100 Years After Insulin's Discovery, Disparities Persist

This November marks 100 years since the discovery of insulin, an event that transformed diabetes care “from a death sentence to a chronic condition,” the Endocrine Society states. And although progress has been made with regard to access and distribution throughout the last century, a new review published in The Lancet details current challenges faced by children and adolescents with type 1 diabetes (T1D) in low- and middle-income countries (LMICs).

“Most insulin types are still given by subcutaneous injection and do not fully mimic the time-action profile of physiological insulin secretion,” authors explained. But despite “improvements in newer insulin formulations and clinical development of biosimilar insulin in recent years, the metabolic outcomes of diabetes have not changed remarkably,” they said.

Reports estimated a total of 463 million individuals worldwide had T1D in 2019, and one study found T1D incidence among children and adolescents increased by an average of 2.8% between 1990 and 1999.

However, due to the scarcity of representative population-based data, estimates likely underestimate the true cost and burden of T1D—a problem compounded by potential premature deaths prior to diagnosis. For example, in Africa, few countries report data on relevant indicators, meaning estimates can be based on extrapolation from neighboring countries, researchers said, leading to potential inaccuracies.

Furthermore, different regions report variability in the management of pediatric T1D. Data show the proportion of children with optimal glycemic control (glycated hemoglobin [A1C] <7.5%) is 32.4% in high-income countries (HICs) compared with just 12.7% in low-income countries (LICs).

Estimates from the Global Health Observatory indicate less than half of countries in central Asia, east Asia, and western sub-Saharan Africa have existing diabetes registries, availability of insulin, existence of operational policies, and facilities for diabetes testing at the primary health-care level. “Only 20% of the countries in central and south Asia have insulin generally available,” authors noted.

A combination of these factors, in addition to inadequate infrastructure, diagnostic tools, and personnel, lead to reduced and delayed T1D diagnoses in LMICs.

Because T1D involves β-cell destruction, which could begin months or years prior to diagnosis, the process is often non-linear. Although several landmark studies have been published on risk factors for T1D, ethnic minorities and populations from LMICs are often underrepresented.

More inclusive analyses are needed “to explore risk factors in various settings with varied risks, including those related to consanguinity,” researchers stressed.

When it comes to T1D treatment and management, the focus has shifted from symptomatic treatment to disease-modifying interventions. One development in this field is the development of teplizumab for individuals who are antibody positive and at high risk for T1D.

“Stage 3 prevention trials aim to preserve some β-cell function to potentially delay the complications of T1D and enroll children within 100 days of diagnosis of T1D,” authors said. But the need to undertake similar studies among existing cohorts in LMICs remains crucial.

When conducting a review of literature published after 2015 on T1D pediatric management, investigators found the majority of data focused on health and quality-of-life outcome interventions were reported from studies in HICs; available data from LMICs were too sparse to draw meaningful conclusions.

While technological advances in insulin delivery—mostly implemented in HICs— have revolutionized the lives of individuals with T1D, these advances “do not take away from the reality of differences and inequity in access to care, even in HICs such as the USA, where price gouging and availability of insulin negatively affected the care of children and young people with diabetes,” researchers wrote.

In recent years, continuous glucose monitoring (CGM) use among children and adolescents has taken off, as parents can remotely monitor glucose levels and help reduce the risk of hospital admissions due to diabetic ketoacidosis. Such promising results necessitate the implementation of these interventions among children in LICs.

Throughout the past century, life expectancy of pediatric patients with T1D has progressed, although gains have been much slower in LMICs. Despite a lack of longitudinal studies on long-term T1D prognoses in LMICs, one analysis conducted in South Africa found that over 20 years, mortality among patients with T1D was 43%, with renal failure, hypoglycemia, and ketoacidosis as the main causes of death. Overall, “patients with T1D in LMICs have high mortality rates and high burden of disease,” with poor treatment administration due in large part to availability and pricing of insulin.

According to authors, one important step in addressing these hurdles is implementation of universal health coverage (UHC).

“Regardless of the path taken by countries to reach UHC, there are few interventions more essential and lifesaving than those for the management of T1D in children and adolescents, and it is crucial that these interventions, especially those for treatment, be available to people who are poor and be publicly financed,” they said.

“For these objectives to be realized, countries must seek to reach a level of 80% availability of essential medicines and technologies as proposed in the WHO Global Action Plan for non-communicable diseases.”

It is estimated that among countries without public health-system coverage for T1D, basic care supplies for the condition have a median cost of 56% of individuals’ mean annual income, or 153% in the lowest income group. Training physicians in LMICs in the management of T1D and investing in community health workers could help alleviate some of the hurdles to care.

To mitigate insulin costs, duties and taxes could be eliminated while price regulation and transparency could improve affordability in the context of LMICs, authors said.

“As the world rebuilds itself from the ravages of COVID-19, it is imperative that the needs of children and adolescents with T1D receive full attention,” they concluded.

Reference

Bhutta ZA, Salam RA, Gomber A, et al. A century past the discover of insulin: global progress and challenges for type 1 diabetes among children and adolescents in low-income and middle-income countries. The Lancet. Published online November 13, 2021. doi:10.1016/S0140-6736(21)02247-9