Anti-inflammatory agents in the treatment of diabetes and its vascular complications

Diabetes Care

Volumn 39, Issue , 2016, Pages S244-S252

  Pollack, Rena M ^a   Donath, Marc Y ^b   LeRoith, Derek ^c   Leibowitz, Gil ^a  

^a HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^b UNIVERSITY HOSPITAL BASEL   (Switzerland)

^c Laboratory of Oral Biology   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

ADENYLATE KINASE; ALOGLIPTIN; ANTIDIABETIC AGENT; ANTIINFLAMMATORY AGENT; C REACTIVE PROTEIN; CHLOROQUINE; CRYOPYRIN; DIACEREIN; EMPAGLIFLOZIN; EXENDIN 4; GLIBENCLAMIDE; GLICLAZIDE; GLUCOSE; INSULIN; INSULIN DERIVATIVE; IPRAGLIFLOZIN; LINAGLIPTIN; METFORMIN; PHLORIZIN; PIOGLITAZONE; PLACEBO; REACTIVE OXYGEN METABOLITE; RECOMBINANT INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); SALSALATE; SAXAGLIPTIN; THIOREDOXIN INTERACTING PROTEIN; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG; VILDAGLIPTIN; GLUCOSE BLOOD LEVEL;

ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ARTICLE; CELL FUNCTION; CHOLESTEROL BLOOD LEVEL; CYTOKINE PRODUCTION; DIABETIC ANGIOPATHY; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG SAFETY; GLUCONEOGENESIS; GLYCEMIC CONTROL; HUMAN; HYPERGLYCEMIA; HYPOGLYCEMIA; IMMUNOMODULATION; INFLAMMATION; INJECTION SITE REACTION; INSULIN RESISTANCE; INSULIN SENSITIVITY; MULTICENTER STUDY (TOPIC); NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SIDE EFFECT; CARDIOVASCULAR DISEASES; COMPLICATION; DIABETES MELLITUS, TYPE 2; DIABETIC ANGIOPATHIES; DRUG EFFECTS; GLUCOSE BLOOD LEVEL; METABOLISM;

ANTI-INFLAMMATORY AGENTS; BLOOD GLUCOSE; CARDIOVASCULAR DISEASES; DIABETES MELLITUS, TYPE 2; DIABETIC ANGIOPATHIES; HUMANS; HYPERGLYCEMIA; INFLAMMATION; INSULIN RESISTANCE;

EID: 84979517869     PISSN: 01495992     EISSN: 19355548     Source Type: Journal    
DOI: 10.2337/dcS15-3015     Document Type: Article

References (111)

1. International Diabetes Federation. IDF Diabetes Atlas, 7 ed. Brussels, Belgium, International Diabetes Federation, 2015
2. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factoralpha: direct role in obesity-linked insulin resistance. Science 1993;259:87-91
3. Maedler K, Sergeev P, Ris F, et al. Glucoseinduced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest 2002;110:851-860
4. Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol 2010;11:136-140
5. Isoda K, Young JL, Zirlik A, et al. Metformin inhibits proinflammatory responses and nuclear factor-kappaB in human vascular wall cells. Arterioscler Thromb Vasc Biol 2006;26: 611-617
6. Lee HM, KimJJ, KimHJ, ShongM, Ku BJ, Jo EK. Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes. Diabetes 2013; 62:194-204
7. Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 1998;391:79-82
8. Jiang C, Ting AT, Seed B. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 1998;391:82-86
9. Omar BA, Vikman J, Winzell MS, et al. Enhanced beta cell function and anti-inflammatory effect after chronic treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin in an advancedaged diet-induced obesity mousemodel. Diabetologia 2013;56:1752-1760
10. Makdissi A, Ghanim H, Vora M, et al. Sitagliptin exerts an antinflammatory action. J Clin Endocrinol Metab 2012;97:3333-3341
11. Chaudhuri A, Ghanim H, Vora M, et al. Exenatide exerts a potent antiinflammatory effect. J Clin Endocrinol Metab 2012;97:198-207
12. FerdaoussiM,Abdelli S, Yang JY, et al. Exendin-4 protects beta-cells from interleukin-1 betainduced apoptosis by interfering with the c-Jun NH2-terminal kinase pathway. Diabetes 2008;57: 1205-1215
13. Donath MY, Dalmaś E, Sauter NS, Böni-Schnetzler M. Inflammation in obesity and diabetes: islet dysfunction and therapeutic opportunity. Cell Metab 2013;17:860-872
14. Böni-Schnetzler M, Boller S, Debray S, et al. Free fatty acids induce a proinflammatory response in islets via the abundantly expressed interleukin-1 receptor I. Endocrinology 2009; 150:5218-5229
15. Ehses JA, Perren A, Eppler E, et al. Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 2007;56: 2356-2370
16. Richardson SJ, Willcox A, Bone AJ, Foulis AK,Morgan NG. Islet-associated macrophages in type 2 diabetes. Diabetologia 2009;52: 1686-1688
17. Nguyen MT, Favelyukis S, Nguyen AK, et al. A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. J Biol Chem 2007;282:35279-35292
18. Vandanmagsar B, YoumYH, Ravussin A, et al. The NLRP3 inflammasome instigates obesityinduced inflammation and insulin resistance. Nat Med 2011;17:179-188
19. Cai D, Yuan M, Frantz DF, et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med 2005;11:183-190
20. Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 2009;27:519-550
21. Böni-Schnetzler M, Thorne J, Parnaud G, et al. Increased interleukin (IL)-1beta messenger ribonucleic acid expression in beta-cells of individuals with type 2 diabetes and regulation of IL-1beta in human islets by glucose and autostimulation. J Clin Endocrinol Metab 2008;93: 4065-4074
22. Williams MD, Nadler JL. Inflammatory mechanisms of diabetic complications. Curr Diab Rep 2007;7:242-248
23. Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation 2006;113:1888-1904
24. Masters SL, Dunne A, Subramanian SL, et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1b in type 2 diabetes. Nat Immunol 2010;11:897-904
25. Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic endotoxemiainduced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008;57: 1470-1481
26. Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A 2005; 102:11070-11075
27. Sell H, Habich C, Eckel J. Adaptive immunity in obesity and insulin resistance. Nat Rev Endocrinol 2012;8:709-716
28. Ye J. Emerging role of adipose tissue hypoxia in obesity and insulin resistance. Int J Obes 2009;33:54-66
29. van der Zijl NJ, Moors CC, Goossens GH, Blaak EE, Diamant M. Does interference with the renin-angiotensin system protect against diabetes? Evidence and mechanisms. Diabetes Obes Metab 2012;14:586-595
30. Jandeleit-Dahm KA, Tikellis C, Reid CM, Johnston CI, Cooper ME. Why blockade of the renin-angiotensin system reduces the incidence of new-onset diabetes. J Hypertens 2005;23: 463-473
31. Fliser D, Buchholz K, Haller H; EUropean Trial on Olmesartan and Pravastatin in Inflammation and Atherosclerosis (EUTOPIA) Investigators. Antiinflammatory effects of angiotensin II subtype 1 receptor blockade in hypertensive patients with microinflammation. Circulation 2004;110:1103-1107
32. Manabe S, Okura T, Watanabe S, Fukuoka T, Higaki J. Effects of angiotensin II receptor blockade with valsartan on pro-inflammatory cytokines in patients with essential hypertension. J Cardiovasc Pharmacol 2005;46:735-739
33. Sauter NS, Thienel C, Plutino Y, et al. Angiotensin II induces interleukin-1b-mediated islet inflammation and b-cell dysfunction independently of vasoconstrictive effects. Diabetes 2015;64:1273-1283
34. Foretz M, Guigas B, Bertrand L, Pollak M, Viollet B. Metformin: from mechanisms of action to therapies. Cell Metab 2014;20:953-966
35. Kelly B, Tannahill GM, Murphy MP, O'Neill LA. Metformin inhibits the production of reactive oxygen species from NADH:ubiquinone oxidoreductase to limit induction of interleukin-1b (IL-1b) and boosts interleukin-10 (IL-10) in lipopolysaccharide (LPS)-activated macrophages. J Biol Chem 2015;290:20348-20359
36. KimSA, Choi HC.Metformin inhibits inflammatory response via AMPK-PTEN pathway in vascular smooth muscle cells. Biochem Biophys Res Commun 2012;425:866-872
37. Vasamsetti SB, Karnewar S, Kanugula AK, Thatipalli AR, Kumar JM, Kotamraju S. Metformin inhibits monocyte-to-macrophage differentiation via AMPK-mediated inhibition of STAT3 activation: potential role in atherosclerosis. Diabetes 2015;64:2028-2041
38. ShakedM, Ketzinel-GiladM, Cerasi E, KaiserN, Leibowitz G. AMP-activated protein kinase (AMPK) mediates nutrient regulation of thioredoxininteracting protein (TXNIP) in pancreatic beta-cells. PLoS One 2011;6:e28804
39. Haffner S, Temprosa M, Crandall J, et al.; Diabetes Prevention Program Research Group. Intensive lifestyle intervention or metformin on inflammation and coagulation in participants with impaired glucose tolerance. Diabetes 2005;54:1566-1572
40. Caballero AE, Delgado A, Aguilar-Salinas CA, et al. The differential effects of metformin on markers of endothelial activation and inflammation in subjects with impaired glucose tolerance: a placebo-controlled, randomized clinical trial. J Clin Endocrinol Metab 2004;89: 3943-3948
41. Pradhan AD, Everett BM, Cook NR, Rifai N, Ridker PM. Effects of initiating insulin and metformin on glycemic control and inflammatory biomarkers among patients with type 2 diabetes: the LANCET randomized trial. JAMA 2009; 302:1186-1194
42. Gallagher EJ, LeRoith D. Diabetes, cancer, and metformin: connections of metabolism and cell proliferation. Ann N Y Acad Sci 2011; 1243:54-68
43. Koh SJ, Kim JM, Kim IK, Ko SH, Kim JS. Antiinflammatory mechanism of metformin and its effects in intestinal inflammation and colitisassociated colon cancer. J Gastroenterol Hepatol 2014;29:502-510
44. Lamkanfi M, Mueller JL, Vitari AC, et al. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J Cell Biol 2009;187:61-70
45. Räkel A, Renier G, Roussin A, Buithieu J, Mamputu JC, Serri O. Beneficial effects of gliclazide modified release compared with glibenclamide on endothelial activation and low-grade inflammation in patients with type 2 diabetes. Diabetes Obes Metab 2007; 9:127-129
46. Derosa G, Cicero AF, Fogari E, D'Angelo A, Bianchi L,Maffioli P: Pioglitazone compared to glibenclamide on lipid profile and inflammation markers in type 2 diabetic patients during an oral fat load. Horm Metab Res 2011;43: 505-512
47. Derosa G, Maffioli P, Salvadeo SA, et al. Exenatide versus glibenclamide in patients with diabetes. Diabetes Technol Ther 2010; 12:233-240
48. Schöndorf T, Musholt PB, Hohberg C, et al. The fixed combination of pioglitazone and metformin improves biomarkers of platelet function and chronic inflammation in type 2 diabetes patients: results from the PIOfix study. J Diabetes Sci Technol 2011;5:426-432
49. Erem C, Ozbas HM, Nuhoglu I, Deger O, Civan N, Ersoz HO. Comparison of effects of gliclazide, metformin and pioglitazone monotherapies on glycemic control and cardiovascular risk factors in patients with newly diagnosed uncontrolled type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 2014;122:295-302
50. Wajchenberg BL. beta-Cell failure in diabetes and preservation by clinical treatment. Endocr Rev 2007;28:187-218
51. LeBrasseur NK, Kelly M, Tsao TS, et al. Thiazolidinediones can rapidly activate AMPactivated protein kinase in mammalian tissues. Am J Physiol Endocrinol Metab 2006;291: E175-E181
52. Ceriello A. Thiazolidinediones as antiinflammatory and anti-atherogenic agents. Diabetes Metab Res Rev 2008;24:14-26
53. Esterson YB, Zhang K, Koppaka S, et al. Insulin sensitizing and anti-inflammatory effects of thiazolidinediones are heightened in obese patients. J Investig Med 2013;61:1152-1160
54. Boettcher E, Csako G, Pucino F, Wesley R, Loomba R. Meta-analysis: pioglitazone improves liver histology and fibrosis in patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2012;35:66-75
55. Reiss AB, Vagell ME. PPARgamma activity in the vessel wall: anti-atherogenic properties. Curr Med Chem 2006;13:3227-3238
56. Zhao Y, He X, Huang C, et al. The impacts of thiazolidinediones on circulating C-reactive protein levels in different diseases: a meta-analysis. Diabetes Res Clin Pract 2010;90:279-287
57. Esposito K, Ciotola M, Carleo D, et al. Effect of rosiglitazone on endothelial function and inflammatory markers in patients with the metabolic syndrome. Diabetes Care 2006; 29:1071-1076
58. Stocker DJ, Taylor AJ, Langley RW, Jezior MR, Vigersky RA. A randomized trial of the effects of rosiglitazone and metformin on inflammation and subclinical atherosclerosis in patients with type 2 diabetes. Am Heart J 2007; 153:445.e1-6
59. Hanefeld M, Pfützner A, Forst T, Kleine I, Fuchs W. Double-blind, randomized, multicentre, and active comparator controlled investigation of the effect of pioglitazone, metformin, and the combination of both on cardiovascular risk in patients with type 2 diabetes receiving stable basal insulin therapy: the PIOCOMB study. Cardiovasc Diabetol 2011;10:65
60. Nitta Y, Tahara N, Tahara A, et al. Pioglitazone decreases coronary artery inflammation in impaired glucose tolerance and diabetes mellitus: evaluation by FDG-PET/CT imaging. JACC Cardiovasc Imaging 2013;6:1172-1182
61. Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a metaanalysis of randomized trials. JAMA 2007;298: 1180-1188
62. Scheen AJ. Cardiovascular effects of gliptins. Nat Rev Cardiol 2013;10:73-84
63. Ussher JR, Drucker DJ. Cardiovascular biology of the incretin system. Endocr Rev 2012;33: 187-215
64. Zhao Y, Yang L, Zhou Z. Dipeptidyl peptidase-4 inhibitors: multitarget drugs, not only antidiabetes drugs. J Diabetes 2014;6:21-29
65. Dai Y, Wang X, Ding Z, Dai D, Mehta JL. DPP-4 inhibitors repress foam cell formation by inhibiting scavenger receptors through protein kinase C pathway. Acta Diabetol 2014;51: 471-478
66. Matsubara J, Sugiyama S, Akiyama E, et al. Dipeptidyl peptidase-4 inhibitor, sitagliptin, improves endothelial dysfunction in association with its anti-inflammatory effects in patients with coronary artery disease and uncontrolled diabetes. Circ J 2013;77:1337-1344
67. Derosa G, Maffioli P, Salvadeo SA, et al. Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients. Metabolism 2010;59:887-895
68. Derosa G, Carbone A, D'Angelo A, et al. Variations in inflammatory biomarkers following the addition of sitagliptin in patients with type 2 diabetes not controlled with metformin. Intern Med 2013;52:2179-2187
69. Khan S, Khan S, ImranM, Pillai KK, AkhtarM, Najmi AK. Effects of pioglitazone and vildagliptin on coagulation cascade in diabetes mellitus-targeting thrombogenesis. Expert Opin Ther Targets 2013;17:627-639
70. Yamagishi S, Ishibashi Y, Ojima A, Sugiura T, Matsui T. Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor, decreases serum uric acid levels in type 2 diabetic patients partly by suppressing xanthine oxidase activity. Int J Cardiol 2014;176:550-552
71. Scirica BM, Bhatt DL, Braunwald E, et al.; SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013;369:1317-1326
72. White WB, Bakris GL, Bergenstal RM, et al. EXamination of cArdiovascular outcoMes with alogliptIN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE): a cardiovascular safety study of the dipeptidyl peptidase 4 inhibitor alogliptin in patients with type 2 diabetes with acute coronary syndrome. Am Heart J 2011;162:620-626.e1
73. Green JB, Bethel MA, Armstrong PW, et al.; TECOS Study Group. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015;373:232-242
74. Hogan AE, Gaoatswe G, Lynch L, et al. Glucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus. Diabetologia 2014;57:781-784
75. Wu JD, Xu XH, Zhu J, et al. Effect of exenatide on inflammatory and oxidative stress markers in patients with type 2 diabetes mellitus. Diabetes Technol Ther 2011;13:143-148
76. Sun Q, Li J, Gao F. New insights into insulin: the anti-inflammatory effect and its clinical relevance. World J Diabetes 2014;5:89-96
77. Dandona P, Aljada A, Mohanty P. The antiinflammatory and potential anti-atherogenic effect of insulin: a new paradigm. Diabetologia 2002;45:924-930
78. Mao XM, Liu H, Tao XJ, Yin GP, Li Q, Wang SK. Independent anti-inflammatory effect of insulin in newly diagnosed type 2 diabetes. Diabetes Metab Res Rev 2009;25:435-441
79. Gerstein HC, Bosch J, Dagenais GR, et al.; ORIGIN Trial Investigators. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012;367:319-328
80. Tahara A, Kurosaki E, Yokono M, et al. Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol 2013; 715:246-255
81. Zinman B,Wanner C, Lachin JM, et al.; EMPAREG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-2128
82. Donath MY. Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat Rev Drug Discov 2014;13:465-476
83. Ofei F, Hurel S, Newkirk J, SopwithM, Taylor R. Effects of an engineered human anti-TNFalpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 1996;45:881-885
84. Paquot N, Castillo MJ, Lefèbvre PJ, Scheen AJ. No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients. J Clin Endocrinol Metab 2000;85:1316-1319
85. Stanley TL, Zanni MV, Johnsen S, et al. TNFalpha antagonism with etanercept decreases glucose and increases the proportion of high molecular weight adiponectin in obese subjects with features of the metabolic syndrome. J Clin Endocrinol Metab 2011;96:E146-E150
86. Bernstein LE, Berry J, Kim S, Canavan B, Grinspoon SK. Effects of etanercept in patients with the metabolic syndrome. Arch Intern Med 2006;166:902-908
87. Dominguez H, Storgaard H, Rask-Madsen C, et al. Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes. J Vasc Res 2005;42:517-525
88. van Asseldonk EJ, Stienstra R, Koenen TB, Joosten LA, Netea MG, Tack CJ. Treatment with Anakinra improves disposition index but not insulin sensitivity in nondiabetic subjects with the metabolic syndrome: a randomized, doubleblind, placebo-controlled study. J Clin Endocrinol Metab 2011;96:2119-2126
89. Cavelti-Weder C, Babians-Brunner A, Keller C, et al. Effects of gevokizumab on glycemia and inflammatory markers in type 2 diabetes. Diabetes Care 2012;35:1654-1662
90. Sloan-Lancaster J, Abu-Raddad E, Polzer J, et al. Double-blind, randomized study evaluating the glycemic and anti-inflammatory effects of subcutaneous LY2189102, a neutralizing IL-1b antibody, in patients with type 2 diabetes. Diabetes Care 2013;36:2239-2246
91. Hensen J, Howard CP, Walter V, Thuren T. Impact of interleukin-1b antibody (canakinumab) on glycaemic indicators in patients with type 2 diabetes mellitus: results of secondary endpoints from a randomized, placebo-controlled trial. Diabetes Metab 2013;39:524-531
92. Larsen CM, FaulenbachM, Vaag A, Ehses JA, Donath MY, Mandrup-Poulsen T. Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes. Diabetes Care 2009;32: 1663-1668
93. Yuan M, Konstantopoulos N, Lee J, et al. Reversal of obesity-and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 2001;293:1673-1677
94. Fleischman A, Shoelson SE, Bernier R, Goldfine AB. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care 2008;31:289-294
95. Goldfine AB, Conlin PR, Halperin F, et al. A randomised trial of salsalate for insulin resistance and cardiovascular risk factors in persons with abnormal glucose tolerance. Diabetologia 2013;56:714-723
96. Goldfine AB, Fonseca V, Jablonski KA, et al.; Targeting Inflammation Using Salsalate in Type 2 Diabetes Study Team. Salicylate (salsalate) in patients with type 2 diabetes: a randomized trial. Ann Intern Med 2013;159:1-12
97. Goldfine AB, Fonseca V, Jablonski KA, Pyle L, Staten MA, Shoelson SE; TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) Study Team. The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann InternMed 2010;152:346-357
98. Goldfine AB, Silver R, Aldhahi W, et al. Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes. Clin Transl Sci 2008;1:36-43
99. Koska J, Ortega E, Bunt JC, et al. The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study. Diabetologia 2009;52:385-393
100. Faghihimani E, Aminorroaya A, Rezvanian H, Adibi P, Ismail-Beigi F, Amini M. Salsalate improves glycemic control in patients with newly diagnosed type 2 diabetes. Acta Diabetol 2013;50:537-543
101. Ramos-Zavala MG, Gonźalez-Ortiz M, Martnez-Abundis E, Robles-Cervantes JA, Gonźalez-Ĺopez R, Santiago-Herńandez NJ. Effect of diacerein on insulin secretion and metabolic control in drug-naive patients with type 2 diabetes: a randomized clinical trial. Diabetes Care 2011;34:1591-1594
102. Wasko MC, Hubert HB, Lingala VB, et al. Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis. JAMA 2007; 298:187-193
103. Chen YM, Lin CH, Lan TH, et al. Hydroxychloroquine reduces risk of incident diabetes mellitus in lupus patients in a dose-dependent manner: a population-based cohort study. Rheumatology (Oxford) 2015;54:1244-1249
104. Emami J, Gerstein HC, Pasutto FM, Jamali F. Insulin-sparing effect of hydroxychloroquine in diabetic rats is concentration dependent. Can J Physiol Pharmacol 1999;77: 118-123
105. Emami J, Pasutto FM, Mercer JR, Jamali F. Inhibition of insulin metabolism by hydroxychloroquine and its enantiomers in cytosolic fraction of liver homogenates from healthy and diabetic rats. Life Sci 1999;64:325-335
106. Gerstein HC, Thorpe KE, Taylor DW, Haynes RB. The effectiveness of hydroxychloroquine in patients with type 2 diabetes mellitus who are refractory to sulfonylureas-a randomized trial. Diabetes Res Clin Pract 2002;55:209-219
107. Rekedal LR, Massarotti E, Garg R, et al. Changes in glycosylated hemoglobin after initiation of hydroxychloroquine or methotrexate treatment in diabetes patients with rheumatic diseases. Arthritis Rheum 2010;62:3569-3573
108. Quatraro A, Consoli G, Magno M, et al. Hydroxychloroquine in decompensated, treatmentrefractory noninsulin-dependent diabetes mellitus. A new job for an old drug? Ann Intern Med 1990; 112:678-681
109. Kang L, Mikuls TR, O'Dell JR. Hydroxychloroquine: a diabetic drug in disguise? BMJ Case Rep 2009;pii: bcr08.2008.0654. DOI: 10.1136/bcr.08.2008.0654
110. Shojania K, Koehler BE, Elliott T. Hypoglycemia induced by hydroxychloroquine in a type II diabetic treated for polyarthritis. J Rheumatol 1999;26:195-196
111. Powrie JK, Smith GD, Shojaee-Moradie F, Sönksen PH, Jones RH. Mode of action of chloroquine in patients with non-insulin-dependent diabetes mellitus. Am J Physiol 1991;260: E897-E904