Type 2 diabetes patients with mild to moderate chronic kidney disease (CKD) are at 2 to 3 times higher cardiovascular risk than diabetes patients without CKD, according to a new analysis of the landmark Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Furthermore, tight glucose control substantially increases both cardiovascular and all-cause mortality among diabetics with CKD stage 1 to 3.

“To our knowledge, this is the first report to show that aggressive glucose control is detrimental in patients with mild and moderate CKD,” revealed Vasilios Papademetriou, MD, of Veteran Affairs Medical Center and Georgetown University in Washington DC, and colleagues. “It is of paramount importance, therefore, that CKD status be established in all newly diagnosed and existing diabetic patients and be taken into account in tailoring hypoglycemic therapy.”

The original ACCORD trial of more than 10,000 diabetes patients found intensive glucose lowering (hemoglobin A1c below 6%) increased cardiovascular and all-cause mortality. To assess the contribution of mild to moderate CKD, the investigators involved in the current study stratified patients by kidney function. More than 3,600 patients met criteria for CKD stages 1 to 3 (patients with stage 4 and 5 CKD were excluded from ACCORD).

Compared with diabetes patients without CKD, the combined risk of non-fatal heart attack, stroke, and cardiovascular death was 87% higher in patients with mild to moderate CKD, according to results published online ahead of print in Kidney International. The risks of all-cause and cardiovascular mortality and related outcomes were 1.5 to 3 times more frequent.

Intensive glucose-lowering was significantly associated with 31% higher all-cause mortality and 41% higher cardiovascular mortality. These results were in line with recent findings from a large Canadian study of diabetes patients with CKD. Diabetic patients without CKD, even if intensively treated, did not appear to carry the same risks.

Hypoglycemia has been linked to increased mortality. In the current study, investigators found hypoglycemia was both more frequent and more severe in CKD patients.

The higher rate of hypoglycemia may be due to prolonged exposure to insulin and oral hypoglycemic agents, they noted. Other possibilities include adverse medication effects. Twice the percentage of CKD patients in the intensive glycemic control group were taking 3or more of these medications compared with the standard therapy group. Insulin was also used in higher dosages in diabetics with CKD.

“These findings underscore the special attention that is needed for the proper and safe management of diabetes in patients with CKD,” according to the researchers.

Although this post hoc study is hypothesis-generating, it signals that new clinical approaches are needed to alter the cardiovascular risks of diabetic CKD patients.

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