Effects of intraperitoneal versus subcutaneous insulin administration on lipoprotein metabolism in type I diabetes

Ruotolo, Giacomo; Micossi, P.; Galimberti, Gloria; Librenti, M. C.; Petrella, Giovanna; Marcovina, Santica M.; Pozza, G.; Howard, Barbara V.

doi:10.1016/0026-0495(90)90025-8

Cited by 43 publications

(23 citation statements)

References 43 publications

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“…31 That virtually the same HbA]C and integrated 24-hour blood glucose levels observed after ISC were maintained with the same total dose of insulin given by IP delivery despite a substantial reduction in circulating insulin levels is consistent with the occurrence of normal hepatic extraction of insulin.…”

Section: Discussionsupporting

confidence: 52%

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

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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

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Section: Discussionsupporting

confidence: 52%

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

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“…In type 2 diabetes insulin appears unable to inhibit acutely the release of VLDL1 from the liver, despite efficient suppression of serum NEFA [23]. However, the decrease in circulating VLDL particles following acute insulin action in insulin sensitive individuals appears to be the result not only of a decreased hepatic production [24], but also an increased clearance.…”

Section: Elevated Fasting Triglyceridesmentioning

confidence: 85%

Dyslipidemia of the metabolic syndrome

Ruotolo

Howard²

2002

Curr Cardiol Rep

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130

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The three major components of dyslipidemia associated with the metabolic syndrome are increased fasting and postprandial triglyceride-rich lipoproteins (TRLs), decreased high-density lipoprotein (HDL), and increased small, dense low-density lipoprotein (LDL) particles. Insulin resistance and compensatory hyperinsulinemia lead to overproduction of very low-density lipoprotein particles. A relative deficiency of lipoprotein lipase, an insulin-sensitive enzyme, is partly responsible for the decreased clearance of fasting and postprandial TRLs, and the decreased production of HDL particles. The resulting increased concentration of cholesteryl ester-rich fasting and postprandial TRLs is the central lipoprotein abnormality of the metabolic syndrome. The increase of small, dense LDL particles, and decrease of large, buoyant HDL particles are consequential events. All these lipoprotein defects contribute largely to the increased cardiovascular disease risk in individuals with insulin resistance. Peroxisome proliferator-activated receptor (PPAR)a, PPARg, and PPARd agonists seem to improve dyslipidemia of the metabolic syndrome by regulating the expression of important genes involved in the deranged lipoprotein metabolism associated with insulin resistance.

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“…Experiments in diabetic dogs have demonstrated that intraperitoneal insulin is almost entirely absorbed by the portal circulation (19). Reported changes in lipoprotein concentration and composition in IDDM patients treated with intraperitoneal insulin (20)(21)(22)(23)(24), however, have been contradictory; this may be attributable to the many intrinsic differences of patients, like different degrees of glucose control and different duration of follow-up.…”

mentioning

confidence: 94%

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

et al. 1994

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The increased activity of hepatic lipase after intraperitoneal insulin administration in IDDM patients appears to be one of the main determinants of lipoprotein changes observed, resulting in the normalization of lipoprotein composition during this mode of therapy. The normal inverse relationship between VLDL triglycerides and HDL cholesterol, which was not present in IDDM patients with subcutaneous therapy, was restored with intraperitoneal insulin regimen.

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Effects of intraperitoneal versus subcutaneous insulin administration on lipoprotein metabolism in type I diabetes

Cited by 43 publications

References 43 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.

Dyslipidemia of the metabolic syndrome

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

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