Treatment with intravenous insulin followed by continuous subcutaneous insulin infusion improves glycaemic control in severely resistant Type 2 diabetic patients

Pouwels, M.J.M.; Tack, Cees J.; Hermus, A.R.M.M.; Lutterman, J.A.

doi:10.1046/j.1464-5491.2003.00848.x

Cited by 46 publications

(38 citation statements)

References 22 publications

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“…This is in contrast to previous reports using high doses of vanadium as an antidiabetes agent, which is thought to work through a different set of mechanisms than described in this report. Because, arylalkylamine vanadium salts stimulate insulin signaling at a step downstream of the insulin receptor, we propose that development of these compounds may be appropriate for not only type 1 and 2 diabetes but particularly for the treatment of conditions characterized by the lack of insulin receptor activity such as in patients affected by type A or type B insulin-resistance syndromes or in other types of severe insulin resistance that are refractory to treatment with insulin sensitizers and in which the only effective therapy is the use of large doses of insulin (12,41). We thank Tanya Yates for her editorial support.…”

Section: Resultsmentioning

confidence: 99%

Oral Insulin-Mimetic Compounds That Act Independently of Insulin

García-Vicente

Yraola²,

Marti

et al. 2007

Diabetes

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The hallmarks of insulin action are the stimulation and suppression of anabolic and catabolic responses, respectively. These responses are orchestrated by the insulin pathway and are initiated by the binding of insulin to the insulin receptor, which leads to activation of the receptor's intrinsic tyrosine kinase. Severe defects in the insulin pathway, such as in types A and B and advanced type 1 and 2 diabetes lead to severe insulin resistance, resulting in a partial or complete absence of response to exogenous insulin and other known classes of antidiabetes therapies. We have characterized a novel class of arylalkylamine vanadium salts that exert potent insulin-mimetic effects downstream of the insulin receptor in adipocytes. These compounds trigger insulin signaling, which is characterized by rapid activation of insulin receptor substrate-1, Akt, and glycogen synthase kinase-3 independent of insulin receptor phosphorylation. Administration of these compounds to animal models of diabetes lowered glycemia and normalized the plasma lipid profile. Arylalkylamine vanadium compounds also showed antidiabetic effects in severely diabetic rats with undetectable circulating insulin. These results demonstrate the feasibility of insulin-like regulation in the complete absence of insulin and downstream of the insulin receptor. This represents a novel therapeutic approach for diabetic patients with severe insulin resistance. Diabetes 56: 486 -493, 2007

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Section: Resultsmentioning

confidence: 99%

Oral Insulin-Mimetic Compounds That Act Independently of Insulin

García-Vicente

Yraola²,

Marti

et al. 2007

Diabetes

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show abstract

“…Afterward, blood glucose control can be achieved by using CSII (42), although this combined intravenous/subcutaneous approach has not been widely adopted. CSII has also been considered in recent years as a potential routine means of improving blood glucose control in type 2 diabetic patients who remain difficult to control while using insulin injections, because it provides a more physiological plasma insulin profile and because of the notable successes in controlling type 1 diabetes (described above) (43).…”

Section: Csii As a Management Strategy In Type 2 Diabetesmentioning

confidence: 99%

Long-Acting Insulin Analogs Versus Insulin Pump Therapy for the Treatment of Type 1 and Type 2 Diabetes

Pickup

Renard

2008

Diabetes Care

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Insulin pump therapy (continuous subcutaneous insulin infusion [CSII]) is now an established form of intensive insulin treatment. It is pertinent to ask, however, if multiple daily injection (MDI) regimens based on new long-acting insulin analogs such as glargine and detemir have now replaced the need for CSII. In type 1 diabetes, CSII reduces the frequency of severe hypoglycemia compared with isophane-based MDIs, but the rate of severe hypoglycemia is usually similar on glargine-or detemir-based MDIs compared with isophane-based MDIs. CSII reduces A1C and glycemic variability compared with isophane-based MDIs; but glargine and detemir do not improve A1C or variability in many patients, particularly those who are prone to hypoglycemia. Head-to-head comparisons of CSII with MDI based on glargine indicate lower A1C, fructosamine, or glucose levels on CSII. It can be concluded that long-acting insulin analogs have not yet replaced the need for insulin pump therapy in type 1 diabetes, and CSII is the best current therapeutic option for some type 1 diabetic subjects. In type 2 diabetes, CSII and MDI produce similar glycemic control, although there is little study of MDI based on long-acting analogs compared with pumps. It is possible that CSII will be beneficial in selected patient groups with type 2 diabetes, but this requires further study. Diabetes Care 31 (Suppl. 2):S140-S145, 2008F or many decades, it has been accepted that poor glycemic control in insulin injection-treated diabetes is mainly due to the inadequacies of insulin pharmacology (1,2). Regular (shortacting) insulin is absorbed too slowly from the subcutaneous site to control postprandial hyperglycemia, and the delayed absorption then results in late hypoglycemia. Both of these problems have now been much improved by the introduction of more quickly absorbed monomeric insulins (3). The problems of longacting insulin formulations such as isophane and lente have taken longer to improve: they produce "hill-like" blood concentration and action profiles, resulting in a peak of over-insulinization in the middle of the night with a consequent risk of hypoglycemia, and a waning in insulinization before breakfast, resulting in fasting hyperglycemia (1,2,4). Moreover, these delayed-action insulin suspensions also have huge variability of subcutaneous absorption (1), contributing to much of the unpredictability in within-and between-day blood glucose control.The development of insulin pump therapy (continuous subcutaneous insulin infusion [CSII]) nearly 30 years ago (5) did much to overcome the problems of long-acting insulin injections. The constancy of the basal delivery allows for a near-flat blood insulin profile, adjustable at preset times to suit the changing needs of the patient throughout the day. The controlled delivery of small insulin amounts substantially reduces glycemic variability (6,7). For many years, these advantages have allowed a superiority of insulin pump therapy over insulin injection regimens, at least as far as the frequency of hypoglycem...

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“…In a study by Boullu-Sanchis et al using CIVII for 5 days, glycaemic control improvement was observed after 12 hours of infusion [6]. Pouwels et al, continued CIVII for as long as 31 ± 10 days [7].…”

Section: Discussionmentioning

confidence: 99%

“…Pouwelsa et al used CIVII in a study performed in type 2 diabetes patients with insufficient metabolic control and achieved marked reduction of insulin requirement immediately following CIVII and HbA 1c level reduction 6 and 12 months later. However, it should be mentioned that after termination of CIVII, continuous insulin infusion using portable insulin pump was continued for 12 months, which could have significant impact on HbA 1c reduction [7].…”

Section: Discussionmentioning

confidence: 99%