Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Dec 15;12(12):2036-2049.
doi: 10.4239/wjd.v12.i12.2036.

Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention

Afif Nakhleh  1 , Naim Shehadeh  2
Affiliations
Review

Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention

Afif Nakhleh et al. World J Diabetes. .

Abstract

Hypoglycemia is a common complication in patients with diabetes, mainly in those treated with insulin, sulfonylurea, or glinide. Impairments in counterregulatory responses and hypoglycemia unawareness constitute the main risk factors for severe hypoglycemia. Episodes of hypoglycemia are associated with physical and psychological morbidity. The fear of hypoglycemia constitutes a barrier that impairs the patient's ability to reach good glycemic control. To prevent hypoglycemia, much effort must be invested in patient education regarding risk factors, warning signs, and treatment of hypoglycemia at an early stage, together with setting personalized goals for glycemic control. In this review, we present a comprehensive update on the treatment and prevention of hypoglycemia in type 1 and type 2 diabetic patients.

Keywords: Continuous glucose monitoring; Diabetes mellitus; Glucagon; Glucose; Hypoglycemia; Insulin.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest statement: The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Percentage of severe hypoglycemic events in ACCORD, ADVANCE, and VADT. Adapted from Frier et al[8] with permission from the American Diabetes Association. Citation: Frier BM, Schernthaner G, Heller SR. Hypoglycemia and cardiovascular risks. Diabetes Care 2011; 34 Suppl 2: S132-S137. Copyright ©The American Diabetes Association.
Figure 2
Figure 2
Putative mechanisms of hypoglycemia unawareness. Recurrent hypoglycemia results in a reduced autonomic response to hypoglycemia with attenuation of autonomic warning symptoms. The maladaptive response in the brain is characterized by increased glucose transporter 1 (GLUT1) activity in a bid to preserve brain function and alter glucose sensing in the ventromedial hypothalamus (VMH), mediated by elevated levels of gamma aminobutyric acid (GABA). Adapted from Iqbal et al[12] with permission from Elsevier. Citation: Iqbal A, Heller S. Managing hypoglycaemia. Best Pract Res Clin Endocrinol Metab 2016; 30: 413-430. Copyright © Elsevier.
Figure 3
Figure 3
Mechanisms by which hypoglycemia may affect cardiovascular events. Hypoglycemic events may induce inflammation by stimulating the release of C-reactive protein (CRP), IL-6, and vascular endothelial growth factor (VEGF). Hypoglycemia also increases the activation of platelets and neutrophils. Sympathoadrenal response during hypoglycemia increases adrenaline release and may lead to arrhythmias and increased cardiac workload. Endothelial dysfunction may also contribute to cardiovascular risk. Adapted from Desouza et al[25] with permission from the American Diabetes Association. Citation: Desouza CV, Bolli GB, Fonseca V. Hypoglycemia, diabetes, and cardiovascular events. Diabetes Care 2010; 33: 1389-1394. Copyright ©The American Diabetes Association.
Figure 4
Figure 4
Algorithm of the approach to hypoglycemia. CGM: Continuous glucose monitoring; SMBG: Self-monitoring of blood glucose. Adapted from Blumer et al[57] with permission from Elsevier. Citation: Blumer I, Clement M. Type 2 Diabetes, Hypoglycemia, and Basal Insulins: Ongoing Challenges. Clin Ther 2017; 39: S1-S11. Copyright © Elsevier.
See this image and copyright information in PMC

References

    1. Pettus JH, Zhou FL, Shepherd L, Preblick R, Hunt PR, Paranjape S, Miller KM, Edelman SV. Incidences of Severe Hypoglycemia and Diabetic Ketoacidosis and Prevalence of Microvascular Complications Stratified by Age and Glycemic Control in U.S. Adult Patients With Type 1 Diabetes: A Real-World Study. Diabetes Care. 2019;42:2220–2227. - PubMed
    1. Gangji AS, Cukierman T, Gerstein HC, Goldsmith CH, Clase CM. A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin. Diabetes Care. 2007;30:389–394. - PubMed
    1. Thrasher J. Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies. Am J Med. 2017;130:S4–S17. - PubMed
    1. . Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854–865. - PubMed
    1. ACCORD Study Group , Buse JB, Bigger JT, Byington RP, Cooper LS, Cushman WC, Friedewald WT, Genuth S, Gerstein HC, Ginsberg HN, Goff DC Jr, Grimm RH Jr, Margolis KL, Probstfield JL, Simons-Morton DG, Sullivan MD. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Am J Cardiol. 2007;99:21i–33i. - PubMed