Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 27  |  Issue : 2  |  Page : 215-225

Study of insulin resistance in patients with systemic lupus erythematosus and rheumatoid arthritis


1 Department of Internal Medicine, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt
2 Department of Internal Medicine, Rheumatology Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt
3 Department of Clinical Pathology, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt

Date of Submission04-Feb-2013
Date of Acceptance09-Apr-2013
Date of Web Publication26-Sep-2014

Correspondence Address:
Khaled El-zorkany
Department of Internal Medicine, Rheumatology Unit, Faculty of Medicine, Menoufiya University, Menoufiya
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.141634

Rights and Permissions
  Abstract 

Objective
The aim of the study was to study insulin resistance (IR) and pancreatic b-cell function in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and their relationship with disease activity.
Background
IR is an important contributor to the increased cardiovascular risk attributed to the metabolic syndrome, a constellation of cardiovascular risk factors that includes central obesity, dyslipidemia, hypertension, and disturbed glucose metabolism, in patients with RA or SLE.
Patients and methods
The study included 35 SLE and 35 RA patients and 20 controls. Disease activity was assessed by Systemic Lupus Activity Measure score and Disease Activity Score-28. BMI, C-reactive protein, erythrocyte sedimentation rate, lipid profile, fasting glucose and insulin, and c-peptide were determined. The homeostasis model of assessment (HOMA) was used to evaluate IR and secretion.
Results
SLE patients had high-grade systemic inflammation, IR, and secretion compared with controls (P < 0.05). RA patients revealed high-grade systemic inflammation, IR, and secretion compared with controls (P < 0.001). Active SLE and RA patients were more insulin resistant than nonactive patients.
Conclusion
The present study demonstrated that both SLE and RA patients had a higher IR and abnormal insulin secretion than age-matched apparently healthy controls. This conclusion was based on the measurement of fasting insulin concentration, HOMA IR, and HOMA b-cells. IR and abnormal insulin secretion were associated with markers for inflammation (erythrocyte sedimentation rate and C-reactive protein) and disease activity indices (Systemic Lupus Activity Measure and Disease Activity Score-28). Higher IR and abnormal insulin secretion were found in RA patients in comparison with SLE patients.


How to cite this article:
Gazareen S, Fayez D, El-Najjar M, Dawood A, Essa E, El-zorkany K. Study of insulin resistance in patients with systemic lupus erythematosus and rheumatoid arthritis. Menoufia Med J 2014;27:215-25

How to cite this URL:
Gazareen S, Fayez D, El-Najjar M, Dawood A, Essa E, El-zorkany K. Study of insulin resistance in patients with systemic lupus erythematosus and rheumatoid arthritis. Menoufia Med J [serial online] 2014 [cited 2024 Mar 28];27:215-25. Available from: http://www.mmj.eg.net/text.asp?2014/27/2/215/141634


  Introduction Top


Systemic lupus erythematosus (SLE) is a chronic, multifaceted inflammatory disease that can attack every organ system of the body. SLE is protean in its manifestations and follows a relapsing and remitting course [1].

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of unknown etiology. The classic feature of this disease is persistent symmetric polyarthritis that usually involves the peripheral joints in a symmetric distribution but can affect any joint lined by a synovial membrane [2].

Insulin resistance (IR), a common metabolic state defined as a suboptimal biological response to given physiological levels of insulin, plays an important role in the pathogenesis of several human metabolic disorders such as obesity and diabetes mellitus [3].

Several factors that are associated with increased cardiovascular risk are more prevalent in SLE and RA than in the general population. These factors include microalbuminuria, hyperhomocysteinemia, proinflammatory lipid profiles including proinflammatory high-density lipoprotein (HDL), and IR [4].

There are several mechanisms that could contribute to altered insulin sensitivity and that may be important in patients with RA or SLE, and they provide insights into the pathogenesis of IR associated with inflammation. These include obesity [5], glucocorticoids, which are commonly used in SLE and RA therapy and are expected to contribute to IR [6], and chronic inflammation, which also appears to predispose to development of both IR and diabetes mellitus [7].

Therefore, the present study was designed to study IR and pancreatic b-cell function in patients with SLE and RA and their relationship with disease activity.


  Patients and methods Top


Patients and controls

Thirty-five SLE patients who fulfilled the 1997 revised American College of Rheumatology criteria of SLE [8] and 35 RA patients who fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA [9] attending the outpatient clinic and inpatient Rheumatology and Internal Medicine Departments in Menoufiya University and Ain Shams University Hospitals, Egypt between June 2010 and June 2012 were included in the study.

Disease activity was assessed by measuring Systemic Lupus Activity Measure (SLAM) and Disease Activity Score-28 (DAS28) for SLE and RA patients, respectively.

Twenty apparently healthy nonsmokers, matched for age and sex with the patient groups were enrolled in the study as controls.

All participants gave written informed consent. The study design was approved by the local ethical committee.

We excluded patients with history of smoking, BMI of at least 30 kg/m 2 , diabetes, hypertension, and concomitant renal, hepatic, cardiac, or endocrine diseases.

Experimental assays

Blood was drawn in the morning after an overnight fast for at least 12 h. Whole blood was used for hematocrit and hemoglobin; EDTA-plasma was used for glucose, insulin, and lipids; and serum was used for other biochemical assays. Glucose was measured by the glucose oxidase method. Total cholesterol and triglycerides (TGs) were measured enzymatically (Beckman TG Reagent). HDL cholesterol was measured after precipitating apolipoprotein B-containing lipoproteins with dextran sulfate and magnesium chloride. Non-HDL cholesterol was calculated by subtracting HDL cholesterol from total cholesterol. Low-density lipoprotein (LDL) cholesterol was calculated according to the Friedewald formula [10]. Other measurements were made by routine methods.

Quantitative measurement of patients' fasting insulin concentrations was conducted using the enzyme-linked immunosorbent assay method. Homeostasis model of assessment (HOMA) IR and HOMA b-cell were calculated according to the formulas in the HOMA model [11].

On the basis of the Study of Inherited Risk of Coronary Atherosclerosis (SIRCA) data, we defined a HOMA index of greater than 2.114 as representing the top quartile of a nondiabetic population [12].

Statistical analysis

Data obtained were tabulated and analyzed by SPSS statistical package version 18 on IBM compatible computer. Quantitative data were expressed as mean and SD (X+SD). Qualitative data were expressed as number and percentage and analyzed by applying the c2 -test. Comparisons between groups were conducted using the unpaired t-test. Pearson's correlation (r) was used to detect association between quantitative variables. P-values of less than 0.05 were considered significant.


  Results Top


Demographic and clinical characteristics of SLE patients and controls

There was no statistically significant difference with respect to age, sex, BMI, fasting blood glucose, and lipid profiles (P > 0.05) between SLE patients and healthy controls. SLE patients had significantly higher fasting insulin, HOMA IR, HOMA b-cell, and c-peptide (P < 0.05) than healthy controls, and they also showed statistically significant higher mean erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) [Table 1].
Table 1: Demographic and laboratorial characteristics of SLE patients and controls

Click here to view


Clinical and laboratory characteristics of SLE patients according to the SLAM scoring

There were significantly higher TGs, ESR, CRP, fasting blood glucose, fasting insulin, HOMA IR, HOMA b-cell, and c-peptide in SLE patients with high SLAM scoring, but there was no statistically significant difference with respect to age, BMI, disease duration, total cholesterol, LDL, and HDL [Table 2].
Table 2: Characteristics of SLE patients according to SLAM scoring

Click here to view


Characteristics of patients with SLE according to IR

SLE patients with IR (HOMA IR > 2.11) had significantly higher TGs, ESR, serum CRP, SLAM score, fasting serum glucose, fasting insulin, HOMA b-cell, and c-peptide (P < 0.05) than SLE patients without IR, but there was no statistically significant difference with respect to age, BMI, disease duration, total cholesterol, and LDL [Table 3].
Table 3: Characteristics of patients with SLE according to IR

Click here to view


Correlations between HOMA IR, SLAM score, and the clinical and laboratorial parameters in SLE patients

Pearson's correlation revealed a statistically significant positive correlation between HOMA IR and fasting serum insulin values, TGs, ESR, serum CRP, SLAM scoring [Figure 1], fasting glucose, HOMA b-cell, and c-peptide in SLE patients [Table 4].
Figure 1:

Click here to view
Table 4: Correlations between HOMA IR, SLAM score, and the clinical and laboratorial parameters in SLE patients

Click here to view


Demographic and clinical characteristics of RA patients and controls

There was no statistically significant difference with respect to age, sex, BMI, total cholesterol, LDL, and HDL (P > 0.05) between RA patients and healthy controls. RA patients had higher TGs, fasting blood glucose (P < 0.05), fasting insulin, HOMA IR, HOMA b-cell, and c-peptide (P < 0.001) than healthy controls, and they also showed statistically significant higher mean ESR and serum CRP (P < 0.001; [Table 5]).
Table 5: Demographic and clinical characteristics of RA patients and controls

Click here to view


Clinical and laboratory characteristics of RA patients according to DAS28 scoring

There was no statistically significant difference with respect to age, BMI, disease duration, LDL, HDL, and fasting blood glucose between active and nonactive RA patients, but there was significantly higher total cholesterol, TGs, fasting insulin, HOMA IR, HOMA b-cell, and c-peptide in active RA patients [Table 6].
Table 6: Clinical and laboratory characteristics of RA patients according to DAS28 scoring

Click here to view


Characteristics of patients with RA according to IR

RA patients with IR (HOMA IR > 2.11) had significantly higher total cholesterol, TGs, ESR, serum CRP, DAS28 score, fasting insulin, HOMA b-cell, and c-peptide (P < 0.001) and significantly lower HDL (P < 0.05) than RA patients without IR, but there was no statistically significant difference with respect to age, BMI, disease duration, LDL, and fasting serum glucose (P > 0.05; [Table 7]).
Table 7: Characteristics of patients with RA according to IR

Click here to view


Correlations between HOMA IR, DAS28 score, and the clinical and laboratorial parameters in RA patients

Pearson's correlation revealed a statistically significant positive correlation between HOMA IR and fasting serum insulin values, total cholesterol, TGs, LDL, ESR, serum CRP, DAS28 score [Figure 2], fasting glucose, HOMA b-cell, and c-peptide in RA patients [Table 8].
Figure 2:

Click here to view
Table 8: Correlations between HOMA IR, DAS28 score, and the clinical and laboratorial parameters in RA patients

Click here to view


Insulin sensitivity profile in SLE and RA patients

RA patients had significantly higher fasting blood glucose, fasting insulin, HOMA IR, HOMA b-cell, and c-peptide (P < 0.05) than SLE patients [Table 9].
Table 9: Insulin sensitivity profile in SLE and RA patients

Click here to view



  Discussion Top


IR represents a major public health problem, as it plays a major role in the pathophysiology of type 2 diabetes mellitus; it is also associated with increased cardiovascular risk and atherogenic dyslipidemia and is a central component of the cluster of metabolic abnormalities that comprise the metabolic syndrome [13].

In the general population, IR may be fundamental to the increased cardiovascular risk attributed to the metabolic syndrome. Individuals in the highest quartile of IR had more than twice the increased risk for incident cardiovascular events compared with those in the lowest quartile. Thus, identification of IR and the mechanisms underlying it are of interest [14].

A bimodal mortality pattern is observed in patients with SLE. Early mortality is more likely to be related to disease itself such as lupus nephritis, whereas late mortality is mainly associated with comorbidities, coronary artery disease being one of the most common causes of morbidity and mortality at this stage of disease [15].

As in the general population, cardiovascular diseases are the leading cause of death in RA patients. Large epidemiological studies in the last several decades confirmed that patients with RA are 30-60% more likely to suffer a cardiovascular event than individuals from the general population [16].

In the present study, there was no statistically significant difference between SLE patients and controls in one hand and between SLE patients with or without IR on other hand with respect to age, sex, and BMI, and this is in agreement with the studies by other investigators [17],[18],[19],[20],[21].

In the current study, there were no statistically significant differences between SLE patients and controls with respect to total cholesterol, TGs, LDL, and HDL, and this is in agreement with the study by Tso and Huang [3] who found similar results in a study conducted on 87 SLE patients and 32 healthy controls, but this did not agree with the studies by Wierzbicki [22] and Formiga et al. [23] who found that lipid and lipoprotein profiles in SLE are often abnormal compared with those of the general population.

Sabio et al. [18] and Chung et al. [19] also found that patients with lupus had significantly lower levels of total and LDL cholesterol and higher TGs than controls, and Lozovoy and colleagues [20] reported that patients with lupus had significantly higher levels of TGs and lower HDL than controls in a study conducted on 58 SLE patients and 105 controls.

In the present study, although the mean levels of lipids and lipoproteins in our patients are within normal range based on the National Cholesterol Education Program (NCEP) criteria, we found that SLE patients with IR had higher TG levels than SLE patients without IR and HOMA IR, and fasting serum insulin positively correlated with TGs in SLE patients. This is in agreement with the study by Chung et al. [24] who found that SLE patients with IR had higher TG levels than SLE patients without IR in a study conducted on 102 SLE patients and 101 controls and also with the study by Lozovoy and colleagues [20].

This is also supported by the study by Tso and Huang [3] who found that SLE patients with hyperinsulinemia had higher plasma TG levels than SLE patients without hyperinsulinemia, and fasting insulin levels positively correlated with TG in patients overall.

There are three sources of higher TG observed in IR individuals. First, lipolysis of TG from the adipose tissue causes elevated serum fatty acid levels, which results in increased fatty acid flux to the liver. Second, because lipoprotein lipase (LPL) levels are decreased, there is an inhibition of lipolysis of chylomicrons and very low-density lipoprotein and TG, which leads to elevations in TG-rich remnants that eventually are delivered to the liver. Third, IR states lead to increased hepatic de-novo TG synthesis [25].

We also found that SLE patients with high SLAM scoring had higher TG levels than SLE patients with low score. The underlying mechanism of this lipid pattern is unclear, but a possible role of tumor necrosis factor-a (TNF-a), by its ability to inhibit LPL, has been suggested by Mikdashi et al. [26]. LPL hydrolyzes circulating TGs, and LPL impairment results in hypertriglyceridemia. In SLE, the binding of auto-Abs to LPL impairs its enzymatic activity, and titers of anti-LPL Ab correlate with TG levels, disease activity, and markers of inflammation [27],[28].

Corticosteroids in SLE patients can also promote an increase in triacylglycerol levels, which seems mediated by increased plasma insulin levels and lipid production by the liver and also by impaired lipid catabolism [29].

In the present study, with respect to acute-phase reactants (ESR and CRP), there was statistically significant higher ESR and CRP in SLE patients than in controls; there was statistically significant higher ESR and CRP in SLE patients with IR and high SLAM scoring; and there was positive correlation between IR and ESR and serum CRP. This is in agreement with the studies by Chung et al. [24] and Lozovoy et al. [20] who showed that SLE patients with hyperinsulinemia had significantly higher ESR and CRP. This was supported by the study by Hotamisligil [30] who concluded that systemic chronic inflammation has been proposed to have a prominent role in the pathogenesis of IR and metabolic syndrome.

The association between inflammation and IR is also supported by Lakka et al. [31] and Reilly et al. [12], and this is considered to be fundamental to the increased cardiovascular risk.

In the general population, CRP is also associated with the presence of metabolic syndrome, especially in women [32].

In current study, there was significantly higher SLAM score in SLE patients with IR than in SLE patients without IR, and there was positive correlation between IR and SLAM scoring. This is in agreement with the studies by Sabio et al. [18] and Negrón and colleagues [15] who concluded that there was an association of metabolic syndrome with higher disease activity but did not agree with the study by Tso and Huang [3] who reported that SLEDAI as an activity index was not significantly different among SLE patients with or without hyperinsulinemia.

El Magadmi et al. [17] and Chung et al. [24] revealed that they did not find any association of metabolic syndrome with lupus disease activity.

IR is associated with a state of chronic low-grade inflammation, and several mediators released from various cell types, including immune cells and adipocytes, have been identified as being involved in the development of IR. Among those are several proinflammatory cytokines such as TNF-a, interleukin (IL)-1, IL-6, and various adipocytokines [33].

Inflammation and IR are closely linked and inflammatory cytokines such as TNF, IL-6, IL-1, and IL-8 may inhibit insulin signaling by multiple mechanisms [34]. TNF induces phosphorylation of IRS-1 at serine instead of tyrosine residues and promotes IR. Both IL-6 and TNF may inhibit the transcription of IRS-1 and glucose transporter (GLUT)-4 genes, thus reducing glucose transport and enhancing IR in obese patients [35].

Inflammation in SLE leads to tissue injury, and thus increases reactive oxygen species and reactive nitrogen species and subsequent oxidative stress. Oxidants and oxidative stress may contribute to the pathogenesis of IR or vice versa [36].

However, whether lupus activity is a factor in the development of IR or IR is contributing to disease activity is unclear.

In present study with respect to insulin sensitivity profile, SLE patients have significantly higher fasting insulin, HOMA IR, HOMA b-cell, and c-peptide (P < 0.05) than controls, and there is positive correlation between IR and fasting glucose, HOMA b-cell, and c-peptide in SLE patients. This relationship is independent of age, sex, BMI, total cholesterol, LDL, and HDL.

This is similar to what is reported by other investigators such as Gheita et al. [37] who found that SLE patients had high HOMA IR and HOMA b-cell and are associated with increase in disease activity and damage.

These data also are supported by Tso and Huang [3] who found that there was an elevation of fasting insulin levels and IR in SLE patients, and this is associated with cardiovascular disease risk in SLE.

In contrast, Ormseth et al. [21] found no statistically significant difference between SLE patients and controls with respect to HOMA IR.

In the current study, HOMA b-cell was significantly higher in SLE patients than in controls and was positively correlated with HOMA IR and fasting insulin, which suggests that slight adjustments for IR might occur, resulting in abnormal b-cell function and increased insulin secretion in patients with SLE, and this is in agreement with the study by Tso and colleagues [38].

In the present study, in RA patients, there was no statistically significant difference between RA patients and controls with respect to age, sex, and BMI, and this is in agreement with other studies [39],[40],[41],[42],[43].

In the present study, there was no statistically significant difference between RA patients and controls with respect to total cholesterol, LDL, and HDL, but there was significantly higher TGs in RA patients than in healthy controls, and this is in agreement with other studies [41],[44],[45].

In contrast, other investigators [39],[40],[46] found that there were no differences in lipid profiles between patients with RA and controls, and Ormseth et al. [43] found that RA patients had higher LDL cholesterol but not TGs than controls.

In the present study, RA patients with IR have higher total cholesterol and TG levels than RA patients without IR, and HOMA IR and fasting serum insulin positively correlated with total cholesterol, TGs, and LDL in RA patients, and this is in agreement with the studies by other investigators [41],[44],[45] but is not in agreement with the study by Dessein and Joffe [47] who reported no difference in lipid profile between RA patients with and without IR except for lower HDL in RA patients with IR.

In the current study, RA patients with high DAS28 scoring have higher TG and total cholesterol levels than RA patients with low score. This is in agreement with the findings of other investigators [40],[41],[44],[45],[48].

Systemic inflammation may contribute to the alteration in lipid profile [49]. This is supported by Feingold et al. [50] who found that increased TNF-a in patients with RA led to increase in hepatic lipogenesis in the form of hypertriglyceridemia, and circulating cholesterol and TG levels are elevated after TNF-a administration; this is also supported by Papa et al. [51] and Steiner and Urowitz [52] who reported improvement in lipid profile following immunointervention.

This does not agree with the study by Dessein and Joffe [47] who reported no difference in lipid profile between RA patients with low-grade and high-grade inflammation except for lower HDL in RA patients with high-grade inflammation.

In the present study with respect to acute-phase reactants (ESR and CRP), there was statistically significant higher ESR and CRP in RA patients than in controls, and this is in agreement with the studies by Shahin et al. [41] and Ormseth et al. [43]; in addition, there was statistically significant higher ESR and CRP in RA patients with IR, and there was positive correlation between IR and fasting insulin, ESR, and serum CRP. This is in agreement with the findings of other investigators [40],[41],[44],[46],[47],[53] and also in agreement with the study by Seriolo et al. [54] who found that IR correlates with CRP levels and can also be reduced with successful control of RA activity.

This does not agree with the studies by Karimi et al. [45] and Stagakis et al. [48] who found no statistically significant higher ESR and CRP in RA patients with an without IR.

In the current study with respect to insulin sensitivity profile, RA patients had significantly higher fasting insulin, HOMA IR, HOMA b-cell, and c-peptide (P < 0.05) than healthy controls, and this is in agreement with the studies by other investigators [39],[41],[43],[55],[56].

A possible explanation for basal hyperinsulinemia in RA patients is that insulin is not merely metabolic related to glucose metabolism; it has an anti-inflammatory effect. Insulin has shown to suppress several proinflammatory transcription factors and their regulating genes [57]. This was supported by the finding in the present study that basal hyperinsulinemia was correlated to markers of systemic inflammation. This higher HOMA b-cell score indicates the potential to compensate for reduced insulin sensitivity.

The current study showed that more than 54% of the studied RA patients demonstrated IR as assessed by HOMA IR index. This is in agreement with previous reports by Chung et al. [40]; higher figures were reported by La Montagna et al. [39], Shahin et al. [41], and Dessein and Joffe [47], whereas lower figures were estimated by Douglas and coworkers [58]. The contradiction in prevalence of IR in RA patients in different studies is likely to depend on differences in study design, methods used to assess IR, and genetic background.

In the present study, RA patients with IR (HOMA IR > 2.11) have significantly higher total cholesterol and TGs and lower HDL, ESR, serum CRP, DAS28 score, fasting insulin, HOMA b-cell, and c-peptide. This is in agreement with the studies by Chung et al. [40], Dessein and Joffe [47], and Stagakis et al. [48].

To our knowledge, the only study that contradicts the relationship between IR and RA is provided by Garcia Díaz et al. [59] who found no differences in HOMA and QUICKI values between RA patients and controls, and no relationship was found between IR and disease activity and CRP.

In the present study, there were significant correlations of IR with DAS28, a composite disease activity index in RA, ESR, and CRP, which support the role of systemic inflammation in the pathogenesis of IR in RA, confirming previous findings of other investigators [40],[47],[48],[60]. This was also supported by Sattar et al. [49] who reported that RA is a disease characterized by increased level of circulating proinflammatory cytokines that induce IR through direct interfering with insulin signaling and by Escαrcega et al. [57] who found that IR promotes further inflammation by an increase in free fatty acid fluxes and interference with the anti-inflammatory effects of insulin. This does not agree with the study by Karimi et al. [45].

In the present study, RA patients have significantly higher fasting blood glucose, fasting insulin, HOMA IR, HOMA b-cell, and c-peptide (P < 0.05) than SLE patients. This is in agreement with the study by Chung et al. [40]. This can be explained by some factors such as older age in RA patients than SLE and longer duration of disease in RA patients reflecting the burden of such disease.

Some differences are noted between the present study and others examining IR in SLE and IR. These differences could be related to variability in the study sample (e.g. ethnicity), length of disease duration, and methodology to assess clinical and outcome variables.

The present study has some limitations. First, as this is a cross-sectional study, it is possible that some patients had IR before study visit. Second, other factors known to be associated with IR, particularly proinflammatory cytokines or procoagulant factors such as TNF-a, IL-6, fibrinogen, and PAI-1, were not measured [61],[62],[63],[64]. The presence of these factors could have a role in the emergence of IR in SLE and RA patients.


  Conclusion Top


The present study demonstrated that both SLE and RA patients had a higher IR and abnormal insulin secretion than age-matched apparently healthy controls. This conclusion was based on measurement of fasting insulin concentration, HOMA IR, and HOMA b-cells. IR and abnormal insulin secretion were associated with markers for inflammation (ESR and CRP) and disease activity indices (SLAM and DAS28) and also with dyslipidemia and could be risk factor for cardiovascular disease in these patients. Higher IR and abnormal insulin secretion were found in RA patients in comparison with SLE patients. Hence, there is a pressing need for strategies for control of inflammation, dyslipidemia, and evaluation of IR in patients with SLE and RA and for intervention studies for modifying IR in SLE and RA patients and whether drugs that ameliorate IR such as metformin and thiazolidinedione could be part of the treatment and regimen of these patients.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.Bartels MC, Hildebrand J, Muller D. Systemic lupus erythematosus. eMedicine 2012.  Back to cited text no. 1
    
2. Temprano K. Rheumatoid arthritis. eMedicine 2012.  Back to cited text no. 2
    
3. Tso TK, Huang WN. Elevation of fasting insulin and its association with cardiovascular disease risk in women with systemic lupus erythematosus. Rheumatol Int 2009; 29 :735-742.  Back to cited text no. 3
    
4. Kaplan MJ. Premature vascular damage in systemic lupus erythematosus: an imbalance of damage and repair? Transl Res 2009; 154 :61-9.  Back to cited text no. 4
    
5. Carr MC, Brunzell JD. Abdominal obesity and dyslipidemia in the metabolic syndrome: importance of type 2 diabetes and familial combined hyperlipidemia in coronary artery disease risk. J Clin Endocrinol Metab 2004; 89 :2601-2607.  Back to cited text no. 5
    
6. Dessein PH, Joffe BI, Stanwix AE. Inflammation, insulin resistance, and aberrant lipid metabolism as cardiovascular risk factors in rheumatoid arthritis. J Rheumatol 2004; 30 :1403-1405.  Back to cited text no. 6
    
7. Simard JF, Mittleman MA. Prevalent rheumatoid arthritis and diabetes among NHANES III participants aged 60 and older. J Rheumatol 2007; 34 :469-473.  Back to cited text no. 7
    
8. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40 :1725.  Back to cited text no. 8
    
9. Basu N, Watts R, Bajema I, et al. The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis. Ann Rheum Dis 2010; 69:1589-1595   Back to cited text no. 9
    
10.Arthritis Rheum 1988; 31 :315e24.  Back to cited text no. 10
    
11.Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem 1972; 18 :499-502.  Back to cited text no. 11
    
12.Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RL. Homeostasis model assessment: insulin resistance and b-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28 :412-419.  Back to cited text no. 12
    
13.Reilly MP, Wolfe ML, Rhodes T, Girman C, Mehta N, Rader DJ. Measures of insulin resistance add incremental value to the clinical diagnosis of metabolic syndrome in association with coronary atherosclerosis. Circulation 2004; 110 :803-809.  Back to cited text no. 13
    
14.Antuna-Puente B, Disse E, Rabasa-Lhoret R, Laville M, Capeau J, Bastard JP. How can we measure insulin sensitivity/resistance. Diabetes Metab 2011; 37 :179-188.  Back to cited text no. 14
    
15.Chung CP, Oeser A, Solus JF, et al. Inflammation-associated insulin resistance: differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms. Arthritis Rheum 2008; 58:2105-2112.  Back to cited text no. 15
    
16.Negron AM, Molina MJ, Mayor AM, Rodriguez VE, Vila LM. Factors associated with metabolic syndrome in patients with systemic lupus erythematosus from Puerto Rico. Lupus 2008; 17 :348-354.  Back to cited text no. 16
    
17.Gremese E, Ferraccioli G. The metabolic syndrome: the crossroads between rheumatoid arthritis and cardiovascular risk. Autoimmun Rev 2011; 10 :582-589.  Back to cited text no. 17
    
18.El-Magadmi M, Ahmad Y, Turkie W, et al. Hyperinsulinemia, insulin resistance, and circulating oxidized low density lipoprotein in women with systemic lupus erythematosus. J Rheumatol 2006; 33 :50-56.  Back to cited text no. 18
    
19.Sabio JM, Zamora-Pasadas M, Jimenez-Jaimez J, et al. Metabolic syndrome in systemic lupus erythematosus from Southern Spain. Lupus 2008; 17 :849-859.  Back to cited text no. 19
    
20.Chung CP, Long AG, Solus JF, et al. Adipocytokines in systemic lupus erythematosus: relationship to inflammation, insulin resistance and coronary atherosclerosis. Lupus 2009; 18 :799-806.  Back to cited text no. 20
    
21.Lozovoy MAB, Simão ANC, Hohmann MSN, Simão TNC, Barbosa DS, Morimoto HK, et al. Inflammatory biomarkers and oxidative stress measurements in patients with systemic lupus erythematosus with or without metabolic syndrome. Lupus 2011; 1356-1364.  Back to cited text no. 21
    
22.Ormseth MJ, Swift LL, Fazio S, Linton MF, Raggi P, Solus JF, et al. Free fatty acids are associated with metabolic syndrome and insulin resistance, but not inflammation in SLE patients. Lupus 2012; ??:1-8.  Back to cited text no. 22
    
23.Wierzbicki AS. Lipids, cardiovascular disease and atherosclerosis in systemic lupus erythematosus. Lupus 2000; 9 :194-201.  Back to cited text no. 23
    
24.Formiga F, Meco JF, Pinto X, Jacob J, Moga I, Pujol R. Lipid and lipoprotein levels in premenopausal systemic lupus erythematosus patients. Lupus 2001; 10 :359-363.  Back to cited text no. 24
    
25.Chung CP, Avalos I, Oeser A, et al. High frequency of the metabolic syndrome in patients with systemic lupus erythematosus: association with disease characteristics and cardiovascular risk factors. Ann Rheum Dis 2007; 66 :208-214.  Back to cited text no. 25
    
26.Lann D, LeRoith D. Insulin resistance as the underlying cause for the metabolic syndrome. Med Clin North Am 2007; 91 :1063-1077.  Back to cited text no. 26
    
27.Mikdashi J, Handwerger B, Langenberg P, Miller M, Kittner S. Baseline disease activity, hyperlipidemia, and hypertension are predictive factors for ischemic stroke and stroke severity in systemic lupus erythematosus. Stroke 2007; 38 :281-285.  Back to cited text no. 27
    
28.Reichlin M, Fesmire J, Quintero-Del-Rio AI, Wolfson-Reichlin M. Autoantibodies to lipoprotein lipase and dyslipidemia in systemic lupus erythematosus. Arthritis Rheum 2002; 46 :2957-2963.  Back to cited text no. 28
    
29.De Carvalho JF, Borba EF, Viana VS, Bueno C, Leon EP, Bonfa E. Anti-lipoprotein lipase antibodies: a new player in the complex atherosclerotic process in systemic lupus erythematosus? Arthritis Rheum 2004; 50 :3610-3615.  Back to cited text no. 29
    
30.Borba EF, Carvalho JF, Bonfa E. Mechanism of dyslipoproteinemias in systemic lupus erythematosus. Clin Dev Immunol 2006; 13 :203-208.  Back to cited text no. 30
    
31.Hotamisligil GS. Molecular mechanisms of insulin resistance and the role of the adipocyte. Int J Obes Relat Metab Disord 2000; 24 :23-27.  Back to cited text no. 31
    
32.Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002; 288 :2709-2716.  Back to cited text no. 32
    
33.Rutter MK, Meigs JB, Sullivan LM, D′Agostino RB Sr, Wilson PW. C-reactive protein, the metabolic syndrome, and prediction of cardiovascular events in the Framingham Offspring Study. Circulation 2004; 110 :380-385.  Back to cited text no. 33
    
34.Tilg H, Moschen AR. Inflammatory mechanisms in the regulation of insulin resistance. Mol Med 2008; 14 :222-231.  Back to cited text no. 34
    
35.Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest 2005; 115 :1111-1119.  Back to cited text no. 35
    
36.Rotter V, Nagaev I, Smith U. Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem 2003; 278 :45777-45784.  Back to cited text no. 36
    
37.Posadas-Romero C, Torres-Tamayo M, Zamora-Gonzalez J, Aguilar-Herrera BE, Posadas-Sanchez R, Cardoso-Saldana G, et al. High insulin levels and increased low-density lipoprotein oxidizability in pediatric patients with systemic lupus erythematosus. Arthritis Rheum 2004; 50 :160-165.  Back to cited text no. 37
    
38.Koca SS, Karaca I, Yavuzkir MF, Daðli N, Ozgen M, Ustündað B, Iþik A. Insulin resistance is related with oxidative stress in systemic lupus erythematosus - Original Investigation. Anadolu Kardiyol Derg 2009; 9 :23-28.  Back to cited text no. 38
    
39.Gheita TA, Raafat HA, Sayed S, El-Fishawy H, Nasrallah MM, Abdel-Rasheed E. Metabolic syndrome and insulin resistance comorbidity in systemic lupus erythematosus: effect on carotid intima-media thickness. Z Rheumatol 2012.  Back to cited text no. 39
    
40.La Montagna G, Cacciapuoti F, Buono R, Manzella D, Mennillo GA, Arciello A, et al. Insulin resistance is an independent risk factor for atherosclerosis in rheumatoid arthritis. Diab Vasc Dis Res 2007; 4 :130-135.  Back to cited text no. 40
    
41.Chung CP, Oeser A, Solus JF, Avalos I, Gebretsadik T, Shintani A, et al. Prevalence of the metabolic syndrome is increased in rheumatoid arthritis and is associated with coronary atherosclerosis. Atherosclerosis 2008; 196 :756-763.  Back to cited text no. 41
    
42.Shahin D, Eltoraby E, Mesbah A, et al. Insulin resistance in early untreated rheumatoid arthritis patients. Clin Biochem 2010; 43 :661-665.  Back to cited text no. 42
    
43.Dao HH, Do QT, Sakamoto J. Increased frequency of metabolic syndrome among Vietnamese women with early rheumatoid arthritis: a cross-sectional study. Arthritis Res Ther 2010; 12 :R218.  Back to cited text no. 43
    
44.Ormseth MJ, Swift LL, Fazio S, Linton MF, et al. Free fatty acids are associated with insulin resistance but not coronary artery atherosclerosis in rheumatoid arthritis. Atherosclerosis 2011; 219 :869-874.  Back to cited text no. 44
    
45.Dessein PH, Joffe BI, Stanwix A, Botha AS, Moomal Z. The acute phase response does not fully predict the presence of insulin resistance and dyslipidemia in inflammatory arthritis. J Rheumatol 2002; 29 :462-466.  Back to cited text no. 45
    
46.Karimi M, Mazloomzadeh S, Kafan S, Amirmoghadami H. The frequency of metabolic syndrome in women with rheumatoid arthritis and in controls. Int J Rheum Dis 2011; 14 :248-254.  Back to cited text no. 46
    
47.Pamuk ON, Unlu E, Cakir N. Role of insulin resistance in increased frequency of atherosclerosis detected by carotid ultrasonography in rheumatoid arthritis. J Rheumatol 2006; 33 :2447-2452.  Back to cited text no. 47
    
48.Dessein PH, Joffe BI. Insulin resistance and impaired beta cell function in rheumatoid arthritis. Arthritis Rheum 2006; 54 :2765-2775.  Back to cited text no. 48
    
49.Stagakis I, Bertsias G, Karvounaris S, Kavousanaki M, et al. Anti-tumor necrosis factor therapy improves insulin resistance, beta cell function and insulin signaling in active rheumatoid arthritis patients with high insulin resistance. Arthritis Res Ther 2012; 14 :R141.  Back to cited text no. 49
    
50.Sattar N, McCarey DW, Capell H, McInnes IB. Explaining how ′high grade′ systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation 2003; 108 :2957-2963.  Back to cited text no. 50
    
51.Feingold KR, Soued M, Staprans I, Gavin LA, Donahue ME, Huang B, et al. Effect of tumor necrosis factor (TNF) on lipid metabolism in the diabetic rat: evidence that inhibition of adipose tissue lipoprotein lipase activity is not required for TNF-induced hyperlipidemia. J Clin Invest 1989; 83 :1116-1121.  Back to cited text no. 51
    
52.Papa C, Netea MG, Radstake T, Van derMeer JWM, Stalenhoef AFH, van Riel PLC, et al. Influence of anti-tumour necrosis factor therapy on cardiovascular risk factors in patients with active rheumatoid arthritis. Ann Rheum Dis 2005; 64 :303-305.  Back to cited text no. 52
    
53.Steiner G, Urowitz MB. Lipid profiles in patients with rheumatoid arthritis: mechanisms and the impact of treatment. Semin Arthritis Rheum 2009; 38 :372-381.  Back to cited text no. 53
    
54.Dessein PH, Norton GR, Woodiwiss AJ, Joffe BI, Solomon A. Independent role of conventional cardiovascular risk factors as predictors of C-reactive protein concentrations in rheumatoid arthritis. J Rheumatol 2007; 34 :681-688.  Back to cited text no. 54
    
55.Seriolo B, Ferrone C, Cutolo M. Long term anti-tumor necrosis factor-alpha treatment in patients with refractory rheumatoid arthritis: relationship between insulin resistance and disease activity. J Rheumatol 2008; 35 :355-357.  Back to cited text no. 55
    
56.Önde ME, Top C, Öncül O. The correlation of insulin resistance with serum tumor necrosis factor-alpha levels in patients with rheumatoid arthritis. Endocrinologist 2008; 18 :178-181.  Back to cited text no. 56
    
57.Hoes JN, van der Goes MC, van Raalte DH, van der NJ, et al. Glucose tolerance, insulin sensitivity and b-cell function in patients with rheumatoid arthritis treated with or without low-to-medium dose glucocorticoids. Ann Rheum Dis 2011; 70 :1887-1894.  Back to cited text no. 57
    
58.Escárcega RO, García-Carrasco M, Fuentes-Alexandro S, Jara LJ, Rojas-Rodriguez J, Escobar-Linares LE, et al. Insulin resistance, chronic inflammatory state and the link with systemic lupus erythematosus-related coronary disease. Autoimmun Rev 2006; 6 :48-53.  Back to cited text no. 58
    
59.Douglas KMJ, Smith J, Stavropoulos-Kalinoglou A, Metsios G, Antonopoulos Y, Koutedakis Y, et al. Prevalence and associations of insulin resistance in rheumatoid arthritis. Ann Rheum Dis 2006; 65:166 Poster presentations (THU0168) session: rheumatic arthritis - other clinical aspects and comorbidity.  Back to cited text no. 59
    
60.Garcia Diaz Jde D, Lopez de Guzman A, Sivera Monzo L, Cuende Quintana E. Significado de la resistencia a la insulina en la enfermedad vascular asociada a la artritis reumatoide. Med Clin (Barc) 2008; 130 :197-198.  Back to cited text no. 60
    
61.Georgiadis AN, Voulgari PV, Argyropoulou MI, Alamanos Y, Elisaf M, Tselepis AD, et al. Early treatment reduces the cardiovascular risk factors in newly diagnosed rheumatoid arthritis patients. Semin Arthritis Rheum 2008; 38 :13-19.  Back to cited text no. 61
    
62.Miranda PJ, DeFronzo RA, Califf RM, Guyton JR. Metabolic syndrome: definition, pathophysiology, and mechanisms. Am Heart J 2005; 149 :33-45.  Back to cited text no. 62
    
63.Tso TK, Huang HY, Chang CK, Liao YJ, Huang WN. Clinical evaluation of insulin resistance and b-cell function by the homeostasis model assessment in patients with systemic lupus erythematosus. Clin Rheumatol 2004; 23 :416-420.  Back to cited text no. 63
    
64.Grundy SM. Metabolic syndrome: connecting and reconciling cardiovascular and diabetes worlds. J Am Coll Cardiol 2006; 47 :1093-1100.  Back to cited text no. 64
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]


This article has been cited by
1 Anti-Carbamylated Protein Antibodies, Tumour Necrosis Factor Alpha and Insulin Resistance in Egyptian Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus
Mohamed Sherif El Hawary, Sarah A. Hassan, Sahar Abd ELatty, Noha M. Khalil
Reumatología Clínica (English Edition). 2022; 18(8): 469
[Pubmed] | [DOI]
2 A STUDY OF INSULIN RESISTANCE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Sreemanta Madhab Baruah, John Kumar Das, Imdadul Hossain, Sanjeeb kakati
INTERNATIONAL JOURNAL OF SCIENTIFIC RESEARCH. 2022; : 57
[Pubmed] | [DOI]
3 Anti-Carbamylated Protein Antibodies, Tumour Necrosis Factor Alpha and Insulin Resistance in Egyptian Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus
Mohamed Sherif El Hawary,Sarah A. Hassan,Sahar Abd ELatty,Noha M. Khalil
Reumatología Clínica. 2021;
[Pubmed] | [DOI]
4 Serum and expression profiles of glucose-dependent insulinotropic polypeptide in correlation with cardiometabolic risk factors among patients with systemic lupus erythematosus
Nearmeen M. Rashad, Reem M. Allam, Amany M. Ebaid, Mohammed S. Yousef, Maha A. Fathy
The Egyptian Journal of Internal Medicine. 2019; 31(4): 754
[Pubmed] | [DOI]
5 Fasting triglycerides and glucose index: a useful screening test for assessing insulin resistance in patients diagnosed with rheumatoid arthritis and systemic lupus erythematosus
Betsabe Contreras-Haro,Sandra Ofelia Hernandez-Gonzalez,Laura Gonzalez-Lopez,Maria Claudia Espinel-Bermudez,Leonel Garcia-Benavides,Edsaul Perez-Guerrero,Maria Luisa Vazquez-Villegas,Jose Antonio Robles-Cervantes,Mario Salazar-Paramo,Diana Mercedes Hernandez-Corona,Arnulfo Hernan Nava-Zavala,Jorge I. Gamez-Nava
Diabetology & Metabolic Syndrome. 2019; 11(1)
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and methods
Results
Discussion
Conclusion
Acknowledgements
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed5233    
    Printed91    
    Emailed0    
    PDF Downloaded350    
    Comments [Add]    
    Cited by others 5    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]