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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
Commissione
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.<br>Objective To assess remission and investigate insulin sensitivity and ß-cell function after BPD in non-morbidly obese patients with long-standing T2DM.<br>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.<br>Intervention BPD (gastric resection, distal jejunum anastomosed to remaining stomach, biliopancreatic tract anastomosed to ileum 75cm from the ileocecal valve).<br>Results Glycemia improved in all patients, but remission (HbA1c&lt;6.5% and normal OGTT) occurred in 6/15. Insulin resistance (19.8±0.8 µmol.min-1.kgffm-1, p&lt;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&lt;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]).<br>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.<br>
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