Effect of Diet versus Gastric Bypass on Metabolic Function in Diabetes

Castagneto-Gissey, Lidia; Casella, Giovanni; Mingrone, Geltrude

doi:10.1056/nejmc2030030

Cited by 4 publications

(3 citation statements)

References 15 publications

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“…Based on the post-surgery reduction in insulin resistance and improvement in glycine metabolism, we argued that hypoglycinemia is a metabolic consequence of insulin resistance. However, some investigators have speculated that weight-independent factors also contribute to the post-bariatric surgery improvement in insulin resistance ( 51 , 52 ). We could not be sure if the increase in glycine availability after bariatric surgery played a role as insulin resistance improved contemporaneously with other factors such as weight, body composition, and dietary carbohydrate intake.…”

Section: Discussionmentioning

confidence: 99%

De Novo Glycine Synthesis Is Reduced in Adults With Morbid Obesity and Increases Following Bariatric Surgery

Tan

Hsu²,

Tai³

et al. 2022

Front. Endocrinol.

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BackgroundGlycine is a dietary non-essential amino acid that is low in obesity and increases following bariatric surgery. However, the exact mechanism responsible remains unclear and it is unknown whether hypoglycinemia is a cause or consequence of insulin resistance.ObjectiveUsing multiple isotopically labeled tracers, we aimed to determine the underlying kinetic changes responsible for hypoglycinemia in obesity by: 1) Comparing glycine kinetics between participants with morbid obesity (BMI ≥ 32.5 kg/m2) to those with healthy weight (BMI < 25 kg/m2), and 2) Comparing glycine kinetic changes in participants with morbid obesity after bariatric surgery.Methods[1,2-13C2] glycine, [2,3,3-2H3] serine, and [2H5] phenylalanine were infused to compare the glycine kinetic parameters between 21 participants with morbid obesity and 21 controls with healthy weight. Participants with morbid obesity then underwent bariatric surgery and 17 were re-studied 6 months later. Data were analyzed by non-parametric methods and presented as median (interquartile range).ResultsCompared to controls, participants with morbid obesity had significantly lower plasma glycine concentrations at 163 (153-171) vs. 201 (172-227) µmol/L and significantly reduced de novo glycine synthesis rate at 86.2 (64.5-111) vs.124 (103-159) µmol·kg LBM-1·h1, p < 0.001. Following surgery, body weight and insulin resistance decreased and this was accompanied by significant increases in plasma glycine concentration to 210 (191-243) µmol/L as well as the de novo glycine synthesis rate to 127 (98.3-133) µmol·kg LBM-1·h-1, p < 0.001 vs. baseline.ConclusionHypoglycinemia in participants with morbid obesity was associated with impaired de novo glycine synthesis. The increase in plasma glycine concentration and de novo glycine synthesis plus the marked improvement in insulin resistance after bariatric surgery suggest that hypoglycinemia may be secondary to impaired glycine synthesis because of obesity-induced insulin resistance.Clinical Trial Registration[https://tinyurl.com/6wfj7yss], identifier [NCT04660513].

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Section: Discussionmentioning

confidence: 99%

De Novo Glycine Synthesis Is Reduced in Adults With Morbid Obesity and Increases Following Bariatric Surgery

Tan

Hsu²,

Tai³

et al. 2022

Front. Endocrinol.

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“…Roux-en-Y gastric bypass, diet-induced weight loss, and increased physical activity all have beneficial effects. [46][47][48] However, these approaches are invasive and face a host of compliance-related issues, demonstrating the need for pharmacological interventions. In addition to drug therapy, for example, with GLP-1 (glucagon-like peptide-1) agonists or agents targeting inflammatory interleukins, [49][50][51][52] addressing oxylipins and KCNQ5 channels may improve outcomes further.…”

Section: Discussionmentioning

confidence: 99%

KCNQ5 Controls Perivascular Adipose Tissue–Mediated Vasodilation

Tsvetkov,

Schleifenbaum,

Wang

et al. 2024

Hypertension

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BACKGROUND: Small arteries exhibit resting tone, a partially contracted state that maintains arterial blood pressure. In arterial smooth muscle cells, potassium channels control contraction and relaxation. Perivascular adipose tissue (PVAT) has been shown to exert anticontractile effects on the blood vessels. However, the mechanisms by which PVAT signals small arteries, and their relevance remain largely unknown. We aimed to uncover key molecular components in adipose-vascular coupling. METHODS: A wide spectrum of genetic mouse models targeting Kcnq3 , Kcnq4 , and Kcnq5 genes ( Kcnq3 –/– , Kcnq4 –/– , Kcnq5 –/– , Kcnq5 dn/dn , Kcnq4 –/– / Kcnq5 dn/dn , and Kcnq4 –/– / Kcnq5 –/– ), telemetry blood pressure measurements, targeted lipidomics, RNA-Seq profiling, wire-myography, patch-clamp, and sharp-electrode membrane potential measurements was used. RESULTS: We show that PVAT causes smooth muscle cell K V 7.5 family of voltage-gated potassium (K + ) channels to hyperpolarize the membrane potential. This effect relaxes small arteries and regulates blood pressure. Oxygenation of polyunsaturated fats generates oxylipins, a superclass of lipid mediators. We identified numerous oxylipins released by PVAT, which potentiate vasodilatory action in small arteries by opening smooth muscle cell K V 7.5 family of voltage-gated potassium (K + ) channels. CONCLUSIONS: Our results reveal a key molecular function of the K V 7.5 family of voltage-gated potassium (K + ) channels in the adipose-vascular coupling, translating PVAT signals, particularly oxylipins, to the central physiological function of vasoregulation. This novel pathway opens new therapeutic perspectives.

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“… 45 Importantly, lifestyle interventions may offer all the metabolic benefits of gastric bypass with adequate calorie-restricted weight reduction. 46 Many patients with long-standing diabetes showed reversal of metabolic abnormalities and could discontinue diabetic medications following a 20% weight reduction. 40 …”

Section: Management and Outcomesmentioning

confidence: 99%

Early Recognition of Overweight Hyperglycaemia May Improve Clinical Outcomes in Type 2 Diabetes

Chockalingam¹,

Pandiyan²,

Dorairajan³

et al. 2023

European Endocrinology

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Diabetes is the ninth leading cause of death, directly accounting for 1.5 million deaths annually worldwide. Despite several breakthrough discoveries, little progress has been made in type 2 diabetes outcomes over the past 100 years. Younger age (below 60 years), a diet high in calories and processed food, and severe obesity (body mass index >35 kg/m2) may identify reversible beta cell dysfunction. Much of the clinical presentation pertains to flooding the body’s adaptive limits with overnutrition. Recognizing this as a global societal trend brought about by lifestyle changes, sedentary work, mental stress and unlimited access to calorie-dense foods is crucial. Insulin resistance and genetic abnormalities cannot account for the dramatic increase in diabetes, from only 1% five decades ago to nearly 10% today. Obesity – and not insulin resistance – is at the core of the problem. As well as hyperglycaemia, end-organ damage can also be reversed with diet and weight loss in many affected individuals. We present the evolution of our understanding and compelling reasons to reframe diabetes in the severely obese to what it really is – overweight hyperglycaemia. This may shift societal perception, governmental funding, workplace reformations and individual engagement with healthy lifestyles. The objective of this review is to better understand global trends and the potential to improve outcomes by reframing the diabetes narrative towards remission. This may shift societal perception, governmental funding, workplace reformations and individual engagement with healthy lifestyles.

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Effect of Diet versus Gastric Bypass on Metabolic Function in Diabetes

Abstract: interferon in tissue up-regulates other proteins that are toxic to endothelial cells, muscle, and the lung. The findings in the muscle-biopsy specimen from this patient suggest that his SARS-CoV-2 myopathy may also have been due to type I interferonopathy.

Cited by 4 publications

References 15 publications

De Novo Glycine Synthesis Is Reduced in Adults With Morbid Obesity and Increases Following Bariatric Surgery

De Novo Glycine Synthesis Is Reduced in Adults With Morbid Obesity and Increases Following Bariatric Surgery

KCNQ5 Controls Perivascular Adipose Tissue–Mediated Vasodilation

Early Recognition of Overweight Hyperglycaemia May Improve Clinical Outcomes in Type 2 Diabetes

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