Improved electrochemical performance and solid electrolyte interphase properties of electrolytes based on lithium bis(fluorosulfonyl)imide for high content silicon anodes.

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.

LDL cholesterol level as a risk factor for retinopathy and nephropathy in children and adults with type 1 diabetes mellitus: A nationwide cohort study.

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.

Mortality and extent of coronary artery disease in 2776 patients with type 1 diabetes undergoing coronary angiography: A nationwide study.

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.

Glycaemic control and excess risk of ischaemic and haemorrhagic stroke in patients with type 1 diabetes: a cohort study of 33 453 patients.

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.

Risk of future microvascular and macrovascular disease in people with Type 1 diabetes of very long duration: a national study with 10-year follow-up.

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.

Long-term excess risk of stroke in people with Type 2 diabetes in Sweden according to blood pressure level: a population-based case-control study.

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.

LDL cholesterol is not a good marker of cardiovascular risk in Type 1 diabetes.

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.

Glycaemic control of Type 1 diabetes in clinical practice early in the 21st century: an international comparison.

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.

The association between BMI and hospitalization for heart failure in 83,021 persons with Type 2 diabetes: a population-based study from the Swedish National Diabetes Registry.

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.

The relationship between glycaemic control and heart failure in 83,021 patients with type 2 diabetes.

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.

Glucose-lowering treatment and clinical results in 163 121 patients with type 2 diabetes: an observational study from the Swedish national diabetes register.

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.

New aspects of HbA1c as a risk factor for cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register (NDR).

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.

Holocene thinning of the Greenland ice sheet.

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.

Case report: exacerbation of hemolytic anemia requiring multiple incompatible RBC transfusions.

RBC transfusions in a patient with a history of autoimmune hemolytic anemia (AIHA) can represent both a laboratory and a clinical challenge. The development of high-titer low-avidity antibodies and antibodies to high-frequency antigens may further impair the ability to identify compatible donor RBCs. Not infrequently, incompatible RBCs must be used and the desire to increase oxygen carrying capacity conflicts with the desire to avoid exacerbating the autoimmune hemolytic process with RBC transfusions. A 66-year-old Caucasian female with coronary artery disease and a history of refractory AIHA had recently developed anemia and required multiple RBC transfusions. The patient had maintained adequate RBC counts with erythropoietin and prednisone therapy for the previous 16 months. With the recent worsening of her hemolytic anemia, she had developed angina that was treated with RBC transfusions in an outpatient setting. However, her angina increased as her RBC counts decreased, leading to hospital admission for further management of her hemolytic anemia and angina. She subsequently required multiple incompatible RBC transfusions despite increased prednisone therapy and did not improve until after coronary artery stent placement and high dose IVIG therapy. This case demonstrates the usefulness of early patient phenotyping in a case of accelerating hemolytic anemia to aid in donor RBC selection, the value of communicating with clinicians and the patient regarding the use of least-incompatible RBCs, and the importance of optimizing the patient's clinical condition to avoid ischemia. In addition, it demonstrates the value of repeated attempts with IVIG treatment despite previous refractoriness to this treatment.

Pancreatic islet blood flow during pregnancy in the rat: an increased islet mass is associated with decreased islet blood flow.

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.

Clinical implications of early ST-segment variability. A report from the ASSENT 2 ST-monitoring sub-study.

OBJECTIVES: Evolution of the ST-segment during acute myocardial infarction has been shown to yield more information on prognosis than invasive measurements. By continuous ST-monitoring even very occasional dynamic changes can be analysed. We have recently suggested these variations to be of prognostic importance and possibly reflect individual abilities to deal with a vascular event. We wanted to confirm these findings. METHODS: Four hundred and forty-eight patients were included in the vectorcardiographic sub-study of the second Assessment of Safety and Efficacy of a New Thrombolytic (ASSENT 2) trial. Patients underwent 24 h of ST-monitoring. ST-trend curves were blindly analysed by two independent observers. RESULTS: ST-variability, defined as an increase of the ST-segment shift of > or = 25 microV for 2 min or more, was found to predict death, reinfarction at 30 days or urgent revascularization. By combining variability with resolution of the ST-segment elevation we could identify a high-risk group with 9.9%, and a low-risk group with only 0.8% 30-day mortality. Hypertensive patients, suggested to have an impaired secretion of endogenous t-PA, expressed significantly more ST-variability, possibly a non-invasive marker of impaired capability of dissolving and preventing thrombi. CONCLUSION: Small variations in ST-segment shift during the first 4 h of acute myocardial infarction predict worse outcome.

Age-induced changes in pancreatic islet blood flow: evidence for an impaired regulation in diabetic GK rats.

The present study aimed to compare longitudinal variations in islet blood perfusion in rats with different degrees of impairment of glucose metabolism. For this purpose, mildly diabetic Goto-Kakizaki (GK) rats, glucose intolerant F(1) hybrids of GK and Wistar (W) rats (H), and control W rats were examined at 5 wk, 12 wk, or 1 yr of age, using the microsphere technique for blood flow measurements. W rats showed progressively increasing islet blood flow (IBF) throughout the experiment. Both GK and H rats demonstrated increasing IBF between 5 and 12 wk. However, H rats showed no further increment in IBF at 1 yr, whereas GK rats displayed a pronounced decrease in IBF between 12 wk and 1 yr of age. The augmented IBF seen in older W rats may constitute an adaptation to the increasing demand for insulin secretion in aging rats. The inability to adapt to the increased demand for insulin secretion by upregulation of islet blood flow could contribute to the progressive deterioration of glucose metabolism seen in the aging GK rat.

Prolactin regulation of islet-derived INS-1 cells: characteristics and immunocytochemical analysis of STAT5 translocation.

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.