Complete blood counts with red blood cell determinants associate with reduced beta‐cell function in seroconverted Swedish TEDDY children

Abstract

Objectives: To investigate whether changes in complete blood count (CBC) in islet autoantibody positive children with increased genetic risk for type 1 diabetes are associated with oral glucose tolerance tests (OGTT) and HbA1c over time. Methods:The Environmental Determinants of Diabetes in the Young (TEDDY) study follows children with increased risk for type 1 diabetes in the United States, Germany, Sweden and Finland. In the current study, 89 Swedish TEDDY children (median age 8.8 years) positive for one or multiple islet autoantibodies were followed up to 5 (median 2.3) years for CBC, OGTT and HbA1c. A statistical mixed effect model was used to investigate the association between CBC and OGTT or HbA1c.Results: HbA1c over time increased by the number of autoantibodies (p < .001).Reduction in mean corpuscular haemoglobin (MCH) and mean cell volume (MCV) was both associated with an increase in HbA1c (p < .001). A reduction in red blood cell (RBC) counts (p = .003), haemoglobin (p = .002) and haematocrit (p = .006) levels was associated with increased fasting glucose. Increased red blood cells, haemoglobin, haematocrit and MCH but decreased levels of red blood cell distribution widths (RDW) were all associated with increased fasting insulin. Conclusions:The decrease in RBC indices with increasing HbA1c and the decrease in RBC and its parameters with increasing fasting glucose in seroconverted children may reflect an insidious deterioration in glucose metabolism associated with islet beta-cell autoimmunity. K E Y W O R D Sautoimmunity, glucose metabolism, HbA1c, red blood cells, type 1 diabetesThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The relationship between red blood cell distribution width and islet β-cell function indexes in patients with latent autoimmune diabetes in adults

“…Therefore, it might be speculated that innate increasing of beta-cell secretion, may be an underlying factor for erythrocyte metabolism. However, unlike our study, Salami et al found decreased levels of RDW were associated with increased fasting insulin among islet autoantibody positive children with increasing risk for type 1 diabetes [ 9 ]. On the other hand, some of the patients in our study were treated with exogenous insulin which might affect erythropoiesis.…”

“…Studies pointed that an increase in RDW level has been shown to be closely related to T2DM or its complications and a marker of worsening diabetes control [ 6 – 8 ]. A reduction in counts of red blood cells and levels of haemoglobin in Swedish TEDDY children with multiple islet autoantibodies has been shown, and RDW values are significantly associated with HOMA-β and HbA1c[ 9 ].However, there are currently little clinical research on the correlation between red blood cell distribution and islet β-cell function among patients with LADA. Considering the importance of patients with LADA, the purpose of this study was to investigate the relationship between RDW and islet β-cell function in patients with LADA.…”

Genetic relations between leukocyte counts, type 1 diabetes, and coronary artery disease

“…Similar to lymphocyte counts, neutrophil count had an inverse association with T1D risk and displayed a negative genome-wide genetic correlation with T1D, albeit statistically insignificant. Clinical observations have documented reduced lymphocyte and neutrophil counts in patients with of T1D [16–19, 37]. Our findings thus suggest that these altered counts could contribute to disease.…”

“…In line with this hypothesis, clinical observations have documented altered leukocyte counts that correlate with the progression of T1D [16–19] and CAD [20]. In particular, the counts of neutrophils, which constitute the bulk of circulating leukocytes and are short-lived, requiring continuous replenishment by hematopoiesis [21], are consistently diminished in genetically at-risk individuals for T1D and in those diagnosed with the disease [16–19]. However, it is unknown whether these altered leukocyte counts causally contributes to disease and the co-occurrence of T1D and CAD, or these altered leukocyte counts are simply a consequence of disease.…”

HbA1c as a time predictive biomarker for an additional islet autoantibody and type 1 diabetes in seroconverted TEDDY children

“…This HbA1c increase is still within normoglycemic ranges detected up to years before onset. We have previously shown in autoantibody positive TEDDY children an inverse association of mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) with HbA1c, 23 indicating a decrease in iron levels generally caused by an aberrant erythropoiesis or a reduction in iron intake or absorption. 24 , 25 Thus, further research is required to clarify whether there are common factors associated with erythropoiesis and development of type 1 diabetes.…”