Prevalence, Clinical Features, and Predictors of Adrenal Insufficiency in Adults With Tuberculosis or HIV: A Systematic Review and Meta-analysis.

Background: Despite the high frequency of adrenal insufficiency (AI) in patients with tuberculosis or HIV, its diagnosis is often missed or delayed resulting in increased mortality. This systematic review and meta-analysis aimed to document the prevalence, significant clinical features, and predictors of AI in adult patients with tuberculosis or HIV. Methods: We systematically searched databases (Medline, Embase, CINAHL, Cochrane Library, and Africa Journal Online) for published studies on AI in adult patients with tuberculosis or HIV. The pooled prevalence of AI was determined by a random-effect model meta-analysis. A narrative review was used to describe the significant clinical features and predictors of AI in adult patients with tuberculosis or HIV. Results: A total of 46 studies involving 4044 adults were included: 1599 with tuberculosis and 2445 with HIV. The pooled prevalence of AI was 33% (95% CI, 22%-45%; I2 = 97.7%, P < .001) in participants with tuberculosis and 28% (95% CI, 18%-38%; I2 = 98.9%, P < .001) in those with HIV. Presentation with multidrug-resistant tuberculosis, abdominal pain, salt craving, myalgia, increased severity and duration of tuberculosis disease, and the absence of nausea predicted AI in participants with tuberculosis in 4 studies. Cytomegalovirus antigenemia positivity, rifampicin therapy, and eosinophilia >3% predicted AI in participants with HIV in 2 studies. Conclusions: AI is relatively common in adults with tuberculosis or HIV. Its timely screening, diagnosis, and management in patients with these 2 conditions should be encouraged to avert mortality.

Tuberculosis and diabetes mellitus comorbidity in an adult Ugandan population.

BACKGROUND: Diabetes mellitus (DM) has a direct impact on the clinical manifestation and prognosis of active tuberculosis disease (TB) and is known to increase the chance of developing the condition. We sought to determine the prevalence of DM in adult Ugandan patients with recently diagnosed TB and the associated sociodemographic, anthropometric, and metabolic characteristics of TB-DM comorbidity. METHODS: In this cross-sectional study conducted at the adult TB treatment centres of three tertiary healthcare facilities in Uganda, we screened adult participants with recently diagnosed TB (diagnosed in < 2 months) for DM. All participants were screened with five tests; initially with a random blood glucose (RBG) test, and then later with fasting blood glucose (FBG), laboratory-based glycated hemoglobin (HbA1c), point-of-care (POC) HbA1c, and oral glucose tolerance test (OGTT) if the RBG was ≥ 6.1 mmol/l. The WHO guidelines for diagnosing and managing DM were used to support the DM diagnosis. To identify the factors associated with DM-TB comorbidity, logistic regression was used. RESULTS: A total of 232 participants with recently diagnosed TB were screened for DM. Of these, 160 (69%) were female. The median (IQR) age, body mass index, and RBG of all study participants was 35 (27-42) years, 19.2 (17.6-21.3) kg/m2, and 6.1 (5.5-7.2) mmol/l, respectively. About half of the participants (n = 117, 50.4%) had RBG level ≥ 6.1 mmol/l. Of these, 75 (64.1%) participants returned for re-testing. Diabetes mellitus was diagnosed in 32 participants, corresponding to a prevalence of 13.8% (95% CI 9.9-18.9). A new diagnosis of DM was noted in 29 (90.6%) participants. On logistic regression, age ≥ 40 years was associated with increased odds of TB and DM comorbidity (AOR 3.12, 95% CI 1.35-7.23, p = 0.008) while HIV coinfection was protective (AOR 0.27, 95% CI 0.10-0.74, p = 0.01). CONCLUSION: TB and DM comorbidity was relatively common in this study population. Routine screening for DM in adult Ugandan patients with recently diagnosed TB especially among those aged ≥ 40 years and HIV-negative patients should be encouraged in clinical practice.

Diagnostic accuracy of two confirmatory tests for diabetes mellitus in adult Ugandans with recently diagnosed tuberculosis.

Objective: The optimal confirmatory tests for diabetes mellitus (DM) in patients with tuberculosis (TB) vary across populations. This study aimed to evaluate the performance of two confirmatory tests for DM against the oral glucose tolerance test (OGTT) as the reference test in adult Ugandans with recently diagnosed TB. Methods: A total of 232 adult participants receiving TB treatment underwent initial screening for DM with random blood glucose (RBG) measurement. Participants with a RBG level ⩾6.1 mmol/l received additional screening with fasting blood glucose (FBG), laboratory-measured glycated haemoglobin (HbA1c) and an OGTT. Using the latter as the gold standard and reference test, we evaluated the diagnostic accuracy of laboratory-measured HbA1c and FBG. Results: Of the 232 participants initially screened for DM using RBG measurement, 117 participants (50.4%) had RBG level ⩾6.1 mmol/l and were scheduled to return for additional blood glucose testing. Of these, 75 (64.1%) participants returned for FBG and HbA1c measurements. A diagnosis of DM was made in 32 participants, corresponding to a prevalence of 13.8% [95% CI 9.9-18.9].The areas under the curve (AUC) for FBG and laboratory-measured HbA1c were 0.69 [95% CI 0.47-0.90] and 0.65 [95% CI 0.43-0.87], respectively. The sensitivity and specificity of a FBG level of ⩾7 mmol/l were 57.1% [95% CI 18.4-90.1] and 74.6% [95% CI 62.5-84.5], respectively, whereas the sensitivity and specificity for laboratory-measured HbA1c of ⩾6.5 mmol/l (48 mmol/mol) were 14.3% [95% CI 0.40-57.9] and 95.3% (86.9-99.0%), respectively. Conclusion: FBG may be better than laboratory-measured HbA1c in confirming DM in adult Ugandans with recently diagnosed TB. However, because of the small study sample size, larger studies evaluating the diagnostic utility of these diabetes screening tests in adult Ugandans with TB are needed to confirm these findings.

Appropriate diabetes test in patients with tuberculosis Diabetes mellitus (DM) is a common condition in patients with tuberculosis and proactively screening for the condition is encouraged in all adult patients with tuberculosis. In this study, a total of 232 adult Ugandans with recently diagnosed tuberculosis were screened for DM using random glucose test, fasting blood glucose test, glycated haemoglobin test and an oral glucose tolerance test (OGTT), as the gold-standard and reference test. Compared with the OGTT, a fasting blood glucose test was noted to be a better screening test for diabetes mellitus than glycated haemoglobin in these patients and may be used as a follow-up test to random blood glucose in the screening and diagnosis of DM in adult Ugandans with tuberculosis.

Burden and associated phenotypic characteristics of tuberculosis infection in adult Africans with diabetes: a systematic review.

Diabetes mellitus (DM) increases the risk of developing tuberculosis infection (TBI). However, the evidence on the burden and phenotypic characteristics of TBI in African patients with DM is limited. This study aimed to determine the prevalence and characterisation of TBI in native African patients living with DM. We searched PubMed, EMBASE, and African Journals Online for original studies reporting information on the prevalence and characteristics of TBI in adult Africans with DM. A forest plot was used to describe the pooled prevalence estimate of TBI and the corresponding 95% confidence intervals (CI). Six studies conducted in four African countries involving 721 participants with DM were included in this systematic review. The pooled prevalence estimate of TBI was 40% (95% CI 20-60%, I2 = 98.52%, p < 0.001). Age ≥ 40 years and glycated haemoglobin levels independently predicted TBI positivity in patients with DM in three studies. Africans with DM have a high prevalence of TBI, especially those who are older or with poorly controlled diabetes. This justifies the need for studies to explore how to screen and manage TBI to avert the progression to active TB disease.

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.

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.

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.

Atherogenic index of plasma and its cardiovascular risk factor correlates among patients with type 2 diabetes in Uganda.

Background: Atherogenic Index of Plasma (AIP) is a reliable predictor of coronary artery disease. There is paucity of data on AIP and its correlates among patients with type 2 diabetes (T2D) in Uganda. Objective: To assess the profile of AIP and its cardiovascular risk factor correlates among patients with T2D in Uganda. Methods: This was a cross-sectional study conducted in 8 health facilities with established T2D clinics in Central-Uganda. The study enrolled 500 patients aged 40 to 79 years. Data was collected on socio-demographic characteristics, lipid profile and glycated haemoglobin (HbA1c). The AIP was derived using log (triglycerides/high-density cholesterol) and further categorised as low cardiovascular disease (CVD) risk if the AIP was <0.1, intermediate risk (0.1-0.24) and high risk (≥0.24). Cardiovascular risk factors were defined according to international guidelines.Stata version 14 was used to analyse data, Pearson correlation analyses were conducted. Statistical significance was set at p<0.05. Results: There were 389(77.4%) females with a mean age of 55.07±8. 979 years. Low-risk was found in 43.6%, intermediate risk in 20.2% and high risk in 36.2% of the participants. AIP significantly correlated with waist circumference (r=0.1095, p<0.0147), waist-hip ratio (r=0.1926, p<0.001), Casteri Risk Index I (r=0.506, r=<0.001), Casteri Risk Index II (r=0.246, p<0.001) and atherogenic coefficient (r=0.186, p<0.001). Insignificant correlation was observed between AIP and fasting blood sugar (r=0.017, p=0.7042), HBA1C (r=0.0108, p=0.8099) and diabetes duration (r=0.0445, p=0.32). Conclusions: AIP is significantly elevated and correlated with cardiovascular risk factors in patients with T2D. In clinical management, this may be a useful tool in risk stratifying patients with T2D.

Effect of COVID-19 pandemic on inpatient service utilization and patient outcomes in Uganda.

COVID-19 has had devastating effects on health systems but reports from sub-Saharan Africa are few. We compared inpatient admissions, diagnostic tests performed, clinical characteristics and inpatient mortality before and during the COVID-19 pandemic at an urban tertiary facility in Uganda. We conducted a retrospective chart review of patients admitted at Kiruddu National Referral Hospital in Uganda between January-July 2019 (before the pandemic) and January-July 2020 (during the pandemic). Of 3749 inpatients, 2014 (53.7%) were female, and 1582 (42.2%) had HIV. There was a 6.1% decline in admissions from 1932 in 2019 to 1817 in 2020. There were significantly fewer diagnostic tests performed in 2020 for malaria, tuberculosis, and diabetes. Overall, 649 (17.3%) patients died. Patients admitted during the COVID-19 pandemic (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.04-1.5, p = 0.018), patients aged ≥ 60 years (aOR 1.6, 95% CI 1.2-2.1, p = 0.001), HIV co-infected (aOR 1.5, 95% CI 1.2-1.9, p < 0.001), and those admitted as referrals (aOR 1.5, 95% CI 1.2-1.9, p < 0.001) had higher odds of dying. The COVID-19 pandemic disrupted inpatient service utilization and was associated with inpatient mortality. Policy makers need to build resilience in health systems in Africa to cope with future pandemics.

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.

Availability and affordability of essential medicines and diagnostic tests for diabetes mellitus in Africa.

OBJECTIVE: To investigate the current status of the availability and affordability of specific essential medicines and diagnostics for diabetes in Africa. METHODS: Systematic review and meta-analysis. Studies conducted in Africa that reported any information on the availability and affordability of short-acting, intermediate-acting, and premixed insulin, glibenclamide, metformin, blood glucose, glycated haemoglobin or HbA1c, and lipid profile tests were included. Random-effect model meta-analysis and descriptive statistics were performed to determine the pooled availability and affordability, respectively. RESULTS: A total of 21 studies were included. The pooled availability of each drug was as follows: short-acting insulin 33.5% (95% CI: 17.8%-49.2%, I2  = 95.02%), intermediate-acting insulin 23.1% (95% CI: 6.3%-39.9%, I2  = 91.6%), premixed insulin 49.4% (95% CI: 24.9%-73.9%, I2  = 90.57%), glibenclamide 55.9% (95% CI: 43.8%-68.0%, I2  = 96.7%), and metformin 47.0% (95% CI: 34.6%-59.4%, I2  = 97.54%). Regarding diagnostic tests, for glucometers the pooled availability was 49.5% (95% CI: 37.9%-61.1%, I2  = 97.43%), for HbA1c 24.6% (95% CI: 3.1%-46.1%, I2  = 91.64), and for lipid profile tests 35.7% (95% CI: 19.4%-51.9%, I2  = 83.77%). The median (IQR) affordability in days' wages was 7 (4.7-7.5) for short-acting insulin, 4.4 (3.9-4.9) for intermediate-acting insulin, 7.1 (5.8-16.7) for premixed insulin, 0.7 (0.7-0.7) for glibenclamide, and 2.1 (1.8-2.8) for metformin. CONCLUSION: The availability of the five essential medicines and three diagnostic tests for diabetes in Africa is suboptimal. The relatively high cost of insulin, HbA1c, and lipid profile tests is a significant barrier to optimal diabetes care. Pragmatic country-specific strategies are urgently needed to address these inequities in access and cost.

HIV, tuberculosis, diabetes mellitus and hypertension admissions and premature mortality among adults in Uganda from 2011 to 2019: is the tide turning?

BACKGROUND: The growing burden of diabetes mellitus (DM) and hypertension (HTN) on the background of endemic Human Immuno-deficiency Virus (HIV) and tuberculosis (TB) is a concern in low- and middle-income countries. We aimed to describe annual trends in admissions, mortality rates and premature mortality (years of potential life lost-YPLLs) due to HIV, tuberculosis (TB), diabetes mellitus (DM) and hypertension (HTN) in Uganda. METHODS: We conducted a retrospective cohort study, retrieving electronic records of adults admitted to Mulago and Kiruddu national referral hospitals medical wards between 1st January 2011 and 31st December 2019. We used STATA BE 17.0 and GraphPad Prism 8.0.2 to compute total admissions, inpatient crude mortality rates, and YPLLs; and demonstrate trends using Mann-Kendall test. RESULTS: Of 108,357 admissions, 55,620 (51.3%) were female, 15,300 (14.1%) were recorded in 2012, and 22,997 (21.2%) were aged 21-30 years. HIV, TB, DM and HTN accounted for 26,021 (24.0%); 9537 (8.8%); 13,708 (12.7) and 13,252 (12.2%) of all admissions, respectively. Overall inpatient mortality was 16.7% (18,099/108,357), 53.5% (9674/18,099) were male, 21.5% (3898) were aged 31-40 years and 2597 (14.4%) were registered in 2013. HIV, TB, DM and HTN accounted for 35.6% (6444), 14.6% (2646), 9.1% (1648) and 11.8% (2142) of all deaths, respectively. Total admissions (Kendall's tau-B = - 0.833, p < 0.001) and deaths declined (Kendall's tau-B = - 0.611, p = 0.029). A total of 355,514 (mean = 20.8 years, SD 30.0) YPLLs were recorded, of which 54.6% (191,869) were in males; 36.2% (128,755) were among those aged 21-30 years and were recorded in 2012 (54,717; 15.4%). HIV, TB, DM and HTN accounted for 46.5% (165,352); 19.5% (69,347); 4.8% (16,991) and 4.5% (16,167) of YPLLs, respectively. Proportionate contribution of HIV to deaths and YPLLs declined, remained stagnant for TB; and increased for both DM and HTN. CONCLUSION: TB and HIV account for higher though declining, while DM and HTN account for lower albeit rising morbidity and premature mortality among adult medical patients in Uganda. TB prevention and treatment; and DM/HTN service integration in HIV care should be optimized and scaled up.

Rifapentine and isoniazid for prevention of tuberculosis in people with diabetes (PROTID): protocol for a randomised controlled trial.

BACKGROUND: Diabetes mellitus (DM) increases the risk of tuberculosis (TB) and will hamper global TB control due to the dramatic rise in type 2 DM in TB-endemic settings. In this trial, we will examine the efficacy and safety of TB preventive therapy against the development of TB disease in people with DM who have latent TB infection (LTBI), with a 12-week course of rifapentine and isoniazid (3HP). METHODS: The 'Prevention of tuberculosis in diabetes mellitus' (PROTID) consortium will randomise 3000 HIV-negative eligible adults with DM and LTBI, as evidenced by a positive tuberculin skin test or interferon gamma release assay, to 12 weeks of 3HP or placebo. Participants will be recruited through screening adult patients attending DM clinics at referral hospitals in Tanzania and Uganda. Patients with previous TB disease or treatment with a rifamycin medication or isoniazid (INH) in the previous 2 years will be excluded. The primary outcome is the occurrence of definite or probable TB disease; secondary outcome measures include adverse events, all-cause mortality and treatment completion. The primary efficacy analysis will be intention-to-treat; per-protocol analyses will also be carried out. We will estimate the ratio of TB incidence rates in intervention and control groups, adjusting for the study site using Poisson regression. Results will be reported as efficacy estimates (1-rate ratio). Cumulative incidence rates allowing for death as a competing risk will also be reported. Approximately 1000 LTBI-negative, HIV-negative participants will be enrolled consecutively into a parallel cohort study to compare the incidence of TB in people with DM who are LTBI negative vs positive. A number of sub-studies will be conducted among others to examine the prevalence of LTBI and active TB, estimate the population impact and cost-effectiveness of LTBI treatment in people living with DM in these African countries and address gaps in the prevention and therapeutic management of combined TB-DM. DISCUSSION: PROTID is anticipated to generate key evidence to guide decisions over the use of TB preventive treatment among people with DM as an important target group for better global TB control. TRIAL REGISTRATION: ClinicalTrials.gov NCT04600167 . Registered on 23 October 2020.

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.

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.

Apparent Insulin Deficiency in an Adult African Population With New-Onset Type 2 Diabetes.

Identifying patients with new-onset type 2 diabetes who have insulin deficiency can aid in timely insulin replacement therapy. In this study, we measured fasting C-peptide concentration to assess endogenous insulin secretion and determine the prevalence and characteristics of patients with insulin deficiency in adult Ugandan patients with confirmed type 2 diabetes at presentation. Methods: Adult patients with new-onset diabetes were recruited from seven tertiary hospitals in Uganda. Participants who were positive for the three islet autoantibodies were excluded. Fasting C-peptide concentrations were measured in 494 adult patients, and insulin deficiency was defined as a fasting C-peptide concentration <0.76 ng/ml. The socio-demographic, clinical, and metabolic characteristics of participants with and without insulin deficiency were compared. Multivariate analysis was performed to identify independent predictors of insulin deficiency. Results: The median (IQR) age, glycated haemoglobin (HbA1c), and fasting C-peptide of the participants was 48 (39-58) years,10.4 (7.7-12.5) % or 90 (61-113) mmol/mol, and 1.4 (0.8-2.1) ng/ml, respectively. Insulin deficiency was present in 108 (21.9%) participants. Participants with confirmed insulin deficiency were more likely to be male (53.7% vs 40.4%, p=0.01), and had a lower body mass index or BMI [p<0.001], were less likely to be hypertensive [p=0.03], had reduced levels of triglycerides, uric acid, and leptin concentrations [p<0.001]), but higher HbA1c concentration (p=0.004). On multivariate analysis, BMI (AOR 0.89, 95% CI 0.85-0.94, p<0.001), non-HDLC (AOR 0.77, 95% CI 0.61-0.97, p=0.026), and HbA1c concentrations (AOR 1.08, 95% CI 1.00-1.17, p=0.049) were independent predictors of insulin deficiency. Conclusion: Insulin deficiency was prevalent in this population, occurring in about 1 in every 5 patients. Participants with insulin deficiency were more likely to have high HbA1c and fewer markers of adiposity and metabolic syndrome. These features should increase suspicion of insulin deficiency and guide targeted testing and insulin replacement therapy.

Latent Tuberculosis Infection Status of Pregnant Women in Uganda Determined Using QuantiFERON TB Gold-Plus.

BACKGROUND: The risk of progression of latent tuberculosis infection (LTBI) to active disease increases with pregnancy. This study determined the prevalence and risk factors associated with LTBI among pregnant women in Uganda. METHODS: We enrolled 261 pregnant women, irrespective of gestational age. Participants who had known or suspected active tuberculosis (TB) on the basis of clinical evaluation or who had recently received treatment for TB were excluded. LTBI was defined as an interferon-γ concentration ≥0.35 IU/mL (calculated as either TB1 [eliciting CD4+ T-cell responses] or TB2 [eliciting CD8+ T-cell responses] antigen minus nil) using QuantiFERON TB Gold-Plus (QFT-plus) assay. RESULTS: LTBI prevalence was 37.9% (n = 99) (95% confidence interval [CI], 32.3-44.0). However, 24 (9.2%) subjects had indeterminate QFT-plus results. Among participants with LTBI, TB1 and TB2 alone were positive in 11 (11.1%) and 18 (18.2%) participants, respectively. In multivariable analysis, human immunodeficiency virus (HIV) infection (adjusted odds ratio [aOR], 4.4 [95% confidence interval {CI}, 1.1-18.0]; P = .04) and age 30-39 years (aOR, 4.0 [95% CI, 1.2-12.7]; P = .02) were independently associated with LTBI. Meanwhile, smoking status, alcohol use, nature of residence, crowding index, and TB contact were not associated with LTBI. CONCLUSIONS: Our findings are in keeping with the evidence that HIV infection and advancing age are important risk factors for LTBI in pregnancy. In our setting, we recommend routine screening for LTBI and TB preventive therapy among eligible pregnant women.

Optimizing diabetes mellitus care to improve COVID-19 outcomes in resource-limited settings in Africa.

Diabetes mellitus (DM) is an important risk factor for both severe disease and death due to coronavirus-2019 (COVID-19). About 19 million of the 463 million persons living with DM (PLWD) globally are found in sub-Saharan Africa (SSA). The dual burden of DM and poverty in SSA, coupled with the rising number of cases of COVID-19 in this region, predisposes PLWD to inadequate care and poor glycemic controls due to the disruption to the economy and the healthcare system. The risk of acquisition of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) among PLWD is the same as those in the general population. Therefore, the standard preventive measures outlined by the World Health Organization must be strictly adhered to. In addition, maintaining adequate glycemic control is associated with better outcomes in DM patients with COVID-19. In SSA, adequate supply of DM medication while patients stay at home is crucial to minimize routine hospital visits since DM clinics are usually overcrowded and have longer waiting times, which may maximize risk of SARS-CoV-2 transmission to PLWD across the region. Psychosocial support to improve adherence to anti-hyperglycemic medications may improve COVID-19 outcomes. Trained healthcare professionals should diagnose and evaluate severity comprehensively as well as evaluate the need for in-patient care for PLWD with COVID-19 irrespective of disease severity. Due to the increased risk of severe disease, a multi-disciplinary approach to the management of COVID-19 in PLWD should preferably be in a setting where close monitoring is available, typically a health facility, even for mild disease that may require home management according to local guidelines. In conclusion, DM complicates COVID-19 outcomes and the on-going COVID-19 pandemic adversely affects DM care at individual and global public health levels. PLWD should be prioritized as COVID-19 vaccines are being rolled out.