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1.
J Colloid Interface Sci ; 605: 582-591, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34343731

RESUMO

Diabetes is a metabolic disease that is affecting an ever-increasing number of people worldwide, resulting in increased burdens on healthcare systems and societies. Constant monitoring of blood glucose levels is required to prevent serious or even deadly complications. One major challenge of diabetes management is the simple and timely administration of insulin to facilitate consistent blood glucose regulation and reduce the incidence of hypoglycemia. With this research, we construct an insulin delivery system, the delivery system is comprised of phenylboronic acid based fluorescent probes, which is used as glucose responsive linkers, mesoporous silica nanoparticles providing an insulin reservoir, and zinc oxide nanoparticles used as gate keepers. The system with glucose sensitive responsive linker exhibits controlled release of insulin under high glucose concentrations, providing prolonged blood glucose regulation and no risks of hypoglycemia. Furthermore, the system is combined with a hyaluronic-acid based microneedle patch, which exhibit efficient skin penetration for transdermal delivery. With our system, the nanoparticles provide outstanding in vivo glucose regulation when administrated by subcutaneous injection or via transdermal microneedle patch. We anticipate that our biocompatible smart glucose responsive microneedle patch (SGRM patch) will facilitate the development of clinically useful systems.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Hipoglicemia , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Humanos , Hipoglicemia/tratamento farmacológico , Insulina , Agulhas
2.
Cir Cir ; 89(S1): 70-75, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34762634

RESUMO

Hypoglycemia due to endogenous hyperinsulinism usually occurs in 2 pathological situations: the most frequent is insulinoma and, secondly, nesidioblastosis or also known as non-insulinoma pancreatic hypoglycemic syndrome. Nesidioblastosis is a rare cause of hyperinsulinic hypoglycemia in adults. We present the clinical case of an adult patient with recurrent hypoglycemia secondary to nesidioblastosis.


Assuntos
Hiperinsulinismo , Hipoglicemia , Nesidioblastose , Adulto , Humanos , Hiperinsulinismo/etiologia , Hipoglicemia/etiologia , Hipoglicemiantes , Nesidioblastose/complicações , Nesidioblastose/diagnóstico , Pâncreas
3.
Br J Community Nurs ; 26(11): 544-552, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34731035

RESUMO

Type 1 diabetes is a lifelong condition which affects all age ranges, for reasons unknown, and the UK has one of the highest incidences of this complex condition in the world. Type 1 diabetes is caused by autoimmune damage to the insulin-producing ß-cells found in the pancreatic islet cells, leading to severe insulin deficiency. People with diabetes need to achieve a target glyosylated haemoglobin level to avoid macro- and microvascular complications, but there is the associated risk of hypoglycaemic events. These can vary in severity and consequences but will likely always cause worry for the person living with diabetes. There are many risk factors and reasons to be explored when looking at hypoglycaemia. This case study explores the nursing interventions that can be safely worked through and prioritised, within the community setting, to allow people with diabetes to be safe from severe hypoglycaemia, thus improving their quality of life and safety, as well as reducing costs for the NHS.


Assuntos
Automonitorização da Glicemia/métodos , Diabetes Mellitus Tipo 1/enfermagem , Hemoglobina A Glicada/análise , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemia/etiologia , Hipoglicemia/enfermagem , Hipoglicemiantes/uso terapêutico , Qualidade de Vida
4.
Rev Med Suisse ; 17(757): 1883-1887, 2021 Nov 03.
Artigo em Francês | MEDLINE | ID: mdl-34738763

RESUMO

Improving glycaemia level is helpful to the clinician in diabetes management. Elderly diabetics make up a group that is non-homogeneous and with a very varied health status, whose treatment must be adjusted to take into account comorbidities, degree of frailty and both functional and mental disability, in addition to their life expectancy and personal preferences. Thus, the target of treatment should be defined along three categories of patients: robust, vulnerable and dependent. This article reviews information from the literature high-lighting current recommendations for treatment, the clear inclination towards overtreatment of the elderly diabetic and the resulting noxious effects of occurring hypoglycemia, that are often not recognized by the patient and his doctor.


Assuntos
Diabetes Mellitus , Fragilidade , Hipoglicemia , Idoso , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Idoso Fragilizado , Fragilidade/terapia , Avaliação Geriátrica , Nível de Saúde , Humanos , Hipoglicemia/epidemiologia
5.
Am J Manag Care ; 27(10): e349-e354, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34668677

RESUMO

OBJECTIVES: Residents with diabetes in long-term care (LTC) settings often have recognized risk factors for developing hypoglycemia, including advanced age, dementia, and polypharmacy; however, data regarding hypoglycemia in LTC and associated hospitalizations are lacking. Our aim was to describe health care resource use and costs for patients with diabetes and hypoglycemia upon hospital admission. STUDY DESIGN: Retrospective, descriptive study using a US hospital billing database, October 2015 through September 2019. METHODS: Eligible patients were those 18 years and older with type 1 or 2 diabetes who (1) were hospitalized with hypoglycemia upon admission from LTC or from home and (2) received insulin during hospitalization. We described the percentages of patients admitted from LTC or from home with hypoglycemia and their characteristics, length of hospitalization, and hospital costs (2019 US$). RESULTS: Of 106,602 patients with diabetes admitted from LTC and 4,315,571 from home, 6609 (6%) and 182,756 (4%), respectively, presented with hypoglycemia on hospital admission. Mean ages of patients admitted with hypoglycemia from LTC and home were 73 and 66 years, respectively. The percentages of patients in LTC and home cohorts with dementia were 34% and 12%, respectively; with renal disease, 60% and 52%; and with type 2 diabetes, 95% and 89%. Mean hospital stays were 8.0 days for patients admitted from LTC and 6.7 days for those admitted from home; mean total hospital costs were $19,800 and $16,800, respectively. CONCLUSIONS: These findings highlight the importance of providing optimal diabetes management for patients in LTC settings to prevent hypoglycemia and potential hospitalizations and costs.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Atenção à Saúde , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hospitalização , Hospitais , Humanos , Hipoglicemia/epidemiologia , Assistência de Longa Duração , Estudos Retrospectivos
6.
Psychiatr Danub ; 33(Suppl 10): 43-51, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34672271

RESUMO

BACKGROUND: In addition to its neuroprotective effect, Brain-derived neurotrophic factor (BDNF) also plays a role in glucose and lipid metabolism. This study aims: a) to find changes in the BDNF concentration during pregnancy in type 1 diabetes. b) to prove the effect of DHA and EPA supplementation on changes in BDNF concentrations c) to investigate the impact of hypoglycemia on BDNF concentration. SUBJECTS AND METHODS: The data from this study were from the PRE-HYPO cohort study. Twenty-one of them were on a standard diabetic diet enriched with EPA and DHA (EPA 120 mg/day and DHA 616 mg/day; Exposed group), and nineteen pregnant diabetic women were on the standard diabetic diet without EPA and DHA supplementation (Non-exposed group). In the first trimester of pregnancy, fifteen pregnant women developed hypoglycemia episodes (≤3.9 mmol/L; HYPO+ group), and twenty-five pregnant women did not have hypoglycemia episodes (HYPO- group). RESULTS: BDNF concentration significantly decreased during pregnancy from the first to the third trimester, in Non-exposed from 25.1 (22.0-30.2) to 22.1 (16.3-28.2), P<0.05, in the Exposed group from 22.1 (19.8-25.9) to 18.1 (14.8-18.9), P<0.01. Pregnant patients with hypoglycemia episodes (HYPO+ subgroup) had significantly higher BDNF in the third trimester of pregnancy [22.5 (20.6-28.4)] when compared with patients who did not develop hypoglycemia [16.3 (14.3-18.8), P<0.001]. In the third trimester of pregnancy, BDNF and n-6 PUFAs were associated with hypoglycemia (OR 1.818 95 % CI 1.079-3.003, P=0.025; OR 1.103 95 % CI 1.001-1.217, P=0.048). Total F.A.s were inversely associated with hypoglycemia (OR 0.969 95% CI 0.939-0.998, P=0.048). CONCLUSION: Pregnant women with hypoglycemia (HYPO+ group) had higher concentrations of BDNF in the first and third trimesters of pregnancy compared to those without hypoglycemia. An increase in body weight during pregnancy leads to a decrease in BDNF concentration.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Fator Neurotrófico Derivado do Encéfalo , Estudos de Coortes , Diabetes Mellitus Tipo 1/tratamento farmacológico , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/tratamento farmacológico , Gravidez , Gestantes , Estudos Prospectivos
9.
BMC Pediatr ; 21(1): 442, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625039

RESUMO

BACKGROUND: Congenital disorders of glycosylation (CDG) are a group of metabolic diseases with clinical and genetic heterogeneity, and CDG-IIg is one of the rare reported types of CDG. The aim of this study is to report the clinical manifestations and gene-phenotype characteristics of a rare case of CDG caused by a COG1 gene mutation and review literatures of CDG disease. CASE PRESENTATION: The patient was male, and the main clinical symptoms were developmental retardation, convulsion, strabismus, and hypoglycemia, which is rarely reported in CDG-IIg. We treated the patient with glucose infusion and he was recovered from hypoglycemia. Genetic analysis showed that the patient carried the heterozygous intron mutation c.1070 + 3A > G (splicing) in the coding region of the COG1 gene that was inherited from the mother, and the heterozygous mutation c.2492G > A (p. Arg831Gln) in exon 10 of the COG1 gene that was inherited from the father. The genes interacting with COG1 were mainly involved in the transport and composition of the Golgi. The clinical data and laboratory results from a patient diagnosed with CDG-IIg were analyzed, and the causative gene mutation was identified by high-throughput sequencing. The genes and signal pathways related to COG1 were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. CONCLUSIONS: The c.2492G > A (p. Arg831Gln) mutation in exon 10 of the COG1 gene may be a potential pathogenetic variant for CDG-IIg. Because of the various manifestations of CDG in clinical practice, multidisciplinary collaboration is important for the diagnosis and treatment of this disease.


Assuntos
Defeitos Congênitos da Glicosilação , Hipoglicemia , Proteínas Adaptadoras de Transporte Vesicular/genética , Defeitos Congênitos da Glicosilação/diagnóstico , Defeitos Congênitos da Glicosilação/genética , Complexo de Golgi , Heterozigoto , Humanos , Hipoglicemia/genética , Masculino , Mutação
11.
Rev Assoc Med Bras (1992) ; 67(6): 822-827, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34709324

RESUMO

OBJECTIVE: The aims of this study were to observe the regularity of blood glucose changes in hemodialysis patients with diabetes, time of onset of hypoglycemia and blood glucose level during dialysis, and to explore the sensitive early warning indicators of hypoglycemia in dialysis patients. BACKGROUND: Diabetes patients have a high incidence of hypoglycemia during hemodialysis. METHODS: A total of 124 maintenance hemodialysis patients with diabetes were selected for this study. Before dialysis, one, two, and three h after dialysis, and when hypoglycemia symptoms occurred, the blood glucose changes were monitored, the blood glucose drop range was observed when hypoglycemia symptoms occurred, and the correlation between the two was analyzed. RESULTS: After the start of the dialysis, the patient's blood glucose showed a downward trend. The symptoms of hypoglycemia were most obvious within one-two hours, with an incidence rate of 57.9%. When the blood glucose drop percentage reached 37.7%, the specificity and sensitivity of early warning hypoglycemia symptoms were 84.6 and 73%, respectively. CONCLUSIONS: For hemodialysis patients with diabetes, attention should be paid to the symptoms of hypoglycemia during dialysis, and blood glucose should be monitored before dialysis and after 1-2 h of dialysis. If the blood glucose drop percentage is greater than 37.7%, the timely measures should be taken.


Assuntos
Diabetes Mellitus , Hipoglicemia , Glicemia , Humanos , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Incidência , Diálise Renal/efeitos adversos
12.
J Investig Med High Impact Case Rep ; 9: 23247096211051918, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34654342

RESUMO

Hyperinsulinemic hypoglycemia (HH) has the potential to cause acute neurologic dysfunction and neurodevelopmental impairment. Parieto-occipital neuronal injuries have been reported in hypoglycemic infants, but intraparenchymal hemorrhage is rare. On day 5 of life, a late preterm infant was transferred to our care with recurrent asymptomatic hypoglycemia. Prior to arrival, plasma glucose levels were at a median of 1.25 mmol/L (22.5 mg/dL) in the first 6 hours of life, and he required a glucose infusion rate (GIR) of 22.6 mg/kg/min. Hyperinsulinism was confirmed in the presence of detectable insulin, low ketones, and fatty acid when hypoglycemic. A left grade 4 intraventricular hemorrhage (IVH) was noted in the cranial ultrasound scan during the workup for sepsis on the day of admission. However, magnetic resonance imaging of the brain on day 7 of life revealed extensive bilateral IVH. On day 9, he was initiated on diazoxide, and HH resolved within 48 to 72 hours, allowing increment of feeds while weaning GIR. Ventricular drain for post-hemorrhagic ventriculomegaly was advised but not performed. At 3 months, post-hemorrhagic ventriculomegaly was stable, and there were early signs of neurodevelopmental delay. After discontinuing diazoxide at 4 months of age, he passed an 8-hour fasting study confirming the resolution of HH. Severe hypoglycemia has been associated with cerebral hyperperfusion in preterm infants and potentially could cause IVH. Close monitoring and prompt intervention in preterm infants to prevent severe hypoglycemia are paramount. In addition to long-term neurodevelopmental follow-up, infants with recurrent hypoglycemia may benefit from neuroimaging and thereby early intervention if required.


Assuntos
Hiperinsulinismo , Hipoglicemia , Doenças do Prematuro , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Humanos , Hipoglicemia/etiologia , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/diagnóstico
13.
Artigo em Inglês | MEDLINE | ID: mdl-34620618

RESUMO

INTRODUCTION: To prevent medical sequelae of severe hypoglycemic emergencies, prompt and reliable rescue intervention is critically important. A ready-to-use, liquid stable glucagon, administered subcutaneously by glucagon autoinjector (GAI), Gvoke HypoPen (glucagon injection; Xeris Pharmaceuticals), was evaluated for rescue treatment of severe hypoglycemia. RESEARCH DESIGN AND METHODS: Two phase III, randomized, controlled, blinded, non-inferiority crossover studies were conducted in 161 adults with type 1 diabetes to compare 1 mg doses of GAI versus glucagon emergency kit (GEK) for treating insulin-induced severe hypoglycemia. Efficacy was evaluated as either a return of plasma glucose to >70 mg/dL (3.9 mmol/L) or increase ≥20 mg/dL (1.1 mmol/L) from a baseline glucose of <50 mg/dL (2.9 mmol/L), within 30 min of dosing. RESULTS: For successful plasma glucose recovery within 30 min, treatment with GAI was non-inferior to GEK. Treatment with GAI was non-inferior to GEK for a plasma glucose >70 mg/dL (3.9 mmol/L) or neuroglycopenic symptom relief within 30 min. From administration of glucagon, the mean time to achieve plasma glucose >70 mg/dL (3.9 mmol/L) or increase ≥20 mg/dL (1.1 mmol/L) was 13.8±5.6 min for GAI and 10.0±3.6 min for GEK. This mean time does not account for the significantly shorter (p<0.0001) drug preparation and administration time for GAI (27.3±19.7 s) versus GEK (97.2±45.1 s). The incidence of treatment emergent adverse events was comparable in both groups. CONCLUSIONS: A ready-to-use GAI was non-inferior to GEK, with a similar tolerability profile. GAI is an effective, safe, and well-tolerated rescue treatment for severe hypoglycemia and is a viable alternative to GEK. TRIAL REGISTRATION NUMBERS: NCT02656069 and NCT03439072.


Assuntos
Glucagon , Hipoglicemia , Glicemia , Estudos Cross-Over , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/tratamento farmacológico , Insulina
15.
Sr Care Pharm ; 36(11): 556-567, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34717787

RESUMO

Objective To review current guidelines and literature regarding continuous glucose monitoring (CGM) use in the management of type 2 diabetes mellitus (T2DM) in older people. Data Sources A PubMed search of articles published through August 2020 using a combination of the following: older people, T2DM, continuous glucose monitoring, hypoglycemia, and hyperglycemia. Study Selection/Data Extraction Relevant randomized control trials, meta-analyses, and guidelines were assessed for the use of CGM in older patients with T2DM. Articles were included based on relevance to the topic, detailed methods, and complete results. Data Synthesis CGM use in T2DM management in older people is not well defined. CGM may be a valuable technology in older people who face unique challenges, such as hypoglycemia, decline in cognitive function, and variable glucose levels. This article provides a review of recommendations for glucose monitoring in T2DM and discusses the role of specific CGM products. Conclusion CGM is a viable option for older people with T2DM to help improve overall diabetes control. Pharmacists can play an important role in educating patients about this technology.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Hipoglicemia , Idoso , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle
16.
Diabetes Res Clin Pract ; 181: 109093, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34653567

RESUMO

AIM: To analyse the real-life outcomes of two sensor-augmented pumps (SAP) with predictive low glucose suspend (PLGS) function, Medtronic Minimed 640G™ with SmartGuard (MM640G) and Tandem T Slim X2™ with Basal-IQ™ (TTSX2), in Type 1 Diabetes Mellitus (T1DM) patients. METHODS: Observational cross-sectional study using data obtained from computerized clinical records. All T1DM patients on TTSX2 therapy were compared (1:1) with MM640G treated patients selected through stratified sampling. Primary efficacy outcome was to describe time in rage (TIR, 70-180 mg/dL, 3.9-10 mmol/L) interstitial glucose differences according to a non-inferiority hypothesis with TTSX2 compared to MM640G. RESULTS: Forty-four patients were analyzed (female 66%). Mean age was 38.9 yrs. (range 23-59 yrs.) and mean diabetes duration was 23.4 ± 9.2 yrs. Patients treated with TTSX2 showed a numerically slightly lower, but non-statistically significantly different, TIR from the MM640G pump group (64.9 ± 16.4% vs. 72.4 ± 17.0%, P = 0.108). Similarly, we did no find differences in HbA1c between T1D patients treated with TTSX2 and MM640G (6.8 ± 1.0% vs. 7.0 ± 0.9%, 51 ± 11 mmol/mol vs. 53 ± 10 mmol/mol, P = 0.312). Moreover, rest of evaluated glycemic outcomes were similar between both treatment groups. CONCLUSIONS: Patients using two different SAP with PLGS automatic function showed similar glycaemic control in a real-world scenario. NCT04741685.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Glucose/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Sistemas de Infusão de Insulina
17.
Therapie ; 76(6): 559-566, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34656290

RESUMO

The pathophysiological study of diabetes mellitus took an important place in the school of Montpellier since the end of the XIXth century with Emmanuel Hedon's (1863-1933) contribution to the demonstration of the endocrine function of the pancreas. In 1942, a new sulfonamide compound (2254RP) was tested in the infectious diseases department of Pr M. Janbon (1898-1996) on cases of typhoid fever, leading to several deaths rapidly related to hypoglycaemia. The physiologist Auguste Loubatières (1912-1977) rapidly demonstrated that this hypoglycaemic effect required the presence of pancreas and was explained by stimulation of insulin secretion. He contributed to the description of a hypoglycaemic effect of several other sulphonamide compounds. He considered the diagnostic and therapeutic relevance of this class of drugs. This is a good example of a medical discovery combining a favourable local environment, serendipity and perfect experimental approach.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Hipoglicemia , Humanos , Hipoglicemiantes , Insulina , Masculino , Sulfonamidas
18.
Med Clin North Am ; 105(6): 967-982, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34688421

RESUMO

Continuous glucose monitoring system is a convenient wearable device that provides glucose readings from the interstitial fluid every few minutes. Continuous glucose monitoring has revolutionized diabetes care. Patients with type 1 diabetes mellitus and type 2 diabetes mellitus, regardless of the type of treatment regimen, can benefit from continuous glucose monitoring. Continuous glucose monitoring systems provide patients with diabetes and their providers with an ambulatory glucose report that summarizes and also gives graphical representations of the glucose data. This wealth of information helps to better understand patients' glycemic patterns, and thereby reduces hemoglobin A1c and hypoglycemia.


Assuntos
Automonitorização da Glicemia/instrumentação , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Aplicativos Móveis , Smartphone
19.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638984

RESUMO

The goal of diabetes care is to achieve and maintain good glycemic control over time, so as to prevent or delay the development of micro- and macrovascular complications in type 1 (T1D) and type 2 diabetes (T2D). However, numerous barriers hinder the achievement of this goal, first of all the frequent episodes of hypoglycemia typical in patients treated with insulin as T1D patients, or sulphonylureas as T2D patients. The prevention strategy and treatment of hypoglycemia are important for the well-being of patients with diabetes. Hypoglycemia is strongly associated with an increased risk of cardiovascular disease in diabetic patients, due probably to the release of inflammatory markers and prothrombotic effects triggered by hypoglycemia. Treatment of hypoglycemia is traditionally based on administration of carbohydrates or of glucagon via intramuscular (IM) or subcutaneous injection (SC). The injection of traditional glucagon is cumbersome, such that glucagon is an under-utilized drug. In 1983, it was shown for the first time that intranasal (IN) glucagon increases blood glucose levels in healthy volunteers, and in 1989-1992 that IN glucagon is similar to IM glucagon in resolving hypoglycemia in normal volunteers and in patients with diabetes, both adults and children. IN glucagon was developed in 2010 and continued in 2015; in 2019 IN glucagon obtained approval in the US, Canada, and Europe for severe hypoglycemia in children and adults. In the 2010s, two ready-to-use injectable formulations, a stable non-aqueous glucagon solution and the glucagon analog dasiglucagon, were developed, showing an efficacy similar to traditional glucagon, and approved in the US in 2020 and in 2021, respectively, for severe hypoglycemia in adults and in children. Fast-acting glucagon (nasal administration and injected solutions) appears to represent a major breakthrough in the treatment of severe hypoglycemia in insulin-treated patients with diabetes, both adults and children. It is anticipated that the availability of fast-acting glucagon will expand the use of glucagon, improve overall metabolic control, and prevent hypoglycemia-related complications, in particular cardiovascular complications and cognitive impairment.


Assuntos
Administração Intranasal/métodos , Cuidados Críticos/métodos , Glucagon/análogos & derivados , Hipoglicemia/tratamento farmacológico , Adulto , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucagon/administração & dosagem , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Injeções Subcutâneas , Insulina/efeitos adversos , Insulina Regular Humana/uso terapêutico , Pós/administração & dosagem , Compostos de Sulfonilureia/efeitos adversos , Resultado do Tratamento
20.
Arterioscler Thromb Vasc Biol ; 41(11): 2740-2755, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34615372

RESUMO

Objective: MR (mineralocorticoid receptor) activation associates with increased risk of cardiovascular ischemia while MR inhibition reduces cardiovascular-related mortality and plaque inflammation in mouse atherosclerosis. MR in myeloid cells (My-MR) promotes inflammatory cell infiltration into injured tissues and atherosclerotic plaque inflammation by unclear mechanisms. Here, we examined the role of My-MR in leukocyte trafficking and the impact of sex. Approach and Results: We confirm in vivo that My-MR deletion (My-MR-KO) in ApoE-KO mice decreased plaque size. Flow cytometry revealed fewer plaque macrophages with My-MR-KO. By intravital microscopy, My-MR-KO significantly attenuated monocyte slow-rolling and adhesion to mesenteric vessels and decreased peritoneal infiltration of myeloid cells in response to inflammatory stimuli in male but not female mice. My-MR-KO mice had significantly less PSGL1 (P-selectin glycoprotein ligand 1) mRNA in peritoneal macrophages and surface PSGL1 protein on circulating monocytes in males. In vitro, MR activation with aldosterone significantly increased PSGL1 mRNA only in monocytes from MR-intact males. Similarly, aldosterone induced, and MR antagonist spironolactone inhibited, PSGL1 expression in human U937 monocytes. Mechanistically, aldosterone stimulated MR binding to a predicted MR response element in intron-1 of the PSGL1 gene by ChIP-qPCR. Reporter assays demonstrated that this PSGL1 MR response element is necessary and sufficient for aldosterone-activated, MR-dependent transcriptional activity. Conclusions: These data identify PSGL1 as a My-MR target gene that drives leukocyte trafficking to enhance atherosclerotic plaque inflammation. These novel and sexually dimorphic findings provide insight into increased ischemia risk with MR activation, cardiovascular protection in women, and the role of MR in atherosclerosis and tissue inflammation.


Assuntos
Aorta Torácica/metabolismo , Doenças da Aorta/metabolismo , Aterosclerose/metabolismo , Adesão Celular , Migração e Rolagem de Leucócitos , Macrófagos Peritoneais/metabolismo , Glicoproteínas de Membrana/metabolismo , Monócitos/metabolismo , Receptores de Mineralocorticoides/metabolismo , Adulto , Animais , Aorta Torácica/patologia , Doenças da Aorta/genética , Doenças da Aorta/patologia , Doenças da Aorta/prevenção & controle , Aterosclerose/genética , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Adesão Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Hipoglicemia/tratamento farmacológico , Hipoglicemia/genética , Hipoglicemia/metabolismo , Migração e Rolagem de Leucócitos/efeitos dos fármacos , Macrófagos Peritoneais/patologia , Masculino , Glicoproteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Monócitos/efeitos dos fármacos , Monócitos/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Mineralocorticoides/efeitos dos fármacos , Receptores de Mineralocorticoides/genética , Fatores Sexuais , Transdução de Sinais , Espironolactona/uso terapêutico , Transcrição Genética , Migração Transendotelial e Transepitelial , Resultado do Tratamento , Células U937 , Adulto Jovem
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