Prevalence and patterns of multimorbidity in Australian baby boomers: the Busselton healthy ageing study.

BACKGROUND AND OBJECTIVE: Chronic medical conditions accumulate within individuals with age. However, knowledge concerning the trends, patterns and determinants of multimorbidity remains limited. This study assessed the prevalence and patterns of multimorbidity using extensive individual phenotyping in a general population of Australian middle-aged adults. METHODS: Participants (n = 5029, 55% female), born between 1946 and 1964 and attending the cross-sectional phase of the Busselton Healthy Ageing Study (BHAS) between 2010 and 2015, were studied. Prevalence of 21 chronic conditions was estimated using clinical measurement, validated instrument scores and/or self-reported doctor-diagnosis. Non-random patterns of multimorbidity were explored using observed/expected (O/E) prevalence ratios and latent class analysis (LCA). Variables associated with numbers of conditions and class of multimorbidity were investigated. RESULTS: The individual prevalence of 21 chronic conditions ranged from 2 to 54% and multimorbidity was common with 73% of the cohort having 2 or more chronic conditions. (mean ± SD 2.75 ± 1.84, median = 2.00, range 0-13). The prevalence of multimorbidity increased with age, obesity, physical inactivity, tobacco smoking and family history of asthma, diabetes, myocardial infarct or cancer. There were 13 pairs and 27 triplets of conditions identified with a prevalence > 1.5% and O/E > 1.5. Of the triplets, arthritis (> 50%), bowel disease (> 33%) and depression-anxiety (> 33%) were observed most commonly. LCA modelling identified 4 statistically and clinically distinct classes of multimorbidity labelled as: 1) "Healthy" (70%) with average of 1.95 conditions; 2) "Respiratory and Atopy" (11%, 3.65 conditions); 3) "Non-cardiometabolic" (14%, 4.77 conditions), and 4) "Cardiometabolic" (5%, 6.32 conditions). Predictors of multimorbidity class membership differed between classes and differed from predictors of number of co-occurring conditions. CONCLUSION: Multimorbidity is common among middle-aged adults from a general population. Some conditions associated with ageing such as arthritis, bowel disease and depression-anxiety co-occur in clinically distinct patterns and at higher prevalence than expected by chance. These findings may inform further studies into shared biological and environmental causes of co-occurring conditions of ageing. Recognition of distinct patterns of multimorbidity may aid in a holistic approach to care management in individuals presenting with multiple chronic conditions, while also guiding health resource allocation in ageing populations.

A comparison of obesity indices in relation to mortality in type 2 diabetes: the Fremantle Diabetes Study.

AIMS/HYPOTHESIS: This prospective association study aimed to compare the relationship between each of four obesity indices and mortality risk in people with type 2 diabetes. METHODS: The associations of BMI, waist circumference, WHR and A Body Shape Index (ABSI) with all-cause mortality were analysed in 1282 participants of the Fremantle Diabetes Study, followed for up to 20 years after baseline assessment. Models were adjusted for age and other confounders; assessments as continuous measures and by quintile were carried out for men and women separately. Sensitivity analyses were conducted to minimise reverse causality. RESULTS: When indices were assessed as continuous variables, there were significant bivariate associations with mortality for: ABSI, which was greater in both men and women who died (p < 0.001); WHR, which was greater in women only (p = 0.033); and BMI, which was lower in women only (p < 0.001). When assessed by quintile, there were significant bivariate associations with mortality for ABSI in men and women (p < 0.001) and BMI in women only (p = 0.002). In Cox models of time to death, adjusted for age, diabetes duration, ethnicity and smoking, ABSI quintiles showed a linear trend for both men (p = 0.003) and women (p = 0.035). Men in the fifth ABSI quintile had an increased mortality risk compared with those in the first quintile (HR [95% CI]: 1.74 [1.24, 2.44]) and women in the fifth ABSI quintile had an increased mortality risk that approached statistical significance (1.42 [0.97, 2.08], p = 0.08). Men in the fifth WHR quintile had an increased mortality risk (1.47 [1.05, 2.06]). There was no association between mortality and BMI or waist circumference in either sex. CONCLUSIONS/INTERPRETATION: ABSI was the obesity index most strongly associated with all-cause mortality in Australians with type 2 diabetes. There was no evidence for an obesity paradox with any of the assessed indices. ABSI may be a better index of central obesity than waist circumference, BMI or WHR when assessing mortality risk in type 2 diabetes.

Prevalence and incidence of thyroid dysfunction in type 1 diabetes, type 2 diabetes and latent autoimmune diabetes of adults: The Fremantle Diabetes Study Phase II.

OBJECTIVE: Since the results of published studies assessing thyroid dysfunction complicating diabetes have been variable in quality, inconsistent and may not reflect contemporary clinical care, the aim of this study was to determine its prevalence and incidence in a large, well-characterized, representative cohort. DESIGN: Community-based, longitudinal, observational study. PATIENTS: A total of 1617 participants from the Fremantle Diabetes Study Phase II (FDS2), including 130 (8.0%) with type 1 diabetes, 1408 (87.1%) with type 2 diabetes, and 79 (4.9%) with latent autoimmune diabetes of adults (LADA). MEASUREMENTS: Serum thyrotropin (TSH) and free thyroxine (FT4) at baseline between 2008 and 2011 and in those attending Year 4 follow-up. RESULTS: The prevalence of known thyroid disease (ascertained from baseline self-reported thyroid medication use or hospitalization data) was 11.7% (189/1617). Of the remaining 1428 participants, 5.1% (73/1428) had biochemical evidence of subclinical hypothyroidism, 1.1% (15/1428) overt hypothyroidism, 0.1% (2/1428) subclinical hyperthyroidism and 0.2% (3/1428) overt hyperthyroidism, representing an overall baseline prevalence of thyroid disease of 17.4% (282/1617). During 5694 patient-years of follow-up, 25 (3.0%) of the 844 with a normal baseline TSH and follow-up data developed known thyroid disease. Of the remaining 819, 3.4% developed subclinical hypothyroidism, 0.2% overt hypothyroidism and 0.5% subclinical hyperthyroidism. There were no statistically significant differences in the prevalence or incidence of thyroid dysfunction by diabetes type. CONCLUSIONS: Thyroid dysfunction, known or detected through screening, is common in diabetes. These data suggest the need for periodic clinical and biochemical screening for thyroid disease in all types of diabetes.

Retinopathy predicts stroke but not myocardial infarction in type 2 diabetes: the Fremantle Diabetes Study Phase II.

BACKGROUND: Microangiopathy in type 2 diabetes (T2D) is associated with cardiovascular disease (CVD), but most relevant studies were performed > 10 years ago. CVD risk factor management has since improved. The aim of this study was to determine whether diabetic retinopathy (DR) and its severity increases stroke and myocardial infarction (MI) risk in a contemporary cohort. METHODS: Fremantle Diabetes Study Phase II participants with T2D had DR graded from fundus photography at baseline between 2008 and 2011. Subsequent hospitalizations and mortality for MI or stroke were ascertained through validated data linkage to end-2016. Cox regression modelling identified predictors of first stroke and MI including DR presence and severity. RESULTS: The 1521 participants with T2D and known DR status (mean age 65.6 years, 52.1% males, median diabetes duration 9.0 years) were followed for a mean of 6.6 years. After excluding those with prior MI/stroke, there were 126 incident MIs among 1393 eligible participants and 53 incident strokes in 1473 eligible participants, respectively. Moderate non-proliferative DR (NPDR) or worse was significantly and independently associated with an increased risk of incident stroke (adjusted hazard ratio 2.55 (95% CI 1.19, 5.47), p = 0.016). Retinopathy presence and severity increased the risk of incident MI in unadjusted models (p ≤ 0.001), but these associations were no longer statistically significant after adjusting for other risk factors. CONCLUSIONS: Moderate NPDR or worse was associated with an increased risk of first stroke in Australians with T2D. Intensified CVD risk factor management should be considered for patients with at least moderate NPDR.

Temporal changes in the incidence and predictors of severe hypoglycaemia in type 2 diabetes: The Fremantle Diabetes Study.

AIM: To determine the incidence of severe hypoglycaemia and its predictors in community-based patients with type 2 diabetes studied between 2008 and 2013 compared with those in a cohort of patients with type 2 diabetes from the same geographical area assessed a decade earlier. METHODS: We studied 1551 participants (mean age 65.7 years, 51.9% men) with type 2 diabetes from the longitudinal observational Fremantle Diabetes Study Phase II (FDS2). Severe hypoglycaemia was ascertained as that requiring ambulance attendance, emergency department services and/or hospitalization. Cox proportional hazards modelling was used to determine predictors of a first episode of severe hypoglycaemia, and negative binomial regression was used to identify predictors of frequency. RESULTS: Sixty-three participants (4.1%) experienced 83 episodes, representing an incidence of 1.34/100 participant-years (95% confidence interval [CI] 1.08 to 1.67; vs 1.67/100 participant-years [95% CI 1.31-2.13] in the Fremantle Diabetes Study Phase I [FDS1]; P = 0.18). Those experiencing severe hypoglycaemia experienced one to four episodes in both cohorts. The independent predictors of incident severe hypoglycaemia in the FDS2 were: older age; higher educational attainment; alcohol consumption; current smoking; sulphonylurea/insulin treatment; prior severe hypoglycaemia; renal impairment; and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP). The same variables except smoking were associated with frequency of severe hypoglycaemia. Most of these risk factors paralleled those in the FDS1, but current smoking and plasma NT-proBNP were novel. CONCLUSIONS: The incidence and frequency of severe hypoglycaemia did not change between the Fremantle Diabetes Study phases but novel risk factors, including plasma NT-proBNP, were observed in the FDS2.

Glycaemic control and mortality in older people with type 2 diabetes: The Fremantle Diabetes Study Phase II.

AIM: To investigate whether tight glycaemic control achieved with metformin, insulin or sulphonylurea-based pharmacotherapy increases all-cause mortality in older people with type 2 diabetes. MATERIALS AND METHODS: We conducted a prospective cohort study of individuals with known diabetes recruited between 2008 and 2011 and followed until 2016. The impact of baseline glycated haemoglobin (HbA1c) on mortality hazards was investigated in participants aged ≥75 years. Proportional hazards models for time to death were constructed from the baseline clinical assessment, then the variables of interest (HbA1c, treatment category and their interactions) were entered. RESULTS: There were 367 participants (mean age 80.1 ± 3.9 years, median [interquartile range] HbA1c 50 [45-56] mmol/mol or 6.7 [6.3-7.3]%) who were followed for a median (interquartile range) 6.7 (4.5-7.7) years, during which 40.9% of the participants died. At baseline, 60.4% were on metformin-based treatment, 35.3% on sulphonylurea-based treatment and 23.2% on treatment including insulin. Baseline HbA1c was significantly associated with mortality in a model that included interactions between HbA1c and the three treatment-based groups compared with non-pharmacological treatment. The metformin treatment group had higher mortality when HbA1c levels were <48 mmol/mol (<6.5%) and the sulphonylurea and insulin treatment groups had higher mortality when HbA1c levels were <52 mmol/mol (<7.0%), with hazard ratios of 2.63 (95% confidence interval [CI] 1.39-4.97), 2.49 (95% CI 1.14-5.44) and 2.22 (95% CI 1.12-4.43), respectively. CONCLUSIONS: Tight glycaemic control may be hazardous in older people with type 2 diabetes when achieved with pharmacotherapy with metformin, and especially with insulin or sulphonylureas. These data confirm that overtreatment is likely to be an important clinical problem in this vulnerable population.

Prevalence of diabetes in Australia: insights from the Fremantle Diabetes Study Phase II.

BACKGROUND: Accurate diabetes prevalence estimates are important for health service planning and prioritisation. Available data have limitations, suggesting that the contemporary burden of diabetes in Australia is best assessed from multiple sources. AIMS: To use systematic active detection of diabetes cases in a postcode-defined urban area through the Fremantle Diabetes Study Phase II (FDS2) to complement other epidemiological and survey data in estimating the national prevalence of diabetes and its types. METHODS: People with known diabetes in a population of 157 000 were identified (n = 4639) from a variety of sources and those providing informed consent (n = 1668 or 36%) were recruited to the FDS2 between 2008 and 2011. All FDS2 participants were assigned a type of diabetes based on clinical and laboratory (including serological and genetic) features. Data from people identified through the FDS2 were used to complement Australian Health Survey and National Diabetes Services Scheme prevalence estimates (the proportions of people well controlled on no pharmacotherapy and registering with the National Diabetes Services Scheme respectively) in combination with Australian Bureau of Statistics data to generate the prevalence of diabetes in Australia. RESULTS: Based on data from multiple sources, 4.8% or 1.1 million Australians had diabetes in 2011-2012, of whom 85.8% had type 2 diabetes, 7.9% type 1 diabetes and 6.3% other types (latent autoimmune diabetes of adults, monogenic diabetes and secondary diabetes). CONCLUSIONS: Approximately 1 in 20 Australians has diabetes. Although most have type 2 diabetes, one in seven has other types that may require more specialised diagnosis and/or management.

Dementia onset, incidence and risk in type 2 diabetes: a matched cohort study with the Fremantle Diabetes Study Phase I.

AIMS/HYPOTHESIS: The study aimed to assess the incidence, age of onset, survival and relative hazard of dementia in well-categorised community-based patients with type 2 diabetes compared with a matched cohort of individuals without diabetes. METHODS: A longitudinal observational study was undertaken involving 1291 participants with type 2 diabetes from the Fremantle Diabetes Study and 5159 matched residents without documented diabetes. Linkage with health-related databases was used to detect incident dementia. Relative hazards were assessed using both cause-specific and subdistribution proportional hazards models. RESULTS: During 13.8 ± 5.8 years of follow-up, incident dementia occurred in 13.9% and 12.4% of the groups of participants with and without diabetes, respectively (p = 0.15). With type 2 diabetes, the incidence of dementia was higher (incidence rate ratio [IRR] 1.28, 95% CI 1.08, 1.51), as was the competing risk of death (IRR 1.50, 95% CI 1.38, 1.64). The ages when dementia was first recorded and when death with dementia occurred were both earlier with diabetes, by 1.7 (95% CI 0.6, 2.9) and 2.3 (95% CI 1.1, 3.6) years, respectively (both p ≤ 0.004). Type 2 diabetes was associated with an adjusted subdistribution HR of 1.18 (95% CI 1.00, 1.39), and a cause-specific HR of 1.51 (95% CI 1.27, 1.78) for all-cause dementia. CONCLUSIONS/INTERPRETATION: Type 2 diabetes is associated with an increased incidence of dementia, and dementia onset occurs at a younger age. The relative hazards of both dementia and premature mortality are increased and, as a consequence, the increased risk of dementia in type 2 diabetes is not as marked as suggested by cause-specific HRs.

Comorbid Anxiety and Depression and Their Impact on Cardiovascular Disease in Type 2 Diabetes: The Fremantle Diabetes Study Phase II.

BACKGROUND: The aims were to determine whether anxious depression, defined by latent class analysis (LCA), predicts cardiovascular outcomes in type 2 diabetes and to compare the predictive power of anxious depression with Diagnostic & Statistical Manual Versions IV and 5 (DSM-IV/5) categories of depression and generalized anxiety disorder (GAD). METHODS: Prospective observational study of 1,337 type 2 participants. Baseline assessment with the 9-item Patient Health Questionnaire and the GAD Scale; LCA-defined groups with minor or major anxious depression based on anxiety and depression symptoms. Cox modeling used to compare the independent impact of: (1) LCA anxious depression, (2) DSM-IV/5 depression, (3) GAD on incident cardiovascular events and deaths after 4 years. RESULTS: LCA minor and major anxious depression was present in 21.9 and 7.8% of participants, respectively, DSM-IV/5 minor and major depression in 6.2 and 6.1%, respectively, and GAD in 4.8%. There were 110 deaths, 31 cardiovascular deaths, and 199 participants had incident cardiovascular events. In adjusted models, minor anxious depression (Hazard ratio (95% confidence intervals): 1.70 (1.15-2.50)) and major anxious depression (1.90 (1.11-3.25)) predicted incident cardiovascular events and major anxious depression also predicted cardiovascular mortality (4.32 (1.35-13.86)). By comparison, incident cardiovascular events were predicted by DSM-IV/5 major depression (2.10 (1.22-3.62)) only and cardiovascular mortality was predicted by both DSM-IV/5 major depression (3.56 (1.03-12.35)) and GAD (5.92 (1.84-19.08)). CONCLUSIONS: LCA-defined anxious depression is more common than DSM-IV/5 categories and is a strong predictor of cardiovascular outcomes in type 2 diabetes. These data suggest that this diagnostic scheme has predictive validity and clinical relevance.

A Randomized, Placebo-Controlled, Double-Blind Efficacy Study of Nefiracetam to Treat Poststroke Apathy.

BACKGROUND: To evaluate the efficacy of treatment with nefiracetam compared to placebo in poststroke apathy. METHODS: A parallel group, randomized, placebo-controlled, double-blind two-center trial in patients with recent stroke and apathy was conducted in 2 tertiary teaching hospitals in Perth, Western Australia, between March 2010 and October 2014. Consenting patients hospitalized with stroke were screened for participation at the time of hospitalization and, if diagnosed with apathy 8-36 weeks later, they were randomized to 12 weeks of 900 mg/day nefiracetam or placebo. The primary efficacy parameter was change in apathy at 12 weeks defined by the 14-item Apathy Scale (AS). RESULTS: Of 2514 patients screened, only 377 (15%) were eligible for the study after the first screening, 233 declined further participation, and 144 were assessed for apathy at 8-36 weeks post stroke to confirm eligibility. Twenty patients out of 106 with a complete psychiatric assessment had apathy (19%). Of this sample, 13 patients were randomized. Overall, the AS score decreased by a mean of 7.0 points (95% CI = -14.6 to .6), but there was no significant between-group difference at week 12 (mean paired t-tests, P > .14). CONCLUSIONS: Treatment with nefiracetam did not prove to be more efficacious than placebo in ameliorating apathy in stroke. The main limitation was the very small sample randomized, highlighting the limitations of conducting drug trials for behavioral problems among stroke patients. Pharmacological studies of apathy in stroke will require a large multicenter study and a massive sample of patients.

Apathy in older patients with type 2 diabetes.

OBJECTIVE: To determine the prevalence, incidence, persistence, likely causes, and consequences of apathy in patients with Type 2 diabetes and to compare the prevalence with a healthy control sample. DESIGN: Cross-sectional comparison of diabetic and nondiabetic samples; longitudinal follow-up of diabetic sample. SETTING: Academic research department. PARTICIPANTS: Non-demented, older patients with long-standing Type 2 diabetes (N = 122) recruited from a community-based cohort study and 69 healthy volunteers. MEASUREMENTS: Clinical assessments of apathy and potential causative conditions, repeated in the diabetic sample after 16.7 ± 2.5 months. Informant rated symptoms from the 14-item Apathy Scale were used to generate apathy diagnoses based on standardized criteria. Cognition was assessed by Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). RESULTS: The diabetic and comparison samples had the same age and MMSE scores, but the diabetic sample had a higher frequency of depression, cerebrovascular history, and cognitive deficits. Apathy was more prevalent in diabetes (diabetic 13.9% versus control sample 1.4%, p = 0.005) and was independently associated with CDR 0.5 status (OR [95% CI]: 3.66 [1.25-19.70]) and depression (8.48 [2.74-26.21]). In 108 diabetic patients who were followed up, incident apathy occurred in 7.4% of cases, and persisted in 50% of those with baseline apathy. Baseline apathy was independently associated with lnHbA1c levels (ß: 0.20, t = 2.29, df = 119, p = 0.024; model R(2) = 0.10) and incident/persistent apathy was associated with greater risk of cognitive decline (6.72 [1.19-37.87]). CONCLUSION: Apathy is a frequent neuropsychiatric syndrome in older patients with Type 2 diabetes, and is associated with poor glycaemic control and cognitive decline.

Australian population trends and disparities in cholinesterase inhibitor use, 2003 to 2010.

BACKGROUND: The Australian Pharmaceutical Benefits Scheme (PBS) first subsidized cholinesterase inhibitors (CEIs) for Alzheimer's disease in 2001, introducing a novel therapy for a previously untreatable common condition. This study aims to determine Australian rates of CEI use and to assess equality of access to treatment based on socioeconomic status and geographic remoteness. METHODS: Pharmaceutical claims records were used to identify all Australians prescribed CEIs between January 2003 and December 2010. Age-standardized and sex-adjusted index prescription rates were derived using the total Australian population as the denominator to examine temporal trends and the impacts of socioeconomic and geographic disadvantage on CEI index prescription rates. RESULTS: Index prescription rates peaked in 2004 at 92.5 per 100,000 person-years, declining to between 70.2 and 73.5 for years 2006 to 2010. Rates were highest in the 85- to 89-year age group and 2.6-fold higher in the least socioeconomic disadvantaged population when compared with the most disadvantaged population. In major cities in Australia, index prescription rates were 1.4 to 1.7 times greater compared with remote areas. CONCLUSIONS: Increasing geographic remoteness and socioeconomic disadvantage are associated with lower CEI index prescription rates, indicating inequities in the management of Alzheimer's disease in Australia.

A comprehensive investigation of variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/R2), and their association with serum adiponectin, type 2 diabetes, insulin resistance and the metabolic syndrome.

BACKGROUND: Low levels of serum adiponectin have been linked to central obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. Variants in ADIPOQ, the gene encoding adiponectin, have been shown to influence serum adiponectin concentration, and along with variants in the adiponectin receptors (ADIPOR1 and ADIPOR2) have been implicated in metabolic syndrome and type 2 diabetes. This study aimed to comprehensively investigate the association of common variants in ADIPOQ, ADIPOR1 and ADIPOR2 with serum adiponectin and insulin resistance syndromes in a large cohort of European-Australian individuals. METHODS: Sixty-four tagging single nucleotide polymorphisms in ADIPOQ, ADIPOR1 and ADIPOR2 were genotyped in two general population cohorts consisting of 2,355 subjects, and one cohort of 967 subjects with type 2 diabetes. The association of tagSNPs with outcomes were evaluated using linear or logistic modelling. Meta-analysis of the three cohorts was performed by random-effects modelling. RESULTS: Meta-analysis revealed nine genotyped tagSNPs in ADIPOQ significantly associated with serum adiponectin across all cohorts after adjustment for age, gender and BMI, including rs10937273, rs12637534, rs1648707, rs16861209, rs822395, rs17366568, rs3774261, rs6444175 and rs17373414. The results of haplotype-based analyses were also consistent. Overall, the variants in the ADIPOQ gene explained <5% of the variance in serum adiponectin concentration. None of the ADIPOR1/R2 tagSNPs were associated with serum adiponectin. There was no association between any of the genetic variants and insulin resistance or metabolic syndrome. A multi-SNP genotypic risk score for ADIPOQ alleles revealed an association with 3 independent SNPs, rs12637534, rs16861209, rs17366568 and type 2 diabetes after adjusting for adiponectin levels (OR=0.86, 95% CI=(0.75, 0.99), P=0.0134). CONCLUSIONS: Genetic variation in ADIPOQ, but not its receptors, was associated with altered serum adiponectin. However, genetic variation in ADIPOQ and its receptors does not appear to contribute to the risk of insulin resistance or metabolic syndrome but did for type 2 diabetes in a European-Australian population.

Group-Based Trajectory Modelling of Changes in Mobility over Six Years in Type 2 Diabetes: The Fremantle Diabetes Study Phase II.

To investigate temporal changes in mobility in community-based people with type 2 diabetes, Fremantle Diabetes Study Phase II (FDS2) data were analysed. The baseline assessment included the Timed Up and Go (TUG) test, which was repeated biennially for up to six years. Group-based trajectory modelling (GBTM) identified TUG trajectory groups in participants with ≥2 tests. Independent associates of group membership were assessed using multinomial regression. Of 1551 potential FDS2 participants, 1116 (72.0%; age 64.9 ± 11.0 years, 45.6% female) were included in the modelling. The best-fitting GBTM model identified two groups with linear, minimally changing trajectories (76.2% and 19.4% of participants; baseline TUG times 8 ± 2 and 12 ± 3 s, respectively), and a third (4.5%; baseline TUG 17 ± 5 s) with a TUG that increased over time then fell at Year 6, reflecting participant attrition. Both slower groups were older, more likely to be female, obese, and had greater diabetes-associated complications and comorbidities. Almost one-quarter of the FDS2 cohort had clinically relevant mobility impairment that persisted or worsened over six years, was multifactorial in origin, and was associated with excess late withdrawals and deaths. The TUG may have important clinical utility in assessing mobility and its consequences in adults with type 2 diabetes.

The Clinical Relevance of Diabetes Distress versus Major Depression in Type 2 Diabetes: A Latent Class Analysis from the Fremantle Diabetes Study Phase II.

BACKGROUND: The nosological position and clinical relevance of the concept of diabetes distress (DD) are uncertain. The aim of this study was to use latent class analysis (LCA) to categorise classes of people with type 2 diabetes and to compare their characteristics. METHODS: Data from 662 participants in the longitudinal observational Fremantle Diabetes Study Phase II were analysed. LCA identified latent subgroups based on individual responses to the Patient Health Questionnaire-9, the Generalised Anxiety Disorder Scale, and the 5-item Problem Areas in Diabetes Scale. RESULTS: Four classes were identified: Class 1 (65.7%, no symptoms), Class 2 (14.0%, DD), Class 3 (12.6%, subsyndromal depression (SSD)), and Class 4 (7.6%, major depression (MD)). Multinomial regression analysis with Class 1 as reference showed significant associations between the DD class and Southern European and Asian ethnic background, HbA1c, and BMI. The SSD class was significantly associated with HbA1c, cerebrovascular disease, and coronary heart disease (CHD). The MD class had significant associations with age (inversely), Southern European ethnic background, HbA1c, BMI, and CHD. In conclusion, LCA identified a pure DD group comprising 14.0% of participants. The only variable uniquely associated with the DD class was Asian ethnic background. CONCLUSION: Although identification of DD may have some utility in assessing the psychological wellbeing of individuals with type 2 diabetes, it adds little to the assessment of depressive disorder and its significant clinical sequalae.

Long-term mortality risks associated with mild anaemia in older persons: the Busselton Health Study.

BACKGROUND: up to 25% of older people in the USA and other Western countries are anaemic by World Health Organization (WHO) criteria. The objective of this study was to examine the long-term relationships of haemoglobin concentration with all-cause and cause-specific mortality in a community-based sample of Australian adults surveyed in 1978. METHODS: a community survey of 2,194 adults aged 40+ years in Busselton, Western Australia in 1978 with mortality follow-up to 2001. Cox regression models were used to investigate the relationships of haemoglobin as a continuous measure and anaemia by WHO criteria (women <12 g/dl (7.5 mmol/l); men <13 g/dl (8.1 mmol/l)) with all-cause, cardiovascular and cancer mortality. RESULTS: anaemia was predominantly mild (>10 g/dl) and normocytic. There was an increased risk of death from all causes and from cancer for men with low haemoglobin. Cancers were predominantly of the prostate and genito-urinary organs, and to a lesser extent the gastrointestinal tract. There was no increased risk of all cause or cancer death in women. CONCLUSION: mild, normocytic anaemia is associated with survival reductions in middle-aged and older men, where it often occurs with prostate, gastrointestinal and other cancers, and should be investigated to exclude treatable causes.

Temporal Trends in Mortality Associated with Comorbid Type 2 Diabetes and Schizophrenia: The Fremantle Diabetes Study.

BACKGROUND: In Phase I of the community-based Fremantle Diabetes Study (FDS1), there was evidence of a deleterious interactive effect of schizophrenia and type 2 diabetes on mortality. Our aim was to investigate whether the mortality gap had improved in FDS Phase II (FDS2) conducted 15 years later. METHODS: Participants with type 2 diabetes from FDS1 (n = 1291 recruited 1993-1996) and FDS2 (n = 1509 recruited 2008-2011) were age-, sex- and postcode-matched 1:4 to people without diabetes. Schizophrenia at entry and incident deaths were ascertained from validated administrative data. RESULTS: Schizophrenia affected 50/11,195 (0.45%) of participants without diabetes and 17/2800 (0.61%) of those with type 2 diabetes (p = 0.284). During 142,304 person-years of follow-up, the mortality rate (95% CI) was lowest for the FDS2 subgroup without diabetes/schizophrenia (18.2 (16.9, 19.6)/1000 person-years) and highest in FDS2 and FDS1 subgroups with type 2 diabetes/schizophrenia (53.3 (14.5, 136.6) and 98.0 (31.8, 228.8)/1000 person-years, respectively). Compared to the respective FDS subgroup without diabetes/schizophrenia, the mortality rate ratio was approximately 50% higher in the type 2 diabetes subgroup, and three times higher in those with type 2 diabetes/schizophrenia. In Cox regression, unadjusted hazard ratios were highest in those with type 2 diabetes/schizophrenia in FDS1 (HR (95% CI): 3.71 (1.54, 8.93) and FDS2 (2.96 (1.11, 7.91)), increasing to 5.61 (2.33, 13.5) and 26.9 (9.94, 72.6), respectively, after adjustment for age. CONCLUSIONS: Although limited by small numbers of schizophrenia cases, these data suggest that comorbid type 2 diabetes and schizophrenia remains associated with a substantial and possibly increasing mortality gap.

The relationship between thyroid dysfunction, cardiovascular morbidity and mortality in type 2 diabetes: The Fremantle Diabetes Study Phase II.

AIMS: It is uncertain whether subclinical thyroid dysfunction is associated with cardiovascular disease (CVD) events and mortality in people with type 2 diabetes. The aim of this study was to determine whether undetected thyroid disease increases the risk of incident CVD and death in type 2 diabetes. METHODS: One thousand two hundred fifty participants with type 2 diabetes (mean age 65.3 years, 56.5% males, median diabetes duration 8.0 years) without known thyroid disease and not taking medications known to affect thyroid function were categorised, based on baseline serum free thyroxine (FT4) and thyrotropin (TSH) concentrations, as euthyroid, overt hypothyroid (increased TSH, low FT4), subclinical hypothyroid (increased TSH, normal FT4), overt thyrotoxic (decreased TSH, raised FT4) or subclinical thyrotoxic (decreased TSH, normal FT4). Incident myocardial infarction, incident stroke, all-cause and cardiovascular mortality were ascertained during a mean 6.2-6.7 years of follow-up. RESULTS: Most participants with newly-detected thyroid dysfunction had subclinical hypothyroidism (77.2%) while overt/subclinical thyrotoxicosis was infrequent. Compared to participants with TSH 0.34-2.9 mU/L, those with TSH > 5.1 mU/L were not at increased risk of incident myocardial infarction (adjusted hazard ratio (95% confidence limits) 1.77 (0.71, 2.87)), incident stroke (1.66 (0.58, 4.78)), all-cause mortality (0.78 (0.44, 1.37)) or cardiovascular mortality (1.16 (0.38, 3.58)). Independent baseline associates of subclinical hypothyroidism included estimated glomerular filtration rate and systolic blood pressure. CONCLUSIONS: Subclinical hypothyroidism was not independently associated with CVD events or mortality in community-dwelling people with type 2 diabetes despite its associations with CVD risk factors, questioning strategies to identify and/or treat mild thyroid dysfunction outside usual care.

Cognitive Impairment in People with Diabetes-Related Foot Ulceration.

AIMS: To determine whether there is an excess of cognitive impairment in patients with type 2 diabetes and foot ulceration. METHODS: 55 patients with type 2 diabetes and foot ulcers attending Multidisciplinary Diabetes Foot Ulcer clinics (MDFU cohort) were compared with 56 patients with type 2 diabetes attending Complex Diabetes clinics (CDC cohort) using commonly used screening tests for cognitive impairment (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA)), as well as foot self-care, mood and health literacy. MMSE was also compared between the MDFU cohort and a historical community-based cohort of patients with type 2 diabetes (FDS2 cohort). RESULTS: Median MMSE scores were the same in all three groups (28/30). Median MOCA scores did not differ between the MDFU and CDC cohorts (25/30). There were no significant differences in the percentages of patients with MMSE ≤ 24 or MOCA ≤ 25 between MDFU and CDC cohorts (3.6% versus 10.7%, p = 0.27 and 56.4% versus 51.8%, p = 0.71, respectively), findings that did not change after adjustment for age, sex, education, diabetes duration, and random blood glucose. CONCLUSIONS: Using conventionally applied instruments, patients with type 2 diabetes and foot ulceration have similar cognition compared with patients without, from either hospital-based clinic or community settings.

Relationship between brain R(2) and liver and serum iron concentrations in elderly men.

Studies of iron overload in humans and animals suggest that brain iron concentrations may be related in a regionally specific way to body iron status. However, few quantitative studies have investigated the associations between peripheral and regional brain iron in a normal elderly cohort. To examine these relationships, we used MRI to measure the proton transverse relaxation rate (R(2)) in 13 gray and white matter brain regions in 18 elderly men (average age, 75.5 years) with normal cognition. Brain R(2) values were compared with liver iron concentrations measured using the FerriScan MRI technique and serum iron indices. R(2) values in high-iron gray matter regions were significantly correlated (positively) with liver iron concentrations (globus pallidus, ventral pallidum) and serum transferrin saturation (caudate nucleus, globus pallidus, putamen) measured concurrently with brain R(2), and with serum iron concentrations (caudate nucleus, globus pallidus) measured three years before the current study. Our results suggest that iron levels in specific gray matter brain regions are influenced by systemic iron status in elderly men.