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2.
Diabetes Res Clin Pract ; 193: 110144, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36351486

RESUMO

AIMS: To assess the efficacy and safety of ultra-rapid insulin analogues used with continuous subcutaneous insulin infusion systems (CSII) in adults with type 1 diabetes (T1DM). METHODS: We searched MEDLINE and Cochrane Library up to May 2022 for randomized controlled trials comparing ultra-rapid with rapid-acting insulin analogues (RAIAs) used with CSII. We performed random effects meta-analyses for % of 24-h time in range of 70-180 mg/dl (TIR), time in hypoglycaemia (<70 mg/dl) and hyperglycaemia (>180 mg/dl), 1- and 2-hour post-prandial glucose [PPG] increment after a meal test, HbA1c and average insulin dose at endpoint, unplanned infusion set changes and severe hypoglycaemia. RESULTS: Nine studies (1,156 participants) were included. Ultra-rapid insulins were superior to RAIAs on TIR (mean difference [MD] 1.1 %, 95 % CI 0.11-2.11), time spent in hypoglycaemia (MD -0.47 %, 95 % CI -0.63 to -30), and 1- and 2-hour PPG (MD -12.20 mg/dl, 95 % CI -19.85 to -4.54 and MD -17.61 mg/dl, 95 % CI -28.55 to -6.66, respectively). Ultra-rapid insulins increased odds of unplanned infusion set changes (odds ratio 1.60, 95 % CI 1.26-2.03). CONCLUSION: Ultra-rapid acting insulins provided better PPG control compared to RAIAs but their use might result in more infusion set changes.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adulto , Humanos , Insulina/efeitos adversos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Insulina Regular Humana , Insulina de Ação Curta
3.
Front Endocrinol (Lausanne) ; 13: 953879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36237197

RESUMO

Objective: Studies investigating strategies to limit the risk of nocturnal hypoglycemia associated with physical activity (PA) are scarce and have been conducted in standardized, controlled conditions in people with type 1 diabetes (T1D). This study sought to investigate the effect of daily PA level on nocturnal glucose management in free-living conditions while taking into consideration reported mitigation strategies to limit the risk of nocturnal hyoglycemia in people with T1D. Methods: Data from 25 adults (10 males, 15 females, HbA1c: 7.6 ± 0.8%), 20-60 years old, living with T1D, were collected. One week of continuous glucose monitoring and PA (assessed using an accelerometer) were collected in free-living conditions. Nocturnal glucose values (midnight-6:00 am) following an active day "ACT" and a less active day "L-ACT" were analyzed to assess the time spent within the different glycemic target zones (<3.9 mmol/L; 3.9 - 10.0 mmol/L and >10.0 mmol/L) between conditions. Self-reported data about mitigation strategies applied to reduce the risk of nocturnal hypoglycemia was also analyzed. Results: Only 44% of participants reported applying a carbohydrate- or insulin-based strategy to limit the risk of nocturnal hypoglycemia on ACT day. Nocturnal hypoglycemia occurrences were comparable on ACT night versus on L-ACT night. Additional post-meal carbohydrate intake was higher on evenings following ACT (27.7 ± 15.6 g, ACT vs. 19.5 ± 11.0 g, L-ACT; P=0.045), but was frequently associated with an insulin bolus (70% of participants). Nocturnal hypoglycemia the night following ACT occurred mostly in people who administrated an additional insulin bolus before midnight (3 out of 5 participants with nocturnal hypoglycemia). Conclusions: Although people with T1D seem to be aware of the increased risk of nocturnal hypoglycemia associated with PA, the risk associated with additional insulin boluses may not be as clear. Most participants did not report using compensation strategies to reduce the risk of PA related late-onset hypoglycemia which may be because they did not consider habitual PA as something requiring treatment adjustments.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adulto , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Exercício Físico , Feminino , Glucose , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prevalência , Condições Sociais , Adulto Jovem
4.
Front Endocrinol (Lausanne) ; 13: 1011383, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313766

RESUMO

Diabetic cardiomyopathy (DCM) is a severe complication of diabetes mellitus that is characterized by aberrant myocardial structure and function and is the primary cause of heart failure and death in diabetic patients. Endothelial dysfunction plays an essential role in diabetes and is associated with an increased risk of cardiovascular events, but its role in DCM is unclear. Previously, we showed that S-nitroso-L-cysteine(CSNO), an endogenous S-nitrosothiol derived from eNOS, inhibited the activity of protein tyrosine phosphatase 1B (PTP1B), a critical negative modulator of insulin signaling. In this study, we reported that CSNO treatment induced cellular insulin-dependent and insulin-independent glucose uptake. In addition, CSNO activated insulin signaling pathway and promoted GLUT4 membrane translocation. CSNO protected cardiomyocytes against high glucose-induced injury by ameliorating excessive autophagy activation, mitochondrial impairment and oxidative stress. Furthermore, nebulized CSNO improved cardiac function and myocardial fibrosis in diabetic mice. These results suggested a potential site for endothelial modulation of insulin sensitivity and energy metabolism in the development of DCM. Data from these studies will not only help us understand the mechanisms of DCM, but also provide new therapeutic options for treatment.


Assuntos
Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , S-Nitrosotióis , Camundongos , Animais , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/induzido quimicamente , S-Nitrosotióis/efeitos adversos , S-Nitrosotióis/metabolismo , Insulina/efeitos adversos
5.
Indian J Pharmacol ; 54(4): 244-252, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36204807

RESUMO

OBJECTIVE: Compliance to insulin injections is poor due to difficulty in subcutaneous administration. Hence, there is a need of an oral formulation of insulin. Oral insulin is currently under investigation. The present analysis aimed to evaluate oral insulin versus placebo for patients with diabetes mellitus (type-1 and type-2). MATERIALS AND METHODS: Results from PUBMED and MEDLINE were searched and compiled from January 1, 2000 to January 9, 2020. Postprandial blood glucose excursions (2PPG), glycated hemoglobin (HbA1c), C-peptide levels, and immune antibody (IAA) levels were compared between the arms. In addition, time to diabetes and safety of oral insulin were discussed. RESULTS: Thirteen out of 1778 trials were included to the analysis. Oral insulin was found to induce significant reduction in mean 2PPG excursion (standardized mean difference [SMD]: -1.94, 95% CI: -3.20 to -0.68, I2 = 91.81, P < 0.005) and mean IAA levels (SMD:-0.49, 95% CI: -0.82 to -0.16, I2 = 27.12, P < 0.005) compared with placebo. Mean C-peptide levels were notably lower in the oral insulin arm. However, the difference was not statistically significant. No significant difference was observed in mean HbA1c levels. The rate of development of type-1 diabetes was not significantly influenced by oral insulin. No deaths or treatment-related serious adverse events were reported. CONCLUSION: Oral insulin provided significant benefits for acute maintenance of diabetes mellitus. It elicited lower immune response and was well tolerated. This new formulation has potential to augment the management of diabetes mellitus. More studies are required to assess its long-term effects.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Glicemia/análise , Peptídeo C/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos
6.
Arch Endocrinol Metab ; 66(6): 784-791, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36191264

RESUMO

Objective: The aim of this study was to investigate the factors associated with hypoglycemia and severe hypoglycemia (SH) in individuals with type 1 diabetes mellitus (T1D) in Brazil. Materials and Methods: This multicenter, cross-sectional study was conducted between August 2011 and August 2014 across 10 Brazilian cities. The data were obtained from 1,760 individuals with T1D. Sociodemographic and clinical characteristics related to hypoglycemic events in the previous 4 weeks were evaluated. Results: Of 1,760 individuals evaluated, 1,319 (74.9%) reported at least one episode of hypoglycemia in the previous 4 weeks. The main factors associated with hypoglycemia were lower hemoglobin A1c (HbA1c) level, better adherence to self-monitoring of blood glucose (SMBG), and higher education level. Episodes of SH were reported by 251 (19%) individuals who, compared with subjects with nonsevere hypoglycemia, received lower doses of prandial insulin and higher doses of basal insulin, in addition to reporting less frequent use of long-acting basal insulin analogs. The percentage of SH episodes was evenly distributed across all ranges of HbA1c levels, and there were no correlations between the mean number of nonsevere or severe hypoglycemic events and HbA1c values. Higher alcohol consumption and more frequent hospitalizations were independently associated with SH. Conclusion: Although individuals presenting with hypoglycemia had lower HbA1c values than those not presenting hypoglycemia, there were no correlations between the number of nonsevere hypoglycemia or SH and HbA1c values. Also, the frequency of SH was evenly distributed across all ranges of HbA1c values. Better adherence to SMBG and higher education level were associated with hypoglycemia, while alcohol consumption, higher doses of basal insulin, and more frequent hospitalizations in the previous year were associated with SH.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Humanos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Estudos Transversais , Hemoglobina A Glicada/análise , Brasil/epidemiologia , Hipoglicemia/epidemiologia , Hipoglicemia/etiologia , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Fatores de Risco , Glicemia
7.
Mayo Clin Proc ; 97(11): 1994-2004, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36210202

RESUMO

OBJECTIVE: To overcome the limitations of commercially available insulin immunoassays which have variable detection of analog insulin and can lead to clinically discordant results and misdiagnosis in the workup of factitious hypoglycemia. PATIENTS AND METHODS: We performed analytical validation of a liquid chromatography high resolution accurate mass (LC-HRAM) immunoassay to detect insulin analogs. We completed clinical assessment using a large cohort of human serum samples from 78 unique individuals, and subsequently used the assay in the evaluation of eight individuals with high diagnostic suspicion for factitious hypoglycemia. RESULTS: The performance characteristics show that the LC-HRAM immunoassay can be applied to detect five commonly used synthetic insulin analogs (lispro, glulisine, aspart, glargine metabolite, and detemir) in human serum. Our clinical cases show that this assay could be used in the diagnosis of factitious hypoglycemia by identifying the analog insulin(s) in question. CONCLUSION: The LC-HRAM immunoassay reported here overcomes a gap in our diagnostic pathway for hypoglycemia. The results obtained from our studies suggest that this method is appropriate for use in clinical laboratories when factitious hypoglycemia is considered as a differential diagnosis.


Assuntos
Hipoglicemia , Insulina , Humanos , Insulina/efeitos adversos , Insulina/análise , Hipoglicemia/induzido quimicamente , Hipoglicemia/diagnóstico , Imunoensaio/métodos , Hipoglicemiantes/efeitos adversos
8.
Prim Care Diabetes ; 16(6): 753-759, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36216752

RESUMO

AIMS: To analyse if antidiabetic treatment was associated with better COVID-19 outcomes in type 2 diabetic patients, measured by hospital admission and mortality rates as severe outcomes. METHODS: Cohort study including COVID-19 patients registered in the Primary Care electronic records, in March-June 2020, comparing exposed to metformin in monotherapy with exposed to any other antidiabetic. DATA SOURCE: SIDIAP (Information System for Research in Primary Care), which captures clinical information of 5,8 million people from Catalonia, Spain. RESULTS: We included 31,006 diabetic patients infected with COVID-19, 43.7% previously exposed to metformin, 45.5% of them in monotherapy. 16.4% were admitted to hospital and 15.1% died. Users of insulin in monotherapy (OR 1.29, 95% CI 1.11-1.50), combined with metformin (OR 1.38, 1.13-1.69) or IDPP4 alone (OR 1.29, 1.03-1.63) had higher risk of severe outcomes than those in metformin monotherapy. Users of any insulin (OR 1.61, 1.32-1.97) or combined with metformin (OR 1.69, 1.30-2.20) had a higher risk of mortality. CONCLUSIONS: Patients receiving metformin monotherapy in our study showed a lower risk of hospitalization and death in comparison to those treated with other frequent antidiabetic agents. We cannot distinguish if better outcomes are related with the antidiabetic therapy or with other factors, such as metabolic control or interventions applied during the hospital admission.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Metformina , Humanos , Hipoglicemiantes/efeitos adversos , Espanha/epidemiologia , Pandemias , Estudos de Coortes , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Metformina/efeitos adversos , Insulina/efeitos adversos , Atenção Primária à Saúde
9.
Diabet Med ; 39(12): e14973, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36251572

RESUMO

AIMS: People with type 1 and type 2 diabetes still frequently experience hypoglycaemia, which can be severe, leading to loss of consciousness. This review will examine the cellular consequences of recurrent hypoglycaemia. METHODS: This review, based on the Dorothy Hodgkin Lecture given at the Diabetes UK 2022 annual symposium by the author, will discuss our current understanding of the mechanisms by which hypoglycaemia is detected and the consequences of recurrent exposure to hypoglycaemia. RESULTS: Glucose-responsive cells found in the periphery as well as multiple areas of the brain are organised in a classical sensori-motor integrative network encompassing peripheral, hindbrain and hypothalamic components. The mechanism used by glucose-responsive neurons to detect hypoglycaemia parallel those of the classical glucose sensor the pancreatic ß-cell, namely in their use of glucokinase, KATP channels and AMP-activated protein kinase. Recurrent exposure to hypoglycaemia results in a series of cellular adaptations that may be designed to increase the resilience of cells to future hypoglycaemia. This review also highlights how hypoglycaemia, as an oxidative stressor, may also exacerbate chronic hyperglycaemia-induced increases in oxidative stress and inflammation, leading to damage to vulnerable brain regions. CONCLUSIONS: Impaired awareness of hypoglycaemia follows the adaptation of central glucose-responsive neurons to repeated hypoglycaemia and may represent a form of memory called habituation. In diabetes, recurrent hypoglycaemia may have tissue consequences as a result of a profound disruption in the cellular response to a hypoglycaemic challenge that increases vulnerability to oxidative damage.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hipoglicemia , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Glucose/farmacologia , Glicemia/metabolismo , Insulina/efeitos adversos
10.
PLoS One ; 17(9): e0264545, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36136973

RESUMO

AIMS: To characterizes Emiratis patients with Type 1 diabetes (T1D) and compares outcomes between continuous subcutaneous insulin infusion (CSII) versus multiple daily insulin injections (MDI) users. The WHO-Five Well-Being Index (WHO-5) score was used to screen for depression. METHODS: In this cross-sectional study; sociodemographic, clinical characteristics and insulin replacement regimens were collected on patients with T1D between 2015-2018. RESULTS: 134 patients with mean age of 20.9±7.5 years were included. Females constitute 56.7% and 50.7% had diabetes duration of >10 years. Diabetic ketoacidosis (DKA) at presentation was reported in 46.3%. Average glycemic control over preceding 12months was satisfactory (less than 7.5%), suboptimal (7.5-9%), and poor (more than 9%) in 26.6%, 42.7% & 30.6% of the patients, respectively. Higher proportion of patients using CSII achieved satisfactory or suboptimal glycemic control compared to patients with MDI (P = 0.003). The latest median /IQR HbA1c was significantly lower (P = 0.041) in patients using CSII (8.2 /1.93%) compared to MDI (8.5/2.45%). There was no significant difference between two groups in DKA, severe hypoglycemia or total WHO-5 score. CONCLUSIONS: CSII usage was associated with better glycemic control than MDI, although no difference in DKA and severe hypoglycemia. The overall glycemic control among Emiratis subjects with T1D is unsatisfactory and needs more rigorous patient counseling and education.


Assuntos
Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Hipoglicemia , Adolescente , Adulto , Glicemia , Estudos Transversais , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cetoacidose Diabética/epidemiologia , Feminino , Hemoglobina A Glicada/análise , Controle Glicêmico , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Injeções Subcutâneas , Insulina/efeitos adversos , Sistemas de Infusão de Insulina , Emirados Árabes Unidos/epidemiologia , Adulto Jovem
11.
Front Public Health ; 10: 990281, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091534

RESUMO

Objective: Regarding the effects and practical application of insulin pumps on patients with type 1 diabetes mellitus (T1DM), the real-world evidence is limited especially concerning the incidence of hypoglycemia. This study aimed to compare the efficacy of continuous subcutaneous insulin infusion (CSII) therapy with multiple daily injection (MDI) therapy on glycemic metrics evaluated by retrospective continuous glucose monitoring (CGM) in Chinese patients with T1DM. Methods: In total, 362 T1DM Chinese patients from the outpatient department of the Second Xiangya Hospital, Central South University, who underwent intensive insulin therapy and used a retrospective CGM system were included in this retrospective cross-sectional study. Comprehensive analysis of clinical and biological features and retrospective CGM derived-metrics was performed on the 362 enrolled T1DM patients who underwent CSII (n = 61) or MDI (n = 301) therapy (defined as 4 or more insulin injections per day). Results: Our findings demonstrated that patients who underwent CSII therapy, compared with those who received MDI therapy, had lower levels of hemoglobin A1c (HbA1c) and fasting blood glucose; moreover, CSII therapy was associated with better glycemic outcomes in terms of increasing time in range (TIR), decreasing time above range (TAR), and achieving CGM-associated targets of TIR ≥70% and TAR <25%. However, patients who underwent CSII therapy did not experience decreasing time below range (TBR), achieving CGM-associated targets of TBR <4%, and reduction of the risk of hypoglycemia as evidenced by comparing TBR and low blood glucose index (LBGI) between the two treatment regimens. The parameters of glycemic variability, such as standard deviation of glucose (SD), mean amplitude glycemic excursion (MAGE), and large amplitude glycemic excursion (LAGE) in T1DM patients who underwent CSII therapy outperformed. Conclusion: Our results provided further evidence that CSII therapy is safe and effective for management of Chinese T1DM patients, which was confirmed by a lower HbA1c level and better CGM-derived metrics but no demonstration of improvment in the risk of hypoglycemia. To achieve more satisfactory glycemic outcomes through the utilization of CSII therapy for Chinese T1DM patients, a strong physician-patient relationship is essential.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Glicemia/análise , Automonitorização da Glicemia/efeitos adversos , Estudos Transversais , Análise de Dados , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucose/uso terapêutico , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/uso terapêutico , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/efeitos adversos , Insulina/uso terapêutico , Sistemas de Infusão de Insulina/efeitos adversos , Estudos Retrospectivos
12.
N Engl J Med ; 387(13): 1161-1172, 2022 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-36170500

RESUMO

BACKGROUND: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting. METHODS: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed. RESULTS: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group. CONCLUSIONS: In this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.).


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemiantes , Insulina Aspart , Sistemas de Infusão de Insulina , Insulina Lispro , Adolescente , Adulto , Idoso , Biônica/instrumentação , Glicemia/análise , Automonitorização da Glicemia/instrumentação , Automonitorização da Glicemia/métodos , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/efeitos adversos , Insulina/uso terapêutico , Insulina Aspart/administração & dosagem , Insulina Aspart/efeitos adversos , Insulina Aspart/uso terapêutico , Sistemas de Infusão de Insulina/efeitos adversos , Insulina Lispro/administração & dosagem , Insulina Lispro/efeitos adversos , Insulina Lispro/uso terapêutico , Pessoa de Meia-Idade , Adulto Jovem
13.
Trials ; 23(1): 788, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123593

RESUMO

BACKGROUND: It remains controversial whether critical illness-related hyperglycemia should be treated or not, since randomized controlled trials (RCTs) have shown context-dependent outcome effects. Whereas pioneer RCTs found improved outcome by normalizing blood glucose in patients receiving early parenteral nutrition (PN), a multicenter RCT revealed increased mortality in patients not receiving early PN. Although withholding early PN has become the feeding standard, the multicenter RCT showing harm by tight glucose control in this context has been criticized for its potentially unreliable glucose control protocol. We hypothesize that tight glucose control is effective and safe using a validated protocol in adult critically ill patients not receiving early PN. METHODS: The TGC-fast study is an investigator-initiated, multicenter RCT. Patients unable to eat, with need for arterial and central venous line and without therapy restriction, are randomized upon ICU admission to tight (80-110 mg/dl) or liberal glucose control (only initiating insulin when hyperglycemia >215 mg/dl, and then targeting 180-215 mg/dl). Glucose measurements are performed on arterial blood by a blood gas analyzer, and if needed, insulin is only administered continuously through a central venous line. If the arterial line is no longer needed, glucose is measured on capillary blood. In the intervention group, tight control is guided by the validated LOGIC-Insulin software. In the control arm, a software alert is used to maximize protocol compliance. The intervention is continued until ICU discharge, until the patient is able to eat or no longer in need of a central venous line, whatever comes first. The study is powered to detect, with at least 80% power and a 5% alpha error rate, a 1-day difference in ICU dependency (primary endpoint), and a 1.5% increase in hospital mortality (safety endpoint), for which 9230 patients need to be included. Secondary endpoints include acute and long-term morbidity and mortality, and healthcare costs. Biological samples are collected to study potential mechanisms of organ protection. DISCUSSION: The ideal glucose target for critically ill patients remains debated. The trial will inform physicians on the optimal glucose control strategy in adult critically ill patients not receiving early PN. TRIAL REGISTRATION: ClinicalTrials.gov NCT03665207. Registered on 11 September 2018.


Assuntos
Hiperglicemia , Insulina , Adulto , Algoritmos , Glicemia , Estado Terminal/terapia , Jejum , Glucose , Controle Glicêmico , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/tratamento farmacológico , Hiperglicemia/prevenção & controle , Insulina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Trials ; 23(1): 795, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36131291

RESUMO

BACKGROUND: Pregnancies affected by gestational diabetes mellitus (GDM) are associated with an increased risk of adverse maternal and foetal outcomes. Current treatments for GDM involve initial medical nutritional therapy (MNT) and exercise and pharmacotherapy in those with persistent hyperglycaemia. Insulin is considered first-line pharmacotherapy but is associated with hypoglycaemia, excessive gestational weight gain (GWG) and an increased caesarean delivery rate. Metformin is safe in selected groups of women with GDM but is not first-line therapy in many guidelines due to a lack of long-term data on efficacy. The EMERGE trial will evaluate the effectiveness of early initiation of metformin in GDM. METHODS: EMERGE is a phase III, superiority, parallel, 1:1 randomised, double-blind, placebo-controlled trial comparing the effectiveness of metformin versus placebo initiated by 28 weeks (+6 days) plus usual care. Women aged 18-50 years will be recruited. Women with established diabetes, multiple pregnancies, known major congenital malformation or small for gestational age (<10th centile), intolerance or contraindication to the use of metformin, shock or sepsis, current gestational hypertension or pre-eclampsia, significant gastrointestinal problems, congestive heart failure, severe mental illness or galactose intolerance are excluded. INTERVENTION: Immediate introduction of metformin or placebo in addition to MNT and usual care. Metformin is initiated at 500mg/day and titrated to a maximum dose of 2500mg over 10 days. Women are followed up at 4 and 12 weeks post-partum to assess maternal and neonatal outcomes. The composite primary outcome measure is initiation of insulin or fasting blood glucose ≥ 5.1 mmol/L at gestational weeks 32 or 38. The secondary outcomes are the time to insulin initiation and insulin dose required; maternal morbidity at delivery; mode and time of delivery; postpartum glucose status; insulin resistance; postpartum body mass index (BMI); gestational weight gain; infant birth weight; neonatal height and head circumference at delivery; neonatal morbidities (neonatal care unit admission, respiratory distress, jaundice, congenital anomalies, Apgar score); neonatal hypoglycaemia; cost-effectiveness; treatment acceptability and quality of life determined by the EQ5D-5L scale. DISCUSSION: The EMERGE trial will determine the effectiveness and safety of early and routine use of metformin in GDM. TRIAL REGISTRATION: EudraCT Number 2016-001644-19l; NCT NCT02980276 . Registered on 6 June 2017.


Assuntos
Diabetes Gestacional , Ganho de Peso na Gestação , Hipoglicemia , Metformina , Glicemia , Ensaios Clínicos Fase III como Assunto , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/tratamento farmacológico , Feminino , Galactose , Humanos , Hipoglicemia/induzido quimicamente , Recém-Nascido , Insulina/efeitos adversos , Metformina/efeitos adversos , Gravidez , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Aumento de Peso
15.
Prim Care Diabetes ; 16(6): 786-790, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36117090

RESUMO

AIM: To study the effect of real time continuous glucose monitor (RT-CGM) use on glycemic parameters in patients with diabetes mellitus (DM) in real world practice. METHODS: We retrospectively studied 91 adult subjects with DM who had been using Dexcom™ RT-CGM. Two consecutive hemoglobin A1c (HbA1c), both prior to and after at least 3 months of RT-CGM initiation, were collected. A total of 31 subjects completed a 5-14 day user blinded CGM using a Freestyle Libre™ prior to RT-CGM initiation. The first two week period following at least 3 months use of RT-CGM was analyzed for CGM metrics. RESULTS: A total of 51.6 % of subjects had T1DM, 34.1 % used continuous subcutaneous insulin infusion (CSII), and 62.6 % had DM for > 10 years. Both HbA1c obtained following RT-CGM initiation decreased significantly compared to baseline (8.11 + 1.47% vs 7.69 + 1.25 %; P = 0.002 & 8.16 + 1.51 % vs 7.62 + 1.06 %; P = 0.001). Subjects with baseline HbA1c > 7.0 % showed even more robust reduction in both HbA1c after RT-CGM initiation (8.74 + 1.24 % vs 7.99 + 1.22 %; P = 0.000 & 8.74 + 1.32 % vs 7.85 + 1.07 %; P = 0.001). On comparison of CGM metrics, there was a significant reduction in time spent in hypoglycemia (sugars < 70 mg/dl) including severe hypoglycemia (sugars < 54 mg/dl) after initiation of the RT-CGM (9.16 + 8.68 % vs 1.29 + 2.21 %; P = <0.001 & 4.58 + 5.43 % vs 0.28 + 0.58 %; P = <0.001). CoV of glucose was also decreased significantly (39.61 + 9.36 % vs 31.06 + 6.74 %; P = <0.001) with RT- CGM use. CONCLUSION: RT-CGM use for at least 3 months in patients with DM results in meaningful HbA1c reductions with stable glycemic control without increasing the risk of hypoglycemia.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adulto , Humanos , Automonitorização da Glicemia/métodos , Glicemia , Hemoglobina A Glicada/análise , Controle Glicêmico/efeitos adversos , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Estudos Retrospectivos , Hipoglicemia/induzido quimicamente , Hipoglicemia/diagnóstico , Hipoglicemia/prevenção & controle , Insulina/efeitos adversos , Glucose
16.
Diabetes Res Clin Pract ; 192: 110083, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36122865

RESUMO

AIMS: We aimed to determine if severe hypoglycemia (SH) independently increases the risk of hospitalization for heart failure (hHF) in type 2 diabetes, regardless of the prevalent or incident cardiovascular disease (CVD). METHODS: This was a nationwide population-based propensity score-matched study using Korean National Health Insurance Service data (2002-2018). The hazards of hHF were compared in individuals who experienced SH (n = 8,965) and 1:3 matched controls, among adults with diabetes using oral anti-diabetes medications (OADs) with or without insulin and without previous hHF at baseline. RESULTS: During 236,417 person-years, 1,189 cases of hHF occurred. The hazard of hHF was higher in individuals with SH compared to matched controls (adjusted hazard ratio [aHR] 1.503, 95 % confidence interval [CI] 1.324-1.707). The increase in aHR remained significant when excluding participants with prevalent or incident major adverse cardiovascular events (MACE; aHR 1.352, 95 % CI 1.228-1.622) and any CVD (aHR 1.342, 95 % CI 1.025-1.756). Two or more SH events were associated with further increase in hHF risk. CONCLUSION: SH was associated with increased risks of hHF among adults with diabetes using OAD with or without insulin. The increased risk was attenuated but remained significant in those without prevalent or incident MACE or CVDs.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Hipoglicemia , Adulto , Humanos , Insulina/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Fatores de Risco , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemia/complicações , Insuficiência Cardíaca/terapia , Hospitalização , Insulina Regular Humana/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/complicações
17.
Prog Transplant ; 32(4): 327-331, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36114645

RESUMO

Introduction: Insulin is commonly prescribed to manage early post-kidney transplant hyperglycemia due to its flexibility. Studies comparing the effectiveness of oral therapies on glycemic outcomes remain limited. Project aims: The purpose of this program evaluation was to analyze our experience using oral antiglycemic agents immediately post-kidney transplant, compared to patients managed with insulin monotherapy. Design: This was a single-center, retrospective review of adult kidney transplant recipients with new or worsening hyperglycemia between 01/2014-05/2020. Patients were excluded if they had a prior or combined organ transplant, type 1 diabetes, or were previously on intensive insulin. Patients discharged on oral medications were 1:1 matched to patients receiving intensive insulin based on pre-specified clinical parameters. The primary endpoint was the number of diabetes-related readmissions within 6-months of transplant. Key secondary endpoints included mean serum glucose and hemoglobin A1c levels. Results: Thirty patients prescribed oral therapies were successfully matched to patients receiving intensive insulin. Baseline characteristics were similar between groups, except for more whites in the insulin group. There were no differences in diabetes-related (6.7% vs 3.3%; P = 1.00) or all-cause readmissions within 6-months. Mean serum glucose (P = .99) and hemoglobin A1c (P = .49) levels were also similar between patients receiving oral agents and insulin. However, 7 patients in the oral group were eventually converted to standing insulin. Conclusion: Our experience suggested that the early use of oral antiglycemics post-kidney transplant in select patients can result in similar outcomes relative to insulin. Meticulous follow-up is necessary as one-quarter of patients may require conversion to insulin within 1-month.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Transplante de Rim , Adulto , Humanos , Insulina/uso terapêutico , Insulina/efeitos adversos , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/uso terapêutico , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Transplante de Rim/efeitos adversos , Controle Glicêmico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/etiologia , Glicemia , Hiperglicemia/tratamento farmacológico , Hiperglicemia/induzido quimicamente
18.
BioDrugs ; 36(6): 761-772, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36114990

RESUMO

BACKGROUND: MYL-1601D is a proposed biosimilar of originator insulin aspart, Novolog®/NovoRapid® (Ref-InsAsp-US/Ref-InsAsp-EU). OBJECTIVE: This study assessed the immunogenicity, efficacy, and safety of MYL-1601D with Ref-InsAsp-US in patients with type 1 diabetes mellitus (T1D). METHODS: This was a 24-week, open-label, randomized, phase III study. Patients were randomized 1:1 to mealtime MYL-1601D or Ref-InsAsp-US in combination with insulin glargine (Lantus SoloSTAR®) once daily. The treatment-emergent antibody response (TEAR) rate (defined as patients who were anti-insulin antibody [AIA] negative at baseline and became positive at any timepoint post-baseline or patients who were AIA positive at baseline and demonstrated a 4-fold increase in titer values at any timepoint post-baseline) was the primary endpoint. The study also compared the change from baseline in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), prandial, basal, and total daily insulin, 7-point self-monitored blood glucose (SMBG) profiles, immunogenicity, and adverse events (AEs) including hypoglycemia. RESULTS: In total, 478 patients were included in the intent-to-treat analysis (MYL-1601D: 238; Ref-InsAsp-US: 240) set. The 90% confidence interval (CI) for the primary endpoint was within the pre-defined equivalence margin of ±11.7% and the treatment differences (SE) in TEAR responders between the treatment groups was - 2.86 (4.16) with 90% CI - 9.71 to 3.99. The mean (SD) changes from baseline for HbA1c, FPG, and insulin dosages were similar in both groups at week 24. The safety profiles including hypoglycemia, immune-related events, AEs, and other reported variables were similar between the treatment groups at week 24. CONCLUSIONS: MYL-1601D demonstrated similar immunogenicity, efficacy, and safety profiles to Ref-InsAsp-US in patients with T1D over 24 weeks. CLINICAL TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03760068.


Assuntos
Medicamentos Biossimilares , Diabetes Mellitus Tipo 1 , Hipoglicemia , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina Aspart/efeitos adversos , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/uso terapêutico , Medicamentos Biossimilares/efeitos adversos , Hipoglicemiantes/efeitos adversos , Glicemia , Insulina Glargina/efeitos adversos , Hipoglicemia/induzido quimicamente , Insulina/efeitos adversos
19.
Endocrinol Diabetes Metab ; 5(6): e375, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36117266

RESUMO

INTRODUCTION: Factitious hypoglycaemia is defined as the surreptitious use of insulin or oral hypoglycaemic agents to deliberately induce self-harm. It represents a challenging diagnosis and misdiagnosis is associated with significant morbidity and mortality. The aim of this study was to assess the prevalence and the associated factors of factitious hypoglycaemia in non-diabetic patients. METHODS: This was a single-centre, retrospective study including 70 non-diabetic patients who were admitted for the investigation of hypoglycaemia. All patients fulfilled the Whipple triad. Epidemiological parameters, medical history, clinical and paraclinical data and the aetiology of hypoglycaemia were collected from medical records. RESULTS: The diagnosis of factitious hypoglycaemia was held in 11 patients (9 women and 2 men) corresponding to a prevalence of 16%. It was secondary to intentional insulin use in six patients and the ingestion of glibenclamide in five patients. The median age of the patients was 28 years (interquartile range: 21-43). Two patients with factitious hypoglycaemia had a personal history of psychiatric disorders. The other causes of hypoglycaemia were adrenal insufficiency (34%), prediabetes (24%), insulinoma (6%), iatrogenic hypoglycaemia (10%), criminal hypoglycaemia (1%) and alcohol intoxication (2%). Age ≤ 35 years (Odds Ratio = 5.6, p = .017), family history of diabetes mellitus (Odds Ratio = 1.29, p = .015), attention disorders during hypoglycaemia (Odds Ratio = 12.5, p = .017) and fasting glucose level <0.7 g/L (Odds Ratio = 5.75, p = .017) were positively associated with factitious hypoglycaemia. CONCLUSION: Factors significantly associated with factitious hypoglycaemia were young age, family history of diabetes and a low fasting glucose level.


Assuntos
Diabetes Mellitus , Hipoglicemia , Neoplasias Pancreáticas , Masculino , Humanos , Feminino , Adulto , Prevalência , Estudos Retrospectivos , Hipoglicemia/diagnóstico , Hipoglicemia/epidemiologia , Hipoglicemia/etiologia , Insulina/efeitos adversos , Diabetes Mellitus/epidemiologia , Neoplasias Pancreáticas/induzido quimicamente , Neoplasias Pancreáticas/complicações , Glucose
20.
Cardiovasc Diabetol ; 21(1): 191, 2022 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-36138441

RESUMO

INTRODUCTION: Duodenal Mucosal Resurfacing (DMR) is an endoscopic ablation technique aimed at improving glycaemia and metabolic health in patients with type 2 diabetes mellitus (T2DM). DMR has an insulin sensitizing effect in patients with T2DM. Reducing hyperinsulinemia can improve cardiovascular health. In the INSPIRE trial, we combined a single DMR with a glucagon-like-peptide-1 receptor agonist (GLP-1RA) and demonstrated elimination of insulin treatment in 69% of patients at 6 months and 53% of patients at 18 months while improving glycaemic control and metabolic health. We hypothesized that this treatment approach is associated with improved cardiovascular health, by reducing hyperinsulinemia. METHODS: Before and 6 months after starting the combination treatment to replace insulin, the following assessments were performed to evaluate cardiovascular health: magnetic resonance imaging (MRI) to measure abdominal visceral adipose tissue volume, ambulatory 24 h blood pressure (ABPM) analysis, postprandial insulin and triglycerides, fasting lipid panel and urine microalbumin. The Atherosclerotic Cardiovascular Disease (ASCVD) score was calculated to estimate 10-year risk of cardiovascular disease or stroke and the diabetes lifetime-perspective prediction (DIAL) score was calculated to estimate years free of cardiovascular disease. RESULTS: Six months after replacing exogenous insulin by DMR and GLP-1RA, visceral adipose tissue decreased significantly by 24%. Postprandial triglyceride and insulin concentrations decreased significantly (p < 0.001), as did total cholesterol (from median 3.64 (IQR 3.34-4.89) to 3.48 (3.18-3.97) mmol/l, p = 0.008), LDL (from median 1.92 (IQR 1.49-2.30) to 1.79 (1.49-2.08 mmol/l, p = 0.044), and urine microalbumin (from median 7 (IQR 3-27) to 4 (3-8) mg/l, p = 0.018). All daytime blood pressure values decreased significantly. The ASCVD 10-year risk score decreased (from median 13.6 (IQR 5.7-26.0) to 11.5 (4.2-22.5) %, p = 0.030)) and the DIAL score increased (from median 82 (IQR 81-83) to 83 (81-84) years, (p = 0.039)). DISCUSSION: The combination of DMR and GLP-1RA to replace insulin therapy in patients with T2DM is associated with a positive effect on multiple parameters of cardiovascular health. Taken together, they show a pattern of overall improvement in cardiovascular health, as evidenced by decreased risk scores for cardiovascular complications. However, it is not yet clear whether these improvements will translate into a true reduction in cardiovascular events.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Hiperinsulinismo , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/etiologia , Colesterol , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hiperinsulinismo/induzido quimicamente , Hiperinsulinismo/complicações , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Lipídeos , Fatores de Risco , Triglicerídeos
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