Risk factors and outcomes of anxiety symptom trajectories in type 2 diabetes: the Fremantle Diabetes Study Phase II.

AIM: To identify determinants and outcomes of 4-year trajectories of anxiety symptoms in a community-based cohort with type 2 diabetes. METHODS: Some 1091 participants in the Fremantle Diabetes Study-Phase II with type 2 diabetes completed the Generalized Anxiety Disorder Scale at baseline and biennially for 4 years, in addition to psychological, biomedical and self-management measures. Latent growth mixture modelling identified trajectories of anxiety symptom severity, and regression models determined predictors of trajectory membership and associated outcomes. RESULTS: Two distinct groups of participants were identified: those with continuously low-no anxiety symptoms (87%) and those with improving but consistently high anxiety symptoms (elevated anxiety; 13%). Higher HbA1c and BMI, macrovascular complications and a history of generalized anxiety and/or major depressive disorder increased the risk of elevated anxiety. Elevated anxiety did not predict change in health-related outcomes over time. Elevated anxiety and depression symptoms were highly comorbid and those with both displayed the most persistent anxiety symptoms. CONCLUSIONS: A subgroup of individuals with type 2 diabetes are at risk of persistently elevated anxiety symptoms. Routine monitoring of the severity of psychological symptoms over time in this population should facilitate earlier and more intensive mood management.

Clinical risk factors for depressive syndrome in Type 2 diabetes: the Fremantle Diabetes Study.

AIMS: To identify early clinical predictors of depressive syndrome in people with Type 2 diabetes. METHODS: Depressive syndrome was assessed in 325 individuals with Type 2 diabetes 15 years after a baseline assessment, which included information on antidepressant use and depressive symptoms obtained using a quality-of-life scale. Follow-up current and lifetime depressive syndrome were assessed using the nine-item Patient Health Questionnaire and the Brief Lifetime Depression Scale and taking account of antidepressant use. Analyses were conducted inclusive and exclusive of antidepressant use where Patient Health Questionnaire criteria were not met. RESULTS: At baseline, the participants were aged 57.2±9.3 years and the median (interquartile range) diabetes duration was 2.2 (0.6-6.0) years. After a mean of 14.7±1.1 years' follow-up, 81 participants (24.9%) had depressive syndrome (14.8% defined by the Patient Health Questionnaire, 10.2% defined by antidepressants) and 31.4% reported lifetime depression, and in 10.2% of participants this preceded diabetes onset. With logistic regression (inclusive of antidepressants), follow-up depressive syndrome was negatively associated with education level [odds ratio 0.39 (95% CI 0.20-0.75)] and antidepressant use [odds ratio 0.11 (95% CI 0.03-0.36)] and was positively associated with depression history before diabetes onset [odds ratio 2.79 (95% CI 1.24-6.27)]. In the model exclusive of antidepressants, depressive syndrome was positively associated with baseline depressive symptoms [odds ratio 2.57 (95% CI 1.32-5.03)] and antidepressant use [odds ratio 3.54 (95% CI 1.20-10.42)] and was negatively associated with education level [odds ratio 0.39 (95% CI 0.19-0.81)]. CONCLUSIONS: Risk factors for depressive syndrome can be identified early after the onset of Type 2 diabetes. The early presence of depressive symptoms or its treatment and/or history of depression are likely indicators of vulnerability. Early risk stratification for late depressive syndrome is feasible in people with Type 2 diabetes and could assist with depression treatment or prevention.

Depression symptoms are persistent in Type 2 diabetes: risk factors and outcomes of 5-year depression trajectories using latent class growth analysis.

AIMS: To describe the long-term trajectories of depression symptom severity in people with Type 2 diabetes, and to identify predictors and associates of these trajectories. METHODS: A community-dwelling cohort of 1201 individuals with Type 2 diabetes from the Fremantle Diabetes Study Phase II was followed for 5 years. The nine-item version of the Patient Health Questionnaire was administered annually to assess depression symptoms, and biomedical and psychosocial measures were assessed at baseline and biennially. Latent class growth analysis was used to identify classes of depression severity trajectories and associated outcomes, and logistic regression models were used to determine predictors of class membership. RESULTS: Three trajectories of depression symptoms were identified: continuously low depression symptoms (85.2%); gradually worsening symptoms that then began to improve (persistent depression - low-start; 7.3%); and gradually improving symptoms which later worsened (persistent depression - high-start; 7.5%). Younger age, being a woman, and a lifetime history of major depressive disorder, were associated with greater risk of persistent depression symptoms. Persistent depression was associated with consistently higher BMI over time, but not with changes in HbA1c or self-monitoring of blood glucose. CONCLUSIONS: A subset of individuals with Type 2 diabetes is at risk of depression symptoms that remain elevated over time. Younger, overweight individuals with a history of depression may benefit from early and intensive depression management and ongoing follow-up as part of routine Type 2 diabetes care.

Lifetime depression and anxiety increase prevalent psychological symptoms and worsen glycemic control in type 2 diabetes: The Fremantle Diabetes Study Phase II.

AIMS: To determine the contribution of lifetime major depressive disorder (L-MDD) and lifetime generalized anxiety disorder (L-GAD) to current psychological symptom severity, health behaviour and glycaemic control in type 2 diabetes. METHODS: 1285 community-dwelling people with type 2 diabetes (Fremantle Diabetes Study Phase-II; FDS2) completed the PHQ-9 and Brief Life-Time Depression Scale (BLDS) to assess current and past MDD. The Generalized Anxiety Disorder Scale (GADS) and the Generalized Anxiety Disorder Scale-Lifetime (GAD-LT), designed for FDS2, assessed current and past anxiety. Data were analysed using analysis of covariance and multiple mediation models, controlling for age, gender, marital status, and diabetes duration. RESULTS: L-MDD and L-GAD were independently associated with more severe current depression (both P<0.001) and anxiety (both P<0.001) symptoms. Mediation models revealed that, through increasing the severity of current depressive symptoms, L-MDD was associated with higher HbA1c and body mass index (BMI), greater likelihood of current smoking, and reduced self-monitoring of blood glucose (SMBG) (indirect regression path ab, all P<0.001). In combination, L-MDD+L-GAD additionally elevated the risk of higher HbA1c and worse diabetes management, by increasing the severity of current depressive symptoms (indirect regression path ab, all P<0.001). CONCLUSIONS: Lifetime depression and anxiety increase risk of more severe psychological symptoms, hyperglycaemia, and difficulties with health behaviour in type 2 diabetes. Early screening for these disorders at diabetes diagnosis may be warranted to maximize long-term health outcomes.

Metabolic memory and all-cause death in community-based patients with type 2 diabetes: the Fremantle Diabetes Study.

AIMS: To validate the findings, in a usual care setting, of glycaemic intervention trials, which have shown that tight control in patients with recently diagnosed type 2 diabetes protects against death during post-study monitoring, but that it may be deleterious in long-duration diabetes with vascular complications. METHODS: A subset of 531 patients with type 2 diabetes from the community-based observational Fremantle Diabetes Study Phase 1, who attended ≥5 annual reviews (mean follow-up 15.9 years), were categorized by baseline diabetes duration [<1 year (Group 1); 1 to <5 years (Group 2); and ≥5 years (Group 3)]. Glycated haemoglobin (HbA1c) trajectories over the first 5 years were determined [low, medium and high; equivalent to mean HbA1c ≤6.6% (<49 mmol/mol), 6.7-8.0% (50-64 mmol/mol) and ≥8.0% (>64 mmol/mol), respectively]. Kaplan-Meier analysis was used to assess survival by duration and HbA1c trajectory. Cox proportional hazards modelling identified predictors of all-cause death. RESULTS: There was greater mortality in patients with a medium versus those with a low trajectory in Group 1: hazard ratio (HR) 1.99 [95% confidence interval (CI) 1.003-3.94; p = 0.049], and in patients with a high versus a low trajectory in Group 2: HR 2.02 (95% CI 1.11-3.71; p = 0.022). In Group 3, both medium [HR 0.57 (95% CI 0.35-0.92; p = 0.022)] and high [HR 0.56 (95% CI 0.32-0.96); p = 0.035] trajectories were independently and inversely associated with death. CONCLUSIONS: In community-based patients with newly or recently diagnosed type 2 diabetes, poor glycaemic control was an adverse prognostic indicator. Tight control was independently associated with death in patients with diabetes duration ≥5 years. These data parallel intervention trial findings and support individualization of HbA1c targets.

Risk of suicide in Australian adults with diabetes: the Fremantle Diabetes Study.

Type 1 diabetes is associated with increased suicide risk. Data for older diabetic individuals are inconsistent. In longitudinal data from 1413 adults recruited to the Fremantle Diabetes Study from 1993-1996 and 5660 matched non-diabetic residents, followed to end-2012, the age and sex-adjusted sub-hazard ratio (95% confidence interval) for suicide in diabetic versus non-diabetic individuals was 1.16 (0.38-3.51). Older Australians with diabetes are not at increased suicide risk.

Personality traits, self-care behaviours and glycaemic control in type 2 diabetes: the Fremantle diabetes study phase II.

AIMS: To determine whether the personality traits of conscientiousness and agreeableness are associated with self-care behaviours and glycaemia in Type 2 diabetes. METHODS: The Big Five Inventory personality traits Agreeableness, Conscientiousness, Extraversion, Neuroticism and Openness were determined along with a range of other variables in 1313 participants with Type 2 diabetes (mean age 65.8 ± 11.1 years; 52.9% men) undertaking their baseline assessment as part of the community-based longitudinal observational Fremantle Diabetes Study Phase II. Age- and sex-adjusted generalized linear modelling was used to determine whether personality was associated with BMI, smoking, self-monitoring of blood glucose and medication taking. Multivariable regression was used to investigate which traits were independently associated with these self-care behaviours and HbA1c . RESULTS: Patients with higher conscientiousness were less likely to be obese or smoke, and more likely to perform self-monitoring of blood glucose and take their medications (P ≤ 0.019), with similar independent associations in multivariate models (P ≤ 0.024). HbA1c was independently associated with younger age, indigenous ethnicity, higher BMI, longer diabetes duration, diabetes treatment, self-monitoring of blood glucose (negatively) and less medication taking (P ≤ 0.009), but no personality trait added to the model. CONCLUSIONS: Although there was no independent association between personality traits and HbA1c , the relationship between high conscientiousness and low BMI and beneficial self-care behaviours suggests an indirect positive effect on glycaemia. Conscientiousness could be augmented by the use of impulse control training as part of diabetes management.

Earlier age of dementia onset and shorter survival times in dementia patients with diabetes.

Diabetes is a risk factor for dementia, but relatively little is known about the epidemiology of the association. A retrospective population study using Western Australian hospital inpatient, mental health outpatient, and death records was used to compare the age at index dementia record (proxy for onset age) and survival outcomes in dementia patients with and without preexisting diabetes (n = 25,006; diabetes, 17.3%). Inpatient records from 1970 determined diabetes history in this study population with incident dementia in years 1990-2005. Dementia onset and death occurred an average 2.2 years and 2.6 years earlier, respectively, in diabetic compared with nondiabetic patients. Age-specific mortality rates were increased in patients with diabetes. In an adjusted proportional hazard model, the death rate was increased with long-duration diabetes, particularly with early age onset dementia. In dementia diagnosed before age 65 years, those with a ≥15-year history of diabetes died almost twice as fast as those without diabetes (hazard ratio = 1.9, 95% confidence interval: 1.3, 2.9). These results suggest that, in patients with diabetes, dementia onset occurs on average 2 years early and survival outcomes are generally poorer. The effect of diabetes on onset, survival, and mortality is greatest when diabetes develops before middle age and after 15 years' diabetes duration. The impact of diabetes on dementia becomes progressively attenuated in older age groups.

Antenatal monitoring of anti-D and anti-c: could titre scores determined by column agglutination technology replace continuous flow analyser quantification?

OBJECTIVE: To determine if column agglutination technology (CAT) for titration of anti-D and anti-c concentrations produces comparable results to those obtained by continuous flow analyser (CFA). BACKGROUND: Anti-D and anti-c are the two commonest antibodies that contribute to serious haemolytic disease of the foetus and neonate (HDFN). Current practice in the UK is to monitor these antibodies by CFA quantification, which is considered more reproducible and less subjective than manual titration by tube IAT (indirect antiglobulin test). CAT is widely used in transfusion laboratory practice and provides a more objective endpoint than tube technique. MATERIALS AND METHODS: Antenatal samples were (i) quantified using CFA and (ii) titrated using CAT with the reaction strength recorded by a card reader and expressed as a titre score (TS). RESULTS: The TS rose in accordance with levels measured by quantification and was able to distinguish antibody levels above and below the threshold of clinical significance. CONCLUSION: CAT titre scores provided a simple and reproducible method to monitor anti-D and anti-c levels. The method was sensitive to a wide range of antibody levels as determined by quantification. This technique may have the potential to replace CFA quantification by identifying those cases that require closer monitoring for potential HDFN.

Economic impact of moderate weight loss in patients with Type 2 diabetes: the Fremantle Diabetes Study.

AIM: To assess the change in the cost of diabetes medication attributable to moderate weight loss in patients with Type 2 diabetes. METHODS: Longitudinal data collected annually from 590 patients participating in the observational, community-based Fremantle Diabetes Study were examined to determine whether moderate weight loss (≥ 5% of initial body weight) was independently associated with diabetes medication cost during 4 years' follow-up. RESULTS: Overall, the weight of the cohort decreased significantly during 4.3 ± 0.4 years' follow-up by 1.3 ± 6.2 kg (-1.4 ± 7.9% baseline body weight; trend P < 0.001). Moderate weight loss was achieved by 31%. HbA(1c) improved significantly in the group with moderate weight loss compared with the group without moderate weight loss [-4 ± 16 mmol/mol (-0.3 ± 1.5%) vs. 0 ± 17 mmol/mol (0.0 ± 1.5%), P = 0.015]. Mean (bias-corrected 95% confidence intervals) diabetes medication costs were $A820 ($A744-907) during follow-up. As the cost distribution was highly right-skewed and contained zeros, it was square root (√) transformed before multiple linear regression analysis. The most parsimonious model of baseline associates of √(diabetes medication cost) included glycaemic control, diabetes treatment, diabetes duration, BMI, systolic blood pressure, serum HDL cholesterol (negative), taking lipid-lowering medication and age (negative) (adjusted R(2) = 73.6%). After adjusting for these variables, √(diabetes medication cost) was negatively associated with moderate weight loss (P = 0.026). After entering average values for the cohort into the model, the cost of diabetes medications between baseline and fourth review for an average patient with no weight loss was $A752 compared with $A652 for a patient who attained moderate weight loss, a saving of $A100 (-13.3%). DISCUSSION: These data highlight the economic and clinical benefits of moderate weight loss in Type 2 diabetes.

The C282Y polymorphism of the hereditary hemochromatosis gene is associated with increased sex hormone-binding globulin and normal testosterone levels in men.

BACKGROUND: Hereditary hemochromatosis resulting either from homozygosity for the C282Y polymorphism of the HFE gene, or compound heterozygosity for C282Y and H63D, manifests with liver disease and hypogonadism. However, it is unclear whether men who are heterozygotes for C282Y or H63D exhibit subtle abnormalities of sex hormone status. AIMS: To evaluate whether heterozygosity for either of the HFE gene polymorphisms C282Y or H63D is associated with circulating testosterone and SHBG in men. SUBJECTS AND METHODS: We performed a cross-sectional analysis of 388 community-dwelling men. Men were genotyped for C282Y and H63D. Sera were analysed for testosterone and SHBG, and insulin resistance was estimated using a homeostatic model (HOMA2-IR). RESULTS: Mean age of men in the cohort was 56.9 yr. Men who were heterozygous for the C282Y polymorphism in the HFE gene had higher SHBG levels than men who did not carry this polymorphism (mean ± SE, 38.2 ± 1.64 vs 32.8 ± 0.71 nmol/l, p=0.006). Total and free testosterone levels did not differ in the two groups. In multivariate analysis adjusting for potential confounders including age, waist circumference, testosterone, and HOMA2-IR, C282Y heterozygosity remained associated with SHBG levels (p<0.001). CONCLUSION: The C282Y polymorphism is associated with SHBG levels in men who do not manifest iron overload. Further studies are needed to clarify potential mechanisms and determine the clinical relevance of this finding.

Severe hypoglycaemia and cognitive impairment in older patients with diabetes: the Fremantle Diabetes Study.

AIMS/HYPOTHESIS: The aim was to investigate the relationship between severe hypoglycaemia and cognitive impairment in older patients with diabetes. METHODS: A sample of 302 diabetic patients aged >/=70 years was assessed for dementia or cognitive impairment without dementia in 2001-2002 and a subsample of non-demented patients (n = 205) was followed to assess cognitive decline. A history of severe hypoglycaemia was determined from self-reports, physician assessments and records of health service use for hypoglycaemia (HSH). Prospective HSH was determined up to 2006. Data analysis, including multiple logistic and Cox regression models, was used to determine whether: (1) there were cross-sectional associations between hypoglycaemia and cognitive status, (2) historical hypoglycaemia predicted cognitive decline, and (3) baseline cognitive status predicted subsequent HSH. RESULTS: There were significant cross-sectional associations between both cognitive impairment and dementia and hypoglycaemia. Independent risk factors for future HSH included dementia (hazard ratio 3.00, 95% CI 1.06-8.48) and inability to self-manage medications (hazard ratio 4.17, 95% CI 1.43-12.13). However, there were no significant associations between historical hypoglycaemia, incident HSH and cognitive decline. CONCLUSIONS/INTERPRETATION: Dementia is an important risk factor for hypoglycaemia requiring health service utilisation. We found no evidence that hypoglycaemia contributes to cognitive impairment in older patients with diabetes.

Serum testosterone levels correlate with haemoglobin in middle-aged and older men.

BACKGROUND: Lower testosterone levels are associated with anaemia in older men and women. The relation between testosterone and haemoglobin (Hb) in younger and middle-aged men is less well defined. The aim of the study was to examine the association between testosterone and Hb levels in men spanning middle to older ages. METHODS: A cross-sectional analysis of 492 men aged 30.7-94.5 years from the Busselton Health Survey, Western Australia, was carried out. Haemoglobin (Hb), early-morning serum total testosterone and sex hormone-binding globulin (SHBG) were measured. Free testosterone was calculated using mass action equations. RESULTS: Haemoglobin correlated to total and free testosterone concentrations (r= 0.13, P= 0.003 and r= 0.20, P < 0.001, respectively). Hb and SHBG were inversely correlated (r=-0.14, P= 0.001). Hb increased across lowest to highest quartiles of total testosterone (P= 0.02) and free testosterone (P < 0.001), but not SHBG. After adjusting for age, waist circumference, smoking status, alcohol consumption, renal function and ferritin, total testosterone was associated with Hb (beta= 0.037, P= 0.003) as was free testosterone (beta= 2.32, P < 0.001), whereas SHBG was not associated. CONCLUSION: Testosterone concentration modulates Hb levels in community-dwelling men across a wide age range. Further studies are needed to clarify implications of this association between testosterone and Hb in men.

Chronic complications and mortality in community-based patients with latent autoimmune diabetes in adults: the Fremantle Diabetes Study.

AIMS: To compare (i) the prevalence and incidence of chronic complications and (ii) cardiac and all-cause mortality in community-based patients with latent autoimmune diabetes in adults (LADA) with those in Type 2 diabetic patients without antibodies to glutamic acid decarboxylase (GAD). METHODS: Of the 1294 patients with clinically-defined Type 2 diabetes recruited to the longitudinal, observational Fremantle Diabetes Study between 1993 and 1996, 1255 (97%) had GAD antibodies measured at baseline. Complications were ascertained using standard criteria in patients returning for annual assessments until November 2001. Data on hospital admissions and mortality were available to the end of June 2006. Cox proportional hazards modelling was used to determine independent predictors of first occurrence of complications and cardiac and all-cause mortality. RESULTS: Forty-five (3.6%) subjects had LADA. Compared with the GAD antibody-negative patients, they had a similar prevalence and incidence of coronary heart (P = 0.48 and 0.80, respectively) and cerebrovascular (P = 0.64 and 0.29) disease and cardiac and all-cause mortality (P = 0.62 and 0.81, respectively). There was also a similar prevalence and incidence of retinopathy (P = 0.22 and 0.64, respectively) and neuropathy (P = 0.25 and 0.95), but microalbuminuria was less frequent both at baseline and during follow-up in the LADA subgroup in unadjusted models (P = 0.046) and after adjustment for other risk factors (P = 0.014 and 0.013). CONCLUSIONS: Except for a lower prevalence and incidence of nephropathy, LADA patients have a similar risk of complications and death to patients with clinically-diagnosed Type 2 diabetes without GAD antibodies. Cardiovascular risk factor management in LADA should, therefore, be as intensive as that for GAD antibody-negative patients.

Lipid-lowering therapy and peripheral sensory neuropathy in type 2 diabetes: the Fremantle Diabetes Study.

AIMS/HYPOTHESIS: The aim of this study was to assess the relationships between lipid-lowering therapy and the prevalence and incidence of peripheral sensory neuropathy in type 2 diabetes mellitus. METHODS: We analysed data from an observational cohort study, the Fremantle Diabetes Study (FDS), specifically, (1) a cross-sectional sample comprising 1,237 FDS participants with type 2 diabetes mellitus, and (2) a longitudinal subgroup of 531 individuals who had attended six consecutive annual assessments. Neuropathy was identified using the clinical portion of the Michigan Neuropathy Screening Instrument. RESULTS: At entry, the cross-sectional sample had a mean +/- SD age of 63.8+/-11.3 years, 48.7% were men, median (interquartile range) diabetes duration was 4.0 (1.0-9.0) years, and 30.9% had peripheral neuropathy. Fibrates and statins were used by 3.5 and 6.8%, respectively. Multiple logistic regression analysis showed that older age, longer diabetes duration, central adiposity, increased height, higher fasting serum glucose, albuminuria and aboriginality were significant independent positive predictors of prevalent neuropathy, while systolic blood pressure and fibrate use (odds ratio 0.30, 95% CI 0.10-0.86; p=0.025) were negatively associated. In the longitudinal subgroup, fibrate and statin use increased to 10.4 and 36.5%, respectively, over 5 years. In time-dependent Cox proportional hazards modelling, fibrate use [hazard ratio (HR) 0.52, 95% CI 0.27-0.98] and statin use (HR 0.65, 95% CI 0.46-0.93) were significant determinants of incident neuropathy (p

Predictors of cognitive impairment and dementia in older people with diabetes.

AIMS/HYPOTHESIS: Diabetes is associated with an increased risk of dementia but the reasons for this association are unclear because there are many potential mechanisms. We explored the relative contribution of diabetes-related variables as predictors of dementia in older individuals with diabetes. METHODS: Survivors, aged > or =70 or more, were recruited from an existing observational cohort study 7.6 +/- 1.0 years after baseline, when they underwent a comprehensive assessment of diabetes, complications and cardiovascular risk factors. Dementia, probable Alzheimer's disease and cognitive impairment without dementia were diagnosed clinically. Logistic regression modelling determined independent predictors of cognitive diagnoses. RESULTS: Of 302 participants, aged 75.7 +/- 4.6 years, 28 (9.3%) had dementia (16 with probable Alzheimer's disease) and 60 (19.9%) had cognitive impairment without dementia. The major independent longitudinal predictors of dementia were older age (per decade; odds ratio 4.0, 95% CI 1.59-10.10), diabetes duration (for each 5 years; odds ratio 1.69, 95% CI 1.24-2.32), peripheral arterial disease (odds ratio 5.35, 95% CI 2.08-13.72) and exercise (which was protective; odds ratio 0.26, 95% CI 0.09-0.73). For Alzheimer's disease, diabetes duration was an independent predictor in addition to age and diastolic blood pressure. The results of the cross-sectional analyses were similar with respect to diabetes duration and peripheral arterial disease. CONCLUSIONS/INTERPRETATION: Peripheral arterial disease is a strong independent risk factor for dementia in diabetes. After adjustment for a wide range of potential risk factors, diabetes duration remains independently associated with dementia and probable Alzheimer's disease, indicating that factors not measured in this study may be important in the pathogenesis of dementia in diabetes.

Characteristics and outcome of type 2 diabetes in urban Aboriginal people: the Fremantle Diabetes Study.

We analysed data from Aboriginal patients with type 2 diabetes recruited to the community-based Fremantle Diabetes Study and compared them with those from the Anglo-Celt participants. Diabetes prevalence among Aboriginal people in the Fremantle area was more than double that of Anglo-Celts and the average age at diagnosis was 14 years or younger. Glycaemic control, urinary albumin :creatinine and the proportion of smokers were all higher in the Aboriginal group and there was evidence of lower diabetes-related quality of life and high rates of disability at a young age. The Aboriginal patients died 18 years or younger than their Anglo-Celt counterparts. Specialized, culturally-sensitive and sustainable programmes are urgently needed to improve the management of diabetes in urban Aboriginal communities.

Does self-monitoring of blood glucose improve outcome in type 2 diabetes? The Fremantle Diabetes Study.

AIMS/HYPOTHESIS: To assess whether self-monitoring of blood glucose (SMBG) is an independent predictor of improved outcome in a community-based cohort of type 2 diabetic patients. MATERIALS AND METHODS: We used longitudinal data from (1) 1,280 type 2 diabetic participants in the observational Fremantle Diabetes Study (FDS) who reported SMBG and diabetes treatment status at study entry (1993-1996), and (2) a subset of 531 participants who attended six or more annual assessments (referred to as the 5-year cohort). Diabetes-related morbidity, cardiac death and all-cause mortality were ascertained at each assessment, supplemented by linkage to the Western Australian Data Linkage System. RESULTS: At baseline, 70.2% (898 out of 1,280) of type 2 patients used SMBG. During 12,491 patient-years of follow-up (mean 9.8+/-3.5 years), 486 (38.0%) type 2 participants died (196 [15.3%] from cardiac causes). SMBG was significantly less prevalent in those who died during follow-up than in those who were still alive at the end of June 2006 (65.4 vs 73.0%, p=0.005). In Cox proportional hazards modelling, after adjustment for confounding and explanatory variables, SMBG was not independently associated with all-cause mortality, but was associated with a 79% increased risk of cardiovascular mortality in patients not treated with insulin. For the 5-year cohort, time-dependent SMBG was independently associated with a 48% reduced risk of retinopathy. CONCLUSIONS/INTERPRETATION: SMBG was not independently associated with improved survival. Inconsistent findings relating to the association of SMBG with cardiac death and retinopathy may be due to confounding, incomplete covariate adjustment or chance.

Vascular depression in older people with diabetes.

AIMS/HYPOTHESIS: Cerebrovascular disease may be causal or a vulnerability factor in late-onset depression and may explain the high rate of depression in older adults with diabetes. We explored a wide range of potential explanatory variables of depression in a longitudinal study of older diabetic subjects to investigate the vascular depression hypothesis in these patients. METHODS: We recruited 207 subjects with diabetes selected for potential cognitive deficits from an existing observational cohort study (average age 75.7 +/- 4.6 years, 52.2% men) for an assessment of depression using a standardised diagnostic instrument (Cambridge Examination for Mental Disorders of the Elderly -- Revised). All subjects underwent a detailed clinical assessment at baseline and at follow-up (after 7.5 +/- 1.1 years). RESULTS: Major depression was present in 45 subjects (21.7%) and minor depression in ten (4.8%). A positive history of strokes and the presence of peripheral arterial disease were significantly associated with depression at the time of diagnosis. In a subsample of 93 cases who underwent structural neuroimaging, the presence of cerebral infarcts was also significantly associated with depression. Treatment with glucose-lowering therapy, higher serum cholesterol levels and difficulties with activities of daily living at baseline were significant predictors of depression at follow-up. CONCLUSIONS/INTERPRETATION: A history of cerebrovascular disease was strongly associated with depression and cerebrovascular risk factors were significant predictors of depression in older diabetic patients. Our findings are consistent with the hypothesis that the excess risk of depression in older diabetic patients is related to underlying cerebrovascular disease.

Predictors, consequences and costs of diabetes-related lower extremity amputation complicating type 2 diabetes: the Fremantle Diabetes Study.

AIMS/HYPOTHESIS: The aims of this study were to assess the incidence, predictors, consequences, and inpatient cost of lower extremity amputation (LEA) in a community-based cohort of type 2 diabetic patients. METHODS: Between 1993 and 1996, 1,294 patients with type 2 diabetes were recruited to the longitudinal, observational Fremantle Diabetes Study. LEAs and mortality from cardiac causes were monitored until 30 June 2005. Inpatient costs (in Australian dollars in year 2000), derived using a case-mix approach, were available for the period from 1 July 1993 to 30 June 2000. RESULTS: During follow-up 44 patients without LEA at baseline had a first-ever diabetes-related LEA, an incidence of 3.8 per 1,000 patient-years. Independent predictors of first-ever LEA included foot ulceration (hazard ratio [95% CI]: 5.56 [1.24-25.01]), an ankle brachial index < or =0.90 (2.21 [1.11-4.42]), HbA(1c) (increase of 1%: 1.30 [1.10-1.54]) and neuropathy (2.65 [1.30-5.44]). The risk of cardiac death was significantly increased in patients with LEA at baseline, although this was not an independent risk factor. The median (interquartile range) inpatient cost per LEA admission was 12,485 Australian dollars (6,037 Australian dollars-24,415 Australian dollars), with a median length of stay of 24 (10-43) days. CONCLUSIONS/INTERPRETATION: First-ever LEAs in type 2 patients were associated with poor glycaemic control, foot ulceration and evidence of microvascular and macrovascular disease. Patients with LEA were at increased risk of cardiac death. LEAs contribute disproportionately to diabetes-related inpatient costs.