Biomedical subjects

R K Menon

Publications and source records attributed to R K Menon.

At least 19 recordsLinked to original sources

PubMed1992

Diminished growth hormone-binding protein in children with insulin-dependent diabetes mellitus.

Two distinct GH-binding proteins (GHBP) are present in circulation in the human. The major GHBP (high affinity GHBP) is homologous to the extracellular portion of the GH receptor and the concentration of this protein in circulation may reflect the status of the GH receptor in the tissues. To gain information about the concentration of GHBPs in children with insulin-dependent diabetes mellitus (IDDM), we measured GHBP in the serum of 46 children with IDDM and compared it to that in 53 healthy control subjects matched for age and sexual maturity. The total GHBP concentration in the group of pubertal and postpubertal IDDM patients was lower than that measured in the control group (mean +/- SEM: 7.8 +/- 0.4 vs. 9.0 +/- 0.5%, P = 0.05). The diabetic children in stages II to IV of puberty had a lower GHBP level compared to their healthy controls (7.6 +/- 0.4 vs. 9.1 +/- 0.5%, P = 0.02), whereas the difference between the diabetic and control group of postpubertal children was not statistically different (8.3 +/- 0.7 vs. 9.7 +/- 0.7%, P = 0.1). In a randomly selected subset of eight patients and eight controls, the concentration of the individual GHBPs (i.e. high affinity and low affinity (GHBP) was estimated by gel chromatography. There was no difference in the low affinity GHBP between the two groups (9.9 +/- 0.6% vs. 9.9 +/- 0.4%), but the high affinity GHBP was less in the diabetic group than in the control group (10.5 +/- 0.9 vs. 15.6 +/- 1.0%, P less than 0.01). In the diabetic group, there was no correlation between the GHBP levels and age, duration of diabetes, hemoglobin A1, or insulin dose. We conclude that in IDDM there is less of the high affinity GHBP, suggesting a decrease in the number of GH receptors in these patients. This decrease may contribute to GH resistance manifesting as decreased insulin-like growth factor-I levels despite high GH levels in patients with IDDM.

Adolescent↗

PubMed1992

Muscle blood flow in diabetes mellitus. Evidence of abnormality after exercise.

OBJECTIVE: To determine whether muscle blood flow before and after exercise is abnormal in patients with diabetes mellitus. RESEARCH DESIGN AND METHODS: Muscle blood flow (MBF) was measured with the 133Xe clearance technique in 15 nondiabetic subjects, 10 patients with insulin-dependent diabetes mellitus (IDDM), and 11 patients with non-insulin-dependent diabetes (NIDDM) at rest and after exercise. None of the patients had neuropathy. RESULTS: The median resting MBF was similar in all three groups. The median postexercise MBF was significantly greater in nondiabetic subjects (40.1 ml.min-1.100 g-1 of tissue) than in patients with IDDM (25.7 ml.min-1.100 g-1 of tissue; P less than 0.01) or NIDDM (14 ml.min-1.100 g-1 of tissue; P less than 0.01). The difference between IDDM and NIDDM was not significant. CONCLUSIONS: Diabetic patients have abnormalities of MBF in response to exercise. This abnormality occurs in the absence of clinical diabetic neuropathy.

Adult↗

PubMed1991

Ontogeny of insulin-like growth factor I and insulin receptor kinase activity in rat liver.

IGF-I and insulin receptors possess tyrosine-kinase enzymatic activity considered to be essential for signal transduction and thereby mediating the putative effects of these hormones on fetal growth and development. We investigated the ontogeny of IGF-I and insulin receptor tyrosine-kinase activity in at least 3 separate membrane preparations from liver of rats at 21 day of embryonic life (21ED), 1 and 5 day of postnatal life (1PD and 5PD respectively) and adult. Receptors purified by wheat germ agglutinin chromatography (WGA) were exposed to graded concentrations of IGF-I or insulin, and tyrosine-kinase activity was measured by quantifying incorporation of 32P into the exogenous substrate poly[Glu,Tyr; 4:1]. IGF-I stimulated tyrosine-kinase solely at 1 PD as documented by a maximal increase of 346 +/- 167% over basal kinase activity with 6.6 nmol/L IGF-I. While the lack of response in adult animals could be explained by a striking decrease in receptors at that age, 125I-IGF-I binding and affinity labelling of the WGA preparations indicated substantial IGF-I receptors were present in the liver at each of the perinatal ages. Furthermore, this dissociation between IGF-I binding and the tyrosine-kinase activity of these IGF-I receptors could not be attributed to the presence/absence of IGF-I binding proteins as judged by affinity labelling. In contrast, insulin-stimulated tyrosine-kinase activity was observed at all ages tested although it appeared greatest at 1PD. We conclude that (i) expression of IGF-I tyrosine-kinase activity is linked to developmental events and differs from that found for the insulin receptor tyrosine-kinase activity, (ii) during the perinatal period there is an apparent dissociation between ligand binding by the IGF-I receptor and receptor tyrosine-kinase activity. These observations suggest modulation of IGF-I receptor tyrosine-kinase activity may be an important regulator of IGF-I action during the perinatal period.

Animals↗

PubMed1990

Transplacental passage of insulin in pregnant women with insulin-dependent diabetes mellitus. Its role in fetal macrosomia.

BACKGROUND AND METHODS: Fetal macrosomia occurs despite nearly normal maternal blood glucose levels in women with diabetes treated with insulin. We examined the hypothesis that it may be caused by insulin transferred as an insulin-antibody complex from the mother to her fetus. We adapted and validated a method based on high-performance liquid chromatography and used it to quantitate insulin in small volumes (0.5 to 1.0 ml) of cord serum from 51 infants born to mothers with insulin-dependent diabetes mellitus. RESULTS: In mothers receiving only human insulin (n = 6), only human insulin was detected in cord serum. Of the remaining 45 infants, whose mothers received animal insulin during pregnancy, 28 (group 1) had levels of animal (bovine or porcine) insulin (mean [+/- SE], 707 +/- 163 pmol per liter) that constituted 27.4 +/- 2.5 percent of the total insulin concentration (2393 +/- 500 pmol per liter) measured in the cord serum. The cord-serum insulin concentration in the remaining 17 infants (group 2), in whom only human insulin was detected (381 +/- 56 pmol per liter), was only 15 percent of that in group 1 (P less than 0.001). There was a significant correlation between the maternal and the cord-serum concentrations of anti-insulin antibody and the concentration of animal insulin in the baby (r = 0.77, P less than 0.01, and r = 0.76, P less than 0.001, respectively), suggesting that the animal insulin was transferred as an insulin-antibody complex. In group 1 the mean concentration of animal insulin in cord serum was higher in the 12 infants with macrosomia than in the 16 infants without the condition (1113 +/- 321 vs. 402 +/- 110 pmol per liter; P less than 0.05), and the concentration of animal insulin in cord serum correlated with birth weight (r = 0.39, P less than 0.05). The maternal glycosylated hemoglobin values and the incidence of respiratory distress syndrome were similar in groups 1 and 2. CONCLUSIONS: Considerable amounts of antibody-bound insulin are transferred from mother to fetus during pregnancy in some women with insulin-dependent diabetes mellitus; the extent of transfer correlates with the maternal concentration of anti-insulin antibody. The correlation between macrosomia and the concentrations of animal insulin in cord serum indicates that the transferred insulin has biologic activity and suggests that the formation of antibody to insulin in the mother is a determinant of fetal outcome independent of maternal blood glucose levels.

Adult↗

PubMed1990

Estimation of glucose kinetics in fetal-maternal studies: potential errors, solutions, and limitations.

We investigated whether errors occur in the estimation of ovine maternal-fetal glucose (Glc) kinetics using the isotope dilution technique when the Glc pool is rapidly expanded by exogenous (protocol A) or endogenous (protocol C) Glc entry and sought possible solutions (protocol B). In protocol A (n = 8), after attaining steady-state Glc specific activity (SA) by [U-14C]glucose (period 1), infusion of Glc (period 2) predictably decreased Glc SA, whereas. [U-14C]glucose concentration unexpectedly rose from 7,208 +/- 367 (means +/- SE) in period 1 to 8,558 +/- 308 disintegrations/min (dpm) per ml in period 2 (P less than 0.01). Fetal endogenous Glc production (EGP) was negligible during period 1 (0.44 +/- 1.0), but yielded a physiologically impossible "negative" value of -2.1 +/- 0.72 mg.kg-1.min-1 during period 2. When the fall in Glc SA during Glc infusion was prevented by addition of [U-14C]glucose admixed with the exogenous Glc (protocol B; n = 7), EGP was no longer "negative." In protocol C (n = 6), sequential infusions of four increasing doses of epinephrine serially decreased SA, whereas tracer Glc increased from 7,483 +/- 608 to 11,525 +/- 992 dpm/ml plasma (P less than 0.05), imposing an obligatory underestimation of EGP. Thus a tracer "mixing" problem leads to erroneous estimations of fetal Glc utilization and Glc production via the three-compartment model in sheep when the Glc pool is expanded exogenously or endogenously. These errors can be minimized by maintaining the Glc SA relatively constant.

Animals↗

PubMed1990

The modified minimal model: application to measurement of insulin sensitivity in children.

The modified minimal model (MMM), a recently introduced method that assesses insulin sensitivity (SI) by a computed mathematical analysis of the relation between the change in insulin and glucose clearance after a bolus of iv glucose, followed 20 min later by a bolus of tolbutamide, has been standardized in adults, but this method has not been validated in children. We performed an abbreviated 90-min MMM test in 50 children who were siblings of patients with insulin-dependent diabetes mellitus and 7 healthy adult volunteers and compared the results to the standard 180-min MMM test in 11 of these subjects. The cohort consisted of 29 prepubertal children [16 males and 13 females; 8.7 +/- 2.0 (mean +/- SEM) yr old]; 16 pubertal children defined as less than 17 yr of age and Tanner stage 2-5 (8 males and 8 females; 13.4 +/- 1.8 yr old), and 12 postpubertal subjects (7 males and 5 females; 18.2 +/- 0.9 yr old), with no significant difference in the weight for length index (WLI) among the 3 groups and with sera of all subjects negative for islet cell antibodies and insulin autoantibodies. The test procedure consisted of 3 baseline blood samples over 30 min, followed at zero time by 0.3 g/kg 25% dextrose infused iv over 1 min and an iv injection of tolbutamide (5 mg/kg) 20 min later; sequential blood samples for glucose and insulin measurements were withdrawn from zero time until completion 90 or 180 min later. In the 11 subjects who underwent both the standard and the abbreviated tests, there was no significant difference between the SI estimated by the 2 methods provided that glucose and insulin values were interpolated at 180 min during the computer calculations of the abbreviated test. Using the 90-min abbreviated test, the SI of the pubertal subjects (2.92 +/- 0.45) was markedly less than that of the prepubertal subjects (6.57 +/- 0.45; P = 0.0001). While the postpubertal group value of 4.63 +/- 0.86 was significantly higher than that of the pubertal group (P = 0.0001), the pre- and postpubertal groups remained significantly different (P = 0.0001). The 10 obese subjects with WLI greater than 120% had a lower SI (3.5 +/- 0.53) than the 47 nonobese subjects with WLI less than 120% (SI = 5.48 +/- 0.42; P less than 0.04), and there was a negative correlation between SI and WLI. None of the study subjects experienced symptomatic hypoglycemia during the test.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1989

Choroideremia and hypopituitarism: an association.

Choroideremia is a rare X-linked, progressive, degenerative disease of the retina and choroid. We describe 2 patients, one a female, with choroideremia documented to have hypopituitarism and neurological abnormalities. We hypothesize that this previously undescribed association results from a degenerative process involving tissues of neural origin, or from contiguous submicroscopic gene deletions in the X chromosome region that define choroideremia and possibly hypopituitarism.

Adolescent↗

PubMed1989

Normal ionized calcium, parathyroid hypersecretion, and elevated osteocalcin in a family with fluorosis.

Sera from five patients with skeletal fluorosis were investigated for total calcium, ionized calcium, phosphate, alkaline phosphatase, 25 hydroxyvitamin D (25 OHD), 1,25 dihydroxyvitamin D (1,25[OH]2D), parathyroid hormone, and osteocalcin concentrations. Total and ionized calcium concentrations were normal in four and subnormal in one, but PTH concentration was elevated in all five. The patient with a subnormal calcium concentration also had subnormal 25 OHD and 1,25(OH)2D concentrations and a supranormal PTH concentration. The remaining four had supranormal PTH concentrations despite normal total and ionized calcium concentration, and normal 25 OHD and 1,25(OH)2D levels. Osteocalcin concentration was markedly elevated in all patients, as was alkaline phosphatase activity. These observations show for the first time that patients with fluorosis have markedly elevated osteocalcin, a marker of osteoblastic activity, and that they may have significantly elevated PTH concentrations in the presence of normal total and ionized calcium concentrations.

1-Carboxyglutamic Acid↗

PubMed1988

Childhood diabetes.

The child with diabetes mellitus has special problems that require skilled attention best achieved by a team of professionals. The goals of managing a child with diabetes are summarized in Table 7. The features that distinguish the child from an adult with diabetes are inability to communicate or verbalize symptoms, unpredictable eating and exercise patterns, special nutritional requirements of growth, and the emotional and psychological upheavals experienced during adolescence.

Adolescent↗

PubMed1988

Effects of somatostatin and glucose infusion on glucose kinetics in fetal sheep.

We examined the contribution of glucose, independently of insulin, on fetal glucose kinetics in the sheep by infusing somatostatin (SRIF), followed by SRIF plus glucose (protocol A) or reversing the initial infusion sequence (protocol B). In protocol A (n = 8), infusion of SRIF at 200 micrograms/h decreased plasma insulin (IRI) and blood glucose (G) by 2.8 +/- 1.0 microU/ml and 1.34 +/- 0.2 mg/dl from their respective basal concentrations of 6.8 +/- 1.4 microU/ml and 16.47 +/- 0.91 mg/dl (P less than 0.05; P less than 0.005). There were no significant changes in plasma glucagon (IRG) or the rates of umbilical G uptake or of G utilization, but G turnover decreased by 1.77 +/- 0.34 mg.kg-1.min-1 (P less than 0.005). Addition of G at a rate of 5.6 +/- 0.8 mg.kg-1.min-1 had no effect on IRI and IRG. Total G uptake (G infusion rate plus umbilical G uptake) increased from 6.37 +/- 0.77 to 10.25 +/- 1.0 mg.kg-1.min-1 (P less than 0.01), despite suppression of umbilical G uptake by 33%. Fetal G reached a new steady state of 23.08 +/- 1.37 mg/dl, and G turnover increased by 4.81 +/- 0.96 mg.kg-1.min-1 from its SRIF-induced nadir (P less than 0.005). Since G concentration was maintained at steady state, the rate of G utilization was equivalent to the rate of total G uptake, an increase of 60% from basal despite suppressed IRI.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Carbohydrate metabolism.

In summary, the surges of glucagon and epinephrine at birth, coupled with the fall in insulin secretion, are in accord with appropriate receptor changes, as well as genetic ontogenic patterns of enzyme development. Enzyme activities are further stimulated by the hormonal changes at birth; phosphorylase is activated by glucagon and epinephrine, while PEPCK is activated by glucagon and its expression is facilitated by the fall in insulin. In concert, these changes permit rapid activation of catabolic processes and the mobilization and utilization of endogenous fuel stores. Glucose homeostasis is maintained by glycogenolysis and gluconeogenesis supported by the appropriate enzyme inductions. The free fatty acids released, via lipolysis, also serve to sustain gluconeogenesis, since hepatic fatty acid oxidation is necessary for gluconeogenesis by providing the essential cofactors. This framework permits a rational interpretation of the mechanisms underlying the remarkable transition from intrauterine dependence on maternal glucose to extrauterine autonomy of newborn energy integration. This framework can also explain several causes of neonatal hypoglycemia and act as a base for future investigations.

Animals↗

PubMed1987

Increase in plasma potassium concentration following indomethacin administration: absence of a role for membrane Na-K ATPase.

To elucidate whether indomethacin-induced hyperkalaemia is due to an inhibition of Na-K ATPase in the membranes, indomethacin (25 mg t.d.s.) was administered to 7 normal subjects for 7 days. This resulted in an increase in plasma potassium concentrations in all 7 subjects: median (range) for the entire group increased from 4.19 (3.98-4.79) mmol/l to 4.29 (4.13-4.87) mmol/l. Leucocytes prepared from these subjects prior to and after indomethacin were tested for 86Rb influx and [3H]-ouabain binding (an index of Na-K ATPase sites). Neither 86Rb influx (total, ouabain sensitive and ouabain insensitive) nor [3H]-ouabain binding changed significantly following indomethacin. We conclude that (a) indomethacin-induced hyperkalaemia is not due to alterations in potassium influx into cells and (b) the modulation of Na-K ATPase sites/activity is in leucocytes not dependent upon prostaglandins.

Adult↗

PubMed1987

Endocrine and metabolic effects of simple hysterectomy.

A survey of 60 women who had undergone simple hysterectomy with preservation of ovaries revealed a high prevalence of menopausal flushes. Only 5 (8%) had menopausal concentrations of gonadotropins and estradiol. This is similar to the prevalence of natural menopause in population of comparable age. Of the remaining 55 women, 28 (47% of the total) had normal gonadotrophins and estradiol concentrations although they complained of hot flushes; these levels were not significantly different from those in 27 women who did not flush. The "flushers" did, however, have significantly diminished bone mineral index and higher serum uric acid concentrations than the "non-flushers". Flushes disappeared in those women who took estrogen replacement therapy. These data show that although full-blown menopause does not increase in frequency following simple hysterectomy, a subtle diminution in estrogenisation is frequent. This hypo-estrogenisation is sufficient to cause: (a) hot flushes; (b) demineralisation of the skeleton and (c) an elevation in serum uric acid concentrations. There may be a case for estrogen therapy in all women who develop hot flushes following simple hysterectomy.

Adult↗

PubMed1987

Serum 1,25 dihydroxyvitamin D and osteocalcin concentrations in thalassaemia major.

In view of the claim that low 25-hydroxyvitamin D (25-OHD) concentrations may contribute to the pathogenesis of bone disease in patients with beta thalassaemia major and iron overload, we have assessed the concentrations of 25-OHD, 1 alpha,25 dihydroxyvitamin D (1 alpha,25(OH)2D), parathyroid hormone, and osteocalcin in such patients. 25-OHD concentrations were significantly lower in patients with thalassaemia major and iron overload than in controls and in some patients were subnormal or undetectable. 1 alpha,25(OH)2D concentrations were, however, normal in all patients and were similar to those in controls. Serum parathyroid hormone and plasma calcium concentrations were also normal and not significantly different from those in controls. Although 25-OHD concentrations increased significantly between January and June, there was no change in 1 alpha,25(OH)2D concentrations. 25-OHD concentrations remained lower than control values, even in June. Parathyroid hormone concentrations fell, but not significantly, between January and June, but calcium concentrations did not alter. Osteocalcin concentrations were normal in all patients except one, who had extremely low concentrations of this protein. The concentration of osteocalcin was not related to 25-OHD or 1 alpha,25(OH)2D concentrations. Thus normal calcium homeostasis is maintained in patients with thalassaemia major despite low or low-normal 25-OHD concentrations; this is probably achieved through the maintenance of normal 1 alpha,25(OH)2D concentrations, which were indistinguishable from those in controls. Normal 1 alpha,25(OH)2D, parathyroid hormone, and osteocalcin concentrations argue against an important role for vitamin D deficiency in the pathogenesis of thalassemia bone disease.

Adolescent↗

PubMed1987

Insulinoma presenting as alcoholic stupor.

We report a case of prolonged loss of consciousness due to hypoglycaemia following ethanol abuse in a non-diabetic. The patient also reported symptoms compatible with hypoglycaemia following heavy manual work. Further investigations revealed a pancreatic insulinoma, which was successfully removed surgically. The patient remains asymptomatic 18 months later, despite occasional episodes of ethanol abuse. This case illustrates how heavy exercise and/or alcohol abuse can aggravate spontaneous hypoglycaemia.

Adenoma, Islet Cell↗

PubMed1987

Calcium, vitamin D and parathyroid hormone relationships in pregnant Caucasian and Asian women and their neonates.

Plasma calcium, serum 25 hydroxyvitamin D [25(OH)D], 1,25 dihydroxyvitamin D[1,25(OH)2D] and parathyroid hormone (PTH) have been measured in pregnant and newborn Caucasians and Asians. Calcium and 25(OH)D concentrations were lower in Caucasian than in Asian women at all four stages (three trimesters and during labour) of pregnancy. PTH concentrations were greater in Asian than in Caucasian women during the three trimesters, but not at labour, and increased in both groups through pregnancy, without a concomitant change in plasma calcium concentrations. There was a significant inverse correlation between calcium and PTH, as well as 25(OH)D and PTH, concentrations. These data demonstrate the presence of progressive 'hyperparathyroidism' during pregnancy in Caucasian and Asian women. The higher PTH concentrations in Asian women may reflect the necessity of maintaining adequate plasma calcium concentrations through PTH-induced osteolysis in the face of vitamin D deficiency. Relative hyperparathyroidism in Asians may contribute to net loss of calcium from the skeleton and osteopenia in Asian women. Calcium, 25(OH)D and 1,25(OH)2D concentrations were lower, and those of PTH higher, in Asian newborns compared with Caucasian newborns. Serum 1,25(OH)2D concentrations in the Asian newborn, though lower than respective maternal levels, were comparable with normal adult levels, indicating that 1,25(OH)2D biosynthesis is stimulated in the Asian newborn to compensate for the low serum 25(OH)D concentrations.

Alkaline Phosphatase↗

PubMed1987

Impaired carboxylation of osteocalcin in warfarin-treated patients.

The total circulating osteocalcin and ratio of inactive (noncarboxylated; GLU) to active (carboxylated; GLA) form of circulating osteocalcin were measured in patients receiving long term warfarin treatment (n = 20), age-matched control patients not receiving warfarin treatment (n = 10), and normal subjects before and after the administration of 30 mg warfarin (n = 7). There was no significant difference in the total osteocalcin concentrations between the control patients and the patients receiving long term warfarin treatment, and it did not significantly change after warfarin ingestion in the normal subjects. The GLU/GLA ratio was significantly increased (P less than 0.002) in the patients receiving long term warfarin treatment compared with that in the control patients. There was a significant increase (P less than 0.01) in the GLU/GLA ratio after warfarin ingestion in the normal subjects. This study demonstrates that osteocalcin carboxylation in humans is a vitamin K-dependent process and that circulating osteocalcin is structurally altered by warfarin administration. This finding has pathophysiological implications for the fetal warfarin embryopathy syndrome, bone disease associated with chronic liver diseases, and possibly for osteoporosis, in which vitamin K deficiency has been implicated.

1-Carboxyglutamic Acid↗

PubMed1987

Hyperparathyroidism and low serum osteocalcin despite vitamin D replacement in primary biliary cirrhosis.

Thirty-six patients with primary biliary cirrhosis (PBC) receiving calcium and calciferol supplements (100,000 IU monthly by im injection) were investigated for their calcium, vitamin D, PTH, and osteocalcin status. The corrected plasma calcium concentrations in PBC patients were significantly greater than those in normal subjects. While the mean serum 25-hydroxycholecalciferol and 1,25-dihydroxyvitamin D concentrations in these patients were similar to those in normal subjects, the mean serum PTH concentration was significantly greater, and it was supranormal in 11 patients. Three patients had elevated corrected calcium concentrations; 1 of them had a concomitant increase in ionized calcium and a supranormal PTH level, and another had a high normal PTH. Ionized calcium concentrations were normal in the rest. Serum osteocalcin concentrations were significantly lower in the patients compared with those in normal subjects. These results indicate that PTH concentrations are frequently elevated in PBC patients despite adequate vitamin D supplementation and normal or even supranormal plasma calcium concentrations. Nonsuppression of PTH concentrations and autonomy of PTH secretion suggest that vitamin D deficiency and secondary hyperparathyroidism in such patients probably occur much earlier in the natural history of this disease than is currently realized. Persistent nonsuppressible hypersecretion of PTH probably contributes to the bone disease of primary biliary cirrhosis. The low osteocalcin concentrations probably reflect diminished osteoblastic activity, which may also contribute to osteopenia in these patients.

Adult↗