User requirements for non-invasive and minimally invasive glucose self-monitoring devices in low-income and middle-income countries: a qualitative study in Kyrgyzstan, Mali, Peru and Tanzania.

AIMS: Development of non-invasive and minimally invasive glucose monitoring devices (NI-MI-GMDs) generally takes place in high-income countries (HICs), with HIC's attributes guiding product characteristics. However, people living with diabetes (PLWD) in low-income and middle-income countries (LMICs) encounter different challenges to those in HICs. This study aimed to define requirements for NI-MI-GMDs in LMICs to inform a target product profile to guide development and selection of suitable devices. METHODS: This was a multiple-methods, exploratory, qualitative study conducted in Kyrgyzstan, Mali, Peru and Tanzania. Interviews and group discussions/activities were conducted with healthcare workers (HCWs), adults living with type 1 (PLWD1) or type 2 diabetes (PLWD2), adolescents living with diabetes and caregivers. RESULTS: Among 383 informants (90 HCW, 100 PLWD1, 92 PLWD2, 24 adolescents, 77 caregivers), a range of differing user requirements were reported, including preferences for area of glucose measurement, device attachment, data display, alert type and temperature sensitivity. Willingness to pay varied across countries; common requirements included ease of use, a range of guiding functions, the possibility to attach to a body part of choice and a cost lower than or equal to current glucose self-monitoring. CONCLUSIONS: Ease-of-use and affordability were consistently prioritised, with broad functionality required for alarms, measurements and attachment possibilities. Perspectives of PLWD are crucial in developing a target product profile to inform characteristics of NI-MI-GMDs in LMICs. Stakeholders must consider these requirements to guide development and selection of NI-MI-GMDs at country level, so that devices are fit for purpose and encourage frequent glucose monitoring among PLWD in these settings.

Formative research to adapt the 'Diabetes Prevention Program- Power to Prevent' for implementation in Bamako, Mali.

BACKGROUND: There are few community-level behaviors change interventions for reducing diabetes and hypertension risk in Africa, despite increasing cases of type 2 diabetes and cardiovascular diseases. Thus, this study was designed to adapt the United States Centers for Disease Control and Prevention's "Diabetes Prevention Program Power to Prevent" (DPP-P2P) for use in low-income urban communities of Bamako, Mali. METHODS: Feedback was elicited on an initial French PowerPoint adaptation of the DPP-P2P session guidelines from stakeholders at the ministry of health, organizational partners, and medical care providers. Two community health centers in districts with high levels of diabetes or hypertension were selected to assist in developing the Malian adaptation. Focus groups were conducted with 19 community health workers (CHWs) of these centers. Based on feedback from these discussions, more graphics, demonstrations, and role plays were added to the PowerPoint presentations. The 19 CHWs piloted the proposed 12 sessions with 45 persons with diabetes or at-risk patients over a one-month period. Feedback discussions were conducted after each session, and changes in dietary and exercise habits were assessed pre and post participation in the program. This feedback contributed to finalization of a 14-session sequence. RESULTS: The DPP-P2P session guidelines were adapted for use by low-literacy CHWs, converting the written English guidelines into French PowerPoint presentations with extensive use of pictures, role plays and group discussions to introduce diabetes, diet, and exercise concepts appropriately for the Bamako context. CHWs recommendations for a strong family-oriented program led to expanded sessions on eliciting support from all adults in the household. The 45 participants in the pilot adaptation were enthusiastic about the program. At the end of the program, there were significant increases in the frequency of daily exercise, efforts to limit fat intake, and goals for more healthy diets and exercise levels. CONCLUSION: This study documents how an iterative process of developing the DPP-P2P adaptation led to the development of a culturally appropriate set of materials welcomed by participants and having promise for reaching the low-income, low-literacy population with or at risk for diabetes in Bamako, Mali.

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.

Strengthening Health Literacy Through Structured Sessions for Non-Communicable Diseases in Low-Resource Settings: The Learning Nest Model.

Health literate self-management education is at stake for the prevention and management of non-communicable diseases in low resources settings and countries. Here we describe the Learning Nest in Ordinary Context (NA-CO in French, Nids d'Apprentissage en Contexte Ordinaire) aiming at the structuring of health education programs at the micro- (education sessions) and the meso-levels (adapted to context). The Learning Nest model was designed based on a combination on health literacy principles and on studies conducted with vulnerable people with non-communicable diseases. Observation of NA-CO active-learning sessions found them to be operational and relevant as they center on access, understanding, and use of health information while integrating the ordinary context of learners. The Learning Nest packages (including several adapted thematic sessions, training of trainers and development in context) were shown to be feasible and realistic in diverse locations (Reunion, Mali, Mayotte, Mauritius, Burundi). Qualitative and intervention studies have documented the potential usefulness of the Learning Nest model for context- and setting-specific health literacy interventions.

Caecal digestibility as an approximation of ileal protein digestibility evaluation in rats.

The rat model can be used to assess ileal protein digestibility rapidly and in first intention, but no standardised method exists. Our objective was to compare methods to assess protein digestibility, depending on collection site (ileum/caecum) and use of a non-absorbable marker. A meal containing either casein, gluten or pea protein and chromium oxide as non-absorbable marker was given to male Wistar rats and the entire digestive content was collected 6 h later. Total chromium recovery was incomplete and variable, depending on protein source. We observed no significant difference in digestibility between the methods for any of the protein sources tested. Although none of the methods tested is optimal, our results suggest that caecal digestibility can be used as a proxy of ileal digestibility in rats without using a non-absorbable marker. This simple method makes it possible to evaluate protein digestibility of new alternative protein sources for human consumption.

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.

The role of non-governmental organizations in strengthening healthcare systems in low- and middle-income countries: Lessons from Santé Diabète in Mali.

Non-governmental organizations play a vital part in the achievement of the Sustainable Development Goals as defined by the United Nations. These Goals also include targets related to noncommunicable diseases. However, non-governmental organizations have played a limited role in this area despite such diseases causing the bulk of morbidity and mortality worldwide. Through their activities, non-governmental organizations should aim to strengthen health systems, yet they often only support these for a single disease. Mali, like many other low- and middle-income countries, is facing an increasing burden of diabetes and a health system not adapted to address this challenge. Santé Diabète, a non-governmental organization based in Mali since 2003, has been working specifically on diabetes, and has developed a wide range of activities to improve the national health system. This paper describes changes in the diabetes environment in Mali between 2004 and 2018 based on two health system assessments carried out using a Rapid Assessment Protocol. Over this period, the health system was strengthened with regard to financing and access to medical products. Leadership and governance, service delivery and health workforce were all improved but still partially rely on sustained support from Santé Diabète. The key lesson from this study is that to be effective in changing the management of noncommunicable diseases in a low- and middle-income country, non-governmental organizations need to play a variety of roles, many of which may change over time.

Management of type 1 diabetes in low- and middle-income countries: Comparative health system assessments in Kyrgyzstan, Mali, Peru and Tanzania.

AIMS: To describe and compare the health system responses for type 1 diabetes in Kyrgyzstan, Mali, Peru and Tanzania. METHODS: The Rapid Assessment Protocol for Insulin Access, a multi-level assessment of the health system, was implemented in Kyrgyzstan, Mali, Peru and Tanzania using document reviews, site visits and interviews to assess the delivery of care and access to insulin. RESULTS: Despite the existence of noncommunicable or diabetes strategies and Universal Health Coverage policies including diabetes-related supplies, this has not necessarily translated into access to insulin or diabetes care for all. Insulin and related supplies were often unavailable and unaffordable. Across the four countries test strips and insulin, when paid for by the individual, represented respectively 48-82% and 25-36% of total costs. Care was mainly delivered at tertiary-level hospitals by specialists. Only Kyrgyzstan had data collection systems integrated into the Ministry of Health structure. In addition, issues with healthcare worker training and education and empowerment of people with diabetes were present in these health systems. CONCLUSIONS: People with type 1 diabetes in these countries face different barriers, including the cost of insulin and care. Given the renewed attention to diabetes on the global health agenda tailored health system responses for type 1 diabetes are needed. Insulin should be prioritized as it is the foundation of type 1 diabetes care, but other elements of care and support need to be fostered by different actors.

Strengthening Diabetes Care in Humanitarian Crises in Low- and Middle-income Settings.

Amid the growing global diabetes epidemic, the scale of forced displacement resulting from armed conflict and humanitarian crises is at record-high levels. More than 80% of the displaced population lives in lower- and middle-income countries, which also host 81% of the global population living with diabetes. Most crises are protracted, often lasting decades, and humanitarian aid organizations are providing long-term primary care to both the local and displaced populations. Humanitarian crises are extremely varied in nature and occur in contexts that are diverse and dynamic. The scope of providing diabetes care varies depending on the phase of the crisis. This paper describes key challenges and possible solutions to improving diabetes care in crisis settings. It focuses on (1) ensuring a reliable supply of life preserving medications and diagnostics, (2) restoring and maintaining access to health care, and (3) adapting service design to the context. These challenges are illustrated through case studies in Ukraine, Mali, the Central African Republic, and Jordan.

Hemoglobin A1c trajectories in the first 18 months after diabetes diagnosis in the SWEET diabetes registry.

AIM: A majority of youth with type 1 diabetes do not meet recommended hemoglobin A1c (HbA1c) targets. The SWEET diabetes registry is a multi-national registry of youth with diabetes. We used data from this registry to identify characteristics associated with glycemic control. METHODS: Patients in the SWEET diabetes registry with at least one HbA1c value within 10 days of diagnosis and three follow up measurements in the first 18 months of diagnosis were included (~10% of the SWEET diabetes registry). Locally weighted scatterplot smoothing was used to generate curves of HbA1c. Wilcoxon, Kruskal-Wallis, or χ2-tests were used to calculate differences between groups. RESULTS: The mean HbA1c of youth in the SWEET diabetes registry is highest at diagnosis and lowest between months 4 and 5 post-diabetes diagnosis. HbA1c continues to increase steadily through the first 18 months of diagnosis. There are no differences in HbA1c trajectories based on sex or use of diabetes technology. Youth in North America/Australia/New Zealand had the highest HbA1c throughout the first 18 months of diagnosis. The trajectory of youth from countries with nationalized health insurance was lower than those countries without nationalized health insurance. Youth from countries with the highest gross domestic product (GDP) had the highest HbA1c throughout the first 18 months of diagnosis. CONCLUSIONS: In this subset of patients, the trajectory of youth from countries with nationalized health insurance was lower than those countries without nationalized health insurance. High GDP and high use of technology did not seem to protect from a higher trajectory.

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.

Worldwide differences in childhood type 1 diabetes: The SWEET experience.

OBJECTIVE: To study worldwide differences in childhood diabetes, comparing relevant indicators among five regions within the SWEET initiative. SUBJECTS: We investigated 26 726 individuals with type 1 diabetes (T1D) from 54 centers in the European region; 7768 individuals from 30 centers in the Asia/Middle East/Africa region; 2642 people from five centers in Australia/New Zealand; 10 839 individuals from seven centers in North America, and 1114 patients from five centers in South America. METHODS: The SWEET database was analyzed based on the following inclusion criteria: T1D, time period 2015-2019, and age < 21 years, with analysis of the most recent documented year of therapy. For the statistical analysis, we used multivariable linear and logistic regression models to adjust for age (<6 years, 6- < 12 years, 12- < 18 years, 18- < 21 years), gender, and duration of diabetes (<2 years, 2- < 5 years, 5- < 10 years, ≥10 years). RESULTS: Adjusted HbA1c means ranged from 7.8% (95%-confidence interval: 7.6-8.1) in Europe to 9.5% (9.2-9.8) in Asia/Middle East/Africa. Mean daily insulin dose ranged from 0.8 units/kg in Europe (0.7-0.8) and Australia/New Zealand (0.6-0.9) to 1.0 unit/kg 0.9-1.1) in Asia/Middle East/Africa. Percentage of pump use was highest in North America (80.7% [79.8-81.6]) and lowest in South America (4.2% [3.2-5.6]). Significant differences between the five regions were also observed with regards to body mass index SD scores, frequency of blood glucose monitoring and presence of severe hypoglycaemia. CONCLUSIONS: We found significant heterogeneity in diabetes care and outcomes across the five regions. The aim of optimal care for each child remains a challenge.

Global and regional estimates and projections of diabetes-related health expenditure: Results from the International Diabetes Federation Diabetes Atlas, 9th edition.

AIMS: Diabetes and its complications have a significant economic impact on individuals and their families, health systems and national economies. METHODS: The direct health expenditure of diabetes was calculated relying on the following inputs: diagnosed and undiagnosed diabetes prevalence estimates, United Nations population estimates, World Health Organization health expenditure per capita and ratios of health expenditure for people with diabetes compared to people without diabetes. RESULTS: The estimated global direct health expenditure on diabetes in 2019 is USD 760 billion and is expected to grow to a projected USD 825 billion by 2030 and USD 845 billion by 2045. There is a wide variation in annual health expenditures on diabetes. The United States of America has the highest estimated expenditure with USD 294.6 billion, followed by China and Brazil, with USD 109.0 billion and USD 52.3 billion, respectively. The age group with the largest annual diabetes-related health expenditure is 60-69 years with USD 177.7 billion, followed by 50-59 years, and 70-79 years with USD 173.0 billion and USD 171.5 billion, respectively. Slightly higher diabetes-related health expenditure is seen in women than in men (USD 382.6 billion vs. USD 377.6 billion, respectively). The same difference is expected to be present in 2030 and 2045. CONCLUSIONS: There were large disparities between high-, middle- and low-income countries with total health expenditures in high-income countries being over 300 times those in low-income countries. The ratio for annual direct health expenditure per person between these groups of countries is more than 38-fold.

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.