Severe hypoglycemia in type 2 diabetes patients treated with standard therapy for blood glucose control is associated with the progression of coronary artery calcium (CAC), which increases the risk of a heart attack, according to a new study.
A small study conducted by the Pheonix VA Health Care System, United States aimed to determine if a relationship exists between severe hypoglycemia and the progression of atherosclerosis, a disease where arteries become clogged up by fatty substances.
Using a substudy of the Veterans Affairs Diabetes Trials (VADT), the glycemic control of 197 participants with type 2 diabetes was evaluated to assess if it influenced the relationship between severe hypoglycemia and CAC. People with higher measurements of CAC, and therefore increased atherosclerosis, have a higher risk of suffering a heart attack or stroke.
The progression of CAC was determined in patients using computed tomography scans. Scans were conducted before the study and during follow-up – the average follow-up time between the scans was 4.6 years.
Patients were assigned either standard or intensive treatment for glycemic control. The standard group were treated with 500 mg of metformin, 4mg of rosiglitazone, 2mg of glimepiride and one unit of insulin per nine pounds of body weight. Their aim was to maintain HbA1c between 64-75 mmol/mol (8-9 per cent).

The intensive treatment group had to aim to keep their HbA1c lower than 42 mmol/mol (6.0 per cent) and were treated with 500mg of metformin (up to 2000mg), 4mg of rosiglitazone, 8mg of glimepiride and one unit of insulin per nine pounds of body weight.
97 participants experienced one of more severe hypos; occurring in 74 per cent in the intensive treatment group and 21 per cent of the standard therapy group. The authors defined severe hypoglycemia “as severe episodes with loss of consciousness or requiring assistance or documented glucose Study findings
Severe hypos were not linked to CAC progressio, but an interaction was observed between severe hypos and treatment type. Patients treated with standard therapy who had a severe hypo had greater CAC progression compared to those who didn’t have a severe hypo. This relationship remained after adjustments for differences between patients with and without severe hypos.
In both treatment groups, greater CAC progression was found in participants with a mean HbA1c of 58.5 mmol/mol (7.5 per cent) or over who had experienced severe hypoglycemia. Higher HbA1c was associated with CAC progression among severe hypo patients, but not in those who did not experience a severe hypo. In the standard therapy group, CAC progression increased with increasing incidences of severe hypoglycemia.
The researchers concluded: “This study shows that serious hypoglycemia is associated with increased progression of [coronary artery calcium] in patients undergoing standard therapy for glycemic control and in those with higher HbA1c (> 7.5%) during the VADT, despite a nearly threefold higher frequency of serious hypoglycemia with intensive therapy.
“The results may provide additional insights into long-term cardiovascular benefits of intensive glycemic control and support the importance of avoiding hypoglycemia, particularly in elderly patients with long-standing, poorly controlled type 2 diabetes.”
Editor of, Benedict Jephcote said: “The results show that those at greatest risk of CAC, and therefore heart disease and stroke, were those with relatively poorly controlled diabetes despite being on strong medication, glimepiride and insulin, which can induce hypos.
“The study did not look into how the risk of heart disease and stroke could best be prevented but it is likely that a stronger focus on improving diet and physical activity, with close review of medication doses, would help lower the heart and stroke risk.”
The findings appear in Diabetes Care.

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