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1.
Food Res Int ; 188: 114508, 2024 Jul.
Article En | MEDLINE | ID: mdl-38823847

Procyanidins, which are oligomerized flavan-3-ols with a polyphenolic structure, are bioactive substances that exhibit various biological effects. However, the relationship between the degree of polymerization (DP) of procyanidins and their bioactivities remains largely unknown. In this study, the preventive effects of procyanidins with different DP (EC, PB2 and PC1) on glucose improvement and liver lipid deposition were investigated using a high-fat diet/streptozotocin-induced diabetes mouse model. The results demonstrated that all the procyanidins with different DP effectively reduced fasting blood glucose and glucose/insulin tolerance, decreased the lipid profile (total cholesterol, triglyceride, and low-density lipoprotein cholesterol content) in serum and liver tissue as well as the liver oil red staining, indicating the improvement of glucose metabolism, insulin sensitivity and hepatic lipid deposition in diabetic mice. Furthermore, the procyanidins down-regulated expression of glucose regulated 78-kDa protein (GRP78) and C/EBP homologous protein (CHOP), indicating a regulation role of endoplasmic reticulum (ER) stress. The inhibition of ER stress by tauroursodeoxycholic acid (TUDCA) treatment abolished the effects of procyanidins with different DP in PA-induced HepG2 cells, confirming that procyanidins alleviate liver hyperlipidemia through the modulation of ER stress. Molecular docking results showed that EC and PB2 could better bind GRP78 and CHOP. Collectively, our study reveals that the structure of procyanidins, particularly DP, is not directly correlated with the improvement of blood glucose and lipid deposition, while highlighting the important role of ER stress in the bioactivities of procyanidins.


Blood Glucose , Diabetes Mellitus, Experimental , Diet, High-Fat , Endoplasmic Reticulum Chaperone BiP , Lipid Metabolism , Liver , Proanthocyanidins , Animals , Proanthocyanidins/pharmacology , Diet, High-Fat/adverse effects , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Male , Lipid Metabolism/drug effects , Mice , Blood Glucose/metabolism , Blood Glucose/drug effects , Liver/drug effects , Liver/metabolism , Hep G2 Cells , Humans , Polymerization , Endoplasmic Reticulum Stress/drug effects , Molecular Docking Simulation , Biflavonoids/pharmacology , Mice, Inbred C57BL , Streptozocin , Insulin Resistance , Catechin/pharmacology
2.
J Cardiovasc Pharmacol Ther ; 29: 10742484241258381, 2024.
Article En | MEDLINE | ID: mdl-38828542

BACKGROUND: Moxonidine, an imidazoline I1 receptor agonist, is an effective antihypertensive drug that was shown to improve insulin sensitivity. RAAS-blockers are recommended as first-line therapy in patients with diabetes, alone or in combination with a calcium-channel antagonist or a diuretic. AIMS: This study compared the effects of moxonidine and ramipril on blood pressure (BP) and glucose metabolism in overweight patients with mild-to-moderate hypertension and impaired fasting glucose or type 2 diabetes. METHODS: Treatment-naïve patients for hypertension and dysglycemia were randomized to 12 weeks of double-blind moxonidine 0.4 mg or ramipril 5 mg once-daily treatment. At 12 weeks, for a further 12 weeks non-responders received combination of mox/ram, while responders continued blinded treatment. RESULTS: Moxonidine and ramipril were equivalent in lowering SiDBP and SiSBP at the end of the first 12 weeks. The responder rate was approximately 50% in both groups, with a mean SiDBP and SiSBP decrease of 10 and 15 mm Hg in the responders, respectively. The normalization rate (SiDBP < 85 mm Hg) was non significantly different between treatments groups. Moxonidine reduced heart rate (HR) (average -3.5 bpm, p = 0.017) during monotherapy, and when added to ramipril. HbA1c decreased significantly at Week 12 in both groups. Neither drug affected glucose or insulin response to the oral glucose tolerance test. In non-responders, moxonidine/ramipril combination further reduced BP without compromising metabolic parameters. CONCLUSION: Moxonidine 0.4 mg and ramipril 5 mg were equally effective on BP lowering and were well tolerated and mostly metabolically neutral either as monotherapies or in combination. HR was lowered on moxonidine treatment.


Antihypertensive Agents , Blood Glucose , Blood Pressure , Diabetes Mellitus, Type 2 , Drug Therapy, Combination , Heart Rate , Hypertension , Imidazoles , Overweight , Ramipril , Humans , Ramipril/administration & dosage , Ramipril/therapeutic use , Ramipril/pharmacology , Hypertension/drug therapy , Hypertension/physiopathology , Male , Middle Aged , Female , Blood Pressure/drug effects , Heart Rate/drug effects , Double-Blind Method , Imidazoles/pharmacology , Imidazoles/therapeutic use , Imidazoles/administration & dosage , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/pharmacology , Antihypertensive Agents/adverse effects , Blood Glucose/drug effects , Blood Glucose/metabolism , Overweight/drug therapy , Overweight/physiopathology , Overweight/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/physiopathology , Aged , Adult , Treatment Outcome , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/adverse effects
3.
Acta Vet Scand ; 66(1): 23, 2024 May 31.
Article En | MEDLINE | ID: mdl-38822394

BACKGROUND: Alpha2-adrenoceptor agonists (α2-agonists) are widely used in animals as sedatives and for pre-anaesthetic medication. Medetomidine has often been given subcutaneously (SC) to rats, although its absorption rate is slow and the individual variation in serum drug concentrations is high via this route. In addition, α2-agonists have various effects on metabolic and endocrine functions such as hypoinsulinaemia, hyperglycaemia and diuresis. Vatinoxan is a peripherally acting α2-adrenoceptor antagonist that, as a hydrophilic molecule, does not cross the blood-brain barrier in significant quantities and thus alleviates peripheral cardiovascular effects and adverse metabolic effects of α2-agonists. Aim of this study was to evaluate the effects of vatinoxan on sedation, blood glucose concentration, voiding and heart and respiratory rates and arterial oxygen saturation in rats sedated with subcutaneous medetomidine, midazolam and fentanyl. RESULTS: Onset of sedation and loss of righting reflex occurred significantly faster with vatinoxan [5.35 ± 1.08 (mean ± SD) versus 12.97 ± 6.18 min and 6.53 ± 2.18 versus 14.47 ± 7.28 min, respectively]. No significant differences were detected in heart and respiratory rates and arterial oxygen saturation between treatments. Blood glucose concentration (18.3 ± 3.6 versus 11.8 ± 1.2 mmol/L) and spontaneous urinary voiding [35.9 (15.1-41.6), range (median) versus 0.9 (0-8.0) mL /kg/min] were significantly higher without vatinoxan. CONCLUSIONS: Acceleration of induction of sedation, alleviation of hyperglycaemia and prevention of profuse diuresis by vatinoxan may be beneficial when sedating rats for clinical and experimental purposes with subcutaneous medetomidine, midazolam and fentanyl.


Fentanyl , Hypnotics and Sedatives , Medetomidine , Midazolam , Animals , Medetomidine/pharmacology , Medetomidine/administration & dosage , Hypnotics and Sedatives/pharmacology , Hypnotics and Sedatives/administration & dosage , Fentanyl/pharmacology , Fentanyl/administration & dosage , Rats , Male , Midazolam/pharmacology , Midazolam/administration & dosage , Quinolizines/pharmacology , Quinolizines/administration & dosage , Blood Glucose/drug effects , Heart Rate/drug effects , Rats, Sprague-Dawley , Rats, Wistar
4.
Pak J Pharm Sci ; 37(2(Special)): 459-462, 2024 Mar.
Article En | MEDLINE | ID: mdl-38822550

The purpose of this study was to examine the potential hypoglycemic effects of administering ginger (Zingiber officinale) and garlic (Allium sativum) to rats with induced type 2 diabetes. A total of forty-five male adult albino rats were randomly assigned to five groups. The groups were named Normal Control, Diabetic Control, Ginger group, Garlic group and a combination group of ginger and garlic. Diabetes was produced in all groups, except the normal control group, using an intraperitoneal injection of streptozotocin at a dosage of 60 mg/body weight. During the course of two months, rats were administered varying amounts of ginger and garlic powders as part of their treatment After the experiment concluded, measurements were taken for glycated hemoglobin, serum glucose, insulin, cholesterol, high density protein, low density protein and liver glycogen levels. These groups exhibited considerably greater serum insulin and high-density lipoprotein concentrations (P<0.05) compared to the diabetic control group. Conversely, body weight, fasting blood glucose, total cholesterol, low density lipoprotein, and glycated hemoglobin levels were significantly lower (P<0.05) in all groups compared to the diabetic control group. A statistically significant increase (P<0.05) increase shown in liver glycogen levels. This study proposes that the utilization of ginger and garlic powders improve the condition of type 2 diabetes and maybe reduce the risk of subsequent diabetic complications.


Blood Glucose , Diabetes Mellitus, Experimental , Garlic , Hypoglycemic Agents , Insulin , Powders , Zingiber officinale , Animals , Garlic/chemistry , Zingiber officinale/chemistry , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/blood , Male , Blood Glucose/drug effects , Blood Glucose/metabolism , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Rats , Insulin/blood , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Glycated Hemoglobin/metabolism , Plant Extracts/pharmacology , Phytotherapy , Liver Glycogen/metabolism , Streptozocin
5.
Nutr Diabetes ; 14(1): 37, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38824123

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic medical condition affecting more than 95% of people with diabetes. Traditionally, some medicinal plants have been considered as an effective approach in management of T2DM. This trial evaluated the effects of date seed powder (DSP) on glycemia indices and oxidative stress in T2DM patients. METHODS: In this trail, 43 patients with T2DM were randomized to two groups: either 5 g/d of the DSP or placebo for 8 weeks. Levels of glycemic indices, lipolpolysaccharide (LPS), and soluble receptor for advanced glycation end products (s-RAGE), as well as other parameters associated with oxidative stress were assessed at baseline and after 8 weeks. Independent t-test and analysis of covariance (ANCOVA) were used for between-groups comparisons at baseline and the post-intervention phase, respectively. RESULTS: The results showed that supplementation with DSP significantly decreased HbA1c (-0.30 ± 0.48%), insulin (-1.70 ± 2.21 µU/ml), HOMA-IR (-1.05 ± 0.21), HOMA-B (-0.76 ± 21.21), lipopolysaccharide (LPS) (-3.68 ± 6.05 EU/mL), and pentosidine (118.99 ± 21.67 pg/mL) (P < 0.05, ANCOVA adjusted for baseline and confounding factors). On the other hand, DSP supplementation significantly increased total antioxidant capacity (TAC) (0.50 ± 0.26 mmol/L), superoxide dismutase (SOD) (0.69 ± 0.32 U/ml), and s-RAGE (240.13 ± 54.25 pg/mL) compared to the placebo group. FPG, hs-CRP, GPx, CML, and uric acid had no significant within- or between-group changes. CONCLUSION: Supplementation of DSP could be considered an effective strategy to improve glycemic control and oxidative stress in T2DM patients (Registration ID at www.irct.ir : IRCT20150205020965N10).


Blood Glucose , Diabetes Mellitus, Type 2 , Glycated Hemoglobin , Glycation End Products, Advanced , Oxidative Stress , Seeds , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Male , Female , Middle Aged , Glycation End Products, Advanced/blood , Oxidative Stress/drug effects , Glycated Hemoglobin/analysis , Blood Glucose/drug effects , Receptor for Advanced Glycation End Products/blood , Insulin/blood , Adult , Glycemic Index/drug effects , Aged
6.
BMC Endocr Disord ; 24(1): 82, 2024 Jun 06.
Article En | MEDLINE | ID: mdl-38844885

There is equivocal evidence that psyllium can prevent or attenuate increases in fasting blood sugar. Therefore, this systematic review and meta-analysis sought to investigate the influence of psyllium on hemoglobin A1C (HbA1c), fasting blood sugar (FBS), insulin, and Homeostatic Model Assessment of Insulin Resistance (HOMA IR). We searched PubMed, ISI Web of Science (WOS), and Scopus for eligible publications, up to 15 July 2022, including randomized controlled trials (RCT) assessing the effect of psyllium on HbA1c, FBS, insulin, and HOMA IR levels in adults. Using a random effects model, we report the weighted mean differences (WMD) with 95% confidence intervals (CI). In this article, 19 RCT studies, consisting of 962 participants, were included. Psyllium significantly decreased FBS, HbA1c, and HOMA IR levels, but not insulin levels, as compared to placebo (FBS: WMD): -6.89; 95% CI: -10.62, -3.16; p < .001), HbA1c: (WMD: -0.75; 95% CI: -1.21, -0.29; p < .001), HOMA IR: (WMD: -1.17; 95% CI: -2.11, -0.23; p < .05), and insulin: (WMD: -2.08; 95% CI: -4.21, -0.035; p > .05)). Subgroup analyses illustrated differences in the effects of psyllium on FBS: dosages less than and more than 10 g/d showed significant differences (p value < 0.05). However, it was not significant in intervention durations less than 50 days (p value > 0.05). For HbA1c: psyllium consumption less than 10 g/d (p value > 0.05) was non-significant. For HOMA IR and insulin: no significant changes were noted with psyllium consumption less than vs. more than 10 g/d. In conclusion, we found that psyllium could significantly decrease FBS, HbA1c, and HOMA IR levels, but not insulin levels, as compared to placebo.


Blood Glucose , Fasting , Glycated Hemoglobin , Insulin Resistance , Insulin , Psyllium , Randomized Controlled Trials as Topic , Humans , Psyllium/therapeutic use , Glycated Hemoglobin/analysis , Insulin/blood , Blood Glucose/analysis , Blood Glucose/metabolism , Blood Glucose/drug effects , Fasting/blood
9.
J Diabetes Res ; 2024: 3470654, 2024.
Article En | MEDLINE | ID: mdl-38846063

Aims: We compared the glycaemic and cardiorenal effects of combination therapy involving metformin, pioglitazone, sodium-glucose-linked-cotransporter-2 inhibitor (SGLT2i), and glucagon-like peptide-1 receptor agonist (GLP-1RA) versus a more conventional glucocentric treatment approach combining sulphonylureas (SU) and insulin from the point of type 2 diabetes (T2D) diagnosis. Methods: We performed a retrospective cohort study using the Global Collaborative Network in TriNetX. We included individuals prescribed metformin, pioglitazone, an SGLT2i, and a GLP-1 RA for at least 1-year duration, within 3 years of a T2D diagnosis, and compared with individuals prescribed insulin and a SU within the same temporal pattern. Individuals were followed up for 3 years. Results: We propensity score-matched (PSM) for 26 variables. A total of 1762 individuals were included in the final analysis (n = 881 per cohort). At 3-years, compared to the insulin/SU group, the metformin/pioglitazone/SGLT2i/GLP-1 RA group had a lower risk of heart failure (HR 0.34, 95% CI 0.13-0.87, p = 0.018), acute coronary syndrome (HR 0.29, 95% CI 0.12-0.67, p = 0.002), stroke (HR 0.17, 95% CI 0.06-0.49, p < 0.001), chronic kidney disease (HR 0.50, 95% CI 0.25-0.99, p = 0.042), and hospitalisation (HR 0.59, 95% CI 0.46-0.77, p < 0.001). Conclusions: In this real-world study, early, intensive polytherapy, targeting the distinct pathophysiological defects in T2D, is associated with significantly more favourable cardiorenal outcomes, compared to insulin and SU therapy.


Diabetes Mellitus, Type 2 , Drug Therapy, Combination , Glucagon-Like Peptide-1 Receptor , Hypoglycemic Agents , Insulin , Metformin , Sodium-Glucose Transporter 2 Inhibitors , Sulfonylurea Compounds , Humans , Diabetes Mellitus, Type 2/drug therapy , Female , Male , Hypoglycemic Agents/therapeutic use , Retrospective Studies , Middle Aged , Aged , Metformin/therapeutic use , Sulfonylurea Compounds/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Insulin/therapeutic use , Glucagon-Like Peptide-1 Receptor/agonists , Pioglitazone/therapeutic use , Databases, Factual , Blood Glucose/metabolism , Blood Glucose/drug effects , Treatment Outcome
10.
Sultan Qaboos Univ Med J ; 24(2): 243-249, 2024 May.
Article En | MEDLINE | ID: mdl-38828248

Objectives: This study aimed to evaluate the safety and efficacy of remogliflozin compared to vildagliptin as an add-on drug to metformin in type 2 diabetes mellitus (T2DM) treatment. Metformin is considered a first-line drug in T2DM. However, as the disease progresses with heightened insulin resistance and declining ß-cell function, the use of metformin alone is often inadequate to achieve optimum glucose levels. Methods: This prospective, randomised study was conducted at Maulana Azad Medical College and Associated Hospital in New Delhi, India, between February 2020 to January 2021. This study recruited 60 T2DM patients aged 35-70 years with glycated haemoglobin (HbA1c) >6.5% taking metformin at a daily dosage of 1,500-3,000 mg for ≥3 months. Patients were randomly assigned in a 1:1 ratio to receive either vildagliptin (50 mg) or remogliflozin (100 mg) twice daily for 90 days. The primary endpoint was a change in HbA1c levels from baseline to the end of 90 days whereas secondary endpoints were changes in lipid profile and weight. Results: The decrement in mean HbA1c levels was significantly higher in the remogliflozin group than in the vildagliptin group (-8.1% versus -2.4%; P <0.001). In addition, more significant weight loss was found in remogliflozin-treated patients (-5.2% versus -0.6%; P <0.01). Both treatments were well tolerated throughout the study. Conclusion: Compared to vildagliptin, remoglilflozin was significantly more effective in glycaemic control and weight loss in patients with T2DM and can therefore be considered as an add-on drug in T2DM not adequately controlled by metformin monotherapy.


Diabetes Mellitus, Type 2 , Drug Therapy, Combination , Hypoglycemic Agents , Metformin , Vildagliptin , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Vildagliptin/pharmacology , Vildagliptin/therapeutic use , Metformin/therapeutic use , Metformin/pharmacology , Middle Aged , Male , Female , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/pharmacology , Prospective Studies , Aged , Adult , Drug Therapy, Combination/methods , India , Glycated Hemoglobin/analysis , Glycated Hemoglobin/drug effects , Glucosides/therapeutic use , Glucosides/pharmacology , Treatment Outcome , Blood Glucose/analysis , Blood Glucose/drug effects , Sorbitol/analogs & derivatives , Sorbitol/therapeutic use , Sorbitol/pharmacology , Sorbitol/adverse effects , Sorbitol/administration & dosage , Pyrazoles
11.
BMJ Open Diabetes Res Care ; 12(3)2024 May 06.
Article En | MEDLINE | ID: mdl-38719505

INTRODUCTION: There has been increasing evidence that the gut microbiota is closely related to type 2 diabetes (T2D). Metformin (Met) is often used in combination with saxagliptin (Sax) and repaglinide (Rep) for the treatment of T2D. However, little is known about the effects of these combination agents on gut microbiota in T2D. RESEARCH DESIGN AND METHODS: A T2D mouse model induced by a high-fat diet (HFD) and streptozotocin (STZ) was employed. The T2D mice were randomly divided into six groups, including sham, Met, Sax, Rep, Met+Sax and Met+Rep, for 4 weeks. Fasting blood glucose level, serum biochemical index, H&E staining of liver, Oil red O staining of liver and microbiota analysis by 16s sequencing were used to access the microbiota in the fecal samples. RESULTS: These antidiabetics effectively prevented the development of HFD/STZ-induced high blood glucose, and the combination treatment had a better effect in inhibiting lipid accumulation. All these dosing regimens restored the decreasing ratio of the phylum Bacteroidetes: Firmicutes, and increasing abundance of phylum Desulfobacterota, expect for Met. At the genus level, the antidiabetics restored the decreasing abundance of Muribaculaceae in T2D mice, but when Met was combined with Rep or Sax, the abundance of Muribaculaceae was decreased. The combined treatment could restore the reduced abundance of Prevotellaceae_UCG-001, while Met monotherapy had no such effect. In addition, the reduced Lachnospiraceae_NK4A136_group was well restored in the combination treatment groups, and the effect was much greater than that in the corresponding monotherapy group. Therefore, these dosing regimens exerted different effects on the composition of gut microbiota, which might be associated with the effect on T2D. CONCLUSIONS: Supplementation with specific probiotics may further improve the hypoglycemic effects of antidiabetics and be helpful for the development of new therapeutic drugs for T2D.


Adamantane , Blood Glucose , Carbamates , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Diet, High-Fat , Dipeptides , Gastrointestinal Microbiome , Hypoglycemic Agents , Metformin , Piperidines , Animals , Gastrointestinal Microbiome/drug effects , Metformin/pharmacology , Metformin/therapeutic use , Mice , Diet, High-Fat/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/microbiology , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Carbamates/pharmacology , Dipeptides/pharmacology , Male , Adamantane/analogs & derivatives , Adamantane/pharmacology , Adamantane/therapeutic use , Piperidines/pharmacology , Piperidines/therapeutic use , Blood Glucose/analysis , Blood Glucose/drug effects , Mice, Inbred C57BL , Drug Therapy, Combination , Streptozocin
12.
Eur Rev Med Pharmacol Sci ; 28(8): 3275-3286, 2024 Apr.
Article En | MEDLINE | ID: mdl-38708486

OBJECTIVE: This study aimed to compare two routes of administration and different dosages of streptozotocin (STZ) for the pharmacological induction of gestational diabetes mellitus (GDM) in pregnant CD1 females. MATERIALS AND METHODS: 35 female CD1 mice were divided into 5 groups (n = 7). Diabetes mellitus (DM) was induced with STZ by two routes and two doses: 1) Control Group without administration of STZ (CL), 2) Intraperitoneal Group with 200 mg of STZ/Kg of weight (IP200), 3) Intraperitoneal Group with 230 mg of STZ/Kg of weight (IP230), 4) Subcutaneous Group with 200 mg of STZ/Kg of weight (SC200) and 5) Subcutaneous Group with 230 mg of STZ/Kg of weight (SC230). Body weight, food and water intake, glycemia, Homeostatic Model Assessment of Insulin Resistance Index (HOMA-IR), survival, and birth rate were identified. RESULTS: The SC230 group turned out to be the most effective dose and route for the induction of GDM in pregnant females. This scheme managed to reproduce sustained hyperglycemia with high HOMA-IR, the presence of polyphagia, polydipsia, and weight loss. In addition, the birth rate and survival were high compared to the other doses and routes of administration. CONCLUSIONS: The administration of a single dose of 230 mg/kg of weight by subcutaneous route supposes advantages compared to previously used models since it decreases the physiological stress due to manipulation and the costs since it does not require repeated doses or adjuvants such as high lipid diets to potentiate the diabetogenic effect of STZ. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/Graphical-abstract-12.jpg.


Diabetes Mellitus, Experimental , Diabetes, Gestational , Streptozocin , Animals , Female , Pregnancy , Mice , Diabetes Mellitus, Experimental/chemically induced , Streptozocin/administration & dosage , Injections, Subcutaneous , Blood Glucose/metabolism , Blood Glucose/drug effects , Dose-Response Relationship, Drug , Injections, Intraperitoneal , Insulin Resistance , Body Weight/drug effects
13.
Front Endocrinol (Lausanne) ; 15: 1369908, 2024.
Article En | MEDLINE | ID: mdl-38803473

Background: A phenomenon known as legacy effect was observed that poor glycemic control at early stage of patients with newly-diagnosed type 2 diabetes (T2D) increases the risk of subsequent cardiovascular diseases (CVD). Early use of some novel anti-hyperglycemic agents, such as sodium-glucose transport protein 2 inhibitors (SGLT-2i), may attenuate this effect, but the evidence is limited. Methods: Two retrospective cohorts of newly diagnosed T2D patients from 2010-2023 were assembled using the Yinzhou Regional Health Care Database (YRHCD) with different definitions of the early exposure period - the 1-year exposure cohort and 2-year exposure cohort, which were comprised of subjects who had HbA1c measurement data within 1 year and 2 years after their T2D diagnosis, respectively. Using Cox proportional hazards models, we examined the association between high HbA1c level (HbA1c>7%) during the early exposure period and the risk of subsequent CVD. This analysis was performed in the overall cohort and three subpopulations with different treatments during the early exposure period, including patients initiating SGLT-2i or glucagon-like peptide-1 receptor agonists (GLP-1RA), patients using dipeptidyl peptidase-4 inhibitors (DPP-4i), and patients without using SGLT-2i, GLP-1RA, and DPP-4i. Besides, subgroup analyses were performed by stratifying patients into age <55 and ≥55 years. Results: A total of 21,477 and 22,493 patients with newly diagnosed T2D were included in the two final cohorts. Compared with patients with mean HbA1c ≤ 7% during the early exposure period, those with HbA1c>7% had higher risks of incident CVD, with a HR of 1.165 (95%CI, 1.056-1.285) and 1.143 (95%CI, 1.044-1.252) in 1-year and 2-year exposure period cohort. Compared to non-users, in patients initiating SGLT-2i/GLP-1RA within 1 or 2 years after T2D diagnosis, higher HbA1c level at baseline was not associated with CVD in both two cohorts. In subgroup analyses, results were generally consistent with the main analysis. Conclusions: Poor glycemic control in the early stage of T2D increased later CVD risk in Chinese adults with newly diagnosed T2D. Compared to non-users, this association was smaller and non-significant in patients receiving SGLT-2i/GLP-1RA during the early stage of T2D, indicating early use of these drugs may have the potential to mitigate legacy effects of hyperglycemia.


Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Glucagon-Like Peptide-1 Receptor , Hyperglycemia , Sodium-Glucose Transporter 2 Inhibitors , Humans , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Female , Male , Middle Aged , Glucagon-Like Peptide-1 Receptor/agonists , Retrospective Studies , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Hyperglycemia/epidemiology , Hyperglycemia/chemically induced , Aged , Cardiovascular Diseases/epidemiology , Blood Glucose/metabolism , Blood Glucose/analysis , Blood Glucose/drug effects , Glycated Hemoglobin/analysis , Glycated Hemoglobin/metabolism , Hypoglycemic Agents/therapeutic use , Adult , Follow-Up Studies , Glycemic Control , Glucagon-Like Peptide-1 Receptor Agonists
14.
Front Endocrinol (Lausanne) ; 15: 1379830, 2024.
Article En | MEDLINE | ID: mdl-38803476

Background and objective: Psychological insulin resistance (PIR), which refers to the reluctance of diabetic patients to use insulin, is a frequently encountered clinical issue. Needle-free injection (NFI) offers advantages in terms of expediting insulin absorption and mitigating adverse reactions related to injection. To evaluate the effects of subcutaneous injection of insulin aspart 30 with NFI on PIR and insulin dosage in patients with type 2 diabetes mellitus (T2DM). Methods: Sixty-four patients with T2DM participated in this randomized, prospective, open, crossover study. Insulin aspart 30 was administered subcutaneously to each subject via QS-P NFI and Novo Pen 5 (NP) successively. The effects of NFI on PIR were analyzed. Differences in insulin dosage, glycemic variability, and injection safety were compared at similar levels of glycemic control. Results: After the administration of NFI, the insulin treatment attitude scale score decreased (53.7 ± 7.3 vs. 58.9 ± 10.7, p<0.001), the insulin treatment adherence questionnaire score increased (46.3 ± 4.9 vs. 43.8 ± 7.1, p<0.001), and the insulin treatment satisfaction questionnaire score increased (66.6 ± 10.5 vs. 62.4 ± 16.5, p<0.001). At the same blood glucose level, NFI required a smaller dosage of insulin aspart 30 compared with that of NP (30.42 ± 8.70 vs. 33.66 ± 9.13 U/d, p<0.001). There were no differences in glycemic variability indices (standard deviation, mean amplitude of glycemic excursion or coefficient of variation) between the two injection methods. Compared with NP, NFI did not increase the incidence of hypoglycemia (17.2% vs. 14.1%, p=0.774), and it decreased the incidence of induration (4.7% vs. 23.4%, p=0.002) and leakage (6.3% vs. 20.3%, p=0.022) while decreasing the pain visual analog scale score (2.30 ± 1.58 vs. 3.11 ± 1.40, p<0.001). Conclusion: NFI can improve PIR in patients with T2DM and be used with a smaller dose of insulin aspart 30 while maintaining the same hypoglycemic effect. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2400083658.


Blood Glucose , Cross-Over Studies , Diabetes Mellitus, Type 2 , Hypoglycemic Agents , Insulin Aspart , Insulin Resistance , Insulin , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/psychology , Male , Female , Middle Aged , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Injections, Subcutaneous , Insulin Aspart/administration & dosage , Insulin Aspart/therapeutic use , Aged , Prospective Studies , Insulin/administration & dosage , Insulin/therapeutic use , Insulin/analogs & derivatives , Blood Glucose/analysis , Blood Glucose/drug effects , Adult , Insulin, Isophane/administration & dosage , Insulin, Isophane/therapeutic use
15.
Pak J Pharm Sci ; 37(1(Special)): 199-203, 2024 Jan.
Article En | MEDLINE | ID: mdl-38747270

This study investigates the combined effect of vitamin C and chromium on BMI, lipid profile, LFTs and HbA1c of Diabetes Mellitus type 2 patients. This is randomized controlled trial study. For this study a total of 60 patients (n=28 female, n=32 male) Diabetes Mellitus type 2 patients were selected. They were divided into treatment group (vitamin C (500mg) Chromium (200µg) and control group (placebo) comprising thirty patients per group. Mean age in control group and treatment group is 33± 5.729 and 33±7.017 respectively. Statistical analysis showed significant results of lipid profile; total cholesterol (mg/dl) 198±66.1 P=0.008, High-Density Lipoprotein 38±7.5, P<0.001, Low Density Lipoprotein (LDL) (mg/dl) 105.1±22.4, P=0.002 and Triglycerides 191±64.3, P=0.02 are respectively. Levels of serum ALT (u/l) (34.7±9.1, P<0.001) and AST (u/l) (31.6 ±8.6, P<0.001) were significantly lower as compared to control group. HbA1c percentages were also normalized (5.45±0.2, P<.001) as compared to group 2. BMI values were also improved (P=0.01) after treatment. Combined supplementation of vitamin C and chromium reduce the plasma lipid percentage, blood glucose levels and also improve the ALT and AST functions.


Ascorbic Acid , Body Mass Index , Chromium , Diabetes Mellitus, Type 2 , Glycated Hemoglobin , Humans , Female , Male , Ascorbic Acid/therapeutic use , Chromium/therapeutic use , Adult , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Glycated Hemoglobin/metabolism , Hyperglycemia/drug therapy , Hyperglycemia/blood , Hyperlipidemias/drug therapy , Hyperlipidemias/blood , Lipids/blood , Liver/drug effects , Liver/enzymology , Liver/metabolism , Blood Glucose/drug effects , Blood Glucose/metabolism , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Middle Aged
17.
Pak J Pharm Sci ; 37(1): 65-70, 2024 Jan.
Article En | MEDLINE | ID: mdl-38741401

Diabetic nephropathy (DN), a micro vascular complication of diabetes, is the main cause of end-stage renal disease, with a morbidity over 40% of diabetes. High glucose and lipid metabolism dysfunction are the leading cause of the development of DN. Previous study demonstrated that increased expression or activation of SREBPs in models of DN. Leonuride (LE), as an active constituent of Leonurus japonicus Houttuyn, has multiple biological activities, including antioxidant and anti-inflammatory effects. Previous studies showed that increasing the degradation of mature SREBPs is a robust way of lowering lipids and improve lipid metabolism dysfunction. However, effective regulation method of SREBPs degradation are still lacking. Herein, this study indicated that LE can effectively improve glucose and lipid metabolism disorders. In addition, the kidney function was also improved by inhibition of SREBPs activities in streptozocin (STZ)-induced type II diabetic mice. To our knowledge, this is the first time to describe the detailed mechanism of LE on the inhibition of precursor SREBPs, which would present a new direction for diabetic nephropathy treatment.


Diabetes Mellitus, Experimental , Diabetic Nephropathies , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/prevention & control , Animals , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/complications , Male , Mice , Lipid Metabolism/drug effects , Blood Glucose/drug effects , Blood Glucose/metabolism , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Signal Transduction/drug effects , Mice, Inbred C57BL , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications
18.
Pak J Pharm Sci ; 37(1): 79-84, 2024 Jan.
Article En | MEDLINE | ID: mdl-38741403

Vanadyl sulfate (VS), is a component of some food supplements and experimental drugs. This study was carried out to present a novel method for induction of Type 2 diabetes in rats, then for the first time in literature, for evaluating the effect of VS on metabolic parameters and gene expression, simultaneously. 40 male wistar rats were distributed between the four groups, equally. High fat diet and fructose were used for diabetes induction. Diabetic rats treated by two different dose of VS for 12 weeks. Metabolic profiles were evaluated by commercial available kits and gene expression were assayed by real time-PCR. Compared to controls, in non-treated diabetic rats, weight, glucose, triglyceride, total cholesterol, insulin and insulin resistance were increased significantly (p-value <0.05) that indicated induction of type 2 diabetes. Further, the results showed that VS significantly reduced weight, insulin secretion, Tumor Necrosis Factor-alpha (TNF-α) genes expression, lipid profiles except HDL that we couldn't find any significant change and increased Peroxisome Proliferator-Activated Receptor- gamma (PPAR-γ) gene expression in VS-treated diabetic animals in comparison with the non-treated diabetics. Our study demonstrated that vanadyl supplementation in diabetic rats had advantageous effects on metabolic profiles and related gene expression.


Blood Glucose , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , PPAR gamma , Rats, Wistar , Tumor Necrosis Factor-alpha , Vanadium Compounds , Animals , Male , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , PPAR gamma/metabolism , PPAR gamma/genetics , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/genetics , Blood Glucose/drug effects , Blood Glucose/metabolism , Vanadium Compounds/pharmacology , Insulin Resistance , Rats , Insulin/blood , Hypoglycemic Agents/pharmacology , Diet, High-Fat/adverse effects , Gene Expression Regulation/drug effects
19.
Pak J Pharm Sci ; 37(1): 71-78, 2024 Jan.
Article En | MEDLINE | ID: mdl-38741402

Diabetes mellitus, recognized by elevated glucose level in the body fluids is commonly caused by less insulin production or its action. To overcome the complications of diabetes, chemical drugs are never preferred over herbal medicines. Present study was designed to find out the anti-diabetic and health-promoting effects of ethanolic leaf extracts of Cucumis melo and Citrullus lanatus in induced-diabetic albino rats. Thirty male albino rats were bought from the animal house of the university and divided randomly into five feeding groups (n=6). Diabetes was induced in rats of groups A, B, C & D by a single dose of intra-peritoneal injection of streptozotocin (55 mg/Kg), whereas, the rats of group E were considered as control. The rats of groups A, B & C were fed basal diet supplemented with plant extracts (150mg/Kg body weight), whereas; only basal diet was offered to rats of groups D & E. After 28 days of the experiment, blood was collected for biochemical analysis. Results revealed that body weight, glucose, AST, ALB, GGT, HDL, cholesterol, triglyceride, urea and creatinine level differed significantly among treatment groups. It was therefore concluded that ethanolic leaf extracts of Cucumis melo and Citrullus lanatus can be used separately or in combination for the management of diabetes.


Blood Glucose , Citrullus , Cucumis melo , Diabetes Mellitus, Experimental , Hypoglycemic Agents , Lipids , Plant Extracts , Animals , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/blood , Plant Extracts/pharmacology , Cucumis melo/chemistry , Male , Blood Glucose/drug effects , Blood Glucose/metabolism , Citrullus/chemistry , Rats , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/isolation & purification , Lipids/blood , Plant Leaves/chemistry , Kidney/drug effects , Kidney/metabolism , Liver/drug effects , Liver/metabolism , Streptozocin
20.
Pak J Pharm Sci ; 37(1): 163-171, 2024 Jan.
Article En | MEDLINE | ID: mdl-38741413

Medicinal plants contain a wide variety of bioactive phytoconstituents which can serve as new therapeutic agents for several diseases. This study examines the antidiabetic potential of Aitchisonia rosea in alloxan-induced diabetic rats and identifies its bioactive phytoconstituents using GC-MS. In vitro, antidiabetic potential was established using the α-amylase inhibition assay. In vivo, antidiabetic potential was investigated by employing the oral glucose tolerance test (OGTT). GC-MS analysis was used to identify the bioactive phytoconstituents. The in vitro and in vivo tests showed that the aqueous extract of A. rosea possesses better antidiabetic potential. The α-amylase inhibition assay highlighted an IC50 value of 134.87µg/ml. In an oral glucose tolerance test, rats given an aqueous A. rosea extract significantly lowered their blood sugar levels significant reduction in the blood glucose concentration was observed in the oral glucose tolerance test in rats treated with the aqueous A. rosea extract. GC-MS investigation revealed many phytoconstituents, with serverogenin acetate and cycloheptasiloxane tetradecamethyl being important antidiabetic agents. This study found anti-diabetic properties in A. rosea extract. The phytochemical and GC-MS investigation also found serverogenin acetate and cycloheptasiloxane tetradecamethyl, which could be used to develop new antidiabetic drugs.


Blood Glucose , Diabetes Mellitus, Experimental , Gas Chromatography-Mass Spectrometry , Hypoglycemic Agents , Plant Components, Aerial , Plant Extracts , Animals , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/isolation & purification , Hypoglycemic Agents/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/chemically induced , Plant Components, Aerial/chemistry , Male , Blood Glucose/drug effects , Rats , Glucose Tolerance Test , alpha-Amylases/antagonists & inhibitors , alpha-Amylases/metabolism , Rats, Wistar , Phytochemicals/pharmacology , Phytochemicals/analysis , Alloxan
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