Heterogeneous behavior of lipids according to HbA1(c) levels undermines the plausibility of metabolic syndrome in type 1 diabetes: data from a nationwide multicenter survey

BACKGROUND: Cardiovascular risk factors (CVRF) may cluster in type 1 diabetes, analogously to the metabolic syndrome described in type 2 diabetes. The threshold of HbA1(c) above which lipid variables start changing behavior is unclear. This study aims to 1) assess the behavior of dyslipidemia according to HbA1(c) values; 2) detect a threshold of HbA1(c) beyond which lipids start to change and 3) compare the clustering of lipids and other non-lipid CVRF among strata of HbA1(c) individuals with type 1 diabetes. METHODS: Effects of HbA1(c) 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 HbA1(c) quintiles, respectively. Hypertriglyceridemia increased in the 5th quintile of HbA1(c), 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 HbA1(c) quintiles, respectively. HDL-cholesterol correlated positively (0.437) with HbA1(c) in the 3rd quintile. HDL-cholesterol and insulin dose correlated inversely in all levels of glycemic control. CONCLUSIONS: Correlation of serum lipids with HbA1(c) is heterogeneous across the spectrum of glycemic control in type 1 diabetes individuals. LDL-cholesterol and triglycerides worsened alongside HbA1(c) 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 HbA1(c), refuting a unified explanation for cardiovascular risk in type 1 diabetes.