Early Glycemic Control and Future Implications

Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Dahlia Elimairi, Pharm D Student, UC Denver Skaggs School of Pharmacy

Immediate, intensive treatment for newly diagnosed patients with type 2 diabetes may be necessary to avoid irreversible long-term risk for diabetic complications and mortality.

New studies have shown that intensive sugar control during the first year can reduce the risk of future microvascular and macrovascular complications substantially.

A patient’s lifetime history of glycemic control may be necessary to understand why patients with longstanding diabetes develop complications despite excellent control later during their disease. Treating patients with diabetes earlier and more intensively has the potential to confer substantial, long term improvements in public health.

A recent study examined for a legacy effect of early glycemic control on diabetic complications and death. The study hypothesized that a glycemic legacy effect exists in real-world populations, begins as early as the 1st year after diabetes diagnosis, and depends on the level of glycemic exposure.

This cohort study of managed care patients with newly diagnosed type 2 diabetes and 10 years of survival examined associations between HbA1c <6.5% (<48 mmol/mol), 6.5% to <7.0% (48 to <53 mmol/mol), 7.0% to <8.0% (53 to <64 mmol/mol), 8.0% to <9.0% (64 to <75 mmol/mol), or ≥9.0% (≥75 mmol/mol) for various periods of early exposure (0–1, 0–2, 0–3, 0–4, 0–5, 0–6, and 0–7 years) and incident future microvascular (end-stage renal disease, advanced eye disease, amputation) and macrovascular (stroke, heart disease/failure, vascular disease) events and death, adjusting for demographics, risk factors, comorbidities, and later HbA1c.

In patients with newly diagnosed diabetes and at least 10 years of survival after diagnosis, the study found that diabetes control during the first year after diagnosis was strongly associated with future risk for diabetic complications and mortality, even after adjusting for glycemic control after the first year. Overall, the duration and intensity of early glycemic control were both closely aligned with outcomes. Compared with an HbA1c <6.5% (<48 mmol/mol) for the 1st year after diagnosis, higher HbA1c levels were associated with a higher risk for microvascular and macrovascular events, and HbA1c levels ³7.0% (³ 58 mmol/mol) were associated with a higher risk for mortality. The risk of complications did not increase significantly when the early period was characterized by longer periods of HbA1c levels of 6.5% to < 8.0% (48 to < 64 mmol/mol) (rather than just the 1st year after diabetes diagnosis). However, longer exposure to HbA1c levels ³ 8.0% (³ 64 mmol/mol) was associated with an increased risk for microvascular events and mortality.

The current study suggests that failure to achieve an HbA1c < 6.5% (<48 mmol/mol) within the 1st year after diabetes diagnosis is enough to establish an irremediable long-term future risk of microvascular and macrovascular complications. In addition, failure to achieve an HbA1c < 7.0% (< 53 mmol/mol) within the 1st year after diabetes diagnosis may lead to an irreversible increased risk of mortality. These findings are supported by previous cohort studies that showed that failure to intensify diabetes treatments in patients with elevated HbA1c values is associated with increased retinopathy and cardiovascular events.

The study concluded that the legacy effect exists outside of trial populations, begins as early as the 1st year after diagnosis, and depends on the level of glycemic exposure. These findings underscore the urgency of early diagnosis of diabetes and the future consequences of failing to achieve near-normal glycaemia soon after patients are diagnosed with diabetes.

Practice Pearls: Diabetes control during the 1st year after diagnosis was strongly associated with future risk for diabetic complications and mortality, even after adjusting for glycemic control after the 1st year.

Failure to intensify diabetes treatments within the first year after diabetes diagnosis is associated with an irreversible increased risk of mortality.

The association between the first years of glycemic control and outcomes also should be considered when formulating public health and health care policy regarding the intensity of efforts to control hyperglycemia to improve diabetes outcomes for patients with longstanding diabetes.

References:

> Laiteerapong N, Ham SA, Gao Y, Moffet HH, Liu JY, Huang ES, Karter AJ. The Legacy Effect in Type 2 Diabetes: Impact of Early Glycemic Control on Future Complications (The Diabetes & Aging Study). Diabetes Care. 2019 Mar;42(3):416-426.

Dahlia Elimairi, Pharm D Student, Skaggs School of Pharmacy UC Denver

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