Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28324110
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Clin+Endocrinol+Metab
2017 ; 102
(5
): 1511-1519
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Effects of Metreleptin in Pediatric Patients With Lipodystrophy
#MMPMID28324110
Brown RJ
; Meehan CA
; Cochran E
; Rother KI
; Kleiner DE
; Walter M
; Gorden P
J Clin Endocrinol Metab
2017[May]; 102
(5
): 1511-1519
PMID28324110
show ga
CONTEXT: Lipodystrophy syndromes are rare disorders of deficient adipose tissue.
Metreleptin, a human analog of leptin, improved metabolic abnormalities in mixed
cohorts of children and adults with lipodystrophy and low leptin. OBJECTIVE:
Determine effects of metreleptin on diabetes, hyperlipidemia, nonalcoholic fatty
liver disease (NAFLD), growth, and puberty in pediatric patients with
lipodystrophy and low leptin. DESIGN: Prospective, single-arm, open-label studies
with continuous enrollment since 2000. SETTING: National Institutes of Health,
Bethesda, Maryland. PATIENTS: Fifty-three patients aged 6 months to <18 years
with lipodystrophy, leptin level <8 ng/mL (male patients) or <12 ng/mL (female
patients), and ?1 metabolic abnormality (diabetes, insulin resistance, or
hypertriglyceridemia). INTERVENTION: Subcutaneous metreleptin injections (0.04 to
0.19 mg/kg/d). MAIN OUTCOME MEASURES: Change in A1c, lipid, and transaminase
levels after a mean ± standard deviation (SD) of 12 ± 0.2 months and 61 ± 39
months. Changes in liver histology, growth, and pubertal development throughout
treatment. RESULTS: After 12 months, the A1c level (mean ± SD) decreased from
8.3% ± 2.4% to 6.5% ± 1.8%, and median triglyceride level decreased from 374
mg/dL [geometric mean (25th,75th percentile), 190, 1065] to 189 mg/dL (112, 334;
P < 0.0001), despite decreased glucose- and lipid-lowering medications. The
median [geometric mean (25th,75th percentile)] alanine aminotransferase level
decreased from 73 U/L (45, 126) to 41 U/L (25, 59; P = 0.001), and that of
aspartate aminotransferase decreased from 51 U/L (29, 90) to 26 U/L (18, 42; P =
0.0002). These improvements were maintained over long-term treatment. In 17
patients who underwent paired biopsies, the NAFLD activity score (mean ± SD)
decreased from 4.5 ± 2.0 to 3.4 ± 2.0 after 3.3 ± 3.2 years of metreleptin
therapy (P = 0.03). There were no clinically significant changes in growth or
puberty. CONCLUSION: Metreleptin lowered A1c and triglyceride levels, and
improved biomarkers of NAFLD in pediatric patients with lipodystrophy. These
improvements are likely to reduce the lifetime burden of disease.
|*Insulin Resistance
[MESH]
|Adolescent
[MESH]
|Alanine Transaminase/blood
[MESH]
|Aspartate Aminotransferases/blood
[MESH]
|Blood Glucose/metabolism
[MESH]
|Body Height
[MESH]
|Child
[MESH]
|Child, Preschool
[MESH]
|Cohort Studies
[MESH]
|Diabetes Mellitus, Type 2/drug therapy/*metabolism
[MESH]
|Female
[MESH]
|Glycated Hemoglobin/metabolism
[MESH]
|Humans
[MESH]
|Hyperlipidemias/*blood/drug therapy
[MESH]
|Hypoglycemic Agents/therapeutic use
[MESH]
|Hypolipidemic Agents/therapeutic use
[MESH]
|Infant
[MESH]
|Leptin/*analogs & derivatives/blood/therapeutic use
[MESH]
free
free
free
