Hyperglycemia defines diabetes and is directly related to the incidence of complications. Therefore, glycemic control is fundamental to diabetes management. The Diabetes Control and Complications Trial (DCCT) was a prospective randomized controlled study comparing intensive versus standard glycemic control in patients diagnosed with type 1 diabetes relatively recently. The DCCT demonstrated that achieving an A1C of <7% reduced the incidence of microvascular complications of type 1 diabetes compared with standard control, which achieved an A1C of ~9% during the period of the randomized trial. The Epidemiology of Diabetes Interventions and Complications (EDIC) study[44,45] was a follow-up of the DCCT cohorts. The EDIC study remarkably demonstrated persistent microvascular and cardiovascular benefits in subjects who had previously received intensive treatment, even though their glycemic control had deteriorated over time.
While A1C and blood glucose targets are needed, the ADA emphasizes that glycemic targets should be individualized with the goal of achieving the best possible control while minimizing the risk of severe hyperglycemia and hypoglycemia (Table 7). Goals should be individualized based on duration of diabetes, age/life expectancy, comorbid conditions, known CVD or advanced microvascular complications, hypoglycemia unawareness, and individual patient considerations. More or less stringent glycemic goals may be appropriate for individual patients. Postprandial glucose may be targeted if A1C goals are not met despite reaching preprandial glucose goals.
Lifestyle, psychosocial, and medical circumstances should be considered when recommending glycemic goals for all age-groups. (E)
Glycemic Control Goals in Pediatrics
As the DCCT only included pediatric patients aged ≥13 years (195 adolescents aged 13–17 years at entry), treatment guidelines for pediatric patients have been based nearly exclusively on professional, expert advice. Furthermore, despite the overall A1C goal of <7% for adults with type 1 diabetes, pediatric patients, aged 13–19 years, had an A1C target of <7.5%. This slightly higher A1C target for adolescents with type 1 diabetes was based on expert recommendations and the clinical reality that optimizing glycemic control in adolescent patients with type 1 diabetes is especially challenging, given the physiological and behavioral challenges that confront this age-group.
The ADA's blood glucose and A1C goals traditionally have been developmentally or age based in the pediatric population, but it is now time to alter the traditional goals based on recent data. The traditional recommendations are an A1C goal of <8.5% for youth under the age of 6 years, <8% for those 6–12 years old, and <7.5% for those 13–19 years old. Lower blood glucose levels and lower A1C targets should be pursued as long as patients can avoid severe, recurrent hypoglycemia. Thus, the overall recommendation has included the goal to achieve as close to normal blood glucose and A1C levels as is possible without the occurrence of severe, recurrent hypoglycemia.
Historically, the ADA recommended higher A1C targets for young children. This recommendation arose from a combination of two lines of unsubstantiated evidence. First, an older body of literature, reflecting therapy in the premodern era, devoid of insulin analogs, easy-to-use blood glucose monitors, "smart pumps," and CGM devices, indicated that severe recurrent hypoglycemia with seizure and/or coma in young children was associated with neurocognitive compromise. The second line of evidence arose from literature that questioned what, if any, impact blood glucose and A1C levels prior to puberty have on the risk for the development of future long-term complications of diabetes.[47,48] With the combination of these two independent lines of reports, it is not surprising that earlier recommendations regarding glycemic targets focused on the avoidance of severe hypoglycemia in order to reduce risk of neurocognitive dysfunction, especially in young children and even school-aged children.
Currently, treatment strategies for children recommend physiological insulin replacement with modern strategies and treatment tools. More recent investigation and active ongoing research have dispelled concerns regarding hypoglycemia and neurocognitive dysfunction.[49,50]
Studies assessing neurocognitive function have failed to identify adverse effects of a past history of hypoglycemia in the young child; however, as always, further research needs to be conducted.
There are also questions regarding the premise that the years prior to puberty do not impact the future risk of complications. Many investigators and clinicians believe in the importance of controlling blood glucose and A1C levels prior to puberty to reduce risk for both micro- and macrovascular complications. Additionally, there is burgeoning evidence that elevated blood glucose levels and glycemic variability in the very young child with diabetes may produce adverse outcomes in the short term on neurocognitive function and the central nervous system.[52,53] These recent articles suggest that hyperglycemia and glycemic variability are associated with changes in the central nervous system white matter, as observed in MRI scans.
Taking into account the combination of spotty past evidence related to the adverse effects of hypoglycemia on the developing brain and increasing evidence from more recent investigations focused on the potential risks of hyperglycemia and glucose variability on the central nervous system, the ADA has decided to alter the recommendations for glycemic targets in pediatric patients with type 1 diabetes and harmonize with other organizations. The International Society for Pediatric and Adolescent Diabetes (ISPAD) uses a single A1C goal of <7.5% across all pediatric age-groups. This recommendation is based on clinical studies and expert opinion, as rigorous evidence does not currently exist. Specifically, the recommendation is derived from a combination of clinical experience and intensive management strategies that provide opportunities to achieve as near-normal glycemic control as possible without the occurrence of severe hypoglycemia.
In light of the above evidence, the ADA will harmonize its glycemic goals with those of ISPAD (as well as the Pediatric Endocrine Society and the International Diabetes Federation) by using a single A1C goal of <7.5% across all pediatric age-groups.
However, as mentioned previously, it must be emphasized that the ADA strongly believes that blood glucose and A1C targets should be individualized with the goal of achieving the best possible control while minimizing the risk of severe hyperglycemia and hypoglycemia and maintaining normal growth and development.
An A1C goal of <7.5% is recommended across all pediatric age-groups. (E)
Glycemic Control Goals in Adults
Similar to in children, the care of older adults with diabetes is complicated by their clinical and functional heterogeneity. Unlike the large older adult population with type 2 diabetes, which includes patients with both long-standing and new-onset diabetes, most older adults with type 1 diabetes have long-standing disease. Even so, there is a wide spectrum of health across older individuals. They may have advanced complications, or they may have lived with diabetes for many years without the development of complications. Some older patients have multiple comorbid conditions and/or impairments of physical or cognitive functioning, while others have little comorbidity and high functional status. Life expectancy is highly variable and is defined by comorbidity and functional status more than it is by age.
Health care providers caring for older adults with diabetes must take this heterogeneity into consideration when setting and prioritizing treatment goals. The benefits of interventions such as stringent glycemic control may not apply to those with advanced complications of diabetes or to those with a life expectancy of less than the anticipated time frame of benefit. Conversely, the risks of interventions such as tight glycemic control (hypoglycemia, treatment burden) may be greater in older patients. Although individualization is critical, in general, older patients with long life expectancy and little comorbidity should have treatment targets similar to those of middle-aged or younger adults. In more frail patients, treatment targets might reasonably be relaxed, while symptomatic hyperglycemia or the risk of DKA should still be avoided.
Lowering A1C to below or around 7% has been shown to reduce microvascular complications of diabetes, and, if achieved soon after the diagnosis of diabetes, is associated with long-term reduction in macrovascular disease. Therefore, a reasonable A1C goal for many nonpregnant adults with type 1 diabetes is <7%. (B)
Providers might reasonably suggest more stringent A1C goals (such as <6.5%) for select individual patients, if this can be achieved without significant hypoglycemia or other adverse effects of treatment. Appropriate patients might include those with a short duration of diabetes, a long life expectancy, hypoglycemia awareness, and no significant CVD. (C)
Less stringent A1C goals (such as <8.5%) may be appropriate for patients with a history of severe hypoglycemia, hypoglycemia unawareness, limited life expectancy, advanced microvascular/macrovascular complications, or extensive comorbid conditions. (B)
Glycemic control for those of any age with type 1 diabetes should be assessed based on frequent SMBG levels (and CGM data, if available) in addition to A1C in order to direct changes in therapy. (B)
Diabetes Care. 2014;37(7):2034-2054. © 2014 American Diabetes Association, Inc.