Levels of C3 in patients with severe, morbid and extreme obesity: its relationship to insulin resistance and different cardiovascular risk factors

Abstract

Objective: Increased C3 has been related to body mass index (BMI) and insulin resistance, although there are not sufficient studies in subjects with morbid obesity. The purpose of this study was to evaluate the levels of C3 as a function of the BMI in subjects of both sexes, with severe, morbid and extreme obesity, and their possible relationship to insulin resistance or associated diseases such as diabetes, hypertension and dyslipidemia. Subjects: The study included a total of 316 patients (110 men and 206 women) with severe obesity (17.1%), morbid obesity (54.4%) and extreme obesity (28.4%), with an average BMI of 46.7077.37 kg/m 2 . Measurements: The glucose and insulin levels were determined baseline, and 2 h after a 75 g of oral glucose load. The homeostasis model of assessment for insulin resistance (HOMA-IR) was calculated. A lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein AI and apolipoprotein B100) was obtained and C3 levels determined by nephelometry. Results: When distributing the patients by quartiles of BMI, we found a progressive increase in the levels of C3, and no significant differences in the rest of analytical variables studied were found; the mean values of C3 were 127.78729.7 mg/dl. A significant correlation was found between C3 and the BMI (r ¼ 0.263, Po0.001), baseline insulin (r ¼ 0.237, P ¼ 0.001) and HOMA-IR (r ¼ 0.237, P ¼ 0.001). High blood pressure was found in 111 patients, type 2 diabetes in 74 patients and dyslipidemia in 139 cases. When distributing the levels of C3 according to the number of associated risk factors (hypertension, diabetes and dyslipidemia), we found significant differences between these patients and those who presented no associated diseases (Po0.01). Conclusion: A relationship between C3 and the progressive increase of BMI in subjects with severe, morbid or extreme obesity was established. This increase in C3 was closely related to insulin levels and the values for HOMA-IR. Furthermore, we also found an increase in C3 as more diseases related to insulin resistance, such as diabetes, hypertension and dyslipidemia, were associated with the obesity.

Complement Factor 3 Is Associated With Insulin Resistance and With Incident Type 2 Diabetes Over a 7-Year Follow-up Period: The CODAM Study

“…This may to some extent be interpreted as simple confounding since abdominal obesity is a known determinant of both IR and plasma C3 levels (3,(41)(42)(43). However, the relationship of waist circumference with C3 is not straightforward, because abdominal obesity may also be considered an ascending proxy in the causal pathway between C3 and IR (Supplementary Fig.…”

“…Complement factor 3 (C3) is an emerging risk marker for cardiovascular and metabolic diseases (1,2), and systemic C3 concentrations are closely linked to several measures of body fat and components of the metabolic syndrome (3,4). Complement C3 is produced mainly by the liver (5), but other production sites, such as adipose tissue, may also contribute to systemic C3 levels (6).…”

Complement factors C4 and C3 are down regulated in response to short term overfeeding in healthy young men

“…Insulin resistance has consistently been associated with a high serum level of C3 in a potentially causal manner [13][14][15][16] . However, the physiological mechanisms remain unclear.…”

“…We used the gold standard hyperinsulinemic euglycemic clamp technique enabling us to distinguish between hepatic and peripheral insulin resistance. Previous studies have reported associations between high circulating levels of C3 and insulin resistance using the more indirect homeostasis model assessment of insulin resistance (HOMA-IR) [13][14][15][16] . HOMA-IR predominantly reflects hepatic insulin resistance indirectly supporting our results.…”

“…Both C3a and C5a are anaphylatoxins and mediate a variety of biological functions including chemotaxis and inflammatory responses via specific receptors 12 . Several of the complement proteins have been linked to obesity and the metabolic syndrome, and especially a high level of C3 has been shown to associate with insulin resistance, obesity and cardiovascular risk factors [13][14][15][16][17] . Several animal studies suggest that improper complement activation mediates high-fat-diet-induced insulin resistance through the action of the anaphylatoxins [18][19][20] , but still it remains unclear whether there is a causal link between complement activation and insulin resistance in humans.…”