Psychological factors and socioeconomic status (SES) have a notable impact on health disparities, including type 2 diabetes risk. However, the link between childhood psychosocial factors, such as ...childhood adversities or parental SES, and metabolic disturbances is less well established. In addition, the lifetime perspective including adult socioeconomic factors remains of further interest.We carried out a systematic review with the main question if there is evidence in population- or community-based studies that childhood adversities (like neglect, traumata and deprivation) have considerable impact on type 2 diabetes incidence and other metabolic disturbances. Also, parental SES was included in the search as risk factor for both, diabetes and adverse childhood experiences. Finally, we assumed that obesity might be a mediator for the association of childhood adversities with diabetes incidence. Therefore, we carried out a second review on obesity, applying a similar search strategy.
Two systematic reviews were carried out. Longitudinal, population- or community-based studies were included if they contained data on psychosocial factors in childhood and either diabetes incidence or obesity risk.
We included ten studies comprising a total of 200,381 individuals. Eight out of ten studies indicated that low parental status was associated with type 2 diabetes incidence or the development of metabolic abnormalities. Adjustment for adult SES and obesity tended to attenuate the childhood SES-attributable risk but the association remained. For obesity, eleven studies were included with a total sample size of 70,420 participants. Four out of eleven studies observed an independent association of low childhood SES on the risk for overweight and obesity later in life.
Taken together, there is evidence that childhood SES is associated with type 2 diabetes and obesity in later life. The database on the role of psychological factors such as traumata and childhood adversities for the future risk of type 2 diabetes or obesity is too small to draw conclusions. Thus, more population-based longitudinal studies and international standards to assess psychosocial factors are needed to clarify the mechanisms leading to the observed health disparities.
Context: Adipocytes are known to release a variety of factors that may contribute to the proinflammatory state characteristic for obesity. This secretory function is considered to provide the basis ...for obesity-related complications such as type 2 diabetes and atherosclerosis.
Objective: To get a better insight into possible underlying mechanisms, we investigated the effect of adipocyte size on adipokine production and secretion.
Design, Patients, and Main Outcome Measures: Protein secretion and mRNA expression in cultured adipocytes separated according to cell size from 30 individuals undergoing elective plastic surgery were investigated.
Results: The mean adipocyte volume of the four fractions ranged from 205 ± 146 to 1.077 ± 471 pl. There were strong linear correlations for the secretion of adipokines over time. Secretion of leptin, IL-6, IL-8, TNF-α, monocyte chemoattractant protein-1, interferon-γ-inducible protein 10, macrophage inflammatory protein-1β, granulocyte colony stimulating factor, IL-1ra, and adiponectin was positively correlated with cell size. After correction for cell surface, there was still a significant difference between fraction IV (very large) and fraction I (small cells), for leptin, IL-6, IL-8, monocyte chemoattractant protein-1, and granulocyte colony-stimulating factor. In contrast, antiinflammatory factors such as IL-1ra and adiponectin lost their association after correction for cell surface area comparing fraction I and IV. In addition, there was a decrease of IL-10 secretion with increasing cell size.
Conclusions: The results clearly suggest that adipocyte size is an important determinant of adipokine secretion. There seems to be a differential expression of pro- and antiinflammatory factors with increasing adipocyte size resulting in a shift toward dominance of proinflammatory adipokines largely as a result of a dysregulation of hypertrophic, very large cells.
Patients with type 2 diabetes (T2D) exhibit chronic activation of the innate immune system in pancreatic islets, in insulin-sensitive tissues, and at sites of diabetic complications. This results ...from a pathological response to overnutrition and physical inactivity seen in genetically predisposed individuals. Processes mediated by the proinflammatory cytokine interleukin-1 (IL-1) link obesity and dyslipidemia and have implicated IL-1β in T2D and related cardiovascular complications. Epidemiological, molecular, and animal studies have now assigned a central role for IL-1β in driving tissue inflammation during metabolic stress. Proof-of-concept clinical studies have validated IL-1β as a target to improve insulin production and action in patients with T2D. Large ongoing clinical trials will address the potential of IL-1 antagonism to prevent cardiovascular and other related complications.
Prediabetes (intermediate hyperglycaemia) is a high-risk state for diabetes that is defined by glycaemic variables that are higher than normal, but lower than diabetes thresholds. 5–10% of people per ...year with prediabetes will progress to diabetes, with the same proportion converting back to normoglycaemia. Prevalence of prediabetes is increasing worldwide and experts have projected that more than 470 million people will have prediabetes by 2030. Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction—abnormalities that start before glucose changes are detectable. Observational evidence shows associations between prediabetes and early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease. Multifactorial risk scores using non-invasive measures and blood-based metabolic traits, in addition to glycaemic values, could optimise estimation of diabetes risk. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention, with evidence of a 40–70% relative-risk reduction. Accumulating data also show potential benefits from pharmacotherapy.
Muscle insulin resistance is a key feature of obesity and type 2 diabetes and is strongly associated with increased intramyocellular lipid content and inflammation. However, the cellular and ...molecular mechanisms responsible for causing muscle insulin resistance in humans are still unclear. To address this question, we performed serial muscle biopsies in healthy, lean subjects before and during a lipid infusion to induce acute muscle insulin resistance and assessed lipid and inflammatory parameters that have been previously implicated in causing muscle insulin resistance. We found that acute induction of muscle insulin resistance was associated with a transient increase in total and cytosolic diacylglycerol (DAG) content that was temporally associated with protein kinase (PKC)θ activation, increased insulin receptor substrate (IRS)-1 serine 1101 phosphorylation, and inhibition of insulin-stimulated IRS-1 tyrosine phosphorylation and AKT2 phosphorylation. In contrast, there were no associations between insulin resistance and alterations in muscle ceramide, acylcarnitine content, or adipocytokines (interleukin-6, adiponectin, retinol-binding protein 4) or soluble intercellular adhesion molecule-1. Similar associations between muscle DAG content, PKCθ activation, and muscle insulin resistance were observed in healthy insulin-resistant obese subjects and obese type 2 diabetic subjects. Taken together, these data support a key role for DAG activation of PKCθ in the pathogenesis of lipid-induced muscle insulin resistance in obese and type 2 diabetic individuals.
Background: Cross-sectional and ecological studies indicate that air pollution may be a risk factor for type 2 diabetes, but prospective data are lacking. Objective: We examined the association ...between traffic-related air pollution and incident type 2 diabetes. Design: Between 1985 and 1994, cross-sectional surveys were performed in the highly industrialized Ruhr district (West Germany); a follow-up investigation was conducted in 2006 using data from the Study on the Influence of Air Pollution on Lung, Inflammation and Aging (SALIA) cohort. Participants: 1,775 nondiabetic women who were 54-55 years old at baseline participated in both baseline and follow-up investigations and had complete information available. Materials and Methods: Using questionnaires, we assessed 16-year incidence (1990-2006) of type 2 diabetes and information about covariates. Complement factor C3c as marker for subclinical inflammation was measured at baseline. Individual exposure to traffic-related particulate matter (PM) and nitrogen dioxide was determined at different spatial scales. Results: Between 1990 and 2006, 87 (10.5%) new cases of diabetes were reported among the SALIA cohort members. The hazards for diabetes were increased by 15-42% per interquartile range of PM or traffic-related exposure. The associations persisted when different spatial scales were used to assess exposure and remained robust after adjusting for age, body mass index, socioeconomic status, and exposure to several non—traffic-related sources of air pollution. C3c was associated with PM pollution at baseline and was a strong independent predictor of incident diabetes. Exploratory analyses indicated that women with high C3c blood levels were more susceptible for PM-related excess risk of diabetes than were women with low C3c levels. Conclusions: Traffic-related air pollution is associated with incident type 2 diabetes among elderly women. Subclinical inflammation may be a mechanism linking air pollution with type 2 diabetes. Relevance to clinical practice: Our study identifies traffic-related air pollution as a novel and potentially modifiable risk factor of type 2 diabetes.
The current classification of diabetes, based on hyperglycaemia, islet-directed antibodies and some insufficiently defined clinical features, does not reflect differences in aetiological mechanisms ...and in the clinical course of people with diabetes. This review discusses evidence from recent studies addressing the complexity of diabetes by proposing novel subgroups (subtypes) of diabetes. The most widely replicated and validated approach identified, in addition to severe autoimmune diabetes, four subgroups designated severe insulin-deficient diabetes, severe insulin-resistant diabetes, mild obesity-related diabetes and mild age-related diabetes subgroups. These subgroups display distinct patterns of clinical features, disease progression and onset of comorbidities and complications, with severe insulin-resistant diabetes showing the highest risk for cardiovascular, kidney and fatty liver diseases. While it has been suggested that people in these subgroups would benefit from stratified treatments, RCTs are required to assess the clinical utility of any reclassification effort. Several methodological and practical issues also need further study: the statistical approach used to define subgroups and derive recommendations for diabetes care; the stability of subgroups over time; the optimal dataset (e.g. phenotypic vs genotypic) for reclassification; the transethnic generalisability of findings; and the applicability in clinical routine care. Despite these open questions, the concept of a new classification of diabetes has already allowed researchers to gain more insight into the colourful picture of diabetes and has stimulated progress in this field so that precision diabetology may become reality in the future.
Graphical abstract
Dietary intake of saturated fat is a likely contributor to nonalcoholic fatty liver disease (NAFLD) and insulin resistance, but the mechanisms that initiate these abnormalities in humans remain ...unclear. We examined the effects of a single oral saturated fat load on insulin sensitivity, hepatic glucose metabolism, and lipid metabolism in humans. Similarly, initiating mechanisms were examined after an equivalent challenge in mice.
Fourteen lean, healthy individuals randomly received either palm oil (PO) or vehicle (VCL). Hepatic metabolism was analyzed using in vivo 13C/31P/1H and ex vivo 2H magnetic resonance spectroscopy before and during hyperinsulinemic-euglycemic clamps with isotope dilution. Mice underwent identical clamp procedures and hepatic transcriptome analyses.
PO administration decreased whole-body, hepatic, and adipose tissue insulin sensitivity by 25%, 15%, and 34%, respectively. Hepatic triglyceride and ATP content rose by 35% and 16%, respectively. Hepatic gluconeogenesis increased by 70%, and net glycogenolysis declined by 20%. Mouse transcriptomics revealed that PO differentially regulates predicted upstream regulators and pathways, including LPS, members of the TLR and PPAR families, NF-κB, and TNF-related weak inducer of apoptosis (TWEAK).
Saturated fat ingestion rapidly increases hepatic lipid storage, energy metabolism, and insulin resistance. This is accompanied by regulation of hepatic gene expression and signaling that may contribute to development of NAFLD.REGISTRATION. ClinicalTrials.gov NCT01736202.
Germany: Ministry of Innovation, Science, and Research North Rhine-Westfalia, German Federal Ministry of Health, Federal Ministry of Education and Research, German Center for Diabetes Research, German Research Foundation, and German Diabetes Association. Portugal: Portuguese Foundation for Science and Technology, FEDER - European Regional Development Fund, Portuguese Foundation for Science and Technology, and Rede Nacional de Ressonância Magnética Nuclear.
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