title: The progression from obesity to type 2 diabetes in Alström syndrome.
abstract: BACKGROUND
  Alström syndrome (ALMS) is a rare autosomal recessive monogenic disease associated with obesity, hyperinsulinemia, and alterations of glucose metabolism that often lead to the development of type 2 diabetes at a young age.
  
  
  OBJECTIVE
  To study the relationship between weight and metabolism in a group of ALMS patients and matched controls.
  
  
  METHODS
  Fifteen ALMS patients (eight males, seven females; aged 3-51) were compared in a cross-sectional study with an age- and weight-matched control population. Anthropometric parameters, fat mass, glucose and insulin secretion in basal and dynamic oral glucose tolerance test (OGTT) conditions were measured. Furthermore, anthropometric and body composition data were obtained from an international group of 27 ALMS patients (13 males, 14 females, age range: 4-29 yr).
  
  
  RESULTS
  In ALMS we observed an inverse correlation between age and standard deviation scores for height, weight, and body mass index. The OGTT glycemic curves of ALMS subjects were similar to those of age-matched controls, whereas insulin response was clearly greater. In ALMS individuals the insulin response showed a reduction with age. We documented pathologic values of the derived indices homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity index, HOMA%β-cell and insulinogenic index in ALMS, but unlike the insulin-resistance indices, the β-cell function indices showed a significant reduction with age.
  
  
  CONCLUSIONS
  In ALMS the progression from the early onset obesity toward the impaired fasting glucose or impaired glucose tolerance and overt diabetes is mostly because of a progressive failure of β-cell insulin secretion without any further worsening of insulin resistance with age, even in the presence of weight reduction.
authors: Department of Medical and Surgical Sciences, School of Medicine, University of Padua, Padua, Italy.
authors: Vera
authors: V
authors: Bettini
authors: Pietro
authors: P
authors: Maffei
authors: Claudio
authors: C
authors: Pagano
authors: Sara
authors: S
authors: Romano
authors: Gabriella
authors: G
authors: Milan
authors: Francesca
authors: F
authors: Favaretto
authors: Jan D
authors: JD
authors: Marshall
authors: Richard
authors: R
authors: Paisey
authors: Francesco
authors: F
authors: Scolari
authors: Nella A
authors: NA
authors: Greggio
authors: Ilaria
authors: I
authors: Tosetto
authors: Jürgen K
authors: JK
authors: Naggert
authors: Nicola
authors: N
authors: Sicolo
authors: Roberto
authors: R
authors: Vettor
mesh_terms: D000293:Adolescent; D000328:Adult; D056769:Alstrom Syndrome / Q000150:complications* / Q000453:epidemiology; D001823:Body Composition / Q000235:genetics / Q000502:physiology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000209:etiology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000453:epidemiology; D055815:Young Adult