In a new study, patients with type 1 diabetes and a glycated hemoglobin level of 6.9% or lower (≤52 mmol per mole) were found to have a risk of death from any cause or from cardiovascular causes that was twice as high as that for matched controls.
The excess risks of death from any cause and from cardiovascular causes in patients with diabetes who have varying degrees of glycemic control, as compared with the risks in the general population, have not been evaluated. This study undertook an evaluation using the Swedish National Diabetes Register, which includes information on glycemic control for most adults with type 1 diabetes in Sweden.
• Why is glycemic control important for patients with type 1 diabetes?
Type 1 diabetes is associated with a substantially increased risk of premature death as compared with that in the general population. Among persons with diabetes who are younger than 30 years of age, excess mortality is largely explained by acute complications of diabetes, including diabetic ketoacidosis and hypoglycemia; cardiovascular disease is the main cause of death later in life. Improving glycemic control in patients with type 1 diabetes substantially reduces their risk of microvascular complications and cardiovascular disease. Accordingly, diabetes treatment guidelines emphasize good glycemic control, which is indicated by the glycated hemoglobin level, a measure of the mean glycemic level recorded during the preceding 2 to 3 months. Although a target level of less than 7.0% (53 mmol per mole) is generally recommended and is considered to be associated with a lower risk of diabetic complications, as compared with higher levels, in two national registries, only 13 to 15% of patients with type 1 diabetes met this target, whereas more than 20% had very poor glycemic control (i.e., a glycated hemoglobin level >8.8%, or greater than or equal to 73 mmol per mole).
• What is the risk of all-cause and cardiovascular mortality at different levels of HbA1c?
This nationwide Swedish study of 33,915 patients with type 1 diabetes and 169,249 controls matched for age and sex shows that for patients with type 1 diabetes who had on-target glycemic control, the risk of death from any cause and the risk of death from cardiovascular causes were still more than twice the risks in the general population. Analyses of outcomes within the group of patients with diabetes showed that the risk of death from any cause and the risk of death from cardiovascular causes increased incrementally with higher updated mean glycated hemoglobin levels. The hazard ratio for death from any cause among patients with diabetes was 2.36 (95% CI, 1.97 to 2.83) at an updated mean glycated hemoglobin level of 6.9% or lower and increased to 8.51 (95% CI, 7.24 to 10.01) for a level of 9.7% or higher (greater than or equal to 83 mmol per mole). For death from cardiovascular causes, the corresponding hazard ratios ranged from 2.92 (95% CI, 2.07 to 4.13) to 10.46 (95% CI, 7.62 to 14.37).
Table 3. Adjusted Hazard Ratios for Death from Any Cause and Death from Cardiovascular Causes among Patients with Type 1 Diabetes versus Controls, According to Time-Updated Mean Glycated Hemoglobin Level and Renal Disease Status, Model 3.
Morning Report Questions
Q: How does the risk of all-cause or cardiovascular mortality differ by gender or change over time?
A: As compared with men, women with type 1 diabetes had a significantly greater excess risk of death from cardiovascular disease but not of death from any cause. The excess risk of death associated with diabetes did not diminish over time, with increases during the last 7 calendar years of the study (2005 through 2011) that were similar to those during the first 7 years (1998 through 2004).
Q: Is there an explanation for the increased risk of all-cause and cardiovascular mortality in type 1 diabetes patients with HbA1c less than or equal to 6.9%?
A: Unlike patients with type 2 diabetes, those with type 1 diabetes generally do not have excess rates of obesity, hypertension, or hypercholesterolemia; thus, the increased risks of death from any cause and of death from cardiovascular causes among patients with type 1 diabetes who have good glycemic control is unexplained. In this study, beginning with the year 2005, patients with type 1 diabetes were four to five times as likely as controls to receive a prescription for statins or renin-angiotensin-aldosterone system inhibitors. Thus, the omission of currently recommended cardioprotective treatment cannot explain the remaining excess risk of death; determination of the underlying reasons will require further research.