Point-of-care glycated hemoglobin a1c testing for the identification of hyperglycemia severity among individuals with dual tuberculosis and diabetes mellitus in Tanzania.

Background: Poor glycemic control during tuberculosis (TB) treatment is challenging, as the optimum treatment strategy remains unclear. We assessed hyperglycemia severity using glycated hemoglobin (HbA1c) test and predictors of severe hyperglycemia at the time of TB diagnosis in three resources-diverse regions in Tanzania. Methods: This was a substudy from a large cohort study implemented in three regions of Tanzania. TB individuals with diabetes mellitus (DM) (prior history of DM or newly diagnosed DM) were assessed for hyperglycemic levels using HbA1c test and stratified as mild (<53 mmol/mol), moderate (≥53-<86 mmol/mol), and severe (≥86 mmo/mol). Results: From October 2019 to September 2020, 1344 confirmed TB individuals were screened for DM and 105 (7.8%) individuals had dual TB/DM and were assessed for glycemic levels. Of these, 69 (67.7%) had a prior history of DM and 26 (24.8%) were living with human immunodeficiency virus. Their mean age was 49.0 (±15.0) years and 56.2% were male. The majority (77.1%) had pulmonary TB, and 96.2% were newly diagnosed TB individuals. HbA1c test identified 41(39.0%), 37 (35.2%), and 27 (25.7%) individuals with severe, moderate, and mild the hyperglycaemia respectively. Female sex (odds ratio [OR]: 3.55, 95% confidence interval [CI]: 1.06-11.92, P = 0.040) and previous history of DM (OR: 3.71, 95% CI: 1.33-10.33, P = 0.013) were independent risk factors for severe hyperglycemic at the time of TB diagnosis. Conclusion: By integrating early HbA1c testing, a substantial proportion of individuals with severe hyperglycemia were identified. HbA1c testing can be recommended to identify and triage patients requiring personalized intensified DM management in resource-limited programmatic settings.

Implementing Innovative Approaches to Improve Health Care Delivery Systems for Integrating Communicable and Non-Communicable Diseases Using Tuberculosis and Diabetes as a Model in Tanzania.

Background: Many evidence-based health interventions, particularly in low-income settings, have failed to deliver the expected impact. We designed an Adaptive Diseases Control Expert Programme in Tanzania (ADEPT) to address systemic challenges in health care delivery and examined the feasibility, acceptability and effectiveness of the model using tuberculosis (TB) and diabetes mellitus (DM) as a prototype. Methods: This was an effectiveness-implementation hybrid type-3 design that was implemented in Dar es Salaam, Iringa and Kilimanjaro regions. The strategy included a stepwise training approach with web-based platforms adapting the Gibbs' reflective cycle. Health facilities with TB services were supplemented with DM diagnostics, including glycated haemoglobin A1c (HbA1c). The clinical audit was deployed as a measure of fidelity. Retrospective and cross-sectional designs were used to assess the fidelity, acceptability and feasibility of the model. Results: From 2019-2021, the clinical audit showed that ADEPT intervention health facilities more often identified median 8 (IQR 6-19) individuals with dual TB and DM, compared with control health facilities, median of 1 (IQR 0-3) (p = 0.02). Likewise, the clinical utility of HbA1c on intervention sites was 63% (IQR:35-75%) in TB/DM individuals compared to none in the control sites at all levels, whereas other components of the standard of clinical management of patients with dual TB and DM did not significantly differ. The health facilities showed no difference in screening for additional comorbidities such as hypertension and malnutrition. The stepwise training enrolled a total of 46 nurse officers and medical doctors/specialists for web-based training and 40 (87%) attended the workshop. Thirty-one (67%), 18 nurse officers and 13 medical doctors/specialists, implemented the second step of training others and yielded a total of 519 additional front-line health care workers trained: 371 nurses and 148 clinicians. Overall, the ADEPT model was scored as feasible by metrics applied to both front-line health care providers and health facilities. Conclusions: It was feasible to use a stepwise training and clinical audit to support the integration of TB and DM management and it was largely acceptable and effective in differing regions within Tanzania. When adapted in the Tanzania health system context, the model will likely improve quality of services.

Skeletal muscle fibre type and enzymatic activity in adult offspring following placental and peripheral malaria exposure in foetal life.

Background: Maternal malaria may restrict foetal growth. Impaired utero-placental blood flow due to malaria infection may cause hypoxia-induced altered skeletal muscle fibre type distribution in the offspring, which may contribute to insulin resistance and impaired glucose metabolism. This study assessed muscle fibre distribution 20 years after placental and/or peripheral in-utero malaria exposure compared to no exposure, i.e., PPM+, PM+, and M-, respectively. Methods: We traced 101 men and women offspring of mothers who participated in a malaria chemosuppression study in Muheza, Tanzania. Of 76 eligible participants, 50 individuals (29 men and 21 women) had skeletal muscle biopsy taken from m. vastus lateralis in the right leg. As previously reported, fasting and 30 min post-oral glucose challenge plasma glucose values were higher, and insulin secretion disposition index was lower, in the PPM+ group. Aerobic capacity (fitness) was estimated by an indirect VO2max test on a stationary bicycle. Muscle fibre sub-type (myosin heavy chain, MHC) distribution was analysed, as were muscle enzyme activities (citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase, myophosphorylase, phosphofructokinase, lactate dehydrogenase, and creatine kinase activities. Between-group analyses were adjusted for MHC-I %. Results: No differences in aerobic capacity were found between groups. Despite subtle elevations of plasma glucose levels in the PPM+ group, there was no difference in MHC sub-types or muscle enzymatic activities between the malaria-exposed and non-exposed groups. Conclusion: The current study did not show differences in MHC towards glycolytic sub-types or enzymatic activity across the sub-groups. The results support the notion of the mild elevations of plasma glucose levels in people exposed to placental malaria in pregnancy being due to compromised pancreatic insulin secretion rather than insulin resistance.

Energy expenditure and intensity of ritual jumping-dancing in male Maasai.

OBJECTIVES: Traditional jumping-dance rituals performed by Maasai men involve prolonged physical exertion that may contribute significantly to overall physical activity level. We aimed to objectively quantify the metabolic intensity of jumping-dance activity and assess associations with habitual physical activity and cardiorespiratory fitness (CRF). METHODS: Twenty Maasai men (18-37 years) from rural Tanzania volunteered to participate in the study. Habitual physical activity was monitored using combined heart rate (HR) and movement sensing over 3 days, and jumping-dance engagement was self-reported. A 1-h jumping-dance session resembling a traditional ritual was organized, during which participants' vertical acceleration and HR were monitored. An incremental, submaximal 8-min step test was performed to calibrate HR to physical activity energy expenditure (PAEE) and assess CRF. RESULTS: Mean (range) habitual PAEE was 60 (37-116) kJ day-1 kg-1 , and CRF was 43 (32-54) mL O2 min-1 kg-1 . The jumping-dance activity was performed at an absolute HR of 122 (83-169) beats·min-1 , and PAEE of 283 (84-484) J min-1 kg-1 or 42 (18-75)% when expressed relative to CRF. The total PAEE for the session was 17 (range 5-29) kJ kg-1 , ~28% of the daily total. Self-reported engagement in habitual jumping-dance frequency was 3.8 (1-7) sessions/week, with a total duration of 2.1 (0.5-6.0) h/session. CONCLUSIONS: Intensity during traditional jumping-dance activity was moderate, but on average sevenfold higher than habitual physical activity. These rituals are common, and can make a substantial contribution to overall physical activity in Maasai men, and thus be promoted as a culture-specific activity to increase energy expenditure and maintain good health in this population.

Experiences and perceptions of participants on the pathway towards clinical management of dual tuberculosis and diabetes mellitus in Tanzania.

BACKGROUND: Diabetes mellitus (DM) is a common comorbidity among people with tuberculosis (TB). Despite the availability of guidelines on how to integrate dual TB/DM in Tanzania, the practice of integration at various healthcare levels is unclear. OBJECTIVE: To explore the participants' experiences and perceptions on the pathway towards clinical management of dual TB/DM. METHOD: The research was carried out in Dar es Salaam, Iringa, and Kilimanjaro regions between January and February 2020. A qualitative, in-depth interview approach was used to collect participants' experiences and perspectives on the acquisition of dual TB/DM services at various levels of healthcare facilities. The information gathered were coded and classified thematically. RESULTS: The participants' perception of TB services within the healthcare facilities was positive due to the support they received from the healthcare providers. On the other hand, participants reported difficulty receiving management in various health facilities for each condition in terms of access to dual TB/DM care and access to DM medication. This was viewed as a significant challenge for the participants with dual TB/DM. CONCLUSIONS: The current disjunction and disruption in healthcare for people with dual TB/DM makes it difficult to access services at various levels of health facilities. For optimal clinical management for people with dual TB/DM, patient-centered strategies and integrated approaches are urgently needed.

Where can Tanzania health system integrate clinical management of patients with dual tuberculosis and diabetes mellitus? A cross-sectional survey at varying levels of health facilities.

Objective: To assess the current Tanzania health facilities readiness in integrating clinical management of dual Tuberculosis (TB) and Diabetes Mellitus (DM) by using the Service Availability and Readiness Assessment (SARA) manual of the World Health Organization prior to implementing an integrated service model. Study design: Cross-sectional study. Methods: A needs assessment survey was conducted at varying levels of health care facilities. The SARA manual evaluated the service delivery outcomes in terms of availability of guidelines, medicines and diagnostic equipment, training of healthcare workers in providing TB and DM care, and patient record review. Data were analyzed using Statistical Package for Social Science version 26. Results: Among 29 health facilities selected, three were regional referral hospitals, eight were district hospitals and eighteen were health centers. Baseline investigations revealed that GeneXpert MTB/RIF machines were present in 10 (34.5%) facilities, and glycated hemoglobin devices were present in two (6.9%) facilities, while all health facilities had a glucometer. The presence of an attending medical doctor in 19 (65.5%) facilities and the presence of operating biochemistry analyzers in 15 (51.7%) facilities were two mandatory variables used to assess readiness. Among the various guidelines observed, none of the facilities had the 2016 DM guidelines. Overall, 15 (51.7%) health facilities were ready to integrate dual TB and DM services. Conclusion: Integrative TB/DM screening and management activities can be achieved only if integration initiatives are prioritized at all levels of health facilities and among health policy makers in Tanzania. At least half of the health facilities were prepared to integrate the management of dual TB/DM. However, there is an urgent need to mobilize significant resources to improve the integration in these facilities, such as management guidelines and diagnostics..

Impact of early diagnosis of impaired glucose regulation in tuberculosis: Comparison of clinical outcomes in people with tuberculosis in Tanzania.

OBJECTIVE: Diabetes mellitus (DM) has been known to compromise tuberculosis (TB) treatment outcomes. Association data are limited for early hyperglycaemia detection and TB treatment outcomes. Thus, we assessed treatment outcomes including time to sputum conversion and death in TB participants with or without hyperglycaemia. METHODS: A prospective cohort study recruited TB participants receiving anti-TB treatment at health facilities in Tanzania between October 2019 and September 2020. Hyperglycaemia was defined as having pre-existing DM or pre-treatment random blood glucose of ≥7.8 mmol/L, in combination categorised as impaired glucose regulation (IGR). Those with IGR were further screened for hyperglycaemia severity using glycated haemoglobin. In case of unknown status, participants were tested for HIV. Time to death was determined at 6 months of TB treatment. RESULTS: Of 1344 participants, 187 (13.9%) had IGR, of whom 44 (23.5%) were HIV co-infected. Overall treatment success was 1206 (89.7%), and was similar among participants with or without IGR (p > 0.05). Time to death for participants with and without IGR was 18 versus 28 days (p = 0.870), respectively. Age ≥ 40 years (p = 0.038), bacteriological positive (p = 0.039), HIV (p = 0.009), or recurrent TB (p = 0.017) predicted death or treatment success during TB treatment in adjusted multivariable models. CONCLUSION: IGR did not influence clinical outcomes in TB patients with or without IGR in a programme of early IGR diagnosis and integration TB, HIV and DM care. Early detection and co-management of multi-morbidities among people diagnosed with TB may reduce likelihood of poor treatment outcomes in a programmatic setting.

Directly measured aerobic fitness in male Maasai of Tanzania.

OBJECTIVES: The agro-pastoralist Maasai of East Africa are highly physically active, but their aerobic fitness has so far only been estimated using heart rate (HR) response to submaximal exercise and not directly measured. Thus, we aimed to measure aerobic fitness directly using respiratory gas analysis in a group of Maasai, and habitual physical activity energy expenditure (PAEE) as explanatory variable. METHODS: In total, 21 (10 rural, 11 semi-urban) of 30 volunteering Tanzanian Maasai men were eligible to participate. Respiratory gas exchange was measured during a graded exercise test until exhaustion on a stationary bicycle to determine aerobic fitness. Maximal effort criteria were at least two of the following (1) leveling off, (2) respiratory exchange ratio (RER) >1.10, and (3) maximum HR within 10 bpm of age-estimated maximum HR. Habitual PAEE was estimated using combined accelerometry and HR monitoring. Anthropometry, biochemistry, blood pressure, resting HR, and dietary intake information were collected for background information. RESULTS: Mean age was 43.2 (range 26-60) years, and hemoglobin was higher in the rural versus semi-urban Maasai (16.9 vs. 15.4 g/dl, p = .02). Mean aerobic fitness (34.4 vs. 33.3 mlO2 /min/kg, p = .79), and mean PAEE (58.5 vs. 52.9 kJ/day/kg, p = .64) were similar in rural and semi-urban Maasai, respectively. CONCLUSIONS: Aerobic fitness was low to moderate in male rural and semi-urban Maasai. This may be explained by relatively low PAEE in comparison to previous objectively measured activity levels in Maasai, which indicates recent lifestyle changes.

Diabetes in developing countries.

There has been a rapid escalation of type 2 diabetes (T2D) in developing countries, with varied prevalence according to rural vs urban habitat and degree of urbanization. Some ethnic groups (eg, South Asians, other Asians, and Africans), develop diabetes a decade earlier and at a lower body mass index than Whites, have prominent abdominal obesity, and accelerated the conversion from prediabetes to diabetes. The burden of complications, both macro- and microvascular, is substantial, but also varies according to populations. The syndemics of diabetes with HIV or tuberculosis are prevalent in many developing countries and predispose to each other. Screening for diabetes in large populations living in diverse habitats may not be cost-effective, but targeted high-risk screening may have a place. The cost of diagnostic tests and scarcity of health manpower pose substantial hurdles in the diagnosis and monitoring of patients. Efforts for prevention remain rudimentary in most developing countries. The quality of care is largely poor; hence, a substantial number of patients do not achieve treatment goals. This is further amplified by a delay in seeking treatment, "fatalistic attitudes", high cost and non-availability of drugs and insulins. To counter these numerous challenges, a renewed political commitment and mandate for health promotion and disease prevention are urgently needed. Several low-cost innovative approaches have been trialed with encouraging outcomes, including training and deployment of non-medical allied health professionals and the use of mobile phones and telemedicine to deliver simple health messages for the prevention and management of T2D.

Capacity and capability of Tanzania health facilities to diagnose and manage diabetes mellitus in pregnancy.

AIMS: Gestational Diabetes Mellitus (GDM) remains a neglected cause of maternal and foetal morbidity and mortality in developing countries exacerbated by limited screening and management strategies. This study aimed to understanding how the RCH health system works in Tanzania, so as to provide opportunity for improving GDM screening and management. METHODS: A questionnaire was administered to facility staff and physical performance observed in 30 randomly selected public RCH facilities. RESULTS: Deficiencies identified included limited understaffing, late booking at ANC, and limited screening for GDM due to lack of equipment and supplies. Most women (96%) attending ANCs and postnatal care (87%) were managed at respective facilities with only 12% and 22% respectively being referred to higher levels of care. Facility staff were less trained or received fewer refresher courses in diabetes (0-5%), hypertension (4-6%), and other NCDs (0-16%) compared to training in PMCTC (39%), management of postpartum bleeding (31%) and HIV/AIDs (31%). CONCLUSION: Diabetes during pregnancy is rarely sought in public health facilities and its management is suboptimal. Training and refresher courses of staff in diabetes and hypertension should be uplifted and health systems should be strengthened to improve capacity and capability of facilities for better quality of care.

Gestational diabetes mellitus risk score: A practical tool to predict gestational diabetes mellitus risk in Tanzania.

BACKGROUND: Universal screening for hyperglycemia during pregnancy may be in-practical in resource constrained countries. Therefore, the aim of this study was to develop a simple, non-invasive practical tool to predict undiagnosed Gestational diabetes mellitus (GDM) in Tanzania. METHODS: We used cross-sectional data of 609 pregnant women, without known diabetes, collected in six health facilities from Dar es Salaam city (urban). Women underwent screening for GDM during ante-natal clinics visit. Smoking habit, alcohol consumption, pre-existing hypertension, birth weight of the previous child, high parity, gravida, previous caesarean section, age, MUAC ≥ 28 cm, previous stillbirth, haemoglobin level, gestational age (weeks), family history of type 2 diabetes, intake of sweetened drinks (soda), physical activity, vegetables and fruits consumption were considered as important predictors for GDM. Multivariate logistic regression modelling was used to create the prediction model, using a cut-off value of 2.5 to minimise the number of undiagnosed GDM (false negatives). RESULTS: Mid-upper arm circumference (MUAC) ≥ 28 cm, previous stillbirth, and family history of type 2 diabetes were identified as significant risk factors of GDM with a sensitivity, specificity, positive predictive value, and negative predictive value of 69%, 53%, 12% and 95%, respectively. Moreover, the inclusion of these three predictors resulted in an area under the curve (AUC) of 0.64 (0.56-0.72), indicating that the current tool correctly classifies 64% of high risk individuals. CONCLUSION: The findings of this study indicate that MUAC, previous stillbirth, and family history of type 2 diabetes significantly predict GDM development in this Tanzanian population. However, the developed non-invasive practical tool to predict undiagnosed GDM only identified 6 out of 10 individuals at risk of developing GDM. Thus, further development of the tool is warranted, for instance by testing the impact of other known risk factors such as maternal age, pre-pregnancy BMI, hypertension during or before pregnancy and pregnancy weight gain.

Hyperglycaemia is inversely correlated with live M. bovis BCG-specific CD4+ T cell responses in Tanzanian adults with latent or active tuberculosis.

INTRODUCTION: The rising prevalence of Diabetes mellitus (DM) in high TB-endemic countries may adversely affect sustainability of TB control since DM constitutes a risk factor for development of active tuberculosis (TB). The impact of DM on TB specific adaptive immune responses remains poorly addressed, particularly in people living in Sub-Saharan countries. We performed a functional characterization of TB specific cellular immune response in Tanzanian subjects with active or latent Mycobacterium tuberculosis (Mtb) infection stratified by their diabetic status. METHODS: HIV negative active TB patients (≥18 years) with Xpert MTB/RIF positive pulmonary TB were included before starting TB treatment in Dar es Salaam, Tanzania between April and December 2013. HIV negative healthy controls latently infected with TB but without past TB history were also included. Active and latent TB patients were stratified in two groups according to their diabetic status. Peripheral Blood Mononuclear cells were stimulated with either live M. bovis BCG or Mtb-specific peptide pools and analyzed by intracellular cytokine staining and polychromatic flow cytometry. RESULTS: Our results show a lower frequency of IFN-γ CD4+ T cells in patients with active TB and DM compared to patients with active TB only after live M. bovis BCG (p = 0.04) but not after Mtb peptide pools re-stimulation. Irrespective of TB status, level of glycaemia is selectively inversely correlated with IFN-γ and TNF-α CD4+ T cell production (p = 0.02 and p = 0.03) after live M. bovis BCG stimulation. CONCLUSIONS: These results support the hypothesis that hyperglycaemia negatively impacts antigen processing and/or presentation of whole mycobacteria delaying secretion of key cytokines involved in TB immunity.

Association between tuberculosis, diabetes and 25 hydroxyvitamin D in Tanzania: a longitudinal case control study.

BACKGROUND: Vitamin D level is inversely associated with tuberculosis (TB) and diabetes (DM). Vitamin D could be a mediator in the association between TB and DM. We examined the associations between vitamin D, TB and DM. METHODS: Consecutive adults with TB and sex- and age-matched volunteers were included in a case-control study in Dar es Salaam, Tanzania. Glycemia and total vitamin D (25(OH)D) were measured at enrolment and after TB treatment in cases. The association between low 25(OH)D (<75 nmol/l) and TB was evaluated by logistic regression adjusted for age, sex, body mass index, socioeconomic status, sunshine hours, HIV and an interaction between low 25(OH)D and hyperglycemia. RESULTS: The prevalence of low 25(OH)D was similar in TB patients and controls (25.8 % versus 31.0 %; p = 0.22). In the subgroup of patients with persistent hyperglycemia (i.e. likely true diabetic patients), the proportion of patients with low 25(OH)D tended to be greater in TB patients (50 % versus 29.7 %; p = 0.20). The effect modification by persistent hyperglycemia persisted in the multivariate analysis (pinteraction = 0.01). CONCLUSIONS: Low 25(OH)D may increase TB risk in patients with underlying DM. Trials should examine if this association is causal and whether adjunct vitamin D therapy is beneficial in this population.

Transient Hyperglycemia in Patients With Tuberculosis in Tanzania: Implications for Diabetes Screening Algorithms.

BACKGROUND: Diabetes mellitus (DM) increases tuberculosis risk while tuberculosis, as an infectious disease, leads to hyperglycemia. We compared hyperglycemia screening strategies in controls and patients with tuberculosis in Dar es Salaam, Tanzania. METHODS: Consecutive adults with tuberculosis and sex- and age-matched volunteers were included in a case-control study between July 2012 and June 2014. All underwent DM screening tests (fasting capillary glucose [FCG] level, 2-hour CG [2-hCG] level, and glycated hemoglobin A1c [HbA1c] level) at enrollment, and cases were tested again after receipt of tuberculosis treatment. Association of tuberculosis and its outcome with hyperglycemia was assessed using logistic regression analysis adjusted for sex, age, body mass index, human immunodeficiency virus infection status, and socioeconomic status. Patients with tuberculosis and newly diagnosed DM were not treated for hyperglycemia. RESULTS: At enrollment, DM prevalence was significantly higher among patients with tuberculosis (n = 539; FCG level > 7 mmol/L, 4.5% of patients, 2-hCG level > 11 mmol/L, 6.8%; and HbA1c level > 6.5%, 9.3%), compared with controls (n = 496; 1.2%, 3.1%, and 2.2%, respectively). The association between hyperglycemia and tuberculosis disappeared after tuberculosis treatment (adjusted odds ratio [aOR] for the FCG level: 9.6 [95% confidence interval {CI}, 3.7-24.7] at enrollment vs 2.4 [95% CI, .7-8.7] at follow-up; aOR for the 2-hCG level: 6.6 [95% CI, 4.0-11.1] vs 1.6 [95% CI, .8-2.9]; and aOR for the HbA1c level, 4.2 [95% CI, 2.9-6.0] vs 1.4 [95% CI, .9-2.0]). Hyperglycemia, based on the FCG level, at enrollment was associated with tuberculosis treatment failure or death (aOR, 3.3; 95% CI, 1.2-9.3). CONCLUSIONS: Transient hyperglycemia is frequent during tuberculosis, and DM needs confirmation after tuberculosis treatment. Performance of DM screening at tuberculosis diagnosis gives the opportunity to detect patients at risk of adverse outcome.

Type 2 diabetes control and complications in specialised diabetes care centres of six sub-Saharan African countries: the Diabcare Africa study.

AIM: The Diabcare Africa project was carried out across six sub-Saharan African countries to collect standardised and comparable information for the evaluation of diabetes control, management and late complications in diabetic populations at specialist clinics. METHODS: A cross-sectional, descriptive study of 2352 type-2 diabetes patients who were treated at specialist clinics for at least 12 months prior to the study. RESULTS: The mean age of patients was 53.0±16.0 years and had 8.0±6.0 years known duration of diabetes. 47% had their HbA1c assessed in the past year (mean 8.2±2.4%) with 29% achieving a level <6.5%. 21% had BP within 130/80 mmHg and 65% were treated for hypertension. Fasting lipids were assessed in 45% of the patients with mean cholesterol level of 4.9±1.2 mmol/L, HDL-cholesterol of 1.3±0.7 mmol/L and triglycerides of 1.2±0.7 mmol/L. 13% of the patients were treated for hyperlipidaemia, mostly with statins. Background retinopathy (18%) and cataract (14%) were the most common eye complications. Macrovascular disease was rare, and 48% had neuropathy. CONCLUSIONS: Half of the patients benefitted from standard care, and a third had appropriate glycaemic control - attributed to access to, rather than quality of care. This study provided evidence to support appropriate interventions to diabetic populations of sub-Saharan origin.