Type 1 diabetes incidence is rising

Incidence represents the number of new cases (of T1DM) diagnosed within a well-defined period of time (one year), in a given population, usually expressed per 100,000 persons per year. Incidence shows you how often new diabetes cases appear and reflects the pace at which new diagnoses are being recorded in the community [1].

Prevalence represents the total number of people living with T1DM at a given point in time, relative to the total population. The prevalence of T1DM in young people under 19 years is estimated at approximately two cases per 1,000 persons [2]. In practical terms, incidence shows you how quickly new cases appear, while prevalence shows you how many people are living with the disease in total.

Knowing the incidence of T1DM is essential for public health resource planning. Both the incidence and the prevalence of T1DM are increasing globally. This means that health systems must anticipate growing needs for access to insulin, blood glucose monitoring sensors and insulin pumps [3].

Furthermore, monitoring incidence allows identification of risk factors, evaluation of the effectiveness of potential prevention programs and adequate planning of emergency services. These data help researchers and physicians develop intervention strategies to limit the impact on the population [4].

Although T1DM can occur at any age, most new cases are diagnosed in childhood and adolescence. There are two main incidence peaks. The first peak is between ages 4 and 6, and the second between ages 10 and 14 (at puberty). Overall, approximately 20% of people with T1DM are under 20 years of age [4].

At the same time, we find that the majority of T1DM patients are adults. One in five T1DM patients is elderly, but their proportion will very likely increase in the future. In other words, although incidence peaks in childhood, the cumulative impact of the disease is reflected in a majority of adults living with T1DM [2].

In children and adolescents, T1DM remains the most common form of diabetes. T2DM does not generally occur before the age of 10. In the 10-14 age group, T1DM incidence is 2-3 times higher compared to T2DM [5].

T2DM incidence in the 15-19 age group is similar to that of T1DM, and in countries where childhood obesity is a significant problem, it even exceeds it. T2DM incidence in children and adolescents is increasing much more rapidly compared to T1DM, primarily as a result of the increasing prevalence of obesity [6].

Yes, T1DM can be first diagnosed in adulthood. T1DM defined by severe insulin deficiency can also occur after the age of 30 and is often treated initially as T2DM. Sometimes, adults with T1DM can maintain sufficient beta cell function to prevent ketoacidosis for several years, which makes diagnosis more difficult [7].

One such slowly progressive form is latent autoimmune diabetes of adults (LADA), which accounts for 2-10% of all diabetes cases. LADA is characterized by the presence of autoantibodies specific to T1DM, a slower progression of insulin secretion deficit and is frequently confused with T2DM. This underscores the importance of autoantibody testing in adults with diabetes who do not respond adequately to oral treatment, especially without a clinical picture typical of T2DM [8].

Cumulative incidence represents the probability that a person will develop T1DM from birth to a certain age. The cumulative risk of developing T1DM by the age of 15 varies significantly by region. In high-incidence countries it reaches approximately 0.5% (5 in 1,000), while in low-incidence ones it falls below 0.01% (1 in 10,000) [4].

Several prospective studies have followed children with high genetic risk who develop at least two pancreatic autoantibodies. Their combined analysis has shown that nearly 85% of them will be diagnosed with T1DM within the next 15 years. These data apply to both familial and sporadic cases, which suggests a similar biological progression regardless of the presence or absence of family history [9].

Sex-based differences in incidence are small and vary by region and age. In children under 14 years, the incidence is equal or only slightly higher in boys than in girls. Data from international registries show a boy/girl ratio of approximately 1.1-1.2:1 in many European countries. These differences are attenuated or reversed in some geographical regions [10].

In general, in adults T1DM affects mostly men compared to women, but there are many countries and regions where the proportions are approximately equal. Sex differences are not a major risk factor for T1DM, unlike genetic predisposition (the HLA, human leukocyte antigen group of genes, which helps the immune system tell your own cells apart from foreign ones), autoimmunity and environmental factors [4].

Yes, T1DM incidence varies greatly from one continent to another. Europe records the highest number of people with T1DM worldwide and generally has the highest incidence rates. North America and Australia also present high incidences. In contrast, East Asia, Southeast Asia and sub-Saharan Africa have significantly lower incidence rates [2] [11].

This geographical distribution suggests a complex interaction between genetic factors, environmental factors and other factors still incompletely elucidated. Among the genetic factors, what matters is the frequency of HLA susceptibility genes. Environmental factors include exposure to viruses, vitamin D, diet and hygiene conditions. It is important to note that in some regions with low incidence (such as areas in Asia or Africa), the data may in fact be underreported for multiple reasons [12].

The highest T1DM incidence rates are reported in the Nordic countries of Europe. Finland has held the top position worldwide for decades, with an incidence of approximately 50 new cases per 100,000 per year. Other countries with very high incidence include:

• Sweden;
• Norway;
• Kuwait;
• Qatar;
• Canada;
• the United Kingdom;
• the island of Sardinia in Italy (a particular case with an incidence comparable to that of the Nordic countries) [4] [13].

At the opposite end, the lowest T1DM incidence rates, with values of under 5 new cases per 100,000 per year, are reported in the areas shown in the figure below:

• China;
• Japan;
• South Korea;
• generally, countries in South Asia;
• South America (with the exception of certain regions);
• sub-Saharan Africa.

The difference between the highest and lowest incidence rates worldwide exceeds a factor of 100 [12].

Given the same geographical area, there are significant differences in T1DM incidence according to ethnic origin. People of European (Caucasian) descent have the highest incidence rates, while people of East Asian descent have significantly lower rates. These differences are largely explained by the different frequency of the HLA variants that increase susceptibility (mainly those labeled HLA-DR3/DQ2 and HLA-DR4/DQ8) in different populations [14] [15].

For example, in the USA, young people of European descent who are not also of Hispanic origin have the highest T1DM incidence rates, followed by youth of African American and Hispanic descent. However, ethnic differences regarding T1DM are not limited to genetics. Environmental factors, access to diagnosis and differences in epidemiological surveillance systems can significantly influence rates. Studies on migrant populations have shown that T1DM incidence tends to approach that of the host country over time, which underscores the role of environmental factors [15].

Yes, in most countries in temperate zones, T1DM diagnosis shows a clear seasonal variation. A higher number of newly diagnosed cases is observed in the autumn and winter months and a lower number in the summer months. This seasonal pattern is more evident in children aged between 5 and 15 years and in countries located at latitudes where there are four well-differentiated seasons [16].

Proposed explanations for this variation start with the higher frequency of viral infections in the cold season. Vitamin D levels also fall in winter, because of reduced sun exposure. Seasonal changes in immune function are possible as well. These observations support the hypothesis that environmental factors play an important role in triggering stage 3 of T1DM (with hyperglycemia) [17].

Yes, T1DM incidence has increased steadily in recent decades worldwide. Both the incidence and the prevalence of T1DM are increasing. Prevalence is rising partly because survival with T1DM keeps improving [18]. The average annual rate of increase in incidence has been estimated at approximately 3-4% per year in many regions, especially in Europe. Current projections suggest that the number of new T1DM cases could even double by 2040 worldwide [3].

This increase is too rapid to be explained solely by changes in the genetic background of populations, which indicates a major role of environmental factors. The implicated factors include:

• changes in lifestyle;
• alterations of the intestinal microbiota;
• increasing incidence of obesity, which may accelerate the autoimmune process;
• exposure to new viral agents;
• changes in infant nutrition;
• reduced contact with infectious agents in early childhood (the hygiene hypothesis) [4].

At the onset of the COVID-19 pandemic, several reports noted an increase in the incidence of hyperglycemia, ketoacidosis and new T1DM cases. They suggested that SARS-CoV-2 could be a triggering or accelerating factor of the disease in genetically predisposed individuals. Subsequent studies on large cohorts and from registries in several countries have reported mixed results. Some show a modestly increased risk of T1DM after COVID-19 infection. Others attribute the apparent increase mainly to difficulties in accessing medical services and to diagnostic delays caused by the pandemic [17] [19].

Current data suggest that both direct viral effects (SARS-CoV-2 can infect pancreatic beta cells) and indirect pandemic-related factors contributed to the initial increase observed in T1DM cases. Research is ongoing, including through the global CoviDIAB registry, to clarify the long-term relationship between SARS-CoV-2 infection and T1DM risk [19].