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Interaction of HSD11B1 and H6PD polymorphisms in subjects with type 2 diabetes are protective factors against obesity: a cross-sectional study.

ABSTRACT: Background:The enzyme 11-beta hydroxysteroid dehydrogenase type 1 (HSD11B1) converts inactive cortisone to active cortisol in a process mediated by the enzyme hexose-6-phosphate dehydrogenase (H6PD). The generation of cortisol from this reaction may increase intra-abdominal cortisol levels and contribute to the physiopathogenesis of obesity and metabolic syndrome (MetS). The relationship of HSD11B1 rs45487298 and H6PD rs6688832 polymorphisms with obesity and MetS was studied. We also studied how HSD11B1 abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) gene expression is related to body fat distribution. Methods:Rates of obesity and MetS features were cross-sectionally analyzed according to these polymorphisms in 1006 Brazilian white patients with type 2 diabetes (T2DM). Additionally, HSD11B1 expression was analyzed in VAT and SAT in a different cohort of 28 participants with and without obesity who underwent elective abdominal operations. Results:Although polymorphisms of the two genes were not individually associated with MetS features, a synergistic effect was observed between both. Carriers of at least three minor alleles exhibited lower BMI compared to those with two or fewer minor alleles adjusting for gender and age (27.4?±?4.9 vs. 29.3?±?5.3 kg/m2; P?=?0.005; mean?±?SD). Obesity frequency was also lower in the first group (24.4% vs. 41.6%, OR?=?0.43, 95% CI 0.21-0.87; P?=?0.019). In the second cohort of 28 subjects, HSD11B1 gene expression in VAT was inversely correlated with BMI (r?=?- 0.435, P?=?0.034), waist circumference (r?=?- 0.584, P?=?0.003) and waist-to-height ratio (r?=?- 0.526, P?=?0.010). Conclusions:These polymorphisms might interact in the protection against obesity in T2DM individuals. Obese individuals may have decreased intra-abdominal VAT HSD11B1 gene expression resulting in decreasing intra-abdominal cortisol levels as a compensatory mechanism against central and general adiposity.

SUBMITTER: Chedid MF

PROVIDER: S-EPMC6755690 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Interaction of <i>HSD11B1</i> and <i>H6PD</i> polymorphisms in subjects with type 2 diabetes are protective factors against obesity: a cross-sectional study.

Chedid Marcio F MF do Nascimento Filipe V FV de Oliveira Fernanda S FS de Souza Bianca M BM Kruel Cleber R P CRP Gurski Richard R RR Canani Luis H LH Crispim Daisy D Gerchman Fernando F

Diabetology & metabolic syndrome 20190923

<h4>Background</h4>The enzyme 11-beta hydroxysteroid dehydrogenase type 1 (HSD11B1) converts inactive cortisone to active cortisol in a process mediated by the enzyme hexose-6-phosphate dehydrogenase (H6PD). The generation of cortisol from this reaction may increase intra-abdominal cortisol levels and contribute to the physiopathogenesis of obesity and metabolic syndrome (MetS). The relationship of <i>HSD11B1</i> rs45487298 and <i>H6PD</i> rs6688832 polymorphisms with obesity and MetS was studie ...[more]

PMID: 31558916

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Project description:Obstructive sleep apnea (OSA) is a common yet underdiagnosed condition. The aim of our study is to test whether prediabetes and type 2 diabetes are associated with obstructive sleep apnea (OSA) in extremely obese (BMI ? 40 kg/m²) subjects.One hundred and thirty seven consecutive extremely obese patients (99 females) from a controlled clinical trial [MOBIL-study (Morbid Obesity treatment, Bariatric surgery versus Intensive Lifestyle intervention Study) (ClinicalTrials.gov number NCT00273104)] underwent somnography with Embletta® and a 2-hour oral glucose tolerance test (OGTT). OSA was defined by an apnea-hypopnea index (AHI) ? 5 events/hour. Patients were categorized into three groups according to criteria from the American Diabetes Association: normal glucose tolerance, pre-diabetes and type 2 diabetes. Multiple logistic regression analysis was used to identify possible determinants of OSA.The patients had a mean (SD) age of 43 (11) years and a body mass index (BMI) of 46.9 (5.7) kg/m². Males had significantly higher AHI than females, 29 (25) vs 12 (17) events/hour, p < 0.001. OSA was observed in 81% of men and in 55% of women, p = 0.008. Twenty-nine percent of subjects had normal glucose tolerance, 42% had pre-diabetes and 29% had type 2 diabetes. Among the patients with normal glucose tolerance 33% had OSA, while 67% of the pre-diabetic patients and 78% of the type 2 diabetic patients had OSA, p < 0.001. After adjusting for age, gender, BMI, high sensitive CRP and HOMA-IR, both pre-diabetes and type 2 diabetes were still associated with OSA, odds ratios 3.18 (95% CI 1.00, 10.07), p = 0.049 and 4.17 (1.09, 15.88), p = 0.036, respectively. Mean serum leptin was significantly lower in the OSA than in the non-OSA group, while other measures of inflammation did not differ significantly between groups.Type 2 diabetes and pre-diabetes are associated with OSA in extremely obese subjects.MOBIL-study (Morbid Obesity treatment, Bariatric surgery versus Intensive Lifestyle intervention Study) (ClinicalTrials.gov number NCT00273104).

Dataset Information

Interaction of HSD11B1 and H6PD polymorphisms in subjects with type 2 diabetes are protective factors against obesity: a cross-sectional study.

Publications

Interaction of <i>HSD11B1</i> and <i>H6PD</i> polymorphisms in subjects with type 2 diabetes are protective factors against obesity: a cross-sectional study.

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