medwireNews: Researchers have identified 24 clinical and lifestyle variables associated with a significantly increased risk for severe hypoglycemia among people using insulin for type 2 diabetes.
“Scrutiny of current therapies and comorbidities are advised in addition to additional glucose monitoring and education, when identifying and managing [severe hypoglycemia] in vulnerable populations,” Julie Settles (Eli Lilly and Company, Indianapolis, Indiana, USA) and co-authors remark.
Using an administrative healthcare claims database, Settles and team identified 3153 adults with type 2 diabetes who developed severe hypoglycemia that required emergency medical care after initiating insulin. Each of these individuals was matched to a control on the basis of age, sulfonylurea use, prior severe hypoglycemia, renal disease, and insulin exposure time.
The participants had a median age of 57 years, just over half were men (52% of cases and 55% of controls), and the mean time “at risk” before the first severe hypoglycemia event was 11.2 months.
The researchers report in Diabetes, Obesity and Metabolism that pregnancy in the previous 6 months was the strongest risk factor for severe hypoglycemia, at an odds ratio (OR) of 3.20, followed by alcohol abuse, at an OR of 2.43.
Individuals using short-acting insulin were a significant 2.22 times more likely to experience severe hypoglycemia than those using other types of insulin, while rapid-acting insulin users had a significant 1.47-fold increased risk.
Current use (within 1 month of the hypoglycemia event) of several comedications was independently associated with a significantly increased risk for severe hypoglycemia, including antipsychotics (OR=1.59), anxiolytics (OR=1.51), β-adrenoceptor agonists (OR=1.40), opioids (OR=1.38), and corticosteroids (OR=1.35).
In addition, long-term use (2–6 months exposure prior to hypoglycemia) of adrenergic-corticosteroid combinations was associated with a 1.45-fold increased risk whereas long-term β-adrenoceptor agonist use was associated with a decreased risk (OR=0.78).
Individuals currently using non-insulin glucose-lowering medications also had a significantly lower risk for severe hypoglycemia relative to people not taking these drugs, at an OR of 0.81.
The investigators found that comorbidity was another risk factor for severe hypoglycemia, at ORs of 1.28, 1.41, and 1.57 for individuals with Charlson Comorbidity Index scores of 2, 3, and 4 or higher, respectively, relative to those with a score of 0 or 1.
Among individual comorbidities, cancer (OR=1.87), dementia or Alzheimer's disease (OR=1.73), peripheral vascular disease (OR=1.59), paralysis, hemiplegia, or paraplegia (OR=1.51), hepatitis (OR=1.50), congestive heart failure (OR=1.47), cardiac arrhythmia (OR=1.29), liver/gallbladder/pancreatic disease (OR=1.26), and hypertension (OR=1.19) were each independently associated with a significantly increased hypoglycemia risk.
Finally, smoking conferred a significant 1.28-fold increased risk for severe hypoglycemia.
Based on their findings, Settles et al conclude that “clinicians should take a detailed clinical history that includes documentation of comorbid conditions occurring during the previous six months and either recent or current medication usage, if they are to identify ‘high-risk’ patients.”
They add: “Therapeutic regimens and individualised targets may have to be modified in the presence of factors highlighted in the present study.”
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