Blood sugar back door exits

After living with their condition for a while, most persons with type 1 diabetes begin to notice inconsistencies in what happens to their blood sugars (or those of their d-kids) under what are believed to be identical circumstances and/or insulin doses and meals. The most common mystery I hear is when insulin requirements may seem almost non-existent for a period of time and prolonged low or normal range blood sugars reign during or following an illness. Carb containing foods may seem to be consumed in large amounts with little effect on sugar levels. Another common scenario is when someone has repeatedly low blood sugars all day despite repeated efforts to treat them. And these events occurred long after the classic 'honeymoon phase' has ended. 


These events raise many questions. Is my body making insulin again? Is my diabetes going away? Is there something 'special' about my diabetes? These are all logical questions and deserving of answers. Let me give some perspective on what might be happening. And most of these considerations are NOT mutually exclusive. But understanding them can help us move forward and better manage the ebb and flow of our blood sugars with more confidence.

I'll start with the most common 'suspects', as they say. These include an unintentional insulin overdose, under eating food for insulin, and increased physical activity. These are human factors that may be under appreciated as playing a role in the ups and downs in blood sugar levels. Insulin over treatment can sometimes be recorded if done through an insulin pump, but not always. I often get calls from parents who realized too late that they incorrectly overdosed their insulin and need help to remedy the situation. But there are many cases when this error is not discovered up front and can only be speculated about after the fact. I recently learned of a family who was dosing insulin for scheduled snacks, even when low. This can be problematic.  After decades of working with diabetes families and adults, you hear all kinds of stories.

 

Taking doses of rapid-acting insulin in an overlapping fashion without a rationale is better known as insulin stacking. It's a common accidental cause for unexpected low sugars. This is in contrast to the Sugar Surfing method known as I-chaining, which is a calculated move with close follow up glancing.

Next on the list of possible explanations are unanticipated mismatches in food, insulin and exercise. Plus all three of these categories can be affected by their timing and duration relative to each other. The result can be an "unexpected" low blood sugar (or high) that might persist for hours. It’s important to accept that there is always a huge “human” element to our care and the potential for human error always exists. We can at best minimize, but never truly eliminate this. I've made many mistakes over my 52 years living with type 1 diabetes.

But our technology is limiting to us as well. Blood sugar meters can provide erroneous results for many user-related and user-unrelated reasons. The same applies to continuous glucose sensors. I refer you to the discussion on the Clarke Error Grid for a review of these devices on diabetes self-care and their impact on our decision making. Of course human factors can dramatically influence blood sugar meter data, starting with who is doing the checking (child or adult) and the quality/integrity of their checking technique.

There are more possible reasons for unexpected low blood sugars.

Insulin is injected into various parts of the body each day. If these sites have become thickened through repeated use (called lipohypertrophy), this physical change of the body actually slows down the rate of insulin absorption (pick up) from the area, delaying its action and even appearing to prolong the insulin effect. This is a potential problem for all insulin types.

And there are always other co-related conditions with diabetes that can upset a previous balance that might have existed. These include celiac disease, which can cause unexpected lows due to poor intestinal absorption of carbohydrates due to damage to the gut lining from gluten sensitivity. Gastrointestinal infections can temporarily strip off the top layer of the intestines and reduce the gut's effectiveness in absorbing the energy from food, including the carbs. This will recover once the infection (often viral) passes and the gut has time to heal. 

 

Addison disease can cause fasting lows due to lack of an anti-insulin hormone (cortisol). It also causes bronzing of the skin and strong craving for salty foods.  An overactive thyroid gland can increase the metabolic rate and increase physical activity burning sugar faster and causing lows. These are all possible conditions that might develop during the course of type 1 diabetes. Low growth hormone activity could also raise the risk of low blood sugars, but it's quite rare.

Most of us with type 1 diabetes are active each day, but our activity changes quite a bit from day to day. Sometimes this can be extreme. If engaged in organized sports or personal fitness routines, our bodies can be depleted of internally stored sugar (called glycogen). The body maintains a storage depot of glycogen in the liver and muscles to maintain our blood sugar levels between meals and for powering muscles for immediate physical activity. If these supplies are depleted by a long day on the practice field, prolonged work in and around the house or garden, or any extended physical activity, then the body is obligated to replace these sugar depots over the next day or two. That replenishment is done through subtracting sugar from the blood stream to "recharge" the human sugar batteries. And here's the surprise: this process DOES NOT require insulin to occur. The end result is a second "drain" into which blood sugar can be siphoned out of the blood stream. It's another possible explanation for an unexpected low blood sugar. Athletes call this "post-exercise hypoglycemia". It's a bit of a misnomer since exercise per se is not required. Just prolonged physical activity of any source.

The ability to produce insulin can be retained in some people with diabetes. This is most pronounced during the partial remission or "honeymoon" phase of diabetes. But insulin doesn't simply shut off like and on and off switch. It slowly, irregularly, declines over time. It's not out the realm of possibility that some insulin response might still be possible some years after diagnosis, but this would require proper testing to prove and would not be the first consideration. Search the recent work by Bart Roep PhD to learn how insulin producing beta cells can survive well past the honeymoon phase. Roep's work doesn't mean diabetes is cured or going away...yet.

 

For years, there have been tests to measure internal insulin production but they are rarely used clinically unless there is a strong reason to do so. Furthermore, the hormone responses that aggressively oppose insulin-induced low blood sugar (glucagon and adrenaline) can fade in their intensity over time too, giving the appearance or illusion of more insulin being produced. Daily insulin requirements change with time and age. They also change through the day and from day to day. Exercise alters insulin sensitivity too. 


What about things that work like insulin but somehow "bypass" insulin itself? Yes, such things exist. Insulin is a hormone that attaches to a receptor molecule on many cell surfaces. That's the simple explanation. But this system is far more complex and there are many pressure points along the path of insulin action when it might be either blocked, or even hijacked thereby decreasing or increasing the ability of cells to take up sugar. Are there substances which trigger the same sugar disposal process as insulin does, but by a different direction? There are several.

If you were inclined to look at this from a research point of view, topics like altered IRS-1 and IRS-2 activity, increased Akt phosphorylation and AMP-dependent kinase activity would reveal possible clues to non-insulin mediated glucose lowering mechanisms. The only reason I even mention this is that the insulin "black box" has been fairly well explored and continues to be a gold mine of information for new diabetes drug designers. Beware: if you go searching those terms, they might seem like another language to decipher!

Chromium and Vanadium are elements on the periodic table. These two substances have shown to mimic the action of insulin in certain ways. But don't think about tossing out the insulin pen. These cannot replace insulin itself in persons with type 1 diabetes. But they point out that there are ways around insulin in regards to mimicking its effect.

For completeness sake and in the vein of "if you can't raise the bridge, lower the river", there are now prescription medicines for persons with diabetes which increase the loss of sugar through the urine. They have been proven to lower average blood sugar levels by acting as a pop-off valve of sorts. But this effect would not make any sense in explaining prolonged lows. Plus these new medicines, called SGLT inhibitors, are only for persons with type 2 diabetes.

Science has unraveled the function of each step along the path of how insulin does its job at the cellular level. While quite sophisticated, it can be appreciated that at each step along the way insulin works, there might be a way to bypass insulin. Such a ‘bypass’ could either block or enhance insulin’s effect. Maybe even eliminate the need for insulin altogether. Not surprisingly, this has been and will remain a hotbed of diabetes research for years to come.

 

Injected insulin is inactivated and removed by the kidneys. Persons with failing kidneys require less insulin because of this fact. 

So where does that leave us in answering the question: why do unexplained lows occur? Well, just take your pick of known answers and speculative ones. And here's the kicker: none of these are exclusive of one another. There are dozens of combinations of these which might occur over time and in different rearrangements, giving rise to a "mystery" low blood sugar pattern. Over my half century of diabetes, I've had my share of "low sugars". I see many of you have had similar episodes as well based on the posts I read daily.

I try to best explain the ones I can but never know for sure. It's always tempting to speculate on possible causes. Try not to perseverate on them. It's just part of the mystery of diabetes self-care that requires me to be reactive up to half the time, no matter how proactive I try to be. The explanations above form the foundation of my proactive-reactive philosophy to diabetes self-care.

 

 Please share this post and I invite you to share your low blood sugar mystery stories here. I find them all quite fascinating and a challenge to reconcile whenever possible.

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