The cross-sectional association between insulin resistance and circulating complement C3 is partly explained by plasma alanine aminotransferase, independent of central obesity and general inflammation (the CODAM study)

Greevenbroek, Marleen M.J. van; Jacobs, Madelon; Kallen, Carla; Vermeulen, Vicky M. M.-J.; Jansen, Eugène; Schalkwijk, Casper G.; Ferreira, Isabel; Feskens, Edith J. M.; Stehouwer, Coen D. A.

doi:10.1111/j.1365-2362.2010.02418.x

Cited by 67 publications

(72 citation statements)

References 41 publications

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“…Additionally, systemic C3 levels have been associated with several diabetes risk factors, including adiposity (waist, BMI), serum triacylglycerol and insulin resistance (as reviewed in [3]). Plasma C3 levels are also higher in non-alcoholic fatty liver disease (NAFLD) [4], a common comorbidity associated with obesity and in type 2 diabetes, and possibly also in type 1 diabetes; in agreement with this observation, alanine aminotransferase—a marker of liver dysfunction—was also associated with plasma levels of C3 [5]. The link between systemic C3 and adiposity is substantiated by the observations that adipose tissue secretes C3, that weight gain is associated with an increase in C3 and that C3 decreases upon weight loss [3].…”

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confidence: 78%

Complement C3: an emerging risk factor in cardiometabolic disease

2012

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C3 is the central component of the complement system and activation of C3 via any of the three major activation pathways—the classical, the lectin and the alternative pathways—results in initiation of the terminal complement pathway and release of the anaphylatoxin C3a. Both terminal pathway activation and signalling of C3a and its inactivation product C3a-desarg via the C3a receptor and C5a-like receptor 2, respectively, can induce inflammatory, immunomodulatory and metabolic responses. C3 has been implicated in metabolic disorders, notably adiposity, dyslipidaemia, insulin resistance, liver dysfunction and diabetes, and C3 is increasingly recognised as a cardiometabolic risk factor. C3 may play a role in the macrovascular, as well as microvascular, complications of diabetes. Moreover, C3 may interact with the coagulation system and as such also contribute to a procoagulant, hypofibrinolytic and, ultimately, prothrombotic state. Recent data suggest a diabetes-dependent incorporation of C3 into fibrin clots, with concomitant effects on clot characteristics. Taken together, epidemiological and experimental evidence concordantly point to a role of complement C3 in metabolic, atherosclerotic/atherothrombotic and microangiopathic processes and further research should be directed towards the elucidation of complement function and activation in cardiometabolic disorders.

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confidence: 78%

Complement C3: an emerging risk factor in cardiometabolic disease

2012

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“…In the present study, we did not observe a relationship of serum ALT activity with VLDL subfraction characteristics. Although hepatic fat accumulation is regarded as driving force for enhanced VLDL secretion [32,35], it remains uncertain whether serum ALT activity, which we used as a surrogate of hepatic fat accumulation [36][37][38], was sensitive enough to discern relationships with VLDL particle characteristics.…”

Section: Model 1 Triglyceridesmentioning

confidence: 99%

Low normal thyroid function as a determinant of increased large very low density lipoprotein particles

Tienhoven-Wind

Dullaart

2015

Clinical Biochemistry

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“…CODAM includes 574 individuals with an elevated risk of type 2 diabetes and cardiovascular disease [8], who were extensively characterised at baseline with regard to their lifestyle and cardiovascular and metabolic profile during two visits to the university's metabolic research unit. After a median follow-up period of 7.0 years (interquartile range [IQR] 6.9-7.1 years), 491 individuals participated in the follow-up measurements (overall attrition rate 14%).…”

Section: Methodsmentioning

confidence: 99%

Discriminatory ability of simple OGTT-based beta cell function indices for prediction of prediabetes and type 2 diabetes: the CODAM study

et al. 2016

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Aims/hypothesis The hyperglycaemic clamp technique and the frequently sampled IVGTT are unsuitable techniques to assess beta cell function (BCF) in large cohorts. Therefore, the aim of this study was to evaluate the discriminatory ability of simple OGTT-based BCF indices for prediction of prediabetes (meaning impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes. Methods Glucose metabolism status was assessed by 2 h 75 g OGTT at baseline (n = 476, mean age 59.2 years, 38.7% women) and after 7 years of follow-up (n = 416) in the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study (1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009). Baseline plasma glucose, insulin and Cpeptide values during OGTTs were used to calculate 21 simple indices of BCF. Disposition indices (BCF index × Matsuda index), to compensate for the prevailing level of insulin resistance, were calculated for the BCF indices with the best discriminatory abilities. The discriminatory ability of the BCF indices was estimated by the area under the receiver operating characteristics curve (ROC AUC) with an outcome of incident prediabetes (n = 73) or type 2 diabetes (n = 60 and n = 18 cases, respectively, in individuals who were nondiabetic or had normal glucose metabolism at baseline). Results For incident prediabetes (n = 73), all ROC AUCs were less than 70%, whereas for incident type 2 diabetes, I 30 /I 0 , CP 30 /CP 0 , ΔI 30 /ΔG 30 , ΔCP 30 /ΔG 30 (where I, CP and G are the plasma concentrations of insulin, C-peptide and glucose, respectively, at the times indicated), and corrected insulin response at 30 min had ROC AUCs over 70%. In at-baseline non-diabetic individuals, disposition indices ΔI 30 /ΔG 30 , ΔCP 30 /ΔG 30 and corrected insulin response at 30 min had ROC AUCs of over 80% for incident type 2 diabetes. Moreover, these BCF disposition indices had significantly better discriminatory abilities for incident type 2 diabetes than the Matsuda index alone. Conclusions/interpretation BCF indices reflecting earlyphase insulin secretion have the best ability to discriminate individuals who will develop prediabetes and type 2 diabetes. Of these, ΔCP 30 /ΔG 30 , often referred to as the Cpeptidogenic index, performed consistently well.

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The cross-sectional association between insulin resistance and circulating complement C3 is partly explained by plasma alanine aminotransferase, independent of central obesity and general inflammation (the CODAM study)

Abstract: Plasma ALT can explain 14·2% of the strong association between insulin resistance and circulating concentrations of complement C3, independent of central obesity and general inflammation.

Cited by 67 publications

References 41 publications

Complement C3: an emerging risk factor in cardiometabolic disease

Complement C3: an emerging risk factor in cardiometabolic disease

Low normal thyroid function as a determinant of increased large very low density lipoprotein particles

Discriminatory ability of simple OGTT-based beta cell function indices for prediction of prediabetes and type 2 diabetes: the CODAM study

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