HDL Composition Predicts New-Onset Cardiovascular Disease in Patients With Type 1 Diabetes

Groop, Per Henrik; Thomas, Merlin C; Rosengård-Bärlund, Milla; Mills, Vashti; Rönnback, Mats; Thomas, Stephen; Forsblom, Carol; Taskinen, Marja‐Riitta; Viberti, Giancarlo

doi:10.2337/dc07-0030

Cited by 24 publications

(13 citation statements)

References 12 publications

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“…The impact of ApoA-II and small dense HDL particles on atherosclerosis have been controversial [21][22][23], but it has been speculated that HDL particles containing both ApoA-I and ApoA-II (lipoprotein (Lp)A-I-A-II) would be less effective than particles containing ApoA-I (LpA-I), with respect to reverse cholesterol transport [24,25]. Also, an association between new cardiovascular events and a decreased ratio of LpA-I to LpA-I-A-II particles was observed in patients with type 1 diabetes [26]. In severe renal disease HDL 3 -cholesterol and ApoA-II levels are often reduced, as also [15].…”

Section: Discussionmentioning

confidence: 99%

Lipid abnormalities predict progression of renal disease in patients with type 1 diabetes

et al. 2009

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Aims/hypothesis We studied the impact of baseline lipid variables on the progression of renal disease in a large nationwide prospective cohort of patients with type 1 diabetes. Methods A total of 2,304 adult patients with type 1 diabetes and available lipid profiles participating in the Finnish Diabetic Nephropathy Study (FinnDiane) were evaluated. Data on progression of renal disease were verified from medical files and patients were followed for 5.4±2.0 (mean ± SD) years. Results High triacylglycerol, apolipoprotein (Apo) B, ApoA-II and HDL 3 -cholesterol concentrations predicted incident microalbuminuria. Progression to macroalbuminuria was predicted by high triacylglycerol and ApoB. When AER was entered into the model, triacylglycerol was no longer an independent predictor, but when patients with normal AER and microalbuminuria at baseline were pooled, triacylglycerol, HbA 1c , male sex and AER were all independent predictors of renal disease. High total cholesterol, LDLcholesterol, non-HDL-cholesterol and triacylglycerol as well as low HDL-cholesterol, HDL 2 -cholesterol, ApoA-I and ApoA-II concentrations were predictive of progression to end-stage renal disease. However, when estimated GFR was entered into the model, only total cholesterol remained an independent predictor of progression. Conclusions/interpretation Lipid abnormalities, particularly high triacylglycerol concentrations, increase the risk of progression of renal disease.

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Section: Discussionmentioning

confidence: 99%

Lipid abnormalities predict progression of renal disease in patients with type 1 diabetes

et al. 2009

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“…Lipid abnormalities have been previously linked with diabetic kidney disease [ 31 - 33 ] and low HDL and high IDL have been implicated in cardiovascular risk [ 34 - 36 ]. In this study, the estimated IDL cholesterol had the strongest link with albuminuria, which is concordant with a mortality analysis of the same dataset [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Network of vascular diseases, death and biochemical characteristics in a set of 4,197 patients with type 1 diabetes (The FinnDiane Study)

Mäkinen

Forsblom

Thorn

et al. 2009

Cardiovasc Diabetol

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Background: Cardiovascular disease is the main cause of premature death in patients with type 1 diabetes. Patients with diabetic kidney disease have an increased risk of heart attack or stroke. Accurate knowledge of the complex interdependencies between the risk factors is critical for pinpointing the best targets for research and treatment. Therefore, the aim of this study was to describe the association patterns between clinical and biochemical features of diabetic complications.Methods: Medical records and serum and urine samples of 4,197 patients with type 1 diabetes were collected from health care centers in Finland. At baseline, the mean diabetes duration was 22 years, 52% were male, 23% had kidney disease (urine albumin excretion over 300 mg/24 h or end-stage renal disease) and 8% had a history of macrovascular events. All-cause mortality was evaluated after an average of 6.5 years of follow-up (25,714 patient years). The dataset comprised 28 clinical and 25 biochemical variables that were regarded as the nodes of a network to assess their mutual relationships. Results:The networks contained cliques that were densely inter-connected (r > 0.6), including cliques for high-density lipoprotein (HDL) markers, for triglycerides and cholesterol, for urinary excretion and for indices of body mass. The links between the cliques showed biologically relevant interactions: an inverse relationship between HDL cholesterol and the triglyceride clique (r < -0.3, P < 10 -16 ), a connection between triglycerides and body mass via C-reactive protein (r > 0.3, P < 10 -16 ) and intermediate-density cholesterol as the connector between lipoprotein metabolism and albuminuria (r > 0.3, P < 10 -16 ). Aging and macrovascular disease were linked to death via working ability and retinopathy. Diabetic kidney disease, serum creatinine and potassium, retinopathy and blood pressure were inter-connected. Blood pressure correlations indicated accelerated vascular aging in individuals with kidney disease (P < 0.001). Conclusion:The complex pattern of links between diverse characteristics and the lack of a single dominant factor suggests a need for multifactorial and multidisciplinary paradigms for the research, treatment and prevention of diabetic complications.

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“…Regarding HDL, not only quantitative, but also qualitative and compositional alterations are related to its antiatherogenic properties (13)(14)(15)(16). In particular, circulating HDL 2 was found to protect from atherosclerosis (17,18).…”

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confidence: 99%

Fatty Liver Is Independently Associated With Alterations in Circulating HDL2 and HDL3 Subfractions

Kantartzis

Rittig²,

Cegan³

et al. 2008

Diabetes Care

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Fatty liver is associated with insulin resistance, atherosclerosis, and the metabolic syndrome (1-7) and predicts future cardiovascular events (4 -8).The pro-atherogenic serum lipid profile in subjects with fatty liver is characterized by elevated levels of triglycerides, low HDL cholesterol, and an increase in small dense LDL particles (9 -12). Regarding HDL, not only quantitative, but also qualitative and compositional alterations are related to its antiatherogenic properties (13-16). In particular, circulating HDL 2 was found to protect from atherosclerosis (17,18). In the present study, we first investigated whether fatty liver is associated with altered circulating HDL cholesterol subfractions and second whether this relationship is independent of insulin sensitivity, thus possibly representing a direct link between fatty liver and cardiovascular disease.RESEARCH DESIGN AND METHODS -In our ongoing study on the pathophysiology of type 2 diabetes, ϳ300 Caucasians were carefully characterized for fatty liver and its associated metabolic characteristics (19). To select a subgroup that was representative for the percentage of subjects having fatty liver (liver fat Ͼ5.56%) (20) in our large cohort (ϳ40%) and in whom enough sample volume was available to measure the HDL cholesterol subfractions, we randomly selected 8 men and 8 women with fatty liver and 24 control subjects.The subjects underwent a 75-g oral glucose tolerance test to exclude diabetes and calculate insulin sensitivity (21). Total body fat was measured by bioelectrical impedance, visceral fat by magnetic resonance (MR) tomography, and liver fat by 1 H-MR spectroscopy (19). Serum total, HDL, and LDL cholesterol, as well as triglyceride concentrations, were measured by standard colorimetry, plasma adiponectin by radioimmunoassay, and apolipoprotein (apo)B 100 and apoA-I by immunonephelometry. Circulating HDL 2 and HDL 3 cholesterol levels were quantified after ultracentrifugation of 1.5 ml serum (22), and the fatty acid pattern of these subfractions was determined by gas chromatography (23) within the entire particle, thereafter, in a subgroup of 34 subjects in whom sufficient sample volume was available after ultracentrifugation and chemical derivatization. A total of 15 subjects had fatty liver, and 19 were control subjects. Intima-media thickness (IMT) of the carotid artery was measured by high-resolution ultrasound. Relationships between parameters were tested using univariate correlations, and multivariate linear regression models were used to investigate independent relationships. P Յ 0.05 was considered statistically significant.RESULTS -Altogether, 25 women and 15 men were studied. While age (P ϭ 0.08) and total body fat (P ϭ 0.23) were not different between subjects with fatty liver and control subjects, individuals with fatty liver had higher body weight (P ϭ 0.02), BMI (P ϭ 0.002), waist circumference (P ϭ 0.003), and visceral fat (P Ͻ 0.0001), as well as higher IMT (P ϭ 0.04). Furthermore, they had higher fasting (P ϭ 0.006) and 2-h (P ϭ 0...

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HDL Composition Predicts New-Onset Cardiovascular Disease in Patients With Type 1 Diabetes

Cited by 24 publications

References 12 publications

Lipid abnormalities predict progression of renal disease in patients with type 1 diabetes

Lipid abnormalities predict progression of renal disease in patients with type 1 diabetes

Network of vascular diseases, death and biochemical characteristics in a set of 4,197 patients with type 1 diabetes (The FinnDiane Study)

Fatty Liver Is Independently Associated With Alterations in Circulating HDL2 and HDL3 Subfractions

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