagon acts to break down the glycogen in our muscles and liver (glycogenolysis) in order to supply our brain and cells with glucose. Insulin acts to inhibit glucagon’s action, which signals the body to stop making new glucose from its glycogen stores. When our glycogen stores run out (such as when we are fasting), the body turns to non-carbohydrate sources such as fat to make the glucose it needs for essential functions (gluconeogenesis).

When we are insulin resistant, insulin continues to act on the liver to signal it to store energy. When glycogen stores are “full”, it stores the excess energy as fat. When fat stores are “full”, the body starts storing the excess fat that the liver keeps making, inside the liver itself.  There shouldn’t be fat in the liver, but when we are insulin resistant, such as in Type 2 Diabetes excess fat gets stored in the liver in a condition known as “fatty liver disease”.

In insulin resistance, the liver becomes more sensitive to insulin’s signal to make fat (and as a result keeps making more and more fat) yet at the same time, the liver becomes less sensitive to insulin’s inhibition of glucagon – resulting in more and more glucose being produced and released in the blood.

High levels of glucose remain in the blood despite adequate insulin, and it is this high level of blood glucose that is the hallmark symptom of Type 2 Diabetes. For the same quantity of insulin released, the body moves less and less glucose into the cell. 

What does the body do to compensate? It makes more insulin!

KEY POINT: Insulin resistance results in the increased production of insulin. Increasing blood sugar CAN a symptom, caused by the insulin resistance, but blood glucose can be normal and one can still be insulin resistant (see Featured Article on Insulin Resistance).

When we are insulin resistant and keep eating a carb-based diet, the body requires more and more insulin in order to move the same amount of glucose into the cell.

The main issue then becomes too much insulin (hyperinsulinemia).

Defining the Problem Defines the Treatment

In Type 2 Diabetes (which is in essence, very high insulin resistance), the symptom is high levels of glucose in the blood. That is not the cause. It is the symptom.

High levels of glucose in the blood resulting from uncontrolled Type 2 Diabetes, results in proteins in the body becoming “glycosylated”. Glucose, is a highly reactive molecule and easily accepts (or “shares”) electrons from other molecules – especially from the amino acid Lysine, which is found in virtually every protein in the body. When Lysine and glucose share an electron, it creates an irreversible chemical bond between the glucose molecule and the protein – and that protein is said to have become glycosylated. It is this glycosylation that lies behind the complications found in Diabetes.

To reduce the glucose in the blood and the glycosylation of the body’s proteins, current treatment for Type 2 Diabetes involves medications that move glucose from the blood into the cells. This doesn’t really remove the excess glucose from the body, it simply moves it to a different location in the body. While these medications can be very helpful in the short term (until people begin to address the underlying dietary causes), over time these medications become less and less effective at removing glucose from the blood. In a sense, we become “medication resistant”, so additional medications are added.  Once the various combinations of medications loose their effectiveness, people with Type 2 Diabetes are prescribed insulin as a treatment – because insulin moves excess glucose into the cells. But the cells are already overflowing with too much glucose!

Insulin is added as a treatment when the body is already producing too much insulin.  The problem is the cells aren’t responding to the signal from insulin. The body doesn’t need more insulin – it needs the cells that are sensitive to respond to insulin’s signal.

Diabetes as a “chronic, progressive disease”

Type 2 Diabetes is described as a “chronic, progressive disease” because with current medication treatment, people eventually get worse. When they no longer respond to the initial medications  prescribed that help move excess glucose from the blood into the cells, they are prescribed insulin which they take by injection – in order to force more glucose into already over-full cells.  While people’s blood glucose gets better (i.e. the symptom improves), they gain weight as a result of the insulin injections and develop complications such as heart disease, stroke, kidney disease, blindness etc..

In the end, they don’t get better, but worse, fulfilling the belief that T2D is a chronic, progressive disease.

Redefining the Problem, Redefines the Solution

Rather than looking at the symptom (high blood glucose) as something that needs to be “fixed” with medications and later with insulin (when the medications are no longer effective), when we define insulin resistance and Type 2 Diabetes as a problem of excess insulin, we approach addressing the problem differently.

By changing what we eat, we can lower the amount of glucose in the body, which in turn causes the body to produce less insulin.  With less insulin being produced, the cells begin to respond to normal amounts of insulin  – reversing insulin resistance and yes, reversing the symptoms of Type 2 Diabetes.

Eating a low carb high fat diet and extending the amount of time between meals (intermittent fasting) lowers the production of insulin, resulting in the cells become more sensitive to its signal. Rather than addressing the symptom (which is high blood glucose) we are addressing the problem of too much insulin.

Have questions? Would like to know how I could help you?

Why not send me a note using the “Contact Us” form on the tab above.

To our good health!

Joy

In Part 2, I will explain how insulin resistance is measured and how we can track insulin sensitivity returning, as we continue to eat a low carb diet and increase the time between meals.

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Copyright ©2017 BetterByDesign Nutrition Ltd.  LEGAL NOTICE: The contents of this blog, including text, images and cited statistics as well as all other material contained here (the “content”) are for information purposes only.  The content is not intended to be a substitute for professional advice, medical diagnosis and/or treatment and is not suitable for self-administration without regular monitoring by a Registered Dietitian and with the knowledge of your physician. Do not disregard medical advice and always consult your physician with any questions you may have regarding a medical condition or before implementing something you have read or heard in our content. 

 

 

 

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