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OBJECTIVES: Cardiovascular disease (CVD) and associated risk factors within the prison population often present at a younger age in this cohort. Given CVD is largely preventable, it warrants investigation to fully quantify this risk. This study explored the relative predicted 10-year CVD risk and examined the calculated heart age in a representative sample of male individuals aged 25-84 years within the prison environment. STUDY DESIGN: This was a cross-sectional study. METHODS: Data were collected on 299 men who underwent a cardiometabolic risk assessment in HMP Parc, Bridgend. The QRISK2 algorithm was used to calculate 10-year CVD risk, relative risk (to general population) and the predicted heart age of an individual. Between-group differences (prison population vs general community) in cardiovascular risk predictions (10-year CVD risk and heart age) were assessed. RESULTS: We observed that at all age groups, the relative risk of predicted 10-year CVD scores in the prison population was double that of the community risk (2.1 ± 0.6), and this was most apparent in the oldest age group (≥50 years: 17.0% compared to 8.8%; P < 0.001). Overall, the heart age of the sample was 7.5 (6.7-8.2) years higher than their own chronological age, and this difference increased to above 9 years in those aged ≥40 years. CONCLUSIONS: This study provides quantifiable evidence to the elevated CVD risk in prison. Heart age predictions were almost a decade higher in those aged ≥40 years. Lowering the screening age for CVD by around 5 years in the prison population should be considered.
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Doenças Cardiovasculares , Humanos , Masculino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Estudos Transversais , Prisões , Fatores de Risco , Medição de RiscoRESUMO
AIM: To evaluate the performance of the current, pre-production version of a novel home oral glucose tolerance test (Home OGTT) device when administered by trained research nurses, compared with a reference laboratory glucose analyser and a second laboratory analyser, incorporating a sample processing delay to simulate normal practice. METHODS: One hundred women (aged 19-48 years), with and without known glucose intolerance were recruited. Following an overnight fast, participants attended for a 75-g OGTT. A fasting capillary sample was applied to the Home OGTT device with a corresponding venous sample collected and measured immediately on the reference YSI 2300 stat plus analyser, and following a 1-h delay on the Randox Daytona Plus analyser. The sampling process was repeated 2 h after the oral glucose load. RESULTS: Some 97% of tested devices gave complete data for analysis. Good agreement was observed between the reference glucose analyser and the Home OGTT device, with the Home OGTT device displaying a small negative bias (-0.18 mmol/l, -1.75 to 1.39 mmol/mol; -1.0%, -26.4% to 24.5%; absolute and relative mean, 95% limits of agreement). When classified as normal glucose tolerant or glucose intolerant, the Home OGTT device showed 100% and 90% sensitivity, and 99% and 99% specificity using fasting plasma glucose and 2-h glucose respectively. Similar sensitivity (100% and 100%) and specificity (96% and 99%) for fasting plasma glucose and 2-h glucose were observed using the secondary analyser. CONCLUSIONS: The novel Home OGTT device was reliable and easy to use and showed excellent agreement with two separate laboratory analysers. The Home OGTT offers potential as an effective alternative for clinic-based OGTT testing.
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Glicemia/metabolismo , Jejum/sangue , Intolerância à Glucose/sangue , Teste de Tolerância a Glucose/instrumentação , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Autoadministração , Adulto JovemRESUMO
AIM: To examine the impact of structured self-monitoring of blood glucose, with or without TeleCare support, on glycaemic control in people with sub-optimally controlled Type 2 diabetes. METHODS: We conducted a 12-month, multicentre, randomized controlled trial in people with established (>1 year) Type 2 diabetes not on insulin therapy, with sub-optimal glycaemic control [HbA1c ≥58 to ≤119 mmol/mol (≥7.5% to ≤13%)]. A total of 446 participants were randomized to a control group (n =151) receiving usual diabetes care, a group using structured self-monitoring of blood glucose alone (n =147) or a group using structured self-monitoring of blood glucose with additional monthly 'TeleCare' support (n =148). The primary outcome was HbA1c at 12 months. RESULTS: A total of 323 participants (72%) completed the study; 116 (77%) in the control group, 99 (67%) in the self-monitoring of blood glucose alone group and 108 (73%) in the self-monitoring of blood glucose plus TeleCare group. Compared to baseline, the mean HbA1c was lower in all groups at 12 months, with reductions of 3.3 mmol/mol (95% CI -5.71 to -0.78) or 0.3% (95% CI -0.52 to -0.07; P=0.01) in the control group, 11.4 mmol/mol (95% CI -14.11 to -8.76) or 1.1% (-1.29 to -0.81; P<0.0001) in the group using self-monitoring of blood glucose alone and 12.8 mmol/mol (95% CI -15.34 to -10.31) or 1.2% (95% CI -1.40 to -0.94; P<0.0001) in the group using self-monitoring of blood glucose plus TeleCare. This represents a reduction in HbA1c of 8.9 mmol/mol (95% CI -11.97 to -5.84) or 0.8% (95% CI -1.10 to -0.54; P≤0.0001) with structured self-monitoring of blood glucose compared to the control group. Participants with lower baseline HbA1c , shorter duration of diabetes and higher educational achievement were more likely to achieve HbA1c ≤53 mmol/mol (7.0%). CONCLUSIONS: Structured self-monitoring of blood glucose provides clinical and statistical improvements in glycaemic control in Type 2 diabetes. No additional benefit, over and above the use of structured self-monitoring of blood glucose, was observed in glycaemic control with the addition of once-monthly TeleCare support. (Clinical trial registration no.: ISRCTN21390608).
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Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Autocuidado/métodos , Telemedicina , Idoso , Automonitorização da Glicemia/métodos , Sistemas de Apoio a Decisões Clínicas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Telemedicina/métodos , Resultado do TratamentoRESUMO
AIMS: To investigate the relationship between HbA1c and glucose in people with co-existing liver disease and diabetes awaiting transplant, and in those with diabetes but no liver disease. METHODS: HbA1c and random plasma glucose data were collected for 125 people with diabetes without liver disease and for 29 people awaiting liver transplant with diabetes and cirrhosis. Cirrhosis was caused by non-alcoholic fatty liver disease, hepatitis C, alcoholic liver disease, hereditary haemochromatosis, polycystic liver/kidneys, cryptogenic/non-cirrhotic portal hypertension and α-1-antitrypsin-related disease. RESULTS: The median (interquartile range) age of the diabetes with cirrhosis group was 55 (49-63) years compared to 60 (50-71) years (P=0.13) in the group without cirrhosis. In the diabetes with cirrhosis group there were 21 men (72%) compared with 86 men (69%) in the group with diabetes and no cirrhosis (P=0.82). Of the group with diabetes and cirrhosis, 27 people (93%) were of white European ethnicity, two (7%) were South Asian and none was of Afro-Caribbean/other ethnicity compared with 94 (75%), 16 (13%), 10 (8%)/5 (4%), respectively, in the group with diabetes and no cirrhosis (P=0.20). Median (interquartile range) HbA1c was 41 (32-56) mmol/mol [5.9 (5.1-7.3)%] vs 61 (52-70) mmol/mol [7.7 (6.9-8.6)%] (P<0.001), respectively, in the diabetes with cirrhosis group vs the diabetes without cirrhosis group. The glucose concentrations were 8.4 (7.0-11.2) mmol/l vs 7.3 (5.2-11.5) mmol/l (P=0.17). HbA1c was depressed by 20 mmol/mol (1.8%; P<0.001) in 28 participants with cirrhosis but elevated by 28 mmol/mol (2.6%) in the participant with α-1-antitrypsin disorder. Those with cirrhosis and depressed HbA1c had fewer larger erythrocytes, and higher red cell distribution width and reticulocyte count. This was reflected in the positive association of glucose with mean cell volume (r=0.39) and haemoglobin level (r=0.49) and the negative association for HbA1c (r=-0.28 and r=-0.26, respectively) in the diabetes group with cirrhosis. CONCLUSION: HbA1c is not an appropriate test for blood glucose in people with cirrhosis and diabetes awaiting transplant as it reflects altered erythrocyte presentation.
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Nefropatias Diabéticas/metabolismo , Hemoglobinas Glicadas/metabolismo , Cirrose Hepática/metabolismo , Transplante de Fígado , Idoso , Glicemia , Nefropatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/cirurgia , Gerenciamento Clínico , Contagem de Eritrócitos , Eritrócitos Anormais , Feminino , Humanos , Cirrose Hepática/fisiopatologia , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
AIMS: To determine the proportion of people with diabetes who have HbA1c measured, what proportion achieve an HbA1c level of < 58 mmol/mol (7.5%), the frequency of testing and if there was any change in HbA1c level in the year before and the year after an incident stroke. METHODS: This study used the Secure Anonymised Information Linkage (SAIL) databank, which stores hospital data for the whole of Wales and ~ 65% of Welsh general practice records, to identify cases of stroke in patients with diabetes between 2000 and 2010. These were matched against patients with diabetes but without stroke disease. We assessed the frequency of HbA1c testing and change in HbA1c in the first year after stroke. Estimation was made of the proportion of patients achieving an HbA1c measurement ≤ 58 mmol/mol (7.5%). RESULTS: There were 1741 patients with diabetes and stroke. Of these, 1173 (67.4%) had their HbA1c checked before their stroke and 1137 (65.3%) after their stroke. In the control group of 16 838 patients with diabetes but no stroke, 8413 (49.9%) and 9288 (55.1%) had their HbA1c checked before and after the case-matched stroke date, respectively. In patients with diabetes and stroke, HbA1c fell from 61-56 mmol/mol (7.7-7.3%) after their stroke (P < 0.001). Before the study, 55.0% of patients with stroke had an HbA1c ≥ 58 mmol/mol compared with 65.2% of control patients, these figures were 62.5% and 65.3% after the stroke. CONCLUSIONS: The frequency of diabetes testing was higher in patients who had experienced a stroke before and after their incident stroke compared with control patients but did not increase after their stroke. Glucose control improved significantly in the year after a stroke.
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Diabetes Mellitus/tratamento farmacológico , Angiopatias Diabéticas/sangue , Monitoramento de Medicamentos , Hemoglobinas Glicadas/análise , Hiperglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Acidente Vascular Cerebral/sangue , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Anonimização de Dados , Registros Eletrônicos de Saúde , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Registro Médico Coordenado , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , País de GalesRESUMO
STUDY QUESTION: Are arterial stiffness, carotid intima-media thickness and diastolic dysfunction increased in young women with polycystic ovary syndrome (PCOS) independently of the effects of obesity? SUMMARY ANSWER: Insulin resistance and central obesity are associated with subclinical cardiovascular dysfunction in young women, but a diagnosis of PCOS does not appear to confer additional risk at this age. WHAT IS KNOWN ALREADY: Some studies have shown that young women with PCOS may have increased measures of cardiovascular risk, including arterial stiffness, carotid intima-media thickness and myocardial dysfunction. However, it is difficult to establish how much of this risk is due to PCOS per se and how much is due to obesity and insulin resistance, which are common in PCOS and themselves associated with greater vascular risk. STUDY DESIGN, SIZE, DURATION: This cross-sectional study comprised 84 women with PCOS and 95 healthy volunteers, aged 16-45 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted in a university hospital. Subjects underwent a comprehensive assessment of body composition (including computed tomography (CT) assessment of visceral fat; VF), measurements of arterial stiffness (aortic pulse wave velocity; aPWV), common carotid intima-media thickness (ccIMT), diastolic function (longitudinal tissue velocity; e':a') and endocrinological measures. A sample size of 80 in each group gave 80% power for detecting a difference of 0.45 m/s in aPWV or a difference of 0.25 in e':a'. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment for age and body mass index (BMI), PCOS subjects had a greater insulin response (insulin area under the curve-IAUC) following glucose challenge (adjusted difference [AD] 35 900 pmol min/l, P < 0.001) and higher testosterone (AD 0.57 nmol/l, P < 0.001) and high molecular weight adiponectin than controls (AD 3.01 µg/ml, P = 0.02), but no significant differences in aPWV (AD -0.13 m/s, P = 0.33), ccIMT (AD -0.01 mm, P = 0.13), or e':a' (AD -0.01, P = 0.86) were observed. After adjustment for age, height and central pulse pressure, e':a' and aPWV were associated with logVF and IAUC. ccIMT was not related to logVF. The relationships between e':a' or aPWV and insulin resistance were only partly attenuated by adjusting for logVF. There was no significant relationship between aPWV or e':a' and either testosterone or adiponectin. LIMITATIONS, REASONS FOR CAUTION: The study recruited young women meeting the Rotterdam criteria for PCOS diagnosis; hence our findings may not be generalizable to older patients or those meeting other definitions of the syndrome. Biochemical hyperandrogenism was based solely on measurement of total testosterone. Cases and controls were not matched in advance for age and BMI, although the influence of these variables on the cardiovascular outcome measures was adjusted for. WIDER IMPLICATIONS OF THE FINDINGS: This study shows that central arterial stiffness and diastolic dysfunction are not increased in young women with PCOS, whereas they are associated with both insulin resistance and central obesity. Obesity thus represents the greatest modifiable risk factor for cardiovascular disease in young women with PCOS and lifestyle measures which target weight reduction are critical. STUDY FUNDING/COMPETING INTERESTS: This study received no specific grant support from any funding body. The authors have no conflicts of interest to declare.
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Doenças Cardiovasculares/complicações , Resistência à Insulina , Obesidade Abdominal/complicações , Síndrome do Ovário Policístico/complicações , Rigidez Vascular , Adolescente , Adulto , Composição Corporal , Feminino , Testes de Função Cardíaca , Humanos , Pessoa de Meia-Idade , Medição de RiscoRESUMO
AIMS: The ever-increasing prevalence of diabetes places pressure on the provision of diabetic retinopathy screening services. As the first study of its kind, we aimed to determine preferences for diabetic retinopathy screening in people with diabetes and to examine the trade-offs between frequency of screening and other service attributes. METHODS: A questionnaire including a discrete choice experiment was administered to people (n = 198) attending diabetic retinopathy screening at eight clinics across Wales, United Kingdom. The discrete choice experiment contained eight pairwise choices in which screening provision was described by five attributes: frequency of screening; travel time; results time; ability of screening to detect other changes; and explanation of results. Data were analysed using logistic regression techniques. RESULTS: We gained a response rate of 86.4% from the 198 questionnaires administered at clinics; 160 complete responses were analysed. Respondents valued four out of the five attributes [ability of screening to detect other changes (P = 0.000), explanation of results (P = 0.024), frequency of screening (P = 0.000) and travel time (P = 0.007)]. Results time was insignificant (P = 0.122). Respondents were willing to wait an additional 12, 2 and 1 month between screening tests to have a test that was able to detect additional changes, to have their results explained in person rather than by letter and to have a 15-min reduction in travel time, respectively. CONCLUSIONS: Respondents were willing to accept a longer screening interval, as long as preferences for other attributes of service provision (ability of screening to detect other changes, explanation of results and travel time) were made available.
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Comportamento de Escolha , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/diagnóstico , Programas de Rastreamento/métodos , Preferência do Paciente/estatística & dados numéricos , Encaminhamento e Consulta , Adulto , Idoso , Idoso de 80 Anos ou mais , Comunicação , Retinopatia Diabética/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Inquéritos e Questionários , Fatores de Tempo , Viagem , País de Gales/epidemiologia , Adulto JovemRESUMO
AIMS: To obtain the views of people with diabetes about the provision of diabetic retinopathy screening services; and the interval of screening. METHODS: Between October 2009 and January 2010, people with diabetes attending diabetic retinopathy screening clinics across Wales were asked to complete a questionnaire comprising of two parts: the first asking about their health, diabetes history, demographic characteristics and views about the diabetic retinopathy screening service, and the second asking about the costs of attending the screening. RESULTS: The response rate was 40% (n = 621) from 1550 questionnaires distributed at diabetic retinopathy clinics, with 600 complete responses analysed. Respondents had a mean known duration of diabetes of 8.5 years (sd 7.8) and had attended for screening on average 3.2 times (sd 1.6) in the last 5 years. Sixty-eight per cent (n = 408) of respondents reported having their eyes screened approximately once a year. Eighty-five per cent (n = 507) felt that they should have their eyes screened every year. However, 65% (n = 390) of respondents would accept screening at 2- or 3-year intervals if medical evidence showed that it was safe. The reported personal costs incurred by respondents attending diabetic retinopathy screening were low. CONCLUSION: Our study suggests that people with diabetes undergoing diabetic retinopathy screening would accept a greater screening interval, provided that adequate clinical evidence and medical reassurance were given.
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Retinopatia Diabética/diagnóstico , Retinopatia Diabética/economia , Hemoglobinas Glicadas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Efeitos Psicossociais da Doença , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/sangue , Retinopatia Diabética/epidemiologia , Feminino , Humanos , Masculino , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Preferência do Paciente , Qualidade de Vida , Inquéritos e Questionários , País de Gales/epidemiologia , Adulto JovemRESUMO
Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune ß-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies.
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AIM: Stepwise intensification of insulin treatment to match the progressive decline of endogenous insulin secretion has been shown to be an effective management strategy in type 2 diabetes mellitus (T2DM). The efficacy of initiating and titrating a single bolus dose of insulin glulisine to baseline insulin glargine plus oral hypoglycaemic agents (OHAs) was investigated. METHODS: This was a 6-month, parallel-group, randomized, open-label, Phase IV study conducted in the US, UK and Russia. People with T2DM (HbA(1c) 7.5-9.5%) using any basal insulin underwent a 3-month run-in period on insulin glargine titrated to optimize fasting blood glucose (BG) control. Those with HbA(1c) >7.0% were randomized to either continue prior therapy (n = 57) or to add a single dose of insulin glulisine (n = 49) immediately prior to the main meal for a further 3 months. Two different titration algorithms were employed for the bolus dose, targeting 2-h postprandial BG ≤135 mg/dL (≤7.5 mmol/l; Russia and UK) or pre-meal/bedtime BG 100-120 mg/dl (5.5-6.7 mmol/l; US). RESULTS: HbA(1c) and fasting plasma glucose levels decreased during the run-in period. In the 3 months after randomization, more participants in the basal-plus-bolus group reached HbA(1c) <7.0% than the basal-only control group (22.4 vs. 8.8%; p < 0.05), with significantly greater reduction of HbA(1c) (-0.37 vs. -0.11%; p = 0.0290). Rates of hypoglycaemia and mean weight change were comparable between the treatment groups. CONCLUSIONS: In people with T2DM inadequately controlled on basal insulin plus OHAs, adding a single injection of insulin glulisine prior to the main meal significantly improves glucose control without undesired side effects.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Insulina/análogos & derivados , Período Pós-Prandial , Adolescente , Adulto , Idoso , Algoritmos , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Jejum , Feminino , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/administração & dosagem , Insulina Glargina , Masculino , Pessoa de Meia-Idade , Federação Russa/epidemiologia , Resultado do Tratamento , Reino Unido/epidemiologia , Estados Unidos/epidemiologia , Adulto JovemRESUMO
AIMS: To study the variation in daytime glucose tolerance and pancreatic B-cell function at different levels of glycated haemoglobin (HbA(1c)) in subjects with Type 2 diabetes (T2DM). METHODS: T2DM subjects (n = 49; 34 men) had 12-h daytime plasma glucose (PG), insulin (PI), total (PTp) and intact proinsulin (PIp) profiles determined in response to three identical test meals at 4-h intervals. Subjects were divided into three groups according to HbA(1c)--group 1: < 7.3% (n = 18); group 2: 7.3-8.0% (n = 17); group 3: > 8.0% (n = 14). Fasting and preprandial (prior to meals 2 and 3) concentrations, total area under the curve (AUC), AUC above fasting (dAUC) and maximum postprandial metabolic concentrations (C(max)) were compared between the three meals and across the groups. RESULTS: Subjects in group 1 had significantly higher fasting plasma glucose (FPG) compared with preprandial PG concentrations (7.1 +/- 0.2 vs. 5.9 +/- 0.3 vs. 5.4 +/- 0.2; P < 0.01). Subjects in groups 2 and 3 had significantly higher FPG compared with preprandial PG levels prior to meal 3. PG.dAUC was highest in response to meal 1 and lowest following meal 2 (P < 0.05). FPI concentrations were significantly lower compared with preprandial PI concentrations. Subjects in group 1 had significantly higher PI prior to meal 2 compared with meal 3. PI.dAUC was highest in response to meal 1. Subjects in group 1 had lowest PI.dAUC following meal 2. FTp and FIp concentrations were also significantly lower compared with preprandial concentrations. PTp.dAUC and PIp.dAUC was highest in response to meal 1. CONCLUSIONS: There appears to be a shift in diurnal variation in glucose homeostasis and pancreatic B-cell function. Subjects had decreased glucose tolerance in response to the first and third meal of the day irrespective of glycaemic control. The variability in glucose tolerance was reflected by both quantitative and qualitative dysfunction of the pancreatic B-cell.
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Glicemia/metabolismo , Ritmo Circadiano , Diabetes Mellitus Tipo 2/fisiopatologia , Células Secretoras de Insulina/metabolismo , Período Pós-Prandial/fisiologia , Área Sob a Curva , Diabetes Mellitus Tipo 2/sangue , Jejum , Feminino , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/análise , Humanos , Insulina/metabolismo , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Proinsulina/metabolismoRESUMO
AIM: Randomized, open, single-centre, two-way crossover study comparing the pharmacokinetic (PK) and pharmacodynamic (PD) properties of subcutaneous (sc) regular human insulin (Actrapid) and oral insulin in a capsule form (Capsulin). METHODS: Sixteen persons (12 males) with type 2 diabetes on oral hypoglycaemic agents (OHAs) participated. Mean (s.d.) age 60.2 (5.5) years, BMI 28.3 (3.4) kg/m(2), haemoglobin A(1c) (HbA(1c)) 7.4% (1.1). Two 6-h isoglycaemic glucose clamp studies were conducted 11 days apart. All subjects received in random order 12U sc Actrapid on one clamp study day and either 150U or 300U Capsulin (Cap) on the other day. Glucose infusion rates (GIRs), plasma insulin and C-peptide concentrations were determined throughout each 6-h isoglycaemic clamp. Between the clamp study days, all patients received 150U Capsulin twice daily, dropping all their standard OHAs apart from metformin. Self-monitored blood glucose (SMBG) levels were taken four times a day between the clamp study days. RESULTS: Administration of either Actrapid or Capsulin (150 and 300U) increased GIRs reaching a maximum values at approximately 280-330 min. Overall values for maximum GIR values were higher for Actrapid than either dose of Capsulin (p < 0.05). The significantly greater systemic insulin concentrations following Actrapid were reflected in the AUC(0-6 h) (910 +/- 270 vs. 472 +/- 245 pmol h/L; 950 +/- 446 vs. 433 +/- 218 pmol h/L; both p < 0.05 for Actrapid vs. 150U Capsulin and 300U Capsulin respectively). No difference was observed between 150U and 300U Capsulin. During the repeat-dosing period, good safety and tolerability were observed with Capsulin, and SMBG levels remained stable. At the poststudy visit, significant falls in HbA(1c), weight and triglycerides were observed. CONCLUSIONS: Administration of the oral insulin Capsulin preparation demonstrated a significant hypoglycaemic action over a period of 6 h associated with only a small increase in circulating plasma insulin concentrations.
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Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacocinética , Insulina/farmacocinética , Administração Oral , Glicemia/metabolismo , Cápsulas , Estudos Cross-Over , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Técnica Clamp de Glucose , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Insulina Regular de Porco , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
AIMS: To determine the relative and absolute contributions of postprandial glucose (PPG) and fasting or preprandial plasma glucose (FPG) to daytime hyperglycaemia and HbA(1c) respectively, in persons with type 2 diabetes (T2DM). METHODS: Subjects (n = 52; 37 men) had 12hr plasma glucose (PG) profiles determined in response to three serial identical test meals. PPG exposure was calculated for each meal. Excess hyperglycaemia was calculated above a PG concentration of 5.5 mmol/l. Fasting hyperglycaemia was the difference between excess hyperglycaemia and PPG exposure. Subjects were divided into three groups according to HbA(1c)-(Gp1:<7.3%;Gp2:7.3%-8.0%;Gp3:>8.0%) and the relative contribution of PPG exposure and fasting hyperglycaemia to excess hyperglycaemia calculated for each meal. The absolute contribution of PPG and fasting hyperglycaemia to excess HbA(1c) (mean HbA(1c)-5.1%) was also calculated. RESULTS: The relative contributions of PPG exposure to excess hyperglycaemia for the three groups were: 58.3%, 54.3% and 35.4% (P = 0.483-Group 1 vs. Group 2; P = 0.002-Group 2 vs. Group 3) for meal 1; 69.8%, 54.7% and 23.7% (P = 0.163-Group 1 vs. Group 2; P = 0.005-Group 2 vs. Group 3) for meal 2; 85.8%, 70.2% and 48.6% (P = 0.153-Group 1 vs. Group 2; P = 0.046-Group 2 vs. Group 3) for meal 3. Absolute contributions of PPG to excess HbA(1c) in the three groups were 1.4%, 1.6% and 1.3% (P = NS). CONCLUSION: The relative contribution of postprandial glucose to excess hyperglycaemia decreases as glycaemic control deteriorates, being dominant with HbA(1c)= 7.3%, irrespective of the timing of the meal during the day. However, the absolute contribution of postprandial glucose to excess HbA(1c) does not differ significantly ( approximately 1.5%) with varying glycaemic control.
Assuntos
Glicemia/metabolismo , Hemoglobinas Glicadas/metabolismo , Hiperglicemia/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/sangue , Jejum/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial/fisiologiaRESUMO
AIMS: As the use of Point of Care Testing (POCT) devices for measurement of glycated haemoglobin (HbA1c) increases, it is imperative to determine how their performance compares to laboratory methods. This study compared the performance of the automated Quo-Test POCT device (EKF Diagnostics), which uses boronate fluorescence quenching technology, with a laboratory based High Performance Liquid Chromatography (HPLC) method (Biorad D10) for measurement of HbA1c. METHODS: Whole blood EDTA samples from subjects (n=100) with and without diabetes were assayed using a BioRad D10 and a Quo-Test analyser. Intra-assay variation was determined by measuring six HbA1c samples in triplicate and inter-assay variation was determined by assaying four samples on 4 days. Stability was determined by assaying three samples stored at -20 °C for 14 and 28 days post collection. RESULTS: Median (IQR) HbA1c was 60 (44.0-71.2) mmol/mol (7.6 (6.17-8.66) %) and 62 (45.0-69.0) mmol/mol (7.8 (6.27-8.46) %) for D10 and Quo-Test, respectively, with very good agreement (R2=0.969, P<0.0001). Mean (range) intra- and inter-assay variation was 1.2% (0.0-2.7%) and 1.6% (0.0-2.7%) for the D10 and 3.5% (0.0-6.7%) and 2.7% (0.7-5.1%) for the Quo-Test. Mean change in HbA1c after 28 days storage at -20 °C was -0.7% and +0.3% for D10 and Quo-Test respectively. Compared to the D10, Quo-Test showed 98% agreement for diagnosis of glucose intolerance (IGT and T2DM) and 100% for diagnosis of T2DM. CONCLUSION: Good agreement between the D10 and Quo-Test was seen across a wide HbA1c range. The Quo-Test POCT device provided similar performance to a laboratory based HPLC method.
RESUMO
Minimal model (MINMOD) analysis of the frequently sampled intravenous glucose tolerance test (FSIVGTT) is dependent on an adequate insulin response to the glucose load. As this is characteristically deficient in subjects with non-insulin-dependent diabetes mellitus (NIDDM), the technique has been modified by the use of an intravenous bolus of insulin. Previous validation of this modification in humans has relied on agreement between insulin sensitivity indexes (SI) estimated from tolbutamide- and insulin-modified tests and not on direct comparison with estimates derived from the isoglycemic glucose clamp. We have compared estimates of insulin sensitivity derived from minimal modeling of a 4-h insulin-modified FSIVGTT and the glucose clamp in subjects with NIDDM. Twelve subjects underwent an insulin-modified FSIVGTT and an isoglycemic hyperinsulinemic clamp in random order 2-4 weeks apart. Fasting plasma glucose (8.4 vs. 9.0 mmol/l) and immunoreactive insulin (IRI) concentrations (104.5 vs. 101.5 pmol/l) were not different between the 2 study days. SI(clamp) was derived from the steady-state glucose infusion rate during the 3rd h of the clamp, corrected for the ambient insulin and glucose concentrations. SI(ivgtt) was derived using MINMOD. SI(ivgtt) was 1.06 +/- 0.18 min-1.mU-1.ml x 10(4), and mean SI(clamp) was 4.97 +/- 0.69 l.min-1/pmol.l-1 x 10(4) (mean +/- SE). SI(ivgtt) was positively correlated with SI(clamp) (r = 0.73, P = 0.004) and negatively correlated with body mass index (r = -0.7, P = 0.005) and fasting IRI(ivgtt) (r = -0.64, P = 0.008). In summary, MINMOD analysis of the insulin-modified FSIVGTT provides a valid measure of insulin sensitivity in subjects with NIDDM.
Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Insulina/sangue , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A cohort of 132 well-documented White Welsh non-insulin-dependent diabetic (NIDDM) subjects were genotyped for 5 restriction-fragment-length polymorphisms (RFLPs) at the insulin-receptor gene (IRG) locus and a polymorphic locus 5' to the insulin gene. There was no significant difference in RFLP frequencies between the NIDDM subjects and a group of 87 matched White control subjects. Paired haplotype analysis of the IRG RFLPs suggested a difference between NIDDM and control groups for the endonuclease combinations Bgl II-Rsa I and Bgl II-Xba I. Analysis of implied haplotypes defined by the endonucleases Bgl II, Rsa I, and Xba I revealed one haplotype to be more prevalent in the NIDDM group; whereas, another haplotype was associated with the control group (P less than 0.02). Subset analysis within the NIDDM cohort compared the metabolic response of NIDDM subjects with the differing IRG haplotypes to a standard meal tolerance test. Both groups showed equivalent basal and postprandial glucose excursions, but one group revealed a significantly exaggerated plasma insulin response compared with the other (P less than 0.05). This may reflect the influence of genetic variation at the IRG locus on insulin sensitivity in patients with NIDDM.
Assuntos
Alelos , Mapeamento Cromossômico , Diabetes Mellitus Tipo 2/fisiopatologia , Variação Genética/genética , Insulina/genética , Receptor de Insulina/genética , Adulto , Suscetibilidade a Doenças , Feminino , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , País de GalesRESUMO
Recent work in healthy subjects, the aged, and subjects with gestational diabetes or drug-induced insulin resistance using minimal model analysis of the tolbutamide-modified frequently sampled intravenous glucose tolerance test suggested that a reduced sampling regimen of 12 time points produced unbiased and generally acceptable estimates of insulin sensitivity (SI) and glucose effectiveness (SG) compared with a full sampling schedule of 30 time points. We have used data from 26 insulin-modified frequently sampled intravenous glucose tolerance tests in 21 subjects with NIDDM to derive and compare estimates of SI and SG from the full sampling schedule (SI(30), SG(30)) with those estimated from the suggested 12 time points (SI(12), SG(12)) and those estimated with the addition of a 25-min time point (SI(13), SG(13)). Percentage relative errors were calculated relative to the corresponding 30 time-point values. A statistically significant bias of 15% (97% confidence interval from 7.4 to 25.6%, interquartile range 25%) was introduced by the estimation of SI(12) but not SI(13) (1%, 97% confidence interval from -9.4 to 9.3%, interquartile range 21%). Results for SG(12) (-12%, 97% confidence interval from -46.7 to 1.2%, interquartile range 49%) and SG(13) (-5%, 97% confidence interval from -27.8 to 6.8%, interquartile range 37%) were statistically equivocal. The precision of estimation of SI(12), SG(12), and SG(13) measured by the interquartile range of the percentage relative errors was poor. The precision of determination measured by the median minimal model coefficient of variation was 18, 29, and 27% for SI(30), SI(12), and SI(13) and 9, 11, and 11% for SG(30), SG(12), and SG(13), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Resistência à Insulina/fisiologia , Insulina/farmacologia , Adulto , Idoso , Protocolos Clínicos , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Teste de Tolerância a Glucose/métodos , Teste de Tolerância a Glucose/normas , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Estudos de Amostragem , Viés de SeleçãoRESUMO
OBJECTIVE: To examine the dose-related pharmacodynamics and pharmacokinetics of a single preprandial oral dose of repaglinide in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 16 Caucasian men with type 2 diabetes participated in two placebo-controlled double-blind randomized cross-over studies. Patients were randomized to receive a single oral dose of repaglinide (0.5, 1.0, and 2.0 mg in study 1 and 4.0 mg in study 2) or placebo (both studies) administered 15 min before the first of two sequential identical standard meals (breakfast and lunch) that were 4 h apart. During each of the study days, which were 1 week apart, blood samples were taken at frequent intervals over a period of approximately 8 h for measurement of plasma glucose, insulin, C-peptide, and repaglinide concentrations. RESULTS: During the first meal period (0-240 min), administration of repaglinide reduced significantly the area under the curve (AUC) for glucose concentration and significantly increased the AUC for insulin levels, C-peptide levels, and the insulin secretion rate. These results, compared with those of administering placebo, were dose dependent and log linear. The effect of repaglinide administration on insulin secretion was most pronounced in the early prandial period. Within 30 min, it caused a relative increase in insulin secretion of up to 150%. During the second meal period (240-480 min), there was no difference between repaglinide and placebo administration in the AUC for glucose concentration, C-peptide concentration, and the estimated insulin secretion rate. CONCLUSIONS: A single dose of repaglinide (0.5-4.0 mg) before breakfast improves insulin secretion and reduces prandial hyperglycemia dose-dependently Administration of repaglinide had no effect on insulin secretion with the second meal, which was consumed 4 h after breakfast.
Assuntos
Glicemia/metabolismo , Carbamatos/uso terapêutico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/metabolismo , Piperidinas/uso terapêutico , Administração Oral , Área Sob a Curva , Peptídeo C/sangue , Carbamatos/administração & dosagem , Estudos de Coortes , Estudos Cross-Over , Método Duplo-Cego , Esquema de Medicação , Ingestão de Alimentos , Humanos , Hiperglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Insulina/sangue , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Piperidinas/administração & dosagemRESUMO
OBJECTIVE: To determine the subcutaneous absorption rates and the appearance in plasma of 3 formulations of the long-acting human insulin analog insulin glargine (HOE 901) differing only in zinc content (15, 30, and 80 microg/ml). RESEARCH DESIGN AND METHODS: We conducted 2 studies. Study 1 compared the subcutaneous abdominal injection of 0.15 U/kg of 125I-labeled insulin glargine[15], insulin glargine[80], NPH insulin, and placebo. In study 2, 0.2 U/kg of insulin glargine[30] was injected into the arm, leg, and abdominal regions. Both studies had a randomized crossover design; each enrolled 12 healthy men, aged 18-50 years. RESULTS: In study 1, the time in hours for 25% of the administered radioactivity to disappear after bolus subcutaneous injection (T75%) for NPH insulin indicated a significantly faster absorption rate compared with the 2 insulin glargine formulations (3.2 vs. 8.8 and 11.0 h, respectively P < 0.0001). Mean residual radioactivity with NPH insulin was also significantly lower at 24 h (21.9 vs. 43.8 and 52.2%, P < 0.0001). The calculated plasma exogenous insulin concentrations after NPH insulin were substantially higher than those with insulin glargine, reaching a peak within the first 6 h after administration before declining. Insulin glargine, however, did not exhibit a distinct peak. Weighted average plasma glucose concentration between 0 and 6 h was significantly lower after NPH compared with insulin glargine (P < 0.001). In study 2, there were no significant differences in the absorption characteristics of insulin glargine between the 3 injection sites (T75% = 11.9, 15.3, and 13.2 h for arm, leg, and abdomen, respectively) or in residual radioactivity at 24 h. CONCLUSIONS: Subcutaneous absorption of insulin glargine is delayed compared with NPH insulin. There is little or no difference in the absorption rate of insulin glargine between the main subcutaneous injection sites.
Assuntos
Insulina Isófana/farmacocinética , Insulina/análogos & derivados , Adulto , Estudos Cross-Over , Humanos , Injeções Subcutâneas , Insulina/administração & dosagem , Insulina/sangue , Insulina/farmacocinética , Insulina Glargina , Insulina Isófana/administração & dosagem , Insulina Isófana/sangue , Insulina de Ação Prolongada , Radioisótopos do Iodo/farmacocinética , Masculino , Valores de Referência , Método Simples-CegoRESUMO
OBJECTIVE: To determine the day-to-day intraindividual variability of fasting plasma glucose (FPG) in newly diagnosed Caucasian type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: A total of 193 newly diagnosed, previously untreated, Caucasian type 2 diabetic subjects (135 men, 58 women) had FPG measured on two consecutive days (FPG1, FPG2). Ethical approval and subjects' full informed consent were obtained. Subjects fasted for 12 h before each study day and rested for at least 30 min before blood was taken. Plasma glucose was analyzed by a glucose oxidase method with intra- and interassay coefficients of variation (CVs) < 2%. Variability of FPG was assessed by comparison of percentage differences (PDs): PD = 100 (FPG2 - FPG1)/FPG1, with averaged FPG (FPGaver = [FPG1 + FPG2]/2). Biological and analytical variability were determined by use of SD2total = SD2biological + SD2analytical, where SD2analytical approximately equal to 2 x (CVglucose measurement)2. Given normally distributed data with zero mean, 95% of daily percentage differences will be expected to fall within a range of +/- 2 SDtotal. RESULTS: Subjects were age 54 +/- 10 years (mean +/- SD) and had BMI of 29.3 +/- 5.3 kg/m2. FPG values for both days were 12.2 +/- 3.4 mmol/l (FPG1) and 12.1 +/- 3.3 mmol/l (FPG2), with a mean paired difference (95% CI) of 0.1 (0.0 to 0.3) mmol/l. The variance of these differences increased with increasing FPGaver. The PDs did not exhibit this effect and were normally distributed (mean -0.6% [-1.7 to 0.4]; SD 7.4% [6.8 to 8.3]), giving a 95% variability (2 SD) of 14.8%. Biological variability (2 SDbiological) was 13.7%. No significant difference in PD was found between men and women (mean difference 1.3% [-1.0 to 3.6]; SDmale 7.4%, SDfemale 7.3%; P = 0.62). CONCLUSIONS: A total of 95% of the FPG values for this group of newly diagnosed type 2 diabetic subjects varied within approximately +/- 15% on a daily basis, with approximately 14% caused by biological variability. As these results are expressed in percentage terms, subjects in the group with higher FPG values are likely to experience larger changes in FPG values measured from day to day. This variability should be considered when using FPG for the diagnosis and/or monitoring of response to treatment in patients with type 2 diabetes.