title: Biliopancreatic diversion in nonobese patients with type 2 diabetes: impact and mechanisms.
abstract: BACKGROUND
  Diabetes remission is frequent after biliopancreatic diversion (BPD) in morbidly obese patients with type 2 diabetes (T2D). Data, mechanisms, and clinical indications in nonobese T2D patients are scanty.
  
  
  OBJECTIVE
  The objective of the study was to assess remission and investigate insulin sensitivity and β-cell function after BPD in nonobese patients with long-standing T2D.
  
  
  METHODS
  This was a clinical research study comparing 15 T2D patients (aged 55 ± 1 years, duration of 16 ± 2 years, body mass index of 28.3 ± 0.6 kg/m², glycosylated hemoglobin 8.6% ± 1.3%) with 15 gender-, age-, and body mass index-matched nondiabetic controls. Before surgery and 2 months and 1 year later, a 3-hour oral glucose tolerance test, a 5-hour mixed-meal test, and a 3-hour euglycemic clamp were performed.
  
  
  METHODS
  The intervention included a BPD (distal gastrectomy, proximal ileum anastomosed to remaining stomach, biliopancreatic limb anastomosed to ileum 50 cm from the ileocecal valve).
  
  
  RESULTS
  Glycemia improved in all patients, but remission (glycosylated hemoglobin < 6.5% and normal oral glucose tolerance test) occurred in 6 of 15 patients. Insulin resistance (19.8 ± 0.8 μmol · min⁻¹ · kg(ffm)⁻¹, P < .001 vs 40.9 ± 5.3 of controls) resolved already at 2 months (34.2 ± 2.8) and was sustained at 1 year (34.7 ± 1.6), although insulin-mediated suppression of endogenous glucose production remained impaired. In contrast, β-cell glucose sensitivity (19 [12] pmol · min⁻¹ · m⁻² · mM⁻¹ vs 96 [73] of controls, P < .0001) rose (P = .02) only to 31 [26] at 1 year and was lower in nonremitters (16 [18]) than remitters (46 [33]).
  
  
  CONCLUSIONS
  In nonobese patients with long-standing T2D, BPD improves metabolic control but induces remission in only approximately 40% of patients. Peripheral insulin sensitivity is restored early after surgery and similarly in remitters and nonremitters, indicating a weight-independent effect of the operation. The initial extent of β-cell incompetence is the main predictor of the metabolic outcome.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa School of Medicine, 56100 Pisa, Italy.
authors.forename: Brenno
authors.initials: B
authors.lastname: Astiarraga
authors.forename: Amalia
authors.initials: A
authors.lastname: Gastaldelli
authors.forename: Elza
authors.initials: E
authors.lastname: Muscelli
authors.forename: Simona
authors.initials: S
authors.lastname: Baldi
authors.forename: Stefania
authors.initials: S
authors.lastname: Camastra
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
authors.forename: Francesco
authors.initials: F
authors.lastname: Papadia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camerini
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Adami
authors.forename: Nicola
authors.initials: N
authors.lastname: Scopinaro
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
mesh_terms: D050110:Bariatric Surgery; D015904:Biliopancreatic Diversion; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D061386:Insulin, Regular, Human; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D007558:Italy; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000150:complications* / Q000601:surgery; D011994:Recombinant Proteins; D012074:Remission Induction; D015431:Weight Loss
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061386:Insulin, Regular, Human; D011994:Recombinant Proteins; C517652:hemoglobin A1c protein, human