Tag Archives: blood sugar

Could Glucagon Be Just as Important as Insulin in Diabetes?

I couldn't find a pertinent picture

I couldn’t find a pertinent picture

Everybody knows that insulin is the key hormone gone haywire in diabetes, right? Did you know it’s not the only one out of whack? Roger Unger and Alan Cherrington in The Journal of Clinical Investigation point out that another hormone—glucagon—is also very important in regulation of blood sugar in both types of diabetes.

Insulin has a variety of actions the ultimately keep blood sugar levels from rising dangerously high. Glucagon, on the other hand, keeps blood sugar from dropping too low. For instance, when you stop eating food, as in an overnight or longer fast, glucagon stimulates glucose (sugar) production by your liver so you don’t go into a hypoglycemic coma and die. It does the same when you exercise, as your muscles soak up glucose from your blood stream.

Glucagon works so well to raise blood sugar that we inject it into diabetics who are hypoglycemic but comatose or otherwise unable to swallow carbohydrates.

Glucagon also has effects on fatty acid metabolism, ketone production, and liver protein metabolism, but this post is already complicated enough.

So where does glucagon come from? The islets of Langherhans, for one. You already know the healthy pancreas has beta cells that produce insulin. The pancreas has other cells—alpha or α cells—that produce glucagon. Furthermore, the stomach and duodenum (the first part of the small intestine) also have glucagon-producing alpha cells. The insulin and glucagon work together to keep blood sugar in an fairly narrow range. Insulin lowers blood sugar, glucagon raises it. It’s sort of like aiming for a hot bath by running a mix of cold and very hot water.

Update: I just licensed this from Shutterstock.com

Update: I just licensed this from Shutterstock.com

Ungar and Cherrington say that one reason it’s so hard to tightly control blood sugars in type 1 diabetes is because we don’t address the high levels of glucagon. The bath water’s not right because we’re fiddling with just one of the faucets. Maybe we’ll call this the Goldilocks Theory of Diabetes.

When you eat carbohydrates, your blood sugar starts to rise. Beta cells in the healthy pancreas start secreting insulin to keep a lid on the blood sugar rise. This is not the time you want uncontrolled release of glucagon from the alpha cells, which would work to raise blood sugars further. Within the pancreas, beta and alpha cells are in close proximity. Insulin from the beta cells directly affects the nearby alpha cells to suppress glucagon release. This localized hormone effect is referred to as “paracrine guidance” in the quote below, and it takes very little insulin to suppress glucagon.

From the Ungar and Cherrington article:

Here, we review evidence that the insulinocentric view of metabolic homeostasis is incomplete and that glucagon is indeed a key regulator of normal fuel metabolism, albeit under insulin’s paracrine guidance and control. Most importantly, we emphasize that, whenever paracrine control by insulin is lacking, as in T1DM, the resulting unbridled hyperglucagonemia is the proximal cause of the deadly consequences of uncontrolled diabetes and the glycemic volatility of even “well-controlled” patients.

*  *  *

All in all, it would seem that conventional monotherapy with insulin is incomplete because it can provide paracrine suppression of glucagon secretion only by seriously overdosing the extrapancreatic tissues.

So What?

Elucidation of diabetes’ disease mechanisms (pathophysiology) can lead to new drugs or other therapies that improve the lives of diabetics. A potential drug candidate is leptin, known to suppress glucagon hyper secretion in rodents with type 1 diabetes.

RTWT.

Steve Parker, M.D.

PS: Amylin is yet another hormone involved in blood sugar regulation, but I’ll save that for another day. If you can’t wait, read about it here in my review of pramlintide, a drug for type 1 diabetes.

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Filed under Causes of Diabetes

High Blood Sugar Raises Risk for Dementia, Even For Non-Diabetics

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

“Let’s work on getting those blood sugars down, honey.”

On the heels of a report finding no association between Alzheimer’s disease and abnormal blood sugar metabolism, MedPageToday features an new study linking high blood sugars to future development of dementia. And diabetics with sugar levels higher than other diabetics were more prone to develop dementia.

Some of you have already noted that not all cases of dementia are Alzheimer’s dementia. But Alzheimer’s accounts for a solid majority of dementia cases, about eight in 10 cases.

Some quotes from MedPageToday:

During a median follow-up of 6.8 years, 524 participants [of the 2,000 total] developed dementia, consisting of 74 with diabetes and 450 without. Patients without diabetes and who developed dementia had significantly higher average glucose levels in the 5 years before diagnosis of dementia (P=0.01). The difference translated into a hazard ratio of 1.18 (95% CI 1.04-1.33).

Among the patients with diabetes, glucose levels averaged 190 mg/dL in those who developed dementia versus 160 mg/dL in those who did not. The difference represented a 40% increase in the hazard for dementia (HR 1.40, 95% CI 1.12-1.76).

Steve Parker, M.D.

Reference: Crane PK et al. “Glucose Levels and Risk of Dementia” N Engl J Med 2013; 369: 540-548.

Reminder: Conquer Diabetes and Prediabetes is now available on Kindle.

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Filed under Dementia, Diabetes Complications

Deteriorating Brain Function Linked to High Insulin Levels and Insulin Resistance: Here’s How You Fight Back

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. K 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.

Dr. Krikorian 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, or aim for that if you’re overweight

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

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Filed under Carbohydrate, Dementia, Glycemic Index and Load, ketogenic diet

Upper Normal Blood Sugars Linked To Brain Shrinkage

MRI scan of brain

MRI scan of brain

Healthy bodies keep blood sugar levels in a fairly narrow range.  You might think you’re fine if you’re anywhere within the defined normal range.  Think again.  Australian researchers found that folks with fasting blood sugars toward the upper end of the normal range had more degeneration (atrophy) in parts of the brain called the hippocampus and amygdala, compared to those in the low normal range.  Degeneration in those areas is often manifested as dementia.

The hippocampus is critical for learning and memory formation and retention.  The amygdala is also involved in memory as well as emotion.  The two areas are intimately connected, literally.

How Was the Study Done?

Over 250 study participants aged 60 to 64 years had normal brains at baseline and were free of prediabetes and diabetes.  They were mostly caucasian.  MRI brain scans were done at baseline and again four years later.  Significant atrophy (shrinkage) was seen in the hippocampus and amygdala over time, with greater atrophy seen in those with higher baseline fasting glucose levels.

Fasting blood sugar was measured only once, at the start, and ranged from 58 to 108 mg/dl (3.2 to 6.0 mmol/l).  (Fasting glucose of 108 would be prediabetes according to the American Diabetes Association, but not by the World Health Organization.)  Participants weren’t tested for deterioration of cognition (actual thinking).

So What?

The results of the study at hand are consistent with others that link higher rates of dementia with diabetes.  Diabetics, even when under treatment, usually have higher average blood sugars than non-diabetics.  The study authors speculate that damage from higher blood sugars may be mediated by inflammation and abnormal blood clotting (prothrombotic factors and platelet activation).

The Mayo Clinic recently reported that diets high in carbohydrates and sugar increase the odds of developing cognitive impairment in the elderly years.

It’s interesting to contemplate whether non-diabetics and diabetics would have less risk of developing dementia if blood sugars could be kept in the lower end of the normal range.  How could you do that?  Possibilities include:

  • avoid sugars and other refined carbohydrates
  • limit all carbohydrates
  • favor low-glycemic-index foods over high
  • regular exercise, which helps maintain insulin sensitivity (insulin is a major blood sugar regulator)
  • avoid overweight and obesity, which helps maintain insulin sensitivity
  • for diabetics: all of the above plus drugs that control blood sugar

Steve Parker, M.D.

Reference:  Cherbuin, Nicolas, et al.  Higher normal fasting plasma glucose is associated with hippocampal atrophy: The PATH Study.  Neurology, September 4, 2012, vol. 79, No. 10, pp: 1,010-1,026.  doi:10.1212/WNL.0b013e31826846de

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Filed under Dementia, Diabetes Complications

What’s Dr. Bernstein Got Against Tomatoes?

Eat greens for vitamin K

Looks reasonable to me

Dr. Richard Bernstein cautions his diabetic patients and readers of Diabetes Solution to keep a tight lid on consumption of tomatoes.  An excerpt from page 149:

If you have them uncooked in salad, limit yourself to one slice or a single cherry tomato per cup of salad.

His concern is that tomatoes will raise your blood sugar too high.

That doesn’t make sense to me.  A 3-inch diameter tomato has 7 grams of carbohydrate, 2 of which are fiber.  So the digestible carb count is only 5 grams.  That’s not much.  So do tomatoes have a high glycemic index?  Unlikely, although it’s hard to be sure.  Good luck finding a reliable GI for tomatoes on the Internet.

I think Dr. Bernstein’s wrong about this one, which is rare.  I suppose it’s possible that tomatoes deliver some other substance to the bloodstream that interferes with carbohydrate metabolism, but Dr. Bernstein doesn’t mention that.

Do tomatoes play havoc with your blood sugars?

Steve Parker, M.D.

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Filed under Carbohydrate, Vegetables

Does Dietary Protein Affect Blood Sugars?

The protein in this can raise your blood sugar

I’m considering whether I should advise my patients with diabetes to pay careful attention to the protein content of their diet, assuming they’re not malnourished.  It’s an important issue to Dr. Richard K. Bernstein, who definitely says it has to be taken into account.

Protein can undoubtedly raise blood sugar levels.  But is the effect clinically significant?  Most  dietitians and physicians pay little attention to it as a source of hyperglycemia.  Here are some of Dr. Bernstein’s ideas pulled from the current edition of Diabetes Solution:

  • The liver (and the kidneys and intestines to a lesser extent) can convert protein to glucose, although it’s a slow and inefficient process.
  • Since the conversion process—called gluconeogenesis—is slow and inefficient, diabetics don’t see the high blood sugar spikes they would see from many ingested carbohydrates.
  • For example, 3 ounces (85 g) of hamburger patty could be converted to 6.5 g of glucose under the right circumstances.
  • Protein foods from animals (e.g., meat, fish, chicken, eggs) are about 20% protein by weight.
  • Dr. B recommends keeping protein portions in a particular meal consistent day-to-day (for example 6 ounces with each lunch).
  • He recommends at least 1–1.2 g of protein per kilogram of ideal body weight for non-athletic adults.  That’s more than the usual 0.8 g per kilogram.
  • The minimum protein he recommends for a 155-lb non-athletic adult is 11.7–14 ounces daily.
  • Growing children and athletes need more protein.
  • Each uncooked ounce of the foods on his “protein foods” list (page 181) provides about 6 g of protein.
  • On his eating plan, you choose the amount of protein in a meal that would satisfy you, which might be 3 ounces or 6–9 ounces.
  • If you have gastroparesis, however, you should limit your evening meal protein to 2 ounces of eggs, cheese, fish, or ground meat, while eating more protein at the two earlier meals in the day.

“In many respects—and going against the grain of a number of the medical establishment’s accepted notions about diabetics and protein—protein will become the most important part of our diet if you are going to control blood sugars just as it was for our hunter-getherer ancestors.”

Conclusions

I haven’t changed my thinking on this issue yet, but will let you know if and when I do.  I don’t talk much about protein in Conquer Diabetes and Prediabetes in part because I wanted to keep the program simpler than Dr. Bernstein’s.  Albert Einstein reportedly said, “Everything should be made as simple as possible, but not simpler.”

As with most aspects of diabetes, your mileage may vary.  The effect of dietary protein on blood sugars will depend on type 1 versus type 2 diabetes, and will vary from one person to another.  So it may be impossible to set rigid guidelines.

If interested, you can determine how much protein is in various foods at NutritionData.

Steve Parker, M.D.

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What About Sugar Alcohols?

Dietitian Brenna at Eating Simple recently posted an article on artificial sweeteners exclusive of sugar alcohols.  Now she’s reviewed sugar alcohols.  Many who have a sweet tooth, including myself, use sugar substitutes such as sugar alcohols.  Sometimes they affect blood sugar levels, although not as much as sugar.

Dr. Maria Collazo-Clavell at the Mayo Clinic wrote about use of artificial sweeteners by people with diabetes.  Like Brenna, she notes that sugar alcohols can raise blood sugar levels in people with diabetes.  The Mayo Clinic has another article on sugar substitutes.

Steve Parker, M.D.

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