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

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

Level of education and preferred language of informed consent for clinical research in a multi-lingual community.

BACKGROUND: Low education levels and language barriers present challenges in obtaining informed consent for clinical research. OBJECTIVE: To describe and correlate the association between the level of education and the participant's preferred language of consent. DESIGN: Descriptive-analytical cross-sectional study. PARTICIPANTS: Adults being consented for participation in tuberculosis(TB) research studies in an East African community with varying levels of education. PROCEDURES: We analyzed data on demographic and educational characteristics collected from adults being consented for participation in TB studies .Only participants who could understand and speak Luganda (the main local language) or English (the official language of Uganda) were included in this analysis. RESULTS: A total of 523 participants were consented between April 2015 and December 2017 and included in this analysis; 250 below Senior four ( 13yrs of education). We noted that the preference for English rises with the rising levels of education and peaked at beyond senior six (83%Vs17%,OR=49,95%CI:22.8-106.3,p<0.001).Participants below senior four preferred Luganda Vs senior four and above(OR=16.9,95%CI:9.9-28.8,p<0.001). CONCLUSION: Rising education levels of participants were associated with preference for English language usage during initial consent for clinical research studies

Level of education and preferred language of informed consent for clinical research in a multi-lingual community

Background: Low education levels and language barriers present challenges in obtaining informed consent for clinical research. Objective: To describe and correlate the association between the level of education and the participant\u2019s preferred language of consent. Design: Descriptive-analytical cross-sectional study. Participants: Adults being consented for participation in tuberculosis(TB) research studies in an East African community with varying levels of education. Procedures: We analyzed data on demographic and educational characteristics collected from adults being consented for participation in TB studies .Only participants who could understand and speak Luganda (the main local language) or English ( the official language of Uganda) were included in this analysis. Results: A total of 523 participants were consented between April 2015 and December 2017 and included in this analysis; 250 below Senior four (&lt; 11yrs of education), 114 senior four (at 11yrs of education),73 senior five-senior six (12-13yrs of education) and 86 beyond senior six (&gt; 13yrs of education). We noted that the preference for English rises with the rising levels of education and peaked at beyond senior six (83%Vs17%,OR=49,95%CI:22.8-106.3,p&lt;0.001).Participants below senior four preferred Luganda Vs senior four and above(OR=16.9,95%CI:9.9-28.8,p&lt;0.001) Conclusion: Rising education levels of participants were associated with preference for English language usage during initial consent for clinical research studies

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.MethodsAdult 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 &lt;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.ResultsThe 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&lt;0.001], were less likely to be hypertensive [p=0.03], had reduced levels of triglycerides, uric acid, and leptin concentrations [p&lt;0.001]), but higher HbA1c concentration (p=0.004). On multivariate analysis, BMI (AOR 0.89, 95% CI 0.85-0.94, p&lt;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.ConclusionInsulin 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

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 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

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

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

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

Effectiveness of low-dose theophylline for the management of biomass-associated COPD (LODOT-BCOPD): study protocol for a randomized controlled trial.

BACKGROUND: COPD is a leading cause of death globally, with the majority of morbidity and mortality occurring in low- and middle-income country (LMIC) settings. While tobacco-smoke exposure is the most important risk factor for COPD in high-income settings, household air pollution from biomass smoke combustion is a leading risk factor for COPD in LMICs. Despite the high burden of biomass smoke-related COPD, few studies have evaluated the efficacy of pharmacotherapy in this context. Currently recommended inhaler-based therapy for COPD is neither available nor affordable in most resource-limited settings. Low-dose theophylline is an oral, once-a-day therapy, long used in high-income countries (HICs), which has been proposed for the management of COPD in LMICs in the absence of inhaled steroids and/or bronchodilators. The Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD) trial investigates the clinical efficacy and cost-effectiveness of low-dose theophylline for the management of biomass-related COPD in a low-income setting. METHODS: LODOT-BCOPD is a randomized, double-blind, placebo-controlled trial to test the efficacy of low-dose theophylline in improving respiratory symptoms in 110 participants with moderate to severe COPD in Central Uganda. The inclusion criteria are as follows: (1) age 40 to 80 years, (2) full-time resident of the study area, (3) daily biomass exposure, (4) post-bronchodilator FEV1/FVC below the 5th percentile of the Global Lung Initiative mixed ethnic reference population, and (5) GOLD Grade B-D COPD. Participants will be randomly assigned to receive once daily low-dose theophylline (200 mg ER, Unicontin-E) or placebo for 52 weeks. All participants will receive education about self-management of COPD and rescue salbutamol inhalers. We will measure health status using the St. George's Respiratory Questionnaire (SGRQ) and quality of life using the EuroQol-5D (EQ-5D) at baseline and every 6 months. In addition, we will assess household air pollution levels, serum inflammatory biomarkers (fibrinogen, hs-CRP), and theophylline levels at baseline, 1 month, and 6 months. The primary outcome is change in SGRQ score at 12 months. Lastly, we will assess the cost-effectiveness of the intervention by calculating quality-adjusted life years (QALYs) from the EQ-5D. TRIAL REGISTRATION: ClinicalTrials.gov  NCT03984188 . Registered on June 12, 2019 TRIAL ACRONYM: Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD)