Effect of Insulin-Like Growth Factor-1 on Diabetic Retinopathy in Pubertal Age Patients With Type 1 Diabetes

Raman, Premnath; Singal, Anuj Kumar; Behl, Anish

doi:10.1097/apo.0000000000000250

Cited by 14 publications

(9 citation statements)

References 20 publications

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“…Hepatocytes secrete IGF1 upon stimulation with insulin and growth hormone (GH) (40). T1D patients with very low or undetectable levels of insulin also exhibit reduced plasma IGF1 levels (41). Reduced serum insulin and IGF1 concentrations in STZ induced T1D mice may trigger enhanced expression of IGF1 and IGF1R on CD8 + T cells upon cognate (tumor) antigen stimulation.…”

Section: Discussionmentioning

confidence: 99%

Experimental type 1 diabetes metabolically rejuvenates CD8⁺T cells for improved control of tumor growth through an IGF1-IGF1R axis

Sarkar,

Dhar,

Bera

et al. 2024

Preprint

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Epidemiological studies suggest that patients with pre-existing type 1 diabetes (T1D) have a decreased risk of developing melanoma, prostate cancer, and breast cancer, although the underlying mechanism remains to be elucidated. In translational modelling, we observed that streptozotocin (STZ) induced T1D mice exhibited restricted melanoma and carcinoma (mammary, lung and colon) growth in association with extended overall survival. Tumor-infiltrating CD8+T cells were found to be responsible for tumor growth restriction. Tumor infiltrating CD8+T cells but not tumor cells themselves exhibited higher glycolytic and cytotoxic activities in T1D hosts. Such improved anti-tumor T cell function was linked to selective upregulated expression of insulin-like growth factor 1, insulin-like growth factor 1 receptor, and phospho-mTOR in CD8+T cells in the TME. T1D patient derived CD8+T cells displayed superior activationin vitroafter tumor antigen stimulation vs. non-diabetic CD8+T cells. Activation of T1D patient derived CD8+T cells was sensitive to targeted antagonism of IGF1R and mTOR, supporting the operational involvement of the IGF1R-mTOR signaling axis. Our results suggest that selective activation of the intrinsic IGF1R-mTOR signaling axis in CD8+T cells represents a preferred endpoint to achieving more effective immunotherapy outcomes and improved cancer patient management.SignificanceExperimental type 1 diabetes decelerates tumor growth through metabolic activation of cytotoxic T cells dependent on an IGF1R-mTOR signaling pathway. CD8+IGF1R+IGF1+T cells play a crucial role in T1D dependent tumor control.

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Section: Discussionmentioning

confidence: 99%

Experimental type 1 diabetes metabolically rejuvenates CD8⁺T cells for improved control of tumor growth through an IGF1-IGF1R axis

Sarkar,

Dhar,

Bera

et al. 2024

Preprint

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“…DR very rarely develops before 10 years of age [30] and ISPAD guidelines suggest to start screening for DR from age 11 years [31] and also individuals aged between 10 to 24 year are defined as young people [32] are the reasons behind choosing this age range.…”

Section: Discussionmentioning

confidence: 99%

Association of Vitamin D Deficiency with Diabetic Retinopathy in Young People with Type 1 Diabetes Mellitus

Sajj¹,

Zabeen²,

Khaled³

et al. 2023

OJOph

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Background: Diabetic retinopathy is among the most common diabetic complications, and is one of the leading causes of blindness in the world. Recent studies have linked vitamin D to the pathogenesis of diabetes and there is growing evidence that vitamin D can interfere with the mechanisms involved in diabetes and its complications. Despite improvements in treatment, diabetic retinopathy remains a significant complication of type 1 diabetes mellitus. Identification of early treatable predictors of diabetic retinopathy such as vitamin D deficiency, may allow more aggressive management of those at high risk. Purpose: To assess the association of vitamin D deficiency with diabetic retinopathy in young people with type 1 diabetes mellitus. Design: Observational study with case control design. Method: 60 young people with type 1 diabetes aged between 11 to 24 years were included in this study. Among them, 30-young people have diabetic retinopathy and 30-young people do not have diabetic retinopathy. Purposive sampling technique was applied as per inclusion criteria. Statistical analysis of the results was done by using computer-based software, SPSS version 26. P value of less than 0.05 was considered as statistically significant. Results: Vitamin D deficiency was present in 83% of the young people with diabetic retinopathy and in 53% without diabetic retinopathy. The mean vitamin D level in young people with and without diabetic retinopathy was 17.38 ± 3.77 ng/ml and 20.15 ± 5.06 ng/ml respectively and the difference was statistically significant (p = 0.019). Vitamin D deficiency was increased with the severity of diabetic retinopathy.

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“…The mechanism underlying decreased retinal vessel density after insulin intensification in patients with type 2 diabetes mellitus is unclear. Studies have shown [ 37 – 39 ] that insulin-like growth factor (IGF-1) can affect the function of retinal endothelial progenitor cells under hypoxia and promote retinal angiogenesis, which plays a vital role in the occurrence and development of DR and causes EWDR.…”

Section: Discussionmentioning

confidence: 99%

Effects of intensive insulin therapy on the retinal microvasculature in patients with type 2 diabetes mellitus: a prospective observational study

Yang

Peng

2022

BMC Ophthalmol

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Background We examined the retinal microvascular changes and associated factors in type 2 diabetes mellitus (T2DM) before and after intensive insulin therapy. Methods This prospective observational study recruited patients with T2DM and divided them into intensive insulin therapy and oral hypoglycemic agent groups. All patients enrolled in this study had diabetes without retinopathy or non-proliferative diabetic retinopathy. Optical coherence tomography angiography (OCTA) was used in all patients before treatment and at 1, 3, and 6 months after treatment. Vessel density (VD) and thickness changes in the macular and optic disc areas were assessed. Results The study included 36 eyes in the intensive insulin therapy group and 36 in the oral hypoglycemic agent group. One month after treatment, VD in the deep capillary plexus (DCP) and peripapillary capillary VD (ppVD) were significantly decreased by intensification (P = 0.009, 0.000). At three months after treatment, decreases in VD induced by intensification were found in the superficial capillary plexus (SCP), DCP, foveal density in a 300-μm-wide region around the foveal avascular area (FD-300), and ppVD (P = 0.032, 0.000, 0.039, 0.000). Six months after treatment, decreases in VD by intensification were observed in the DCP and ppVD groups (P = 0.000, 0.000). Vessel density showed no significant change in the oral hypoglycemic agent group after treatment. The amount of DCP-VD reduction was correlated with macular thickening (r = 0.348, P = 0.038; r = 0.693, P = 0.000 and r = 0.417, P = 0.011, respectively) after intensive insulin therapy. Conclusions Insulin-intensive treatment caused a transient reduction in vessel density in the macular and optic disc areas. DCP-VD and ppVD were more susceptible at an earlier stage. Retinal microvasculature monitoring using OCTA is vital for patients with type 2 diabetes receiving intensive insulin therapy.

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Effect of Insulin-Like Growth Factor-1 on Diabetic Retinopathy in Pubertal Age Patients With Type 1 Diabetes

Cited by 14 publications

References 20 publications

Experimental type 1 diabetes metabolically rejuvenates CD8⁺T cells for improved control of tumor growth through an IGF1-IGF1R axis

Experimental type 1 diabetes metabolically rejuvenates CD8⁺T cells for improved control of tumor growth through an IGF1-IGF1R axis

Association of Vitamin D Deficiency with Diabetic Retinopathy in Young People with Type 1 Diabetes Mellitus

Effects of intensive insulin therapy on the retinal microvasculature in patients with type 2 diabetes mellitus: a prospective observational study

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Effect of Insulin-Like Growth Factor-1 on Diabetic Retinopathy in Pubertal Age Patients With Type 1 Diabetes

Cited by 14 publications

References 20 publications

Experimental type 1 diabetes metabolically rejuvenates CD8+T cells for improved control of tumor growth through an IGF1-IGF1R axis

Experimental type 1 diabetes metabolically rejuvenates CD8+T cells for improved control of tumor growth through an IGF1-IGF1R axis

Association of Vitamin D Deficiency with Diabetic Retinopathy in Young People with Type 1 Diabetes Mellitus

Effects of intensive insulin therapy on the retinal microvasculature in patients with type 2 diabetes mellitus: a prospective observational study

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Experimental type 1 diabetes metabolically rejuvenates CD8⁺T cells for improved control of tumor growth through an IGF1-IGF1R axis

Experimental type 1 diabetes metabolically rejuvenates CD8⁺T cells for improved control of tumor growth through an IGF1-IGF1R axis