Hyperinsulinism of Hepatic Cirrhosis: Diminished Degradation or Hypersecretion?

Johnston, Desmond G.; Kim, Albert; Faber, O. K.; Binder, Christian; Wright, Ralph

doi:10.1016/s0140-6736(77)91652-x

Cited by 204 publications

(88 citation statements)

References 12 publications

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“…C-peptide and insulin are secreted in equimolar quantities (6)(7)(8), and C-peptide is not extracted to any significant degree by the liver (12). Consequently, the simultaneous determination of C-peptide and insulin in peripheral venous plasma has been used as a relative measure of hepatic insulin uptake (32,33), and C-peptide measurements alone provide an adequate means for assessing the insulin secretion. However, this latter approach has been limited by our incomplete knowledge of the kinetics of C-peptide.…”

Section: Resultsmentioning

confidence: 99%

Kinetics of human connecting peptide in normal and diabetic subjects.

Faber¹,

Hagen²,

Binder³

et al. 1978

J. Clin. Invest.

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206

116

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A B S T R A C T The metabolic clearance rate (MCR) of synthetic human connecting peptide (C-peptide) was measured with a single-dose injection technique in six normal and seven diabetic subjects and with a constant infusion technique in one normal subject.The MCR of C-peptide did not differ in normal subjects (4.4 ml/min per kg; range, 3.7-4.9) and in diabetic subjects (4.7 ml/min per kg; range, 3.7-5.8). Employment of both techniques in one subject gave similar MCR. The average half-life of C-peptide in plasma calculated from the last 1-h period of the singledose injection studies was longer in the insulin-dependent diabetics (42.5 min; range, 39.4-48.5) than in the normal subjects (33.5 min; range, 24.9-45.3).These results indicate that the 13-cell secretory capacity of normal and insulin-dependent diabetic subjects can be compared by measuring the C-peptide concentration in peripheral venous plasma. The difference in the half-life of C-peptide in plasma between diabetics and normals suggests an altered kinetics of the disappearance of the peptide, while the overall metabolism, as expressed by the MCR, is similar.

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Section: Resultsmentioning

confidence: 99%

Kinetics of human connecting peptide in normal and diabetic subjects.

Faber¹,

Hagen²,

Binder³

et al. 1978

J. Clin. Invest.

Self Cite

206

116

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“…[2][3][4] In addition, a number of disorders of the liver are associated with pancreatic disease including hemochromatosis and alcoholic liver disease.…”

mentioning

confidence: 99%

Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection

et al. 1999

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Non-insulin-dependent diabetes mellitus (NIDDM) may be associated with chronic hepatitis C virus (HCV) infection. This was studied further in two parts. First, 1,151 patients with HCV-related cirrhosis and 181 patients with hepatitis B virus (HBV)-related cirrhosis, well matched for age, sex, and severity of cirrhosis, were reviewed retrospectively. The prevalence of diabetes mellitus was higher in HCV-related cirrhosis (23.6%) than in HBV-related cirrhosis (9.4%; odds ratio [OR], 2.78; 95% confidence interval [CI], 1.6-4.79; P ‫؍‬ .0002). The prevalence of diabetes mellitus was associated closely with the Child-Pugh score (OR, 3.83; 95% CI, 2.38-6.17; P F .0001) and increasing age (OR, 1.02; 95% CI, 1.00-1.03; P ‫؍‬ .0117). Second, 235 patients with biopsy confirmed chronic HBV or HCV underwent an oral glucose tolerance test. Only 1 of 70 patients with chronic viral hepatitis without cirrhosis was diabetic. However, 31 of 127 patients with HCV-related cirrhosis (24.4%) were diabetic compared with 3 of 38 patients with HBVrelated cirrhosis (7.9%, P ‫؍‬ .0477). The major variables associated with NIDDM were cirrhosis (OR, 14.39; 95% CI, 1.91-108; P ‫؍‬ .0096) and male sex (OR, 4.64; 95% CI, 1.32-16.18; P ‫؍‬ .0161). Fasting insulin levels in 30 patients with HCV-related cirrhosis and diabetes mellitus were elevated significantly, which was consistent with insulin resistance. However, acute insulin responsiveness was reduced in all patients with HCV infection and diabetes suggesting concomitant B-cell dysfunction. This study confirms an association between HCV and NIDDM. (HEPATOL-OGY 1999;30:1059-1063.)An association between cirrhosis and abnormalities of glucose metabolism has been recognized for over 20 years. 1

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“…5 Its pathogenesis involves many factors, and hyperinsulinaemia and peripheral insulin resistance are thought to play major roles. [6][7][8] The growth rate of a tumour is a critical factor for the prognosis of cancer patients. The growth of HCC can be measured by determining the doubling time (DT) with imaging analyses.…”

mentioning

confidence: 99%

Augmentation effect of postprandial hyperinsulinaemia on growth of human hepatocellular carcinoma

Saito

Inoue

Saito

et al. 2002

Gut

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Background: Cirrhotic patients with hepatocellular carcinoma (HCC) frequently have impaired glucose metabolism. Aims: To investigate whether impaired glucose metabolism affects the growth rate of the tumour. Patients and methods: Tumour doubling time (DT), assessed by ultrasound imaging analysis, was measured in 60 patients with single small HCC (diameter <30 mm). DT was compared with plasma insulin and glucose concentrations following the oral glucose tolerance test (OGTT). The effect of continuous infusion of octreotide (a somatostatin analogue 200 µg/day) for three months on DT in five cases was assessed. Results: The 60 patients were divided into two groups because the median DT was 140 days: rapid growth group (DT <140 days, n=30) and slow growth group (DT >140 days, n=30). Fasting plasma insulin concentration and area under the plasma insulin curve (AUC ins ) of the OGTT (10.4 (6.2) µU/ml and 262 (152) µU/ml/h, respectively; mean (SD)) in the rapid growth group were significantly higher than those in the slow growth group (7.6 (4.3) and 146 (140), respectively) (p=0.041 and p=0.0006, respectively). In contrast, fasting plasma glucose concentration and area under the plasma glucose curve (AUC gluc ) in the rapid growth group were significantly lower than those in the slow growth group (p=0.0003 and p=0.0012, respectively). Univariate and multivariate analyses of logistic regression models demonstrated that AUC ins was a significant factor contributing to the growth rate of HCC (p=0.001 and p=0.016, respectively). AUC ins significantly decreased after octreotide treatment (p<0.02) but AUC gluc did not significantly change. DT after treatment increased in three of the five patients and could not be calculated in the remaining two patients because of no change in the diameter of the tumour. Conclusions: These data suggest that postprandial hyperinsulinaemia is associated with accelerated HCC growth.

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Hyperinsulinism of Hepatic Cirrhosis: Diminished Degradation or Hypersecretion?

Cited by 204 publications

References 12 publications

Kinetics of human connecting peptide in normal and diabetic subjects.

Kinetics of human connecting peptide in normal and diabetic subjects.

Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection

Augmentation effect of postprandial hyperinsulinaemia on growth of human hepatocellular carcinoma

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