Higher pulse wave velocity in young adult offspring of mothers with type 1 diabetes : a case-control study

Background Offspring of mothers with type 1 diabetes have an increased risk for acquiring early onset cardiovascular disease (CVD). Arterial stiffness, measured as pulse wave velocity (PWV), is a non-invasive biomarker for CVD risk assessment. Our aim is to determine whether PWV is increased in young adult offspring of mothers with type 1 diabetes. Methods This is a case-control study carried out in the hospital district of Helsinki and Uusimaa, Finland. 75 offspring of mothers with type 1 diabetes (cases) and 84 offspring of mothers without diabetes (controls), aged 18-23 years, were enrolled in this study. All participants attended clinical assessments, including questionnaires and laboratory tests. Carotid-femoral PWV (cfPWV), carotid-radial PWV (crPWV), and PWV ratio were measured from each participant using the Complior Analyse mechanotransducer (Alam Medical, France). Student's t-test and chi-squared test were used to assess differences between the groups. Stata 17.0, StataCorp LP (College Station, TX, USA) statistical package was used for the analysis. Results We did not observe any differences in conventional CVD risk factors: systolic blood pressure, LDL, Hb(A1c), and smoking between cases and controls. We detected higher cfPWV in cases 6.5 (SD +/- 1.2) m/s than in controls 6.2 (SD +/- 0.7) m/s, p = 0.049, after adjustments for BMI, smoking, mean arterial pressure, height, and pulse rate was made. We did not observe any difference between cases and controls regarding crPWV or PWV ratio. Additionally, we detected no sex differences. Conclusions We report a novel finding of signs of increased arterial stiffness already in young adult offspring of mothers with type 1 diabetes compared to matched offspring of mothers without diabetes. Our finding suggests that exposure to an adverse intrauterine environment of type 1 diabetes mothers may affect the vascular health of offspring already in young adulthood. Additional research within this topic is warranted.Peer reviewe

Low-cost exercise interventions improve long-term cardiometabolic health independently of a family history of type 2 diabetes : a randomized parallel group trial

Introduction To investigate the effect of an exercise prescription and a 1-year supervised exercise intervention, and the modifying effect of the family history of type 2 diabetes (FH), on long-term cardiometabolic health. Research design and methods For this prospective randomized trial, we recruited non-diabetic participants with poor fitness (n=1072, 30-70 years). Participants were randomly assigned with stratification for FH either in the exercise prescription group (PG, n=144) or the supervised exercise group (EG, n=146) group and compared with a matched control group from the same population study (CON, n=782). The PG and EG received exercise prescriptions. In addition, the EG attended supervised exercise sessions two times a week for 60 min for 12 months. Cardiometabolic risk factors were measured at baseline, 1 year, 5 years, and 6 years. The CON group received no intervention and was measured at baseline and 6 years. Results The EG reduced their body weight, waist circumference, diastolic blood pressure, and low-density lipoprotein-cholesterol (LDL-C) but not physical fitness (p=0.074) or insulin or glucose regulation (p>0.1) compared with the PG at 1 year and 5 years (p Conclusions Low-cost physical activity programs have long-term beneficial effects on cardiometabolic health regardless of the FH of diabetes. Given the feasibility and low cost of these programs, they should be advocated to promote cardiometabolic health.Peer reviewe

Power of lower extremities and age were the main determinants on the agility test for adults in a cohort of men aged 66-91 years

Study Design: Cross-sectional study. Objective: To evaluate the relationship between agility and personal factors, muscle strength and power, mobility, self-reported balance and physical activity among older men. Methods: Agility was measured by using the Agility Test for Adults (ATA). We studied 100 Finnish male former elite athletes (endurance n = 50; power n = 50) and 50 matched controls aged 66 to 91 years (mean age 75.5 years). The associations between agility and other variables were similar between three groups; thus, multiple linear regression analyses were done by using the pooled data of the participants. Results: On the basis of multiple linear regression analyses, combination of age (p = .02), self-reported Activities-specific Balance Confidence scale (ABC scale), jumping height (p = .001) and self-rated health explained 26% of the variance in execution time of ATA (R-2 = 0.26; p = .000002) among elderly men. Conclusion: Power of lower extremities and age were the main determinants of the results of ATA in a cohort of men aged 66-91 years. From a clinical point of view, power of lower extremities measured by test demanding explosive power plays an important role to maintain or enhance capacity of agility.Peer reviewe

Early exposure to social disadvantages and later life body mass index beyond genetic predisposition in three generations of Finnish birth cohorts

BackgroundThe study aimed to explore the association between early life and life-course exposure to social disadvantage and later life body mass index (BMI) accounting for genetic predisposition and maternal BMI.MethodsWe studied participants of Helsinki Birth Cohort Study born in 1934-1944 (HBCS1934-1944, n=1277) and Northern Finland Birth Cohorts born in 1966 and 1986 (NFBC1966, n=5807, NFBC1986, n=6717). Factor analysis produced scores of social disadvantage based on social and economic elements in early life and adulthood/over the life course, and was categorized as high, intermediate and low. BMI was measured at 62years in HBCS1934-1944, at 46years in NFBC1966 and at 16years in NFBC1986. Multivariable linear regression analysis was used to explore associations between social disadvantages and BMI after adjustments for polygenic risk score for BMI (PRS BMI), maternal BMI and sex.ResultsThe association between exposure to high early social disadvantage and increased later life BMI persisted after adjustments (beta =0.79, 95% CI, 0.33, 1.25, p 0.22, 95% CI -0.91,1.35, p=0.700). In HBCS1934-1944 and NFBC1966, participants who had reduced their exposure to social disadvantage during the life-course had lower later life BMI than those who had increased their exposure (beta -1.34, [-2.37,-0.31], p=0.011; beta -0.46, [-0.89,-0.03], p=0.038, respectively).ConclusionsHigh social disadvantage in early life appears to be associated with higher BMI in later life. Reducing exposure to social disadvantage during the life-course may be a potential pathway for obesity reduction.Peer reviewe

Overexpression of cathepsin f, matrix metalloproteinases 11 and 12 in cervical cancer

BACKGROUND: Cervical carcinoma (CC) is one of the most common cancers among women worldwide and the first cause of death among the Mexican female population. CC progression shows a continuum of neoplastic transitions until invasion. Matrix metalloproteinases (MMPs) and cathepsins play a central role on the enhancement of tumor-induced angiogenesis, cell migration, proliferation, apoptosis and connective tissue degradation. MMPs -2 and -9 expression has been widely studied in cervical cancer. Nevertheless, no other metalloproteinases or cathepsins have been yet related with the progression and/or invasion of this type of cancer. METHODS: Three HPV18 CC cell lines, two HPV16 CC cell lines and three HPV16 tumor CC tissues were compared with three morphologically normal, HPV negative, cervical specimens by cDNA arrays. Overexpression of selected genes was confirmed by end point semiquantitative reverse transcription-PCR with densitometry. In situ hybridization and protein expression of selected genes was further studied by means of two tissue microarrays, one consisting of 10 HSIL and 15 CC and the other one of 15 normal cervical and 10 LSIL tissues. RESULTS: TIMP1, Integrins alpha 1 and 4, cadherin 2 and 11, Cathepsins F, B L2, MMP 9, 10 11 and 12 were upregulated and Cathepsin S, L, H and C, Cadherins 3 and 4, TIMP3, MMP 13, Elastase 2 and Integrin beta 8 were found to be downregulated by cDNA arrays. Endpoint RT-PCR with densitometry gave consistent results with the cDNA array findings for all three genes selected for study (CTSF, MMP11 and MMP12). In situ hybridization of all three genes confirmed overexpression in all the HSIL and CC. Two of the selected proteins were detected in LSIL, HSIL and CC by immunohistochemistry. CONCLUSION: Novel undetected CC promoting genes have been identified. Increased transcription of these genes may result in overexpression of proteins, such as CTSF, MMP11 and MMP12 which could contribute to the pathogenesis of CC

Identification of ChIP-seq mapped targets of HP1β due to bombesin/GRP receptor activation

Epithelial cells lining the adult colon do not normally express gastrin-releasing peptide (GRP) or its receptor (GRPR). In contrast, GRP/GRPR can be aberrantly expressed in human colorectal cancer (CRC) including Caco-2 cells. We have previously shown that GRPR activation results in the up-regulation of HP1β, an epigenetic modifier of gene transcription. The aim of this study was to identify the genes whose expression is altered by HP1β subsequent to GRPR activation. We determined HP1β binding positions throughout the genome using chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq). After exposure to GRP, we identified 9,625 genomic positions occupied by HP1β. We performed gene microarray analysis on Caco-2 cells in the absence and presence of a GRPR specific antagonist as well as siRNA to HP1β. The expression of 97 genes was altered subsequent to GRPR antagonism, while the expression of 473 genes was altered by HP1β siRNA exposure. When these data were evaluated in concert with our ChIP-seq findings, 9 genes showed evidence of possible altered expression as a function of GRPR signaling via HP1β. Of these, genomic PCR of immunoprecipitated chromatin demonstrated that GRPR signaling affected the expression of IL1RAPL2, FAM13A, GBE1, PLK3, and SLCO1B3. These findings provide the first evidence by which GRPR aberrantly expressed in CRC might affect tumor progression

Early exposure to social disadvantages and later life body mass index beyond genetic predisposition in three generations of Finnish birth cohorts

BackgroundThe study aimed to explore the association between early life and life-course exposure to social disadvantage and later life body mass index (BMI) accounting for genetic predisposition and maternal BMI.MethodsWe studied participants of Helsinki Birth Cohort Study born in 1934-1944 (HBCS1934-1944, n=1277) and Northern Finland Birth Cohorts born in 1966 and 1986 (NFBC1966, n=5807, NFBC1986, n=6717). Factor analysis produced scores of social disadvantage based on social and economic elements in early life and adulthood/over the life course, and was categorized as high, intermediate and low. BMI was measured at 62years in HBCS1934-1944, at 46years in NFBC1966 and at 16years in NFBC1986. Multivariable linear regression analysis was used to explore associations between social disadvantages and BMI after adjustments for polygenic risk score for BMI (PRS BMI), maternal BMI and sex.ResultsThe association between exposure to high early social disadvantage and increased later life BMI persisted after adjustments (beta = 0.79, 95% CI, 0.33, 1.25, pConclusionsHigh social disadvantage in early life appears to be associated with higher BMI in later life. Reducing exposure to social disadvantage during the life-course may be a potential pathway for obesity reduction.</div