Coagulation factor XII (FXII) is involved in pathological thrombus formation and is a suggested target of anticoagulants. It is unclear whether FXII levels are correlated with cardiovascular risk ...factors and whether they are associated with myocardial infarction or ischemic or hemorrhagic stroke. The aim of this study was to investigate the correlation between FXII and cardiovascular risk factors in the general population. We also aimed to study the associations between FXII levels and future myocardial infarction and ischemic and hemorrhagic stroke.
This prospective cohort study measured FXII levels in 1,852 randomly selected participants in a health survey performed in northern Sweden in 1994. Participants were followed until myocardial infarction, stroke, death, or until December 31, 2011.
During the median follow-up of 17.9 years, 165 individuals were diagnosed with myocardial infarction, 108 with ischemic stroke, and 30 with hemorrhagic stroke. There were weak correlations between FXII and body mass index, cholesterol, and hypertension. There was no association between FXII and myocardial infarction or ischemic stroke, neither in univariable Cox regression analysis nor after adjustment for age, sex, smoking, body mass index, cholesterol, hypertension, and diabetes. In univariable Cox regression analysis, the hazard ratio for the association between FXII levels and hemorrhagic stroke was 1.42 per SD (95% confidence interval: 0.99-2.05). In the multivariable model, higher levels of FXII were associated with increased risk of hemorrhagic stroke (hazard ratio 1.51 per SD; 95% confidence interval: 1.03-2.21).
We found an independent association between FXII levels and the risk of hemorrhagic stroke, but not between FXII levels and ischemic stroke or myocardial infarction.
Background Elevated blood glucose is associated with higher mortality in patients with acute myocardial infarction (AMI). Although clinical guidelines recommend targeted glucose control in this ...group, clinical trials have yielded inconclusive results. Our objective was to understand how this lack of evidence impacts the management of severe hyperglycemia in routine practice. Methods We examined insulin use among 4,297 AMI admissions with a mean hospitalization blood glucose of ≥200 mg/dL across 55 US hospitals from 2000 to 2008. Temporal trends and interhospital variation in 2 measures of insulin use during hospitalization—any (subcutaneous, intravenous IV, short acting, long acting) and IV insulin—were examined using hierarchical Poisson regression models. Results Of the 4,297 admissions, 2,618 (61%) received any insulin and 538 (13%) received IV insulin. After multivariable adjustment, a slight increase in insulin use was observed per admission year (relative risk RR 1.06, 95% CI 1.01-1.11). There was a modest (albeit nonsignificant) increase in IV insulin use seen before May 2004 (RR 1.18, 95% CI 0.96-1.47), with no significant change thereafter (RR 0.99, 95% CI 0.92-1.09). Marked variability in insulin use was observed across hospitals (median rate ratio 1.5 any insulin and 1.8 IV insulin), which did not change over time. Conclusions Insulin use among patients with AMI and severe hyperglycemia has remained low over the past decade, with substantial and persistent interhospital variation. These observations reflect marked clinical uncertainty with regard to glucose management in AMI, underscoring the imperative for a definitive clinical trial in this field.
IMPORTANCE: The majority of individuals with type 1 diabetes do not meet recommended glycemic targets. OBJECTIVE: To evaluate the effects of continuous glucose monitoring in adults with type 1 ...diabetes treated with multiple daily insulin injections. DESIGN, SETTING, AND PARTICIPANTS: Open-label crossover randomized clinical trial conducted in 15 diabetes outpatient clinics in Sweden between February 24, 2014, and June 1, 2016 that included 161 individuals with type 1 diabetes and hemoglobin A1c (HbA1c) of at least 7.5% (58 mmol/mol) treated with multiple daily insulin injections. INTERVENTIONS: Participants were randomized to receive treatment using a continuous glucose monitoring system or conventional treatment for 26 weeks, separated by a washout period of 17 weeks. MAIN OUTCOMES AND MEASURES: Difference in HbA1c between weeks 26 and 69 for the 2 treatments. Adverse events including severe hypoglycemia were also studied. RESULTS: Among 161 randomized participants, mean age was 43.7 years, 45.3% were women, and mean HbA1c was 8.6% (70 mmol/mol). A total of 142 participants had follow-up data in both treatment periods. Mean HbA1c was 7.92% (63 mmol/mol) during continuous glucose monitoring use and 8.35% (68 mmol/mol) during conventional treatment (mean difference, −0.43% 95% CI, −0.57% to −0.29% or −4.7 −6.3 to −3.1 mmol/mol; P < .001). Of 19 secondary end points comprising psychosocial and various glycemic measures, 6 met the hierarchical testing criteria of statistical significance, favoring continuous glucose monitoring compared with conventional treatment. Five patients in the conventional treatment group and 1 patient in the continuous glucose monitoring group had severe hypoglycemia. During washout when patients used conventional therapy, 7 patients had severe hypoglycemia. CONCLUSIONS AND RELEVANCE: Among patients with inadequately controlled type 1 diabetes treated with multiple daily insulin injections, the use of continuous glucose monitoring compared with conventional treatment for 26 weeks resulted in lower HbA1c. Further research is needed to assess clinical outcomes and longer-term adverse effects. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02092051
This Swedish National Diabetes Register study showed that mortality varies greatly among patients with type 2 diabetes, as compared with the general population. There is excess risk in large patient ...groups, yet lower risks of death depending on age, glycemic control, and renal complications.
The global burden of diabetes has risen dramatically over the past two decades and is expected to affect more than 500 million adults by 2030, with most having type 2 diabetes.
1
Myocardial infarction is the most common cause of death in these patients.
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,
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Although factors that are known to reduce the risk of myocardial infarction,
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,
4
,
5
including the use of lipid-lowering and antihypertensive medications and better glycemic control over time,
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have been noted in persons with type 2 diabetes, an excess risk of death still exists.
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Population-based studies have generally not evaluated the excess risks of death . . .
Abstract
Background
The relationship between alcohol intake and risk of venous thromboembolism (VTE) is unclear. Men and women differ in their drinking habits, which may affect a possible ...association.
Objective
This article investigates the association between alcohol consumption, alcohol dependence and VTE in the total population as well as in men and women separately.
Methods
We performed a prospective, population-based cohort study in northern Sweden. Study participants were 108,025 (51% women) persons aged 30 to 60 years who underwent a health examination between 1985 and 2014. We assessed alcohol consumption and defined alcohol dependence using a questionnaire. The outcome was a validated first-time VTE.
Results
The mean follow-up time was 13.9 years, and 2,054 participants had a first-time VTE. The mean alcohol consumption was 3.5 standard drinks weekly in men and 1.5 in women. Alcohol dependence was found in 10% of men and 3% of women. There was an association between alcohol consumption (hazard ratio HR, 1.02; 95% confidence interval CI, 1.00–1.03 per standard drink weekly) as well as alcohol dependence (HR, 1.27; 95% CI, 1.06–1.52) and VTE after adjustments. In men, the risk of VTE increased over quartiles of weekly alcohol consumption (
p
for trend 0.02), with a HR of 1.22 (95% CI, 1.01–1.47) for the highest quartile. Alcohol dependence was associated with VTE in men (HR, 1.30; 95% CI, 1.07–1.59). In women, there were no significant associations.
Conclusion
High alcohol consumption and alcohol dependence were associated with increased risk of first-time VTE in men, but not in women.
In this study, patients with type 1 diabetes and a glycated hemoglobin level of 6.9% or lower (≤52 mmol per mole) were found to have a risk of death from any cause or from cardiovascular causes that ...was twice as high as that for matched controls.
Type 1 diabetes is associated with a substantially increased risk of premature death as compared with that in the general population.
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Among persons with diabetes who are younger than 30 years of age, excess mortality is largely explained by acute complications of diabetes, including diabetic ketoacidosis and hypoglycemia
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; cardiovascular disease is the main cause of death later in life.
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Improving glycemic control in patients with type 1 diabetes substantially reduces their risk of microvascular complications and cardiovascular disease.
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Accordingly, diabetes treatment guidelines emphasize good glycemic control,
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which is indicated by the glycated hemoglobin level, . . .
Abstract Glucagon-like peptide 1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors are two classes of treatments for type 2 diabetes, which enhance the well-known ‘incretin effect’ of ...increased insulin secretion in response to food intake. This concise review introduces both types of incretin-based therapies and focuses on the extra-pancreatic effect of GLP-1 on body weight. As well as improving glycaemic control in subjects with type 2 diabetes, these treatments have the additional benefits of improving weight management in these patients, with GLP-1 receptor agonists causing weight loss and DPP-4 inhibitors being weight neutral.
To evaluate if the lowest target level for glycated haemoglobin (HbA
) of <6.5% is associated with lower risk for retinopathy and nephropathy than less tight control in children and adults with type ...1 diabetes.
Population based cohort study.
Swedish National Diabetes Registry, 1 January 1998 to 31 December 2017.
10 398 children and adults with type 1 diabetes followed from diagnosis, or close thereafter, until end of 2017.
Relative risk (odds ratios) for retinopathy and nephropathy for different mean levels of HbA
.
Mean age of participants was 14.7 years (43.4% female), mean duration of diabetes was 1.3 years, and mean HbA
level was 8.0% (63.4 mmol/mol). After adjustment for age, sex, duration of diabetes, blood pressure, blood lipid levels, body mass index, and smoking, the odds ratio for mean HbA
<6.5% (<48 mmol/mol) compared with 6.5-6.9% (48-52 mmol/mol) for any retinopathy (simplex or worse) was 0.77 (95% confidence interval 0.56 to 1.05, P=0.10), for preproliferative diabetic retinopathy or worse was 3.29 (0.99 to 10.96, P=0.05), for proliferative diabetic retinopathy was 2.48 (0.71 to 8.62, P=0.15), for microalbuminuria or worse was 0.98 (0.60 to 1.61, P=0.95), and for macroalbuminuria was 2.47 (0.69 to 8.87, P=0.17). Compared with HbA
levels 6.5-6.9%, HbA
levels 7.0-7.4% (53-57 mmol/mol) were associated with an increased risk of any retinopathy (1.31, 1.05 to 1.64, P=0.02) and microalbuminuria (1.55, 1.03 to 2.32, P=0.03). The risk for proliferative retinopathy (5.98, 2.10 to 17.06, P<0.001) and macroalbuminuria (3.43, 1.14 to 10.26, P=0.03) increased at HbA
levels >8.6% (>70 mmol/mol). The risk for severe hypoglycaemia was increased at mean HbA
<6.5% compared with 6.5-6.9% (relative risk 1.34, 95% confidence interval 1.09 to 1.64, P=0.005).
Risk of retinopathy and nephropathy did not differ at HbA
levels <6.5% but increased for severe hypoglycaemia compared with HbA
levels 6.5-6.9%. The risk for severe complications mainly occurred at HbA
levels >8.6%, but for milder complications was increased at HbA
levels >7.0%.
Objective: Coefficient of variation (CV) and standard deviation (SD) are key metrics of glucose variability (GV) in clinical care and research. We evaluated the adequacy of CV and SD as GV metrics ...over a wide range of mean blood glucose (MBG) levels in people with (T1D).
Methods: Analyses were performed on data from the randomized clinical GOLD and SILVER trials (n=160). Mixed effects models were used to evaluate the SD in relation to MBG during stable therapy, accounting for subject-specific trends and correlations in repeated measures data.
Results: The SD of blood glucose levels did not increase linearly with MBG level during CGM and blood glucose monitoring (BGM) treatments (both p<0.0001). The lack-of-fit of the constant CV model was most distinct at high glucose levels >12 mmol/L (Fig.). During BGM, a 33% reduction in MBG from 12 to 8 mmol/L was associated with a 20% (95% CI 14.9 to 24.9%) reduction in SD. The treatment effect on MBG-adjusted GV measured by CV was underestimated by 27%, compared to an adjusted analysis accounting for a quadratic relation between SD and MBG.
Conclusion: CV is not an optimal GV measure since SD changes less than the MBG during stable glucose-lowering therapy. A quadratic model adjusting SD to MBG is instead suggested when evaluating glucose-lowering therapies in people with T1D.
Fig. - Association between SD and MBG in the GOLD and SILVER trials during stable glucose-monitoring method CGM/SMBG.
Disclosure
P.J.Fatulla: None. H.Imberg: None. I.B.Hirsch: Consultant; Abbott Diabetes, Lifecare, Inc., Hagar, Research Support; Beta Bionics, Inc., Insulet Corporation, Dexcom, Inc. T.Heise: Advisory Panel; Novo Nordisk, Consultant; Gan & Lee Pharmaceuticals, Research Support; Adocia, AstraZeneca, Biocon, Crinetics Pharmaceuticals, Inc., Eli Lilly and Company, Genova, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. M.Lind: Consultant; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Research Support; Eli Lilly and Company.
Aims/hypothesis
The aim of this study was to determine the contemporary rate ratio of mortality and changes over time in individuals with vs without diabetes.
Methods
Annual age- and sex-adjusted ...mortality rates were compared for adults (>20 years) with and without diabetes in Ontario, Canada, and the UK from January 1996 to December 2009 using The Health Improvement Network (THIN) and Ontario databases. The total number of individuals evaluated increased from 8,757,772 in 1996 to 12,696,305 in 2009.
Results
The excess risk of mortality for individuals with diabetes in both cohorts was significantly lower during later vs earlier years of the follow-up period (1996–2009). In Ontario the diabetes mortality rate ratio decreased from 1.90 (95% CI 1.86, 1.94) in 1996 to 1.51 (1.48, 1.54) in 2009, and in THIN from 2.14 (1.97, 2.32) to 1.65 (1.57, 1.72), respectively. In Ontario and THIN, the mortality rate ratios among diabetic patients in 2009 were 1.67 (1.61, 1.72) and 1.81 (1.68, 1.94) for those aged 65–74 years and 1.11 (1.10, 1.13) and 1.19 (1.14, 1.24) for those aged over 74 years, respectively. Corresponding rate ratios in Ontario and THIN were 2.45 (2.36, 2.54) and 2.64 (2.39, 2.89) for individuals aged 45–64 years, and 4.89 (4.35, 5.45) and 5.18 (3.73, 6.69) for those aged 20–44 years.
Conclusions/interpretation
The excess risk of mortality in individuals with vs without diabetes has decreased over time in both Canada and the UK. This may be in part due to earlier detection and higher prevalence of early diabetes, as well as to improvements in diabetes care.
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