Terry Dwyer

Risk of Cardiovascular and All-Cause Mortality in Individuals With Diabetes Mellitus, Impaired Fasting Glucose, and Impaired Glucose Tolerance The Australian Diabetes, Obesity, and Lifestyle Study (AusDiab)

Background— Diabetes mellitus increases the risk of cardiovascular disease (CVD) and all-cause mortality. The relationship between milder elevations of blood glucose and mortality is less clear. This study investigated whether impaired fasting glucose and impaired glucose tolerance, as well as diabetes mellitus, increase the risk of all-cause and CVD mortality. Methods and Results— In 1999 to 2000, glucose tolerance status was determined in 10 428 participants of the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). After a median follow-up of 5.2 years, 298 deaths occurred (88 CVD deaths). Compared with those with normal glucose tolerance, the adjusted all-cause mortality hazard ratios (HRs) and 95% confidence intervals (CIs) for known diabetes mellitus and newly diagnosed diabetes mellitus were 2.3 (1.6 to 3.2) and 1.3 (0.9 to 2.0), respectively. The risk of death was also increased in those with impaired fasting glucose (HR 1.6, 95% CI 1.0 to 2.4) and impaired glucose tolerance (HR 1.5, 95% CI 1.1 to 2.0). Sixty-five percent of all those who died of CVD had known diabetes mellitus, newly diagnosed diabetes mellitus, impaired fasting glucose, or impaired glucose tolerance at baseline. Known diabetes mellitus (HR 2.6, 95% CI 1.4 to 4.7) and impaired fasting glucose (HR 2.5, 95% CI 1.2 to 5.1) were independent predictors for CVD mortality after adjustment for age, sex, and other traditional CVD risk factors, but impaired glucose tolerance was not (HR 1.2, 95% CI 0.7 to 2.2). Conclusions— This study emphasizes the strong association between abnormal glucose metabolism and mortality, and it suggests that this condition contributes to a large number of CVD deaths in the general population. CVD prevention may be warranted in people with all categories of abnormal glucose metabolism.

Sun exposure and vitamin D are independent risk factors for CNS demyelination

Objectives: To examine whether past and recent sun exposure and vitamin D status (serum 25-hydroxyvitamin D [25(OH)D] levels) are associated with risk of first demyelinating events (FDEs) and to evaluate the contribution of these factors to the latitudinal gradient in FDE incidence in Australia. Methods: This was a multicenter incident case-control study. Cases (n = 216) were aged 18–59 years with a FDE and resident within one of 4 Australian centers (from latitudes 27°S to 43°S), from November 1, 2003, to December 31, 2006. Controls (n = 395) were matched to cases on age, sex, and study region, without CNS demyelination. Exposures measured included self-reported sun exposure by life stage, objective measures of skin phenotype and actinic damage, and vitamin D status. Results: Higher levels of past, recent, and accumulated leisure-time sun exposure were each associated with reduced risk of FDE, e.g., accumulated leisure-time sun exposure (age 6 years to current), adjusted odds ratio (AOR) = 0.70 (95% confidence interval [CI] 0.53–0.94) for each ultraviolet (UV) dose increment of 1,000 kJ/m2 (range 508–6,397 kJ/m2). Higher actinic skin damage (AOR = 0.39 [95% CI 0.17–0.92], highest grade vs the lowest) and higher serum vitamin D status (AOR = 0.93 [95% CI 0.86–1.00] per 10 nmol/L increase in 25(OH)D) were independently associated with decreased FDE risk. Differences in leisure-time sun exposure, serum 25(OH)D level, and skin type additively accounted for a 32.4% increase in FDE incidence from the low to high latitude regions. Conclusions: Sun exposure and vitamin D status may have independent roles in the risk of CNS demyelination. Both will need to be evaluated in clinical trials for multiple sclerosis prevention.

Prevalence and concurrence of anxiety, depression and fatigue over time in multiple sclerosis

Background: Anxiety, depression and fatigue are commonly reported by persons with multiple sclerosis (PwMS). Objectives: We estimated the prevalence of each factor in a representative sample of PwMS, and in subgroups defined by age, sex and disease duration, at cohort entry and over time. We further examined whether and how these factors clustered together. Methods: A population-based longitudinal cohort of 198 PwMS was followed 6-monthly for 2.5 years. The Hospital Anxiety and Depression Scale (HADS) was used to measure anxiety (cut-point >7) and depression (>7) and the Fatigue Severity Scale (FSS) to measure fatigue (≥5). Results: At cohort entry, prevalence of anxiety was 44.5% (95%CI 37–51%), depression 18.5% (95%CI 12.6–23.4%), and fatigue 53.7% (95%CI 47–61%). Fatigue was more common in males than females (RR 1.29, p=0.01), with attenuation of the effect after adjustment for Expanded Disability Status Scale (adjusted RR 1.18, p=0.13). Prevalence of anxiety (but not depression or fatigue) decreased by 8.1% per year of cohort observation (RR 0.92, 95%CI 0.86–0.98, p=0.009), with the effect more pronounced in women (14.6%, RR 0.85, 95%CI 0.79–0.93, –<0.001) than men (2.6%, RR 1.03, 95%CI 0.90–1.17, p=0.77). There was no apparent seasonal variation in the prevalence of any of the three factors (p>0.05). All three factors occurred contemporaneously at cohort entry in a higher proportion of the cohort than expected by chance (p<0.001). Conclusions: Anxiety, depression and fatigue are common in PwMS and tend to cluster together. The findings are important for clinical management of PwMS and to the exploration of possible shared causal biological pathways.

Smoking is associated with progressive disease course and increased progression in clinical disability in a prospective cohort of people with multiple sclerosis

BackgroundMultiple sclerosis has a variable disease course. The contribution of modifiable lifestyle factors to disease course has not been well studied, although one cohort has reported that smoking is associated with conversion to secondary progressive MS course and another that smoking is not.MethodsWe conducted a prospective cohort study of people with MS in Southern Tasmania from 2002 to 2004 with 78 % (203/259) of eligible participating and 198 with one or more reviews and confirmed MS. The cohort had a high retention rate (90 % (183/203)). The median follow- up time was 909 days. Smoking data were collected at baseline and six-monthly reviews. Clinical disability assessments were conducted annually in conjunction with a real time clinical notification system for relapses. A repeated measures analysis and other statistical methods were used.ResultsCumulative pack-years (p-y) smoked after cohort entry was associated with an increase in longitudinal MSSS (p < 0.001). Relative to the 0 pack years (p-y) category (in the year prior to the MSSS measure) those in the 0 to 1 p-y category had an adjusted mean difference in MSSS of 0.34 (95 % CI 0.28, 0.66); those in the 1 to 2 p-y category had a 0.41 (95 % CI −0.03, 0.85) increase; and those in the 2 or more p-y category had a 0.99 (95 % CI 0.41, 1.58) increase in MSSS. Similar results were found using a variety of statistical approaches or EDSS as a clinical outcome. Smoking during the cohort period was not associated with relapse (cumulative pack years smoked after cohort entry, HR 0.94 (0.69, 1.26) per pack year).ConclusionA better understanding of the mechanisms underlying smoking and multiple sclerosis, particularly progressive forms of the disease, may provide new insights for the eventual goal of better treatment and prevention of multiple sclerosis.

The role of latitude, ultraviolet radiation exposure and vitamin D in childhood asthma and hayfever: an Australian multicenter study.

To cite this article: Hughes AM, Lucas RM, Ponsonby A‐L, Chapman C, Coulthard A, Dear K, Dwyer T, Kilpatrick TJ, McMichael AJ, Pender MP, Taylor BV, Valery P, van der Mei IAF, Williams D. The role of latitude, ultraviolet radiation exposure and vitamin D in childhood asthma and hayfever: an Australian multicenter study. Pediatr Allergy Immunol 2011; 22: 327–333.

Depression and Insulin Resistance: Cross-sectional associations in young adults

OBJECTIVE To examine the association between depressive disorder and insulin resistance in a sample of young adults using the Composite International Diagnostic Interview to ascertain depression status. RESEARCH DESIGN AND METHODS Cross-sectional data were collected from 1,732 participants aged between 26 and 36 years. Insulin resistance was derived from blood chemistry measures of fasting insulin and glucose using the homeostasis model assessment method. Those identified with mild, moderate, or severe depression were classified as having depressive disorder. RESULTS The 12-month prevalence of depressive disorder was 5.4% among men and 11.7% among women. In unadjusted models mean insulin resistance was 17.2% (95% CI 0.7–36.0%, P = 0.04) higher in men and 11.4% (1.5–22.0%, P = 0.02) higher in women with depressive disorder. After adjustment for behavioral and dietary factors, the increased level of insulin resistance associated with depressive disorder was 13.2% (−3.1 to 32.3%, P = 0.12) in men and 6.1% (−4.1 to 17.4%, P = 0.25) in women. Waist circumference was identified as a mediator in the relationship between depression and insulin resistance, reducing the β coefficient in the fully adjusted models in men by 38% and in women by 42%. CONCLUSIONS A positive association was found between depressive disorder and insulin resistance in this population-based sample of young adult men and women. The association seemed to be mediated partially by waist circumference.

Current and past Epstein-Barr virus infection in risk of initial CNS demyelination

Objectives: To assess risk of a first clinical diagnosis of CNS demyelination (FCD) in relation to measures of Epstein-Barr virus (EBV) infection within the context of other known risk factors. Methods: This was a multicenter incident case-control study. FCD cases (n = 282) aged 18–59 years and controls (n = 558, matched on age, sex, and region) were recruited from 4 Australian centers between November 1, 2003, and December 31, 2006. A nested study (n = 215 cases, n = 216 controls) included measurement of whole blood quantitative EBV DNA load and serum EBV-specific antibodies. Conditional logistic regression was used to analyze case-control differences. Results: There were no significant case-control differences in the proportion with detectable EBV DNA (55.8% vs 50.5%, respectively, p = 0.28), or in quantitative EBV DNA load (p = 0.33). Consistent with previous work, higher anti-EBV–specific immunoglobulin G (IgG) titers and a history of infectious mononucleosis were associated with increased FCD risk and there was an additive interaction with HLA-DRB1*1501 status. We found additional interactions between high anti-EBNA IgG titer and SNPs in HLA-A (adjusted odds ratios [AOR] = 19.84 [95% confidence interval (CI) 5.95 to 66.21] for both factors compared to neither) and CTLA-4 genes (AOR = 0.31 [95% CI 0.13 to 0.76] for neither factor compared to both). EBV DNA load was lower at higher serum 25-hydroxyvitamin D concentrations in controls (r = −0.17, p = 0.01). An adverse effect of higher EBV DNA load on FCD risk was increased with higher 25-hydroxyvitamin D concentration (p[interaction] = 0.02). Conclusion: Past infection with EBV, but not current EBV DNA load in whole blood, is significantly associated with increased FCD risk. These associations appear to be modified by immune-related gene variants.

Childhood and adolescent predictors of leisure time physical activity during the transition from adolescence to adulthood: a population based cohort study.

BackgroundFew studies have investigated factors that influence physical activity behavior during the transition from adolescence to adulthood. This study explores the associations of sociodemographic, behavioral, sociocultural, attitudinal and physical factors measured in childhood and adolescence with physical activity behavior during the transition from adolescence to adulthood.MethodsChildhood and adolescent data (at ages 7-15 years) were collected as part of the 1985 Australian Health and Fitness Survey and subdivided into sociodemographics (socioeconomic status, parental education), behavioral (smoking, alcohol, sports diversity, outside school sports), sociocultural (active father, active mother, any older siblings, any younger siblings, language spoken at home), attitudinal (sports/recreational competency, self-rated health, enjoyment physical education/physical activity, not enjoying school sports) and physical (BMI, time taken to run 1.6 km, long jump) factors. Physical activity between the ages 15 and 29 years was reported retrospectively using the Historical Leisure Activity Questionnaire at follow-up in 2004-2006 by 2,048 participants in the Childhood Determinants of Adult Health Study (CDAH). Australias physical activity recommendations for children and adults were used to categorize participants as persistently active, variably active or persistently inactive during the transition from adolescence to adulthood.ResultsFor females, perceived sports competency in childhood and adolescence was significantly associated with being persistently active (RR = 1.88, 95% CI = 1.39, 2.55). Smoking (RR = 0.31 CI = 0.12, 0.82) and having younger siblings (RR = 0.69 CI = 0.52, 0.93) were inversely associated with being persistently active after taking physical and attitudinal factors into account. For males, playing sport outside school (RR = 1.47 CI = 1.05, 2.08), having active fathers (RR = 1.25 CI = 1.01, 1.54) and not enjoying school sport (RR = 4.07 CI = 2.31, 7.17) were associated with being persistently active into adulthood. Time taken to complete the 1.6 km run was inversely associated with being persistently active into adulthood (RR = 0.85 CI = 0.78, 0.93) after adjusting for recreational competency.ConclusionsPerceived sports competency (females) and cardiorespiratory fitness, playing sport outside school and having active fathers (males) in childhood and adolescence were positively associated with being persistently active during the transition from adolescence to adulthood.

Higher maternal dietary protein intake in late pregnancy is associated with a lower infant ponderal index at birth.

Aim:A high ponderal index at birth has been associated with later obesity and it has been suggested that intervention to prevent obesity and its sequela should consider the antenatal period. In this context, we investigated the association between maternal nutrition and birth anthropometry.Design:We analyzed data on 1040 mother–infant pairs collected during the Tasmanian Infant Health Survey (TIHS), Tasmania, 1988–1989. Maternal dietary intake during pregnancy was measured by food frequency questionnaire (FFQ) applied soon after birth. Outcomes of interest were birth weight, birth length, head circumference, ponderal index, head circumference –to-ponderal index ratio, placenta-to-birth weight ratio and head circumference-to-birth length index.Results:In multiple regression model, an increase of 10 g of absolute protein intake/day was associated with a reduction in birth weight of 17.8 g (95% CI: −32.7, −3.0; P=0.02). Protein intake was also associated negatively with ponderal index (β=−0.01; 95% CI: −0.02, −0.00; P=0.01). A 1 % increase in carbohydrate intake resulted in a 1% decline in placental weight relative to birth weight. Higher protein intake in the third trimester was associated with a reduced ponderal index among large birth weight infants but not low birth weight infants.Conclusions:This raises the possibility that any effect of high protein in altering infant anthropometry at birth may involve changes in body composition and future work to examine how a high-protein diet influences body composition at birth is warranted.

Parental smoking and smoking experimentation in childhood increase the risk of being a smoker 20 years later. The childhood determinants of adult health study

AIMS To examine the long-term effects of childhood smoking experimentation and exposure to parental smoking on adult smoking risk. METHODS Data were from a 20-year follow-up of 9-15-year-olds who completed questionnaires in the 1985 Australian Schools Health and Fitness Survey (n=6559). The relative risks (RR) of adult current smoking in 2004-05 for childhood exposure to smoking experimentation (never, a few puffs, <10 cigarettes, >10 cigarettes) and parental smoking (none, father, mother, both parents) in 1985, with adjustment for confounders, were estimated by log binomial modelling. Analyses were stratified by age (9-13 and 14-15 years) and sex. FINDINGS Participation at follow-up was 54% (n=3559). Childhood smoking experimentation increased the risk of being a current smoker particularly for 14-15-year-old experimenters of more than 10 cigarettes [males, RR 2.72, 95% confidence interval (CI) 1.74-4.25; females, RR 6.39, 95% CI 2.85-14.33]. Parental smoking was associated with adult current smoking risk, particularly for 9-13-year-olds with two smoking parents (males, RR 1.53, 95% CI 1.19-1.96; females, RR 1.99, 95% CI 1.52-2.61) and older males with smoking mothers (RR 1.82, 95% CI 1.22-2.73). Parental smoking was not associated with childhood smoking experimentation. CONCLUSIONS These findings suggest that any childhood smoking experimentation increases the risk of being a smoker 20 years later. As exposure to parental smoking predicted current smoking, parents should be aware of the association between their own smoking behaviour and that of their children.