Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Low metformin dose and its therapeutic serum concentration in prediabetes.

ABSTRACT: This prospective study aimed to analyze whether the patients with pre-diabetes (pre-DM) reach the TC (therapeutic concentration) of the metformin during repeated, low, constant drug dose. The guidelines do not recommend any metformin dose for this group of patients. Based on the previous study after a dose of 1700 mg/day the patients seem to reach the therapeutic drug concentration, which guarantees the glycemic effect. Twenty patients with new-diagnosed pre-DM were treated with a 1500 mg/day regimen of the metformin for 15 weeks. The serum concentration of the drug was assessed by liquid chromatography-mass spectrometry technique at 6 and 15 week of the treatment. The correlation of the serum metformin concentration with BMI (body mass index) and patients' weight was also performed. The mean metformin concentration was: 4.65 μmol/L (± 2.41) and 5.41 μmol/L (± 3.44) (p = 0.27) after 6 and 15 weeks of the treatment respectively. There was a positive correlation between the serum concentration of the metformin and body weight (but not BMI) in the 15th week of the therapy (p = 0.04)- the higher body weight the higher concentration of the metformin. Patients with pre-diabetes can be successfully treated with a low dose of metformin, to reach the drug's therapeutic concentration. Body weight can impact the metformin serum concentration during long-term treatment what should be taken into consideration when choosing the dose because of its pleiotropic effect e.g. on the cardiovascular system via reduction of the oxidative stress and would be not connected with the drug's hypoglycemic effect.ClinicalTrials.gov number: NCT03398356; date of first registration: 01/07/2018.

SUBMITTER: Sutkowska E

PROVIDER: S-EPMC8175603 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Therapeutic Use of Metformin in Prediabetes and Diabetes Prevention.

Project description:People with elevated, non-diabetic, levels of blood glucose are at risk of progressing to clinical type 2 diabetes and are commonly termed 'prediabetic'. The term prediabetes usually refers to high-normal fasting plasma glucose (impaired fasting glucose) and/or plasma glucose 2 h following a 75 g oral glucose tolerance test (impaired glucose tolerance). Current US guidelines consider high-normal HbA1c to also represent a prediabetic state. Individuals with prediabetic levels of dysglycaemia are already at elevated risk of damage to the microvasculature and macrovasculature, resembling the long-term complications of diabetes. Halting or reversing the progressive decline in insulin sensitivity and ?-cell function holds the key to achieving prevention of type 2 diabetes in at-risk subjects. Lifestyle interventions aimed at inducing weight loss, pharmacologic treatments (metformin, thiazolidinediones, acarbose, basal insulin and drugs for weight loss) and bariatric surgery have all been shown to reduce the risk of progression to type 2 diabetes in prediabetic subjects. However, lifestyle interventions are difficult for patients to maintain and the weight loss achieved tends to be regained over time. Metformin enhances the action of insulin in liver and skeletal muscle, and its efficacy for delaying or preventing the onset of diabetes has been proven in large, well-designed, randomised trials, such as the Diabetes Prevention Program and other studies. Decades of clinical use have demonstrated that metformin is generally well-tolerated and safe. We have reviewed in detail the evidence base supporting the therapeutic use of metformin for diabetes prevention.

| S-EPMC4498279 | biostudies-literature

Metformin improves the therapeutic efficacy of low-dose albendazole against experimental alveolar echinococcosis.

Project description:Alveolar echinococcosis (AE) is a severe disease caused by Echinococcus multilocularis. Its chemotherapeutic treatment is based on benzimidazoles, which are rarely curative and cause several adverse effects. Therefore, it is necessary to develop alternative and safer chemotherapeutic strategies against AE. It has previously been shown that metformin (Met) exhibits considerable in vivo activity on an early-infection model of AE when administered at 50 mg kg−1 day−1 for 8 weeks. Here, the challenge is heightened by a 2-fold increase in parasite inoculum or by starting the treatment 6 weeks post-infection. In both cases, only the combination of Met (100 mg kg−1 day−1) together with a sub-optimal dose of albendazole (ABZ) (5 mg kg−1 day−1) led to a significant reduction in parasite weight compared to the untreated group. Coincidentally, drug combination showed the highest level of damage in E. multilocularis metacestodes. Likewise, Met alone or combined with ABZ led to a decrease in parasite glucose availability, which was evidenced as a lower intracystic glucose concentration. Therefore, the results demonstrate that combination therapy with Met and ABZ offers an alternative to improve the efficacy and reduce the toxicity of the high-dose ABZ monotherapy currently employed.

| S-EPMC11010535 | biostudies-literature

Low-dose metformin targets the lysosome-AMPK pathway through PEN2

Project description:Metformin is the most prescribed anti-diabetic medicine, and has also been shown to have other various benefits, such as anti-aging and anti-cancer effects. For clinical doses of metformin, it is known that AMPK plays a major role; however, the direct molecular target of metformin remains unclear. Here, we found that clinically relevant concentrations of metformin inhibits the lysosomal proton pump (v-ATPase), which has been shown to be a central node for AMPK activation upon glucose starvation. We synthesised a photoactive metformin probe, and identified that PEN2, a subunit of γ-secretases, is a binding partner of metformin with KD at micromolar levels. Metformin-bound PEN2 then forms a complex with ATP6AP1, a subunit of the v-ATPase, leading to inhibition of v-ATPase and activation of AMPK without affecting cellular AMP levels. Knockout of PEN2, or re-introduction of a PEN2 mutant that fails to bind ATP6AP1, blunts AMPK activation. In vivo, liver-specific knockout of PEN2 abolishes metformin-mediated reduction of hepatic fat content, and intestine-specific knockout of PEN2 impairs its glucose-lowering effects. Furthermore, knockdown of PEN2 in Caenorhabditis elegans abrogates metformin-induced extension of lifespan. Together, these findings reveal that metformin binds to PEN2, initiating a signalling route that intersects, via ATP6AP1, the lysosomal glucose-sensing pathway for AMPK activation, ensuring that metformin manifests therapeutic benefits without significant drawbacks in patients.

2021-12-01 | PXD030090 |

Low-dose metformin targets the lysosomal AMPK pathway through PEN2.

Project description:Metformin, the most prescribed antidiabetic medicine, has shown other benefits such as anti-ageing and anticancer effects1-4. For clinical doses of metformin, AMP-activated protein kinase (AMPK) has a major role in its mechanism of action4,5; however, the direct molecular target of metformin remains unknown. Here we show that clinically relevant concentrations of metformin inhibit the lysosomal proton pump v-ATPase, which is a central node for AMPK activation following glucose starvation6. We synthesize a photoactive metformin probe and identify PEN2, a subunit of γ-secretase7, as a binding partner of metformin with a dissociation constant at micromolar levels. Metformin-bound PEN2 forms a complex with ATP6AP1, a subunit of the v-ATPase8, which leads to the inhibition of v-ATPase and the activation of AMPK without effects on cellular AMP levels. Knockout of PEN2 or re-introduction of a PEN2 mutant that does not bind ATP6AP1 blunts AMPK activation. In vivo, liver-specific knockout of Pen2 abolishes metformin-mediated reduction of hepatic fat content, whereas intestine-specific knockout of Pen2 impairs its glucose-lowering effects. Furthermore, knockdown of pen-2 in Caenorhabditis elegans abrogates metformin-induced extension of lifespan. Together, these findings reveal that metformin binds PEN2 and initiates a signalling route that intersects, through ATP6AP1, the lysosomal glucose-sensing pathway for AMPK activation. This ensures that metformin exerts its therapeutic benefits in patients without substantial adverse effects.

| S-EPMC8891018 | biostudies-literature

Metformin Use in Prediabetes Among U.S. Adults, 2005-2012.

Project description:ObjectiveTo determine the prevalence of and characteristics associated with metformin use among U.S. adults with prediabetes using the National Health and Nutrition Examination Survey (NHANES) 2005-2012.Research design and methodsThe American Diabetes Association's guidelines for metformin use in prediabetes have evolved, with 2017 recommendations suggesting metformin be considered in patients with prediabetes and additional risk factors (BMI ≥35 kg/m2, age <60 years, or prior gestational diabetes mellitus) or rising hemoglobin A1c (HbA1c). We estimated the age-adjusted prevalence of metformin use among individuals with prediabetes (defined by HbA1c 5.7-6.4%, fasting glucose 100-125 mg/dL, 2-h poststimulated glucose 140-199 mg/dL, or self-report) and used multivariate logistic regression to evaluate characteristics associated with metformin use.ResultsOf 22,174 adults, 7,652 had prediabetes. The age-adjusted prevalence of metformin use among those with prediabetes was 0.7%. Metformin use was associated with higher mean BMI (35.1 kg/m2 vs. 29.6 kg/m2, P < 0.01) and higher glucose (fasting glucose 114 mg/dL vs. 105 mg/dL, P = 0.03; 2-h poststimulated glucose 155 mg/dL vs. 128 mg/dL, P = 0.003; and HbA1c 6.0% [42 mmol/mmol] vs. 5.6% [38 mmol/mmol], P < 0.01). Metformin use was low even among those with BMI ≥35 kg/m2, a group for whom metformin use is recommended. Metformin use did not vary by race, poverty-to-income ratio, or education.ConclusionsMetformin use was <1% among U.S. adults with prediabetes and only slightly more common among those with additional risk factors for diabetes.

| S-EPMC5481991 | biostudies-literature

Serum amyloid P component: a new biomarker for low sperm concentration?

Project description:Serum amyloid P component (SAP) is present in seminal plasma, on spermatozoa, and in different tissues of the male reproductive tract, but its function is not known. The aims of this study were to determine if the concentration of SAP in seminal plasma is associated with commonly assessed semen parameters and to investigate if SAP could be a new, indirect biomarker for these parameters. In a cross-sectional study of 203 young volunteers, the concentration of SAP in seminal plasma was measured with a in-house developed enzyme-linked immunosorbent assay. Scatter plots, Pearson's correlation coefficients (r), and linear regression models were produced, and SAP showed a statistically significant correlation with sperm concentration (r = 0.75), sperm number (r = 0.68), semen volume (r = -0.19), progressive sperm motility (r = 0.24), and sperm immotility (r = -0.20). When the study group was dichotomized, SAP could be used to discriminate samples with a sperm concentration < or ≥5 × 106 ml-1, 15 × 106 ml-1, or 40 × 106 ml-1, and in receiver operating characteristic curves, the corresponding areas under the curves were 0.97, 0.93, and 0.82, respectively, with P < 0.001 for all three cutoff values studied. The concentration of SAP in seminal plasma showed a strong, positive correlation with the concentration of spermatozoa in semen. SAP may be used as a new indirect potential biomarker for sperm concentration in fresh and in frozen, stored samples. In addition, it is envisaged that the assay could be developed into a home fertility test to differentiate between a low and a normal sperm concentration.

| S-EPMC8451485 | biostudies-literature

Increase in serum albumin concentration is associated with prediabetes development and progression to overt diabetes independently of metabolic syndrome.

Project description:AimSerum albumin concentration is associated with both type 2 diabetes and metabolic syndrome (MetS). We sought to investigate whether baseline serum albumin and change in serum albumin could be independent risk factors for prediabetes in subjects without MetS. We further examined the effect of serum albumin on progression to overt diabetes in subjects who developed prediabetes.MethodsAmong 10,792 participants without diabetes and MetS who consecutively underwent yearly health check-ups over six years, 9,807 subjects without incident MetS were enrolled in this longitudinal retrospective study. The risk of developing prediabetes (impared fasting glucose or hemoglobin A1c) was analyzed according to baseline and percent change in serum albumin concentration using Cox regression analysis. Serial changes in serum albumin concentration were measured from baseline to one year before prediabetes diagnosis, and then from the time of prediabetes diagnosis to progression to overt diabetes or final follow-up.ResultsA total of 4,398 incident cases of prediabetes developed during 35,807 person-years (median 3.8 years). The hazard ratio for incident prediabetes decreased as percent change in serum albumin concentration (quartiles and per 1%) increased in a crude and fully adjusted model. However, baseline serum albumin concentration itself was not associated with prediabetic risk. Serum albumin levels kept increasing until the end of follow-up in prediabetic subjects who returned to normal glycemic status, whereas these measures did not change in prediabetic subjects who developed type 2 diabetes. Serum albumin concentration measured at the end of follow-up was the highest in the regression group, compared to the stationary (p = 0.014) or progression groups (p = 0.009).ConclusionsIncrease in serum albumin concentration might protect against early glycemic deterioration and progression to type 2 diabetes even in subjects without MetS.

| S-EPMC5400249 | biostudies-literature

Efficacy of glimepiride/metformin fixed-dose combination vs metformin uptitration in type 2 diabetic patients inadequately controlled on low-dose metformin monotherapy: A randomized, open label, parallel group, multicenter study in Korea.

Project description:To compare the efficacy and safety of early combination therapy with glimepiride/metformin to metformin uptitration in reducing glycated hemoglobin (HbA1c) levels in Korean type 2 diabetic patients inadequately controlled on low-dose metformin monotherapy.In a randomized, open label, parallel group, multicenter study, 209 Korean type 2 diabetic patients (HbA1c 7.0-10.0%, on metformin 500-1,000 mg/day) received glimepiride/metformin fixed-dose combination (G/M FDC) or metformin uptitration treatment (Met UP). The primary end-point was the change in HbA1c from baseline to week 24.G/M FDC therapy provided significantly greater adjusted mean decreases vs Met UP therapy in HbA1c (-1.2 vs -0.8%, P < 0.0001), and fasting plasma glucose (-35.7 vs -18.6 mg/dL, P < 0.0001). A significantly greater proportion of patients with G/M FDC therapy achieved HbA1c < 7% (74.7 vs 46.6%, P < 0.0001) at the end of the study. More patients experienced hypoglycemia with G/M FDC therapy compared with Met UP therapy (41 vs 5.6%, P < 0.0001), but there was no serious hypoglycemia in any group. A modest increase in mean bodyweight occurred in the patients who were treated with G/M FDC therapy (1.0 kg), whereas a slight decrease was observed in the patients who were treated with Met UP therapy (-0.7 kg).The present study showed that glimepiride/metformin fixed-dose combination therapy was more effective in glycemic control than metformin uptitration, and was well tolerated in type 2 diabetic patients inadequately controlled by low-dose metformin monotherapy in Korea. This trial was registered with ClinicalTrial.gov (no. NCT00612144).

| S-EPMC4234234 | biostudies-literature

Metformin ameliorates diabetic nephropathy in a rat model of low-dose streptozotocin-induced diabetes.

Project description:The present study aimed to explore the renoprotective effect of metformin on diabetic nephropathy in type 2 diabetic rats. A rat model of type 2 diabetic nephropathy (T2DN) was successfully induced via a high-fat diet combined with a single low-dose of streptozotocin. Metformin was administered intragastrically for 13 weeks, and fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), HDL-c, LDL-c, urinary and serum creatinine levels were subsequently examined at the end of administration. Renal function was determined after the treatment protocol. Expression levels of transforming growth factor (TGF)-?1 and connective tissue growth factor (CTGF) were assessed via immunohistochemical analysis. Superoxide dismutase activity, malondialdehyde content and glutathione peroxidase levels were assessed in kidney tissues using commercially available kits. The results of the present study demonstrated that metformin administration significantly decreased the levels of serum blood urea nitrogen, serum creatinine, creatinine clearance, urinary albumin excretion and fasting blood glucose in rats with T2DN. Furthermore, TG, TC and LDL-c levels were significantly decreased following metformin treatment, whereas HDL-c was increased. Metformin treatment significantly increased SOD activity and significantly decreased malondialdehyde levels, as compared with the model group. It was also demonstrated that metformin administration significantly decreased the expression levels of TGF-?1 and attenuated the morphological changes associated with T2DN in rats. These data clearly demonstrated the renoprotective effects of metformin against the development and progression of T2DN in rats. The underlying mechanism of this protective effect may be associated with glycemic control, lipid metabolism, and anti-oxidative and anti-inflammatory functions.

| S-EPMC5488633 | biostudies-literature

Hyperglucagonemia Mitigates the Effect of Metformin on Glucose Production in Prediabetes.

Project description:The therapeutic mechanism of metformin action remains incompletely understood. Whether metformin inhibits glucagon-stimulated endogenous glucose production (EGP), as in preclinical studies, is unclear in humans. To test this hypothesis, we studied nine prediabetic individuals using a randomized, placebo-controlled, double-blinded, crossover study design. Metformin increased glucose tolerance, insulin sensitivity, and plasma glucagon. Metformin did not alter average basal EGP, although individual variability in EGP correlated with plasma glucagon. Metformin increased basal EGP in individuals with severe hyperglucagonemia (>150 pg/ml). Decreased fasting glucose after metformin treatment appears to increase glucagon to stimulate EGP and prevent further declines in glucose. Similarly, intravenous glucagon infusion elevated plasma glucagon (>150 pg/ml) and stimulated a greater increase in EGP during metformin therapy. Metformin also counteracted the protein-catabolic effect of glucagon. Collectively, these data indicate that metformin does not inhibit glucagon-stimulated EGP, but hyperglucagonemia may decrease the ability of the metformin to lower EGP in prediabetic individuals.

| S-EPMC4871720 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data