Genomic DNA Methylation in Diabetic Chronic Complications in Patients With Type 2 Diabetes Mellitus

Wang, Xixi; Yang, Wei; Zhu, Yunyan; Zhang, Shiyu; Jiang, Miao; Ji, Hu; Zhang, Honghong

doi:10.3389/fendo.2022.896511

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…Second, recent studies point to common pathology/pathophysiological mechanisms. For instance, a recent report shows a low level of genomic DNA methylation in DPN of type 2 diabetic patients but not in other complications of diabetes, such as diabetic retinopathy or nephropathy, indicating that a reduced level of genomic DNA methylation is a relatively specific risk factor for DPN [68]. Similarly, when investigating DNA methylation and gene expression in human sural nerve biopsies, Guo et al found that DNA methylation is a mechanism in the regulation of gene expression in DPN [69,70].…”

Section: B 12 Deficiency-induced Neuropathy and Diabetic Neuropathy S...mentioning

confidence: 99%

Clinical Pathobiochemistry of Vitamin B12 Deficiency: Improving Our Understanding by Exploring Novel Mechanisms with a Focus on Diabetic Neuropathy

et al. 2023

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Vitamin B12 (B12) is an essential cofactor of two important biochemical pathways, the degradation of methylmalonic acid and the synthesis of methionine from homocysteine. Methionine is an important donor of methyl groups for numerous biochemical reactions, including DNA synthesis and gene regulation. Besides hematological abnormalities (megaloblastic anemia or even pancytopenia), a deficiency in B12 may cause neurological symptoms, including symptoms resembling diabetic neuropathy. Although extensively studied, the underlining molecular mechanism for the development of diabetic peripheral neuropathy (DPN) is still unclear. Most studies have found a contribution of oxidative stress in the development of DPN. Detailed immunohistochemical investigations in sural nerve biopsies obtained from diabetic patients with DPN point to an activation of inflammatory pathways induced via elevated advanced glycation end products (AGE), ultimately resulting in increased oxidative stress. Similar results have been found in patients with B12 deficiency, indicating that the observed neural changes in patients with DPN might be caused by cellular B12 deficiency. Since novel results show that B12 exerts intrinsic antioxidative activity in vitro and in vivo, B12 may act as an intracellular, particularly as an intramitochondrial, antioxidant, independent from its classical, well-known cofactor function. These novel findings may provide a rationale for the use of B12 for the treatment of DPN, even in subclinical early states.

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Section: B 12 Deficiency-induced Neuropathy and Diabetic Neuropathy S...mentioning

confidence: 99%

Clinical Pathobiochemistry of Vitamin B12 Deficiency: Improving Our Understanding by Exploring Novel Mechanisms with a Focus on Diabetic Neuropathy

et al. 2023

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“…The level of DNA methylation was also altered in peripheral blood leukocytes of T2DM patients with late complications. Lower levels of genomic DNA methylation were significantly associated with the risk of diabetic polyneuropathy but were not associated with DKD or other chronic T2DM complications [ 94 ]. As shown in a recent EWAS study in an Indian population, specific methylation patterns can be used as biomarkers for stratification of T2DM patients with different clinical outcomes as they enable separating patients with good glycemic control and dyslipidemia from the other patients [ 95 ].…”

Section: Molecular Mechanisms and Molecular Genetics Of Sglt Action—p...mentioning

confidence: 99%

SGLT2 Inhibitors in the Treatment of Diabetic Kidney Disease: More than Just Glucose Regulation

Klen

Dolžan

2023

Pharmaceutics

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Diabetic kidney disease (DKD) is a severe and common complication and affects a quarter of patients with type 2 diabetes mellitus (T2DM). Oxidative stress and inflammation related to hyperglycemia are interlinked and contribute to the occurrence of DKD. It was shown that sodium–glucose cotransporter-2 (SGLT2) inhibitors, a novel yet already widely used therapy, may prevent the development of DKD and alter its natural progression. SGLT2 inhibitors induce systemic and glomerular hemodynamic changes, provide metabolic advantages, and reduce inflammatory and oxidative stress pathways. In T2DM patients, regardless of cardiovascular diseases, SGLT2 inhibitors may reduce albuminuria, progression of DKD, and doubling of serum creatinine levels, thus lowering the need for kidney replacement therapy by over 40%. The molecular mechanisms behind these beneficial effects of SGLT2 inhibitors extend beyond their glucose-lowering effects. The emerging studies are trying to explain these mechanisms at the genetic, epigenetic, transcriptomic, and proteomic levels.

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“…A recent metaanalysis of 27 studies of 5924 youths with T2D showed prevalence of diabetic retinopathy of 2% at <2.5 years diabetes duration, of 5% at 2.5–5 years duration, and of 29% at >5 years duration 14 . There is evidence of genomic factors contributing to risk of the development of complications in T2D youths 15 . Understanding this burgeoning epidemic and developing more effective therapeutic approaches will be crucial in the coming years.…”

Section: Country Cases Person‐years Cases/100000 Person‐yearsmentioning

confidence: 99%

“…14 There is evidence of genomic factors contributing to risk of the development of complications in T2D youths. 15 Understanding this burgeoning epidemic and developing more effective therapeutic approaches will be crucial in the coming years.…”

mentioning

confidence: 99%

Diabetes trends in youth

Bloomgarden

Rapaport

2023

Journal of Diabetes

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Type 2 diabetes (T2D) prevalence in the 10-to 19-year-old population has doubled over the past two decades in the United States. 1 It is present in nearly 2 persons per 1000 among Black and American Indian youth, in about 1 per 1000 among Hispanic youth, but in 0.2 per 1000 among non-Hispanic white youth, the incidence of T2D has similarly doubled among adolescents in the United States over this period, from 9 to 18 cases per 100 000 per year, with incidence again particularly high in Black and American Indian youth. 2 The incidence of type 1 diabetes (T1D) in the United States also increased, from 20 to 22 per 100 000 persons age <20 during the same period, 2 and its prevalence increased from 1.5 to 2.2 per 1000, 1 with a different racial and ethnic composition, more common in non-Hispanic white, then Black, then Hispanic, then Asian and then American Indian.

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Genomic DNA Methylation in Diabetic Chronic Complications in Patients With Type 2 Diabetes Mellitus

Cited by 7 publications

References 29 publications

Clinical Pathobiochemistry of Vitamin B12 Deficiency: Improving Our Understanding by Exploring Novel Mechanisms with a Focus on Diabetic Neuropathy

Clinical Pathobiochemistry of Vitamin B12 Deficiency: Improving Our Understanding by Exploring Novel Mechanisms with a Focus on Diabetic Neuropathy

SGLT2 Inhibitors in the Treatment of Diabetic Kidney Disease: More than Just Glucose Regulation

Diabetes trends in youth

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