medwireNews: A randomized crossover trial shows that both hypoglycemia and rebound hyperglycemia trigger persistent increases in left ventricular (LV) function in people with type 1 diabetes.
“An increase in LV systolic function may increase cardiac workload and partly explain the link between hypoglycaemia, high glycaemic variability, and CVD [cardiovascular disease],” suggest Tina Vilsbøll (Steno Diabetes Center Copenhagen, Denmark) and co-researchers.
They acknowledge that an increase in LV function during high-intensity exercise is positive and has been shown to be cardioprotective in people with CVD. Conversely, they note that a usual LV ejection fraction (EF) above 65% was associated with increased mortality in a recent study.
“Exposure to low stress levels likely leads to protective and beneficial responses, while exposures to high levels (and frequent elevated LVEF) are damaging and detrimental,” the team speculates.
Their study involved 24 people with type 1 diabetes (57% women) who were an average age of 52 years and had an average glycated hemoglobin level of 7.4% (57 mmol/mol). About half had microvascular complications and a quarter had impaired awareness of hypoglycemia.
All participants were given a continuous glucose monitor, and the study procedures were postponed if level 2 hypoglycemia (<3.0 mmol/L, 54 mg/dL) had occurred in the previous 48 hours.
On the study days, participants received infusions of insulin and glucose to achieve a 45-minute phase of hyperinsulinemia but normal blood glucose levels, after which hyperinsulinemia was continued for 60 minutes but their blood glucose was allowed to dip below 2.5 mmol/L, 45 mg/dL.
The researchers assessed four measures of LV systolic function – LVEF, global longitudinal strain (GLS), GLS rate, and peak systolic velocity of the mitral annulus – and found that all four significantly increased during the hypoglycemic phase, along with systolic blood pressure and heart rate.
The hypoglycemic clamp phase was followed by a 60-minute recovery phase in which the participants were randomly assigned to have blood glucose held either in the hyperglycemic range (average 20.1 mmol/L, 362 mg/dL) or in euglycemia (average 6.7 mmol/L, 121 mg/dL). After a 30-day break, the whole procedure was repeated with the alternative recovery condition.
All measures of LV function remained elevated during the recovery phase if blood glucose was hyperglycemic, and even in euglycemia LVEF and GLS remained high relative to at baseline. For example, LVEF averaged 58.5–59.2% at baseline and 65.0–65.7% during hypoglycemia, but 63.5% and 61.5% during recovery in hyperglycemia and euglycemia, respectively.
Systolic blood pressure and heart rate returned to baseline values during recovery, however.
Writing in Diabetes, Obesity and Metabolism, Vilsbøll and team speculate that increases in LVEF “may mask heart failure” and result in treatment delays.
“Thus, clinicians should be aware of the risk of falsely elevated LVEF in patients with type 1 diabetes,” they conclude.
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Diabetes Obes Metab 2022; doi:10.1111/dom.14790