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Tesi etd-08142013-125858


Thesis type
Tesi di dottorato di ricerca
Author
DOMINGUEZ ASTIARRAGA, BRENNO
URN
etd-08142013-125858
Title
Biliopancreatic diversion in patients with type 2 diabetes and moderate obesity: impact and mechanisms.
Settore scientifico disciplinare
MED/09
Corso di studi
FISIOPATOLOGIA CLINICA E SCIENZE DEL FARMACO
Supervisors
tutor Ferrannini, Eleuterio
Parole chiave
  • euglycemic hyperinsulinemic clamp
  • endogenous glucose production
  • diabetes mellitus
  • beta-cell function
  • insulin resistance
Data inizio appello
01/10/2013;
Consultabilità
Completa
Riassunto analitico
Context Diabetes remission is frequent after biliopancreatic diversion (BPD) in morbidly obese patients with type 2 diabetes (T2DM). Data, mechanisms, and clinical indications in nonobese T2DM patients are scanty.
Objective To assess remission and investigate insulin sensitivity and ß-cell function after BPD in non-morbidly obese patients with long-standing T2DM.
Design, setting and patients Clinical research study comparing 15 T2DM patients (age 551 years, duration 16±2 years, BMI=28.3±0.6 kg/m2, HbA1c=8.6±1.3%) with 15 gender-, age-, and BMI-matched nondiabetic controls. Before surgery, and 2 months and one year later, a 3-hour OGTT, a 5-hour mixed meal test, and a 3-hour euglycemic clamp were performed.
Intervention BPD (gastric resection, distal jejunum anastomosed to remaining stomach, biliopancreatic tract anastomosed to ileum 75cm from the ileocecal valve).
Results Glycemia improved in all patients, but remission (HbA1c<6.5% and normal OGTT) occurred in 6/15. Insulin resistance (19.8±0.8 µmol.min-1.kgffm-1, p<0.001 vs 40.9±5.3 of controls) resolved already at 2 months (34.2±2.8) and was sustained at one year (34.7±1.6), although insulin-mediated suppression of endogenous glucose production remained impaired. In contrast, ß-cell glucose sensitivity (19[12] pmol.min-1.m-2.mM-1 vs 96[73] of controls, p<0.0001) rose (p=0.02) only to 31[26] at one year, and was lower in non-remitters (16[18]) than remitters (46[33]).
Conclusions In nonobese patients with long-standing T2DM, BPD improves metabolic control but induces remission in only ~30% of patients. Peripheral insulin sensitivity is restored early after surgery, and similarly in remitters and non-remitters, indicating a weight-independent effect of the operation. The initial extent of ß-cell incompetence is the main predictor of the metabolic outcome.
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