Risk factors for hypoglycemia

They are divided into major and secondary factors. The major risk factors for hypoglycemia are the following:

• A level 2 or 3 episode in the last 3–6 months.
• Intensive insulin therapy.
• Loss of the warning signs.
• Stage 5 chronic kidney disease (kidney failure).
• Memory problems or dementia.
• A history of metabolic surgery.
• No steady access to food.
• Low income.
• Insecure housing.
• Lack of health insurance.
• Fasting for religious or cultural reasons.

The secondary risk factors for hypoglycemia are the following:

• Several recent level 1 episodes.
• Basal insulin therapy.
• Age 75 or older.
• Female sex.
• Large swings in blood glucose from one day to the next or within the same day.
• A large number of medicines (of any kind).
• Cardiovascular disease.
• Stage 1–4 chronic kidney disease.
• Diabetic neuropathy.
• Diabetic retinopathy.
• Major depression.
• Severe mental illness.
• Slow stomach emptying (gastroparesis).
• Treatment with beta-blockers.
• Difficulty understanding medical information.
• Alcohol or other substance use disorders.

A single major factor is enough for you to be considered at high risk of hypoglycemia. The same classification applies when several secondary factors add up, and the decision rests with your doctor [1]. Intensive insulin therapy means multiple daily injections, an insulin pump or an automated insulin delivery system [1]. In type 1 diabetes, this is the recommended treatment for most adults [2]. As a result, practically every adult with type 1 diabetes has at least one major factor and is at high risk of hypoglycemia.

Yes, and it is the strongest risk factor of all. Previous episodes, especially level 2 or 3 ones, are the best predictor of another one [1]. The reason is twofold. The original cause of the hypoglycemia often persists, and each episode further lowers the body's alarm threshold [3].

The practical consequence is that a hypoglycemic episode should never be overlooked. It is not bad luck, but information. Reviewing it with your doctor, followed by a dose adjustment, breaks the chain in which one hypoglycemic episode leads to another [1]. Without adjusting the treatment plan, the pattern can repeat itself.

Yes, at both ends. Young children, especially those under six, cannot recognize or describe hypoglycemia, so they depend entirely on adults and on a glucose sensor [4]. Age 75 and older is listed among the secondary risk factors. However, in type 1 diabetes young patients also have a very high risk [1].

In older age, several other reasons add up, such as irregular meals, declining kidney function, a large number of medicines and memory problems. The link works both ways, because repeated hypoglycemia in turn affects memory. That is why glucose targets are relaxed with age [5].

Yes. Stage 5 chronic kidney disease is listed among the major factors. Chronic kidney disease with a filtration rate below 60 mL/min/1.73 m² or with albuminuria (stages 1–4) appears among the secondary ones [1]. The kidney clears insulin from the blood. As a result, when its function declines, insulin stays active in the body for longer. In other words, the same dose has a longer and stronger effect [6].

The kidney also helps produce glucose when you fast, for example overnight [7]. When kidney function declines, this contribution declines too, and blood glucose is harder to maintain [6]. That is why insulin doses need to be reassessed as kidney function declines.

Yes. Blood glucose that rises and falls with large swings will reach the lower threshold more often, even if the average is very good [8]. In this way, two patients with the same glycated hemoglobin (HbA1c) can have a completely different risk of hypoglycemia, as the figure below shows [9]. High glycemic variability is listed among the secondary risk factors [1].

A glucose sensor measures this with the coefficient of variation, and the target is a value below 36% [10]. Reducing glucose swings lowers the number of hypoglycemic episodes without raising average glucose [11]. That is why glucose sensor reports are read together with HbA1c, sometimes even before it, but never instead of it.

No, and this is an important change from the past [12]. In the older clinical trials, intensified glucose control did increase the number of hypoglycemic episodes. In today's practice, however, a J-shaped relationship is described, meaning that both low and high HbA1c values are associated with hypoglycemia [1].

What matters is how you reach that value. A low HbA1c achieved through large swings and repeated corrections will inevitably also bring many hypoglycemic episodes. The same value achieved with stable blood glucose and little time spent below 70 mg/dL (3.9 mmol/L) does not. Keep in mind that the percentage of time below 70 mg/dL (3.9 mmol/L) shows the overall risk of hypoglycemia better than HbA1c does [10].

Some do. Beta-blockers, used for the heart and for blood pressure, weaken the adrenergic part of the alarm. As a result, trembling and palpitations decrease, because the medicine blocks beta-adrenergic receptors. Sweating is unaffected, because it is controlled by acetylcholine, through a different nerve pathway. The alarm signal becomes weaker, not absent [13].

Taking many medicines at the same time is itself a risk factor, listed separately among the secondary factors [1]. Alcohol also increases the risk of hypoglycemia [14]. Tell your doctor everything you take, including supplements and over-the-counter medicines. You cannot spot interactions yourself just by looking at the list.

Yes. Major depression and severe mental illness are listed among the secondary risk factors, and memory problems and dementia among the major ones [1]. Depression and severe mental illness are associated with a higher risk through irregular meals, forgotten or double doses and low motivation.

Memory problems have a two-way link. They increase the risk of mistakes when taking insulin, and repeated severe hypoglycemia is in turn associated with a greater decline in mental function [15]. That is why regular memory assessment is recommended in older patients with diabetes [1].

Yes. Female sex is listed among the secondary risk factors, based on several observational studies. The mechanism is not known, and further research in this direction is needed [1].

However, the association is weaker than for the major factors and does not change practical recommendations. There is no different treatment for women and men for this reason. It is useful to know as context, not as a reason for extra worry.

Starting from three questions. Have you had a severe episode or one below 54 mg/dL (3.0 mmol/L) in recent months? Do you always notice when hypoglycemia begins? Do you have one of the conditions or situations on the list of major factors?

Add your glucose sensor reports from the last two weeks, with the time spent below the hypoglycemia threshold [10] [16]. The discussion takes place at every checkup, not only when a problem arises [1]. Its result is not a label, but a wiser choice of targets and of the technology that suits you.