title: Diabetic Retinopathy in Newly Diagnosed Subjects With Type 2 Diabetes Mellitus: Contribution of β-Cell Function.
abstract: OBJECTIVE
  The association of hyperglycemia and diabetic retinopathy (DR) in established type 2 diabetes mellitus (T2DM) subjects is well accepted. However, the association between β-cell responsiveness and insulin sensitivity leading to fasting and postprandial hyperglycemia with DR in newly diagnosed treatment-naïve T2DM subjects remain unreported.
  
  
  METHODS
  A total of 544 newly diagnosed treatment-naïve T2DM subjects were screened for DR (digital photography) and underwent a standardized meal tolerance test. Serial plasma glucose and insulin levels were measured, and fasting (M0) and postprandial β-cell responsiveness calculated Calculating Pancreatic Response Program along with homeostasis model assessment-β cell function (HOMA-B) and HOMA-Insulin Sensitivity. A subgroup of 201 subjects also underwent a frequently sampled IV glucose tolerance test and the acute insulin response to glucose, insulin sensitivity, and glucose effectiveness (SG) estimated (MINMOD model).
  
  
  RESULTS
  A total of 16.5% (90) subjects had DR at diagnosis. Subjects with DR had significantly reduced M0, HOMA-B and SG leading to higher fasting and postprandial (2 hour) glucose and significantly lower fasting and postprandial (2 hour) insulin. Factors independently associated with DR in multivariate logistic regression analysis were M0, HOMA-B, and SG with fasting and postprandial (2 hour) glucose and insulin. There was no statistical difference in glycated hemoglobin, systolic blood pressure, acute insulin response to glucose, and insulin sensitivity between those with or without DR.
  
  
  CONCLUSIONS
  In this cohort of newly diagnosed T2DM subjects, DR is associated with reduced β-cell responsiveness, resulting from β-cell failure rather than insulin resistance, leading to fasting and postprandial hyperglycemia and hypoinsulinemia.
authors.affiliation: Diabetes Research Unit (S.R.C.), Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Cardiff, UK CF14 4XN; Diabetes Research Group (R.L.T., G.J.D., S.D.L., D.R.O.), Swansea University, Singleton Park, Swansea, UK SA2 8PP; Centre for Endocrine and Diabetes Sciences (D.A.R.), Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, UK CF14-4XN; School of Optometry & Vision Sciences (R.V.N.), Cardiff University, Cardiff, UK CF24 4HQ.
authors.forename: Sharmistha
authors.initials: S
authors.lastname: Roy Chowdhury
authors.affiliation: Diabetes Research Unit (S.R.C.), Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Cardiff, UK CF14 4XN; Diabetes Research Group (R.L.T., G.J.D., S.D.L., D.R.O.), Swansea University, Singleton Park, Swansea, UK SA2 8PP; Centre for Endocrine and Diabetes Sciences (D.A.R.), Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, UK CF14-4XN; School of Optometry & Vision Sciences (R.V.N.), Cardiff University, Cardiff, UK CF24 4HQ.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Thomas
authors.affiliation: Diabetes Research Unit (S.R.C.), Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Cardiff, UK CF14 4XN; Diabetes Research Group (R.L.T., G.J.D., S.D.L., D.R.O.), Swansea University, Singleton Park, Swansea, UK SA2 8PP; Centre for Endocrine and Diabetes Sciences (D.A.R.), Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, UK CF14-4XN; School of Optometry & Vision Sciences (R.V.N.), Cardiff University, Cardiff, UK CF24 4HQ.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Dunseath
authors.affiliation: Diabetes Research Unit (S.R.C.), Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Cardiff, UK CF14 4XN; Diabetes Research Group (R.L.T., G.J.D., S.D.L., D.R.O.), Swansea University, Singleton Park, Swansea, UK SA2 8PP; Centre for Endocrine and Diabetes Sciences (D.A.R.), Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, UK CF14-4XN; School of Optometry & Vision Sciences (R.V.N.), Cardiff University, Cardiff, UK CF24 4HQ.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Peter
authors.affiliation: Diabetes Research Unit (S.R.C.), Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Cardiff, UK CF14 4XN; Diabetes Research Group (R.L.T., G.J.D., S.D.L., D.R.O.), Swansea University, Singleton Park, Swansea, UK SA2 8PP; Centre for Endocrine and Diabetes Sciences (D.A.R.), Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, UK CF14-4XN; School of Optometry & Vision Sciences (R.V.N.), Cardiff University, Cardiff, UK CF24 4HQ.
authors.forename: D Aled
authors.initials: DA
authors.lastname: Rees
authors.affiliation: Diabetes Research Unit (S.R.C.), Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Cardiff, UK CF14 4XN; Diabetes Research Group (R.L.T., G.J.D., S.D.L., D.R.O.), Swansea University, Singleton Park, Swansea, UK SA2 8PP; Centre for Endocrine and Diabetes Sciences (D.A.R.), Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, UK CF14-4XN; School of Optometry & Vision Sciences (R.V.N.), Cardiff University, Cardiff, UK CF24 4HQ.
authors.forename: Rachel V
authors.initials: RV
authors.lastname: North
authors.affiliation: Diabetes Research Unit (S.R.C.), Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Cardiff, UK CF14 4XN; Diabetes Research Group (R.L.T., G.J.D., S.D.L., D.R.O.), Swansea University, Singleton Park, Swansea, UK SA2 8PP; Centre for Endocrine and Diabetes Sciences (D.A.R.), Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, UK CF14-4XN; School of Optometry & Vision Sciences (R.V.N.), Cardiff University, Cardiff, UK CF24 4HQ.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Luzio
authors.affiliation: Diabetes Research Unit (S.R.C.), Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Cardiff, UK CF14 4XN; Diabetes Research Group (R.L.T., G.J.D., S.D.L., D.R.O.), Swansea University, Singleton Park, Swansea, UK SA2 8PP; Centre for Endocrine and Diabetes Sciences (D.A.R.), Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, UK CF14-4XN; School of Optometry & Vision Sciences (R.V.N.), Cardiff University, Cardiff, UK CF24 4HQ.
authors.forename: David R
authors.initials: DR
authors.lastname: Owens
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000473:pathology*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012160:Retina / Q000473:pathology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose