Effects of Spontaneous Portal-Systemic Shunting on Insulin Metabolism

Smith‐Laing, G.; Sherlock, Sheila; Faber, O. K.

doi:10.1016/s0016-5085(79)80166-3

Cited by 61 publications

(12 citation statements)

References 15 publications

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“…Several authors presented convincing data that in the postabsorptive state, creation of a porta-caval shunt does not appear to exert a major influence on either hepatic glucose release or peripheral glucose disposal. [30][31][32][33] Another possible explanation may be a defect of insulin secretion with a consequent reduction of hepatic insulinization, which in turn determines increased hepatic glucose production. 28,29 After the oral glucose challenge, as shown in Table 2, cirrhotic diabetic patients had insulin and c-peptide ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Contribution of reduced insulin sensitivity and secretion to the pathogenesis of hepatogenous diabetes: Effect of liver transplantation

Perseghin¹,

Mazzaferro²,

Sereni³

et al. 2000

Hepatology

124

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Diabetes mellitus frequently complicates cirrhosis but the pathogenic mechanisms are unknown. To assess the contribution of reduced insulin action and secretion, 24 cirrhotic-diabetic patients waiting for liver transplant because of an unresectable hepatocarcinoma underwent an oral glucose tolerance test (OGTT) to assess the ␤-cell function and an insulin clamp combined with [3-3 H]glucose infusion to measure whole body glucose metabolism before and 2 years after the transplant. Seven cirrhotic nondiabetic patients, 11 patients with chronic uveitis on similar immunosuppressive therapy, and 7 healthy subjects served as control groups. Cirrhotic patients showed a profound insulin resistance, and diabetics in addition also showed increased endogenous glucose production (P Ͻ .05) and insulin deficiency during the OGTT (P Ͻ .05). Liver transplantation normalized endogenous glucose production and insulin sensitivity but failed to cure diabetes in 8 of the 24 patients because a markedly low insulin response during the OGTT. Age, body mass index, family history of diabetes, immunosuppressive drugs, and pathogenesis of cirrhosis did not predict in whom liver transplant was going to cure diabetes. On the contrary, a reduced secretory response characterized the patients in whom the transplant would not be curative. In summary, insulin resistance was a primary event complicating cirrhosis but additional ␤-cell secretory defects were crucial for development of diabetes. Liver transplantation, lessening insulin resistance, cured hepatogenous diabetes in 67% of cirrhotic-diabetic patients; nevertheless 33% were still diabetics because the persistence of a reduced ␤-cell function, which makes these patients eventually eligible for combined islet transplantation. (HEPATOLOGY 2000;31:694-703.)Cirrhotic patients are characterized by impaired glucose metabolism 1 ; 60% to 80% are glucose intolerant and 10% to 15% develop overt diabetes mellitus. [2][3][4] The development of diabetes following liver cirrhosis seems also to be relatively rapid; during a period of 5 years nearly 15% to 20% of cirrhotic patients develop frank hyperglycemia. 5 The high incidence of diabetes among cirrhotic patients was recognized to be secondary to the hepatic disease since 1906 when the term ''hepatogenous diabetes'' was first coined. 6 Diabetes does not affect short-term survival, but it seems to be significantly correlated with poor prognosis in long-term follow-up, the higher mortality rate being mainly caused by an increased risk of hepatocellular failure. 7 The sequence, the relative importance, and the molecular mechanisms of the pathogenic factors are still largely unknown because liver cirrhosis is characterized by heterogeneous clinical pictures related to etiologic and environmental factors, nutritional state, complex physiologic endocrine interactions, and stage and stability of the liver disease. Recently liver transplantation was found to be an effective treatment for small unresectable hepatocellular carcinomas in patients with cirrhosis,...

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Section: Discussionmentioning

confidence: 99%

Contribution of reduced insulin sensitivity and secretion to the pathogenesis of hepatogenous diabetes: Effect of liver transplantation

Perseghin¹,

Mazzaferro²,

Sereni³

et al. 2000

Hepatology

124

View full text Add to dashboard Cite

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“…As regards Mg, various factors may account for its reduction: hormonal imbalance with decreased renal tubular reabsorption, hyperaldosteronism and peripheral insulino-resistance are well documented in cirrhotic patients [32,33]; as a consequence, protein turnover imbalance and hypercatabolic conditions which invariably follow [2] may contribute to Mg depletion through the increased loss of aminoacids and urea nitrogen. The present results point to a severe impairment of protein carriers due to nitrogen catabolism derangement as the leading factor in trace-element imbalance in liver cirrhosis, whether of alcoholic aetiology or not.…”

Section: ) [24]mentioning

confidence: 99%

Zinc and magnesium in liver cirrhosis

Rocchi

Borella

Borghi

et al. 1994

Eur J Clin Investigation

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The Authors determined zinc (Zn) and magnesium (Mg) in the plasma, urine, erythrocytes (RBCs), mono- and polymorphonuclear cells (MNCs and PMNs) of patients with overt alcoholic and non-alcoholic liver cirrhosis. In order to obtain a clearer clinical picture, biochemical and nutritional parameters (retinol, tocopherol, six different carotenoids, creatinine-height index and tricipital skinfold), as well as markers of portal hypertension (spleno-portal size and platelet count) were also evaluated. The plasma levels of Zn and Mg were found to be reduced, as were the urine levels of Mg. Urine Zn, on the other hand, was higher than normal. Plasma Zn correlated inversely, and urine Zn directly, with the severity of the disease, rather than with alcohol consumption or treatment with diuretics. Protein metabolism impairment would appear to affect the plasma transport of Zn rather than its overall availability in the organism; the opposite was found in the case of Mg, the availability of which appeared to be reduced. Determination of the two elements in RBCs, MNCs and PMNs suggested that a true nutritional deficit cannot be demonstrated. MNCs, rather than RBCs or PMNs seem better to reflect tissue status of trace elements.

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“…To elucidate the contributions of portasystemic shunting vs intrinsic liver disease to the observed peripheral hyperinsulinemia, Smith-Laing et al 32 compared the C-peptide and insulin responses during an oral glucose tolerance test in three groups (Figure 3); (1) patients with portal vein occlusion, extensive portasystemic shunts, but normal liver function; (2) cirrhotic patients with a similar degree of portasystemic shunting but impaired hepatic function; and (3) control subjects. Hyperinsulinemia was observed only in the cirrhotic group (Figure 3).…”

Section: B Diminished Hepatic Extraction and Portasystemic Shuntsmentioning

confidence: 99%