Cotherapy with recombinant human insulin-like growth factor I and insulin improves glycemic control in type 1 diabetes. RhIGF-I in IDDM Study Group.

Thrailkill, Kathryn M.; Quattrin, Teresa; Baker, Lester; Kuntze, Joyce; Compton, Peter; Martha, Paul M.

doi:10.2337/diacare.22.4.585

Cited by 85 publications

(57 citation statements)

References 6 publications

(9 reference statements)

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“…Similarly, IGF-I administration to type 1 diabetics has been shown to suppress GH secretion (33,34), and several studies have hypothesized that suppression of GH significantly improves insulin sensitivity (12)(13)(14)(15)(33)(34)(35). In keeping with that finding, in this study, we found a 77% reduction in overnight GH secretion, suggesting that eliminating the counterregulatory effect of GH on gluconeogenesis and hepatic glucose output may have been an important determinant of the change in insulin requirements.…”

Section: Discussionsupporting

confidence: 78%

The Combination of Insulin-Like Growth Factor I and Insulin-Like Growth Factor-Binding Protein-3 Reduces Insulin Requirements in Insulin-Dependent Type 1 Diabetes: Evidence forin VivoBiological Activity¹

Clemmons

Moses

McKay³

et al. 2000

The Journal of Clinical Endocrinology & Metabolism

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Insulin-like growth factor-I (IGF-I) enhances insulin action in normal subjects and in patients with both type 1 and 2 diabetes; however, its administration is associated with significant side effects in a high percentage of patients. The coadministration of IGF binding protein-3 (IGFBP-3, the predominant IGF binding protein in serum) with IGF-I limits IGF-I inducible side effects, but it does not attenuate the ability of IGF-I to enhance protein synthesis and bone accretion; therefore, we determined whether IGF-I/IGFBP-3 would retain biological activity in type 1 DM and limit side effects associated with free IGF-I administration.Twelve patients received recombinant human IGF-I plus IGFBP-3 (2 mg/kg⅐day) by continuous sc infusion for 2 weeks. Each subject served as his own control; and, during a paired 2-week period, each received a placebo infusion. The order of the treatments was randomized. Subjects were placed on a constant caloric intake but were allowed to adjust insulin doses to maintain appropriate levels of glycemic control. Subjects measured blood glucose four times per day at home and kept a log of their insulin use. Frequent sampling for glucose, insulin, and GH was conducted during four inpatient study periods, one at the beginning and one at the end of each 2-week study interval.During IGF-I/IGFBP-3, insulin doses were reduced by 49%, and mean serum glucose was reduced by 23%. Free insulin levels obtained during frequent sampling in hospital fell 47% on IGF-I/IGFBP-3, compared with control, but showed no change with placebo. Concomitant glucose measurements did not differ in the two treatment groups. There was no change in body weight. Fructosamine levels decreased by 12%, but this was not significant (P Ͻ 0.1). Fasting triglyceride was unchanged, but cholesterol declined from 170 Ϯ 24 to 149 Ϯ 31 mg/dL (P Ͻ 0.05). IGFBP-2 (an IGF-I-dependent responsive variable) rose from 141 Ϯ 56 to 251 Ϯ 98 ng/mL (P Ͻ 0.01) on IGF-I/IGFBP-3. To analyze the mechanism by which IGF-I/IGFBP-3 might reduce insulin requirements, the change in serum GH was quantified. Mean GH levels were reduced by 72%, from 2.48 to 0.55 ng/mL (P Ͻ 0.001). An equal number (40%) of drug-and placebotreated subjects had minor hypoglycemic episodes at home that required adjustment of insulin doses. No episode was classified as severe. In contrast to previous studies with free IGF-I, there were no cases of edema, headache, jaw pain, retinal edema, or Bell's palsy. No subject withdrew because of drug complications. These findings indicate that IGF-I/IGFBP-3 is biologically active on carbohydrate metabolism, as measured by a decrease in insulin requirements in patients with type 1 diabetes. Further studies will be required to determine the long-term safety and efficacy of this combination in patients with insulin resistance and diabetes. (J Clin Endocrinol

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Section: Discussionsupporting

confidence: 78%

The Combination of Insulin-Like Growth Factor I and Insulin-Like Growth Factor-Binding Protein-3 Reduces Insulin Requirements in Insulin-Dependent Type 1 Diabetes: Evidence forin VivoBiological Activity¹

Clemmons

Moses

McKay³

et al. 2000

The Journal of Clinical Endocrinology & Metabolism

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“…However, human studies with recombinant IGF-I treatment, although beneficial in alleviating diabetes and insulin resistance, require supraphysiological doses that carry many harmful side effects (1,8,50,51,53,65). Also, reversal of diabetes was not complete or permanent, and concomitant insulin therapy is required in addition to IGF-I.…”

Section: Discussionmentioning

confidence: 99%

Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant

Gunawardana

Piston

2015

American Journal of Physiology-Endocrinology and Metabolism

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Gunawardana SC, Piston DW. Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant. Am J Physiol Endocrinol Metab 308: E1043-E1055, 2015. First published April 21, 2015; doi:10.1152/ajpendo.00570.2014.-Traditional therapies for type 1 diabetes (T1D) involve insulin replacement or islet/pancreas transplantation and have numerous limitations. Our previous work demonstrated the ability of embryonic brown adipose tissue (BAT) transplants to establish normoglycemia without insulin in chemically induced models of insulin-deficient diabetes. The current study sought to extend the technique to an autoimmune-mediated T1D model and document the underlying mechanisms. In nonobese diabetic (NOD) mice, BAT transplants result in complete reversal of T1D associated with rapid and longlasting euglycemia. In addition, BAT transplants placed prior to the onset of diabetes on NOD mice can prevent or significantly delay the onset of diabetes. As with streptozotocin (STZ)-diabetic models, euglycemia is independent of insulin and strongly correlates with decrease of inflammation and increase of adipokines. Plasma insulinlike growth factor-I (IGF-I) is the first hormone to increase following BAT transplants. Adipose tissue of transplant recipients consistently express IGF-I compared with little or no expression in controls, and plasma IGF-I levels show a direct negative correlation with glucose, glucagon, and inflammatory cytokines. Adipogenic and anti-inflammatory properties of IGF-I may stimulate regeneration of new healthy white adipose tissue, which in turn secretes hypoglycemic adipokines that substitute for insulin. IGF-I can also directly decrease blood glucose through activating insulin receptor. These data demonstrate the potential for insulin-independent reversal of autoimmune-induced T1D with BAT transplants and implicate IGF-I as a likely mediator in the resulting equilibrium. type 1 diabetes; brown adipose tissue; insulin independent; transplantation; insulin-like growth factor I TYPE 1 DIABETES (T1D) is characterized by autoimmune-mediated destruction of pancreatic ␤-cells, resulting in absolute deficiency of insulin and loss of glycemic control. Treatments for T1D, despite having been refined over many years, are geared mainly toward replacing insulin, which involves numerous risks and limitations. Direct insulin replacement via daily injections or insulin pump does not cure the disease and requires life-long repeated administration. In addition to the inconvenience, direct insulin therapy requires careful monitoring of dosage and blood glucose levels and can lead to potentially fatal hypoglycemic episodes. Pancreas transplantation, the only available treatment with a good chance of long-term insulin independence, requires invasive surgery and life-long immunosuppressive therapy. Islet transplantation, although less invasive, is limited by the availability of donor tissue and the need for immunosuppression, and patients often return to insulin dependence in the long...

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“…IGF-I is also increased in vitreous samples from patients with PDR (Merimee et al, 1983). In support of a possible connection between IGF-I and diabetic retinopathy, is the observation that administration of recombinant IGF-I in to the vitreous cavity of animals results in diabetic retinopathy-like pathologic changes (Thrailkill et al, 1999).…”

Section: Insulin-like Growth Factor-i (Igf-i)mentioning

confidence: 99%

Growth Factors in Proliferative Diabetic Retinopathy

Khan

Chakrabarti

2003

Journal of Diabetes Research

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Many growth factors are implicated in the pathogenesis of proliferative diabetic retinopathy. Alteration of growth factors and their receptors in diabetes has been shown in both experimental and clinical studies. Sustained hyperglycemia resulting from long-standing diabetes leads to several biochemical abnormalities that consequently result in retinal hypoxia. Retinal oxygenation state regulates various growth factors that promote angiogenesis in order to meet the oxygen demands of the tissue. However, unregulated expression of these growth factors and induction of complex cascades leading to augmentation of other proangiogenic factors, which may not be regulated by tissue oxygenation, leads to uncontrolled retinal neovascularization and blindness in diabetic patients.

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Cotherapy with recombinant human insulin-like growth factor I and insulin improves glycemic control in type 1 diabetes. RhIGF-I in IDDM Study Group.

Abstract: These results demonstrate that rhIGF/insulin cotherapy improves glycemic control in patients with type 1 diabetes better than optimized insulin management alone; longer-term trials would be required to determine an acceptable benefit-risk profile.

Cited by 85 publications

References 6 publications

The Combination of Insulin-Like Growth Factor I and Insulin-Like Growth Factor-Binding Protein-3 Reduces Insulin Requirements in Insulin-Dependent Type 1 Diabetes: Evidence forin VivoBiological Activity¹

The Combination of Insulin-Like Growth Factor I and Insulin-Like Growth Factor-Binding Protein-3 Reduces Insulin Requirements in Insulin-Dependent Type 1 Diabetes: Evidence forin VivoBiological Activity¹

Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant

Growth Factors in Proliferative Diabetic Retinopathy

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Cotherapy with recombinant human insulin-like growth factor I and insulin improves glycemic control in type 1 diabetes. RhIGF-I in IDDM Study Group.

Abstract: These results demonstrate that rhIGF/insulin cotherapy improves glycemic control in patients with type 1 diabetes better than optimized insulin management alone; longer-term trials would be required to determine an acceptable benefit-risk profile.

Cited by 85 publications

References 6 publications

The Combination of Insulin-Like Growth Factor I and Insulin-Like Growth Factor-Binding Protein-3 Reduces Insulin Requirements in Insulin-Dependent Type 1 Diabetes: Evidence forin VivoBiological Activity1

The Combination of Insulin-Like Growth Factor I and Insulin-Like Growth Factor-Binding Protein-3 Reduces Insulin Requirements in Insulin-Dependent Type 1 Diabetes: Evidence forin VivoBiological Activity1

Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant

Growth Factors in Proliferative Diabetic Retinopathy

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Product

Resources

About

The Combination of Insulin-Like Growth Factor I and Insulin-Like Growth Factor-Binding Protein-3 Reduces Insulin Requirements in Insulin-Dependent Type 1 Diabetes: Evidence forin VivoBiological Activity¹

The Combination of Insulin-Like Growth Factor I and Insulin-Like Growth Factor-Binding Protein-3 Reduces Insulin Requirements in Insulin-Dependent Type 1 Diabetes: Evidence forin VivoBiological Activity¹