Temporal patterns of tuberculosis-associated hyperglycaemia and its effect on treatment outcomes in individuals not previously diabetic: A prospective cohort study

BACKGROUND: Active tuberculosis (TB) infection can induce hyperglycaemia and insulin resistance, increasing the risk of type 2 diabetes mellitus and worsening TB disease severity. However, data on the dynamics of TB-associated hyperglycaemia and its effect on TB treatment outcomes among individuals not previously diabetic remain limited, particularly in high TB-burden settings. In this study, we aimed to investigate the prevalence and temporal patterns of TB-associated hyperglycaemia and its impact on disease presentation and TB treatment outcomes among a cohort of individuals not previously diabetic. METHODS: This was a five-month longitudinal prospective cohort study conducted at two urban specialized TB healthcare facilities in Kenya among adults aged >18 years with bacteriologically confirmed pulmonary TB (PTB). Known diabetes mellitus (DM) or prediabetic individuals were excluded during enrolment. Glycaemic status was assessed at baseline and months two and five using glycated haemoglobin (HbA1c) according to the American Diabetes Association guideline. Hyperglycaemia was defined as HbA1c ≥5.7% and categorized as normoglycaemia, persistent, transient, or incident hyperglycaemia based on longitudinal measurements. Socio-demographic and clinical data were collected using a structured questionnaire and analysed using SPSS version 26.0 and GraphPad Prism version 9.0. Longitudinal trends in HbA1c levels and the association of hyperglycaemia with DM-related symptoms, as well as TB treatment outcomes, were assessed using the Friedman test and the Generalized Estimating Equations (GEE), respectively. RESULTS: We enrolled and followed 87 individuals newly diagnosed with PTB. Of these, 66 were tested for hyperglycaemia in month two after 7 died and 14 were lost to follow-up/transferred out (LTFU/TO), and 70 in month 5, after an additional death, 7 re-engagements, and 2 LTFU/TO were reported. At enrolment, the cohort was predominantly male (76%), not married (53%), and HIV-negative (84%), with a median age of 37 years (IQR 29-44). Prevalence of hyperglycaemia at baseline was 75% (95% Confidence Interval [CI] 65-83), with 45% of the individuals presenting as prediabetic and 30% as diabetic. At the month-two and month-five time points, the proportion of participants with prediabetes (pre-DM) increased from 24% (16/66) to 30% (21/70), while the prevalence of DM declined from 21% (14/66) to 9% (6/70). Across the time points, HbA1c levels varied significantly (p < 0.001). In GEE analysis, hyperglycaemic participants were more likely to experience classic symptoms of DM such as frequent micturition (adjusted Relative Risk [aRR] 1.76, 95% CI 1.12-2.77), increased thirst (aRR 2.37, 95% CI 1.38-4.05), unintentional weight loss (aRR 1.84, 95% CI 1.24-2.75), and blurred vision (aRR 1.95, 95% CI 1.20-3.18). After adjusting for age, BMI, HIV, alcohol use, and smoking, hyperglycaemia was independently associated with an increased risk of sputum positivity (aRR 4.22, 95% CI 2.09-8.52). Glycaemic variability was significantly associated with unfavourable TB treatment outcomes (p < 0.001). CONCLUSIONS: New-onset hyperglycaemia was highly prevalent in adults newly diagnosed with TB and persisted through the fifth month of TB treatment. Hyperglycaemia was associated with classic diabetic symptoms and persisting sputum positivity, highlighting the need to integrate glycaemic monitoring and management into routine TB follow-up care.