Intensive glucose control in elderly T2DM patients may do more harm than good

In older adults with type 2 diabetes mellitus (T2DM), glucose control appears to influence survival such that both high and low glycated haemoglobin values are associated with increased risk of all-cause mortality, as shown in a study from Hong Kong. More importantly, very low HbA1c levels (<6.0 percent) pose the highest risk increase.

“The findings in the present study highlighted the complex nature of T2DM management for community-dwelling elderly [patients] who might benefit from less stringent glycaemic treatment targets and more individualized care. These have clinical implications on our daily practice,” the authors said.

“[P]rimary care physicians may consider tapering down oral hypoglycaemic agents (ie, sulphonylureas) when glycaemic target of HbA1c <6.5 percent is reached for those aged ≥65 years, especially for those with previous smoking status, lower body mass indices (BMIs) and higher low-density lipoprotein cholesterol (LDL-C) levels,” they added.

The current analysis included 344 deceased elderly T2DM patients (mean age, 78.47 years; 57.5 percent male) and 344 matched alive controls. Deaths had been attributed to ischaemic heart disease in 14.5 percent of patients, cerebrovascular events in 6.4 percent and noncardiovascular-related causes (eg, chest infection, sepsis, malignancy) in 69.4 percent. Renal and heart failures together accounted for 8.8 percent of the mortality.

Compared with controls, the deceased patients tended to have longer diabetes duration (mean, 10.2 vs 9.0 years; p=0.066) and were more likely to be smokers/ex-smokers (p=0.003), have a prior history of ischaemic heart disease (p<0.001), have lower BMIs (p=0.000) but higher LDL-C levels (p=0.001). There were no obvious differences in drug profiles, except that more deceased patients than controls used sulphonylureas (p=0.039). Both patient groups had similar mean HbA1c values (6.75 percent vs 6.84 percent).

Logistic regression models using HbA1c 6.5–8.0 percent as the reference category revealed that elevated HbA1c levels (>8 percent) were associated with an 88-percent higher likelihood of all-cause death (odds ratio [OR], 1.88, 95 percent confidence interval [CI], 1.13–3.13). The OR associated with HbA1c levels <6.5 percent was much higher at 1.94 (95 percent CI, 1.41–2.68). [Prim Care Diabetes 2020;doi:10.1016/j.pcd.2020.02.012]

Looking at the low ends of HbA1c range, the risk of all-cause mortality was modestly elevated at HbA1c 6.0–6.4 percent (OR, 1.39, 95 percent CI, 0.95–2.04) but increased threefold at <6.0 percent (OR, 3.03, 95 percent CI, 1.96–4.71).

Risk factors for all-cause mortality in elderly T2DM patients included smoker status, lower BMIs, elevated LDL-C levels and use of sulphonylureas.

In light of the present data, the authors pointed out that “the harm of achieving overaggressive glycaemic targets might possibly outweigh the potential benefits for diabetic elderly [patients] in our primary care. This could be because attaining and maintaining very low HbA1c levels not only indicated overtreatment, but also the presence of morbidity and worse health.

“The subsequent increased mortality observed in patients with very low HbA1c levels might be explained through increased occurrence of hypoglycaemia and presence of liver disease,” they added. [Circ Cardiovasc Qual Outcomes 2010;3:661-667; J Invest Dermatol 2011;131:2121-2127]

The authors urged further research to establish the HbA1c levels, as well as those of other factors such as blood pressure, LDL-C and BMI, associated with the lowest risk of all-cause mortality.