Differential Role of Type 2 Diabetes as a Risk Factor for Tuberculosis in the Elderly versus Younger Adults

Abstract

The elderly are understudied despite their high risk of tuberculosis (TB). We sought to identify factors underlying the lack of an association between TB and type 2 diabetes (T2D) in the elderly, but not adults. We conducted a case–control study in elderly (≥65 years old; ELD) vs. younger adults (young/middle-aged adults (18–44/45–64 years old; YA|MAA) stratified by TB and T2D, using a research study population (n = 1160) and TB surveillance data (n = 8783). In the research study population the adjusted odds ratio (AOR) of TB in T2D was highest in young adults (AOR 6.48) but waned with age becoming non-significant in the elderly. Findings were validated using TB surveillance data. T2D in the elderly (vs. T2D in younger individuals) was characterized by better glucose control (e.g., lower hyperglycemia or HbA1c), lower insulin resistance, more sulphonylureas use, and features of less inflammation (e.g., lower obesity, neutrophils, platelets, anti-inflammatory use). We posit that differences underlying glucose dysregulation and inflammation in elderly vs. younger adults with T2D, contribute to their differential association with TB. Studies in the elderly provide valuable insights into TB-T2D pathogenesis, e.g., here we identified insulin resistance as a novel candidate mechanism by which T2D may increase active TB risk.

Tuberculosis presentation and outcomes in older Hispanic adults from Tamaulipas, Mexico

“…[3,14] This contrasts with fewer studies in Hispanics. [15][16][17] We have begun addressing this gap among Hispanics in the Texas-Mexico border. Secondary analysis of TB surveillance data from Mexico suggests that OA comprise about 10% of all adult TB patients, [18] and our prospective studies are revealing unique features of TB pathogenesis in OA (e.g., diabetes, Bacille Calmette-Guiren [BCG] vaccination).…”

“…Secondary analysis of TB surveillance data from Mexico suggests that OA comprise about 10% of all adult TB patients, [18] and our prospective studies are revealing unique features of TB pathogenesis in OA (e.g., diabetes, Bacille Calmette-Guiren [BCG] vaccination). [16,17,19] Thus, further studies in older Latin American Hispanics are warranted given that risk factors for TB such as poverty, migration, homelessness, incarceration, and diabetes have increased in this region in the last decade. [20,21] Given the impact of older age on TB elimination efforts, it is important to study the older adult TB group with the goals of improving patient outcomes and preventing additional TB cases.…”

Tuberculosis presentation and outcomes in elderly Hispanics from Tamaulipas, Mexico

“…The prevalence of type 2 diabetes increases with age, as observed in our TB cohort [35, 36]. Diabetes is a risk for TB in adults, this includes findings using prospective or retrospective cohorts from Hispanics in US and Mexican communities [18, 37, 38] but not in older people [13, 14]. We posit that differences between diabetes in younger versus older adults may be explained by differences in the pathophysiology and/or the management of type 2 diabetes [13].…”

“…Diabetes is a risk for TB in adults, this includes findings using prospective or retrospective cohorts from Hispanics in US and Mexican communities [18, 37, 38] but not in older people [13, 14]. We posit that differences between diabetes in younger versus older adults may be explained by differences in the pathophysiology and/or the management of type 2 diabetes [13]. While diabetes in the elderly may not be a risk factor for TB development, in the present study, we evaluated if it would be associated with higher odds of death.…”

“…Despite their high vulnerability, TB in the elderly is understudied, and the available literature is mostly from Asian populations, with few in Hispanics [12][13][14]. Studies in Latin American Hispanics are warranted given that risk factors for TB such as poverty, migration, homelessness, incarceration, and diabetes have increased in the last decade [15,16].…”