Phenotypic characterization of nonautoimmune diabetes in adult Ugandans with low body mass index.

Background: Type 2 diabetes is common in relatively lean individuals in sub-Saharan Africa. It is unclear whether phenotypic differences exist between underweight and normal-weight African patients with type 2 diabetes. This study compared specific characteristics between underweight (body mass index <18.5 kg/m2) and normal-weight (body mass index of 18.5-24.9 kg/m2) adult Ugandans with new-onset nonautoimmune diabetes. Methods: We collected the demographic, clinical, anthropometric, and metabolic characteristics of 160 participants with nonobese new-onset type 2 diabetes (defined as diabetes diagnosed <3 months, body mass index <25 kg/m2, and absence of islet-cell autoimmunity). These participants were categorized as underweight and normal weight, and their phenotypic characteristics were compared. Results: Of the 160 participants with nonobese new-onset type 2 diabetes, 18 participants (11.3%) were underweight. Compared with those with normal weight, underweight participants presented with less co-existing hypertension (5.6% versus 28.2%, p = 0.04) and lower median visceral fat levels [2 (1-3) versus 6 (4-7), p < 0.001], as assessed by bioimpedance analysis. Pathophysiologically, they presented with a lower median 120-min post-glucose load C-peptide level [0.29 (0.13-0.58) versus 0.82 (0.39-1.50) nmol/l, p = 0.04] and a higher prevalence of insulin deficiency (66.7% versus 31.4%, p = 0.003). Conclusion: This study demonstrates that nonautoimmune diabetes occurs in underweight individuals in sub-Saharan Africa and is characterized by the absence of visceral adiposity, reduced late-phase insulin secretion, and greater insulin deficiency. These findings necessitate further studies to inform how the prevention, identification, and management of diabetes in such individuals can be individualized.

Type 2 diabetes in underweight Ugandans In this study that investigated how type 2 diabetes presents in adult Ugandans with normal body mass index, about one in ten were underweight. Type 2 diabetes in these individuals was characterized by a low prevalence of hypertension, lower body fat levels, and features of reduced insulin production by the pancreas.

Patient level barriers to accessing TB care services during the COVID-19 pandemic in Uganda, a mixed methods study.

INTRODUCTION: Lockdown measure has been utilized widely to mitigate COVID-19 pandemic transmission and recently during the 2022 Sudan Ebola Virus Disease outbreak in Uganda. These have setback effects on the continuity of essential health services such as tuberculosis (TB) care, reversing progress made in the fight against tuberculosis (TB) over the past decade. We set out to understand patient-reported barriers to accessing TB care services during the COVID-19 pandemic in Uganda. METHODS: Mixed methods study involving review of medical records of TB patients who received TB care from January to September 2020. We used quantitative and qualitative methods including phone questionnaires and in-depth interviews. We carried out descriptive statistics, a chi-square test and conducted a thematic analysis. RESULTS: We carried out phone interviews with 672 participants. The majority (60%) were male and with an average of 35 years (SD:11). A significantly higher proportion of patients reported a barrier to TB care access during the COVID-19 lockdown than pre-lockdown (79.9% vs. 68.1% p = 0.027). We carried out in-depth interviews with 28 participants (54% (15/28): male). Barriers experienced by these participants included lack of a means of transport to reach the health facility, lack of money to pay the transport fares, long distances to the facility, fear of COVID-19 infection, stigma due to overlap between TB and COVID-19 symptoms, and few health care workers available during the lockdown period. CONCLUSION: Lockdown measures instituted to mitigate the transmission of COVID1-19 affected access to TB care services in Uganda. Uganda is at risk of future emerging and re-emerging diseases of epidemic potential. Therefore, there should be measures to ensure the continuity of essential services such as tuberculosis care during the implementation of future epidemic response interventions such as a lockdown.

Challenges to Implementation of Community Health Worker-Led Chronic Obstructive Pulmonary Disease (COPD) Screening and Referral in Rural Uganda: A Qualitative Study using the Implementation Outcomes Framework.

Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. The burden of COPD is expected to increase in low- and middle-income countries (LMICs). COPD screening and diagnostics tools are often inaccessible in rural settings of LMICs. To contribute to the growing body of evidence on the effectiveness of Community Health Worker (CHW) interventions, this study aims to understand the facilitators and barriers of implementing a CHW-led COPD screening and referral program in rural Uganda. Methods: This qualitative study was conducted from September to October 2022 to explore Community Members, CHWs, and Healthcare Providers (HCPs) perceptions on the challenges of CHW-delivered COPD programming in Nakaseke, rural Uganda. In total, we held eight individual in-depth interviews with CHWs, ten in-depth interviews with HCPs and six focus group discussions with 34 Community Members. Research assistants audio-recorded and transcribed interviews verbatim. The implementation outcomes framework guided the thematic analysis. Results: Implementation acceptability was constrained by a lack of COPD awareness, a lack of perceived utility in COPD screening as well as stigma around the diagnostic process. Limited spirometry adoption was also attributed to Community Member accessibility and willingness to participate in the COPD diagnostic referral process. The high patient volume and the complex, time-consuming diagnostic and referral process hindered successful implementation. To enhance program sustainability, all participants suggested increasing CHW support, medication access, decentralizing COPD care and upscaling follow-up of Community Members by CHWs. Conclusion: CHW-led interventions remain a potentially critical tool to alleviate barriers to treatment and self-management in settings where access to care is limited. While community-based interventions can create sustainable infrastructure to improve health outcomes, formative assessments of the potential barriers prior to intervention are required. Evidence-based, localized approaches and sustained funding are imperative to achieve this.

Epidemiology of multimorbidity in low-income countries of sub-Saharan Africa: Findings from four population cohorts.

We investigated prevalence and demographic characteristics of adults living with multimorbidity (≥2 long-term conditions) in three low-income countries of sub-Saharan Africa, using secondary population-level data from four cohorts; Malawi (urban & rural), The Gambia (rural) and Uganda (rural). Information on; measured hypertension, diabetes and obesity was available in all cohorts; measured hypercholesterolaemia and HIV and self-reported asthma was available in two cohorts and clinically diagnosed epilepsy in one cohort. Analyses included calculation of age standardised multimorbidity prevalence and the cross-sectional associations of multimorbidity and demographic/lifestyle factors using regression modelling. Median participant age was 29 (Inter quartile range-IQR 22-38), 34 (IQR25-48), 32 (IQR 22-53) and 37 (IQR 26-51) in urban Malawi, rural Malawi, The Gambia, and Uganda, respectively. Age standardised multimorbidity prevalence was higher in urban and rural Malawi (22.5%;95% Confidence intervals-CI 21.6-23.4%) and 11.7%; 95%CI 11.1-12.3, respectively) than in The Gambia (2.9%; 95%CI 2.5-3.4%) and Uganda (8.2%; 95%CI 7.5-9%) cohorts. In multivariate models, females were at greater risk of multimorbidity than males in Malawi (Incidence rate ratio-IRR 1.97, 95% CI 1.79-2.16 urban and IRR 2.10; 95%CI 1.86-2.37 rural) and Uganda (IRR- 1.60, 95% CI 1.32-1.95), with no evidence of difference between the sexes in The Gambia (IRR 1.16, 95% CI 0.86-1.55). There was strong evidence of greater multimorbidity risk with increasing age in all populations (p-value <0.001). Higher educational attainment was associated with increased multimorbidity risk in Malawi (IRR 1.78; 95% CI 1.60-1.98 urban and IRR 2.37; 95% CI 1.74-3.23 rural) and Uganda (IRR 2.40, 95% CI 1.76-3.26), but not in The Gambia (IRR 1.48; 95% CI 0.56-3.87). Further research is needed to study multimorbidity epidemiology in sub-Saharan Africa with an emphasis on robust population-level data collection for a wide variety of long-term conditions and ensuring proportionate representation from men and women, and urban and rural areas.

Design Research to Embed mHealth into a Community-Led Blood Pressure Management System in Uganda: Protocol for a Mixed Methods Study.

BACKGROUND: Uncontrolled hypertension is a leading risk factor for cardiovascular diseases. In Uganda, such diseases account for approximately 10% of all deaths, with 1 in 5 adults having hypertension (>90% of the hypertensive cases are uncontrolled). Although basic health care in the country is available free of cost at government facilities, regularly accessing medication to control hypertension is difficult because supply chain challenges impede availability. Clients therefore frequently suspend treatment or buy medication individually at private facilities or pharmacies (incurring significant costs). In recent years, mobile health (mHealth) interventions have shown increasing potential in addressing health system challenges in sub-Saharan Africa, but the acceptability, feasibility, and uptake conditions of mobile money approaches to chronic disease management remain understudied. OBJECTIVE: This study aims to design and pilot-test a mobile money-based intervention to increase the availability of antihypertensive medication and lower clients' out-of-pocket payments. We will build on existing local approaches and assess the acceptability, feasibility, and uptake of the designed intervention. Furthermore, rather than entering the study setting with a ready-made intervention, this research will place emphasis on gathering applied ethnographic insights early, which can then inform the parameters of the intervention prototype and concurrent trial. METHODS: We will conduct a mixed methods study following a human-centered design approach. We will begin by conducting extensive qualitative research with a range of stakeholders (clients; health care providers; religious, cultural, and community leaders; academics; and policy makers at district and national levels) on their perceptions of hypertension management, money-saving systems, and mobile money in the context of health care. Our results will inform the design, iterative adaptation, and implementation of an mHealth-facilitated pooled financing intervention prototype. At study conclusion, the finalized prototype will be evaluated quantitatively via a randomized controlled trial. RESULTS: As of August 2023, qualitative data collection, which started in November 2022, is ongoing, with data analysis of the first qualitative interviews underway to inform platform and implementation design. Recruitment for the quantitative part of this study began in August 2023. CONCLUSIONS: Our results aim to inform the ongoing discourse on novel and sustainable pathways to facilitate access to medication for the management of hypertension in resource-constrained settings. TRIAL REGISTRATION: German registry of clinical trials DRKS00030922; https://drks.de/search/en/trial/DRKS00030922. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46614.

Growth Profiles of Children and Adolescents Living with and without Perinatal HIV Infection in Southern Africa: A Secondary Analysis of Cohort Data.

Impaired linear growth and slower pubertal growth can be associated with perinatal HIV infection. We characterised growth relative to population norms, among the full adolescent period in southern Africa to better understand processes leading to morbidity in adulthood. We conducted a secondary analysis of 945 adolescents aged 8-20 years from urban Malawi and Zimbabwe; we included children with HIV (CWH), an uninfected comparison group from a cohort study, and CWH with co-morbid chronic lung disease (CLD) from a randomised controlled trial. We used latent class analysis of anthropometric Z-scores generated from British 1990 reference equations at two annual time-points, to identify growth trajectory profiles and used multinomial logistic regression to identify factors associated with growth profiles. Growth faltering (one or more of weight-for-age, height-for-age, or BMI-for-age Z-scores < -2) occurred in 38% (116/303) of CWH from the cohort study, 62% (209/336) of CWH with CLD, and 14% (44/306) of HIV-uninfected participants. We identified seven different growth profiles, defined, relatively, as (1) average growth, (2) tall not thin, (3) short not thin, (4) stunted not thin, (5) thin not stunted, (6) thin and stunted and (7) very thin and stunted. Females in profile 3 exhibited the highest body fat percentage, which increased over 1 year. Males at older age and CWH especially those with CLD were more likely to fall into growth profiles 4-7. Improvements in height-for-age Z-scores were observed in profiles 6-7 over 1 year. Interventions to target those with the worst growth faltering and longer-term follow-up to assess the impact on adult health are warranted.

Type 2 diabetes progression in an adult Ugandan population with new-onset diabetes: an observational prospective study.

BACKGROUND: The rate of progression of type 2 diabetes following diagnosis varies across individuals and populations. Studies investigating the progression of type 2 diabetes in adult African populations with newly diagnosed diabetes are limited. We aimed to investigate the prevalence and predictors of short-term (one year) diabetes progression in an adult Ugandan population with new-onset type 2 diabetes (type 2 diabetes diagnosed in < 3 months) initiated on oral hypoglycaemic agents (OHA). METHODS: Two hundred and seven adult participants with type 2 diabetes diagnosed within the previous three months were followed up for 12 months. We investigated the association of specific demographic, clinical, and metabolic characteristics, and short-term diabetes progression (defined as glycated haemoglobin or HbA1c ≥ 8% on ≥ 2 OHA and/or treatment intensification). RESULTS: One hundred sixteen participants (56%) completed the follow-up period. Sixty-four participants (55.2%, 95% CI 45.7-64.4) showed evidence of diabetes progression during the 12-month period of follow-up. An HbA1c ≥ 8% on ≥ 2 OHA and treatment intensification were noted in 44.8% and 29.3% of the participants, respectively. On multivariate analysis, only the female gender (AOR 3.2, 95% CI 1.1-9.2, p = 0.03) was noted to be independently associated with short-term diabetes progression. CONCLUSION: Short-term diabetes progression was relatively common in this study population and was independently associated with the female gender. Early intensified diabetes therapy in adult Ugandan female patients with new-onset type 2 diabetes should be emphasised to avert rapid short-term diabetes progression.

Medium-to-long term sustainability of a health systems intervention to improve service readiness and quality of non-communicable disease (NCD) patient care and experience at primary care settings in Uganda.

BACKGROUND: With the double burden of rising chronic non-communicable diseases (NCDs) and persistent infectious diseases facing sub-Saharan Africa, integrated health service delivery strategies among resource-poor countries are needed. Our study explored the post-trial sustainability of a health system intervention to improve NCD care, introduced during a cluster randomised trial between 2013 and 2016 in Uganda, focusing on hypertension (HT) and type-2 diabetes mellitus (DM) services. In 2020, 19 of 38 primary care health facilities (HFs) that constituted the trial's original intervention arm until 2016 and 3 of 6 referral HFs that also received the intervention then, were evaluated on i) their facility performance (FPS) through health worker knowledge, and service availability and readiness (SAR), and ii) the quality-of-patient-care-and-experience (QoCE) received. METHODS: Cross-sectional data from the original trial (2016) and our study (2020) were compared. FPS included a clinical knowledge test with 222 health workers: 131 (2016) and 91 (2020) and a five-element SAR assessment of all 22 HFs. QoCE assessment was performed among 420 patients: 88 (2016) and 332 (2020). Using a pair-matched approach, FPS and QoCE summary scores were compared. Linear and random effects Tobit regression models were also analysed. RESULTS: The mean aggregate facility performance (FPS) in 2020 was lower than in 2016: 70.2 (95%CI = 66.0-74.5) vs. 74.8 (95%CI = 71.3-78.3) respectively, with no significant difference (p = 0.18). Mean scores declined in 4 of 5 SAR elements. Overall FPS was negatively affected by rural or urban HF location relative to peri-urban HFs (p < 0.01). FPS was not independently predicted but patient club functionality showed weak association (p = 0.09). QoCE declined slightly to 8.7 (95%CI = 8.4-91) in 2020 vs 9.5 (95%CI = 9.1-9.9) in 2016 (p = 0.02) while the proportion of patients receiving adequate quality care also declined slightly to 88.2% from 98.5% respectively, with no statistical difference (p = 0.20). Only the parent district weakly predicted QoCE (p = 0.05). CONCLUSIONS: Four years after the end of research-related support, overall facility performance had declined as expected because of the interrupted supplies and a decline in regular supervision. However, both service availability and readiness and quality of HT/DM care were surprisingly well preserved. Sustainability of an NCD intervention in similar settings may remain achievable despite the funding instability following a trial's end but organisational measures to prepare for the post-trial phase should be taken early on in the intervention process.

Burden and predictors of diabetic kidney disease in an adult Ugandan population with new-onset diabetes.

BACKGROUND: Despite the growing evidence of diabetic kidney disease (DKD) in adult patients with long-standing diabetes in sub-Saharan Africa, data on its burden and correlates in adult African patients with new-onset diabetes are limited. We, therefore, undertook this study to determine the burden and predictors of DKD in an adult population with new-onset diabetes in Uganda. METHODS: We collected data on the relevant sociodemographic, clinical, anthropometric, and metabolic characteristics in 519 participants with newly diagnosed diabetes recruited from seven tertiary hospitals. A spot mid-stream urine sample was collected for determination of the urine albumin creatinine ratio (UACR) using Clinitek® microalbumin strips and a point-of-care Clinitek® status analyser. The estimated glomerular filtration rate (e-GFR) was determined using the Chronic Kidney Disease Epidemiology formula. The presence of DKD was defined as a spot UACR ≥ 3 mg/mmol with or without an e-GFR < 60 ml/min/1.73m2. RESULTS: The median (IQR) age, UACR, and e-GFR of the participants were 48 years (39-57), 2.27 mg/mmol (1.14-3.41), and 121.8 ml/min/1.73m2 (105.4-133.9). UACR ≥ 3 mg/mmol and e-GFR < 60 ml/min/1.73m2 was noted in 175 (33.7%) and 7 (1.4%) participants, respectively. DKD was documented in 175 participants (33.7%). Compared with those without DKD, participants with DKD were more likely to be ≥ 50 years of age (53.7% vs. 43%, p = 0.02) and to have co-existing hypertension at the time of diagnosis (40.6% vs. 30.1%, p = 0.02). On multivariate analysis, self-reported hypertension comorbidity (OR 1.76 95% CI 1.24-2.48, p = 0.002) and body mass index (BMI) ≥ 30 kg/m2 (OR 0.61 95% CI 0.41-0.91, p = 0.02) were noted to independently predict DKD. CONCLUSION: In this study population, DKD was relatively common and was independently associated with self-reported hypertension comorbidity and BMI ≥ 30 kg/m2.

Identification and characterisation of diabetes in Uganda: protocol for the nested, population-based 'Diabetes in low-resource Populations' (DOP) Study.

INTRODUCTION: Sub-Saharan Africa is experiencing an increasing burden of diabetes, but there are little reliable data, particularly at the community level, on the true prevalence or why this condition affects young and relatively lean individuals. Moreover, the detection of diabetes in Africa remains poor, not only due to a lack of resources but because the performance of available diagnostic tests is unclear. METHODS: This research aims to (1) determine the prevalence and risk factors of diabetes in a rural Ugandan population, (2) use clinical and biochemical markers to define different diabetes phenotypes and (3) study the progression of diabetes in this population. We will also assess the utility of the widely used tests (glycated haemoglobin (HbA1c), oral glucose tolerance test (OGTT) and fasting glucose) in diagnosing diabetes. DESIGN: This is a population-based study nested within the longstanding general population cohort in southwestern Uganda. We will undertake a population survey to identify individuals with diabetes based on fasting glucose, HbA1c, OGTT results or history of pre-existing diabetes. PARTICIPANTS: The study intends to enrol up to 11 700 individuals aged 18 years and above, residing within the study area and not pregnant or within 6 months post-delivery date. All participants will have detailed biophysical and biochemical/metabolic measurements. Individuals identified to have diabetes and a random selection of controls will have repeat tests to test reproducibility before referral and enrolment into a diabetic clinic. Participants will then be followed up for 1 year to assess the course of the disease, including response to therapy and diabetes-related complications. CONCLUSIONS: These data will improve our understanding of the burden of diabetes in Uganda, the risk factors that drive it and underlying pathophysiological mechanisms, as well as better ways to detect this condition. This will inform new approaches to improve the prevention and management of diabetes. ETHICS AND DISSEMINATION: This study protocol was approved by the Uganda Virus Research Institute Research Ethics Committee (REC) (number: G.C./127/21/09/858), the London School of Hygiene and Tropical Medicine REC (number: 26638) and the Uganda National Council for Science and Technology (protocol number: HS1791ES). Written informed consent will be obtained from all participants before being enrolled on to the study and conducting study-related procedures. Research findings will be disseminated in policy briefs, seminars, local and international conferences and publications in peer-reviewed open-access journals. As part of the dissemination plans, findings will also be disseminated to patient care groups and to clinicians. TRIAL REGISTRATION NUMBER: NCT05487079.

Sustainability capacity and health worker normalisation of a successful non-communicable disease (NCD) health systems intervention within primary care settings in Uganda: a quantitative approach to a qualitative question.

BACKGROUND: Interventions for non-communicable diseases are increasingly implemented and evaluated in sub-Saharan Africa, but little is known about their medium- to long-term sustainability beyond the end of research funding. A cluster randomised trial conducted between 2013 and 2016 in Uganda and Tanzania showed that an intervention package to improve hypertension (HT) and type-2 diabetes mellitus (DM) care was highly effective in increasing service readiness and quality of care. The present study assesses the sustainability of the intervention 4 years after the trial in Uganda. METHODS: The study was conducted in 2020 in 22 primary care health facilities (HFs) (3 referrals and 19 lower-level units) that had received the intervention package until trial end (2016), to assess their current capacity and practice to sustain ongoing intervention activities for HT and DM care. Through a cross-sectional survey, 4 pre-defined domains (i.e., cognitive participation, coherence, collective action, and reflexive monitoring) were examined with regard to health worker (HW) normalization and 8 pre-defined domains for intervention sustainability (i.e., organisational capacity, local environment, funding stability, partnerships, communication, evaluation, adaptation, and strategic planning), using the normalisation tool and the program sustainability tool (PSAT). Summary scores were assessed by domains and facility level. RESULTS: Overall normalization strength was adequate at 4.0 (IQR: 3.8, 4.2) of a possible 5 with no evidence of association with HF level (p = 0.40); cognitive participation (buy-in) and reflexive monitoring (appraisal) were strongest at > 4 across all HF levels. All HF levels were weak (< 4) on collective action (teamwork) and coherence (sense-making). Only collective action differed by level (p < 0.002). Overall intervention sustainability was suboptimal at 3.1 [IQR: 1.9, 4.1] of a possible 7 with weak scores on funding stability (2.0), supportive partnerships (2.2), and strategic planning (2.6). Domain differences by HF level were significant for environmental support (p = 0.02) and capacity in organisation (p = 0.01). Adequate strength at a cut-off mean of ≥5 did not differ by HF level for any domain. CONCLUSIONS: Four years after their introduction, practice-dependent intervention elements e.g., local organisational context, HW knowledge or dedication were sustained, but external elements e.g., new funding support or attracting new partners to sustain intervention efforts were not. Whenever new interventions are introduced into an existing health service, their long-term sustainability including the required financial support should be ensured. The quality of services should be upheld by providing routine in-service training with dedicated support supervision.

HIV infection in adult Ugandans with new-onset type 2 diabetes: exploring its influence on the anthropometric and metabolic profile.

OBJECTIVE: HIV infection increases the risk of type 2 diabetes and may influence its phenotypic profile. In this study, we aimed to compare the anthropometric and metabolic characteristics of HIV-infected and uninfected adult Ugandans with new-onset type 2 diabetes to evaluate the influence of HIV infection on specific surrogate markers of adiposity, insulin resistance, and pancreatic beta-cell function. METHODS: We consecutively recruited 500 HIV-infected and uninfected adult Ugandans with new-onset type 2 diabetes (diagnosed in < 3 months) from seven tertiary hospitals over a 20-month period and compared their anthropometric and metabolic characteristics to identify any significant differences. RESULTS: Of the 500 participants with new-onset type 2 diabetes, 59 (11.8%) had a self-reported history of HIV infection. Compared with HIV-uninfected participants with type 2 diabetes, participants with HIV infection and type 2 diabetes had a lower median (IQR) hip circumference (97.8 [91.0-106.0] cm vs. 104.0 [96.0-112.0], p = 0.002) and visceral fat level (8 [6-11] vs. 10 [7-12], p < 0.001) assessed using bioimpedance analysis. No statistically significant difference was noted with the markers of pancreatic beta-cell function (fasting, 30-minute, and 120-minute C-peptide concentrations, oral insulinogenic index, and homeostatic model assessment 2-beta cell function) and insulin resistance (homeostatic model assessment 2-insulin resistance) between both groups. CONCLUSION: In our study population, HIV infection was not associated with increased adiposity, pancreatic beta-cell function, and insulin resistance. Large prospective studies are needed to investigate the effect of HIV on the pathogenesis of type 2 diabetes in adult Ugandans.

Risk factors for disruptions in tuberculosis care in Uganda during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, TB mortality increased while diagnoses decreased, likely due to care disruption. In March, 2020, Uganda-a country with high TB burden, implemented a COVID-19 lockdown with associated decrease in TB diagnoses. This study aims to examine patient level risk factors for disruption in TB care during the COVID-19 pandemic in Uganda. This retrospective cross-sectional cohort study included six TB clinics in Uganda. Clustered sampling included phases of TB care and three time-periods: pre-lockdown, lockdown and post-lockdown. Characteristics of patients with TB care disruption (TBCD), defined as those with > 2 months of symptoms prior to diagnosis or who missed a TB clinic, and those without TB care disruption (non-TBCD) were analyzed between time-periods. 1,624 charts were reviewed; 1322 were contacted, 672 consented and completed phone interview; pre-lockdown (n = 213), lockdown (n = 189) and post-lockdown (n = 270). TBCD occurred in 57% (385/672) of patients. There was an increase in the proportion of urban patients in the TBCD and non-TBCD groups during post-lockdown (p <0.001). There was no difference in demographics, HIV co-infection, socioeconomic status, or distance to TB clinic between TBCD and non-TBCD groups or within TBCD by time-period. There were few differences amongst TBCD and all TB patients by time-period. The increase in urban patients' post-lockdown may represent a portion of urban patients who delayed care until post-lockdown. Insignificant trends suggesting more TBCD amongst those who lived further from clinics and those without HIV-coinfection require more investigation.

Principles for task shifting hypertension and diabetes screening and referral: a qualitative study exploring patient, community health worker and healthcare professional perceptions in rural Uganda.

BACKGROUND: A shortage of healthcare workers in low- and middle-income countries (LMICs) combined with a rising burden of non-communicable diseases (NCDs) like hypertension and diabetes mellitus has resulted in increasing gaps in care delivery for NCDs. As community health workers (CHWs) often play an established role in LMIC healthcare systems, these programs could be leveraged to strengthen healthcare access. The objective of this study was to explore perceptions of task shifting screening and referral for hypertension and diabetes to CHWs in rural Uganda. METHODS: This qualitative, exploratory study was conducted in August 2021 among patients, CHWs and healthcare professionals. Through 24 in-depth interviews and ten focus group discussions, we investigated perceptions of task shifting to CHWs in the screening and referral of NCDs in Nakaseke, rural Uganda. This study employed a holistic approach targeting stakeholders involved in the implementation of task shifting programs. All interviews were audio-recorded, transcribed verbatim, and analyzed thematically guided by the framework method. RESULTS: Analysis identified elements likely to be required for successful program implementation in this context. Fundamental drivers of CHW programs included structured supervision, patients' access to care through CHWs, community involvement, remuneration and facilitation, as well as building CHW knowledge and skills through training. Additional enablers comprised specific CHW characteristics such as confidence, commitment and motivation, as well as social relations and empathy. Lastly, socioemotional aspects such as trust, virtuous behavior, recognition in the community, and the presence of mutual respect were reported to be critical to the success of task shifting programs. CONCLUSION: CHWs are perceived as a useful resource when task shifting NCD screening and referral for hypertension and diabetes from facility-based healthcare workers. Before implementation of a task shifting program, it is essential to consider the multiple layers of needs portrayed in this study. This ensures a successful program that overcomes community concerns and may serve as guidance to implement task shifting in similar settings.

Indicators of optimal diabetes care and burden of diabetes complications in Africa: a systematic review and meta-analysis.

OBJECTIVE: Contemporary data on the attainment of optimal diabetes treatment goals and the burden of diabetes complications in adult populations with type 2 diabetes in Africa are lacking. We aimed to document the current status of attainment of three key indicators of optimal diabetes care and the prevalence of five diabetes complications in adult African populations with type 2 diabetes. METHODS: We systematically searched Embase, PubMed and the Cochrane library for published studies from January 2000 to December 2020. Included studies reported any information on the proportion of attainment of optimal glycated haemoglobin (HbA1c), blood pressure (BP) and low-density lipoprotein cholesterol (LDLC) goals and/or prevalence of five diabetes complications (diabetic peripheral neuropathy, retinopathy, nephropathy, foot ulcers and peripheral arterial disease). Random effect model meta-analysis was performed to determine the pooled proportion of attainment of the three treatment goals and the prevalence of five diabetes complications. RESULTS: In total, 109 studies with a total of 63 890 participants (53.3% being females) were included in the meta-analysis. Most of the studies were conducted in Eastern African countries (n=44, 40.4%). The pooled proportion of attainment of an optimal HbA1c, BP and LDLC goal was 27% (95% CI 24 to 30, I2=94.7%), 38% (95% CI 30 to 46, I2=98.7%) and 42% (95% CI 32 to 52, I2=97.4%), respectively. The pooled prevalence of diabetic peripheral neuropathy, retinopathy, diabetic nephropathy, peripheral arterial disease and foot ulcers was 38% (95% CI 31 to 45, I2=98.2%), 32% (95% CI 28 to 36, I2=98%), 31% (95% CI 22 to 41, I2=99.3%), 19% (95% CI 12 to 25, I2=98.1%) and 11% (95% CI 9 to 14, I2=97.4%), respectively. CONCLUSION: Attainment of optimal diabetes treatment goals, especially HbA1c, in adult patients with type 2 diabetes in Africa remains a challenge. Diabetes complications, especially diabetic peripheral neuropathy and retinopathy, are highly prevalent in adult populations with type 2 diabetes in Africa.

Clinical, metabolic, and immunological characterisation of adult Ugandan patients with new-onset diabetes and low vitamin D status.

BACKGROUND: Low vitamin D concentrations are associated with metabolic derangements, notably insulin resistance and pancreatic beta-cell dysfunction in Caucasian populations. Studies on its association with the clinical, metabolic, and immunologic characteristics in black African adult populations with new-onset diabetes are limited. This study aimed to describe the clinical, metabolic, and immunologic characteristics of a black Ugandan adult population with recently diagnosed diabetes and hypovitaminosis D. METHODS: Serum vitamin D concentrations were measured in 327 participants with recently diagnosed diabetes. Vitamin D deficiency, vitamin D insufficiency, and normal vitamin D status were defined as serum 25 hydroxyvitamin D levels of < 20 ng/ml, 21-29 ng/ml, and ≥ 30 ng/ml, respectively. RESULTS: The median (IQR) age, glycated haemoglobin, and serum vitamin D concentration of the participants were 48 years (39-58), 11% (8-13) or 96 mmol/mol (67-115), and 24 ng/ml (18-30), respectively. Vitamin D deficiency, vitamin D insufficiency, and normal vitamin D status were noted in 105 participants (32.1%), 140 participants (42.8%), and 82 participants (25.1%), respectively. Compared with those having normal serum vitamin D levels, participants with vitamin D deficiency and insufficiency had higher circulating concentrations of interleukin (IL) 6 (29 [16-45] pg/ml, 23 [14-40] pg/ml vs 18 [14-32] pg/ml, p = 0.01), and IL-8 (24 [86-655] pg/ml, 207 [81-853] pg/ml vs 98 [67-224], p = 0.03). No statistically significant differences were noted in the markers of body adiposity, insulin resistance, and pancreatic beta-cell function between both groups. CONCLUSION: Vitamin D deficiency and insufficiency were highly prevalent in our study population and were associated with increased circulating concentrations of pro-inflammatory cytokines. The absence of an association between pancreatic beta-cell function, insulin resistance, and low vitamin D status may indicate that the latter does not play a significant role in the pathogenesis of type 2 diabetes in our adult Ugandan population.

The influence of fasting and post-load glucose levels on maternal and neonatal outcomes in women with hyperglycaemia in pregnancy in Uganda: A prospective observational cohort study.

AIMS: The study aims to evaluate the strength of fasting versus post-load glucose levels in predicting adverse outcomes in women with hyperglycaemia in pregnancy (HIP). METHODS: Women attending antenatal clinics in urban and peri-urban Uganda had oral glucose tolerance test between 24 and 28 weeks of gestation to screen for HIP, and were followed up to collect data on maternal and neonatal outcomes. Univariable and multivariable Poisson regression models were used to estimate the relative risk adverse outcome associated with fasting hyperglycaemia alone post-load hyperglycaemia alone, or elevation of both fasting and post-load glucose levels. RESULTS: We included 3206 participants in the final analysis. HIP was associated with increased risk of Caesarean section, large for gestaional age babies, and neonatal intensive care admission. The risk was highest (2.54-fold compared to normal glycaemic women) when both FBG and post-load glucose levels were elevated. After adjustment for potential confounders, having elevated post-load glucose alone was not associated with increased risk of any of the outcomes, but elevated FBG alone increased the risk of Caesarian section by 1.36-fold. CONCLUSION: Fasting hyperglycemia appears to be more strongly associated with adverse pregnancy outcomes than post-load hyperglycaemia, but the risk is even higher in women with elevation of both fasting and post-load glucose levels.

Islet autoantibody positivity in an adult population with recently diagnosed diabetes in Uganda.

AIMS: This study aimed to investigate the frequency of islet autoantibody positivity in adult patients with recently diagnosed diabetes in Uganda and its associated characteristics. METHODS: Autoantibodies to glutamic acid decarboxylase-65 (GADA), zinc transporter 8 (ZnT8-A), and tyrosine phosphatase (IA-2A) were measured in 534 adult patients with recently diagnosed diabetes. Islet autoantibody positivity was defined based on diagnostic thresholds derived from a local adult population without diabetes. The socio-demographic, clinical, and metabolic characteristics of islet autoantibody-positive and negative participants were then compared. The differences in these characteristics were analysed using the x2 test for categorical data and the Kruskal Wallis test for continuous data. Multivariate analysis was performed to identify predictors of islet autoantibody positivity. RESULTS: Thirty four (6.4%) participants were positive for ≥1 islet autoantibody. GADA, IA-2A and ZnT8-A positivity was detected in 17 (3.2%), 10 (1.9%), and 7 (1.3%) participants, respectively. Compared with those negative for islet autoantibodies, participants positive for islet autoantibodies were more likely to live in a rural area (n = 18, 52.9% Vs n = 127, 25.5%, p = 0.005), to be initiated on insulin therapy (n = 19, 55.9% Vs n = 134, 26.8%, p<0.001), to have a lower median waist circumference (90 [80-99] cm Vs 96 [87-104.8], p = 0.04), waist circumference: height ratio (0.55 [0.50-0.63] vs 0.59 [0.53-0.65], p = 0.03), and fasting C-peptide concentration (0.9 [0.6-1.8] Vs 1.4 [0.8-2.1] ng/ml, p = 0.01). On multivariate analysis, living in a rural area (odds ratio or OR 3.62, 95%CI 1.68-7.80, p = 0.001) and being initiated on insulin therapy (OR 3.61, 95% CI 1.67-7.83, p = 0.001) were associated with islet autoantibody positivity. CONCLUSION: The prevalence of islet autoantibody positivity was relatively low, suggesting that pancreatic autoimmunity is a rare cause of new-onset diabetes in this adult Ugandan population. Living in a rural area and being initiated on insulin therapy were independently associated with islet autoantibody positivity in this study population.

Association of impaired kidney function with mortality in rural Uganda: results of a general population cohort study.

OBJECTIVE: To determine the association between baseline kidney function and subsequent all-cause mortality. DESIGN AND SETTING: A general population-based cohort study from rural Uganda. PARTICIPANTS: People aged 18 years and above with measured baseline estimated glomerular filtration rate (eGFR), recruited from survey rounds in 2011-2012 or 2014-2015 and followed up to March 2019. OUTCOME MEASURE: The primary outcome was all-cause mortality, identified through reports from community health workers and verified by verbal autopsy. The association between baseline eGFR category and mortality was determined using multivariable Cox regression. RESULTS: Of 5812 participants in both rounds, we included 5678 (97.7%) participants with kidney function and mortality data; the median age was 36 years (IQR 24-50), 60.7% were female, 10.3% were hypertensive, 9.8% were HIV-positive and 1.5% were diabetic. During a median follow-up of 5.0 years (IQR 3.7-6.0) there were 140 deaths. In age-adjusted and sex-adjusted analyses, eGFR <45 mL/min/1.73 m2 at baseline was associated with a 5.97 (95% CI 2.55 to 13.98) increased risk of mortality compared with those with baseline eGFR >90 mL/min/1.73 m2. After inclusion of additional confounders (HIV, body mass index, diabetes, hypertension, alcohol and smoking status) into the model, eGFR <45 mL/min/1.73 m2 at baseline remained strongly associated with mortality (HR 6.12, 95% CI 2.27 to 16.45), although the sample size fell to 3102. Test for trend showed strong evidence (p<0.001) that the rate of mortality increased progressively as the category of baseline kidney function decreased. When very high eGFR was included as a separate category in age-adjusted and sex-adjusted analyses, baseline eGFR ≥120 mL/min/1.73 m2 was associated with increased risk of mortality (HR 2.68, 95% CI 1.47 to 4.87) compared with the reference category of 90-119 mL/min/1.73 m2. CONCLUSION: In a prospective cohort in rural Uganda we found that impaired baseline kidney function was associated with subsequently increased total mortality. Improved understanding of the determinants of kidney disease and its progression is needed in order to inform interventions for prevention and treatment.

Understanding the pathogenesis of lean non-autoimmune diabetes in an African population with newly diagnosed diabetes.

AIMS/HYPOTHESIS: Apparent type 2 diabetes is increasingly reported in lean adult individuals in sub-Saharan Africa. However, studies undertaking robust clinical and metabolic characterisation of lean individuals with new-onset type 2 diabetes are limited in this population. This cross-sectional study aimed to perform a detailed clinical and metabolic characterisation of newly diagnosed adult patients with diabetes in Uganda, in order to compare features between lean and non-lean individuals. METHODS: Socio-demographic, clinical, biophysical and metabolic (including oral glucose tolerance test) data were collected on 568 adult patients with newly diagnosed diabetes. Participants were screened for islet autoantibodies to exclude those with autoimmune diabetes. The remaining participants (with type 2 diabetes) were then classified as lean (BMI <25 kg/m2) or non-lean (BMI ≥25 kg/m2), and their socio-demographic, clinical, biophysical and metabolic characteristics were compared. RESULTS: Thirty-four participants (6.4%) were excluded from analyses because they were positive for pancreatic autoantibodies, and a further 34 participants because they had incomplete data. For the remaining 500 participants, the median (IQR) age, BMI and HbA1c were 48 years (39-58), 27.5 kg/m2 (23.6-31.4) and 90 mmol/mol (61-113) (10.3% [7.7-12.5]), respectively, with a female predominance (approximately 57%). Of the 500 participants, 160 (32%) and 340 (68%) were lean and non-lean, respectively. Compared with non-lean participants, lean participants were mainly male (60.6% vs 35.3%, p<0.001) and had lower visceral adiposity level (5 [4-7] vs 11 [9-13], p<0.001) and features of the metabolic syndrome (uric acid, 246.5 [205.0-290.6] vs 289 [234-347] µmol/l, p<0.001; leptin, 660.9 [174.5-1993.1] vs 3988.0 [1336.0-6595.0] pg/ml, p<0.001). In addition, they displayed markedly reduced markers of beta cell function (oral insulinogenic index 0.8 [0.3-2.5] vs 1.6 [0.6-4.6] pmol/mmol; 120 min serum C-peptide 0.70 [0.33-1.36] vs 1.02 [0.60-1.66] nmol/l, p<0.001). CONCLUSIONS/INTERPRETATION: Approximately one-third of participants with incident adult-onset non-autoimmune diabetes had BMI <25 kg/m2. Diabetes in these lean individuals was more common in men, and predominantly associated with reduced pancreatic secretory function rather than insulin resistance. The underlying pathological mechanisms are unclear, but this is likely to have important management implications.