Serum Soluble CD163 Predicts Risk of Type 2 Diabetes in the General Population

BACKGROUND Activation of adipose tissue macrophages with concomitant low-grade inflammation is believed to play a central role in the development of type 2 diabetes. We tested whether a new macrophage-derived biomarker, soluble CD163 (sCD163), identifies at-risk individuals before overt disease has developed. METHODS A prospective cohort study of 8849 study participants from the general population, the Copenhagen City Heart Study, was followed for 18 years for incidence of type 2 diabetes. Risk of disease was calculated according to age- and sex-adjusted percentile categories of serum sCD163 concentrations: 0%–33%, 34%–66%, 67%–90%, 91%–95%, and 96%–100%. RESULTS A total of 568 participants developed type 2 diabetes. The cumulative incidence increased with increasing baseline sCD163 (trend P < 0.001), and sCD163 was strongly associated with known risk factors such as physical inactivity, body mass index, C-reactive protein, and triglycerides (all P < 0.001). Multifactorially adjusted hazard ratios for type 2 diabetes were 1.4 (95% CI, 1.0–1.9), 2.4 (1.8–3.2), 3.8 (2.6–5.5), and 5.2 (3.6–7.6) for categories 34%–66%, 67%–90%, 91%–95%, and 96%–100%, respectively, vs the 0%–33% category. In overweight men 50–70 and >70 years of age, serum sCD163 concentrations in the top 5% group predicted an absolute 10-year risk of type 2 diabetes of 29% and 36% vs 7% and 8% in the lowest percentile group. Equivalent values in women were 19% and 24% vs 4% and 5%. CONCLUSIONS Increased concentrations of sCD163 predict increased risk of type 2 diabetes in the general population and may be useful for identification of high-risk overweight individuals.

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Low-Grade Inflammation in the Association between Mild-to-Moderate Hypertriglyceridemia and Risk of Acute Pancreatitis: A Study of More Than 115000 Individuals from the General Population

Clinical Chemistry ◽

10.1373/clinchem.2018.294926 ◽

2019 ◽

Vol 65 (2) ◽

pp. 321-332 ◽

Cited By ~ 19

Author(s):

Signe E J Hansen ◽

Christian M Madsen ◽

Anette Varbo ◽

Børge G Nordestgaard

Keyword(s):

Acute Pancreatitis ◽

General Population ◽

Low Grade ◽

General Population Study ◽

Reactive Protein ◽

Hazard Ratios ◽

Heart Study ◽

Blood Leukocyte ◽

Low Grade Inflammation ◽

Multivariable Adjustment

Abstract BACKGROUND How mild-to-moderate hypertriglyceridemia (2–10 mmol/L; 177–886 mg/dL) potentially causes acute pancreatitis is unknown; however, cellular studies indicate that inflammation might be a driver of disease progression. We tested the hypotheses that (a) mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and that (b) the association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis depends on low-grade inflammation. METHODS From the Copenhagen General Population Study and the Copenhagen City Heart Study, 117865 men and women 20–100+ years of age with measurements of nonfasting plasma triglycerides at baseline were followed prospectively for development of acute pancreatitis. RESULTS After multivariable adjustment, a 1 mmol/L (89 mg/dL) higher nonfasting triglyceride concentration was associated with 17% (95% CI, 16%–18%, P = 3 × 10−17) higher plasma C-reactive protein (CRP) and a 4.2% (4.0%–4.4%, P = 6 × 10−17) higher blood leukocyte count. Higher concentrations of nonfasting triglycerides were associated almost linearly with higher risk of acute pancreatitis (P for trend = 5 × 10−6), with hazard ratios of 1.5 (95% CI, 0.9–2.5), 2.0 (95% CI, 1.1–3.6), 2.2 (95% CI, 1.0–4.7), 4.2 (95% CI, 1.6–11.5), and 7.7 (95% CI, 3.0–19.8) in individuals with nonfasting triglycerides of 1.00–1.99 mmol/L (89–176 mg/dL; 46% of the population), 2.00–2.99 mmol/L (177–265 mg/dL; 17%), 3.00–3.99 mmol/L (266–353 mg/dL; 6%), 4.00–4.99 mmol/L (354–442 mg/dL; 2%), and ≥5mmol/L(443 mg/dL; 2%), respectively, vs individuals with <1 mmol/L (89 mg/dL; 27%). The association with risk of acute pancreatitis appeared more pronounced in individuals with CRP of ≥1.39 mg/L (P for trend = 0.001) and leukocytes of ≥7 × 109/L (P = 2 × 10−4) than in those with CRP <1.39 mg/L (P = 0.03) and leukocytes <7 × 109/L (P = 0.04); however, there was no formal evidence of statistical interaction (P = 0.38 for CRP and P = 0.41 for leukocytes). CONCLUSIONS Mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and higher risk of acute pancreatitis. The association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis is possibly partly mediated by low-grade inflammation.

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Association between fasting insulin and C-reactive protein among adults without diabetes using a two-part model: NHANES 2005–2010

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00645-4 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Amanda L. Missel ◽

Laura R. Saslow ◽

Dina H. Griauzde ◽

Donna Marvicsin ◽

Ananda Sen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Waist Circumference ◽

Low Grade ◽

Fasting Insulin ◽

C Reactive Protein ◽

Glucose Levels ◽

Reactive Protein ◽

Part Model

Abstract Introduction Chronic inflammation is associated with the development, progression and long-term complications of type 2 diabetes. Hyperglycemia is associated with chronic low-grade inflammation, and thus has become the focus of many screening and treatment recommendations. We hypothesize that insulin may also be associated with inflammation and may be an additional factor to consider in screening and treatment. Methods This study used National Health and Nutrition Examination Survey data from 2005 to 2010 to analyze the association between fasting insulin and C-reactive protein (CRP). A two-part model was used due to the high number of values reported as 0.1 mg/L. Two models were analyzed, both with and without the addition of waist circumference to other covariates in the model. Results The final sample included 4527 adults with a mean age of 43.31 years. In the first model, higher fasting insulin was associated with increased odds of CRP > 0.1 mg/L (OR = 1.02, p < .001) and with higher CRP (β = 0.03, p < .001). In the adjusted model, including waist circumference as a covariate, higher fasting insulin was not associated with CRP > 0.1 mg/L (OR = 1.00, p = .307) but the association between higher fasting insulin and higher continuous CRP remained significant (β = 0.01, p = .012). Conclusion This study found that higher fasting insulin is associated with higher CRP. These results suggest that treatment approaches that simultaneously decrease insulin levels as well as glucose levels may provide additive anti-inflammatory effects, and therefore may improve long-term outcomes for adults with type 2 diabetes.

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C-reactive protein: a marker or a player?

Clinical Science ◽

10.1042/cs20070121 ◽

2007 ◽

Vol 113 (2) ◽

pp. 79-81 ◽

Cited By ~ 18

Author(s):

Thomas Nyström

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Events ◽

Protein A ◽

Low Grade ◽

Phase Reaction ◽

Clinical Markers ◽

C Reactive Protein ◽

Reactive Protein ◽

Hs Crp

It has been suggested that Type 2 diabetes may, in part, be precipitated or accelerated by an acute-phase reaction as part of the innate immune response, in which large amounts of cytokines are released from adipose tissue, creating a low-grade inflammatory milieu. There is also firm evidence that atherosclerosis is an immune-mediated inflammatory disease. Therefore it is reasonable to imply that low-grade inflammation is an important pathogenetic factor in atherosclerosis and cardiovascular events in patients with Type 2 diabetes. Over the last few years, there have been a lot of promising clinical markers proposed to link inflammation and atherosclerosis. Of these markers, hs-CRP (high-sensitivity C-reactive protein) might be a prognostic marker for further cardiovascular events, although this has been refuted recently. In this issue of Clinical Science, Castoldi and co-workers have demonstrated that, in patients with Type 2 diabetes categorized into low (<1.0 mg/l), medium (1.0–3.0 mg/l) and high (>3.0 mg/l) hs-CRP groups, serum levels of hs-CRP correlated with lipopolysaccharide-stimulated release of interleukin-1β and interleukin-6 in whole blood. This finding may indicate that low-grade inflammatory activity might influence cytokine production in these patients.

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CRP Gene Polymorphism and Their Risk Association With Type 2 Diabetes Mellitus

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.014 ◽

2019 ◽

Vol 7 (1) ◽

pp. 33-37

Author(s):

Hakim Bahlok Jebur ◽

Mirza Masroor ◽

Hafiz Ahmad ◽

Naushad Ahmad Khan ◽

Juheb Akther ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gene Polymorphism ◽

Inflammatory Marker ◽

Genotype Distribution ◽

Reactive Protein ◽

Specific Pcr ◽

Increased Risk ◽

Significant Difference ◽

Allele Specific

BACKGROUND: C-reactive protein (CRP) is an inflammatory marker associated with T2DM, obesity, insulin resistance, and cardiovascular disease. AIM: The present study evaluates the association of CRP +1059 G/C polymorphism of the CRP gene in 100 T2D cases and 100 healthy controls. METHODS: Present study was done by allele specific PCR method to study the CRP gene polymorphism in study subjects. RESULTS: Study found that CRP (+1059 G/C) genotype distribution among case and controls was found to be significant (p=0.001), Higher CRP C allele frequency (0.16) was observed compared to controls (0.04). CRP +1059 GC and CC had 2.72 (1.12-6.61), 20.56 (1.16-362.1) risk for T2D. It has been observed, HTN, Obesity, Smoking and alcoholism was found to be associated with increased risk of T2D, and a significant difference was observed in biochemical parameters. CONCLUSION: Study concluded that CRP gene polymorphism was found to be associated with risk of Type 2 Diabetes and risk was linked with heterozygosity and mutant homozygosity. Hypertension, Obesity, Smoking and alcoholism increases the risk of occurrence of Type 2 Diabetes.

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Role of Circulating Microparticles in Type 2 Diabetes Mellitus: Implications for Pathological Clotting

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0041-1740150 ◽

2021 ◽

Author(s):

Siphosethu Cassandra Maphumulo ◽

Etheresia Pretorius

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Systemic Inflammation ◽

Blood Cells ◽

Low Grade ◽

Chronic Hyperglycemia ◽

Increased Risk

AbstractType 2 diabetes mellitus (T2DM) is a multifactorial chronic metabolic disease characterized by chronic hyperglycemia due to insulin resistance and a deficiency in insulin secretion. The global diabetes pandemic relates primarily to T2DM, which is the most prevalent form of diabetes, accounting for over 90% of all cases. Chronic low-grade inflammation, triggered by numerous risk factors, and the chronic activation of the immune system are prominent features of T2DM. Here we highlight the role of blood cells (platelets, and red and white blood cells) and vascular endothelial cells as drivers of systemic inflammation in T2DM. In addition, we discuss the role of microparticles (MPs) in systemic inflammation and hypercoagulation. Although once seen as inert by-products of cell activation or destruction, MPs are now considered to be a disseminated storage pool of bioactive effectors of thrombosis, inflammation, and vascular function. They have been identified to circulate at elevated levels in the bloodstream of individuals with increased risk of atherothrombosis or cardiovascular disease, two significant hallmark conditions of T2DM. There is also general evidence that MPs activate blood cells, express proinflammatory and coagulant effects, interact directly with cell receptors, and transfer biological material. MPs are considered major players in the pathogenesis of many systemic inflammatory diseases and may be potentially useful biomarkers of disease activity and may not only be of prognostic value but may act as novel therapeutic targets.

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Ethnic differences in participation in diabetes education programmes

European Journal of Public Health ◽

10.1093/eurpub/ckz186.063 ◽

2019 ◽

Vol 29 (Supplement_4) ◽

Author(s):

A Juul ◽

C Glümer ◽

S S Jervelund ◽

N F Hempler

Keyword(s):

Type 2 Diabetes ◽

General Population ◽

Social Relations ◽

Diabetes Education ◽

Household Composition ◽

Participation Rates ◽

Increased Risk ◽

Depth Analysis ◽

Study Population

Abstract Background Immigrants from non-Western countries have a higher prevalence of type 2 diabetes. In addition, immigrants have an increased risk of developing diabetes complications, compared with the general population. Diabetes education programmes facilitate essential knowledge and skills that enable people to manage their condition in daily life. However, fewer immigrants attend and complete diabetes education compared with the general population. The aim of this study is to explore what characterises those who decline and accept participation in diabetes education in relation to ethnicity, household composition and diabetes burden in the family. Methods The study population consisted of adults with type 2 diabetes referred to a municipal diabetes centre (n = 1819). Individual medical record data was linked to national registry data. Descriptive statistics and logistic regression models were applied. Results Preliminary results showed that 23% of individuals from the study population participated in diabetes education. We found no overall differences in participation rates between the general population and non-Western immigrants (24% vs. 18%, P = 0.12). However, when examining the immigrant groups by language (Arabic, Urdu and Turkish), the results indicated a non-significant tendency: Urdu speaking groups’ participation was similar to the general population (24%), whereas Arabic and Turkish speaking groups had lower participation rates (17% and 11%, P = 0.25/0.40). Conclusions The results suggest that there are differences in participation between some immigrant groups and the general population. Increased knowledge about which mechanisms affecting participation in diabetes education programme is required to ensure equal access. Further studies and analyses will explore how immigrants’ social relations enable and/or hamper participation in diabetes education and investigate which factors can be changed to improve participation rates. Key messages There are differences in participation in diabetes education programmes across different ethnic groups, which suggests a need for in-depth analysis into which mechanisms that affect participation. The results will be used to give input for future practices that can increase immigrant’s participation and retention in diabetes education programmes.

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High-Sensitivity C-Reactive Protein Is Associated With Incident Type 2 Diabetes Among African Americans: The Jackson Heart Study

Diabetes Care ◽

10.2337/dc15-0221 ◽

2015 ◽

Vol 38 (9) ◽

pp. 1694-1700 ◽

Cited By ~ 34

Author(s):

Valery S. Effoe ◽

Adolfo Correa ◽

Haiying Chen ◽

Mary E. Lacy ◽

Alain G. Bertoni

Keyword(s):

Type 2 Diabetes ◽

African Americans ◽

High Sensitivity ◽

Jackson Heart Study ◽

C Reactive Protein ◽

Incident Type ◽

Reactive Protein ◽

Heart Study ◽

Incident Type 2 Diabetes

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Correction to: Soluble CD163, adiponectin, C-reactive protein and progression of dysglycaemia in individuals at high risk of type 2 diabetes mellitus: the ADDITION-PRO cohort

Diabetologia ◽

10.1007/s00125-017-4498-6 ◽

2017 ◽

Vol 61 (2) ◽

pp. 498-503

Author(s):

Pia Deichgræber ◽

Daniel R. Witte ◽

Holger J. Møller ◽

Mette V. Skriver ◽

Bjørn Richelsen ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

High Risk ◽

C Reactive Protein ◽

Reactive Protein ◽

Soluble Cd163

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Diabetes increases the risk of breast cancer: a meta-analysis

Endocrine Related Cancer ◽

10.1530/erc-12-0242 ◽

2012 ◽

Vol 19 (6) ◽

pp. 793-803 ◽

Cited By ~ 58

Author(s):

Prue J Hardefeldt ◽

Senarath Edirimanne ◽

Guy D Eslick

Keyword(s):

Breast Cancer ◽

Type 2 Diabetes ◽

Reference Lists ◽

Meta Analysis ◽

Statistical Significance ◽

Increased Risk ◽

And Gender ◽

Study Participants

The aim of this meta-analysis was to collate and analyse all primary observational studies investigating the risk of breast cancer (BC) associated with diabetes. In addition, we aimed to complete subgroup analyses by both type of diabetes and gender of study participants to further clarify the origin of any such association between the two. Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar with additional cross-checking of reference lists. Collated data were assessed for heterogeneity and a pooled odds ratio (OR) calculated. Forty-three studies were included in the meta-analysis with 40 studies investigating BC in women and six studies investigating BC in men. Overall, we found a significantly increased risk of BC associated with diabetes in women (OR 1.20, 95% confidence interval (CI) 1.13–1.29). After subgroup analysis by type of diabetes, the association was unchanged with type 2 diabetes (OR 1.22, 95% CI 1.07–1.40) and nullified with gestational diabetes (OR 1.06, 95% CI 0.79–1.40). There were insufficient studies to calculate a pooled OR of the risk of BC associated with type 1 diabetes. There was an increased risk of BC in males with diabetes mellitus; however, the results did not reach statistical significance (OR 1.29, 95% CI 0.99–1.67). In conclusion, diabetes increases the risk of BC in women. This association is confirmed in women with type 2 diabetes and supports the hypothesis that diabetes is an independent risk factor for BC.

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Kringle IV Type 2, Not Low Lipoprotein(a), as a Cause of Diabetes: A Novel Genetic Approach Using SNPs Associated Selectively with Lipoprotein(a) Concentrations or with Kringle IV Type 2 Repeats

Clinical Chemistry ◽

10.1373/clinchem.2017.277103 ◽

2017 ◽

Vol 63 (12) ◽

pp. 1866-1876 ◽

Cited By ~ 14

Author(s):

Andra Tolbus ◽

Martin B Mortensen ◽

Sune F Nielsen ◽

Pia R Kamstrup ◽

Stig E Bojesen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Odds Ratio ◽

Plasma Concentrations ◽

Nucleotide Polymorphisms ◽

Genetic Approach ◽

Lipoprotein A ◽

Heart Study ◽

Increased Risk ◽

Per Se

Abstract BACKGROUND Low plasma lipoprotein(a) concentrations are associated with type 2 diabetes. Whether this is due to low lipoprotein(a) concentrations per se or to a large number of kringle IV type 2 (KIV-2) repeats remains unclear. We therefore aimed to identify genetic variants associated selectively with lipoprotein(a) concentrations or with the number of KIV-2 repeats, to investigate which of these traits confer risk of diabetes. METHODS We genotyped 8411 individuals from the Copenhagen City Heart Study for 778 single-nucleotide polymorphisms (SNPs) in the proximity of the LPA gene, and examined the association of these SNPs with plasma concentrations of lipoprotein(a) and with KIV-2 number of repeats. SNPs that were selectively associated with lipoprotein(a) concentrations but not with KIV-2 number of repeats, or vice versa, were included in a Mendelian randomization study. RESULTS We identified 3 SNPs (rs12209517, rs12194138, and rs641990) that were associated selectively with lipoprotein(a) concentrations and 3 SNPs (rs1084651, rs9458009, and rs9365166) that were associated selectively with KIV-2 number of repeats. For SNPs selectively associated with lipoprotein(a) concentrations, an allele score of 4–6 vs 0–2 had an odds ratio for type 2 diabetes of 1.03 (95% CI, 0.86–1.23). In contrast, for SNPs selectively associated with KIV-2 number of repeats, an allele score of 4–6 vs 0–2 had an odds ratio for type 2 diabetes of 1.42 (95% CI, 1.17–1.69). CONCLUSIONS Using a novel genetic approach, our results indicate that it is a high number of KIV-2 repeats that are associated causally with increased risk of type 2 diabetes, and not low lipoprotein(a) concentrations per se. This is a reassuring finding for lipoprotein(a)-lowering therapies that do not increase the KIV-2 number of repeats.

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