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2.
Medicine (Baltimore) ; 99(11): e18831, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32176027

RESUMEN

This study aimed to investigate diabetes distress, happiness, and its associated factors of patients with type 2 diabetes mellitus (T2DM) treated by different therapies, and to analyze the related impact factors. A total of 1512 patients with T2DM were randomly selected from 18 tertiary hospitals in Hunan province from January 2016 to April 2016 who has been treated with oral antidiabetics monotherapy, insulin monotherapy, and combination therapy. Use the general information questionnaire, WHO-5 (the World Health Organization 5 well-being index) and PAID (the problem areas in diabetes scale) to collect the data. There are 846 (55.95%) patients that have serious emotional disorders, and the diabetes related distress in insulin treatment group was higher than that in combination treatment group (P < .05). Happiness of T2DM patients in combination therapy was higher than oral antidiabetic drug monotherapy and insulin monotherapy (P < .05). There was a negative correlation between diabetic suffering and happiness in patients with different treatments (R ranged from -0.335 to -0.436, P < .001). Age and happiness experience could explain 14.8% of the variance. Acute and chronic complications, controlled blood glucose level, lifestyle, therapies, and school education can explain 18.3% variance. Under different therapies, the suffering and happiness of T2DM patients differed from each other. The suffering and happiness of T2DM were related to different therapies, age, complications, glycaemic control, lifestyle, school education, and so on.


Asunto(s)
Diabetes Mellitus Tipo 2/psicología , Felicidad , Estrés Psicológico/etiología , Adulto , Anciano , China , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Estrés Psicológico/terapia , Encuestas y Cuestionarios
3.
Medicine (Baltimore) ; 99(11): e19501, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32176092

RESUMEN

BACKGROUND: Clinical and basic research supports that blood glucose fluctuation is an important predictor of diabetic vascular disease and an etiology of lower extremity atherosclerosis, which is an important pathological basis for lower extremity vascular diseases. Previous Chinese National Natural Science Foundation trials (No. 81503566) have reported that the traditional Chinese medicine Shenqi compound can reduce blood glucose fluctuation and low-grade inflammation, and protect blood vessels; however, there are no high-quality clinical evidences available to support the same. This multicenter randomized controlled trial aims to obtain more clinical evidence to confirm the efficacy and safety of Shenqi compound in type 2 diabetes with lower extremity atherosclerosis. METHODS: A multicenter RCT will be implemented in this study for a 32-week study period (8 weeks for intervention and 24 weeks for follow-up). Participants will be recruited from the Teaching Hospital of Chengdu University of TCM, Mianyang Hospital of TCM, and Shuangliu Hospital of TCM. Sixty participants will be randomly divided into a treatment group (basic treatment combined with traditional Chinese medicine Shenqi Compound) or a control group (basic treatment combined with Chinese medicine placebo) with 30 participants in each group. Patients will be selected considering the following inclusion criteria: age between 35 and 65 years, and a positive diagnosis for type 2 diabetes with lower extremity atherosclerosis and TCM syndromes. Primary outcome indicator is an arterial color Doppler ultrasound. Secondary outcome indicators include: blood glucose fluctuation indicators (MBG, SDBG, LAGE), islet ß-cell function evaluation indicators (Homa-IR, Homa-islet, SG, SCP), inflammation indicators (NLR, CRP, IL-6), blood lipids, and HbA1c. Safety index includes vital signs (T, P, R, BP), blood, urine, stool routine, liver and renal function, electrocardiogram, and adverse event records. The endpoint event is defined as the presence of gangrene in the lower limbs. DISCUSSION: Explore the clinical effect of traditional Chinese medicine "Shenqi Compound" to reduce blood glucose fluctuation and use HOMA-IR, the area under the glucose curve, and the area under the C-peptide curve to evaluate the effect of protecting islet ß cell function. TRIAL REGISTRATION: Chinese clinical trial registry (ChiCTR-1900027693). Registered on November 23, 2019. http://www.chictr.org.cn.


Asunto(s)
Aterosclerosis/tratamiento farmacológico , Diabetes Mellitus Tipo 2 , Angiopatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Extremidad Inferior/irrigación sanguínea , Medicina China Tradicional , Aterosclerosis/sangre , Aterosclerosis/fisiopatología , Glucemia , China , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/fisiopatología , Medicamentos Herbarios Chinos/administración & dosificación , Humanos , Hipoglucemiantes/administración & dosificación , Fitoterapia , Flujo Pulsátil , Ensayos Clínicos Controlados Aleatorios como Asunto , Flujo Sanguíneo Regional , Proyectos de Investigación
5.
Rev Med Suisse ; 16(680): 264-267, 2020 Feb 05.
Artículo en Francés | MEDLINE | ID: mdl-32022491

RESUMEN

Considering the progressive nature of type 2 diabetes, glycated hemoglobin (HbA1c) goals and treatment plans should be regularly tailored to the patient's need to prevent hypoglycemia. There are individual HbA1c target levels that take into account factors such as age, comorbidity, and risks of treatment. The emergence of new therapeutic classes reducing hypoglycemia has changed ongoing practices. This article presents a potentially preventable case of a patient with hypoglycemia and reflects on the latest European and American recommendations for antidiabetic treatment in elderly patients.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemia/inducido químicamente , Hipoglucemia/prevención & control , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Administración Oral , Anciano , Glucemia/efectos de los fármacos , Hemoglobina A Glucada/análisis , Humanos
6.
Eur J Endocrinol ; 182(4): 447-457, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32069218

RESUMEN

Context: Altered tissue-specific glucocorticoid metabolism has been described in uncomplicated obesity and type 2 diabetes. We hypothesized that weight loss induced by diet and exercise, which has previously been shown to reverse abnormal cortisol metabolism in uncomplicated obesity, also normalizes cortisol metabolism in patients with type 2 diabetes. Objective: Test the effects of a diet intervention with added exercise on glucocorticoid metabolism. Design: Two groups followed a Paleolithic diet (PD) for 12 weeks with added 180 min of structured aerobic and resistance exercise per week in one randomized group (PDEX). Setting: Umeå University Hospital. Participants: Men and women with type 2 diabetes treated with lifestyle modification ± metformin were included. Twenty-eight participants (PD, n = 15; PDEX, n = 13) completed measurements of glucocorticoid metabolism. Main outcome measures: Changes in glucocorticoid metabolite levels in 24-h urine samples, expression of HSD11B1 mRNA in s.c. adipose tissue and conversion of orally administered cortisone to cortisol measured in plasma. Body composition and insulin sensitivity were measured using a hyperinsulinemic-euglycemic clamp, and liver fat was measured by magnetic resonance spectroscopy. Results: Both groups lost weight and improved insulin sensitivity. Conversion of orally taken cortisone to plasma cortisol and the ratio of 5α-THF + 5ß-THF/THE in urine increased in both groups. Conclusions: These interventions caused weight loss and improved insulin sensitivity with concomitant increases in the conversion of cortisone to cortisol, which is an estimate of hepatic HSD11B1 activity. This suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction.


Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Dieta Reductora/métodos , Ejercicio/fisiología , Glucocorticoides/metabolismo , Pérdida de Peso/fisiología , Adulto , Anciano , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/terapia , Dieta Paleolítica , Terapia por Ejercicio/métodos , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/sangre , Resistencia a la Insulina , Hígado/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Metformina/uso terapéutico , Persona de Mediana Edad , Resultado del Tratamiento
7.
Life Sci ; 245: 117367, 2020 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-32001265

RESUMEN

AIMS: The present study determines the effect of administration of novel antioxidant astaxanthin-s-allyl cysteine biconjugate (AST-SAC) against streptozotocin-induced diabetes mellitus (DM) in rats. MAIN METHODS: AST-SAC (1 mg/kg/day) was treated against DM in rats for 45 days. The oxidative stress, antioxidants level, insulin secretion, activities of various carbohydrate metabolizing enzymes were studied. The glucose uptake in L6 myotubes was studied. In addition, in silico analysis of interaction of AST-SAC with proteins such as insulin receptor (IR) and 5'-adenosine monophosphate-activated protein kinase (AMPK) were carried out. KEY FINDINGS: Administration of AST-SAC in DM rats has protected the mitochondrial function (decreased oxidative stress and normalized oxidative phosphorylation activities) and antioxidant capacity of the pancreas which has resulted in beta cells rejuvenation and insulin secretion restoration. AST-SAC decreased the alpha-glucosidases activities to bring glycemic control in DM rats. Due to these effects the glycoprotein components and lipids were restored to near normalcy in DM rats. AST-SAC protected the antioxidant status of liver, kidney and plasma; and curbed the progression of secondary complications of DM. AST-SAC treatment stimulated glucose uptake in L6 myotubes in in vitro. To support this observation, AST-SAC interacted with proteins such as IR and AMPK in silico. SIGNIFICANCE: AST-SAC can be considered as "multi-target-directed ligand", that is, through these manifold effects, AST-SAC has been able to prevail over DM in rats.


Asunto(s)
Antioxidantes/uso terapéutico , Cisteína/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Colesterol/metabolismo , Cisteína/farmacología , Diabetes Mellitus Experimental/metabolismo , Glucosa/metabolismo , Masculino , Mitocondrias/metabolismo , Simulación del Acoplamiento Molecular , Ratas , Ratas Sprague-Dawley , Triglicéridos/metabolismo
8.
Life Sci ; 245: 117361, 2020 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-32001268

RESUMEN

AIMS: Evaluation of the anti-diabetic effect of superparamagnetic iron oxide nanoparticles (SPIONs) on Type 2 diabetic rats and compared their effect to metformin treatment. MAIN METHODS: Diabetic rats were treated with different doses of nanoparticles one time per week for 4 weeks. Fasting blood glucose level was determined for studied groups during the experimental period (30 days). At the end of the experiment, oral glucose tolerance test was carried out, serum samples were collected for biochemical assays. Then animals were sacrificed to obtain tissues for assessment of glucose transporters, insulin receptors and insulin signaling proteins. KEY FINDING: SPIONs treatment normalized fasting blood glucose and lowering insulin level in diabetic rats compared to untreated diabetic rats. SPIONs significantly ameliorate the glucose sensing and the active components of insulin signaling pathway. The anti-diabetic effects of SPIONs may be mediated through its effect on (i) hepatic peroxisome proliferator-activated receptor gamma coactivator 1-alpha content, which induced by SPIONs treatment in a dose-dependent manner, (ii) adipocytokines as SPIONs treated diabetic rats showed significantly higher levels of adiponectin and lower retinol binding protein 4 compared to untreated diabetic rats, (iii) lipid profile as SPIONs treatment significantly corrected the lipid profile in a dose-dependent manner and to a similar extent as metformin or even better. SIGNIFICANCE: To our knowledge, this is the first study that explores the anti-diabetic effects of SPIONs on diabetic model.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Compuestos Férricos/uso terapéutico , Glucosa/metabolismo , Hipoglucemiantes/uso terapéutico , Insulina/sangre , Nanopartículas de Magnetita/uso terapéutico , Animales , Glucemia/análisis , Prueba de Tolerancia a la Glucosa , Masculino , Metformina/uso terapéutico , Ratas , Ratas Sprague-Dawley
9.
Life Sci ; 246: 117404, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32035128

RESUMEN

AIMS: The study aims to investigate the effect of plasminogen activator inhibitor 1 (PAI-1), a primary inhibitor of fibrinolytic process, on blood glucose in type 2 diabetes mellitus (T2DM) and its mechanism. MATERIALS AND METHODS: We developed a highly potent and highly specific PAI-1 inhibitor, named PAItrap3, based on the inactivated urokinase. Meanwhile, a single point mutation of PAItrap3 (i.e., PAItrapNC) was parallelly prepared as negative control. PAItrap3 was intravenously injected into type 2 diabetic (T2D) mice and its effect on metabolic system was evaluated by measuring the levels of blood glucose, PAI-1, and tumor necrosis factor alpha (TNF-α) in T2D mice. KEY FINDINGS: PAItrap3 significantly reduced the high blood glucose level and PAI-1 level in streptozotocin-induced T2D mice. PAItrapNC did not have any hypoglycemic effect at all on T2D mice. Mechanistically, both PAI-1 and TNF-α levels were attenuated by the administration of PAItrap3. In addition, we observed that PAItrap3 reduced the amount of fat droplets in adipocytes. SIGNIFICANCE: These findings provide clear evidence for PAI-1 to participate in inflammation and obesity mediated hyperglycemia, and open up a new prospect for the treatment of T2DM by PAI-1 inhibition.


Asunto(s)
Glucemia/análisis , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Fragmentos de Péptidos/uso terapéutico , Inhibidor 1 de Activador Plasminogénico/efectos de los fármacos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Activador de Plasminógeno de Tipo Uroquinasa/uso terapéutico , Adipocitos/efectos de los fármacos , Animales , Masculino , Inhibidor 1 de Activador Plasminogénico/sangre
10.
Niger J Clin Pract ; 23(1): 98-102, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31929214

RESUMEN

Aims: This study aimed to explore barriers regarding insulin initiation in patients with Type 2 diabetes and investigate the relationship of some demographic characters of patients. Materials and Methods: A cross-sectional study was conducted with 142 patients with Type 2 diabetes whose doctors had recommended insulin therapy and who had been unwilling to comply. The participants were patients at an endocrine outpatient clinic in Kovancilar State Hospital in the rural area in Elazig, from November 2016 to May 2017. Results: Half of the patients were illiterate, 60.6% of the participants were female, and the mean age was 57.33 ± 10.56. The most commonly reported barrier was injection-related anxiety (63.4%). In total, 58.5% of the patients refused insulin therapy because they felt it indicated that their disease had worsened and that they had failed at diabetes management. Female patients were 6.9 times more likely to think injection-related anxiety that affecting their decision about insulin therapy than male patients. Elderly patients were 8.2 times more likely to think of their disease worsened than younger patient. Conclusions: Patients' beliefs related to insulin therapy were very much influenced by their gender, educational status, and age. Giving patient-centered education is a cost-effective way to decrease negative health behaviors.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Conocimientos, Actitudes y Práctica en Salud , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Anciano , Ansiedad , Estudios Transversales , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/psicología , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Inyecciones , Insulina/administración & dosificación , Masculino , Persona de Mediana Edad , Estigma Social , Turquia/epidemiología
12.
Food Chem Toxicol ; 135: 110953, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31707032

RESUMEN

Edible Sonchus oleraceus Linn is a medicinal plant with many bioactivities such as anti-diabetic activity and anti-inflammatory activity. However, the main bioactive components such as polyphenols in S. oleraceus Linn are poorly absorbed in gastrointestinal tract and rapidly metabolized. Thereby, a self-emulsifying delivery system containing S. oleraceus Linn extracts (SSEDDS) was introduced to evade these problems. Herein, the anti-inflammatory effect of SSEDDS on streptozotocin-induced diabetic rats was investigated. The plasma glucose level was increased and plasma insulin level was decreased in diabetic rats. The levels of NF-κB, TNF-α, and IL-6 in the liver were significantly improved in diabetic rats (p < 0.05). Conversely, daily fed diabetic rats with 100, 200 and 400 mg/kg/day of SSEDS and 1 mg/kg/day metformin for 4 weeks, significantly (p < 0.05) restored all the above mentioned parameters to near normal levels. The immuno-histochemical studies confirmed the anti-inflammatory effects of SSEDDS.


Asunto(s)
Antiinflamatorios/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Emulsiones/uso terapéutico , Extractos Vegetales/uso terapéutico , Sonchus/química , Animales , Glucemia/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Hipoglucemiantes/uso terapéutico , Insulina/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratas Sprague-Dawley , Estreptozocina
13.
Expert Opin Pharmacother ; 21(1): 121-130, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31689132

RESUMEN

Background: Vildagliptin is a dipeptidyl peptidase-4 inhibitor that reduces glycemia in patients with type 2 diabetes mellitus (T2DM). When approved in 2013, data on vildagliptin combined with >750 mg/day metformin in Japanese patients were limited. There is a need to confirm the safety and efficacy of vildagliptin in combination with oral antidiabetic drugs (OADs).Research design and methods: This 52-week post-marketing surveillance (PMS) observational study in Japanese T2DM patients evaluated the safety and efficacy of vildagliptin in combination with OADs including high-dose metformin or insulin but excluding combination with sulfonylureas alone.Results: During this survey of 3006 Japanese T2DM patients, 13.61% of patients experienced adverse events (AEs) and 2.20% reported a serious AE (SAE). The frequency of AEs/SAEs was similar when in combination with biguanides (12.93%/1.46%), metformin ≥1000 mg/day (12.92%/1.22%), metformin <1000 mg/day (12.62%/1.54%), thiazolidine derivatives (16.71%/2.86%), α-glucosidase inhibitors (13.18%/1.90%), rapid-acting insulin secretagogues  (glinides) (20.41%/5.71%), or insulin (15.87%/2.47%). The mean ± SD changes from baseline at endpoint in glycated hemoglobin and fasting blood glucose were -0.76 ± 1.27% and -23.3 ± 57.3 mg/dL, respectively, and these changes were consistent, regardless of concomitant OAD.Conclusions: Long-term vildagliptin combination therapy is safe and effective in Japanese T2DM patients in real-world settings.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Hipoglucemiantes/administración & dosificación , Vildagliptina/administración & dosificación , Anciano , Glucemia/efectos de los fármacos , Estudios de Cohortes , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Quimioterapia Combinada , Femenino , Hemoglobina A Glucada/análisis , Inhibidores de Glicósido Hidrolasas/uso terapéutico , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/administración & dosificación , Insulina/uso terapéutico , Japón , Masculino , Metformina/administración & dosificación , Metformina/uso terapéutico , Persona de Mediana Edad , Vigilancia de Productos Comercializados , Compuestos de Sulfonilurea/uso terapéutico , Vildagliptina/efectos adversos
14.
Life Sci ; 240: 117090, 2020 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-31765648

RESUMEN

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are a relatively newer class of anti-hyperglycemic medications that reduce blood glucose by inhibition of renal glucose re-uptake, thereby increasing urinary glucose excretion. Although glycosuria is the primary mechanism of action of these agents, there is some evidence suggesting they can reduce insulin resistance and induce peripheral insulin sensitivity. Identifying the molecular mechanisms by which these medications improve glucose homeostasis can help us to develop newer forms of SGLT2i with lesser side effects. We have reviewed the molecular mechanisms and signaling pathways by which SGLT2i therapy improve insulin sensitivity and ameliorates insulin resistance.


Asunto(s)
Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/metabolismo , Hipoglucemiantes/farmacología , Resistencia a la Insulina , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Transportador 2 de Sodio-Glucosa/metabolismo , Animales , Humanos , Hipoglucemiantes/uso terapéutico
15.
Anal Bioanal Chem ; 412(2): 377-388, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31773226

RESUMEN

Insulin oligosaccharide conjugates hold promise as potential glucose-responsive insulins (GRIs), which can improve the therapeutic index of insulins and mitigate the risk of hypoglycemia. A key challenge for the analytical development of such molecules is finding an efficient method to characterize the purity and impurities of conjugated insulins. Using the S-Matrix Fusion QbD-ultrahigh performance liquid chromatography (UHPLC) integrated system, we were able to quickly screen and develop two short UHPLC methods. These methods were used to support process development, clinical batch drug substance (DS) release, and stability studies of MK-2640, an insulin oligosaccharide conjugate. Both methods used a Waters CSH C18 column, with a shallow gradient of acetonitrile to aqueous mobile phase containing 25 mM sodium perchlorate and 0.05% perchloric acid. The 10-min run time method was well suited for process development and monitoring as it was able to separate the main product, MK-2640, six oligosaccharide-substituted recombinant human insulin (RHI) impurities, A21 deamidated MK-2640, and the starting material RHI. The 13-min run time method provided improved separation of the major impurities and demonstrated good chromatographic reproducibility on different instruments or using columns from different lots of stationary phase, which made it ideal for the final DS release. Validation of the 13-min method demonstrated great linearity for both the MK-2640 main peak and its related impurities, low limit of detection (0.02%), and limit of quantitation (0.05%). The high specificity of the method allowed the separation of the degradation products from main peak, thus makes it suitable for stability monitoring. The major impurities in the DS were characterized by two-dimensional liquid chromatography-mass spectrometry (2D-LC-MS).


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Glucosa/metabolismo , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Humanos , Límite de Detección , Espectrometría de Masas/métodos , Reproducibilidad de los Resultados
16.
Expert Opin Pharmacother ; 21(3): 275-285, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31790314

RESUMEN

Introduction: The prevalence of obesity is increasing worldwide and associated conditions, particularly type 2 diabetes mellitus (T2DM), also show increasing prevalence. Lifestyle intervention should be the first line of management for obesity but additional pharmacotherapy is often required and bariatric surgery is appropriate in more severe cases. Drugs acting as glucagon-like peptide-1 receptor agonists (GLP-1RAs) developed for the management of T2DM reduce body weight and liraglutide is the first GLP-1RA to be approved for the treatment of obesity in patients with and without T2DM.Areas covered: In this review of relevant published material, the authors summarize the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of liraglutide for the treatment of obesity.Expert opinion: Liraglutide effectively reduces body weight and body fat through mechanisms involving reduced appetite and lowered energy intake, independent of its glucose-lowering effects. Like most of the other medications currently available for obesity, liraglutide has some common adverse effects, although generally not serious ones. Liraglutide has additional benefits in reducing cardiovascular events in patients with T2DM but the cost and the need for daily injections may limit its use in obesity. Newer GLP-1RAs, such as semaglutide, or other drugs in development for obesity may have advantages over liraglutide.


Asunto(s)
Hipoglucemiantes/uso terapéutico , Liraglutida/uso terapéutico , Obesidad/tratamiento farmacológico , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Péptidos Similares al Glucagón/uso terapéutico , Humanos
17.
Curr Diabetes Rev ; 16(2): 117-136, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31237215

RESUMEN

BACKGROUND: Among the millions of people around the world, the most prevalent metabolic disorder is diabetes mellitus. Due to the drawbacks which are associated with commercially available antidiabetic agents, new therapeutic approaches are needed to be considered. Alpha-amylase is a membrane- bound enzyme which is responsible for the breakdown of polysaccharides such as starch to monosaccharides which can be absorbed. METHODS: We searched the scientific database using alpha-amylase, diabetes, antidiabetic agents as the keywords. Here in, only peer-reviewed research articles were collected which were useful to our current work. RESULTS: To overcome the research gap, the alpha-amylase enzyme is regarded as a good target for antidiabetic agents to design the drug and provide an alternate approach for the treatment of type 2 diabetes mellitus. Basically, alpha-amylase inhibitors are classified into two groups: proteinaceous inhibitors, and non-proteinaceous inhibitors. Recently, non-proteinaceous inhibitors are being explored which includes chalcones, flavones, benzothiazoles, etc. as the potential antidiabetic agents. CONCLUSION: Herein, we discuss various potential antidiabetic agents which are strategically targeted alpha-amylase enzyme. These are having lesser side effects as compared to other antidiabetic agents, and are proposed to prevent the digestion and absorption of glucose leading to a decrease in the blood glucose level.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Hipoglucemiantes/uso terapéutico , alfa-Amilasas/antagonistas & inhibidores , Glucemia/metabolismo , Humanos
18.
Gut ; 69(2): 295-303, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31331994

RESUMEN

BACKGROUND: The duodenum has become a metabolic treatment target through bariatric surgery learnings and the specific observation that bypassing, excluding or altering duodenal nutrient exposure elicits favourable metabolic changes. Duodenal mucosal resurfacing (DMR) is a novel endoscopic procedure that has been shown to improve glycaemic control in people with type 2 diabetes mellitus (T2D) irrespective of body mass index (BMI) changes. DMR involves catheter-based circumferential mucosal lifting followed by hydrothermal ablation of duodenal mucosa. This multicentre study evaluates safety and feasibility of DMR and its effect on glycaemia at 24 weeks and 12 months. METHODS: International multicentre, open-label study. Patients (BMI 24-40) with T2D (HbA1c 59-86 mmol/mol (7.5%-10.0%)) on stable oral glucose-lowering medication underwent DMR. Glucose-lowering medication was kept stable for at least 24 weeks post DMR. During follow-up, HbA1c, fasting plasma glucose (FPG), weight, hepatic transaminases, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), adverse events (AEs) and treatment satisfaction were determined and analysed using repeated measures analysis of variance with Bonferroni correction. RESULTS: Forty-six patients were included of whom 37 (80%) underwent complete DMR and 36 were finally analysed; in remaining patients, mainly technical issues were observed. Twenty-four patients had at least one AE (52%) related to DMR. Of these, 81% were mild. One SAE and no unanticipated AEs were reported. Twenty-four weeks post DMR (n=36), HbA1c (-10±2 mmol/mol (-0.9%±0.2%), p<0.001), FPG (-1.7±0.5 mmol/L, p<0.001) and HOMA-IR improved (-2.9±1.1, p<0.001), weight was modestly reduced (-2.5±0.6 kg, p<0.001) and hepatic transaminase levels decreased. Effects were sustained at 12 months. Change in HbA1c did not correlate with modest weight loss. Diabetes treatment satisfaction scores improved significantly. CONCLUSIONS: In this multicentre study, DMR was found to be a feasible and safe endoscopic procedure that elicited durable glycaemic improvement in suboptimally controlled T2D patients using oral glucose-lowering medication irrespective of weight loss. Effects on the liver are examined further. TRIAL REGISTRATION NUMBER: NCT02413567.


Asunto(s)
Diabetes Mellitus Tipo 2/cirugía , Duodenoscopía/métodos , Duodeno/cirugía , Resección Endoscópica de la Mucosa/métodos , Mucosa Intestinal/cirugía , Adulto , Anciano , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Resección Endoscópica de la Mucosa/efectos adversos , Estudios de Factibilidad , Femenino , Hemoglobina A Glucada/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Estudios Prospectivos
19.
Food Chem Toxicol ; 135: 110965, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31743741

RESUMEN

Perilla oil (PerO), a natural oil with a high unsaturated fatty acid content derived from the mature seeds of Perilla frutescens, is a homology of medicine and food. The type 2 diabetes mellitus (T2DM) model was successfully established using a high-fat and high-sugar diet combined with a single low-dose of streptozocin (STZ). PerO intervention reduced the levels of fasting blood glucose and the level, size and accumulation of lipid droplets, increased the insulin level and diminished the body weight loss. PerO pretreatment markedly promoted the serum levels of alanine transaminase (ALT) and aspartate transaminase alanine (AST) and inhibited the levels of glucose (GLU), glucose-6-phosphate dehydrogenase (G6PD), triglycerides (TGs) and total cholesterol (TC). Moreover, PerO treatment enhanced the expression of phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) and activated the expression of glucose transporter 4 (Glut4) and phospho-AKT serine/threonine kinase (p-AS160) in the liver. Additionally, PerO treatment distinctly decreased the abundance of Aerococcus and facilitated the richness of Alloprevotella in the intestine, as well as accelerated the restoration of the gut microflora diversity. Thus, PerO regulates intestinal microbiota and alleviates insulin resistance through the PI3K/AKT signaling pathway in type-2 diabetic KKAy mice and may be a potential functional food for diabetic treatment.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Hipoglucemiantes/uso terapéutico , Resistencia a la Insulina/fisiología , Transducción de Señal/efectos de los fármacos , Ácido alfa-Linolénico/uso terapéutico , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/fisiopatología , Insulina/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones Endogámicos C57BL , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Perilla/química , Fosfatidilinositol 3-Quinasa/metabolismo , Aceites Vegetales/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Estreptozocina
20.
Expert Opin Investig Drugs ; 29(2): 205-208, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31829750

RESUMEN

Background: We aimed to estimate population-based trends in the prevalence of coexisting type 2 diabetes (T2D) and suspected nonalcoholic fatty liver disease (NAFLD) and pioglitazone use among U.S. adults.Research design and methods: We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey from 2003 to 2016. We included people aged ≥18 years who had HbA1C >6.4%, fasting plasma glucose >125 mg/dL, or were told they had diabetes by a doctor. Suspected NAFLD was defined using a hepatic steatosis index of >36. Prevalence was estimated for each 2-year survey cycle. Trends were analyzed using logistic regression, accounting for the complex survey design.Results: Total sample size was 40,323 U.S. adults, of which 5690 had T2D. Age-adjusted prevalence of T2D with NAFLD increased from 5.6% in 2003-2004 to 6.8% in 2015-2016 (p-value <0.001). Pioglitazone use peaked at 20% in 2005-2006 and then declined to 4.1% in 2013-2014. Patients with suspected NAFLD were not more likely to receive pioglitazone; 3.8% of patients received the drug in 2015-2016.Conclusions: The prevalence of T2D with suspected NALFD increased among U.S. adults, but pioglitazone use decreased significantly over 2003-2016. Our study suggested a missed opportunity to prevent a future epidemic of cirrhosis due to NAFLD in patients with T2D.


Asunto(s)
Diabetes Mellitus Tipo 2/epidemiología , Hipoglucemiantes/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Pioglitazona/uso terapéutico , Adulto , Estudios Transversales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Prevalencia , Estudios Retrospectivos , Estados Unidos
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