Type 1 Diabetes

Aveni Haynes, PhD, on How Lower HbA1c Targets Have Impacted SH Rates Over Time in Pediatric T1D

Previous research demonstrated an inverse association between the risk of severe hypoglycemia and lower glycemic targets in type 1 diabetes,1 often leading to challenges when it came to pursuing lower glycemic targets in this patient population. However, with the advent of advanced diabetes therapies and technologies, this has likely changed.

New findings published in Diabetes Care suggests that improvements in hemoglobin A1c (HbA1c) and decreases in severe hypoglycemia rates have occurred concurrently over the past 2 decades in the United States, Western Australia, Germany, and Austria.2

Researchers arrived at their conclusion after assessing data from patients under age 15 years with type 1 diabetes from the DPV (N = 59,883) and WACDD (N = 2,595) cohorts.2 Ultimately, the researchers found that the annual mean HbA1c had decreased from 8.3% to 7.8% in the DPV cohort and from 9.2 to 8.3% in the WACDD cohort from 1995 to 2016. The severe hypoglycemia rate had decreased by an annual average of 2% (relative risk 0.983) in the DPV cohort and 6% (relative risk 0.935) in the WACDD cohort over the same time period.2 Notably, the researchers observed concomitant decreasing trends in both HbA1c and severe hypoglycemia rates in boys and girls, all age-groups, and injection therapy/pump regimen groups.2

Endocrinology Consultant discussed these findings further with lead study author Aveni Haynes, PhD, epidemiology research theme leader at the Children’s Diabetes Centre at the Telethon Kids Institute in Perth, Western Australia.

Endocrinology Consultant: What prompted you to conduct this study?

Dr Haynes: Children and adolescents diagnosed with type 1 diabetes need lifelong, daily insulin replacement therapy for survival. In addition, maintaining as close to normal glucose levels as possible is essential for reducing their risk of developing diabetes-related complications such as retinopathy, diabetic kidney disease, neuropathy and cardiovascular disease. An ever-present risk of insulin therapy is being given too much insulin, causing hypoglycemia. If severe, this can result in coma or convulsion, and if left untreated, can lead to death. Therefore, the ongoing challenge for individuals with type 1 diabetes is to optimize insulin therapy to minimize their long-term risk of diabetes-related complications without increasing their risk of severe hypoglycemia. 

Several studies over recent decades have reported improvements in glycemic control of pediatric patients with type 1 diabetes without concomitant increases in severe hypoglycemia rates, including a study from our research team, which analyzed cross-sectional data from Western Australia, Germany/Austria, and the United States. This study was conducted to further investigate the relationship between glycemic control and severe hypoglycemia using longitudinal data available since 1995 from Western Australia and Germany/Austria.

Endocrinology Consultant: Could you discuss the clinical implications of your new study findings, especially in the context of previous findings from the Diabetes Control and Complications Trial that indicated an inverse association between the risk of severe hypoglycemia and lower glycemic targets?

Dr Haynes: Evidence for the benefits of good glycemic control on acute and chronic diabetes-related outcomes has informed current international targets for optimal glycemic control. Current targets have been set at unprecedented low levels, with the optimal target HbA1c for children and adolescents ranging from 6.5% or lower to 7.5% or lower, depending on country and working group guidelines. The requirement for individualizing HbA1c targets, taking into account factors including an individual’s age, hypoglycemia awareness, duration of diabetes, history of severe hypoglycemia and presence of other risks for hypoglycemia, is crucial. However, population-level studies such as this one have provided strong evidence for the lack of association between glycemic control and risk of severe hypoglycemia in the modern era of diabetes management in developed countries with access to multidisciplinary health care and health care providers experienced in the use of advanced diabetes therapies and technologies.

Endocrinology Consultant: How can these findings help reduce clinicians’ and patients’ fears of severe hypoglycemia occurring with lower HbA1c targets?

Dr Haynes: These findings provide further evidence that children and adolescents with type 1 diabetes being treated by multidisciplinary teams with expertise in, and access to, modern diabetes therapies are able to achieve lower HbA1c targets without necessarily increasing their risk of severe hypoglycemia.  Over the past decade, the lack of association between HbA1c and severe hypoglycemia has been observed in several population-based studies, resulting in the lowering of HbA1c targets in the Standards of Diabetes Care published by the American Diabetes Association, as well the International Society of Pediatric and Adolescent Diabetes guidelines and the UK’s National Institute for Health and Care Excellence guidelines.3,4,5 Although, the fear of severe hypoglycemia will always be present, clinicians and patients can work together to set individualized targets, taking into account factors such as age, impaired hypoawareness, past history of severe hypoglycemia, and compliance with use of technology and psycho-social settings to optimize glycemic control while minimizing the risk of severe hypoglycemia.

Endocrinology Consultant: How have advances in diabetes therapies and related factors over the past couple of decades impacted the association between glycemic control and severe hypoglycemia risk?

Dr Haynes: Over the past decades there have been significant advances in diabetes therapies and technologies including newer improved insulin analogues, continuous subcutaneous insulin infusion, or pump therapy, and continuous glucose monitoring (CGM). This study reports improvements in both the average glycemic control and severe hypoglycemia rates in 2 independent populations of children and adolescents with type 1 diabetes being treated under real-world conditions since 1995. This is likely due to advances in diabetes therapies such as newer, faster-acting insulin analogues, the availability of CGM and continuous insulin infusion technology, as well as improvements in patient and caregiver education on hypoglycemia awareness and prevention.

Endocrinology Consultant: What are the next steps for research in this area?

Dr Haynes: Ongoing evaluation of glycemic outcomes will continue in both populations investigated in this study to continue monitoring both individual and population-level glycemic control and rates of severe hypoglycemia. Both of these glycemic outcomes provide important data relating to clinical care of children and adolescents diagnosed with type 1 diabetes. In addition, since April 2017, CGM has been fully subsidized under the Australian Government healthcare rebate scheme for all individuals diagnosed with type 1 diabetes under the age of 21 years. Research to evaluate the impact of this on potential further improvements in both glycemic control and severe hypoglycemia rates will be the subject of future research.

—Christina Vogt

References:

  1. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977-986. doi:10.1056/NEJM199309303291401
  2. Haynes A, Hermann JM, Clapin H, et al. Decreasing trends in mean HbA1c are not associated with increasing rates of severe hypoglycemia in children: A longitudinal analysis of two contemporary population-based pediatric type 1 diabetes registries from Australia and Germany/Austria between 1995 and 2016. Diabetes Care. 2019;42(11). https://doi.org/10.2337/dc18-2448
  3. American Diabetes Association. Standards of medical care in diabetes—2019. Diabetes Care. 2019;42(Suppl 1):S1-S2. https://doi.org/10.2337/dc19-Sint01
  4. International Society for Pediatric and Adolescent Diabetes. ISPAD clinical practice consensus guidelines 2018. https://www.ispad.org/page/ISPADGuidelines2018. Accessed October 24, 2019.
  5. National Institute for Health and Care Excellence. Diabetes in children and young people: quality standard [QS125]. 2016. https://www.nice.org.uk/guidance/qs125. Accessed October 24, 2019.