Tag Archives: hyperinsulinemia

Do High Insulin Levels Cause Memory Loss and Dementia?

dementia, memory loss, Mediterranean diet, low-carb diet, glycemic index, dementia memory loss

Don’t wait to take action until it’s too late

Insulin resistance and high blood insulin levels promote age-related degeneration of the brain, leading to memory loss and dementia according to Robert Krikorian, Ph.D. He’s a professor in the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati Academic Health Center.  He has an article in a recent issue of Current Psychiatry – Online.

Proper insulin signaling in the brain is important for healthy functioning of our brains’ memory centers.  This signaling breaks down in the setting of insulin resistance and the associated high insulin levels.  Dr. Krikorian makes much of the fact that high insulin levels and insulin resistance are closely tied to obesity.  He writes that:

Waist circumference of ≥100 cm (39 inches) is a sensitive, specific, and independent predictor of hyperinsulinemia for men and women and a stronger predictor than body mass index, waist-to-hip ratio, and other measures of body fat.

Take-Home Points

Dr. Krikorian thinks that dietary approaches to the prevention of dementia are effective yet underutilized.  He mentions reduction of insulin levels by restricting calories or a ketogenic diet: they’ve been linked with improved memory in middle-aged and older adults. His theory is also consistent with the commonly seen association of type 2 diabetes with dementia: overweight and obese type 2’s quite often have high insulin levels, at least in the early years.

Dr. K suggests the following measures to prevent dementia and memory loss:

  • eliminate high-glycemic foods like processed carbohydrates and sweets
  • replace high-glycemic foods with fruits and vegetables (the higher polyphenol intake may help by itself)
  • certain polyphenols, such as those found in berries, may be particularly helpful in improving brain metabolic function
  • keep your waist size under 39 inches (99 cm), or aim for that if you’re higher and overweight

Nearly all popular versions of the paleo diet would qualify as being low glycemic index.

I must mention that many dementia experts, probably most, are not as confident  as Dr. Krikorian that these dietary changes are effective.  I think they are, to a degree.

The Mediterranean diet is high in fruits and vegetables and relatively low-glycemic.  It’s usually mentioned by experts as the diet that may prevent dementia and slow its progression.

Read the full article.

I’ve written before about how blood sugars in the upper normal range are linked to brain degeneration.  Dr. Krikorian’s recommendations would tend to keep blood sugar levels in the lower end of the normal range.

Steve Parker, M.D.

PS: Speaking of dementia and ketogenic, have you ever heard of the Ketogenic Mediterranean Diet?  (Free condensed version here.)

In T2 Diabetes, Which Comes First: High Insulin Levels or Insulin Resistance?

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I couldn’t find a decent picture of a liver or pancreas, so this will have to do….

I’ve written elsewhere about the potential causes of T2 diabetes (here and here, for example). There’s a new theory on the block.

Excessive insulin output by the pancreas (hyperinsulinemia) is the underlying cause of type 2 diabetes, according to a hypothesis from Walter Pories, M.D., and G. Lynis Dohm, Ph.D.  The cause of the hyperinsulinemia is a yet-to-be-identified “diabetogenic signal” to the pancreas from the gastrointestinal tract.

This is pretty sciencey, so you’re excused if you stop reading now.  You probably should.

They base their hypothesis on the well-known cure or remission of many cases of type 2 diabetes quite soon after roux-en-y gastric bypass surgery (RYGB) done for weight loss.  (Recent data indicate that six years after surgery, the diabetes has recurred in about a third of cases.)  Elevated fasting insulin levels return to normal within a week of RYGB and remain normal for at least three months.  Also soon after surgery, the pancreas recovers the ability to respond to a meal with an appropriate insulin spike.  Remission or cure of type 2 diabetes after RYGB is independent of changes in weight, insulin sensitivity, or free fatty acids.

Bariatric surgery provides us with a “natural” experiment into the mechanisms behind type 2 diabetes.

The primary anatomic change with RYGB is exclusion of food from a portion of the gastrointestinal tract, which must send a signal to the pancreas resulting in lower insulin levels, according to Pories and Dohm. (RYGB prevents food from hitting most of the stomach and the first part of the small intestine.)

Why would fasting blood sugar levels fall so soon after RYGB?  To understand, you have to know that fasting glucose levels primarily reflect glucose production by the liver (gluconeogenesis).  It’s regulated by insulin and other hormones.  Insulin generally suppresses gluconeogenesis.  The lower insulin levels after surgery should raise fasting glucose levels then, don’t you think?  But that’s not the case.

Pories and Dohm surmise that correction of hyperinsulinemia after surgery leads to fewer glucose building blocks (pyruvate, alanine, and especially lactate) delivered from muscles to the liver for glucose production.  Their explanation involves an upregulated Cori cycle, etc.  It’s pretty boring and difficult to follow unless you’re a biochemist.

The theory we’re talking about is contrary to the leading theory that insulin resistance causes hyperinsulinemia.  Our guys are suggesting it’s the other way around: hyperinsulinemia causes insulin resistance.  It’s a chicken or the egg sort of thing.

If they’re right, Pories and Dohm say we need to rethink the idea of treating type 2 diabetes with insulin except in the very late stages when there may be no alternative.  (I would add my concern about using insulin secretagogues (e.g., sulfonylureas) in that case also.)  If high insulin levels are the culprit, you don’t want to add to them.

We’d also need to figure out what is the source of the “diabetogenic signal” from the gastrointestinal tract to the pancreas that causes hyperinsulinemia.  A number of stomach and intestinal hormones can affect insulin production by the pancreas; these were not mentioned specifically by Pories and Dohm.  Examples are GIP and GLP-1 (glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1).

Keep these ideas in mind when you come across someone who’s cocksure that they know the cause of type 2 diabetes.

Steve Parker, M.D.

Reference:  Pories, Walter and Dohm, G. Lynis.  Diabetes: Have we got it all wrong?  Hyperinsulinism as the culprit: surgery provides the evidence.  Diabetes Care, 2012, vol. 35, p. 2438-2442.

What’s Wrong With Type 2 Diabetics?

Type 2 diabetes and prediabetes are epidemics because of excessive consumption of refined sugars and starches, and lack of physical activity.  I can’t prove it; nevertheless that’s my impression after years of reading the nutrition science literature and thinking about it.

I could be wrong.  I reserve the option to change my mind based on evidence as it becomes available.  That’s one of the great things about science.  Accurately identifying the cause of diabetes could provide strong clues about optimal prevention and treatment strategies.

Genetics undoubtedly plays a major role in diabetes, but the gene pool hasn’t changed much over the last several decades as type 2 diabetes rates have soared.

The problem in type 2 diabetes and prediabetes is that the body cannot handle ingested carbohydrates in the normal fashion. In a way, dietary carbohydrates (carbs) have become toxic instead of nourishing. This is a critical point, so let’s take time to understand it.


The major components of food are proteins, fats, and carbohydrates. We digest food either to get energy, or to use individual components of food in growth, maintenance, or repair of our own body parts.

We need some sugar (also called glucose) in our bloodstream at all times to supply us with immediate energy. “Energy” refers not only to a sense of muscular strength and vitality, but also to fuel for our brain, heart, and other automatic systems. Our brains especially need a reliable supply of bloodstream glucose.

In a normal, healthy state, our blood contains very little sugar—about a teaspoon (5 ml) of glucose. (We have about one and a third gallons (5 liters) of blood circulating. A normal blood sugar of 100 mg/dl (5.56 mmol/l) equates to about a teaspoon of glucose in the bloodstream.)

Our bodies have elaborate natural mechanisms for keeping blood sugar normal. They work continuously, a combination of adding and removing sugar from the bloodstream to keep it in a healthy range (70 to 140 mg/dl, or 3.9 to 7.8 mmol/l). These homeostatic mechanisms are out of balance in people with diabetes and prediabetes.

By the way, glucose in the bloodstream is commonly referred to as “blood sugar,” even though there are many other types of sugar other than glucose. In the U.S., blood sugar is measured in units of milligrams per deciliter (mg/dl), but other places measure in millimoles per liter (mmol/l).

When blood sugar levels start to rise in response to food, the pancreas gland—its beta cells, specifically—secrete insulin into the bloodstream to keep sugar levels from rising too high. The insulin drives the excess sugar out of the blood, into our tissues. Once inside the tissues’ cells, the glucose will be used as an immediate energy source or stored for later use. Excessive sugar is stored either as body fat or as glycogen in liver and muscle.

When we digest fats, we see very little direct effect on blood sugar levels. That’s because fat contains almost no carbohydrates. In fact, when fats are eaten with high-carb foods, they tend to slow the rise and peak in blood sugar you would see if you had eaten the carbs alone.

Ingested protein can and does raise blood sugar, usually to a mild degree. As proteins are digested, our bodies can make sugar (glucose) out of the breakdown products. The healthy pancreas releases some insulin to keep the blood sugar from going too high.

In contrast to fats and proteins, carbohydrates in food cause significant—often dramatic—rises in blood sugar. Our pancreas, in turn, secretes higher amounts of insulin to prevent excessive elevation of blood glucose. Carbohydrates are easily digested and converted into blood sugar. The exception is fiber, which is indigestible and passes through us unchanged.

During the course of a day, the pancreas of a healthy person produces an average of 40 to 60 units of insulin. Half of that insulin is secreted in response to meals, the other half is steady state or “basal” insulin. The exact amount of insulin depends quite heavily on the amount and timing of carbohydrates eaten. Dietary protein has much less influence. A pancreas in a healthy person eating a very-low-carb diet will release substantially less than 50 units of insulin a day.

To summarize thus far: dietary carbs are the major source of blood sugar for most people eating “normally.” Carbs are, in turn, the main cause for insulin release by the pancreas, to keep blood sugar levels in a safe, healthy range.

Hang on, because we’re almost done with the basic science!

You deserve a break


Type 2 diabetics and prediabetics absorb carbohydrates and break them down into glucose just fine. Problem is, they can’t clear the glucose out of the bloodstream normally. So blood sugar levels are often in the elevated, poisonous range, leading to many of the complications of diabetes.

Remember that insulin’s primary function is to drive blood glucose out of the bloodstream, into our tissues, for use as immediate energy or stored energy (as fat or glycogen).

In diabetes and prediabetes, this function of insulin is impaired.

The tissues have lost some of their sensitivity to insulin’s action. This critical concept is called insulin resistance. Insulin still has some effect on the tissues, but not as much as it should. Different diabetics have different degrees of insulin resistance, and you can’t tell by just looking.  (There are several other hormones involved in regulation of blood sugar.)

Did you know that people who work at garbage dumps, sewage treatment plants, and cattle feedlots get used to the noxious fumes after a while? They aren’t bothered by them as much as they were at first. Their noses are less sensitive to the fumes. You could call it fume resistance. In the same fashion, cells exposed to high insulin levels over time become resistant to insulin.

Insulin resistance occurs in most cases of type 2 diabetes and prediabetes. So what causes the insulin resistance? It’s debatable. In many cases it’s related to overweight, physical inactivity, and genetics. A high-carbohydrate diet may contribute. A few cases are caused by drugs. Some cases are a mystery.

To overcome the body tissue’s resistance to insulin’s effect, the pancreas beta cells pump even more insulin into the bloodstream, a condition called hyperinsulinemia. Some scientists believe high insulin levels alone cause some of the damage associated with diabetes. Whereas a healthy person without diabetes needs about 50 units of insulin a day, an obese non-diabetic needs about twice that to keep blood sugars in check. Eventually, in those who develop diabetes or prediabetes, the pancreas can’t keep up with the demand for more insulin to overcome insulin resistance. The pancreas beta cells get exhausted and start to “burn out.” That’s when blood sugars start to rise and diabetes and prediabetes are easily diagnosed. So, insulin resistance and high insulin production have been going on for years before diagnosis. By the time of diagnosis, 50% of beta cell function is lost.

Steve Parker, M.D.


You’ve learned that insulin’s main action is to lower blood sugar by transporting it into the cells of various tissues. But that’s not all insulin does. It also 1) impairs breakdown of glycogen into glucose, 2) stimulates glycogen formation, 3) inhibits formation of new glucose molecules by the body, 4) promotes storage of triglycerides in fat cells (i.e., lipogenesis, fat accumulation), 5) promotes formation of fatty acids (triglyceride building blocks) by the liver, 6) inhibits breakdown of stored triglycerides, and 7) supports body protein production.

In his fascinating book, Cheating Destiny: Living With Diabetes, America’s Biggest Epidemic, James Hirsch describes what happened to type 1 diabetics before insulin injections were available. Type 1 diabetics produce no insulin. Until Frederick Banting and Charles Best isolated and injected insulin in the 1920s, type 1 diabetes was a death sentence characterized not only by high blood sugars, but also extreme weight loss as muscle and fat tissue wasted away. The tissue wasting reflects insulin actions No. 4, 5, 6, and 7 above.

Banting and Best worked at the University of Toronto in Canada. Their “discovery” of insulin is one of the greatest medical achievements of all time.