Hydroxychloroquine reduces risk of incident diabetes mellitus in lupus patients in a dose-dependent manner: a population-based cohort study

Chen, Yiming; Lin, Ching-Heng; Lan, Tsuo-Hung; Chen, Hsin‐Hua; Chang, Shang‐Tzen; Chen, Yi-Hsing; Wang, Jun‐Sing; Hung, Wei‐Ting; Lan, Joung‐Liang; Chen, Der‐Yuan

doi:10.1093/rheumatology/keu451

Cited by 117 publications

(102 citation statements)

References 20 publications

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“…This suggests that PRED may exacerbate the early insulin response to nutrient load, thus potentially worsening IR and the predisposition to long-term b cell dysfunction. In contrast to PRED, HCQ has been associated with lower levels of fasting glucose and HOMA IR and a reduced risk of type 2 DM in SLE patients (39). We did not observe any association between HCQ use and insulin sensitivity estimates.…”

contrasting

confidence: 79%

Increased Insulin Resistance and Glucagon Levels in Mild/Inactive Systemic Lupus Erythematosus Patients Despite Normal Glucose Tolerance

Miyake

Gualano

Dantas

et al. 2017

Arthritis Care & Research

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Objective. To assess insulin sensitivity in patients with systemic lupus erythematosus (SLE) in response to a meal tolerance test (MTT). Methods. In this cross-sectional study, 33 adult females with mild/inactive SLE (SLE group) and 16 age-and body mass index-matched female healthy controls (CTRL group) underwent an MTT and were assessed for insulin sensitivity and beta cell function. Skeletal muscle protein expressions of total and membrane insulin-dependent glucose transporter 4 (GLUT-4) were also evaluated (SLE group: n = 10, CTRL group: n = 5); muscle biopsies were performed after MTT. Further measurements included inflammatory cytokines, adipocytokines, physical activity level, body composition, and food intake. Results. SLE and CTRL groups showed similar fasting glucose, glucose response, and skeletal muscle GLUT-4 translocation after MTT. However, the SLE group demonstrated higher fasting insulin levels (P = 0.01; effect size [ES] 1.2), homeostatic model assessment insulin resistance (IR) (P = 0.03; ES 1.1), insulin-to-glucose ratio response to MTT (P = 0.02; ES 1.2), fasting glucagon levels (P = 0.002; ES 2.7), glucagon response to MTT (P = 0.0001; ES 2.6), and a tendency toward lower Matsuda index of whole-body insulin sensitivity (P = 0.06; ES À0.5) when compared with the CTRL group. Fasting proinsulin-to-insulin ratio and proinsulin-to-insulin ratio response to MTT were similar between groups (P > 0.05), while the SLE group showed a higher insulinogenic index when compared with the CTRL group (P = 0.02; ES = 0.9). Conclusion. We have identified that SLE patients had a bi-hormone metabolic abnormality characterized by increased IR and hyperglucagonemia despite normal glucose tolerance and preserved beta cell function and skeletal muscle GLUT-4 translocation. Strategies capable of ameliorating insulin sensitivity to reduce the risk of type 2 diabetes mellitus and cardiovascular disease in SLE may require more than targeting IR alone.

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contrasting

confidence: 79%

Increased Insulin Resistance and Glucagon Levels in Mild/Inactive Systemic Lupus Erythematosus Patients Despite Normal Glucose Tolerance

Miyake

Gualano

Dantas

et al. 2017

Arthritis Care & Research

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“…The precise anti-inflammatory mechanism of HCQ is not known and is probably related to alkalinization of endosomal organelles in immune cells. HCQ has been shown to reduce the incidence of diabetes among patients with rheumatoid arthritis and lupus and to improve glycemia in patients with rheumatic disorders and diabetes (102,103). Animal studies have shown that antimalarials improve insulin secretion and peripheral insulin sensitivity in diabetic rats (104).…”

Section: Salsalatementioning

confidence: 99%

Anti-inflammatory Agents in the Treatment of Diabetes and Its Vascular Complications

et al. 2016

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The association between hyperglycemia and inflammation and vascular complications in diabetes is now well established. Antidiabetes drugs may alleviate inflammation by reducing hyperglycemia; however, the anti-inflammatory effects of these medications are inconsistent and it is unknown whether their beneficial metabolic effects are mediated via modulation of chronic inflammation. Recent data suggest that immunomodulatory treatments may have beneficial effects on glycemia, b-cell function, and insulin resistance. However, the mechanisms underlying their beneficial metabolic effects are not always clear, and there are concerns regarding the specificity, safety, and efficacy of immune-based therapies. Herein, we review the anti-inflammatory and metabolic effects of current antidiabetes drugs and of anti-inflammatory therapies that were studied in patients with type 2 diabetes. We discuss the potential benefit of using anti-inflammatory treatments in diabetes and important issues that should be addressed prior to implementation of such therapeutic approaches.The prevalence of diabetes is on the rise, with 415 million people affected worldwide according to recent data from the International Diabetes Federation (1). This number is predicted to increase further, with 642 million people expected to develop diabetes by 2040. While many factors are known to contribute to the development of diabetes and its complications, the involvement of the immune system in the pathogenesis of metabolic diseases has been gaining interest. It has long been appreciated that inflammation is central to the pathology of the pancreatic islet in type 1 diabetes. However, growing evidence suggests that inflammation also plays an important role in the pathogenesis of type 2 diabetes, including obesity-related insulin resistance, impaired insulin secretion, and diabetes-related vascular complications. Pioneering studies suggest that immunomodulatory treatments may improve glycemia, b-cell function, and/or insulin resistance in patients with type 2 diabetes (2,3). These studies constitute a proof of concept that chronic inflammation is implicated in the pathophysiology of type 2 diabetes, and therefore targeting inflammation may ameliorate diabetes, preventing its progression and vascular complications. However, the effects of immunomodulatory treatments are not limited to tissues involved in disease pathophysiology and thus might have unwarranted side effects. Moreover, current antidiabetes drugs may alleviate systemic and tissue-specific inflammation (4-12), and therefore the added value of using specific immunomodulatory treatments needs to be confirmed. Herein, we review the anti-inflammatory and metabolic effects of standard antidiabetes medications and of novel anti-inflammatory treatments. We further discuss issues that should be addressed prior to implementation of immune-based therapy in the treatment of diabetes.

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“…As the reduction in FBG, PPBG were 8%, 6.5 % respectively therefore, this meant a significant difference between the patients before and after using HCQ therapy [29,33]. Plasma levels of fasting insulin, glucose and lipids were measured in a certain number of Finally, like many studies, SLE patients and showed higher plasma levels in insulin, TC, LDL, TG, and lower levels in HDL than control subjects.…”

Section: Discussionmentioning

confidence: 91%

The Effect of Hydroxychloroquine Treatment on Blood Sugar Level, Serum Lipid Profile and the Retina in Systemic Lupus Erythematosus Patients

Sarhan¹,

Shaban²,

Hamid³

et al. 2016

Med-Science

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Hydroxychloroquine reduces risk of incident diabetes mellitus in lupus patients in a dose-dependent manner: a population-based cohort study

Abstract: In SLE patients, the use of HCQ is associated with reduced risk of incident diabetes mellitus in a dose-dependent manner. High-dose glucocorticoids increase the risk of diabetes, which can be decreased by concomitant HCQ use.

Cited by 117 publications

References 20 publications

Increased Insulin Resistance and Glucagon Levels in Mild/Inactive Systemic Lupus Erythematosus Patients Despite Normal Glucose Tolerance

Increased Insulin Resistance and Glucagon Levels in Mild/Inactive Systemic Lupus Erythematosus Patients Despite Normal Glucose Tolerance

Anti-inflammatory Agents in the Treatment of Diabetes and Its Vascular Complications

The Effect of Hydroxychloroquine Treatment on Blood Sugar Level, Serum Lipid Profile and the Retina in Systemic Lupus Erythematosus Patients

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