Biological Activity of c-Peptide in Microvascular Complications of Type 1 Diabetes—Time for Translational Studies or Back to the Basics?

Рык, А. А.; Łosiewicz, Aleksandra; Michalak, Arkadiusz; Fendler, Wojciech

doi:10.3390/ijms21249723

Cited by 17 publications

(12 citation statements)

References 68 publications

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“…Early clinical trials of C‐peptide supplementation showed some improvement in renal function of patients with type 1 diabetes, 65,66 but later trials reported only limited clinical benefit in terms of ameliorating microvascular disease‐induced complications (see Ryk et al. for a recent review 67 ). It is important, however, to consider the limitations of the clinical trials including the timing and duration of the treatment in relation to disease development.…”

Section: Discussionmentioning

confidence: 99%

Long‐term efficacy and safety of porcine islet macrobeads in nonimmunosuppressed diabetic cynomolgus macaques

Holdcraft

Graham

Bemrose

et al. 2022

Xenotransplantation

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Although human islet transplantation has proven to provide clinical benefits, especially the near complete amelioration of hypoglycemia, the supply of human islets is limited and insufficient to meet the needs of all people that could benefit from islet transplantation. Porcine islets, secreting insulin nearly identical to that of human insulin, have been proposed as a viable supply of unlimited islets. Further, encapsulation of the porcine islets has been shown to reduce or eliminate the use of immunosuppressive therapy that would be required to prevent rejection of the foreign islet tissue.The goal of the current study was to determine the long-term safety and efficacy of agarose encapsulated porcine islets (macrobeads) in diabetic cynomolgus macaques, in a study emulating a proposed IND trial in which daily exogenous insulin therapy would be reduced by 50% with no loss of glucose regulation. Four of six animals implanted with macrobeads demonstrated ≥ 30% reduction in insulin requirements in year 1 of follow-up. Animals were followed for 2, 3.5, and 7.4 years with no serious adverse events, mortality or evidence of pathogen transmission. This study supports the continued pursuit of encapsulated porcine islet therapy as a promising treatment option for diabetes mellitus.

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Section: Discussionmentioning

confidence: 99%

Long‐term efficacy and safety of porcine islet macrobeads in nonimmunosuppressed diabetic cynomolgus macaques

Holdcraft

Graham

Bemrose

et al. 2022

Xenotransplantation

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“…Classically chronological age, age at T1D diagnosis, duration of T1D, average systolic blood pressure and HbA 1c are associated with chronic diabetic complications, but the relation of latter with residual β-cell function has been shown heterogenous results [4][5][6][7], besides there is great evidence that C-peptide counteracts the detrimental changes causes by hyperglycemia at the cellular level in animal studies [8].…”

Section: Introductionmentioning

confidence: 99%

Residual β-cell function in Brazilian Type 1 diabetes after 3 years of diagnosis: prevalence and association with low presence of nephropathy

Gabbay

Crispim

Dib

2023

Diabetol Metab Syndr

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Background Persistence of β cell-function in Type 1 diabetes (T1D) is associated with glycaemia stability and lower prevalence of microvascular complications. We aimed to assess the prevalence of residual C- peptide secretion in long-term Brazilian childhood onset T1D receiving usual diabetes care and its association to clinical, metabolic variables and microvascular complications. Methods A cross-sectional observational study with 138 T1D adults with ≥ 3 years from the diagnosis by routine diabetes care. Clinical, metabolic variables and microvascular complications were compared between positive ultra-sensitive fasting serum C-peptide (FCP +) and negative (FCP-) participants. Results T1D studied had ≥ 3 yrs. of diagnosis and 60% had FCP > 1.15 pmol/L. FCP + T1D were older at diagnosis (10 vs 8 y.o; p = 0.03) and had less duration of diabetes (11 vs 15 y.o; p = 0.002). There was no association between the FCP + and other clinical and metabolic variable but there was inversely association with microalbuminuria (28.6% vs 13.4%, p = 0.03), regardless of HbA1c. FCP > 47 pmol/L were associated with nephropathy protection but were not related to others microvascular complications. Conclusion Residual insulin secretion is present in 60% of T1D with ≥ 3 years of diagnosis in routine diabetes care. FCP + was positively associated with age of diagnosis and negatively with duration of disease and microalbuminuria, regardless of HbA1c.

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“…Environmental factors include unhealthy diet, old age, and sedentary lifestyle, playing essential roles in T2DM progression ( Lee et al, 2000 ). As depicted by a follow-up epidemiology of diabetes intervention and complication study, patients with diabetes who underwent standard insulin therapy show persistent slight inflammation and progressive vascular complications despite the intensified therapy afterward, indicating a potential metabolic memory signature prompted by hyperglycemia ( Ryk et al, 2020 ). However, the pathogenesis of this disease is complicated by genetic and environmental factors, which need further study.…”

Section: Introductionmentioning

confidence: 99%

Epigenetics and Beyond: Targeting Histone Methylation to Treat Type 2 Diabetes Mellitus

Yang

Luan

et al. 2022

Front. Pharmacol.

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Diabetes mellitus is a global public health challenge with high morbidity. Type 2 diabetes mellitus (T2DM) accounts for 90% of the global prevalence of diabetes. T2DM is featured by a combination of defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. However, the pathogenesis of this disease is complicated by genetic and environmental factors, which needs further study. Numerous studies have demonstrated an epigenetic influence on the course of this disease via altering the expression of downstream diabetes-related proteins. Further studies in the field of epigenetics can help to elucidate the mechanisms and identify appropriate treatments. Histone methylation is defined as a common histone mark by adding a methyl group (-CH3) onto a lysine or arginine residue, which can alter the expression of downstream proteins and affect cellular processes. Thus, in tthis study will discuss types and functions of histone methylation and its role in T2DM wilsed. We will review the involvement of histone methyltransferases and histone demethylases in the progression of T2DM and analyze epigenetic-based therapies. We will also discuss the potential application of histone methylation modification as targets for the treatment of T2DM.

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Biological Activity of c-Peptide in Microvascular Complications of Type 1 Diabetes—Time for Translational Studies or Back to the Basics?

Cited by 17 publications

References 68 publications

Long‐term efficacy and safety of porcine islet macrobeads in nonimmunosuppressed diabetic cynomolgus macaques

Long‐term efficacy and safety of porcine islet macrobeads in nonimmunosuppressed diabetic cynomolgus macaques

Residual β-cell function in Brazilian Type 1 diabetes after 3 years of diagnosis: prevalence and association with low presence of nephropathy

Epigenetics and Beyond: Targeting Histone Methylation to Treat Type 2 Diabetes Mellitus

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