title: Insulin sensitivity and β-cell function in normoglycemic offspring of individuals with type 2 diabetes mellitus: Impact of line of inheritance.
abstract: OBJECTIVE
  The aim was to study the effect of family history of type 2 diabetes mellitus (T2DM) on insulin sensitivity and β-cell function in normoglycemic offspring.
  
  
  METHODS
  Offspring of T2DM patients (cases) and individuals without family history of T2DM (controls) were the subjects for this cross-sectional study. All participants underwent 75 g OGTT and samples were collected for plasma insulin, C-peptide, and proinsulin at 0, 30, 60, and 120 minutes.
  
  
  RESULTS
  A total of 271 cases (age 22 ± 10 years; 53% males) and 259 controls (28 ± 10 years, 66% males) were enrolled for the study. BMI, plasma insulin, C-peptide, proinsulin, HOMA-IR, and insulinogenic index (0-120) were significantly higher and whole-body insulin sensitivity (WBISI) and disposition index (0-120) [DI 120] were lower in cases compared to controls. After adjusting for BMI, proinsulin at 120 minutes, area under the curve (AUC) of proinsulin (during OGTT) and AUC proinsulin/AUC C-peptide were significantly higher in cases. Cases were subdivided into four groups according to inheritance pattern; paternal DM (PDM), maternal DM (MDM), grandparental DM (GPDM), and both parents DM (BPDM). The magnitude of differences varied with relationship (greater when both parents and grandparents were affected). Mean HOMA-IR was higher by 127% and 50% and DI 120 was lower by 33% and 18% (adjusted for age and gender) in the BPDM and GPDM groups respectively compared to controls.
  
  
  CONCLUSIONS
  We observed higher BMI, plasma insulin, C-peptide, and proinsulin and lower insulin sensitivity and β-cell compensation in normoglycemic offspring of T2DM subjects compared to controls. Differences were greater when both parents and grandparents had T2DM.
authors.affiliation: Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Edavan P
authors.initials: EP
authors.lastname: Praveen
authors.forename: Jayaprakash
authors.initials: J
authors.lastname: Sahoo
authors.forename: Madan L
authors.initials: ML
authors.lastname: Khurana
authors.forename: Bindu
authors.initials: B
authors.lastname: Kulshreshtha
authors.forename: Rajesh
authors.initials: R
authors.lastname: Khadgawat
authors.forename: Nandita
authors.initials: N
authors.lastname: Gupta
authors.forename: Sada Nand
authors.initials: SN
authors.lastname: Dwivedi
authors.forename: Guresh
authors.initials: G
authors.lastname: Kumar
authors.forename: Dorairaj
authors.initials: D
authors.lastname: Prabhakaran
authors.forename: Ariachery C
authors.initials: AC
authors.lastname: Ammini