161 research outputs found
Lower insulin clearance is associated with increased risk of type 2 diabetes in Native Americans
No full textAims/hypothesis
Impaired insulin clearance is implicated in the pathogenesis of type 2 diabetes, but prospective evidence remains limited. Therefore, we sought to identify factors associated with the metabolic clearance rate of insulin (MCRI) and to investigate whether lower MCRI is associated with increased risk of incident type 2 diabetes.
Methods
From a longitudinal cohort, 570 adult Native Americans without diabetes living in the Southwestern United States were characterised at baseline and 448 participants were monitored over a median follow-up period of 7.9 years with 146 (32%) incident cases of diabetes identified (fasting plasma glucose ≥7.0 mmol/l, 2 h plasma glucose [2-h PG] ≥11.1 mmol/l, or clinical diagnosis). At baseline, participants underwent dual-energy x-ray absorptiometry or hydrodensitometry to assess body composition, a 75 g OGTT, an IVGTT to assess acute insulin response (AIR), and a hyperinsulinaemic–euglycaemic clamp to assess MCRI and insulin action (M).
Results
In adjusted linear models, MCRI was inversely associated with body fat percentage (r = −0.35), fasting plasma insulin (r = −0.55) and AIR (r = −0.22), and positively associated with M (r = 0.17; all p < 0.0001). In multivariable Cox proportional hazard models, lower MCRI was associated with an increased risk of diabetes after adjustment for age, sex, heritage, body fat percentage, AIR, M, fasting plasma glucose, 2-h PG, and fasting plasma insulin (HR per one-SD difference in MCRI: 0.77; 95% CI 0.61, 0.98; p = 0.03).
Conclusions/interpretation
Lower MCRI is associated with an unfavourable metabolic phenotype and is associated with incident type 2 diabetes independent of established risk factors
Sex-specific associations between birthweight and objectively measured energy intake in healthy indigenous American adults
No full textThe present analysis investigated associations between birth weight
and objectively measured food intake in adulthood among 65 healthy
Indigenous Americans. We discovered a sex difference such that birthweight was negatively associated with adult food intake in males and
positively associated with adult food intake in females. Lower birthweight males consumed more fat as adults, whereas higher birthweight
females consumed more fat and protei
Insulin resistance before type 2 diabetes onset is associated with increased risk of albuminuria after diabetes onset: A prospective cohort study
No full textAim: Reduced renal insulin signalling is implicated in the pathogenesis of albuminuria. We sought to investigate whether insulin action and secretion, measured before diabetes onset, are associated with the development of albuminuria after diabetes onset. Materials and methods: Baseline body composition, insulin sensitivity by hyperinsulinaemic-euglycaemic clamp at submaximal and maximal insulin stimulation (240 and 2400 pmol/m2 /min; M-low and M-high), and insulin secretion by intravenous glucose tolerance test [acute insulin response (AIR)] were measured in 170 Southwestern Indigenous American adults who subsequently developed diabetes. After diabetes onset and during the median follow-up of 13.6 years, 81 participants (48%) developed albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g). Separate associations of M-low, M-high and AIR (per 1-SD change) with the risk of albuminuria were assessed by Cox regression models adjusted for age, sex and body fat (%). Results: Participants who developed albuminuria were of similar age (26.4 ± 5.4 vs. 27.5 ± 6.1 years), sex (46% vs. 48% male), body fat (36.4 ± 7.5 vs. 35.7 ± 7.9%) and AIR [2.3 ± 0.3 vs. 2.3 ± 0.3, pmol/L (log)] as those who did not develop albuminuria but had lower insulin sensitivity [M-low: 0.33 ± 0.08 vs. 0.36 ± 0.12, p = .03; M-high: 0.87 ± 0.11 vs. 0.91 ± 0.12, p = .02; mg/kg-metabolic body size/min (log)]. In separate adjusted models, lower M-low and M-high were both associated with an increased risk for albuminuria [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.14, 2.00, p = .004; HR 1.31, 95% CI 1.06, 1.63, p = .01), whereas AIR was not (HR 1.15, 95% CI 0.87, 1.56, p = .3). Conclusions: Lower insulin sensitivity is associated with the development of albuminuria, suggesting a role for insulin signalling in the pathogenesis of proteinuria
Progression of diabetes retinal status within community screening programs and potential implications for screening intervals
No full textOBJECTIVE: This study aimed to follow the natural progression of retinal changes in patients with diabetes. Such information should inform decisions with regard to the screening intervals for such patients.RESEARCH DESIGN AND METHODS: An observational study was undertaken linking the data from seven diabetes retinal screening programs across the U.K. for retinal grading results between 2005 and 2012. Patients with absent or background retinopathy were followed up for progression to the end points referable retinopathy and treatable retinopathy (proliferative retinopathy).RESULTS: In total 354,549 patients were observed for up to 4 years during which 16,196 patients progressed to referable retinopathy. Of patients with no retinopathy in either eye for two successive screening episodes at least 12 months apart, the conditions of between 0.3% (95% CI 0.3-0.8%) and 1.3% (1.0-1.6%) of patients progressed to referable retinopathy, and rates of treatable eye disease were <0.3% at 2 years. The corresponding progression rates for patients with bilateral background retinopathy in successive screening episodes were 13-29% and up to 4%, respectively, in the different programs.CONCLUSIONS: It may be possible to stratify patients for risk, according to baseline retinal criteria, into groups with low and high risk of their conditions progressing to proliferative retinopathy. Screening intervals for such diverse groups of patients could safely be modified according to their risk.</p
Metformin is the key factor in elevated plasma growth differentiation factor-15 levels in type 2 diabetes : A nested, case–control study
No full textProduced as a tissue defence response to hypoxia and inflammation, growth differentiation factor-15 (GDF-15) is elevated in people receiving metformin treatment. To gain insight into the relationship of GDF-15 with metformin and major cardiovascular risk factors, we analysed the data from the SUMMIT cohort (n = 1438), a four-centre, nested, case–control study aimed at verifying whether biomarkers of atherosclerosis differ according to the presence of type 2 diabetes and cardiovascular disease. While in univariate analysis, major cardiovascular risk factors, with the exception of gender and cholesterol, increased similarly and linearly across GDF-15 quartiles, the independent variables associated with GDF-15, both in participants with and without diabetes, were age, plasma creatinine, N-terminal pro-brain natriuretic peptide, diuretic use, smoking exposure and glycated haemoglobin. In participants with diabetes, metformin treatment was associated with a 40% rise in GDF-15 level, which was independent of the other major factors, and largely explained their elevated GDF-15 levels. The relatively high GDF-15 bioavailability might partly explain the protective cardiovascular effects of metformin
Automated Sample Ratio Mismatch (SRM) Detection and Analysis
No full textBackground: Sample Ratio Mismatch (SRM) checks can help detect data quality issues in online experimentation [3]. Not all experimentation platforms provide these checks as part of their solution. Users of these platforms must therefore manually check for SRM, or rely on additional processes—such as checklists [2]—or automation. Objective: To ensure reliable and early detection of SRM, we wanted to automate the detection and analysis of SRM in experiments running on third-party experimentation platforms. Method: A set of Looker dashboards were built to facilitate self-serve SRM detection and root cause analysis. In addition, we added email and chat based alerting to pro-actively inform experimenters of SRM and guide them towards these dashboards when needed. Results: Several cases of SRM have been detected and experimenters have been warned. Bad decisions based on flawed data were avoided. We provide one such example as an illustration. Conclusions: SRM checks are relatively straightforward to automate and can be useful for data quality monitoring even for companies who rely on third-party experimentation platforms. Pro-active alerting—rather than passive reporting—can reduce time to detection and help non-experts avoid making decisions based on biased data.Software Engineerin
Elevated plasma levels of MMP-12 are associated with atherosclerotic burden and symptomatic cardiovascular disease in subjects with type 2 diabetes
No full textObjective-Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins and play important roles in development and tissue repair. They have also been shown to have both protective and pathogenic effects in atherosclerosis, and experimental studies have suggested that MMP-12 contributes to plaque growth and destabilization. The objective of this study was to investigate the associations between circulating MMPs, atherosclerosis burden, and incidence of cardiovascular disease with a particular focus on type 2 diabetes mellitus. Approach and Results-Plasma levels of MMP-1, -3, -7, -10, and -12 were analyzed by the Proximity Extension Assay technology in 1500 subjects participating in the SUMMIT (surrogate markers for micro-and macrovascular hard end points for innovative diabetes tools) study, 384 incident coronary cases, and 409 matched controls in the Malmö Diet and Cancer study and in 205 carotid endarterectomy patients. Plasma MMP-7 and -12 were higher in subjects with type 2 diabetes mellitus, increased with age and impaired renal function, and was independently associated with prevalent cardiovascular disease, atherosclerotic burden (as assessed by carotid intima-media thickness and ankle-brachial pressure index), arterial stiffness, and plaque inflammation. Baseline MMP-7 and -12 levels were increased in Malmö Diet and Cancer subjects who had a coronary event during follow-up. Conclusions-The plasma level of MMP-7 and -12 are elevated in type 2 diabetes mellitus, associated with more severe atherosclerosis and an increased incidence of coronary events. These observations provide clinical support to previous experimental studies, demonstrating a role for these MMPs in plaque development, and suggest that they are potential biomarkers of atherosclerosis burden and cardiovascular disease risk.</p
Public duty and private interest: report of the Committee of Inquiry established by the Prime Minister on 15 February 1978
No full textThis was the first report to set out the principles that underpin public servants\u27 and politicians\u27 obligations to disclose and manage conflicts of interest.
Tabled in 1979, this is the first time a digitised version of this report, known as the \u27Bowen report\u27, has been made publically available.
The intention to establish this inquiry was announced in a press statement issued by the then Prime Minister Malcolm Fraser on 16 December 1977. The statement mentioned the difficult position in which a Prime Minister finds himself when he is called upon to pass judgment on colleagues with whom he has worked closely, particularly as the Prime Minister must act as a judge and jury when allegations of impropriety are raised.
Fraser expressed his disatisfaction with a previous inquiry on the topic, conducted by a Parliamentary committee. He stated that he would instead he would appoint a judge or Queen\u27s Counsel, to be assisted by a businessman and an accountant, to carry out a new inquiry.
On 15 February 1978 Fraser stated that the new inquiry would be conducted by the Chief Judge of the Federal Court of Australia, the Hon. Sir Nigel Bowen, K.B.E., as well as Sir Cecil Looker, and Sir Edward Cain, C.B.E.
The terms of reference were:
1. To recommend whether a statement of principles can be drawn up on the nature of private interests, pecuniary or otherwise, which could conflict with the public duty of any or all persons holding positions of public trust in relation to the Commonwealth.
2. To recommend whether principles can be defined which would promote the avoidance and if necessary the resolution of any conflicts of interest which the Inquiry may, under paragraph (1) above, find to be possible.
3. In the event of a finding under paragraph (2) above that principles can be defined, to recommend what those principles should be.
4. Without limiting the scope of paragraph (3) above, to recommend whether or not a register under judicial or other supervision should be maintained so that, in the event of allegations of impropriety, the allegation may be open to judicial investigation and report.
5. For the purposes of paragraph(1) above, \u27persons holding positions of public trust in relation to the Commonwealth\u27 to include the following:
(a) Ministers;
(b) Senators and Members of the House of Representatives;
(c) Staff of (a) and (b);
(d) Members of the Australian Public Service; and
(e) Such other persons or classes of persons which in the opinion of the Committee ought to be included.
This is the final report of the inquiry, which has helped shaped the conduct of the public service to this day.
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Part of the Policy History Collection. Digitisation of this report has been supported by the National Library of Australia.
Reproduced with permission of the Department of Prime Minister and Cabinet
Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes: The SUMMIT VIP Study
No full textCardiovascular disease (CVD) risk prediction represents an increasing clinical challenge in the treatment of diabetes. We used a panel of vascular imaging, functional assessments, and biomarkers reflecting different disease mechanisms to identify clinically useful markers of risk for cardiovascular (CV) events in subjects with type 2 diabetes (T2D) with or without manifest CVD
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