Plasma Insulin Disappearance Curve After Intravenous Insulin Injection in Human Hyperthyroidism

Wajchenberg, B. L.; Cesar, F. P.; Leme, Carlos Eduardo; Didio, Renato; Kieffer, J

doi:10.1111/j.1365-2265.1978.tb01499.x

Cited by 10 publications

(3 citation statements)

References 10 publications

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“…Although proinsulin cross-reacts in the standard insulin radioimmunoassay, it has only 5% of the biological activity of insulin (Sonksen et al, 1973). Enhanced degradation of insulin has been reported in some studies (Elgee & Williams, 1955;Maracek & Feldman, 1973) but not all (Wajchenberg et al, 1978) although, it is clear from the present study that metabolic clearance rates are unchanged. Increased clearance of insulin cannot in any case explain glucose intolerance as both the action and degradation of insulin are effected via its receptors (Terris & Steiner, 1975).…”

Section: Discussionmentioning

confidence: 43%

Insulin Sensitivity in Hyperthyroidism: Measurement by the Glucose Clamp Technique

McCulloch

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Heine

et al. 1983

Clinical Endocrinology

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Sensitivity to porcine insulin has been compared in overnight fasted hyperthyroid and control subjects using a euglycaemic clamp technique. Basal values for blood glucose, lactate, pyruvate, alanine, serum insulin and C-peptide were similar in the two groups, whilst blood glycerol (hyperthyroid 0.11 +/- 0.02 (mean +/- S.E.) vs. control 0.06 +/- 0.01 mmol/l, P less than 0.01) and blood 3-hydroxybutyrate (0.28 [0.03-0.79, range ]vs 0.09 [0.01-0.29 ]mmol/l, P less than 0.05) were increased in hyperthyroidism. During the 2 hour insulin infusion (0.05 U/kg/h), serum insulin plateaued at the same level (44 +/- 4 vs 44 +/- 1 mU/l) and insulin metabolic clearance rates were similar (1.21 +/- 0.10 vs 1.25 +/- 0.03 l/min). Serum C-peptide levels also decreased by similar amounts (40 +/- 8 vs 47 +/- 6%). The amount of glucose infused to maintain euglycaemia was identical during the second hour of insulin infusion (290 +/- 50 vs 330 +/- 30 mg/kg) as were the increments in lactate and pyruvate concentrations. Blood glycerol values decreased in both groups although values in hyperthyroid patients remained significantly higher than in controls. 3-Hydroxybutyrate concentrations fell to similar values in the two groups. These findings suggest that insulin-stimulated glucose metabolism and inhibition of ketogenesis are normal in hyperthyroidism.

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Section: Discussionmentioning

confidence: 43%

Insulin Sensitivity in Hyperthyroidism: Measurement by the Glucose Clamp Technique

McCulloch

Home

Heine

et al. 1983

Clinical Endocrinology

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“…Studies of insulin sensitivity in hyperthyroid man have been equivocal showing a normal [27], increased [5] or decreased [28] blood glucose response to exogenous insulin. Enhanced insulin degradation in hyperthyroidism, noted by some [29] but not all workers [30], may not explain the coexistence of normal insulin and elevated blood glucose concentrations as insulin degradation and biological effect are inextricably linked [3 11.…”

Section: Discussionmentioning

confidence: 99%

Diurnal metabolic profiles in hyperthyroidism

McCulloch

Johnston

Burrin

et al. 1982

Eur J Clin Investigation

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Abstract. Hormone and metabolite profiles during a 12 h period of normal meals and activity were examined in nine hyperthyroid subjects with Graves' disease and sixteen matched controls. Six hyperthyroid subjects were restudied when euthyroid on carbimazole and thyroxine. Thyrotoxic patients had mild fasting hyperglycaemia (mean pL SEM blood glucose, 5·5 pL 0·2 v. 4·8 pL 0·1 mmol/l, P < 0·01), elevated blood glycerol (0·15 pL 0·02 v. 0·08 pL 0·01 mmol/l, P < 0·001) and elevated plasma non‐esterified fatty acid (NEFA) concentrations (0·91 pL 0·06 v. 0·58 pL 0·03 mmol/l, P < 0·001) when compared to controls. Fasting blood concentrations of the gluconeogenic precursors lactate, pyruvate and alanine, blood ketone body concentrations and circulating insulin and growth hormone levels were similar in hyperthyroid and control subjects. Blood glucose responses to meals were exaggerated and the mean 12 h blood glucose was increased (6·1 pL 0·1 v. 5·5 pL 0·1 mmol/l, P < 0·01) in hyperthyroidism. Similarly, hyperlactataemia and hyperpyruvicaemia were observed after meals. Blood ketone body, blood glycerol and plasma NEFA levels showed exaggerated pre‐prandial peaks and the mean 12 h values for blood glycerol (0·12 pL 0·01 v. 0·08 pL 0·01 mmol/l, P < 0·01) and plasma NEFA (0·71 pL 0·03 v. 0·53 pL 0·04 mmol/l, P < 0·01) were increased. Concentrations of insulin and growth hormone remained similar to control values throughout the study period. Blocking therapy with carbimazole and thyroid hormone replacement with thyroxine for 5–10 months suppressed blood glycerol, plasma NEFA and blood ketone body levels to normal or subnormal values but had no effect on the elevated blood glucose, blood lactate or blood pyruvate profiles. Graves' disease with hyperthyroidism is thus associated with abnormalities of carbohydrate metabolism which are not restored to normal by 5–10 months oral antithyroid therapy. The changes in lipid metabolism in hyperthyroidism are normalized by this treatment.

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“…A combination of decreased insulin secretion and normal circulating insulin concentrations may be explained by a decreased rate of degradation of insulin in hyperthyroidism, but there is no direct evidence for this in man [20,21]. Proinsulin can displace native insulin from the insulin receptor [22,23], but the affinity of proinsulin for the insulin receptor and its biological effect is only about 2% of that of insulin [22,23].…”

Section: Discussionmentioning

confidence: 99%

Hypersecretion of proinsulin in thyrotoxicosis

Sestoft

Hedïng

1981

Diabetologia

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Summary. The plasma insulin, C-peptide and proinsulin concentrations were investigated in thyrotoxic patients and in normal controls after an overnight fast, during a 36 h fasting period, an intravenous glucose tolerance test and an oral glucose tolerance test. The main finding was a significantly raised concentration of proinsulin in plasma of patients with thyrotoxicosis. After an overnight fast the plasma proinsulin was 0.048 + 0.005 pmol/ml in 15 thyrotoxic patients compared with 0.023 _ 0.012 pmol/ml in 15 euthyroid controls. A twofold rise of plasma proinsulin concentration was also found in thyrotoxic patients during a prolonged fast, and during intravenous and oral glucose tolerance tests. The immunoreactivity of proinsulin in the insulin radioimmunoassay gave rise to slightly elevated concentrations of immunoreactive insulin in thyrotoxic patients in all the conditions investigated. When insulin values were corrected for proinsulin crossreactivity, they were similar in euthyroid controls and thyrotoxic patients. The concentration of plasma Cpeptide was not significantly altered in thyrotoxic patients during intravenous and oral glucose tolerance tests.

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Plasma Insulin Disappearance Curve After Intravenous Insulin Injection in Human Hyperthyroidism

Cited by 10 publications

References 10 publications

Insulin Sensitivity in Hyperthyroidism: Measurement by the Glucose Clamp Technique

Insulin Sensitivity in Hyperthyroidism: Measurement by the Glucose Clamp Technique

Diurnal metabolic profiles in hyperthyroidism

Hypersecretion of proinsulin in thyrotoxicosis

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