Prevalence and prognostic significance of cardiac autonomic neuropathy in community-based people with type 2 diabetes: the Fremantle Diabetes Study Phase II.

BACKGROUND: There is a paucity of contemporary data on the prevalence and prognostic significance of cardiac autonomic neuropathy (CAN) from community-based cohorts with type 2 diabetes assessed using gold standard methods. The aim of this study was to assess these aspects of CAN in the longitudinal observational Fremantle Diabetes Study Phase II (FDS2). METHODS: FDS2 participants were screened at baseline using standardised cardiovascular reflex tests (CARTs) of heart rate variation during deep breathing, Valsalva manoeuvre and standing. CAN (no/possible/definite) was assessed from the number of abnormal CARTs. Multinomial regression identified independent associates of CAN status. Cox proportional hazards modelling determined independent baseline predictors of incident heart failure (HF) and ischaemic heart disease (IHD), and all-cause mortality. RESULTS: Of 1254 participants assessed for CAN, 86 (6.9%) were outside CART age reference ranges and valid CART data were unavailable for 338 (27.0%). Of the remaining 830 (mean age 62.3 years, 55.3% males, median diabetes duration 7.3 years), 51.0%, 33.7% and 15.3% had no, possible or definite CAN, respectively. Independent associates of definite CAN (longer diabetes duration, higher body mass index and resting pulse rate, antidepressant and antihypertensive therapies, albuminuria, distal sensory polyneuropathy, prior HF) were consistent with those reported previously. In Kaplan-Meier analysis, definite CAN was associated with a lower likelihood of incident IHD and HF versus no/possible CAN (P < 0.001) and there was a graded increase in all-cause mortality risk from no CAN to possible and definite CAN (P < 0.001). When CAN category was added to the most parsimonious models, it was not a significant independent predictor of IHD (P ≥ 0.851) or HF (P ≥ 0.342). Possible CAN (hazard ratio (95% CI) 1.47 (1.01, 2.14), P = 0.046) and definite CAN (2.42 (1.60, 3.67), P < 0.001) increased the risk of all-cause mortality versus no CAN. CONCLUSIONS: Routine screening for CAN in type 2 diabetes has limited clinical but some prognostic value.

Serum vitamin B12, distal symmetrical polyneuropathy and anaemia in type 2 diabetes: the Fremantle Diabetes Study Phase 2.

BACKGROUND: There are limited data relating to the effects of metformin-associated vitamin B12 deficiency on the risk of distal symmetrical polyneuropathy (DSPN) and megaloblastic anaemia in well-characterised community-based cohorts. AIMS: To assess inter-relationships between metformin therapy, vitamin B12 deficiency assessed using serum active B12 concentrations, and DSPN and anaemia in 1492 Fremantle Diabetes Study Phase 2 (FDS2) participants with type 2 diabetes. METHODS: Prevalence rates of vitamin B12 deficiency (total <80 pmol/L, active <23 pmol/L) and borderline deficiency (total ≥80 and ≤200 pmol/L, active ≥23 and ≤35 pmol/L) were determined using baseline sera. The relationship between vitamin B12 status and both DSPN and anaemia was assessed using multivariable analyses. RESULTS: Most FDS2 participants (94.4%) were vitamin B12 replete (total serum concentration >200 pmol/L, active >35 pmol/L), 2.0% were deficient (total <80 pmol/L, active <23 pmol/L) and the remainder (3.6%) borderline. Although metformin treatment increased the odds of deficiency (4.2%, 3.1% borderline) in a dose-dependent fashion (odds ratio (95% confidence interval) 39.4 (4.90-316) for >2000 mg daily compared with no treatment; P < 0.001), there was no significant association between vitamin B12 status and DSPN, anaemia (haemoglobin ≤130 g/L males, ≤120 g/L females), haemoglobin concentration or mean corpuscular volume (P ≥ 0.147). Metformin increased the likelihood of anaemia, especially at high doses, independent of vitamin B12 deficiency. CONCLUSIONS: Since nutritional sources likely attenuate metformin-associated vitamin B12 malabsorption and its clinical sequelae in developed countries such as Australia, there is no need for routine/opportunistic serum vitamin B12 screening in metformin-treated patients.

Temporal trends in chronic complications of diabetes by sex in community-based people with type 2 diabetes: the Fremantle Diabetes Study.

BACKGROUND: Whether recent reductions in cardiovascular disease (CVD) events and mortality in type 2 diabetes apply equally to both sexes is largely unknown. The aim of this study was to characterize temporal changes in CVD events and related outcomes in community-based male and female Australian adults with type 2 diabetes or without known diabetes. METHODS: Participants from the longitudinal observational Fremantle Diabetes Study Phases I (FDS1; n = 1291 recruited 1993-1996) and II (FDS2; n = 1509 recruited 2008-2011) and four age-, sex- and postcode-matched individuals without diabetes (FDS1 n = 5159; FDS2 n = 6036) were followed for first myocardial infarction, stroke, heart failure hospitalization, lower extremity amputation, CVD death and all-cause mortality. Five-year incidence rates (IRs) for males versus females in FDS1 and FDS2 were calculated, and IR ratios (IRRs) derived. RESULTS: The FD1 and FDS2 participants were of mean age 64.0 and 65.4 years, respectively, and 48.7% and 51.8% were males. For type 2 diabetes, IRRs for all endpoints were 11-62% lower in FDS2 than FDS1 for both sexes. For participants without diabetes, IRRs were 8-56% lower in FDS2 versus FDS1 apart from stroke in females (non-significantly 41% higher). IRRs for males versus females across FDS phases were not significantly different for participants with type 2 diabetes or those without diabetes (P-values for male * FDS2 interaction ≥ 0.0.083 adjusted for age). For risk factors in participants with type 2 diabetes, greater improvements between FDS1 and FDS2 in smoking rates in males were offset by a greater reduction in systolic blood pressure in females. CONCLUSIONS: The incidence of chronic complications in Australians with type 2 diabetes and without diabetes has fallen similarly in both sexes over recent decades, consistent with comparably improved overall CVD risk factor management.

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.

The pharmacokinetic properties of artemether and lumefantrine in Malaysian patients with Plasmodium knowlesi malaria.

AIMS: The aim of this study was to assess the pharmacokinetic properties of artemether, lumefantrine and their active metabolites in Plasmodium knowlesi malaria. METHODS: Malaysian adults presenting with uncomplicated P. knowlesi infections received six doses of artemether (1.7 mg/kg) plus lumefantrine (10 mg/kg) over 3 days. Venous blood and dried blood spot (DBS) samples were taken at predetermined time-points over 28 days. Plasma and DBS artemether, dihydroartemisinin, lumefantrine and desbutyl-lumefantrine were measured using liquid chromatography-mass spectrometry. Multi-compartmental population pharmacokinetic models were developed using plasma with or without DBS drug concentrations. RESULTS: Forty-one participants (mean age 45 years, 66% males) were recruited. Artemether-lumefantrine treatment was well tolerated and parasite clearance was prompt. Plasma and DBS lumefantrine concentrations were in close agreement and were used together in pharmacokinetic modelling, but only plasma concentrations of the other analytes were used because of poor correlation with DBS levels. The areas under the concentration-time curve (AUC0-∞ ) for artemether, dihydroartemisinin and lumefantrine (medians 1626, 1881 and 625 098 µg.h/L, respectively) were similar to those reported in previous pharmacokinetic studies in adults and children. There was evidence of auto-induction of artemether metabolism (mean increase in clearance relative to bioavailability 25.2% for each subsequent dose). The lumefantrine terminal elimination half-life (median 9.5 days) was longer than reported in healthy volunteers and adults with falciparum malaria. CONCLUSION: The disposition of artemether, dihydroartemisinin and lumefantrine in knowlesi malaria largely parallels that in other human malarias. DBS lumefantrine concentrations can be used in pharmacokinetic studies but DBS technology is currently unreliable for the other analytes.

The relationship between pancreatic cancer and type 2 diabetes: the Fremantle Diabetes Study Phase I.

Pancreatic cancer incidence was double (incidence rate ratio 2.06) in community-based adults with (n = 1291) versus without (n = 5158) type 2 diabetes followed for up to 25 years in the Fremantle Diabetes Study Phase 1. Sustained higher fasting plasma glucose reflecting insulin resistance and fewer comorbidities were statistically significant risk factors in the cohort with diabetes. Past pancreatitis was an aetiologically significant determinant in the cohort as a whole.

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.

Incidence and predictors of idiopathic pulmonary fibrosis complicating Type 2 diabetes: the Fremantle Diabetes Study Phase I.

During 106 865 person-years of follow up, 17 (1.3%) Fremantle Diabetes Study Phase I participants with Type 2 diabetes and 57 (1.1%) matched individuals without diabetes developed idiopathic pulmonary fibrosis (IPF), an incidence rate ratio (95% confidence interval) of 1.40 (0.76-2.44) (P = 0.22). In the diabetes cohort, age at diabetes diagnosis and total serum cholesterol (inversely) predicted incident IPF in competing risk multivariable models. The incidence of IPF was low in community-based cohorts, regardless of Type 2 diabetes status.

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.

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.

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.

Complementary medicine use and its cost in Australians with type 2 diabetes: the Fremantle Diabetes Study Phase II.

BACKGROUND: Few studies have examined complementary medicine (CM) use in diabetes. Australian data are inconsistent, limited in scope and have not considered cost. AIMS: To evaluate the prevalence, associates and costs of CM in a contemporary Australian urban, community-based cohort of people with type 2 diabetes. METHODS: Baseline CM use was determined as part of a detailed assessment in 1543 of 1551 Fremantle Diabetes Study Phase II (FDS2) participants with type 2 diabetes (mean age 65.7 years, 51.8% males, median diabetes duration 9.0 years) recruited to the FDS2 between 2008 and 2011 who self-reported medication use including CM defined as non-prescription medicinal products. RESULTS: A total of 672 FDS2 type 2 participants (43.6%) used at least one type of CM, 92% of which were nutritional supplements (omega-3 fatty acids/fish oil in 24% of CM users followed by calcium in 11%, glucosamine in 10% and others in <10%). Independent associates of CM use included older age, female sex, any mobility problem, and, inversely, Southern European or Indigenous Australian background, lack of English fluency, ex/current smoking status, taking oral glucose-lowering medications and higher HbA1c . The total annual estimated cost of CM used by FDS2 participants with type 2 diabetes was A$121 640 or A$79 ± 208 per person (range A$0-2993). Extrapolating these data, the 1 million Australians with type 2 diabetes spend A$79 million/year on CM. CONCLUSIONS: CM use in type 2 diabetes is both common and costly. Healthcare professionals should consider discussing safe and cost-effective use of CM with their patients with type 2 diabetes.

Incidence, Risk Factors, and Outcomes of Intra-Abdominal Hypertension in Critically Ill Patients-A Prospective Multicenter Study (IROI Study).

OBJECTIVES: To identify the prevalence, risk factors, and outcomes of intra-abdominal hypertension in a mixed multicenter ICU population. DESIGN: Prospective observational study. SETTING: Fifteen ICUs worldwide. PATIENTS: Consecutive adult ICU patients with a bladder catheter. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four hundred ninety-one patients were included. Intra-abdominal pressure was measured a minimum of every 8 hours. Subjects with a mean intra-abdominal pressure equal to or greater than 12 mm Hg were defined as having intra-abdominal hypertension. Intra-abdominal hypertension was present in 34.0% of the patients on the day of ICU admission (159/467) and in 48.9% of the patients (240/491) during the observation period. The severity of intra-abdominal hypertension was as follows: grade I, 47.5%; grade II, 36.6%; grade III, 11.7%; and grade IV, 4.2%. The severity of intra-abdominal hypertension during the first 2 weeks of the ICU stay was identified as an independent predictor of 28- and 90-day mortality, whereas the presence of intra-abdominal hypertension on the day of ICU admission did not predict mortality. Body mass index, Acute Physiology and Chronic Health Evaluation II score greater than or equal to 18, presence of abdominal distension, absence of bowel sounds, and positive end-expiratory pressure greater than or equal to 7 cm H2O were independently associated with the development of intra-abdominal hypertension at any time during the observation period. In subjects without intra-abdominal hypertension on day 1, body mass index combined with daily positive fluid balance and positive end-expiratory pressure greater than or equal to 7 cm H2O (as documented on the day before intra-abdominal hypertension occurred) were associated with the development of intra-abdominal hypertension during the first week in the ICU. CONCLUSIONS: In our mixed ICU patient cohort, intra-abdominal hypertension occurred in almost half of all subjects and was twice as prevalent in mechanically ventilated patients as in spontaneously breathing patients. Presence and severity of intra-abdominal hypertension during the observation period significantly and independently increased 28- and 90-day mortality. Five admission day variables were independently associated with the presence or development of intra-abdominal hypertension. Positive fluid balance was associated with the development of intra-abdominal hypertension after day 1.

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.

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.