Comparison of Pancreas-Transplanted Type 1 Diabetic Patients with Portal-Venous Versus Systemic-Venous Graft Drainage: Impact on Glucose Regulatory Hormones and the Growth Hormone/Insulin–Like Growth Factor-I Axis

Frystyk, Jan; Ritzel, Robert; Maubach, Julie; Büsing, M.; Lück, R.; Klempnauer, Jürgen; Schmiegel, Wolff; Nauck, Michael A.

doi:10.1210/jc.2007-2350

Cited by 31 publications

(29 citation statements)

References 41 publications

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“…This is consistent with previous studies in patients with type 1 diabetes showing a clear relationship between beta cell function and HbA 1c levels during glucose-lowering treatment [27,28]. The mechanisms underling this association have not been completely clarified yet, but may involve the effects of endogenous insulin on alpha cell function [29][30][31] as well as the direct intra-portal drainage of endogenous insulin vs systemic delivery of exogenously administered insulin [32]. Taken together, these studies emphasise the importance of endogenous insulin secretion for glucose control and support the concept of enhancing beta cell function in the treatment of patients with diabetes [33].…”

Section: Discussionsupporting

confidence: 91%

Determinants of glucose control in patients with chronic pancreatitis

et al. 2010

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Aims/hypothesis Diabetes frequently develops in patients with chronic pancreatitis (CP). Partial pancreatectomy has emerged as a treatment option for such patients. We addressed whether the development of diabetes in CP patients is related to pancreatic beta cell area or clinical variables, and which factors predict the diabetes risk after partial pancreatectomy. Methods Fractional beta cell area was determined in pancreatic tissue samples obtained from 114 CP patients undergoing pancreatic surgery and related to measures of glucose control, as well as clinical and anthropometric data. Seventy-four patients without diabetes at the time of surgery were contacted again 2.5±1.0 years after partial pancreatectomy in order to obtain information about the post-operative development of diabetes. Results In the surgical samples in the whole cohort, pancreatic beta cell area was 0.40±0.06% in patients with and 0.64±0.06% in those without previously known diabetes (p=0.039). There was an inverse non-linear relationship between pancreatic beta cell area and fasting glucose concentrations (r=0.29) as well as HbA 1c levels (r=0.36). Nineteen out of 74 previously normoglycaemic patients (26%) developed diabetes over an average period of 2.5 years of follow-up. Pre-operative fasting glucose levels, HbA 1c and BMI were identified as predictors of diabetes after partial pancreatectomy. However, pancreatic beta cell area did not differ in those who subsequently developed diabetes (0.66±0.15%) and those who did not (0.62± 0.08%, p=0.45). Conclusions/interpretation Hyperglycaemia in CP patients is associated with reduced beta cell area. However, reduced beta cell area does not predict the development of diabetes, suggesting that other factors are more important determinants of alterations in glucose metabolism in patients with CP.

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Section: Discussionsupporting

confidence: 91%

Determinants of glucose control in patients with chronic pancreatitis

et al. 2010

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“…5,6 When exo genous insulin is administered subcutaneously or intravenously, as in the treatment of patients with T1DM, this ratio is approximately 1:2. 5, 6 The administration of sufficient exogenously administered insulin to control the liver, therefore, results in peripheral hyperinsulinemia.…”

Section: Metabolic Dysfunction In Treated T1dmmentioning

confidence: 99%

Adjunct therapy for type 1 diabetes mellitus

Lebovitz

2010

Nat Rev Endocrinol

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Insulin replacement therapy in type 1 diabetes mellitus (T1DM) is nonphysiologic. Hyperinsulinemia is generated in the periphery to achieve normal insulin concentrations in the liver. This mismatch results in increased hypoglycemia, increased food intake with weight gain, and insufficient regulation of postprandial glucose excursions. Islet amyloid polypeptide is a hormone synthesized in pancreatic beta cells and cosecreted with insulin. Circulating islet amyloid polypeptide binds to receptors located in the hindbrain and increases satiety, delays gastric emptying and suppresses glucagon secretion. Thus, islet amyloid polypeptide complements the effects of insulin. T1DM is a state of both islet amyloid polypeptide and insulin deficiency. Pramlintide, a synthetic analog of islet amyloid polypeptide, can replace this hormone in patients with T1DM. When administered as adjunctive therapy to such patients treated with insulin, pramlintide decreases food intake and causes weight loss. Pramlintide therapy is also associated with suppression of glucagon secretion and delayed gastric emptying, both of which decrease postprandial plasma glucose excursions. Pramlintide therapy improves glycemic control and lessens weight gain. Agents that decrease intestinal carbohydrate digestion (alpha-glucosidase inhibitors) or decrease insulin resistance (metformin) might be alternative adjunctive therapies in T1DM, though its benefits are marginally supported by clinical data.

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“…Circulating IGF-1 is produced primarily by the liver and decreased levels in TIDM may result from reduced hepatic delivery of insulin [11, 12]. However, IGF-1 is also produced locally in muscle and bone tissue.…”

Section: Introductionmentioning

confidence: 99%

Increased circulating IL-8 is associated with reduced IGF-1 and related to poor metabolic control in adolescents with type 1 diabetes mellitus

et al. 2009

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Background-A dysregulated growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis is well-recognized in children and adolescents with type 1 diabetes mellitus (T1DM). Decreased IGF-1 levels can also be found in chronic inflammatory diseases, while hyperglycemia promotes inflammatory cytokine production. Therefore, inflammatory cytokines may link poor metabolic control with GH/IGF-1 axis changes. This study examined the relationship between serum inflammatory cytokines and IGF-1 in adolescents (age 13-18) with TIDM in chronic poor (n=17) or favorable (n=19) glucose control. Poor control (PC) was defined as ≥ 3, consistent HbA1C > 9% during the previous 2 years, while favorable control (FC) was consistent levels of HbA1C < 9%.Results-HbA1C (FC: 7.5±0.6%; PC: 10.5±0.9%, p<0.001) and interleukin (IL)-8 (FC: 3.7±4.0 pg/ml; PC: 7.4±4.3 pg/ml, p=0.01) were increased and IGF-1 (FC: 536.5±164.3 ng/ml; PC: 408.9 ±157.1 ng/ml, p=0.03) was decreased in patients with poor control compared to patients with favorable control. Moreover, IL-8 was inversely correlated with IGF-1 (r=−0.40, p=0.03) and positively correlated with HbA1C (r=0.36, p=0.03).Conclusions-In adolescents with T1DM and chronic, poor glucose control, increased serum IL-8 is associated with reduced IGF-1 suggesting a pro-inflammatory milieu that may contribute to alterations in the GH/IGF-1 axis.

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Comparison of Pancreas-Transplanted Type 1 Diabetic Patients with Portal-Venous Versus Systemic-Venous Graft Drainage: Impact on Glucose Regulatory Hormones and the Growth Hormone/Insulin–Like Growth Factor-I Axis

Cited by 31 publications

References 41 publications

Determinants of glucose control in patients with chronic pancreatitis

Determinants of glucose control in patients with chronic pancreatitis

Adjunct therapy for type 1 diabetes mellitus

Increased circulating IL-8 is associated with reduced IGF-1 and related to poor metabolic control in adolescents with type 1 diabetes mellitus

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