Cutis verticis gyrata (CVG) is a rare disorder; it is characterized by thickening of the scalp wh... more Cutis verticis gyrata (CVG) is a rare disorder; it is characterized by thickening of the scalp which becomes raised to form ridges and furrows resembling the cerebral gyri. We report a case of CVG associated with the autosomal dominant insulin resistance syndrome. This syndrome is characterized by obesity, mild mental retardation, delayed puberty, acanthosis nigricans and hyperinsulinaemia. The association of CVG and autosomal dominant insulin resistance has not been previously described.
SummaryOBJECTIVE Adult patients with growth hormone deflciency are thought to be at higher risk o... more SummaryOBJECTIVE Adult patients with growth hormone deflciency are thought to be at higher risk of mortallty from cardiovascular disease. We therefore investlgated the effect of recombinant human growth hormone (rhGH) replacement therapy on fasting serum concentrations of IIplds, lipoproteins and cholesterol precursors in adult growth hormone deficient patients.DESIGN Double‐blind placebo controlled trial. Patients were randomly allocated to placebo or rhGH replacement therapy (0·018 Ulkglday for 1 month followed by 0·036 Ufkglday for 1 month).PATIENTS Eighteen patients with severe growth hormone deficiency.MEASUREMENTS Fasting lipid, lipoprotein and cholesterol precursors (lathosterol and mevalonic acid) were measured at baseline and after 2 months.RESULTS In the rhGH treated group there was a significant fall in serum cholesterol (P < 0·01) (6·44 ±0·49 to 5·71 ± 0·48 mmol/l), LDL cholesterol (P < 0·02) (4·29 ± 0·49 to 3·62 ± 0·44 mmol/l), LDL cholesterollHDL cholesterol ratio (P < 0·02) (3·99 · 0·62 to 3·26 ± 0·39), apollpo‐protein B (P>0·01 (1·30 ± 0·11 to 1·15 ± 0·11 g/l) and mevalonic acid (P<0·05) (13·4 ±10·96 to 6·21 ± 1·91 μg/l). There were no significant changes In triglycerides, HDL cholesterol, apolipoprotein A1, lipoprotein (a) or lathosterol concentrations. In the GH treated group the rise in serum insulln was inversely correlated wlth the fall in cholesterol (P < 0·05), LDL cholesterol (P < 0·01) and apolipoproteln B (P < 0·01). There were no significant changes in any of the measured variables in the placebo group.CONCLUSION We conclude that GH may be involved in the regulation of lipid and lipoprotein metabolism and that rhGH replacement therapy of adult GHD patients is associated with beneficial changes in lipid and lipoprotein profiles. The reduction in mevalonic acid is consistent with up‐regulation of hepatic LDL receptors caused by GH and this may explain the fall in LDL cholesterol and apolipoprotein B concentrations.
Computer Methods and Programs in Biomedicine, Jul 1, 1990
This paper describes the architecture of, and the main reasoning methods involved in, a computer ... more This paper describes the architecture of, and the main reasoning methods involved in, a computer system developed to assist in diabetic management. The system integrates (i) a database module used for blood glucose moni'~oring, (ii) an interpreter module used to analyse the adequacy of diet and insulin treatment for diabetics, and (iii~ an advisory module suggesting alterations in diet and/or insulin regimen in order to improve glycaemic control. The analysis of blood glucose profiles and hypoglycaemic episodes, as well as the suggestions for altered diet and insulin therapy, are based on qualitative and quantitative models of insulin effect and carbohydrate absorption using mealtime related glucose balance and distance from the preselected target (DFT) glucose values as focal concepts in the reasoning process. During the sequence of consultations with the system, a dynamic model of carbohydrate metabolism is gradually adjusted in order to constitute an appropriate simulation for the specific patient. This model is used to confirm the suggestions made by the ADVISOR program and to assist the health care professional in selecting the best control action by predicting the blood glucose profiles resulting from alternative control policies.
Background Growth Hormone is abused by athletes for its lipolytic and anabolic properties. Its us... more Background Growth Hormone is abused by athletes for its lipolytic and anabolic properties. Its use is prohibited by the World Anti-Doping Agency. The GH-2000 project developed a methodology to detect its abuse using the concentrations of two GH-dependent biomarkers, IGF-I and type 3 procollagen (P-III-P). The sensitivity of this method may be improved by considering intraindividual variability. Aim The aim of this study was to examine the intra-individual variability of IGF-I, P-III-P and the GH-2000 score. Subjects and methods IGF-I, P-III-P and GH-2000 score were evaluated in four longitudinal studies involving 303 elite and 78 amateur athletes. Samples were collected over a period of up to 12 months from a total of 238 men and 143 women aged between 17 and 53 years (mean 24AE2). Results The four studies showed good agreement with no apparent difference in within-individual variation between amateur and elite athletes. The intra-individual variability for IGF-I ranged between 14-16% while the variability for P-III-P was 7-18%. No athlete tested positive for growth hormone during any of the studies. The overall mean intra-individual variability of the GH-2000 score was less than 0AE6 units in all studies. Conclusions The high stability of marker levels suggests that concentrations are largely genetically determined. Adopting a test based on the concept of an athlete's 'passport' or 'profiling' would take advantage of this and most likely increase the sensitivity of the test. These data also provide strong evidence that a positive test result for GH abuse would not occur as a result of chance variability.
Journal of Diabetes and Its Complications, Apr 1, 1992
The potential of the aldose reductase inhibitor ponalrestat (600 mg daily) to ameliorate diabetic... more The potential of the aldose reductase inhibitor ponalrestat (600 mg daily) to ameliorate diabetic neuropathy was evaluated in 259 diabetes mellitus patients with peripheral neuropathy (defined by abnormal vibration perception threshold and abnormal peroneal motor conduction velocity) in a double-blind placebo-controlled clinical trial running for 18 months. Overall, no beneficial effect of ponalrestat on vibration perception thresholds, nerve conduction velocities, and nerve action potential amplitudes was detected. Because vibration perception thresholds and conduction velocities in median, peroneal, and sural nerves did not deteriorate in the placebo group, the potential of ponalrestat to prevent the expected deterioration in peripheral nerve function that occurs with an increased duration of diabetes was not tested. Patients with an abnormal heart rate reaction to standing (abnormal 30: 15 ratio; n = 84) on ponalrestat did not deteriorate in this autonomic nerve function test as shown in those on placebo. In conclusion, ponalrestat did not improve peripheral nerve function in diabetes mellitus patients with signs of peripheral neuropathy, although it did ameliorate a deterioration in autonomic nerve function in diabetic patients with signs of autonomic neuropathy. (The Journal of Diabetes and Its Complications 6:123-130, 1992.
1. One- and two-dimensional (correlated shift spectroscopy) high resolution proton n.m.r. spectra... more 1. One- and two-dimensional (correlated shift spectroscopy) high resolution proton n.m.r. spectra of human cerebrospinal fluid (CSF) are reported. The merits of water suppression by freeze drying or irradiation, and spectral simplification by spin-echo methods, are discussed. 2. Well-resolved resonances for a range of low molecular weight metabolites such as lactate, 3-d-hydroxybutyrate, alanine, acetate, citrate, glucose, valine and formate were observed. Resonances for glutamine were observed only from freeze dried samples. Concentrations determined by n.m.r. were in reasonable agreement with those from conventional methods. 3. The n.m.r. spectra of CSF were related to the clinical conditions of the subjects. No resonances for citrate were present in spectra of CSF from subjects (three infants) with bacterial meningitis; high lactate and lowered glucose levels were observed. Strong resonances for glucose and glycine were observed for mildly diabetic subjects. Both the aromatic and the aliphatic regions of the CSF spectra from subjects suffering from liver failure contained distinctive features characteristic for hepatic coma: intense resonances for lactate, alanine, valine, methionine, tyrosine, phenylalanine and histidine. In some cases guanine was also present, which does not appear to have been reported previously. The two-dimensional spectrum suggested the presence of abnormally high levels of a number of endogenous metabolites. Such assignments were not possible using one-dimensional spectra alone because of signal overlap.
Growth hormone treatment given to adult growth hormone deficient patients leads to an increase in... more Growth hormone treatment given to adult growth hormone deficient patients leads to an increase in lean body mass by an unknown mechanism. The aim of this study was to investigate the actions of growth hormone treatment on protein metabolism in adult growth hormone deficient patients. Double-blind, placebo controlled trial of recombinant human growth hormone (0.018 U/kg/day for 1 month followed by 0.036 U/kg/day for 1 month) with isotopic whole body protein turnover studies at 0 and 2 months. Eighteen adult growth hormone deficient patients (nine male, nine female of mean age 46.6 (range 30-56). Whole body isotopic leucine turnover using L-1-13C-leucine measuring leucine Ra (a measure of protein degradation), non-oxidative leucine Rd (a measure of protein synthesis) and leucine oxidation rate. Lean body mass (P < 0.02), circulating insulin-like growth factor I (P < 0.01) and insulin (P < 0.02) were significantly increased at 2 months in the treatment group but there was no change in the placebo group. When expressed in relation to body weight, leucine Ra and non-oxidative leucine Rd increased (P < 0.01) and leucine oxidation decreased (P < 0.02) after 2 months growth hormone treatment. When expressed in relation to lean body mass non-oxidative leucine Rd increased (P < 0.02) and leucine oxidation decreased (P < 0.02) but there was no significant change in leucine Ra after 2 months growth hormone treatment. In the placebo group there were no significant changes in leucine metabolism expressed as lean body mass or body weight after 2 months. changes in leucine metabolism expressed as lean body mass or body weight after 2 months. These results indicate that the increase in lean body mass resulting from growth hormone treatment in adult growth hormone deficient patients is due to an increase in protein synthesis.
Background Growth Hormone is abused by athletes for its lipolytic and anabolic properties. Its us... more Background Growth Hormone is abused by athletes for its lipolytic and anabolic properties. Its use is prohibited by the World Anti-Doping Agency. The GH-2000 project developed a methodology to detect its abuse using the concentrations of two GH-dependent biomarkers, IGF-I and type 3 procollagen (P-III-P). The sensitivity of this method may be improved by considering intraindividual variability. Aim The aim of this study was to examine the intra-individual variability of IGF-I, P-III-P and the GH-2000 score. Subjects and methods IGF-I, P-III-P and GH-2000 score were evaluated in four longitudinal studies involving 303 elite and 78 amateur athletes. Samples were collected over a period of up to 12 months from a total of 238 men and 143 women aged between 17 and 53 years (mean 24AE2). Results The four studies showed good agreement with no apparent difference in within-individual variation between amateur and elite athletes. The intra-individual variability for IGF-I ranged between 14-16% while the variability for P-III-P was 7-18%. No athlete tested positive for growth hormone during any of the studies. The overall mean intra-individual variability of the GH-2000 score was less than 0AE6 units in all studies. Conclusions The high stability of marker levels suggests that concentrations are largely genetically determined. Adopting a test based on the concept of an athlete's 'passport' or 'profiling' would take advantage of this and most likely increase the sensitivity of the test. These data also provide strong evidence that a positive test result for GH abuse would not occur as a result of chance variability.
A simple model of the distribution and metabolism of insulin in vivo has been evaluated using dat... more A simple model of the distribution and metabolism of insulin in vivo has been evaluated using data from insulin infusion into a group of normal subjects. The major rate-limiting step for access to degradation pathways is assumed to consist of binding of the ligand to a single population of insulin receptor sites, except that provision is made for the possibility of linear non-receptor-mediated degradation and for the phenomenon of negative cooperativity. The model has been shown to accommodate the non-linearity of insulin metabolism , allows evaluation of receptor association and dissociation constants and provides for the first time an estimate of total accessible receptor number in the intact organism. For normal fasting man the model predicts 1.00 _+ 0.05 nmol accessible binding sites/kg (mean + SD).
... Dr. GF Watts BSC DM MRCP Lecturer in Endocrinology 1,* ,; C Lowy MSc FRCP Reader in Endocrino... more ... Dr. GF Watts BSC DM MRCP Lecturer in Endocrinology 1,* ,; C Lowy MSc FRCP Reader in Endocrinology 1 ,; PH Sönksen MD FRCP Professor 1 ,; ... How to Cite. Watts, GF, Lowy, C., Sönksen, PH and Shaw, KM (1992), Setting the standards for diabetes care: Microalbuminuria. ...
American Journal of Physiology-endocrinology and Metabolism, May 1, 2002
Abnormal lipid metabolism may be related to the increased cardiovascular risk in type 1 diabetes.... more Abnormal lipid metabolism may be related to the increased cardiovascular risk in type 1 diabetes. Secretion and clearance rates of very low density lipoprotein (VLDL) apolipoprotein B100 (apoB) determine plasma lipid concentrations. Type 1 diabetes is characterized by increased growth hormone (GH) secretion and decreased insulin-like growth factor (IGF) I concentrations. High-dose IGF-I therapy improves the lipid profile in type 1 diabetes. This study examined the effect of low-dose (40 g ⅐ kg Ϫ1 ⅐ day Ϫ1) IGF-I therapy on VLDL apoB metabolism, VLDL composition, and the GH-IGF-I axis during euglycemia in type 1 diabetes. Using a stable isotope technique, VLDL apoB kinetics were estimated before and after 1 wk of IGF-I therapy in 12 patients with type 1 diabetes in a double-blind, placebo-controlled trial. Fasting plasma triglyceride (P Ͻ 0.03), VLDL-triglyceride concentrations (P Ͻ 0.05), and the VLDL-triglyceride-to-VLDL apoB ratio (P Ͻ 0.002) significantly decreased after IGF-I therapy, whereas VLDL apoB kinetics were not significantly affected by IGF-I therapy. IGF-I therapy resulted in a significant increase in IGF-I and a significant reduction in GH concentrations. The mean overnight insulin concentrations during euglycemia decreased by 25% after IGF-I therapy. These results indicate that low-dose IGF-I therapy restores the GH-IGF-I axis in type 1 diabetes. IGF-I therapy changes fasting triglyceride concentrations and VLDL composition probably because of an increase in insulin sensitivity.
We have established a records linkage between 'Diabeta' (the computerized clinica... more We have established a records linkage between 'Diabeta' (the computerized clinical records system in the Diabetes Unit of St Thomas' Hospital) and the National Health Services Central Register (NHSCR) of the United Kingdom. Over 7000 diabetic patient records have been collected since 1973. Demographic data on all diabetic patients were retrieved and submitted to the NHSCR via a floppy disk. A matching system (automatic or manual) was used by the NHSCR to identify deceased patients and the most recent demographic data was provided on patients alive. This linkage resulted in an update of 91% of records in Diabeta. The findings of the update included: (1) 86% of diabetic patient's death had not been notified to the hospital and were not recorded on Diabeta. Mortality can now be assessed accurately as an outcome measure in our diabetic population. (2) Provision of the NHS number to Diabeta, as before it was not available on many patients seen in the hospital. The NHS number is a key patient identifier which can be used to exchange information within the NHS-wide network. (3) Diabetes was recorded as a cause of death in only 36% of death certificates. Analyses of death certificates alone must thus give poor information about mortality in diabetes. (4) Geographical location of patients on the database was updated, enabling tracing of patients for long-term studies and analyses of movement.
Page 1. Dm WORKSHOP REPORT A Role for Computers in Diabetes Care? CD Williams, FE Harvey, P. H. S... more Page 1. Dm WORKSHOP REPORT A Role for Computers in Diabetes Care? CD Williams, FE Harvey, P. H. Sonksen Department of Medicine, Sf Thomas' Hospital, London, UK. KEY WORDS Computers Diabetes care Contents Preface Introduction ...
American Journal of Physiology-endocrinology and Metabolism, Jun 1, 1991
Clinical studies have demonstrated that chloroquine and hydroxychloroquine improve glucose metabo... more Clinical studies have demonstrated that chloroquine and hydroxychloroquine improve glucose metabolism in patients with insulin-resistant diabetes mellitus. The mechanism of action has not been determined. We undertook a randomized double-blind placebo-controlled trial of 3 days of oral chloroquine phosphate, 250 mg four times daily, in 20 patients with non-insulin-dependent diabetes mellitus controlled by diet. Rates of glucose appearance (Ra) and disappearance (Rd) were evaluated by infusion of stable isotopically labeled D-glucose ([6,6-2H2]glucose) during hyperinsulinemic euglycemic clamps before and after treatment with chloroquine or placebo. Chloroquine significantly improved fasting plasma glucose from 199.8 +/- 8.6 to 165.6 +/- 7.6 mg/dl (P less than 0.01). Total exogenous glucose infusion required to maintain euglycemia significantly increased (1,792.6-2,040.1 mg.kg-1.330 min-1, P less than 0.05) due to an increase in Rd (2,348.0-2,618.9 mg.kg-1.330 min-1, P less than 0.01) without change in Ra. Metabolic clearance rate of insulin decreased by 39% from 14.4 +/- 1.3 to 11.0 +/- 0.6 ml.kg-1.min-1 (P less than 0.01) at plasma insulin levels of 150-200 mU/l but not at levels of 2,000-3,000 mU/l. In addition, chloroquine increased fasting C-peptide secretion by 17% and reduced feedback inhibition of C-peptide by 9.1 and 10.6% during low- and high-dose insulin infusions, respectively.
Cutis verticis gyrata (CVG) is a rare disorder; it is characterized by thickening of the scalp wh... more Cutis verticis gyrata (CVG) is a rare disorder; it is characterized by thickening of the scalp which becomes raised to form ridges and furrows resembling the cerebral gyri. We report a case of CVG associated with the autosomal dominant insulin resistance syndrome. This syndrome is characterized by obesity, mild mental retardation, delayed puberty, acanthosis nigricans and hyperinsulinaemia. The association of CVG and autosomal dominant insulin resistance has not been previously described.
SummaryOBJECTIVE Adult patients with growth hormone deflciency are thought to be at higher risk o... more SummaryOBJECTIVE Adult patients with growth hormone deflciency are thought to be at higher risk of mortallty from cardiovascular disease. We therefore investlgated the effect of recombinant human growth hormone (rhGH) replacement therapy on fasting serum concentrations of IIplds, lipoproteins and cholesterol precursors in adult growth hormone deficient patients.DESIGN Double‐blind placebo controlled trial. Patients were randomly allocated to placebo or rhGH replacement therapy (0·018 Ulkglday for 1 month followed by 0·036 Ufkglday for 1 month).PATIENTS Eighteen patients with severe growth hormone deficiency.MEASUREMENTS Fasting lipid, lipoprotein and cholesterol precursors (lathosterol and mevalonic acid) were measured at baseline and after 2 months.RESULTS In the rhGH treated group there was a significant fall in serum cholesterol (P < 0·01) (6·44 ±0·49 to 5·71 ± 0·48 mmol/l), LDL cholesterol (P < 0·02) (4·29 ± 0·49 to 3·62 ± 0·44 mmol/l), LDL cholesterollHDL cholesterol ratio (P < 0·02) (3·99 · 0·62 to 3·26 ± 0·39), apollpo‐protein B (P>0·01 (1·30 ± 0·11 to 1·15 ± 0·11 g/l) and mevalonic acid (P<0·05) (13·4 ±10·96 to 6·21 ± 1·91 μg/l). There were no significant changes In triglycerides, HDL cholesterol, apolipoprotein A1, lipoprotein (a) or lathosterol concentrations. In the GH treated group the rise in serum insulln was inversely correlated wlth the fall in cholesterol (P < 0·05), LDL cholesterol (P < 0·01) and apolipoproteln B (P < 0·01). There were no significant changes in any of the measured variables in the placebo group.CONCLUSION We conclude that GH may be involved in the regulation of lipid and lipoprotein metabolism and that rhGH replacement therapy of adult GHD patients is associated with beneficial changes in lipid and lipoprotein profiles. The reduction in mevalonic acid is consistent with up‐regulation of hepatic LDL receptors caused by GH and this may explain the fall in LDL cholesterol and apolipoprotein B concentrations.
Computer Methods and Programs in Biomedicine, Jul 1, 1990
This paper describes the architecture of, and the main reasoning methods involved in, a computer ... more This paper describes the architecture of, and the main reasoning methods involved in, a computer system developed to assist in diabetic management. The system integrates (i) a database module used for blood glucose moni'~oring, (ii) an interpreter module used to analyse the adequacy of diet and insulin treatment for diabetics, and (iii~ an advisory module suggesting alterations in diet and/or insulin regimen in order to improve glycaemic control. The analysis of blood glucose profiles and hypoglycaemic episodes, as well as the suggestions for altered diet and insulin therapy, are based on qualitative and quantitative models of insulin effect and carbohydrate absorption using mealtime related glucose balance and distance from the preselected target (DFT) glucose values as focal concepts in the reasoning process. During the sequence of consultations with the system, a dynamic model of carbohydrate metabolism is gradually adjusted in order to constitute an appropriate simulation for the specific patient. This model is used to confirm the suggestions made by the ADVISOR program and to assist the health care professional in selecting the best control action by predicting the blood glucose profiles resulting from alternative control policies.
Background Growth Hormone is abused by athletes for its lipolytic and anabolic properties. Its us... more Background Growth Hormone is abused by athletes for its lipolytic and anabolic properties. Its use is prohibited by the World Anti-Doping Agency. The GH-2000 project developed a methodology to detect its abuse using the concentrations of two GH-dependent biomarkers, IGF-I and type 3 procollagen (P-III-P). The sensitivity of this method may be improved by considering intraindividual variability. Aim The aim of this study was to examine the intra-individual variability of IGF-I, P-III-P and the GH-2000 score. Subjects and methods IGF-I, P-III-P and GH-2000 score were evaluated in four longitudinal studies involving 303 elite and 78 amateur athletes. Samples were collected over a period of up to 12 months from a total of 238 men and 143 women aged between 17 and 53 years (mean 24AE2). Results The four studies showed good agreement with no apparent difference in within-individual variation between amateur and elite athletes. The intra-individual variability for IGF-I ranged between 14-16% while the variability for P-III-P was 7-18%. No athlete tested positive for growth hormone during any of the studies. The overall mean intra-individual variability of the GH-2000 score was less than 0AE6 units in all studies. Conclusions The high stability of marker levels suggests that concentrations are largely genetically determined. Adopting a test based on the concept of an athlete's 'passport' or 'profiling' would take advantage of this and most likely increase the sensitivity of the test. These data also provide strong evidence that a positive test result for GH abuse would not occur as a result of chance variability.
Journal of Diabetes and Its Complications, Apr 1, 1992
The potential of the aldose reductase inhibitor ponalrestat (600 mg daily) to ameliorate diabetic... more The potential of the aldose reductase inhibitor ponalrestat (600 mg daily) to ameliorate diabetic neuropathy was evaluated in 259 diabetes mellitus patients with peripheral neuropathy (defined by abnormal vibration perception threshold and abnormal peroneal motor conduction velocity) in a double-blind placebo-controlled clinical trial running for 18 months. Overall, no beneficial effect of ponalrestat on vibration perception thresholds, nerve conduction velocities, and nerve action potential amplitudes was detected. Because vibration perception thresholds and conduction velocities in median, peroneal, and sural nerves did not deteriorate in the placebo group, the potential of ponalrestat to prevent the expected deterioration in peripheral nerve function that occurs with an increased duration of diabetes was not tested. Patients with an abnormal heart rate reaction to standing (abnormal 30: 15 ratio; n = 84) on ponalrestat did not deteriorate in this autonomic nerve function test as shown in those on placebo. In conclusion, ponalrestat did not improve peripheral nerve function in diabetes mellitus patients with signs of peripheral neuropathy, although it did ameliorate a deterioration in autonomic nerve function in diabetic patients with signs of autonomic neuropathy. (The Journal of Diabetes and Its Complications 6:123-130, 1992.
1. One- and two-dimensional (correlated shift spectroscopy) high resolution proton n.m.r. spectra... more 1. One- and two-dimensional (correlated shift spectroscopy) high resolution proton n.m.r. spectra of human cerebrospinal fluid (CSF) are reported. The merits of water suppression by freeze drying or irradiation, and spectral simplification by spin-echo methods, are discussed. 2. Well-resolved resonances for a range of low molecular weight metabolites such as lactate, 3-d-hydroxybutyrate, alanine, acetate, citrate, glucose, valine and formate were observed. Resonances for glutamine were observed only from freeze dried samples. Concentrations determined by n.m.r. were in reasonable agreement with those from conventional methods. 3. The n.m.r. spectra of CSF were related to the clinical conditions of the subjects. No resonances for citrate were present in spectra of CSF from subjects (three infants) with bacterial meningitis; high lactate and lowered glucose levels were observed. Strong resonances for glucose and glycine were observed for mildly diabetic subjects. Both the aromatic and the aliphatic regions of the CSF spectra from subjects suffering from liver failure contained distinctive features characteristic for hepatic coma: intense resonances for lactate, alanine, valine, methionine, tyrosine, phenylalanine and histidine. In some cases guanine was also present, which does not appear to have been reported previously. The two-dimensional spectrum suggested the presence of abnormally high levels of a number of endogenous metabolites. Such assignments were not possible using one-dimensional spectra alone because of signal overlap.
Growth hormone treatment given to adult growth hormone deficient patients leads to an increase in... more Growth hormone treatment given to adult growth hormone deficient patients leads to an increase in lean body mass by an unknown mechanism. The aim of this study was to investigate the actions of growth hormone treatment on protein metabolism in adult growth hormone deficient patients. Double-blind, placebo controlled trial of recombinant human growth hormone (0.018 U/kg/day for 1 month followed by 0.036 U/kg/day for 1 month) with isotopic whole body protein turnover studies at 0 and 2 months. Eighteen adult growth hormone deficient patients (nine male, nine female of mean age 46.6 (range 30-56). Whole body isotopic leucine turnover using L-1-13C-leucine measuring leucine Ra (a measure of protein degradation), non-oxidative leucine Rd (a measure of protein synthesis) and leucine oxidation rate. Lean body mass (P < 0.02), circulating insulin-like growth factor I (P < 0.01) and insulin (P < 0.02) were significantly increased at 2 months in the treatment group but there was no change in the placebo group. When expressed in relation to body weight, leucine Ra and non-oxidative leucine Rd increased (P < 0.01) and leucine oxidation decreased (P < 0.02) after 2 months growth hormone treatment. When expressed in relation to lean body mass non-oxidative leucine Rd increased (P < 0.02) and leucine oxidation decreased (P < 0.02) but there was no significant change in leucine Ra after 2 months growth hormone treatment. In the placebo group there were no significant changes in leucine metabolism expressed as lean body mass or body weight after 2 months. changes in leucine metabolism expressed as lean body mass or body weight after 2 months. These results indicate that the increase in lean body mass resulting from growth hormone treatment in adult growth hormone deficient patients is due to an increase in protein synthesis.
Background Growth Hormone is abused by athletes for its lipolytic and anabolic properties. Its us... more Background Growth Hormone is abused by athletes for its lipolytic and anabolic properties. Its use is prohibited by the World Anti-Doping Agency. The GH-2000 project developed a methodology to detect its abuse using the concentrations of two GH-dependent biomarkers, IGF-I and type 3 procollagen (P-III-P). The sensitivity of this method may be improved by considering intraindividual variability. Aim The aim of this study was to examine the intra-individual variability of IGF-I, P-III-P and the GH-2000 score. Subjects and methods IGF-I, P-III-P and GH-2000 score were evaluated in four longitudinal studies involving 303 elite and 78 amateur athletes. Samples were collected over a period of up to 12 months from a total of 238 men and 143 women aged between 17 and 53 years (mean 24AE2). Results The four studies showed good agreement with no apparent difference in within-individual variation between amateur and elite athletes. The intra-individual variability for IGF-I ranged between 14-16% while the variability for P-III-P was 7-18%. No athlete tested positive for growth hormone during any of the studies. The overall mean intra-individual variability of the GH-2000 score was less than 0AE6 units in all studies. Conclusions The high stability of marker levels suggests that concentrations are largely genetically determined. Adopting a test based on the concept of an athlete's 'passport' or 'profiling' would take advantage of this and most likely increase the sensitivity of the test. These data also provide strong evidence that a positive test result for GH abuse would not occur as a result of chance variability.
A simple model of the distribution and metabolism of insulin in vivo has been evaluated using dat... more A simple model of the distribution and metabolism of insulin in vivo has been evaluated using data from insulin infusion into a group of normal subjects. The major rate-limiting step for access to degradation pathways is assumed to consist of binding of the ligand to a single population of insulin receptor sites, except that provision is made for the possibility of linear non-receptor-mediated degradation and for the phenomenon of negative cooperativity. The model has been shown to accommodate the non-linearity of insulin metabolism , allows evaluation of receptor association and dissociation constants and provides for the first time an estimate of total accessible receptor number in the intact organism. For normal fasting man the model predicts 1.00 _+ 0.05 nmol accessible binding sites/kg (mean + SD).
... Dr. GF Watts BSC DM MRCP Lecturer in Endocrinology 1,* ,; C Lowy MSc FRCP Reader in Endocrino... more ... Dr. GF Watts BSC DM MRCP Lecturer in Endocrinology 1,* ,; C Lowy MSc FRCP Reader in Endocrinology 1 ,; PH Sönksen MD FRCP Professor 1 ,; ... How to Cite. Watts, GF, Lowy, C., Sönksen, PH and Shaw, KM (1992), Setting the standards for diabetes care: Microalbuminuria. ...
American Journal of Physiology-endocrinology and Metabolism, May 1, 2002
Abnormal lipid metabolism may be related to the increased cardiovascular risk in type 1 diabetes.... more Abnormal lipid metabolism may be related to the increased cardiovascular risk in type 1 diabetes. Secretion and clearance rates of very low density lipoprotein (VLDL) apolipoprotein B100 (apoB) determine plasma lipid concentrations. Type 1 diabetes is characterized by increased growth hormone (GH) secretion and decreased insulin-like growth factor (IGF) I concentrations. High-dose IGF-I therapy improves the lipid profile in type 1 diabetes. This study examined the effect of low-dose (40 g ⅐ kg Ϫ1 ⅐ day Ϫ1) IGF-I therapy on VLDL apoB metabolism, VLDL composition, and the GH-IGF-I axis during euglycemia in type 1 diabetes. Using a stable isotope technique, VLDL apoB kinetics were estimated before and after 1 wk of IGF-I therapy in 12 patients with type 1 diabetes in a double-blind, placebo-controlled trial. Fasting plasma triglyceride (P Ͻ 0.03), VLDL-triglyceride concentrations (P Ͻ 0.05), and the VLDL-triglyceride-to-VLDL apoB ratio (P Ͻ 0.002) significantly decreased after IGF-I therapy, whereas VLDL apoB kinetics were not significantly affected by IGF-I therapy. IGF-I therapy resulted in a significant increase in IGF-I and a significant reduction in GH concentrations. The mean overnight insulin concentrations during euglycemia decreased by 25% after IGF-I therapy. These results indicate that low-dose IGF-I therapy restores the GH-IGF-I axis in type 1 diabetes. IGF-I therapy changes fasting triglyceride concentrations and VLDL composition probably because of an increase in insulin sensitivity.
We have established a records linkage between 'Diabeta' (the computerized clinica... more We have established a records linkage between 'Diabeta' (the computerized clinical records system in the Diabetes Unit of St Thomas' Hospital) and the National Health Services Central Register (NHSCR) of the United Kingdom. Over 7000 diabetic patient records have been collected since 1973. Demographic data on all diabetic patients were retrieved and submitted to the NHSCR via a floppy disk. A matching system (automatic or manual) was used by the NHSCR to identify deceased patients and the most recent demographic data was provided on patients alive. This linkage resulted in an update of 91% of records in Diabeta. The findings of the update included: (1) 86% of diabetic patient's death had not been notified to the hospital and were not recorded on Diabeta. Mortality can now be assessed accurately as an outcome measure in our diabetic population. (2) Provision of the NHS number to Diabeta, as before it was not available on many patients seen in the hospital. The NHS number is a key patient identifier which can be used to exchange information within the NHS-wide network. (3) Diabetes was recorded as a cause of death in only 36% of death certificates. Analyses of death certificates alone must thus give poor information about mortality in diabetes. (4) Geographical location of patients on the database was updated, enabling tracing of patients for long-term studies and analyses of movement.
Page 1. Dm WORKSHOP REPORT A Role for Computers in Diabetes Care? CD Williams, FE Harvey, P. H. S... more Page 1. Dm WORKSHOP REPORT A Role for Computers in Diabetes Care? CD Williams, FE Harvey, P. H. Sonksen Department of Medicine, Sf Thomas' Hospital, London, UK. KEY WORDS Computers Diabetes care Contents Preface Introduction ...
American Journal of Physiology-endocrinology and Metabolism, Jun 1, 1991
Clinical studies have demonstrated that chloroquine and hydroxychloroquine improve glucose metabo... more Clinical studies have demonstrated that chloroquine and hydroxychloroquine improve glucose metabolism in patients with insulin-resistant diabetes mellitus. The mechanism of action has not been determined. We undertook a randomized double-blind placebo-controlled trial of 3 days of oral chloroquine phosphate, 250 mg four times daily, in 20 patients with non-insulin-dependent diabetes mellitus controlled by diet. Rates of glucose appearance (Ra) and disappearance (Rd) were evaluated by infusion of stable isotopically labeled D-glucose ([6,6-2H2]glucose) during hyperinsulinemic euglycemic clamps before and after treatment with chloroquine or placebo. Chloroquine significantly improved fasting plasma glucose from 199.8 +/- 8.6 to 165.6 +/- 7.6 mg/dl (P less than 0.01). Total exogenous glucose infusion required to maintain euglycemia significantly increased (1,792.6-2,040.1 mg.kg-1.330 min-1, P less than 0.05) due to an increase in Rd (2,348.0-2,618.9 mg.kg-1.330 min-1, P less than 0.01) without change in Ra. Metabolic clearance rate of insulin decreased by 39% from 14.4 +/- 1.3 to 11.0 +/- 0.6 ml.kg-1.min-1 (P less than 0.01) at plasma insulin levels of 150-200 mU/l but not at levels of 2,000-3,000 mU/l. In addition, chloroquine increased fasting C-peptide secretion by 17% and reduced feedback inhibition of C-peptide by 9.1 and 10.6% during low- and high-dose insulin infusions, respectively.
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