Selective autophagy in inflammayion microvascular Hyperglycemua macrovascular Hyperglycemia and inflammation. b Fasted animals received saline solution with glucose 0, 0. Insulin resistance and its treatment by thiazolidinediones. Edgar L, Akbar N, Braithwaite AT, Krausgruber T, Gallart-Ayala H, Bailey J, et al.

Hyperglycemia and inflammation -

Covariates included age, sex, race, clinic site, education, body height, total body fat, visceral fat, health status, use of anti-inflammatory drugs, statins, and estrogen, smoking, and alcohol intake.

Body height was measured to the nearest millimeter using a wall-mounted stadiometer. Total body fat kilograms was measured by dual-energy X-ray absorptiometry QDR A, software version 8. Visceral fat at the L4-L5 level was quantified from computerized tomography scanning of the abdomen.

Scans were performed on a General Electric Advantage in Pittsburgh and a Siemens Somatron and Picker PQS in Memphis. All data from the computerized tomography scans were analyzed at the University of Colorado Health Sciences Center according to a standardized protocol Several diseases with a potential association with inflammation or with diabetes were considered in the analysis, including cardiovascular disease, hypertension, peripheral arterial disease, renal insufficiency, arthritis, and respiratory disease.

For hypertension, we used self-report, medications, and measured blood pressure. Current anti-inflammatory, statin, and estrogen use were assessed at the clinic visit.

Of the Health ABC participants, 2, had complete information on inflammation markers and glucose parameters and constituted the study sample for the analysis. For all the other categorical variables with missing data, a separate category for those with missing data within each variable was used so that all observations remained in the analysis.

Because the distributions of CRP, IL-6, and TNF-α were skewed, median values with 25th—75th percentile ranges were reported, and we used the t test on log-transformed values to compare the different groups. The first model was adjusted for age, race, sex, education, smoking, alcohol intake, and clinic site.

The second model was adjusted additionally for total body fat and visceral fat. When total body fat was included in the models, an additional adjustment was made for body height to normalize total body fat. The fully adjusted model took into account the comorbidities and medication use.

Because high levels of two or more inflammatory markers represent a more specific indicator of systemic inflammation 21 than a high level of just one, a composite inflammation index was calculated. The high extreme group included those who had at least two of the inflammatory markers in the highest quartile.

The low extreme group, considered as the reference category in the analysis, included participants with all three inflammation markers below or equal to the median, and the intermediate group included individuals with all other possible combinations of cytokine levels.

Statistical analyses were performed using SAS software SAS Institute, Cary, NC. Among the 2, participants with complete information, Participants with diabetes were more likely to be male and black and had a lower level of education Table 1.

Diabetic individuals had more cardiovascular diseases and peripheral arterial disease than their counterparts with NGT. Plasma levels of inflammatory markers were moderately correlated. The correlation between IL-6 and TNF-α was 0. Table 2 shows the plasma concentrations of the inflammatory markers by diabetes and hyperglycemic status.

Multivariate analyses on the risk of high inflammation associated with diabetes and hyperglycemic status are shown in Table 3. Compared with those without diabetes, after adjustments for age, sex, race, smoking status, alcohol intake, education, and site, diabetic individuals continued to exhibit higher inflammation levels with an OR of 1.

Diabetic women compared with those without diabetes had an OR of 2. The association between diabetes and higher inflammation level was weakened by adjustments for body fat and visceral fat, inflammation, and diabetes comorbidities and potential confounders Table 3 , models 2 and 3 but still remained significant, except for high CRP in men.

Total body fat and visceral fat accounted for most of the attenuation of the association between diabetes and higher inflammation. Adjustment for body fat and visceral fat attenuated these associations so that only IL-6 remained statistically significant. Diabetic participants with poorer glycemic control also showed higher inflammatory levels of CRP with an OR of 1.

Adjustment for body fat and visceral fat attenuated the relationships, but they still remained statistically significant even with further adjustment for comorbidities and potential confounders.

The association between diabetes and a high level of inflammation remained even after adjustments for possible confounders, such as demographics, lifestyle habits, total body fat, visceral fat, and comorbidities.

We also found that the association between diabetes and inflammation was stronger when we used a composite inflammation index of the three inflammatory markers, which is a more specific indicator of systemic inflammation Older diabetic individuals have a 2.

For the association between diabetes and CRP, we observed a sex difference; the association was stronger in women and not statistically significant in men. This sex difference was not found with any of the other inflammatory markers. Our results are consistent with those for other cross-sectional studies in younger populations in which an increase of CRP was found with diabetes 5 , 7 , 8 and increases of CRP, IL-6, and TNF-α were found with IGT 22 , It has also been shown in several longitudinal studies that inflammation is a predictor of development of diabetes 9 , 10 , 12 , Thus, the link between diabetes and inflammation could be due to a reciprocal process, in that inflammation may contribute to diabetes onset and diabetes may then contribute to continued inflammation.

In addition, hyperglycemia is known to mediate formation of advanced glycosylation end products. These advanced glycosylation end products may also contribute to inflammation, producing a chronic stimulation for secretion of cytokines Adipose tissue could be a mediator in the relationship.

Data emerging over the past several years have established the fact that adipocytes express and secrete the cytokine TNF-α and that enlarged adipocytes from obese animals and humans overexpress this factor The findings from the Third National Health and Nutrition Examination Survey showed a higher prevalence of increased levels of CRP in both overweight and obese participants Adiposity, in particular visceral adipose tissue, has been found to be a key promoter of low-grade chronic inflammation 28 , Obesity appears to be a state of chronic inflammation with increased production of cytokines and other acute-phase reactants that play a crucial role in regulation of systemic insulin action; it has been shown that TNF-α—deficient mice show increased insulin action Is the elevation of inflammatory markers the result of vascular and renal disease due to diabetes or a causal pathway?

Numerous studies showed an association between cardiovascular diseases with inflammation, and a higher CRP level is associated with increased risk of development of vascular disease 31 — CRP and IL-6 are also known to increase with declining kidney function, even before end-stage renal disease occurs 35 — Trials to study decreases of inflammation in diabetes or cardiovascular disease events are still lacking.

A better understanding of the actions of cytokines with other factors in the pathogenesis of diabetes may lead to improved understanding of its cause and open new approaches for its prevention. We found an association between poor glycemic control and an increased level of CRP.

Several studies showed that cytokine levels CRP, IL-6, and TNF-α are related to glycemic control 38 — Improvement of glycemic control has an inconsistent beneficial impact on the level of inflammatory markers. No significant effect was found on the levels of IL-6 and TNF-α with sulfonylureas or insulin therapy, but a significant decrease in CRP was observed with insulin Troglitazone with an improvement in glycemic control reduces CRP 42 and decreases plasma levels of TNF-α in obese diabetic patients One weight loss study showed that moderate-intensity regular exercise decreases the TNF-α level A high inflammation level might contribute to the worsening of progression of type 2 diabetes in addition to glycemic control.

Our study has several strengths. First, we have several measures of inflammatory markers and can create an inflammatory index. Second, the study includes a large sample size and a biracial population with a high percentage of blacks. One limitation of our study is that because of the study design cross-sectional study , the direction of these associations cannot be conclusively determined and a causal relationship cannot be inferred.

Additionally, the study population includes well-functioning relatively healthy participants; our findings may not be generalized to a frail older population. Among those with diabetes, poorer glycemic control was associated with higher levels of CRP.

Whether baseline levels of inflammatory markers in those without pre-diabetes or diabetes would be predictors of the onset of pre-diabetes and diabetes should be determined, and we plan to explore this in our longitudinal data.

Plasma levels of inflammatory markers of the diabetic and the hyperglycemic groups compared with the NGT group. For risk of high inflammation level associated with diabetes and hyperglycemic status, model 1 is adjusted on age, sex, race, smoking status, alcohol intake, education, and site.

Model 2 adds total body fat, visceral fat, and height. Model 3 adds cardiovascular diseases, hypertension, peripheral arterial disease, renal insufficiency, arthritis, pulmonary disease, anti-inflammatory, statin, and estrogen use.

For relationship between glycemic control and inflammation in diabetes, models 1 and 2 are the same and model 3 adds diabetes duration. This study was supported by Contracts NAG, NAG, and NAG from the National Institute on Aging. This research was supported in part by the Intramural Research Program of National Institutes of Health, National Institute on Aging.

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Cardiovascular and Metabolic Risk August 01 Diabetes, Hyperglycemia, and Inflammation in Older Individuals : The Health, Aging and Body Composition study Nathalie de Rekeneire, MD, MS ; Nathalie de Rekeneire, MD, MS.

This Site. Google Scholar. Rita Peila, PHD ; Rita Peila, PHD. Jingzhong Ding, PHD ; Jingzhong Ding, PHD. Lisa H. Colbert, PHD ; Lisa H. Colbert, PHD.

Marjolein Visser, PHD ; Marjolein Visser, PHD. Ronald I. Shorr, MD, MS ; Ronald I. Shorr, MD, MS. Stephen B. Kritchevsky, PHD ; Stephen B. Kritchevsky, PHD. Lewis H. Kuller, MD, DRPH ; Lewis H. Kuller, MD, DRPH. Elsa S. Strotmeyer, PHD ; Elsa S. Strotmeyer, PHD. Ann V.

Schwartz, PHD ; Ann V. Schwartz, PHD. Bruno Vellas, MD, PHD ; Bruno Vellas, MD, PHD. Tamara B. Harris, MD, MS Tamara B. Harris, MD, MS. Address correspondence and reprint requests to Nathalie de Rekeneire, MD, Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Gateway Building, Suite 3C, Wisconsin Ave.

E-mail: rekenein nia. Diabetes Care ;29 8 — Article history Received:. Get Permissions. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Table 1— Baseline characteristics by diabetes and hyperglycemic status. Eating too much of any type of sugar can lead to spikes in your blood glucose levels, also called hyperglycemia.

In most healthy people, the body responds to these spikes by releasing insulin, a hormone that works to bring glucose levels back down to normal. This state is known as insulin resistance and it is proinflammatory, potentially causing damage throughout your body.

One target of these harmful effects is your endothelial cells , the cells that line your blood vessels. Repeated levels of high blood sugar can cause your blood vessels to produce damaging reactive molecules called free radicals, via compounds called advanced glycation end products AGEs.

Too much free radical activity generates oxidative stress , damage to endothelial cell function, and inflammation in the blood vessels.

Hyperglycemia can also cause oxidation of free fatty acids stored in your fat cells , which contributes to inflammation. In addition, glucose causes the oxidation of low-density lipoprotein LDL , increasing your risk of plaque build-up in your blood vessels.

Another negative effect is that high blood sugar levels promote blood vessel constriction and platelet clumping , which can promote blood clots. Lastly, we all know that excess sugar leads to weight gain, which in turn increases your risk of other medical problems like obesity, high blood pressure, and many more.

Diabetes, which is fundamentally a disease of glucose dysregulation, is itself a severe proinflammatory state. In light of the detrimental effects that high blood glucose levels can have on the body, it should not come as a surprise that many health problems are related to hyperglycemia and inflammation.

Long-term inflammatory diseases are the most significant cause of death worldwide. While chronic inflammation may be present without symptoms or only mild findings initially, it contributes to many long-term health problems, including :. While it may seem like inflammation is everywhere, there are steps that you can take to limit it.

Changes in your diet are among the easiest ways to decrease inflammation. Avoid refined carbohydrates, sugary beverages, and other foods that cause spikes in your blood glucose levels.

Instead, increase your consumption of fiber, fruits, vegetables, nuts, seeds, and other low-glycemic-index foods , all of which may help lower your risks of cardiovascular disease and diabetes. The plant chemicals called polyphenols in green and black teas have been shown to lower levels of inflammatory markers, like CRP.

Curcumin, present in turmeric , has been shown to help with inflammation in animal studies. You already know that exercise, especially moderate intensity exercise , can help with weight loss—but it may also decrease the levels of proinflammatory chemicals in your body, regardless of how much weight you lose.

Smoking and stress are two other factors that can increase inflammation. However, it can also wreak havoc in your body if left unchecked, especially over the long run. Positive lifestyle choices that limit inflammation can go a long way toward keeping your body healthy.

Why are antioxidants good for you? They reduce oxidative stress, a condition of electron imbalance in your cells that underlies metabolic dysfunction. Emma Betuel.

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Kristen Mascia. Ami Kapadia. Omega-3 fatty acids improve cellular health, help reduce inflammation and promote metabolic health. Here's the science behind them and how you can get more. Kaitlin Sullivan. Rich Joseph, MD. The glycemic index provides insight into how particular foods affect glucose but has limitations.

Stephanie Eckelkamp. The Explainer. Being aware of these causes of inaccurate data can help you identify—and avoid—surprising and misleading feedback. Joy Manning, RD. Inside Levels. Levels Co-Founder's new book—Good Energy: The Surprising Connection Between Metabolism and Limitless Health—releases May 14; available for pre-order today.

The Levels Team. Metabolic flexibility means that your body can switch easily between burning glucose and fat, which means you have better energy and endurance. Jennifer Chesak. Dominic D'Agostino, PhD. Inflammation and glucose levels: How high blood sugar can turn a good system bad.

Written By Esti Schabelman, MD. Article highlights Inflammation is a natural defense system in which your body attacks something it sees as a harm, such as a cut, an infection or even stress.

That response produces symptoms like redness, pain, swelling, warmth, and loss of function.

Nathalie de Rekeneire Hyperglycemia and inflammation, Rita PeilaJingzhong Ding inflammatiom, Lisa H. ColbertMarjolein VisserRonald I. ShorrStephen B. KritchevskyLewis H. KullerElsa S. StrotmeyerAnn V.