Posted February 1, 2023
Updated on April 22, 2023
In a recent video and blog post, I shared my view that there is considerable uncertainty that people with ‘normal’ blood sugar levels benefit from further ‘optimizing’ their blood sugar levels, and suggested that any benefits for long-term chronic disease risks are likely small. In this context, I suggested that ‘normal’ levels mean blood sugar between 70 and 140 mg/dL most of the time (green bar in the figure below) and that regular spikes to 180 mg/dL or higher are probably an early sign of glucose intolerance (leftmost orange bar in the figure below).
This post resulted in discussions with several people who argued that they are perfectly glucose tolerant by clinical standards, but have major sugar spikes exceeding 180 or even 200 mg/dL to some foods.
In this blog post, I wanted to provide more information on my thinking and discuss the pertinent literature to specifically address the question of whether regular blood sugar spikes exceeding 180 mg/dL in people with otherwise normal glucose tolerance are a sign of early glucose intolerance not captured by standardized clinical testing, or whether such spikes are the normal result of eating highly glycemic foods even in the healthiest people.
How Is Normal Glucose Tolerance Defined Clinically?
If you haven’t seen my prior blog post on the topic, you may wonder why I am even writing about what constitutes normal blood sugar levels. Isn’t this entirely clear?
Yes and no. We do have clear clinical guidance about what normal fasting blood glucose concentrations should be, what normal glucose levels should be exactly 2 hours after drinking a 75-g glucose beverage as part of an oral glucose tolerance test (OGTT), and what our average blood glucose should be, as measured by the glycated hemoglobin or HbA1c test. For example, the American Diabetes Association has identified clear cut-offs that differentiate normal glucose tolerance, prediabetes, and diabetes. Other national and international diabetes organizations have created similar guidelines for the diagnosis of pre-diabetes and diabetes.
At the same time, we have little clear guidance on what kind of blood sugar spikes are consistent with healthy glucose tolerance, and what a normal range of blood sugar values throughout the day is.
That is partly because the American Diabetes Association criteria shown in the table above are based on very standardized tests, specifically an oral glucose tolerance test that includes drinking a beverage containing 75g of pure glucose. Blood sugar responses to normal meals are quite different.
Also, the criteria don’t tell us anything about what a normal level would be 30 min or 1 hour after a meal. For example, we may wonder whether a spike up to 180 mg/dL is OK and still consistent with normal glucose tolerance, as long as our level comes down below 140 mg/dL within two hours of the meal.
Blood Sugar Levels Throughout The Day In Healthy People Eating Mixed Diets
Several studies have characterized the circulating sugar concentrations throughout the day and night, as measured by continuous glucose monitor (CGM), of populations who had normal glucose tolerance, pre-diabetes, or diabetes (by standardized clinical tests).
One such study that is often cited is one by Michael Snyder’s group at Stanford. They looked at CGM data of people with prediabetes or supposedly normal glucose tolerance. Most of the participants who had normal glucose tolerance by standardized clinical tests had low or moderate variability in circulating glucose levels, with values mostly in the 70-140 mg/dL range. Some, however, exhibited severe variability, with sugar levels exceeding 200 mg/dL regularly.
This observation raises the question we are interested in here: do those individuals just eat the wrong, high glycemic load foods all the time, and that explains their regular sugar spikes; or, do they have an early defect in their glucose tolerance and are well on their way to pre-diabetes? Or both?
Snyder and colleagues did not assess what people ate in that part of their study, so we don’t know whether the glucose spikes >200 mg/dL were always triggered by meals of high glycemic load. From this study, this certainly remains a possibility.
However, a noteworthy observation about the study population was that they had enrolled many older participants, and also many with obesity. Because higher age and higher levels of body fat mass are both associated with insulin resistance and glucose intolerance, this raises the possibility that those experiencing excessive circulating sugar spikes >200 mg/dL were, in fact, suffering from an early stage of glucose intolerance that had not (yet) transitioned to pre-diabetes.
To provide some more data points on this latter hypothesis, let’s look at a few other studies in which CGM data of healthy people were analyzed.
A particularly insightful one was published by Freckmann and colleagues in 2007. Their study shows that in healthy, young, and lean men and women, the highest peak blood sugar that ever occurred was 171 mg/dL, even after standardized very high glycemic load meals. The average peak glucose was between 130 and 140 mg/dL, even under these very high glycemic load conditions, and CGM glucose concentrations in these healthy participants were below 140 mg/dL 99.2% of the time.
Very similar data were generated by the Juvenile Diabetes Research Foundation CGM Study Group. According to their data, circulating glucose concentrations >140 mg/dL are uncommon in healthy individuals with normal glucose tolerance, as their cohort of youth and younger adults spent only 0.4% of their time with glucose levels > 140 mg/dL.
That figure was a bit higher in a study by Mazze and colleagues, who found that people with normal glucose tolerance (by clinical criteria) spend 4% of their time in the range >140 mg/dL, but only 0.1% of their time > 200 mg/dL.
Another 2018 study by Rodriguez-Segade and colleagues compared CGM data in men and women with prediabetes or normal glucose tolerance, as determined by standardized clinical testing. Both groups were quite heterogeneous by age and adiposity, i.e., both the prediabetes and normal glucose tolerance groups had some older and heavier participants. Overall, participants in the healthy group spent 97.4% of their time in the 70-140 mg/dL range, but 5% of them experienced at least one sugar spike over 200 mg/dL. Notably, those 5% with peaks >200 mg/dL exhibited overall CGM glucose concentrations more similar to the prediabetic group than those of their healthy peers who did not experience any spike over 200 mg/dL. Similarly, those healthy participants who spent the most time in CGM sugar range >140 mg/dL were the older and higher BMI participants.
Additional evidence that only few people with normal glucose tolerance experience blood sugar spikes, and that those tend to be the older and heavier individuals, was published by Shah et al. in 2019. They studied the CGM data of 153 participants who were 7 to 80 years old. Those participants who were younger than 18 years spent only 1.5% of their time with sugar levels >140 mg/dL, while that figure was 4.1% in those older than 60 years.
Further evidence that increased body weight leads to impaired glucose tolerance, even if it has not (yet) been detected by standardized clinical tests, was provided by Chan and colleagues in 2015. They looked at CGM data of youth with obesity who had normal glucose tolerance, as defined by fasting glucose < 100 mg/dL, 2-hour glucose <140 mg/dL during an oral glucose tolerance test, and HbA1c < 5.7%. In that group, some youth experienced sugar spikes up to 239 mg/dL, strongly suggesting impaired glucose tolerance.
Zhou et al. published in 2009 that among 434 healthy Chinese men and women, CGM data showed that time >140 mg/dL averaged 4.1%, but that only 1.8% of participants experienced any spike >200 mg/dL. As in other studies that had investigated the impact of age, mean CGM glucose levels and time >140 mg/dL increased with age.
Taken together, these data suggest that CGM glucose concentrations exceeding 140 mg/dL are rare in healthy, young, and lean individuals with truly normal glucose tolerance, and levels greater than 200 mg/dL almost never occur. In all studies, those who spend more time with glucose levels >140 mg/dL or even 200 mg/dL tend to be older or have an elevated body mass index, both factors that are associated with reduced glucose tolerance. These data provide support for the idea that any increase above 200 mg/dL is indicative of reduced glucose tolerance, even in those that – according to standardized clinical tests – do not have pre-diabetes or diabetes.
How To Think About Blood Sugar Spikes
Major defects in blood sugar regulation, such as diabetes and even pre-diabetes, don’t occur overnight. These processes are gradual, and it’s more accurate to think of glucose tolerance as a continuous variable rather than in categories. In other words, we are not suddenly jumping from 100% healthy to prediabetic to diabetic. It does make sense to me that even prediabetes is preceded by a deterioration in glucose tolerance even before we can clinically diagnose prediabetes by the current clinical cut-offs.
The available CGM data are very consistent with the hypothesis that circulating glucose levels will rarely ever cross 140 mg/dL and never cross 200 mg/dL in truly 100% healthy, glucose-tolerant individuals and that extended times throughout the day > 140 mg/dL and any increase >200 mg/dL should be seen as an early sign of mild glucose intolerance. As I mentioned in a previous blog post, this group is likely to benefit from wearing a CGM for some time to be able to identify these excessive sugar spikes to above 200 mg/dL, and do something about it by either avoiding those spiking foods, eating them in a way that blunts their impact on circulating sugar levels, or improving their glucose tolerance.
If you read this and you have never worn a CGM device, this may make you wonder whether you need to wear one for some time as well to figure out whether you belong to the group with – supposedly – normal glucose tolerance that exhibits a frequent spiking pattern. I would not discourage you from doing that, but there are some additional data that can provide some additional guidance. Barua and colleagues published a paper in 2021 that showed that among Hispanic adults at risk of diabetes, spending any time outside the 70-140 mg/dL or 70-180 mg/dL range was strongly associated with HbA1c. This suggests that HbA1c at the high end of the normal range could be an indication of frequent blood sugar spikes. Similarly, and this is no surprise, higher age and higher body mass index should be seen as risk factors for glucose intolerance even among those who have not yet been diagnosed with pre-diabetes or diabetes. If you are young, normal weight, and have a HbA1c on the low end of the normal range, I don’t think there is any reason to worry about excessive blood sugar spikes.
Now, please keep in mind that such glucose intolerance could be temporal and could almost certainly be reversed. And one could obviously minimize eating those foods that result in major blood sugar spikes or eat them in a way that blunts their ability to raise sugar levels. I’ll publish a lot of content about how to improve glucose tolerance over the next few weeks and months, and how to blunt the glucose effects of high-glycemic load foods. If you are interested in that, please consider signing up for my newsletter below so that I can let you know whenever I publish new content.
As always, don’t hesitate to leave a comment below or reach out to me by way of the contact form if you have any questions or requests for future content.
Update April 22, 2023
A new paper has just been published online in the prestigious journal Cell Metabolism. The objective of the paper was to characterize the CGM data of over 7,000 individuals without diabetes. The paper includes a lot of data, but most relevant for our discussion here was their finding that – in this cohort – 6% of all CGM readings were greater than 180 mg/dL. Given that none of the participants had diabetes, this could be interpreted as suggesting that blood sugar spikes to 180 mg/dL or higher are a normal part of blood sugar regulation. I disagree with this interpretation.
The fact that so far, increases in blood sugar levels above 180 mg/dL are never seen, and even increases above 140 mg/dL are rare in populations of healthy, young, and lean people suggest to me that the body defends against such blood sugar levels in those with 100% normal glucose tolerance. And vice versa, it suggests that increases to 180 mg/dL or higher are a sign of early-stage glucose intolerance. As I emphasized above, higher age and higher levels of body fat mass are risk factors for impaired glucose tolerance. And because this study included men and women with pre-diabetes as well as older people and some with overweight or obesity, these data are quite consistent with those published earlier and discussed above. Increases in blood sugar concentrations above 180 mg/dL are probably signs of early glucose intolerance. And given that a fully healthy body is able to defend against such high concentrations (i.e., doesn’t allow blood sugar levels to rise to 180 mg/dL) suggests that such high levels are undesirable and not physiological.
References
- American Diabetes Association. Diagnosis. Accessed on Jan 30, 2023.
- Hall et al.; Glucotypes reveal new patterns of glucose dysregulation. Plos Biology 2018; 16: e2005143.
- Freckmann et al.; Continuous glucose profiles in healthy subjects under everyday life conditions and after different meals. Journal of Diabetes Science and Technology 2007; 1: 695-703.
- Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Variation of interstitial glucose measurements assessed by continuous glucose monitors in healthy, nondiabetic individuals. Diabetes Care 2010; 33: 1297-9.
- Mazze et al.; Characterizing glucose exposure for individuals with normal glucose tolerance using continuous glucose monitoring and ambulatory glucose profile analysis. Diabetes Technology & Therapeutics 2008; 10: 149-159.
- Rodriguez-Segade et al.; Continuous glucose monitoring is more sensitive than HbA1c and fasting glucose in detecting dysglycemia in a Spanish population without diabetes. Diabetes Research and Clinical Practice 2018; 142: 100-9.
- Shah et al.; Continuous glucose monitoring profiles in healthy nondiabetic participants: a multicenter prospective study. Journal of Clinical Endocrinology and Metabolism 2019; 104: 4356-64.
- Chan et al.; Continuous glucose monitoring and its relationship to hemoglobin A1c and oral glucose tolerance testing in obese and prediabetic youth. Journal of Clinical Endocrinology and Metabolism 2015; 100: 902-10.
- Zhou et al.; Reference values for continuous glucose monitoring in Chinese subjects. Diabetes Care 2009; 32: 1188-93.
- Barua et al.; Dysglycemia in adults at risk for living with non-insulin treated type 2 diabetes: insights from continuous glucose monitoring. E Clinical Medicine 2021; 35: 100853.
- Keshet et al.; CGMap: characterizing continuous glucose monitor data in thousands of non-diabetic individuals. Cell Metabolism 2023; 35: 1-12.
5 Responses
Insightful analysis. Very helpful.
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Thank you for the feedback, Gloria!
Warm wishes,
Mario
Thank you for your really good job 👍
I agree. I have found that as a diabetic is is possible to eat a diet and stay under 140 mg/dl for weeks as a time. I have many days where I can stay under 120 mg/dl the entire day.