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1.
Science ; 381(6665): eabl7398, 2023 09 29.
Article in English | MEDLINE | ID: mdl-37769095

ABSTRACT

Systemic metabolism has to be constantly adjusted to the variance of food intake and even be prepared for anticipated changes in nutrient availability. Therefore, the brain integrates multiple homeostatic signals with numerous cues that predict future deviations in energy supply. Recently, our understanding of the neural pathways underlying these regulatory principles-as well as their convergence in the hypothalamus as the key coordinator of food intake, energy expenditure, and glucose metabolism-have been revealed. These advances have changed our view of brain-dependent control of metabolic physiology. In this Review, we discuss new concepts about how alterations in these pathways contribute to the development of prevalent metabolic diseases such as obesity and type 2 diabetes mellitus and how this emerging knowledge may provide new targets for their treatment.


Subject(s)
Brain-Gut Axis , Diabetes Mellitus, Type 2 , Eating , Energy Metabolism , Hypothalamus , Neural Pathways , Obesity , Humans , Diabetes Mellitus, Type 2/physiopathology , Homeostasis , Hypothalamus/physiology , Obesity/physiopathology , Neural Pathways/physiopathology
2.
J Diabetes Res ; 2022: 9537741, 2022.
Article in English | MEDLINE | ID: mdl-35242882

ABSTRACT

BACKGROUND: Several experimental studies have suggested beneficial effects of Ceriporia lacerata on glucose metabolism. However, there has been no human study assessing the effects of C. lacerata on glucose metabolism. Therefore, we investigated whether C. lacerata improves glucose control and insulin resistance in type 2 diabetes patients. METHODS: Ninety patients diagnosed with type 2 diabetes (T2DM) for more than 6 months were enrolled. Subjects were randomly divided into placebo (n = 45) or C. lacerata (n = 45) groups and then assigned to take placebo or C. lacerata capsules (500 mg/capsule) for a 12-week intervention period. Biochemical markers, including fasting glucose, 2-hour postprandial plasma glucose, and lipid profile levels, as well as insulin, c-peptide, and Hba1c, were measured. Furthermore, insulin sensitivity indices, such as HOMA-IR, HOMA-beta, and QUICKI, were assessed before and after the 12-week administration. RESULTS: Eighty-four patients completed the study. There were no significant differences in fasting, postprandial glucose, HbA1c, or lipid parameters. HOMA-IR and QUICKI indices were improved at week 12 in the C. lacerata group, especially in subjects with HOMA-IR of 1.8 or more (p < 0.05). Fasting, postprandial c-peptide, and insulin levels decreased at week 12 in the C. lacerata group (p < 0.05). These significant differences were not observed in the placebo group. CONCLUSION: Twelve-week administration of C. lacerata in T2DM patients resulted in significant improvement in insulin resistance, especially in those with lower insulin sensitivity. A larger population study with a longer follow-up period and an effort to elucidate the mechanism is warranted to further assess the effects of C. lacerata on T2DM patients.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Insulin Resistance/physiology , Plant Extracts/pharmacology , Polyporales/metabolism , Adult , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/physiopathology , Female , Glycated Hemoglobin/metabolism , Humans , Insulin/blood , Male , Middle Aged , Plant Extracts/metabolism , Plant Extracts/therapeutic use
3.
Article in English | MEDLINE | ID: mdl-35219959

ABSTRACT

The gut microbiota (GM) and metabolites are important factors in mediating the development of type-2 diabetes mellitus (T2DM). An imbalance in the gut microbiota and metabolites can disrupt the function of the intestinal barrier, cause changes in the permeability of the intestinal mucosa and promote the immune inflammatory response, thereby aggravating the fluctuation of blood glucose level and promoting the occurrence and development of the chronic complications of DM. Manipulating the GM and metabolites is a promising therapeutic intervention and is being studied extensively. Shenqi compound (SQC) is a traditional Chinese medicine formulation, which has been widely used to improve T2DM. Studies have demonstrated that SQC can reduce glycemic variability, alleviate the inflammatory response, etc. However, its underlying mechanism remains unknown. Therefore, in this experiment, We administered SQC to Goto-Kakizaki (GK) rats and evaluated its effect on blood glucose homeostasis and the intestinal mucosal barrier. We identified the profiles of the GM and metabolites with the aid of 16S rDNA gene sequencing and non-target metabolomics analysis. It showed that SQC intervention could reduce glycemic variability, regulate serum levels of glucagon and insulin, and improve injury to the intestinal mucosal barrier of GK rats. In the gut, the ratio of bacteria of the phyla Bacteroidetes/Firmicutes could be improved after SQC intervention. SQC also regulated the relative abundance of Prevotellaceae, Butyricimonas, Bacteroides, Blautia, Roseburia, Lactobacillus, and Rothia. We found out that expression of 40 metabolites was significantly improved after SQC intervention. Further analyses of metabolic pathways indicated that the therapeutic effect of SQC might be related predominantly to its ability to improve gluconeogenesis/glycolysis, amino acid metabolism, lipid metabolism, citrate cycle, and butanoate metabolism. These results suggest that SQC may exert a beneficial role in T2DM by modulating the GM and metabolites in different pathways.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/microbiology , Drugs, Chinese Herbal/administration & dosage , Gastrointestinal Microbiome/drug effects , Amino Acids/metabolism , Animals , Bacteria/classification , Bacteria/drug effects , Bacteria/genetics , Bacteria/isolation & purification , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/physiopathology , Gluconeogenesis/drug effects , Glycolysis/drug effects , Humans , Insulin/blood , Male , Rats , Rats, Wistar
4.
Int J Mol Sci ; 23(2)2022 Jan 09.
Article in English | MEDLINE | ID: mdl-35054888

ABSTRACT

Diabetes mellitus, especially type 2 (T2DM), is a major public health problem globally. DM is characterized by high levels of glycemia and insulinemia due to impaired insulin secretion and insulin sensitivity of the cells, known as insulin resistance. T2DM causes multiple and severe complications such as nephropathy, neuropathy, and retinopathy causing cell oxidative damages in different internal tissues, particularly the pancreas, heart, adipose tissue, liver, and kidneys. Plant extracts and their bioactive phytochemicals are gaining interest as new therapeutic and preventive alternatives for T2DM and its associated complications. In this regard, isorhamnetin, a plant flavonoid, has long been studied for its potential anti-diabetic effects. This review describes its impact on reducing diabetes-related disorders by decreasing glucose levels, ameliorating the oxidative status, alleviating inflammation, and modulating lipid metabolism and adipocyte differentiation by regulating involved signaling pathways reported in the in vitro and in vivo studies. Additionally, we include a post hoc whole-genome transcriptome analysis of biological activities of isorhamnetin using a stem cell-based tool.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Quercetin/analogs & derivatives , Animals , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/physiopathology , Gene Expression Profiling , Humans , Inflammation , Lipid Metabolism , Oxidative Stress , Quercetin/pharmacology , Quercetin/therapeutic use
5.
Int J Mol Sci ; 23(1)2022 Jan 03.
Article in English | MEDLINE | ID: mdl-35008933

ABSTRACT

Type 2 diabetes mellitus (T2DM) patients are at a higher risk of developing Alzheimer's disease (AD). Mounting evidence suggests the emerging important role of circadian rhythms in many diseases. Circadian rhythm disruption is considered to contribute to both T2DM and AD. Here, we review the relationship among circadian rhythm disruption, T2DM and AD, and suggest that the occurrence and progression of T2DM and AD may in part be associated with circadian disruption. Then, we summarize the promising therapeutic strategies targeting circadian dysfunction for T2DM and AD, including pharmacological treatment such as melatonin, orexin, and circadian molecules, as well as non-pharmacological treatments like light therapy, feeding behavior, and exercise.


Subject(s)
Alzheimer Disease/physiopathology , Circadian Rhythm , Diabetes Mellitus, Type 2/physiopathology , Melatonin/therapeutic use , Animals , Humans
6.
Article in English | MEDLINE | ID: mdl-33475080

ABSTRACT

BACKGROUND & AIM: This meta-analysis was performed to quantify the effects of probiotics on renal and glycemic biomarkers among patients with Diabetic Nephropathy (DN). METHODS: Electronic databases were searched on May 10, 2020. All trials that investigated the effect of probiotics on serum glycemic markers (Fasting Plasma Glucose [FPG], Hemoglobin A1C, Insulin, Homeostatic Model Assessment-Insulin Resistance [HOMA-IR], and Quantitative Insulin Sensitivity Check Index [QUICKI]), and renal status markers (Creatinine [Cr], Blood Urea Nitrogen [BUN], and Glomerular Filtration Rate [GFR]) were included. RESULTS: Seven trials that included 340 patients were identified for analysis. The results indicated that probiotics significantly reduced FPG (WMD= -19.08 mg/dl; 95% CI= -32.16, -5.99; P=0.004), HOMA-IR (WMD= -1.88; 95% CI= -3.63, -0.12; P=0.036), and Cr (WMD= -0.18 mg/dl; 95% CI= -0.26, -0.09; P<0.001) levels in DN patients; however, there was no statistically significant change in Hemoglobin A1C, Insulin, QUICKI, BUN, and GFR. CONCLUSION: This meta-analysis supports the potential use of probiotics in the improvement of some glycemic and renal biomarkers in patients with DN.


Subject(s)
Blood Glucose/drug effects , Diabetic Nephropathies/diet therapy , Kidney/drug effects , Probiotics/therapeutic use , Biomarkers/blood , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diet therapy , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/physiopathology , Diabetic Nephropathies/blood , Diabetic Nephropathies/physiopathology , Dietary Supplements , Glycated Hemoglobin/drug effects , Glycated Hemoglobin/metabolism , Humans , Insulin/blood , Insulin Resistance/physiology , Kidney/physiology , Kidney Function Tests , Probiotics/pharmacology , Treatment Outcome
7.
Nitric Oxide ; 118: 17-25, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34718145

ABSTRACT

AIMS: Patients with type 2 diabetes mellitus (T2DM) have reduced vasodilatory responses during exercise partially attributable to low nitric oxide (NO) levels. Low NO contributes to greater α-adrenergic mediated vasoconstriction in contracting skeletal muscle. We hypothesized boosting NO bioavailability via 8wks of active beetroot juice (BRA, 4.03 mmol nitrate, 0.29 mmol nitrite, n = 19) improves hyperemia, via reduced α-mediated vasoconstriction, during handgrip exercise relative to nitrate/nitrite-depleted beetroot juice (BRP, n = 18) in patients with T2DM. METHODS: Forearm blood flow (FBF) and vascular conductance (FVC) were calculated at rest and during handgrip exercise (20%max, 20contractions·min-1). Phenylephrine (α1-agonist) and dexmedetomidine (α2-agonist) were infused intra-arterially during independent trials to determine the influence of α-mediated vasoconstriction on exercise hyperemia. Vasoconstriction was quantified as the percent-reduction in FVC during α-agonist infusion, relative to pre-infusion, as well as the absolute change in %FVC during exercise relative to the respective rest trial (magnitude of sympatholysis). RESULTS: ΔFBF (156 ± 69 to 175 ± 73 ml min-1) and ΔFVC (130 ± 54 to 156 ± 63 ml min-1·100 mmHg-1, both P < 0.05) during exercise were augmented following BRA, but not BRP (P = 0.96 and 0.51). Phenylephrine-induced vasoconstriction during exercise was blunted following BRA (-17.1 ± 5.9 to -12.6 ± 3.1%, P < 0.01), but not BRP (P = 0.58) supplementation; the magnitude of sympatholysis was unchanged by either (beverage-by-time P = 0.15). BRA supplementation reduced dexmedetomidine-induced vasoconstriction during exercise (-23.3 ± 6.7 to -19.7 ± 5.2%) and improved the corresponding magnitude of sympatholysis (25.3 ± 11.4 to 34.4 ± 15.5%, both P < 0.05). CONCLUSIONS: BRA supplementation improves the hyperemic and vasodilatory responses to exercise in patients with T2DM which appears to be attributable to reduced α-adrenergic mediated vasoconstriction in contracting skeletal muscle.


Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Exercise/physiology , Nitrates/pharmacology , Nitrites/pharmacology , Vasoconstriction/drug effects , Adrenergic alpha-1 Receptor Agonists/pharmacology , Aged , Beta vulgaris/chemistry , Dexmedetomidine/pharmacology , Dietary Supplements , Female , Fruit and Vegetable Juices , Humans , Male , Middle Aged , Muscle, Skeletal/drug effects , Nitric Oxide/metabolism , Phenylephrine/pharmacology , Plant Roots/chemistry
8.
J Ethnopharmacol ; 285: 114786, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-34763043

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes is a common, complex, chronic metabolic disease. A randomized, double-blind, placebo-parallel controlled clinical study has shown that Gegen Qinlian Decoction (GQD) can reduce glycosylated hemoglobin in type 2 diabetes mellitus (T2DM) intestinal damp-heat syndrome patients in a dose-dependent manner. AIM: To explore the pathogenesis of T2DM intestinal damp-heat syndrome and the therapeutic effect of GQD from the perspective of exosomal microRNA (miRNA). METHODS: Eligible patients were selected and treated with GQD for 3 months to evaluate their clinical efficacy. Effective cases were matched with healthy volunteers, and saliva samples were collected. Exosomal miRNA was extracted from saliva and analyzed by chip sequencing. Subsequently, the function of the differential gene and the signal transduction pathway were analyzed using bioinformatics technology. Finally, three target miRNAs were randomly selected from the T2DM group/healthy group, and two target miRNAs in the T2DM before treatment/after treatment group were randomly selected for qPCR verification. Finally, we conducted a correlation analysis of the miRNAs and clinical indicators. The registration number for this research is ChiCTR-IOR-15006626. RESULTS: (1) The expression of exosomal miRNA chips showed that there were 14 differentially expressed miRNAs in the T2DM group/healthy group, and 26 differentially expressed miRNAs in the T2DM before treatment/after treatment group. (2) Enrichment results showed that in the T2DM group/healthy group, it was primarily related to cell development, body metabolism, TGF-ß, and ErbB signaling pathways. In the T2DM before treatment/after treatment group, it was mainly related to cellular metabolic regulation processes, and insulin, Wnt, and AMPK signaling pathways. (3) The qPCR verification showed that the expressions of hsa-miR-9-5p, hsa-miR-150-5p, and hsa-miR-216b-5p in the T2DM group was higher (P<0.05). Following GQD treatment, hsa-miR-342-3p and hsa-miR-221-3p were significantly downregulated (P<0.05). (4) hsa-miR-9-5p was positively correlated with BMI (P<0.05), and hsa-miR-150-5p was positively correlated with total cholesterol and triglycerides (P<0.05). The GQD efficacy-related gene hsa-miR-342-3p was positively correlated with the patient's initial blood glucose level (P<0.05), and hsa-miR-221-3p was positively correlated with total cholesterol and triglycerides (P<0.05). CONCLUSION: The exosomal miRNA expression profile and signaling pathways related to T2DM intestinal damp-heat syndrome and the efficacy of GQD were established, which provides an alternative strategy for precision traditional Chinese medicine treatment.


Subject(s)
Diabetes Mellitus, Type 2 , Drugs, Chinese Herbal , Exosomes/genetics , Insulin , Intestines , MicroRNAs/analysis , Sequence Analysis, RNA/methods , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/physiopathology , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Female , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Insulin/deficiency , Insulin/metabolism , Intestines/metabolism , Intestines/microbiology , Intestines/physiopathology , Male , Medicine, Chinese Traditional/methods , Middle Aged , Patient Acuity , Signal Transduction/drug effects , Transforming Growth Factor beta/metabolism , Treatment Outcome
9.
J Vasc Res ; 59(1): 24-33, 2022.
Article in English | MEDLINE | ID: mdl-34784595

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the effect of oral supplementation with L-arginine on serum biochemical profile, blood pressure, microcirculation, and vasoreactivity/endothelial function in young controls, and elderly women with and without type 2 diabetes mellitus (T2DM). METHODS: Healthy young (n = 25), healthy elderly (n = 25), and elderly women with type 2 diabetes mellitus (T2DME, n = 23, glycated Hb ≥6.4% and mean of 7.7 years for duration of the disease), aged 18-30 and older than 65 years, respectively, were included in the study. All patients underwent biochemical analysis (fasting glycemia and lipidogram), arterial blood pressure, nailfold videocapillaroscopy (capillary diameters, functional capillary density [FCD], peak red blood cell velocity [RBCVmax] after 1 min ischemia, time to reach peak RBCV [TRBCVmax]), and venous occlusion plethysmography (vasoreactivity), before and after 14 days of oral supplementation with L-arginine (5 g/day). RESULTS: L-Arginine did not change fasting glycemia and lipidogram, but it decreased systolic, diastolic, and mean arterial pressure in elderly women, increased RBCVmax in all groups, and did not decrease TRBCVmax in T2DME. Capillary diameters and FCD remained unchanged in all groups. L-Arginine improved vasoreactivity during reactive hyperemia and after sublingual nitroglycerin (0.4 mg) in all groups. CONCLUSION: L-Arginine supplementation (5g/day during 14 days) was able to improve vascular/microvascular health in the elderly women with or without T2DM.


Subject(s)
Arginine/administration & dosage , Diabetes Mellitus, Type 2/drug therapy , Dietary Supplements , Forearm/blood supply , Hemodynamics/drug effects , Microcirculation/drug effects , Nails/blood supply , Administration, Oral , Adult , Age Factors , Aged , Aged, 80 and over , Arterial Pressure/drug effects , Biomarkers/blood , Case-Control Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/physiopathology , Female , Humans , Microscopic Angioscopy , Plethysmography , Sex Factors , Time Factors , Treatment Outcome , Vasodilation/drug effects , Young Adult
10.
Biomed Res Int ; 2021: 7240046, 2021.
Article in English | MEDLINE | ID: mdl-34746307

ABSTRACT

The dysregulation of glucose metabolism that includes the modification of biomolecules with the help of glycation reaction results in the formation of advanced glycation end products (AGEs). The formation of AGEs may activate receptors for advanced glycation end products which induce intracellular signaling, ultimately enhancing oxidative stress, a well-known contributor to type 2 diabetes mellitus. In addition, AGEs are possible therapeutic targets for the treatment of type 2 diabetes mellitus and its complications. This review article highlights the antioxidant, anti-inflammatory, and antidiabetic properties of the Nymphaea species, and the screening of such aquatic plants for antiglycation activity may provide a safer alternative to the adverse effects related to glucotoxicity. Since oxidation and glycation are relatively similar to each other, therefore, there is a possibility that the Nymphaea species may also have antiglycating properties because of its powerful antioxidant properties. Herbal products and their derivatives are the preeminent resources showing prominent medicinal properties for most of the chronic diseases including type 2 diabetes mellitus. Among these, the Nymphaea species has also shown elevated activity in scavenging free radicals. This species has a load of phytochemical constituents which shows various therapeutic and nutritional value including anti-inflammatory and antioxidant profiles. To the best of our knowledge, this is the first article highlighting the possibility of an antiglycation value of the Nymphaea species by inhibiting AGEs in mediation of type 2 diabetes mellitus. We hope that in the next few years, the clinical and therapeutic potential may be explored and highlight a better perspective on the Nymphaea species in the inhibition of AGEs and its associated diseases such as type 2 diabetes mellitus.


Subject(s)
Diabetes Mellitus, Type 2/metabolism , Glycosylation/drug effects , Nymphaea/metabolism , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Diabetes Mellitus, Type 2/physiopathology , Glycation End Products, Advanced/metabolism , Humans , Hypoglycemic Agents/pharmacology , Oxidation-Reduction , Oxidative Stress/physiology , Phytochemicals/therapeutic use , Plant Extracts/pharmacology
11.
J Diabetes Res ; 2021: 7692447, 2021.
Article in English | MEDLINE | ID: mdl-34805412

ABSTRACT

Reports indicate the increasing prevalence of liver disorders in diabetes mellitus (DM) patients. Clinically, it has also been revealed that the existence of nonalcoholic fatty liver disease (NAFLD) enhances the incidence of type 2 diabetes mellitus (T2DM), while T2DM exacerbates NAFLD to extremely severe forms of steatohepatitis, cirrhosis, and hepatocellular carcinoma. This implies the coexistence and bidirectional nature of NAFLD and T2DM, which function synergistically to drive adverse consequences in clinical practice. For treatment of such comorbid state, though the existing practices such as lifestyle management, traditional Chinese medicines (TCM), and pharmaceuticals have offered somewhat relief, the debate continues about the optimal therapeutic impacts. Recent developments in the field of tissue engineering have led to a renewed interest in novel biomaterial alternatives such as stem cells. This might be attributable to their differentiation potential towards hepatic and pancreatic lineage. These cellular therapies could be further complemented by platelet-derived biomaterials, TCM formulations, or any specific drug. Based on these abovementioned approaches, we aimed to comprehensively analyze various preclinical and clinical studies from traditional to regenerative therapeutic approaches in managing concomitant NAFLD and T2DM.


Subject(s)
Diabetes Mellitus, Type 2/therapy , Drugs, Chinese Herbal/therapeutic use , Healthy Lifestyle , Hypoglycemic Agents/therapeutic use , Liver/physiopathology , Non-alcoholic Fatty Liver Disease/therapy , Regenerative Medicine , Stem Cell Transplantation , Tissue Engineering , Comorbidity , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/physiopathology , Diffusion of Innovation , Drugs, Chinese Herbal/adverse effects , Humans , Hypoglycemic Agents/adverse effects , Incidence , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/physiopathology , Prevalence , Risk Reduction Behavior , Stem Cell Transplantation/adverse effects , Treatment Outcome
12.
Nutrients ; 13(11)2021 Oct 25.
Article in English | MEDLINE | ID: mdl-34836025

ABSTRACT

Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFß-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.


Subject(s)
Diabetic Neuropathies/therapy , Dietary Supplements , Neural Conduction/drug effects , Tocotrienols/administration & dosage , Vitamin E/administration & dosage , Aged , Biomarkers/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/physiopathology , Diabetic Neuropathies/etiology , Diabetic Neuropathies/physiopathology , Double-Blind Method , Female , Humans , Male , Median Nerve/drug effects , Middle Aged , Motor Neurons/drug effects , Sural Nerve/drug effects , Tibia/innervation , Transforming Growth Factor beta1/blood , Treatment Outcome , Vascular Endothelial Growth Factor A/blood
13.
Clin Nutr ; 40(11): 5587-5594, 2021 11.
Article in English | MEDLINE | ID: mdl-34656955

ABSTRACT

BACKGROUND & AIMS: Microalbuminuria is an early sign of vascular complications of type 2 diabetes and predicts cardiovascular disease and mortality. Monomeric and oligomeric flavanols (MOFs) are linked to improved vascular health. The aim of this study was to assess the effect of 3 months MOFs on albuminuria and endothelial function markers in patients with type 2 diabetes and microalbuminuria. METHODS: We conducted a double-blind, placebo-controlled trial among patients with type 2 diabetes and microalbuminuria. Patients with type 2 diabetes received either 200 mg MOFs or placebo daily on top of their habitual diet and medication. The primary endpoint was the between-group difference of the change in 24-h Albumin Excretion Rate (AER) over three months. Secondary endpoints were the between-group differences of the change in plasma levels of different markers of endothelial dysfunction. Mixed-modelling was applied for the longitudinal analyses. RESULTS: Participants (n = 97) were 63.0 ± 9.5 years old; diabetes-duration was 15.7 ± 8.5 years. Median baseline AER was 60 (IQR 20-120) mg/24 h. There was no within-group difference in median change of AER from baseline to 3 months in the intervention (0 (-35-21) mg/24 h, p = 0.41) or the control group (0 (-20-10) mg/24 h, p = 0.91). There was no between-group difference in the course of AER over three months (log-transformed data: ß = -0.02 (95%CI -0.23-0.20), p = 0.88), nor in the plasma levels of the endothelial dysfunction markers. CONCLUSION: Daily 200 mg MOFs for three months on top of habitual diet and usual care did not reduce AER and plasma markers of endothelial dysfunction compared to placebo, in patients with long-term type 2 diabetes and microalbuminuria. CLINICAL TRIALS REGISTRATION: NTR4669, www.trialregister.nl.


Subject(s)
Albuminuria/therapy , Diabetes Mellitus, Type 2/therapy , Dietary Supplements , Endothelium, Vascular/drug effects , Flavonols/administration & dosage , Aged , Albuminuria/complications , Albuminuria/physiopathology , Biomarkers/blood , Biomarkers/urine , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/physiopathology , Double-Blind Method , Female , Flavonols/chemistry , Humans , Male , Middle Aged , Treatment Outcome
14.
Life Sci ; 286: 120068, 2021 Dec 01.
Article in English | MEDLINE | ID: mdl-34688697

ABSTRACT

Cardiovascular disease (CVD) remains the leading cause of mortality in patients with type 2 diabetes (T2D). The conventional therapies seem to offer minimal long-term cardioprotection against diabetes-related complications in patients living with T2D. There is a growing interest in understanding the therapeutic effects of food-derived bioactive compounds in protecting or managing these metabolic diseases. This includes uncovering the therapeutic potential of fat-soluble micronutrients such as vitamin K, which are abundantly found in green leafy vegetables. We searched the major electronic databases including PubMed, Web of Sciences, Scopus, Google Scholar and Science direct. The search retrieved randomized clinical trials and preclinical studies, reporting on the impact of vitamin K on CVD-related complications in T2D. The current review updates clinical evidence on the therapeutic benefits of vitamin K by attenuating CVD-risk factors such as blood lipid profiles, blood pressure, as well as markers of oxidative stress and inflammation in patients with T2D. Importantly, the summarized preclinical evidence provides a unique perspective into the pathophysiological mechanisms that could be targeted by vitamin K in the primary prevention of T2D-related complications. Lastly, this review further explores the controversies related to the cardioprotective effects of vitamin K, and also provides the basic information such as the source and bioavailability profile of this micronutrient is covered to highlight its therapeutic potential.


Subject(s)
Cardiovascular Diseases/prevention & control , Vitamin K/metabolism , Vitamin K/physiology , Cardiotonic Agents/pharmacology , Diabetes Complications/prevention & control , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/physiopathology , Dietary Supplements , Humans , Micronutrients/metabolism , Primary Prevention , Trace Elements , Vitamins
15.
Naunyn Schmiedebergs Arch Pharmacol ; 394(11): 2167-2185, 2021 11.
Article in English | MEDLINE | ID: mdl-34542667

ABSTRACT

The link between diabetes and cognitive dysfunction has been reported in many recent articles. There is currently no disease-modifying treatment available for cognitive impairment. Boswellia serrata (B. serrata) is used traditionally to treat chronic inflammatory diseases such as type 2 diabetes (T2D), insulin resistance (IR), and Alzheimer's disease (AD). This review aims to highlight current research on the potential use of boswellic acids (BAs)/B. serrata extract in T2D and AD. We reviewed the published information through June 2021. Studies have been collected through a search on online electronic databases (Academic libraries as PubMed, Scopus, Web of Science, and Egyptian Knowledge Bank). Accumulating evidence in preclinical and small human clinical studies has indicated that BAs/B. serrata extract has potential therapeutic effect in T2D and AD. According to most of the authors, the potential therapeutic effects of BAs/B. serrata extract in T2D and AD can be attributed to immunomodulatory, anti-inflammatory, antioxidant activity, and elimination of the senescent cells. BAs/B. serrata extract may act by inhibiting the IκB kinase/nuclear transcription factor-κB (IKK/NF-κB) signaling pathway and increasing the formation of selective anti-inflammatory LOX-isoform modulators. In conclusion, BAs/B. serrata extract may have positive therapeutic effects in prevention and therapy of T2D and AD. However, more randomized controlled trials with effective, large populations are needed to show a definitive conclusion about therapeutic efficacy of BAs/B. serrata extract in T2D and AD.


Subject(s)
Boswellia/chemistry , Plant Extracts/pharmacology , Triterpenes/pharmacology , Alzheimer Disease/drug therapy , Alzheimer Disease/physiopathology , Alzheimer Disease/prevention & control , Animals , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antioxidants/isolation & purification , Antioxidants/pharmacology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/prevention & control , Humans , Immunomodulating Agents/isolation & purification , Immunomodulating Agents/pharmacology , Randomized Controlled Trials as Topic , Triterpenes/isolation & purification
16.
Sci Rep ; 11(1): 14892, 2021 07 21.
Article in English | MEDLINE | ID: mdl-34290310

ABSTRACT

The objective of this retrospective observational cohort study was to measure glycemic variability and reductions in body mass index (BMI), blood pressure (BP), and use of antihypertensive medications in type 2 diabetes (T2D) patients participating in the digital twin-enabled Twin Precision Treatment (TPT) Program. Study participants included 19 females and 45 males with T2D who chose to participate in the TPT Program and adhered to program protocols. Nine additional enrollees were excluded due to major program non-adherence. Enrollees were required to have adequate hepatic and renal function, no myocardial infarction, stroke, or angina ≤ 90 days before enrollment, and no history of ketoacidosis or major psychiatric disorders. The TPT program uses Digital Twin technology, machine learning algorithms, and precision nutrition to aid treatment of patients with T2D. Each study participant had ≥ 3 months of follow-up. Outcome measures included glucose percentage coefficient of variation (%CV), low blood glucose index (LBGI), high blood glucose index (HBGI), systolic and diastolic BP, number of antihypertensive medications, and BMI. Sixty-four patients participated in the program. Mean (± standard deviation) %CV, LBGI, and HBGI values were low (17.34 ± 4.35, 1.37 ± 1.37, and 2.13 ± 2.79, respectively) throughout the 90-day program. BMI decreased from 29.23 ± 5.83 at baseline to 27.43 ± 5.25 kg/m2. Systolic BP fell from 134.72 ± 17.73 to 124.58 ± 11.62 mm Hg. Diastolic BP decreased from 83.95 ± 10.20 to 80.33 ± 7.04 mm Hg. The percent of patients taking antihypertensive medications decreased from 35.9% at baseline to 4.7% at 90 days. During 90 days of the TPT Program, patients achieved low glycemic variability and significant reductions in BMI and BP. Antihypertensive medication use was eliminated in nearly all patients. Future research will focus on randomized case-control comparisons.


Subject(s)
Blood Glucose , Blood Pressure , Body Mass Index , Diabetes Mellitus, Type 2/drug therapy , Precision Medicine/methods , Adult , Antihypertensive Agents/therapeutic use , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/physiopathology , Female , Follow-Up Studies , Humans , Machine Learning , Male , Middle Aged , Nutrition Therapy , Outcome Assessment, Health Care , Retrospective Studies
17.
Biomed Res Int ; 2021: 6637656, 2021.
Article in English | MEDLINE | ID: mdl-34258275

ABSTRACT

Despite benefits of physical activity, the level of physical activity is not desirable in patients with type 2 diabetes. The aim of this study is the using of integration of intervention based on the theory of protection motivation and implementation intention in order to improve the level of activity in patients with diabetes. This field trial study has been performed on 125 patients with type 2 diabetes. Samples have been randomly selected, and they are divided into two intervention and control groups. In the intervention group, training sessions were conducted based on the protection motivation theory and implementation intention. Physical activity levels, VO2 max, and hemoglobin A1C were measured before and three months after the intervention in the two groups. Data were analyzed by using SPSS 18, and independent t-test, paired t-test, and equivalent nonparametric tests were used for analyzing abnormal data. The results of this study showed that the level of physical activity was higher in the intervention group (p = 0.02). Also, the amount of hemoglobin A1c in the intervention group has been decreased significantly three months later (p < 0.001). In this study, VO2 max and blood lipids were not significantly different in the two groups. However, there was higher VO2 max compared to before the intervention in the intervention group. The present study showed that combining motivational interventions and implementing intention intervention can be effective in promoting the physical activity of patients with type 2 diabetes.


Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/therapy , Exercise , Health Promotion/methods , Oxygen Consumption , Patient Education as Topic/methods , Adolescent , Adult , Aged , Diabetes Mellitus, Type 2/complications , Female , Glycated Hemoglobin/metabolism , Humans , Iran/epidemiology , Lipids/blood , Male , Middle Aged , Motivation , Motivational Interviewing , Sedentary Behavior , Surveys and Questionnaires , Urban Population , Young Adult
18.
J Ethnopharmacol ; 280: 114464, 2021 Nov 15.
Article in English | MEDLINE | ID: mdl-34329715

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic cognitive dysfunction (DCD) is mainly one of the complications of type 2 diabetes mellitus (T2DM) with complex and obscure pathogenesis. Extensive evidence has demonstrated the effectiveness and safety of traditional Chinese medicine (TCM) for DCD management. AIM OF THE STUDY: This review attempted to systematically summarize the possible pathogenesis of DCD and the current Chinese medicine on the treatment of DCD. MATERIALS AND METHODS: We acquired information of TCM on DCD treatment from PubMed, Web of Science, Science Direct and CNKI databases. We then dissected the potential mechanisms of currently reported TCMs and their active ingredients for the treatment of DCD by discussing the deficiencies and giving further recommendations. RESULTS: Most TCMs and their active ingredients could improve DCD through alleviating insulin resistance, microvascular dysfunction, abnormal gut microbiota composition, inflammation, and the damages of the blood-brain barrier, cerebrovascular and neurons under hyperglycemia conditions. CONCLUSIONS: TCM is effective in the treatment of DCD with few adverse reactions. A large number of in vivo and in vitro, and clinical trials are still needed to further reveal the potential quality markers of TCM on DCD treatment.


Subject(s)
Cognitive Dysfunction/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Drugs, Chinese Herbal/pharmacology , Animals , Cognitive Dysfunction/etiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/physiopathology , Drugs, Chinese Herbal/adverse effects , Humans , Hyperglycemia/drug therapy , Medicine, Chinese Traditional/methods
19.
J Sci Food Agric ; 101(14): 6083-6092, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33899246

ABSTRACT

BACKGROUND: Recent investigations have proposed that sesame and canola oils might affect body fat distribution. The present study aimed to examine the effects of sesame, canola and sesame-canola (a blend of sesame and canola oils) oils on body weight and composition in adults with type 2 diabetes mellitus in the context of a randomized, triple-blind, three-way, cross-over clinical trial. RESULTS: Eligible participants were randomized to replace their regular dietary oil with sesame oil (SO), canola oil (CO) and sesame-canola oil (SCO) (with 40% SO and 60% CO). Treatment periods lasted 9 weeks and were separated by 4-week wash-out periods. Body weight and composition were measured at the beginning, in the middle and at the end of each intervention phase. In total, 93 participants completed the study. After adjustment for confounders, within-period changes were observed following SO and CO intake for body weight (0.34 ± 0.16 kg and 0.33 ± 0.17 kg) and visceral fat (0.13 ± 0.06% and 0.13 ± 0.05%, P < 0.05), respectively. Body mass index was increased within SO intake (0.13 ± 0.05 kg m-2 , P = 0.031). All of the treatment oils resulted in reduced waist circumference and index of central obesity (P < 0.05). A significant difference in change values was observed for visceral fat between SCO (-0.14 ± 0.07%) and SO (0.12 ± 0.08%) treatment periods in females (P = 0.02). CONCLUSION: Sesame and canola oils might lead to a modest favorable body fat redistribution by reducing central adiposity, particularly in females; however, the changes were of little clinical importance. © 2021 Society of Chemical Industry.


Subject(s)
Adipose Tissue/metabolism , Diabetes Mellitus, Type 2/diet therapy , Rapeseed Oil/metabolism , Sesame Oil/metabolism , Adiposity , Body Composition , Body Mass Index , Body Weight , Cross-Over Studies , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/physiopathology , Female , Humans , Male , Middle Aged
20.
J Manipulative Physiol Ther ; 44(3): 205-220, 2021 03.
Article in English | MEDLINE | ID: mdl-33902943

ABSTRACT

OBJECTIVE: The present study aimed to investigate the electromyographic (EMG) indices of muscle fatigue along with biochemical marker of fatigue-that is, blood lactate-during a dynamic fatigue protocol in individuals with type 2 diabetes mellitus (T2DM) vs a healthy control group. Secondarily, it aimed to examine the association between EMG indices of muscle fatigue and blood lactate in these patients. METHODS: Thirty-four participants took part in the study: 19 individuals with T2DM (age, 53.5 ± 6.85 years) and 15 age-matched healthy controls (age, 50.2 ± 3.55 years). Participants performed a dynamic fatigue protocol consisting of 5 sets of 10 repetitions each at an intensity of the 10-repetition maximum. Surface EMG of the vastus medialis and vastus lateralis muscles was recorded during the dynamic fatigue protocol, and EMG indices such as median frequency (MF), slope of MF (MFslope), Dimitrov muscle fatigue spectral index, and root-mean-square were evaluated for each contraction across all the 5 sets. Blood lactate concentrations were also assessed 3 times during the fatigue protocol. RESULTS: Findings revealed that EMG muscle fatigue indices such as MF, MFslope, and Dimitrov muscle fatigue spectral index were significantly altered in individuals with T2DM vs healthy individuals across the sets and repetitions for both the vastus medialis (P < .001) and vastus lateralis muscles (P < .001). There was a significantly greater rise in blood lactate in individuals with T2DM than in healthy individuals (P < .001), which was not found to be associated with changes in EMG indices of muscle fatigue. CONCLUSION: Findings suggest the existence of significantly greater fatigue in the knee extensor muscles of individuals with T2DM than healthy individuals.


Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Muscle Contraction/physiology , Muscle Fatigue/physiology , Muscle, Skeletal/physiology , Adult , Case-Control Studies , Electromyography/methods , Humans , Knee Joint/physiology , Male , Middle Aged , Physical Endurance/physiology , Range of Motion, Articular
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