High-density lipoprotein subspecies between patients with type 1 diabetes and type 2 diabetes without / with intensive insulin therapy

Fukui, Tetsuya; Hirano, Tsutomu

doi:10.1507/endocrj.ej11-0329

Cited by 16 publications

(10 citation statements)

References 30 publications

(30 reference statements)

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“…Our data is in agreement with a previous study which has reported that intensive insulin therapy is associated with increased large buoyant HDL subspecies in type 2 diabetic patients [32]. The observed increase in both LDL-1 and large HDL fractions following insulin therapy may be attributed to the reduction in circulating triglycerides.…”

Section: Discussionsupporting

confidence: 93%

Effect of insulin analog initiation therapy on LDL/HDL subfraction profile and HDL associated enzymes in type 2 diabetic patients

2013

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BackgroundInsulin treatment can lead to good glycemic control and result in improvement of lipid parameters in type 2 diabetic patients. This study was designed to evaluate the effect of insulin analog initiation therapy on low-density lipoprotein (LDL)/ high-density lipoprotein (HDL) sub-fractions and HDL associated enzymes in type 2 diabetic patients during early phase.MethodsTwenty four type 2 diabetic patients with glycosylated hemoglobin (HbA1c) levels above 10% despite ongoing combination therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs (0.4 U/kg/day) plus metformin. Glycemic profiles were determined over 72 hours by continuous glucose monitoring system (CGMS) and blood samples were obtained from all patients at 24 and 72 hours. Plasma levels of cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-I) were determined by enzyme-linked immunosorbent assay (ELISA). Measurement of CETP and LCAT activity was performed via fluorometric analysis. Paraoxonase (PON1) enzyme activity was assessed from the rate of enzymatic hydrolysis of phenyl acetate to phenol formation. LDL and HDL subfraction analysis was done by continuous disc polyacrylamide gel electrophoresis.ResultsMean blood glucose, total cholesterol (TC), triglyceride (TG) and very low-density lipoprotein cholesterol (VLDL-C) levels were significantly decreased while HDL-C levels were significantly increased after insulin treatment. Although LDL-C levels were not significantly different before and after insulin initiation therapy a significant increase in LDL-1 subgroup and a significant reduction in atherogenic LDL-3 and LDL-4 subgroups were observed. Insulin analog initiation therapy caused a significant increase in HDL-large, HDL- intermediate and a significant reduction in HDL-small subfractions. CETP protein level and activity was significantly increased while apoB levels were significantly decreased following insulin analog initiation therapy. No significant difference was found in LCAT mass, LCAT activity, apoA-I and PON-1 arylesterase levels following insulin initiation therapy.ConclusionThese findings indicate that insulin analog initiation therapy activates lipid metabolism via up-regulating CETP and shows anti-atherogenic effects by increasing HDL-large and decreasing LDL-3 and LDL-4 subfractions in a short time period.

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Section: Discussionsupporting

confidence: 93%

Effect of insulin analog initiation therapy on LDL/HDL subfraction profile and HDL associated enzymes in type 2 diabetic patients

2013

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“…This was not observed in men, most likely due to higher smoker representation, but also because of worse glycaemic compensation (evaluated by HbA1c) when compared to women. The increase of HDL-C after switch on intensified insulin treatment in T1D patients was also observed by other authors [26-28] and recently also in T2D patients as shown in the OpT2mise study [29]. …”

Section: Discussionsupporting

confidence: 81%

Insulin Pump Therapy – Influence on Body Fat Redistribution, Skeletal Muscle Mass and Ghrelin, Leptin Changes in T1D Patients

et al. 2018

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Background: To report changes in body composition and biochemical parameters in patients with type 1 diabetes mellitus (T1D) after switching from multiple daily injection (MDI) to continuous subcutaneous insulin infusion (CSII). Methods: 31 patients switched over from MDI to CSII. Body composition, biochemical parameters, glycaemic variability (GV) and level of physical activity were evaluated before and 6 months on CSII. Results: In both sexes, we found an increase in skeletal muscle mass (SMM), (p = 0.008; 0.008). In men, there was mainly a decrease in visceral fat area (VFA), (p = 0.028) and in women there was decrease of total body fat (TBF), (p = 0.020) and non-significant decrease of VFA (p = 0.098). SMM inversely correlated with VFA in men (p = –0.001) and with TBF in women (p = –0.005 ). GV was decreased generally and correlated inversely with TBF in men only (p = –0.026). Physical activity was increased and correlated inversely with VFA in men (p = –0.002) and in women (p = –0.006). Conclusions: Using CSII in T1D leads to a significant increase of SMM in both sexes to a decrease of VFA in men and to a non-significant decrease of VFA in women. Changes in adipose tissue and SMM were also related to increased physical activity and to decreased GV.

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“…Okazaki et al also reported that large HDL-C levels were inversely associated with visceral fat area 74 ) . Patients with type 1 diabetes treated with insulin had higher HDL2-C than type 2 diabetes, and insulin-treated type 2 diabetes had higher HDL2-C levels than non-insulin-treated type 2 diabetes 88 ) . These results suggest that exogenous insulin increases HDL2-C, and conversely insulin resistance blunts the raising effect of insulin on HDL2-C levels.…”

Section: Hdl Heterogeneitymentioning

confidence: 96%

Pathophysiology of Diabetic Dyslipidemia

Hirano

2018

J Atheroscler Thromb

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361

235

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Accumulating clinical evidence has suggested serum triglyceride (TG) is a leading predictor of atherosclerotic cardiovascular disease, comparable to low-density lipoprotein (LDL)-cholesterol (C) in populations with type 2 diabetes, which exceeds the predictive power of hemoglobinA1c. Atherogenic dyslipidemia in diabetes consists of elevated serum concentrations of TG-rich lipoproteins (TRLs), a high prevalence of small dense low-density lipoprotein (LDL), and low concentrations of cholesterol-rich high-density lipoprotein (HDL)2-C. A central lipoprotein abnormality is an increase in large TG-rich very-low-density lipoprotein (VLDL)1, and other lipoprotein abnormalities are metabolically linked to increased TRLs. Insulin critically regulates serum VLDL concentrations by suppressing hepatic VLDL production and stimulating VLDL removal by activation of lipoprotein lipase. It is still debated whether hyperinsulinemia compensatory for insulin resistance is causally associated with the overproduction of VLDL. This review introduces experimental and clinical observations revealing that insulin resistance, but not hyperinsulinemia stimulates hepatic VLDL production. LDL and HDL consist of heterogeneous particles with different size and density. Cholesterol-depleted small dense LDL and cholesterol-rich HDL2 subspecies are particularly affected by insulin resistance and can be named “Metabolic LDL and HDL,” respectively. We established the direct assays for quantifying small dense LDL-C and small dense HDL(HDL3)-C, respectively. Subtracting HDL3-C from HDL-C gives HDL2-C. I will explain clinical relevance of measurements of LDL and HDL subspecies determined by our assays. Diabetic kidney disease (DKD) substantially worsens plasma lipid profile thereby potentiated atherogenic risk. Finally, I briefly overview pathophysiology of dyslipidemia associated with DKD, which has not been so much taken up by other review articles.

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High-density lipoprotein subspecies between patients with type 1 diabetes and type 2 diabetes without / with intensive insulin therapy

Cited by 16 publications

References 30 publications

Effect of insulin analog initiation therapy on LDL/HDL subfraction profile and HDL associated enzymes in type 2 diabetic patients

Effect of insulin analog initiation therapy on LDL/HDL subfraction profile and HDL associated enzymes in type 2 diabetic patients

Insulin Pump Therapy – Influence on Body Fat Redistribution, Skeletal Muscle Mass and Ghrelin, Leptin Changes in T1D Patients

Pathophysiology of Diabetic Dyslipidemia

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