Associations of Circulating Lymphocyte Subpopulations with Type 2 Diabetes: Cross-Sectional Results from the Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

ObjectiveDistinct lymphocyte subpopulations have been implicated in the regulation of glucose homeostasis and obesity-associated inflammation in mouse models of insulin resistance. Information on the relationships of lymphocyte subpopulations with type 2 diabetes remain limited in human population-based cohort studies.MethodsCirculating levels of innate (γδ T, natural killer (NK)) and adaptive immune (CD4+ naive, CD4+ memory, Th1, and Th2) lymphocyte subpopulations were measured by flow cytometry in the peripheral blood of 929 free-living participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Cross-sectional relationships of lymphocyte subpopulations with type 2 diabetes (n = 154) and fasting glucose and insulin concentrations were evaluated by generalized linear models.ResultsEach standard deviation (SD) higher CD4+ memory cells was associated with a 21% higher odds of type 2 diabetes (95% CI: 1–47%) and each SD higher naive cells was associated with a 22% lower odds (95% CI: 4–36%) (adjusted for age, gender, race/ethnicity, and BMI). Among participants not using diabetes medication, higher memory and lower naive CD4+ cells were associated with higher fasting glucose concentrations (p<0.05, adjusted for age, sex, and race/ethnicity). There were no associations of γδ T, NK, Th1, or Th2 cells with type 2 diabetes, glucose, or insulin.ConclusionsA higher degree of chronic adaptive immune activation, reflected by higher memory and lower naive CD4+ cells, was positively associated with type 2 diabetes. These results are consistent with a role of chronic immune activation and exhaustion augmenting chronic inflammatory diseases, and support the importance of prospective studies evaluating adaptive immune activation and type 2 diabetes.

Natural killer cell levels in adults living with type 2 diabetes: a systematic review and meta-analysis of clinical studies

“…The 13 included studies were published in between 2008 and 2019. Additionally, the geographic distribution of the included studies comprised of Europe ( n = 6) [ 14 – 17 , 21 , 27 ], Northern America ( n = 2) [ 20 , 23 ], Africa ( n = 1) [ 24 ], and Asia ( n = 4) [ 19 , 25 , 27 , 28 ]. Two studies were longitudinal prospective studies [ 22 ] and the remaining 9 studies were cross-sectional studies [ 15 – 17 , 21 , 23 , 26 , 27 , 29 – 31 ].…”

“…In total, 13 studies fulfilled the study selection criteria and were included in the qualitative analysis [14-22, 24, 25, 27, 28, 35]. While only six studies were included in the meta-analysis [14,15,[19][20][21]35].…”

“…The characteristics of the included studies are provided in Table 1. The 13 included studies were published in [20,23], Africa (n = 1) [24], and Asia (n = 4) [19,25,27,28]. Two studies were longitudinal prospective studies [22] and the remaining 9 studies were cross-sectional studies [15-17, 21, 23, 26, 27, 29-31].…”

“…The risk of bias and quality of included studies was independently assessed by VM and TMN, using the modified Downs and Black's checklist [37]. The overall scores were graded as, excellent (24)(25)(26)(27); good (19)(20)(21)(22)(23); fair (13)(14)(15)(16)(17)(18) and poor (≤12). Overall, the included studies were rated as…”

Type 2 Diabetes Mellitus Associated with Premature Aging

“…In non-insulin-dependent diabetes mellitus (NIDDM) subjects, a report that analyzed the T-cell subsets after phytohemagglutinin stimulation by flow cytometry indicated no statistically significant differences between the subsets of CD4 + and CD8 + T-cells from peripheral blood of patients with diabetes and the healthy controls (21). Olson et al investigated whether high degree of chronic adaptive immune activation, characterized by higher memory and lower naive CD4 + T-cells, was positively associated with type 2 DM (22). It was revealed that the associations of higher memory and lower naive CD4 + Tcells with type 2 DM was consistent with the role of chronic adaptive immune activation.…”