For the last ten years or so I've struggled with reactive hypoglycemia related to CFRD (cystic fibrosis-related diabetes). In the last couple of years it has become very difficult to manage. Reactive hypoglycemia is a condition where the blood sugar crashes 1-3 hours after a meal containing carbohydrates, leading to distressing hypoglycemia symptoms such as shakiness, anxiety, weakness, brain fog, fatigue, tachycardia, and in severe cases, unconsciousness or even coma. Reactive hypoglycemia is more common in CFRD than many CF-specialists realize. Despite avoiding simple carbohydrates and adhering to a Paleo-ish diet for many years, my reactive hypoglycemia has only gotten worse. That is, until I started a ketogenic diet in October of 2020. I've made a remarkable improvement in my blood sugar control and I'd like to report my success in detail here.

What is "reactive" hypoglycemia and why does it happen? Hypoglycemia is a symptom that your pancreas is not producing insulin correctly. I started getting hypoglycemic episodes in high school after I would eat a sugary breakfast (oh yes, I used to eat pop-tarts back in the day, I'm sad to admit). About 3 hours after breakfast I would start getting weak, shakey, very hungry, and have a hard time concentrating on anything except that fact that I needed to eat. This is a manifestation of the step before CFRD, and is caused by "impaired glucose tolerance" (IGT). Normally, when glucose is absorbed by the small intestine and hits the blood stream, it is detected by the beta-cells of the pancreas and starts a chain reaction inside the cell that stimulates the excretion of insulin into the blood [1]. But it turns out that all CFers, whether or not they have normal glucose tolerance, IGT,  or CFRD, have a delayed insulin response [2,3]. This means that somehow this system of glucose detection and insulin excretion gets hung up, and your pancreas ends up releasing insulin an hour or so late. So for a while you have high blood sugar, but then all of the sudden the insulin hits your blood stream, pushes that glucose quickly into the cells and leaves you with hypoglycemia, or low blood sugar (technically means below 70 mg/dL, but I start to feel symptoms at about 60 or below). This wouldn't have been a problem if the insulin release had been immediate because the amount of insulin released is measured to match the amount of glucose that was originally detected in the blood. However, in the hour or two between the moment of detection and the moment of insulin release, your background "basal" level of insulin has been reducing your blood sugar, albeit at a slower rate. The pancreas produces insulin "on demand" when you eat carbs and sugars, and also produces this basal level of insulin 24/7 in much smaller amounts. Basal insulin production is usually normal in CF, even with CFRD, and that is why morning fasting blood sugars are often normal or low [4]. Also, when your blood sugar gets above 180, your kidneys filter the glucose out of your blood and start dumping it into your urine to pee it out. So when the delayed insulin load hits your blood, it is now overshooting your need for it and you are now at risk for reactive hypoglycemia. 

For many CFers, they can get hypoglycemic but their blood sugar drops to a certain point and remains stable, not dropping below any dangerous level. But for me, somehow my blood sugar can drop extremely low and so I'm at risk for a reaction because there's no glucagon back up system to save me. Studies have shown that the severity of delayed insulin response and hypoglycemic reactions does correspond to what kind of mutation you have [5]. It is likely that just like delayed insulin production in CF, glucagon production is also delayed in reaction to hypoglycemia. So if I feel hypoglycemia coming on, I've got to eat some glucose or it won't be pretty. If you've got IGT or CFRD, it's a good idea to keep a small hit of glucose with you at all times, preferably a fruit like dried apricots or a fruit leather. I keep a fruit leather in my backpack and every one of my jackets to use in emergencies (and ONLY emergencies, they're too sugary for us under normal circumstances). If you've eat a moderately carby meal with a lower glycemic index and get a reaction, you're likely not at risk for passing out because your insulin overshoot won't be too big, since your pancreas won't be wanting to excrete as much insulin in reaction. But if you've just eaten a high carb meal with a high glycemic index, watch out and keep a snack with you for a few hours.

The take away message here is that reactive hypoglycemia is completely avoidable. What causes an insulin overshoot? Only higher carb meals with a higher glycemic index, meaning foods with quickly available sugars that hit the blood stream and cause a dramatic spike in blood glucose. This means sodas, candy, pastries, anything with a lot of sugar, any simple starches like potatoes, and anything with refined carbs (e.g. white flour) that are not eaten with a significant amount of fiber, fat, or protein to slow the absorption of glucose in the small intestine. I have a hypoglycemic reaction anytime I eat more than 30 grams of carbs in the morning, so I try to avoid eating carbs before noon. If we avoid these higher carb "foods" (most of these are toxins and should be avoided anyway) and make sure we choose to eat low glycemic index foods and meals, including fiber, fat, OR protein (but not all together), then hypoglycemia can be avoided. In addition, I believe that having a low-carb breakfast is very important in hypo prevention. Since the digestive tract is relatively clear after about 12 hours of fasting during the night, your body can absorb carbs a lot more quickly in the morning than at any other point during the day. This may be why I have historically only developed reactive hypo after breakfast. In the morning, the insulin response is not as quick as carb absorption, so there is greater risk of reactive hypo. Instead of loading up on cereal, oatmeal, a muffin, or a fruit smoothie in the morning, try eating a lot of fat or protein. A few eggs (if tolerated) plus bacon is a good choice, or some nuts or nut butter lathered on something fibrous like celery. My digestion is quicker in the morning, so a couple hours later I am ready for second breakfast, which can be slightly more liberal with the carbs. 

The concept of the glycemic index is very helpful to use in conjunction with other dietary concepts that I discuss, and I suggest browsing through the food database to check our the glycemic load of the foods that you eat here. 

By the way, cinnamon modulates insulin secretion and boosts insulin sensitivity, so when consuming something with a bunch of carbs or sugars in them, make sure to take cinnamon in pill form or add a lot of cinnamon to the meal. Cinnamon is truly effective, it may not prevent a hypoglycemic reaction with a high carb meal (more than 30 g of carbs). In addition, using digestive bitters before your meal is helpful to prepare the digestive system for your impending meal, increasing insulin sensitivity, and slowing upper-GI motility to reduce rapid absorption of carbs, which cause blood sugar spikes and crashes. 

Also, here's a useful link that outlines a few of the long-term effects of having frequent bouts of hypoglycemia. I have noticed several of these symptoms myself. The most concerning of which is that I now don't feel the symptoms of hypoglycemia until I'm close to 40-50 mg/dL, whereas I used to get shaky and hungry at 60-70. This is not good, and shows that I am allowing myself to get too low too often, so I need to change my dietary habits, or else one day I won't be able to detect my hypoglycemia until it's too late and I pass out. 

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[1] http://en.wikipedia.org/wiki/Insulin_signal_transduction_pathway_and_regulation_of_blood_glucose
[2] Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients. <http://www.eje-online.org/content/165/1/69.full.pdf>
[3] Insulin secretion, glycosylated haemoglobin and islet cell antibodies in cystic fibrosis children and adolescents with different degrees of glucose tolerance. <http://www.ncbi.nlm.nih.gov/pubmed/1761281>
[4] Cystic Fibrosis-Related Diabetes and Abnormal Glucose Tolerance: Overview and Medical Nutrition Therapy. <http://spectrum.diabetesjournals.org/content/15/2/124.full>
[5] Spontaneous hypoglycemia in patients with cystic fibrosis. <http://eje-online.org/content/156/3/369.long>