Therefore, a change of cytosolic free NAD/NADH could infer a metabolic alteration and is closely linked to physiological or pathological states. How to correctly apply this method to estimate cytosolic free NAD/NADH remains a problematic issue. Many studies seem to have the measurement problem which apparently persists and has not been recognized at all. The reason that leads to the incorrect measurement is owing to the misuse of the equation of chemical equilibrium. In the cited studies, simply assuming that the conversion in cells was at near equilibrium without verifying how near it was. This is rationally incorrect, because the mass action ratio at near-equilibrium could differ from the Keq at equilibrium by 1 or 2 orders of magnitude. Hence, cytosolic NAD/NADH estimated as such could be deviated from the true values by 1 or 2 orders of magnitude. This has been a blind spot that misleads the estimation ever since. Another equally important issue is the relationship between NAD/NADH and L/P, which is not clear. The cytosolic free NAD/NADH ratio seems to be regarded as a variable that is dependent on the cytosolic L/P ratio, hence a change of L/P under different physiological and patholological conditions represents a corresponding change of NAD/NADH. However, it should be borne in mind that NAD/NADH is not necessarily a dependent variable that responds to the change of cytosolic L/P ratio.Furthermore, we found a high prevalence of impaired glycaemia and diabetes among controls, randomly selected from neighbours with the same sex and similar age as index cases, but without evidence of TB. Considering that the controls were generally poor, normal weight and young the observed prevalence of diabetes of more than 9% was surprisingly high. According to estimates by the International Diabetes Foundation, the prevalence of diabetes in Tanzanian adults between 20?C79 years of age is 3.2% in 2010. Our data suggest that this in an underestimate. This increase may be due to the ongoing nutritional transition, i.e. increased access to refined fat and sugar combined with reduced physical activity. The observed association between diabetes and pulmonary TB is in accordance with reports from several other recent studies. A review of 13 observational studies, of which only one was from a low-income country and none from Africa, found that diabetes was associated with TB regardless of study design. Based on the three cohort studies included in the review, the summary estimate of the relative risk was 3.1. The results of the seven case-control studies included were heterogeneous, with odds ratios ranging from 1.2 to 7.8. The only data available from sub-Saharan Africa was from a hospitalbased study from Tanzania effect astrocytes reporting a 6.5% prevalence of diabetes among hospitalized TB patients, which was then compared to a prevalence of 0.9% found in a separate community survey.