Factors affecting the development of type 2 diabetes and cardiovascular disease, with special reference to vitamin D

There is increasing evidence that vitamin D may influence several non-skeletal conditions, including cardiovascular disease (CVD), diabetes, cancer, autoimmune disorders and infectious diseases. Vitamin D is among the few vitamins that can be produced by the skin in response to ultraviolet B radiation. Vitamin D is also a prohormone that is converted to 25-hydroxyvitamin D (25(OH)D) in the liver and 1,25-dihydroxyvitamin D (a hormone) in the kidneys. In addition, vitamin D receptors are present in most tissues and cells in the body. Many tissues and cells, including, colon, prostate, pancreatic β-cells and macrophages, express the enzyme 1α-hydroxylase to locally produce 1,25-dihydroxyvitamin D, which has the potential to regulate a number of genes. The pleiotropic effect of vitamin D may favorably influence diabetes and cardiovascular health through multiple mechanisms, including downregulation of the renin-angiotensin system, enhancement of insulin secretion and insulin sensitivity, protection against angiogenesis and modulation of inflammatory processes. Epidemiological evidence suggests that vitamin D may reduce the risk of developing type 2 diabetes (T2D) and CVD. However, so far, studies found mixed results and data have been inconclusive. We aimed to investigate: 1) Whether low serum 25(OH)D concentrations predict the development of prediabetes and T2D; 2) The relationships between serum 25(OH)D concentration and established or emerging cardiovascular risk factors and risk of myocardial infarction (MI); 3) Serum 25(OH)D in relation to baseline severity and rate of progression of carotid intima-media thickness (cIMT); and 4) Whether vitamin D is causally implicated in CVD using vitamin D-associated genetic variants, serum 25(OH)D concentration and progression of subclinical carotid atherosclerosis. In Paper I, subjects aged 35-56 years, without known T2D, underwent a health examination, including measurements of weight, height and blood pressure (BP), an oral glucose tolerance test (OGTT) was performed, and questionnaires covering life-style factors were answered at baseline and at follow-up. Serum 25(OH)D and serum insulin growth factor peptides were measured at baseline. Participants having prediabetes or T2D at follow-up 8-10 years later were selected as cases, age- and sex-matched to controls with normal glucose tolerance at both baseline and follow-up, in total 980 women and 1398 men. We found that high serum 25(OH)D concentrations predict reduced T2D risk in subjects having prediabetes but not in subjects with normal glucose tolerance. In Paper II, a total of 387 survivors of a first MI before the age of 60 and 387 sex- and age-matched controls were examined. Fasting blood samples, drawn three months after MI in cases and at the same time in matched controls, were used for biochemical analyses. Low 25(OH)D levels were associated with a range of cardiovascular risk factors but were not related to MI. Both Paper III and IV are based on the IMPROVE study, which is a European, multicentre, longitudinal cohort study that enrolled individuals aged 54 to 80 years, who had at least three cardiovascular risk factors and no history of CVD, from 7 centers in Finland, Sweden, the Netherlands, France, and Italy. Participants underwent carotid ultrasound examinations at baseline, month 15 and month 30. Blood samples, clinical data and information about life-style factors were collected at baseline from a total of 3,711 subjects, upwards of 900 of whom had diabetes. The results reported in Paper III demonstrated that levels of 25(OH)D differed across Europe and were not consistently, independently related to measures of cIMT. In Paper IV, we found one genetic variant (rs3829251) in the DHCR7 (7-dehydrocholesterol reductase) gene which influenced progression of cIMT in a manner dependent on T2D status but independent of 25(OH)D levels

Correction to: Severity of depression, anxious distress and the risk of type 2 diabetes - a population-based cohort study in Sweden

Abstract It was highlighted that the original article [1] contained an error in the flow chart in Fig. 1

Направления реализации образовательно-профилактической программы "Здоровую улыбку - детям" и их эффективность

СТОМАТОГНАТИЧЕСКИЕ БОЛЕЗНИ /профЗУБНЫХ БОЛЕЗНЕЙ ПРОФИЛАКТИКАДЕТИПРОФИЛАКТИЧЕСКАЯ СТОМАТОЛОГИ

Whole-genome informed circulating tumor DNA analysis by multiplex digital PCR for disease monitoring in B-cell lymphomas: a proof-of-concept study

IntroductionAnalyzing liquid biopsies for tumor-specific aberrations can facilitate detection of measurable residual disease (MRD) during treatment and at follow-up. In this study, we assessed the clinical potential of using whole-genome sequencing (WGS) of lymphomas at diagnosis to identify patient-specific structural (SVs) and single nucleotide variants (SNVs) to enable longitudinal, multi-targeted droplet digital PCR analysis (ddPCR) of cell-free DNA (cfDNA).MethodsIn 9 patients with B-cell lymphoma (diffuse large B-cell lymphoma and follicular lymphoma), comprehensive genomic profiling at diagnosis was performed by 30X WGS of paired tumor and normal specimens. Patient-specific multiplex ddPCR (m-ddPCR) assays were designed for simultaneous detection of multiple SNVs, indels and/or SVs, with a detection sensitivity of 0.0025% for SV assays and 0.02% for SNVs/indel assays. M-ddPCR was applied to analyze cfDNA isolated from serially collected plasma at clinically critical timepoints during primary and/or relapse treatment and at follow-up.ResultsA total of 164 SNVs/indels were identified by WGS including 30 variants known to be functionally relevant in lymphoma pathogenesis. The most frequently mutated genes included KMT2D, PIM1, SOCS1 and BCL2. WGS analysis further identified recurrent SVs including t(14;18)(q32;q21) (IGH::BCL2), and t(6;14)(p25;q32) (IGH::IRF4). Plasma analysis at diagnosis showed positive circulating tumor DNA (ctDNA) levels in 88% of patients and the ctDNA burden correlated with baseline clinical parameters (LDH and sedimentation rate, p-value <0.01). While clearance of ctDNA levels after primary treatment cycle 1 was observed in 3/6 patients, all patients analyzed at final evaluation of primary treatment showed negative ctDNA, hence correlating with PET-CT imaging. One patient with positive ctDNA at interim also displayed detectable ctDNA (average variant allele frequency (VAF) 6.9%) in the follow-up plasma sample collected 2 years after final evaluation of primary treatment and 25 weeks before clinical manifestation of relapse.ConclusionIn summary, we demonstrate that multi-targeted cfDNA analysis, using a combination of SNVs/indels and SVs candidates identified by WGS analysis, provides a sensitive tool for MRD monitoring and can detect lymphoma relapse earlier than clinical manifestation

Treatment pattern of contemporary dual antiplatelet therapies after acute coronary syndrome: a Swedish nationwide population based cohort study.

New dual antiplatelet therapies (DAPTs) have been introduced in clinical practice for patients with acute coronary syndrome (ACS). This nationwide study investigated DAPT patterns over time and patient characteristics associated with the various treatments in a population with ACS

Ten years with biosimilar rhGH in clinical practice in Sweden : experience from the prospective PATRO children and adult studies

Background: In 2007, Omnitrope (R) was the first biosimilar recombinant human growth hormone (rhGH) to be approved in Sweden for treatment in adults and children. Over 10 years' safety and effectiveness data for biosimilar rhGH can now be presented. Methods: PATRO Children and PATRO Adults are multicenter, longitudinal, observational, post-marketing surveillance studies. Eligible patients include children 0-18 years and adults receiving biosimilar rhGH treatment. Adverse events (AEs) are monitored for safety evaluation. Growth variables in children and metabolic data in adults are recorded for effectiveness evaluation. Results: As of January 2019, data from 136 children (48% male) were reported from Swedish centers. Mean age in rhGH treatment-naive patients at study entry (n = 114) was 7.5 years, with mean 3.6 years treatment duration. No severe AEs of diabetes, impaired glucose tolerance, or malignancy were reported. The most frequently reported AE was nasopharyngitis (n = 16 patients). No clinically relevant anti-hGH or neutralizing antibodies were observed. The mean change from baseline in height standard deviation score (SDS) in naive prepubertal GH deficiency patients was + 0.79 at 1 year, + 1.27 at 2 years, and + 1.55 at 3 years. Data from 293 adults (44% rhGH-naive, 51% male) were included. Fatigue was the most frequently reported AE (n = 26 patients). The incidence of new neoplasms or existing neoplasm progression was 23.8 patients per 1000 patient-years. Type 2 diabetes mellitus was reported in four patients. At baseline in rhGH-naive adults, mean (SD) body mass index (BMI) was 29.1 (5.6) kg/m(2) and mean (SD) insulin-like growth factor (IGF)-I SDS was - 3.0 (1.4). Mean daily dose increased from 0.1 mg at baseline to 0.3 mg after 4 years. IGF-I SDS normalized during the first year of treatment. Mean BMI and glucose were unchanged over 4 years, while low-/high-density lipoprotein cholesterol ratio decreased. Conclusions: For the first time, Swedish data from the PATRO Children and Adults studies are presented. The 10-year data suggest that biosimilar rhGH is well tolerated across pediatric and adult indications. Safety and effectiveness were similar to previous reports for other rhGH preparations. These results need to be confirmed in larger cohorts, highlighting the importance of long-term post-marketing studies

Impact of symptomatic hypoglycemia on medication adherence, patient satisfaction with treatment, and glycemic control in patients with type 2 diabetes

Background: The purpose of this study was to evaluate the impact of symptomatic hypoglycemia on medication adherence, satisfaction with treatment, and glycemic control in patients with type 2 diabetes based on the treatment goals stated in the Swedish national guidelines. Methods: This cross-sectional, multicenter study was carried out between January and August 2009 in 430 consecutive primary health care patients on stable doses of metformin and sulfonylureas for at least 6 months. The patients completed questionnaires covering their experiences of low blood glucose and adherence, as well as barriers to and satisfaction with drug treatment (using the Treatment Satisfaction Questionnaire for Medication). Physicians collected the data from medical records. Results: Patients who experienced moderate or worse symptoms of hypoglycemia reported poorer adherence to medication (46% versus 67%; P less than 0.01) and were more likely to perceive barriers such as "bothered by medication side effects" (36% versus 14%; P less than 0.001) compared with patients with no or mild symptoms. Patients with moderate or worse symptoms of hypoglycemia were less satisfied with their treatment than those with no or mild symptoms as determined by the Treatment Satisfaction Questionnaire for Medication-Global satisfaction (67.0 versus 71.2; P less than 0.05). Overall, achievement of target glycated hemoglobin (HbA(1c)) based on the treatment goals stated in the Swedish national guidelines was 40%. Despite poorer adherence, patients who experienced moderate or worse symptoms of hypoglycemia had lower mean HbA(1c) values than patients with no or mild symptoms (7.0% versus 7.3% [Diabetes Control and Complications Trial standard]; P less than 0.05). Conclusion: Symptomatic hypoglycemia in patients with type 2 diabetes on metformin and sulfonylureas was associated with nonadherence and decreased treatment satisfaction despite lower mean HbA(1c) values. A broader understanding of patient preferences and self-reported outcomes could improve the management of patients with type 2 diabetes

Clinical factors associated with initiation of and persistence with ADP receptor-inhibiting oral antiplatelet treatment after acute coronary syndrome: a nationwide cohort study from Finland

OBJECTIVES: To study patient selection for and persistence with ADP receptor-inhibiting oral antiplatelet (OAP) treatment after acute coronary syndrome (ACS). DESIGN: Observational, retrospective, cohort study linking real-life patient-level register data. SETTING: Nationwide drug usage study using data of patients with ACS discharged from hospitals in Finland. PARTICIPANTS: The study population consisted of 54 416 patients (aged ≥18 years) following hospital admission for unstable angina pectoris or myocardial infarction during 2009–2013. Patients were classified as either OAP or non-OAP users based on drug purchases within 7 days of discharge. OUTCOME MEASURES: Initiation of and a 12-month persistence with OAP medication. RESULTS: In total, 49% of patients with ACS received OAP treatment after hospital discharge. Women represented 40% of the population, but only 32% of them became OAP users (adjusted OR for initiation compared with men 0.8; p<0.001). Patients not treated with percutaneous coronary intervention (PCI), elderly and patients with dementia/Alzheimer's disease, atrial fibrillation or warfarin treatment were less likely to be treated with OAP. If initiated, they were less likely to complete the recommended 12 months’ medication (adjusted risk increment >38% and p<0.001 for all). The OAP users showed good compliance with immediate initiation (92% within 1 day of discharge) and high mean medication possession rate (99%). Among OAP users, the usage of other secondary prevention drugs after ACS was more common than in non-OAP-treated patients (difference >20 percentage points for each). CONCLUSIONS: Only half of the patients with ACS received guideline-recommended ADP receptor-inhibiting OAP treatment after hospital discharge, suggesting suboptimal treatment practices. Non-PCI-treated patients and patients with increased age, unstable angina, dementia or atrial fibrillation appear to have the highest risk of deficient treatment with OAPs. OAP users, however, showed good compliance during drug usage