medwireNews: The risk for adverse cardiorenal events begins to increase well below the glycemic level associated with type 2 diabetes, with the largest proportion of events occurring in people with prediabetic levels, shows a UK Biobank analysis.
There was “a substantial gradient of risk” across glycated hemoglobin (HbA1c) levels, with the lowest risk seen below 5.0% (31 mmol/mol), report Michael Honigberg (Massachusetts General Hospital, Boston, USA) and co-workers.
They say: “These findings lend support to the notion that prevention strategies targeting pre-diabetic individuals should include comprehensive and aggressive [cardiovascular disease] risk factor modification, not simply interventions to prevent glycemic progression from prediabetes to [type 2 diabetes].”
After accounting for demographics and other variables, the risk for atherosclerotic cardiovascular disease (ASCVD) significantly rose from within the normal glycemic range, starting from an HbA1c of 5.4% (36 mmol/mol), and the risk for chronic kidney disease (CKD) rose from within the prediabetic range, starting at 6.2% (44 mmol/mol).
Only heart failure risk remained relatively low within the prediabetic range, with risk for this outcome significantly increasing from an HbA1c of 7.0% (53 mmol/mol).
“HbA1c may be better considered as a continuous measure of risk, rather than dichotomized” at 6.5% (48 mmol/mol), say the researchers.
The team followed up 336,709 people from the UK Biobank (average age 56 years, 55% women) who did not have ASCVD, CKD, or heart failure at baseline. Of these people, 82.3% had normal baseline HbA1c levels, 13.9% were in the prediabetic range, and 3.8% had type 2 diabetes.
Over a median 11.1 years of follow-up, an outcome event occurred in 7.9%, 13.8%, and 23.7% of these groups, respectively. However, owing to the larger absolute number of people with prediabetes than type 2 diabetes, the population attributable risk proportions were greater for the former than the latter for both ASCVD and HF, at 8.1% versus 5.9% and 9.9% versus 7.1%, respectively. The corresponding values for CKD were 9.8% and 10.5%.
These findings bolster “evidence that pre-diabetes represents a relevant entity among middle-aged individuals,” write the researchers in the Journal of the American College of Cardiology.
The analysis was based on glycemic status at enrollment and Honigberg and team stress that only 12.4% of people with prediabetes who had a cardiorenal event had progressed to type 2 diabetes by the time of that event, and less than a third progressed at any time during follow-up.
Their analysis also identified a high-risk subgroup of people with prediabetes, comprising people who were also current or former smokers or had high levels of systolic blood pressure, non-high-density lipoprotein cholesterol, or C-reactive protein. These people accounted for 6% of those with prediabetes.
In the cohort overall, having a first cardiorenal event markedly increased the risk for a second, and the researchers add that “the time to a second event was short irrespective of baseline glycemic status, with many experiencing a second event within the subsequent year.”
They conclude: “These findings highlight the importance of both comprehensive primary prevention as well as rapid implementation of secondary prevention measures once cardiovascular or kidney disease is diagnosed, including consideration of [sodium-glucose cotransporter 2] inhibitors and [glucagon-like peptide-1 receptor agonists] in eligible at-risk individuals.”
The findings were also presented at the virtual American College of Cardiology 70th Annual Scientific Session.
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