Rotating night shift work disrupts circadian rhythms and has been associated with obesity, metabolic syndrome, and glucose dysregulation. However, its association with type 2 diabetes remains ...unclear. Therefore, we aimed to evaluate this association in two cohorts of US women.
We followed 69,269 women aged 42-67 in Nurses' Health Study I (NHS I, 1988-2008), and 107,915 women aged 25-42 in NHS II (1989-2007) without diabetes, cardiovascular disease, and cancer at baseline. Participants were asked how long they had worked rotating night shifts (defined as at least three nights/month in addition to days and evenings in that month) at baseline. This information was updated every 2-4 years in NHS II. Self-reported type 2 diabetes was confirmed by a validated supplementary questionnaire. We documented 6,165 (NHS I) and 3,961 (NHS II) incident type 2 diabetes cases during the 18-20 years of follow-up. In the Cox proportional models adjusted for diabetes risk factors, duration of shift work was monotonically associated with an increased risk of type 2 diabetes in both cohorts. Compared with women who reported no shift work, the pooled hazard ratios (95% confidence intervals) for participants with 1-2, 3-9, 10-19, and ≥20 years of shift work were 1.05 (1.00-1.11), 1.20 (1.14-1.26), 1.40 (1.30-1.51), and 1.58 (1.43-1.74, p-value for trend <0.001), respectively. Further adjustment for updated body mass index attenuated the association, and the pooled hazard ratios were 1.03 (0.98-1.08), 1.06 (1.01-1.11), 1.10 (1.02-1.18), and 1.24 (1.13-1.37, p-value for trend <0.001).
Our results suggest that an extended period of rotating night shift work is associated with a modestly increased risk of type 2 diabetes in women, which appears to be partly mediated through body weight. Proper screening and intervention strategies in rotating night shift workers are needed for prevention of diabetes.
Prevailing dietary guidelines have widely recommended diets relatively low in red and processed meats and high in minimally processed plant foods for the prevention of chronic diseases. However, an ...ad hoc research group called the Nutritional Recommendations (NutriRECS) consortium recently issued "new dietary guidelines" encouraging individuals to continue their current meat consumption habits due to "low certainty" of the evidence, difficulty of altering meat eaters' habits and preferences, and the lack of need to consider environmental impacts of red meat consumption. These recommendations are not justified, in large part because of the flawed methodologies used to review and grade nutritional evidence. The evidence evaluation was largely based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria, which are primarily designed to grade the strength of evidence for clinical interventions especially pharmacotherapy. However, the infeasibility for conducting large, long-term randomized clinical trials on most dietary, lifestyle, and environmental exposures makes the criteria inappropriate in these areas. A separate research group proposed a modified and validated system for rating the meta-evidence on nutritional studies (NutriGRADE) to address several limitations of the GRADE criteria. Applying NutriGRADE, the evidence on the positive association between red and processed meats and type 2 diabetes was rated to be of "high quality," while the evidence on the association between red and processed meats and mortality was rated to be of "moderate quality." Another important limitation is that inadequate attention was paid to what might be replacing red meat, be it plant-based proteins, refined carbohydrates, or other foods. In summary, the red/processed meat recommendations by NutriRECS suffer from important methodological limitations and involve misinterpretations of nutritional evidence. To improve human and planetary health, dietary guidelines should continue to emphasize dietary patterns low in red and processed meats and high in minimally processed plant foods such as fruits and vegetables, whole grains, nuts, and legumes.
Protein kinase C (PKC) isozymes have remained elusive cancer targets despite the unambiguous tumor promoting function of their potent ligands, phorbol esters, and the prevalence of their mutations. ...We analyzed 8% of PKC mutations identified in human cancers and found that, surprisingly, most were loss of function and none were activating. Loss-of-function mutations occurred in all PKC subgroups and impeded second-messenger binding, phosphorylation, or catalysis. Correction of a loss-of-function PKCβ mutation by CRISPR-mediated genome editing in a patient-derived colon cancer cell line suppressed anchorage-independent growth and reduced tumor growth in a xenograft model. Hemizygous deletion promoted anchorage-independent growth, revealing that PKCβ is haploinsufficient for tumor suppression. Several mutations were dominant negative, suppressing global PKC signaling output, and bioinformatic analysis suggested that PKC mutations cooperate with co-occurring mutations in cancer drivers. These data establish that PKC isozymes generally function as tumor suppressors, indicating that therapies should focus on restoring, not inhibiting, PKC activity.
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•Cancer-associated PKC mutations are LOF and can act in a dominant-negative manner•Correcting a heterozygous PKCβ LOF mutation reduces tumor volume•Hemizygous deletion shows PKC is haploinsufficient for tumor suppression•Therapeutic strategies should aim to restore PKC activity instead of inhibiting it
Cancer-associated kinase mutations have generally been characterized as oncogenic, but an analysis of PKC mutations reveals that the majority are loss of function, indicating a tumor-suppressive role for this kinase and a shift in therapeutic strategies targeting PKC.
Obesity and diabetes mellitus have reached epidemic proportions in the past few years. During 2011 to 2012, more than one-third of the US population was obese. Although recent trend data indicate ...that the epidemic has leveled off, prevalence of abdominal obesity continues to rise, especially among adults. As seen for obesity, the past few decades have seen a doubling of the diabetes mellitus incidence with an increasing number of type 2 diabetes mellitus cases being diagnosed in children. Significant racial and ethnic disparities exist in the prevalence and trends of obesity and diabetes mellitus. In general, in both adults and children, non-Hispanic blacks and Mexican Americans seem to be at a high risk than their non-Hispanic white counterparts. Secular changes in agricultural policies, diet, food environment, physical activity, and sleep have all contributed to the upward trends in the diabesity epidemic. Despite marginal improvements in physical activity and the US diet, the food environment has changed drastically to an obesogenic one with increased portion sizes and limited access to healthy food choices especially for disadvantaged populations. Interventions that improve the food environment are critical as both obesity and diabetes mellitus raise the risk of cardiovascular disease by ≈2-fold. Among those with type 2 diabetes mellitus, significant sex differences occur in the risk of cardiovascular disease such that diabetes mellitus completely eliminates or attenuates the advantages of being female. Given the substantial burden of obesity and diabetes mellitus, future research efforts should adopt a translational approach to find sustainable and holistic solutions in preventing these costly diseases.
In recent decades, global life expectancies have risen significantly, accompanied by a marked increase in chronic diseases and population aging. This narrative review aims to summarize recent ...findings on the dietary factors influencing chronic diseases and longevity, primarily from large cohort studies. First, maintaining a healthy weight throughout life is pivotal for healthy aging and longevity, mirroring the benefits of lifelong, moderate calorie restriction in today's obesogenic food environment. Second, the specific types or food sources of dietary fat, protein, and carbohydrates are more important in influencing chronic disease risk and mortality than their quantity. Third, some traditional diets (e.g., the Mediterranean, Nordic, and Okinawa) and contemporary dietary patterns, such as healthy plant‐based diet index, the DASH (dietary approaches to stop hypertension) diet, and alternate healthy eating index, have been associated with lower mortality and healthy longevity. These patterns share many common components (e.g., a predominance of nutrient‐rich plant foods; limited red and processed meats; culinary herbs and spices prevalent in global cuisines) while embracing distinct elements from different cultures. Fourth, combining a healthy diet with other lifestyle factors could extend disease‐free life expectancies by 8–10 years. While adhering to core principles of healthy diets, it is crucial to adapt dietary recommendations to individual preferences and cultures as well as nutritional needs of aging populations. Public health strategies should aim to create a healthier food environment where nutritious options are readily accessible, especially in public institutions and care facilities for the elderly. Although further mechanistic studies and human trials are needed to better understand molecular effects of diet on aging, there is a pressing need to establish and maintain long‐term cohorts studying diet and aging in culturally diverse populations.
Health effects of dietary fats have been extensively studied for decades. However, controversies exist on the effects of various types of fatty acids, especially saturated fatty acid (SFA), on ...cardiovascular disease (CVD). Current evidence supports that different types of dietary fatty acids have divergent effects on CVD risk, and the effects also depend strongly on the comparison or replacement macronutrient. A significant reduction in CVD risk can be achieved if SFAs are replaced by unsaturated fats, especially polyunsaturated fatty acids. Intake of industrially produced
trans
fat is consistently associated with higher CVD risk. Both n-6 and n-3 polyunsaturated fatty acids are associated with lower CVD risk, although the effects of fish oil supplementation remains inconsistent. The 2015-2020 Dietary Guidelines for Americans place greater emphasis on types of dietary fat than total amount of dietary fat and recommend replacing SFAs with unsaturated fats, especially polyunsaturated fatty acids for CVD prevention.
The application of metabolomics in nutrition epidemiology holds great promise and there is a high expectation that it will play a leading role in deciphering the interactions between diet and health. ...However, while significant progress has been made in the identification of putative biomarkers, more work is needed to address the use of the biomarkers in dietary assessment. The aim of this review is to critically evaluate progress in these areas and to identify challenges that need to be addressed going forward. The notable applications of dietary biomarkers in nutritional epidemiology include 1) determination of food intake based on biomarkers levels and calibration equations from feeding studies, 2) classification of individuals into dietary patterns based on the urinary metabolic profile, and 3) application of metabolome wide–association studies. Further work is needed to address some specific challenges to enable biomarkers to reach their full potential.
Biomarkers of food intake have immense potential in nutritional epidemiology. To date significant progress has been made in their use in two areas: 1) Biomarkers can be used to determine food intake through the use of well‐defined calibration curves. Using a biomarker level, the amount of food intake in g day−1 can be estimated. 2) Combinations of biomarkers or the metabolic profile can be used to classify individuals into dietary patterns.
Referred to as slow slip events, the transient aseismic slip that occurs along plate boundaries can be indirectly characterized through colocated seismicity, such as tectonic tremor and low‐frequency ...earthquakes (LFEs). Using the timing of cataloged LFE and tremor activity in Guerrero, Mexico, and northern Cascadia, I decompose the interaseismic GPS displacement, defined as the surface deformation between previously detected slow slip events, into separate regimes of tectonic loading and release. In such a way, previously undetected slow slip events that produce less than a millimeter of surface deformation are extracted from the geodetic noise. These new observations demonstrate that the interaseismic period is not quiescent and that slow slip occurs much more often than previously thought. This suggests that the plate interface where slow slip and tremor occur is in fact strongly coupled and that slow aseismic release occurs over a wide spectrum of time scales.
Key Points
Tectonic tremor and low‐frequency earthquakes used to extract slow slip out of the geodetic noise
Interaseismic loading is interrupted by slow slip events that generate surface deformations less than 1 mm
Transient stress release on many time scales shows that plate interfaces are strongly coupled where slow slip occurs
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