title: Heterogeneous behavior of lipids according to HbA1c levels undermines the plausibility of metabolic syndrome in type 1 diabetes: data from a nationwide multicenter survey.
abstract: BACKGROUND
  Cardiovascular risk factors (CVRF) may cluster in type 1 diabetes, analogously to the metabolic syndrome described in type 2 diabetes. The threshold of HbA1c above which lipid variables start changing behavior is unclear. This study aims to 1) assess the behavior of dyslipidemia according to HbA1c values; 2) detect a threshold of HbA1c beyond which lipids start to change and 3) compare the clustering of lipids and other non-lipid CVRF among strata of HbA1c individuals with type 1 diabetes.
  
  
  METHODS
  Effects of HbA1c quintiles (1st: ≤7.4%; 2nd: 7.5-8.5%; 3rd: 8.6-9.6%; 4th: 9.7-11.3%; and 5th: >11.5%) and covariates (gender, BMI, blood pressure, insulin daily dose, lipids, statin use, diabetes duration) on dyslipidemia were studied in 1275 individuals from the Brazilian multi-centre type 1 diabetes study and 171 normal controls.
  
  
  RESULTS
  Body size and blood pressure were not correlated to lipids and glycemic control. OR (99% CI) for high-LDL were 2.07 (1.21-3.54) and 2.51 (1.46-4.31), in the 4th and 5th HbA1c quintiles, respectively. Hypertriglyceridemia increased in the 5th quintile of HbA1c, OR 2.76 (1.20-6.37). OR of low-HDL-cholesterol were 0.48 (0.24-0.98) and 0.41 (0.19-0.85) in the 3rd and 4th HbA1c quintiles, respectively. HDL-cholesterol correlated positively (0.437) with HbA1c in the 3rd quintile. HDL-cholesterol and insulin dose correlated inversely in all levels of glycemic control.
  
  
  CONCLUSIONS
  Correlation of serum lipids with HbA1c is heterogeneous across the spectrum of glycemic control in type 1 diabetes individuals. LDL-cholesterol and triglycerides worsened alongside HbA1c with distinct thresholds. Association of lower HDL-cholesterol with higher daily insulin dose is consistent and it points out to a role of exogenous hyperinsulinemia in the pathophysiology of the CVRF clustering. These data suggest diverse pathophysiological processes depending on HbA1c, refuting a unified explanation for cardiovascular risk in type 1 diabetes.
authors.affiliation: Centro de Endocrinologia do Estado da Bahia, Salvador, Brazil. fernando.giuffrida@me.com
authors.forename: Fernando M A
authors.initials: FM
authors.lastname: Giuffrida
authors.forename: Alexis D
authors.initials: AD
authors.lastname: Guedes
authors.forename: Eloa R
authors.initials: ER
authors.lastname: Rocco
authors.forename: Denise B
authors.initials: DB
authors.lastname: Mory
authors.forename: Patricia
authors.initials: P
authors.lastname: Dualib
authors.forename: Odelisa S
authors.initials: OS
authors.lastname: Matos
authors.forename: Reine M
authors.initials: RM
authors.lastname: Chaves-Fonseca
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Cobas
authors.forename: Carlos Antonio
authors.initials: CA
authors.lastname: Negrato
authors.forename: Marilia B
authors.initials: MB
authors.lastname: Gomes
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Dib
mesh_terms: D000293:Adolescent; D000328:Adult; D001938:Brazil; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications*; D050171:Dyslipidemias / Q000097:blood / Q000150:complications; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000150:complications*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D006442:Glycated Hemoglobin; D008055:Lipids; C517652:hemoglobin A1c protein, human