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10-31-2018 | Complications | Review | Article

Update on Therapeutic Options in Lipodystrophy

Journal: Current Diabetes Reports

Authors: Baris Akinci, Rasimcan Meral, Elif Arioglu Oral

Publisher: Springer US

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Abstract

Purpose of Review

The purpose of this review is to summarize the therapeutic approach for lipodystrophy syndromes with conventional treatment options and metreleptin therapy in detail and to point out the current investigational treatments in development.

Recent Findings

The observation of leptin deficiency in patients with lipodystrophy and the potential of leptin replacement to rescue metabolic abnormalities in animal models of lipodystrophy were followed by the first clinical study of leptin therapy in patients with severe lipodystrophy. This and several other long-term studies demonstrated important benefits of recombinant human leptin (metreleptin) to treat metabolic abnormalities of lipodystrophy. These studies ultimately led to the recent FDA approval of metreleptin for the treatment of generalized lipodystrophy and EMA approval for both generalized and partial lipodystrophy. Additional research efforts in progress focus on novel treatment options, predominantly for patients with partial lipodystrophy.

Summary

Current treatment of generalized lipodystrophy includes metreleptin replacement as an adjunct to diet and standard treatment approach for metabolic consequences of lipodystrophy. Beyond metreleptin, a number of different compounds and treatment modalities are being studied for the treatment of partial lipodystrophy.
Literature
1.
Chan JL, Oral EA. Clinical classification and treatment of congenital and acquired lipodystrophy. Endocr Pract. 2010;16(2):310–23. https://​doi.​org/​10.​4158/​EP09154.​RA. CrossRefPubMed
2.
Garg A. Acquired and inherited lipodystrophies. N Engl J Med. 2004;350(12):1220–34. https://​doi.​org/​10.​1056/​NEJMra025261. CrossRefPubMed
3.
Garg A, Misra A. Lipodystrophies: rare disorders causing metabolic syndrome. Endocrinol Metab Clin N Am. 2004;33(2):305–31. https://​doi.​org/​10.​1016/​j.​ecl.​2004.​03.​003. CrossRef
4.
Garg A. Clinical review#: Lipodystrophies: genetic and acquired body fat disorders. J Clin Endocrinol Metab. 2011;96(11):3313–25. https://​doi.​org/​10.​1210/​jc.​2011-1159. CrossRefPubMedPubMedCentral
5.
• Brown RJ, Araujo-Vilar D, Cheung PT, Dunger D, Garg A, Jack M, et al. The diagnosis and management of lipodystrophy syndromes: a multi-society practice guideline. J Clin Endocrinol Metab. 2016;101(12):4500–11. https://​doi.​org/​10.​1210/​jc.​2016-2466. A multisociety practice guideline summarizing the diagnosis and management of lipodystrophy syndromes. CrossRefPubMedPubMedCentral
6.
Akinci B, Sahinoz M, Oral E. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, et al., editors. Lipodystrophy syndromes: presentation and Treatment. South Dartmouth: Endotext; 2000.
7.
Papendieck L, Araujo MB. Clinical outcome in a series of pediatric patients with congenital generalized lipodystrophies treated with dietary therapy. J Pediatr Endocrinol Metab. 2018;31(1):77–83. https://​doi.​org/​10.​1515/​jpem-2017-0355. CrossRefPubMed
8.
Handelsman Y, Oral EA, Bloomgarden ZT, Brown RJ, Chan JL, Einhorn D, et al. The clinical approach to the detection of lipodystrophy - an AACE consensus statement. Endocr Pract. 2013;19(1):107–16. CrossRefPubMedPubMedCentral
9.
Akinci G, Topaloglu H, Akinci B, Onay H, Karadeniz C, Ergul Y, et al. Spectrum of clinical manifestations in two young Turkish patients with congenital generalized lipodystrophy type 4. Eur J Med Genet. 2016;59(6–7):320–4. https://​doi.​org/​10.​1016/​j.​ejmg.​2016.​05.​001. CrossRefPubMedPubMedCentral
10.
Hayashi YK, Matsuda C, Ogawa M, Goto K, Tominaga K, Mitsuhashi S, et al. Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy. J Clin Invest. 2009;119(9):2623–33. https://​doi.​org/​10.​1172/​JCI38660. CrossRefPubMedPubMedCentral
11.
Cummings DE, Overduin J, Foster-Schubert KE. Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. J Clin Endocrinol Metab. 2004;89(6):2608–15. https://​doi.​org/​10.​1210/​jc.​2004-0433. CrossRefPubMed
12.
Lager CJ, Esfandiari NH, Subauste AR, Kraftson AT, Brown MB, Cassidy RB, et al. Roux-en-Y gastric bypass Vs. sleeve gastrectomy: balancing the risks of surgery with the benefits of weight loss. Obes Surg. 2017;27(1):154–61. https://​doi.​org/​10.​1007/​s11695-016-2265-2. CrossRefPubMed
13.
Melvin A, Adams C, Flanagan C, Gaff L, Gratton B, Gribble F, et al. Roux-en-Y gastric bypass surgery in the management of familial partial lipodystrophy type 1. J Clin Endocrinol Metab. 2017;102(10):3616–20. https://​doi.​org/​10.​1210/​jc.​2017-01235. CrossRefPubMedPubMedCentral
14.
Utzschneider KM, Trence DL. Effectiveness of gastric bypass surgery in a patient with familial partial lipodystrophy. Diabetes Care. 2006;29(6):1380–2. https://​doi.​org/​10.​2337/​dc06-0130. CrossRefPubMed
15.
Ciudin A, Baena-Fustegueras JA, Fort JM, Encabo G, Mesa J, Lecube A. Successful treatment for the Dunnigan-type familial partial lipodystrophy with Roux-en-Y gastric bypass. Clin Endocrinol. 2011;75(3):403–4. https://​doi.​org/​10.​1111/​j.​1365-2265.​2011.​04057.​x. CrossRef
16.
Grundfest-Broniatowski S, Yan J, Kroh M, Kilim H, Stephenson A. Successful treatment of an unusual case of FPLD2: the role of Roux-en-Y gastric bypass-case report and literature review. J Gastrointest Surg. 2017;21(4):739–43. https://​doi.​org/​10.​1007/​s11605-016-3300-2. CrossRefPubMed
17.
Vantyghem MC, Vigouroux C, Magre J, Desbois-Mouthon C, Pattou F, Fontaine P, et al. Late-onset lipoatrophic diabetes. Phenotypic and genotypic familial studies and effect of treatment with metformin and lispro insulin analog. Diabetes Care. 1999;22(8):1374–6. CrossRefPubMed
18.
Luedtke A, Boschmann M, Colpe C, Engeli S, Adams F, Birkenfeld AL, et al. Thiazolidinedione response in familial lipodystrophy patients with LMNA mutations: a case series. Horm Metab Res. 2012;44(4):306–11. https://​doi.​org/​10.​1055/​s-0031-1301284. CrossRefPubMed
19.
Moreau F, Boullu-Sanchis S, Vigouroux C, Lucescu C, Lascols O, Sapin R, et al. Efficacy of pioglitazone in familial partial lipodystrophy of the Dunnigan type: a case report. Diabetes Metab. 2007;33(5):385–9. https://​doi.​org/​10.​1016/​j.​diabet.​2007.​04.​005. CrossRefPubMed
20.
McLaughlin PD, Ryan J, Hodnett PA, O'Halloran D, Maher MM. Quantitative whole-body MRI in familial partial lipodystrophy type 2: changes in adipose tissue distribution coincide with biochemical improvement. AJR Am J Roentgenol. 2012;199(5):W602–6. https://​doi.​org/​10.​2214/​AJR.​11.​8110. CrossRefPubMed
21.
•• Arioglu E, Duncan-Morin J, Sebring N, Rother KI, Gottlieb N, Lieberman J, et al. Efficacy and safety of troglitazone in the treatment of lipodystrophy syndromes. Ann Intern Med. 2000;133(4):263–74. This is an open-label prospective study showing the benefits of TZDs in patients with partial lipodystrophy.
22.
Agostini M, Schoenmakers E, Beig J, Fairall L, Szatmari I, Rajanayagam O, et al. A pharmacogenetic approach to the treatment of patients with PPARG mutations. Diabetes. 2018;67(6):1086–92. https://​doi.​org/​10.​2337/​db17-1236. CrossRefPubMed
23.
Sleilati GG, Leff T, Bonnett JW, Hegele RA. Efficacy and safety of pioglitazone in treatment of a patient with an atypical partial lipodystrophy syndrome. Endocr Pract. 2007;13(6):656–61. https://​doi.​org/​10.​4158/​EP.​13.​6.​656. CrossRefPubMed
24.
Iwanishi M, Ebihara K, Kusakabe T, Chen W, Ito J, Masuzaki H, et al. Clinical characteristics and efficacy of pioglitazone in a Japanese diabetic patient with an unusual type of familial partial lipodystrophy. Metabolism. 2009;58(12):1681–7. https://​doi.​org/​10.​1016/​j.​metabol.​2009.​04.​043. CrossRefPubMed
25.
Cochran E, Musso C, Gorden P. The use of U-500 in patients with extreme insulin resistance. Diabetes Care. 2005;28(5):1240–4. CrossRefPubMed
26.
Banning F, Rottenkolber M, Freibothe I, Seissler J, Lechner A. Insulin secretory defect in familial partial lipodystrophy Type 2 and successful long-term treatment with a glucagon-like peptide 1 receptor agonist. Diabet Med. 2017;34(12):1792–4. https://​doi.​org/​10.​1111/​dme.​13527. CrossRefPubMed
27.
Oliveira J, Lau E, Carvalho D, Freitas P. Glucagon-like peptide-1 analogues - an efficient therapeutic option for the severe insulin resistance of lipodystrophic syndromes: two case reports. J Med Case Rep. 2017;11(1):12. https://​doi.​org/​10.​1186/​s13256-016-1175-1. CrossRefPubMedPubMedCentral
28.
Joubert M, Jagu B, Montaigne D, Marechal X, Tesse A, Ayer A, et al. The sodium-glucose cotransporter 2 inhibitor dapagliflozin prevents cardiomyopathy in a diabetic lipodystrophic mouse model. Diabetes. 2017;66(4):1030–40. https://​doi.​org/​10.​2337/​db16-0733. CrossRefPubMed
29.
Johns KW, Bennett MT, Bondy GP. Are HIV positive patients resistant to statin therapy? Lipids Health Dis. 2007;6:27. https://​doi.​org/​10.​1186/​1476-511X-6-27. CrossRefPubMedPubMedCentral
30.
Macallan DC, Baldwin C, Mandalia S, Pandol-Kaljevic V, Higgins N, Grundy A, et al. Treatment of altered body composition in HIV-associated lipodystrophy: comparison of rosiglitazone, pravastatin, and recombinant human growth hormone. HIV Clin Trials. 2008;9(4):254–68. https://​doi.​org/​10.​1310/​hct0904-254. CrossRefPubMed
31.
•• Oral EA, Simha V, Ruiz E, Andewelt A, Premkumar A, Snell P, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med. 2002;346(8):570–8. https://​doi.​org/​10.​1056/​NEJMoa012437. This is the first clinical study showing dramatic benefits of leptin therapy in patients with lipodystrophy.
32.
Ahmad Z, Subramanyam L, Szczepaniak L, Simha V, Adams-Huet B, Garg A. Cholic acid for hepatic steatosis in patients with lipodystrophy: a randomized, controlled trial. Eur J Endocrinol. 2013;168(5):771–8. https://​doi.​org/​10.​1530/​EJE-12-0969. CrossRefPubMedPubMedCentral
33.
Shimomura I, Hammer RE, Ikemoto S, Brown MS, Goldstein JL. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature. 1999;401(6748):73–6. https://​doi.​org/​10.​1038/​43448. CrossRefPubMed
34.
Brown RJ, Oral EA, Cochran E, Araújo-Vilar D, Savage DB, Long A, et al. Long-term effectiveness and safety of metreleptin in the treatment of patients with generalized lipodystrophy. Endocrine. 2018;60(3):479–89. https://​doi.​org/​10.​1007/​s12020-018-1589-1.
35.
Araujo-Vilar D, Sánchez-Iglesias S, Guillín-Amarelle C, Castro A, Lage M, Pazos M, et al. Recombinant human leptin treatment in genetic lipodystrophic syndromes: the long-term Spanish experience. Endocrine. 2015;49(1):139–47. https://​doi.​org/​10.​1007/​s12020-014-0450-4.
36.
Araújo-Vilar D, Santini F. Diagnosis and treatment of lipodystrophy: a step-by-step approach. J Endocrinol Invest. 2018;27. https://​doi.​org/​10.​1007/​s40618-018-0887-z.
37.
Tsoukas MA MC. Endocrinology Adult and Pediatric. In: Jameson JL DL, editor. 7 ed.: Saunders, In Press.
38.
McDuffie JR, Riggs PA, Calis KA, Freedman RJ, Oral EA, DePaoli AM, et al. Effects of exogenous leptin on satiety and satiation in patients with lipodystrophy and leptin insufficiency. J Clin Endocrinol Metab. 2004;89(9):4258–63. https://​doi.​org/​10.​1210/​jc.​2003-031868. CrossRefPubMed
39.
Moran SA, Patten N, Young JR, Cochran E, Sebring N, Reynolds J, et al. Changes in body composition in patients with severe lipodystrophy after leptin replacement therapy. Metabolism. 2004;53(4):513–9. CrossRefPubMed
40.
Ebihara K, Kusakabe T, Hirata M, Masuzaki H, Miyanaga F, Kobayashi N, et al. Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy. J Clin Endocrinol Metab. 2007;92(2):532–41. https://​doi.​org/​10.​1210/​jc.​2006-1546. CrossRefPubMed
41.
Schlogl H, Muller K, Horstmann A, Miehle K, Puschel J, Villringer A, et al. Leptin substitution in patients with lipodystrophy: neural correlates for long-term success in the normalization of eating behavior. Diabetes. 2016;65(8):2179–86. https://​doi.​org/​10.​2337/​db15-1550. CrossRefPubMed
42.
Schlogl H, Muller K, Horstmann A, Pleger B, Miehle K, Moller H et al. Leptin-substitution in patients with congenital lipodystrophy increases connectivity in reward-related brain structures: an fMRI study. Exp Clin Endocrinol Diabetes 2014;122(3). doi: https://​doi.​org/​10.​1055/​s-0034-1371982.
43.
Schlogl H, Muller K, Horstmann A, Miehle K, Pleger B, Moller H, et al. Leptin-substitution increases connectivity in reward-related brain areas in patients with congenital lipodystrophy. Diabetologia. 2015;58:S71–S.
44.
• Petersen KF, Oral EA, Dufour S, Befroy D, Ariyan C, Yu C, et al. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J Clin Invest. 2002;109(10):1345–50. https://​doi.​org/​10.​1172/​JCI15001. This study shows the efficacy of leptin treatment to improve insulin-stimulated hepatic and peripheral glucose metabolism in lipodystrophic patients. CrossRefPubMedPubMedCentral
45.
Vatier C, Fetita S, Boudou P, Tchankou C, Deville L, Riveline J, et al. One-year metreleptin improves insulin secretion in patients with diabetes linked to genetic lipodystrophic syndromes. Diabetes Obes Metab. 2016;18(7):693–7. https://​doi.​org/​10.​1111/​dom.​12606. CrossRefPubMed
46.
Muniyappa R, Brown RJ, Mari A, Joseph J, Warren MA, Cochran EK, et al. Effects of leptin replacement therapy on pancreatic beta-cell function in patients with lipodystrophy. Diabetes Care. 2014;37(4):1101–7. https://​doi.​org/​10.​2337/​dc13-2040. CrossRefPubMedPubMedCentral
47.
• Diker-Cohen T, Cochran E, Gorden P, Brown RJ. Partial and generalized lipodystrophy: comparison of baseline characteristics and response to metreleptin. J Clin Endocrinol Metab. 2015;100(5):1802–10. https://​doi.​org/​10.​1210/​jc.​2014-4491. This study defines predictors for treatment response to metreleptin. CrossRefPubMedPubMedCentral
48.
Chan JL, Lutz K, Cochran E, Huang W, Peters Y, Weyer C, et al. Clinical effects of long-term metreleptin treatment in patients with lipodystrophy. Endocr Pract. 2011;17(6):922–32. https://​doi.​org/​10.​4158/​EP11229.​OR. CrossRefPubMedPubMedCentral
49.
Chong AY, Lupsa BC, Cochran EK, Gorden P. Efficacy of leptin therapy in the different forms of human lipodystrophy. Diabetologia. 2010;53(1):27–35. https://​doi.​org/​10.​1007/​s00125-009-1502-9. CrossRefPubMed
50.
Vatier C, Arnaud L, Prieur X, Guyomarch B, Le May C, Bigot E, et al. One-year metreleptin therapy decreases PCSK9 serum levels in diabetic patients with monogenic lipodystrophy syndromes. Diabetes Metab. 2017;43(3):275–9. https://​doi.​org/​10.​1016/​j.​diabet.​2016.​08.​004. CrossRefPubMed
51.
Ajluni N, Dar M, Xu J, Neidert AH, Oral EA. Efficacy and safety of metreleptin in patients with partial lipodystrophy: lessons from an expanded access program. J Diabetes Metab 2016;7(3). doi: https://​doi.​org/​10.​4172/​2155-6156.​1000659.
52.
Simha V, Subramanyam L, Szczepaniak L, Quittner C, Adams-Huet B, Snell P, et al. Comparison of efficacy and safety of leptin replacement therapy in moderately and severely hypoleptinemic patients with familial partial lipodystrophy of the Dunnigan variety. J Clin Endocrinol Metab. 2012;97(3):785–92. https://​doi.​org/​10.​1210/​jc.​2011-2229. CrossRefPubMed
53.
Park JY, Javor ED, Cochran EK, DePaoli AM, Gorden P. Long-term efficacy of leptin replacement in patients with Dunnigan-type familial partial lipodystrophy. Metabolism. 2007;56(4):508–16. https://​doi.​org/​10.​1016/​j.​metabol.​2006.​11.​010. CrossRefPubMedPubMedCentral
54.
Simha V, Szczepaniak LS, Wagner AJ, DePaoli AM, Garg A. Effect of leptin replacement on intrahepatic and intramyocellular lipid content in patients with generalized lipodystrophy. Diabetes Care. 2003;26(1):30–5. CrossRefPubMed
55.
Javor ED, Ghany MG, Cochran EK, Oral EA, DePaoli AM, Premkumar A, et al. Leptin reverses nonalcoholic steatohepatitis in patients with severe lipodystrophy. Hepatology. 2005;41(4):753–60. https://​doi.​org/​10.​1002/​hep.​20672. CrossRefPubMed
56.
• Safar Zadeh E, Lungu AO, Cochran EK, Brown RJ, Ghany MG, Heller T, et al. The liver diseases of lipodystrophy: the long-term effect of leptin treatment. J Hepatol. 2013;59(1):131–7. https://​doi.​org/​10.​1016/​j.​jhep.​2013.​02.​007. The study reports the effect of metreleptin on hepatic disease associated with lipodystrophy. CrossRefPubMed
57.
Machado MV, Cortez-Pinto H. Leptin in the treatment of lipodystrophy-associated nonalcoholic fatty liver disease: are we there already? Expert Rev Gastroenterol Hepatol. 2013;7(6):513–5. https://​doi.​org/​10.​1586/​17474124.​2013.​814903. CrossRefPubMed
58.
Brown RJ, Meehan CA, Cochran E, Rother KI, Kleiner DE, Walter M, et al. Effects of metreleptin in pediatric patients with lipodystrophy. J Clin Endocrinol Metab. 2017;102(5):1511–9. https://​doi.​org/​10.​1210/​jc.​2016-3628. CrossRefPubMedPubMedCentral
59.
Casey SP, Lokan J, Testro A, Farquharson S, Connelly A, Proietto J, et al. Post-liver transplant leptin results in resolution of severe recurrence of lipodystrophy-associated nonalcoholic steatohepatitis. Am J Transplant. 2013;13(11):3031–4. https://​doi.​org/​10.​1111/​ajt.​12436. CrossRefPubMed
60.
Friedman J. The long road to leptin. J Clin Invest. 2016;126(12):4727–34. https://​doi.​org/​10.​1172/​JCI91578. CrossRefPubMedPubMedCentral
61.
• Brown RJ, Valencia A, Startzell M, Cochran E, Walter PJ, Garraffo HM, et al. Metreleptin improves insulin sensitivity independent of food intake in humans with lipodystrophy. J Clin Invest. 2018. https://​doi.​org/​10.​1172/​JCI95476. The study shows that metreleptin improves insulin sensitivity and decreases hepatic and circulating triglycerides independent of its effects on food intake.
62.
Javor ED, Moran SA, Young JR, Cochran EK, DePaoli AM, Oral EA, et al. Proteinuric nephropathy in acquired and congenital generalized lipodystrophy: baseline characteristics and course during recombinant leptin therapy. J Clin Endocrinol Metab. 2004;89(7):3199–207. https://​doi.​org/​10.​1210/​jc.​2003-032140. CrossRefPubMed
63.
• Oral EA, Ruiz E, Andewelt A, Sebring N, Wagner AJ, Depaoli AM, et al. Effect of leptin replacement on pituitary hormone regulation in patients with severe lipodystrophy. J Clin Endocrinol Metab. 2002;87(7):3110–7. https://​doi.​org/​10.​1210/​jcem.​87.​7.​8591. The study investigates the effect of metreleptin on pituitary hormones in patients with lipodystrophy. CrossRefPubMed
64.
Musso C, Cochran E, Javor E, Young J, Depaoli AM, Gorden P. The long-term effect of recombinant methionyl human leptin therapy on hyperandrogenism and menstrual function in female and pituitary function in male and female hypoleptinemic lipodystrophic patients. Metabolism. 2005;54(2):255–63. https://​doi.​org/​10.​1016/​j.​metabol.​2004.​08.​021. CrossRefPubMed
65.
Abel BS, Muniyappa R, Stratton P, Skarulis MC, Gorden P, Brown RJ. Effects of recombinant human leptin (metreleptin) on nocturnal luteinizing hormone secretion in lipodystrophy patients. Neuroendocrinology. 2016;103(3–4):402–7. https://​doi.​org/​10.​1159/​000439432. CrossRefPubMed
66.
Lungu AO, Zadeh ES, Goodling A, Cochran E, Gorden P. Insulin resistance is a sufficient basis for hyperandrogenism in lipodystrophic women with polycystic ovarian syndrome. J Clin Endocrinol Metab. 2012;97(2):563–7. https://​doi.​org/​10.​1210/​jc.​2011-1896. CrossRefPubMed
67.
Oral EA, Javor ED, Ding L, Uzel G, Cochran EK, Young JR, et al. Leptin replacement therapy modulates circulating lymphocyte subsets and cytokine responsiveness in severe lipodystrophy. J Clin Endocrinol Metab. 2006;91(2):621–8. https://​doi.​org/​10.​1210/​jc.​2005-1220. CrossRefPubMed
68.
Maguire M, Lungu A, Gorden P, Cochran E, Stratton P. Pregnancy in a woman with congenital generalized lipodystrophy: leptin’s vital role in reproduction. Obstet Gynecol. 2012;119(2 Pt 2):452–5. https://​doi.​org/​10.​1097/​AOG.​0b013e31822cecf7​. CrossRefPubMedPubMedCentral
69.
Meehan CA, Cochran E, Kassai A, Brown RJ, Gorden P. Metreleptin for injection to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. Expert Rev Clin Pharmacol. 2016;9(1):59–68. https://​doi.​org/​10.​1586/​17512433.​2016.​1096772. CrossRefPubMed
70.
Kamran F, Rother KI, Cochran E, Safar Zadeh E, Gorden P, Brown RJ. Consequences of stopping and restarting leptin in an adolescent with lipodystrophy. Horm Res Paediatr. 2012;78(5–6):320–5. https://​doi.​org/​10.​1159/​000341398. CrossRefPubMed
71.
Lebastchi J, Ajluni N, Neidert A, Oral EA. A report of three cases with acquired generalized lipodystrophy with distinct autoimmune conditions treated with metreleptin. J Clin Endocrinol Metab. 2015;100(11):3967–70. https://​doi.​org/​10.​1210/​jc.​2015-2589. CrossRefPubMedPubMedCentral
72.
Christensen JD, Lungu AO, Cochran E, Collins MT, Gafni RI, Reynolds JC, et al. Bone mineral content in patients with congenital generalized lipodystrophy is unaffected by metreleptin replacement therapy. J Clin Endocrinol Metab. 2014;99(8):E1493–500. https://​doi.​org/​10.​1210/​jc.​2014-1353. CrossRefPubMedPubMedCentral
73.
Simha V, Zerwekh JE, Sakhaee K, Garg A. Effect of subcutaneous leptin replacement therapy on bone metabolism in patients with generalized lipodystrophy. J Clin Endocrinol Metab. 2002;87(11):4942–5. https://​doi.​org/​10.​1210/​jc.​2002-020792. CrossRefPubMed
74.
Chan JL, Koda J, Heilig JS, Cochran EK, Gorden P, Oral EA, et al. Immunogenicity associated with metreleptin treatment in patients with obesity or lipodystrophy. Clin Endocrinol. 2016;85(1):137–49. https://​doi.​org/​10.​1111/​cen.​12980. CrossRef
75.
Beltrand J, Lahlou N, Le Charpentier T, Sebag G, Leka S, Polak M, et al. Resistance to leptin-replacement therapy in Berardinelli-Seip congenital lipodystrophy: an immunological origin. Eur J Endocrinol. 2010;162(6):1083–91. https://​doi.​org/​10.​1530/​EJE-09-1027. CrossRefPubMed
76.
• Brown RJ, Chan JL, Jaffe ES, Cochran E, DePaoli AM, Gautier JF, et al. Lymphoma in acquired generalized lipodystrophy. Leuk Lymphoma. 2016;57(1):45–50. https://​doi.​org/​10.​3109/​10428194.​2015.​1040015. This article focuses on lymphoma development in patients with lipodystrophy. CrossRefPubMed
77.
Aslam A, Savage DB, Coulson IH. Acquired generalized lipodystrophy associated with peripheral T cell lymphoma with cutaneous infiltration. Int J Dermatol. 2015;54(7):827–9. https://​doi.​org/​10.​1111/​ijd.​12185. CrossRefPubMed
78.
Bae MJ, Kim SS, Kim WJ, Yi YS, Jeon YK, Kim BH, et al. High prevalence of papillary thyroid cancer in Korean women with insulin resistance. Head Neck. 2016;38(1):66–71. https://​doi.​org/​10.​1002/​hed.​23848. CrossRefPubMed
79.
Pitoia F, Abelleira E, Bueno F, Urciuoli C, Schmidt A, Niepomniszcze H. Insulin resistance is another factor that increases the risk of recurrence in patients with thyroid cancer. Endocrine. 2015;48(3):894–901. https://​doi.​org/​10.​1007/​s12020-014-0416-6. CrossRefPubMed
80.
Guler HP, Zapf J, Froesch ER. Short-term metabolic effects of recombinant human insulin-like growth factor I in healthy adults. N Engl J Med. 1987;317(3):137–40. https://​doi.​org/​10.​1056/​NEJM198707163170​303. CrossRefPubMed
81.
Kuzuya H, Matsuura N, Sakamoto M, Makino H, Sakamoto Y, Kadowaki T, et al. Trial of insulinlike growth factor I therapy for patients with extreme insulin resistance syndromes. Diabetes. 1993;42(5):696–705. CrossRefPubMed
82.
Moses AC, Morrow LA, O'Brien M, Moller DE, Flier JS. Insulin-like growth factor I (rhIGF-I) as a therapeutic agent for hyperinsulinemic insulin-resistant diabetes mellitus. Diabetes Res Clin Pract. 1995;28(Suppl):S185–94. CrossRefPubMed
83.
Satoh M, Yoshizawa A, Takesue M, Saji T, Yokoya S. Long-term effects of recombinant human insulin-like growth factor I treatment on glucose and lipid metabolism and the growth of a patient with congenital generalized lipodystrophy. Endocr J. 2006;53(5):639–45. CrossRefPubMed
84.
Grimberg A. Mechanisms by which IGF-I may promote cancer. Cancer Biol Ther. 2003;2(6):630–5. CrossRefPubMed
85.
Chernausek SD, Backeljauw PF, Frane J, Kuntze J, Underwood LE, Group GHISC. Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity. J Clin Endocrinol Metab. 2007;92(3):902–10. https://​doi.​org/​10.​1210/​jc.​2006-1610. CrossRefPubMed
86.
Bang P, Polak M, Woelfle J, Houchard A, Group EIRS. Effectiveness and safety of rhIGF-1 therapy in children: the European Increlex® Growth Forum Database Experience. Horm Res Paediatr. 2015;83(5):345–57. https://​doi.​org/​10.​1159/​000371798. CrossRefPubMed
87.
Norata GD, Tsimikas S, Pirillo A, Catapano AL. Apolipoprotein C-III: from pathophysiology to pharmacology. Trends Pharmacol Sci. 2015;36(10):675–87. https://​doi.​org/​10.​1016/​j.​tips.​2015.​07.​001. CrossRefPubMed
88.
Gaudet D, Digenio A, Alexander V, Arca M, Jones A, Stroes E, et al. The APPROACH study: a randomized, double-blind, placebo-controlled, phase 3 study of volanesorsen administered subcutaneously to patients with familial chylomicronemia syndrome (Fcs). Clin Cardiol. 2017;40:14.
89.
Gouni-Berthold I, Alexander V, Digenio A, DuFour R, Steinhagen-Thiessen E, Martin S, et al. Apolipoprotein C-III inhibition with volanesorsen in patients with hypertriglyceridemia (COMPASS): a randomized, double-blind, placebo-controlled trial. Atheroscler Suppl. 2017;28:E1–2. https://​doi.​org/​10.​1016/​j.​atherosclerosiss​up.​2017.​08.​003. CrossRef
90.
Olkkonen VM, Sinisalo J, Jauhiainen M. New medications targeting triglyceride-rich lipoproteins: can inhibition of ANGPTL3 or apoC-III reduce the residual cardiovascular risk? Atherosclerosis. 2018;272:27–32. https://​doi.​org/​10.​1016/​j.​atherosclerosis.​2018.​03.​019. CrossRefPubMed
91.
Stahel P, Xiao C, Hegele RA, Lewis GF. The atherogenic dyslipidemia complex and novel approaches to cardiovascular disease prevention in diabetes. Can J Cardiol. 2017;34:595–604. https://​doi.​org/​10.​1016/​j.​cjca.​2017.​12.​007. CrossRefPubMed
92.
Gaudet D, Gipe DA, Pordy R, Ahmad Z, Cuchel M, Shah PK, et al. ANGPTL3 inhibition in homozygous familial hypercholesterolemia. N Engl J Med. 2017;377(3):296–7. https://​doi.​org/​10.​1056/​NEJMc1705994. CrossRefPubMed
93.
Bisgaier CL, Essenburg AD, Barnett BC, Auerbach BJ, Haubenwallner S, Leff T, et al. A novel compound that elevates high density lipoprotein and activates the peroxisome proliferator activated receptor. J Lipid Res. 1998;39(1):17–30. PubMed
94.
Srivastava RAK, Cornicelli JA, Markham B, Bisgaier CL. Gemcabene, a first-in-class lipid-lowering agent in late-stage development, down-regulates acute-phase C-reactive protein via C/EBP-delta-mediated transcriptional mechanism. Mol Cell Biochem. 2018. https://​doi.​org/​10.​1007/​s11010-018-3353-5.
95.
Stein E, Bays H, Koren M, Bakker-Arkema R, Bisgaier C. Efficacy and safety of gemcabene as add-on to stable statin therapy in hypercholesterolemic patients. J Clin Lipidol. 2016;10(5):1212–22. https://​doi.​org/​10.​1016/​j.​jacl.​2016.​08.​002. CrossRefPubMed
96.
Bays HE, McKenney JM, Dujovne CA, Schrott HG, Zema MJ, Nyberg J, et al. Effectiveness and tolerability of a new lipid-altering agent, gemcabene, in patients with low levels of high-density lipoprotein cholesterol. Am J Cardiol. 2003;92(5):538–43. CrossRefPubMed
97.
Markham A. Baricitinib: first global approval. Drugs. 2017;77(6):697–704. https://​doi.​org/​10.​1007/​s40265-017-0723-3. CrossRefPubMed
98.
Sanchez GAM, Reinhardt A, Ramsey S, Wittkowski H, Hashkes PJ, Berkun Y, et al. JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies. J Clin Invest. 2018;128:3041–52. https://​doi.​org/​10.​1172/​JCI98814. CrossRefPubMedPubMedCentral
99.
Abulizi A, Perry RJ, Camporez JPG, Jurczak MJ, Petersen KF, Aspichueta P, et al. A controlled-release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice. FASEB J. 2017;31(7):2916–24. https://​doi.​org/​10.​1096/​fj.​201700001R. CrossRefPubMedPubMedCentral
100.
Baptista LS, da Silva KR, da Pedrosa CS, Claudio-da-Silva C, Carneiro JR, Aniceto M, et al. Adipose tissue of control and ex-obese patients exhibit differences in blood vessel content and resident mesenchymal stem cell population. Obes Surg. 2009;19(9):1304–12. https://​doi.​org/​10.​1007/​s11695-009-9899-2. CrossRefPubMed
101.
Baptista LS, Silva KR, Borojevic R. Obesity and weight loss could alter the properties of adipose stem cells? World J Stem Cells. 2015;7(1):165–73. https://​doi.​org/​10.​4252/​wjsc.​v7.​i1.​165. CrossRefPubMedPubMedCentral
102.
Matsushita K, Dzau VJ. Mesenchymal stem cells in obesity: insights for translational applications. Lab Investig. 2017;97(10):1158–66. https://​doi.​org/​10.​1038/​labinvest.​2017.​42. CrossRefPubMed

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