Clinic Chat: Counterregulatory hormones
Updated: Sep 14
Ever wondered why your blood glucose level seems to have booked a ticket to the moon, even though you haven't eaten anything? Blood glucose management is so much more than carbs and insulin – indeed, 42 factors have been identified that can impact glucose levels, including hormones. In this month’s Clinic Chat, we discuss the impact of the hormones that are secreted as a result of stress, illness, or as a consequence of insulin deficiency itself. There are known as insulin counterregulatory hormones, and include glucagon, epinephrine (also known as adrenaline), cortisol, and growth hormone.
Counterregulatory hormones have the opposite effect of insulin: they increase blood glucose levels. They do this by increasing the release of glucose that is stored in the liver, reducing the uptake of glucose by muscle cells, and making cells resistant to insulin.
Glucagon is secreted by the alpha cells of the pancreas, which, unlike the beta cells which make insulin, remain intact and functioning in a person with type 1 diabetes. Glucagon increases blood glucose levels by signaling the liver to release its stored glucose. Glucagon has an important job – it is released through the night and during the day between meals to maintain the body’s blood glucose level and fuel its cells.
Insulin and glucagon perform a complex dance. Insulin not only helps bring your blood glucose levels down, it also inhibits glucagon secretion. Your basal/long-acting insulin helps keep your blood glucose level stable in between meals because it both helps you manage the glucose your liver releases, and simultaneously keeps glucagon release in check, preventing your liver from releasing too much extra glucose.
If you don’t have enough insulin onboard, there is no ‘brake’ on the alpha cells, and therefore no control on the glucagon they release. The glucagon will signal your liver to push more and more glucose into your bloodstream, and your blood glucose level will rise. This can occur if your basal insulin is missed, or you don’t dose enough insulin.
Cortisol is a steroid hormone produced by the adrenal glands. It is released in the early morning to help the body wake up, and in response to stressors, including some types of exercise and intense emotion.
Cortisol causes a rapid but temporary increase in glucose production, designed to supply a quick energy source to large muscles if a ‘fight or flight’ response is required. At the same time, it makes cells resistant to the action of insulin, keeping glucose in the bloodstream available for immediate use rather than being stored.
Many people with type 1 diabetes experience both the “dawn” and “foot to the floor” phenomena, which involve increased blood glucose levels and insulin resistance in the hours before or immediately after they wake up. Both are related to cortisol release. Adjusting basal insulin rates or doses can help, or some people may need a small dose of rapid-acting insulin dose upon waking to counteract the glucose-raising impact of cortisol. Studies have shown that cortisol levels are higher when people wake up in light rather than darkness, so black-out blinds may be a good investment – although if this means you need a machine-gun alarm clock to wake you from your slumber, then you may not enjoy the full cortisol-minimising effect of waking in darkness!
We also release cortisol when we are nervous, anxious or under intense stress, or doing high intensity or anaerobic exercise such as HIIT training or weight-lifting. It’s hard to predict how much elevated cortisol will impact blood glucose levels in the short-term, so pre-empting a stressful situation with a bolus or increased basal rate is not a good idea unless you’ve experienced a clear and repeated pattern of elevated levels related to a known stressor. Alternatively, reducing your cortisol response with breath work or other calming exercises can help reduce or avoid the spike. If you are under significant stress for an extended time, blood glucose levels may become consistently elevated and insulin resistance can increase, and will require longer-term insulin dose adjustment.
Synthetic cortisol, known as cortisone, may be injected into painful joints to ease inflammation caused by certain conditions or injuries. People with type 1 diabetes usually notice a significant, rapid increase in their blood glucose levels from a cortisone injection, which may last for several days.
Epinephrine (adrenaline) is released from nerve endings and the adrenal glands and, like cortisol, is also a ‘fight or flight’ hormone that is released in response to stress and intense emotion or activity. Epinephrine both signals the liver to produce glucose and increases insulin resistance of the cells, increasing blood glucose levels.
Exercise is perceived by the body as a form of stress and epinephrine is released to meet the increased glucose demands of the muscles for fuel. Everyone reacts differently to exercise, and you may find that some types of exercise increase your blood glucose levels, and others do not. Some people notice that their exercise-related blood glucose spikes are predictable enough to be able to dose insulin around. Many people find that as they become fitter and exercise becomes less stressful for the body, their epinephrine response declines.
Growth hormone is released from the pituitary gland in the brain and acts to promote growth in children and to maintain body composition, cell repair and metabolism in adults. Growth hormone levels are higher during sleep, acute stress and exercise. Growth hormone increases most during puberty, when more rapid growth is occurring.
Growth hormone increases glucose production and release from the liver and kidneys, and free fatty acid release from the breakdown of fat cells. This supplies the body with the fuels it needs to grow. High levels of growth hormone cause insulin resistance and this can translate to high blood glucose levels in people with type 1 diabetes if insulin is not adjusted accordingly.
Managing counterregulatory hormones
The impact of counterregulatory hormones can be a real challenge for people with type 1 diabetes. Their glucose-raising effect can only be countered with insulin, but knowing which insulin to take, how much to take and when to take it feels more like art than science. Unlike carbohydrate, which sticks around for a relatively predictable amount of time, when the body switches off its counterregulatory hormone release the glucose-raising effect also switches off, and blood glucose levels can fall rapidly if you have increased insulin onboard.
Increased counterregulatory hormone release may become predictable enough to handle with an adjustment to your basal insulin. An example would be a growth spurt in a child, quite often seen as overnight highs for several consecutive nights. Another example is a prominent dawn phenomenon.
In both examples, the night-time basal dose or rates could be increased. However, in the case of the child having a growth spurt, this may only last a few days, and the increased hormone release could drop off at any time. You will need to be very vigilant around the possibility of overnight hypoglycaemia, and a CGM is a good idea to help monitor for this.
Dawn phenomenon is easier to manage, as it is generally quite consistent. If you see a regular rise in your blood glucose levels from the early hours of the morning, increasing your night-time basal dose may help. If you take a once daily basal dose at night, be careful that increasing this could lead to hypoglycaemia during the following day. If you split your basal dose into a night and morning dose, the dose to increase is the one you give at night-time. If you use an insulin pump, you can simply program the pump to increase your basal rates during the hours you need it. Start the increased basal rate from the hour before you see the rise starting to happen to catch it before it takes off. You may need to keep the increased basal running for an hour or so after you wake up. Work conservatively with dose increases to prevent hypoglycaemia.
A rapid release of counterregulatory hormones that is caused by a known stressor, such as a particular gym session, may warrant a proactive bolus. It is important to remember that the hormone response in these cases is short-lived, but bolus insulin will be active for 2.5-4 hours and may cause a hypo if not dosed at the right time or in the right amount. Do some detective work into exactly what happens to your blood glucose level in these scenarios: consider how much it rises by, when it peaks, and whether it comes back down on its own. Experiment yourself, or take this information to your diabetes educator for help figuring out how to bolus for hormones.
Counterregulatory hormones have a powerful impact on glucose levels, and knowing more about them can help you to improve your diabetes management. If you need help, contact the Family Centre’s clinic here.