Cardiovascular disease in diabetes, beyond glucose

Eckel, Robert H.; Bornfeldt, Karin E.; Goldberg, Ira J.

doi:10.1016/j.cmet.2021.07.001

Cited by 101 publications

(85 citation statements)

References 336 publications

(290 reference statements)

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“…Although diabetic patients are characterized by hyperglycemia, a recent study has shown that renormalization of blood glucose has a mild impact on the progression of diabetic complications [ 1 , 2 ], suggesting the role of additional mechanistic factors in the development of diabetic complications. One such factor could be methylglyoxal (MG).…”

Section: Introductionmentioning

confidence: 99%

The activity of glyoxylase 1 is regulated by glucose-responsive phosphorylation on Tyr136

Cortizo

Pfaff

Wirth

et al. 2022

Molecular Metabolism

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Objective Methylglyoxal (MG) is a highly reactive α-oxoaldehyde that glycates proteins. MG has been linked to the development of diabetic complications: MG is the major precursor of advanced glycation end products (AGEs), a risk marker for diabetic complications in humans. Furthermore, flies and fish with elevated MG develop insulin resistance, obesity, and hyperglycemia. MG is detoxified in large part through the glyoxalase system, whose rate-limiting enzyme is glyoxalase I (Glo1). Hence, we aimed to study how Glo1 activity is regulated. Methods We studied the regulation and effect of post-translational modifications of Glo1 in tissue culture and in mouse models of diabetes. Results We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. We find that Glo1 Y136 phosphorylation responds in a bimodal fashion to glucose levels, increasing in cell culture from 0 mM to 5 mM (physiological) glucose, and then decreasing at higher glucose concentrations, both in cell culture and in mouse models of hyperglycemia. Conclusions These data, together with published findings that elevated MG leads to hyperglycemia, suggest the existence of a deleterious positive feedback loop whereby hyperglycemia leads to reduced Glo1 activity, contributing to elevated MG levels, which in turn promote hyperglycemia. Hence, perturbations elevating either glucose or MG have the potential to start an auto-amplifying feedback loop contributing to diabetic complications.

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Section: Introductionmentioning

confidence: 99%

The activity of glyoxylase 1 is regulated by glucose-responsive phosphorylation on Tyr136

Cortizo

Pfaff

Wirth

et al. 2022

Molecular Metabolism

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“…Hyperglycemia and hyperlipidemia commonly coexist in patients with T2D, and both are main risk factors for ASCVDs events. 56 Statins, the current main hypolipidemia medication to reduce major adverse cardiovascular events (MACEs) in T2D patients, 3 exhibits unfavorable effects, such as increasing intestinal cholesterol absorption, blood glucose level and diabetes incidence, as well as the hepatoxicity and myotoxicity. These side effects (SE) have brought concerns to the clinical practice , 57 , 58 particularly in East Asia population, including the Chinese, who is more susceptible to the SEs of statins.…”

Section: Discussionmentioning

confidence: 99%

Combined berberine and probiotic treatment as an effective regimen for improving postprandial hyperlipidemia in type 2 diabetes patients: a double blinded placebo controlled randomized study

et al. 2021

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Non-fasting lipidemia (nFL), mainly contributed by postprandial lipidemia (PL), has recently been recognized as an important cardiovascular disease (CVD) risk as fasting lipidemia (FL). PL serves as a common feature of dyslipidemia in Type 2 Diabetes (T2D), albeit effective therapies targeting on PL were limited. In this study, we aimed to evaluate whether the therapy combining probiotics (Prob) and berberine (BBR), a proven antidiabetic and hypolipidemic regimen via altering gut microbiome, could effectively reduce PL in T2D and to explore the underlying mechanism. Blood PL (120 min after taking 100 g standard carbohydrate meal) was examined in 365 participants with T2D from the Probiotics and BBR on the Efficacy and Change of Gut Microbiota in Patients with Newly Diagnosed Type 2 Diabetes (PREMOTE study), a random, placebo-controlled, and multicenter clinical trial. Prob+BBR was superior to BBR or Prob alone in improving postprandial total cholesterol (pTC) and low-density lipoprotein cholesterol (pLDLc) levels with decrement of multiple species of postprandial lipidomic metabolites after 3 months follow-up. This effect was linked to the changes of fecal Bifidobacterium breve level responding to BBR alone or Prob+BBR treatment. Four fadD genes encoding long-chain acyl-CoA synthetase were identified in the genome of this B. breve strain, and transcriptionally activated by BBR. In vitro BBR treatment further decreased the concentration of FFA in the culture medium of B. breve compared to vehicle. Thus, the activation of fadD by BBR could enhance FFA import and mobilization in B. breve and diliminish the intraluminal lipids for absorption to mediate the effect of Prob+BBR on PL. Our study confirmed that BBR and Prob ( B. breve ) could exert a synergistic hypolipidemic effect on PL, acting as a gut lipid sink to achieve better lipidemia and CVD risk control in T2D.

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“…Diabetes is a global public health problem that affects human physical and mental health, and it is also an independent risk factor for major diseases such as kidney failure, cardiovascular disease, and stroke. [ 12 , 13 ] Although many new drugs for the treatment of T2DM, such as glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, have been successfully developed, researchers are looking for better blood-glucose-lowering treatment programs. Controlling glucose levels and reducing complications from T2DM involves continual disease management.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of acupuncture combined with Chinese herbal medicine in the treatment of type 2 diabetes mellitus

Bao

et al. 2021

Medicine

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Background: Diabetes has become a global public health problem and danger to human health. Diabetes is the main cause of blindness, kidney failure, heart attack, stroke, and lower limb amputation. According to the latest epidemiological survey and research, the overall prevalence of diabetes in mainland China is 11.2%, of which type 2 diabetes mellitus (T2DM) accounts for more than 90% acupuncture combined with Chinese herbal medicine have been widely used in the treatment of T2DM. However, we have not found a meta-analysis of their synergistic effects. Therefore, this systematic review and meta-analysis aims to evaluate the efficacy and safety of acupuncture combined with Chinese herbal medicine in the treatment of T2DM.Method: From inception up to September 20, 2021, the PubMed, Web of Science, Embase, AMED, Cochrane Library, CNKI, VIP, CBM, and Wanfang databases will be searched. The publication date or language will not be limited. We will apply a combination of medical keywords, including "acupuncture", "Chinese herbal medicine", and "type 2 diabetes mellitus". We will also check other ongoing and unpublished studies in the clinical trial registry. At the same time, we will manually search all reference lists from relevant systematic reviews to find other eligible studies. We will use Review Manager software (REVMAN v5.3 Cochrane Collaboration) to meta-analyze the selected literature. The study for acupuncture combined with Chinese herbal medicine in the treatment of T2DM was a randomized controlled study. Two researchers will independently review the research selection, data extraction, and research quality assessments. Finally, we will observe the outcome measures.Results: This study will generate evidence-based data on the treatment of T2DM with acupuncture combined with Chinese herbal medicine and will provide new ideas and treatment modalities to investigate in future research.

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Cardiovascular disease in diabetes, beyond glucose

Cited by 101 publications

References 336 publications

The activity of glyoxylase 1 is regulated by glucose-responsive phosphorylation on Tyr136

The activity of glyoxylase 1 is regulated by glucose-responsive phosphorylation on Tyr136

Combined berberine and probiotic treatment as an effective regimen for improving postprandial hyperlipidemia in type 2 diabetes patients: a double blinded placebo controlled randomized study

Efficacy and safety of acupuncture combined with Chinese herbal medicine in the treatment of type 2 diabetes mellitus

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