In a series of previous blogs on mysportscience, the role of blood glucose was discussed and we highlighted what insights Continuous Glucose Monitoring (CGM) can provide athletes now and possibly in the future. In this blog, Dr Nicola Guess highlights the multifactorial nature of glucose metabolism, challenging the notion of straightforward causal links between food intake and glycemic responses.
In previous blogs Dr Mike Riddell and I discussed opportunities and also some limitations of CGM.
There are many ways in which we can look at CGM data. We could simply look at a value, or an average over 24 hours. We could look at the glucose variability (GV), or simply count the numbers of peaks and troughs, or perhaps the time spent in a certain zone, or time spent above or below a predetermined value. We could look at the slope of a peak, we could average glucose values during sleep or during exercise, or just in response to one meal. The possibilities are endless.
Like many wearables, CGM produces a lot of data and the interpretation of that data is key to its potential usefulness or even harmfulness. This will be the topic of this guest blog by Dr Nicola Guess, a Registered Dietitian with a PhD in the dietary management of prediabetes from Imperial College London who currently works at the University of Oxford. In this blog she will talk about common misconceptions and misinterpretations. She will also discuss the modifying effects of exercise on glucose responses and some of the essential differences in glucose behaviour between those individuals living with diabetes and healthy individuals.
We don't know what "normal" is yet on continuous glucose monitors!
A common first question from someone using CGM is: “my value is 7.8 mmol/L [140 mg/dL], is this good or bad?” The use of CGM devices in individuals (including athletes) without diabetes is very recent, and while there's emerging data, we can’t define any specific cut-offs for “good” and “bad”. CGMs have been used for a lot longer in type 1 diabetes, and it’s only in the past couple of years that we have been able to establish some of the glycaemic targets people with type 1 diabetes should aim for on a CGM. This has been possible because we now have large datasets of people with type 1 diabetes, so we can determine the glycaemic parameters from a CGM and see how they relate to the risk of things like hypoglycaemic episodes and diabetic complications. We have zero useful data on CGM-derived glycaemic measures in populations without diabetes and health outcomes! So how can we know for sure what glucose is “ok” on a CGM in a person without diabetes? We don’t, and we won’t for a while.
We have zero useful data on CGM-derived glycaemic measures in populations without diabetes and health outcomes!
The best we can do is look at the CGM profiles of people with a “healthy” HbA1c.
What is HbA1c?
The term HbA1c refers to glycated heamoglobin. It develops when haemoglobin, a protein within red blood cells that carries oxygen throughout the body, joins with glucose in the blood, becoming ‘glycated’. By measuring glycated haemoglobin (HbA1c), clinicians are able to get an overall picture of what our average blood sugar levels have been over a period of weeks/months.
HbA1c | mmol/mol | % |
Normal | Below 42 mmol/mol | Below 6.0% |
Pre-diabetes* | 42 to 47 mmol/mol | 6.0 to 6.4% |
Diabetes | 48 mmol/mol and over | 6.5% and over |
*the cut-off point for pre-diabetes can vary between countries. For example, pre-diabetes in the USA starts at 5.7%.
Observations from studies investigating the CGM profiles of people with a “healthy” HbA1c (under 5.7%), CGM-derived glucose readings typically show infrequent excursions above 7.8 mmol/L (140 mg/dL), albeit with some variability across age groups. However, caveats exist, including potential alterations in behavior during study participation, which might lead to underestimation of typical glucose peaks. Despite these challenges, data from multiple studies hint that occasional post-meal excursions into the 9-11 mmol/L (162-198 mg/dL) range may be common among individuals with satisfactory HbA1c levels, possibly reflecting a normal aspect of human glucose metabolism.
We also don’t know if glycaemic variability (peaks and troughs) in people without diabetes even matter, and if so, how much. Instinctively it might seem that of course glucose going up and down a lot must be a bad thing…? But we don’t actually have evidence of this yet. Studies conducted in vivo (in humans) and in vitro (in cells) primarily focus on the type of glucose variability you get in diabetes, where they are much, much higher (and usually sustained for longer) and the drops are lower. Such studies demonstrate the potential for high glucose variability to induce endothelial damage and other complications – but do not accurately reflect glucose variability in individuals without diabetes, where glucose fluctuations are typically less pronounced and of shorter duration.
Despite claims regarding the benefits of stabilising blood glucose levels, empirical evidence linking glucose variability to health outcomes, particularly in normoglycemic individuals, remains scant. While observational studies suggest weak associations between glucose fluctuations and factors like hunger and energy intake, randomised controlled trials fail to establish a significant relationship between glycaemic peaks and dips and appetite regulation. The complex interplay of biological, psychological, and environmental factors influencing appetite suggests that glycaemic variability alone may not play a meaningful role in driving appetite responses.
Glycaemic variability alone may not play a meaningful role in driving appetite responses.
A transient high glucose doesn't mean you have prediabetes or type 2 diabetes
Impaired glucose tolerance (prediabetes) is diagnosed by measuring a person’s blood glucose 2 hours after a drink with 75g glucose in it. If a person’s glucose is 7.8mmol/L (140 mg/dL) or above 2 hours after the drink, we call this impaired glucose tolerance. However, this does not mean that if your glucose gets to 7.8mmol/L (140 mg/dL) at any time, that you have prediabetes. It is completely normal for your blood glucose to get to 7.8mmol/L (140 mg/dL) 30 mins after a drink of 75g glucose or a similar carbohydrate load. The point is that it comes down afterwards.
The same is true with diabetes. We diagnose diabetes when fasting glucose is 7.0 mmol/L (126 mg/dL) or more, or when 2-hour glucose is 11.0 mmol/L (198 mg/dL) or more. But this doesn’t mean that if your glucose ever gets to 7.0mmol/L (126 mg/dL) or 11.0 mmol/L (198 mg/dL) that you have diabetes!
In fact, calling a glucose spike up to e.g. 7.8mmol/L (140 mg/dL) “prediabetes” or a spike up to 11.0 mmol/L (198 mg/dL) “diabetes” completely misunderstands the nature of these conditions. Both prediabetes and diabetes are characterized by chronically elevated glucose.
If a person’s glucose is still at 7.8mmol/L (140 mg/dL) 120 minutes after the glucose drink it’s an indication their glucose has been at least 7.8mmol/L (140 mg/dL) for the better part of 90 mins. Likewise, if a person’s fasting glucose is 7.0mmol/L (126 mg/dL) it’s probably been this high most of the night. And if their 2-hour glucose is 11.0 mmol/L (198 mg/dL), their glucose is probably elevated at least this high most of the day.
In short, it’s crucial to discern between acute and continuous glucose elevations. What distinguishes pathological from normal glucose regulation is the duration of elevation. If glucose remains persistently elevated at 7.8 mmol/L (140 mg/dL) beyond the expected postprandial period, it could signify underlying issues such as impaired beta-cell function or insulin resistance. Yet, brief excursions to this level, followed by a return to baseline, are not indicative of chronic hyperglycemia. Therefore, interpreting glucose readings within a broader temporal context is vital to avoid misinterpretation and unnecessary concern regarding prediabetes or diabetes.
It's crucial to discern between acute and continuous glucose elevations.
Many factors which affect your glucose response to a meal have nothing to do with what you ate at that meal
Proponents of CGM often tout its potential for revealing individualised responses to food, promoting a tailored approach to diet based on personal metabolic responses. However, this narrative oversimplifies the relationship between food intake and glucose excursions, disregarding numerous factors that can influence postprandial glycemic responses independently of meal composition. For instance, the second meal effect is a well-documented phenomenon where preceding meals impact subsequent glucose responses. Additionally, physiological adaptations resulting from dietary changes, such as low-carbohydrate diets, can lead to exaggerated glucose responses to subsequent carbohydrate consumption, often causing undue anxiety and dietary restrictions.
Furthermore, non-dietary factors like stress, sleep patterns, menstrual cycles, and exercise habits exert significant influences on glucose homeostasis, complicating the direct interpretation of CGM data in relation to dietary choices. Stress-induced cortisol release, sleep deprivation, and menstrual cycle phases can all alter glucose tolerance, while the timing and intensity of physical activity can modulate immediate glucose homeostasis and long-term insulin sensitivity. These findings challenge the claims of straightforward causal links between food intake and glycemic responses.
If you look at the figure above, the glucose excursion (the area under the glucose curve) is much decreased (improved) after exercise and then reverts back to baseline after several days. Let’s imagine you eat a bowl of oats with whole milk on day 1 - you’ll have a glucose response that looks fairly low. Now let’s imagine you run out of whole milk on day 5 and have semi-skimmed milk with your oats - you’ll get a larger rise in glucose. You might think this is due to the type of milk and resolve to have whole milk to better control your glucose. But hopefully you can see with this example the change in glucose tolerance may well be due to the exercise you did - and the milk has nothing to do with it.
CGM technology offers insights into glucose dynamics, its utility for pinpointing individualised dietary responses is limited by the myriad of non-dietary factors affecting glycemic control.
In conclusion, while CGM technology offers insights into glucose dynamics, its utility for pinpointing individualised dietary responses is limited by the myriad of non-dietary factors affecting glycemic control.
For people without diabetes, glucose is a symptom of disease, not a cause
A major misunderstanding is the idea that you can prevent the development of type 2 diabetes if you take steps to lower your glucose excursions. The correct answer here is that it depends on what you do to lower your glucose excursions.
Glucose that is creeping up over time and type 2 diabetes are both caused by insulin resistance and failing beta-cells. So, to prevent type 2 diabetes, you need to improve insulin resistance and improve the function of the beta cells.
In other words, glucose is a marker for the underlying metabolic dysfunction which may eventually lead to type 2 diabetes.
This distinction between symptom and cause is also critical when we consider other diseases such as cardiovascular disease. Insulin resistance, characterised by disruptions in intricate signaling cascades, not only hampers glucose regulation but also impacts amino acid, lipid metabolism, and vascular function, which all contribute to cardiovascular dysfunction and other health complications.
Focusing solely on minimising glucose excursions, especially in individuals with normoglycemia concerned about spikes, may overlook the broader metabolic dysregulation underlying elevated glucose levels. Such an approach risks neglecting other aspects of cardiovascular health and may inadvertently exacerbate the underlying pathophysiology associated with insulin resistance.
Here you can see the problem with eating with the sole aim of lowering your glucose excursions - particularly in people with normoglycaemia who are worried about glucose spikes. At best, you might be eating in such a way that makes zero difference to your actual risk of disease (and maybe unnecessarily depriving yourself of foods you enjoy!) Or you could even be making the underlying pathophysiology worse!
Even if you have diabetes, glucose levels are a tiny part of your cardiovascular health
It might surprise you to know that even in type 2 diabetes, medications which substantially lower glucose don’t necessarily prevent major cardiovascular events like heart attacks and strokes. The reason for this is complex (and it’s not to say lowering glucose is not a critical part of diabetes management) but it really underscores the importance of other CVD risk factors including high blood pressure and high cholesterol.
This is important context for when we consider people with (as far as we know now) normal glucose. At least a third of people in the UK have high blood pressure and about half have high cholesterol. So, in terms of the components of metabolic and cardiovascular health people would benefit from focusing on, it’s those. And right now, we don’t have neat little devices you can stick on your arm to measure them so tech companies are not rushing to tell you how important these are.
It's also worth mentioning that a lot of people (probably about 60% of the population) have elevated insulin to a degree that it is also increasing their cardiovascular risk (and other health problems too). Insulin is a way better marker of metabolic health than glucose is.
Elevated triglycerides are also an important part of cardiovascular and metabolic health not captured with a CGM. This risk factor has added importance because some things that a person might do to lower glucose can increase post-prandial triglycerides, such as consuming more fat or consuming a low carbohydrate diet. It’s also worth noting that GPs measure fasting triglycerides, not post-prandial triglycerides. So if you’re relying on a CGM to measure your metabolic health, it will miss a lot!
In summary, a glucose monitor really only gives you an absolutely minuscule picture of your metabolic health. And the actions you take to reduce glucose (if that becomes your focus) are not necessarily going to address these far more important risk factors.
What can a CGM tell you and how can glucose monitoring help if you don't have type 2 diabetes?
I have heard from some patients that they have found a CGM useful for just making them more mindful of what they’re eating, and they’ve been able to improve their diets and improve their health by using one. On the other hand, I have seen patients become incredibly anxious, and actively worsen their health (including significant rises in cholesterol) by using a CGM.
The best advice I can give is that CGMs do not change the dietary and lifestyle guidance that we know helps improve the underlying pathophysiology of type 2 diabetes and other diseases. But, using one might help you stick to these changes. In addition, we can’t know with any certainty whether or not frequent glucose excursions to +11mmol/L (+198 mg/dL) could cause damage in the long run. So if you’re worried your glucose is creeping up a bit or you’re concerned (of course see your doctor to check), I think it’s perfectly reasonable to make adjustments to one’s lifestyle here to limit these rises. And whether you want to do this with a CGM for peace of mind is up to you.
For most people, the following are a bunch of things you could do (you don’t have to do all of them) that would be sufficient to lower post-prandial glucose rises substantially:
Lose weight - we have incredibly strong evidence that even modest weight loss of 3-5% body weight lowers glucose and prevents the development of type 2 diabetes.
Engaging in regular physical activity will reduce your glucose acutely and chronically if you keep it consistent.
Replace half of your starch (rice, potatoes, bread) serving with veges.
Switch your starch to a legume-based pasta.
Have a legume side instead of starch.
Each of these not only acutely lower glucose but much more importantly, they also target the underlying pathophysiology driving elevated glucose levels – and will improve your overall metabolic and cardiometabolic health.
