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Type 2 diabetes mellitus (t2dm) and prediabetes are age-related: Results from the senior labor study
Abstracts
expression regarding regulation of transcription and translation. Working along this line we were able to identify several hundred genes which show age-dependent changes in gene expression. Candidate genes were next analyzed by quantitative RT-PCR, Western blotting and ELISA. Preliminary results indicated that, both at the transcriptional and translational level, the Leptin Receptor/CD295 as well as the Insulin-like Growth Factor Binding Protein 3 (IGBP3) are increased with age whereas High Temperature Requirement serine peptidase 3 (HTRA3) is being decreased. The here presented transcriptomic/translatomic method is a novel way of assessing cellular agingrelated changes. It efficiently enables gaining a comprehensive view of gene and protein expression and moreover allows appreciating further aspects of the regulatory complexity thereof.
doi:10.1016/j.exger.2015.01.014
Type 2 diabetes mellitus (t2dm) and prediabetes are age-related: Results from the senior labor study Pedro Medina, Zeno Stanga, Urs Nydegger, Martin Risch, Lorenz Risch Labormedizinisches zentrum Dr. Risch, Bern-Liebefeld, Switzerland University Hospital Inselspital Bern, Switzerland Zentrallabor Kantonsspital Graubünden, Chur, Switzerland Private University Triesen, Liechtenstein Introduction: The aging organism is confronted with reduced glucose disposal hence to metabolize carbohydrates due, at least in part, to increased insulin-resistance. Type 2 Diabetes Mellitus (T2DM) and its precursor condition prediabetes (PreD) are the consequence. The extent of impairment is now conveniently expressed with HOMA-IR cut-offs (homeostasis model assessment of insulin resistance). Decrease in adiponectin concentration, along with obesity, IR and glucose transporter (GLUT1) expression, are predictors for the metabolic syndrome as part of inflammaging. Procedures: The Senior Labor Study has so far recruitet over 1600 subjectively healthy Caucasian inhabitants ≥ 60 years of age. Venous blood samples were drawn after an overnight fasting period. HbA1c was measured by IFCC approved chromatography (HPLC D-10, Biorad, Reinach, Switzerland) and fasting plasma glucose (FPG) was measured using an enzymatic hexokinase procedure on the Roche Integra 800 (Rotkreuz, Switzerland). The present American Diabetes Association (ADA) cut-offs for diagnosis of PreD (HbA1c 5.7–6.4%, FPG 5.6–6.9 mmol/L) and T2DM (HbA1c ≥6.4%, FPG ≥7.0 mmol/L) were applied. According to the ADA criteria for the diagnosis of T2DM the following cut-off points were applied: HbA1c: ≥6.5%or FBG: ≥7.0 mmol/L. Results: Of 448 individuals with normal HbA1c (33.04% [95% CI: 30.59; 35.59]), we found 369 participants (82.4% [95% CI: 78.56; 85.61]) who had a normal FPG, 77 participants (17.2% [95% CI: 13.98; 20.96]) were displaying a prediabetic FPG, and 2 participants (0.45% [95% CI: 0.14; 1.60]) had a diabetic state according to the FPG. Of the 803 participants with a prediabetic HbA1c (59.22% [95% CI: 56.6; 61.8]), we found 547 subjects (68.1%; [95% CI: 64.81; 71.25]) who had a normal FPG, 250 subjects (31.1% [95% CI: 28.02; 34.42]) were displaying a prediabetic FPG, and 6 subjects (0.74% [95% CI: 0.35; 1.61]) had a diabetic state according to the FPG. In 1269 partakers, the HOMA-IR oscillated between 0.5 and 10.4. Conclusion: With the conviction that prediabetes heralds T2DM within the quinquennium following its detection, our study purports a high rate of advanced glycation with long-lived cells (nerves, brain cells) and long-lasting proteins (retina photoreceptors and insulinproducing beta cells) impairing their functional performance. Besides the clinical interest to prevent T2DM by screening for prediabetes,
95
we hope basic research will help to elucidate age-related increments in IR. A high prevalence of prediabetes is seen in the elderly.
doi:10.1016/j.exger.2015.01.015
HIV infection is independently associated with frailty in middle-aged HIV-infected individuals compared to uninfected controls K.W. Kooija, F.W.N.M. Wita,c, J. Schoutena,b, M. van der Valkc, I. Stolted, P. Reissa,c,e, on behalf of the AGEhIV Cohort Study Group a Department of Global Health, Academic Medical Center and Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands b Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands c Division of Infectious diseases, Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands d Public Health Service Amsterdam, Infectious Diseases Research, Amsterdam, The Netherlands e HIV Monitoring Foundation, Amsterdam, The Netherlands Background: Frailty is an age-related syndrome of decreased reserve and resistance to stressors, and has been associated with increased morbidity and mortality in the general population. Chronic inflammation may contribute to its development. An increased prevalence of frailty has been reported amongst HIV-infected individuals. Methods: Frailty was systematically assessed in a standardized manner in HIV-infected and otherwise comparable HIV-uninfected participants aged ≥45 years at enrolment into the AGEhIV cohort study in Amsterdam. Frailty was defined as the presence of ≥3 out of 5 factors, pre-frailty as 1–2 out of 5: 1) unintentional weight loss, 2) low physical activity, 3) exhaustion (each by self-report), 4) time to walk 4.57 m and 5) grip-strength (each within the lowest quintile observed for the combined study population). We examined whether HIV and HIVrelated characteristics were independently associated with pre-frailty and frailty by multivariable ordinal logistic regression, adjusted for potential confounders. Biologically plausible interactions were explored. Results: Data were analyzed from 570 HIV-infected and 539 HIVuninfected individuals. Overall median age was 52.4 years, 86.3% were male; median BMI in HIV-negatives and HIV-positives was 24.2 and 24.5 kg/m2 (p = 0.02). Median known duration of HIV infection was 11.9 years. 94.6% of HIV-infected were currently on cART, of whom 96.7% had undetectable HIV-1 RNA (b40 c/mL). Prevalence rates of frailty (11.1% vs. 3.2%) and pre-frailty (50.5% vs. 36.2%) were significantly higher in HIV-infected individuals (p b 0.001). HIV-infected individuals scored significantly worse for all 5 factors. HIV infection remained statistically significantly associated with (pre-)frailty after adjustment for potentially confounding determinants (Table 1). Gender, region of origin, other comorbidity than mentioned in the table, heavy alcohol intake or IDU were not associated. Soluble (s)CD163, but not hs-CRP, D-dimer or sCD14, was associated with (pre-)frailty. Lower BMI was associated with (pre-)frailty in HIV-infected, but not in HIV-uninfected individuals (p(interaction) = 0.005). Within the HIV-positives, duration of having CD4 b 200/mm3, but not nadir CD4 count or history of AIDS, was associated with (pre-)frailty (OR 1.17/year, 95% CI 1.03–1.33). This association no longer remained significant following adjustment for lowest ever recorded BMI or weight loss N5 kg, and duration of protease inhibitor (PI) use (Table 2). Conclusions: HIV infection was independently associated with a higher prevalence of frailty and pre-frailty in middle-aged HIVinfected patients compared to HIV-uninfected controls. The observed independent association amongst HIV-positives with ever recorded lowest BMI or weight loss, rather than indicators of immunodeficiency, could be indicative of HIV-associated wasting being the more important driver of frailty development in HIV.
expression regarding regulation of transcription and translation. Working along this line we were able to identify several hundred genes which show age-dependent changes in gene expression. Candidate genes were next analyzed by quantitative RT-PCR, Western blotting and ELISA. Preliminary results indicated that, both at the transcriptional and translational level, the Leptin Receptor/CD295 as well as the Insulin-like Growth Factor Binding Protein 3 (IGBP3) are increased with age whereas High Temperature Requirement serine peptidase 3 (HTRA3) is being decreased. The here presented transcriptomic/translatomic method is a novel way of assessing cellular agingrelated changes. It efficiently enables gaining a comprehensive view of gene and protein expression and moreover allows appreciating further aspects of the regulatory complexity thereof.
doi:10.1016/j.exger.2015.01.014
Type 2 diabetes mellitus (t2dm) and prediabetes are age-related: Results from the senior labor study Pedro Medina, Zeno Stanga, Urs Nydegger, Martin Risch, Lorenz Risch Labormedizinisches zentrum Dr. Risch, Bern-Liebefeld, Switzerland University Hospital Inselspital Bern, Switzerland Zentrallabor Kantonsspital Graubünden, Chur, Switzerland Private University Triesen, Liechtenstein Introduction: The aging organism is confronted with reduced glucose disposal hence to metabolize carbohydrates due, at least in part, to increased insulin-resistance. Type 2 Diabetes Mellitus (T2DM) and its precursor condition prediabetes (PreD) are the consequence. The extent of impairment is now conveniently expressed with HOMA-IR cut-offs (homeostasis model assessment of insulin resistance). Decrease in adiponectin concentration, along with obesity, IR and glucose transporter (GLUT1) expression, are predictors for the metabolic syndrome as part of inflammaging. Procedures: The Senior Labor Study has so far recruitet over 1600 subjectively healthy Caucasian inhabitants ≥ 60 years of age. Venous blood samples were drawn after an overnight fasting period. HbA1c was measured by IFCC approved chromatography (HPLC D-10, Biorad, Reinach, Switzerland) and fasting plasma glucose (FPG) was measured using an enzymatic hexokinase procedure on the Roche Integra 800 (Rotkreuz, Switzerland). The present American Diabetes Association (ADA) cut-offs for diagnosis of PreD (HbA1c 5.7–6.4%, FPG 5.6–6.9 mmol/L) and T2DM (HbA1c ≥6.4%, FPG ≥7.0 mmol/L) were applied. According to the ADA criteria for the diagnosis of T2DM the following cut-off points were applied: HbA1c: ≥6.5%or FBG: ≥7.0 mmol/L. Results: Of 448 individuals with normal HbA1c (33.04% [95% CI: 30.59; 35.59]), we found 369 participants (82.4% [95% CI: 78.56; 85.61]) who had a normal FPG, 77 participants (17.2% [95% CI: 13.98; 20.96]) were displaying a prediabetic FPG, and 2 participants (0.45% [95% CI: 0.14; 1.60]) had a diabetic state according to the FPG. Of the 803 participants with a prediabetic HbA1c (59.22% [95% CI: 56.6; 61.8]), we found 547 subjects (68.1%; [95% CI: 64.81; 71.25]) who had a normal FPG, 250 subjects (31.1% [95% CI: 28.02; 34.42]) were displaying a prediabetic FPG, and 6 subjects (0.74% [95% CI: 0.35; 1.61]) had a diabetic state according to the FPG. In 1269 partakers, the HOMA-IR oscillated between 0.5 and 10.4. Conclusion: With the conviction that prediabetes heralds T2DM within the quinquennium following its detection, our study purports a high rate of advanced glycation with long-lived cells (nerves, brain cells) and long-lasting proteins (retina photoreceptors and insulinproducing beta cells) impairing their functional performance. Besides the clinical interest to prevent T2DM by screening for prediabetes,
95
we hope basic research will help to elucidate age-related increments in IR. A high prevalence of prediabetes is seen in the elderly.
doi:10.1016/j.exger.2015.01.015
HIV infection is independently associated with frailty in middle-aged HIV-infected individuals compared to uninfected controls K.W. Kooija, F.W.N.M. Wita,c, J. Schoutena,b, M. van der Valkc, I. Stolted, P. Reissa,c,e, on behalf of the AGEhIV Cohort Study Group a Department of Global Health, Academic Medical Center and Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands b Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands c Division of Infectious diseases, Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands d Public Health Service Amsterdam, Infectious Diseases Research, Amsterdam, The Netherlands e HIV Monitoring Foundation, Amsterdam, The Netherlands Background: Frailty is an age-related syndrome of decreased reserve and resistance to stressors, and has been associated with increased morbidity and mortality in the general population. Chronic inflammation may contribute to its development. An increased prevalence of frailty has been reported amongst HIV-infected individuals. Methods: Frailty was systematically assessed in a standardized manner in HIV-infected and otherwise comparable HIV-uninfected participants aged ≥45 years at enrolment into the AGEhIV cohort study in Amsterdam. Frailty was defined as the presence of ≥3 out of 5 factors, pre-frailty as 1–2 out of 5: 1) unintentional weight loss, 2) low physical activity, 3) exhaustion (each by self-report), 4) time to walk 4.57 m and 5) grip-strength (each within the lowest quintile observed for the combined study population). We examined whether HIV and HIVrelated characteristics were independently associated with pre-frailty and frailty by multivariable ordinal logistic regression, adjusted for potential confounders. Biologically plausible interactions were explored. Results: Data were analyzed from 570 HIV-infected and 539 HIVuninfected individuals. Overall median age was 52.4 years, 86.3% were male; median BMI in HIV-negatives and HIV-positives was 24.2 and 24.5 kg/m2 (p = 0.02). Median known duration of HIV infection was 11.9 years. 94.6% of HIV-infected were currently on cART, of whom 96.7% had undetectable HIV-1 RNA (b40 c/mL). Prevalence rates of frailty (11.1% vs. 3.2%) and pre-frailty (50.5% vs. 36.2%) were significantly higher in HIV-infected individuals (p b 0.001). HIV-infected individuals scored significantly worse for all 5 factors. HIV infection remained statistically significantly associated with (pre-)frailty after adjustment for potentially confounding determinants (Table 1). Gender, region of origin, other comorbidity than mentioned in the table, heavy alcohol intake or IDU were not associated. Soluble (s)CD163, but not hs-CRP, D-dimer or sCD14, was associated with (pre-)frailty. Lower BMI was associated with (pre-)frailty in HIV-infected, but not in HIV-uninfected individuals (p(interaction) = 0.005). Within the HIV-positives, duration of having CD4 b 200/mm3, but not nadir CD4 count or history of AIDS, was associated with (pre-)frailty (OR 1.17/year, 95% CI 1.03–1.33). This association no longer remained significant following adjustment for lowest ever recorded BMI or weight loss N5 kg, and duration of protease inhibitor (PI) use (Table 2). Conclusions: HIV infection was independently associated with a higher prevalence of frailty and pre-frailty in middle-aged HIVinfected patients compared to HIV-uninfected controls. The observed independent association amongst HIV-positives with ever recorded lowest BMI or weight loss, rather than indicators of immunodeficiency, could be indicative of HIV-associated wasting being the more important driver of frailty development in HIV.