Middle aged man with type 2 diabetes using blood sugar measurement device to monitor type 2 diabetes
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A research study led by Massachusetts General Hospital reveals four blood biomarkers that can help predict risk for kidney and heart disease in people with type 2 diabetes and high levels of albumin in their urine.

The study, which is published in the journal Circulation, showed that high levels of N-terminal pro–B-type natriuretic peptide (BNP); high-sensitivity cardiac troponin T; growth differentiation factor-15; and insulin-like growth factor binding protein 7 (IGFBP7) were linked to higher risk for cardiac and renal outcomes in those with type 2 diabetes and albuminuria.

The research was carried out as part of the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial. This study was designed to test the efficacy of a diabetes treatment called canagliflozin, an SGLT2 inhibitor developed by Mitsubishi Tanabe Pharma and licensed by Janssen, a division of Johnson & Johnson.

Overall, 2627 participants with type 2 diabetes and albuminuria, an early sign of kidney disease, took part in the study. Some were assigned to placebo and some canagliflozin treatment and all had the four biomarkers measured at the beginning of the study and one and three years after the study started.

The team assessed the extent to which each biomarker contributed to kidney disease and cardiovascular outcomes including: dialysis, transplantation, or a sustained low estimated glomerular filtration rate (<15 mLmin−11.73 m−2), doubling of the serum creatinine level, or renal or cardiovascular death.

At baseline, high levels of the four biomarkers predicted a worse outcome for participants. When combined together, those with high biomarker risk scores were four times more likely to experience a poor renal or a cardiovascular outcome and those with moderate biomarker risk scores had a 2.4-fold higher risk for poor outcomes compared with those with low initial scores.

Looking at the placebo group, those who had a 50% increase in N-terminal pro–BNP; high-sensitivity cardiac troponin T; and growth differentiation factor-15 at one year had 11%, 86%, and 45%, increases in primary outcome risk, respectively. Similarly, a 50% increase in IGFBP7 at one year increased the risk of a poor outcome almost fourfold.

Notably, individuals in the canagliflozin groups had significantly lower levels of the four biomarkers at year one and three than those in the placebo groups suggesting that the SGLT2 inhibitor helps keep levels of these biomarkers down.

“High levels of certain biomarkers are indicators of heart and kidney complications and may help predict future risk of disease progression,” said lead author James Januzzi, the Hutter Family Professor of Medicine at Harvard Medical School and a cardiologist at the Massachusetts General Hospital, in a press statement.

“It was reassuring to discover that canagliflozin helped reduce risks the most in people with the highest chances for complications. Future studies are needed to better understand how Type 2 diabetes in conjunction with kidney disease develops and progresses so that we may initiate life-saving therapies earlier, before symptoms of heart and kidney disease have occurred.”

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