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Journal of Developmental and Behavioral... Dec 2023We compared cognitive profile and neuropsychological performance in 9-year-old offspring of mothers who were treated with metformin or insulin for gestational diabetes... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
We compared cognitive profile and neuropsychological performance in 9-year-old offspring of mothers who were treated with metformin or insulin for gestational diabetes mellitus (GDM).
METHODS
A total of 172 children whose mothers were randomly assigned to receive either metformin or insulin for GDM were studied at the age of 9 years. Of these children, 127 were from Turku, Finland (63 metformin and 64 insulin), and 45 from Oulu, Finland (19 metformin and 26 insulin). Clinical and demographic background characteristics were obtained at enrolment, birth, and 9-year follow-up. Cognitive profiles were examined at age 9 years with the Wechsler Intelligence Scale for Children. Neuropsychological functions were examined with 2 subtests of the Developmental Neuropsychological Assessment test battery assessing comprehension of instructions and narrative memory, Trail Making Test assessing attention and with Behavioral Rating Inventory of Executive Functioning, including parent-rated and teacher-rated evaluations. Academic functioning was studied with reading fluency subtest of the Screening test for reading, writing, and calculus for first to sixth grades and information about educational support received at school reported by parents.
RESULTS
The cognitive profiles, including indexes of verbal comprehension, perceptual reasoning, working memory, and processing speed, did not differ significantly between metformin-treated and insulin-treated groups. Significant differences were not found between the treatment groups in assessed neuropsychological functions, reading fluency, or received level of support at school.
CONCLUSION
Cognitive and neuropsychological outcomes were similar in 9-year-old children whose mothers had either metformin or insulin treatment of GDM.
Topics: Child; Humans; Female; Pregnancy; Insulin; Diabetes, Gestational; Mothers; Metformin; Cognition
PubMed: 38019468
DOI: 10.1097/DBP.0000000000001233 -
Biosensors & Bioelectronics Sep 2022Conventional in vitro study often involves the destruction of the cells followed by purification and dilution steps before applying enzymatic assay or metabolomic...
Conventional in vitro study often involves the destruction of the cells followed by purification and dilution steps before applying enzymatic assay or metabolomic analysis. It is a costly and laborious process, and it cannot monitor changes as a function of time. Recently, we have developed a new label-free live-cell FTIR approach that can directly measure biochemical compositional changes within living cells in situ and the spectral changes are shown to be highly specific to the drug applied. In this work, we have demonstrated for the first time the effect of two anti-diabetic drugs, metformin and Resveratrol, on insulin-resistant liver cells (HepG2). Using live-cell FTIR with principal component analysis, we have shown the differences in the biochemical profiles between normal and insulin-resistant cells (p < 0.05), the lack of response/difference from the insulin-resistant cell to insulin (p > 0.05) and the restoration of the biochemical profile and sensitivity to insulin from the insulin-resistant cells after the drug treatment (p < 0.05). Particularly, a rise in the glycogen level, marked by three distinctive peaks at 1150, 1080 and 1020 cm, within the living cells after the anti-diabetic drug treatments is observed. The live-cell FTIR results are confirmed by a parallel gold-standard biochemical assay, demonstrating the restoration of insulin sensitivity of the insulin-resistance cells. Live-cell FTIR can be a complementary tool for drug efficacy screening, especially for insulin sensitizers.
Topics: Biosensing Techniques; Glycogen; Humans; Insulin; Insulin Resistance; Metformin; Resveratrol; Spectroscopy, Fourier Transform Infrared
PubMed: 35671692
DOI: 10.1016/j.bios.2022.114416 -
International Journal of Biological... Apr 2024Combining a Sodium-Glucose-Cotransporter-2-inhibitor (SGLT2i) with metformin is recommended for managing hyperglycemia in patients with type 2 diabetes (T2D) who have...
Combining a Sodium-Glucose-Cotransporter-2-inhibitor (SGLT2i) with metformin is recommended for managing hyperglycemia in patients with type 2 diabetes (T2D) who have cardio-renal complications. Our study aimed to investigate the metabolic effects of SGLT2i and metformin, both individually and synergistically. We treated leptin receptor-deficient (db/db) mice with these drugs for two weeks and conducted metabolite profiling, identifying 861 metabolites across kidney, liver, muscle, fat, and plasma. Using linear regression and mixed-effects models, we identified two SGLT2i-specific metabolites, X-12465 and 3-hydroxybutyric acid (3HBA), a ketone body, across all examined tissues. The levels of 3HBA were significantly higher under SGLT2i monotherapy compared to controls and were attenuated when combined with metformin. We observed similar modulatory effects on metabolites involved in protein catabolism (e.g., branched-chain amino acids) and gluconeogenesis. Moreover, combination therapy significantly raised pipecolate levels, which may enhance mTOR1 activity, while modulating GSK3, a common target of SGLT2i and 3HBA inhibition. The combination therapy also led to significant reductions in body weight and lactate levels, contrasted with monotherapies. Our findings advocate for the combined approach to better manage muscle loss, and the risks of DKA and lactic acidosis, presenting a more effective strategy for T2D treatment.
Topics: Mice; Animals; Humans; Metformin; Diabetes Mellitus, Type 2; 3-Hydroxybutyric Acid; Lactic Acid; Glycogen Synthase Kinase 3; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38503370
DOI: 10.1016/j.ijbiomac.2024.130962 -
International Journal of Epidemiology Apr 2017Existing observational studies provide conflicting evidence for the causal effect of metformin use on cancer risk in patients with type-2 diabetes, and there are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Existing observational studies provide conflicting evidence for the causal effect of metformin use on cancer risk in patients with type-2 diabetes, and there are concerns about bias affecting a number of studies.
METHODS
MEDLINE was used to identify observational studies investigating the association between metformin and overall or site-specific cancer in people with type-2 diabetes. A systematic data extraction and bias assessment was conducted, in which risk of eight bias domains (outcome, exposure, control selection, baseline confounding, time-dependent confounding, immortal time, missing data, censoring methods) were assessed against pre-defined criteria, and rated as unlikely, low, medium or high.
RESULTS
Of 46 studies identified, 21 assessed the effect of metformin on all cancer. Reported relative risks ranged from 0.23 to 1.22, with 12/21 reporting a statistically significant protective effect and none a harmful effect. The range of estimates was similar for site-specific cancers; 3/46 studies were rated as low or unlikely risk of bias in all domains. Two of these had results consistent with no effect of metformin; one observed a moderate protective effect overall, but presented further analyses that the authors concluded were inconsistent with causality. However, 28/46 studies were at risk from bias through exposure definition, 22 through insufficient baseline adjustment and 35 from possible time-dependent confounding.
CONCLUSIONS
Observational studies on metformin and cancer varied in design, and the majority were at risk of a range of biases. The studies least likely to be affected by bias did not support a causal effect of metformin on cancer risk.
Topics: Bias; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Neoplasms; Observational Studies as Topic
PubMed: 28031313
DOI: 10.1093/ije/dyw275 -
Journal of Experimental & Clinical... Dec 2019Growing evidence showed the increased prevalence of cancer incidents, particularly colorectal cancer, among type 2 diabetic mellitus patients. Antidiabetic medications... (Review)
Review
Growing evidence showed the increased prevalence of cancer incidents, particularly colorectal cancer, among type 2 diabetic mellitus patients. Antidiabetic medications such as, insulin, sulfonylureas, dipeptyl peptidase (DPP) 4 inhibitors and glucose-dependent insulinotropic peptide (GLP-1) analogues increased the additional risk of different cancers to diabetic patients. Conversely, metformin has drawn attention among physicians and researchers since its use as antidiabetic drug exhibited beneficial effect in the prevention and treatment of cancer in diabetic patients as well as an independent anticancer drug. This review aims to provide the comprehensive information on the use of metformin at preclinical and clinical stages among colorectal cancer patients. We highlight the efficacy of metformin as an anti-proliferative, chemopreventive, apoptosis inducing agent, adjuvant, and radio-chemosensitizer in various colorectal cancer models. This multifarious effects of metformin is largely attributed to its capability in modulating upstream and downstream molecular targets involved in apoptosis, autophagy, cell cycle, oxidative stress, inflammation, metabolic homeostasis, and epigenetic regulation. Moreover, the review highlights metformin intake and colorectal cancer risk based on different clinical and epidemiologic results from different gender and specific population background among diabetic and non-diabetic patients. The improved understanding of metformin as a potential chemotherapeutic drug or as neo-adjuvant will provide better information for it to be used globally as an affordable, well-tolerated, and effective anticancer agent for colorectal cancer.
Topics: Animals; Antineoplastic Agents; Cell Proliferation; Cell Survival; Clinical Trials as Topic; Colorectal Neoplasms; Humans; Metformin
PubMed: 31831021
DOI: 10.1186/s13046-019-1495-2 -
Cells Sep 2022For over 60 years, metformin has been widely prescribed by physicians to treat type 2 diabetes. Along with more in-depth research on metformin and its molecular... (Review)
Review
For over 60 years, metformin has been widely prescribed by physicians to treat type 2 diabetes. Along with more in-depth research on metformin and its molecular mechanism in recent decades, metformin has also been proposed as an effective drug to prevent or delay musculoskeletal disorders, including osteoarthritis (OA). The occurrence and development of OA are deemed to be associated with the impaired mitochondrial functions of articular chondrocytes. Metformin can activate the pathways and expressions of both AMPK and SIRT1 so as to protect the mitochondrial function of chondrocytes, thereby promoting osteoblast production. Moreover, the clinical significance of the metformin combination therapy in preventing OA has also been demonstrated. This review aimed to comprehensively summarize the current research progress on metformin as a proposed drug for OA prevention or treatment.
Topics: AMP-Activated Protein Kinases; Diabetes Mellitus, Type 2; Humans; Metformin; Osteoarthritis; Sirtuin 1
PubMed: 36230974
DOI: 10.3390/cells11193012 -
Biomedicine & Pharmacotherapy =... Sep 2023In addition to the anti-diabetic effect of metformin, a growing number of studies have shown that metformin has some exciting properties, such as anti-oxidative... (Review)
Review
In addition to the anti-diabetic effect of metformin, a growing number of studies have shown that metformin has some exciting properties, such as anti-oxidative capabilities, anticancer, genomic stability, anti-inflammation, and anti-fibrosis, which have potent, that can treat other disorders other than diabetes mellitus. We aimed to describe and review the protective and antidotal efficacy of metformin against biologicals, chemicals, natural, medications, pesticides, and radiation-induced toxicities. A comprehensive search has been performed from Scopus, Web of Science, PubMed, and Google Scholar databases from inception to March 8, 2023. All in vitro, in vivo, and clinical studies were considered. Many studies suggest that metformin affects diseases other than diabetes. It is a radioprotective and chemoprotective drug that also affects viral and bacterial diseases. It can be used against inflammation-related and apoptosis-related abnormalities and against toxins to lower their effects. Besides lowering blood sugar, metformin can attenuate the effects of toxins on body weight, inflammation, apoptosis, necrosis, caspase-3 activation, cell viability and survival rate, reactive oxygen species (ROS), NF-κB, TNF-α, many interleukins, lipid profile, and many enzymes activity such as catalase and superoxide dismutase. It also can reduce the histopathological damages induced by many toxins on the kidneys, liver, and colon. However, clinical trials and human studies are needed before using metformin as a therapeutic agent against other diseases.
Topics: Humans; Metformin; Hypoglycemic Agents; Antioxidants; Apoptosis; Liver; Inflammation; Oxidative Stress
PubMed: 37541178
DOI: 10.1016/j.biopha.2023.115263 -
Frontiers in Endocrinology 2022Metformin is the first-line oral treatment for type 2 diabetes mellitus and is prescribed to more than 150 million people worldwide. Metformin's effect as a...
Metformin is the first-line oral treatment for type 2 diabetes mellitus and is prescribed to more than 150 million people worldwide. Metformin's effect as a glucose-lowering drug is well documented but the precise mechanism of action is unknown. A recent finding of an association between paternal metformin treatment and increased numbers of genital birth defects in sons and a tendency towards a skewed secondary sex ratio with less male offspring prompted us to focus on other evidence of reproductive side effects of this drug. Metformin in humans is documented to reduce the circulating level of testosterone in both men and women. In experimental animal models, metformin exposure induced sex-specific reproductive changes in adult rat male offspring with reduced fertility manifested as a 30% decrease in litter size and metformin exposure to fish, induced intersex documented in testicular tissue. Metformin is excreted unchanged into urine and feces and is present in wastewater and even in the effluent of wastewater treatment plants from where it spreads to rivers, lakes, and drinking water. It is documented to be present in numerous freshwater samples throughout the world - and even in drinking water. We here present the hypothesis that metformin needs to be considered a potential reproductive toxicant for humans, and probably also for wildlife. There is an urgent need for studies exploring the association between metformin exposure and reproductive outcomes in humans, experimental animals, and aquatic wildlife.
Topics: Humans; Male; Female; Rats; Animals; Metformin; Diabetes Mellitus, Type 2; Drinking Water; Reproduction; Fertility
PubMed: 36339411
DOI: 10.3389/fendo.2022.1000872 -
Ugeskrift For Laeger Dec 2015Polycystic ovary syndrome (PCOS) is associated with insulin resistance, infertility, obesity and gestational complications. Metformin is widely used in fertility... (Review)
Review
Polycystic ovary syndrome (PCOS) is associated with insulin resistance, infertility, obesity and gestational complications. Metformin is widely used in fertility treatment of women with PCOS, due to a suggested positive effect of continued metformin treatment beyond the first trimester on pregnancy complications. Larger randomized trials have failed to confirm this. Metformin treatment has not been found to be superior to insulin treatment in women with gestational diabetes and may be associated with long-term consequences in the children in the form of overweight and disturbed glucose metabolism.
Topics: Breast Feeding; Diabetes, Gestational; Female; Humans; Hypoglycemic Agents; Metformin; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Prenatal Exposure Delayed Effects
PubMed: 26651913
DOI: No ID Found -
International Journal of Molecular... Mar 2022Myotonic dystrophy type 1 (DM1) is a multisystemic disorder of genetic origin. Progressive muscular weakness, atrophy and myotonia are its most prominent neuromuscular... (Review)
Review
Myotonic dystrophy type 1 (DM1) is a multisystemic disorder of genetic origin. Progressive muscular weakness, atrophy and myotonia are its most prominent neuromuscular features, while additional clinical manifestations in multiple organs are also common. Overall, DM1 features resemble accelerated aging. There is currently no cure or specific treatment for myotonic dystrophy patients. However, in recent years a great effort has been made to identify potential new therapeutic strategies for DM1 patients. Metformin is a biguanide antidiabetic drug, with potential to delay aging at cellular and organismal levels. In DM1, different studies revealed that metformin rescues multiple phenotypes of the disease. This review provides an overview of recent findings describing metformin as a novel therapy to combat DM1 and their link with aging.
Topics: Humans; Hypoglycemic Agents; Metformin; Muscle Weakness; Myotonic Dystrophy; Phenotype
PubMed: 35270043
DOI: 10.3390/ijms23052901