Effect of Beta-Blockers on Glucose Metabolism and Their Use in Diabetics with Hypoglycemic Episodes

Hypo- and Hyperglycemia During Beta-Blocker Treatment

Due to their blocking effect on the sympathetic nervous system, which is activated during hypoglycemia, beta-blocker treatment through the blockade of β₁ receptors can mask symptoms of hypoglycemia such as tachycardia and tremors. The blockade of β₂ receptors leads to a reduction in the body's ability to release glucose from liver glycogen, potentially resulting in the development of hypoglycemia. In non-diabetic patients, the risk of hypoglycemia is not commonly described, but in diabetics, who are often more prone to hypoglycemia due to their antidiabetic treatment, the concurrent administration of beta-blockers further increases the risk of hypoglycemia.

In individuals with preserved pancreatic insulin secretion, β₂ receptor blockers can reduce the release of insulin from the pancreas, which can, in contrast, induce hyperglycemia through this mechanism.

Risk of Glycemic Complications Varies

The risk of developing hypoglycemia or hyperglycemia with the use of beta-blockers depends on many factors: the selectivity of the administered beta-blocker, whether the patient is diabetic with a risk of developing hypoglycemia due to antidiabetic treatment, and last but not least, the underlying condition for which the beta-blocker is being administered.

The association between beta-blockers, their selectivity, and the risk of cardiovascular events and overall mortality in patients with and without hypoglycemic episodes has been unclear until recently. An observational study published in 2019 aimed to shed some light on this issue.

Analyzed Data

The retrospective study utilized data from the UK's Clinical Practice Research Datalink and included 13,682 type 1 and type 2 diabetics treated with insulin (44.1% women, average age 64 ± 14 years). All deaths, cardiovascular events, and hypoglycemic episodes were recorded to evaluate their association with beta-blocker therapy and their selectivity.

Findings

In the entire cohort of included patients, 2036 (14.9%) had at least one hypoglycemic episode. During the follow-up period, which averaged 4.65 years for those without hypoglycemia and 2.34 years for those with hypoglycemia, there were 3148 deaths and 1235 cardiovascular events; beta-blocker treatment did not lead to an increased risk of death.

After adjustment and inclusion of missing data, higher mortality risk was observed in patients treated with non-selective beta-blockers and without hypoglycemia compared to those not treated with beta-blockers; this relationship wasn’t observed in patients with hypoglycemia, and the association was not statistically significant.

Use of selective β₁ blockers was associated with a lower risk of death in patients with hypoglycemia. The association of beta-blocker therapy with the risk of hypoglycemia, cardiovascular events, and modification of this association by hypoglycemia was not proven.

Conclusion

The data suggest that in diabetics without hypoglycemic episodes, treatment with non-selective beta-blockers might increase the risk of death, whereas treatment with selective β₁ blockers in diabetics with hypoglycemia might reduce this risk. However, these results need to be verified in further studies.

The impact of beta-blockers on glucose levels has been epidemiologically proven several times, and if these substances are appropriate for use in diabetic patients, cardioselective β₁ blockers should be preferred. Regular monitoring of glucose levels and observing for hypoglycemia symptoms are also important.

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Source: Zaccardi F., Nystrup Husemoen L. L., Thorsted B. L. et al. Selectivity of beta-blockers, cardiovascular and all-cause mortality in people with hypoglycaemia: an observational study. Nutr Metab Cardiovasc Dis 2019 May; 29 (5): 481−488, doi: 10.1016/j.numecd.2019.01.006.