Prominent Insulin Resistance in Congenital Generalized Lipoatrophy

  • Jun WadaEmail author
  • Yashpal S. Kanwar


A 35-year-old female was admitted to the division of endocrinology and metabolism for generalized lipoatrophy and hyperglycemia. She was markedly deficient of adipose tissue since birth and developed diabetes and hypertension at the age of 20 years. She began receiving premixed biosynthetic human insulin with a ratio of 30% regular and 70% NPH (neutral protamine Hagedorn) insulin at the age of 27 years. The glycemic control remained poor despite the increase in her insulin dose to 60–80 units/day. Her hemoglobin A1c levels remained high, and they varied between 8 and 11%. Current admission revealed a female with 161 cm height, body weight 53.0 kg, body mass index (BMI) 20.4 kg/m2, and systemic blood pressure of 146/86 mm Hg. She had muscular stature with generalized loss of subdermal fatty tissue. She also had umbilical hernia and acromegalic features with slight enlargement of her hands, feet, and mandible (Fig. 3.1a). She had difficulty in controlling her excessive appetite.


Lipodystrophy Fatty liver Insulin resistance Leptin Diabetes 


  1. Brown RJ, Araujo-Vilar D, Cheung PT et al (2016) The diagnosis and Management of Lipodystrophy Syndromes: a multi-society practice guideline. J Clin Endocrinol Metab 101(12):4500–4511. published Online First: 2016/10/07CrossRefPubMedPubMedCentralGoogle Scholar
  2. Covey SD, Wideman RD, McDonald C et al (2006) The pancreatic beta cell is a key site for mediating the effects of leptin on glucose homeostasis. Cell Metab 4(4):291–302. CrossRefPubMedGoogle Scholar
  3. Farooqi IS, Jebb SA, Langmack G et al (1999) Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 341(12):879–884. CrossRefGoogle Scholar
  4. Foo JP, Polyzos SA, Anastasilakis AD et al (2014) The effect of leptin replacement on parathyroid hormone, RANKL-osteoprotegerin axis, and Wnt inhibitors in young women with hypothalamic amenorrhea. J Clin Endocrinol Metab 99(11):E2252–E2258. CrossRefPubMedPubMedCentralGoogle Scholar
  5. Huang W, Dedousis N, Bandi A et al (2006) Liver triglyceride secretion and lipid oxidative metabolism are rapidly altered by leptin in vivo. Endocrinology 147(3):1480–1487. CrossRefPubMedGoogle Scholar
  6. Huang-Doran I, Sleigh A, Rochford JJ et al (2010) Lipodystrophy: metabolic insights from a rare disorder. J Endocrinol 207(3):245–255. published Online First: 2010/09/28CrossRefPubMedGoogle Scholar
  7. Kunitomi M, Wada J, Takahashi K et al (2002) Relationship between reduced serum IGF-I levels and accumulation of visceral fat in Japanese men. Int J Obes Relat Metab Disord 26(3):361–369. CrossRefPubMedGoogle Scholar
  8. Lee Y, Wang MY, Du XQ et al (2011) Glucagon receptor knockout prevents insulin-deficient type 1 diabetes in mice. Diabetes 60(2):391–397. CrossRefPubMedPubMedCentralGoogle Scholar
  9. Mantzoros CS, Flier JS, Rogol AD (1997) A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. V. Rising leptin levels may signal the onset of puberty. J Clin Endocrinol Metab 82(4):1066–1070. CrossRefPubMedGoogle Scholar
  10. Mori E, Fujikura J, Noguchi M et al (2016) Impaired adipogenic capacity in induced pluripotent stem cells from lipodystrophic patients with BSCL2 mutations. Metabolism 65(4):543–556. CrossRefPubMedGoogle Scholar
  11. Muoio DM, Dohm GL, Tapscott EB et al (1999) Leptin opposes insulin’s effects on fatty acid partitioning in muscles isolated from obese ob/ob mice. Am J Phys 276(5 Pt 1):E913–E921Google Scholar
  12. Oral EA, Simha V, Ruiz E et al (2002) Leptin-replacement therapy for lipodystrophy. N Engl J Med 346(8):570–578. CrossRefPubMedGoogle Scholar
  13. Perry RJ, Zhang XM, Zhang D et al (2014) Leptin reverses diabetes by suppression of the hypothalamic-pituitary-adrenal axis. Nat Med 20(7):759–763. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Ravussin E, Smith SR, Mitchell JA et al (2009) Enhanced weight loss with pramlintide/metreleptin: an integrated neurohormonal approach to obesity pharmacotherapy. Obesity (Silver Spring) 17(9):1736–1743. CrossRefGoogle Scholar
  15. Siegrist-Kaiser CA, Pauli V, Juge-Aubry CE et al (1997) Direct effects of leptin on brown and white adipose tissue. J Clin Invest 100(11):2858–2864. CrossRefPubMedPubMedCentralGoogle Scholar
  16. Tsoukas MA, Farr OM, Mantzoros CS (2015) Leptin in congenital and HIV-associated lipodystrophy. Metabolism 64(1):47–59. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Nephrology, Rheumatology, Endocrinology and MetabolismOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  2. 2.Department of Pathology, Feinberg School of MedicineNorthwestern UniversityChicagoUSA

Personalised recommendations