Pulmonary Function Trajectories Over 6 Years and Their Determinants in Type 2 Diabetes: The Fremantle Diabetes Study Phase II.

OBJECTIVE: To assess whether there are clusters of people with type 2 diabetes with distinct temporal profiles of lung function changes and characteristics. RESEARCH DESIGN AND METHODS: Group-based trajectory modeling (GBTM) identified groups of participants with type 2 diabetes from the community-based observational Fremantle Diabetes Study Phase II (FDS2) who had at least two biennial measurements of forced expiratory volume in 1 s as a percentage of predicted (FEV1%pred) over 6 years. Independent associates of group membership were assessed using multinomial regression. RESULTS: Of 1,482 potential FDS2 participants, 1,074 (72.5%; mean age, 65.2 years; 45.5% female; median diabetes duration, 8.0 years) were included in the modeling. The best fitting GBTM model identified four groups categorized by FEV1%pred trajectory: high (19.5%; baseline FEV1%pred, 106.5 ± 9.5%; slope 0%/year), medium (47.7%; FEV1%pred, 87.3 ± 8.7%; slope, -0.32%/year), low (25.0%; baseline FEV1%pred, 68.9 ± 9.8%; slope, -0.72%/year), and very low (7.9%; baseline FEV1%pred, 48.8 ± 9.6%; slope, -0.68%/year). Compared with the high group, the other groups were characterized by nonmodifiable and modifiable risk factors associated with lung function decline in the general population (including ethnicity, marital status, smoking, obesity, coronary heart disease, and chronic respiratory disease). The main, diabetes-specific, significant predictor of group membership was a higher HbA1c in the very low group. There was a graded increase in mortality from 6.7% in the high group to 22.4% in the very low group. CONCLUSIONS: Measurement of lung function in type 2 diabetes could help optimize clinical management and improve prognosis, including addressing glycemic control in those with a very low FEV1%pred.

A systematic review of diabetic retinopathy screening intervals.

The current evidence on whether annual diabetic retinopathy (DR) screening intervals can be extended was reviewed. A systematic review protocol was followed (PROSPERO ID: CRD42022359590). Original longitudinal articles that specifically assessed DR screening intervals were in English and collected data after 2000 were included. Two reviewers independently conducted the search and reviewed the articles for quality and relevant information. The heterogeneity of the data meant that a meta-analysis was not appropriate. Twelve publications were included. Studies were of good quality and many used data from DR screening programs. Studies fit into three categories; those that assessed specific DR screening intervals, those that determined optimal DR screening intervals and those that developed/assessed DR screening risk equations. For those with type 2 diabetes, extending screening intervals to 3- to 4-yearly in those with no baseline DR appeared safe. DR risk equations considered clinical factors and allocated those at lower risk of DR progression screening intervals of up to five years. Those with baseline DR or type 1 diabetes appeared to have a higher risk of progression to STDR and needed more frequent screening. DR screening intervals can be extended to 3-5 yearly in certain circumstances. These include patients with type 2 diabetes and no current DR, and those who have optimal management of other risk factors such as glucose and blood pressure.

Retinopathy prevalence, incidence and trajectories in type 2 diabetes: The Fremantle diabetes study phase II.

AIMS: To determine diabetic retinopathy (DR) prevalence, incidence, and whether distinct trajectories are associated with DR-complicating Type 2 diabetes. METHODS: Retinal photographs from Fremantle Diabetes Study Phase II (FDS2) participants with Type 2 diabetes recruited in 2008-2011 and who attended biennial assessments for up to 6 years were graded as no DR, mild non-proliferative DR (NPDR), moderate NPDR or severe NPDR/proliferative DR. Baseline DR prevalence, and the cumulative incidence of moderate NPDR or worse in those without DR at baseline, were calculated. Group-based DR trajectory modelling was performed. Logistic regression determined independent associates of incident moderate NPDR or worse and trajectory group membership. RESULTS: Of 1521 participants (mean age 65.6 years, 52.1% males, median diabetes duration 9.0 years; 98% of all FDS2 participants with Type 2 diabetes) with gradable baseline photographs, 563 (37.0%) had DR. During a median 6.1 years of follow-up, 23 (3.2%) without baseline DR developed at least moderate NPDR (crude incidence 6.1/1000 person-years) with HbA1c the sole independent predictor (odds ratio [95% CI]: 1.62 [1.30-2.02] per 1% [11 mmol/mol] increase). Trajectory analysis showed two distinct groups, those with baseline/persistent DR (20%) and those remaining DR free (80%). Longer diabetes duration, insulin use, higher mean HbA1c , higher mean systolic blood pressure and higher mean urinary albumin: creatinine ratio all increased the odds (p ≤ 0.014) of being in the persistent DR trajectory group. CONCLUSIONS: The low incidence of at least moderate NPDR reflects the trajectory analysis. The currently recommended biennial retinal screening frequency for individuals without DR could potentially be extended.

Pharmacokinetic properties of the antimalarial combination therapy artemether-lumefantrine in normal-weight, overweight and obese healthy male adults.

The component drugs in the widely used antimalarial artemisinin combination therapy artemether-lumefantrine are lipophilic, with the possibility that recommended fixed doses in adults may lead to subtherapeutic concentrations and consequent treatment failure in overweight/obese individuals with malaria. The aim of this study was to investigate the pharmacokinetic properties of artemether, lumefantrine and their active metabolites dihydroartemisinin and desbutyl-lumefantrine in 16 normal-weight, overweight and obese healthy male volunteers [body mass index (BMI) categories ≤25 kg/m², >25-≤30 kg/m² and >30 kg/m², respectively; absolute range 19.3-37.2 kg/m²]. Participants received the conventional six doses of artemether-lumefantrine over 3 days, each dose comprising 80 mg artemether plus 480 mg lumefantrine administered with 6.7 g fat, and blood samples were collected at pre-specified time-points over 14 days. Plasma drug/metabolite concentrations were measured using liquid chromatography-mass spectrometry and included in multi-compartmental population pharmacokinetic models. There was a non-significant trend to a lower area under the plasma concentration-time curve with a higher body weight or BMI for dihydroartemisinin and especially artemether which was attenuated when normalized for mg/kg dose, but this relationship was not evident in the case of the more lipophilic lumefantrine and its metabolite desbutyl-lumefantrine. Simulated Day 7 plasma lumefantrine concentrations were >200 µg/L (the threshold at which Plasmodium falciparum recrudescences are minimized) in all participants. These results indicate that there is no need for artemether-lumefantrine dose modification in overweight and obese patients with malaria.

Differences in retinopathy prevalence and progression between Anglo-Celt and Aboriginal Australians: the Fremantle Diabetes Study Phase II.

BACKGROUND: Indigenous populations have higher rates of diabetes and diabetic complications, yet there is a paucity of contemporary data on diabetic retinopathy (DR) prevalence and incidence in urban dwelling Aboriginal Australians. AIMS: The aim of the study was to compare the prevalence of DR and incidence of new or worsening DR between Aboriginal Australians and Anglo-Celts with Type 2 diabetes. METHODS: Participants from the community-based Fremantle Diabetes Study Phase II (817 Anglo-Celts, 94 Aboriginal people) recruited between 2008 and 2011 underwent fundus photography at baseline and biennial reviews. The prevalence of any DR and moderate non-proliferative DR (NPDR), and the incidence of new or worsening DR were ascertained using baseline and 4-year follow-up data. RESULTS: Compared with Anglo-Celts, the Aboriginal participants had a higher prevalence of any DR (33.0% vs 52.1%) and moderate NPDR or worse (5.1% vs 24.4%), and new or worsening DR during follow up (6.7% vs 23.5%). The unadjusted odds ratios (95% confidence interval) of any DR and moderate NPDR at baseline were 2.21 (1.43, 3.39) and 5.98 (3.40, 10.50), respectively, and of new or worsening DR 4.32 (1.33, 13.98). In adjusted models, Aboriginal ethnicity was only associated with the prevalence of moderate NPDR or worse (5.58 (2.44, 12.76)). CONCLUSIONS: Aboriginal participants had a higher prevalence of DR and new or worsening DR, reflecting conventional risk factors including suboptimal glycaemic control. Their significantly higher odds of moderate NPDR or worse in adjusted models suggest ethnic-specific determinants of DR severity. These findings highlight the need for equitable, culturally appropriate diabetes/ophthalmic care.

A prospective six-month audit of inpatient hypoglycemia in step-down general medical and geriatric wards.

This study aimed to assess the incidence and associates of hypoglycemia in patients transferred after stabilization on an Acute Medical Unit to two general medical or two geriatric wards at an urban Australian hospital. In a six-month audit representing 20,284 patient-days of observation, 59 inpatients experienced hypoglycaemia (blood glucose ≤3.9 mmol/L) during 65 hospitalizations. Inpatients experiencing hypoglycemia accounted for 7.2% of all inpatient bed-days, a figure that was greater for general medical (9.2% of bed-days) compared with geriatric (6.0% of bed-days) wards (P<0.001). Inpatient hypoglycemia often had no precipitant such as a missed/delayed meal, occurred disproportionately at night (41% of episodes), was severe (blood glucose ≤3.0 mmol/L) in one-third of cases, and appeared more frequent in patients with psychiatric/cognitive issues. These data highlight the ongoing issue of hypoglycemia in relatively stable inpatients in an era of blood glucose-lowering therapies associated with a low rate of this acute metabolic complication.

Knowledge of ocular complications of diabetes in community-based people with type 2 diabetes: The Fremantle Diabetes Study II.

AIMS: To assess knowledge of diabetes-related eye disease in Australians with type 2 diabetes and its associations with diabetic retinopathy (DR), other ocular complications and vision-related quality of life. METHODS: A random sample from the Fremantle Diabetes Study Phase II cohort (n = 360) was invited to participate. Knowledge was assessed using 10 multiple-choice questions covering how diabetes affects the eyes, frequency of ophthalmic screening, risk factors, prevention, available treatments, and prognosis. DR was assessed from fundus photographs. Multiple linear regression was used to identify independent associates of the knowledge score (KS). RESULTS: We included 264 participants (mean ± SD age 72.1 ± 9.2 years, 56.8% male, median [IQR] diabetes duration 15.4 [11.1-22.3] years). The mean ± SD KS out of 10 was 5.3 ± 1.8. Most (67%) participants knew diabetes can affect the eye and lead to blindness. Only 13.6% knew that DR screening intervals depend on risk factors. Those with moderate non-proliferative DR (NPDR) or worse had a better knowledge score (B = 1.37,P = 0.008) after adjusting for age (B = -0.03, P = 0.004) and education beyond primary school (B = 1.75, P < 0.001). CONCLUSIONS: Overall knowledge of diabetes-related ocular complications was suboptimal. Education targeting eye disease may benefit people with type 2 diabetes who are older, less well educated and/or who have no DR/mild NPDR.

Assessment of biomarkers associated with rapid renal decline in the detection of retinopathy and its progression in type 2 diabetes: The Fremantle Diabetes Study Phase II.

AIMS: To determine whether biomarkers for diabetic kidney disease (DKD) can be used to determine the prevalence, progression and/or incidence of diabetic retinopathy (DR) complicating type 2 diabetes. METHODS: Proteomic biomarkers were measured in baseline fasting plasma from 958 Fremantle Diabetes Study Phase II participants whose baseline and, in those returning for follow-up (n = 764), Year 4 fundus photographs were graded for DR presence/severity. The performance of PromarkerD (three biomarkers and readily available clinical variables which identify prevalent DKD and predict incident DKD and estimated glomerular filtration rate decline ≥30% over four years) for detecting DR prevalence, progression and incidence was assessed using the area under the receiver operating curve (AUC). Logistic regression determined whether individual proteins were associated with DR outcomes after adjusting for the most parsimonious model. RESULTS: Plasma apolipoprotein A-IV (APOA4) was independently associated with moderate non-proliferative DR at baseline (OR (95% CI): 1.64 (1.01, 2.67), P = 0.047). Model discrimination was poor for all PromarkerD predicted probabilities against all DR outcomes (AUC ≤0.681). CONCLUSIONS: PromarkerD and its constituent biomarkers were not consistently associated with DR prevalence or temporal change. APOA4 was associated with prevalent DR, but not DR incidence or progression. Distinct pathophysiological mechanisms may underlie DKD and DR.

Community-based management of complex type 2 diabetes: adaptation of an integrated model of care in a general practice setting.

BACKGROUND: Overburdened hospital clinics can have adverse outcomes. AIMS: To evaluate the effectiveness and patient acceptability of an integrated model of complex type 2 diabetes care delivered in a community-based general practice by upskilled general practitioners (GP) co-located with an endocrinologist and diabetes nurse educator. METHODS: Patients transferred from hospital clinic lists or referred by local GP were assessed in two southern Perth practices. An upskilled GP and endocrinologist developed a management plan which was communicated to the participant's usual GP. Up to two follow-up visits over 6 months ensured that management was acceptable and effective. RESULTS: A total of 464 people with type 2 diabetes (mean ± standard deviation age = 59.3 ± 13.7 years, 52.2% males) was enrolled. Their mean glycated haemoglobin (HbA1c ) was 9.3% (78 mmol/mol) and their mean body mass index 33.7 kg/m2 . Use of injectable blood glucose-lowering therapies increased between the initial and final visit in association with a median HbA1c reduction of 1.2% (13 mmol/mol) which was sustained to 12 months in assessable participants. There were also reductions in blood pressure, and serum low-density lipoprotein cholesterol and triglyceride concentrations. Patient satisfaction with current treatment, time for self-management, time spent in diabetes-related appointments and diabetes knowledge increased significantly. Non-attendance for scheduled appointments was <10%. Local hospital referrals and waiting lists reduced over the study period. CONCLUSIONS: This study confirms the value of integrated community-based care of complex type 2 diabetes which could represent a sustainable solution to overburdened hospital diabetes outpatient clinics.

Gender and ethnic differences in pterygium prevalence: an audit of remote Australian clinics.

CLINICAL RELEVANCE: Developing an accurate picture of the demographic profile and refractive status of Aboriginal and non-Aboriginal individuals with pterygium will facilitate health planning and appropriate deployment of health-care resources in rural Australia. BACKGROUND: To date, there is a paucity of reports in the literature regarding Aboriginal ocular health and refractive error. This study examines clinical data from a rural ophthalmology outreach clinic - a predominantly Aboriginal population. METHODS: An assessment was undertaken of data of 293 patients noted to have pterygium present in at least one eye, from a sample of 2,072 individuals seen in rural northern Western Australia in 2017 by the Lions Outback Vision Visiting Optometry Service. RESULTS: Pterygium was found in 14.1 per cent (n = 293) of patients using the Lions Outback Vision service. The mean age of those with pterygium (n = 293) was 57.1 ± 11.9-years (mean ± standard deviation); 188 were female (64.1 per cent); 260 identified as Aboriginal (88.7 per cent), 22 identified as non-Aboriginal (7.5 per cent) and 11 did not specify (3.8 per cent). There were more males than females with pterygium in the non-Aboriginal group (18.0 per cent versus 6.4 per cent); however, the reverse was true in the Aboriginal group (11.7 per cent versus 17.0 per cent). Analysis of the subjective refractive data in those with pterygium revealed an overall mean spherical equivalent value of +0.66 ± 1.28 DS. The median (interquartile range) best-corrected visual acuity was 0.0 (-0.1 to 0.0) logMAR (6/6 Snellen equivalent). CONCLUSIONS: This paper increases our knowledge of ocular health in a remote Australian population, with an emphasis on the differences between Aboriginal and non-Aboriginal individuals, males and females.

Carotid Disease and Retinal Optical Coherence Tomography Angiography Parameters in Type 2 Diabetes: The Fremantle Diabetes Study Phase II.

OBJECTIVE: To use optical coherence tomography angiography (OCTA) to determine whether retinal microvascular parameters are associated with carotid arterial disease in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: Participants (community-based) underwent detailed assessments including carotid ultrasonography and OCTA. Ultrasound images were assessed for mean intima-media thickness (IMT) and the presence of stenosis. OCTA image analysis provided measures of vessel density, foveal avascular zone (FAZ) area, blood flow areas, and retinal thickness. For each OCTA variable, the most parsimonious model was generated using generalized estimating equations, then ipsilateral and contralateral carotid disease-related variables were added to determine their significance. RESULTS: A total of 474 eyes from 261 participants (mean ± SD age 72.0 ± 9.3 years, 57.1% males, median diabetes duration 15.4 years [interquartile range 11.1-22.4]) were analyzed. When carotid variables were added to the most parsimonious models, the ipsilateral natural logarithm of common carotid artery IMT (coefficient -2.56 [95% CI -4.76, -0.35], P = 0.023) and presence of any ipsilateral stenosis (-0.82 [-1.48, -0.17], P = 0.014) were statistically significantly associated with a lower parafoveal density in the deep capillary plexus. A mean bifurcation IMT ≥1 mm was associated with a decreased vessel density in the 300-µm ring surrounding the FAZ (coefficient -0.79 [-1.50, -0.08], P = 0.030)). Contralateral carotid disease-related variables were also significantly associated with retinal microvascular parameters. CONCLUSIONS: This is the first study to show that carotid disease is an independent associate of retinal microvascular disease assessed by OCTA in type 2 diabetes. Appropriately intensive management of carotid disease may improve the retinal microcirculation.

The relationship between carotid disease and retinopathy in diabetes: a systematic review.

BACKGROUND: Since studies of the relationship between carotid disease and diabetic retinopathy (DR) have shown apparent inconsistencies, the aim of this study was to conduct a systematic review of available published data. METHODS: Electronic databases were searched independently by two reviewers, according to an iterative protocol, for relevant articles. The search term used was "diabetes AND (carotid disease OR intima-media OR carotid plaque OR carotid stenosis OR carotid arterial disease OR carotid artery disease OR carotid atherosclerosis) AND (retinopathy OR diabetic retinopathy)". RESULTS: From 477 publications, 14 studies were included. There were differences in the variables used as markers of carotid disease and DR across the included studies. Ten studies used carotid disease as the dependent variable, and the remainder used DR. All but one study involved cross-sectional data. Most studies reported a statistically significant association between at least one parameter of carotid disease as assessed by ultrasound and DR presence or severity. Only four studies reported no significant association. A common limitation was the use of convenience participant sampling. CONCLUSIONS: There appears to be an increased likelihood of DR when there is ultrasonographic evidence of carotid disease, and vice versa. The available studies suggest that there may be a direct relationship between DR and carotid macrovascular disease and/or that these complications co-exist due to shared risk factors. If carotid disease is detected, retinal assessment should be performed. If DR is identified, intensive cardiovascular disease risk management should be considered. Additional longitudinal studies are needed to assess the directionality of the association.

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.

Incidence and predictors of vision loss complicating type 2 diabetes: The Fremantle Diabetes Study Phase II.

BACKGROUND AND PURPOSE: Although diabetes is associated with multiple ocular complications, there are limited data on the incidence and predictors of visual acuity (VA) loss in type 2 diabetes. The aim of this study was to determine the 4-year cumulative incidence of visual impairment and blindness, and the predictors of vision loss, in a representative community-based cohort. METHODS: The longitudinal Fremantle Diabetes Study Phase II recruited 1551 participants with type 2 diabetes between 2008 and 2011. Participants attended biennial face-to-face assessments including VA measurement. Multivariable logistic regression was used to determine the predictors of vision loss (defined as a decrease in VA by >10 letters at the Year 4 assessment), excluding those with visual impairment (VA >6/19 and ≤6/48) and blindness (VA >6/48) at baseline. RESULTS: 882 participants with normal/near normal vision at baseline had VA data at Year 4 available. During a median [interquartile range] 4.1 [4.0-4.4] years of follow-up, the cumulative incidences of visual impairment and vision loss were 0.9% (n = 8) and 2.9% (n = 26), respectively. No participants developed blindness and 1.9% (n = 17) improved their VA. Multivariable logistic regression showed baseline smoking (OR: 3.17 (95% CI: 1.15-8.76)), prior severe hypoglycemia (5.59 (1.32-23.61)) and urinary albumin:creatinine ratio (uACR) (1.42 (1.09-1.84) for an increase of 1 in ln(uACR)) had higher odds of vision loss during follow-up. CONCLUSIONS: Smoking cessation and management strategies that avoid severe hypoglycemia and preserve kidney function may potentially prevent vision loss in people with type 2 diabetes.

Incidence and Determinants of Intraocular Lens Implantation in Type 2 Diabetes: The Fremantle Diabetes Study Phase II.

OBJECTIVE: To compare the incidence of intraocular lens (IOL) implantation for cataracts between people with and without type 2 diabetes and to determine associated risk factors in those with type 2 diabetes. RESEARCH DESIGN AND METHODS: Participants with type 2 diabetes (n = 1,499) from the community-based observational Fremantle Diabetes Study Phase II (FDS2) were age, sex, and zip code matched 1:4 with residents without diabetes. IOL implantation status was ascertained between entry (2008-2011) and the end of 2016 using validated data linkage. Age-specific incidence rates and incidence rate ratios (IRRs) for cataract surgery were calculated. Predictors of IOL implantation in FDS2 participants were assessed using proportional hazards and competing risk regression modeling. RESULTS: The crude IRR (95% CI) for cataract surgery in FDS2 participants (mean ± SD age 62.8 ± 10.8 years at entry) versus the matched group without diabetes was 1.50 (1.32-1.71), with the highest relative risk in those aged 45-54 years at the time of surgery (7.12 [2.05-27.66]). Competing risk analysis showed that age at entry, diabetes duration, serum HDL cholesterol, serum triglycerides, a severe hypoglycemic episode in the past year, and Asian and southern European ethnicity increased the risk of cataract surgery in participants with type 2 diabetes (P ≤ 0.025). CONCLUSIONS: People with type 2 diabetes, especially those in younger age-groups, are at a significantly increased risk of cataract surgery than matched people without diabetes. Multifaceted prevention strategies should be incorporated as part of routine care. As well as limiting ultraviolet light exposure, these might include lipid-modifying treatment and strategies to avoid severe hypoglycemia.

A systematic review of risk factors for cataract in type 2 diabetes.

Type 2 diabetes (T2D) is a risk factor for cataract development. With T2D prevalence increasing, the burden of cataract-associated vision loss will also increase. We aimed to characterise cataract diabetes-specific risk factors to assist prevention and management strategies. As part of a systematic review, two investigators independently searched online electronic databases according to a predetermined protocol for relevant published data to end-March 2018. Studies were included if they were longitudinal with ≥100 participants, diabetes was defined, a description of cataract assessment was provided, data were from humans, and the reports were in English. Study quality was assessed using the Newcastle Ottawa Scale and GRADE. Of 5255 publications identified, 19 from 13 study populations were included. The overall risk of bias was low. There was between-study variability. Age and glycaemic control were consistently associated with cataract development in T2D, but blood pressure, diabetes duration, sex, and aspirin use were not. Serum lipids and smoking remain possible risk factors, but available data are inconclusive. Glycaemia is the only consistent modifiable risk factor amongst a range of candidate variables. Due to the lack of consistency of the available evidence, and since mortality associated with T2D is declining with the likelihood of increased cataract-associated vision loss, additional well-conducted longitudinal studies are needed to identify modifiable risk factors that could prevent or delay cataract formation.

A 10-Year Prospective Study of Bone Mineral Density and Bone Turnover in Males and Females With Type 1 Diabetes.

Context: In a previous community-based, cross-sectional study, males with type 1 diabetes (T1D) had lower bone mineral density (BMD) than did matched people without diabetes but females with T1D had normal BMD. Objective: To determine whether BMD in the males continued to decline, the neutral effect of T1D on BMD in females persisted, and whether temporal BMD changes reflected changes in bone turnover markers. Design: Longitudinal observational study. Setting: Urban community. Patients: Forty-eight of the original 102 original cross-sectional study participants (20 males, 28 females) of mean age 42.0 years and median diabetes duration 14.6 years at baseline who were restudied a mean of 10.3 years later. Main Outcome Measures: BMD at total hip, femoral neck, lumbar spine (L1 to L4), and distal forearm. Biochemical bone turnover markers. Results: After adjustment for age, body mass index (BMI), and renal function, there was no temporal change in BMD at the hip or forearm in the males (P ≥ 0.12), but lumbar spine BMD increased (P = 0.009). Females exhibited no statistically significant change in BMD in similar multivariable models that also included postmenopausal status, except a mild increase at the forearm (P = 0.046). Age- and sex-related changes in bone turnover markers paralleled those in general population studies. Conclusions: There is a reduction in BMD in males with T1D that occurs early in the course of the disease but then stabilizes. BMD in females with T1D remains similar to that expected for age, BMI, and postmenopausal status.

Ultrasonographic assessment of joint pathology in type 2 diabetes and hyperuricemia: The Fremantle Diabetes Study Phase II.

AIMS: The prevalence and consequences (articular and extra-articular) of hyperuricemia in type 2 diabetes, especially when asymptomatic (ASH), are incompletely understood. The aim of this study was to use ultrasonography to assess pathology associated with monosodium urate deposition in the joints of well-characterized hyperuricemic patients with type 2 diabetes. METHODS: A subset of 101 participants (mean age 70.4 years, 59.8% males, median diabetes duration 14.6 years) with hyperuricemia (fasting serum uric acid ≥0.42 mmol/L) from the community-based observational Fremantle Diabetes Study Phase II were assessed by ultrasound for signs of intra-articular urate deposition and inflammation in 14 joints at increased risk of involvement in patients with gout. RESULTS: Most participants had evidence of crystal deposition comprising aggregates (59.4%), tophi (19.8%) or a double contour sign (27.7%), and 37% had a power Doppler signal indicative of inflammation in at least one joint. There was no difference between the prevalence of these abnormalities in those with ASH (n = 60) versus participants with a history of gout (n = 41; P ≥ 0.15). There was no association between a history of ischemic heart disease (reported by 17.8% of participants) and either any abnormality on joint ultrasound or inflammatory changes assessed by power Doppler (P ≥ 0.41). CONCLUSIONS: Joint inflammation and/or urate deposition were present in the majority of community-based patients with type 2 diabetes and hyperuricemia regardless of whether there was a history of gout. Given the potential consequences of chronic inflammation for joint damage and extra-articular complications such as cardiovascular disease, these data have potential clinical implications.