SUN-LB032 Severe Insulin Resistance and Nephrotic Range Proteinuria Reversed by Pioglitazone in a Patient With Dunnigan Type Lipodystrophy

Abstract

Background: Familial partial lipodystrophy (FPLD 2 or Dunnigan lipodystrophy [DL]) is a rare disorder associated severe insulin resistance, elevated triglycerides (TG), and low serum HDL cholesterol. Proteinuric renal disease is a prevalent feature of generalized lipodystrophy, usually secondary to focal segmental glomerulosclerosis (FSGS) and membranoproliferative glomerulonephritis. Case series reported that metreleptin have shown to improve proteinuria in patients with generalized lipodystrophy. Here we report a reversal of nephrotic syndrome using PPARγ agonist pioglitazone. Case: 37 yo female presented with type 2 diabetes mellitus [DM2] with severe insulin resistance. A diagnosis of DL was made based on loss of peripheral subcutaneous fat with accentuation of fat distribution in the head and face with a similar presentation in her mother. The patient developed DM2 in her 20’s. She was treated with U500 Insulin 90 U BID, Metformin 1000 mg BID, fenofibrate 145 mg, lisinopril 20 mg and Fish oil 2 g BID. Lab tests showed HBA1C 7.3%, serum creatinine (Cr) 0.7mg/dL, total cholesterol (CHOL) 280mg/dL, TG 1631 mg/dL and HDL 27mg/dL. For her proteinuria (urine albumin/Cr (1581 mg/mg), she underwent a renal biopsy which showed FSGS. She was started on pioglitazone 15 mg/day and increased to 45 mg/day. Insulin requirements improved to glargine insulin 30 units BID. Results after 22 months of treatment were HBA1C 8.1%, Cr 0.9mg/dL, CHOL 207 mg/dL, TG 168mg/dL, HDL 34mg/dL. Urine albumin/Cr ratio improved to 89 mg/mg. Discussion: Pioglitazone is a thiazolidinedione (TZD) which acts as an agonist to PPARγ. In lipodystrophy syndromes it is used to “re-differentiate” peripheral adipose tissue to more physiological locations away from liver to generalized adipose tissue, with the expectation of improving the severe insulin resistance. Her insulin requirements decreased from 180 units/day to 60 units/day. Also, serum TG improved with presumed shunting of lipids away from the liver toward peripheral adipose tissue. The reversal of the nephrotic syndrome exceeded our expectations. The mechanism for reversal of nephrotic syndrome is unknown. The blood glucose and presumed renal tubular exposure to glycosuria may not have changed as the A1c did not change significantly for the better. There may be TZD mediated downregulation of renin angiotensin aldosterone system, decreased inflammatory cytokines or adipokines which may have been associated with the nephropathy. Further studies are needed to explore this finding. Conclusion: TZD therapy is an effective mediator of improving insulin resistance and nephrotic syndrome in congenital lipodystrophy. The mechanism of action may also help in understanding the etiology of FSGS. Reference: Sarafidis, P, et al. Effect Of Thiazolidinediones On Albuminuria And Proteinuria In Diabetes Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session beg...