Special Issue "Carbohydrates, Metabolism and Therapies in Diabetes"

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: closed (15 July 2020).

Special Issue Editors

Prof. Dr. Francesco Andreozzi
Website
Guest Editor
Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
Interests: molecular mechanisms of insulin action and regulation of insulin secretion; genetic of insulin resistance, type 2 diabetes, and obesity; controlled clinical trials
Dr. Francesco Prattichizzo
Website
Guest Editor
IRCCS Multimedica, 20099 Sesto San Giovanni, Italy
Interests: type 2 diabetes and complications; glucose-lowering terapies; low-grade inflammation

Special Issue Information

Dear Colleagues,

Type 2 diabetes mellitus (T2DM) is a complex disease driven by genetic and environmental factors. Among the latter, diet plays a prominent role in T2DM development and progression, and accumulating evidence suggests the potential of dietetic approaches, e.g., the Mediterranean diet, to decrease the incidence of T2DM and to help glucose control. Although patients with T2DM are characterized by a plethora of additional metabolic alterations, carbohydrate metabolism still represents the main feature of the disease.

Given the latest evidence about dietary and therapeutic approaches, the old “glucocentric” view of T2DM management is progressively being replaced by a multidimensional approach aimed at minimizing all risk factors for the development of invalidating and life-threatening complications. Considering these multiple layers of complexity, this Special Issue aims at collecting contributions covering different T2DM aspects, with a preference for the effect of dietary approaches (novel or consolidated) for T2DM prevention and management. Manuscripts describing alterations of metabolic pathways, and in particular of carbohydrate metabolism, are also in the scope of this Special Issue. Pharmacological approaches targeting specific aspects of T2DM are also welcome, as long as they deal with metabolic alterations relevant to the disease, e.g., lipid metabolism and ketone bodies.

Dr. Francesco Andreozzi
Dr. Francesco Prattichizzo
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Type 2 diabetes mellitus
  • Diabetes complications
  • Dietetic approach for T2DM prevention and management
  • Metabolic alterations of T2DM
  • Carbohydrate metabolism
  • Glucose-lowering diets
  • Dietary approaches for risk factor reduction
  • Pharmacological approaches for T2DM

Published Papers (9 papers)

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Research

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Open AccessArticle
Circulating Levels of the Soluble Receptor for AGE (sRAGE) during Escalating Oral Glucose Dosages and Corresponding Isoglycaemic i.v. Glucose Infusions in Individuals with and without Type 2 Diabetes
Nutrients 2020, 12(10), 2928; https://doi.org/10.3390/nu12102928 - 24 Sep 2020
Abstract
Postprandial glucose excursions are postulated to increase the risk for diabetes complications via the production of advanced glycation end products (AGEs). The soluble receptor of AGEs (sRAGE) likely acts as a decoy receptor, mopping up AGEs, diminishing their capacity for pro-inflammatory and pro-apoptotic [...] Read more.
Postprandial glucose excursions are postulated to increase the risk for diabetes complications via the production of advanced glycation end products (AGEs). The soluble receptor of AGEs (sRAGE) likely acts as a decoy receptor, mopping up AGEs, diminishing their capacity for pro-inflammatory and pro-apoptotic signaling. Recent evidence suggests that AGEs and soluble receptor for AGEs (sRAGE) may be altered under postprandial and fasting conditions. Here, we investigated the effects of increasing oral glucose loads during oral glucose tolerance tests (OGTT) and matched isoglycaemic intravenous (i.v.) glucose infusions (IIGI) on circulating concentrations of sRAGE. Samples from eight individuals with type 2 diabetes and eight age-, gender-, and body mass index (BMI)-matched controls, all of whom underwent three differently dosed OGTTs (25 g, 75 g, and 125 g), and three matched IIGIs were utilised (NCT00529048). Serum concentrations of sRAGE were measured over 240 min during each test. For individuals with diabetes, sRAGE area under the curve (AUC0–240min) declined with increasing i.v. glucose dosages (p < 0.0001 for trend) and was lower during IIGI compared to OGTT at the 125 g dosage (p = 0.004). In control subjects, sRAGE AUC0–240min was only lower during IIGI compared to OGTT at the 25 g dose (p = 0.0015). sRAGE AUC0–240min was negatively correlated to AUC0–240min for the incretin hormone glucagon-like peptide −1 (GLP-1) during the 75 g OGTT and matched IIGI, but only in individuals with type 2 diabetes. These data suggest that gastrointestinal factors may play a role in regulating sRAGE concentrations during postprandial glucose excursions, thus warranting further investigation. Full article
(This article belongs to the Special Issue Carbohydrates, Metabolism and Therapies in Diabetes)
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Open AccessArticle
Uric Acid and Vascular Damage in Essential Hypertension: Role of Insulin Resistance
Nutrients 2020, 12(9), 2509; https://doi.org/10.3390/nu12092509 - 19 Aug 2020
Abstract
Increased levels of uric acid (UA) have been shown to be correlated with many clinical conditions. Uric acid may adversely affect the insulin signalling pathway inducing insulin resistance (IR). Several studies report the association between arterial stiffness (AS), an early indicator of atherosclerosis, [...] Read more.
Increased levels of uric acid (UA) have been shown to be correlated with many clinical conditions. Uric acid may adversely affect the insulin signalling pathway inducing insulin resistance (IR). Several studies report the association between arterial stiffness (AS), an early indicator of atherosclerosis, and UA. The purpose of the present study was to evaluate the association between UA and AS, considering the potential role of IR. We enrolled 1114 newly diagnosed, never-treated hypertensive patients. Insulin resistance was assessed by the homeostatic model assessment (HOMA) index. Arterial stiffness was evaluated as the measurement of the carotid–femoral pulse wave velocity (PWV). The study cohort was divided into subgroups, according to increasing tertiles of UA. The mean values of UA were 5.2 ± 1.6 mg/dL in the overall population. Pulse wave velocity was linearly correlated with UA (p < 0.0001), HOMA (p < 0.0001), high sensitivity C-reactive protein (p < 0.0001), systolic blood pressure (p < 0.0001) and LDL cholesterol (p = 0.005). Uric acid was the strongest predictor of PWV and was associated with the highest risk for increased AS. The interaction analysis showed that the joint effect of increased UA and HOMA was significantly higher than that expected in the absence of interaction under the additive model, indicating that the two biomarkers synergically interacted for promoting vascular damage. Our data showed that UA interacted with IR to increase AS in a large cohort of newly diagnosed, never-treated hypertensive patients. Full article
(This article belongs to the Special Issue Carbohydrates, Metabolism and Therapies in Diabetes)
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Open AccessArticle
Design and Validation of a Diet Rich in Slowly Digestible Starch for Type 2 Diabetic Patients for Significant Improvement in Glycemic Profile
Nutrients 2020, 12(8), 2404; https://doi.org/10.3390/nu12082404 - 11 Aug 2020
Abstract
This study aimed at designing a—diet high in slowly digestible starch (SDS) by carefully selecting high-SDS starchy products and to validate its implementation, acceptance, and impact on the postprandial glycemic response in patients with type 2 diabetes (T2D). Starchy products were screened and [...] Read more.
This study aimed at designing a—diet high in slowly digestible starch (SDS) by carefully selecting high-SDS starchy products and to validate its implementation, acceptance, and impact on the postprandial glycemic response in patients with type 2 diabetes (T2D). Starchy products were screened and classified as being either high (high-SDS) or low (low-SDS) in SDS (in vitro SDS method). A randomized controlled cross-over pilot study was performed: Eight patients with T2D consumed randomly a high-SDS or a low-SDS diet for one week each, while their glycemic profile was monitored for 6 days. Based on 250 food product SDS analyses and dietary recommendations for patients with T2D, the high-SDS and low-SDS diets were designed. The high-SDS diet significantly increased SDS intake and the SDS/carbohydrates proportion compared to the low-SDS diet (61.6 vs. 11.6 g/day and 30% vs. 6%; p < 0.0001, respectively). Increasing the SDS/carbohydrate proportion to 50% of the meal was significantly correlated with a 12% decrease in tAUC0–120 min and a 14% decrease in the glycemic peak value (p < 0.001 for both). A high-SDS diet can be easily designed by carefully selecting commercial starchy products and providing relevant recommendations for T2D to improve their glycemic profile. Full article
(This article belongs to the Special Issue Carbohydrates, Metabolism and Therapies in Diabetes)
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Open AccessArticle
The Effects of a Low Calorie Ketogenic Diet on Glycaemic Control Variables in Hyperinsulinemic Overweight/Obese Females
Nutrients 2020, 12(6), 1854; https://doi.org/10.3390/nu12061854 - 22 Jun 2020
Cited by 1
Abstract
Diet is a factor which can influence both glycaemic variables and body mass. The aim of this study was to compare the influence of a 12-week, well-planned, low-calorie ketogenic diet (LCKD) on hyperglycaemic, hyperinsulinemic and lipid profile in adult, overweight or obese females. [...] Read more.
Diet is a factor which can influence both glycaemic variables and body mass. The aim of this study was to compare the influence of a 12-week, well-planned, low-calorie ketogenic diet (LCKD) on hyperglycaemic, hyperinsulinemic and lipid profile in adult, overweight or obese females. Ninety-one females who participated in the study were divided into two groups: a LCKD group who followed a hypocaloric ketogenic diet (8% of carbohydrate, 72% of fat and 20% of proteins) (n = 46), and a control group (CG) (n = 45) who continued their typical diet (50% of carbohydrates, 32% of fat and 18% of proteins). Methods: Baseline and post-intervention glucose (Gl), insulin (I), glycated haemoglobin (HbA1c), Homeostatic model assessment HOMA-IR, triglycerides (TG) and high-density cholesterol (HDL-C) were evaluated. Also, body mass (BM), waist circumference (WC), hip circumference (HC) and thigh circumference (TC) were measured. Results: Compared with the CG, there were significant changes observed in the LCKD group regarding all biochemical variables. Also, BM, TC, WC and AC changed significantly in the LCKD group compared with the CG. Conclusions: The 12-week LCKD intervention changed the glucose control variables, body mass, as well as waist, hip and thigh circumferences. A low-calorie ketogenic diet may be recommended for adult females with glucose control variables disturbance and excess body mass. Full article
(This article belongs to the Special Issue Carbohydrates, Metabolism and Therapies in Diabetes)
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Open AccessArticle
Citrus aurantium L. Dry Extracts Ameliorate Adipocyte Differentiation of 3T3-L1 Cells Exposed to TNFα by Down-Regulating miR-155 Expression
Nutrients 2020, 12(6), 1587; https://doi.org/10.3390/nu12061587 - 28 May 2020
Cited by 1
Abstract
Citrus aurantium L. dry extracts (CAde) improve adipogenesis in vitro. These effects are dependent from an early modulation of CCAAT/enhancer-binding protein beta (C/Ebpβ) expression and cyclic Adenosine Monophosphate (cAMP) response element-binding protein (CREB) activation. C/Ebpβ and Creb [...] Read more.
Citrus aurantium L. dry extracts (CAde) improve adipogenesis in vitro. These effects are dependent from an early modulation of CCAAT/enhancer-binding protein beta (C/Ebpβ) expression and cyclic Adenosine Monophosphate (cAMP) response element-binding protein (CREB) activation. C/Ebpβ and Creb are also targets of miR-155. This study investigated whether CAde regulates miR-155 expression in the early stages of adipogenesis and whether it ameliorates adipocyte differentiation of cells exposed to tumor necrosis factor-alpha (TNFα). Adipogenic stimuli (AS) were performed in 3T3-L1 pre-adipocytes treated with CAde, TNFα, or both. Gene and miRNA expression were determined by quantitative real-time PCR. Adipogenesis was evaluated by Oil-Red O staining. CAde treatment enhanced AS effects during the early adipogenesis phases by further down-regulating miR-155 expression and increasing both C/Ebpβ and Creb mRNA and protein levels. At variance, TNFα inhibited 3T3-L1 adipogenesis and abolished AS effects on miR-155, C/Ebpβ, and Creb expression. However, in cells exposed to TNFα, CAde improved adipocyte differentiation and restored the AS effects on miRNA and gene expression at early time points. In conclusion, this study identified miR-155 down-regulation as part of the mechanism through which CAde enhances adipogenesis of pre-adipocytes in vitro. Furthermore, it provides evidence of CAde efficacy against TNFα negative effects on adipogenesis. Full article
(This article belongs to the Special Issue Carbohydrates, Metabolism and Therapies in Diabetes)
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Open AccessArticle
Association between Serum Mg2+ Concentrations and Cardiovascular Organ Damage in a Cohort of Adult Subjects
Nutrients 2020, 12(5), 1264; https://doi.org/10.3390/nu12051264 - 29 Apr 2020
Cited by 1
Abstract
Magnesium (Mg2+) levels are associated with insulin resistance, hypertension, atherosclerosis, and type 2 diabetes (T2DM). We evaluated the clinical utility of physiological Mg2+ in assessing subclinical cardiovascular organ damage including increased carotid artery intima- media thickness (c-IMT) and left ventricular [...] Read more.
Magnesium (Mg2+) levels are associated with insulin resistance, hypertension, atherosclerosis, and type 2 diabetes (T2DM). We evaluated the clinical utility of physiological Mg2+ in assessing subclinical cardiovascular organ damage including increased carotid artery intima- media thickness (c-IMT) and left ventricular mass index (LVMI) in a cohort of well-characterized adult non-diabetic individuals. Age- and gender-adjusted correlations between Mg2+ and metabolic parameters showed that Mg2+ circulating levels were correlated negatively with body mass index (BMI), fasting glucose, and 2h-oral glucose tolerance test (OGTT) glucose. Similarly, Mg2+ levels were significantly and negatively related to c-IMT and LVMI. A multivariate regression analysis revealed that age (β = 0.440; p < 0.0001), BMI (β = 0.225; p < 0.0001), and Mg2+ concentration (β = −0.122; p < 0.01) were independently associated with c-IMT. Age (β = 0.244; p = 0.012), Mg2+ (β = −0.177; p = 0.019), and diastolic blood pressure (β = 0.184; p = 0.038) were significantly associated with LVMI in women, while age (β = 0.211; p = 0.019), Mg2+ (β = −0.171; p = 0.038) and the homeostasis model assessment index of insulin resistance (HOMA-IR) (β = −0.211; p = 0.041) were the sole variables associated with LVMI in men. In conclusion, our data support the hypothesis that the assessment of Mg2+ as part of the initial work-up might help unravel the presence of subclinical organ damage in subjects at increased risk of cardiovascular complications. Full article
(This article belongs to the Special Issue Carbohydrates, Metabolism and Therapies in Diabetes)
Open AccessArticle
Lysophosphatidylcholine Containing Anisic Acid Is Able to Stimulate Insulin Secretion Targeting G Protein Coupled Receptors
Nutrients 2020, 12(4), 1173; https://doi.org/10.3390/nu12041173 - 22 Apr 2020
Cited by 3
Abstract
Diabetes mellitus is a worldwide health problem with high rates of mortality and morbidity. Management of diabetes mellitus by dietary components is achievable especially at the initial stage of the disease. Several studies confirmed the antidiabetic activities of simple phenolic acids and lysophosphatidylcholine [...] Read more.
Diabetes mellitus is a worldwide health problem with high rates of mortality and morbidity. Management of diabetes mellitus by dietary components is achievable especially at the initial stage of the disease. Several studies confirmed the antidiabetic activities of simple phenolic acids and lysophosphatidylcholine (LPC). The main goal of this study was to identify new potential insulin secretion modulators obtained by combining the structures of two natural compounds, namely O-methyl derivatives of phenolic acids and phospholipids. LPC and phosphatidylcholine bearing methoxylated aromatic carboxylic acids were tested as potential agents able to improve glucose-stimulated insulin secretion (GSIS) and intracellular calcium mobilization in MIN6 β pancreatic cell line. Our results show that LPC with covalently bonded molecule of p-anisic acid at the sn-1 position was able to induce GSIS and intracellular calcium flux. Notably, 1-anisoyl-2-hydroxy-sn-glycero-3-phosphocholine did not affect the viability of MIN6 cells, suggesting its potential safe use. Furthermore, we have shown that three G protein coupled receptors, namely GPR40, GPR55, and GPR119, are targeted by this LPC derivative. Full article
(This article belongs to the Special Issue Carbohydrates, Metabolism and Therapies in Diabetes)
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Open AccessArticle
Natural Magnesium-Enriched Deep-Sea Water Improves Insulin Resistance and the Lipid Profile of Prediabetic Adults: A Randomized, Double-Blinded Crossover Trial
Nutrients 2020, 12(2), 515; https://doi.org/10.3390/nu12020515 - 18 Feb 2020
Abstract
Previous in vitro and in vivo studies have shown that the antidiabetic effect of balanced deep-sea water (BDSW) works through the suppression of hyperglycemia and improvement of glucose tolerance. Based on these promising results, we conducted an eight week randomized, double-blinded crossover trial [...] Read more.
Previous in vitro and in vivo studies have shown that the antidiabetic effect of balanced deep-sea water (BDSW) works through the suppression of hyperglycemia and improvement of glucose tolerance. Based on these promising results, we conducted an eight week randomized, double-blinded crossover trial of the effects of BDSW in prediabetic adults. The subjects consumed 440 mL of BDSW (hardness 4000) per day, and maintained an otherwise normal lifestyle and diet throughout. Efficacy assessments were made by measuring fasting glucose, postprandial glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), C-peptide, glycosylated hemoglobin, lipid metabolism indicators, and physical metrics, along with safety assessments. Fasting insulin and HOMA-IR values of the BDSW group were significantly lower than those of the placebo group after eight weeks of BDSW ingestion. Total cholesterol and low-density lipoprotein–cholesterol were also significantly decreased in the BDSW group after eight weeks of BDSW ingestion compared with the placebo group. There were no statistically and clinically meaningful changes in adverse events, physical examination, laboratory medicine examination, or vital signs of the BDSW intake group. These results suggested that the intake of BDSW in prediabetic adults can improve glucose metabolism and lipid profiles and is safe for human consumption. Full article
(This article belongs to the Special Issue Carbohydrates, Metabolism and Therapies in Diabetes)
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Review

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Open AccessReview
A Review of Recent Findings on Meal Sequence: An Attractive Dietary Approach to Prevention and Management of Type 2 Diabetes
Nutrients 2020, 12(9), 2502; https://doi.org/10.3390/nu12092502 - 19 Aug 2020
Abstract
While adjustment of total energy and nutritional balance is critically important, meal sequence, a relatively simple method of correcting postprandial hyperglycemia, is becoming established as a practical dietary approach for prevention and management of diabetes and obesity. Meal sequence, i.e., consumption of protein [...] Read more.
While adjustment of total energy and nutritional balance is critically important, meal sequence, a relatively simple method of correcting postprandial hyperglycemia, is becoming established as a practical dietary approach for prevention and management of diabetes and obesity. Meal sequence, i.e., consumption of protein and/or fat before carbohydrate, promotes secretion of glucagon-like peptide-1 (GLP-1) from the gut and ameliorates secretions of insulin and glucagon and delays gastric emptying, thereby improving postprandial glucose excursion. GLP-1 is known to suppress appetite by acting on the hypothalamus via the afferent vagus nerve. Thus, enhancement of GLP-1 secretion by meal sequence is expected to reduce body weight. Importantly, consumption of a diet rich in saturated fatty acids such as meat dishes before carbohydrate increases secretions of not only GLP-1 but also glucose-dependent insulinotropic polypeptide (GIP), which promotes energy storage in adipose tissue and may lead to weight gain in the long term. Dietary fiber intake before carbohydrate intake significantly reduces postprandial glucose elevation and may have a weight loss effect, but this dietary strategy does not enhance the secretion of GLP-1. Thus, it is suggested that their combination may have additive effects on postprandial glucose excursion and body weight. Indeed, results of some clinical research supports the idea that ingesting dietary fiber together with meal sequence of protein and/or fat before carbohydrate benefits metabolic conditions of individuals with diabetes and obesity. Full article
(This article belongs to the Special Issue Carbohydrates, Metabolism and Therapies in Diabetes)
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