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Lower HDL, ApoA-I levels may signal glycemic deterioration in type 2 diabetes
In patients with type 2 diabetes, lower HDL cholesterol levels and a lower HDL cholesterol/apolipoprotein A-I ratio are predictive of long-term glycemic deterioration as measured by time to initiation of glucose control treatment, according to study results.
Lower levels of HDL cholesterol (HDL-C) and HDL-C/ApoA-I predicted an earlier and more urgent need for drug-assisted glucose control.
In the study, researchers evaluated 9,785 adults who were enrolled in the FIELD trial, a randomized controlled evaluation of fenofibrate therapy in patients with type 2 diabetes. After taking baseline measurements of fasting blood HDL-C, ApoA-I, plasma glucose, serum insulin and HbA1c, the researchers calculated the HDL-C/ApoA-I ratio. For patients not on an exogenous insulin regimen, the researchers utilized homeostasis-model assessment to determine pancreatic beta-cell secretion (HOMA-B) and insulin resistance (HOMA-IR). The researchers calculated baseline age- and gender-adjusted associations between the HDL-related variables and glycemic variables. Among patients on a lifestyle regimen only (n=2,608), researchers used Cox proportional hazards analysis to assess correlations of HDL-C, ApoA-I and HDL-C/ApoA-I within a regimen of oral hypoglycemic agents or insulin.
After adjusting for age and gender, the investigators discovered an inverse correlation between baseline HDL-C (r=–0.233), ApoA-I (r=–0.134) and HDL-C/ApoA-I (r=–0.23) and HOMA-IR (all P<.001) but no relationship between these variables and HbA1c (all P>.05). Adjustment for age, gender and HOMA-IR also revealed an inverse association between ApoA-I and HOMA-B (r= 0.063; P=.002). Prospective analysis found that lower baseline HDL-C and HDL-C/ApoA-I levels predicted greater utilization (per 1-standard deviation lower: HR=1.13; 95% CI, 1.07–1.19) and more rapid uptake (median 12.9 months vs. 24 months) of oral hypoglycemic agents and insulin, with no difference in annual increases in HbA1c(P=.87 and P=.81). Although both of these correlations were attenuated by adjustment for HOMA-IR and triglycerides, HDL-C/ApoA-I continued to be significant after adjustment.
According to the researchers, the apparent predictive effect of lower HDL-C and lower HDL-C/ApoA-I ratio on pharmacologic treatment uptake is particularly noteworthy because there were no significant baseline associations found between HDL-related parameters and HbA1c levels.
“The inverse association of progression to pharmacologic glucose control with HDL-C/ApoA-I, which estimates HDL sizes, persists after adjustment for multiple metabolic and lifestyle factors,” the researchers wrote. “The results are thus consistent with the emerging concept that HDL biology may play a direct role in the development and progression of type 2 diabetes.”
Disclosure: The researchers reported no relevant financial disclosures.