My fasting blood glucose has been creeping up over several years. (My fasting blood sugar is around 110, and HbA1c=5.7; fasting insulin=3.1, triglycerides=91.) Recently, I tried a continuous glucose monitor for the first time, to see what I could learn about eating and exercise habits that affect my blood glucose. The experiment led me to some reading and thinking that was worthwhile, but the results themselves were disappointing, limited (first) by flaws in the technology and (second) by wide variability that I could not trace to any of the usual behavioral correlates.

Why concern ourselves with blood sugar?

Insulin is generated in the pancreas after we eat, with a cascade of effects on the body. The primary short-term effect is to prevent glucose levels in the blood from getting too high, by notifying the liver of the need to pull glucose out of the blood and store energy as fat.

Loss of insulin sensitivity is a primary hallmark of human aging. Most of the known life extension strategies in lab animals have to do with insulin in one way or another. For example, the worm genedaf-2is the worms only insulin receptor, and mutating (weakening) thedaf-2 gene doubles the worms lifespan. Life extension benefits of exercise and caloric restriction are thought to work, at least in part, through the insulin metabolism.

But glucose is also dangerous, and as we get older we are poisoned by excess sugar in the blood. High blood sugar leads to [list fromMayo Clinic]

So for long-term health, the name of the game is to keep blood sugar down with as little insulin as possible, hence preservation of insulin sensitivity is the target. Metformin is a well-studied drug for keeping blood sugar down without insulin. I have been taking it (irregularly) for the last several years, intermixed with berberine and Gynostemma(Chinese name: jiaogulan =).

This reasoning plus direct evidence for life extension in rodents and indirect evidence of life extension in humans has led me to take metformin, though it is not without side-effects.

Long-term effects of metformin

Metformin is a credible longevity drug, statistically associated with lower risk of cancer, heart disease and especially dementia in humans. Six years ago,this studylaid the foundation for metformin as a longevity drug with the claim that people taking metformin had lower all-cause mortality, despite the fact that a population of type-2 diabetics was being compared to a healthier population. This finding inspired Nir Barzilai to raise support for theTAME study.

But metformin has its risks. A long-time contributor to this site, Dr Paul Rivas pointed me to evidence thatmetformin can interfere with exercise metabolism. Paul notes his personal experience with loss of peak performance while taking metformin. My own experience is consistent with this, though I have never done a rigorous A/B comparison.This study, demonstrating a small but consistent decrease in peak performance, appears to me to be well-designed and analyzed. A plausible mechanism is the interference of metformin with mitochondrial function [ref,ref].This article claims that metformin suppresses synthesis of ATP, which is the reservoir of energy for immediate use in all cell types. Ben Miller has done the most direct and most recently relevant human experiments in this area and his findings suggest the intriguing possibility that metformin blocks exercise adaptations almost completely in about half of individuals, but not at all in the other half. (If you want to know which half youre in, youll have to wait for next years study.)

For the majority of Westerners who exercise little or not at all, metformin may show reduction in long-term risk of age-related disease; but there is no data I know of on the subset of people who do vigorous exercise, comparing metformin to no metformin. Does metformin block the health effects of exercise?Rhonda Patrick citescredible referenceson this subjectas fast as she can get the words out, and her conclusion is that exercise is a better anti-aging program than metformin, and you really cant have both.

Do glucose-control herbs also blunt the benefits of exercise?

I wrote a few years ago listingbotanical alternatives to metformin. Much less research has gone into these herbs, so we must think theoretically about interference with benefits of exercise.

Berberine works by a mechanism of action that overlaps metformin. Both metformin and berberine promote AMPK (which in turn promotes sugar burning). Both metformin and berberine inhibit mitochondrial Complex I (slowing the conversion of sugar to usable energy). There is tentative experimental evidence that (unlike metformin) berberine does not inhibit adaptations to exercise [ref,ref,ref].

Gynostemmais a Chinese herb popularized by Life Extension Foundation in their proprietary compound calledAMPK Activator. Inanimal modelsand in humans,Gynostemmasuppresses blood sugar and blood cholesterol. Like metformin and berberine, it works through AMPK,which appears to be a good thing. It isanti-inflammatory, and has a history in China as cancer therapy, supported bymouse andin vitrostudies. In rodent studies,Gynostemmahas a beneficial effect on strength and endurance [ref,ref,ref]. Theone studyIve found on human diabetes shows modest benefits after 12 weeks. The only counter-indication that I have seen is that itincreases insulin release (in vitro), which I believe to be pro-aging.

Is it more important to suppress postprandial spikes or to depress fasting glucose levels?

HbA1c is a standard blood test for diabetes. It isrelated to average blood glucoselevels over the previous 90 days (= the half-life of hemoglobin in the blood). But the glycation of hemoglobin (as measured by A1c) happenspredominantly during the brief glucose spikes, rather than the much longer periods of average glucose levels. So it might be fairer to say that A1c summarizes peak glucose events over a 90-day period. And we might guess that the long-term health risks of high blood sugar are similarly more sensitive to the peaks than to the average.

I believe that apoptosis is on a hair trigger as we age, and part of the reason for this is too much p53.This studylinks P53 activation to postprandial glucose spikes, rather than to high average glucose levels.This studylinks deterioration in endothelial function (related to arterial disease) with glucose spikes. The same paper lists ROS and oxidative stress as additional risks.

For a long while, it has been established that high fasting blood sugar is associated withcardiovascular risk. Of course, there is also association withobesity and T2 diabetes, but for these, it is natural to think of fasting blood sugar as the result, rather than the cause.

Chris Kressersays the best indicator of metabolic health is blood glucose levels 2 hours after a meal. If you can bring your blood glucose down to normal within 2 hours after eating your insulin sensitivity is good. For me, unmedicated, it was 3 hours after dinner, but less than 2 hours after breakfast. Either berberine or metformin tamed the after dinner spikes within 2 hours.

Kresser claims that these guidelines from the American Diabetes Association are not strict enough, and that statistics show increased future risk of diabetes even for people in the ADA normal range. But he citesPetro Dobromylskyj, who makes an exception for anyone on a low-carb diet (how low isnt specified). Paradoxically, low-carb diets are claimed to be healthy, even though they decrease insulin sensitivity. I have been unable to make sense of this.

Kresser emphasizes that all numbers should be interpreted in the context of a persons other lifestyle and health indicators. In people who are active and not overweight, he is not inclined to worry about statistics in the prediabetic range. (I take comfort in this personally, and who can say if Im fooling myself?) But I can learn something from the way my glucose stats respond to medications, eating and exercising, whether or not I believe the absolute levels are concerning.

Writing inScience Magazinelast year, Charles Piller reviewed the ADA guidelines and found a consensus in the opposite direction that they were probably too strict, and unnecessarily worrisome to a great many people. By ADAs definition, 80 million Americans are pre-diabetic, which is 40% of the adult population. The conflict really is not over the statistics but the interpretation. You can say either People with A1c levels above 6 are at increased risk of progressing to diabetes or equally well, Most people with A1c levels less than 6.4 will never develop diabetes. Both statements are true.

As promised: my experience

The Freestyle Libre was very easy to use and set up. I followed the instructions and used a spring-loaded device to insert the monitor behind my biceps. It was painless. Theres a tiny wire that goes a few millimeters into the skin and an adhesive covering with a button containing the electronics.

The wearable button stores data for up to 8 hours. The other part of the kit is a reader that downloads data every time you bring the reader within an inch or two of the button. As long as you take a reading every 8 hours or less, you wont lose any data. And you can do it as often as you like, to get real time feedback on your glucose state.

The wearable button ($45) is meant to last two weeks, and then it must be discarded. My insurance (Blue Cross Medicare Advantage) wouldnt pay for it because I didnt have a diagnosis of diabetes. I found this out only after several trips to the drug store, interspersed with phone calls to Blue Cross, where I got repeated assurances that it would be covered. The reader ($85) can be reused. Apparently, it doesnt do anything that a cell phone app couldnt do, but Abbott (parent company of Freestyle) has arranged it so that you can only use the cell phone app if you purchase the reader.

To analyze historic data, you can use capabilities built into the phone app, or plug the reader or cell phone into a computer, using a USB cable. The data is uploaded to aweb sitecontaining analysis tools and an option for creating a CSV file for more detailed manipulation in a spreadsheet. (The download button is not so easy to find, but I called Abbotts tech support number, and connected without excessive wait time to a friendly and knowledgeable technician.)

My intention was to vary the glycemic content of my meals, my exercise schedule, eating and fasting schedule, and the medications I was taking (metformin and berberine) to learn what I could about glucose management. The first day I fasted, and I was concerned to see that all day my fasting glucose ranged between 110 and 120. (For reference: the standard healthy range for fasting glucose is 70-100. Below 70 is hypoglycemia. Above 100 is pre-diabetes and above 125 is type 2 diabetes.)

I ate a meal, and glucose shot up to 179 before bedtime, only gradually coming back down during the night. As it turned out, 179 was my high for the week.

The data is cut off after 10 days, though the monitor is supposed to have a lifetime of 14, because it fell off my arm. I looked for patterns in my data, and was able to learn only four things:

(In a long phone support session with an Abbott representative, they acknowledged the reality of my experience: that the monitor can loosen over time, resulting in readings that are anomalously low. They were happy to replace the monitor, and advised me against long periods of swimming. )

Unresolved

I was left wondering all the things I wanted to discover at the beginning of my experiment.

The thing that impressed me most was the natural variability of blood sugar, changing from hour to hour, uncorrelated with either food or exercise. I trust the body knows what its doing. Le corps a ses raisons que la raison ne connait pas.*

I hope to try the monitor for 2 weeks again when swimming season is over.

In the meantime, I am taking a modest, common-sense approach. I am going to leave out metformin but continue daily exercise and low doses of berberine andGynostemma, lightening my evening meal and ending the days food 3 hours before bedtime.

Walking burns calories (pulls sugar from the blood) 3 to 5 times as fast as sitting, and walking after a meal feels like a natural and pleasant thing to do. My doctor recommends it. Im going to try walking half an hour after breakfast and dinner, pending my next experiment with the CGM.

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