Effects of pulsatile intravenous insulin therapy on the progression of diabetic nephropathy

Dailey, George; Boden, Guenther; Creech, Robert H; Johnson, David G.; Gleason, Ray E.; Kennedy, Frank P.; Weinrauch, Larry A.; Weir, Matthew R.; D’Elia, John A.

doi:10.1053/meta.2000.17700

Cited by 27 publications

(33 citation statements)

References 26 publications

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“…In the multicenter study that included a larger group of patients [8], creatinine clearance in the control group decreased by 7.69 mL/(min y) compared with 2.21 mL/ (min y) in the infusion group. The duration of that study was only 18 months.…”

Section: Renal Functionmentioning

confidence: 95%

“…Description of the full protocol was previously published [8]. In brief, the control group received 3 to 4 subcutaneous insulin injections per day; the infusion group received, in addition, three 1-hour infusions in a pulsatile fashion over one 8-hour period each week.…”

Section: Methodsmentioning

confidence: 99%

“…The addition of pulsatile infusion to multiple daily subcutaneous injections has been reported to be of benefit in the prevention of metabolic and microvascular complications in type 1 diabetes mellitus [6,7]. A multicenter, prospective, randomized study has demonstrated preservation of renal function in type 1 diabetes mellitus patients with albuminuria by pulsatile insulin infusion [8].…”

Section: Introductionmentioning

confidence: 99%

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A pilot study to test the effect of pulsatile insulin infusion on cardiovascular mechanisms that might contribute to attenuation of renal compromise in type 1 diabetes mellitus patients with proteinuria

et al. 2007

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Section: Renal Functionmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A pilot study to test the effect of pulsatile insulin infusion on cardiovascular mechanisms that might contribute to attenuation of renal compromise in type 1 diabetes mellitus patients with proteinuria

et al. 2007

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“…It is possible to generate regular insulin oscillations in the portal vein by bolus injections of the hormone into a hand or forearm vein. Sessions of pulsatile intravenous infusion therapy (PIVIT) have been reported to counteract renal and neural complications in diabetes (79–81). Recent progress in the understanding of islet hormone release urges for modifications of the PIVIT protocol to mimic the reversed pulses of insulin and glucagon.…”

Section: Clinical Aspects On Insulin and Glucagon Pulsatilitymentioning

confidence: 99%

Pulsatility of insulin release – a clinically important phenomenon

Hellman

2009

Upsala Journal of Medical Sciences

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The mechanisms and clinical importance of pulsatile insulin release are presented against the background of more than half a century of companionship with the islets of Langerhans. The insulin-secreting β-cells are oscillators with intrinsic variations of cytoplasmic ATP and Ca2+. Within the islets the β-cells are mutually entrained into a common rhythm by gap junctions and diffusible factors (ATP). Synchronization of the different islets in the pancreas is supposed to be due to adjustment of the oscillations to the same phase by neural output of acetylcholine and ATP. Studies of hormone secretion from the perfused pancreas of rats and mice revealed that glucose induces pulses of glucagon anti-synchronous with pulses of insulin and somatostatin. The anti-synchrony may result from a paracrine action of somatostatin on the glucagon-producing α-cells. Purinoceptors have a key function for pulsatile release of islet hormones. It was possible to remove the glucagon and somatostatin pulses with maintenance of those of insulin with an inhibitor of the P2Y1 receptors. Knock-out of the adenosine A1 receptor prolonged the pulses of glucagon and somatostatin without affecting the duration of the insulin pulses. Studies of isolated human islets indicate similar relations between pulses of insulin, glucagon, and somatostatin as found during perfusion of the rodent pancreas. The observation of reversed cycles of insulin and glucagon adds to the understanding how the islets regulate hepatic glucose production. Current protocols for pulsatile intravenous infusion therapy (PIVIT) should be modified to mimic the anti-synchrony between insulin and glucagon normally seen in the portal blood.

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“…While it is well known that control of glycemia is associated with a decrease in microvascular complications of diabetes, recognition that glyce‐mic control affects cardiac mass and autonomic function is less well appreciated. 3–5 We recently demonstrated evidence for significant LV mass and septal thickness regression in those patients (63%) whose HbA 1c improved vs. those (37%) without improvement 6 . Improvement in glycemic control has also been associated with significantly better ambulatory electrocardiographic measures of cardiac autonomic function 7,8 .…”

Section: Discussionmentioning

confidence: 98%

Left Ventricular Mass Reduction in Type 1 Diabetic Patients With Nephropathy

Weinrauch

Burger

Gleason

et al. 2005

J of Clinical Hypertension

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Left ventricular hypertrophy regression was postulated more likely to occur in diabetic patients2 Reduction of LV mass and improvement in diastolic function have been observed over 12 months of intensive control of glycemia and blood pressure (BP) in patients with type 1 diabetes mellitus with proteinuria. The purpose of this study is to determine whether these improvements are dependent upon either level of renal function at the onset of treatment or stability of renal function over time. PATIENTS AND METHODSSeventeen patients (12 men, 5 women) between the ages of 21 and 65 years (mean age 41±2 years), enrolled as part of a cooperative study designed to determine whether aggressive glycemic control slowed progression of renal dysfunction in diabetic nephropathy. 3 All patients had insulin-dependent diabetes with onset before age 35; albuminuria >0.1 g/d and/or proteinuria >0.3 g/d on two separate 24-hour urine collections; creatinine clearance (CrCl) of >30 mL/min; and were without pregnancy, acute or other chronic illness (e.g., drug dependence, active liver disease, recent myocardial infarction, or stroke). All received a daily regimen of four subcutaneous injections of insulin. One half received weekly infusions of IV insulin.4 BP was assessed clinically and by quarterly ambulatory 24-hour BP

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Effects of pulsatile intravenous insulin therapy on the progression of diabetic nephropathy

Cited by 27 publications

References 26 publications

A pilot study to test the effect of pulsatile insulin infusion on cardiovascular mechanisms that might contribute to attenuation of renal compromise in type 1 diabetes mellitus patients with proteinuria

A pilot study to test the effect of pulsatile insulin infusion on cardiovascular mechanisms that might contribute to attenuation of renal compromise in type 1 diabetes mellitus patients with proteinuria

Pulsatility of insulin release – a clinically important phenomenon

Left Ventricular Mass Reduction in Type 1 Diabetic Patients With Nephropathy

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