Normalization of Lipoprotein Composition by Intraperitoneal Insulin in IDDM: Role of increased hepatic lipase activity

Ruotolo, Giacomo; Parlavecchia, Mariella; Taskinen, Marja‐Riitta; Galimberti, Gloria; Zoppo, Adele; Le, Ngoc‐Anh; Ragogna, Francesca; Micossi, P.; Pozza, G.

doi:10.2337/diacare.17.1.6

Cited by 62 publications

(48 citation statements)

References 31 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…46 ' 47 When this type of technology was applied and both fasting and 24-hour free insulin levels were lowered, we did in fact observe a decline in the absolute and specific activity of LPL. In addition, we found a trend toward increases in HTGL during IP treatment, suggesting that IP insulin delivery may have stimulated the activity of hepatic lipase as Ruotolo et al 48 have reported in similarly treated IDDM patients. It is also possible that IP insulin increased the metabolic clearance rate of LPL.…”

Section: Discussionsupporting

confidence: 80%

Intraperitoneal insulin therapy corrects abnormalities in cholesteryl ester transfer and lipoprotein lipase activities in insulin-dependent diabetes mellitus.

Bagdade

Dunn

Eckel

et al. 1994

Arterioscler Thromb

View full text Add to dashboard Cite

Patients with insulin-dependent diabetes mellitus (IDDM) have proatherogenic disturbances in cholesteryl ester transfer (GET) despite intensive subcutaneous insulin therapy (ISC). Since CET is activated by insulin-sensitive lipoprotein lipase (LPL), which normally increases postprandially, we queried whether iatrogenic hyperinsulinism from ISC stimulated LPL and CET by studying well-controlled IDDM patients after ISC and then 6 months after lowering systemic insulin levels by intraperitoneal (IP) insulin delivery. Although glycemic control (HbA,c IDDM, 6.9±1.7%; control, 4.5% to 8%) was excellent during ISC, CET was accelerated (P<.001) and both systemic insulin levels and LPL specific activity were increased (P< .05). Following IP, basal systemic insulin levels declined by more than one half (ISC, 8.22±6.5 versus IP, 2.77±2.4 ^iU/mL; mean±SD; P<.025), and both LPL and CET activities returned to normal. Plasma triglyceride, cholesterol, high-density lipoprotein-2 (HDL 2 ) cholesterol, HDL, cholesterol, cholesteryl ester transfer protein mass, and glyce-A ssiduous diabetic management can reduce the /\ prevalence of the renal and retinal microvascu-.Z \-lar and neuropathic complications of insulindependent diabetes mellitus (IDDM) 12 but not the premature morbidity and mortality attributable to cardiovascular disease. The failure of rigorous glycemic control achieved with multiple daily injections of insulin to slow the development of diabetic macrovascular disease has led to the suspicion that the hyperinsulinemia that inevitably results from insulin therapy might actually promote atherogenesis. C 1994 American Heart Association, Inc.mic control (HbA,c, 6.3±0.8%) were unchanged and remained normal. These findings indicate that ISC is associated with high levels of basal CET and LPL. These alterations both appear to be closely linked to iatrogenic hyperinsulinemia resulting from ISC. The fact that they are both reversed when systemic insulin levels are reduced by IP suggests that insulin, acting through LPL, influences the nature of the interaction of the lipoproteins engaged in CET. Since accelerated CET is believed to result in the enrichment of certain subpopulations of apolipoprotein B-containing lipoproteins with cholesteryl ester, an alteration presumed to enhance their atherogenicity, its correction by IP therapy suggests that this more physiological mode of insulin delivery may reduce cardiovascular risk in IDDM. (Arterioscler Thromb. 1994;14:1933-1939

show abstract

Section: Discussionsupporting

confidence: 80%

Intraperitoneal insulin therapy corrects abnormalities in cholesteryl ester transfer and lipoprotein lipase activities in insulin-dependent diabetes mellitus.

Bagdade

Dunn

Eckel

et al. 1994

Arterioscler Thromb

View full text Add to dashboard Cite

show abstract

“…Alternatively, a low VLDL triglycerides : apoB ratio could be attributable to increased lipoprotein lipase (LPL) activity. However, in several studies, type 1 diabetic patients and control subjects have been shown to have similar levels of LPL activity [22][23][24]. Moreover, if LPL activity were increased in type 1 diabetes mellitus, VLDL catabolism would be expected to be accelerated; however, this was not observed in the present study.…”

Section: Discussioncontrasting

confidence: 59%

Normal metabolism of apolipoprotein B100-containing lipoproteins despite qualitative abnormalities in type 1 diabetic men

et al. 2005

View full text Add to dashboard Cite

Aims/hypothesis: Type 1 diabetic subjects are at increased risk of cardiovascular disease and exhibit multiple qualitative abnormalities of apolipoprotein (apo) B100-containing lipoproteins. This stable isotope kinetic experiment was designed to study whether these abnormalities are associated with changes in the synthesis and fractional catabolic rates of VLDL-, IDL-and LDLapoB100. Methods: Using a bolus followed by a 16-h constant infusion of 13 C-leucine, we performed a kinetic study in eight men with type 1 diabetes treated with a continuous subcutaneous insulin infusion administered by an external pump and in seven healthy men, in the fed state. Results: The mean HbA 1 c level in the type 1 diabetic patients was 8.00±1.48%. Plasma triglyceride, and total, LDL and HDL cholesterol levels were similar in patients and control subjects. VLDL were less triglyceride rich in type 1 diabetic patients than in control subjects (VLDL triglyceride : apoB 6.91±0.81 vs 8.29±1.24 mmol/ g, p=0.05). Conversely, the IDL and LDL of the type 1 diabetic patients contained relatively higher levels of triglycerides (IDL triglycerides : apoB 2.16±0.36 vs 1.57± 0.30 mmol/g, p<0.01; LDL triglycerides : apoB 0.27±0.06 vs 0.16±0.04 mmol/g, p<0.05). The apoB100 pool size, production and fractional catabolic rates in the two groups of subjects were similar for all lipoprotein fractions. Conclusions/interpretation: Despite qualitative abnormalities, especially abnormalities of triglyceride content, the metabolism of apoB100-containing lipoproteins is not altered in type 1 diabetic men with fair glycaemic control with continuous subcutaneous insulin infusion. The high risk of atherosclerosis in these patients cannot be explained by kinetic abnormalities of apoB100-containing lipoproteins.

show abstract

“…Although VLDL subfractions and hepatic lipase activity were not measured in our study, it seems reasonable that similar changes explain the differences we found in postprandial lipaemia between insulin aspart and repaglinide treatment as both repaglinide and sulphonylureas are considered to exclusively act as insulin secretagogues [44]. In a study by Ruotolo et al intraperitoneal insulin administration to patients with type 1 diabetes increased hepatic lipase activity, which is in support of this concept [45]. Our results showed a tendency towards lower postprandial FFA levels during insulin aspart than during repaglinide treatment, which suggest a decrease in FFA flux to the liver causing a lower hepatic TG production.…”

Section: Discussionsupporting

confidence: 83%

Differential lipid profile and hormonal response in type 2 diabetes by exogenous insulin aspart versus the insulin secretagogue repaglinide, at the same glycemic control

Chisalita

Lindström

Jennersjö³

et al. 2008

Acta Diabetol

View full text Add to dashboard Cite

65.0 ± 4.1 years (mean ± SE), body weight 82.5 ± 5.0 kg, BMI (body mass index) 27.7 ± 1.5 kg/m 2 were treated for 10 weeks with repaglinide or insulin aspart in a randomized, cross-over study. At the end of each treatment a 24-h metabolic profile was performed. Blood glucose, Cpeptide, free human insulin, free total (human and analogue) insulin, proinsulin, IAPP, IGF-I, IGFBP-1 (IGF binding protein-1), GHBP (growth hormone binding protein) and plasma lipoprotein concentrations were measured. Similar 24-h blood glucose profiles were obtained with repaglinide and insulin aspart treatment. During the repaglinide treatment the meal related peaks of C-peptide and free human insulin were about twofold higher than during treatment with insulin aspart. Proinsulin, GHBP were higher and IAPP levels tended to be higer during repaglinide compared to insulin aspart. Postprandial plasma total cholesterol, triglycerides and apolipoprotein B concentrations were higher on repaglinide than on insulin aspart treatment.Our results show that, at the same glycaemic control, treatment with exogenous insulin aspart in comparison with the insulin secretagogue repaglinide result in a lower endogenous insulin secretion, and a tendency towards a less atherogenic postprandial lipid profile.

show abstract

Normalization of Lipoprotein Composition by Intraperitoneal Insulin in IDDM: Role of increased hepatic lipase activity

Cited by 62 publications

References 31 publications

Intraperitoneal insulin therapy corrects abnormalities in cholesteryl ester transfer and lipoprotein lipase activities in insulin-dependent diabetes mellitus.

Intraperitoneal insulin therapy corrects abnormalities in cholesteryl ester transfer and lipoprotein lipase activities in insulin-dependent diabetes mellitus.

Normal metabolism of apolipoprotein B100-containing lipoproteins despite qualitative abnormalities in type 1 diabetic men

Differential lipid profile and hormonal response in type 2 diabetes by exogenous insulin aspart versus the insulin secretagogue repaglinide, at the same glycemic control

Contact Info

Product

Resources

About