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BACKGROUND: Microvascular complications are common in people with diabetes, where poor glycaemic control is the major contributor. The aim of this study was to explore the association between elevated LDL cholesterol levels and the risk of retinopathy or nephropathy in young individuals with type 1 diabetes. METHODS: This was a nationwide observational population-based cohort study, including all children and adults with a duration of type 1 diabetes of ≤ 10 years, identified in the Swedish National Diabetes Register between 1998 and 2017. We calculated the crude incidence rates with 95% confidence intervals (CIs) and used multivariable Cox regression to estimate crude and adjusted hazard ratios (HRs) of retinopathy or nephropathy in four LDL cholesterol categories: <2.6 (Reference), 2.6-3.4, 3.4-4.1 and > 4.1 mmol L-1 . RESULTS: In total, 11 024/12 350 (retinopathy/nephropathy, both cohorts, respectively) children and adults (median age 21 years, female 42%) were followed up to 28 years from diagnosis until end of study. Median duration of diabetes when entering the study was 6 and 7 years in the retinopathy and nephropathy cohort, respectively. Median LDL cholesterol was 2.4 mmol L-1 , and median HbA1c level was 61 mmol mol-1 (7.7 %). After multivariable adjustment, the HRs (95% CI) for retinopathy in individuals with LDL cholesterol levels of 2.6-3.4, 3.4-4.1 or > 4.1 mmol L-1 were as follows: 1.13 (1.03-1.23), 1.16 (1.02-1.32) and 1.18 (0.99-1.41), compared with the reference. The corresponding numbers for nephropathy were as follows: 1.15 (0.96-1.32), 1.30 (1.03-1.65) and 1.41 (1.06-1.89). CONCLUSIONS: Young individuals with type 1 diabetes exposed to high LDL cholesterol levels have an increased risk of retinopathy and nephropathy independent of glycaemia and other identified risk factors for vascular complications.
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LDL-Colesterol/sangue , Diabetes Mellitus Tipo 1 , Nefropatias Diabéticas , Retinopatia Diabética , Adolescente , Adulto , Criança , Estudos de Coortes , Diabetes Mellitus Tipo 1/epidemiologia , Nefropatias Diabéticas/epidemiologia , Retinopatia Diabética/epidemiologia , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Fatores de Risco , Suécia/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To estimate the excess risk of stroke in relation to glycaemic control in patients with type 1 diabetes. METHODS: In this prospective, matched cohort study, we identified patients with type 1 diabetes, aged ≥18 years, who were registered in the Swedish National Diabetes Register from 1998-2011 and five control subjects for each case from the general population, matched for age, sex and county of residence. The risks of all strokes, ischaemic stroke and haemorrhagic stroke were estimated using Cox hazard regression. RESULTS: Of 33 453 type 1 diabetes patients [mean age, 35.5 (SD 14.4) years; mean follow-up, 7.9 (SD 4.3) years; and mean diabetes duration, 20.2 years (SD 14.6)], 762 (2.3%) were diagnosed with stroke compared with 1122 (0.7%) of 159 924 control subjects [mean follow-up, 8.2 (SD 4.3) years]. The overall multiple-adjusted hazard ratios (HRs) for type 1 diabetes patients versus control subjects were 3.29 (95% CI: 2.96-3.66) and 2.49 (95% CI: 1.96-3.16) for ischaemic and haemorrhagic stroke, respectively. The risk of ischaemic and haemorrhagic stroke incrementally increased with increasing HbA1c; the risk of ischaemic stroke was significantly increased with HbA1c within target [≤6.9% (≤52 mmol mol-1 )] [multiple-adjusted HR 1.89 (95% CI: 1.44-2.47)]. For HbA1c ≥9.7% (≥83 mmol mol-1 ), there was a markedly increased risk of both ischaemic and haemorrhagic stroke, with multiple-adjusted HRs of 7.94 (95% CI: 6.29-10.03) and 8.17 (95% CI 5.00-13.35), respectively. CONCLUSIONS: Individuals with type 1 diabetes have an increased risk of ischaemic and haemorrhagic stroke, increasing markedly with poor glycaemic control.
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Glicemia/metabolismo , Isquemia Encefálica/epidemiologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/epidemiologia , Hemorragias Intracranianas/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Estudos de Casos e Controles , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Hiperglicemia/complicações , Masculino , Estudos Prospectivos , Suécia/epidemiologiaRESUMO
AIMS: To estimate the risk of stroke in people with Type 2 diabetes with different blood pressure levels compared with the risk in the general population in Sweden. METHODS: This prospective case-control study included 408 076 people with Type 2 diabetes, aged ≥ 18 years, and free of prior stroke, registered in the Swedish National Diabetes Register 1998-2011. Age- and sex-matched control subjects (n = 1 913 507) without stroke from the general population were included. Stroke diagnoses were retrieved using International Classification of Disease codes from the Swedish patient and death registers. Cox hazard ratios and 95% confidence intervals (CIs) were estimated at six different blood pressure levels. RESULTS: During a median follow-up of 4 years, 19 548 (4.8%) people with Type 2 diabetes and 61 690 (3.2%) without diabetes were diagnosed with stroke, corresponding to an adjusted hazard ratio of 1.43 (95% CI 1.41-1.46) for people with Type 2 diabetes as a group. Compared with people without diabetes, the risk of stroke for people with Type 2 diabetes with different blood pressure levels was significantly higher, starting at blood pressure levels > 130/80 mmHg. Hazard ratios for stroke were 1.20 (95% CI 1.16-1.24), 1.47 (95% CI 1.43-1.50), and 1.97 (95% CI 1.90-2.03) for blood pressure categories of 130-139/80-89 mmHg, 140-159/90-99 mmHg and ≥ 160/≥ 100 mmHg, respectively, after adjustment for age, sex, diabetes duration, being born in Sweden, maximum education level and baseline comorbidities. CONCLUSIONS: People with Type 2 diabetes and blood pressure < 130/80 mmHg had a risk of stroke similar to that of the general population.
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Pressão Sanguínea , Diabetes Mellitus Tipo 2/epidemiologia , Hipertensão/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Suécia/epidemiologiaRESUMO
AIMS: To describe factors associated with prevalence or absence of microvascular and macrovascular complications in people with Type 1 diabetes of very long duration and to investigate the risk factors associated with the incidence of such complications. METHODS: We included individuals with Type 1 diabetes who had been entered in the Swedish National Diabetes Register between 2002 and 2004 (n = 18 450). First, risk factor distribution in people with diabetes duration of ≥ 50 years was compared between people with and without complications. Second, the incidence of complications during a 10-year follow-up period was studied in all individuals who had no complications at baseline. RESULTS: Among people with a diabetes duration of ≥ 50 years (n = 1023), 453 (44%) had macrovascular disease, 534 (52%) had microvascular disease and 319 (31%) did not have either of the diagnoses. Factors that differed significantly between people with and without macrovascular disease were gender, age, HbA1c , BMI, LDL cholesterol, HDL cholesterol, triglycerides, systolic blood pressure, albuminuria, antihypertensive medication and lipid-lowering medication. The same factors differed significantly between people with and without microvascular disease, with the exception of gender and HDL cholesterol. During the follow-up period, 6.1% of the study cohort were diagnosed with macrovascular disease and 19.6% with microvascular disease. Incidence of macrovascular disease was significantly associated with HbA1c levels. Hazard ratios decreased with longer diabetes duration. CONCLUSIONS: People with Type 1 diabetes who have survived ≥ 50 years without complications are significantly younger, and have significantly lower HbA1c levels, BMI and triglyceride levels than survivors with complications. HbA1c level is a predictor of macrovascular disease, independently of diabetes duration.
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Envelhecimento , Diabetes Mellitus Tipo 1/terapia , Angiopatias Diabéticas/prevenção & controle , Hiperglicemia/prevenção & controle , Adolescente , Adulto , Idoso , Estudos de Coortes , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/fisiopatologia , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/fisiopatologia , Progressão da Doença , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Incidência , Masculino , Microvasos/fisiopatologia , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Suécia/epidemiologia , Adulto JovemRESUMO
AIM: LDL cholesterol (LDL-C) is considered an important cardiovascular disease (CVD) risk factor. Less is known in Type 1 diabetes. We assessed LDL-C and total cholesterol to HDL cholesterol ratio (TC/HDL-C) as predictors of CVD in Type 1 diabetes. METHODS: The study monitored 30 778 people with Type 1 diabetes, baseline 2003-2006, to 31 December 2011. Cox regression analyses were performed with LDL-C and TC/HDL-C as predictors of fatal/non-fatal CVD. Models were adjusted for traditional CVD risk factors. RESULTS: Hazard ratios (HR) (with 95% CI) per 1 mmol/l increase in LDL-C for CVD were 1.09 (1.01-1.18) in people without lipid-lowering medication and 1.02 (0.95-1.09) in people with lipid-lowering medication (P = 0.02 and 0.65). In people aged 40 years or older having a CVD risk factor, and in people with a history of CVD, HR was 1.07 (0.99-1.16) and 1.02 (0.92-1.13) (P = 0.07 and 0.66). HR per 1 unit increase in TC/HDL-C was 1.12 (1.05-1.20) in people without lipid-lowering medication and 1.08 (1.02-1.15) in people with lipid-lowering medication (P < 0.001 and 0.01). For people aged 40 or older and people with a history of CVD, HR was 1.16 (1.09-1.24) and 1.04 (0.95-1.14) (P < 0.001 and 0.43). Broken down into octiles, LDL-C was not a significant predictor of CVD in any group. Higher octiles of TC/HDL-C were significant predictors for CVD in people without lipid-lowering medication and in those aged 40 years or older. CONCLUSION: In this study of people with Type 1 diabetes in clinical practice, LDL-C was not a good predictor of CVD. We found no support for an LDL-C cut-off point < 2.6 mmol/l. TC/HDL-C seems more reliable as a marker for CVD risk when considering primary prevention.
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Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 1/sangue , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Humanos , Hipolipemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Suécia/epidemiologia , Adulto JovemRESUMO
AIMS: Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries. METHODS: Data were obtained for children and/or adults with Type 1 diabetes from the following countries (or regions): Western Australia, Austria, Denmark, England, Champagne-Ardenne (France), Germany, Epirus, Thessaly and Thessaloniki (Greece), Galway (Ireland), several Italian regions, Latvia, Rotterdam (The Netherlands), Otago (New Zealand), Norway, Northern Ireland, Scotland, Sweden, Volyn (Ukraine), USA and Wales) from population or clinic-based registries. The sample size with available data varied from 355 to 173 880. Proportions with HbA1c < 58 mmol/mol (< 7.5%) and ≥ 75 mmol/mol (≥ 9.0%) were compared by age and sex. RESULTS: Data were available for 324 501 people. The proportions with HbA1c 58 mmol/mol (< 7.5%) varied from 15.7% to 46.4% among 44 058 people aged < 15 years, from 8.9% to 49.5% among 50 766 people aged 15-24 years and from 20.5% to 53.6% among 229 677 people aged ≥ 25 years. Sex differences in glycaemic control were small. Proportions of people using insulin pumps varied between the 12 sources with data available. CONCLUSION: These results suggest that there are substantial variations in glycaemic control among people with Type 1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults.
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Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas/metabolismo , Hipoglicemiantes/uso terapêutico , Sistemas de Infusão de Insulina/estatística & dados numéricos , Insulina/uso terapêutico , Sistema de Registros , Adolescente , Adulto , Áustria , Dinamarca , Diabetes Mellitus Tipo 1/metabolismo , Inglaterra , Feminino , França , Alemanha , Grécia , Fidelidade a Diretrizes , Humanos , Irlanda , Itália , Letônia , Masculino , Países Baixos , Nova Zelândia , Irlanda do Norte , Noruega , Guias de Prática Clínica como Assunto , Escócia , Suécia , Ucrânia , Estados Unidos , País de Gales , Austrália Ocidental , Adulto JovemRESUMO
On entering an era of global warming, the stability of the Greenland ice sheet (GIS) is an important concern, especially in the light of new evidence of rapidly changing flow and melt conditions at the GIS margins. Studying the response of the GIS to past climatic change may help to advance our understanding of GIS dynamics. The previous interpretation of evidence from stable isotopes (delta(18)O) in water from GIS ice cores was that Holocene climate variability on the GIS differed spatially and that a consistent Holocene climate optimum-the unusually warm period from about 9,000 to 6,000 years ago found in many northern-latitude palaeoclimate records-did not exist. Here we extract both the Greenland Holocene temperature history and the evolution of GIS surface elevation at four GIS locations. We achieve this by comparing delta(18)O from GIS ice cores with delta(18)O from ice cores from small marginal icecaps. Contrary to the earlier interpretation of delta(18)O evidence from ice cores, our new temperature history reveals a pronounced Holocene climatic optimum in Greenland coinciding with maximum thinning near the GIS margins. Our delta(18)O-based results are corroborated by the air content of ice cores, a proxy for surface elevation. State-of-the-art ice sheet models are generally found to be underestimating the extent and changes in GIS elevation and area; our findings may help to improve the ability of models to reproduce the GIS response to Holocene climate.
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Efeito Estufa , Camada de Gelo , Altitude , Groenlândia , História Antiga , Oxigênio/análise , Isótopos de Oxigênio , TemperaturaRESUMO
AIM'S: The aim was to To study the relationship between BMI and hospitalization for heart failure in people with Type 2 diabetes. METHODS: We identified 83 021 individuals with Type 2 diabetes from the Swedish National Diabetes Registry during 1998-2003, who were followed until hospitalization for heart failure, death or end of follow-up on 31 December 2009. Cox regression analyses were performed, adjusting for age, sex, HbA(1c), blood pressure, diabetes duration, smoking, microalbuminuria, cardiac co-morbidities, glucose-lowering and anti-hypertensive medications. RESULTS: During a median follow-up of 7.2 years, 10 969 patients (13.2%) were hospitalized with heart failure. By categories of BMI, with BMI 20 to < 25 kg/m(2) as the reference, hazard ratios for patients during follow-up were 1.07 (95% CI 0.91-1.26) for a mean BMI of < 20 kg/m(2), 1.04 (95% CI 0.98-1.11) for BMI 25 to < 27.5 kg/m(2), 1.22 (95% CI 1.15-1.30) for BMI 27.5 to < 30 kg/m(2), 1.54 (95% CI 1.45-1.63) for BMI 30 to < 35 kg/m(2), 2.16 (95% CI 2.00-2.33) for BMI 35 to < 40 kg/m(2) and 3.22 (95% CI 2.88-3.60) for BMI 40 kg/m(2) or higher. There was a significant interaction between BMI and sex (P = 0.0006), with numerically higher hazard ratios for hospitalization for heart failure within each BMI category for men than for women. CONCLUSIONS: Obesity is strongly related to hospitalization for heart failure in people with Type 2 diabetes, and the relationship is somewhat stronger for men than for women. Preventing weight gain and promoting weight loss may be crucial in reducing the incidence of future hospitalizations for heart failure in this population.
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Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Insuficiência Cardíaca/epidemiologia , Hospitalização/estatística & dados numéricos , Obesidade/complicações , Sistema de Registros , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , Análise de Regressão , Fatores de Risco , Fatores Sexuais , Taxa de Sobrevida , Suécia/epidemiologiaRESUMO
AIMS/HYPOTHESIS: The aim of this study was to examine the relationship between glycaemic control and hospitalisation for heart failure in patients with type 2 diabetes. METHODS: Patients included in the Swedish National Diabetes Register (NDR) during 1998-2003 were followed until hospitalisation for heart failure, death or 31 December 2009. Unadjusted and adjusted incidence rates for heart failure were estimated by Poisson regression and relative risk was estimated by Cox regression. RESULTS: In 83,021 patients with type 2 diabetes, 10,969 (13.2%) were hospitalised with a primary or secondary diagnosis of heart failure during a mean follow-up of 7.2 years. The incidence increased by male sex (p < 0.001), older age (p < 0.001) and longer diabetes duration (p < 0.001). In Cox regression adjusting for risk factors of heart failure the HR per each percentage unit higher HbA(1c) (10 mmol/mol) for heart-failure hospitalisation was 1.12 (95% CI 1.10, 1.14). By category of HbA(1c) the HR for heart failure hospitalisation was: HbA(1c) 6.0 to <7.0% (42 to <53 mmol/mol), 0.91 (95% CI 0.84, 0.98); HbA(1c) 7.0 to <8.0% (53 to <64 mmol/mol), 0.99 (95% CI 0.91, 1.07); HbA(1c) 8.0 to <9.0% (64 to < 75 mmol/mol), 1.10 (95% CI 1.01, 1.20); HbA(1c) 9.0 to <10.0% (75 to <86 mmol/mol), 1.27 (95% CI 1.15, 1.41); HbA(1c) ≥ 10.0 % (≥ 86 mmol/mol), 1.71 (1.51, 1.93) (reference HbA(1c) <6% [42 mmol/mol]). The HR for patients with HbA(1c) 7.0 to <8.0% (53 to < 64 mmol/mol) compared with patients with HbA(1c) 6.0 to <7.0% (42 to <53 mmol/mol) was 1.09 (95% CI 1.03, 1.14). CONCLUSIONS/INTERPRETATION: Poor glycaemic control (HbA(1c) >7% [53 mmol/mol]) is associated with an increased risk of hospitalisation for heart failure in patients with type 2 diabetes.
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Diabetes Mellitus Tipo 2/epidemiologia , Insuficiência Cardíaca/epidemiologia , Hospitalização/estatística & dados numéricos , Hiperglicemia/epidemiologia , Distribuição por Idade , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Seguimentos , Hemoglobinas Glicadas/metabolismo , Humanos , Hiperglicemia/metabolismo , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Distribuição por Sexo , Suécia/epidemiologiaRESUMO
AIMS: To analyse clinical characteristics and treatment results in unselected type 2 diabetes mellitus (T2DM) patients, with non-pharmacological treatment as well as the most commonly used pharmacological glucose-lowering treatment regimens, in everyday clinical practice. METHODS: In this population-based cross-sectional study, information was linked from the Swedish National Diabetes Register, Prescribed Drug Register and Patient Register. T2DM patients with non-pharmacological treatment and T2DM patients continuously using the 12 most common pharmacological treatment regimens were included in the study (n = 163121). RESULTS: There were statistically significant differences in clinical characteristics between the groups. Patients with insulin-based treatment regimens had the longest duration of diabetes and more cardiovascular risk factors than the T2DM-population in general. The proportion of patients reaching HbA1c ≤ 7% varied between 70.1% (metformin) and 25.0% [premixed insulin (PMI) + SU) in patients with pharmacological treatment. 84.8% of the patients with non-pharmacological treatment reached target. Compared to patients on metformin, patients on other pharmacological treatments had a lower likelihood, with hazard ratios ranging from 0.58; 95% confidence interval (CI), 0.54-0.63 to 0.97;0.94-0.99, of having HbA1c ≤ 7% (adjusted for covariates). Patients on insulin-based treatments had the lowest likelihood, while non-pharmacological treatment was associated with an increased likelihood of having HbA1c ≤ 7%. CONCLUSION: This nation-wide study shows insufficiently reached treatment goals for haemoglobin A1c (HbA1c) in all treatment groups. Patients on insulin-based treatment regimens had the longest duration of diabetes, more cardiovascular risk factors and the highest proportions of patients not reaching HbA1c target.
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Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metformina/uso terapêutico , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/epidemiologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores de Risco , Suécia/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Electrodes containing 60 wt% micron-sized silicon were investigated with electrolytes containing carbonate solvents and either LiPF6 or lithium bis(fluorosulfonyl)imide (LiFSI) salt. The electrodes showed improved performance, with respect to capacity, cycling stability, rate performance, electrode resistance and cycle life with the LiFSI salt, attributed to differences in the solid electrolyte interphase (SEI). Through impedance spectroscopy, cross sectional analysis using transmission electron microscopy (TEM) and focused ion beam (FIB) in combination with scanning electron microscopy (SEM), and electrode surface characterization by X-ray photoelectron spectroscopy (XPS), differences in electrode morphological changes, SEI composition and local distribution of SEI components were investigated. The SEI formed with LiFSI has a thin, inner, primarily inorganic layer, and an outer layer dominated by organic components. This SEI appeared more homogeneous and stable, more flexible and with a lower resistivity than the SEI formed in LiPF6 electrolyte. The SEI formed in the LiPF6 electrolyte appears to be less passivating and less flexible, with a higher resistance, and with higher capacitance values, indicative of a higher interfacial surface area. Cycling in LiPF6 electrolyte also resulted in incomplete lithiation of silicon particles, attributed to the inhomogeneous SEI formed. In contrast to LiFSI, where LiF was present in small grains in-between the silicon particles, clusters of LiF were observed around the carbon black for the LiPF6 electrolyte.
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AIMS: To analyse the association between glycosylated haemoglobin A1c (HbA1c) and cardiovascular disease (CVD) in patients with type 2 diabetes in the Swedish National Diabetes Register (NDR). METHODS: An observational study of 18 334 patients (age 30-79 years, previous CVD in 18%, baseline HbA1c 5.0-10.9%) who were followed for 6 years (mean 5.6 years) from 1997/1998 until 2003. RESULTS: Hazard ratios per 1% unit increase in baseline or updated mean HbA1c for fatal/nonfatal coronary heart disease (CHD), CVD and total mortality were 1.11-1.13, 1.10-1.11 and 1.09-1.10, respectively (all P < 0.001), adjusted for several risk factors and clinical characteristics in Cox regression. Adjusted 6-year event rates increased with higher baseline or updated mean HbA1c with no J-shaped risk curves, in all patients and also when subgrouping by shorter (mean 3 years) or longer (mean 14 years) diabetes duration, by presence or absence of previous CVD, or by treatment with oral hypoglycaemic agents (OHAs) or insulin. Risk reductions of 20% for CHD and 16% for CVD (P < 0.001) were found in patients with a baseline mean HbA1c of 6.5%, compared to those with a mean level of 7.5%. Compared to OHA-treated patients, insulin-treated patients had an increased risk of total mortality, due almost exclusively to an increased risk of non-CVD mortality, and due less to a weakly significant increased risk of fatal CVD. HbA1c was not associated with non-CVD mortality. CONCLUSIONS: This observational study showed progressively increasing risks of CHD, CVD and total mortality with higher HbA1c, and no risk increase at low HbA1c levels even with longer diabetes duration, previous CVD or treatment with either insulin or OHAs. Patients achieving HbA1c <7% showed benefits for risk reduction.
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Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Hemoglobinas Glicadas/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Doença das Coronárias/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Acidente Vascular Cerebral/epidemiologiaRESUMO
Background In a modern perspective there is limited information on mortality by affected coronary vessels assessed by coronary angiography in patients with type 1 diabetes. The aim of the present study was to characterise distribution of coronary artery disease and impact on long-term mortality in patients with type 1 diabetes undergoing coronary angiography. Design The design of this research was a nationwide population-based cohort study. Methods Individuals ( n = 2776) with type 1 diabetes undergoing coronary angiography 2001-2013 included in the Swedish National Diabetes Registry and Swedish Coronary Angiography and Angioplasty Registry were followed for mortality until 31 December 2013 (mean 7.1 years). In 79% the indication was stable or acute coronary artery disease. Coronary artery disease was categorised into normal (21%), one- (23%), two- (18%), three- (29%) and left main-vessel disease (8%). Results Mean age was 57 years and 58% were male. Mean diabetes duration was 35 years, glycated haemoglobin was 67 mmol/mol and 44% had normal or one-vessel disease. In multivariate Cox proportional analyses hazard ratio for mortality compared with normal findings was 1.09 (95% confidence interval 0.80-1.48) for one, 1.43 (1.05-1.94) for two, 1.47 (1.10-1.96) for three and 1.90 (1.35-2.68) for left main-vessel disease. Renal failure 2.29 (1.77-2.96) and previous heart failure 1.76 (1.46-2.13) were highly associated with mortality. Standard mortality ratio the first year was 5.55 (4.65-6.56) and decreased to 2.80 (2.18-3.54) after five years. Conclusions In patients with type 1 diabetes referred for coronary angiography mortality is influenced by numbers of affected coronary vessels. The overall mortality rate was higher compared with the general population. These results support early intensive prevention of coronary artery disease in this population.
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Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Diabetes Mellitus Tipo 1/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Distribuição de Qui-Quadrado , Diabetes Mellitus Tipo 1/diagnóstico , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Índice de Gravidade de Doença , Suécia/epidemiologia , Fatores de Tempo , Adulto JovemRESUMO
Anesthetized male Sprague-Dawley rats (350-400 g) were injected intravenously with either 0.1, 1, 15, or 25 nmol rat islet amyloid polypeptide (IAPP), 65 or 650 pmol rat calcitonin gene-related peptide (CGRP), or saline alone. IAPP at the two highest doses decreased the mean arterial blood pressure (BP), increased blood glucose concentrations, and decreased serum insulin concentrations. CGRP at both doses decreased the BP but did not affect the blood glucose concentrations. The blood flow to the whole pancreas, pancreatic islets, adrenal glands, colon, duodenum, liver, and kidney was measured with a microsphere technique 30 min after administration of IAPP and 3 min after injection of CGRP. The two higher doses of IAPP (15 and 25 nmol) markedly reduced the whole pancreatic blood flow, whereas the islet blood flow remained unaffected. This resulted in an increase in the fraction of whole pancreatic blood flow diverted through the islets from approximately 10 to 17%. No blood flow changes in the pancreas or the islets were observed when 0.1 or 1 nmol IAPP was injected. CGRP at both doses caused a decrease in both whole pancreatic and islet blood flow. No changes in fractional islet blood flow were observed, despite similar effects on mean arterial BP as observed after IAPP injections. Neither adrenal, duodenal, colonic, hepatic, skeletal muscle, nor renal blood flow were significantly affected by any of the concentrations of IAPP used, whereas 650 pmol CGRP decreased both duodenal and colonic blood flow. We conclude that IAPP and CGRP have different effects on pancreatic islet blood flow and that IAPP may be of importance for islet blood flow regulation.
Assuntos
Amiloide/farmacologia , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Ilhotas Pancreáticas/irrigação sanguínea , Amiloide/administração & dosagem , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/administração & dosagem , Insulina/sangue , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Ilhotas Pancreáticas/efeitos dos fármacos , Cinética , Masculino , Pâncreas/irrigação sanguínea , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVES: This study sought to validate computerized vectorcardiography against the established technique of Holter electrocardiographic (ECG) monitoring and to compare the feasibility of the two methods for monitoring patients with unstable angina pectoris. BACKGROUND: Detection of myocardial ischemic episodes is an important objective in patients admitted to the hospital for unstable angina pectoris. Standard ECG monitoring may be sufficient for detection of symptomatic episodes but will often overlook silent ischemia. Holter ECG monitoring has a higher likelihood of discovering such episodes, but analysis is time-consuming, and the results are not available on-line. METHODS: We simultaneously monitored 53 consecutive patients with unstable angina, 46 of whom had technically adequate 24-h Holter ECGs and computerized vectorcardiograms. RESULTS: The Holter tapes had a mean (+/- SD) of 15.3 +/- 10.3 h of recording with both channels technically adequate for analysis compared with 23.7 +/- 1.77 h of vectorcardiographic recording that could be analyzed (p < 0.01). Of the 15 symptomatic episodes detected by Holter ECG monitoring, 13 were also detected with dynamic vectorcardiography. In contrast, eight patients had 18 episodes of chest pain, with simultaneous ST segment changes detected by dynamic vectorcardiography; only 9 of these episodes were also detected by Holter ECG monitoring. CONCLUSIONS: Monitoring of myocardial ischemia with dynamic vectorcardiography seems to be more efficient than Holter monitoring and may have a higher sensitivity. Computerized, continuous vectorcardiography has a complete real-time capacity, allowing monitoring over prolonged periods of time, and the results are immediately available without time-consuming analysis.
Assuntos
Angina Instável/fisiopatologia , Vetorcardiografia , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletrocardiografia Ambulatorial , Estudos de Viabilidade , Feminino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
The major changes in pancreatic islet function during pregnancy and after exposure to lactogens are an increase in beta-cell proliferation and enhanced insulin secretion. In this study we examined INS-1 cells as a potential model for further inquiry into PRL signaling in beta-cells. Proliferation of beta-cells, insulin secretion, and quantitative immunocytochemical analysis of STAT5 translocation were studied. PRL treatment of INS-1 cells resulted in a 2- to 4-fold increase in cell proliferation compared to that in the control group. In contrast, there was no effect of PRL treatment on HIT cell proliferation and only a very small effect on RIN cell proliferation. A significant effect on INS-1 cell proliferation was observed at 10 ng/ml and reached a maximum at 200 ng/ml. PRL treatment resulted in enhanced insulin secretion from INS-1 cells. There was a time-dependent increase in insulin secretion, which when corrected for cell number was 1.5-fold greater in the PRL-treated cells. The effects of PRL on cell division and insulin secretion were glucose dependent. The presence of the JAK family of tyrosine kinases and the transcription factor STAT5 in INS-1 cells was examined by immunocytochemical techniques. Although all members of the JAK family of kinases were detected, the staining intensity of JAK-2 was noticeably more intense. Initial studies of STAT5 translocation were performed using PRL-dependent Nb2 lymphoma cells, in which PRL treatment resulted in a nearly complete translocation of cytoplasmic STAT5 to the nucleus. Under control conditions there was a near-equal fluorescence intensity of STAT5 staining in the nucleus and cytoplasm of INS-1 cells. PRL treatment resulted in a time-dependent increase in STAT5 staining in the nucleus, with a corresponding decrease in the cytoplasm. The STAT5 staining intensity in the nucleus remained elevated for the duration of PRL treatment. This effect was reversible upon removal of PRL from the medium. Besides PRL, both GH and FBS induced a similar translocation of STAT5 to the nucleus. Although present in RIN cells, no detectable changes in STAT5 were observed in RIN cells after exposure to PRL, GH, or FBS. INS-1 cells should provide a good model for further inquiry into the intracellular signaling pathways used by PRL and how these events alter islet function.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Ilhotas Pancreáticas/citologia , Proteínas do Leite , Prolactina/fisiologia , Transativadores/metabolismo , Animais , Divisão Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Cricetinae , Citoplasma/metabolismo , Feminino , Hormônio do Crescimento Humano/farmacologia , Insulina/metabolismo , Secreção de Insulina , Gravidez , Ratos , Proteínas Recombinantes/farmacologia , Fator de Transcrição STAT5 , Células Tumorais CultivadasRESUMO
To elucidate the effect of nitric oxide (NO) on the blood flow of the pancreatic islets, the NO synthase inhibitor NG-nitro-L-arginine (N-arg; 25 mg/kg BW) was administered iv to rats 10 min before pancreatic blood flow was measured with a nonradioactive microsphere technique. In male Sprague-Dawley rats, N-arg induced a marked decrease in islet blood flow (16 +/- 4 vs. 44 +/- 8 microliters/min.g pancreas; P < 0.001) and a less pronounced decrease in whole pancreatic blood flow (0.27 +/- 0.04 vs. 0.43 +/- 0.06 ml/min.g; P < 0.05), leading to a markedly decreased fractional islet blood flow (5.5 +/- 0.9% vs. 10.3 +/- 1.3%; P < 0.02). In a second experiment, injection of D-glucose (300 mg/kg BW, iv) in male Sprague-Dawley rats induced a selective increase in islet blood flow (P < 0.05). Such an increase has previously been shown to be mediated by a vagal cholinergic mechanism. Administration of N-arg to these rats resulted in decreased pancreatic (P < 0.05), islet (P < 0.001), and fractional (P < 0.001) islet blood flow, which did not differ from those observed in normoglycemic rats after treatment with N-arg. Furthermore, we studied the mechanism behind the previously described increase in islet blood perfusion, mediated by the vagus nerve, in F1-hybrids of the GK (Goto-Kakizaki) rat, a spontaneous animal model of noninsulin-dependent diabetes mellitus. Administration of N-arg to female GK rats resulted in decreases in islet (P < 0.001), pancreatic (P < 0.01), and fractional islet blood flow (P < 0.001) to the levels observed in female Wistar rats treated in parallel. These data are consistent with the possibility that NO is an important physiological regulator of islet blood flow. Furthermore, the vagally dependent high levels of islet blood flow demonstrated in the GK rat appear to be mediated by a mechanism involving NO.
Assuntos
Aminoácido Oxirredutases/antagonistas & inibidores , Arginina/análogos & derivados , Diabetes Mellitus Experimental/fisiopatologia , Ilhotas Pancreáticas/irrigação sanguínea , Animais , Arginina/farmacologia , Diabetes Mellitus Experimental/genética , Feminino , Masculino , Óxido Nítrico Sintase , Nitroarginina , Ratos , Ratos Mutantes , Ratos Sprague-Dawley , Ratos Wistar , Valores de Referência , Fluxo Sanguíneo Regional/efeitos dos fármacosRESUMO
The aim of the present study was to evaluate the effects of diet-induced obesity on pancreatic islet blood perfusion in normal Wistar rats. Furthermore, we investigated to what extent any obesity-associated changes in islet blood flow could be reversed after reversion to a normal diet with normalization of body weight. Young adult female Wistar rats were offered a palatable mixed high-caloric diet (cafeteria diet) in addition to standard pelleted chow. Age-matched control rats received standard pelleted chow only. After 4 weeks the diet-treated rats had a body weight of approximately 15% more than that of the controls. All diet-treated rats had decreased glucose tolerance and increased serum insulin concentrations, but basal blood glucose concentrations were similar in anesthetized diet-treated and control rats. Whole pancreatic and islet blood flow rates were measured with a microsphere technique. The islet blood flow as well as fractional islet blood flow were increased (P < 0.01) in rats fed the cafeteria diet, while blood perfusion of the whole pancreas was similar to that of the control rats. In a second experiment, rats received the cafeteria diet for 4 weeks and were then fed standard pelleted food alone for another 3 weeks, while controls received standard diet for 7 weeks. After this period total body weight, retroperitoneal fat pad weight and glucose tolerance were similar to those of the controls. Whole pancreatic blood flow was unchanged as compared with that of control rats. However, both islet blood flow (P < 0.01) and fractional blood flow (P < 0.01) were increased. We conclude that diet-induced obesity in rats is associated with decreased glucose tolerance, hyperinsulinemia and a specific increase in absolute and fractional islet blood perfusion. This increase persists for at least 3 weeks after the diet is withdrawn despite normalization of body weight and glucose tolerance.
Assuntos
Ingestão de Energia/fisiologia , Ilhotas Pancreáticas/irrigação sanguínea , Obesidade/fisiopatologia , Animais , Peso Corporal , Feminino , Intolerância à Glucose/fisiopatologia , Insulina/sangue , Obesidade/sangue , Obesidade/dietoterapia , Pâncreas/irrigação sanguínea , Ratos , Ratos Wistar , Fluxo Sanguíneo Regional/fisiologiaRESUMO
Increased blood perfusion of pancreatic islets is seen during various conditions of increased demand for insulin secretion. Pregnancy confers an increased need for insulin secretion, met by increased islet mass and volume as well as a decreased threshold for glucose-induced insulin secretion. In the present study, whole pancreatic and islet blood flow were studied with a microsphere technique in Wistar rats on days 15, 18 and 20 of pregnancy and days 2 and 7 post-partum. There were no changes in total pancreatic blood flow during pregnancy and the first post-partum week. Total blood perfusion through islet tissue expressed as flow per weight of whole pancreas was higher at day 15 of pregnancy. When islet blood flow was expressed per gram of islet tissue there was a decrease at day 18 of pregnancy. This decrease of islet blood flow was concomitant to a short-lived increase of the islet mass at the end of pregnancy. We conclude that upregulation of insulin output during late pregnancy does not specifically include increased net blood perfusion through the islets. One possible reason for this might be lack of synchronization between the proliferation of endocrine cells and angiogenesis, resulting in a relative decrease in islet vascular density in the islets.
Assuntos
Ilhotas Pancreáticas/irrigação sanguínea , Prenhez/fisiologia , Animais , Glicemia/análise , Feminino , Insulina/sangue , Ilhotas Pancreáticas/citologia , Gravidez , Ratos , Ratos Wistar , Fluxo Sanguíneo RegionalRESUMO
Previous studies have indicated that various conditions under which an increased functional load is posed on the pancreatic islets, e.g. partial pancreatectomy and continuous glucose infusions, may influence the microcirculation of the pancreas. To investigate further the effects of elevated functional demand on the islets, the blood perfusion of the whole pancreas and the pancreatic islets was measured with a microsphere technique in an animal model presenting impaired glucose tolerance and mild hyperglycemia, namely F1-hybrids of the spontaneously non-insulin-dependent diabetic GK-Wistar rat. Normal Wistar rats served as controls. All hybrids had a pathological intraperitoneal glucose tolerance test 1 week before the blood flow measurements, which were performed in 10-12-week-old rats. Both the whole pancreatic and the islet blood flows were increased in the hybrids compared to controls. The fractional islet blood flow, i.e. the fraction of whole pancreatic blood flow diverted through the islets, also was increased in the hybrid rats (12.6 +/- 0.6% vs 9.8 +/- 0.5% in controls, p < 0.01). A bilateral abdominal vagotomy performed 30 min before the blood flow measurement markedly decreased the blood flow values of the islets and the whole pancreas in both groups of rats. After vagotomy, the islet blood flow in the hybrid rats was similar to that of the vagotomized control animals (8.2 +/- 0.8 and 7.5 +/- 1.4%, respectively). It is concluded that the increased pancreatic and islet blood perfusion observed in F1-hybrids of the GK-Wistar rat depends on a mechanism mediated by the vagus nerve.