Type 1 diabetes affects millions of people globally and requires careful management to avoid serious long-term complications, including heart and kidney disease, stroke, and loss of sight. The type 1 diabetes patient cohort is highly heterogeneous, with individuals presenting with disease at different stages and severities, arising from distinct etiologies, and overlaying varied genetic backgrounds. At present, the “one-size-fits-all” treatment for type 1 diabetes is exogenic insulin substitution therapy, but this approach fails to achieve optimal blood glucose control in many individuals. With advances in our understanding of early-stage diabetes development, diabetes stratification, and the role of genetics, type 1 diabetes is a promising candidate for a personalized medicine approach, which aims to apply “the right therapy at the right time, to the right patient”. In the case of type 1 diabetes, great efforts are now being focused on risk stratification for diabetes development to enable pre-clinical detection, and the application of treatments such as gene therapy, to prevent pancreatic destruction in a sub-set of patients. Alongside this, breakthroughs in stem cell therapies hold great promise for the regeneration of pancreatic tissues in some individuals. Here we review the recent initiatives in the field of personalized medicine for type 1 diabetes, including the latest discoveries in stem cell and gene therapy for the disease, and current obstacles that must be overcome before the dream of personalized medicine for all type 1 diabetes patients can be realized.
Macro- and microvascular complications of type 2 diabetes (T2D), obesity, and dyslipidemia share common metabolic pathways. Here, using a total of 1,300 metabolites from 996 Qatari adults (57% with T2D) and 1,159 metabolites from an independent cohort of 2,618 individuals from the Qatar BioBank (11% with T2D), we identified 373 metabolites associated with T2D, obesity, retinopathy, dyslipidemia and lipoprotein levels, 161 of which were novel. Novel metabolites included phospholipids, sphingolipids, lysolipids, fatty acids, dipeptides, and metabolites of the urea cycle and xanthine, steroid and glutathione metabolism. The identified metabolites enrich pathways of oxidative stress, lipotoxicity, glucotoxicity and proteolysis. Second, we identified 15 patterns we defined as “metabo-clinical signatures.” These are clusters of T2D patients that group together based on metabolite levels and reveal the same clustering in two or more clinical variables (obesity, LDL, HDL, triglycerides, retinopathy). These signatures revealed metabolic pathways associated with different clinical patterns and identified patients with extreme (very high/low) clinical variables associated with extreme metabolite levels in specific pathways. Among our novel findings are the role of N-acetylmethionine in retinopathy in conjunction with dyslipidemia and the possible roles of N-acetylvaline and pyroglutamine in association with high cholesterol levels and kidney function.
Type 1 diabetes (T1D) is an autoimmune condition where the body’s immune cells destroy their insulin-producing pancreatic beta cells leading to dysregulated glycaemia. Individuals with T1D control their blood glucose through exogenous insulin replacement therapy, often using multiple daily injections or pumps. However, failure to accurately mimic intrinsic glucose regulation results in glucose fluctuations and long-term complications impacting key organs such as the heart, kidneys, and/or the eyes. It is well established that genetic and environmental factors contribute to the initiation and progression of T1D, but recent studies show that epigenetic modifications are also important. Here, we discuss key epigenetic modifications associated with T1D pathogenesis and discuss how recent research is finding ways to harness epigenetic mechanisms to prevent, reverse, or manage T1D.
Type 1 diabetes (T1D) is an autoimmune condition where the body’s immune cells destroy their insulin-producing pancreatic beta-cells leading to dysregulated glycaemia. Individuals with T1D control their blood glucose through exogenous insulin replacement therapy, often using multiple daily injections or pumps. However, failure to accurately mimic intrinsic glucose regulation results in glucose fluctuations and long-term complications impacting key organs such as the heart, kidneys, and/or the eyes. It is well-established that genetic and environmental factors contribute to the initiation and progression of type 1 diabetes, but recent studies show that epigenetic modifications are also important. Here, we discuss key epigenetic modifications associated with type 1 diabetes pathogenesis and discuss how recent research is finding ways to harness epigenetic mechanisms to prevent, reverse, or manage type 1 diabetes.
BackgroundWaning immunity following administration of mRNA based COVID-19 vaccines remains a concern for many health systems. We undertook a study of SARS-CoV-2 infections, with and without requirement for intensive care to shed more light on the duration of vaccine effectiveness for protection against the need for intensive care.MethodsWe used a matched case-control study design with the study base being all individuals with first infection with SARS-CoV-2 reported in the State of Qatar between 1 Jan 2021 and 20 Feb 2022. Cases were those requiring intensive care while controls were those who recovered without need for intensive care. Vaccine effectiveness against requiring intensive care and number needed to vaccinate (NNV) to prevent one more case of COVID-19 requiring intensive care were computed for the mRNA (BNT162b2 / mRNA-1273) vaccines.ResultsVaccine effectiveness against requiring intensive care was 59% (95% confidence interval [CI], 50 to 76) between the first and second dose and strengthened to 89% (95% CI, 85 to 92) between the second dose and 4 months post the second dose in persons who received a primary course of the vaccine. There was no waning of vaccine effectiveness in the period from 4 to 12 months after the second dose.ConclusionsThis study demonstrates that vaccine effectiveness against requiring intensive care remains robust till at least 12 months after the second dose of mRNA based vaccines.
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