Introduction
Diabetes mellitus is a group of chronic metabolic diseases characterized by hyperglycemia [
1]. Type 1 diabetes is a heterogeneous disease related to the destruction of pancreatic beta cells and is a result of absolute lack of insulin [
2]. This disease is one of the most common endocrine diseases in children and adolescents. The incidence of this disease in people under 14 years is 0.1-36.8 per 100,000 people, varying among different countries [
3]. Microvascular (retinopathy, neuropathy, and nephropathy) and macrovascular (coronary artery disease, peripheral vascular disease, and cerebrovascular disease) atherothrombotic complications may occur in children and adolescents, depending on the duration of diabetes, the degree of metabolic control, and other factors such as genetics [
4,
5]. Diabetes mellitus can cause blood disorders such as deformity of red blood cells and increase their adhesion [
6]. It has an effect on the function of red blood cells through the interaction with the membrane and intracellular components [
7]. Red blood cell distribution width (RDW) is a measure of the difference in the size of red blood cells. An increase in RDW can be caused by anemia or nutritional deficiencies related to anemia [
9]. Among the indicators of platelet morphology, mean platelet volume (MPV) is a marker associated with increased platelet activity. Platelet activity plays a key role in atherosclerosis. In type 1 and type 2 diabetes, there is an increase in activity, dysfunction and deformation of platelets, which causes clots and acute coronary events. Evidence shows that there is a positive relationship between MPV and diabetes, metabolic syndrome and acute coronary syndrome [
4,
10]. Since checking hematological changes is more accessible and cheaper than checking 3-month sugar, this study aims to review hematological changes in type 1 diabetes and investigate the type and cause of these changes and their relationship with disease prognosis.
Methods
This study is a short review, by searching related articles in Medline, PubMed, Scopus, Google Scholar databases, published from 2000 to 2023, using the keywords type 1 diabetes, hematology, white blood cells, red blood cells, blood platelets, and children. All articles were reviewed and 50 articles were finally selected for the review.
Results
Red blood cells
Studies have shown that the average number of red blood cells, hemoglobin and hematocrit in diabetic patients is lower than the control group, which indicates the presence of anemia in diabetic patients [
13,
14]. Diabetic nephropathy, decreased production of erythropoietin from the kidneys, and increased non-enzymatic glycosylation of red blood cell membrane proteins are among the factors that have been associated with the increased prevalence of anemia in diabetic patients [
15]. Hyperglycemia is related to the increase in the levels of reactive oxygen species in the red blood cells of diabetic patients and the increase in the levels of active carbonyl compounds, which affect their function and cause a decrease in life span and loss of protein function [
17]. Hyperglycemia reduces the lifespan of red blood cells and causes a decrease in the number of red blood cells and hemoglobin [
18]. Several mechanisms have been proposed for oxidative damage during hyperglycemia, including direct autoxidation of glucose and non-enzymatic glycation of proteins, which can be oxidants and cause the activation of nitric oxide synthase, xanthine oxidase, and the polyol pathway, which reduces the nicotinamide adenine dinucleotide phosphate (NADPH)/NADP ratio [
19]. Red blood cells in diabetic patients have higher malondialdehyde (MDA) values, and an increase in membrane MDA may lead to red blood cell dysfunction [
20].
The percentage of RDW is related to the reduction of red blood cell deformability. Increased RDW is associated with increased inflammation and oxidative stress status [
22]. Studies have shown that people with type 1 diabetes have higher RDW than non-diabetics [
14,
23]. Anisocytosis, large changes in cell size due to impaired erythropoiesis, red blood cell agglutination and degranulation with fragmentation occur more often in these patients [
24].
Platelets
It has been reported that MPV and PDW (platelet distribution width) are higher in children with type 1 diabetes than healthy children [
14]. In children with different durations of type 1 diabetes, platelet morphology indicators were reported to be clearly different [
25]. MPV is a direct marker of platelet function and activity [
26]. Studies have shown that people with type 1 or type 2 diabetes have higher MPV and these changes have been associated with metabolic control [
27] Hyperglycemia causes non-enzymatic glycolysis of the surface proteins of platelets, leading to a decrease in silane and an increase in platelet reactivity [
34]. It has been mentioned that the increase in lipid peroxidation and platelet activity leads to early occurrence of acute inflammatory reaction in patients with type 1 diabetes [
35]. In addition, lipid peroxidation may have an increasing effect on metabolic imbalance in diabetes, increased systemic inflammation, and the occurrence of diabetic complications. Studies have shown that the amount of PDW is clearly higher in children with type 1 diabetes than in healthy children [
38].
Leukocytes
Research has shown that patients newly diagnosed with type 1 diabetes have a clear increase in the number of leukocytes and neutrophils compared to healthy individuals [
39]. Also, a positive relationship between the increase in leukocyte and hyperglycemia has been observed. Platelet to lymphocyte ratio is an emerging inflammatory marker and is used as a predictor for diabetes and various cardiovascular diseases. This marker decreases in pre-diabetes and early stages of diabetes and increases in people having diabetes for a long period. An increase in the platelet to lymphocyte ratio is related to an increase in the inflammatory state [
42]. Examining hematological changes helps use blood cells, especially leukocytes (including lymphocytes and neutrophils), as a biomarker for oxidative stress and a diagnostic criterion for clinical evaluation in diabetes [
43]. Considering that a high number of leukocytes is related to the increase of chronic complications of diabetes, the complete blood count (CBC) test can be used as a suitable paraclinical examination to help predict the occurrence of chronic micro- and macro-vascular complications.
Conclusion
High sugar and fat are associated with increased platelet activity. Although antiplatelet therapy is generally used in diabetic patients to suppress platelet reactivity, controlling hyperglycemia with diet can be helpful. Improving blood sugar control and, as a result, the quality of life of people with diabetes, depends on proper education about treatment methods. While a high percentage of patients think that diabetes care should be done only by a doctor, recent studies have addressed the effective role of other medical staff. The effectiveness of teamwork for accurate blood sugar management has been well documented. In studies related to self-care education, a significant decrease in hemoglobin A1C (HbA1c) has been observed in children with type 1 diabetes. One of the reasons for controlling its amount was group and continuous training, along with monitoring and participation of children and their parents in educational sessions. Parents should support children with diabetes in gaining independence and self-control; these children initially do not have the ability to manage the disease and perform self-care on their own, and family support plays an effective role in facilitating it.
The occurrence of blood cell changes in children with type 1 diabetes is related to the prognosis of the disease. Since hematological tests (e.g. CBC) are available, their use can help with early detection of complications.
Ethical Considerations
Compliance with ethical guidelines
This article is a meta-analysis with no human or animal sample.
Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors.
Authors' contributions
Conceptualization, study design and resources: Bahram Darbandi and Setila Dalili; Validation, data acquisition, analysis and curation: Bahram Darbandi, Setila Dalili, Seyede Tahoura Hakemzadeh, Mercedeh Enshaei, Shahin Koohmanaee, Mohammad Hasan Mohammadi and Shohreh Maleknejad; Initial draft preparation: Seyede Tahoura Hakemzadeh and Mercedeh Enshaei; Review and editing: Seyede Tahoura Hakemzadeh, Mercedeh Enshaei, Shahin Koohmanaee, Mohammad Hasan Mohammadi,, Adel Baghersalimi. and Soodeh Salehi; Supervision: Bahram Darbandi and Setila Dalili; and Shahin Koohmanaee.
Conflicts of interest
The authors declared no conflict of interest.
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