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1.
Ann Clin Biochem ; 58(4): 318-326, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33591793

RESUMO

INTRODUCTION: Specific patterns of blood test results are associated with COVID-19 infection. The aim of this study was to identify which blood tests could be used to assist in diagnosing COVID-19. METHOD: A retrospective review was performed on consecutive patients referred to hospital with a clinical suspicion of COVID-19 over a period of four weeks. The patient's clinical presentation and severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction (SARS-CoV-2 RT-PCR) were recorded. The patients were divided by diagnosis into COVID (COVID-19 infection) or CONTROL (an alternate diagnosis). A retrospective review of consecutive patients over a further two-week period was used for the purposes of validation. RESULTS: Overall, 399 patients (53% COVID, 47% CONTROL) were analysed. White cell count, neutrophils and lymphocytes were significantly lower, while lactate dehydrogenase and ferritin were significantly higher, in the COVID group in comparison to CONTROL. Combining the white cell count, lymphocytes and ferritin results into a COVID Combined Blood Test (CCBT) had an area under the curve of 0.79. Using a threshold CCBT of -0.8 resulted in a sensitivity of 0.85 and a specificity of 0.63. Analysing this against a further retrospective review of 181 suspected COVID-19 patients, using the same CCBT threshold, resulted in a sensitivity of 0.73 and a specificity of 0.75. The sensitivity was comparable to the SARS-CoV-2 RT PCR. DISCUSSION: Mathematically combining the blood tests has the potential to assist clinical acumen allowing for rapid streaming and more accurate patient flow pending definitive diagnosis. This may be of particular use in low-resource settings.


Assuntos
Teste de Ácido Nucleico para COVID-19 , COVID-19 , Ferritinas/sangue , L-Lactato Desidrogenase/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , COVID-19/diagnóstico , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Diabet Med ; 37(2): 219-228, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31729775

RESUMO

AIMS: To revisit the data analysis used to inform National Institute of Health and Care Excellence (NICE) NG17 guidance for initiating basal insulin in adults with type 1 diabetes mellitus (diabetes). METHODS: We replicated the data, methodology and analysis used by NICE diabetes in the NG17 network meta-analysis (NMA). We expanded this data cohort to a more contemporary data set (extended 2017 NMA) and restricted the studies included to improve the robustness of the data set (restricted 2017 NMA) and in a post hoc analysis, changed the index comparator from neutral protamine Hagedorn (NPH) insulin twice daily to insulin detemir twice daily. RESULTS: The absolute changes in HbA1c were similar to those reported in the NG17. However, all 95% credible intervals for change in HbA1c point estimates crossed the line of null effect, except for detemir twice daily (in the NICE and extended 2017 NMAs) and NPH four times daily. In the detemir twice-daily centred post hoc analysis, the 95% credible intervals for change in HbA1c crossed the line of null effect for all basal therapies, except NPH. CONCLUSIONS: In NG17, comparisons of basal insulins were based solely on efficacy of glycaemic control. Many of the trials used in this analysis were treat-to-target, which minimize differences in HbA1c . In the NMAs, statistical significance was severely undermined by the wide credible intervals. Despite these limitations, point estimates of HbA1c were used to rank the insulins and formed the basis of NG17 guidance. This study queries whether such analyses should be used to make specific clinical recommendations.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas/metabolismo , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Diabetes Mellitus Tipo 1/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Insulina Detemir/uso terapêutico , Insulina Glargina/uso terapêutico , Insulina Isófana/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Metanálise em Rede , Guias de Prática Clínica como Assunto
5.
Diabet Med ; 35(10): 1320-1328, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29802638

RESUMO

There have been many advances in insulin with a realistic possibility of mimicking nature to improve insulin replacement, with a view to achieving improved metabolic control. Lessons can be learnt from the evolution of insulin, insulin development, and new advances in technology. This may lead to fewer side effects of therapy resulting in a lower risk of hypoglycaemia and less weight gain, which could in turn could reduce long-term complications for people with diabetes.


Assuntos
Desenvolvimento de Medicamentos/métodos , Desenvolvimento de Medicamentos/tendências , Insulina , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Formas de Dosagem , Desenho de Fármacos , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , Insulina/síntese química , Insulina/química , Insulina/uso terapêutico
6.
Diabetes Obes Metab ; 18(12): 1157-1166, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27491724

RESUMO

In common with global trends, the number of individuals with type 2 diabetes in the UK is rising, driven largely by obesity. The increasing prevalence of younger individuals with type 2 diabetes is of particular concern because of the accelerated course of diabetes-related complications that is observed in this population. The importance of good glycaemic control in the prevention of microvascular complications of diabetes is widely accepted, and there is a growing body of evidence to support a benefit in the reduction of cardiovascular events in the long term. Despite the importance of maintaining a healthy weight for the prevention of type 2 diabetes, the results from trials of lifestyle intervention strategies to reduce body weight have been disappointing. New glucose-lowering agents offer some promise in this regard, offering an opportunity to combat the dual burden of hyperglycaemia and obesity simultaneously. The timing and appropriate choice of glucose-lowering therapy has never been more complex as a result of rising prevalence of obesity in the young, concomitant obesity in some 90% of adults with type 2 diabetes and an ever-increasing range of therapeutic options. The present review evaluates performance measures specific to weight and glycaemic control in type 2 diabetes in the UK using data from the Quality and Outcomes Framework in England and Wales, and the Scottish Diabetes Survey. Potential barriers to improvement in standards of care for people with type 2 diabetes are considered, including patient factors, clinical inertia and the difficulties in translating therapeutic guidelines into everyday clinical practice.


Assuntos
Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Obesidade/terapia , Glicemia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Gerenciamento Clínico , Inglaterra , Humanos , Obesidade/complicações , Obesidade/metabolismo , Melhoria de Qualidade , Reino Unido , Programas de Redução de Peso
8.
Diabetes Obes Metab ; 18(11): 1055-1064, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27349219

RESUMO

AIMS: To compare, in a double-blind, randomized, multi-national study, 52- or 78-week treatment with basal insulin peglispro or insulin glargine, added to pre-study oral antihyperglycaemic medications, in insulin-naïve adults with type 2 diabetes. MATERIAL AND METHODS: The primary outcome was non-inferiority of peglispro to glargine with regard to glycated haemoglobin (HbA1c) reduction (margin = 0.4%). Six gated secondary objectives with statistical multiplicity adjustments focused on other measures of glycaemic control and safety. Liver fat content was measured using MRI, in a subset of patients. RESULTS: Peglispro was non-inferior to glargine in HbA1c reduction [least-squares (LS) mean difference: -0.29%, 95% confidence interval (CI) -0.40, -0.19], and had a lower nocturnal hypoglycaemia rate [relative rate 0.74 (95% CI 0.60, 0.91); p = .005), more patients achieving HbA1c <7.0% without nocturnal hypoglycaemia [odds ratio (OR) 2.15 (95% CI 1.60, 2.89); p < .001], greater HbA1c reduction (p < .001), and more patients achieving HbA1c<7.0% [OR 1.97 (95% CI 1.57, 2.47); p < .001]. Total hypoglycaemia rate and fasting serum glucose did not achieve statistical superiority. At 52 weeks, peglispro-treated patients had higher triglyceride (1.9 vs 1.7 mmol/L). alanine transaminase (34 vs 27 IU/L), and aspartate transaminase levels (27 vs 24 IU/L). LS mean liver fat content was unchanged with peglispro at 52 weeks but decreased 3.1% with glargine [difference: 2.6% (0.9, 4.2); p = .002]. More peglispro-treated patients experienced adverse injection site reactions (3.5% vs 0.6%, p < .001). CONCLUSIONS: Compared with glargine at 52 weeks, peglispro resulted in a statistically superior reduction in HbA1c, more patients achieving HbA1c targets, less nocturnal hypoglycaemia, no improvement in total hypoglycaemia, higher triglyceride levels, higher aminotransferase levels, and more injection site reactions.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina Glargina/administração & dosagem , Insulina Lispro/análogos & derivados , Polietilenoglicóis/administração & dosagem , Administração Oral , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Ritmo Circadiano , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Quimioterapia Combinada , Jejum/sangue , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Insulina Glargina/efeitos adversos , Insulina Lispro/administração & dosagem , Insulina Lispro/efeitos adversos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos
9.
Diabetes Obes Metab ; 17(11): 1100-3, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26272173

RESUMO

The aim of the present study was to investigate the effects of subcutaneous detemir on glucose flux, lipid metabolism and brain function. Twelve people with type 1 diabetes received, in random order, 0.5 units/kg body weight detemir or NPH insulin. Glucose concentration was clamped at 5 mmol/l then increased to 10 mmol/l. Glucose production rate (glucose Ra), glucose uptake (glucose Rd) and glycerol production (glycerol Ra) were measured with a constant intravenous infusion of [6,6(2) H(2)]glucose and [(2)H(5)]glycerol. Electroencephalography direct current (DC) and alternating current (AC) potentials were measured. While detemir induced similar effects on glucose Ra, glucose Rd and glycerol Ra during euglycaemia compared with NPH, it triggered a distinct negative shift in DC potentials, with a significant treatment effect in frontal cerebrocortical channels (p < 0.001). AC spectral power showed significant differences in theta and alpha frequencies during euglycaemia (p = 0.03). Subcutaneous detemir exerts different effects on brain function when compared with NPH in people with type 1 diabetes. This may be an important mechanism behind the limitation of weight gain with detemir.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Eletroencefalografia/efeitos dos fármacos , Hipoglicemiantes/administração & dosagem , Insulina Detemir/administração & dosagem , Lipólise/efeitos dos fármacos , Adulto , Encéfalo/efeitos dos fármacos , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Glicerol/metabolismo , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Sistemas de Infusão de Insulina , Insulina Isófana/administração & dosagem , Masculino , Aumento de Peso/efeitos dos fármacos
10.
Nutr Metab Cardiovasc Dis ; 25(10): 898-905, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26232910

RESUMO

BACKGROUND AND AIMS: Basal insulin analogues have a reduced risk of hypoglycaemia compared with NPH insulin, but hypoglycaemia still remains a major impediment to achieving recommended fasting plasma glucose (FPG) targets in patients with diabetes. Insulin degludec (IDeg) is a new basal insulin that forms soluble multihexamers after subcutaneous injection resulting in an ultra-long duration of action and stable glucose-lowering effect. The aim of this analysis was to compare the effect of IDeg on FPG and nocturnal confirmed hypoglycaemia as compared to insulin glargine (IGlar). METHODS AND RESULTS: Data were included from seven phase 3a, randomised, open-label, treat-to-target clinical trials in which once-daily IDeg was compared with once-daily IGlar. Two trials included a total of 957 patients with type 1 diabetes (T1D) and five trials included a total of 3360 patients with type 2 diabetes (T2D); all trials were 26 or 52 weeks in duration. Confirmed hypoglycaemia was defined as plasma glucose <3.1 mmol/L or severe episodes requiring assistance, and nocturnal hypoglycaemia occurred between 00:01 and 05:59. In all trials, the mean end-of-trial FPG was lower for IDeg than IGlar, reaching statistical significance in three trials. Similarly, IDeg was associated with a lower rate of nocturnal confirmed hypoglycaemia vs. IGlar, which was statistically significant in three trials, regardless of type of diabetes or background therapy. CONCLUSION: This analysis shows that the lower rate of nocturnal confirmed hypoglycaemia seen with IDeg relative to IGlar is accompanied by a reduced mean FPG, in particular in patients with T2D.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Insulina Glargina/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Jejum , Humanos , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Diabetes Obes Metab ; 17(10): 919-27, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25974283

RESUMO

Insulin therapy is often associated with adverse weight gain. This is attributable, at least in part, to changes in energy balance and insulin's anabolic effects. Adverse weight gain increases the risk of poor macrovascular outcomes in people with diabetes and should therefore be mitigated if possible. Clinical studies have shown that insulin detemir, a basal insulin analogue, exerts a unique weight-sparing effect compared with other basal insulins. To understand this property, several hypotheses have been proposed. These explore the interplay of efferent and afferent signals between the muscles, brain, liver, renal and adipose tissues in response to insulin detemir and comparator basal insulins. The following models have been proposed: insulin detemir may reduce food intake through direct or indirect effects on the central nervous system (CNS); it may have favourable actions on hepatic glucose metabolism through a selective effect on the liver, or it may influence fluid homeostasis through renal effects. Studies have consistently shown that insulin detemir reduces energy intake, and moreover, it is clear that this shift in energy balance is not a consequence of reduced hypoglycaemia. CNS effects may be mediated by direct action, by indirect stimulation by peripheral mediators and/or via a more physiological counter-regulatory response to insulin through restoration of the hepatic-peripheral insulin gradient. Although the precise mechanism remains unclear, it is likely that the weight-sparing effect of insulin detemir can be explained by a combination of mechanisms. The evidence for each hypothesis is considered in this review.


Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Diabetes Mellitus/tratamento farmacológico , Ingestão de Energia/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Insulina Detemir/farmacologia , Aumento de Peso/efeitos dos fármacos , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Humanos , Rim/metabolismo , Fígado/metabolismo
12.
Diabetes Obes Metab ; 17(5): 459-67, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25580665

RESUMO

AIMS: To investigate, using a novel non-steady-state protocol, the differential effects of subcutaneous (s.c.) detemir and NPH insulin on glucose flux and lipid metabolism after insulin withdrawal. METHODS: After a period of insulin withdrawal resulting in whole-blood glucose concentration of 7 mmol/l, 11 participants (five men, mean age 41.0 years, mean body mass index 25 kg/m(2)) with type 1 diabetes (mean glycated haemoglobin concentration 57 mmol/mol, mean diabetes duration 14 years) received 0.5 units per kg body weight s.c. insulin detemir or NPH insulin in random order. Stable isotopes of glucose and glycerol were infused intravenously throughout the study protocol. RESULTS: Glucose concentration decreased after insulin treatment as a result of suppression of endogenous glucose production, which occurred to a similar extent with both detemir and NPH insulin. The rate of glucose disappearance (Rd) was not increased significantly with either type of insulin. When the effect of detemir and NPH insulin on glucose flux at glucose concentrations between 9 and 6 mmol/l was examined, glucose rate of appearance (Ra) was similar with the two insulins; however, glucose Rd was greater with NPH insulin than with detemir at glucose concentrations of 8.0, 8.5, 7.0 and 6.0 mmol/l (p < 0.05) The percentage change in glycerol Ra, a measure of lipolysis, was greater in the NPH group than in the detemir group (p = 0.04). CONCLUSIONS: The results of the study are consistent with the hypothesis that detemir has a lesser effect on the periphery, as evidenced by a lesser effect on peripheral glucose uptake at specific glucose concentrations.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Insulina Detemir/farmacologia , Lipólise/efeitos dos fármacos , Adulto , Glicemia/biossíntese , Índice de Massa Corporal , Hemoglobinas Glicadas , Glicerol/sangue , Humanos , Hipoglicemiantes/administração & dosagem , Injeções Subcutâneas , Insulina Detemir/administração & dosagem , Insulina Isófana/farmacologia , Masculino
13.
Diabetes Obes Metab ; 17(2): 145-51, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25323312

RESUMO

AIMS: The recent type 2 diabetes American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) position statement suggested insulin is the most effective glucose-lowering therapy, especially when glycated haemoglobin (HbA1c) is very high. However, randomized studies comparing glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide once-weekly [OW; DURATION-3 (Diabetes therapy Utilization: Researching changes in A1c, weight, and other factors Through Intervention with exenatide ONce-Weekly)] and liraglutide once-daily [OD; LEAD-5 (Liraglutide Effect and Action in Diabetes)] with insulin glargine documented greater HbA1c reduction with GLP-1RAs, from baseline HbA1c ∼8.3% (67 mmol/mol). This post hoc analysis of DURATION-3 and LEAD-5 examined changes in HbA1c, fasting glucose and weight with exenatide OW or liraglutide and glargine, by baseline HbA1c quartile. METHODS: Descriptive statistics were provided for change in HbA1c, fasting glucose, weight, and insulin dose, and subjects (%) achieving HbA1c <7.0%, by baseline HbA1c quartile. Inferential statistical analysis on the effect of baseline HbA1c quartile was performed for change in HbA1c. An analysis of covariance (ANCOVA) model was used to evaluate similarity in change in HbA1c across HbA1c quartiles. RESULTS: At 26 weeks, in both studies, HbA1c reduction, and proportion of subjects reaching HbA1c <7.0%, were similar or numerically greater with the GLP-1RAs than glargine for all baseline HbA1c quartiles. Fasting glucose reduction was similar or numerically greater with glargine. Weight decreased with both GLP-1RAs across all quartiles; subjects taking glargine gained weight, more at higher baseline HbA1c. Adverse events were uncommon although gastrointestinal events occurred more frequently with GLP-1RAs. CONCLUSIONS: HbA1c reduction with the GLP-1RAs appears at least equivalent to that with basal insulin, irrespective of baseline HbA1c. This suggests that liraglutide and exenatide OW may be appropriate alternatives to basal insulin in type 2 diabetes, including when baseline HbA1c is very high (≥9.0%).


Assuntos
Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas/efeitos dos fármacos , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Metformina/administração & dosagem , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Exenatida , Jejum/sangue , Feminino , Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina Glargina , Liraglutida , Masculino , Pessoa de Meia-Idade , Peptídeos/administração & dosagem , Resultado do Tratamento , Peçonhas/administração & dosagem
14.
Endocr Connect ; 3(2): 75-84, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24671124

RESUMO

Resistant starch (RS) has been shown to beneficially affect insulin sensitivity in healthy individuals and those with metabolic syndrome, but its effects on human type 2 diabetes (T2DM) are unknown. This study aimed to determine the effects of increased RS consumption on insulin sensitivity and glucose control and changes in postprandial metabolites and body fat in T2DM. Seventeen individuals with well-controlled T2DM (HbA1c 46.6±2 mmol/mol) consumed, in a random order, either 40 g of type 2 RS (HAM-RS2) or a placebo, daily for 12 weeks with a 12-week washout period in between. AT THE END OF EACH INTERVENTION PERIOD, PARTICIPANTS ATTENDED FOR THREE METABOLIC INVESTIGATIONS: a two-step euglycemic-hyperinsulinemic clamp combined with an infusion of [6,6-(2)H2] glucose, a meal tolerance test (MTT) with arterio-venous sampling across the forearm, and whole-body imaging. HAM-RS2 resulted in significantly lower postprandial glucose concentrations (P=0.045) and a trend for greater glucose uptake across the forearm muscle (P=0.077); however, there was no effect of HAM-RS2 on hepatic or peripheral insulin sensitivity, or on HbA1c. Fasting non-esterified fatty acid (NEFA) concentrations were significantly lower (P=0.004) and NEFA suppression was greater during the clamp with HAM-RS2 (P=0.001). Fasting triglyceride (TG) concentrations and soleus intramuscular TG concentrations were significantly higher following the consumption of HAM-RS2 (P=0.039 and P=0.027 respectively). Although fasting GLP1 concentrations were significantly lower following HAM-RS2 consumption (P=0.049), postprandial GLP1 excursions during the MTT were significantly greater (P=0.009). HAM-RS2 did not improve tissue insulin sensitivity in well-controlled T2DM, but demonstrated beneficial effects on meal handling, possibly due to higher postprandial GLP1.

15.
Diabetes Obes Metab ; 16(1): 1-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23679086

RESUMO

In spite of major developments in insulin production, purification, pharmaceutical formulation and methods of delivery, problems remain both in the day to day management of insulin-treated diabetes and with regard to its long-term complications. The risks of hypoglycaemia and weight gain are major concerns particularly for the patient, and the persistence of microvascular and premature macrovascular complications as the main causes of morbidity and mortality in both type 1 and type 2 diabetes is a constant reminder that our therapeutic and management strategies are inadequate. One clear and striking difference between currently available insulin treatments and normal physiology is the relative difference in exposure to insulin of the liver versus peripheral tissues. Hepatoselective insulin analogues have the potential to restore the normal hepatic to peripheral gradient in insulin action. Here, we discuss the possible therapeutic potential that such analogues may have over currently available insulin preparations. These benefits could include a lower risk of hypoglycaemia, less weight gain and a potential reduction in microvascular and macrovascular complications. We explore the evolution of insulin with hepatoselectivity in mind and possible strategies to create hepatoselective insulins.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Insulina , Fígado/metabolismo , Pâncreas/metabolismo , Sistema Porta/metabolismo , Animais , Evolução Biológica , Ensaios Clínicos como Assunto , Angiopatias Diabéticas/prevenção & controle , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/síntese química , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Insulina/análogos & derivados , Insulina/química , Insulina/metabolismo , Insulina/farmacologia , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/efeitos adversos , Fígado/efeitos dos fármacos , Estrutura Molecular , Aumento de Peso
16.
Diabet Med ; 30(11): 1293-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23710902

RESUMO

AIMS: The goal of this study was to compare the long-term safety and efficacy of the basal insulin analogue, insulin degludec with insulin glargine (both with insulin aspart) in Type 1 diabetes, over a 2-year time period. METHODS: This open-label trial comprised a 1-year main trial and a 1-year extension. Patients were randomized to once-daily insulin degludec or insulin glargine and titrated to pre-breakfast plasma glucose values of 3.9-4.9 mmol/l. RESULTS: The rate of nocturnal confirmed hypoglycaemia was 25% lower with insulin degludec than with insulin glargine (P = 0.02). Rates of confirmed hypoglycaemia, severe hypoglycaemia and adverse events, and reductions in glycated haemoglobin and fasting plasma glucose were similar between groups. Despite achieving similar glycaemic control, insulin degludec-treated patients used 12% less basal and 9% less total daily insulin than did insulin glargine-treated patients (P < 0.01). CONCLUSIONS: Long-term basal therapy using insulin degludec in Type 1 diabetes required lower doses and was associated with a 25% lower risk for nocturnal hypoglycaemia than insulin glargine.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulinas/administração & dosagem , Análise de Variância , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina Aspart/administração & dosagem , Insulina Aspart/efeitos adversos , Insulina Glargina , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/efeitos adversos , Insulinas/efeitos adversos , Masculino , Resultado do Tratamento
17.
Diabetes Obes Metab ; 15(11): 978-86, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23551900

RESUMO

The aim of this review is to summarize the clinical efficacy, tolerability and safety data of insulin detemir, and compare its use with that of neutral protamine Hagedorn (NPH) insulin in randomized controlled trials in people with type 1 or type 2 diabetes. A literature search was conducted with PubMed using predefined search terms. Studies were included if they met the following criteria: randomized, controlled trial, comparison of insulin detemir with NPH insulin, non-hospitalized adults aged ≥18 years with either type 1 or type 2 diabetes, and study duration of ≥12 weeks. The following types of studies were excluded: non-randomized controlled trials, studies of mixed cohorts of patients with type 1 or type 2 diabetes that did not report results separately, pharmacokinetic/pharmacodynamic studies, reviews, pooled or meta-analyses or health-economic analyses. Fourteen publications met the inclusion criteria. Nine studies in people with type 1 diabetes and three studies in people with type 2 diabetes, using insulin detemir in a basal-bolus regimen were included. Two studies were in people with type 2 diabetes using insulin detemir with oral antidiabetes medicines. In 14 studies of people with type 1 or type 2 diabetes, insulin detemir treatment provided similar or better glycaemic control, lower within-subject variability, similar or lower frequency of hypoglycaemia and less weight gain when compared with NPH insulin.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Isófana/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Insulina Regular Humana/uso terapêutico , Adulto , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Quimioterapia Combinada , Humanos , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Insulina Detemir , Insulina Isófana/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Insulina Regular Humana/efeitos adversos , Insulina Isófana Humana , Ensaios Clínicos Controlados Aleatórios como Assunto , Aumento de Peso/efeitos dos fármacos
18.
Diabet Med ; 30(7): 864-70, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23398545

RESUMO

AIMS: To conduct a pilot study evaluation of an interprofessional education tool that could improve healthcare professional confidence, knowledge and quality of inpatient diabetes care. METHODS: Diabetes specialists designed an education tool for use in the hospital environment to educate qualified pharmacists, nurses, healthcare assistants and junior doctors. The interprofessional learning enabled professionals to learn from and about each other. The education tool was piloted at four hospitals. Diabetes specialists delivered the education programme to 31 healthcare professionals over 8 h either as three individual teaching blocks or a whole day. Healthcare professionals completed a multiple choice questionnaire before and after the education intervention to evaluate acquisition of knowledge. The maximum score was 20. Confidence was evaluated using categorical questions. Diabetes specialists used a clinical audit form before and after the education programme, to evaluate the quality of diabetes care. RESULTS: Healthcare professional's confidence improved from 58 to 94% (P < 0.05) and knowledge improved from 12.4 ± 0.6 to 15.0 ± 0.6 (mean ± sem, P < 0.05). There was a reduction in management errors from 74 to 44% (P < 0.05) and improvement in appropriate blood glucose monitoring from 67 to 92% (P < 0.05). The number of patients with documented foot assessment improved from15 to 33% (P < 0.05). Improvement in the number of appropriate diabetes referrals and reduction in prescribing errors did not reach statistical significance. CONCLUSION: The education tool improved healthcare professional confidence, knowledge and may improve the quality of inpatient diabetes care.


Assuntos
Diabetes Mellitus/terapia , Pessoal de Saúde/educação , Pacientes Internados , Qualidade da Assistência à Saúde , Glicemia/análise , Diabetes Mellitus/sangue , Educação/métodos , Hospitalização , Hospitais , Humanos , Relações Interprofissionais , Equipe de Assistência ao Paciente , Projetos Piloto , Ensino/métodos , Resultado do Tratamento , Reino Unido
19.
Diabet Med ; 30(1): 81-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22950637

RESUMO

OBJECTIVE: To assess whether the introduction of a management of raised glucose clinical decision tool could improve assessment of patients with hyperglycaemia by non-specialist physicians, leading to early discharge and improved quality of inpatient care. METHODS: Participants were adults aged 18 years or over presenting to the Medical Assessment Unit with a capillary blood glucose level > 11.1 mmol/l. Phase 1 of the study (phase 1) evaluated current clinical practice and potential impact of the clinical decision tool. Phase 2 evaluated the effectiveness of the management of raised glucose tool in clinical practice. Primary outcome measures were inpatient length of stay and same-calendar-day discharges. Secondary outcome measures were diabetes specialist input, patient assessment, intravenous insulin infusion use and patient satisfaction. RESULTS: Implementation of the management of raised glucose clinical decision tool allowed safe, same-calendar-day discharges of 40% of patients with hyperglycaemia as their primary reason for attendance. Median length of stay was lower in the phase 1 than in phase 2 (1.0 vs. 3.5 days, P < 0.01). Early discharge did not result in an increase in readmissions. There was improvement in hyperglycaemia assessment for all patients (P < 0.01), a reduction in the use of intravenous insulin infusions (P < 0.01) and high level of patient satisfaction. CONCLUSION: The management of raised glucose clinical decision tool resulted in a significant increase in the number of same-calendar-day discharges and reduction in hospital length of stay without adverse impact on readmission rates. Additionally, the tool was associated with improvements in inpatient diabetes care and patient satisfaction.


Assuntos
Técnicas de Apoio para a Decisão , Hiperglicemia/terapia , Tempo de Internação/estatística & dados numéricos , Adolescente , Adulto , Idoso , Glicemia/metabolismo , Redução de Custos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/economia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/economia , Humanos , Hiperglicemia/sangue , Hiperglicemia/economia , Tempo de Internação/economia , Pessoa de Meia-Idade , Satisfação do Paciente , Qualidade da Assistência à Saúde , Adulto Jovem
20.
Diabetes Obes Metab ; 15(1): 42-54, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22862847

RESUMO

AIM: We investigated the relationship between weight change and related factors in subjects with type 2 diabetes mellitus (T2DM) treated with liraglutide versus comparator diabetes therapies. METHODS: Twenty-six-week data from seven phase 3, randomized trials in the liraglutide T2DM development programme were analysed by trial and treatment group: liraglutide (1.2 and 1.8 mg), active comparator and placebo. Outcome measures included proportions of subjects in various weight change categories and their percentage weight change from baseline; impact of body mass index (BMI) and gastrointestinal (GI) adverse events (AEs) on weight change and correlation of weight change with change in glycosylated haemoglobin (HbA1c). RESULTS: A number of subjects experienced >5% weight loss during the trials (24.4% liraglutide 1.8 mg and 17.7% liraglutide 1.2 mg; 17.7% exenatide, 10.0% sitagliptin, 3.6-7.0% sulphonylurea, 2.6% thiazolidinedione and 2.6% glargine; 9.9% placebo). More weight loss was seen with liraglutide 1.2 and 1.8 mg than with active comparators except exenatide. Across trials, higher initial BMI was associated with slightly greater weight loss with liraglutide. Mean weight loss increased slightly the longer GI AEs persisted. Although HbA1c reduction was slightly larger in higher weight loss categories across treatments (including placebo), sample sizes were small and no clear correlation could be determined. Liraglutide-treated subjects experienced additional HbA1c reduction beyond that which appeared weight induced; thus, not all HbA1c-lowering effect appears weight mediated. CONCLUSIONS: The majority of liraglutide-treated T2DM subjects experienced weight loss in this analysis. Weight loss was greater and occurred more in glucagon-like peptide-1 receptor agonist-treated subjects than in active comparator-treated subjects.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Hemoglobinas Glicadas/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Redução de Peso/efeitos dos fármacos , Glicemia/metabolismo , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/metabolismo , Exenatida , Feminino , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Insulina Glargina , Insulina de Ação Prolongada/uso terapêutico , Liraglutida , Masculino , Pessoa de Meia-Idade , Peptídeos/uso terapêutico , Pirazinas/uso terapêutico , Fosfato de Sitagliptina , Compostos de Sulfonilureia/uso terapêutico , Tiazolidinedionas/uso terapêutico , Triazóis/uso terapêutico , Peçonhas/uso terapêutico
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