title: Prognostic implications for insulin-sensitive and insulin-resistant normal-weight and obese individuals from a population-based cohort.
abstract: BACKGROUND
  There are few prospective data on the prognosis of insulin-sensitive and insulin-resistant normal-weight (NW) or obese individuals.
  
  
  OBJECTIVE
  The estimated liver fat content, incidences of hyperglycemia and cardiovascular disease, and all-cause and cardiovascular mortality rates were investigated in a population-based cohort of 1658 individuals who were categorized according to BMI and insulin resistance as defined by HOMA-IR values ≥2.5 and the presence of metabolic syndrome.
  
  
  METHODS
  This was a prospective cohort study with a 9-y follow-up. Anthropometric values, blood pressure, and blood metabolic variables were measured, and information on vital status was collected from demographic files at follow-up.
  
  
  RESULTS
  A total of 137 of 677 NW individuals (20%) were classified as insulin resistant and normal weight (IR-NW), and 72 of 330 obese individuals (22%) were classified as insulin sensitive and obese (IS-obese). Incidences of diabetes, impaired fasting glucose, and cardiovascular events were 0.4%, 6.3%, and 3.3%, respectively, in insulin-sensitive and normal-weight (IS-NW) individuals (reference category); 5.8%, 10.2%, and 6.6%, respectively, in IR-NW individuals; and 5.6%, 8.3%, and 8.3%, respectively, in IS-obese individuals. In a multiple logistic regression model, risks of incident hyperglycemia and cardiovascular events increased in both groups compared with in the reference category [HR (95% CI): 2.54 (1.42, 4.55) and 1.98 (0.86, 4.54) in IR-NW subjects; 2.16 (1.01, 4.63) and 2.76 (1.05, 7.28) in IS-obese subjects]. The estimated liver fat content significantly increased during follow-up only in the IR-NW group in the same model. Cardiovascular mortality was 2-3-fold higher in IR-NW and IS-obese than in IS-NW individuals in a Cox regression model.
  
  
  CONCLUSIONS
  Our data refute the existence of healthy obese phenotypes because IS-obese individuals showed increased cardiometabolic risk. The existence of unhealthy NW phenotypes is supported by their increased risk of incident hyperglycemia, fatty liver, cardiovascular events, and death.
authors.affiliation: Department of Internal Medicine, University of Turin, Turin, Italy. sbo@molinette.piemonte.it
authors.forename: Simona
authors.initials: S
authors.lastname: Bo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Musso
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambino
authors.forename: Paola
authors.initials: P
authors.lastname: Villois
authors.forename: Luigi
authors.initials: L
authors.lastname: Gentile
authors.forename: Marilena
authors.initials: M
authors.lastname: Durazzo
authors.forename: Paolo
authors.initials: P
authors.lastname: Cavallo-Perin
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cassader
mesh_terms: D000410:Alanine Transaminase; D000886:Anthropometry; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D007558:Italy; D016015:Logistic Models; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D011379:Prognosis; D011446:Prospective Studies; D012424:Rural Population; D014280:Triglycerides / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D001786:Blood Glucose; D014280:Triglycerides; D002097:C-Reactive Protein; D002784:Cholesterol; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase