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A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Endocrinology".

Deadline for manuscript submissions: closed (30 May 2022) | Viewed by 37235

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Dr. Rocío Barragán

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1. Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain
2. CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain
3. Sleep Center of Excellence, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA
4. Division of General Medicine, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA
Interests: obesity; cardiovascular disease; mediterranean diet; nutrigenetic; nutrigenomic; sleep deprivation; circadian rhythms; taste perception; aging
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Prof. Dr. Dolores Corella

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Co-Guest Editor

1. Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain
2. CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain
Interests: precision nutrition; omics; Mediterranean diet; lifestyle; cardiovascular disease; obesity; nutrigenomics; epigenomics; metabolomics; transcriptomic; gene–diet interaction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The prevalence of diabetes has risen dramatically for decades, being one of the most important health problems in modern society. According to the World Health Organization, 422 million people worldwide have diabetes and 1.6 million deaths are directly attributed to diabetes each year. The presence of diabetes could lead serious long-term complications, such as cardiovascular disease, diabetic retinopathy, or kidney failure. Thus, early detection should be a priority in public health. The current obesogenic environment, favoring non-healthy food intake, physical inactivity, and circadian misalignment (a mismatch between endogenous circadian rhythms and behavior) is a major driver of the growing diabetes epidemic. In addition, genetic variants in specific genes exhibit significant associations with diabetes, although the underlying mechanisms have not been fully elucidated. With these premises, the need arises for more exhaustive approaches focused on the study of lifestyle factors—mainly diet, physical activity, or sleep patterns—or genetic factors in diabetes, as well as the interaction between both to rigorously predict the risk of developing diabetes and optimize its treatment once diagnosed.

Dr. Rocío Barragán
Prof. Dr. Dolores Corella
Guest Editors

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Keywords

diabetes
diet
sleep
polymorphism
gene-diet interaction
circadian misalignment
physical activity
glucose

Published Papers (9 papers)

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Research

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10 pages, 568 KiB

Open AccessArticle

Influence of DNA-Polymorphisms in Selected Circadian Clock Genes on Clock Gene Expression in Subjects from the General Population and Their Association with Sleep Duration

by Rocío Barragán, José V. Sorlí, Oscar Coltell, Inmaculada Gonzalez-Monje, Rebeca Fernández-Carrión, Laura V. Villamil, Olga Portolés, Dolores Corella, Carolina Ortega-Azorín and Eva M. Asensio

Medicina 2022, 58(9), 1294; https://doi.org/10.3390/medicina58091294 - 16 Sep 2022

Cited by 1 | Viewed by 1703

Abstract

Background and Objectives: Circadian rhythms have an important implication in numerous physiological and metabolic processes, including the sleep/wake cycle. Inter-individual differences in factors associated with circadian system may be due to gene differences in gene expression. Although several studies have analyzed the association between DNA polymorphisms and circadian variables, the influence on gene expression has been poorly analyzed. Our goal was to analyze the association of genetic variations in the clock genes and the gene expression level. Materials and Methods: We carried out a cross-sectional study of 102 adults (50.9% women). RNA and DNA were isolated from blood and single-nucleotide polymorphisms (SNPs), and the main circadian clock genes were determined. Gene expression of CLOCK, PER1, and VRK2 genes was measured by Reverse-transcription polymerase chain reaction (RT-PCR). The association between the DNA-SNPs and gene expression was analyzed at the gene level. In addition, a polygenic risk score (PRS), including all the significant SNPs related to gene expression, was created for each gene. Multivariable model analysis was performed. Results: Sex-specific differences were detected in PER1 expression, with these being higher in women (p = 0.034). No significant differences were detected in clock genes expression and lifestyle variables. We observed a significant association between the ARNTL-rs7924734, ARNTL-rs10832027, VRK2- rs2678902 SNPs, and CLOCK gene expression; the PER3-rs228642 and PER3-rs10127838 were related to PER1 expression, and the ARNTL-rs10832027, ARNTL-rs11022778, and MNTR1B-rs10830963 were associated with VRK2 gene expression (p < 0.05). The specific PRS created was significantly associated with each of the gene expressions analyzed (p < 0.001). Finally, sleep duration was associated with PER3-rs238666 (p = 0.008) and CLOCK-rs4580704 (p = 0.023). Conclusion: We detected significant associations between DNA-SNPs in the clock genes and their gene expression level in leukocytes and observed some differences in gene expression per sex. Moreover, we reported for the first time an association between clock gene polymorphisms and CLOCK, PER1, and VRK2 gene expression. These findings need further investigation. Full article

(This article belongs to the Special Issue Diabetes, Lifestyle and Genetics)

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21 pages, 1112 KiB

Open AccessArticle

Association between Microbiome-Related Human Genetic Variants and Fasting Plasma Glucose in a High-Cardiovascular-Risk Mediterranean Population

by Eva M. Asensio, Carolina Ortega-Azorín, Rocío Barragán, Andrea Alvarez-Sala, José V. Sorlí, Eva C. Pascual, Rebeca Fernández-Carrión, Laura V. Villamil, Dolores Corella and Oscar Coltell

Medicina 2022, 58(9), 1238; https://doi.org/10.3390/medicina58091238 - 07 Sep 2022

Cited by 1 | Viewed by 4137

Abstract

Background and Objectives: The gut microbiota has been increasingly recognized as a relevant factor associated with metabolic diseases. However, directly measuring the microbiota composition is a limiting factor for several studies. Therefore, using genetic variables as proxies for the microbiota composition is an important issue. Landmark microbiome–host genome-wide association studies (mbGWAS) have identified many SNPs associated with gut microbiota. Our aim was to analyze the association between relevant microbiome-related genetic variants (Mi-RSNPs) and fasting glucose and type 2 diabetes in a Mediterranean population, exploring the interaction with Mediterranean diet adherence. Materials and Methods: We performed a cross-sectional study in a high-cardiovascular-risk Mediterranean population (n = 1020), analyzing the association of Mi-RSNPs (from four published mbGWAS) with fasting glucose and type 2 diabetes. A single-variant approach was used for fitting fasting glucose and type 2 diabetes to a multivariable regression model. In addition, a Mendelian randomization analysis with multiple variants was performed as a sub-study. Results: We obtained several associations between Mi-RSNPs and fasting plasma glucose involving gut Gammaproteobacteria_HB, the order Rhizobiales, the genus Rumminococcus torques group, and the genus Tyzzerella as the top ranked. For type 2 diabetes, we also detected significant associations with Mi-RSNPs related to the order Rhizobiales, the family Desulfovibrionaceae, and the genus Romboutsia. In addition, some Mi-RSNPs and adherence to Mediterranean diet interactions were detected. Lastly, the formal Mendelian randomization analysis suggested combined effects. Conclusions: Although the use of Mi-RSNPs as proxies of the microbiome is still in its infancy, and although this is the first study analyzing such associations with fasting plasma glucose and type 2 diabetes in a Mediterranean population, some interesting associations, as well as modulations, with adherence to the Mediterranean diet were detected in these high-cardiovascular-risk subjects, eliciting new hypotheses. Full article

(This article belongs to the Special Issue Diabetes, Lifestyle and Genetics)

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8 pages, 802 KiB

Open AccessArticle

Does the SDMQ-9 Predict Changes in HbA1c Levels? An Ecuadorian Cohort

by María José Farfán Bajaña, Jorge Moncayo-Rizzo, Geovanny Alvarado-Villa and Victor J. Avila-Quintero

Medicina 2022, 58(3), 380; https://doi.org/10.3390/medicina58030380 - 04 Mar 2022

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Abstract

Background and Objectives: Diabetes mellitus affects 422 million people around the world, positioning it as a major health problem. According to the WHO(World Health Organization), 90% corresponds to type 2. The shared-decision making (SDM) is a method used to facilitate patient control, medication, maintenance, and assessment of health status according to their priorities and preferences. With the application of SDM in patients with diabetes, it is expected there will be an increase in treatment adherence and a reduction in HbA1c levels. The aim of this study is to determine the predictors of the change in HbA1c. Material and Methods: A sample of 76 participants attending as endocrinology outpatients was obtained. Data collected within the sample included: sex, age, educational level, body mass index, and the level of SDM using the SDMQ-9. In addition, HbA1c levels were measured twice: at baseline and three months after the first measurement. Results: The linear regression indicates that the level of SDM is a significant predictor of the change in HbA1c, specifically in men. However, the direction of the relationship was a somewhat opposite trend than we expected. Higher levels of SDM imply an increase in HbA1c rather than a reduction. Conclusions: Contrary to the literature, our results shows that elevated levels of perceived SDM may be associated with worse diabetic control. However, more investigation is needed as these results are not generalizable, due to the specific population used and the sample size. Furthermore, to better understand the effect of SDM on the change in HbA1c in patients with poorly controlled diabetes. Full article

(This article belongs to the Special Issue Diabetes, Lifestyle and Genetics)

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10 pages, 677 KiB

Open AccessArticle

Serum Cystatin C as a Biomarker for Early Diabetic Kidney Disease and Dyslipidemia in Young Type 1 Diabetes Patients

by Ingrida Stankute, Lina Radzeviciene, Ausra Monstaviciene, Rimante Dobrovolskiene, Evalda Danyte and Rasa Verkauskiene

Medicina 2022, 58(2), 218; https://doi.org/10.3390/medicina58020218 - 01 Feb 2022

Cited by 5 | Viewed by 2374

Abstract

Background and objectives: This study aimed to assess the clinical significance of serum cystatin C in the early diagnosis of renal injury and its association with dyslipidemia in young T1D patients. Materials and Methods: A total of 779 subjects were evaluated for kidney function by estimating glomerular filtration rate (eGFR) based on serum creatinine (eGFRcreat) and cystatin C (eGFRcys). Results: The median age of study subjects was 16.2 years (2.1;26.4), diabetes duration—5.3 years (0.51;24.0). The median of HbA1c was 8% (5.2;19.9) (64 mmol/mol (33.3;194)); 24.2% of participants had HbA1c < 7% (53 mmol/mol). Elevated albumin excretion rate was found in 13.5% of subjects. The median of cystatin C was 0.8 mg/L (0.33;1.71), the median of creatinine—63 µmol/L (6;126). The median of eGFRcys was lower than eGFRcreat (92 mL/min/1.73 m² vs. 101 mL/min/1.73 m², p < 0.001). A total of 30.2% of all patients were classified as having worse kidney function when using cystatin C vs. creatinine for eGFR calculation. Linear correlations were found between cystatin C and HbA1c, r = −0.088, p < 0.05, as well as cystatin C and HDL, r = −0.097, p < 0.01. Conclusions: This study showed that cystatin C might be used as an additional biomarker of early kidney injury in young patients with T1D. Full article

(This article belongs to the Special Issue Diabetes, Lifestyle and Genetics)

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6 pages, 826 KiB

Open AccessCommunication

A Mediterranean-Style Diet Plan Is Associated with Greater Effectiveness and Sustainability in Weight Loss in Patients with Obesity after Endoscopic Bariatric Therapy

by Lidia Rueda-Galindo, María Fernanda Zerón-Rugerio, Antonio J. Sánchez Egea, Gil Serrancolí and Maria Izquierdo-Pulido

Medicina 2022, 58(2), 168; https://doi.org/10.3390/medicina58020168 - 22 Jan 2022

Cited by 2 | Viewed by 2560

Abstract

This study aimed to investigate the impact of a Mediterranean-style diet on weight loss effectiveness and sustainability in patients with obesity who underwent endoscopic bariatric therapies (EBT), relative to a protein diet plan. Thus, 132 patients with obesity (BMI 30–40 kg/m²) who underwent EBT, were asked to follow a Mediterranean-style diet plan (n = 52) or a protein diet plan (n = 26) for six months. General linear models were used to compare outcome variables between dietary intervention groups. Results showed that participants who followed a Mediterranean-style diet plan lost 14.2% more weight (95% CI: 3.0; 25.3), compared with those who followed a protein diet plan. Additionally, following a Mediterranean-style diet plan was associated with the sustainability of weight loss. Note that three months after the end of the dietary intervention, the patients who followed a Mediterranean-style diet plan were still losing weight (−1.2 ± 3.0 kg), while those with a protein diet plan gained, on average, 2.4 ± 3.3 kg (p < 0.001). Therefore, we conclude that combining EBT with a Mediterranean-style diet plan could represent an effective dietary intervention to improve the effectiveness and sustainability of weight loss after an EBT. Full article

(This article belongs to the Special Issue Diabetes, Lifestyle and Genetics)

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13 pages, 2959 KiB

Open AccessArticle

Chronological Appearance of Endocrine and Metabolic Dysfunctions Induced by an Unhealthy Diet in Rats

by María Cecilia Castro, Hernán Gonzalo Villagarcía, Carolina Lisi Román, Bárbara Maiztegui, Luis Emilio Flores, Guillermo Raúl Schinella, María Laura Massa and Flavio Francini

Medicina 2022, 58(1), 8; https://doi.org/10.3390/medicina58010008 - 21 Dec 2021

Cited by 4 | Viewed by 2543

Abstract

Background and Objectives: The work was aimed to determine the chronological sequence of events triggered by a fructose-rich diet (FRD) (10% w/v in the drinking water) in normal rats. Material and Methods: Serum parameters, liver and islet markers of metabolism, inflammation and oxidative stress were determined weekly for 21 days. Results: At the end of the first week, rats fed with a FRD showed an early increase in circulating triglycerides, fat liver deposit, and enzymatic activity of liver glucokinase and glucose-6-phosphate dehydrogenase (G6P-DH). After two weeks of such a diet, liver glucose-6-phosphatase (G6Pase) activity and liver oxidative stress markers were significantly increased. Liver sterol regulatory element-binding protein 1c (SREBP1c) mRNA also increased in the second week while their target genes fatty acid synthase (FAS) and glycerol-3-phosphate dehydrogenase (GPAT) enhanced their expression at the third week. Liver and pancreatic inflammation markers also enhanced their gene expression in the last week of treatment. Whereas both control and FRD rats remained normoglycemic throughout the entire period of treatment, blood insulin levels were significantly higher in FRD animals at the third week, thereby evidencing an insulin-resistant state (higher HOMA-IR, HOMA-B and HIS indexes). Pancreatic islets isolated from rats fed with a FRD for 3 weeks also increased glucose-induced insulin secretion (8.3 and 16.7 mM). Conclusions: FRD induces asynchronous changes involving early hypertriglyceridemia together with intrahepatic lipid deposit and metabolic disturbances from week one, followed by enhanced liver oxidative stress, liver and pancreas inflammation, pancreatic β-cell dysfunction, and peripheral insulin-resistance registered at the third week. Knowledge of time-course adaptation mechanisms involved in our rat model could be helpful in developing appropriate strategies to prevent the progression from prediabetes to Type 2 diabetes (T2D) triggered by unhealthy diets. Full article

(This article belongs to the Special Issue Diabetes, Lifestyle and Genetics)

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17 pages, 669 KiB

Open AccessArticle

The Relation of Body Mass Index to Muscular Viscoelastic Properties in Normal and Overweight Individuals

by Serkan Usgu, Engin Ramazanoğlu and Yavuz Yakut

Medicina 2021, 57(10), 1022; https://doi.org/10.3390/medicina57101022 - 26 Sep 2021

Cited by 7 | Viewed by 7848

Abstract

Background: The body mass index (BMI) is closely related to fat tissue, which may have direct or indirect effects on muscle function. Previous studies have evaluated BMI and muscle viscoelastic properties in vivo in older people or individual sexes; however, the relationship between BMI and muscular viscoelastic properties is still unknown. Aims: The purpose of this study was to determine the correlation of BMI with muscular viscoelastic properties, and to compare these properties in a young sedentary population with normal and overweight individuals. Methods: A total of 172 healthy sedentary individuals (mean age, 26.00 ± 5.45 years) were categorized by sex (male and female) and BMI classification (normal (BMI, 18.50–24.99 kg/m²), overweight (BMI = 25.00–29.99 kg/m²)). Body weight was evaluated using an electronic scale, while height was measured using a standard stadiometer. BMI was calculated by dividing the weight in kilograms by the square of height in meters. The viscoelastic properties (tone, stiffness, and elasticity) of the biceps brachii (BB) and biceps femoris (BF) muscles were measured bilaterally using the MyotonPRO device at rest. Results: The bilateral BF tone and stiffness, right BB stiffness, and elasticity showed weak correlations with BMI in all participants. Furthermore, the bilateral BF tone and stiffness, right BB stiffness and elasticity, and left BB stiffness were weakly positively correlated with male sex. Only the right BB elasticity was weakly positively correlated with BMI in females (p < 0.05). No correlation with BMI was determined for other viscoelastic properties (p > 0.05). The overweight group showed increased bilateral BF stiffness and tone, right BB stiffness, and reduced bilateral BB elasticity compared to the normal-weight group (p < 0.05), while other viscoelastic properties were similar (p > 0.05). Greater bilateral BB tone, BF tone and stiffness, and lower BF elasticity were observed in males than in females (p < 0.05), but other viscoelastic properties were not significantly different (p < 0.05). No effect of BMI–sex interactions was found on viscoelastic properties (p > 0.05). Conclusions: The BB and BF viscoelastic properties were weakly correlated with BMI. Males showed greater muscle tone and stiffness, and lower elasticity. The overweight individuals showed increased stiffness and tone, particularly in lower extremities, and reduced elasticity in upper extremities. The effect of BMI–sex interactions on the viscoelastic properties was not clear. Higher BMI (increased mechanical load) might cause the human body to develop different muscular viscoelastic adaptations in the extremities. Full article

(This article belongs to the Special Issue Diabetes, Lifestyle and Genetics)

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Review

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23 pages, 1809 KiB

Open AccessReview

Recent Advances in the Treatment of Insulin Resistance Targeting Molecular and Metabolic Pathways: Fighting a Losing Battle?

by Marta Wolosowicz, Slawomir Prokopiuk and Tomasz W. Kaminski

Medicina 2022, 58(4), 472; https://doi.org/10.3390/medicina58040472 - 25 Mar 2022

Cited by 19 | Viewed by 10023

Abstract

Diabetes Mellitus (DM) is amongst the most notable causes of years of life lost worldwide and its prevalence increases perpetually. The disease is characterized as multisystemic dysfunctions attributed to hyperglycemia resulting directly from insulin resistance (IR), inadequate insulin secretion, or enormous glucagon secretion. Insulin is a highly anabolic peptide hormone that regulates blood glucose levels by hastening cellular glucose uptake as well as controlling carbohydrate, protein, and lipid metabolism. In the course of Type 2 Diabetes Mellitus (T2DM), which accounts for nearly 90% of all cases of diabetes, the insulin response is inadequate, and this condition is defined as Insulin Resistance. IR sequela include, but are not limited to, hyperglycemia, cardiovascular system impairment, chronic inflammation, disbalance in oxidative stress status, and metabolic syndrome occurrence. Despite the substantial progress in understanding the molecular and metabolic pathways accounting for injurious effects of IR towards multiple body organs, IR still is recognized as a ferocious enigma. The number of widely available therapeutic approaches is growing, however, the demand for precise, safe, and effective therapy is also increasing. A literature search was carried out using the MEDLINE/PubMed, Google Scholar, SCOPUS and Clinical Trials Registry databases with a combination of keywords and MeSH terms, and papers published from February 2021 to March 2022 were selected as recently published papers. This review paper aims to provide critical, concise, but comprehensive insights into the advances in the treatment of IR that were achieved in the last months. Full article

(This article belongs to the Special Issue Diabetes, Lifestyle and Genetics)

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Other

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9 pages, 2918 KiB

Open AccessSystematic Review

The Prevalence of Insulin Resistance in Malaysia and Indonesia: An Updated Systematic Review and Meta-Analysis

by Lucky Poh Wah Goh, Suraya Abdul Sani, Mohd Khalizan Sabullah and Jualang Azlan Gansau

Medicina 2022, 58(6), 826; https://doi.org/10.3390/medicina58060826 - 19 Jun 2022

Cited by 5 | Viewed by 2468

Abstract

Background and Objectives: Noncommunicable diseases such as diabetes are strongly associated with the insulin resistance (IR) status of an individual. However, the prevalence of insulin resistance in Southeast Asia is poorly reported. Hence, this study investigated the prevalence of IR in Southeast Asia from the year 2016 to 2021. Materials and Methods: This study was carried out according to PRISMA guidelines. The literature search was conducted utilizing the PubMed and SCOPUS databases from the year 2016 to 2021 using the keywords ‘(insulin AND resistance) OR (insulin AND sensitivity) OR (prevalence OR incidence) AND (Malaysia OR Thailand OR Singapore OR Brunei OR Cambodia OR Indonesia OR Laos OR Myanmar OR Philippines OR Timor leste OR Vietnam)’. Funnel plot and publication bias were assessed using Egger’s tests. Data were expressed as the prevalence rate. Results: A total of 12 studies with 2198 subjects were considered in the meta-analysis. Significant heterogeneity (I² > 94% and p-value < 0.001) was observed in the meta-analysis. The overall prevalence of IR in Southeast Asia was 44.3%, with Malaysia having the highest prevalence rate at 50.4%, followed by Indonesia at 44.2%. Bias was detected in the meta-analysis. It may be that reports published before the year 2016 met the study selection criteria, but were excluded from the meta-analysis. Conclusions: The results from the meta-analysis indicate that the prevalence of IR in Southeast Asia is very high. This provided insights for healthcare policy makers and public health officials in designing IR screening programs. Full article

(This article belongs to the Special Issue Diabetes, Lifestyle and Genetics)

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