Victor W. Zhong
Among patients with type 1 diabetes, each 1% increase in HbA1c variability nearly doubled the risk for first hypoglycemia hospitalization and was associated with nearly four times higher risk for recurrent hypoglycemia hospitalization. Among those with type 2 diabetes, those risks increased more than fivefold, according to findings from a nested, case-control study.
“HbA1c has been associated with severe hypoglycemia, although the shape of the association remains controversial,” Victor W. Zhong, PhD, a postdoctoral fellow with the Gillings School of Public Health at the University of North Carolina, Chapel Hill, and colleagues wrote. “However, the data regarding the association between HbA1c variability and severe hypoglycemia are limited and inconsistent.”
Zhong and colleagues analyzed data from patients admitted to the hospital for either first or recurrent hypoglycemia, using primary care data from the Clinical Practice Research Database and linked secondary care data from the Hospital Episode Statistics in the United Kingdom. Cases included 193 patients with type 1 diabetes admitted to the hospital for a first hypoglycemia event and 41 patients with type 1 diabetes admitted for recurrent hypoglycemia. In patients with type 2 diabetes, researchers analyzed 1,361 cases of first hypoglycemia hospitalization and 178 cases of recurrent hypoglycemia hospitalization. All cases were age-, sex- and weight-matched with controls who had diabetes but had not experienced a hypoglycemia hospitalization. For type 2 diabetes, cases and controls were also matched according to current use of insulin and other glucose-lowering drugs. HbA1c variability was determined by standard deviation of at least three HbA1c results. Researchers applied conditional logistic models to determine association of HbA1c variability with first and recurrent hospitalization for hypoglycemia.
For patients with type 1 diabetes, researchers observed a linear association between HbA1c variability and first or recurrent hypoglycemia hospitalization. Every 1% increase in HbA1c variability was associated with a 90% higher risk for a first hypoglycemia hospitalization (OR = 1.9; 95% CI, 1.25-2.89), whereas the risk for recurrent hypoglycemia hospitalization was increased by 392% (OR = 4.92; 95% CI, 1.17-20.61). After adjusting for mean HbA1c, risk fell for both first hospitalization (OR = 1.77; 95% CI, 1.15-2.73) and recurrent hypoglycemia hospitalization (OR = 2.75; 95% CI, 0.59-12.71).
In adults with type 2 diabetes, each 1% increase in HbA1c variability was associated with 556% higher risk for first hospitalization for hypoglycemia (OR = 6.56; 95% CI, 3.88-11.08) and a 573% increased risk for recurrent hospitalization for hypoglycemia (OR = 6.73; 95% CI, 1.59-28.51). After adjusting for mean HbA1c, risk among those with type 2 diabetes also fell for both first hospitalization (OR = 4.48; 95% CI, 2.54-7.88) and recurrent hypoglycemia hospitalization (OR = 2.94; 95% CI, 0.6-14.49).
In adults with type 2 diabetes, researchers noted a stronger association between HbA1c variability and first hypoglycemia hospitalization in patients not using insulin or sulfonylureas, whereas the association was similar between current insulin and sulfonylurea users (P < .0001). For recurrent hospitalization for hypoglycemia, there was a stronger association observed in insulin users vs. sulfonylurea users (P = .07).
“HbA1c variability may be an important target for hypoglycemia prevention and management in [type 1 diabetes] and [type 2 diabetes], in addition to HbA1c,” the researchers wrote. “Preventing first hypoglycemia hospitalization is important because the association between HbA1c variability and hypoglycemia hospitalization was strengthened among those with previous hospitalization for hypoglycemia, particularly in insulin users regardless of diabetes type.”
As Endocrine Today has previously reported, Zhong and colleagues’ related research found that hospitalizations for hypoglycemia increased in England by roughly 4% among adults with type 1 diabetes and young and middle-aged adults with type 2 diabetes from 1998 to 2013; however, that trend reversed in older adults with type 2 diabetes beginning in 2009. Overall, 1,591 hypoglycemia hospitalizations occurred during 121,262 follow-up years in participants with type 1 diabetes, 553 occurred during 560,686 person-years of follow-up in young and middle-aged adults with type 2 diabetes, and 3,185 occurred during 784,132 person-years of follow-up in older adults with type 2 diabetes.
“When designing glucose-lowering therapies for individuals with diabetes, physicians need to consider the influence of the designated therapies on HbA1c variability, particularly for people who are already at high risk of developing severe hypoglycemia,” Zhong told Endocrine Today. “Our findings imply that the goal of reducing or minimizing HbA1c variability needs to be personalized, because our study revealed differential association of HbA1c variability with hypoglycemia hospitalization between type 1 and type 2 diabetes and between users with different glucose-lowering drugs.” – by Regina Schaffer
For more information:
Victor W. Zhong, PhD, can be reached at Northwestern University Feinberg School of Medicine, Department of Preventive Medicine, 680 N Lake Shore Dr, Suite 1400, Chicago, IL 60611; email: firstname.lastname@example.org.
Disclosures: Zhong reports he has received financial support from the Sanofi Global Nutrition Scholars program; another researcher is an employee of Sanofi U.S.