Does Elevated Glucose Cause Dementia?

Does elevated glucose cause dementia?  Even in non-diabetics?

This would seem to be the initial conclusion based on a recent study published in the NEJM:

Glucose levels and risk of dementia.  

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Celebrity Diabetes ~ Tom Hanks now

Before Paula Deen got in hot water over racial issues, she was the subject of controversy a few years back with her belated disclosure that she had Type 2 diabetes, and then became a spokesperson for Novo Nordisk's Victoza.  The "mainstream" balked, including rebukes from fellow celebrity chefs for using so much butter in her cooking while hiding the effect it had on her health.  When the news hit the LC community, it of course went nuts.  I discussed this pretty thoroughly HERE.  A quick summary might be that the low carbers didn't like that people blamed the fat in her foods and finger pointed at the carbs (ignoring sedentary lifestyle entirely).  Further, they didn't like that she was dieting per mainstream guidelines and using Victoza rather going on a LC diet.   Stress certainly has taken a toll on Deen, but she seems to have maintained her weight loss, perhaps even losing a few more pounds.  It would be interesting to get an update on her condition, but somehow I doubt we will.

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The Cause of Hyperglycemia in Type 2 Diabetes

I will forever be grateful to (former?) blogger LynMarie Daye of Adipo Insights blog for bringing the following paper to my attention:

Insulin: understanding its action in health and disease

If you're a regular reader and you haven't read it yet, what are you waiting for?  If you're a new reader it's a must (unless of course you're just here for the gossip you claim is boring and inappropriate - grin).   The article is quite long, but it is written in very understandable fashion.  A lot of info, so perhaps best digested in small segments, but well worth the effort. 

The article begins with a history lesson about a physiology professor named Sir Edward Schafer, who "appears to have named insulin and described its actions" in a book published in 1916 entitled The Endocrine Organs.  Schafer, described a substance with dual and simultaneous functions: 

• Autacoid:  excitatory or stimulatory, e.g. glucose transport, lipid synthesis 
• Chalone:  inhibitory, e.g. inhibiting lipolysis, gluconeogenesis, ketogenesis

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Low HbA1c is as bad or worse than high HbA1c in non-diabetics

Low Hemoglobin A1c and Risk of All-Cause Mortality Among US Adults Without Diabetes

This study looked at roughly 14,000 NHANES III participants that were not diabetic.  I think this is an important distinction because it looks at differences in normal range, "free", if you will, of what the frank hyperglycemia associated with metabolic dysfunction might do to mean and/or median values.  Here is the hazard ratio plot:  

Adjusted hazard ratios for the association between HbA1c and all-cause mortality among participants without diabetes using a quadratic spline with knots at the 2.5, 10, 50, 90, and 97.5 percentiles. Adjusted for age, race-ethnicity, sex, lifestyle factors (education, income, current smoking, alcohol consumption, physical activity, body mass index, and aspirin use), cardiovascular factors (systolic blood pressure, antihypertensive medication use, total cholesterol, HDL cholesterol, log triglycerides, elevated C-reactive protein, and history of CVD), metabolic factors (prior diagnosis of thyroid disease, thyroid-stimulating hormone, estimated glomerular filtration rate, and albuminuria), red blood cell indices (hemoglobin, red blood cell distribution width, mean cell volume, and serum folate), iron storage indices (serum albumin, ferritin, and transferrin saturation), and liver function indices (hepatitis C seropositivity, AST, and ALT). Knots were placed at 4.3%, 4.7%, 5.3%, 5.9%, and 6.2%, representing HbA1c levels at the 2.5, 10, 50, 90, and 97.5 percentiles; shaded area represents 95% CI.

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Bump: The Diabetes "Crash" Cure & Pancreatic Fat

Today's 8/15/13 bump was inspired by a comment by Tsimblist (thanks!) alerting me to this paper:  Type 2 Diabetes Etiology and reversibility

Reversal of type 2 diabetes to normal metabolic control by either bariatric surgery or hypocaloric diet allows for the time sequence of underlying pathophysiologic mechanisms to be observed. In reverse order, the same mechanisms are likely to determine the events leading to the onset of hyperglycemia and permit insight into the etiology of type 2 diabetes. Within 7 days of instituting a substantial negative calorie balance by either dietary intervention or bariatric surgery, fasting plasma glucose levels can normalize. This rapid change relates to a substantial fall in liver fat content and return of normal hepatic insulin sensitivity. Over 8 weeks, first phase and maximal rates of insulin secretion steadily return to normal, and this change is in step with steadily decreasing pancreatic fat content.

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Aug. 1 Over the Hump Bump: Baby Your Pancreas? Part II: Go all Jillian Michaels on your Liver?

On Facebook today, Mark Hyman MD (functional medicine doc) posted:

There are no essential carbohydrates. There are essentials fats and essentials proteins, but if you never had any carbohydrates again, you would survive.

The Teaspoon Party

This was brought to my attention but also reminded me that Richard Feinman is at it again with a recent blog post on this no essential dietary carb canard, couched in a history lesson of sorts:  Revolutions. Political and Scientific.  He discusses Claude Bernard finding sugar in a dog that hadn't been fed any carbohydrate.  The question is why ... again ... why ... now?   This idea has earned him an honored place in the group at right.

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Aug. 1 Over the Hump Bump: Baby your Pancreas? Part I: The Tired Pancreas

Another two-fer for the Thursday post bumps again this week.  More explanation for why this set in the next bump.

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Original Publish Date:  7/26/11

In the comments on a recent post on beta cell lipotoxicity, Ned Kock (of Health Correlator blog) posted a link to a post he made a while back entitled:  Lipotoxicity or tired pancreas? Abnormal fat metabolism as a possible precondition for type 2 diabetes.  This article deals with the concept of the "tired pancreas" in the development of diabetes.  It seems that (and hopefully he corrects me if I'm wrong here) Ned and I agree that this is not a likely explanation for diabetes.   Ned summarizes the progression of obesity induced T2 diabetes from Unger & Zhou, 2001.  It is worth mentioning that Unger is often summarily dismissed from the "scientific discussion roundtable" by low carbers because of the unfortunately titled "Gluttony and Sloth" paper, that, even more unfortunately also included a biblical verse.   Unger's hypothesis is very leptin-centric, but not at all incompatible with other lipotoxicity based theories.  Basically, lipotoxicity is the result of dysfunctional adipocytes leading to excessive "spill-over" of fatty acids into circulation and accumulation in ectopic tissues.   Unger & Zhou identify dysfunction in leptin secretion and/or signaling as the initiating factor in this process.  One thing that doesn't quite add up for me here is that I keep finding citations indicating leptin action increases free fatty acids which would seem counterintuitive.  In any case ...

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Biomarkers: Context and Are They Causative Agents?

I received a comment recently on the Blood Sugar 140 series that prompted this post.  Actually, it prompted a post on the best predictor for T2 which will be forthcoming, but in fleshing out some background for that, I realized it was worth a post on its own. Below are links to previous post series I'm referring to:

• Blood Sugar 140: Where did the 140 mg/dL threshold come from?
• Blood Sugar 140: Context is Everything I - Diabetic vs. Non
• Blood Sugar 140: Context is Everything II: The OGTT
• Blood Sugar 140: Diabetic Neuropathy, Is it All About Hyperglycemia?

"Cliff Notes" Blood Sugar 140:  There is a commonly repeated "fact" out there that blood glucose levels over 140 mg/dL lead to nerve damage (and organ damage) generally attributed to the process of glycation.  Also implied in this is that such damage is cumulative such that any excursion over 140 is inflicting a little damage along the way.  This traces back to the following page on Jenny Ruhl's website:  Research Connecting Organ Damage with Blood Sugar Level:

The studies you will read below, some of which are not cited in the AACE guidelines, make a cogent case that post-meal blood sugars of 140 mg/dl (7.8 mmol/L) and higher and fasting blood sugars over 100 mg/dl (5.6 mmol/L) cause permanent organ damage and cause diabetes to progress.  {emphasis mine}

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Toxic!

There hasn't been much buzz about this year's LC Cruise, but a couple of days ago, a tweet from the presentation of one Dr. Dwight Lundell made a little splash on Twitter and FB.  

The most toxic chemical in the human diet is GLUCOSE. -Dr. @dwightlundell #sugarkills #LCCruise13
— Dietitian Cassie, RD (@dietitiancassie) May 7, 2013

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An American Justice System for Food ~ Part I Intro and Carbs in General

The cornerstone of the American justice system:  Innocent until proven guilty.  According to Wikipedia: sometimes referred to by the Latin expression Ei incumbit probatio qui dicit, non qui negat (the burden of proof lies with who declares, not who denies).  I like the first part of that Latin expression and suggest that what is truly needed in nutritional circles is to put the burden of proof on those making claims.  My point here is not a political one, it is not to argue the merits of my country's justice system or its implementation, or anything of the sort.  It is to put forth a suggestion -- that ALL who demonize foods be tasked with proving their charges.   I suggest this because it is darned near impossible to do the opposite especially in the face of baseless charges.  

It is a bit of a stretch, but keep in mind that many of the compounds, such as water, can be toxic at some level of ingestion.  Furthermore, some of the chemical and/or physical properties of many innocuous compounds found in foods can seem quite daunting when taken out of context.   This is an obvious spoof, but hopefully it makes a point.

Now, the vegans and vegetarians and raw and fruitarian crowds are all just as guilty of this, but since I've never been even remotely a part of any of those communities, I'll leave it to someone else to call out their hyperbole, scaremongering and outright disinformation.   I'm also not talking about new non-foods such as artificial sweeteners, chemically modified foods (e.g. hydrogenated fats), non-food chemicals such as preservatives and I'll even throw in GM in with substances that should be considered unsafe until proven otherwise.  

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Chronic Exposure to Free Fatty Acid Reduces Pancreatic β-Cell Insulin Content by Increasing Basal Insulin Secretion That Is Not Compensated For by a Corresponding Increase in Proinsulin Biosynthesis Translation

Coming next in the discussion of diabetes I am going to discuss insulin secretion in greater detail.  I was reminded of this post in the writing process.  So ... Bump!

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Original Publish Date:  4/4/11

Chronic Exposure to Free Fatty Acid Reduces Pancreatic β-Cell Insulin Content by Increasing Basal Insulin Secretion That Is Not Compensated For by a Corresponding Increase in Proinsulin Biosynthesis Translation

JD McGarry contributing author.

{Please note:  Excerpts from the text will be edited somewhat to avoid "cluttering" references, statistical values, and some rounding of numbers.  Text will sometimes be presented in bullet form or with paragraph breaks to ease reading.  It is not my intent to plagiarize nor to alter the content.  If anyone feels I've altered the content in any meaningful way, do please let me know!}  Direct quotes will be indented.

FFA are an important physiological fuel for islets, and act as a supplemental nutrient secretagogue to potentiate insulin release acutely in the presence of glucose.

Translation:   β-cells run on fatty acids but this fuel also serves to stimulate insulin secretion.

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Ketosis and Burning Body Fat

Alternate Title:  Picture Worth More Than 1000 Words.  In speeches and interviews lately, Jimmy Moore has become fond of mentioning a few things (well, in addition to name dropping Robb Wolf)

• Nutritional Ketosis as being somehow unique from run-of-the-mill, what, biochemical ketosis.  NK requires blood ketone testing as this is more accurate.  And,
• Ketosis is evidence of burning body fat which he wasn't doing prior to this experiment.
• Ketones and blood glucose being reciprocal

Tis true that measuring blood ketone levels is more accurate than urine ketones.  For one thing, urine levels vary widely with fluid intake, frequency of urination, etc.  Urine ketones are also "spill-over".  This is why nobody is ever busted for DUI on the basis of a urine test.  But just because urine levels are not necessarily representative of one's ketogenic production doesn't mean a person is, or is not, in NuttyK.  But let's presume that to be truly NuttyK one must also be a prick-er.  

On the right sidebar are Jimmy's NuttyK experiment results from Days 180-209.  Top to bottom we have AM glucose, AM ketones, PM ketones,  and body weight.  Do YOU notice any correlation?   Here's what I see:

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Hyperinsulinemia, Insulin-Suppressive Drugs & Obesity (and Lustig)

The recent buzz about hyperinsulinemia being at the root of obesity (whatever the mechanism) has had me thinking again about the insulin lowering drugs.   Studies in this regard were referenced in the recent article in Cell from Dr. James Johnson's research group at UBC.   If this is really all there is to it, why not just treat obesity with such drugs?  Or at least give them to the reduced-obese so they won't regain the weight, and/or the so-called pre-obese who start gaining at some point in life before they become obese.  This is really the bottom line of studies like the recent one from UBC.  Because if all we need to do is suppress the hyperinsulinemia (however it is caused) to prevent obesity it would be done.  There is a relatively rare condition, called by many names, but most descriptively neo-natal or infant hyperinsulinism.  These children must be treated ASAP to avoid the consequences of hypoglycemic episodes.  I surmise the drugs octreotide and diazoxide were developed at least in part for treating this condition, though often partial removal of the pancreas is required.

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Insulin Secretion and the Corrected Insulin Response (CIR)

I'm working on a post about hyperinsulinemia and obesity in humans.  It may well turn into several posts.  But in one study I will be discussing they identified hypersecreters according to something called the corrected insulin response, CIR.  Sometimes this is further "standardized" as the CIRgp which is evaluated at the peak glucose reading.  The CIR is value calculated following a standard OGTT.  If you have data from your OGTT, you can calculate your own and determine how you rank.

The CIR was developed by Sluiter and colleagues as outlined in:  Glucose Tolerance and Insulin Release, A Mathematical Approach I. Assay of the Beta-cell Response After Oral Glucose Loading.  

From the dose-response relations between glucose and insulin after oral glucose loading, a reproducible parameter for beta-cell response was deduced. The main advantage of this parameter lies in its independence from the initial or reached glucose level.

Units:  glucose in mg/dL , insulin in μU/mL

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Berberine -- Supplement or Pharmaceutical? Does it matter?

I have commented a few times before on supplement usage in "The Community".  For example, here. It always amazes me the litany of pronouncements on the macro/micro nutrient superiority of one's chosen diet that are side-by-side accompanied by an even longer litany of supplements.  It is pervasive, and dare I use the "a" word, addictive.  When I first found the LC web in 2009 I was rather astounded by the amount of supplements some were taking.  At some point, if one is supplementing their diet with a handful of pills, one needs to take a step back and recognize that it may well be those pills responsible for effects in spite of the diet.

But another thing that's rather pervasive in the community is the use of supplements often accompanied by sanctimonious braggadocio regarding how the "diet" enabled a person to come off of all medications!

Berberine has been making the rounds in LC/diabetic circles, and for good reason.  It works!  There's been a veritable sheetload of legit scientific studies on the stuff.   So ... this then begs the question of whether it matters that someone takes, say, prescription Metformin or buys a supplement such as the berberine containing Glycosolve.  

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Blood Sugar 140: Diabetic Neuropathy, Is it All About Hyperglycemia?

Continuing on in this series dealing with the neuropathy study from which the following statement has been repeated regarding blood glucose levels:  

Nerve Damage Occurs when Blood Sugars Rise Over 140 mg/dl After Meals  (as stated by Ruhl , Jaminet (Kindle Locations 712-716), and Kresser.)

At the risk of repetition, this does seem to have originated with Jenny Ruhl's interpretations of this study wherein 50% of 72 individuals with neuropathy were diagnosed as IGT having a BG level over 140 mg/dL at the 2-hour mark of an OGTT.   The IGT group was also more likely to have painful sensory symptoms than the roughly one-third who were normoglycemic (the remaining group were frank diabetic).

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More Diabetes - A Disease by Any Other Name?

This post is somewhat a followup on a post of mine from over a year ago entitled  Diabetes - A Disease by Any Other Name?  The post was mostly inspired by a comment Jenny Ruhl of the Blood Sugar 101 site made in her first podcast interview with Jimmy Moore - to paraphrase:

Diabetes is no more a disease than to say "cough" is a disease.

I tend to agree with the above in the current context of the term diabetes being synonymous with hyperglycemia, as opposed to defining it as pancreatic dysfunction.   This is because many diseases/disorders are called diabetes that just so happen to be characterized by, among other things, the symptom (manifestation) of hyperglycemia (fasting and/or postprandial).  Indeed Jenny herself is a MODY (Maturity Onset Diabetes of the Young), a relatively rare genetic form of diabetes with an underlying defect that has been identified.  Jenny cannot be cured with current treatments because her disease is inherent.    Thus her hyperglycemia (symptom/manifestation) can be likened to a cough, but her diabetes (genetic anomaly) cannot.  I hope that makes sense.  

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Blood Sugar 140: Context is Everything II: The OGTT

In the last installment, I discussed the context of blood glucose readings over 140 mg/dL in diabetics vs. non-diabetics.  In this installment I'm going to discuss it in the context of an Oral Glucose Tolerance Test, OGTT.   The crux of this post is that the results of this study do not justify the Ruhl/Jaminet/(and I'll add Kresser) takeaway message vis a vis diabetes complications and "spikes" in blood glucose.   The fact that 50% of the neuropathy subjects to whom OGTT's were administered had 2 hr. glucose levels over 140 (e.g. diagnosed as Impaired Glucose Tolerance, IGT) simply does not support:  Nerve Damage Occurs when Blood Sugars Rise Over 140 mg/dl (7.8 mmol/L) After Meals as stated on Ruhl's site and in Perfect Health Diet (Kindle Locations 712-716).  (This seems to have been repeated by Chris Kresser as well).

What is an OGTT?  The most common form is conducted in the fasted state, at least 8 hrs, studies seem to favor 10 or 12 hrs.  It involves ingesting 75g of liquid glucose solution in a short period of time.  Glucose (and often insulin) levels are sampled at 30 min (sometimes shorter at early time periods)  intervals for 2 to 3 hours.  There are two values that are assessed:

• 1 hour and/or peak BG:  under 200 mg/dL = normal , 200 mg/dL or over = IGT or diabetic
• 2 hour BG:  under 140 mg/dL = normal, 140-199 mg/dL = IGT, 200 mg/dL or over = diabetic

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Blood Sugar 140: Context is Everything I - Diabetic vs. Non

In Blood Sugar 140: Where did the 140 mg/dL threshold come from?, I laid some groundwork as to the source of the concern over postprandial blood glucose levels over 140.  Before moving on, I thought I'd share an additional example of the 140 mg/dL threshold being evoked.  Here is a thread on Dr. Dansinger's WebMD diabetes forums:  glycation damage.

I ask this question because the consensus is that blood sugars over 140 cause the sugar to stick to vessels and organs. Dr. Gabe Mirkin writes of this on his web site. Others like John McDougall do not seem to worry about sugars over 140.

I can understand that you don't want fasting sugars over 140 but apparently even postprandials over 140 cause damage. I am wondering how long it would take for damage to be recognizable if post prandials are above 140. And does it matter how long they remain over 140 after eating?

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Abnormal OGTT Results - The many causes

direct image link

As often happens, when looking for something a bit more specific, I came across this image at right, which led me to this webpage:  Laboratory Testing for Diabetes Mellitus.

Curve 1 is a normal OGTT, Curve 6 is a diabetic.  The other causes are listed:

Pathologic conditions causing impaired, or diabetic, glucose tolerance results:

• Hypercorticism - curve 5.
• Acromegaly - between curves 4 and 5
• Hyperthyroidism - curve 4.
• Pheochromacytoma (or "emotional hyperglycemia") - between curves 4 and 5

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