Practices in prescribing protein substitutes for PKU in Europe: No uniformity of approach.

BACKGROUND: There appears little consensus concerning protein requirements in phenylketonuria (PKU). METHODS: A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics. RESULTS: The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n=24 centres) (infants <1 year, >2-3g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5 g/kg/day) and Southern Europe (n=10 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, 2 g/kg/day; 4-10 years of age, 1.5-2 g/kg/day), than by Eastern Europe (n=4 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, >2-2.5 g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n=25 centres) giving the least (infants <1 year, >2-2.5 g/kg/day, 1-3 years of age, 1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1-1.5 g/kg/day). CONCLUSIONS: The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population.

Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Study.

AIMS/HYPOTHESIS: This post hoc analysis from the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 trial reports on extended long-term outcome in relation to glucose-lowering agents in patients with myocardial infarction and type 2 diabetes. METHODS: Patients were randomised as follows: group 1, insulin-based treatment; group 2, insulin during hospitalisation followed by conventional glucose control; and group 3, conventional treatment. Treatment according to the above protocol lasted 2.1 years. Using the total DIGAMI 2 cohort as an epidemiological database, this study presents mortality rates in the randomised groups, and mortality and morbidity rates by glucose-lowering treatment during an extended period of follow-up (median 4.1 and max 8.1 years). RESULTS: Follow-up data were available in 1,145 of the 1,253 patients. The mortality rate was 31% (72% cardiovascular) without significant differences between treatment groups. The total number of fatal malignancies was 37, with a trend towards a higher risk in group 1. The HR for death from malignant disease, compared with group 2, was 1.77 (95% CI 0.87-3.61; p = 0.11) and 3.60 (95% CI 1.24-10.50; p = 0.02) compared with group 3. Insulin treatment was associated with non-fatal cardiovascular events (OR 1.89 95% CI 1.35-2.63; p = 0.0002), but not with mortality (OR 1.30, 95% CI 0.93-1.81; p = 0.13). Metformin was associated with a lower mortality rate (HR 0.65, 95% CI 0.47-0.90; p = 0.01) and a lower risk of death from malignancies (HR 0.25, 95% CI 0.08-0.83; p = 0.02). CONCLUSIONS/INTERPRETATION: Patients with type 2 diabetes and myocardial infarction have a poor prognosis. Glucose-lowering drugs appear to be of prognostic importance. Insulin may be associated with an increased risk of non-fatal cardiac events, while metformin seems to be protective against risk of death.

Effect of gender on prognosis in patients with myocardial infarction and type 2 diabetes.

BACKGROUND: Diabetes is associated with a markedly increased cardiovascular risk, but the role of gender on the combined effects of diabetes and myocardial infarction has been less well explored. METHODS: The Diabetes Mellitus and Insulin Glucose Infusion in Acute Myocardial Infarction 2 (DIGAMI2) trial recruited 837 men and 416 women with type 2 diabetes hospitalized due to myocardial infarction and followed for a median of 2.1 years. The effects of gender on diabetes-specific risk factors and conventional cardiovascular risk predictors of unfavourable outcome were analysed using a Cox proportional hazards model. RESULTS: Women were older, more frequently had hypertension and previous heart failure than men, and were more often treated with diuretics. More men were smokers. Treatment during hospitalization, at discharge and during follow-up, did not differ significantly, apart from the more frequent use of diuretics in women. Total mortality did not differ between genders, but the combined cardiovascular end-point of death, re-infarction or stroke was more common in women (38.9% vs. 32.1%). This difference disappeared after age adjustment. Age and previous heart failure were independent risk predictors in both genders, whereas diabetes complications were an additional risk factor in women only. Blood glucose level at randomization and updated glucose concentration during follow-up were independent predictors of poor outcome in men but not in women. CONCLUSIONS: Age and not gender itself explained the increased cardiovascular event rate seen in women compared with men. A heavier risk factor burden was seen amongst women. Improved risk factor control instituted before the development of a myocardial infarction should be attempted as a possible means of improving the outcome.

Identification of a novel KIR3DL1*072 allele by sequence-based typing.

We report a novel KIR3DL1*072 allele that was found using a sequence-based typing approach.

High sense of coherence in adolescence is a protective factor in the longitudinal development of ADHD symptoms.

UNLABELLED: The key feature of salutogenesis is that good health can be directly sustained by positive factors. The Sense of Coherence (SOC) scale was developed by Antonovsky as a measure related to the concept of salutogenesis including aspects of comprehensibility, manageability and meaningfulness. AIM: The aim was to investigate whether Sense of Coherence can serve as a salutogenetic factor modifying the long-term development of Attention Deficit Hyperactivity Disorder (ADHD) Symptoms. SUBJECTS AND METHODS: Twin study of Child and Adolescent Development (TCHAD) is a longitudinal study of all twin pairs born in Sweden between May 1985 and December 1986. The present project is a sub-sample of 312 individuals (135 boys and 177 girls). At 16 years of age, the young persons and their parents were interviewed with K-SADS especially symptoms of ADHD. The young person also completed the SOC questionnaire. At 21 years of age, the young person completed a questionnaire about symptoms of ADHD. FINDINGS: Higher (worse) ADHD scores at 16 years of age were associated with higher (worse) ADHD scores at 21 years of age. However, this relationship was stronger for lower (worse) SOC. A higher (better) SOC at 16 years was associated with lower (better) ADHD at 21 years and this relationship was stronger for higher (worse) ADHD at 16 years. CONCLUSION: A high Sense of Coherence in adolescence was a protective factor for the long-term development of ADHD.

Risk factors associated with the dramatic increase in the prevalence of diabetes in the adult Chinese population in Qingdao, China.

OBJECTIVE: To investigate the major risk factors and their association with the dramatic increase in the prevalence of diabetes from 2001-2002 to 2006 in Qingdao, China. METHODS: Population-based cross-sectional studies on diabetes were performed in 4598 men and 7026 women aged 35-74 years. The 2006 World Health Organization diagnostic criteria for diabetes were used. RESULTS: The crude prevalence of diabetes was 11.3% in both men and women in urban areas and 5.3% and 8.9% in rural areas in 2001-2002. This increased to 19.2% and 16.1% in urban areas and 14.2% and 13.8% in rural areas in 2006 for men and women, respectively. The increase in diabetes prevalence from 2001-2002 to 2006 was paralleled by an increased body mass index in rural areas but not in urban areas. The major risk factors associated with diabetes were age, family history of diabetes, obesity, hypertension and high triglycerides. The multivariate adjusted odds ratio and 95% confidence interval for diabetes corresponding to a one standard deviation increase in waist circumference was 1.81 (1.47, 2.23) in urban men, 1.64 (1.26, 2.13) in rural men, 1.98 (1.66, 2.37) in urban women and 2.02 (1.63, 2.51) in rural women. Low socio-economic classes had a higher risk for diabetes in urban areas but a lower risk in rural areas, both associated with increased waist circumference. CONCLUSION: Established risk factors are of great importance for the prevalence of diabetes in the urban and rural Chinese populations and changes in these factors could explain the recent dramatic increase in diabetes prevalence, particularly in rural areas. Considering the high prevalence of obesity and physical inactivity, intervention is urgently required in China.

Insulin-induced weight gain and cardiovascular events in patients with type 2 diabetes. A report from the DIGAMI 2 study.

AIM: We investigated whether insulin treatment-induced weight gain was accompanied by increased cardiovascular (CV) mortality and morbidity in the second Diabetes Insulin Glucose in Acute Myocardial Infarction (DIGAMI 2) study. METHODS: We studied the 865 patients who survived during 12 months without any change in their glucose-lowering (GL) therapy. They were divided into four subgroups according to GL treatment: group I, no pharmacological GL treatment (n = 99); group II, oral hypoglycaemic agents (n = 250); group III, new insulin treatment (n = 245) and group IV, insulin before inclusion continued during the first year of follow up (n = 271). RESULTS: Patients who started on insulin (group III) experienced an average body weight increase of 2.3 (1.5-3.2) kg during the first year of treatment, whereas weight remained unchanged in groups I, II and IV. The incidence of non-fatal reinfarction was higher in group III compared with the other groups (hazard ratio (HR) = 2.5, p = 0.011) and CV mortality was higher in group IV (HR = 2.4, p = 0.003). When the subjects were grouped in quartiles according to maximal body weight increase, those in the lowest quartile experienced the highest CV mortality. Each kilogram increase in weight reduced the risk for CV death with 6%. The incidence of reinfarction did not differ between quartiles. CONCLUSIONS: Initiation of insulin treatment after myocardial infarction was associated with a significant increase in weight and incidence of reinfarction. The increase in weight did, however, not explain the increased rate of reinfarction.

Innovative therapy, monoclonal antibodies, and beyond: Highlights from the eighth annual meeting.

The eighth annual conference of "Innovative therapy, monoclonal antibodies, and beyond" was held in Milan on Jan. 26, 2018, and hosted by Fondazione IRCCS-Istituto Nazionale dei Tumori (Fondazione IRCCS INT). The conference was divided into two main scientific sessions, of i) pre-clinical assays and novel biotargets, and ii) clinical translation, as well as a third session of presentations from young investigators, which focused on recent achievements within Fondazione IRCCS INT on immunotherapy and targeted therapies. Presentations in the first session addressed the issue of cancer immunotherapy activity with respect to tumor heterogeneity, with key topics addressing: 1) tumor heterogeneity and targeted therapy, with the definition of the evolutionary Index as an indicator of tumor heterogeneity in both space and time; 2) the analysis of cancer evolution, with the introduction of the TRACERx Consortium-a multi-million pound UK research project focused on non-small cell lung cancer (NSCLC); 3) the use of anti-estrogen agents to boost immune recognition of breast cancer cells; and 4) the high degree of functional plasticity within the NK cell repertoire, including the expansion of adaptive NK cells following viral challenges. The second session addressed: 1) the effectiveness of radiotherapy to enhance the proportion of patients responsive to immune-checkpoint blockers (ICBs); 2) the use of MDSC scores in selecting melanoma patients with high probability to be responsive to ICBs; and 3) the relevance of the gut microbiome as a predictive factor, and the potential of its perturbation in increasing the immune response rate to ICBs. Overall, a picture emerged of tumor heterogeneity as the main limitation that impairs the effectiveness of anti-cancer therapies. Thus, the choice of a specific therapy based on reproducible and selective predictive biomarkers is an urgent unmet clinical need that should be addressed in order to increase the proportion of long-term responding patients and to improve the sustainability of novel drugs.

Increasing glucose levels and BMI predict future heart failure experience from the Reykjavík Study.

BACKGROUND: Heart failure is common in diabetes and ischaemic heart disease is the most likely link. Still, it has been suggested that the relation extends beyond such disease. METHODS: 7060 subjects with two or more visits in the Reykjavík Study were followed--during 30 years from 1967. All underwent oral glucose tolerance tests. Disease status was defined according to the glycaemic level and presence of heart failure. The incidence and predictive factors for these diseases were determined. FINDINGS: Age and sex standardized incidence of heart failure was 5.3/1000/year, of diabetes 4.6/1000/year and abnormal glucose regulation 12.6/1000/year. Body mass index (BMI) and fasting glucose predicted the development of these conditions (p<0.001). Increasing fasting glucose by 1 mmol/l increased the risk for heart failure by 14% (p=0.04) after adjusting for IHD, BMI and other risk factors for CVD. There was a strong association between diabetes and heart failure, OR 3.0 (2.3-4.0), and abnormal glucose regulation and heart failure, OR 1.8 (1.5-2.3). Diabetes and heart failure were, however, not independent predictors of each other. INTERPRETATION: There was an independent relationship between increases in fasting glucose and development of heart failure. BMI was a strong predictor of heart failure. Although fasting glucose and BMI were significant risk factors for glucose disturbances and heart failure the conditions themselves did not independently predict each other.

Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study.

BACKGROUND: The Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study addressed prognostic factors and the effects of concomitant treatment and glycometabolic control in diabetic patients with myocardial infarction (AMI). METHODS AND RESULTS: Of 620 diabetic patients with AMI, 306 were randomly assigned to a >/=24-hour insulin-glucose infusion followed by multidose subcutaneous insulin. Three hundred fourteen patients were randomized as controls, receiving routine antidiabetic therapy. Thrombolysis and beta-blockers were administered when possible. Univariate and multivariate statistical analyses were applied to study predictors of long-term mortality. During an average follow-up of 3.4 years (range, 1.6 to 5.6 years), 102 patients (33%) in the intensive insulin group and 138 (44%) in the control group died (P=0. 011). Old age, previous heart failure, diabetes duration, admission blood glucose, and admission Hb AIc were independent predictors of mortality in the total cohort, whereas previous AMI, hypertension, smoking, or female sex did not add independent predictive value. Metabolic control, mirrored by blood glucose and Hb AIc, improved significantly more in patients on intensive insulin treatment than in the control group. beta-Blockers improved survival in control subjects, whereas thrombolysis was most efficient in the intensive insulin group. CONCLUSIONS: Mortality in diabetic patients with AMI is predicted by age, previous heart failure, and severity of the glycometabolic state at admission but not by conventional risk factors or sex. Intensive insulin treatment reduced long-term mortality despite high admission blood glucose and Hb AIc.

Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry.

BACKGROUND: Although unstable coronary artery disease is the most common reason for admission to a coronary care unit, the long-term prognosis of patients with this diagnosis is unknown. This is particularly true for patients with diabetes mellitus, who are known to have a high morbidity and mortality after an acute myocardial infarction. METHODS AND RESULTS: Prospectively collected data from 6 different countries in the Organization to Assess Strategies for Ischemic Syndromes (OASIS) registry were analyzed to determine the 2-year prognosis of diabetic and nondiabetic patients who were hospitalized with unstable angina or non-Q-wave myocardial infarction. Overall, 1718 of 8013 registry patients (21%) had diabetes. Diabetic patients had a higher rate of coronary bypass surgery than nondiabetic patients (23% versus 20%, P:<0.001) but had similar rates of catheterization and angioplasty. Diabetes independently predicted mortality (relative risk [RR], 1.57; 95% CI, 1.38 to 1.81; P:<0.001), as well as cardiovascular death, new myocardial infarction, stroke, and new congestive heart failure. Moreover, compared with their nondiabetic counterparts, women had a significantly higher risk than men (RR, 1.98; 95% CI, 1.60 to 2.44; and RR, 1.28; 95% CI, 1.06 to 1.56, respectively). Interestingly, diabetic patients without prior cardiovascular disease had the same event rates for all outcomes as nondiabetic patients with previous vascular disease. CONCLUSIONS: Hospitalization for unstable angina or non-Q-wave myocardial infarction predicts a high 2-year morbidity and mortality; this is especially evident for patients with diabetes. Diabetic patients with no previous cardiovascular disease have the same long-term morbidity and mortality as nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease.

Clinical and biochemical factors associated with prognosis after myocardial infarction at a young age.

OBJECTIVES: This study examined the effect of metabolic disturbances, hemostatic function, coronary artery disease severity and left ventricular function on the long-term prognosis after myocardial infarction in men < 45 years old. BACKGROUND: Heavy smoking; dyslipoproteinemias involving very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL); a family history of premature coronary artery disease; hyperinsulinemic responses to oral and intravenous glucose challenges; and defective fibrinolytic function characterize the young postinfarction patient, but the influence of these features on the long-term prognosis is virtually unknown. METHODS: Measurements of hemostatic function and metabolic and angiographic indicators of risk were included in a prospective cohort study of variables predictive of reinfarction, cardiac death and major coronary events within 6 to 9 years in 108 unselected nondiabetic men with a first myocardial infarction before age 45 years. RESULTS: During follow-up, 20 patients had sudden cardiac death, and 53 had a major coronary event (reinfarction, sudden cardiac death, bypass surgery or intervention by catheterization). In multivariate analysis, VLDL and global coronary atherosclerosis score predicted reinfarction; plasma plasminogen activator inhibitor-1 (PAI-1) activity and global coronary stenosis score predicted cardiac death; and VLDL triglyceride levels, global coronary atherosclerosis score and age predicted any major coronary event. CONCLUSIONS: This prospective cohort study shows that hypertriglyceridemia, impaired fibrinolytic capacity secondary to plasma PAI-1 activity elevation and extensive coronary artery disease increase the risk of recurrences in men with a first myocardial infarction before age 45 and contribute to the relatively poor long-term prognosis in this patient group.

Dynamic on-line vectorcardiography improves and simplifies in-hospital ischemia monitoring of patients with unstable angina.

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.

Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year.

OBJECTIVES: We tested how insulin-glucose infusion followed by multidose insulin treatment in diabetic patients with acute myocardial infarction affected mortality during the subsequent 12 months of follow-up. BACKGROUND: Despite significant improvements in acute coronary care, diabetic patients with acute myocardial infarction still have a high mortality rate. METHODS: A total of 620 patients were studied: 306 randomized to treatment with insulin-glucose infusion followed by multidose subcutaneous insulin for > or = 3 months and 314 to conventional therapy. RESULTS: The two groups were well matched for baseline characteristics. Blood glucose decreased from 15.4 +/- 4.1 to 9.6 +/- 3.3 mmol/liter (mean +/- SD) in the infusion group during the 1st 24 h, and from 15.7 +/- 4.2 to 11.7 +/- 4.1 among control patients (p < 0.0001). After 1 year 57 subjects (18.6%) in the infusion group and 82 (26.1%) in the control group had died (relative mortality reduction 29%, p = 0.027). The mortality reduction was particularly evident in patients who had a low cardiovascular risk profile and no previous insulin treatment (3-month mortality rate 6.5% in the infusion group vs. 13.5% in the control group [relative reduction 52%, p = 0.046]; 1-year mortality rate 8.6% in the infusion group vs. 18.0% in the control group [relative reduction 52%, p = 0.020]). CONCLUSIONS: Insulin-glucose infusion followed by a multidose insulin regimen improved long-term prognosis in diabetic patients with acute myocardial infarction.

How to improve the cardiac prognosis for diabetes.

Cardiovascular disease is a leading cause of death in diabetic patients. It has been reported to count for almost 80% of all deaths. About three-fourths of these deaths result from coronary artery disease. Studies have shown that diabetic patients who have had an acute myocardial infarction (AMI) have a mortality of about twice that of nondiabetic patients. Various medications have been shown to improve the prognosis among diabetic patients suffering from ischemic heart disease. They include beta-blockers, thrombolytic agents, aspirin, ACE inhibitors, and lipid-lowering drugs. Experiences indicate that treatment with beta-blockers, thrombolytic agents, and ACE inhibitors is particularly advantageous in diabetic patients who have suffered AMI. Metabolic control also may be of major importance during the acute cardiac event because it is assumed that fatty acid metabolism is increased with a compromised glycolysis not only in ischemic but also in the nonischemic areas. One way to suppress free fatty acid oxidation is by the infusion of insulin-glucose. In the Swedish Diabetes Mellitus and Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI) Study, patients with diabetes and AMI were randomized to receive insulin-glucose infusion followed by intensive subcutaneous insulin treatment or to be control subjects. The 1-year mortality was reduced 30% by insulin treatment. Diabetic patients who suffer from coronary artery disease have a particularly adverse prognosis. Previous experiences indicate that treatment with beta-blockers, thrombolytic agents, and ACE inhibitors is particularly advantageous in diabetic patients who have suffered AMI. Aspirin and lipid-lowering drugs should be offered to these patients on traditional indications as well. Metabolic control seems to be of major importance for the outcome.

Feasibility of insulin-glucose infusion in diabetic patients with acute myocardial infarction. A report from the multicenter trial: DIGAMI.

OBJECTIVE: To investigate the effect of insulin-glucose infusion on metabolic control and hypoglycemic episodes and its feasibility and safety in patients with diabetes and myocardial infarction (MI) compared with conventional treatment. RESEARCH DESIGN AND METHODS: Of 327 patients with suspected acute MI 158 were randomized to insulin-glucose infusion for at least 24 h and 169 received conventional therapy. We determined the 24-h blood glucose profile in the infusion group, the degree of metabolic control, hypoglycemic events, and in-hospital complications within the two study groups. RESULTS: Blood glucose fell from 14.6 +/- 2.9 to 9.2 +/- 2.9 mM during the first 24 h in patients receiving insulin-glucose and from 15.8 +/- 4.3 to 12.0 +/- 4.4 mM in control patients (P < 0.01). Serum potassium decreased 0.21 +/- 0.56 mM in the infusion group (P < 0.001) and 0.11 +/- 0.59 mM in the control group (P < 0.05). The difference between the groups was not significant. Twenty-eight of the 158 patients developed an episode of hypoglycemia (blood glucose < 3.0 mM) during the insulin-glucose infusion. There were no significant differences in the number of episodes of ventricular tachyarrhythmias or in ischemic events between patients with and without hypoglycemia. CONCLUSIONS: The protocol outlined in this study gives more rapid and better metabolic control than does conventional treatment. This treatment seems to be a feasible alternative for clinical attempts. Before it can be recommended for general use, the impact on mortality needs to be evaluated.

Admission plasma glucose. Independent risk factor for long-term prognosis after myocardial infarction even in nondiabetic patients.

OBJECTIVE: To investigate whether a relationship exists between admission plasma glucose level and long-term outcome in nondiabetic patients after an acute myocardial infarction. RESEARCH DESIGN AND METHODS: This was a retrospective study with prospective follow-up of 197 consecutive nondiabetic patients with acute myocardial infarction followed for 1.5-2.5 years at the Department of Cardiology at Karolinska Hospital. RESULTS: The mean admission plasma glucose level was 8.15 +/- 3.0 mmol/l. During follow-up, 60 (30%) patients died, 20 (10%) were rehospitalized for heart failure, 12 (6%) were rehospitalized for nonfatal reinfarction, and 79 (40%) had at least one of these events. In univariate analysis, admission plasma glucose level was significantly higher in patients who had any of the predefined events than in those without these events. In a multivariate Cox proportional hazard regression model that allowed for confounding baseline predictors, admission plasma glucose level was an independent predictor of nonfatal reinfarction (P = 0.006), hospitalization for heart failure (P = 0.0034), and a major cardiovascular event (P = 0.0042) and was of borderline significance for death during long-term follow-up (P = 0.09). CONCLUSIONS: Admission plasma glucose level in nondiabetic patients with acute myocardial infarction seems to be an independent predictor of long-term outcome. This indicates that an elevated admission plasma glucose level not only reflects acute stress, but also may be a marker of disturbed glucose metabolism that worsens the prognosis and requires intervention.

Mortality prediction in diabetic patients with myocardial infarction: experiences from the DIGAMI study.

OBJECTIVES: We analysed predictors of 1-year mortality following acute myocardial infarction in patients with diabetes mellitus by applying uni- and multivariate statistics on the DIGAMI cohort. BACKGROUND: Diabetic patients with acute myocardial infarction have a poor prognosis. This may depend on a poor metabolic control, a hypothesis that was tested in DIGAMI, a prospective randomised study. In this trial institution of immediate intensive insulin treatment reduced 1-year mortality by 30%. METHODS: We recruited 620 diabetic patients with acute myocardial infarction, 314 of whom served as controls, while the remaining 306 patients were treated with an acute insulin-glucose infusion followed by multidose subcutaneous insulin. RESULTS: Age, previous myocardial damage, duration of the diabetes and previous insulin therapy were significantly related to 1-year mortality, while conventional risk factors lacked independent prognostic weight. Female sex was not linked to mortality when controlling for the confounding effects of other predictors. One of the strongest predictors of a fatal outcome, in particular during the hospital phase, was blood glucose at hospital admission. Beta-blockade appeared to exert a striking, independent secondary-preventive effect. CONCLUSIONS: It seems that good metabolic control and not conventional risk factors is of major importance for diabetic patients sustaining acute myocardial infarction. Also treatment with beta-blockade seems to be of special importance in this category of patients.

Increased incidence of chronic GvHD and CMV disease in patients with vitamin D deficiency before allogeneic stem cell transplantation.

Vitamin D has emerged as a central player in the immune system, with its deficiency being implicated in the pathogenesis of several autoimmune diseases, including chronic GvHD. This is a retrospective cohort analysis of 166 patients, who underwent allogeneic hematopoietic stem cell transplantation (HSCT) at the Karolinska University Hospital, evaluating GvHD, graft failure, infectious complications and survival after HSCT in relation to pre-transplantation vitamin D levels. Most of the patients were deficient in vitamin D before HSCT (median 42 nmol/L). In multivariate analysis, vitamin D level before HSCT was identified as a significant independent risk factor for development of cGvHD. The increased incidence of cGvHD was not coupled to better disease-free survival; instead there was a trend towards lower overall survival in the vitamin D-deficient patients. In addition, we found a significant correlation between vitamin D deficiency and incidence of CMV disease, with no case of CMV disease occurring in patients with sufficient levels of vitamin D before HSCT. Our results support a role of vitamin D in immune tolerance following HSCT. These findings could be highly relevant for the care of HSCT patients, and prospective, randomized studies on the effect of vitamin D supplementation are therefore needed.

Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview.

BACKGROUND AND PURPOSE: "Stress" hyperglycemia may be associated with increased mortality and poor recovery in diabetic and nondiabetic patients after stroke. A systematic review and meta-analysis of the literature relating acute poststroke glucose levels to the subsequent course were done to summarize and quantify this relationship. METHODS: A comprehensive literature search was done for cohort studies reporting mortality and/or functional recovery after stroke in relation to admission glucose level. Relative risks in hyperglycemic compared with normoglycemic patients with and without diabetes were calculated and meta-analyzed when possible. RESULTS: Thirty-two studies were identified; relative risks for prespecified outcomes were reported or could be calculated in 26 studies. After stroke of either subtype (ischemic or hemorrhagic), the unadjusted relative risk of in-hospital or 30-day mortality associated with admission glucose level >6 to 8 mmol/L (108 to 144 mg/dL) was 3.07 (95% CI, 2.50 to 3.79) in nondiabetic patients and 1.30 (95% CI, 0.49 to 3.43) in diabetic patients. After ischemic stroke, admission glucose level >6.1 to 7.0 mmol/L (110 to 126 mg/dL) was associated with increased risk of in-hospital or 30-day mortality in nondiabetic patients only (relative risk=3.28; 95% CI, 2.32 to 4.64). After hemorrhagic stroke, admission hyperglycemia was not associated with higher mortality in either diabetic or nondiabetic patients. Nondiabetic stroke survivors whose admission glucose level was >6.7 to 8 mmol/L (121 to 144 mg/dL) also had a greater risk of poor functional recovery (relative risk=1.41; 95% CI, 1.16 to 1.73). CONCLUSIONS: Acute hyperglycemia predicts increased risk of in-hospital mortality after ischemic stroke in nondiabetic patients and increased risk of poor functional recovery in nondiabetic stroke survivors.