Publications by authors named "Jaelim Cho"

61 Publications

Association Between Visceral Fat and Brain Cortical Thickness in the Elderly: A Neuroimaging Study.

Front Aging Neurosci 2021 23;13:694629. Epub 2021 Jun 23.

Department of Neurology, Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea.

Background: Despite emerging evidence suggesting that visceral fat may play a major role in obesity-induced neurodegeneration, little evidence exists on the association between visceral fat and brain cortical thickness in the elderly.

Purpose: We aimed to examine the association between abdominal fat and brain cortical thickness in a Korean elderly population.

Methods: This cross-sectional study included elderly individuals without dementia ( = 316). Areas of visceral fat and subcutaneous fat (cm) were estimated from computed tomography scans. Regional cortical thicknesses (mm) were obtained by analyzing brain magnetic resonance images. Given the inverted U-shaped relationship between visceral fat area and global cortical thickness (examined using a generalized additive model), visceral fat area was categorized into quintiles, with the middle quintile being the reference group. A generalized linear model was built to explore brain regions associated with visceral fat. The same approach was used for subcutaneous fat.

Results: The mean (standard deviation) age was 67.6 (5.0) years. The highest quintile (vs. the middle quintile) group of visceral fat area had reduced cortical thicknesses in the global [β = -0.04 mm, standard error (SE) = 0.02 mm, = 0.004], parietal (β = -0.04 mm, = 0.02 mm, = 0.01), temporal (β = -0.05 mm, = 0.02 mm, = 0.002), cingulate (β = -0.06 mm, = 0.02 mm, = 0.01), and insula lobes (β = -0.06 mm, = 0.03 mm, = 0.02). None of the regional cortical thicknesses significantly differed between the highest and the middle quintile groups of subcutaneous fat area.

Conclusion: The findings suggest that a high level of visceral fat, but not subcutaneous fat, is associated with a reduced cortical thickness in the elderly.
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http://dx.doi.org/10.3389/fnagi.2021.694629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261238PMC
June 2021

Pancreatic enzymes and abdominal adipose tissue distribution in new-onset prediabetes/diabetes after acute pancreatitis.

World J Gastroenterol 2021 Jun;27(23):3357-3371

School of Medicine, University of Auckland, Auckland 1142, New Zealand.

Background: New-onset prediabetes/diabetes after acute pancreatitis (NODAP) is the most common sequela of pancreatitis, and it differs from type 2 prediabetes/diabetes mellitus (T2DM).

Aim: To study the associations between circulating levels of pancreatic amylase, pancreatic lipase, chymotrypsin and fat phenotypes in NODAP, T2DM, and health.

Methods: Individuals with NODAP ( = 30), T2DM ( = 30), and sex-matched healthy individuals ( = 30) were included. Five fat phenotypes (intra-pancreatic fat, liver fat, skeletal muscle fat, visceral fat, and subcutaneous fat) were determined using the same magnetic resonance imaging protocol and scanner magnet strength for all participants. One-way analysis of covariance, linear regression analysis, and relative importance analysis were conducted.

Results: Intra-pancreatic fat deposition (IPFD) was higher in NODAP (9.4% ± 1.8%) and T2DM (9.8% ± 1.1%) compared with healthy controls (7.8% ± 1.9%) after adjusting for covariates ( = 0.003). Similar findings were observed in regards to visceral fat volume ( = 0.005), but not subcutaneous fat volume, liver fat, or skeletal muscle fat. Both IPFD (β = -2.201, = 0.023) and visceral fat volume (β = -0.004, = 0.028) were significantly associated with circulating levels of pancreatic amylase in NODAP, but not in T2DM or healthy individuals. Of the five fat phenotypes, IPFD explained the highest amount of variance in pancreatic amylase concentration ( = 15.3% out of 41.2%). None of the phenotypes contributed meaningfully to the variance in pancreatic lipase or chymotrypsin.

Conclusion: Both NODAP and T2DM are characterized by increased IPFD and visceral fat volume. However, only NODAP is characterized by significant inverse associations between the two fat phenotypes and pancreatic amylase.
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http://dx.doi.org/10.3748/wjg.v27.i23.3357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218354PMC
June 2021

The effect of body fatness on regional brain imaging markers and cognitive function in healthy elderly mediated by impaired glucose metabolism.

J Psychiatr Res 2021 Aug 11;140:488-495. Epub 2021 Jun 11.

Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea; Department of Public Health, Yonsei University Graduate School, Seoul, 03722, Republic of Korea; Institute of Human Complexity and Systems Science, Yonsei University, Incheon, 21983, Republic of Korea. Electronic address:

Brain atrophy is related to vascular risk factors and can increase cognitive dysfunction risk. This community-based, cross-sectional study investigated whether glucose metabolic disorders due to body fatness are linked to regional changes in brain structure and a decline in neuropsychological function in cognitively healthy older adults. From 2016 to 2019, 429 participants underwent measurements for cortical thickness and subcortical volume using 3 T magnetic resonance imaging and for cognitive function using the neuropsychological screening battery. The effects of body fatness mediated by impaired glucose metabolism on neuroimaging markers and cognitive function was investigated using partial least square structural equation modeling. Total grey matter volume (β = -0.020; bias-corrected (BC) 95% confidence interval (CI) = -0.047 to -0.006), frontal (β = -0.029; BC 95% CI = -0.063 to -0.005) and temporal (β = -0.022; BC 95% CI = -0.051 to -0.004) lobe cortical thickness, and hippocampal volume (β = -0.029; BC 95% CI = -0.058 to -0.008) were indirectly related to body fatness. Further, frontal/temporal lobe thinning was associated with recognition memory (β = -0.005; BC 95% CI = -0.012 to -0.001/β = -0.005; BC 95% CI = -0.013 to -0.001) and delayed recall for visual information (β = -0.005; BC 95% CI = -0.013 to -0.001/β = -0.005; BC 95% CI = -0.013 to -0.001). Additionally, the smaller the hippocampal volume, the lower the score in recognition memory (β = -0.005; BC 95% CI = -0.012 to -0.001), delayed recall for visual information (β = -0.005; BC 95% CI = -0.012 to -0.001), and verbal learning (β = -0.008; BC 95% CI = -0.017 to -0.002). Our findings indicate that impaired glucose metabolism caused by excess body fatness affects memory decline as well as regional grey matter atrophy in elderly individuals with no neurological disease.
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http://dx.doi.org/10.1016/j.jpsychires.2021.06.011DOI Listing
August 2021

Dietary Fibre Intake in Type 2 and New-Onset Prediabetes/Diabetes after Acute Pancreatitis: A Nested Cross-Sectional Study.

Nutrients 2021 Mar 29;13(4). Epub 2021 Mar 29.

School of Medicine, University of Auckland, Auckland 1023, New Zealand.

The association between intake of dietary fibre and glucose metabolism has been extensively investigated in numerous metabolic disorders. However, little is known about this association in individuals after an attack of acute pancreatitis (AP). The aim was to investigate the associations between intake of dietary fibre and markers of glucose metabolism in individuals with new-onset prediabetes or diabetes after acute pancreatitis (NODAP), pre-exiting type 2 prediabetes or diabetes, and normoglycaemia after acute pancreatitis. This cross-sectional study was nested within the parent prospective longitudinal cohort study. The studied markers of glucose metabolism were fasting plasma glucose and glycated haemoglobin. Habitual intake of dietary fibre was determined using the EPIC-Norfolk food frequency questionnaire. Multivariable linear regression analyses were conducted. The study included a total of 108 individuals after AP. In the NODAP group, increased intakes of total fibre (β = -0.154, = 0.006), insoluble fibre (β = -0.133, = 0.01), and soluble fibre (β = -0.13, = 0.02) were significantly associated with a reduction in fasting plasma glucose. Increased intakes of vegetables (β = -0.069, = 0.004) and nuts (β = -0.039, = 0.038) were significantly associated with a reduction in fasting plasma glucose. Increased intake of nuts (β = -0.054, = 0.001) was also significantly associated with a reduction in glycated haemoglobin. None of the above associations were significant in the other study groups. Habitual intake of dietary fibre was inversely associated with fasting plasma glucose in individuals with NODAP. Individuals after an attack of AP may benefit from increasing their intake of dietary fibre (specifically, vegetables and nuts) with a view to preventing NODAP.
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http://dx.doi.org/10.3390/nu13041112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066410PMC
March 2021

Risk of cause-specific death, its sex and age differences, and life expectancy in post-pancreatitis diabetes mellitus.

Acta Diabetol 2021 Jun 15;58(6):797-807. Epub 2021 Feb 15.

School of Medicine, University of Auckland, Auckland, New Zealand.

Aims: The aim was to investigate sex- and age-stratified risks of cause-specific death and life expectancy in individuals with post-pancreatitis diabetes mellitus (PPDM).

Methods: Nationwide data on mortality in New Zealand were obtained. For two head-to-head comparisons (PPDM versus type 2 diabetes mellitus [T2DM]; PPDM versus type 1 diabetes mellitus [T1DM]), the groups were matched on age, sex, and calendar year of diabetes diagnosis. Multivariable Cox regression analyses were conducted to estimate risks of vascular, cancer, and non-vascular non-cancer mortality. Remaining life expectancy at age of diabetes diagnosis was estimated using the Chiang II method.

Results: A total of 15,848 individuals (1,132 PPDM, 3,396 T1DM, and 11,320 T2DM) were included. The risks of vascular mortality and non-vascular non-cancer mortality did not differ significantly between PPDM and T2DM or T1DM. PPDM was associated with a significantly higher risk of cancer mortality compared with T2DM (adjusted hazard ratio, 1.32; 95% confidence interval, 1.08-1.63) or T1DM (adjusted hazard ratio, 1.65; 95% confidence interval, 1.27-2.13). The risk of cancer mortality associated with PPDM (versus T2DM) was significantly higher in women than in men (p for interaction = 0.003). This sex difference in cancer mortality risk was also significant in the comparison between PPDM and T1DM (p for interaction = 0.006). Adults of both sexes with PPDM had the lowest remaining life expectancy (in comparison with T2DM or T1DM) up to 64 years of age.

Conclusions: People with PPDM have a higher risk of cancer mortality compared with those with T2DM or T1DM. This is especially pronounced in women. Young and middle-aged adults with PPDM have a lower life expectancy compared with their counterparts with T2DM or T1DM.
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http://dx.doi.org/10.1007/s00592-021-01683-0DOI Listing
June 2021

Dietary carbohydrate intake and insulin traits in individuals after acute pancreatitis: Effect modification by intra-pancreatic fat deposition.

Pancreatology 2021 Mar 2;21(2):353-362. Epub 2021 Feb 2.

School of Medicine, University of Auckland, Auckland, New Zealand. Electronic address:

Objectives: Current knowledge of the link between dietary carbohydrate intake and insulin regulation in individuals after an attack of pancreatitis is limited. We aimed to investigate the associations between dietary carbohydrate intake and insulin traits in post-pancreatitis versus healthy individuals, taking into account intrapancreatic fat deposition (IPFD).

Methods: All participants underwent magnetic resonance imaging (using the same protocol and 3T scanner) to quantify IPFD. Dietary carbohydrate intake was assessed using a validated 131-item food frequency questionnaire. Insulin, HOMA-IR, HOMA-β were determined in the fasted state. Linear regression and effect modification analyses were conducted in unadjusted and adjusted models (accounting for age, sex, body mass index, daily energy intake, use of anti-diabetic medications, and recurrence of acute pancreatitis).

Results: The study included 111 post-pancreatitis individuals (categorized into low IPFD (n = 33), moderate IPFD (n = 40), high IPFD (n = 38)) and 47 healthy controls. In the high IPFD group, starch intake was negatively associated with fasting insulin and HOMA-β in both the unadjusted (p < 0.001 both) and fully adjusted models (p < 0.001 both); and with HOMA-IR in the fully adjusted model (p < 0.001) only. Total sugar intake was positively associated with fasting insulin (p = 0.015) and HOMA-β (p = 0.007) in the fully adjusted model but not associated with HOMA-IR. None of the above associations was statistically significant in the low IPFD, moderate IPFD, and healthy controls groups. The studied associations were more pronounced in the high IPFD group but not in the moderate IPFD or low IPFD groups (when compared with the healthy controls group).

Conclusions: Dietary carbohydrate intake is differentially associated with insulin traits in individuals after an attack of pancreatitis and the associations are modified by IPFD. These findings will be helpful for the development of dietary guidelines specifically for individuals after an attack of pancreatitis.
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http://dx.doi.org/10.1016/j.pan.2021.01.018DOI Listing
March 2021

Acute Nutritional Ketosis and Its Implications for Plasma Glucose and Glucoregulatory Peptides in Adults with Prediabetes: A Crossover Placebo-Controlled Randomized Trial.

J Nutr 2021 04;151(4):921-929

School of Medicine, University of Auckland, Auckland, New Zealand.

Background: The potential of a ketone monoester (β-hydroxybutyrate; KEβHB) supplement to rapidly mimic a state of nutritional ketosis offers a new therapeutic possibility for diabetes prevention and management. While KEβHB supplementation has a glucose-lowering effect in adults with obesity, its impact on glucose control in other insulin-resistant states is unknown.

Objectives: The primary objective was to investigate the effect of KEβHB-supplemented drink on plasma glucose in adults with prediabetes. The secondary objective was to determine its impact on plasma glucoregulatory peptides.

Methods: This randomized controlled trial [called CETUS (Cross-over randomizEd Trial of β-hydroxybUtyrate in prediabeteS)] included 18 adults [67% men, mean age = 55 y, mean BMI (kg/m2) = 28.4] with prediabetes (glycated hemoglobin between 5.7% and 6.4% and/or fasting plasma glucose between 100 and 125 mg/dL). Participants were randomly assigned to receive KEβHB-supplemented and placebo drinks in a crossover sequence (washout period of 7-10 d between the drinks). Blood samples were collected from 0 to 150 min, at intervals of 30 min. Paired-samples t tests were used to investigate the change in the outcome variables [β-hydroxybutyrate (βHB), glucose, and glucoregulatory peptides] after both drinks. Repeated measures analyses were conducted to determine the change in concentrations of the prespecified outcomes over time.

Results: Blood βHB concentrations increased to 3.5 mmol/L within 30 minutes after KEβHB supplementation. Plasma glucose AUC was significantly lower after KEβHB supplementation than after the placebo [mean difference (95% CI): -59 (-85.3, -32.3) mmol/L × min]. Compared with the placebo, KEβHB supplementation led to significantly greater AUCs for plasma insulin [0.237 (0.044, 0.429) nmol/L × min], C-peptide [0.259 (0.114, 0.403) nmol/L × min], and glucose-dependent insulinotropic peptide [0.243 (0.085, 0.401) nmol/L × min], with no significant differences in the AUCs for amylin, glucagon, and glucagon-like peptide 1.

Conclusions: Ingestion of the KEβHB-supplemented drink acutely increased the blood βHB concentrations and lowered the plasma glucose concentrations in adults with prediabetes. Further research is needed to investigate the dynamics of repeated ingestions of a KEβHB supplement by individuals with prediabetes, with a view to preventing new-onset diabetes. This trial was registered at www.clinicaltrials.gov as NCT03889210.
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http://dx.doi.org/10.1093/jn/nxaa417DOI Listing
April 2021

Pancreatitis, Pancreatic Cancer, and Their Metabolic Sequelae: Projected Burden to 2050.

Clin Transl Gastroenterol 2020 11;11(11):e00251

School of Medicine, University of Auckland, Auckland, New Zealand.

Introduction: Future burden has been modeled from population-based data for several common gastrointestinal diseases. However, as we enter the third decade in the 21st century, there are no such data on diseases of the pancreas holistically. The study aimed to estimate future incidence of pancreatitis, pancreatic cancer, diabetes of the exocrine pancreas (DEP), and exocrine pancreatic dysfunction (EPD) as well as years of life lost (YLL) due to premature death in individuals with those diseases up to 2050.

Methods: Historical New Zealand nationwide data on hospital discharge, pharmaceutical dispensing, cancer, and mortality were obtained. Annual incidence of each disease and annual YLLs due to premature death in individuals with each disease were calculated. A time series analysis using the stepwise autoregressive method was conducted.

Results: Pancreatitis yielded the highest projected incidence (123.7 per 100,000; 95% confidence interval, 116.7-130.7) and YLL (14,709 years; 13,642-15,777) in 2050. The projected incidence and YLL of pancreatic cancer were 18.6 per 100,000 (95% confidence interval, 13.1-24.1) and 14,247 years (11,349-17,144) in 2050, respectively. Compared with pancreatitis and pancreatic cancer, DEP and EPD yielded lower but more steeply increasing projected incidence rates and YLLs.

Discussion: The findings suggest that the burden of pancreatitis, pancreatic cancer, DEP, and EPD will rise in the next 3 decades unless healthcare systems introduce effective prevention or early treatment strategies for diseases of the pancreas and their sequelae.
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http://dx.doi.org/10.14309/ctg.0000000000000251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594914PMC
November 2020

Particulate matter (PM) as a newly identified environmental risk factor for acute gout flares: A time-series study.

Joint Bone Spine 2021 Mar 19;88(2):105108. Epub 2020 Nov 19.

Division of Rheumatology, Department of Internal Medicine, Gachon University College of Medicine Gil Medical Center, 21 Namdongdae-ro 774-gil, Namdong-gu, Incheon, 21565, Republic of Korea. Electronic address:

Objectives: This study aimed to investigate the effect of short-term exposure to ambient particulate matter less than 10μm in diameter (PM) on occurrence of acute gout flares in the general population and identify susceptible groups accordingly.

Methods: The data of emergency department (ED) cases with acute gout flare in Incheon city, Korea between January 1st 2008 and December 31st 2015 were collected from the National Health Insurance Service claims data. The levels of PM and meterological measurements were provided by the Ministry of Environment and the National Meterological Office, respectively. To estimate the risk of daily ED visits due to acute gout flare, these time-series data set were analyzed using generalized additive models with Poisson distribution, including daily average PM level, temperature, relative humidity, day of the week, national holiday, season, and date.

Results: The risk of daily ED visits for acute gout flares per interquartile range increment of the average daily PM levels significantly increased in the cumulative lag 0-7 model (relative risk, 1.018; 95% confidence interval, 1.008-1.027, P<0.001). In particular, men aged≥40 years and those with a history of diabetes mellitus or gout were significantly at a high risk of acute gout flares by subgroup analysis.

Conclusions: Our time-series study demonstrated a modest, but significant effect of short-term exposure to PM on ED visits for acute gout flares. Ambient PM may be a newly identified environmental risk factor for acute gout flares.
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http://dx.doi.org/10.1016/j.jbspin.2020.105108DOI Listing
March 2021

Long-Term Ambient Air Pollution Exposures and Brain Imaging Markers in Korean Adults: The Environmental Pollution-Induced Neurological EFfects (EPINEF) Study.

Environ Health Perspect 2020 11 20;128(11):117006. Epub 2020 Nov 20.

Institute of Human Complexity and Systems Science, Yonsei University, Incheon, Republic of Korea.

Background: Only a limited number of neuroimaging studies have explored the effects of ambient air pollution in adults. The prior studies have investigated only cortical volume, and they have reported mixed findings, particularly for gray matter. Furthermore, the association between nitrogen dioxide () and neuroimaging markers has been little studied in adults.

Objectives: We investigated the association between long-term exposure to air pollutants (, particulate matter (PM) with aerodynamic diameters of (PM10) and (PM2.5), and neuroimaging markers.

Methods: The study included 427 men and 530 women dwelling in four cities in the Republic of Korea. Long-term concentrations of PM10, , and PM2.5 at residential addresses were estimated. Neuroimaging markers (cortical thickness and subcortical volume) were obtained from brain magnetic resonance images. A generalized linear model was used, adjusting for potential confounders.

Results: A increase in PM10 was associated with reduced thicknesses in the frontal [ (95% CI: , )] and temporal lobes [ (95% CI: , )]. A increase in PM2.5 was associated with a thinner temporal cortex [ (95% CI: , )]. A 10-ppb increase in was associated with reduced thicknesses in the global [ (95% CI: , 0.00)], frontal [ (95% CI: , )], parietal [ (95% CI: , )], temporal [ (95% CI: , )], and insular lobes [ (95% CI: , 0.00)]. The air pollutants were also associated with increased thicknesses in the occipital and cingulate lobes. Subcortical structures associated with the air pollutants included the thalamus, caudate, pallidum, hippocampus, amygdala, and nucleus accumbens.

Discussion: The findings suggest that long-term exposure to high ambient air pollution may lead to cortical thinning and reduced subcortical volume in adults. https://doi.org/10.1289/EHP7133.
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http://dx.doi.org/10.1289/EHP7133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678746PMC
November 2020

The influence of cholecystectomy and recurrent biliary events on the risk of post-pancreatitis diabetes mellitus: a nationwide cohort study in patients with first attack of acute pancreatitis.

HPB (Oxford) 2021 Jun 26;23(6):937-944. Epub 2020 Oct 26.

Department of Surgery, University of Auckland, Auckland, New Zealand. Electronic address:

Background: It is unknown whether cholecystectomy for acute pancreatitis (AP) affects the risk of post-pancreatitis diabetes mellitus (PPDM). We aimed to investigate the associations between cholecystectomy, recurrent biliary events prior to cholecystectomy, and the risk of PPDM in patients with AP.

Methods: Using New Zealand nationwide data from 2007 to 2016, patients with first admission for AP were identified (n = 10,870). Cholecystectomy was considered as a time-dependent exposure. Timing of cholecystectomy was categorized as same-admission, readmission, and delayed cholecystectomy. Recurrent biliary events prior to cholecystectomy were identified. Multivariable Cox regression analyses were conducted.

Results: Among 2147 patients who underwent cholecystectomy, 141 (6.6%) developed PPDM. Overall, cholecystectomy was not significantly associated with the risk of PPDM (adjusted hazard ratio, 1.14; 95% confidence interval, 0.94-1.38). Delayed cholecystectomy was significantly associated with an increased risk of PPDM (adjusted hazard ratio, 1.36; 95% confidence interval, 1.01-1.83). Patients who had 2 or ≥3 recurrent biliary events prior to cholecystectomy were at a significantly increased risk of PPDM.

Conclusion: Cholecystectomy in general was not associated with the risk of PPDM in patients with AP. Two or more repeated attacks of AP (or other biliary events) were associated with a significantly increased risk of PPDM.
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http://dx.doi.org/10.1016/j.hpb.2020.10.010DOI Listing
June 2021

The Relationship between Abdominal Fat Phenotypes and Insulin Resistance in Non-Obese Individuals after Acute Pancreatitis.

Nutrients 2020 Sep 21;12(9). Epub 2020 Sep 21.

School of Medicine, University of Auckland, Auckland 1023, New Zealand.

Both type 2 prediabetes/diabetes (T2DM) and new-onset prediabetes/diabetes after acute pancreatitis (NODAP) are characterized by impaired tissue sensitivity to insulin action. Although the outcomes of NODAP and T2DM are different, it is unknown whether drivers of insulin resistance are different in the two types of diabetes. This study aimed to investigate the associations between abdominal fat phenotypes and indices of insulin sensitivity in non-obese individuals with NODAP, T2DM, and healthy controls. Indices of insulin sensitivity (homeostasis model assessment of insulin sensitivity (HOMA-IS), Raynaud index, triglyceride and glucose (TyG) index, Matsuda index) were calculated in fasting and postprandial states. Fat phenotypes (intra-pancreatic fat, intra-hepatic fat, skeletal muscle fat, visceral fat, and subcutaneous fat) were determined using magnetic resonance imaging and spectroscopy. Linear regression and relative importance analyses were conducted. Age, sex, and glycated hemoglobin A1c were adjusted for. A total of 78 non-obese individuals (26 NODAP, 20 T2DM, and 32 healthy controls) were included. Intra-pancreatic fat was significantly associated with all the indices of insulin sensitivity in the NODAP group, consistently in both the unadjusted and adjusted models. Intra-pancreatic fat was not significantly associated with any index of insulin sensitivity in the T2DM and healthy controls groups. The variance in HOMA-IS was explained the most by intra-pancreatic fat (R = 29%) in the NODAP group and by visceral fat (R = 21%) in the T2DM group. The variance in the Raynaud index was explained the most by intra-pancreatic fat (R = 18%) in the NODAP group and by visceral fat (R = 15%) in the T2DM group. The variance in the TyG index was explained the most by visceral fat in both the NODAP group (R = 49%) and in the T2DM group (R = 25%). The variance in the Matsuda index was explained the most by intra-pancreatic fat (R = 48%) in the NODAP group and by visceral fat (R = 38%) in the T2DM group. The differing association between intra-pancreatic fat and insulin resistance can be used to differentiate NODAP from T2DM. Insulin resistance in NODAP appears to be predominantly driven by increased intra-pancreatic fat deposition.
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http://dx.doi.org/10.3390/nu12092883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551376PMC
September 2020

Associations between ambient air pollution and medical care visits for atopic dermatitis.

Environ Res 2021 04 12;195:110153. Epub 2020 Sep 12.

Department of Dermatology, Gil Medical Center, Gachon University, Incheon, Republic of Korea. Electronic address:

Background: Previous studies have reported numerous environmental factors for atopic dermatitis (AD), such as allergens and chemical stimulants. However, few studies have addressed the relationship between ambient air pollution and AD at a population level.

Objective: To evaluate the effect of air pollutants on medical care visits for AD and to identify susceptible populations.

Methods: In this time-series study conducted on 513,870 medical care visits for AD from 2012 to 2015 identified by reviewing national health insurance claim data in Incheon, Republic of Korea. Treating daily number of medical care visits for AD as a dependent variable, generalized additive models with Poisson distributions were constructed, which included air pollutant levels, ambient temperature, relative humidity, day of the week, national holiday, and season. Risks were expressed as relative risks (RR) with 95% confidence intervals (95% CIs) per interquartile range increase of each air pollutant.

Results: Higher levels of particulate matter of diameter ≤10 μm (PM) (RR, 1.009; 95% CI, 1.007-1.012), ozone (1.028; 1.023-1.033), and sulfur dioxide (1.033; 1.030-1.037) were significantly associated with increased risk of medical care visits for AD on same days. In all age and sex groups, ozone was associated with a significantly higher risk of medical care visits, with the greatest risk among 13- to 18-year-old males (RR, 1.127; 95% CI, 1.095-1.159).

Conclusion: This study suggests relationships of ambient PM, ozone, and sulfur dioxide levels with medical care visits for AD.
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http://dx.doi.org/10.1016/j.envres.2020.110153DOI Listing
April 2021

Chronic Pancreatitis Is Characterized by Elevated Circulating Periostin Levels Related to Intra-Pancreatic Fat Deposition.

J Clin Med Res 2020 Sep 15;12(9):568-578. Epub 2020 Aug 15.

School of Medicine, University of Auckland, Auckland, New Zealand.

Background: Periostin is a matricellular protein that induces fibrillogenesis and activates cell migration. It is overexpressed in common fibrotic diseases and is also associated with abdominal adiposity/ectopic fat phenotypes. The study aimed to investigate circulating levels of periostin in health and after an attack of pancreatitis, as well as their associations with abdominal adiposity/ectopic fat phenotypes.

Methods: Blood samples were obtained from healthy controls, as well as definite chronic pancreatitis (CP) and acute pancreatitis (AP) individuals during follow-up visits. Fat depositions in the pancreas, liver, skeletal muscle, as well as visceral and subcutaneous fat volumes, were quantified with the use of magnetic resonance imaging. A series of multivariable analyses were conducted, accounting for possible confounders.

Results: A total of 121 individuals were included. Periostin levels were significantly higher in the CP group compared with the other groups in both unadjusted (F = 3.211, P = 0.044) and all adjusted models (F = 4.165, P = 0.019 in the most adjusted model). Intra-pancreatic fat deposition (but not the other fat phenotypes) was significantly associated with periostin concentration in the CP group (β = 49.63, P = 0.034) and explained most of its variance (32.0%).

Conclusions: Individuals with CP, but not healthy individuals or those after clinical resolution of AP, are characterized by elevated circulating levels of periostin that are positively associated with intra-pancreatic fat deposition.
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http://dx.doi.org/10.14740/jocmr4279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430919PMC
September 2020

Estimating the disease burden of lung cancer attributable to residential radon exposure in Korea during 2006-2015: A socio-economic approach.

Sci Total Environ 2020 Dec 11;749:141573. Epub 2020 Aug 11.

Department of Preventive Medicine, Yonsei University, College of Medicine, Seoul, Republic of Korea; Institute of Human Complexity and Systems Science, Yonsei University, Seoul, Republic of Korea; Institute for Environmental Research, Yonsei University, College of Medicine, Seoul, Republic of Korea. Electronic address:

Estimating the lung cancer disease burden can provide evidence for public health practitioners, researchers, and policymakers. This study uses claim data from lung cancer patients for 2006-2015 from the Korean National Health Insurance Service to estimate the lung cancer burdens attributable to residential radon in Korea using disability-adjusted life years (DALY) and patients' annual economic burden with societal perspectives using the cost-of-illness (COI) method. The number of patients increased during our study period (from 35,866 to 59,168). The disease burden and that attributable to residential radon, respectively, increased from 517.57 to 695.74 and 64.62 (95%; CIs 61.33-67.69) to 86.99 (95%; CIs 82.7-91.1) DALYs per 100,000 patients. The percentage of years lost due to disability among the DALY doubled from 8% to 17%. The cost for all the patients was US$2.33 billion, with US$292 (95%; CIs 278-306) million attributable to residential radon. During the last decade, the lung cancer disease burden increased by 1.34 times, with a doubled percentage of non-fatal burden and average annual growth rate of 9.5% of the total cost. Hence, the burden and cost of lung cancer in Korean provinces have been steadily increasing. The findings could be used as input data for future cost-effectiveness analysis of policies regarding radon reduction.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141573DOI Listing
December 2020

Association between exposure to polycyclic aromatic hydrocarbons and brain cortical thinning: The Environmental Pollution-Induced Neurological EFfects (EPINEF) study.

Sci Total Environ 2020 Oct 9;737:140097. Epub 2020 Jun 9.

Institute of Human Complexity and Systems Science, Yonsei University, Seoul, Republic of Korea; Institute for Environmental Research, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Although some studies have suggested that exposure to polycyclic aromatic hydrocarbons (PAHs) induces neurodevelopmental disturbances in children and neurodegeneration in animals, the neurotoxic effect of PAH exposure is unclear in adults. The aim was to examine the associations of PAH exposure with brain structure and neuropsychological function in adults without known neurological diseases.

Methods: This study included 421 men and 528 women dwelling in four cities in the Republic of Korea. Urinary concentrations of four PAH metabolites (1-hydroxypyrene, 2-naphthol, 1-hydroxyphenanthrene, and 2-hydroxyfluorene) were obtained. Participants underwent brain 3 T magnetic resonance imaging and neuropsychological tests. Cortical thickness and volume were estimated using the region-of-interest method. Separate generalized linear models were constructed for each sex, adjusting for age, years of education, cohabitation status, income, tobacco use, alcohol consumption, and vascular risk factors.

Results: The mean (standard deviation) age was 68.3 (6.6) years in men and 66.4 (6.1) years in women. In men, those in quartile 4 (versus quartile 1, the lowest) of urinary 2-naphthol concentration had cortical thinning in the global (β = -0.03, P = .02), parietal (β = -0.04, P = .01), temporal (β = -0.06, P < .001), and insular lobes (β = -0.05, P = .02). Higher quartiles of urinary 2-naphthol concentration were associated with cortical thinning in the global (P = .01), parietal (P = .004), temporal (P < .001), and insular lobes (P = .01). In women, those in quartile 4 (versus quartile 1) of urinary 1-hydroxypyrene concentration had cortical thinning in the frontal (β = -0.03, P = .006) and parietal lobes (β = -0.03, P = .003). Higher quartiles of urinary 1-hydroxypyrene concentration were associated with cortical thinning in the frontal (P = .006) and parietal lobes (P = .001). In both sexes, verbal learning and memory scores significantly declined with an increase in quartile of urinary 1-hydroxypyrene concentration.

Conclusions: PAH exposure was associated with cortical thinning and decline in verbal learning and memory function in cognitively healthy adults. This suggests PAHs as an environmental risk factor for neurodegeneration.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140097DOI Listing
October 2020

Exocrine Pancreatic Dysfunction Increases the Risk of New-Onset Diabetes Mellitus: Results of a Nationwide Cohort Study.

Clin Transl Sci 2021 01 21;14(1):170-178. Epub 2020 Jul 21.

School of Medicine, University of Auckland, Auckland, New Zealand.

It is well established that individuals with diabetes mellitus (DM) may develop exocrine pancreatic dysfunction (EPD) requiring pancreatic enzyme replacement therapy, whereas the converse relationship has been poorly studied. Pancreatitis is a disease that is well suited to investigate the latter as it is often characterized by the development of EPD and/or new-onset DM. The aim was to investigate the association between EPD and the risk of new-onset DM in individuals after the first attack of pancreatitis. Using nationwide pharmaceutical dispensing data and hospital discharge data, this cohort study included a total of 9,124 post-pancreatitis individuals. EPD was defined as having two or more dispensing records of pancreatic enzymes. Considering EPD as a time-dependent variable, multivariable Cox regression analysis was conducted. A 1-year lag period between EPD and DM was introduced to minimize reverse causality. Age, sex, ethnicity, alcohol consumption, tobacco smoking, social deprivation index, Charlson comorbidity index, and use of proton pump inhibitors were adjusted for. In the overall cohort, EPD was associated with a significantly higher risk for new-onset DM (adjusted hazard ratio, 3.83; 95% confidence interval, 2.37-6.18). The association remained statistically significant when a 1-year lag period was applied (adjusted hazard ratio, 2.51; 95% confidence interval, 1.38-4.58), as well as when the analysis was constrained to mild acute pancreatitis (4.65; 2.18-9.93). The findings suggest that individuals with EPD, even those without extensive mechanistic destruction of the pancreas, are at an increased risk for new-onset DM. Purposely designed studies are warranted to investigate mechanisms behind the association and if the mechanisms could be targeted therapeutically.
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http://dx.doi.org/10.1111/cts.12837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877819PMC
January 2021

Implications of Tobacco Smoking and Alcohol Consumption on Ectopic Fat Deposition in Individuals After Pancreatitis.

Pancreas 2020 08;49(7):924-934

From the Department of Surgery, University of Auckland, Auckland, New Zealand.

Objectives: Tobacco smoking and alcohol consumption are established risk factors for pancreatitis. This study investigated the associations between tobacco smoking/alcohol consumption in people after an attack of pancreatitis and intrapancreatic fat deposition (IPFD), intrahepatic fat deposition (IHFD), and skeletal muscle (SMFD) fat deposition.

Methods: In this cross-sectional study, magnetic resonance imaging was used to quantify IPFD, IHFD, and SMFD by 2 independent raters. A validated questionnaire was used to determine tobacco smoking and alcohol consumption.

Results: A total of 119 individuals after an attack of pancreatitis were included. Average tobacco smoking contributed most to variance in IPFD (R = 6.5%) and least to variance in SMFD (R = 0.4%). Average alcohol consumption contributed most to variance in variance in IPFD (R = 2.8%) and least to IHFD (R = 1.1%). Packs/day contributed more than years of smoking to variance in IPFD (R = 4.9 and 0.2%, correspondingly), whereas years of drinking contributed more than average daily alcohol consumption (R = 3.9 and 3.2%, correspondingly).

Conclusions: Tobacco smoking and alcohol consumption contributed more to variance in IPFD than IHFD and SMFD. Smoking contributed more than drinking to variance in IPFD. The daily amount of tobacco smoked appeared to be more important than years of smoking for IPFD.
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http://dx.doi.org/10.1097/MPA.0000000000001600DOI Listing
August 2020

Reduced Skeletal Muscle Volume and Increased Skeletal Muscle Fat Deposition Characterize Diabetes in Individuals after Pancreatitis: A Magnetic Resonance Imaging Study.

Diseases 2020 07 1;8(3). Epub 2020 Jul 1.

School of Medicine, University of Auckland, Auckland 1023, New Zealand.

Background: Skeletal muscle has been implicated in the pathogenesis of type 2 diabetes but it has never been investigated in diabetes after pancreatitis. The aim was to investigate the relationship between psoas muscle volume (PMV) and diabetes in individuals after pancreatitis, as well as its associations with ectopic fat phenotypes and insulin traits.

Methods: Individuals after an attack of pancreatitis and healthy individuals were studied in a cross-sectional fashion. All participants underwent magnetic resonance imaging, based on which PMV, skeletal muscle fat deposition (SMFD), as well as liver and intra-pancreatic fat depositions were derived. Fasting and postprandial blood samples were collected to calculate indices of insulin sensitivity and secretion. Linear regression analyses were conducted, adjusting for possible confounders (age, sex, body composition, comorbidities, use of insulin, and others).

Results: A total of 153 participants were studied. PMV was significantly decreased in the diabetes group compared with healthy controls (β = -30.0 =.034 in the most adjusted model). SMFD was significantly inversely associated with PMV (β = -3.1, p < 0.001 in the most adjusted model). The Matsuda index of insulin sensitivity was significantly directly associated with PMV (β = 1.6, = 0.010 in the most adjusted model).

Conclusions: Diabetes in individuals after pancreatitis is characterized by reduced PMV. Reduced PMV is associated with increased SMFD and decreased insulin sensitivity in individuals after pancreatitis.
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http://dx.doi.org/10.3390/diseases8030025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565190PMC
July 2020

Postpancreatitis Diabetes Confers Higher Risk for Pancreatic Cancer Than Type 2 Diabetes: Results From a Nationwide Cancer Registry.

Diabetes Care 2020 09 2;43(9):2106-2112. Epub 2020 Jul 2.

School of Medicine, University of Auckland, Auckland, New Zealand

Objective: Pancreatitis and diabetes are established risk factors for pancreatic cancer. However, to date, studies have investigated only the risk associated with either of them alone. The aim of this study was to investigate the effect of pancreatitis and diabetes combined, as well as their temporal relationship, on the risk of pancreatic cancer.

Research Design And Methods: Nationwide cancer registry was linked to hospital discharge and mortality data from 1998 to 2015 in New Zealand. Incidence of primary pancreatic cancer in the four study groups (type 2 diabetes [T2D] alone, pancreatitis alone, T2D followed by pancreatitis, and postpancreatitis diabetes mellitus [PPDM]) was identified. Multivariable Cox regression analyses were conducted, with T2D as the reference group. A head-to-head comparison between the T2D followed by pancreatitis and PPDM groups was also performed.

Results: Among 139,843 individuals (735,541 person-years), 913 (0.7%) were diagnosed with pancreatic cancer. The proportion of pancreatic cancer was 3.1%, 2.3%, 2.0%, and 0.6% in individuals with PPDM, T2D followed by pancreatitis, pancreatitis alone, and T2D alone, respectively. PPDM (hazard ratio [HR] 6.94; 95% CI 4.09-11.77) and T2D followed by pancreatitis (HR 5.35; 95% CI 3.52-8.14) were associated with significantly higher risks of pancreatic cancer compared with T2D alone. In the head-to-head comparison, PPDM was associated with a higher risk of pancreatic cancer compared with T2D followed by pancreatitis (HR 2.35; 95% CI 1.12-4.93).

Conclusions: Pancreatitis significantly increases the risk of pancreatic cancer in individuals with diabetes. In particular, PPDM poses the highest risk for pancreatic cancer.
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http://dx.doi.org/10.2337/dc20-0207DOI Listing
September 2020

Associations Between Cannabis Use, Abdominal Fat Phenotypes and Insulin Traits.

J Clin Med Res 2020 Jun 4;12(6):377-388. Epub 2020 Jun 4.

School of Medicine, University of Auckland, Auckland, New Zealand.

Background: General obesity has been linked to dysregulation of the endocannabinoid system in humans. However, there is a lack of studies on the relationship between cannabis use and specific abdominal fat phenotypes. The aim was to investigate the associations between cannabis use and magnetic resonance imaging-derived fat phenotypes, as well as indices of insulin sensitivity and insulin secretion.

Methods: In this cross-sectional study, magnetic resonance imaging was used to quantify subcutaneous fat volume (SFV), visceral fat volume (VFV), intra-hepatic fat deposition (IHFD), intra-pancreatic fat deposition (IPFD) and skeletal muscle fat deposition (SMFD) by two independent observers. Insulin sensitivity was determined based on HOMA-IS, Raynaud index and Matsuda index, whereas insulin secretion was determined based on HOMA-β, insulinogenic index 30' and insulinogenic index 60'. A validated questionnaire was used to ascertain participants' cannabis use. Linear regression models were constructed, adjusting for demographics, glycated hemoglobin, physical activity, tobacco smoking and alcohol consumption.

Results: A total of 120 individuals were included. Cannabis use explained 9.2% of variance in IHFD, 4.4% in SMFD, 3.4% in VFV, 0.4% in SFV and 0.2% in IPFD. Regular cannabis users had significantly greater IHFD compared with never users, in both the unadjusted (P = 0.002) and all adjusted (P = 0.002; P = 0.008) analyses. The other fat phenotypes did not differ significantly between either regular or non-regular users compared with never users. Regular cannabis users had significantly greater insulin secretion (as defined by the insulinogenic index 60') compared with never users, in both the unadjusted (P = 0.049) and all adjusted (P = 0.003; P = 0.004) analyses. Cannabis use explained 20.3% of variance in the insulinogenic index 60', but was not significantly associated with the other indices of insulin secretion. There were no significant differences in indices of insulin sensitivity in either regular or non-regular cannabis users compared with never users.

Conclusion: Regular cannabis use may be a risk factor for non-alcoholic fatty liver disease (but not IPFD) and may alter the neuromodulation of insulin secretion. Further investigations are now warranted to elucidate the mechanisms underlying these associations.
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http://dx.doi.org/10.14740/jocmr4165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295553PMC
June 2020

Trajectories of glycaemia following acute pancreatitis: a prospective longitudinal cohort study with 24 months follow-up.

J Gastroenterol 2020 Aug 3;55(8):775-788. Epub 2020 Jun 3.

School of Medicine, University of Auckland, Room 12.085 A, Level 12, Auckland City Hospital, Auckland, 1142, New Zealand.

Background: New-onset diabetes is the most common sequela of acute pancreatitis (AP). Yet, prospective changes in glycaemia over time have never been investigated comprehensively in this study population. The primary aim was to determine the cumulative incidence of new-onset prediabetes and new-onset diabetes after AP over 24 months of follow-up in a prospective cohort study. The secondary aim was to identify trajectories of glycaemia during follow-up and their predictors at the time of hospitalisation.

Methods: Patients with a prospective diagnosis of AP and no diabetes based on the American Diabetes Association criteria were followed up every 6 months up to 24 months after hospital discharge. Incidence of new-onset prediabetes/diabetes over each follow-up period was calculated. Group-based trajectory modelling was used to identify common changes in glycaemia. Multinomial regression analyses were conducted to investigate the associations between a wide array of routinely available demographic, anthropometric, laboratory, imaging, and clinical factors and membership in the trajectory groups.

Results: A total of 152 patients without diabetes were followed up. The cumulative incidence of new-onset prediabetes and diabetes was 20% at 6 months after hospitalisation and 43% over 24 months of follow-up (p trend < 0.001). Three discrete trajectories of glycaemia were identified: normal-stable glycaemia (32%), moderate-stable glycaemia (60%), and high-increasing glycaemia (8%). Waist circumference was a significant predictor of moderate-stable glycaemia. None of the studied predictors were significantly associated with high-increasing glycaemia.

Conclusions: This first prospective cohort study of changes in glycaemia (determined at structured time points in unselected AP patients) showed that at least one out of five patients develops new-onset prediabetes or diabetes at 6 months of follow-up and more than four out of ten-in the first 2 years. Changes in glycaemia after AP follow three discrete trajectories. This may inform prevention or early detection of critical changes in blood glucose metabolism following an attack of AP and, hence, reduce the burden of new-onset diabetes after acute pancreatitis.
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http://dx.doi.org/10.1007/s00535-020-01682-yDOI Listing
August 2020

Oxyntomodulin May Distinguish New-Onset Diabetes After Acute Pancreatitis From Type 2 Diabetes.

Clin Transl Gastroenterol 2020 02;11(2):e00132

School of Medicine, University of Auckland, Auckland, New Zealand.

Objective: New-onset diabetes is an important sequela of acute pancreatitis, but there are no biomarkers to differentiate it from the much more common type 2 diabetes. The objective was to investigate whether postprandial circulating levels of gut hormones can serve this purpose.

Methods: This was a case-control study nested into a prospective longitudinal cohort study that included 42 insulin-naive cases with new-onset prediabetes/diabetes after acute pancreatitis (NODAP) and prediabetes/diabetes followed by acute pancreatitis (T2D-AP), sex matched with 21 healthy controls. All individuals underwent a standardized mixed-meal test, and blood samples were assayed for gut hormones (glucose-dependent insulinotropic peptide, glucagon-like peptide-1, oxyntomodulin, and peptide YY). Analysis of variance and linear regression analysis were conducted in unadjusted and adjusted models (accounting for age, homeostatic model assessment of β-cell function, and magnetic resonance imaging-derived body fat composition).

Results: Oxyntomodulin levels were significantly lower in NODAP compared with T2D-AP and healthy controls (P = 0.027 and P = 0.001, respectively, in the most adjusted model). Glucagon-like peptide-1 and peptide YY were significantly lower in NODAP compared with T2D-AP (P = 0.001 and P = 0.014, respectively, in the most adjusted model) but not compared with healthy controls (P = 1.000 and P = 0.265, respectively, in the most adjusted model). Glucose-dependent insulinotropic peptide levels were not significantly different between NODAP and T2D-AP.

Discussion: Oxyntomodulin is a promising biomarker to guide the differential diagnosis of new-onset diabetes after acute pancreatitis. However, external validation studies are warranted before it can be recommended for routine use in clinical practice.
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http://dx.doi.org/10.14309/ctg.0000000000000132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145025PMC
February 2020

Marriage as a social tie in the relation of depressive symptoms attributable to air pollution exposure among the elderly.

J Affect Disord 2020 07 1;272:125-131. Epub 2020 May 1.

Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Human Complexity and Systems Science, Yonsei University, Incheon, Republic of Korea; Institute for Environmental Research, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Air pollution is a risk factor for depression or depressive symptoms. However, few studies have examined an effect modifier as a protective factor against depressive symptoms associated with air pollution, including social support. Notably, less is known about a married relationship in the association between exposure to air pollution and depressive symptoms among the elderly.

Methods: This study included 2122 marrieds and 607 non-marrieds, recruited in 2014-2017 from different regions of South Korea. Depressive symptoms were measured by the Korean version of the Geriatric Depression Scale Short Form (SGDS-K). After adjustment for potential confounders using propensity score of being assigned to the marrieds, we examined the extent of whether the effects of exposure to air pollutants (PM, PM, and NO) on depressive symptoms were different between marrieds and non-marrieds. Subgroup analyses by gender and residence area were also performed.

Results: Marrieds than non-marrieds were less likely to have depressive symptoms and had smaller SGDS-K associated with increased exposure to PM and PM concentrations, respectively. After stratification of subjects by gender and residence area, the interaction term appeared to be significant among men and the non-metropolitan group, indicating the protective effect of married relationships on depressive symptoms attributable to air pollution exposure in them.

Limitations: Although we adjusted the propensity score, our findings might be confounded by the contextual effect associated with married relationships.

Conclusions: A married relationship, as a social tie, may attenuate the effect of exposure to air pollution on depressive symptoms among the elderly. Nonetheless, additional research is worthwhile to explore the extent of other social relationships in the association between air pollution exposure and depressive symptoms.
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http://dx.doi.org/10.1016/j.jad.2020.04.059DOI Listing
July 2020

[¹⁸F]THK5351 PET Imaging in Patients with Mild Cognitive Impairment.

J Clin Neurol 2020 Apr;16(2):202-214

Department of Neurology, Gachon University Gil Medical Center, Incheon, Korea.

Background And Purpose: Mild cognitive impairment (MCI) is a condition with diverse clinical outcomes and subgroups. Here we investigated the topographic distribution of tau in vivo using the positron emission tomography (PET) tracer [¹⁸F]THK5351 in MCI subgroups.

Methods: This study included 96 participants comprising 38 with amnestic MCI (aMCI), 21 with nonamnestic MCI (naMCI), and 37 with normal cognition (NC) who underwent 3.0-T MRI, [¹⁸F]THK5351 PET, and detailed neuropsychological tests. [¹⁸F]flutemetamol PET was also performed in 62 participants. The aMCI patients were further divided into three groups: 1) verbal-aMCI, only verbal memory impairment; 2) visual-aMCI, only visual memory impairment; and 3) both-aMCI, both visual and verbal memory impairment. Voxel-wise statistical analysis and region-of-interest -based analyses were performed to evaluate the retention of [¹⁸F]THK5351 in the MCI subgroups. Subgroup analysis of amyloid-positive and -negative MCI patients was also performed. Correlations between [¹⁸F]THK5351 retention and different neuropsychological tests were evaluated using statistical parametric mapping analyses.

Results: [¹⁸F]THK5351 retention in the lateral temporal, mesial temporal, parietal, frontal, posterior cingulate cortices and precuneus was significantly greater in aMCI patients than in NC subjects, whereas it did not differ significantly between naMCI and NC participants. [¹⁸F] THK5351 retention was greater in the both-aMCI group than in the verbal-aMCI and visualaMCI groups, and greater in amyloid-positive than amyloid-negative MCI patients. The cognitive function scores were significantly correlated with cortical [¹⁸F]THK5351 retention.

Conclusions: [¹⁸F]THK5351 PET might be useful for identifying distinct topographic patterns of [¹⁸F]THK5351 retention in subgroups of MCI patients who are at greater risk of the progression to Alzheimer's dementia.
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http://dx.doi.org/10.3988/jcn.2020.16.2.202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174126PMC
April 2020

Psoas muscle size as a magnetic resonance imaging biomarker of progression of pancreatitis.

Eur Radiol 2020 May 10;30(5):2902-2911. Epub 2020 Feb 10.

School of Medicine, University of Auckland, Auckland, New Zealand.

Objective: Pancreatitis often represents a continuous inflammatory process, from the first episode of acute pancreatitis (FAP) to recurrent acute pancreatitis (RAP) to chronic pancreatitis (CP). Psoas muscle size is a validated surrogate for global skeletal mass, changes in which are associated with inflammation. The objective was to investigate psoas muscle size in individuals following FAP, RAP, and CP, as well as its associations with pro-inflammatory cytokines.

Methods: Individuals following pancreatitis and healthy individuals were recruited. All participants underwent magnetic resonance imaging, from which psoas muscle volume was derived independently by two raters in a blinded fashion. Circulating levels of four major cytokines (interleukin-6, tumour necrosis factor-α, C-C motif chemokine ligand 2, and leptin) were measured. Five linear regression additive models were built to adjust for possible confounders (age, sex, body composition, physical activity, tobacco smoking, alcohol consumption, comorbidities, and endocrine and exocrine pancreatic functions).

Results: A total of 145 participants were enrolled. A significant downward trend in psoas muscle volume was observed between healthy controls and individuals following FAP, RAP, and CP in all adjusted models (p = 0.047, 0.005, 0.004, and < 0.001). Leptin was significantly associated with psoas muscle volume in all models (β = - 0.16, p = 0.030 in the most adjusted model). The other studied cytokines were not significantly associated with psoas muscle volume.

Conclusions: Psoas muscle size is significantly reduced along the continuum from FAP to RAP to CP. Leptin appears to be one of the factors implicated in this. Further studies are warranted to investigate the relationship between skeletal muscle and inflammation of the pancreas.

Key Points: • First acute pancreatitis, recurrent acute pancreatitis, and chronic pancreatitis were associated with progressively reduced psoas muscle size. • The findings were independent of age, sex, body fat composition, physical activity, tobacco smoking, alcohol consumption, comorbidities, and exocrine and endocrine functions of the pancreas. • The mechanism underlying the observed findings may involve hyperleptinaemia.
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http://dx.doi.org/10.1007/s00330-019-06633-7DOI Listing
May 2020

Low serum amylase, lipase, and trypsin as biomarkers of metabolic disorders: A systematic review and meta-analysis.

Diabetes Res Clin Pract 2020 Jan 4;159:107974. Epub 2019 Dec 4.

School of Medicine, University of Auckland, Auckland, New Zealand. Electronic address:

Aims: While there is plentiful evidence on elevated serum levels of amylase, lipase, and trypsin in acute illness, low serum levels of these digestive enzymes have been studied infrequently. The aim was to systematically review published studies on the relationship between low serum levels of amylase, lipase, or trypsin and metabolic disorders.

Methods: The search was conducted in MEDLINE and Scopus databases. Studies in humans were included if they reported on the association between serum levels of amylase, lipase, or trypsin within normal range and metabolic disorders. Random-effects meta-analysis was conducted.

Results: A total of 20 studies encompassing 20,916 participants were included. Compared with healthy individuals, individuals with type 2 diabetes mellitus (mean difference = -5.3; p < 0.001), metabolic syndrome (mean difference = -5.1; p < 0.001), and overweight/obesity (mean difference = -0.8; p = 0.02) had significantly lower serum levels of amylase. Both individuals with type 1 diabetes mellitus (mean difference = -1.8; p < 0.001) and type 2 diabetes mellitus (mean difference = -0.8; p < 0.001) had significantly lower serum levels of lipase compared with healthy individuals. Data on serum trypsin were not suitable for meta-analysis. In the pooled analysis, individuals with type 2 diabetes mellitus had 3.1-times lower serum levels of amylase, 2.9-times lower serum levels of lipase, and 2.5-times lower serum levels of trypsin levels than the upper limits of normal for the three digestive enzymes.

Conclusion: Low serum levels of amylase and lipase are significantly associated with type 2 diabetes mellitus, type 1 diabetes mellitus, excess adiposity, and metabolic syndrome. The role of digestive enzymes in the pathogenesis of metabolic disorders warrants further investigations.
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http://dx.doi.org/10.1016/j.diabres.2019.107974DOI Listing
January 2020

Relationship of pancreas volume to tobacco smoking and alcohol consumption following pancreatitis.

Pancreatology 2020 Jan 1;20(1):60-67. Epub 2019 Nov 1.

School of Medicine, University of Auckland, Auckland, New Zealand. Electronic address:

Background: Tobacco smoking and alcohol consumption are established risk factors for diseases of the pancreas. With the recent advances in imaging modalities (such as magnetic resonance (MR) imaging), opportunities have arisen to study pancreas size, in both health and disease. Studies investigating the relationship between tobacco smoking, alcohol consumption, and total pancreas volume (TPV) - a holistic measure of pancreatic exocrine reserve - are lacking. The aim of the present study was to investigate the associations between MR-derived TPV and tobacco smoking/alcohol consumption.

Methods: This cross-sectional study recruited individuals with a history of pancreatitis and healthy controls. A validated questionnaire was used to ascertain current and lifetime tobacco smoking and alcohol consumption. TPV was quantified using MR images by two independent raters. Generalized additive models and linear regression analyses were conducted and adjusted for demographic, metabolic, and pancreatitis-related factors.

Results: A total of 107 individuals following pancreatitis and 38 healthy controls were included. There was no statistically significant difference in TPV between any of the tobacco smoking/alcohol consumption categories of individuals following pancreatitis and healthy controls, in both unadjusted and adjusted analyses. In individuals following pancreatitis, multivariate linear regression found no association between TPV and 7 smoking- and alcohol-related variables. Sensitivity analyses constrained to individuals who did not abstain from either smoking or drinking following their first attack of pancreatitis did not yield statistical significance with TPV. In post-hoc analysis, age was significantly inversely associated with TPV in the most adjusted model (p = 0.016).

Conclusions: This is the first study to investigate the association between tobacco smoking, alcohol consumption, and MR-derived TPV following pancreatitis. It appears that age, but not tobacco smoking or alcohol consumption, is associated with a significantly reduced TPV.
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http://dx.doi.org/10.1016/j.pan.2019.10.009DOI Listing
January 2020

Relationship between Gout and Diabetes Mellitus after Acute Pancreatitis: A Nationwide Cohort Study.

J Rheumatol 2020 06 15;47(6):917-923. Epub 2019 Oct 15.

From the School of Medicine, University of Auckland, Auckland, New Zealand.

Objective: After acute pancreatitis, individuals often have low-grade inflammation, and subsequently develop metabolic sequelae such as post-pancreatitis diabetes mellitus (PPDM). Although numerous studies have investigated the relationship between gout and type 2 diabetes, little is known about the relationship between gout and PPDM. The aim was to investigate the associations between gout and PPDM.

Methods: Using nationwide pharmaceutical dispensing data linked to hospital discharge data in New Zealand, gout and PPDM were identified among individuals after first episode of acute pancreatitis between January 1, 2007, and December 31, 2015. Multivariable Cox regression analyses were conducted, adjusting for age, sex, ethnicity, social deprivation index, alcohol consumption, tobacco smoking, comorbidities, medications (glucocorticoids, statins, and estrogens), and characteristics of acute pancreatitis.

Results: A total of 10,117 individuals were included in the analysis of risk for gout and 9471 in the analysis of risk for PPDM. PPDM was significantly associated with a higher risk of gout in the overall cohort (adjusted HR 1.88, 95% CI 1.15-3.06) and women (2.72, 95% CI 1.31-5.65), but not in men (1.42, 95% CI 0.73-2.78). Preexisting gout was significantly associated with a higher risk of PPDM in the overall cohort (adjusted HR 1.58, 95% CI 1.04-2.41) and women (2.66, 95% CI 1.29-5.49), but not in men (1.31, 95% CI 0.78-2.20).

Conclusion: The relationship between gout and PPDM is bidirectional in the post-pancreatitis setting. A history of gout is a risk factor of PPDM, particularly in women.
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http://dx.doi.org/10.3899/jrheum.190487DOI Listing
June 2020