Hypoglycemia Risk Factors

Detailed Information

Background

The physiological response to decreasing PG concentrations in a healthy individual include

• a decrease in insulin secretion from the β-cell, and

• an increase in glucagon secretion from the α-cell.¹

In the case of β-cell failure in T1DM and advanced T2DM, a decrease in PG does not result in a decrease in insulin secretion from the β-cell. The absence of this signal results in no increase in glucagon secretion from the pancreatic α-cell during hypoglycemia.^1,2

Hypoglycemia is common in individuals treated with exogenous insulin and insulin secretagogues that increase insulin concentrations regardless of the PG concentration.^1-3

Figure 1. Severe Hypoglycemia is a Risk in All Individuals on Insulin, Regardless of the Type of Diabetes^1,2

Abbreviations: T1D = type 1 diabetes; T2D = type 2 diabetes.

Hypoglycemia Risk Factors

Iatrogenic hypoglycemia in diabetes is related to 

• conventional risk factors of therapeutic hyperinsulinemia, or

• risk factors due to compromised hypoglycemia defenses against falling plasma glucose concentrations.^1,3

Conventional risk factors for hypoglycemia include

• wrong dose, type, or dose timing of insulin, SUs, or glinides

• decrease in exogenous glucose delivery due to a missed meal or fasting

• decrease in endogenous glucose production, such as after alcohol intake

• increase in glucose utilization, for example after exercise

• increase in insulin sensitivity experienced late after exercise or with weight loss, and 

• decrease in insulin clearance as a result of renal failure, hepatic failure, hypothyroidism, high level of insulin-binding antibodies.³

Risk factors due to compromised hypoglycemia defenses include

• absolute endogenous insulin deficiency yielding loss of the glucagon response

• history of severe hypoglycemia, impaired awareness, or both, known as hypoglycemia-associated autonomic failure, and 

• intensive glycemic therapy and lower glycemic goal.³

References

1. Cryer PE. Minireview: glucagon in the pathogenesis of hypoglycemia and hyperglycemia in diabetes. Endocrinology. 2012;153(3):1039-1048. http://dx.doi.org/10.1210/en.2011-1499

2. McCrimmon RJ, Sherwin RS. Hypoglycemia in type 1 diabetes. Diabetes. 2010;59:2333-2339. http://dx.doi.org/10.2337/db10-0103

3. International Hypoglycaemia Study Group. Minimizing hypoglycemia in diabetes. Diabetes Care. 2015;38(8):1583-1591. http://dx.doi.org/10.2337/dc15-0279

Glossary

PG = plasma glucose

T1DM = type 1 diabetes mellitus

T2DM = type 2 diabetes mellitus