Effect of metformin on plasma metabolite profile in the Copenhagen Insulin and Metformin Therapy (<scp>CIMT</scp>) trial

Safai, Narges; Suvitaival, Tommi; Ali, Ashfaq; Sartipy, Peter; Al-Majdoub, Mahmoud; Carstensen, Bendix; Vestergaard, Henrik; Ridderstråle, Martin

doi:10.1111/dme.13636

Cited by 24 publications

(29 citation statements)

References 32 publications

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“…In summary, we identified dynamic alterations in plasma metabolite concentrations 3 months after LSG in 15 morbidly obese Japanese patients. Although food intake and the changes of medication might affect the plasma metabolite concentrations 28,29 , the present results support LSG as an effective therapeutic strategy for treating obesity not only as a weight loss surgery, but also as a metabolomic intervention 30 . The present findings have the potential to show how LSG ameliorates obesity and present novel therapeutic targets for treating obesity.…”

Section: Discussionsupporting

confidence: 55%

Metabolic alterations in plasma after laparoscopic sleeve gastrectomy

Yoshida

Kitahama

Yamashita

et al. 2020

J of Diabetes Invest

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Laparoscopic sleeve gastrectomy (LSG) is an important therapeutic option for morbidly obese patients. Although LSG promotes sufficient weight loss, how LSG changes plasma metabolites remains unclear. We assessed changes in plasma metabolite levels after LSG. We collected plasma samples from 15 morbidly obese Japanese patients before and 3 months after LSG. A total of 48 metabolites were quantified using capillary electrophoresis time-of-flight mass spectrometry-based metabolomic profiling. Branched chain amino acids, several essential amino acids, choline, 2-hydroxybutyric acid, 2-oxoisovaleric acid and hypoxanthine were significantly decreased after LSG. Tricarboxylic acid cycle metabolites, including citric acid, succinic acid and malic acid, were significantly elevated after LSG. This is the first report to show dynamic alterations in plasma metabolite concentrations, as assessed using capillary electrophoresis time-of-flight mass spectrometry, in morbidly obese patients after LSG. Our results might show how LSG helps improve obesity, in part through metabolic status changes, and propose novel therapeutic targets to ameliorate obesity.

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Section: Discussionsupporting

confidence: 55%

Metabolic alterations in plasma after laparoscopic sleeve gastrectomy

Yoshida

Kitahama

Yamashita

et al. 2020

J of Diabetes Invest

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“…In addition to alterations in lipid and glucose metabolism, there was also evidence of disturbances in some amino acids; levels of two BCAAs, isoleucine and leucine, as well as phenylalanine were higher in women with GDM. Other studies have reported increases in BCAAs and also other amino acids, such as alanine (28) and leucine (7), or decreases in, for example, L‐valine (29) in women with GDM at the time of OGTT. Furthermore, higher levels of leucine and isoleucine have been reported in association with obesity in nonpregnant and pregnant participants (30‐32).…”

Section: Discussionmentioning

confidence: 99%

“…The extent to which GDM per se and its treatment by diet compared with pharmaceutical treatment is related to the metabolic profile is currently poorly understood. In patients with type 2 diabetes, metformin treatment was associated with lower levels of valine and carnitine and higher levels of lysophosphatidylethanolamines as well as elevated concentrations of leucine and isoleucine (7). Another study conducted in participants with coronary disease revealed a decrease in tyrosine and an increase in alanine in patients treated with metformin (8).…”

Section: Introductionmentioning

confidence: 99%

Distinct Metabolomic Profile Because of Gestational Diabetes and its Treatment Mode in Women with Overweight and Obesity

Mokkala

Vahlberg

Houttu

et al. 2020

Obesity

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Objective Whether the presence of gestational diabetes (GDM) and its treatment mode influence the serum metabolic profile in women with overweight or obesity was studied. Methods The serum metabolic profiles of 352 women with overweight or obesity participating in a mother‐infant clinical study were analyzed with a targeted NMR approach (at 35.1 median gestational weeks). GDM was diagnosed with a 2‐hour 75‐g oral glucose tolerance test. Results The metabolomic profile of the women with GDM (n = 100) deviated from that of women without GDM (n = 252). Differences were seen in 70 lipid variables, particularly higher concentrations of very low‐density lipoprotein particles and serum triglycerides were related to GDM. Furthermore, levels of branched‐chain amino acids and glycoprotein acetylation, a marker of low‐grade inflammation, were higher in women with GDM. Compared with women with GDM treated with diet only, the women treated with medication (n = 19) had higher concentrations of severalizes of VLDL particles and their components, leucine, and isoleucine, as well as glycoprotein acetylation. Conclusions A clearly distinct metabolic profile was detected in GDM, which deviated even more if the patient was receiving medical treatment. This suggests a need for more intense follow‐up and therapy for women with GDM during pregnancy and postpartum to reduce their long‐term adverse health risks.

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“…Recently, several metabolomic techniques were applied to the identification of metabolic signatures associated with T2DM [10,11,12,13,14,15,16,17]. Data in this research field were extensive, revealing new diagnostic/prognostic disease biomarkers [14], or metabolic markers of response to targeted therapies [15,16]. Metabolomics also provided tools for patient’s stratification and recognizable metabolic patterns associated with organ dysfunction [17].…”

Section: Introductionmentioning

confidence: 99%

NMR-Based Metabolomic Approach Tracks Potential Serum Biomarkers of Disease Progression in Patients with Type 2 Diabetes Mellitus

Coco

Vergara

Matteis

et al. 2019

JCM

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Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia associated with alterations in carbohydrate, lipid, and protein metabolism. The prognosis of T2DM patients is highly dependent on the development of complications, and therefore the identification of biomarkers of T2DM progression, with minimally invasive techniques, is a huge need. In the present study, we applied a 1H-Nuclear Magnetic Resonance (1H-NMR)-based metabolomic approach coupled with multivariate data analysis to identify serum metabolite profiles associated with T2DM development and progression. To perform this, we compared the serum metabolome of non-diabetic subjects, treatment-naïve non-complicated T2DM patients, and T2DM patients with complications in insulin monotherapy. Our analysis revealed a significant reduction of alanine, glutamine, glutamate, leucine, lysine, methionine, tyrosine, and phenylalanine in T2DM patients with respect to non-diabetic subjects. Moreover, isoleucine, leucine, lysine, tyrosine, and valine levels distinguished complicated patients from patients without complications. Overall, the metabolic pathway analysis suggested that branched-chain amino acid (BCAA) metabolism is significantly compromised in T2DM patients with complications, while perturbation in the metabolism of gluconeogenic amino acids other than BCAAs characterizes both early and advanced T2DM stages. In conclusion, we identified a metabolic serum signature associated with T2DM stages. These data could be integrated with clinical characteristics to build a composite T2DM/complications risk score to be validated in a prospective cohort.

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Effect of metformin on plasma metabolite profile in the Copenhagen Insulin and Metformin Therapy (CIMT) trial

Cited by 24 publications

References 32 publications

Metabolic alterations in plasma after laparoscopic sleeve gastrectomy

Metabolic alterations in plasma after laparoscopic sleeve gastrectomy

Distinct Metabolomic Profile Because of Gestational Diabetes and its Treatment Mode in Women with Overweight and Obesity

NMR-Based Metabolomic Approach Tracks Potential Serum Biomarkers of Disease Progression in Patients with Type 2 Diabetes Mellitus

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