I mentioned in the article comparing ketosis and diabetic ketoacidosis (DKA) that, in DKA (Diabetic Ketoacidosis), the liver floods the bloodstream with fuels, such as ketones which makes the blood acidic. However, the usual way a diabetic tests for DKA is to see if there are ketones in the blood. The problem with this approach is ketosis also releases ketones into the blood but ketosis is not dangerous. If we find our blood has ketones how do we know if we are in ketosis or DKA?
As usual, for the quick answer, head over to tl;dr.
The other measure often applied is to test the blood glucose level. With the liver flooding the blood with fuels during DKA, including glucose, it makes sense that the blood glucose levels will rapidly rise. This is usually true, unless the liver’s glucose stores are depleted. This situation leads to a condition called eDKA (Euglycemic DKA). This is a big problem for diabetics who follow a low carbohydrate diet as this can put the person into ketosis but can also deplete the glycogen stores of the body which means, if they do head towards DKA, there may not be a corresponding rise in blood glucose levels.
How is DKA Medically Defined?
DKA is not defined by ketone levels, even though this is often the measure used by diabetics to check. It is actually defined by the pH (acidity) of the blood and the amount of bicarbonate in the blood.
The normal pH of blood is between 7.35 and 7.45 and the body goes to great lengths to keep it in this range. In DKA this goes below 7.3. If only there was a way for diabetics to directly check what the pH of their blood was, this would remove the ketone-confusion. I am happy to say there is a way to check.
The Magic Meter
It took some finding but I have found a pH meter which can measure pH levels to one hundredth of a pH (pH is unitless). The meter is the LAQUAtwin-pH-22 by Horiba Scientific.
The tapered end has a flap which lifts up and a liquid sample is placed on the ISFET sensor underneath (0.1 mL or more). This meter costs around $200 so it is not cheap but cheaper alternatives, such as testing strips and immersive meters, simply do not have the accuracy needed.
To set up the meter ready for testing, you need to calibrate it with the provided solutions. Once this is done (and if you follow the instructions it really is quite easy) you are ready for your blood.
Getting a Blood Sample
It turns out getting blood out of the human body was a lot harder than I realized. I initially tried finger pricking but generating 0.1 mL of blood this way proved painful and futile as I struggled to get a reliable reading. In the end I used butterfly needles and vacutainers ordered online. This combo is what the blood collection folk use to collect blood for analysis.
To get the blood, you remove the needle cover, put the needle into your arm and then push the green end of the butterfly needle through the hole in the top of the vacutainer tube. For tips on technique, I highly recommend searching YouTube (this is what I did).
The end result was a vial full of blood.
I did also consider using syringes, given diabetics (or, at least, insulin dependent ones) have easy access to them but this way looked the simplest given I only had one free hand during the process.
For the curious, the vacutainer tube has a vacuum inside and so when the green end of the butterfly needle is pushed into the tube, the vacuum draws the blood out of the arm.
If you intend to try this at home, one other tip is to use the sample quickly. In my case, if I left it too long, the blood in the tube began clotting so get the blood into the meter quickly before coagulation.
The meter lived up to its promise and I got a reading of 7.48. This is a little on the alkaline side of the normal blood range but may have been a minor calibration error. Even accounting for the calibration, this is much higher than the 7.3 ‘danger zone’ so no DKA for me today.
Using the LAQUAtwin-pH-22 you can measure the pH of a liquid down to a sample size of 0.1mL and to an accuracy which is meaningful for checking for DKA. Using a butterfly needle and vacutainer I obtained online, I extracted blood from my arm and, using the meter showed a sensible result, consistent with someone who is not in DKA.
This opens up a new way for diabetics to check whether they are in DKA and is also a way aligned to the actual medical definition of DKA.
I often see people claim on social media that glucose spikes above 110/120/140 mg/dl (roughly 6/7/8 mmol/l) cause damage and diabetics should religiously keep their blood sugars below this level to prevent long term complications.
While the research to verify this assertion could well be done with the wealth of data now captured by continuous glucose monitors (CGMs), to my knowledge, it has not been done. My concern is that being this fixated on your glucose levels would be a great way to drive yourself crazy and a tragedy if it was for no benefit.
So what does science know? In this article I will review the literature as well as show you what to look for in other medical papers. As usual, feel free to go to tl;dr if reading scientific paper summaries is not your thing.
My first source is a recent study from Sweden which suggests there is a ‘goldilocks zone’ for diabetics where the HbA1c is not too high to cause complications and not too low to increase the risk of severe hypoglycemia. Their conclusion is an HbA1c between 6.5% and 6.9% is optimal to avoid these two extremes.
My second list of sources come from Blood Sugar 101. This is a site that claims their cited scientific papers “make a cogent case that post-meal blood sugars of 140 mg/dl … cause both permanent organ damage and the worsening of diabetes.” I am keen to review their papers to see if the papers actually support this position. I have nothing against the site, I barely know it. I chose it simply because it was cited in social media and I assume they have chosen papers to give the most compelling case for their claim.
What To Look For In Medical Papers
When reviewing papers and their findings, I look at two things: their ‘n’ and ‘p’ values. The ‘n’ is the number of people involved in the study (obviously the bigger, the better) and the ‘p’ value which measures statistical significance. The lower the ‘p’ value, the more reliable the conclusions with a value below 0.05 generally considered to be statistically significant.
For example, the Swedish study mentioned above had n=10,398. That is quite a big study. The Results section says the following:
“Mean age of participants was 14.7 years (43.4% female), mean duration of diabetes was 1.3 years, and mean HbA1c level was 8.0% (63.4 mmol/mol). After adjustment for age, sex, duration of diabetes, blood pressure, blood lipid levels, body mass index, and smoking, the odds ratio for mean HbA1c <6.5% (<48 mmol/mol) compared with 6.5-6.9% (48-52 mmol/mol) for any retinopathy (simplex or worse) was 0.77 (95% confidence interval 0.56 to 1.05, P=0.10), for preproliferative diabetic retinopathy or worse was 3.29 (0.99 to 10.96, P=0.05), for proliferative diabetic retinopathy was 2.48 (0.71 to 8.62, P=0.15), for microalbuminuria or worse was 0.98 (0.60 to 1.61, P=0.95), and for macroalbuminuria was 2.47 (0.69 to 8.87, P=0.17). Compared with HbA1c levels 6.5-6.9%, HbA1c levels 7.0-7.4% (53-57 mmol/mol) were associated with an increased risk of any retinopathy (1.31, 1.05 to 1.64, P=0.02) and microalbuminuria (1.55, 1.03 to 2.32, P=0.03). The risk for proliferative retinopathy (5.98, 2.10 to 17.06, P<0.001) and macroalbuminuria (3.43, 1.14 to 10.26, P=0.03) increased at HbA1c levels >8.6% (>70 mmol/mol). The risk for severe hypoglycaemia was increased at mean HbA1c <6.5% compared with 6.5-6.9% (relative risk 1.34, 95% confidence interval 1.09 to 1.64, P=0.005). “
It looks complicated but we can break it down. When it compares the risk of any retinopathy between those with an HbA1c < 6.5% and those with 6.5-6.9% the odds ratio is 0.77 (you are less likely to get retinopathy with the higher HbA1c) BUT the ‘p’ value is 0.10 so it is not statistically significant and we can ignore it. In fact, in comparing the <6.5% group to the 6.5-6.9% group, the only statistically significant result was for preproliferative diabetic retinopathy which was right at the edge of significance (p=0.05).
However, when comparing <6.5% to 7.0-7.4% and >8.6%, across the board, there was a statistically significant increase in risk for all of the examined complications.
Finally, when comparing the risk of severe hypoglycemia between <6.5% and 6.5-6.9% there was a statistically significant increase in risk below 6.5% (34% higher).
The paper’s conclusion is:
“Risk of retinopathy and nephropathy did not differ at HbA1c levels <6.5% but increased for severe hypoglycaemia compared with HbA1c levels 6.5-6.9%. The risk for severe complications mainly occurred at HbA1c levels >8.6%, but for milder complications was increased at HbA1c levels >7.0%”.
This makes sense and I believe the “mainly” is inserted to cover the borderline preproliferative diabetic retinopathy risk increase for the 6.5-6.9% group.
Now let us look at the case for “140 mg/dl does damage” by going through the Blood Sugar 101 sources.
Reviewing the Papers
Some of the Blood Sugar 101 links were broken but here are the ones which actually went somewhere or which I could find by Googling the title.
n=107 of which only 13 had diabetes and 36 had impaired glucose tolerance (IGT) and all had idiopathic (unknown cause) neuropathy.
The paper found people with IGT (defined as having a blood glucose of 140-200 after two hours in an oral glucose tolerance test (OGTT)) had a statistically significant higher change of having neuropathy BUT no such conclusion was made for diabetics. In other words, the low population of the study, combined with the low population of diabetics means this paper offers little value to diabetics and yet I have seen it quoted on a few sites claiming it backs the “over 140 mg/dl does damage” claim. At best, we can say it supports the claim that people who are prediabetic are at a greater risk of neuropathy, but that is about it.
This study mirrored the previous one with n=73. Of these patients, 26 had IGT, and 15 had diabetes. This paper shows that diabetics that have neuropathy have it more severely than those just with IGT. So, in this case, the conclusion is if someone is at 200 after two hours of an OGTT (the definition of ‘frank’ diabetes) if they get neuropathy it will likely be more severe than their prediabetic counterparts.
In this one n=100, all with chronic idiopathic axonal polyneuropathy (CIAP). They were given an OGTT and 62 of them had abnormal results, twice as high as general population groups. Statistical significance was a little light on the ground in this study but it is aligned to the previous two studies’ findings.
This study had n=195 diabetics and n=198 control subjects. It found diabetes was a risk factor for polyneuropathy and, within the diabetic group, age, waist circumference, and peripheral arterial disease were associated with polyneuropathy.
This study tried to keep n=800 critically ill patients patients below 140 mg/dl while in the Intensive Care Unit (ICU) over a period of 11 months and compared them to patients who were not intensively managed. The populations were not all diabetic with the only common factor being admission to ICU.
The following were shown to have a decreased incident rate in the intensively managed patients: poor kidney function (renal insufficiency), blood transfusions, hospital mortality rates, and length of stay in the ICU. Hypoglcemia rates did not significantly change.
This one is in mmol/l but I will convert for the US diabetics. Essentially it showed that when blood glucose goes above 100 mg/dl, the ratio of insulin sensitivity to insulin resistance declined. However, the paper failed to report the level of statistical significance of the results. It did say it used n=388 though of which 250 had IGT or Type 2 diabetes. So, assuming the results were significant, it tells us that either resistance increases or sensitivity decreased as blood glucose levels go up.
This study reviewed the beta cell mass of bodies from 124 autopsies. Of the 124, 91 were obese and 33 were lean. They found that obese patients had roughly a 50% larger beta cell volume (possibly influenced by the younger age at which the obese population died). Of the obese individuals, the Type 2s had a 63% smaller beta cell volume than their non-diabetic obese counterparts.
The rest of the paper talks at the possible mechanisms for this difference is volumes, looking at beta cell replication rates and beta cell death rates.
This is a mice study and, given the number of ‘cures’ for diabetes found for mice, I am a little skeptical to apply the findings to humans. The paper was looking at the survival rate of transplants between mice with insulin treatment to keep their glucose below 150 mg/dl and mice with no such treatment.
The paper found:
“…insulin treatment did not improve the initial preservation of transplanted β-cell mass in the initial days after transplantation. In contrast, increased apoptosis (cell death) and reduced β-cell mass were found in islets exposed to long-term hyperglycemia but not in normoglycemic mice, suggesting that sustained hyperglycemia increased β-cell death in transplanted islets.”
So transplanted beta cells in mice did not appreciate long term exposure to elevated glucose levels.
This study gave n=1062 patients an OGTT and measured their blood glucose after one hour. Those above 155 mg/dl had elevated inflammatory markers and lipid ratios. The author goes on to suggest these increases could be a marker for cardiovascular risk but does not provide evidence linking the markers to heart disease.
This was a link to another Blood Sugar 101 page which had a bunch more links but, given the length of this article already, I am focusing on the ones just on the original page. If enough people call this out, I am happy to review the heart disease one in another article.
Broken link and could not find the source on Google. I did find this summary but without indication of statistical significance it is hard to confirm the findings. Also, the paper focused on pre-diabetes so its relevance to diabetics is limited especially when no blood glucose levels are mentioned. I expect it found conclusions similar to papers (1), (2), (3), and (4).
This paper looked at the data of three populations (n=3162, n=2182, and n=6079). Its conclusion was:
“We saw no evidence of a clear and consistent glycaemic threshold for the presence or incidence of retinopathy across different populations. The current FPG cutoff of 7·0 mmol/l used to diagnose diabetes did not accurately identify people with and without retinopathy.”
In other words, they found that a person’s fasting plasma glucose (FPG) was a poor predictor of retinopathy.
This paper is looking at FPG and HbA1c to see if it is predictive for diabetic retinopathy. With an n=1066 (not all diabetics) they concluded that the greatest increase in prevalence for retinopathy occurred for HbA1c above 5.5% and FPG above 5.8 mmol/L (105mg/dl). It also found that HbA1c was a better predictor than FPG. Here are their curves.
For the HbA1c curve, while the uptick is at 5.5%, we see the dip before this means the prevalence, relative to the baseline prevalence of around 10% only starts inceasing past this above 6%. Similarly, to escape baseline required an FPG above around 6.5 mmol/l
This study combined the results of nine studies to get a whopping n=44,623. They looked at FPG (n=41,411), two-hour OGTT (n=21,344), and HbA1c (n=28,010).
While no ‘p’ values were given, their results concluded that an HbA1c above 6% has an increased prevalence of retinopathy with the threshold for significant risk at above 6.4%. For FPG the threshold was 6.6mmol/l (120 mg/dl). OGTT proved to be a poor predictor.
n=700 with the aim to determine the HbA1c and FPG for predicting retinopathy after 10 years.
Here are the results.
While the paper’s conclusions were thresholds of 108 mg/dL for FPG and from 6.0% for HbA1c, we can see above the prevalence only jumps up significantly after >7.0 mmol/L (126 mg/dl) for FPG and >7.0% for HbA1c.
This was a press release talking about two studies, rather than the studies themselves. Given it is light on details, I am ignoring it for this analysis. It did say this though:
“No one is claiming, based on current evidence, that either fasting glucose or HbA1C is a viable target for therapy of heart failure specifically; that would have to be established in prospective, randomized trials, all three researchers emphasized.”
This paper looked at n=33,293 women and 31,304 men (for a total of n=64,597). Of these, 2,478 people had cancer. The big takeaway of this study was the difference in risk profile between men and women. It found “abnormal glucose metabolism was associated with a statistically significantly increased risk of cancer overall in women but not in men.”
To put it another way: “In men, overall, no statistically significant associations were observed between glucose levels and cancer risk”.
Like study (9), this was a study of cells in a lab, rather than a study of humans. The main conclusion was a fluctuation in glucose levels aligned to the kinds of fluctuations a human body is exposed to through three meals a day and 12 hours of fasting is more damaging than constantly high glucose levels.
n=1871, all diabetics, had their HbA1c measured and then were followed up over a period of 11 years. The groups were split into people with HbA1cs of <6%, 6-7%, 7-8%, and >8%. Groups above <6% had a higher relative risk of chronic kidney disease (CKD).
This means, if there is a threshold for HbA1c, above which CKD begins to increase in risk it probably lies somewhere between 6 and 7%.
This study involves n=19,019 men but the analysis only looked at the non-diabetic ones (n=18,406). The men did a test similar to an OGTT but not quite following modern protocols and if they exceeded 200 mg/dl they were excluded (n=56). Also those with missing data were excluded (n=134) leaving a total of n=18,216.
The study found that for non-diabetics, the risk of stroke mortality increased if the patient’s blood sugar went over 4.6mmol/l (82.8 mg/dl) as part of their pseudo-OGTT. Given my focus is on diabetics, a paper studying non-diabetics is of limited relevance.
Summary Of All The Paper’s Conclusions
So this is what we know from the 21 papers.
If you have impaired glucose tolerance (IGT) you are more likely to get neuropathy
Diabetics who fail an OGTT are at risk of more severe neuropathy than those with just IGT
If you have IGT you are more like to get chronic idiopathic axonal polyneuropathy (CIAP)
Diabetes is a risk factor for polyneuropathy
If you use insulin to keep patients in intensive care under 140 mg/dl, they tend to fare better
Either insulin resistance increases or sensitivity decreases as blood glucose levels go up (this is anecdotally confirmed by Type 1s I know who say it takes much more insulin to come down from a large high than a smaller one.)
Obese Type 2s have a smaller beta cell volume than their obese non-diabetic counterparts
Keeping glucose levels lower in mice with pancreatic transplants improves the longer term prospects of the transplant
Cells in a dish do not like higher glucose levels
People with IGT get inflammation when they spike
Study not found but likely found that people with IGT are at a higher risk of neuropathy
Fasting Plasma Glucose (FPG) is a poor predictor of retinopathy
HbA1c is a better predictor of retinopathy than FPG and to get above the baseline risk, required an HbA1c of greater than 6% or a FPG of 6.5 mmol/l (around 120 mg/dl)
HbA1c above 6% has an increased prevalence of retinopathy with the threshold for significant risk at above 6.4%. For FPG the threshold was 6.6mmol/l (120mg/dl). OGTT proved to be a poor predictor.
The risk for retinopathy significantly increases when HbA1c is above 7% or when FPG is above 7 mmol/l (around 130 mg/dl). There is a smaller increase when the HbA1c is above 6.5%
Neither HbA1c nor FPG were seen as viable targets for heart failure therapy
Women with high glucose levels are at a greater risk of getting cancer
Cells in a lab will tolerate high levels of glucose exposure better than fluctuating levels of glucose
If there is an HbA1c threshold for chronic kidney disease, it is probably somewhere between 6-7%
A study exclusively focusing on non-diabetics using a non-standard OGTT. Therefore it is of limited relevance to Type 1s
You will see above that not one of these papers directly examined blood spikes over 110/120/140 mg/dl. The 140 mg/dl probably comes from the OGTT where IGT is defined as someone who has a blood glucose of 140 mg/dl after two hours. This says nothing about the number of glucose spikes a patient has had before the test or how high those spikes went. The 140 mg/dl limit in an OGTT tells us nothing about the level at which individual glucose spikes do damage to the body.
The 120 mg/dl may come from (15) where it was shown that an FPG above this led to an increased risk of retinopathy but a fasting glucose level says nothing about someone who is below this FPG level and occasionally spikes above 140 mg/dl.
As for the 110 mg/dl, I have no idea where this one comes from. Regardless, none of the 21 references provided evidence to support a “cogent case” that occasional spiking leads to long term damage.
So What Can We Conclude?
Summarizing my summary and including my original Swedish study, we get the following in regards to Type 1s and what blood levels make sense to stay healthy:
(Swedish study) An HbA1c below 6.5% increases the risk of severe hypoglcemia
(Swedish study) An HbA1c above 6.9% increased the risk of complications, including retinopathy
(Swedish study) There is an increased risk of preproliferative diabetic retinopathy above an HbA1c of 6.5%
(1), (2), (3), (4), (12) People who fail an OGTT have an increased risk of neuropathy
(13), (14), (15) FPG is a poor predictor of retinopathy but risk appears to increase above 120 mg/dl
(14), (15) HbA1c is a better predictor of retinopathy and risk increases above 6%, with significant risk above 6.4%
(16) There is a small increase in risk of retinopathy for an HbA1c above 6.4% with a significant risk above 7.0%
(16) An FPG above 130 mg/dl increases the risk of retinopathy
(20) If there is an HbA1c threshold for chronic kidney disease, it is probably somewhere between 6-7%. If there is no threshold, an HbA1c above 6% increases the risk
Clearly Fasting Plasma Glucose (FPG) and HbA1c have multiple studies examining at what point a diabetic has an increased risk of complications with retinopathy being a common complication studied.
Based on the above, it is clear that an HbA1c below 7.0% is desirable (Swedish study, (16)) and, likely, an HbA1c below 6.4% is better (Swedish study, (14), (15), (16), (20)). However, an Hba1c below 6.4% does put an insulin-dependent diabetic at an increased risk of a severe hypo (Swedish study) so, therefore, depending on how well you can manage the fluctuations may determine where your target HbA1c range will sit.
For Fasting Plasma Glucose, while not as strong a predictor as HbA1c, keeping it below 120 mg/dl would be prudent (13), (14), (15), (16).
Reviewing the multiple studies of a site which makes the claim that blood sugars above 140 mg/dl cause damage and worsen diabetes, not one directly studied meal spikes and their long term effects.
However, when these studies were combined with a recent Swedish study, we can conclude that keeping your HbA1c below 7.0%, and for those who have a low risk of hypo, below 6.4% will minimize the risk of complications, especially retinopathy.
For fasting plasma glucose (FPG), keeping this below 120 mg/dl (6.7 mmol/l) is also desirable to reduce the risk of complications but it should be acknowledged that FPG is not as reliable as a predictor of complications as HbA1c.
Finally, given there was no study examining the damage of meal spikes and assessing a ‘safe’ level, it is reasonable to ask whether religiously guarding your blood glucose levels is worth it; whether the mental fatigue of constant monitoring, and risk of burnout, is outweighed by the unproven benefits. Perhaps it is better to focus on longer term measures such as HbA1c, the standard deviation of glucose levels over time, and time in range. Perhaps it is better to see an occasional high spike as an unfortunate day on a much longer journey rather than as a defeat or failure.
If you are a Type 1 diabetic then you will know the truth is there is a myriad of things which can affect your blood sugars and they are inherently unpredictable. It reminds me a little of the stock market. It is impossible to predict what the final price of a stock will be on a given day but you can predict the trend over time. Anyone that tells you differently is, most likely, trying to sell you something.
So too with with blood glucose. It is very hard to accurately predict your body’s reaction to the various forces acting on your blood on a given day but, over time, you can get an idea of the trends and general principles. Anyone that tells you otherwise is probably selling a book or supplements.
The upshot of this is that you should never beat yourself up for having a bad day with your blood sugar. Focus on the game and not a given play. Let measures such as your HbA1c, percentage in range, and the standard deviation be your guide more than a moment in time on your glucometer.
Knowing how different forces act on your blood glucose can help you manage these long term trends so here are some of the big influences on your blood sugar. As usual, there is a tl;dr summary at the end for the time deprived.
Clearly one of the biggest forces on blood glucose are carbohydrates. We can divide carbohydrates into three categories for this discussion:
Fast Acting: Sugars/Simple Carbohydrates/High Glycemic Index (GI) Foods
Slow Acting: Starches/Complex Carbohydrates/Low GI Foods
No Acting: Inedible Carbohydrates/Fiber
Fast acting carbohydrates will spike the blood and make it very difficult to manage. If you take insulin you will need to try and match the insulin activity with the blood sugar spike. Get this wrong and your blood sugar starts roller-coasting. For the diabetics who can still produce their own insulin, fast acting sugars in sufficient quantities can overwhelm your pancreas and spike your blood.
Slower acting carbohydrates still need to be covered by insulin but the slower rise can make it easier to manage. The slower rise also means those with an impaired pancreas may be able to produce enough insulin to stop them spiking too high.
Fiber, by definition, is not broken down by the body so it is physically impossible for it to directly affect blood sugars. This being said, there are insulin dependent diabetics who factor fiber in their calculations. My guess is because, in certain countries like the USA, food labeling puts fiber in with the rest of the carbohydrates so it simply makes things easier to calculate a ratio including the fiber, even if it makes no metabolic sense.
There is no direct metabolic path to convert digested fat into glucose so eating fat will not raise your blood sugars. However, like fiber, it will slow down the absorption of carbohydrates. Also, digested fats readily enter the bloodstream, temporarily increasing insulin resistance. This leads to some people concluding it raises blood sugar when the reality is their insulin is simply not as effective.
As an example, let us consider a slice of toast with 15g of carbohydrates. While this may normally require ‘x’ units of insulin to be covered, if it is eaten with avocado on top, which is 15% fat, this may raise insulin resistance and the normal amount of insulin will be insufficient, leading to a spike. It is not the fat turning to glucose which causes this spike, it is the temporary increase in insulin resistance. Also the insulin resistance may influence the effectiveness of a Type 1’s basal insulin leading to increased glucose output by the liver.
Usually proteins will not significantly affect your glucose as the body does not convert a lot of protein to glucose but, for someone eating a low carbohydrate diet, the body ramps up a metabolic process called gluconeogenesis which is the one which converts protein to glucose. There is no hard rule for bolusing for proteins under these circumstances but some find success by finding a ‘protein ratio’ similar to their insulin to carbohydrate ratio.
This is a bottle of almost pure alcohol (95% alcohol by volume, I use it to make sugar-free liqueurs). Like fats, alcohol does not convert directly to glucose so, in principle, it will not affect blood sugar. However, also like fats, this is not the full story.
Alcohol is seen as a poison in the body so the liver will drop everything to remove it from the blood. This includes releasing glucose into the blood which, usually, the liver does constantly and is the reason Type 1 diabetics use a long acting insulin to keep their liver from releasing too much glucose (basal insulin).
So, in theory, alcohol will lead to a drop in blood glucose but no one drinks pure alcohol. Liqueurs usually contain sugar syrup (sugar dissolved in water) and the fermentation process demands the use of sugars to feed the yeast and residual sugars often end up in the final product.
So alcoholic drinks are a mixed bag. The alcohol has the potential to lower blood sugar but the things it is mixed with may raise blood sugars. This makes alcoholic drinks quite dangerous for Type 1s in large quantities because the effects are inherently unpredictable.
In the short term, aerobic exercise will lower blood glucose as the body makes use of it to run muscles. Moreover, it is believed that the glucose enters the muscles through pathways opened up by exercise which do not require insulin. Short term anaerobic exercise (more strenuous exercise) can raise blood sugar as the liver releases glucose into the blood to help feed the muscles.
Also, the effects of exercise on the blood can continue well after exercise has stopped so monitoring of blood glucose is very important.
In the long term, exercise can reduce fat stores in the body, lowering insulin resistance, as well as increasing muscle mass to store glucose.
The human body is a complex interplay of hormones so when one increases or decreases, this has an effect on others. Insulin is no exception. For diabetics going through puberty this is a minefield. For women, their monthly cycle can also cause insulin resistance to fluctuate, throwing out insulin ratios and interfering with blood glucose management.
Stress and Illness
Given both stress and illness affect hormones in the body, it is unsurprising that they affect blood sugar levels. Try to avoid unnecessary stress and carefully check blood glucose levels during illness. Strategies which work to reduce stress hormones and lower blood glucose for some include meditation and massage.
The act of going to sleep can affect your blood sugar or, more accurately, the act of the waking up. Dawn phenomenon is an increase in blood sugar (probably) due to the shifts in hormones as someone moves from sleep to being awake. There is not a huge amount that can be done about the dawn phenomenon but, if it is causing blood glucose to be consistently high in the mornings at a level to potentially cause long damage to the body, it may be worth discussing, with your health care team, changing your basal insulin routine.
Medications can affect blood sugars with a common complaint coming from the injection or ingestion of steroids for medical treatment. Steroids tend to spike the blood, especially if injected. If you are taking a new medication, it makes sense to ask your health care team how it may affect your blood sugar and insulin resistance.
Strategies For Management
As you can see above, there are a range of factors which can affect blood glucose levels. For this reason, an approach which primarily relies on looking at food, such as Dr Bernstein and Forks Over Knives, may well work for some but has no guarantee of working for everyone.
In my opinion, a better approach is to adjust insulin, rather than trying to adjust everything else. Looping (the linking of a continuous glucose monitor and an insulin pump for automatic blood glucose management) and books like Sugar Surfing or Think Like a Pancreas adopt this approach.
This being said, diet moderation still has a place. Modern insulins have their limitations so it make sense to be careful not to test those limitations with a diet filled with fast-acting carbohydrates.
A healthy human body does a remarkable job of keeping blood sugars in check. For those of us with impaired or non-existent insulin production replicating this job can be very hard. With so many factors affecting blood sugar levels, it is impossible to have perfect management every day. Therefore, it is better to manage glucose levels for the long term, rather than fixating on how your levels are on a given day.
Some of the factors affecting blood glucose are:
Fast and slow acting carbohydrates: Increase blood glucose
Fiber: No direct effect on glucose levels but can slow the absorption of digestible carbohydrates, stretching out the blood glucose response curve
Fats: No direct effect on glucose levels but they can temporarily increase insulin resistance leading to increased liver glucose production, and a spike in blood glucose in response to food as the on board insulin proves to be not as effective as it otherwise would be. In contrast, like fiber, fats can slow the digestion of glucose, widening the response curve.
Proteins: No direct effect unless the person is not eating enough carbohydrate for their body’s needs. In this case, the body uses gluconeogenesis to directly convert proteins to glucose, raising blood glucose levels
Alcohol: While pure alcohol has the potential to lower glucose, not many people drink pure alcohol. Many people drink either a fermented drink like beer which has sugar as an integral part of the process or they drink liqueurs which are a combination of alcohol, sugar syrup and flavoring. Therefore, depending on the alcoholic drink at hand, it can raise or lower blood glucose levels
Exercise: Gentle (aerobic) exercise usually lowers blood glucose while more strenuous (anaerobic) exercise can raise blood glucose levels. In the long term exercise can be beneficial in reducing insulin resistance and increasing muscle mass, used for glucose storage.
Hormones: Different hormones of the body can also affect insulin resistance and, therefore, blood glucose levels. This is especially problematic for diabetics going through puberty and for women who are menstruating
Stress, Illness, and the Dawn Phenomenon: As all of these affect the body’s hormones, it is no surprise they also affect blood glucose levels
Medications: These can affect the body and blood glucose levels. If you are unsure if a specific medication will affect you, talk to your health care team
There are a range of factors which can influence blood glucose levels and, often, in unpredictable ways. While some advocate for strictly controlling major factors, such as food, others advocate adjusting insulin to accommodate all of these influencing factors. Every person is different so it will be a case of taking the elements from both approaches which work for you.
I often see posts asking how to keep continuous and flash glucose sensors on for more than a week. As I pay full retail price for my CGM (it is not easy to get a CGM subsidy in Australia), I try to get every last bit of performance out of them before throwing them away.
My record so far for a Dexcom G5 was seven weeks and I gave up at that point because the sensor wound had healed enough that it was no longer registering the spikes; the line just slowly rose and fell in a dampened response to the glucose levels.
These days I change the sensor in the first weekend of the month, getting around four weeks per sensor.
Here is how I do it.
I bought a bottle of this on eBay but you can also buy wipes with the same name that do the job. The very first thing I do is apply it, using the sponge applicator, to the area where the sensor is going to sit.
To wipe off any excess, simply use Methylated Spirits (Denatured Alcohol).
Prepare the Sensor, Rocktape and Opsite
While the Skin Tac dries and gets sticky, I prepare the other components. Firstly, I take sensor out of its packet ready for application, then I prepare the RockTape.
I use the Rocktape to keep the sensor’s sticky material in place. The white gauze that comes with the Dexcom is good for about one week so the Skin Tac and Rocktape help extend this.
I cut a little rectangle out of the Rocktape for the transmitter to fit through and keep the rectangle for later.
I also cut off the corners of the main piece of Rocktape and this stops it from peeling away from the skin as readily.
With the Skin Tac now nice and sticky, I apply the sensor, attach the transmitter, and start the soak-in period on the receiving app.
If the transmitter looks a little unusual, I use a modified G5 transmitter with a rechargeable battery attached to replace the embedded batteries. It is a little experimental but it has saved me a fortune in new transmitters.
Next I put on the RockTape on top of the gauze.
This is a transparent, breathable covering which sits on the skin. There are cheaper alternatives in the market though so do shop around. The idea is to cover the sensor and Rocktape completely to help prevent the sensor getting knocked out by leaning or bumping into things.
The rectangle of Rocktape we reserved sits in the middle of the Opsite to stop the Opsite getting stuck to the transmitter. The adhesive attaches very strongly to the resin on the transmitter making it difficult to remove when we want to change the dressing.
We now apply the Opsite to the sensor, keeping the backing on the Rocktape rectangle and we have a secure sensor with its own Rocktape camouflage. With the backing on the Rocktape still in place, the dressing comes away easily when we want to replace it.
Once a week I check for peeling and, if it is coming away, I reapply the Rocktape and Opsite, removing the old dressing by peeling sidways to or away from the transmitter to minimize the risk of dislodging.
Diabetics get a lot of blood tests done and sometimes we should ask for others. Here they are broken down so you know what you are getting done and what you should ask for.
Summary at the end for those who find the article tl;dr.
‘Sugariness’ And Insulin Measures
Practically every diabetic knows their HbA1c (Hemoglobin A1c). This is a measure of the number of hemoglobin proteins in the blood with glucose attached. This gives an indication of how sugary a person’s blood has been for the last three months.
Why three months? Hemoglobin is part of your blood’s red blood cells. In a healthy human, red blood cells survive for around three months in the blood before dying.
This has a few implications. Firstly, if you have a disease which affects the life of your red blood cells, such as anemia, this will throw off your HbA1c measure, shortening the time over which the HbA1c is a representative average. Also, the measure is not a linear average; the result is biased to the more recent ‘sugariness’ because not every red blood cell lives for exactly three months. Not all of those ‘born’ three months ago will be around but most of the one born a month ago will.
It should be noted that there is around a 10% relative error in this test so if you have, say, an HbA1c of 7% and it moves on your next test by less than 0.7%, this could be nothing more than measurement error.
Finally, while a lot of emphasis is put on the HbA1c, it is only a number to indicate your average blood glucose level (BGL); it says nothing of the fluctuations. Some doctors will get nervous at lower HbA1c results because they have no visibility of the fluctuations. If you have excellent blood glucose control do not be afraid of lower HbA1c results.
When beta cells produce insulin they actually produce a thing called proinsulin which is two halves of the insulin molecule and a ‘connecting peptide’ (c-peptide) which joins them. Through the magic of biology this eventually transforms into insulin and a residual c-peptide molecule.
By measuring the amount of c-peptide in the blood we can get an indication of how much insulin the pancreas is producing (injected insulin is not in the form of proinsulin so there is no c-peptide residue).
A typical Type 2 will have a high c-peptide reading because their pancreas is trying to overcome their insulin resistance. A typical Type 1 will have a low c-peptide because the immune system has destroyed their beta cells and with it the ability to produce proinsulin. I say typical because for a LADA like me with insulin resistance, my c-peptide is normal/high even though I am Type 1.
This measures the level of insulin in the blood for a fasting individual. Unlike c-peptide this cannot distinguish between insulin made by the body and injected insulin.
The blood sugar level when fasting. For an individual producing enough insulin to keep their liver in check, this should be normal.
The ‘Homeostatic Model Assessment of Insulin Resistance’ (HOMA-IR) and the ‘Homeostasis Model Assessment of β-Cell Function’ (HOMA-β) are mathematical formulae using the blood’s (fasting) insulin and glucose levels to give an indication of the individual’s insulin resistance and beta cell function.
In other words, for someone not using insulin, their fasting insulin and glucose results can be used to determine how much insulin resistance they have and how much beta cell function they still have.
Linked to insulin sensitivity, this may be useful to see if you are low (many of us office workers are).
Vitamin B12/Active B12
If you are taking Metformin/Diabex/Glucophage (different names for the same thing), you should check your B12 levels as Metformin can affect the body’s ability of absorb vitamin B12 from food. The difference between ‘B12’ and ‘Active B12’ is that, while different forms of B12 are circulating in the blood only the ‘active’ form can be used by cells in the body.
Autoantibodies Against Islet Cells (ICA), GAD, IA2, ZnT8, and Insulin
This is the definitive test for determining if someone is a Type 1 diabetic as it proves the immune system is attacking the body’s insulin production machinery.
If this test is positive, you are Type 1, by definition. However, there are people with all the hallmarks of Type 1 diabetes who do not get a positive result on autoantibody tests. Possible reasons for this include:
The person has had Type 1 diabetes for so long that there are no longer any beta cells left to provoke an immune response
Their Type 1 diabetes is caused by an as yet unknown autoantibody
Whether these ‘idiopathic’ Type 1s should be classified as Type 1, given the lack of autoimmunity evidence, is a matter of debate but, from a treatment perspective, it makes sense to align them to ‘classic’ Type 1s.
Body Mass Index and Waist Measurement
While not blood tests, the Body Mass Index (BMI) and a person’s waist measurement give a general indication of obesity. Obesity is linked to insulin resistance so, in an ideal world, diabetics of any Type would stay within a healthy weight range.
Oral Glucose Tolerance Test (OGTT)
Although I never had one of these myself (presenting with mild DKA at diagnosis was enough to establish I had diabetes), it is something often used to determine if a person has diabetes.
The test is relatively simple: the patient, who has fasted, is given a fixed measure of glucose syrup and blood is taken at the one, two, and maybe the three hour mark to measure the patient’s glucose response. If the patient cannot bring the blood glucose levels down fast enough and they go too high, the patient is diabetic.
Heart and Kidney Disease
Diabetics, due to damage from high BGLs, are prone to kidney disease and have a higher rate of heart disease, compared to the general population
Not a blood test, but the test the doctor does with the arm band and an air pump. A high blood pressure can be a risk factor for kidney and heart disease.
This is a urine test and, for healthy functioning kidneys, there should be little to no albumin in the urine. It is measured as a ratio because creatinine is generated at a reasonably constant rate in the body so, if creatinine fluctuates in urine, this is likely due to relative levels of hydration in the body. So, by measuring the ratio, we get a stable indicator of albumin in the urine, independent of hydration levels.
The prevailing thinking in conventional medicine is that the different types of cholesterol play a role in a person’s risk of heart disease. A metastudy (review/compilation of multiple actual studies) in 2016 found the evidence for this was not strong. I am not going to settle this debate in this blog article so discuss this with your health care team and do your own research if it is important to you.
For myself, I eat a lowish carbohydrate diet which means I have moved to eating more proteins and fats. My thinking is that, even if there is an increased risk of long term heart disease, this is outweighed by my short term desire to preserve my beta cells and remain insulin free for as long as I can, while keeping my BGLs in a healthy range.
Assuming cholesterol measures are relevant to a person’s heart health, here are the measures on interest:
Total cholesterol: ideally low
LDL: ideally low
HDL: ideally high
Triglycerides: ideally low
Cholesterol/HDL ratio: ideally low i.e. you want relatively low cholesterol or high HDL with the absolute amount being less important (useful for diets higher in fat)
LDL/HDL ratio: ideally low based on the above and again, talks at relative levels, rather than absolute levels
High levels of sodium can indicate kidney dysfunction.
This is a measure of how acidic your blood is (low levels suggest more acidic blood). Again, this can be an indicator of kidney health but, be warned, if you are engaging in a low carbohydrate diet and producing ketones, these are acidic and may throw off the test. I have seen this in my test results on occasion.
The idea that one blood test can be the result of one of many causes speaks to the need to get multiple tests done to confirm something like kidney disease. While my blood may sometimes be slightly acidic, my albumin/creatinine ratio is always within range, confirming it is my keto-like diet that is the cause and not organ damage.
Like the bicarbonate test, urea can be indicative of a number of things. Most importantly it can indicate kidney damage or heart failure. Urea in the blood is a result of protein breakdown so, again, if you are engaging in a low carbohydrate diet and eating more protein, a higher urea level may be the cause. It is no coincidence that on those blood tests where my bicarbonate was low, my urea was also high and was indicative of nothing more than me being a little more keto than usual.
The other organ that gets a battering from diabetes is the liver. We have a raft of tests available to us to ensure our liver is doing its job and keeping us healthy.
These are enzymes found in the liver and usually only in small amounts in the blood. An elevated level of them in the blood can indicate kidney damage. It can also indicate a bumpy ride on a motorcycle leading up to the test so always regard blood test results with caution until confirmation tests have been conducted.
This is related to the Albumin/Creatinine test as Albumin is a protein. Abnormal total protein levels in the blood can indicate kidney damage but can also indicate liver disease. A high protein diet has no effect on protein in the blood.
Total Protein = Albumin + Globulin so, again this is a protein test where abnormal results can indicate kidney or liver disease, among other things.
Another protein test which can test for severe liver disorders in non-pregnant people.
White Cell Count/ Lymphocytes/ Eosinophils/ Monocytes
Lymphocytes, Eosinophils, and Monocytes are all types of white blood cells. All of these can be tested to get an idea of infections, allergies, and other disorders which may be affecting the body.
While I occasionally have elevated levels of these, it generally settles down by the time of my next quarterly/biannual blood test. If it did not, it could be indicative of an undiagnosed prevailing condition e.g. cancer or infection and would warrant further investigation.
Here is the list of common blood (and other) tests done for diabetics and their meaning.
‘Sugariness’ and Insulin Measures
HbA1c: An average of your last three months of blood sugars
C-Peptide: A measure of how much insulin your body is still producing
Fasting Insulin: How much insulin is in your blood to keep your liver in check
Fasting Glucose: How sugary you are without food
HOMA-IR/HOMA-β: Mathematical formulae using the fasting insulin and glucose used to determine insulin resistance levels and beta cell function
Vitamin D: Low levels can contribute to insulin resistance
Vitamin B12/Active B12: B12 absorption can be hindered by diabetic medications such as metformin
Autoantibodies Against Islet Cells (ICA), GAD, IA2, ZnT8, and Insulin: Tests whether diabetes is caused by an autoimmune response and is therefore Type 1 diabetes
Body Mass Index and Waist Measurement: Body measurement tests to give an indication of obesity and potential insulin resistance
Oral Glucose Tolerance Test (OGTT): A test involving the drinking of glucose syrup to assess whether a person is a diabetic
Heart and Kidney Disease
Blood Pressure: The test with the armband and pump. This can indicate an increased risk of heart and kidney disease
Albumin/Creatinine Ratio: A urine test for kidney health
Cholesterol (LDL/HDL/Triglycerides): Measures of fatty acids and fatty acid transporters in the blood. Abnormal levels are traditionally considered a risk factor for heart disease
Sodium: High levels can indicate kidney disease
Bicarbonate: Low levels can indicate kidney disease but can also result from a ketogenic diet
Urea: Used as an indicator for heart or kidney disease but can also be indicative of a high protein diet
Gamma Glutamyltransferase (GGT)/ Lactate Dehydrogenase (LD, LDH)/ Aspartate Aminotransferase (AST)/ Alanine Transaminase (ALT): Liver enzymes not usually found in the blood which can indicate liver damage
Total Protein: Abnormal levels can indicate liver or kidney damage. Not affected by dietary protein intake
Globulin: Abnormal levels can indicate liver or kidney disease
Alpha-Fetoprotein: Can indicate severe liver damage/disease
White Cell Count/ Lymphocytes/ Eosinophils/ Monocytes: White cell tests which can indicate infection, allergy or disease.
There is some debate over the appropriate amount of carbohydrate in the diet of diabetics (and muggles for that matter). If you want the summary, here is link to tl;dr, otherwise keep reading.
On one side of the argument we have Dr Bernstein and the Type One Grit advocates. They promote very low levels of daily carbohydrate (around 30g) and see excellent control because of this. The risks of hyperglycemia are small because of the lack of carbohydrates and Dr. Bernstein argues the risk of hypoglycemia is small because of the correspondingly smaller amounts of insulin used and the strict control of the carbohydrate count at each meal (typically 6g/12g/12g for breakfast/lunch/dinner).
On the other side we have high carbohydrate advocates, such as Forks Over Knives and the unfortunately named ‘FOK Diet’. FOK promotes a plant-based diet high in carbohydrates and low in animal fats. The thinking here is to reduce insulin resistance in the body and, through this, provide better control. Clearly, the focus is on Type 2 diabetics but the FOK folk also promote this diet for Type 1s. The argument is that while control can be achieved through a low carbohydrate approach, the health cost of high levels of animal fats is too high; you are replacing one problem with another. Hypoglycemia is avoided by eating lots of carbohydrates. Hyperglycemia is avoided by making sure you eat low GI (glycemic index) foods, preferably plant-based. It should be noted that FOK do not say high levels of dietary carbohydrates are necessarily good or essential, they simply say high levels of animal fat are bad.
I am not intending to resolve this debate with this blog article but I do consider where the body gets its energy from and answer just how essential carbohydrates are. From there, it is up to you. In full disclosure, I do not eat a lot of carbohydrate. As a Type 1 LADA in honeymoon, I believe the best thing I can do for my pancreas is to give it as little work to do as possible and a low carbohydrate regimen achieves that.
What Foods Give Us Energy?
There are four main components of food which give us energy. These are:
Fat (yielding 37 kJ/g or 9 kcal/g)
Ethanol (aka alcohol) (yielding 29 kJ/g or 7kcal/g)
Protein (yielding 17 kJ/g or 4 kcal/g)
Carbohydrate (yielding 17kJ/g or 4 kcal/g)
There are a few other sources of energy, such as organic acids and alcoholized sugars, but we will keep things simple with the main ones.
What Food Gives Us Glucose?
Of these foods, the only ones which get converted to glucose are carbohydrates (whenever you eat them) and proteins (significantly when you are fasting via gluconeogenesis). For a recap of what gluconeogenesis is, refer to “What is Ketosis and Diabetic Ketoacidosis?” where I wrote in detail about how the body finds alternative sources of energy when fasting. In short, when there is insufficient dietary carbohydrate, the liver engages the following processes:
Glycogenolysis: The release of glucose into the blood from the glycogen energy stores of the liver and muscles
Gluconeogenesis: The conversion of amino acids from proteins into glucose
Ketosis: The conversion of fatty acids from fat into ketones (an alternative fuel for some parts of the body)
So even if we are not eating carbohydrate, the liver can release glucose into the blood to fuel the body and, when this runs out, it can convert the body’s protein supplies.
What Food Elements Are ‘Essential’?
So we know, from an energy perspective we can possibly make do but perhaps carbohydrates are needed for something else. In fact, while proteins and fats are necessary to build the structures of the body, this is not the case for carbohydrates. Here are some of the uses of fats, proteins, and carbohydrates:
Fats: Break down into fatty acids in the body and used for:
Regulation of vitamin intake
Insulation and protection of organs
Proteins: Break down into amino acids in the body and used for:
Build structures in the body like muscles
Facilitate communication between cells
Act as transporters for other molecules
Carbohydrates: Break down into glucose in the body and used for:
That is it. Carbohydrates are used for energy or stored for use as energy later on. There is nothing essential about carbohydrates.
So, assuming you could eliminate carbohydrates, fats, or proteins completely from your diet, could you survive?
For carbohydrates, as we can make glucose from protein via gluconeogenesis, we know they are not essential.
For fats, there are two essential fatty acids: omega-6 and omega-3. Essential meaning the body cannot synthesize enough of them on its own to maintain function. Without omega-6 and omega-3 the body simply cannot function.
For proteins, there are nine essential amino acids. Of these, you may have heard of Phenylalanine, which is one on the substances the sweetener aspartame breaks down into. Another is Tryptophan, made popular by the myth that it causes the drowsiness of excess turkey eating.
Do Our Bodies Need Glucose?
There is a common myth that the brain requires carbohydrate to function. This is not true; the brain runs primarily on glucose, from any source but, more importantly it can also utilize ketones to run as an alternative fuel source in times when glucose is in short supply. In fact there are four main fuel sources the organs of the body can use to fuel themselves.
Glucose (fuels the kidneys, brain, liver, fatty tissues, and muscles)
Clearly glucose is the most versatile fuel source, covering all the bases but the only parts of the body solely dependent on glucose are the kidneys and fatty tissues. Everything else can supplement with alternatives.
I tried to find the maximum rates of glucose production possible through glycogenolysis and gluconeogenesis but came up short. Of particular interest is the rate of glucose production for gluconeogenesis because the liver only keeps enough glycogen stored for a couple of days. After that the only way for the body to generate glucose is through gluconeogenesis.
The story all students are told before going on school camp is the rule of three: you can survive three days without water and three weeks without food. If this is true, as we know glycogen stores are only good for a couple of days, this means the body can get by on gluconeogenesis alone until, presumably, the available protein stores run out. Of course, with enough protein in the diet, we can keep the glucose production going indefinitely.
Unlike fats and proteins, carbohydrates are not essential because the body has ways of generating glucose outside of the digestion of carbohydrates. This is not true for essential amino acids and essential fatty acids which are needed to maintain the health of the body and which can only be obtained by the dietary intake of proteins and fats, respectively.
Moreover, while the kidneys and fatty tissues rely exclusively on glucose for energy, the rest of the body can access alternative fuel sources, such as amino acids, fatty acids, and ketones.
Finally, we know the body can generate enough glucose for its needs outside of carbohydrate ingestion because a person can survive with no food for up to three weeks. Given the liver and muscle’s glycogen stores are only good for a couple of days this means the process of gluconeogenesis (the body’s conversion of amino acids to glucose) is all that is required to maintain blood glucose levels, and as long as a regular supply of protein is provided, this means the process can continue indefinitely.
There is a lot of confusion around ketosis and diabetic ketoacidosis. Some people think they are the same thing; others think ketosis leads to ketoacidosis. Neither of these notions are true.
To better understand the differences, let us understand precisely what the terms mean. As a disclaimer, the metabolic processes of the body are extremely complicated. There is much more to it all than just the liver and insulin but using these gives us a practical working model. As usual, if time is short you can go to tl;dr.
I have used a lot of internet searches and Wikipedia pages on the human metabolism to put this blog together. A couple of key sources of information were:
To understand ketosis and ketoacidosis, we need to understand the role of insulin in the body. It is generally understood by many diabetics that insulin is needed to move glucose from the blood into cells. What is less well know is that insulin is also a control switch for the liver.
While the pancreas releases insulin based on the levels of glucose in the blood, the liver releases glucose into the blood based on the amount of insulin. Other hormones also influence this process but ignoring these external factors for simplicity, the liver and pancreas work together to keep the glucose in the blood stable, both producing small amounts of glucose and insulin respectively to keep the other in check. The doctors call such an equilibrium ‘homeostasis’.
If we consider the role of food, when carbohydrates are consumed, blood glucose goes up and insulin production is increased to move the glucose out of the blood. Similarly, the liver’s production of glucose goes down. When blood sugars return to a base level, the liver and pancreas also return to their homeostatic rate of production.
When someone chooses not to eat, the opposite occurs. With glucose in the blood not being replenished by food, glucose levels drop and the pancreas produces less insulin. This, in turn, encourages the liver to produce glucose to give the cells of the body the energy it needs.
In a world before widespread food transportation and refrigeration, winter meant a time of limited carbohydrates. Fortunately, the human body has some backup measures when times get tough.
The glucose stores of the liver are good for a day or two. As these run low, and insulin levels continue to drop, a new process ramps up. The protein sources of the body are broken down into amino acids and converted by the liver into glucose in a process called gluconeogenesis (other substances in the body are also used, such as lactate and glycerol but let us keep things simple).
This can keep the body going for a few days to a few weeks, depending on things like diet (protein sources can be found in the winter, after all). After this, and the insulin levels drop a little further, the fat stores of the body are broken down into fatty acids. Different parts of the body can use fatty acids and amino acids as alternative fuel sources to glucose so, even with a low carbohydrate diet, the body can maintain the necessary energy levels.
If carbohydrate fasting continues, insulin levels keep dropping and there are sufficient fatty acid levels in the blood, another process kicks in to convert fatty acids into ketones, yet another fuel source which can be used by the brain and muscles (a commonly held misconception is that the brain can only use glucose as a fuel source; it is simply not true). This final process of converting fatty acids into ketones is called ketosis.
In a body with a low but sufficient level of insulin, ketosis is regulated and poses no threat. In the muggle (non-diabetic person) body, it is very difficult to go below the threshold where ketosis becomes a problem. To do so requires literal starvation or large amounts of alcohol over an extended period of time. Starvation can be understood as an extension of the explanation above. Alcohol causes a problem by blocking the liver’s ability to generate glucose from the energy stores and amino acids, forcing the overproduction of ketones.
For the diabetic, where insulin production is impaired, it is much easier to go below the threshold. This is why insulin-dependent diabetics, whose pancreas cannot maintain a basal level of insulin, do so through a pump or via the injection of long-acting insulin. For non-insulin-dependent diabetics, one path to ketoacidosis is feeding the body fast-acting carbohydrates which flood the blood with glucose and overwhelm the pancreas. The insulin in the blood becomes depleted and the liver goes unchecked.
With no insulin to regulate it, the liver goes into energy production overdrive, running all of the energy production processes as quickly as possible. The body is flooded with glucose and ketones and, while the excess can be removed from the body through urination, even this has its limits. The ketones begin to accumulate, changing the pH (acidity) of the blood. This has knock-on effects throughout the body leading to sickness and often vomiting. If not dealt with, ketoacidosis can lead to coma and death.
The Key Differences
While ketosis is a state of low dietary carbohydrate, ketoacidosis is a state of low insulin in the blood, which is almost impossible to generate through a lack of eating, except in extreme cases of starvation. A diabetic who maintains a basal level of insulin in their blood will not go into diabetic ketoacidosis (DKA) from a low carbohydrate diet. It is simply not possible.
The manifestation of the two in the body is also different. While someone in ketosis will have a low/normal blood glucose and generally feel fine, someone in ketoacidosis will have elevated blood sugar levels, be urinating frequently e.g. a full bladder every 30 minutes, may feel thirsty and be dehydrated, and feel ill. Unfortunately, there is no over-the-counter test for serum insulin levels (the amount of insulin in the blood) or blood acidity levels, which would provide a definitive answer to a concerned diabetic.
A rare form of DKA is Euglycemic DKA (EDKA). In this case, the body is flooded with ketones but blood glucose levels are normal. This usually occurs when there is extremely low insulin levels in the blood and the liver also has low glucose stores. This is something to watch out for if, for example, you are fasting. It is also the reason why it is vital to ensure you always have a sufficient basal level of insulin.
As EDKA does not present with high blood sugars, it is often missed by doctors. If you suspect you could have EDKA tell your health care team of your suspicion and insist they measure your blood pH which is the definitive test for DKA and EDKA (reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5592704/).
In terms of treatment, DKA and EDKA are treated the same way: hydration and insulin to bring ketosis back under control.
Ketosis and diabetic ketoacidosis (DKA) are not the same thing. While ketosis is triggered through an extended lack of dietary carbohydrate, DKA is triggered by the exhaustion of insulin in the blood; the consequence of which is the liver over-producing fuel for the body, including ketones which, when they accumulate, can turn the blood acidic and lead to death.
Treatment for DKA is re-hydration and the re-introduction of insulin back into the blood.
In my last blog I wrote about the different Types of diabetes. In this blog I will dig a bit deeper to create a scorecard so you can see how ‘typical’ you are and, if you are Type 2, give you a way to see if there is a possibility of misdiagnosis.
I am going to ‘borrow’ an idea from “Think Like a Pancreas” and have a tl;drsection at the end. If you want a quick summary to see if it the blog is worth the time to read, you know where to go.
Why is it important? Because treatment, while not defined by Type, is informed by it. For MODY/NDM, the insulin production machinery is broken on a genetic level and for different gene mutations, the most effective treatment is well understood. Trying generic Type 2 treatments will, at best, be as effective but more likely be less effective. For Type 3c, the physical damage to the pancreas means alpha and beta cells are damaged and so it is not just insulin production that is affected. Treatment should account for this. For LADAs, drugs which work the pancreas harder, while appropriate for Type 2s will destroy the pancreas’ beta cells quicker and make the patient insulin-dependent so much quicker.
From a patient’s health perspective, a poorly targeted treatment means blood sugar control will not be managed as well as it could, leading to a higher risk of long term complications. Misdiagnosis is unfortunate for the doctors but can be devastating for the patient.
The Practical Diabetic’s Type Scorecard
Based on key parameters, it is possible to put together a simple scorecard to steer a clinician towards an appropriate diagnosis. I will focus on Type 1, Type 2, LADA, Type 3c, and MODY/NDM simply because Gestational diabetes is routinely tested for and Type 0 presents very differently to the other Types and is more easily diagnosed. I will also assume, like many of us, the patient has presented with a mild DKA for the first time e.g. thirsty, peeing a lot, lethargy, losing weight etc. so we are at the start of the diabetic journey.
For the purposes of the scorecard I am defining LADA as a Type 1 who still has sufficient insulin production to not be insulin dependent. A Type 1 who requires insulin to remain healthy is, for all practical purposes, a ‘normal’ Type 1, possibly in honeymoon.
The idea is to work out which columns result in a positive score and then get the appropriate definitive tests done.
History of pancreatic damage
First degree relative
(*) Some links characterize LADA as having a low c-peptide. From my perspective if you are a Type 1 with a low c-peptide to the point you need insulin, you have transitioned, from a treatment perspective, to a (possibly honeymooning) Type 1.
After my first article I got a lot of requests for the sources of my information (a good fraction of that piece came from “Think Like a Pancreas” and “Dr Bernstein” with NCBI and Google searches to fill in the gaps). Given this article could well end up in the face of someone actually qualified in medicine and you may need to fight for that definitive test, I’ll quote my links here:
These are all from NCBI. NCBI is a collection of peer-reviewed medical papers from around the world and cannot be easily dismissed by a health professional.
Hopefully the terms in the first column are relatively self-explanatory. C-peptide is a measure of your body’s insulin production and obtained from a blood test. “First Degree Relative” means a first degree relative who has some form of diabetes. Insulin Resistance can be determined by examining a patient’s HOMA-IR score (derived from their fasting blood glucose and endogenous insulin). Endogenous just means made by their pancreas as opposed to injected.
So let us run it for a sample patient. In this case I will choose me, two years ago when I first presented with DKA. You can read a bit about this in my About Me blog post.
History of pancreatic damage
First degree relative
The scores suggest either Type 2 or LADA. At the time, the hospital believed I was Type 2 and sent me on my way. It was my family doctor who had the smarts to get the right tests done.
Tests For a Definitive Diagnosis
For Type 1 and LADA, the definitive test is a blood test for the auto-antibodies associated with Type 1 diabetes. In 80-90% of cases these auto-antibodies will be present in the blood. If the progression of the disease is advanced, the immune response may no longer be present making a definitive diagnosis harder.
Assuming the test is positive, the next consideration would be the c-peptide level. If it is still normal/high and blood sugars normal, it may be a case that the patient can be treated similar to a Type 2 with regular monitoring to track the deterioration of the pancreas and the transition to insulin-dependence (a slow progression suggests LADA whereas fast progression suggests a ‘classic’ Type 1). If the c-peptide is low, the best option may be to simply consider the patient as a Type 1 and treat them accordingly.
For Type 3c diabetics, a scan of the pancreas will reveal the damage and provide a definitive diagnosis. With a better understanding of the underlying pathology, treatment can be appropriately designed.
For MODY/NDM, a genetic test will provide a definitive diagnosis. As mentioned before, the optimal treatment for the common variants of MODY are known so it is easier to treat and manage the disease once it is diagnosed. This paper reviews in finer detail some of the symptoms of the different forms of MODY as well as the first-line treatments.
There is a lot of misdiagnosis when it comes to diabetes with many Type 2s (and a few Type 1s) being put in the wrong bucket. The right diagnosis means the treatment can be tailored appropriately to ensure the best long-term outcome for the patient.
Using a simple scorecard we can inform the diagnosis and get the right tests done for a definitive answer.
Diabetics usually know of two Types of diabetes (imaginatively called Type 1 and Type 2). Not surprisingly, most diabetics in the world also fall under one of these two Types but there are others. In fact there are at least 6.5 Types (the half will be explained a bit further down) and not a complete consensus among the world’s diabetes associations. I will focus on the ones where debate in minimal.
For those who do not like to read, here is the list of Types. The rest of this blog will go into detail about each of them, how they are derived, diagnosed and treated.
Type 1: About 10% of all diabetics
LADA, aka Type 1.5: A subcategory of Type 1
Type 2: Almost all of the other 90% of diabetics
Type 3c: 0.5-1% of all diabetics (many others wrongly diagnosed as Type 1 or 2)
MODY/NDM: 0.24% of those with diabetes
Type 0: 1 in 2 million people
Gestational: Approximately 13% of pregnant women (1 in 7)
What Makes a Type?
Diabetes Types are NOT classified by how the disease presents itself. This is important because it means the Type does not solely dictate how to treat the disease. Diabetes Types are ‘etiological’. This is a fancy word which means they are classified by the cause.
Type 1 diabetes is an auto-immune disease. This simply means the body’s immune system attacks the beta cells of the pancreas. How the immune system gets confused and attacks the body is not yet known. So, while the cause of Type 1 diabetes is known (the immune system) the cause of the cause (why the immune system is broken) is unknown.
Many websites out there characterize Type 1 as “not being able to produce insulin” but this is not the full story. As mentioned, diabetic Types are etiological so while most Type 1s produce little to no insulin (because the immune system is very good at its job), there are Type 1s, like me, who still produce enough insulin to live a relatively normal life.
In terms of diagnosis, when the patient first shows symptoms, a blood test for the auto-antibodies (the parts of the immune system which attach the pancreas) will confirm it is Type 1. If the person has been a diabetic for many years, as the beta cells of the pancreas are mostly destroyed, the immune response will be minimal, making a definitive diagnosis harder.
For treatment, while the patient is in ‘honeymoon’ (where their body can still produce some insulin) they may only need pills and a low carbohydrate/low GI diet to keep their blood sugars under control. However, eventually, the honeymoon will pass and they will need to inject insulin.
Type 2 is the most common Type of diabetes and the cause is unknown. This is the bucket all diabetics fall into when the cause cannot be discerned and as this is literally 9 out of 10 diabetics speaks strongly to the fact that we are only beginning to understand this disease and what causes it. Sadly, largely due to unawareness of the various Types in the medical community, there is much misdiagnosis when it comes to a person’s ‘Type’ with far too many being incorrectly dumped into the Type 2 category.
A ‘typical’ Type 2 cannot make enough insulin to meet their body’s needs. The pancreas is limited in its production and the cells of the body do not use the insulin efficiently (insulin resistance). Like Type 1s, the beta cells will show damage in Type 2 patients but the cause of the damage is unknown. One theory is the immune system temporarily attacks the pancreas but then stops, causing partial damage, but this has not yet been proven.
A common myth is that Type 2 diabetes is caused by ‘lifestyle factors’ i.e. eating unhealthy food, being overweight and not exercising. This is completely untrue. Type 2 is associated to things like obesity but it is not the cause. Where the association likely comes from is that a common cause of insulin resistance is fat deposits around the organs (visceral fat). So, if you are overweight, you may be contributing to your insulin resistance. However the underlying production limitation is still there. While reducing your carbohydrate intake and losing weight may get you off the medications, you are not cured, but simply in remission. Your impaired insulin production is still there; you are simply not testing the limit any more.
An analogy would be to suggest that asthma is caused by running because when some people run, they get an asthma attack. While asthma attacks are associated with exertion, the cause is completely separated; the exertion simply tests the limits imposed by the disease.
Unlike Type 1, there is a strong genetic component to Type 2 (although there is no genetic test for the disease). Type 2 runs in families and is significantly more prevalent in some areas of the world more than others.
Given the cause if unknown, diagnosis comes from exhausting the possibility of the other Types (or it should!) and giving the patient a glucose tolerance test to establish they have an abnormal response when processing sugars.
While insulin is sometimes needed, Type 2 is usually managed through pills, diet, and exercise. Progression of the disease is extremely slow and many Type 2s never require insulin to stay healthy.
LADA (Type 1.5)
LADA is also an auto-immune disease and, therefore, is a sub-category of Type 1. LADA stands for ‘Latent Autoimmune Diabetes of Adulthood’ and what makes LADA different to ‘typical’ Type 1 is the rate at which the disease progresses. This is what the word ‘latent’ means and why LADA is different to typical Type 1. While a typical Type 1 will be on insulin somewhere between immediately to a few weeks after diagnosis, LADA patients can survive without insulin for years.
Generally, LADAs are diagnosed later in life (for me it was at the age of 43) whereas ‘normal’ Type 1s are diagnosed much younger. Because LADA affects older people and the patient may not require insulin straight away, it is often misdiagnosed as Type 2. A simple blood test is all it takes to separate the LADAs from the Type 2s.
This was the test that the hospital failed to do in my case. As a male in his early 40s with a bit of extra padding, the ‘experts’ simply assumed I was Type 2. As LADA eventually leads to ‘classic’ Type 1 where the body no longer produces insulin, it differs to Type 2 which often never progresses to such a state. Therefore, the treatment of LADA is different to Type 2 because the focus is on preserving beta cells and prolonging the honeymoon, whereas in Type 2s it is assumed the remaining beta cell population will stay mostly constant for the rest of the patient’s life.
This misdiagnosis leads to many cases where someone who has been told they are Type 2, gets sicker and sicker as the medications become less effective. Often the misdiagnosis is eventually found but only after the patient has been ravaged with diabetic complications which may last the rest of the life e.g. eye damage, organ damage, nerve damage etc. All it takes is a simple blood test when the disease first presents itself to get the diagnosis right and to save the patient’s quality of life and a fortune in medical consultations and treatments.
The first of the lesser-known Types, Type 3c is NOT auto-immune but is where the pancreas is damaged by something else e.g. cancer, pancreatitis, cystic fibrosis, surgery etc. The damage may have also happened years before symptoms begin showing.
Given the cause is different we begin to see that this is important in how we approach the disease. Whereas the immune system selectively targets the beta cells (the cells of the pancreas which produce insulin) but usually ignores the alpha cells (which produce other hormones used for blood sugar regulation), damage caused by cancer or a car accident is less selective. Therefore, treatment which assumes the patient is Type 1 or 2 may miss the mark and, like the misdiagnosis of LADAs, may lead to diabetic damage before the error is revealed.
Diagnosis is through examining the patient’s history to see if there is a likelihood of damage and scanning of the pancreas to see the physical damage.
MODY (Maturity Onset Diabetes of the Young) and NDM (Neonatal Diabetes Mellitus) are monogenic forms of diabetes. Monogenic simply means caused by one broken gene. The name ‘Maturity Onset Diabetes of the Young’ is similar to terms like ‘Juvenile Diabetes’ and ‘Adult Onset Diabetes’ in that they come from a time when our technology was unable to definitively define the cause. Today, these terms are limited in their meaning but continue to hang around. I, for example, was diagnosed with ‘Juvenile Diabetes’ in my early 40s.
Most cases of MODY/NDM involve one of three specific genes but 11 gene mutations have been discovered so far. As MODY/NDM are genetic they strongly carry down family lines. While as a Type 1, your children have something like an additional 10% risk of having the disease, with MODY/NDM they have a 50% risk, 1 in 2.
The mutated gene means that a patient with MODY/NDM cannot produce insulin effectively and medication which seeks to stimulate the beta cells in some fashion may be useless in MODY/NDM patients. There is also a form of MODY (Glucokinase MODY) which affects blood glucose regulation but the principle that treatment due to misdiagnosis may be ineffective or counterproductive remains the same.
As MODY/NDM are strongly genetic, the patient’s broken beta cell machinery goes into operation at birth (arguably before birth but the mother can help compensate). For NDM, symptoms appear in the first 6-12 months of life (it is very rare for Type 1 to make an appearance this early), while for MODY symptoms usually appear in adolescence.
Definitive diagnosis comes from genetic testing, which is readily available. While misdiagnosis is, again, common, the correct diagnosis is vital as different forms of MODY/NDM respond to different drugs or, in the case of Glucokinase MODY, no treatment may be needed at all (Glucokinase MODY has the patient run a slightly high blood glucose but often not dangerously so). The other reason correct diagnosis is important is because of the risk to a patient’s children of having the same disease. Knowing this means it can be tested for and treated before complications arise.
Type 0 Diabetes
This disease is also called Glycogen Storage Disease Type 0. While also caused by genetic mutations, rather than affecting the machinery that produces insulin, it affects the machinery which uses the insulin to move blood sugar into cells for storage.
One of the things insulin does is move glucose out of the blood and into cells. Excess glucose is usually converted to ‘glycogen’ and stored in the cells (mainly in the liver but also in muscles) as an emergency energy source in times of exertion. In patients with Type 0, they cannot produce glycogen and therefore they have no energy backup.
The upshot of this is a patient with Type 0 can faint doing something as simple as climbing a set of stairs. Because there is no backup energy source and because it is hard to shift excess glucose out of the blood, a Type 0 patient will have wildly fluctuating blood glucose levels and the usual diabetic treatments (insulin and glucagon injections) are completely ineffective. If you think you have it tough as a Type 1, consider the plight of the Type 0.
As the disease presents in a very different way to the other Types e.g. fainting when climbing stairs, misdiagnosis is less common. Treatment is difficult and the best protocols are still being determined.
As the name suggests, gestational diabetes occurs during pregnancy so this one is exclusively female. The mechanism is broadly understood; to grow a baby, glucose needs to reach the fetus. To make this happen, the woman’s body releases hormones which increase insulin resistance in her own body, limiting access to glucose and allowing it to get to the baby.
With increased insulin resistance, the pancreas needs to release more insulin to keep up with the woman’s energy demands (up to three times as much in fact) which can test the pancreas’ limits and lead to diabetes. Excess glucose in the blood can make the baby grow excessively, leading to birthing complications but can also damage the baby leading to miscarriage or stillbirth so it is important that Gestational Diabetes is managed during pregnancy and, thankfully, screening for it is common.
Once the baby is born and the pregnancy hormones disappear, the diabetes usually goes as well. However, in some cases, the damage is done and the diabetes remains, generally classified as Type 2 and treated as such. Arguably, the cause is known so it is not really Type 2 and is a continuation of Gestational Diabetes.
What is Your Type?
If you are a Type 2 and your treatment plan is not working well, it is worth considering that you may have been misdiagnosed. If, after reading the above, you feel you may be a candidate for a different Type, reach out to a medical professional to discuss your concerns. While medical professionals hate Dr Google and well meaning blogs, it is your life and you who will have to live with the complications if their guess was wrong. They can organize the tests to make a definitive diagnosis.
My name is Leon Tribe. I was educated as a physicist but now work as the National Director for a large multinational organization and occasionally speak at conferences on technology and diabetes.
I live in Sydney, Australia and I am a Type 1 Diabetic. As I write this it has been two years since my diagnosis and I am still insulin free with normal blood sugars. More of that in another post.
If you are interested in my diabetes story keep reading. If you would prefer to cut to the chase and see what this blog is about, jump to here.
Where It All Began
My diabetic journey started near the beginning of 2017. I had been feeling exhausted for months, which I attributed to poor sleeping habits. My hair was falling out in small round patches (alopecia areata) but it ran in the family so I just accepted it. My ankles ached, making it hard to go up and down stairs, which I had no explanation for, other than being middle aged and not particularly health conscious. I had a rash in places one should not have a rash and this also had no valid explanation. Finally, my eyesight was acting up. I had worn contact lenses for shortsightedness since adolescence but it seemed my prescription was on the move again.
Then things started to get a bit more specific to something I could self-diagnose. I was at a conference away from home and found myself permanently thirsty. This was strange because I rarely got thirsty. I was also needing the bathroom every half hour or so and emptied a full bladder each time. This was a problem because I was supposed to be doing an hour presentation at the conference and one does not normally hop off stage for a quick bio-break.
I got through the presentation and flew home. Pretty much the only thing I knew about diabetes was it made you permanently thirsty and pee a lot so I headed to the doctor.
Sure enough my fasting blood sugar was three times what it should have been and I had ketones. For the uninitiated this meant I had the early stages of Diabetic Ketoacidosis (DKA). In short, my body had a shortage of insulin and was out of control because of it. My blood was slowly going acidic which is a very bad thing. It also confirmed to the doctor that I had some form of diabetes. The doctor recommended I immediately go to hospital, now, right now, like immediately.
Sure enough I headed directly to hospital where they put me on a drip to re-hydrate me and start a bunch of blood tests. The re-hydration stabilised me and given I was a guy with a few extra pounds in his early 40s with diabetes they came to the (wrong) conclusion I was a Type 2 diabetic.
Misdiagnosis of diabetes happens a LOT with many people being thrown into the Type 2 bucket incorrectly. It was my doctor (a generalist with an interest in diabetes but no formal specialization) who had the sense to test my blood for the tell-tale auto-antibodies which confirmed a Type 1 diagnosis; something the ‘experts’ in the hospital had failed to do. I was a middle-aged man with ‘Juvenile Diabetes’.
Type 1 is a relatively rare disease; roughly one in 200 people have it or, 0.5% of the population. For the first 11 months I met no one with Type 1. This was quite isolating so I started up a monthly meetup to meet others and to learn from them. If you live in Sydney, feel free to come along to our monthly gathering.
While I did not need insulin to keep myself healthy, I was taking pills (Metformin at first, and now also Saxagliptin). However, the pill boxes in the market were dull so I created my own out of a pocket watch. Thinking others may also feel the same way, I now sell them on Etsy.
All this time I have also been learning as much as I possibly can about this disease. My training as a physicist means I can absorb quite a large amount of information quickly, which has proved very useful. This blog is a vehicle to share some of the things I have discovered on the way and, hopefully, help others manage this chronic disease (‘chronic’ just means long term).
Why Read This Blog?
There is a lot of complex information and a lot of nonsense out there. My aim is to reduce the noise and provide simple explanations and practical advice (non-medical, of course) for diabetics of all Types. If you have questions about how diabetes works and how to manage it effectively, my sincere hope is that my blog helps you in some way.
What Is In It For Me?
Perhaps one day I will convert this blog to a book (publishers feel free to contact me :P) but until then this is simply a vehicle for me to clarify my ideas and get them in a format I can refer back to. That is it. There are no paid endorsements and I am not yet in the pocket of Big Pharma.
If you have made it this far, well done and welcome aboard. Thank you for taking the first step with me on a journey of 1,000 miles.