Editorial: Obesity, metabolic phenotypes and COVID-19

Background: Desloratadine is a drug with a phenotypic polymorphism in metabolism and has been approved for use in many countries to treat allergic diseases. CYP2C8 and UGT2B10 are metabolic enzymes, which may be involved in the metabolism of desloratadine. Objective: This study aimed to demonstrate bioequivalence between the test product (desloratadine tablet) and the reference product AERIUS (5mg), both orally administered. And the role of UGT2B10 and CYP2C8 genotypes in healthy Chinese subjects with different Desloratadine metabolic phenotypes was examined. Methods: It was a randomized, open-label, and four-sequence, single-dose crossover study conducted on 56 healthy Chinese subjects. The pharmacokinetics (PK) and safety of the test and reference Desloratadine products were compared. UGT2B10 and CYP2C8 genotypes were determined by the TaqMan assay using genomic DNA. Multiple linear regression was applied to analyze the correlation between genotypes and the metabolic ratio. Results: The mean serum concentration-time curves of desloratadine and 3-OH-desloratadine were similar between the test product and the reference product. For the PK similarity comparison, the 90% CIs for the geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ of desloratadine and 3-OH-desloratadine of test and reference product were completely within 80-125%. None of all 56 subjects had serious adverse events. Only 2 subjects were poor-metabolizers in 56 healthy subjects. There was no significant correlation between investigated genotypes of CYP2C8 and UGT2B10 and the metabolic ratio. Conclusion: The test desloratadine tablet was bioequivalent to the reference product. No direct relationship between CYP2C8 and UGT2B10 genotypes and desloratadine metabolic ratio was identified.

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Impact of frailty metabolic phenotypes on the management of older people with type 2 diabetes mellitus

Geriatrics and Gerontology International ◽

10.1111/ggi.14214 ◽

2021 ◽

Author(s):

Ahmed H Abdelhafiz ◽

Demelza Emmerton ◽

Alan J Sinclair

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Older People ◽

Metabolic Phenotypes

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No association between insulin gene variation and adult metabolic phenotypes in a large Finnish birth cohort

Diabetologia ◽

10.1007/s00125-005-1737-z ◽

2005 ◽

Vol 48 (5) ◽

pp. 886-891 ◽

Cited By ~ 14

Author(s):

A. Bennett ◽

U. Sovio ◽

A. Ruokonen ◽

H. Martikainen ◽

A. Pouta ◽

...

Keyword(s):

Birth Cohort ◽

Insulin Gene ◽

Gene Variation ◽

Metabolic Phenotypes

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Correlations between Coffee Consumption and Metabolic Phenotypes, Plasma Folate, and Vitamin B12: NHANES 2003 to 2006

Nutrients ◽

10.3390/nu13041348 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1348

Author(s):

Pratibha V. Nerurkar ◽

Krupa Gandhi ◽

John J. Chen

Keyword(s):

Vitamin B12 ◽

Dietary Intervention ◽

Low Cost ◽

Coffee Consumption ◽

Normal Weight ◽

Dietary Factors ◽

Cross Sectional ◽

Metabolic Phenotypes ◽

Plasma Folate ◽

Prospective Longitudinal

Metabolic syndrome (MetS) is prevalent not only among the overweight and obese but also normal weight individuals, and the phenotype is referred to as a metabolically unhealthy phenotype (MUHP). Besides normal weight individuals, overweight/obese individuals are also protected from MetS, and the phenotype is known as a metabolically healthy phenotype (MHP). Epidemiological studies indicate that coffee and micronutrients such as plasma folate or vitamin B12 (vit. B12) are inversely associated with MetS. However, correlations among coffee consumption metabolic phenotypes, plasma folate, and vit. B12 remain unknown. Our objective was to investigate the correlation between coffee consumption, metabolic phenotypes, plasma folate, and vit. B12 as well as to understand associations between plasma folate, vit. B12, and metabolic phenotypes. Associations among coffee consumption metabolic phenotypes, plasma folate, and vit. B12 were assessed in a cross-sectional study of 2201 participants, 18 years or older, from 2003–2004 and 2005–2006 National Health and Nutrition Examination Surveys (NHANES). MUHP was classified as having > three metabolic abnormalities. Coffee consumption was not associated with metabolic phenotypes, but negatively correlated with several metabolic variables, including BMI (p < 0.001). Plasma folate was positively associated with MUHP (p < 0.004), while vit. B12 was inversely associated with MUHP (p < 0.035). Our results suggest the potential protective impact of coffee on individual components of MetS and indicate a positive correlation between coffee consumption and MUHP among overweight individuals. Identifying possible dietary factors may provide practical and low-cost dietary intervention targets, specifically for early intervention. Larger and randomized intervention studies and prospective longitudinal studies are required to further evaluate these associations.

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Genetic Deletion of Syndecan-4 Alters Body Composition, Metabolic Phenotypes, and the Function of Metabolic Tissues in Female Mice Fed A High-Fat Diet (Running Title: Sdc4 Deficiency Affects Metabolic Phenotypes)

Nutrients ◽

10.3390/nu11112810 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2810 ◽

Cited By ~ 1

Author(s):

Maria De Luca ◽

Denise Vecchie’ ◽

Baskaran Athmanathan ◽

Sreejit Gopalkrishna ◽

Jennifer A. Valcin ◽

...

Keyword(s):

Insulin Sensitivity ◽

High Fat Diet ◽

Fatty Acid Synthase ◽

Serum Triglyceride ◽

Independent Study ◽

Whole Body ◽

Elderly Subjects ◽

Sensitivity Index ◽

High Fat ◽

Metabolic Phenotypes

Syndecans are transmembrane proteoglycans that, like integrins, bind to components of the extracellular matrix. Previously, we showed significant associations of genetic variants in the Syndecan-4 (SDC4) gene with intra-abdominal fat, fasting plasma glucose levels, and insulin sensitivity index in children, and with fasting serum triglyceride levels in healthy elderly subjects. An independent study also reported a correlation between SDC4 and the risk of coronary artery disease in middle-aged patients. Here, we investigated whether deletion of Sdc4 promotes metabolic derangements associated with diet-induced obesity by feeding homozygous male and female Sdc4-deficient (Sdc4-/-) mice and their age-matched wild-type (WT) mice a high-fat diet (HFD). We found that WT and Sdc4-/- mice gained similar weight. However, while no differences were observed in males, HFD-fed female Sdc4-/- mice exhibited a higher percentage of body fat mass than controls and displayed increased levels of plasma total cholesterol, triglyceride, and glucose, as well as reduced whole-body insulin sensitivity. Additionally, they had an increased adipocyte size and macrophage infiltration in the visceral adipose tissue, and higher triglyceride and fatty acid synthase levels in the liver. Together with our previous human genetic findings, these results provide evidence of an evolutionarily conserved role of SDC4 in adiposity and its complications.

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