NON-INSULIN-DEPENDENT diabetes mellitus (NIDDM), which affects 10 to 12 million Americans over the age of 20 years,
1
2
3
is a complex disorder characterized by increased resistance to insulin and ...impaired secretion of insulin
4
and associated with an increased risk of coronary heart disease, peripheral vascular disease, kidney failure, and blindness. The strongest predisposing factors for NIDDM are obesity
5
6
7
8
and a family history of diabetes.
9
,
10
Along with proper diet and weight reduction, exercise has been advocated for the management of NIDDM.
2
,
11
Whether physical activity is effective in preventing diabetes is unknown, but several indirect lines of evidence support the concept that increased . . .
Weight gain and the risk of developing insulin resistance syndrome.
S A Everson ,
D E Goldberg ,
S P Helmrich ,
T A Lakka ,
J W Lynch ,
G A Kaplan and
J T Salonen
Department of Epidemiology, ...University of Michigan School of Public Health, Ann Arbor 48109-2029, USA. severson@umich.edu
Abstract
OBJECTIVE: Obesity and weight gain have been associated independently with hypertension, hyperinsulinemia, and dyslipidemia;
however, prior research has not looked at the relation between weight gain from early adulthood to middle age and the development
of this cluster of risk factors, known as insulin resistance syndrome. RESEARCH DESIGN AND METHODS: The association between
weight gain over 30 years (defined as the difference between measured weight in middle age and participant recall of their
weight at age 20) and the odds of developing insulin resistance syndrome at middle age was examined in a population-based
sample of 2,272 eastern Finnish men. RESULTS: Each 5% increase in weight over the reported weight at age 20 was associated
with nearly a 20% greater risk of insulin resistance syndrome by middle age, after adjustment for age and height. Moreover,
there was a strong graded association between categories of weight gain and risk of insulin resistance syndrome. Men with
weight increases of 10-19%, 20-29%, or > or =30% since age 20 were 3.0, 4.7, or 10.6 times more likely to have insulin resistance
syndrome, respectively, by middle age, compared with men within 10% of their weight at age 20. Adjustments for age, height,
physical activity, smoking, education, and parental history of diabetes did not alter these findings. CONCLUSIONS: The odds
of having developed the hemodynamic and metabolic abnormalities that characterize insulin resistance syndrome by middle adulthood
were increasingly higher the greater the weight gain over the preceding 30 years. This study adds to the literature identifying
deleterious effects of weight gain from young to middle adulthood.
Physical activity has been recommended by physicians in managing patients with noninsulin-dependent diabetes mellitus (NIDDM); however, it is unclear whether physical activity can prevent this ...disease. Several prospective studies have suggested that increased physical activity may lead to the prevention of NIDDM. In the University of Pennsylvania Alumni Health Study, 5990 men were surveyed to determine the relationship between physical activity and the development of NIDDM. A total of 202 men developed NIDDM from 1962 to 1976. Leisure-time physical activity, expressed in kilocalories (kcal) was inversely related to the development of NIDDM. Incidence rates declined as energy expenditure increased. For each 2000-kcal increment in energy expenditure, the risk of NIDDM was reduced by 24% relative risk (RR) 0.76, 95% confidence interval (CI) 0.63-0.92. This association remained when adjusting for obesity, hypertension, and parental history of diabetes. The protective effect of physical activity was strongest in individuals at highest risk for NIDDM. Based on the review of data from several large prospective studies, it is quite likely that increased levels of physical activity are effective in preventing NIDDM, and the protective benefit is especially pronounced in those individuals who have the highest risk of disease.
We assessed the effect of quitting cigarette smoking on the incidence of nonfatal myocardial infarction in men under the age of 55 in a case-control study of 1873 men with first episodes of ...myocardial infarction and 2775 controls. For "current" smokers (men who had smoked in the previous year) as compared with those who had never smoked, the estimated relative risk of myocardial infarction, adjusted for age, was 2.9 (95 per cent confidence interval, 2.4 to 3.4). Among exsmokers (those who had last smoked at least one year previously), the relative-risk estimate declined to a value close to unity for those who had abstained for at least two years; the estimate was 2.0 (1.1 to 3.8) for men who had abstained for 12 to 23 months, and the estimates were about 1.0 for men who had abstained for longer intervals. The results were unchanged by allowance for multiple potential confounding factors. A similar pattern was apparent among exsmokers who had smoked heavily for many years; among those predisposed to a myocardial infarction because of family history, hypertension, or other risk factors; and among those with no apparent predisposition. The results suggest that the risk of myocardial infarction in cigarette smokers decreases within a few years of quitting to a level similar to that in men who have never smoked.
Supporting decisions for patients who present to the emergency department (ED) with COVID-19 requires accurate prognostication. We aimed to evaluate prognostic models for predicting outcomes in ...hospitalized patients with COVID-19, in different locations and across time.
We included patients who presented to the ED with suspected COVID-19 and were admitted to 12 hospitals in the New York City (NYC) area and 4 large Dutch hospitals. We used second-wave patients who presented between September and December 2020 (2137 and 3252 in NYC and the Netherlands, respectively) to evaluate models that were developed on first-wave patients who presented between March and August 2020 (12,163 and 5831). We evaluated two prognostic models for in-hospital death: The Northwell COVID-19 Survival (NOCOS) model was developed on NYC data and the COVID Outcome Prediction in the Emergency Department (COPE) model was developed on Dutch data. These models were validated on subsequent second-wave data at the same site (temporal validation) and at the other site (geographic validation). We assessed model performance by the Area Under the receiver operating characteristic Curve (AUC), by the E-statistic, and by net benefit.
Twenty-eight-day mortality was considerably higher in the NYC first-wave data (21.0%), compared to the second-wave (10.1%) and the Dutch data (first wave 10.8%; second wave 10.0%). COPE discriminated well at temporal validation (AUC 0.82), with excellent calibration (E-statistic 0.8%). At geographic validation, discrimination was satisfactory (AUC 0.78), but with moderate over-prediction of mortality risk, particularly in higher-risk patients (E-statistic 2.9%). While discrimination was adequate when NOCOS was tested on second-wave NYC data (AUC 0.77), NOCOS systematically overestimated the mortality risk (E-statistic 5.1%). Discrimination in the Dutch data was good (AUC 0.81), but with over-prediction of risk, particularly in lower-risk patients (E-statistic 4.0%). Recalibration of COPE and NOCOS led to limited net benefit improvement in Dutch data, but to substantial net benefit improvement in NYC data.
NOCOS performed moderately worse than COPE, probably reflecting unique aspects of the early pandemic in NYC. Frequent updating of prognostic models is likely to be required for transportability over time and space during a dynamic pandemic.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Objective: To investigate whether low vitamin E status is a risk factor for incident non-insulin dependent diabetes mellitus. Design: Population based follow up study with diabetes assessed ...at baseline and at four years. Setting: Eastern Finland. Subjects: Random sample of 944 men aged 42-60 who had no diabetes at the baseline examination. Intervention: Oral glucose tolerance test at four year follow up. Main outcome measures: A man was defined diabetic if he had either (a) a fasting blood glucose concentration >/=6.7 mmol/l, or (b) a blood glucose concentration >/=10.0 mmol/l two hours after a glucose load, or (c) a clinical diagnosis of diabetes with either dietary, oral, or insulin treatment. Results: 45 men developed diabetes during the follow up period. In a multivariate logistic regression model including the strongest predictors of diabetes, a low lipid standardised plasma vitamin E (below median) concentration was associated with a 3.9-fold (95% confidence interval 1.8-fold to 8.6-fold) risk of incident diabetes. A decrement of 1 µmol/l of uncategorised unstandardised vitamin E concentration was associated with an increment of 22% in the risk of diabetes when allowing for the strongest other risk factors as well as serum low density lipoprotein cholesterol and triglyceride concentrations. Conclusions: There was a strong independent association between low vitamin E status before follow up and an excess risk of diabetes at four years. This supports the theory that free radical stress has a role in the causation of non-insulin dependent diabetes mellitus.
•We consider a lot-sizing problem with one global constraint on carbon emissions.•We show that this problem is NP-hard.•We present a Lagrangian heuristic, pseudo-polynomial algorithm and ...FPTAS.•Special attention is paid to an efficient implementation of the FPTAS.•Tests show that a combination of the heuristic and FPTAS is very fast.
We consider a generalisation of the lot-sizing problem that includes an emission capacity constraint. Besides the usual financial costs, there are emissions associated with production, keeping inventory and setting up the production process. Because the capacity constraint on the emissions can be seen as a constraint on an alternative objective function, there is also a clear link with bi-objective optimisation. We show that lot-sizing with an emission capacity constraint is NP-hard and propose several solution methods. Our algorithms are not only able to handle a fixed-plus-linear cost structure, but also more general concave cost and emission functions. First, we present a Lagrangian heuristic to provide a feasible solution and lower bound for the problem. For costs and emissions such that the zero inventory property is satisfied, we give a pseudo-polynomial algorithm, which can also be used to identify the complete set of Pareto optimal solutions of the bi-objective lot-sizing problem. Furthermore, we present a fully polynomial time approximation scheme (FPTAS) for such costs and emissions and extend it to deal with general costs and emissions. Special attention is paid to an efficient implementation with an improved rounding technique to reduce the a posteriori gap, and a combination of the FPTASes and a heuristic lower bound. Extensive computational tests show that the Lagrangian heuristic gives solutions that are very close to the optimum. Moreover, the FPTASes have a much better performance in terms of their actual gap than the a priori imposed performance, and, especially if the heuristic’s lower bound is used, they are very fast.
In a case-control study of the risk of adenocarcinoma of the endometrium in relation to conjugated-estrogen use, we found that 31 per cent of 425 women with endometrial cancer and 15 per cent of 792 ...controls reported having used conjugated estrogens; the rate-ratio estimate was 3.5 with a 95 per cent confidence interval of 2.6 to 4.7. For use that lasted at least one year, the rate-ratio estimate for Stage I or II cancer was 5.2 (95 per cent confidence interval, 3.7 to 7.2), and for Stages III and IV combined it was 3.1 (1.5 to 6.4). Among women who had used estrogen for at least one year and then discontinued it, the risk of endometrial cancer remained significantly elevated even after estrogen-free intervals of over 10 years. The findings suggest that long-term use of conjugated estrogen increases the risk of both localized and widespread endometrial cancer. The data also suggest that women who have taken conjugated estrogen for one or more years remain at increased risk for at least 10 years after they discontinue use. Such women should be considered for long-term gynecologic surveillance.
Given the potentially large ethical and societal implications of human germline gene editing (HGGE) the urgent need for public and stakeholder engagement (PSE) has been repeatedly expressed. However, ...the explicit goals of such PSE efforts often remain poorly defined. In this program report, we outline the goals of our Dutch project called
De DNA dialogen
(The DNA dialogues). We believe that setting explicit goals in advance is essential to enable meaningful PSE efforts. Moreover, it enables the evaluation of our engagement efforts. The following four goals, which result from intensive consultations among the transdisciplinary projects’ consortium members and based on the literature, form the foundation for how we will engage the public and stakeholders in deliberation about HGGE: 1) Enable publics and stakeholders to deliberate on “what if” questions, before considering “whether” and “how” questions regarding HGGE, 2) Investigate agreement and disagreement in values and beliefs regarding HGGE in order to agree and disagree more precisely, 3) Involve diverse publics with various perspectives, with a focus on those that are typically underrepresented in PSE, 4) Enable societally aligned policy making by providing policymakers, health care professionals and legal experts insight into how values are weighed and ascribed meaning in the context of HGGE by various publics, and how these values relate to the principles of democratic rule of law and fundamental rights. The effort to describe our goals in detail may serve as an example and can inform future initiatives striving for open science and open governance in the context of PSE.
The relation of the risk of venous thromboembolism to the use of oral contraceptives was assessed in a hospital-based study of 61 women suffering from a first episode of idiopathic deep vein ...thrombosis or pulmonary embolism (cases) and 1278 women admitted for trauma or respiratory infections (controls). Twenty (33%) of the cases and 121 (9%) of the controls had used oral contraceptives within the previous month, yielding an age-adjusted relative risk estimate of 8.1 (95% confidence interval 3.7 to 18) for recent users relative to never-users. For women using oral contraceptives containing less than 50 micrograms estrogen, the relative risk estimate was 11 (3.7 to 22); for preparations with 50 micrograms estrogen, it was 5.5 (2.1 to 15); and for preparations with more than 50 micrograms estrogen, it was 11 (3.9 to 30). Past use of oral contraceptives was not associated with an increased risk. The data suggest that the risk of venous thromboembolism is increased for recent oral contraceptive users relative to nonusers, even if women use oral contraceptives containing low doses of estrogen. Confidence intervals were wide, however, so that a reduction in the risk for users of lower dose formulations relative to users of higher dose formulations cannot be ruled out. Selection bias, if present, would have resulted in overestimation of the relative risk, but should not have distorted the comparisons according to dosage.
PDF
