Signs and symptoms of hypoglycemia

The first signs come from the autonomic nervous system, which is generally activated when blood glucose falls below 60 mg/dL (3.3 mmol/L), as the figure below shows [1]. The nerves (part of the autonomic nervous system) release two neurotransmitters locally, acetylcholine and noradrenaline. Acetylcholine produces the cold sweat, the sudden hunger and the tingling [2]. Noradrenaline produces the trembling, the palpitations, the nervousness and the pallor of the skin [2]. Adrenaline released by the adrenal glands (a hormone) adds to these effects and helps raise blood glucose, but the signs appear even without it [3]. Everything sets in within a few minutes and is felt throughout the body.

The purpose of the symptoms is to make you stop what you are doing. They are not signs of physical harm, but an alarm signal. If you recognize them in time, treating the low takes a few minutes and the episode ends there. That is why it is worth knowing exactly what your own first signs are, not only the textbook list, which is valid in general.

They come from the same autonomic alarm, but by two different routes. The trembling and the palpitations are adrenergic. Noradrenaline released by the nerves acts, together with the adrenaline from the blood, on the beta receptors in the muscles and in the heart [3]. Sweating is not produced by adrenaline, but by acetylcholine, the substance through which the nerves of the sympathetic nervous system control the sweat glands. The skin turns cold because the small vessels tighten under the effect of noradrenaline. The skin goes pale, and the sweat evaporates from a surface already cooled by the reduced blood flow. Alongside the symptoms, the body defends its blood glucose through hormones. Insulin secretion falls, glucagon rises and, when glucagon is not enough, adrenaline rises as well [4].

In a person without diabetes, glucagon is responsible for most of the defense against hypoglycemia. After a few years of type 1 diabetes, the glucagon response almost disappears, and adrenaline becomes the main hormonal line of defense [4]. This explains why a low corrects itself less easily in a patient with longer-standing diabetes. It is useful to understand that these signs are the brain's alarm, not a sign that it is suffering. They appear before the serious signs and leave you time to react. The more lows you have had in recent weeks, the later the signal appears and the weaker it is.

They include difficulty concentrating, blurred vision, slurred speech, drowsiness, confusion and behavior that is unlike you. In severe forms, seizures and loss of consciousness follow. They are called signs of neuroglycopenia, that is, of insufficient glucose for the brain [2]. In people without diabetes, these signs begin at around 50 mg/dL (2.8 mmol/L) [1]. The threshold is individual, and what counts for treatment is 54 mg/dL (3.0 mmol/L), the level at which signs from the brain can begin [5].

The difference from the warning signs matters. When the signs of the autonomic nervous system appear, you can still help yourself. When the signs of the brain working less well appear, your judgment is already affected. Often you do not even realize it. This is the reason a low is treated at the first signs, not later [5].

Yes, much more than most people imagine. Some sweat, others suddenly become irritable, others feel a hunger that is hard to describe [6]. There are patients whose first sign is numbness around the lips or weakness in the legs. The list of hypoglycemia symptoms in textbooks is the sum of all the variants, not how they appear in any one person.

The order is not guaranteed either. The rule "first the autonomic signs, then the ones from the brain" holds in most patients. However, in those with reduced perception of hypoglycemia, the first sign noticed can come directly from the brain. It can be a mistake in a calculation, slurred speech or unexplained irritation. On the other hand, each patient has a pattern that stays fairly constant over time. It is worth writing down the first two or three signs you usually get and telling those around you [7]. An episode recognized in time costs a five-minute nuisance. One that goes unrecognized can ruin a whole day.

Yes. The warning signs weaken, appear at lower values and become fewer. The main cause is not the duration of diabetes in itself, but the repeated lows of the last days and weeks. The mechanism is called HAAF (hypoglycemia-associated autonomic failure). It is different from classic autonomic neuropathy, a complication of long-standing diabetes [4]. A patient who used to feel a low at 65 mg/dL (3.6 mmol/L) can end up feeling nothing even at 50 mg/dL (2.8 mmol/L).

The good news is that the symptom side can be fixed. After 3–4 weeks of strictly avoiding lows, the perception of symptoms can be regained, with visible improvement after as little as three days [8]. The caveat is that the hormonal response recovers more slowly and often incompletely [5]. In one study, the glucagon and adrenaline deficit persisted even after three months [8]. So you regain the warning more easily than the automatic hormonal defense [5] [8]. The treatment plan is made together with your doctor, by temporarily relaxing the glucose targets and by using the sensor with the alarms switched on [9]. It is one of the few things in diabetes that can be fixed relatively quickly.

No. Hunger is a symptom triggered by the autonomic nervous system, but with low specificity [10]. It can appear at a low blood glucose, but it appears just as readily at a high one, when a meal is late or simply out of habit. Many highs come with a hunger just as intense as in a low.

The practical consequence is not to treat hunger as a low without checking. A blood glucose reading with the glucometer takes a few seconds and saves you from useless calories, but above all from a high afterward [10]. If you have no way to measure and you also have other signs, you treat. If hunger is the only sign, you check first.

Yes. They often are. Anxiety, one coffee too many, exercise or a strong emotion activate the same beta receptors and give the same sensations. A panic attack and a low resemble each other so much that not even doctors can easily tell them apart from the description alone.

There is also the reverse situation, which is worth knowing. If you take a beta-blocker (heart medication), especially a non-selective one such as propranolol, the tremor and the faster pulse can be blunted [11] [12]. Sweating remains, and even becomes stronger, because it travels by the cholinergic route [11]. The alarm signal can become weaker, but it does not disappear [11]. The only thing that tells them apart for certain is the blood glucose. One measurement of it helps more than an hour of questions. The confusion works the other way around as well, and some patients with diabetes put real lows down to emotions, especially in stressful periods.

First of all by behavior. Young children become irritable, cry for no reason, throw a tantrum or, on the contrary, become unusually quiet. Pallor, unsteady movements and lack of interest in play also appear [6]. At this age what the child says is unreliable, so the adult's observation counts for a lot. The decision, however, rests on the measured blood glucose [13].

A child under 6 has no words for the sensations of a low and often does not even recognize them as abnormal. At this age the autonomic signs and the ones from the brain mix, and the usual order is not followed [6]. That is why supervision with a sensor changes the degree of safety a great deal [14]. If unusual behavior appears suddenly, the first check is the blood glucose [13].

Often, yes. Pallor, sweating, a fixed stare or an odd way of speaking are seen better from the outside than from within. Family and close colleagues come to recognize the pattern after a few episodes. The problem is that during a low the natural reaction is to deny it. Refusing help is not stubbornness, it is already a sign of neuroglycopenia [15].

A brain working with too little glucose becomes irritable and rejects suggestions. It is worth making an agreement in advance, calmly, with those close to you. If they tell you that you look odd, you measure your blood glucose without arguing. This simple rule can prevent many severe episodes of hypoglycemia [15].

Usually a headache, an unusual tiredness and difficulty concentrating. They can last an hour or more after blood glucose has returned to normal. Some patients describe a feeling of exhaustion that lasts until the next day.

The explanation is that the recovery of brain function goes more slowly than the recovery of blood glucose. Reaction time stays impaired for up to 40–75 minutes after blood glucose returns to normal [16]. The number on the screen corrects itself in 15 minutes. Brain function comes back gradually. That is why you should not rush to drive, to take an exam or to make an important decision immediately after a low [17]. Wait at least 45 minutes after your measured glucose is back to normal.