Table 2 Clinical evidence of anti-inflammatory adipokines in insulin resistance and atherogenic dyslipidemia

Adiponectin

Standard laboratory assessment of adiponectin, ESAM, ICAM1, and VEGF

Adiponectin serve as markers of endothelial dysfunction and neo angiogenesis

[140]

Fasting total and HMW adiponectin were measured in 86 subjects from the Coronary Artery Calcification in T1D (CACTI) cohort

Adiponectin levels are positively correlated with insulin sensitivity in T1D patients

Insulin sensitivity is lower for patients with T1D

[141]

Plasma levels of adiponectin, the metabolic syndrome and the occurrence of small dense LDL particles

Decreased adiponectin levels is associated with increased small LDL particles

[142]

25 non-obese individuals with low or normal IRS-1 expression in subcutaneous abdominal fat cells were extensively characterized and the results compared with 71 carefully matched subjects with or without a known genetic predisposition for type 2 diabetes

Subjects with low IRS-1 with insulin resistant shows increased carotid artery bulb intima media thickness vs those with normal IRS-1 protein expression

[143]

Determination and correlate among adiponectin, IR and atherosclerosis in non-diabetic hypertensive patients and healthy volunteers

Low adiponectin levels positively correlate with decreased insulin sensitivity increased pro-inflammatory cytokine production and worsening atherosclerosis in hypertensive patients and healthy adults

[144]

Determination of the correlation between plasma adiponectin concentration with insulin resistance and atherosclerosis

Adiponectin directly or indirectly improves insulin resistance

Significant negative correlations are exist between adiponectin concentration with insulin resistance and atherosclerosis

[145]

Adipocytokines, inflammatory biomarkers, parameters of insulin resistance, and lipid sub fractions determination in the early stages of atherosclerosis in juvenile

Serum adiponectin levels provide the evidence of early atherosclerosis linked to hypoadiponectinemia

Adiponectin plays important role in the development of atherosclerosis

[146]

Determination of circulation adiponectin levels, risk factors for atherosclerosis for the human volunteer with type 2 diabetes

Circulating levels of adiponectin were decreased in non-obese volunteer but with insulin resistance

Hypoadiponectinemia plays an important link between cardiovascular disease and IRS

[147]

48 men (aged 40–60) with angiographically confirmed coronary atherosclerosis and 19 healthy men, matched by age, as a control group were taken as sample

Lower adiponectin level is connected with

resistance syndrome and atherogenic lipid profile

[148]

Plasma adiponectin of diabetic patients and non-diabetic patients were compared

Higher levels of adiponectin are associated with lower cases of diabetic patients compared to diabetic patients

[149]

Omentin-1

Impact of omentin-1 in obesity induced diabetes mellitus

Omentin-1 level is decreased in obesity and diabetic condition

Omentin-1 serve as important markers for the obesity and its associated comorbidities

[150]

Patients with impaired glucose regulation, patients with untreated type 2 diabetes mellitus (T2DM), and subjects with normal glucose tolerance were enrolled in this study

Serum omentin-1 and plasma glucose at fasting and at 2 h after glucose load and fasting serum levels of TNF-a, IL-6, insulin, and HbA1c were measured and compared

Decreased serum omentin-1 levels were observed impaired glucose regulation subjects

Decreased levels of omentin-1 or lack of omentin-1 contributes to the development of insulin resistance and diabetes mellitus

[151]

100 and 55 patients with CAD were divided into two groups: acute coronary syndrome (ACS) and stable angina pectoris (SAP). A total of 52 healthy participants served as controls

The association of omentin-1 with CAD and cardiovascular disease risk factors was evaluated

Serum omentin-1 level is negatively associated with CAD

[152]

The impact of 12 weeks of aerobic (cycle ergometer), resistance, and combined exercises on omentin-1 level, glucose and insulin resistance indices in overweight middle age women with T2DM

12 weeks of aerobic and resistance exercises improve HOMA-IR and increase serum omentin-1 among women with T2DM

[155]

Omentin-1 with carotid intima-media thickness and metabolic markers were studied

Lower levels of Omentin-1 is closely associated with metabolic syndrome and play important role in the development of atherosclerosis in metabolic syndrome patients

[156]

80 newly diagnosed female type 2 diabetic patients and 40 age matched female control subjects and comparison of plasma omentin-1 levels

Omentin-1 levels are low in type 2 diabetics and insulin resistant females

Omentin-1 has very important link with metabolic disturbances such as obesity, insulin resistance and the regulation of omentin-1 in diabetic patients

[157]

60 obese type 2 diabetic females and 30 healthy female subjects formed the control group were enrolled

Fasting (blood glucose, insulin, lipid profile, omentin-1) and HbA1c were measured

Lower omentin-1 level was observed in patients with diabetes mellitus

Serum omentin-1 can be used as a biomarker for obesity related metabolic disorders

[158]

75 patients with 2 diabetes and 15 healthy control subjects were enrolled in this study

Insulin levels, interleukin‐6, omentin‐1 and chemerin were compared

Omentin-1 and chemerin play important role in obesity and its associated disorders such as type 2 diabetes and cardiovascular disease

[159]

Sfrp5

Cross-sectional studies of Chinese population including 194 control participants and 90 metabolic syndrome patients

Sfrp5 is linked to metabolic syndrome

[160]

Serum concentrations of Sfrp5, Wnt5a and adiponectin were measured in 47 individuals who participated in a coffee intervention study

Sfrp5 is directly related to HOMA‐IR and oxidative stress in humans

[161]

185 patients suspecting CAD were included in the study and divided into two groups CAD and non-CAD groups as per their results of coronary angiography

Serum Sfrp5 levels of the subjects were measured by ELISA

The serum sfrp5 levels in CAD were significantly lower than non-CAD patients

The serum level of Sfrp5 was negatively correlated with body mass index, insulin resistance, and the severity of CAD

[162]

104 healthy subjects, 101 with impaired glucose tolerance, and 112 with newly diagnosed type 2 diabetes mellitus and, in a separate study, 30 healthy women and 32 women with polycystic ovarian syndrome (PCOS) were included for the study. Oral glucose tolerance test and euglycemic-hyperinsulinemia clamp were performed to assess glucose tolerance and insulin sensitivity

Circulating Sfrp5 was significantly lower in both impaired glucose intolerance and newly diagnosed type 2 diabetes mellitus than in individuals with normal glucose tolerance

[163]

58 type 2 diabetes patients, 22 latent autoimmune diabetes (LADA) in adults patients and 40 healthy controls were enrolled into this study

ELISA was employed to detect the circulating Sfrp5 level in plasma, and other lab tests such as fasting glucose and creatinine were also examined

Circulating Sfrp5 level was significantly decreased in T2D and LADA patients plasma compared with that in healthy control

Sfrp5 was correlated with homeostasis model assessment of insulin resistance (HOMA-IR), diabetes duration and BMI

Sfrp5 was still negatively correlated with HOMA-IR after being adjusted for disease duration and BMI

[164]

82 patients with T2DM and 42 non-diabetic subjects were enrolled for the study

Plasma Sfrp5 and Wnt5a concentrations were measured through ELISA

Elevated Sfrp5 levels in uncomplicated type 2 diabetic subjects indicate that Sfrp5 may play a role in the pathogenesis of T2DM

[165]

70 drug‐naïve T2D patients, 70 pre-diabetic subjects and 70 controls were enrolled for the study

All subjects body mass index matched to the T2D patients and overweight or obese. Sfrp5, hormones and cytokines levels were measured by ELISA

Serum Sfrp5 levels were elevated in T2D patients as compared with pre-diabetic subjects

No differences were found in serum Sfrp5 levels between pre-diabetic subjects and controls

Circulating Sfrp5 levels were independently associated with T2D as compared with prediabetes and normal glucose tolerance state

[166]

Two hundred eighty four subjects 90 with metabolic syndrome and 194 healthy controls, 153 men and 131 women

Circulating levels of Sfrp5 was significantly lower in newly diagnosed metabolic syndrome patients than in control subjects

Sfrp5 may be an adipokine which is associated with the pathogenesis of metabolic syndrome in humans

[159]

CTRPS (CTRP1, CTRP3, CTRP9, CTRP13, etc.)

Serum CTRP3 levels, anthropometric, inflammatory and metabolic parameters were measured in 180 obesity and essential hypertensive patients and in 66 normal weight, normotensive subjects

The serum CTRP3 levels in the obesity group were lower than those in the normal weight group

These levels were also lower in hypertensive subjects than in normotensive subjects

CTRP3 was an independent factor affecting blood pressure and IR and may play an important role in the pathogenesis of obesity and hypertension

[167]

135 subjects were recruited to this study, including 62 type 2 diabetic patients (DM group) and 73 healthy subjects (control group)

Biochemical parameters, CTRP1, TNF-α and adiponectin were measured using enzyme-linked immunosorbent assay (ELISA)

Plasma CTRP1 levels difference were observed between the DM group and the control group

CTRP1 was strongly positively associated with BMI, glucose levels, HbA1c, HOMA-IR and TNF-α in diabetic patient

CTRP1 share similar actions of adiponectin but exhibit opposite compensatory upregulation in the diabetic state

[168]

Plasma CTRP1 level was investigated in type 2 diabetic subjects (35) and non-diabetic subjects (35)

The relationship between CTRP1 and phosphorylation of multi insulin receptor substrate 1 (IRS-1) serine (Ser) sites was further explored

Plasma CTRP1 was higher and have negative correlation with insulin resistance in diabetic subjects

Glucose utilization test revealed that the glucose utilization rate of mature adipocytes was improved by CTRP1 in the presence of insulin

[169]

CTRP1 serum levels in 539 patients undergoing coronary angiography for the evaluation of established or suspected stable CAD

CTRP1 is associated with obesity-linked disorders

CTRP1 is associated with major adverse cardiovascular events

CTRP1 is associated with cardiovascular risk beyond its association with obesity-linked disorders

[170]

Study participants were divided into two groups according to the results of coronary angiography: a control group (63) and a CAD group (76). The concentrations of serum CTRP1 and inflammatory cytokines were determined by ELISA

Serum levels of CTRP1 were significantly higher in CAD patients than in controls, and CTRP1 levels increased with increasing severity of CAD

CTRP1 levels with the prevalence and severity of CAD, indicating that CTRP1 can be regarded as a novel and valuable biomarker for CAD

[171]

357 consecutive patients who had stable angina and at least one lesion with 100% occlusion between January 2010 and September 2012 were screened

Blood samples were collected on the day of angiography after overnight fasting. Serum levels of CTRP1, CTRP3 and high-sensitivity C-reactive protein (hsCRP) were assayed using ELISA kits

Association between increased serum CTRP1 level and low coronary collateralization in patients with stable angina and chronic total occlusion were observed. CTRP1 inhibits in vitro angiogenesis of endothelial progenitor cells from patients with severe coronary artery disease

[172]

Serum CTRP3 levels, anthropometric, inflammatory and metabolic parameters were measured in 180 obesity and essential hypertensive patients and in 66 normal weight, normotensive subjects

The serum CTRP3 levels in the obesity group were lower than those in the normal weight group; these levels were also lower in hypertensive subjects than in normotensive subjects

CTRP3 was an independent factor affecting blood pressure and IR, and may play an important role in the pathogenesis of obesity and hypertension

[167]

Cross-sectional study performed on 55 controls, 54 patients with T2DM, and 55 patients with T2DM-normal patients. Serum levels of CTRP3, adiponectin, TNF-α, and IL-6 were measured by ELISA technique

Serum levels of CTRP3 were significantly lower in patients with T2DM and T2DM-normal patients

Decreased serum levels of CTRP3 in patients with T2DM and diabetic nephropathy and its association with pathologic mechanisms in these patients suggested a possible role for CTRP3 in pathogenesis of diabetic nephropathy

[173]

Circulating progranulin and CTRP3 concentrations in 127 subjects with (44) or without metabolic syndrome (83)

The relationship of progranulin and CTRP3 levels with inflammatory markers and cardiometabolic risk factors, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), estimated glomerular filtration rate (eGFR), and adiponectin serum concentrations, as well as carotid intima-media thickness, was analyzed

Circulating progranulin levels are significantly related with inflammatory markers, hsCRP, whereas CTRP3 concentrations exhibit a significant association with cardiometabolic risk factors

[174]

Subjects with normal glucose tolerance, impaired glucose tolerance and newly diagnosed type 2 diabetes mellitus were recruited to determining the circulating CTRP9 and adiponectin levels by ELISA

Circulating CTRP9 level was higher in both impaired glucose intolerance and newly diagnosed T2DM than in individuals with normal glucose tolerance. Overweight subjects had higher CTRP9 levels than lean individuals, and in all subjects, females also had higher CTRP9 levels than males. Circulating CTRP9 level was positively correlated with markers of obesity and insulin resistance

[175]

337 subjects who underwent coronary angiography and were categorized into four groups according to the presence of CAD and T2DM (control, CAD, T2DM and CAD + T2DM)

Serum levels of CTRP9, adiponectin, sICAM-1, sVCAM-1, sE-Selectin, IL-6 and TNF-α were measured

The circulating CTRP9 levels were independently associated with increased risk of CAD and T2DM in addition to elevated levels of serum CTRP9 in CAD, T2DM and CAD T2DM groups

Circulating levels of CTRP9 in T2DM and CAD individuals which suggests a compensatory response to insulin resistance, inflammatory milieu and endothelial dysfunction

[176]

Circulating levels of CTRP13 and adiponectin were measured by \ELISA in T2D patients (40) and in an age and gender-matched control group (n = 40)

Circulating levels of CTRP13 and adiponectin were significantly lower in T2D patients in comparison with controls

CTRP13 is a novel adipokine associated with T2D in humans as its serum level was significantly lower in T2D patients and was inversely correlated with insulin resistance

[177]

Plasma levels of CTRP13 in healthy control and patients with NAFLD, T2DM and NAFLD + T2DM, and also correlations between CTRP13 plasma levels and clinical and subclinical features

Circulating CTRP13 was examined in 88 male (20 healthy controls, 22 T2DM patients, 22 NAFLD patients and 22 NAFLD + T2DM patients). CTRP13 and adiponectin plasma levels were measured by ELISA method

CTRP13 serum levels were higher in the control group than the other groups

CTRP13 had significant negative correlation with unfavorable anthropometric and metabolic factors including BMI, visceral fat, Insulin, HOMA-IR, TG, AST, ALT and ɣ-GT and have a positive correlation with plasma concentration of adiponectin

[178]

Serum levels of CTRP3, CTRP13, adiponectin and inflammatory cytokines and their gene expression in peripheral blood mononuclear cells (PBMCs) were determined in 172 subjects categorized as group I (without T2DM and CAD), group II (with CAD but no T2DM), group III (with T2DM but no CAD) and group IV (with T2DM and CAD)

Serum levels and gene expression of CTRP3, CTRP13 and adiponectin in the group I were higher compared to other groups

This suggests emerging role of these adipokines in the pathogenesis of CAD

[179]