title: Six and 12 Weeks of Caloric Restriction Increases β Cell Function and Lowers Fasting and Postprandial Glucose Concentrations in People with Type 2 Diabetes.
abstract: BACKGROUND
  Caloric restriction alone has been shown to improve insulin action and fasting glucose metabolism; however, the mechanism by which this occurs remains uncertain.
  
  
  OBJECTIVE
  We sought to quantify the effect of caloric restriction on β cell function and glucose metabolism in people with type 2 diabetes.
  
  
  METHODS
  Nine subjects (2 men, 7 women) with type 2 diabetes [BMI (in kg/m(2)): 40.6 ± 1.4; age: 58 ± 3 y; glycated hemoglobin: 6.9% ± 0.2%] were studied using a triple-tracer mixed meal after withdrawal of oral diabetes therapy. The oral minimal model was used to measure β cell function. Caloric restriction limited subjects to a pureed diet (<900 kcal/d) for the 12 wk of study. The studies were repeated after 6 and 12 wk of caloric restriction.
  
  
  RESULTS
  Fasting glucose concentrations decreased significantly from baseline after 6 wk of caloric restriction with no further reduction after a further 6 wk of caloric restriction (9.8 ± 1.3, 5.9 ± 0.2, and 6.2 ± 0.3 mmol/L at baseline and after 6 and 12 wk of caloric restriction, respectively; P = 0.01) because of decreased fasting endogenous glucose production (EGP: 20.4 ± 1.1, 16.2 ± 0.8, and 17.4 ± 1.1 μmol · kg(-1) · min(-1) at baseline and after 6 and 12 wk of caloric restriction, respectively; P = 0.03). These changes were accompanied by an improvement in β cell function measured by the disposition index (189 ± 51, 436 ± 68, and 449 ± 67 10(-14) dL · kg(-1) · min(-2) · pmol(-1) at baseline and after 6 and 12 wk of caloric restriction, respectively; P = 0.01).
  
  
  CONCLUSIONS
  Six weeks of caloric restriction lowers fasting glucose and EGP with accompanying improvements in β cell function in people with type 2 diabetes. An additional 6 wk of caloric restriction maintained the improvement in glucose metabolism. This trial was registered at clinicaltrials.gov as NCT01094054.
authors.affiliation: Divisions of Endocrinology, Diabetes & Metabolism and.
authors.forename: Matheni
authors.initials: M
authors.lastname: Sathananthan
authors.affiliation: Divisions of Endocrinology, Diabetes & Metabolism and.
authors.forename: Meera
authors.initials: M
authors.lastname: Shah
authors.affiliation: Divisions of Endocrinology, Diabetes & Metabolism and.
authors.forename: Kim L
authors.initials: KL
authors.lastname: Edens
authors.affiliation: Department of Psychiatry & Psychology, Mayo Clinic College of Medicine, Rochester, MN; and.
authors.forename: Karen B
authors.initials: KB
authors.lastname: Grothe
authors.affiliation: Department of Information Engineering, University of Padua, Padua, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Piccinini
authors.affiliation: Divisions of Endocrinology, Diabetes & Metabolism and.
authors.forename: Luca P
authors.initials: LP
authors.lastname: Farrugia
authors.affiliation: Department of Information Engineering, University of Padua, Padua, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Micheletto
authors.affiliation: Department of Information Engineering, University of Padua, Padua, Italy.
authors.forename: Chiara Dalla
authors.initials: CD
authors.lastname: Man
authors.affiliation: Department of Information Engineering, University of Padua, Padua, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
authors.affiliation: Divisions of Endocrinology, Diabetes & Metabolism and.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rizza
authors.affiliation: Gastroenterology & Hepatology.
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.affiliation: Divisions of Endocrinology, Diabetes & Metabolism and vella.adrian@mayo.edu.
authors.forename: Adrian
authors.initials: A
authors.lastname: Vella
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D031204:Caloric Restriction; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy*; D002149:Energy Intake; D005215:Fasting; D005260:Female; D005934:Glucagon / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005934:Glucagon; D006442:Glycated Hemoglobin; D007328:Insulin
keywords: bariatric surgery; caloric restriction; disposition index; endogenous glucose production; gastric emptying; insulin action; insulin secretion