Incidence trends in childhood onset IDDM in four countries around the Baltic sea during 1983-1992

Funding Information: Acknowledgements. This study was partly supported by theWe present secular trends of childhood onset insulin-dependent diabetes mellitus (IDDM) in Finland, Estonia, Latvia and Lithuania during the period of 1983-1992. Incidence data were obtained from the national IDDM registries. The average age-standardized incidence per 100,000/year was 35.0 in Finland, followed by 10.2 in Estonia, 7.1 in Lithuania and 6.5 in Latvia. A male excess in incidence was recorded in Finland (1.15) and Latvia (1.01). In all countries, the highest age-specific risk of IDDM was observed in the 11-13 year age range. The large difference in incidence between Finland and other Baltic countries was seen even in 1-2-year-old children. During the 10-year study period overall changes in incidence of IDDM were relatively small in these four countries. The incidence increased in Finland and Lithuania on average by 1% and 1.4% per year, respectively. A statistically significant increase was recorded only in 0-4 year old children in Finland, at 5.6% per year. In Estonia, an 8.3% increase in this age group, however, was not statistically significant The different trends in the age-group specific incidence rates were confirmed in Finland. In conclusion, from 1983 to 1992 the incidence of childhood onset IDDM was increasing in Finland and Lithuania, while in Latvia and Estonia it was stable. There are still great differences in IDDM incidence between the countries around the Baltic Sea.Peer reviewe

A genome-wide scan for type 1 diabetes susceptibility genes in nuclear families with multiple affected siblings in Finland

<p>Abstract</p> <p>Background</p> <p>A genome-wide search for genes that predispose to type 1 diabetes using linkage analysis was performed using 900 microsatellite markers in 70 nuclear families with affected siblings from Finland, a population expected to be more genetically homogeneous than others, and having the highest incidence of type 1 diabetes in the world and, yet, the highest proportion in Europe of cases (10%) carrying neither of the highest risk <it>HLA </it>haplotypes that include DR3 or DR4 alleles.</p> <p>Results</p> <p>In addition to the evidence of linkage to the <it>HLA </it>region on 6p21 (nominal p = 4.0 × 10^-6), significant evidence of linkage in other chromosome regions was not detected with a single-locus analysis. The two-locus analysis conditional on the <it>HLA </it>gave a maximum lod score (MLS) of 3.1 (nominal p = 2 × 10^-4) on chromosome 9p13 under an additive model; MLS of 2.1 (nominal p = 6.1 × 10^-3) on chromosome 17p12 and MLS of 2.5 (nominal p = 2.9 × 10^-3) on chromosome 18p11 under a general model.</p> <p>Conclusion</p> <p>Our genome scan data confirmed the primary contribution of the <it>HLA </it>genes also in the high-risk Finnish population, and suggest that non-<it>HLA </it>genes also contribute to the familial clustering of type 1 diabetes in Finland.</p

Adding free to total prostate-specific antigen levels in trials of prostate cancer screening

We used a nested case–control design on data from men in four prospective studies (from the UK, Maryland in the USA, and two from Finland) with available stored serum samples to determine whether there was an advantage in measuring both free prostate-specific antigen (PSA) and total PSA as a potential screening test for prostate cancer. Of these men, 247 were verified through national vital statistics offices as having died of prostate cancer, or having developed the disease, and 953 men who did not develop prostate cancer (controls) were selected, matched to cases for age, study centre and sample storage duration. Fixing the false-positive rate at 1%, the prostate cancer detection rate (sensitivity) over the 3 years following serum collection (based on 14 cancers) increased from an estimated 95% using total PSA to 97% using free and bound PSA (that is, bound to α-antichymotrypsin which together with the free form is total PSA). Over a 6-year period (based on 41 cancers) a similar difference occurred (52% and 56% detection rates respectively). We conclude that there is no material advantage in adding free to total PSA in prostate cancer screening trials. © 2000 Cancer Research Campaig

Central obesity as a precursor to the metabolic syndrome in the AusDiab study and Mauritius

Evidence from epidemiologic studies that central obesity precedes future metabolic change and does not occur concurrently with the appearance of the blood pressure, glucose, and lipid abnormalities that characterize the metabolic syndrome (MetS) has been lacking. Longitudinal surveys were conducted in Mauritius in 1987, 1992, and 1998, and in Australia in 2000 and 2005 (AusDiab). This analysis included men and women (aged 25 years) in three cohorts: AusDiab 2000&ndash;2005 (n = 5,039), Mauritius 1987&ndash;1992 (n = 2,849), and Mauritius 1987&ndash;1998 (n = 1,999). MetS components included waist circumference, systolic blood pressure, fasting and 2-h postload plasma glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, and homeostasis model assessment of insulin sensitivity (HOMA-S) (representing insulin sensitivity). Linear regression was used to determine which baseline components predicted deterioration in other MetS components over 5 years in AusDiab and 5 and 11 years in Mauritius, adjusted for age, sex, and ethnic group. Baseline waist circumference predicted deterioration (P &lt; 0.01) in four of the other six MetS variables tested in AusDiab, five of six in Mauritius 1987&ndash;1992, and four of six in Mauritius 1987&ndash;1998. In contrast, an increase in waist circumference between baseline and follow-up was only predicted by insulin sensitivity (HOMA-S) at baseline, and only in one of the three cohorts. These results suggest that central obesity plays a central role in the development of the MetS and appears to precede the appearance of the other MetS components.<br /

Deciphering the Role of Autophagy in Heart Failure

Peer reviewe

Diet, nutrition and the prevention of type 2 diabetes

Objectives: The overall objective of this study was to evaluate and provide evidence and recommendations on current published literature about diet and lifestyle in the prevention of type 2 diabetes. Design: Epidemiological and experimental studies, focusing on nutritional intervention in the prevention of type 2 diabetes are used to make disease-specific recommendations. Long-term cohort studies are given the most weight as to strength of evidence available. Setting and subjects: Numerous clinical trials and cohort studies in low, middle and high income countries are evaluated regarding recommendations for dietary prevention of type 2 diabetes. These include, among others, the Finnish Diabetes Prevention Study, US Diabetes Prevention Program, Da Qing Study; Pima Indian Study; Iowa Women’s Health Study; and the study of the US Male Physicians. Results: There is convincing evidence for a decreased risk of diabetes in adults who are physically active and maintain a normal body mass index (BMI) throughout adulthood, and in overweight adults with impaired glucose tolerance who lose weight voluntarily. An increased risk for developing type 2 diabetes is associated with overweight and obesity; abdominal obesity; physical inactivity; and maternal diabetes. It is probable that a high intake of saturated fats and intrauterine growth retardation also contribute to an increased risk, while non-starch polysaccharides are likely to be associated with a decreased risk. From existing evidence it is also possible that omega-3 fatty acids, low glycaemic index foods and exclusive breastfeeding may play a protective role, and that total fat intake and trans fatty acids may contribute to the risk. However, insufficient evidence is currently available to provide convincing proof. Conclusions: Based on the strength of available evidence regarding diet and lifestyle in the prevention of type 2 diabetes, it is recommended that a normal weight status in the lower BMI range (BMI 21–23) and regular physical activity be maintained throughout adulthood; abdominal obesity be prevented; and saturated fat intake be less than 7% of the total energy intake

TNF-α induces a pro-inflammatory phenotypic shift in monocytes through ACSL1 : Relevance to metabolic inflammation

Background/Aims: TNF-α-mediated pro-inflammatory phenotypic change in monocytes is known to be implicated in the pathogenesis of metabolic inflammation and insulin resistance. However, the mechanism by which TNF-α-induces inflammatory phenotypic shift in monocytes is poorly understood. Since long-chain acyl-CoA synthetase 1 (ACSL1) is associated with inflammatory monocytes/macrophages, we investigated the role of ACSL1 in the TNF-α-driven inflammatory phenotypic shift in the monocytes. Methods: Monocytes (Human monocytic THP-1 cells) were stimulated with TNF-α. Inflammatory phenotypic markers (CD16, CD11b, CD11c and HLA-DR) expression was determined with real time RT-PCR and flow cytometry. IL-1β and MCP-1 were determined by ELISA. Signaling pathways were identified by using ACSL1 inhibitor, ACSL1 siRNA and NF-κB reporter monocytic cells. Phosphorylation of NF-κB was analyzed by western blotting and flow cytometry. Results: Our data show that TNF-α induced significant increase in the expression of CD16, CD11b, CD11c and HLA-DR. Inhibition of ACSL1 activity in the cells with triacsin C significantly suppressed the expression of these inflammatory markers. Using ACSL-1 siRNA, we further demonstrate that TNF-α-induced inflammatory markers expression in monocytic cells requires ACSL1. In addition, IL-1b and MCP-1 production by TNF-α activated monocytic cells was significantly blocked by the inhibition of ACSL-1 activity. Interestingly, elevated NF-κB activity resulting from TNF-α stimulation was attenuated in ACSL1 deficient cells. Conclusion: Our findings provide an evidence that TNF-α-associated inflammatory polarization in monocytes is an ACSL1 dependent process, which indicates its central role in TNF-α-driven metabolic inflammation. © 2019 The Author(s).Peer reviewe

Relationship between baseline physical activity assessed by pedometer count and new-onset diabetes in the NAVIGATOR trial

Objective: Physical activity is related to clinical outcomes, even after adjusting for body mass, but is rarely assessed in randomized clinical trials. Research design and methods: We conducted an observational analysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research trial, in which a total of 9306 people from 40 countries with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors were randomized to receive nateglinide or placebo, in a 2-by-2 factorial design with valsartan or placebo. All were asked to also participate in a detailed lifestyle modification programme and followed-up for a median of 6.4 years with progression to diabetes as a co-primary end point. Seven-day ambulatory activity was assessed at baseline using research-grade pedometers. We assessed whether the baseline amount of physical activity was related to subsequent development of diabetes in individuals with impaired glucose tolerance. Results: Pedometer data were obtained on 7118 participants and 35.0% developed diabetes. In an unadjusted analysis each 2000-step increment in the average number of daily steps, up to 10 000, was associated with a 5.5% lower risk of progression to diabetes (HR 0.95, 95%CI 0.92 to 0.97), with >6% relative risk reduction after adjustment. Conclusions: Physical activity should be measured objectively in pharmacologic trials as it is a significant but underappreciated contributor to diabetes outcomes. It should be a regular part of clinical practice as well. © 2018 Author(s) (or their employer(s).Peer reviewe