Hypoglycemia: Numbers remain unchanged in recent years

Hypoglycemia in diabetes types 1 and 2 patients has not decreased in recent years despite numerous improvements. The role of C-peptide in hypoglycemia and modern techniques to prevent it were discussed.

Focus on C-peptide and modern prevention strategies

Hypoglycemia in patients with diabetes mellitus types 1 and 2 has not decreased in recent years despite numerous improvements. The role of C-peptide in hypoglycemia and the use of modern techniques to prevent it were highlighted by speakers at a symposium during the virtual annual conference of the European Association for the Study of Diabetes in September 2020.

Paul McKeigue (Institute of Genetics and Molecular Medicine, Edinburgh, Scotland) reported results from the Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) health care record data. 6,076 type-1 diabetics were followed up for over 5.2 years on average. C-peptide and autoantibodies were measured at the start of the study. Patients were tracked using electronic records, which included HbA1c, BMI, hospital admissions, and retinopathy screening.

The study participants were of a wide range of ages and had a wide range of diabetes duration. The results show that C-peptide levels only decrease slowly in people with diabetes that starts at an older age, while they decrease rapidly in young patients who get diabetes at an age below 15 years.

Younger patients with long-term diabetes in particular reported a hypoglycemia cognitive dysfunction. Patients with hypoglycemia in need of help were significantly less likely to have hypoglycemia, even below 30 pmol/l, and hospital stays for hypoglycemia were less frequent with low C-peptide levels. So C-peptide seems to protect against hypoglycemia even at low concentrations, concluded McKeigues. The study also found that C-peptide seems to protect patients from retinopathy to some extent.

In contrast, the C-peptide had no effect on hospitalizations for ketoacidosis. C-peptide seems to have a protective effect only at high levels.

Advantages and limitations of modern techniques

Several factors can reduce the risk of hypoglycemia. These include better medication with modern insulin and oral substances and (new) glucagon preparations. New techniques for glucose monitoring, insulin administration, and dose calculation can also help. Training and information for patients are still very important. Julia Mader (Medical University Hospital Graz, Austria) discussed the advantages and disadvantages of new techniques and new medications.

Continuous glucose monitoring (CGM)

CGM can be used to record periods when glucose concentrations are outside the desired range. For example, it can provide insight into the body's response to food intake and insulin injections, detect excessive intervals between injections, and can also detect nocturnal hypoglycemia. However, the glucose concentration is not measured in the blood but in the interstitial fluid. The advantage of the procedure is that it also works without any problems when doing sports, at work, or when traveling.

However, a study carried out in a summer camp with 37 diabetic children aged 11 years showed that the various systems functioned inaccurately, especially below 3.9 mmol/l. Another study of 15 patients with diabetes mellitus type 1 showed that the sensor gave 8% higher values for euglycemia and 19% higher values for hypoglycemia. Accuracy is, however, what users are most likely to expect from CGM.

A study of 3,553 children with type 1 diabetes found that ketoacidosis and severe hypoglycemia were significantly less common 6 and 12 months after starting CGM.

So CGM works, but it requires careful training of the users, who often have unrealistic expectations. In addition, wrong values have to be expected. Carbohydrates still have to be counted.

Insulin pumps

According to the results of a meta-analysis, severe hypoglycemia was 75% less common with insulin pump therapy than with insulin injections several times a day. Postprandial hypoglycemia can be reduced with smart bolus calculators.

Users of insulin pumps must also be trained very carefully and carbohydrates must continue to be counted.

Artificial pancreas

In a closed-loop system of glucose meter and insulin pump, the pump automatically throttles and increases insulin delivery based on the measured glucose values. These systems can significantly reduce the duration of hypoglycemia. Hybrid systems allow users to administer an additional dose of insulin before a meal.

Mader sees uncertainties in the price and availability in the market. The systems require very careful training of the users and still require carbohydrate counting.

New glucagon preparations

Lyophilized glucagon for parenteral use poses a challenge in its application, especially under emergency conditions. Simulation tests have shown that even trained nurses only manage to administer the full dose to the patient in 13% of cases. In 50% of the cases, it was not possible to administer glucagon to the patients at all. The failure rate is even higher among untrained helpers, where the failure rate is 80%, the remaining 20% even managed to administer only a partial dose of glucagon.

The test results with nasally applied glucagon are clearly more favorable. Here, nurses manage to give the full dose in 94% of cases, unskilled helpers manage to do so in 93% of cases. In addition, the application is much faster than with parenteral glucagon

Mader sees pricing and availability in the market as possible hurdles for their application.

Symposium "Assessing the true burden of hypoglycemia", Virtual EASD Annual Meeting 2020. S41