Insulin Treatment for the Early 80s: Facts and Questions About Old and New Insulins and Their Usage

Galloway, John A.

doi:10.2337/diacare.3.5.615

Cited by 37 publications

(7 citation statements)

References 22 publications

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“…The method can also be applied in man [7] if there is no endogenous B cell function and no anti-insulin antibodies, but individual differences [5,20] as well as additional factors influencing the action of the insulin actually available [13,27] must be taken into account. Problems of reproducibility with particular respect to the action of the insulin applied on post-prandial glycaemia still remain to be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…One approach to this problem is to determine individual optimal insulin dose profiles by means of glucose-controlled insulin infusions and to transpose them into a pattern of separate subcutaneous injections of a variety of preparations [19]. On the other hand, continuous subcutaneous insulin infusions by means of open loop systems are becoming increasingly popular [13,22,24].For successful use, however, both methods require not only carefully recorded blood glucose curves [21] but also detailed knowledge regarding the kinetics of insulin absorption from the subcutaneous injection depot to the insulin distribution space [1,12]. A large number of detailed studies on the disappearance of insulin from its injection depot and how it can be influenced have been reported [2-6, 17, 18, 20, 23, 25].…”

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Absorption rates of subcutaneously injected insulin in the dog as calculated from the plasma insulin levels by means of a simple mathematical model

et al. 1983

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Summary.The appearance rate of insulin (calculated insulin secretion rate) in the circulating blood after subcutaneous injection was estimated in diabetic dogs from serial measurements of immunoreactive insulin concentrations using a simple mathematical model based on the insulin half-life and the distribution space. In the case of highly purified monocomponent porcine insulin, maximum concentrations occurred after 30-60min. The duration of insulin appearance was dosedependent and the rate of appearance could be described by a bi-exponential function. It was linearly dose-dependent but the effect on glycaemia showed saturation kinetics. The action of the injected dose on the fasting glycaemia diminished when the appearance rate became < 0.3 mU. kg -~. rain 2. Fractional dose recovery was between 70% and 90% and was not different between depot and regular insulin. Appearance kinetics were not significantly affected by the initial glycaemia. The model presented provides a means for quantitative characterization of different insulin preparations.Key words: Dog, insulin therapy, mathematical model, soluble insulin, depot insulin, absorption, subcutaneous.Until artificial B cells and transplantation are available for the routine long-term treatment of insulin-dependent diabetes, therapeutic research will concentrate mainly on improving the subcutaneous administration of insulin. One approach to this problem is to determine individual optimal insulin dose profiles by means of glucose-controlled insulin infusions and to transpose them into a pattern of separate subcutaneous injections of a variety of preparations [19]. On the other hand, continuous subcutaneous insulin infusions by means of open loop systems are becoming increasingly popular [13,22,24].For successful use, however, both methods require not only carefully recorded blood glucose curves [21] but also detailed knowledge regarding the kinetics of insulin absorption from the subcutaneous injection depot to the insulin distribution space [1,12]. A large number of detailed studies on the disappearance of insulin from its injection depot and how it can be influenced have been reported [2-6, 17, 18, 20, 23, 25]. Moreover Stevenson et al. [26] reported an approach to quantify the absorbed amount of subcutaneously injected insulin by matching the blood glucose response to a programmed intravenous insulin infusion. For practical purposes, a simple mathematical model based on the analysis of pcripheral insulin concentrations and estimation of the rate at which insulin appears in its distribution system seems suitable for obtaining more detailed information [10]. If an organism devoid of functioning B cells is taken as the experimental subject, the rate of insulin appearance can be calculated for any therapeutic dose.The purpose of this study was to use a model to describe the kinetics of insulin appearance after subcutaneous administration of a variety of insulin preparations. The tests were performed on dogs with experimentally induced diabetes because with these a...

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Section: Discussionmentioning

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Absorption rates of subcutaneously injected insulin in the dog as calculated from the plasma insulin levels by means of a simple mathematical model

et al. 1983

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“…The advent of recombinant DNA technology allowed for the production of recombinant human insulin, which largely replaced porcine and beef insulin in clinical use in the 1980s (61). A number of insulin analogs were developed to create a more physiological meal-related insulin profile and to reduce hypoglycemia (48,95).…”

Section: Insulin Therapymentioning

confidence: 99%

Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality

Gallagher

2015

Physiological Reviews

656

434

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Obesity and type 2 diabetes are becoming increasingly prevalent worldwide, and both are associated with an increased incidence and mortality from many cancers. The metabolic abnormalities associated with type 2 diabetes develop many years before the onset of diabetes and, therefore, may be contributing to cancer risk before individuals are aware that they are at risk. Multiple factors potentially contribute to the progression of cancer in obesity and type 2 diabetes, including hyperinsulinemia and insulin-like growth factor I, hyperglycemia, dyslipidemia, adipokines and cytokines, and the gut microbiome. These metabolic changes may contribute directly or indirectly to cancer progression. Intentional weight loss may protect against cancer development, and therapies for diabetes may prove to be effective adjuvant agents in reducing cancer progression. In this review we discuss the current epidemiology, basic science, and clinical data that link obesity, diabetes, and cancer and how treating obesity and type 2 diabetes could also reduce cancer risk and improve outcomes.

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“…For the past 25 years, the literature on insulin treatment has dealt intensively with the immunogenicity of insulin; however, IgE and IgC antibodies directed to protamine from use of NPH insulin or protamine zinc insulin appear to pose a far greater risk for an anaphylactoid reaction than antibodies to insulin (152)(153)(154). Specifically, allergic reactions in individuals receiving intravenous protamine to neutralize heparin anticoagulation instituted during cardiac procedures (e.g., catheterization, coronary bypass) have been found to occur more frequently in diabetic patients who have been treated with protamine insulins (154).…”

Section: Dosage Algorithmsmentioning

confidence: 98%

Treatment of NIDDM With Insulin Agonists or Substitutes

Galloway

1990

Diabetes Care

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Non-insulin-dependent diabetes mellitus (NIDDM) is a common disorder occurring in 3-6% of adults in most western populations. In the United States, 29% of patients with diabetes take insulin; of these, 76% have NIDDM. Insulin therapy is usually required at some time in NIDDM. Insulin therapy improves the abnormalities of NIDDM (reduced beta-cell function, increased hepatic glucose production, reduced peripheral glucose disposal, lipid abnormalities). Insulin and sulfonylurea agents have comparable effects on mild forms of NIDDM, but for more severe forms, insulin is usually superior. Combination insulin-sulfonylurea treatment may improve the response to sulfonylureas, although long-term well-controlled trials have not been conducted. Short-term insulin treatment may restore response to sulfonylureas. Other promising treatments (human proinsulin, nasal insulin, somatostatin) have not shown any advantage over conventional insulin therapy. Insulin causes hypoglycemia and peripheral hyperinsulinemia. The hazards of hyperinsulinemia, e.g., weight gain and hypoglycemia, have been overstated, and questions about its atherogenic effects remain to be resolved. The effect of glycemic control on macro- and microvascular complications has not been established; however, maintaining fasting blood glucose levels of less than 6.7 mM may protect against progression of retinopathy, neuropathy, and nephropathy and reduce the severity of ischemic stroke. Dosage algorithms generally use intermediate- or long-acting insulin to control basal glycemia, with regular insulin added before meals if needed to control postprandial glycemia. Effective therapy depends on the patient being informed, cooperative, and willing to self-monitor blood glucose. Insulin treatment intermittency increases the risk for immune complications (resistance and allergy). Overall, patients with NIDDM can benefit from insulin therapy.

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Insulin Treatment for the Early 80s: Facts and Questions About Old and New Insulins and Their Usage

Cited by 37 publications

References 22 publications

Absorption rates of subcutaneously injected insulin in the dog as calculated from the plasma insulin levels by means of a simple mathematical model

Absorption rates of subcutaneously injected insulin in the dog as calculated from the plasma insulin levels by means of a simple mathematical model

Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality

Treatment of NIDDM With Insulin Agonists or Substitutes

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