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Aims/hypothesis: Previous studies have shown that individuals with similar mean glucose levels (MG) or percentage of time in range (TIR) may have different HbA 1c values. The aim of this study was to further elucidate how MG and TIR are associated with HbA 1c ., Methods: Data from the randomised clinical GOLD trial (n=144) and the follow-up SILVER trial (n=98) of adults with type 1 diabetes followed for 2.5 years were analysed. A total of 596 paired HbA 1c /continuous glucose monitoring measurements were included. Linear mixed-effects models were used to account for intra-individual correlations in repeated-measures data., Results: In the GOLD trial, the mean age of the participants (± SD) was 44±13 years, 63 (44%) were female, and the mean HbA 1c (± SD) was 72±9.8 mmol/mol (8.7±0.9%). When correlating MG with HbA 1c , MG explained 63% of the variation in HbA 1c (r=0.79, p<0.001). The variation in HbA 1c explained by MG increased to 88% (r=0.94, p value for improvement of fit <0.001) when accounting for person-to-person variation in the MG-HbA 1c relationship. Time below range (TBR; <3.9 mmol/l), time above range (TAR) level 2 (>13.9 mmol/l) and glycaemic variability had little or no effect on the association. For a given MG and TIR, the HbA 1c of 10% of individuals deviated by >8 mmol/mol (0.8%) from their estimated HbA 1c based on the overall association between MG and TIR with HbA 1c . TBR and TAR level 2 significantly influenced the association between TIR and HbA 1c . At a given TIR, each 1% increase in TBR was related to a 0.6 mmol/mol lower HbA 1c (95% CI 0.4, 0.9; p<0.001), and each 2% increase in TAR level 2 was related to a 0.4 mmol/mol higher HbA 1c (95% CI 0.1, 0.6; p=0.003). However, neither TIR, TBR nor TAR level 2 were significantly associated with HbA 1c when accounting for MG., Conclusions/interpretation: Inter-individual variations exist between MG and HbA 1c , as well as between TIR and HbA 1c , with clinically important deviations in relatively large groups of individuals with type 1 diabetes. These results may provide important information to both healthcare providers and individuals with diabetes in terms of prognosis and when making diabetes management decisions., (© 2024. The Author(s).)

Background: People with type 1 diabetes generally view it easier to exercise when having continuous information of the glucose levels. We evaluated whether patients with type 1 diabetes managed with multiple daily insulin injections (MDI) exercised more after initiating continuous glucose monitoring (CGM) and whether the improved glycemic control and well-being associated with CGM translates into improved blood lipids and markers of inflammation., Method: The GOLD trial was a randomized cross-over trial over 16 months where patients used either CGM or capillary self-monitoring of blood glucose (SMBG) over six months, with a four-month wash-out period between the two treatment periods. We compared grade of physical activity, blood lipids, apolipoproteins, and high-sensitivity C-reactive protein (hsCRP) levels during CGM and SMBG., Results: There were 116 patients with information of physical activity estimated by the International Physical Activity Questionnaire (IPAQ) during both CGM and SMBG. No changes were found during CGM or SMBG, IPAQ scores 3305 versus 3878 ( P = .16). In 136 participants with information of blood lipid levels with no change in lipid-lowering medication during the two treatment periods, HbA1c differed by 4.2 mmol/mol (NGSP 0.39%) between SMBG and CGM treatment ( P < .001). No significant changes existed in low-density lipoprotein, high-density lipoprotein, triglycerides, total cholesterol, apolipoprotein A1, apolipoprotein B1, or hsCRP, during CGM and SMBG., Conclusion: Although many patients experience it easier to perform physical activity when monitoring glucose levels with CGM, it does not influence the amount of physical activity in persons with type 1 diabetes. Blood lipids, apolipoprotein, and hsCRP levels were similar during CGM and SMBG., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: TN has received unrestricted grants from AstraZeneca and NovoNordisk and has served on national advisory boards of Abbot, Amgen, Novo Nordisk, Sanofi-Aventis, Eli Lilly, MSD, and Boehringer Ingelheim. ML has received research grants from Eli Lilly and Novo Nordisk and been consultant or received honoraria from Astra Zeneca, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. JH has served on advisory boards or lectured for Novo Nordisk, Sanofi, Lilly, Abbot, Rubin Medical, MSD, and Boehringer Ingelheim. MW has served on advisory boards or lectured for MSD, Lilly, Novo Nordisk, and Sanofi and has organized a professional regional meeting sponsored by Lilly, Rubin Medical, Sanofi, Novartis, and Novo Nordisk. JB has received honoraria for consulting and/or lecture fees from Abbott Diabetes Care, Novo Nordisk, and Sanofi.

Background: The GOLD trial demonstrated that continuous glucose monitoring (CGM) in people with type 1 diabetes (T1D) managed with multiple daily insulin injections (MDI) improved not only glucose control but also overall well-being and treatment satisfaction. This analysis investigated which factors contributed to improved well-being and treatment satisfaction with CGM., Methods: The GOLD trial was a randomized crossover trial comparing CGM versus self-monitored blood glucose (SMBG) over 16 months. Endpoints included well-being measured by the World Health Organization-Five Well-Being Index (WHO-5) and treatment satisfaction by the Diabetes Treatment Satisfaction Questionnaire (DTSQ) as well as glucose metrics. Multivariable R 2 -decomposition was used to understand which variables contributed most to treatment satisfaction., Results: A total of 139 participants were included. Multivariable analyses revealed that increased convenience and flexibility contributed to 60% (95% confidence interval [CI] = 50%-69%) of the improvement in treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire change version [DTSQ c ]) observed with CGM, whereas perceived effects on hypoglycemia and hyperglycemia only contributed to 6% (95% CI = 2%-11%) of improvements. Significant improvements in well-being (WHO-5) by CGM were observed for the following: feeling cheerful ( P = .025), calm and relaxed ( P = .024), being active ( P = .046), and waking up fresh and rested ( P = .044). HbA1c reductions and increased time in range (TIR) were associated with increased treatment satisfaction, whereas glycemic variability was not. HbA1c reduction showed also an association with increased well-being and increased TIR with less diabetes-related distress., Conclusions: While CGM improves glucose control in people with T1D on MDI, increased convenience and flexibility through CGM is of even greater importance for treatment satisfaction and patient well-being. These CGM-mediated effects should be taken into account when considering CGM initiation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: D.P. has no conflict of interest to declare. W.P. has served as a consultant for Dexcom and Abbott Diabetes Care. H.I. has no conflict of interest to declare. H.H. has no conflict of interest to declare. J.H. has served on advisory boards or lectured for Abbot, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Nordic Infucare, Novo Nordisk, Rubin Medical, and Sanofi. M.W. has served on advisory boards or lectured for MSD, Lilly, Novo Nordisk, and Sanofi, and has organized a professional regional meeting sponsored by Lilly, Rubin Medical, Sanofi, Novartis, and Novo Nordisk. J.B. has received honoraria for consulting and/or lecture fees from Abbott Diabetes Care, MannKind Corp, Nordic Infucare, NovoNordisk and Sanofi. T.H. has received research funds from Adocia, AstraZeneca, BD, Biocon, Boehringer Ingelheim, Dance Pharmaceuticals, Grünenthal, Eli Lilly, Medtronic, Novo Nordisk, Novartis, Sanofi, and Senseonics. T.H. has participated in advisory panels for Novo Nordisk and received speaker honoraria and travel grants from Eli Lilly, Mylan, and Novo Nordisk. S.D. has no conflict of interest to declare. T.N. has received honoraria on expert group participation from AstraZeneca, Merck Sharp & Dohme, Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim, Abbot and Amgen. E.S. has no conflict of interest to declare. I.H. has received research funding from Dexcom and Insulet. M.L. has received research grants from Eli Lilly and Novo Nordisk and served as a consultant or received honoraria from AstraZeneca, Eli Lilly, and Novo Nordisk.

Objective: To study risk in white-coat hypertension (WCH) by measurement of coronary artery calcium score (CACS), carotid--femoral pulse-wave velocity (PWV) and carotid plaques., Methods: Cross-sectional population-based cohort with randomized selection of participants from Linköping, Sweden. An Omron m10-IT oscillometric device was used for clinic and home blood pressures (HBP) in the morning and evening for 1 week., Results: We recruited 5029 middle-aged and mainly defined WCH as SBP at least 140 mmHg and/or DBP at least 90 mmHg with HBP less than 135/85 mmHg. There were 2680 normotensive participants and 648 had WCH after exclusion of treated participants. More women (59.5%) than men (42.8%, P < 0.001) had WCH. We found higher prevalence of CACS greater than 100 compared with less than 100 (12.4 vs. 7.2%, P < 0.001), PWV (11.5 ± 1.5 vs. 10.4 ± 1.3 m/s, P < 0.001) and a higher prevalence of one or more carotid plaques (59.5 vs. 48%, P < 0.001) in participants with WCH than in normotension. Participants with WCH also had more dyslipidemia and higher glucose levels. Normotensive women scored lower on nervousness than women with WCH (P = 0.022). After matching of 639 participants with WCH to normotensive participants according to age, gender and systolic HBP the prevalence of a high CACS (12.1 vs. 8.6%, P = 0.003,) PWV (11.0 ± 0.068 vs. 11.5 ± 0.068 m/s, estimated marginal means ± SE, P < 0.001 by ANOVA) but not more carotid plaques (59.5 vs. 55.6%, P = 0.23), remained in the participants with WCH compared with the matched normotensive participants., Conclusion: WCH is particularly common in middle-aged women, and it displays metabolic dysfunction and increased prevalence of arteriosclerotic manifestations in both genders. As markers of increased cardiovascular risk were present also after matching normotensive and WCH participants according to systolic HBP, age and gender, the presence of WCH signals an increased cardiovascular risk burden that is not fully explained by elevated BP levels at home., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Hemodynamic responses to exercise in the acute phase after moderate to severe stroke have remained poorly investigated. The aim of this randomized controlled study, in which 52 (32 women) patients with moderate to severe stroke were randomized to three weeks of 20 minutes in-bed cycle exercise 5 days per week or to usual care, was to explore the systolic blood pressure (SBP) response to exercise and to evaluate the impact of the intervention on the resting and post-test systolic and diastolic blood pressures and heart rate, and on the systolic blood pressure response to exercise. We found that resting SBP decreased from baseline to post-intervention in both the intervention group (147.7 ± 18.1 mmHg to 125.3 ± 17.1 mmHg, P < .001) and in the control group (147.8 ± 23.7 mmHg to 131.4 ± 14.8 mmHg, P < .001) without a significant difference between the groups (interaction P = .308). However, there was a significant difference (interaction P = .010) regarding how Δ SBP (change in SBP from pre-test to post-test) changed from baseline to post-intervention. In the intervention group, Δ SBP increased from -1.0 ± 15.0 mmHg to 8.5 ± 9.4 mmHg, P = .009, whereas in the control group, Δ SBP decreased from 7.1 + 10.9 mmHg to 4.5 + 11.8 mmHg, P = .395. We conclude that patients randomized to in-bed cycle exercise seemed to normalize their blood pressure response to exercise to a larger extent than patients in the control group., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Aim: To identify responders to continuous glucose monitoring (CGM) in relation to reductions in HbA1c and percentage of time spent in hypoglycaemia after initiation of CGM for individuals with type 1 diabetes treated with multiple daily insulin injections., Materials and Methods: We analysed data from 142 participants in the GOLD randomized clinical trial. We evaluated how many lowered their HbA1c by more than 0.4% (>4.7 mmol/mol) or decreased the time spent in hypoglycaemia over 24 hours by more than 20 or 30 minutes, and which baseline variables were associated with those improvements., Results: Lower reduction of HbA1c was associated with greater reduction of hypoglycaemia (r = -0.52; P < .0001). During CGM, 47% of participants lowered their HbA1c values by more than 0.4% (>4.7 mmol/mol) than with self-measurement of blood glucose, and 47% decreased the time spent in hypoglycaemia by more than 20 minutes over 24 hours. Overall, 78% either reduced their HbA1c by more than 0.4% (>4.7 mmol/mol) or the time spent in hypoglycaemia by more than 20 minutes over 24 hours, but only 14% improved both. Higher HbA1c, a lower percentage of time at less than 3.0 or 3.9 mmol/L, a lower coefficient of variation (CV) and a higher percentage of time above 13.9 mmol/L (P = .016) were associated with greater HbA1c reduction during CGM. The variables associated with a greater reduction of time in hypoglycaemia were female sex, greater time with glucose levels at less than 3.0 mmol/L, higher CV, and higher hypoglycaemia confidence as evaluated by a hypoglycaemic confidence questionnaire., Conclusion: The majority of people with type 1 diabetes managed by multiple daily insulin injections benefit from CGM; some experienced reduced HbA1c while others reduced the time spent in hypoglycaemia. These factors need to be considered by healthcare professionals and decision-makers for reimbursement and diabetes guidelines., (© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: Continuous glucose monitoring (CGM) reduces HbA 1c and time spent in hypoglycemia in people with type 1 diabetes (T1D) treated with multiple daily insulin injections (MDI) when evaluated over shorter time periods. It is unclear to what extent CGM improves and helps to maintain glucose control, treatment satisfaction, diabetes distress, hypoglycemic concerns, and overall well-being over longer periods of time., Research Design and Methods: The GOLD trial was a randomized crossover trial performed over 16 months of CGM treatment in people with T1D treated with MDI. People completing the trial ( n = 141) were invited to participate in the current SILVER extension study in which 107 patients continued CGM treatment over 1 year along with the support of a diabetes nurse every 3 months., Results: The primary end point of the change in HbA 1c over 1.0-1.5 years of CGM use compared with previous self-monitoring of blood glucose during GOLD showed a decrease in HbA 1c of 0.35% (95% CI 0.19-0.50, P < 0.001). Time spent in hypoglycemia <3.0 mmol/L (54 mg/dL) and <4.0 mmol/L (72 mg/dL) decreased from 2.1% to 0.6% ( P < 0.001) and from 5.4% to 2.9% ( P < 0.001), respectively. Overall well-being (World Health Organization 5-item well-being index, P = 0.009), treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire, P < 0.001), and hypoglycemic confidence ( P < 0.001) increased, while hypoglycemic fear (Hypoglycemia Fear Survey-Worry, P = 0.016) decreased and diabetes distress tended to decrease (Problem Areas in Diabetes Scale, P = 0.06). From randomization and screening in GOLD, HbA 1c was lowered by 0.45% ( P < 0.001) and 0.68% ( P < 0.001) after 2.3 and 2.5 years, respectively., Conclusions: The SILVER study supports beneficial long-term effects from CGM on HbA 1c , hypoglycemia, treatment satisfaction, well-being, and hypoglycemic confidence in people with T1D managed with MDI., (© 2020 by the American Diabetes Association.)

Objective: To investigate the effects of in-bed cycle exercise in addition to usual care in patients with acute stroke, National Institutes of Health Stroke Scale (NIHSS) 7-42, regarding walking ability, functional outcomes, and inpatient care days., Design: Randomized controlled trial., Setting: Hospital care., Participants: Patients (N=56) with stroke NIHSS 7-42 were recruited 24-48 hours after stroke onset from 2 stroke units in Sweden., Interventions: Both groups received usual care. The intervention group also received 20 minutes bed cycling 5 days per week with a maximum of 15 sessions., Main Outcome Measures: The primary outcome was median change in walking ability measured with the 6-minute walk test (6MWT). Secondary outcome measures included the median change in modified Rankin Scale (mRS), Barthel Index (BI) for activities of daily living, and inpatient care days. Measurements were performed at baseline, post intervention (3 weeks), and at 3-month follow-up., Results: There was no significant difference in change of walking ability (6MWT) from baseline to follow-up between the intervention and control groups (median, 105m [interquartile range [IQR, 220m] vs 30m [IQR, 118m], respectively, P =.147, d =0.401). There were no significant differences between groups regarding mRS, BI, or inpatient care days. Patients with less serious stroke (NIHSS 7-12) seemed to benefit from the intervention., Conclusion: Although this study may have been underpowered, patients with stroke NIHSS 7-42 did not benefit from in-bed cycle exercise in addition to usual care after acute stroke. A larger study is needed to confirm our results., (© 2020 The Authors.)

Objective: According to recent guidelines, individuals with type 1 diabetes should spend <4.0% of time per day with glucose levels <3.9 mmol/L (<70 mg/dL) and <1.0% per day with glucose levels <3.0 mmol/L (<54 mg/dL)., Research Design and Methods: In the GOLD randomized crossover trial, 161 individuals with type 1 diabetes treated with multiple daily insulin injections (MDI) were randomized to continuous glucose monitoring (CGM) or conventional therapy with self-monitoring of blood glucose (SMBG) and evaluated over 16 months. We estimated the association between time spent in hypoglycemia and various mean glucose and HbA 1c levels., Results: Time spent in hypoglycemia (<3.9 mmol/L and <3.0 mmol/L) increased significantly with lower mean HbA 1c and mean glucose levels during both CGM and conventional therapy. During CGM, 24 (57.1%) individuals with HbA 1c <7.5% (<58 mmol/mol) had <1.0% time spent in hypoglycemia <3.0 mmol/L and 23 (54.8%) had <4.0% time spent in hypoglycemia <3.9 mmol/L. During CGM, mean time spent in hypoglycemia for individuals with mean HbA 1c 7.0% (52 mmol/mol) was estimated to be 5.4% for <3.9 mmol/L and 1.5% for <3.0 mmol/L. The corresponding values during SMBG were 9.2% and 3.5%, respectively. Individuals with mean glucose levels of 8 mmol/L spent 4.9% units more time with glucose levels <3.9 mmol/L and 2.8% units more time <3.0 mmol/L during SMBG compared with CGM., Conclusions: Reaching current targets for time in hypoglycemia while at the same time reaching HbA 1c targets is challenging for patients with type 1 diabetes treated with MDI both with CGM and SMBG monitoring. However, CGM is associated with considerably less time in hypoglycemia than SMBG at a broad range of HbA 1c levels and is crucial for patients with MDI treatment if they are to have a chance to approach hypoglycemia targets., (© 2020 by the American Diabetes Association.)

Objective: Our aim was to analyze the predictive value of toe brachial index (TBI) as a risk marker for future major adverse cardiovascular events (MACE) and all-cause mortality in patients with type 2 diabetes (T2D)., Methods: TBI was measured in 741 patients with T2D in 2005-2008. Conventional risk factors for vascular disease as well as non-invasive measurements such as pulse-wave velocity (PWV) and intima-media thickness (IMT) of the carotid arteries were estimated. MACE was defined as cardiovascular death or hospitalization for non fatal myocardial infarction or non fatal stroke. Patients were followed for incidence of MACE using the national Swedish Cause of Death Registry and the Inpatient Register., Results: During the follow-up for a period of 9 years MACE occurred in 97 patients and 85 patients died. TBI tertile, 1 versus 3, was significantly related to MACE (HR 2.67, 95%CI 1.60-4.50; p < 0.001) and to all-cause mortality (HR 1.98, 95%CI 1.16-3.83; p = 0.01). TBI tertile 1 as compared to TBI tertile 3 predicted MACE, but not all-cause mortality, independently of age, sex, diabetes duration and treatment, antihypertensive treatment, previous cardiovascular diseases, office systolic blood pressure, HbA1c, LDL cholesterol, estimated glomerular filtration rate, body mass index, current smoking PWV, IMT and carotid plaque presence (HR 3.39, 95%CI 1.53-7.51; p = 0.003 and HR 1.81, 95%CI 0.87-3.76; p = 0.1, respectively)., Conclusions: Low TBI predicts an increased risk for MACE independently of arterial stiffness in patients with type 2 diabetes., Trial Registration: Clinical Trials.gov number NCT01049737. Registered January 14, 2010., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We recruited 78 men and 94 women to investigate if the proportion of subjects with well-controlled home blood pressure levels could be increased when treatment was guided by smartphone-based telemonitoring. All patients were prescribed one to three antihypertensive drugs. The Accumbo smartphone telemonitoring application was downloaded to the Iphones of the participants and home blood pressure information was gathered from semi-automatic oscillometric blood pressure-recorders by Bluetooth. The study physician adjusted the medications based on home blood pressure for 3 months. home blood pressure was controlled (<135/<85 mmHg) in 55 participants at baseline and in 56 subjects after 3 months (Chi-square P = 0.91). The 117 patients with initially uncontrolled home blood pressure had a drop in home blood pressure (from 138.0 ± 9.0/91.3 ± 6.5 mmHg to 133.4 ± 8.0/88.6 ± 6.1 mmHg, P < 0.001) and prescribed antihypertensive drugs increased from 1.71 ± 0.94/day to 2.00 ± 0.92/day, P < 0.0001. Thus, while the proportion of participants with controlled home blood pressure remained unchanged, the home blood pressure levels were lowered in participants who had uncontrolled home blood pressure at study start.

Aims: Obesity is associated with type 2 diabetes mellitus, left ventricular diastolic dysfunction and heart failure but it is unclear to which extent it is related to left ventricular systolic dysfunction. The aim of the study was to explore the effects of overweight and obesity on left ventricular systolic function in patients with type 2 diabetes mellitus and a control group of non-diabetic persons., Methods: We prospectively investigated 384 patients with type 2 diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL studies. The participants were grouped according to body mass index (normal weight < 25 kg/m 2 , overweight 25-29 kg/m 2 , and obesity ≥ 30 kg/m 2 ). Echocardiography was performed at the beginning of the study and after 4-years in the patient group., Results: Univariable and multivariable regression analysis revealed that variations in left ventricular ejection fraction, global longitudinal strain, left ventricular mass and diastolic function expressed as E/é (the ratio between early diastolic mitral flow and annular motion velocities) all are related to body mass index. The mean and standard deviation of left ventricular ejection fraction and global longitudinal strain values were 57% (8%) vs. - 18.6% (2.3%) for normal weight patients, 53% (8%) vs. - 17.5% (2.3%) for overweight, and 49% (9%) vs. - 16.2% (3.0%) for obese (p < 0.05 vs. p < 0.05). Corresponding results in the control group were 58% (6%) vs. - 22.3% (3.0%), 55% (7%) vs. - 20.8% (3.1%) and 54% (8%) - 19.6% (4.0%) (p < 0.05 vs. p < 0.05). Patients who gained weight from baseline to follow-up changed left ventricular ejection fraction (median and interquartile range) by - 1.0 (9.0) % (n = 187) and patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0) % (n = 179) (p < 0.05)., Conclusion: Overweight and obesity impair left ventricular ejection fraction and global longitudinal strain in both patients with type 2 diabetes mellitus and non-diabetic persons. Trial registration ClinicalTrials.gov identifier NCT 01049737.

Background: To evaluate the effects of continuous glucose monitoring (CGM) on nocturnal and daytime hypoglycemia in persons with type 1 diabetes treated with multiple daily insulin injections (MDI); we also evaluated factors related to differences in hypoglycemia confidence in this population., Methods: Evaluations were performed from the GOLD randomized trial, an open-label multicenter crossover randomized clinical trial (n = 161) over 69 weeks comparing CGM to self-measurement of blood glucose (SMBG) in persons with type 1 diabetes treated with MDI. Masked CGM and the hypoglycemia confidence questionnaire were used for evaluations., Results: Time with nocturnal hypoglycemia, glucose levels <70 mg/dL was reduced by 48% (10.2 vs. 19.6 min each night, P < 0.001) and glucose levels <54 mg/dL by 65%. (3.1 vs. 8.9 min, P < 0.001). For the corresponding glucose cutoffs, daytime hypoglycemia was reduced by 40% (29 vs. 49 min, P < 0.001) and 54% (8 vs. 18 min., P < 0.001), respectively. Compared with SMBG, CGM use improved hypoglycemia-related confidence in social situations (P = 0.016) and confidence in more broadly avoiding serious problems due to hypoglycemia (P = 0.0020). Persons also reported greater confidence in detecting and responding to decreasing blood glucose levels (thereby avoiding hypoglycemia) during CGM use (P = 0.0033) and indicated greater conviction that they could more freely live their lives despite the risk of hypoglycemia (P = 0.022)., Conclusion: CGM reduced time in both nocturnal and daytime hypoglycemia in persons with type 1 diabetes treated with MDI and improved hypoglycemia-related confidence, especially in social situations, thus contributing to greater well-being and quality of life., Trial Registration: ClinicalTrials.gov , number NCT02092051.

Aims: The aim was to evaluate the predictive value of aortic pulse wave velocity (aPWV) on incident cardiovascular events in patients with type 2 diabetes without previous cardiovascular disease who were treated in primary care, after adjustment for traditional risk factors., Methods: We measured aPWV in 627 patients who participated in the epidemiological study CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes-a Prospective Study in Primary Care; ClinicalTrials.gov identifier NCT01049737) and who did not have previously known myocardial infarction or stroke. The outcome variable was a composite endpoint consisting of cardiovascular mortality, hospitalization for myocardial infarction and hospitalization for stroke., Results: During a median follow-up time of almost eight years, the unadjusted HR per each increment of aPWV by 1m/s was 1.239 (95% CI 1.114-1.379, P<0.001) for the primary endpoint. Following adjustments for age, sex, diabetes duration, office systolic blood pressure, resting heart rate, total cholesterol, HbA1c, estimated glomerular filtration rate and smoking status, the adjusted hazard ratio was 1.142 (95% CI 1.003-1.301, P=0.044)., Conclusions: In primary preventive patients with type 2 diabetes treated in primary care, aPWV predicted a composite outcome of incident cardiovascular events independently of diabetes-specific and traditional risk factors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: In patients with type 2 diabetes, the prognostic impact of an orthostatic rise in blood pressure is not known. Therefore, the aim of this study was to determine the prognostic implications of the diastolic orthostatic blood pressure response in a cohort of patients with type 2 diabetes. We also evaluated associations between different orthostatic blood pressure responses and markers of subclinical cardiovascular organ damage., Methods: Office blood pressures were measured in the sitting and in the standing position in 749 patients with type 2 diabetes who participated in the CARDIPP study (Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care). Diastolic orthostatic hypertension was defined as a rise of diastolic blood pressure ≥10 mmHg and diastolic orthostatic hypotension was defined as a drop of diastolic blood pressure ≥10 mmHg. Recruitment took place between the years 2005-2008, and patients were followed until any of the primary outcome events (cardiovascular death or hospitalization for either myocardial infarction or stroke) occurred or until December 31st, 2014. Measurements of aortic pulse wave velocity and of carotid intima-media thickness were performed at base-line., Results: Diastolic orthostatic hypertension was found in 140 patients (18.7 %) and was associated with significantly lower risk of cardiovascular events (crude hazard ratio compared with patients with normal systolic and diastolic orthostatic blood pressure response: 0.450, 95 % C.I. 0.206-0.987, P = 0.046). Diastolic orthostatic hypotension was found in 31 patients (4.1 %) and was associated with higher values for aortic pulse wave velocity and carotid intima-media thickness, compared with patients with normal systolic and diastolic orthostatic blood pressure response., Conclusions: Diastolic orthostatic hypertension is common in patients with type 2 diabetes, and may be a novel marker for decreased cardiovascular risk in these patients.

Background: Low levels of vitamin D have been related to increased mortality and morbidity in several non-diabetic studies. We aimed to prospectively study relationships between serum 25-OH vitamin D3 (vitamin D) and of serum parathyroid hormone (PTH) to total mortality in type 2 diabetes. We also aimed to compare the levels of these potential risk-factors in patients with and without diabetes., Methods: The main study design was prospective and observational. We used baseline data from 472 men and 245 women who participated in the "Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care" study. Patients were 55-66 years old at recruitment, and an age-matched non-diabetic sample of 129 individuals constituted controls for the baseline data. Carotid-femoral pulse-wave velocity (PWV) was measured with applanation-tonometry and carotid intima-media thickness (IMT) with ultrasound. Patients with diabetes were followed for all-cause mortality using the national Swedish Cause of Death Registry., Results: Levels of vitamin D were lower in patients with diabetes than in controls, also after correction for age and obesity, while PTH levels did not differ. Nine women and 24 men died during 6 years of median follow up of the final cohort (n = 698). Vitamin D levels were negatively related to all-cause mortality in men independently of age, PTH, HbA1c, waist circumference, 24-h systolic ambulatory-blood pressure (ABP) and serum-apoB (p = 0.049). This finding was also statistically significant when PWV and IMT were added to the analyses (p = 0.028) and was not affected statistically when medications were also included in the regression-analysis (p = 0.01). In the women with type 2 diabetes, levels of PTH were positively related with all-cause mortality in the corresponding calculations (p = 0.016 without PWV and IMT, p = 0.006 with PWV and IMT, p = 0.045 when also adding medications to the analysis), while levels of vitamin D was without statistical significance (p >0.9)., Conclusions: Serum vitamin D in men and serum PTH in women give prognostic information in terms of total-mortality that are independent of regular risk factors in addition to levels of ABP, IMT and PWV., Trial Registration: ClinicalTrials.gov: NCT01049737.

This study examined all group sexual offending cases in the Netherlands between 1995 and 2009 (n = 26) in which at least one juvenile female offender (n = 35) had been adjudicated. Information from court files showed that the majority of juvenile female group sexual offenders have (inter)personal problems and (sexual) abuse experiences. The aims of the offender groups in committing the offense could be categorized in three themes: harassing the victim, sexual gratification, and taking revenge. The reasons why juvenile female offenders participated in a group could be categorized into group dynamics versus instrumental reasons. The findings are contrasted with findings on juvenile male group sexual offenders. Implications of the findings for research and treatment are discussed., (© The Author(s) 2014.)

Aim: To explore risk factors for peripheral arterial disease (PAD) as well as the association between toe blood pressure and subclinical and clinical central vascular disease in patients with type 2 diabetes., Method: Toe brachial index (TBI) was cross-sectionally analyzed in 742 middle-aged (54-66 years) patients with type 2 diabetes as well as non-diabetic controls and related to other vascular measures (e.g. carotid intima media thickness (IMT), presence of carotid plaque, central arterial stiffness and left ventricular mass index) and previous cardiovascular events., Results: A TBI ≤ 0.7 was seen in 22% of the patients but only one patient had severe TBI reduction (TBI ≤ 0.3). The corresponding figures in the controls were 13% and 0%, respectively. Mean TBI was significantly lower in patients with type 2 diabetes than in controls (0.81 ± 0.14 vs. 0.87 ± 0.15, p<0.001). In patients with diabetes, a lower TBI was associated with increased central arterial stiffness (p<0.001), IMT (p<0.001) and carotid plaque (p<0.001) as well as with decreasing glomerular filtration rate (p<0.001). Lower TBI was found in patients with previous macrovascular ischemic events. Furthermore, TBI was negatively correlated with age (p<0.001), diabetes duration (p<0.001) and HbA1c (p=0.01)., Conclusion: PAD, assessed with TBI, is common in a Swedish middle-aged diabetes type 2 cohort, affecting about one-fifth. As ankle pressure may be confounded by falsely high values in patients with diabetes due to media calcification we conclude that information about TBI may improve the risk evaluation regarding arteriosclerotic disease in both small and large vessels in type 2 diabetes., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Both ambulatory and central blood pressures have been reported to correlate more closely than office blood pressure with left ventricular mass index (LVMI). The aim of this study was to test whether ambulatory systolic blood pressure (SBP) predicts LVMI independent of central SBP in patients with type 2 diabetes., Methods: We determined office, ambulatory, and central blood pressures and performed echocardiography in 460 patients with type 2 diabetes, who participated in the CARDIPP (Cardiovascular Risk factors in Patients with Diabetes - a Prospective study in Primary care) study (ClinicalTrials.gov number NCT 01049737)., Results: In separate multivariable regression models, 24-h ambulatory SBP, ambulatory day time SBP, and ambulatory night-time SBP were significantly associated with LVMI, independent of central SBP, age, sex, BMI, ambulatory 24-h heart rate, known duration of diabetes, and the presence or absence of any antihypertensive medications (r=0.19, 0.17, and 0.18, respectively, P<0.01). All ambulatory SBP parameters, but not central SBP, were significantly associated with LVMI independent of office SBP., Conclusion: Ambulatory SBP predicted LVMI independent of central SBP in patients with type 2 diabetes. The use of ambulatory blood pressure measurements may be encouraged as a tool for refined risk stratification of patients with type 2 diabetes.

Context: High resting blood pressure (BP) is among the best studied and established risk factors for cardiovascular disease. However, little is known about the relationship between BP under acute stress, such as in acute chest pain, and subsequent mortality., Objective: To study long-term mortality related to supine BP in patients admitted to the medical intensive care unit (ICU) for acute chest pain., Design, Setting, and Participants: Data from the RIKS-HIA (Registry of Information and Knowledge About Swedish Heart Intensive Care Admissions) was used to analyze the mortality in relation to supine admission systolic BP in 119,151 participants who were treated at the ICU for the symptom of chest pain from 1997 through 2007. Results from this prospective cohort study were presented according to systolic BP quartiles: Q1, less than 128 mm Hg; Q2, from 128 to 144 mm Hg; Q3, from 145 to 162 mm Hg; and Q4, at or above 163 mm Hg., Main Outcome Measure: Total mortality., Results: Mean (SD) follow-up time was 2.47 (1.5) years (range, 1-10 years). One-year mortality rate by Cox proportional hazard model (adjusted for age, sex, smoking, diastolic BP, use of antihypertensive medication at admission and discharge, and use of lipid-lowering and antiplatelet medication at discharge) showed that participants in Q4 had the best prognosis (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.72-0.80, Q4 compared with Q2; corresponding risks for Q1 were HR, 1.46; 95% CI, 1.39-1.52, and for Q3, HR, 0.83; 95% CI, 0.79-0.87). Patients in Q4 had a 21.7% lower absolute risk compared with Q2, patients in Q3 had a 15.2% lower risk than in Q2, and patients in Q1 had a 40.3% higher risk for mortality than in Q2. The worse prognosis in Q2 compared with Q4 was independent of body mass index and previous diagnoses and similar when analysis was restricted to patients with a final diagnosis of angina or myocardial infarction (HR, 0.75; 95% CI, 0.71-0.80, Q4 compared with Q2)., Conclusion: Among patients admitted to the ICU for chest pain, there is an inverse association between admission supine systolic BP and 1-year mortality rate.

Background: Intergenerational continuity in offending has been assessed in several studies. However, this has rarely been studied using more than two prospective generations. Also, within-gender and cross-gender effects have rarely been addressed. The evidence for mechanisms that may explain transmission is mixed., Method: Using conviction data on five generations (n = 6322) that span the years 1882-2007, transmission from parent to child was studied, disaggregating for males and females. Parental conviction before the birth of the child was studied separately from parental conviction after the birth of the child. Transmission was studied using odds ratios., Results: Parental convictions increase the risk of offspring convictions, although the risk increase is, at around two on average, not extremely high. Delinquency by the mother was also associated with offspring criminality, although because of low prevalence the odds ratios were more variable. Parental delinquency before birth does not lead to increased risk. For serious delinquency, these findings were stronger., Conclusions: The study suggests that nurture rather than hereditary or labelling mechanisms may play a role in intergenerational continuity.

The anaesthetic propofol interacts with the GABA(A) receptor, but its cellular signalling pathways are not fully understood. Propofol causes reorganisation of the actin cytoskeleton into ring structures in neurons. Is this reorganisation a specific effect of propofol as apposed to GABA, and which cellular pathways are involved? We used fluorescence-marked actin in cultured rat neurons to evaluate the percentage of actin rings caused by propofol or GABA in combination with rho, rho kinase (ROK), PI3-kinase or tyrosine kinase inhibitors, with or without the presence of extracellular calcium. Confocal microscopy was performed on propofol-stimulated cells and changes in actin between cellular compartments were studied with Western blot. Propofol (3 microg x ml-1), but not GABA (5 microM), caused transcellular actin ring formation, that was dependent on influx of extracellular calcium and blocked by rho, ROK, PI3-kinase or tyrosine kinase inhibitors. Propofol uses rho/ROK to translocate actin from the cytoskeleton to the membrane and its actin ring formation is dependent on an interaction site close to the GABA site on the GABA(A) receptor. GABA does not cause actin rings, implying that this is a specific effect of propofol.