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.

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.

Clinical features, biochemistry, and HLA-DRB1 status in youth-onset type 1 diabetes in Mali.

OBJECTIVE: Limited information is available regarding youth-onset diabetes in Mali. We investigated demographic, clinical, biochemical, and genetic features in new diabetes cases in children and adolescents. RESEARCH DESIGN AND METHODS: The study was conducted at Hôpital du Mali in Bamako. A total of 132 recently-diagnosed cases <21 years were enrolled. Demographic characteristics, clinical information, biochemical parameters (blood glucose, HbA1c, C-peptide, glutamic acid decarboxylase-65 (GAD-65) and islet antigen-2 (IA2) autoantibodies) were assessed. DNA was genotyped for HLA-DRB1 using high-resolution genotyping technology. RESULTS: A total of 130 cases were clinically diagnosed as type 1 diabetes (T1D), one with type 2 diabetes (T2D), and one with secondary diabetes. A total of 66 (50.8%) T1D cases were males and 64 (49.2%) females, with a mean age at diagnosis of 13.8 ± 4.4 years (range 0.8-20.7 years) peak onset of 15 years. 58 (44.6%) presented in diabetic ketoacidosis; with 28 (21.5%) IA2 positive, 76 (58.5%) GAD-65 positive, and 15 (11.5%) positive for both autoantibodies. HLA was also genotyped in 195 controls without diabetes. HLA-DRB1 genotyping of controls and 98 T1D cases revealed that DRB1*03:01, DRB1*04:05, and DRB1*09:01 alleles were predisposing for T1D (odds ratios [ORs]: 2.82, 14.76, and 3.48, p-values: 9.68E-5, 2.26E-10, and 8.36E-4, respectively), while DRB1*15:03 was protective (OR = 0.27; p-value = 1.73E-3). No significant differences were observed between T1D cases with and without GAD-65 and IA2 autoantibodies. Interestingly, mean C-peptide was 3.6 ± 2.7 ng/ml (1.2 ± 0.9 nmol/L) in T1D cases at diagnosis. CONCLUSIONS: C-peptide values were higher than expected in those diagnosed as T1D and autoantibody rates lower than in European populations. It is quite possible that some cases have an atypical form of T1D, ketosis-prone T2D, or youth-onset T2D. This study will help guide assessment and individual management of Malian diabetes cases, potentially enabling healthier outcomes.

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.

Rapid increases in observed incidence and prevalence of Type 1 diabetes in children and youth in Mali, 2007-2016.

AIMS: Determine incidence, prevalence and mortality of Type 1 diabetes (T1D) in children and youth <25 years (y) in Mali during the first 10 years of the Santé Diabète/Life for a Child program. METHODS: Data were collected from the prospective program register. Diagnosis of T1D was clinical, based on presentation, clinical features, immediate requirement for insulin, and no suggestion of other diabetes types. RESULTS: Total of 460 cases were diagnosed with T1D <25 years in 2007-2016. Male-to-female ratio was 1.04:1. Peak age at onset was 15-16 years (range 1.1-24 years). T1D incidence <25 years per 100,000 population/year increased from 0.12 in 2007 to 0.74 in 2016 (an 18% annualized increase, p < 0.001). Incidence peaked at 0.80 in 2014, the year after an education campaign was conducted. Incidence <15 years rose from 0.12 to 0.35 per 100,000/year in 2007 and 2016, respectively, (14% annualized increase, p < 0.001). There was a steep, consistent increase in prevalence (per 100,000) from 0.43 in 2007 to 2.90 in 2016 (p < 0.001). Prevalence <15 years was 0.34/100,000 in 2007 and 1.02/100,000 by 2016 (p < 0.001). Overall crude mortality rate was 30.0/1000 patient years, equating to a standardized mortality rate of 9.0, with vital status known for 99.8% of cases. CONCLUSION: Known incidence and prevalence of diabetes in Mali increased rapidly from 2007 to 2016, contemporaneous with the introduction and development of the Santé Diabète/Life for a Child program. Improved diagnosis and care resulting in lower mortality are likely contributors. True incidence may still be underestimated, with some cases still dying undiagnosed and full study ascertainment being uncertain.

Clinical features, biochemistry, and HLA-DRB1 status in youth-onset type 1 diabetes in Sudan.

OBJECTIVE: To further understand clinical and biochemical features, and HLA-DRB1 genotypes, in new cases of diabetes in Sudanese children and adolescents. RESEARCH DESIGN AND METHODS: Demographic characteristics, clinical information, and biochemical parameters (blood glucose, HbA1c, C-peptide, autoantibodies against glutamic acid decarboxylase 65 [GADA] and insulinoma-associated protein-2 [IA-2A], and HLA-DRB1) were assessed in 99 individuals <18 years, recently (<18 months) clinically diagnosed with T1D. HLA-DRB1 genotypes for 56 of these Arab individuals with T1D were compared to a mixed control group of 198 healthy Arab (75%) and African (25%) individuals without T1D. RESULTS: Mean ± SD age at diagnosis was 10.1 ± 4.3 years (range 0.7-17.6 years) with mode at 9-12 years. A female preponderance was observed. Fifty-two individuals (55.3%) presented in diabetic ketoacidosis (DKA). Mean ± SD serum fasting C-peptide values were 0.22 ± 0.25 nmol/L (0.66±0.74 ng/ml). 31.3% were autoantibody negative, 53.4% were GADA positive, 27.2% were IA-2A positive, with 12.1% positive for both autoantibodies. Association analysis compared to 198 controls of similar ethnic origin revealed strong locus association with HLA-DRB1 (p < 2.4 × 10-14 ). Five HLA-DRB1 alleles exhibited significant T1D association: three alleles (DRB1*03:01, DRB1*04:02, and DRB1*04:05) were positively associated, while three (DRB1*10:01, DRB1*15:02, and DRB1*15:03) were protective. DRB1*03:01 had the strongest association (odds ratio = 5.04, p = 1.7 × 10-10 ). CONCLUSIONS: Young Sudanese individuals with T1D generally have similar characteristics to reported European-origin T1D populations. However, they have higher rates of DKA and slightly lower autoantibody rates than reported European-origin populations, and a particularly strong association with HLA-DRB1*03:01.

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.

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.

Relationship of C-peptide levels to duration of Type 1 diabetes - A study from Sindh, Pakistan.

OBJECTIVE: To determine the relationship of C-peptide levels with duration of type 1 diabetes mellitus. METHODS: This prospective study was conducted at Baqai Institute of Diabetology and Endocrinology (BIDE), Baqai Medical University (BMU), Karachi-Pakistan from December 2013 to December 2015. A total of 184 subjects were recruited during the study period, 100 in Group-A and 84 in Group-B. Subjects clinically diagnosed with type 1 diabetes Mellitus (T1DM) were categorized into two groups based on duration of diabetes: Group-A (with ≤1-year duration of diabetes) and Group-B (with >1-year duration of diabetes). Ninety-nine of the 100 enrolled subjects in Group-A were diagnosed as having T1DM, with one subject who presented at 11.9 years of age and diagnosed with T2DM excluded from this study. Blood samples were drawn for biochemical parameters. Data for baseline characteristics and clinical parameters (HbA1c and C-peptide) were obtained from hospital management system of BIDE. RESULTS: Fifty-seven (57.6%) subjects in Group-A, and 39 (46.4%) in Group-B were males. Mean±SD duration of diabetes (years) was 0.64±0.6 (range 0-1) in Group-A, and 7.65±5.5 (range 1-23) in Group-B. Family history of T1DM and T2DM was 1(1%) and 27(27.3%) in Group-A, and 8(9.52%) and 21(25%) in Group-B, respectively. Twenty-one (21.2%) subjects presented in diabetic ketoacidosis (DKA) in Group-A and 18(21.4%), in Group-B. Mean±SD for HbA1c was non-significantly higher in Group-A 11.12±2.31 compared to Group-B 10.42±1.45. Mean±SD for C-peptide was 1.91±1.53 ng/mL (0.60±0.481 nmol/L) in Group-A, and 1.82±1.01 (0.57±0.32 nmol/L) in Group-B (p=0.984). CONCLUSION: The study found that subjects with longer duration of T1DM had non-significantly decreased C-peptide levels compared to a group in which C-peptide was measured at or soon after diagnosis. Furthermore, C-peptide levels in many subjects with longer duration were higher than expected in classic T1DM.

Levels of type 1 diabetes care in children and adolescents for countries at varying resource levels.

Optimal care for children and adolescents with type 1 diabetes is well described in guidelines, such as those of the International Society for Pediatric and Adolescent Diabetes. High-income countries can usually provide this, but the cost of this care is generally prohibitive for lower-income countries. Indeed, in most of these countries, very little care is provided by government health systems, resulting in high mortality, and high complications rates in those who do survive. As lower-income countries work toward establishing guidelines-based care, it is helpful to describe the levels of care that are potentially affordable, cost-effective, and result in substantially improved clinical outcomes. We have developed a levels of care concept with three tiers: "minimal care," "intermediate care," and "comprehensive (guidelines-based) care." Each tier contains levels, which describe insulin and blood glucose monitoring regimens, requirements for hemoglobin A1c (HbA1c) testing, complications screening, diabetes education, and multidisciplinary care. The literature provides various examples at each tier, including from countries where the life for a child and the changing diabetes in children programs have assisted local diabetes centres to introduce intermediate care. Intra-clinic mean HbA1c levels range from 12.0% to 14.0% (108-130 mmol/mol) for the most basic level of minimal care, 8.0% to 9.5% (64-80 mmol/mol) for intermediate care, and 6.9% to 8.5% (52-69 mmol/mol) for comprehensive care. Countries with sufficient resources should provide comprehensive care, working to ensure that it is accessible by all in need, and that resulting HbA1c levels correspond with international recommendations. All other countries should provide Intermediate care, while working toward the provision of comprehensive care.

Epidemiological data of type 1 diabetes mellitus in children in Uzbekistan, 1998-2014.

AIMS: We aimed to determine the incidence, prevalence and mortality of type 1 diabetes (T1D) in Uzbekistan in children <15 years old. METHODS: In a prospective study from 1998 to 2014 the primary ascertainment of incidence, prevalence and mortality, and cause of death was via data collected by endocrinology dispensaries in Uzbekistan's 14 administrative divisions. A second data collection for 2008-2010 from a national audit in 2011 was used to determine age structure. RESULTS: Over 1998-2014 T1D prevalence roughly doubled (7.8 to 15.3/100,000 population aged <15 years, P = .10), following a doubling of incidence (1.5 to 3.1/100 000 < 15 years), a 5.6% annualized increase, P = .001), with a fall in mortality per 1000 patient years (24.5 to 2.0, P = .001). There was a female preponderance, with a male:female ratio of 0.89 in 2008-2010. In every year, T1D incidence was highest in the 10-14.99 year age-group, although the proportion of diagnoses under 5 years of age increased from 6.0% of total diagnoses in 1998-2002, to 13.4% in 2008-2010. Peak age of onset in 2008-2010 was 13 years. Notable regional variation was evident, with incidence being highest in Tashkent-City (P = .005). The most common cause of death was chronic renal failure-responsible for 31 deaths in children <15 years during the study period. CONCLUSIONS: Our results provide the first long-term epidemiological data for T1D in Uzbekistan and the region. Uzbekistan is country of low but rising T1D incidence and prevalence, and falling mortality. Attention to improving clinical care is warranted, to reduce long-term complications.

Caregiving for children with type 1 diabetes and clinical outcomes in central India: The IDREAM study.

AIMS: Parental care influences outcomes for children's type 1 diabetes (T1D). There is little evidence about the impact of parental caregiving in developing countries, where fixed dose human insulin (conventional) therapy and limited self-monitoring of blood glucose are common. This article investigates whether performance of key T1D management tasks by children or their caregivers impacts hemoglobin A1c (HbA1c). METHODS: We surveyed the caregivers of 179 children with T1D routinely treated in a specialized diabetes clinic in Maharashtra, India to determine who performs key diabetes care tasks: child or parent. We used linear regression to estimate the relationship between parental caregiving and HbA1c, and how this association varies by child age and time since diagnosis. RESULTS: Caregivers of older children were less involved in care tasks, though caregivers of 11- to 18-year olds performed more care for children diagnosed for a longer duration. Parental involvement in key insulin delivery tasks was associated with lower HbA1c levels for all children. These reductions were greatest among children 11 to 14 years old and diagnosed for less than 2 years: mean HbA1c levels were 8.5% (69 mmol/mol) if the caregiver, and 14.4% (134 mmol/mol) if the child, performed the tasks (P < .05). CONCLUSION: Parents of children diagnosed with T1D early in life remain involved in care throughout the child's adolescence. Parents of children diagnosed in late childhood and early adolescence are significantly less involved in care, and this is associated with worse glycemic control. Clinics must know who performs care tasks and tailor diabetes education appropriately.

The IDF Life for a Child Program Index of diabetes care for children and youth.

BACKGROUND AND OBJECTIVES: Care for children and youth with diabetes varies markedly around the world. We developed a standardized, reproducible measure that can be used to document and compare critical factors influencing treatment outcomes. METHODS: A questionnaire consisting of 36 multiple-choice questions covering major components of care (such as insulin therapy, blood glucose monitoring, etc.) was sent to 75 countries: 43 under-resourced countries where the International Diabetes Federation's Life for a Child Program operates, and 32 others (mainly developed nations). Results for each country were scaled to a score with a range of 0-100. RESULTS: Responses were received from 71 countries. Scores varied widely and were highly correlated to per capita gross domestic product (R(2) = 0.72, P < 0.001) and health expenditure (R(2) = 0.77, P < 0.001). For the 37 low- and lower-middle income countries, only two had complete government provision of human insulin and none of blood glucose test strips. Marked differences according to income were also found for access to home refrigeration; usage of insulin pens, multiple daily injections, pumps, glucagon and ketone strips; hemoglobin A1c (HbA1c) testing; and complications screening. CONCLUSIONS: The index is a comprehensive, easily administered survey instrument. It demonstrated stark differences in access to numerous components of care necessary in achieving good outcomes for children and youth with diabetes.

Incidence and prevalence of diabetes in children aged <15 yr in Fiji, 2001-2012.

OBJECTIVE: Determine the incidence and prevalence of diabetes in children <15 yr in Fiji. METHODS: Data on all new cases from 2001 to 2012 was collected from the three paediatric diabetes services through the International Diabetes Federation Life for a Child Program. There was no formal secondary ascertainment source, however the medical community is small and all known cases are believed to be included. RESULTS: Forty-two children aged <15 yr were diagnosed from 2001 to 2012. Twenty-eight were type 1 (66.7%), 13 type 2 (31.0%), and 1 (2.4%) had neonatal diabetes (INS gene mutation). For type 1, the mean ± standard deviation (SD) age of diagnosis was 10.2 ± 2.9 yr, with similar proportions of males and females. Four (14.3%) were native Fijians and 24 (86.7%) were of Indo-Fijian descent (p < 0.001). The mean annual incidence of type 1 in children <15 yr was 0.93/100,000 and prevalence in 2012 was 5.9/100,000. There was no evidence of a rise in incidence, but low numbers would preclude recognition of a small increased rate. For the 13 cases of type 2 diabetes, the mean SD age of diagnosis was 12.2 ± 2.7 yr, 85% were female (p < 0.01), and 85% were of Indo-Fijian descent (p = 0.001). The mean annual incidence of type 2 was 0.43/100,000 and 2012 prevalence was 2.4/100,000. No child with diabetes aged <15 yr died during the 12-yr period. CONCLUSIONS: The incidence of type 1 diabetes in Fiji is very low. Furthermore, its occurrence is markedly more frequent in Indo-Fijians than in native Fijians. Type 2 and neonatal diabetes also occur.

Clinical features, biomarkers and diabetic ketoacidosis at diagnosis of type 1 diabetes among children and adolescents in Sana'a, Yemen.

INTRODUCTION: There is little published information on type 1 diabetes (T1D) in children in Yemen. We aimed to identify the clinical characteristics, biomarkers and diabetic ketoacidosis (DKA) at diagnosis of T1D among children and adolescents in a diabetes centre in Sana'a, Yemen. METHODS: A total of 485 children and adolescents aged ≤18 years diagnosed with T1D during the period 2010-2020 were included in the study. The variables investigated were demographic and clinical characteristics, biomarkers, subtypes of T1D, and the risk factors for severe DKA at diagnosis. RESULTS: At diagnosis, children aged <10 years compared with those aged ≥10 years had higher mean plasma glucose (p<0.001) and mean HbA1c (p=0.026), and lower mean C-peptide (pmol/L) (p=0.019), and a higher frequency of DKA at diagnosis than older children (p<0.001). A majority of the study population (383, 79%) presented in DKA . Children aged <10 years presenting with DKA had significantly longer median appraisal interval (p=0.009) and median total diagnosis interval (p=0.025), and significantly lower mean C-peptide (p=0.001) as compared with their peers without DKA. The prevalence of autoantibody-negative 'idiopathic' T1D was 36 (32%) of the total number tested for autoantibody and familial T1D 61 (12.6%) of all the study population. CONCLUSION: In Yemen children aged <10 years with new-onset T1D frequently faced the challenge of a delay in diagnosis and treatment initiation, with severe hyperglycaemia and a higher risk of DKA at diagnosis.

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.