Expression of CD4<sup>+</sup>CD28<sup>null</sup>T lymphocytes in children and adolescents with type 1 diabetes mellitus: Relation to microvascular complications, aortic elastic properties, and carotid intima media thickness

El-Samahy, Mona H.; Tantawy, Azza Abdel Gawad; Adly, Amira Abdel Moneam; Habeeb, Nevin M.; Ismail, Eman Abdel Rahman; Hamed, Gehan Mostafa; Eladawy, Rasha

doi:10.1111/pedi.12484

Cited by 10 publications

(5 citation statements)

References 46 publications

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“…In the present study, the main alterations in T cells due to DM implicated CD28null cells, affecting both CD4+ and CD8+ compartments. These results agree with previous studies that described increased CD4+CD28null cells even in a pediatric population, correlating with the development of microalbuminuria the presence of neurologic complications [8], microvascular changes, and the progression of atherosclerotic disease [33].…”

Section: Discussionsupporting

confidence: 93%

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus

Sampani

Daikidou

Lioulios

et al. 2021

IJMS

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Background: End-stage renal disease (ESRD) is associated with alterations in T-cell immunity, including increased CD28null and reduced regulatory T cells (Tregs). However, whether immune disturbances are due to ESRD or primary disease is not yet clear. As diabetes mellitus is the leading cause of ESRD, we evaluated its impact on the immune profile of ESRD patients. Methods: CD28null, Tregs, and natural killer cells were initially analyzed by flow cytometry in 30 predialysis ESRD patients due to diabetes (DM), 30 non-DM (NDM), and 25 healthy controls. Measurements were repeated after 6 months on hemodialysis (HD) or peritoneal dialysis (CAPD). Results: The percentage of CD4 + CD28null cells, CD8 + CD28null cells, and Tregs showed significant differences in DM, NDM, and controls; mean rank 33.71 vs. 25.68 vs. 18.88, p = 0.006, 37.79 vs. 28.82 vs. 17.08, p = 0.008, and 20.79 vs. 26.12 vs. 41.33, p = 0.001, respectively. DM vs. NDM had increased CD4 + CD28null and CD8 + CD28null cells, 11.5% (1.5%–24%) vs. 4.1% (0–42.3%), p = 0.02 and 61.3% (24%–76%) vs. 43% (5.7%–85%), p = 0.04, respectively. After 6 months on HD but not CAPD, DM showed a significant further increase in CD4 + CD28null cells, from 30 (14–100) to 52.7 (15–203), p = 0.02; and CD8 + CD28null cells, from 137 (56–275) to 266 (103–456), p = 0.01. Conclusions: Diabetes mellitus affects T-cell subtypes even at predialysis stage, though changes become more prominent after commencement on HD.

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Section: Discussionsupporting

confidence: 93%

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus

Sampani

Daikidou

Lioulios

et al. 2021

IJMS

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“…Hyperglycaemia effects on microvascular and macrovascular complications are well documented in patients with type 1 diabetes (T1D) ( 9 , 10 ). Several studies demonstrated that T1D patients have higher common carotid intima-media thickness (cIMT) as compared with healthy volunteers since childhood ( 11 , 12 ). In children with T1D, especially peripheral systolic blood pressure (pSBP) and body mass index (BMI) were related to the cIMT increase over time, underlining the importance of lifestyle and cardiovascular risk factors control ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Central Systolic Blood Pressure Is Associated With Early Vascular Damage in Children and Adolescents With Type 1 Diabetes

Tagetti

Piona

Marcon

et al. 2021

Front. Cardiovasc. Med.

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Objective of the study: This study aimed to test the effect of multiple cardiovascular risk factors on subclinical indices of atherosclerosis in children and adolescents with type 1 diabetes (T1D).Methods: Carotid intima-media thickness (cIMT), carotid distensibility coefficient (cDC), and carotid–femoral pulse wave velocity (PWV) were measured in children and adolescents with T1D, in a follow-up at the outpatient clinics of Verona. Blood pressure (BP; both central and peripheral), metabolic and other cardiovascular risk factors were evaluated in multivariate linear regressions to assess the association with the measured indices of subclinical vascular damage.Results: One hundred and twenty-six children and adolescents were included. cIMT was above the 95th percentile for age and height in 60.8% of the population, whereas 26% of the sample had cDC impairment (less than the 5th percentile) and 4.8% had an elevated PWV. Independent determinants of cIMT according to the regression models were only gender type of glucose monitoring and central systolic BP (cSBP). PWV was associated with age, sex, heart rate, and cSBP; cDC with age and both cSBP and, alternatively, peripheral BP (pBP). Neither pBP nor any of the tested metabolic parameters, including glycated hemoglobin, was associated with PWV and cIMT.Conclusions: A high proportion of early vascular damage, especially an increased cIMT, is present in children and adolescents with T1D in whom cSBP seems to be a common determinant. In children and adolescents with T1DM, a special focus should be on hemodynamic risk factors beyond metabolic ones.

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“…Some studies focused on hyperglycemia’s role as a major determinant for DSPN in T1DM [ 32 ], by demonstrating that prolonged hyperglycemia may lead to nerve damage by raising reactive oxygen species (ROS) concentration and oxidative stress [ 33 , 34 ], and enhancing the production of advanced glycation end products [ 35 , 36 ]. Other studies focused on the role of chronic inflammation leading to DSPN [ 37 ], some of them underlining the importance of activation of the TNF-alpha system [ 24 , 38 ] and the enhanced expression of pro-inflammatory cells, possibly influenced by persistent poor glycemic control [ 39 ]. Endothelial dysfunction, caused by chronic inflammation, has also been identified as a cornerstone in the development of diabetic complications, including DSPN [ 18 , 40 , 41 ].…”

Section: Pathophysiologymentioning

confidence: 99%

Redefining distal symmetrical polyneuropathy features in type 1 diabetes: a systematic review

Galosi

Michael

et al. 2021

Acta Diabetol

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Diabetic neuropathy is among the most frequent complications of both type 1 (T1DM) and type 2 diabetes (T2DM) and commonly manifests as a distal symmetrical polyneuropathy (DSPN). Despite evidence that T1DM- and T2DM-related DSPN are separate entities, most of our knowledge on diabetic DSPN derives from studies focused on type 2 diabetes. This systematic review provides an overview of current evidence on DSPN in T1DM, including its epidemiological, pathophysiological and clinical features, along with principal diagnostic tests findings. This review included 182 clinical and preclinical studies. The results indicate that DSPN is a less frequent complication in T1DM compared with T2DM and that distinctive pathophysiological mechanisms underlie T1DM-related DSPN development, with hyperglycemia as a major determinant. T1DM-related DSPN more frequently manifests with non-painful than painful symptoms, with lower neuropathic pain prevalence compared with T2DM-associated DSPN. The overt clinical picture seems characterized by a higher prevalence of large fiber-related clinical signs (e.g., ankle reflexes reduction and vibration hypoesthesia) and to a lesser extent small fiber damage (e.g., thermal or pinprick hypoesthesia). These findings as a whole suggest that large fibers impairment plays a dominant role in the clinical picture of symptomatic T1DM-related DSPN. Nevertheless, small fiber diagnostic testing shows high diagnostic accuracy in detecting early nerve damage and may be an appropriate diagnostic tool for disease monitoring and screening.

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Expression of CD4⁺CD28^nullT lymphocytes in children and adolescents with type 1 diabetes mellitus: Relation to microvascular complications, aortic elastic properties, and carotid intima media thickness

Cited by 10 publications

References 46 publications

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus

Central Systolic Blood Pressure Is Associated With Early Vascular Damage in Children and Adolescents With Type 1 Diabetes

Redefining distal symmetrical polyneuropathy features in type 1 diabetes: a systematic review

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Expression of CD4+CD28nullT lymphocytes in children and adolescents with type 1 diabetes mellitus: Relation to microvascular complications, aortic elastic properties, and carotid intima media thickness

Cited by 10 publications

References 46 publications

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus

Central Systolic Blood Pressure Is Associated With Early Vascular Damage in Children and Adolescents With Type 1 Diabetes

Redefining distal symmetrical polyneuropathy features in type 1 diabetes: a systematic review

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Expression of CD4⁺CD28^nullT lymphocytes in children and adolescents with type 1 diabetes mellitus: Relation to microvascular complications, aortic elastic properties, and carotid intima media thickness