The Burden of Undiagnosed Diabetes

First published in 2000, the International Diabetes Federation (IDF) regularly updates its Atlas, shining light on the impact of diabetes across the world. Often most cited is the diabetes prevalence in different areas of the world.

According to the latest 2021 IDF Diabetes Atlas, as reported in Medscape, 1 in 10 adults worldwide currently live with diabetes, accounting for an estimated global health expenditure of $966 billion in US dollars in 2021. Over three quarters of all adults with diabetes now live in low- and middle-income countries.

Though the above may not be news, I found the estimated numbers of those living with undiagnosed diabetes particularly distressing. According to the Atlas, half of those currently living with diabetes, or about 240 million adults, have not yet been diagnosed with diabetes and are unaware that they have elevated blood sugar levels.

Since 2019, when the last Atlas was published as reported in Medscape, the 2021 numbers represent an increase of 73.6 million more adults with diabetes, including 7.8 million more undiagnosed individuals.

How Is Undiagnosed Diabetes Determined?

How did the Atlas come up with estimates of undiagnosed diabetes when these individuals themselves are unaware that they have diabetes?

Population-based scientific studies were reviewed to estimate the prevalence of undiagnosed diabetes worldwide. A sample of the population was surveyed to assess how many people have diabetes. Those who said that they did not have diabetes were then tested. This established the total prevalence of people already diagnosed with diabetes and those who tested positive for diabetes in this population sample.

The number of undiagnosed cases as a proportion of the total number of people living with diabetes was then extrapolated to calculate country-level estimates for undiagnosed diabetes.

In countries without in-country data sources, the proportion of undiagnosed cases was approximated by the average of the estimates from countries with data sources within the same IDF region and World Bank income group. The key was to find a sample that was truly representative of the entire population for which the estimate was being generated.

However, in countries with a sizable population of immigrants and indigenous people, populations are quite heterogenous and data regarding undiagnosed diabetes can differ greatly depending on the geographic location and degree of urbanization of the sample population.

We know that virtually all minority race and/or ethnic groups in the United States are at higher risk for diabetes than the majority non-Hispanic White population. Diabetes rates in the non-Hispanic Black and Mexican American populations are about twice the rate than in the non-Hispanic White population, according to Harris and co-authors. Extrapolation of sample data at a population level may be less accurate in many of these studies.

Complications of Undiagnosed Diabetes

Even when diabetes has not been diagnosed, hyperglycemia will cause ongoing damage to the microvascular and macrovascular compartments in the body.

These complications can worsen depending on the duration and intensity of uncontrolled hyperglycemia. This explains why, at the time of diagnosis, about 20% of US residents already have retinopathy.

Even in the US medical care system, the delay between the advent of type 2 diabetes and its diagnosis can be as much as 10-12 years. This indicates potential complications which could have perhaps been averted had a timelier diagnosis been made. One can only imagine the burden of complications in developing countries where there might be a longer delay in diagnosis.

Alarming Increase in Type 2 Diabetes in Youth

There was also an alarming increase of type 2 diabetes among youth. In 19 studies, the highest reported prevalence of type 2 diabetes in youth was in Brazil, Mexico, indigenous populations of the United States and Canada, and the Black population in the United States, with rates ranging from 160 per 100,000 to 3300 per 100,000.

When diabetes affects youth, the risk for complications is especially high because these individuals will be living with the condition for much longer than those diagnosed at a later age.

In a recent study published by the TODAY Study Group, at the end of a mean follow-up of 10 years, 54% of those with youth-onset diabetes (baseline mean age at diagnosis of 14 years) had two or more cardiovascular risk factors in addition to type 2 diabetes. About 20% had three or more cardiovascular risk factors at the end of the follow-up (with < 1% having three or more risk factors at the baseline age of 14 years).

With the rising rate of diabetes in youth, and considering that undiagnosed diabetes could arguably be quite high in this population owing to lack of routine testing, it is anyone's guess as to the avalanche of cardiovascular events that could be waiting for us in the coming years.

COVID-19 and Diabetes Risk

During the pandemic, early data suggested that there is an increased risk for morbidity and mortality with COVID-19 illness in people with diabetes.

After adjustment for sex, age, body mass index, and several comorbidities, persons with undiagnosed type 2 diabetes had higher odds of severe disease (odds ratio [OR] 7.91; 95% CI, 2.59-28.07) than those with previously diagnosed diabetes (OR 3.14; 95% CI, 1.12-10.31), with both groups being compared with persons with normoglycemia.

Compared with persons with normal A1c, persons with undiagnosed type 2 diabetes had a higher risk for mortality (hazard ratio [HR] 5.51; 95% CI, 1.28-23.81), followed by those with previously diagnosed type 2 diabetes (HR 4.98; 95% CI, 1.19-20.74); however, when adjusted by age, sex, body mass index, and comorbidities, only undiagnosed type 2 diabetes remained associated with mortality.

Another study reported by Medscape found that COVID-19 significantly raised the risk for diabetes by about 40% at 1 year, meaning that blood glucose levels should be monitored after COVID-19 illness.

If the Mountain Won't Come to Muhammad, Then Muhammad Must Go to the Mountain

Four out of 5 people with undiagnosed diabetes live in low- and middle-income countries. Access to care, particularly in rural and remote areas, remains a challenge.

Unique interventions such as mobile diabetes clinics have demonstrated excellent results in screening thousands of patients for chronic conditions, including diabetes. If diagnosed with diabetes, these individuals then get longitudinal education and healthcare using the same mobile clinics, which has shown significant benefit.

However, because of the significant prevalence of anemia and hemoglobinopathies in several African and Asian countries, combined with the high cost of conducting an A1c test, mass screenings continue to suggest the use of fasting glucose, which may not be very practical. Another option would be to screen first using validated questionnaires for detecting those who are at high-risk of diabetes followed by blood testing.

Regardless of the screening strategy employed, these measures may be only a drop in the ocean if we do not make changes at a population level. The less privileged would benefit from access to healthier foods and resources for increasing activity at a community level for the prevention of diabetes as well as ongoing care of those with diabetes.

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