Complete HLA genotyping of type 1 diabetes patients and controls from Mali reveals both expected and novel disease associations.

HLA genotyping was performed on 99 type 1 diabetes (T1D) patients and 200 controls from Mali. Next-generation sequencing of the classical HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1 loci revealed strong T1D association for all loci except HLA-C and -DPA1. Class II association is stronger than class I association, with most observed associations predisposing or protective as expected based on previous studies. For example, HLA-DRB1*03:01, HLA-DRB1*09:01, and HLA-DRB1*04:05 predispose for T1D, whereas HLA-DRB1*15:03 is protective. HLA-DPB1*04:02 (OR = 12.73, p = 2.92 × 10-05 ) and HLA-B*27:05 (OR = 21.36, p = 3.72 × 10-05 ) appear highly predisposing, although previous studies involving multiple populations have reported HLA-DPB1*04:02 as T1D-protective and HLA-B*27:05 as neutral. This result may reflect the linkage disequilibrium between alleles on the extended HLA-A*24:02~HLA-B*27:05~HLA-C*02:02~HLA-DRB1*04:05~HLA-DRB4*01:03~HLA-DQB1*02:02~HLA-DQA1*02:01~HLA-DPB1*04:02~HLA-DPA1*01:03 haplotype in this population rather than an effect of either allele itself. Individual amino acid (AA) analyses are consistent with most T1D association attributable to HLA class II rather than class I in this data set. AA-level analyses reveal previously undescribed differences of the HLA-C locus from the HLA-A and HLA-B loci, with more polymorphic positions, spanning a larger portion of the gene. This may reflect additional mechanisms for HLA-C to influence T1D risk, for example, through expression differences or through its role as the dominant ligand for killer cell immunoglobulin-like receptors (KIR). Comparison of these data to those from larger studies and on other populations may facilitate T1D prediction and help elucidate elusive mechanisms of how HLA contributes to T1D risk and autoimmunity.

Incidence, prevalence, and mortality of type 1 diabetes in children and youth in Burkina Faso 2013-2022.

AIM: There are no data on type 1 diabetes (T1D) incidence and prevalence in Burkina Faso. We aimed to determine these in persons aged <25 years (y) since the implementation of Life for a Child (LFAC) program in 2013. PATIENTS AND METHODS: Data were collected from the prospective program register. Diagnosis of T1D was clinical, based on presentation, abrupt onset of symptomatic hyperglycemia, need for insulin replacement therapy from diagnosis, and no suggestion of other diabetes types. RESULTS: We diagnosed 312 cases of T1D <25y in 2013-2022. Male-to-female ratio was 1:1. T1D incidence <25y per 100,000 population/year increased from 0.08 (CI 95% 0.07-0.60) in 2013 to 0.34 (CI 95% 0.26-0.45) in 2022 (p=0.002). Incidence <15y/y rose from 0.04 (CI 95% 0.01-0.10) to 0.27 (CI 95% 0.18-0.38) per 100,000/year in 2013 and 2022, respectively (p < 0.002). Prevalence per 100,000 population <25y was 0.27 (CI 95% 0.19-0.37) in 2013 and rose to 1.76 (CI 95% 1.546-1.99) in 2022 (p<0.0001). Mortality rate was 20 (CI 95% 13-29.6) per 1,000-person y. CONCLUSIONS: There is a low but sharply rising T1D incidence and prevalence rates in children and youth in Burkina Faso since LFAC program implementation. It is very likely this is partly due to improved case detection. Mortality remains substantial.

The T1D Index: Implications of Initial Results, Data Limitations, and Future Development.

PURPOSE OF THE REVIEW: Current global information on incidence, prevalence, and mortality of type 1 diabetes (T1D) is limited, particularly in low- and middle-income countries. To address this gap in evidence, JDRF, Life for a Child, International Society for Pediatric and Adolescent Diabetes, and International Diabetes Federation have developed the T1D Index, which uses a Markov mathematical model, and machine learning and all available data to provide global estimates of the burden on T1D. This review assesses the methodology, limitations, current findings, and future directions of the Index. RECENT FINDINGS: Global prevalence was estimated at 8.4 million in 2021, with 1.5 million <20 years (y). T1D prevalence varied from 1.5 to 534 per 100,000, with T1D accounting for <0.1-17.8% of all diabetes in different countries. A total of 35,000 young people <25 y are estimated to have died at clinical onset of T1D from non-diagnosis. An estimated 435,000 people <25 y were receiving "minimal care." Health-adjusted life years (HALYs) lost for individuals diagnosed with T1D at age 10 y in 2021 ranged from 14 to 55 y. These results show that interventions to reduce deaths from non-diagnosis, and improve access to at least an intermediate care level, are needed to reduce projected life years lost. The results have significant uncertainties due to incomplete data across the required inputs. Obtaining recent incidence, prevalence, and mortality data, as well as addressing data quality issues, misdiagnoses, and the lack of adult data, is essential for maintaining and improving accuracy. The index will be updated regularly as new data become available.

Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: a modelling study.

BACKGROUND: Accurate data on type 1 diabetes prevalence, incidence, associated mortality and life expectancy are crucial to inform public health policy, but these data are scarce. We therefore developed a model based on available data to estimate these values for 201 countries for the year 2021 and estimate the projected prevalent cases in 2040. METHODS: We fitted a discrete-time illness-death model (Markov model) to data on type 1 diabetes incidence and type 1 diabetes-associated mortality to produce type 1 diabetes prevalence, incidence, associated mortality and life expectancy in all countries. Type 1 diabetes incidence and mortality data were available from 97 and 37 countries respectively. Diagnosis rates were estimated using data from an expert survey. Mortality was modelled using random-forest regression of published type 1 diabetes mortality data, and life expectancy was calculated accordingly using life tables. Estimates were validated against observed prevalence data for 15 countries. We also estimated missing prevalence (the number of additional people who would be alive with type 1 diabetes if their mortality matched general population rates). FINDINGS: In 2021, there were about 8·4 (95% uncertainty interval 8·1-8·8) million individuals worldwide with type 1 diabetes: of these 1·5 million (18%) were younger than 20 years, 5·4 million (64%) were aged 20-59 years, and 1·6 million (19%) were aged 60 years or older. In that year there were 0·5 million new cases diagnosed (median age of onset 39 years), about 35 000 non-diagnosed individuals died within 12 months of symptomatic onset. One fifth (1·8 million) of individuals with type 1 diabetes were in low-income and lower-middle-income countries. Remaining life expectancy of a 10-year-old diagnosed with type 1 diabetes in 2021 ranged from a mean of 13 years in low-income countries to 65 years in high-income countries. Missing prevalent cases in 2021 were estimated at 3·7 million. In 2040, we predict an increase in prevalent cases to 13·5-17·4 million (60-107% higher than in 2021) with the largest relative increase versus 2021 in low-income and lower-middle-income countries. INTERPRETATION: The burden of type 1 diabetes in 2021 is vast and is expected to increase rapidly, especially in resource-limited countries. Most incident and prevalent cases are adults. The substantial missing prevalence highlights the premature mortality of type 1 diabetes and an opportunity to save and extend lives of people with type 1 diabetes. Our new model, which will be made publicly available as the Type 1 Diabetes Index model, will be an important tool to support health delivery, advocacy, and funding decisions for type 1 diabetes. FUNDING: JDRF International.

Incidence of type 1 diabetes in children in Dominican Republic, 2010-2019: A national collaborative study.

The Dominican Republic has no recent data on type 1 diabetes (T1D) incidence in children. Therefore, a study was undertaken to determine this in persons aged <15 years (y). Data were collected on all new T1D diagnoses between 2010-2019 from the four institutions caring for children with T1D. Diagnosis was made according to standard criteria. No secondary ascertainment source was available. The trend and the effect of age and sex of T1D incidence was analyzed using Poisson regression. A total of 1224 new cases of T1D were diagnosed <15 y; mean ± standard deviation (range) 122 ± 12 (96-135) cases per year. Age at T1D diagnosis was 8.8 ± 3.7 y, with a significant female preponderance (n = 708, 57.8%, p < 0.001). When examined per 5-y age group, cases were consistently highest in 10-14 y, and lowest in 0-4 y in all study years. Mean crude T1D annual incidence was 4.3 (95% CI 3.5-5.1) per 100,000 population. There was no significant difference between incidence across the country's three departments (regions): Southeast (4.4 [3.4-5.7]/100,000 population), North (4.1 [2.9-5.6]), and Southwest (3.9 [2.4-5.9]). Mean standardized annual incidence was 4.1 (4.1-4.2) per 100,000 population, with no significant trend of increase over the study period. The incidence of T1D in children aged <15 y is relatively low in Dominican Republic, but consistent with the limited data from other countries in the region. However, the incidence is eight times higher than the previous estimate during 1995-1999. Ongoing surveillance is warranted.

Worldwide estimates of incidence of type 2 diabetes in children and adolescents in 2021.

AIMS: We aimed to conduct a systematic review of published studies on the incidence of type 2 diabetes in children and adolescents aged under 20 years and provide worldwide incidence estimates for 2021. METHODS: We used MEDLINE and EMBASE to identify studies reporting type 2 diabetes incidence in children and adolescents published between Jan 2000 and April 2021. We used a negative binomial regression model to develop a prediction equation to estimate incidence rates from country characteristics. We applied the resulting incidence predictions to country population data to estimate numbers of incident cases in children and adolescents by International Diabetes Federation (IDF) region and World Bank income classification group. RESULTS: We estimate that there are approximately 41,600 new cases of diagnosed type 2 diabetes among children and adolescents in 2021 worldwide. Around 30% and 40% of the worldwide total incident cases are in IDF Western Pacific region and in World Bank upper-middle-income countries, respectively. The three countries with the highest estimated number of incident cases are China, India, and United States of America. CONCLUSIONS: The number of newly diagnosed type 2 diabetes in children and adolescents is substantial. More reliable data are needed to track the incidence of type 2 diabetes in children and adolescents.

Role of the SARS-CoV-2 virus in the appearance of new onset type 1 diabetes mellitus in children in Gran Canaria, Spain.

OBJECTIVES: It has been hypothesized that SARS-CoV-2 may play a role in the development of different forms of diabetes mellitus (DM). The Canary Islands have the highest incidence of type 1 DM (T1DM) reported in Spain (30-35/100,000 children under 14 years/year). In 2020-2021 we observed the highest incidence so far on the island of Gran Canaria, as a result of which we decided to evaluate the possible role of COVID-19 in the increased number of onsets. METHODS: We examined the presence of IgG antibodies against SARS-CoV-2 in children with new onset T1DM between October 2020 and August 2021. We compared recent T1DM incidence with that of the previous 10 years. RESULTS: Forty-two patients were diagnosed with T1DM (48.1/100,000 patients/year), representing a nonsignificant 25.7% increase from the expected incidence. Of the 33 patients who consented to the study, 32 presented negative IgG values, with only one patient reflecting undiagnosed past infection. Forty-four percent of patients presented with ketoacidosis at onset, which was similar to previous years. CONCLUSIONS: We conclude that there is no direct relationship between the increased incidence of T1DM and SARS-CoV-2 in the region. The COVID-19 pandemic did not result in an increased severity of T1DM presentation.

Global estimates of incidence of type 1 diabetes in children and adolescents: Results from the International Diabetes Federation Atlas, 10th edition.

BACKGROUND: Type 1 diabetes (T1D) incidence in children and adolescents varies widely, and is increasing in many nations. The 10th edition of the International Diabetes Federation Atlas estimated incident cases in 2021 for 215 countries/territories ("countries"). METHODS: Studies on T1D incidence for young people aged 0-19 years were sourced and graded using previously described methods. For countries without studies, data were extrapolated from similar nearby countries. RESULTS: An estimated 108,300 children under 15 years will be diagnosed in 2021, a number rising to 149,500 when the age range extends to under 20 years. The ratio of incidence in 15-19 years compared to those aged 0-14 years was particularly high in some countries in sub-Saharan Africa, North Africa/Middle East, and in Mexico. Only 97 countries have their own incidence data, with extrapolation required for some very populous nations. Most data published were not recent, with 27 countries (28%) having data in which the last study year was 2015 or afterwards, and 26 (27%) having no data after 1999. CONCLUSIONS: Many countries have recent data but there are large gaps globally. Such data are critical for allocation of resources, teaching, training, and advocacy. All countries are encouraged to collect and publish current data.

A human rights-based approach to improve access to insulin and other aspects of diabetes care.

Many nations struggle to provide adequate diabetes care. Legal as well as moral obligations may facilitate access. International human rights law places obligations on governments to ensure the accessibility and affordability of insulin (a World Health Organization essential medicine), and other components of diabetes care. Despite this obligation, the global reality is that access remains deficient. A human rights approach facilitating the improvement of diabetes services and equitable access to insulin provides a strong framework, theoretically and practically, for advocacy and policymaking changes. This approach links governments to their international obligations, fosters the ideal of, and adherence to, national essential medicine lists, complements the pursuit of international goals in non-communicable diseases, and should influence the actions of pharmaceutical and device companies. This approach empowers patients, families, and communities living with diabetes, and grounds actions by governments, clinicians, and non-government organisations in the principles of dignity, non-discrimination, and equity of access.

High incidence of type 1 diabetes in adolescents and young adults in Eritrea.

BACKGROUND: Eritrea has no data on type 1 diabetes incidence in children and youth; therefore, a study was undertaken to determine this in persons aged <25 years. METHODS: Data were collected on new type 1 diabetes diagnoses during 2019, from district, provincial and national hospitals. Type 1 diabetes was diagnosed according to standard WHO criteria. No secondary ascertainment source was available. 95% confidence intervals were computed based on approximation to the Poisson distribution, and age and gender effects were analysed with Poisson regression. RESULTS: There were 532 new cases of type 1 diabetes. Mean ± standard deviation (range) age of diagnosis was 16.2 ± 5.7 (1.5-24.9) years, and peak age group was 15-19 years (n = 200, 37.6%), with mode at 18 years. Incidence <15 years was 11.5/100,000 individuals [9.9-13.2], with the highest incidence in the 10-14 years group (19.0/100,000 [15.5-23.1]). Incidence then peaked in the 15-19 years age group (50.2/100,000 [43.5-57.7]) and remained high in the 20-24 years group (46.2/100,000 [39.0-54.3]). There was a male:female ratio of 1.37 (p = 0.001). Two hundred and thirty-eight (44.7%) presented in diabetic ketoacidosis. CONCLUSION: Type 1 diabetes incidence in Eritrea is moderate <15 years, and high 15-24 years. The 15-19 and 20-24 years rates appear to be the highest published to date. Given the study was only for one year, further confirmatory prospective information will clarify the situation and document trends. Assessment of the type 1 diabetes phenotypes that are occurring in Eritrea is also indicated.

'La Vida Normal': Young people adapting to Type 1 diabetes in Bolivia.

OBJECTIVES: To identify challenges and coping strategies of young people with Type 1 diabetes (T1D) and their families in Bolivia through qualitative analysis of interviews with beneficiaries of Centro Vivir con Diabetes (CVCD), a diabetes health center supported by the International Diabetes Federation Life for a Child (LFAC) program. METHODS: Eighteen young people aged 14-33 and at least one caregiver participated in semi-structured interviews in five cities in Bolivia from May to June 2016. Interviews were recorded, transcribed, and analyzed using inductive thematic analysis. RESULTS: Participants described needing guidance at diagnosis and facing stigma in communities. Young people expressed that life with T1D was 'la vida normal' (a normal life), although interpretations of normalcy varied. For some, 'la vida normal' meant resistance to T1D; for others it indicated acceptance. DISCUSSION: Access to interdependent spheres of support allowed young people to form a new normal around T1D. Receiving supplies through the CVCD/LFAC partnership maintained family connection to clinical care, CVCD education helped families share in T1D management, and peer support mitigated stigma for young people. Programs like CVCD that combine supply-based aid with clinical education for whole families, create effective support for young people with T1D in low- and middle-income countries.

Update on Worldwide Trends in Occurrence of Childhood Type 1 Diabetes in 2020.

Epidemiological data on pediatric type 1 diabetes (T1D), mainly incidence, have become increasingly available since the second half of the 20th century. Comparative incidence data across populations were only obtained since the 1980s. The 2019 IDF Atlas provides T1D incidence, prevalence and mortality estimates for children < 15 years for all 211 countries, but actual data were available for only 94 countries (only 3 low-income). The estimated prevalent cases were 600,900 and incident cases 98,200. Incidence remains highest in Finland (60/100,000/ year), Sardinia and Sweden, followed by Kuwait, some other northern European countries, Saudi Arabia, Algeria, Australia, New Zealand, USA and Canada. The lowest incidence is seen across East and South-East Asia. Globally, the average increase in incidence has been 3-4%/year over past decades, being steeper in low-incidence countries. Although T1D mortality has drastically decreased, there is still a higher risk compared with the non-diabetic population, especially in people with diabetic nephropathy.

Costs and outcomes of "intermediate" vs "minimal" care for youth-onset type 1 diabetes in six countries.

OBJECTIVE: Data are needed to demonstrate that providing an "intermediate" level of type 1 diabetes (T1D) care is cost-effective compared to "minimal" care in less-resourced countries. We studied these care scenarios in six countries. METHODS: We modeled the complications/costs/mortality/healthy life years (HLYs) associated with "intermediate" care including two blood glucose tests/day (mean HbA1c 9.0% [75 mmol/mol]) in three lower-gross domestic product (GDP) countries (Mali, Tanzania, Pakistan), or three tests/day (mean HbA1c 8.5% [69 mmol/mol]) in three higher-GDP countries (Bolivia, Sri Lanka, Azerbaijan); and compared findings to "minimal" care (mean HbA1c 12.5% [113 mmol/mol]). A discrete time Markov illness-death model with age and calendar-year-dependent transition probabilities was developed, with inputs of 30 years of complications and Standardized Mortality Rate data from the youth cohort in the Pittsburgh Epidemiology of Diabetes Complications Study, background mortality, and costs determined from international and local prices. RESULTS: Cumulative 30 years incidences of complications were much lower for "intermediate care" than "minimal care", for example, for renal failure incidence was 68.1% (HbA1c 12.5%) compared to 3.9% (9%) and 2.4% (8.5%). For Mali, Tanzania, Pakistan, Bolivia, Sri Lanka, and Azerbaijan, 30 years survival was 50.1%/52.7%/76.7%/72.5%/82.8%/89.2% for "intermediate" and 8.5%/10.1%/39.4%/25.8%/45.5%/62.1% for "minimal" care, respectively. The cost of a HLY gained as a % GDP/capita was 141.1%/110.0%/52.3%/41.8%/17.0%/15.6%, respectively. CONCLUSIONS: Marked reductions in complications rates and mortality are achievable with "intermediate" T1D care achieving mean clinic HbA1c of 8.5% to 9% (69-75 mmol/mol). This is also "very cost-effective" in four of six countries according to the WHO "Fair Choices" approach which costs HLYs gained against GDP/capita.

Incidence, prevalence and mortality of diabetes in children and adolescents aged under 20 years in the Republic of Maldives.

AIM: There is little published data on diabetes in youth in the Maldives. This study aimed to determine incidence, prevalence and mortality of diabetes in children and adolescents <20 years. METHODS: Data on all known existing cases in 2009 and all new cases from 2009 to 2018 was collected from the Diabetes Society of the Maldives registry. RESULTS: Thirty-nine subjects <20 years were known to have diabetes at the start of 2009 and 92 new cases were diagnosed from 2009 to 2018. Of the 92 new cases, 76 had type 1 diabetes (T1D), 15 type 2 diabetes (T2D) and one secondary diabetes. Of the 76 new T1D cases, 64 were diagnosed <15 years. Mean age of onset for T1D <20 years was 10 ± 4.6 years, with 42 (55.3%) female. Ten (13.2%) were diagnosed 0-4 years, 27 (35.5%) 5-9 years, 27 (35.5%) 10-14 years and 12 (15.8%) 15-19 years. Annual T1D mean incidence rates/per 100 000 subjects for <15/<20 years, respectively, increased from 3.6/2.7 in 2009 to 11.0/9.1 in 2018, representing 12.0%/13.0% annualised increases (P = 0.01 for both). T1D prevalence in 2018 for <15 and <20 years was 47.1/100 000 and 52.0/100 000, respectively. No young person with T1D died during this period, with a total of 262 patient-years of follow-up for T1D cases. The child with secondary diabetes died of other causes. CONCLUSION: T1D incidence in Maldives is higher than that reported from other South Asian countries, and an increasing trend was observed. T2D also occurs relatively frequently. A zero mortality rate was observed for children and young adults with T1D and T2D from 2009 to 2018.