| 1. |
- Anderson, J., et al.
(författare)
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Effect on glycemic control by short- and long-term use of continuous glucose monitoring in clinical practice
- 2011
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Ingår i: Journal of diabetes science and technology. - : SAGE Publications. - 1932-2968. ; 5:6, s. 1472-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In Sweden, patients with diabetes mellitus frequently receive short-term (<3 months) continuous glucose monitoring (CGM) to study glucose patterns or long-term CGM to treat poor glycemic control or severe hypoglycemia. The effects of CGM on glycemic control in clinical practice in relation to indication and duration of use has not been completely studied. METHODS: Patients with diabetes, among which 99% were diagnosed as type 1, receiving CGM at 10 outpatient clinics in Sweden were studied retrospectively. Long-term use of CGM was defined as >/= 3 months use of CGM and short-term as <3 months. A control group matched on start date and date of latest value 3 months after the start was selected for both long- and short-term groups. RESULTS: In 34 long-term users of CGM, over a mean follow-up of 1.1 years, the adjusted mean difference of hemoglobin A1c (HbA1c) compared with controls (n = 408) was -0.76 (95% confidence interval -1.17; -0.33, p < .001). Long-term users with indications for high HbA1c (n = 15) had a reduction of 1.2% in HbA1c from 10.1 to 8.9% (p = .003), whereas patients with hypoglycemia as their indication (n = 16) decreased by 0.3% (p = .17). Nonsevere hypoglycemic events decreased in long-term users within the same follow-up period (p = .004). Short-term users showed no statistically significant improvement in HbA1c compared with controls at 1.1 years (n = 41), p = .85 or at 2.6 years (n = 43), p = .19. CONCLUSION: Long-term CGM use was associated with improved glycemic control in clinical practice and a reduction in nonsevere hypoglycemic events, whereas short-term use had no effect on HbA1c. The effect on glycemic control varied by indication.
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| 2. |
- Arnold, S. V., et al.
(författare)
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The reliability of in-hospital diagnoses of diabetes mellitus in the setting of an acute myocardial infarction
- 2014
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Ingår i: BMJ Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Incident diabetes mellitus (DM) is important to recognize in patients with acute myocardial infarction (AMI). To develop an efficient screening strategy, we explored the use of random plasma glucose (RPG) at admission and fasting plasma glucose (FPG) to select patients with AMI for glycosylated hemoglobin (HbA1c) testing. DESIGN SETTING ANDPARTICIPANTS: Prospective registry of 1574 patients with AMI not taking glucose-lowering medication from 24 US hospitals. All patients had HbA1c measured at a core laboratory and admission RPG and >/=2 FPGs recorded during hospitalization. We examined potential combinations of RPG and FPG and compared these with HbA1c>/=6.5%-considered the gold standard for DM diagnosis in these analyses. RESULTS: An RPG>140 mg/dL or FPG>/=126 mg/dL had high sensitivity for DM diagnosis. Combining these into a screening protocol (if admission RPG>140, check HbA1c; or if FPG>/=126 on a subsequent day, check HbA1c) led to HbA1c testing in 50% of patients and identified 86% with incident DM (number needed to screen (NNS)=3.3 to identify 1 case of DM; vs NNS=5.6 with universal HbA1c screening). Alternatively, using an RPG>180 led to HbA1c testing in 40% of patients with AMI and identified 82% of DM (NNS=2.7). CONCLUSIONS: We have established two potential selective screening methods for DM in the setting of AMI that could identify the vast majority of incident DM by targeted screening of 40-50% of patients with AMI with HbA1c testing. Using these methods may efficiently identify patients with AMI with DM so that appropriate education and treatment can be promptly initiated.
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| 3. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 4. |
- Carlsson, Britt-Marie, et al.
(författare)
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Availability of insulin pump therapy in clinical practice
- 2012
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 29:8, s. 1055-1059
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Tidskriftsartikel (refereegranskat)abstract
- Diabet. Med. 29, 10551059 (2012) Aim To examine the availability of insulin pump therapy in patients with Type 1 diabetes. Methods Patients using insulin pumps among a cohort of 7224 patients with Type 1 diabetes were studied. Results In logistic regression, used to evaluate variables not changing over time among the total cohort, use of insulin pumps varied by outpatient clinic (P < 0.001) and sex (P < 0.001). Cox regression analysis in 5854 patients with detailed patient data prior to use of an insulin pump showed higher HbA1c (P < 0.0001), lower creatinine (P = 0.002), high and low insulin doses (P < 0.0001), younger age (P < 0.0001) and female sex (P < 0.0001) to be associated with use of an insulin pump. Women were 1.5-fold more likely to start using an insulin pump (hazard ratio 1.52, 95% confidence interval 1.291.79) and patients in the 20- to 30-years age range were more than twice as likely to begin use of an insulin pump than patients aged 4050 years (hazard ratio 8.63, 95% confidence interval 5.9112.59 and hazard ratio 3.98, 95% confidence interval 2.805.64, respectively). A 10-mu mol/l higher level of creatinine was associated with a hazard ratio of 0.56 (95% confidence interval 0.390.81) of starting use of an insulin pump. Conclusions At 10 hospital outpatient clinics in Sweden, use of insulin pumps therapy varied by clinic. A higher proportion of women began using insulin pumps. Younger patients and patients with fewer complications were also more likely to start using an insulin pump. Further research is needed to confirm these findings in other geographical regions and to understand whether the availability of insulin pumps today is optimized.
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| 5. |
- Carlsson, Britt-Marie, et al.
(författare)
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Insulin Pump-Long-Term Effects on Glycemic Control: An Observational Study at 10 Diabetes Clinics in Sweden
- 2013
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Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert Inc. - 1520-9156 .- 1557-8593. ; 15:4, s. 302-307
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This study examined long-term effects of continuous subcutaneous insulin infusion (CSII) in clinical practice on glycemic control in patients with type 1 diabetes. Subjects and Methods: We evaluated all type 1 diabetes patients at 10 diabetes outpatient clinics in Sweden who had been treated with CSII for at least 5.5 years and had valid glycated hemoglobin (HbA1c) data before starting pump use and at 5 years±6 months. Controls treated with multiple daily insulin injections (MDI) over a time-matched period were also evaluated. Results: There were 331 patients treated with CSII at least 5.5 years at the 10 clinics. Of these, 272 (82%) fulfilled the inclusion criteria. Patients treated with CSII were younger than those treated with MDI (mean age, 38.6 vs. 45.6 years; P<0.001), more were women (56% vs. 43%; P<0.001), and diabetes duration was shorter (mean, 15.1 years vs. 20.1 years; P<0.001). After adjusting for variables differing at baseline and influencing the change in HbA1c over the study period, the reduction in HbA1c remained statistically significant at 5 years and was estimated to be 0.20% (95% confidence interval [CI] 0.07–0.32) (2.17mmol/mol [95% CI 0.81–3.53]) (P=0.002). The corresponding adjusted reduction at years 1 and 2 was 0.42% (95% CI 0.31–0.53) (4.59mmol/mol [95% CI 3.41–5.77]) (P<0.001) and 0.43% (95% CI 0.31–0.55) (4.71mmol/mol [95% CI 3.38–6.04]) (P<0.001), respectively. The effect of insulin pump use versus controls on HbA1c decreased significantly with time (P<0.001). Conclusions: Use of CSII in clinical practice in Sweden is associated with an approximately 0.2% (2mmol/mol) reduction in HbA1c after 5 years.
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| 6. |
- Clements, M. A., et al.
(författare)
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Age at diagnosis predicts deterioration in glycaemic control among children and adolescents with type 1 diabetes
- 2014
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Ingår i: BMJ Open Diabetes Research and Care. - : BMJ. - 2052-4897 .- 2052-4897. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Poor glycemic control early in the course of type 1 diabetes mellitus (T1DM) increases the risk for microvascular complications. However, predictors of deteriorating control after diagnosis have not been described, making it difficult to identify high-risk patients and proactively provide aggressive interventions. OBJECTIVE: We examined whether diagnostic age, gender, and race were associated with deteriorating glycemic control during the first 5 years after diagnosis. PARTICIPANTS: 2218 pediatric patients with T1DM. METHODS: We conducted a longitudinal cohort study of pediatric patients with T1DM from the Midwest USA, 1993-2009, evaluating within-patient glycated hemoglobin (HbA1c) trajectories constructed from all available HbA1c values within 5 years of diagnosis. RESULTS: 52.6% of patients were male; 86.1% were non-Hispanic Caucasian. The mean diagnostic age was 9.0+/-4.1 years. The mean number of HbA1c values/year/participant was 2.4+/-0.9. HbA1c trajectories differed markedly across age groups, with older patients experiencing greater deterioration than their younger counterparts (p<0.001). HbA1c trajectories, stratified by age, varied markedly by race (p for racexdiagnostic age <0.001). Non-Hispanic African-American patients experienced higher initial HbA1c (8.7% vs 7.6% (71.6 vs 59.6 mmol/mol); p<0.001), and greater deterioration in HbA1c than non-Hispanic Caucasian patients across diagnostic ages (rise of 2.04% vs 0.99% per year (22.3 vs 10.8 mmol/mol/year); p<0.0001). CONCLUSIONS: Older diagnostic age and black race are major risk factors for deterioration in glycemic control early in the course of T1DM. These findings can inform efforts to explore the reasons behind these differences and develop preventive interventions for high-risk patients.
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| 7. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 8. |
- Falk Kieri, Catarina, et al.
(författare)
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EDAR-induced hypohidrotic ectodermal dysplasia : a clinical study on signs and symptoms in individuals with a heterozygous c.1072C > T mutation
- 2014
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Ingår i: BMC Medical Genetics. - : BioMed Central. - 1471-2350. ; 15, s. 57-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mutations in the EDAR-gene cause hypohidrotic ectodermal dysplasia, however, the oral phenotype has been described in a limited number of cases. The aim of the present study was to clinically describe individuals with the c.1072C > T mutation (p. Arg358X) in the EDAR gene with respect to dental signs and saliva secretion, symptoms from other ectodermal structures and to assess orofacial function.METHODS: Individuals in three families living in Sweden, where some members had a known c.1072C > T mutation in the EDAR gene with an autosomal dominant inheritance (AD), were included in a clinical investigation on oral signs and symptoms and self-reported symptoms from other ectodermal structures (n = 37). Confirmation of the c.1072C > T mutation in the EDAR gene were performed by genomic sequencing. Orofacial function was evaluated with NOT-S.RESULTS: The mutation was identified in 17 of 37 family members. The mean number of missing teeth due to agenesis was 10.3 ± 4.1, (range 4-17) in the mutation group and 0.1 ± 0.3, (range 0-1) in the non-mutation group (p < 0.01). All individuals with the mutation were missing the maxillary lateral incisors and one or more of the mandibular incisors; and 81.3% were missing all four. Stimulated saliva secretion was 0.9 ± 0.5 ml/min in the mutation group vs 1.7 ± 0.6 ml/min in the non-mutation group (p < 0.01). Reduced ability to sweat was reported by 82% in the mutation group and by 20% in the non-mutation group (p < 0.01). The mean NOT-S score was 3.0 ± 1.9 (range 0-6) in the mutation group and 1.5 ± 1.1 (range 0-5) in the non-mutation group (p < 0.01). Lisping was present in 56% of individuals in the mutation group.CONCLUSIONS: Individuals with a c.1072C > T mutation in the EDAR-gene displayed a typical pattern of congenitally missing teeth in the frontal area with functional consequences. They therefore have a need for special attention in dental care, both with reference to tooth agenesis and low salivary secretion with an increased risk for caries. Sweating problems were the most frequently reported symptom from other ectodermal structures.
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| 9. |
- Glogner, S., et al.
(författare)
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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
- 2014
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 31:5, s. 586-594
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Tidskriftsartikel (refereegranskat)abstract
- 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, HbA1c , 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/m2 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/m2 , 1.04 (95% CI 0.98-1.11) for BMI 25 to < 27.5 kg/m2 , 1.22 (95% CI 1.15-1.30) for BMI 27.5 to < 30 kg/m2 , 1.54 (95% CI 1.45-1.63) for BMI 30 to < 35 kg/m2 , 2.16 (95% CI 2.00-2.33) for BMI 35 to < 40 kg/m2 and 3.22 (95% CI 2.88-3.60) for BMI 40 kg/m2 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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| 10. |
- Jansson-Fröjmark, Markus, 1971-, et al.
(författare)
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Don't worry, be constructive : a randomized controlled feasibility study comparing behaviour therapy singly and combined with constructive worry for insomnia
- 2012
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Ingår i: British Journal of Clinical Psychology. - : Wiley-Blackwell. - 0144-6657 .- 2044-8260. ; 51:2, s. 142-157
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Based on the lack of research on interventions targeting intrusive and worrisome thinking for insomnia, the aim was to examine whether a constructive worry (CW) intervention adds to the effects of behaviour therapy (BT).Design: A randomized, controlled design was used. The design included a 2-week baseline, a 4-week intervention phase (sleep restriction and stimulus control [BT] or sleep restriction and stimulus control plus constructive worry [BT + CW]), and a 2-week follow-up.Methods: Twenty-two patients with primary insomnia participated. The primary outcome was the Anxiety and Preoccupation about Sleep Questionnaire (APSQ), and secondary endpoints were subjective sleep estimates, the Insomnia Severity Index (ISI), and the Work and Social Adjustment Scale (WSAS).Results: Although both conditions produced significant improvements in subjective sleep estimates, no significant group differences over time were shown for total wake time (TWT) and total sleep time (TST). Both interventions resulted in reductions over time in insomnia severity, worry, and dysfunction. Compared to BT, BT + CW led to a larger decrease in insomnia severity at all three time points (controlled d= 1.101.68). In comparison with BT, BT + CW resulted in a larger reduction in worry at two of the time points (controlled d= 0.761.64). No significant differences between the two conditions were demonstrated for dysfunction. While more participants responded positively to treatment in the BT + CW (80100%) than in the BT condition (1827%), none of the participants remitted.Conclusions: The findings suggest that, compared to BT alone, CW might result in additional improvements in insomnia severity and worry. Given the small sample size and short follow-up, future studies are warranted.
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| 11. |
- Johansson, Magdalena, et al.
(författare)
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Incidence of venous thromboembolism in northern Sweden (VEINS) : a population-based study
- 2014
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Ingår i: Thrombosis Journal. - : BioMed Central (BMC). - 1477-9560. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The reported incidence of venous thromboembolism (VTE) varies considerably among studies. The primary aim of this study was to describe the incidence of VTE in relation to age and sex. The secondary aim was to describe the risk factor pattern at the time of diagnosis.METHODS: This retrospective, population-based cohort study included all adult residents in the County of Västerbotten in northern Sweden during the year 2006 (n = 204,836). All potential VTE events were manually validated and classified according to location. The presence of risk factors for VTE at the time of diagnosis was recorded.RESULTS: We identified 517 adult individuals with potential VTE. Among these, 343 individuals (158 men and 185 women) had a verified VTE event in 2006. The mean incidence was 167 individuals per 100,000 person years; 155 for men and 180 for women. The mean age at diagnosis was 67.6 years in men and 72.5 years in women. The incidence of VTE increased with age. The incidence was highest in women aged 85 years or more. Pulmonary embolism with or without concurrent deep vein thrombosis was diagnosed in 161 individuals (46.9%); lower extremity deep vein thrombosis without concurrent pulmonary embolism was diagnosed in 157 individuals (45.8%); and VTE in another location was diagnosed in 25 individuals (7.3%). The most common risk factors for VTE were recent hospitalization and concurrent malignancy.CONCLUSION: The incidence of VTE was 167 per 100,000 person years and increased with age. The incidence was highest among older women. Pulmonary embolism was the most common form of VTE; it affected 47% of individuals with VTE. Malignancy and hospitalization were the most prevalent risk factors for VTE.
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| 12. |
- Lind, Marcus, 1976, et al.
(författare)
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Changes in HbA(1c) and frequency of measuring HbA(1c) and adjusting glucose-lowering medications in the 10 years following diagnosis of type 2 diabetes: a population-based study in the UK
- 2014
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 57:8, s. 1586-1594
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Tidskriftsartikel (refereegranskat)abstract
- Aim/hypothesis The aim of this work was to study levels of HbA(1c) and patterns of adjusting glucose-lowering drugs in patients with impaired glycaemic control over 10 years after diagnosis of type 2 diabetes. Methods We studied 4,529 individuals in The Health Improvement Network Database newly diagnosed with type 2 diabetes in the year 2000. Results From 6 months to 10 years after diagnosis, the HbA(1c) increased from 7.04% (53.4 mmol/mol) to 7.49% (58.3 mmol/mol) (average annual change: 0.047% [0.51 mmol/mol]). The greatest annual change occurred between 6 months and 2 years (0.21% [2.30 mmol/mol] increase per year, p < 0.001), followed by the 2-5 year time period (0.033% [0.36 mmol/mol] increase per year, p < 0.001). No significant increase in HbA(1c) occurred between 5 and 10 years (p = 0.20). In multivariable analyses, patients who were younger (p < 0.001), with higher BMI (p = 0.033) and who were current insulin users (p = 0.024) at diagnosis had greater increases in HbA(1c) between 6 months and 2 years. For individuals with HbA(1c) above 7.0% (53 mmol/mol) the mean time to next measurement of HbA(1c) was 0.53 years and increase in doses or changes to other glucose-lowering medications were performed in 26% of cases. Conclusions/interpretation HbA(1c) increases by approximately 0.5% (5 mmol/mol) over 10 years after diagnosis of type 2 diabetes, with the main increase appearing in the first years after diagnosis. More frequent monitoring of HbA(1c) and adjustments of glucose-lowering drugs may be essential to prevent the decline.
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| 13. |
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| 14. |
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| 15. |
- Lind, Marcus, et al.
(författare)
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Cystatin C and creatinine as markers of bleeding complications, cardiovascular events and mortality during oral anticoagulant treatment
- 2013
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Ingår i: Thrombosis Research. - : Pergamon-Elsevier. - 0049-3848 .- 1879-2472. ; 132:2, s. E77-E82
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Impaired kidney function has been linked to both ischemic events as well as bleeding complications in several clinical conditions. Our aim was to investigate if cystatin C, creatinine and calculated glomerular filtration rate (eGFR) were related to future risk of bleeding complications, cardiovascular events or all-cause mortality during oral anticoagulant treatment.Materials and methods: In a cohort study, 719 patients on long-term vitamin K antagonist (VKA) treatment were followed for a mean of 4.2 years. Blood sampling was taken at inclusion and patients were followed prospectively. Cystatin C and creatinine were analysed and eGFR was calculated. All medical records were reviewed. Major bleeding events, myocardial infarctions, strokes, arterial emboli, and deaths were recorded and classified.Results: After adjustment for age, no association between cystatin C, creatinine or eGFR and major bleeding was found. Cystatin C was independently associated with cardiovascular events (hazard ratio 1.50 (95% CI: 1.27-1.77)) and all-cause mortality (hazard ratio 1.62 (95% CI: 1.38-1.90)). Creatinine was only associated with all-cause mortality, while eGFR was not associated with any of the outcomes.Conclusions: Our findings underscore the superiority of cystatin C as a marker of cardiovascular risk compared to creatinine or eGFR. VKA-treated patients with increased cystatin C levels should be considered to be at an increased risk of cardiovascular events, and not bleeding complications.
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| 16. |
- Lind, Marcus, et al.
(författare)
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D-dimer predicts major bleeding, cardiovascular events and all-cause mortality during warfarin treatment
- 2014
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 47:7-8, s. 570-573
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Previous studies have shown that biomarkers in blood plasma can predict bleeding complications during anticoagulant treatment as well as thromboembolic events and may improve existing risk stratification schemes in patients on or considered for oral anticoagulant treatment. The aim of this study was to investigate if levels of D-dimer, tissue plasminogen activator (tPA) and its complex with plasminogen inhibitor type 1 (tPA/PAI-1 complex) can predict major bleedings, cardiovascular events and all-cause mortality in patients with warfarin treatment.Design and methods: In a longitudinal cohort study, 719 patients on oral anticoagulant treatment were followed for a total of 3001 treatment years. Major bleeding, stroke, arterial emboli, myocardial infarction and death were recorded and classified. Blood samples collected at baseline were analyzed for D-dimer, tPA, and tPA/PAI-1 complex.Results: In multivariate Cox regression analysis, high levels of D-dimer were associated with major bleeding (HR 1.27 per SD; 95% CI: 1.01-1.60), cardiovascular events (HR 1.23 per SD; 95% CI: 1.05-1.45) and all-cause mortality (HR 1.25 per SD; 95% CI: 1.06-1.47). Neither tPA nor the tPA/PAI-1 complex was associated with major bleeding, cardiovascular events or all-cause mortality.Conclusion: We conclude that high levels of D-dimer predict major bleeding, cardiovascular events and all-cause mortality during warfarin treatment. (C) 2014 The Canadian Society of Clinical Chemists.
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| 17. |
- Lind, Marcus, 1975-
(författare)
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Determinants of adverse events during oral anticoagulant treatment
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Treament with oral anticoagulation is highly effective in reducing the burden of thromboembolic complications in several clinical conditions. The number of patients receiving oral anticoagulation is growing steadily. InSwedenabout 1.5 percent of the population receives treatment. Although the treatment is highly effective in preventing thromboembolic complications, it is also associated with a substantial increase in the risk of bleeding. In clinical practice every physician has to balance the potential benefit of treatment against the risk of bleeding complications in the individual patient. To aid in this decision making, risk scores addressing the likelihood of thromboembolic events, as well as the risk of bleeding complications, have been developed. These scores are imperfect and, to some degree limited by the fact that the risk factors predictive of thromboembolic events are also often associated with bleeding complications. The addition of biomarkers has the potential to increase the predictive ability of risk scores and further enhance the net benefit of oral anticoagulant treatment in the individual patient. In this thesis several potential biomarkers for thromoboembolic and haemorrhagic complications of anticoagulant therapy have been investigated in a longitudinal cohort study of 719 patients with a median follow-up time of 4.2 years. Thrombomodulin is a key component in the generation of activated protein C and hence, a coagulation inhibitor. Conversely, it is also a key component in the inhibition of fibrinolysis by activation of trombin-activated fibrinolysis inhibitor. In warfarin-treated patients we demonstrate that thrombomodulin predicts an increased risk of bleeding complications, but not cardiovascular events. Thus, thrombomodulin has potential as a biomarker specifically for bleeding complications. Von Willebrand factor plays a central and intricate role in the aggregation of platelets and low levels of VWF have been associated with bleeding as a manifestation of von Willebrand’s disease. In our study we noted that high levels of von Willebrand factor predict an increased risk of cardiovascular as well as all-cause mortality, possibly as an expression of endothelial dysfunction. We also noted that high levels of WVF seem to be associated with serious bleeding complications. Decreased renal function is usually measured by an increase in the levels of creatinine and cystatin C, or a decrease in the calculated glomerular filtration rate. A decrease in kidney function is regarded as a marker of an increased risk of bleeding complications. We investigated all the mentioned markers of kidney function and no association with bleeding complications became apparent. However, a clear association between a decrease in kidney function and mortality was noted. Our findings indicate that the emphasis on impaired kidney function as a risk marker needs to be shifted from bleeding complications toward thromboembolic events. Fibrinolysis is important in containing coagulation and several constituents of the fibrinolytic pathway have been shown to predict cardiovascular events and mortality. We found that fibrinolytic factors seem to predict cardiovascular events in patients with oral anticoagulation and that D-dimer also predicts bleeding complications. In conclusion, we have found several biomarkers which exhibit different predictive abilities in patients with oral anticoagulation. It is likely that biomarkers, either alone, in combination, or as ancillary components of risk scores, can contribute to improved risk stratification in patients with oral anticoagulation.
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| 18. |
- Lind, Marcus, 1976, et al.
(författare)
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Glucagon-like peptide 1 (GLP-1) analogue combined with insulin reduces HbA1c and weight with low risk of hypoglycemia and high treatment satisfaction
- 2012
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Ingår i: Primary Care Diabetes. - Oxon, United Kingdom : Elsevier BV. - 1751-9918 .- 1878-0210. ; 6:1, s. 41-46
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To evaluate the effects of adding glucagon-like peptide-1 (GLP-1) analogue therapy to insulin on glycated hemoglobin (HbA1c), weight, insulin dosage, treatment satisfaction, and risk of hypoglycaemia. Methods: Type 2 diabetes patients with insulin therapy receiving a GLP-1 analogue at 4 Swedish centers were studied. Hypoglycemia was evaluated using glucometers and patient self-report. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was used to evaluate treatment satisfaction. Results: Among 65 patients studied, 4 discontinued therapy, none due to hypoglycemia, and there were no suspected severe adverse events. Among 61 patients who remained on therapy over a mean of 7.0 months, 40 were treated with liraglutide and 21 with exenatide. HbA1c decreased from a mean of 8.9% (82.4 mmol/mol) to 7.9% (71.9 mmol/mol) (p < 0.001), weight decreased from 111.1 kg to 104.0 kg (p<0.001) and insulin doses were reduced from 91.1U to 52.2 U (p < 0.001). There was one patient with severe hypoglycemia. The mean number of asymptomatic hypoglycemia per patient and month, reported for the last month (0.085 below 4.0 mmol/l and 0 below 3.0 mmol/l) and documented symptomatic hypoglycemia (0.24 below 4.0 mmol/l and 0.068 below 3.0 mmol/l) was low. The DTSQc showed higher treatment satisfaction than with the previous regimen of 11.9 (scale -18 to +18 points, p<0.001). Conclusions: The addition of GLP-1 analogues to insulin in patients with type 2 diabetes is associated with reductions in HbA1c, weight, and insulin dose, along with a low risk of hypoglycemia and high treatment satisfaction.
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| 19. |
- Lind, Marcus, 1976, et al.
(författare)
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Glycaemic control and incidence of heart failure in 20 985 patients with type 1 diabetes: an observational study
- 2011
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Ingår i: Lancet. - : Elsevier BV. - 0140-6736 .- 1474-547X. ; 378:9786, s. 140-146
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Tidskriftsartikel (refereegranskat)abstract
- Background Poor glycaemic control is associated with microvascular and macrovascular complications in type 1 diabetes, but whether glycaemic control is associated with heart failure in such patients is not known. We aimed to assess this association in a large cohort of patients with type 1 diabetes identified from the Swedish national diabetes registry. Methods We identified all patients (aged >= 18 years) with type 1 diabetes and no known heart failure who were registered in the national diabetes registry between January, 1998, and December, 2003. These patients were followed up until hospital admission for heart failure, death, or end of follow-up on Dec 31, 2009. We calculated incidence categorised by glycated haemoglobin A(1c) (HbA(1c)) values, and we assessed the association between patients' characteristics, including HbA(1c), and heart failure. Findings In a cohort of 20 985 patients with mean age of 38.6 years (SD 13.3) at baseline, 635 patients (3%) were admitted to hospital with a primary or secondary diagnosis of heart failure during a median follow-up of 9.0 years (IQR 7.3-11.0), with an incidence of 3.38 events per 1000 patient-years (95% CI 3.12-3.65). Incidence increased monotonically with HbA(1c), with a range of 1.42-5.20 per 1000 patient-years between patients in the lowest (<6.5%) and highest (>= 10.5%) categories of HbA(1c). In a Cox regression analysis, with adjustment for age, sex, duration of diabetes, cardiovascular risk factors, and baseline or intervening acute myocardial infarction and other comorbidities, the hazard ratio for development of heart failure was 3.98 (95% CI 2.23-7.14) in patients with HbA(1c) of 10.5% or higher compared with a reference group of patients with HbA(1c) of less than 6.5%. Risk of heart failure increased with age and duration of diabetes. Other modifiable factors associated with increased risk of heart failure were smoking, high systolic blood pressure, and raised body-mass index. In a subgroup of 18 281 patients (87%) with data for blood lipids, higher HDL cholesterol was associated with lower risk of heart failure, but there was no association with LDL cholesterol. Interpretation The positive association between HbA(1c) and risk of heart failure in fairly young patients with type 1 diabetes indicates a potential for prevention of heart failure with improved glycaemic control.
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| 20. |
- Lind, Marcus, 1976, et al.
(författare)
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Glycemic control and excess mortality in type 1 diabetes
- 2014
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 371:21, s. 1972-1982
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Tidskriftsartikel (refereegranskat)abstract
- Copyright © 2014 Massachusetts Medical Society. All rights reserved. BACKGROUND: The excess risk of death from any cause and of death from cardiovascular causes is unknown among patients with type 1 diabetes and various levels of glycemic control. We conducted a registry-based observational study to determine the excess risk of death according to the level of glycemic control in a Swedish population of patients with diabetes. METHODS: We included in our study patients with type 1 diabetes registered in the Swedish National Diabetes Register after January 1, 1998. For each patient, five controls were randomly selected from the general population and matched according to age, sex, and county. Patients and controls were followed until December 31, 2011, through the Swedish Register for Cause-Specific Mortality. RESULTS: The mean age of the patients with diabetes and the controls at baseline was 35.8 and 35.7 years, respectively, and 45.1% of the participants in each group were women. The mean follow-up in the diabetes and control groups was 8.0 and 8.3 years, respectively. Overall, 2701 of 33,915 patients with diabetes (8.0%) died, as compared with 4835 of 169,249 controls (2.9%) (adjusted hazard ratio, 3.52; 95% confidence interval [CI], 3.06 to 4.04); the corresponding rates of death from cardiovascular causes were 2.7% and 0.9% (adjusted hazard ratio, 4.60; 95% CI, 3.47 to 6.10). The multivariable-adjusted hazard ratios for death from any cause according to the glycated hemoglobin level for patients with diabetes as compared with controls were 2.36 (95% CI, 1.97 to 2.83) for a glycated hemoglobin level of 6.9% or lower (≤52 mmol per mole), 2.38 (95% CI, 2.02 to 2.80) for a level of 7.0 to 7.8% (53 to 62 mmol per mole), 3.11 (95% CI, 2.66 to 3.62) for a level of 7.9 to 8.7% (63 to 72 mmol per mole), 3.65 (95% CI, 3.11 to 4.30) for a level of 8.8 to 9.6% (73 to 82 mmol per mole), and 8.51 (95% CI, 7.24 to 10.01) for a level of 9.7% or higher (≥83 mmol per mole). Corresponding hazard ratios for death from cardiovascular causes were 2.92 (95% CI, 2.07 to 4.13), 3.39 (95% CI, 2.49 to 4.61), 4.44 (95% CI, 3.32 to 5.96), 5.35 (95% CI, 3.94 to 7.26), and 10.46 (95% CI, 7.62 to 14.37). CONCLUSIONS: In our registry-based observational study, patients with type 1 diabetes and a glycated hemoglobin level of 6.9% or lower had a risk of death from any cause or from cardiovascular causes that was twice as high as the risk for matched controls.
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| 21. |
- Lind, Marcus, 1976
(författare)
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Incretin therapy and its effect on body weight in patients with diabetes
- 2012
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Ingår i: Primary Care Diabetes. - : Elsevier BV. - 1751-9918. ; 6:3, s. 187-191
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Tidskriftsartikel (refereegranskat)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. (C) 2012 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
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| 22. |
- Lind, Marcus, 1976, et al.
(författare)
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Mortality trends in patients with and without diabetes in Ontario, Canada and the UK from 1996 to 2009: a population-based study
- 2013
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 56:12, s. 2601-2608
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine the contemporary rate ratio of mortality and changes over time in individuals with vs without diabetes. 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. 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. 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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| 23. |
- Lind, Marcus, 1976, et al.
(författare)
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The Association between HbA1c, Fasting Glucose, 1-Hour Glucose and 2-Hour Glucose during an Oral Glucose Tolerance Test and Cardiovascular Disease in Individuals with Elevated Risk for Diabetes
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine the association between HbA1c, fasting plasma glucose (FPG), 1-hour (1 hPG) and 2-hour (2 hPG) glucose after an oral glucose tolerance test (OGTT) and cardiovascular disease in individuals with elevated risk for diabetes. Design: We studied the relationship between baseline, updated mean and updated (last) value of HbA1c, FPG, 1 hPG and 2 hPG after an oral 75 g glucose tolerance test (OGTT) and acute CVD events in 504 individuals with impaired glucose tolerance (IGT) at baseline enrolled in the Finnish Diabetes Prevention Study. Participants: 504 individuals with IGT were followed with yearly evaluations with OGTT, FPG and HbA1c. Results: Over a median follow-up of 9.0 years 34 (6.7%) participants had a CVD event, which increased to 52 (10.3%) over a median follow-up of 13.0 years when including events that occurred among participants following a diagnosis of diabetes. Updated mean HbA1c, 1 hPG and 2 hPG, HR per 1 unit SD of 1.57 (95% CI 1.16 to 2.11), p = 0.0032, 1.51 (1.03 to 2.23), p = 0.036 and 1.60 (1.10 to 2.34), p = 0.014, respectively, but not FPG (p = 0.11), were related to CVD. In analyses of the last value prior to the CVD event the same three glycaemic measurements were associated with the CVD events, with HRs per 1 unit SD of 1.45 (1.06 to 1.98), p = 0.020, 1.55 (1.04 to 2.29), p = 0.030 and 2.19 (1.51 to 3.18), p < 0.0001, respectively but only 2 hPG remained significant in pairwise comparisons. Including the follow-up period after diabetes onset updated 2 hPG (p = 0.003) but not updated mean HbA1c (p = 0.08) was related to CVD. Conclusions and Relevance: Current 2 hPG level in people with IGT is associated with increased risk of CVD. This supports its use in screening for prediabetes and monitoring glycaemic levels of people with prediabetes.
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| 24. |
- Lind, Marcus, 1976, et al.
(författare)
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The relationship between glycaemic control and heart failure in 83,021 patients with type 2 diabetes
- 2012
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 55:11, s. 2946-2953
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine the relationship between glycaemic control and hospitalisation for heart failure in patients with type 2 diabetes. 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. 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) a parts per thousand yen10.0 % (a parts per thousand yen86 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). 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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| 25. |
- Lind, Marcus, 1976, et al.
(författare)
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The relationship between the exposure time of insulin glargine and risk of breast and prostate cancer: An observational study of the time-dependent effects of antidiabetic treatments in patients with diabetes.
- 2012
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Ingår i: Primary Care Diabetes. - : Elsevier BV. - 1751-9918 .- 1878-0210. ; 6:1, s. 53-59
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To elucidate methodological questions in assessing the relationship between insulin treatment and cancer, since the risk of tumour growth generally increases with longer exposure time and higher dose of a growth promoting substance. METHODS: Continuous hazard functions for risk of breast and prostate cancer were estimated in relation to exposure of insulin glargine among diabetic patients included in the record system, Diab-Base, as well as in the general population in Sweden. RESULTS: In 7942 female diabetic patients, mean follow-up 7.0 years, 2014 patients initiated insulin glargine with a mean follow-up of 3.5 years. Among 11,613 men, mean follow-up 6.9 years, 2760 had a mean follow-up with glargine of 3.4 years. Risk of prostate cancer decreased significantly with longer exposure to insulin glargine (p=0.032), although average risk versus non-glargine was non-significantly higher (HR 1.37, 95% CI 0.78-2.39). The breast cancer risk did not change with longer exposure to insulin glargine (p=0.35) and the mean risk was similar for glargine and non-glargine (p=0.12). With higher dose of insulin glargine, there was an increase in risk of prostate (p=0.037) and breast cancer (p=0.019). In diabetics, the mean risk of prostate cancer was decreased (HR 0.68, 95% CI 0.59-0.79) but similar for breast cancer (HR 0.95, 95% CI 0.78-1.14) compared to the general population and did not change with longer diabetes duration (p=0.68 and p=0.53 respectively). CONCLUSIONS: Analysing continuous hazard functions for cancer risk in relation to exposure time to an antidiabetic agent is an important complementary tool in diabetes and cancer research.
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