E. Vilardell

Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults

objective To investigate the GH response to glucagon in adult patients with GH deficiency and in controls compared with the GH response to the insulin tolerance test (ITT) in patients with GH deficiency and to determine whether the use of glucagon results in a diagnostic utility test.

Signals Derived From Glucose Metabolism Are Required for Glucose Regulation of Pancreatic Islet GLUT2 mRNA and Protein

Pancreatic islet GLUT2 mRNA is known to be regulated in vitro and in vivo by glucose. We have investigated several potential mechanisms mediating the response of islet GLUT2 to glucose. GLUT2 mRNA and protein were measured from isolated rat islets cultured for up to 24 h under selected conditions. Glucose at 11 mM stimulated GLUT2 mRNA 10-fold compared with 2 mM glucose, with no additional increase at 16.7 mM glucose, whereas maximal 4-fold induction of the protein was attained with 16 mM glucose. Time course studies showed a 2.5-fold induction of GLUT2 mRNA apparent after only 8 h of culture at 16.7 mM glucose. Glycolysis inhibitor mannoheptulose suppressed the stimulatory effect of 16.7 mM glucose on GLUT2 mRNA and protein. Metabolizable sugars mannose and glyceraldehyde enhanced transporter mRNA levels, in contrast with the lack of stimulation by nonmetabolizable 2-deoxy-D-glucose. Stimulation by different sugars and glycolysis inhibition led to analogous changes of proinsulin mRNA, suggesting that common signaling mechanisms are shared in glucose regulation of proinsulin and GLUT2 gene expression. Preexposure to mannoheptulose, however, failed to suppress glucose-stimulated insulin release. Tunicamycin, a glycoprotein synthesis inhibitor, did not block the effect of 16 mM glucose on GLUT2 mRNA levels. RNA and protein synthesis inhibitors actinomycin and cycloheximide abolished the enhancing effects of high glucose on GLUT2 mRNA. These findings indicate that glucose metabolism, but not glycoprotein synthesis or substrate interaction with the transporter protein, is instrumental in the stimulatory effects of glucose on β-cell GLUT2 mRNA accumulation. In addition, ongoing RNA and protein synthesis are required for this effect.

PRIMARY LOCALIZED CUTANEOUS AMYLOIDOSIS AND FAMILIAL MEDULLARY THYROID CARCINOMA

We have studied a family with an autosomai dominant Inheritance of primary localized cutaneous amyloidosis (PLCA) and familial medullary thyroid carcinoma (MTC). Ten family members were screened for multiple endocrine neoplasia (MEN) 2; five were found to have MTC and two had C‐cell hyperplasia. None had evidence of phaeochromocytoma or parathyroid abnormalities. Five of these seven patients presented characteristic inter‐scapular hyperpigmented lesions, showing dermal amylold deposits In two of the four patients In which a biopsy was performed. The data are analysed In the light of two recent reports of MEN 2A associated with Identical lesions. We conclude that PLCA should be sought in MTC patients, even If no other endocrinopathies are present. This may be Informative of the familial character of MTC in Index cases and also of the tumour gene status in family members who are being screened

Symptomatic and Hormonal Hypoglycaemic Responses to Human and Porcine Insulin in Patients with Type I Diabetes Mellitus

In recent years there has been great concern that human insulin (HI) may induce fewer hypoglycaemic warning symptoms than porcine insulin (PI). We addressed this issue in eight patients aged 25.6 ± 3.3 (SEM) years with Type I (insulin‐dependent) diabetes mellitus of 15.1 ± 3.7 years duration who complained that hypoglycaemia unawareness had appeared after transferring from PI to HI. Acute induction of hypoglycaemia was induced on two occasions with semisynthetic HI and purified PI under double‐blind conditions. Blood glucose was first clamped for 2 h at 4.4–6.7 mmol I−1 with an intravenous infusion of HI or PI at 50 mU kg−1 h−1 and 20% glucose at a variable rate. Thereafter, insulin infusion alone was maintained for 100 minutes. Heart rate, arterial pressure, reflex times, autonomic and neuroglycopenic signs and symptoms were assessed every 10 min. Arterialized venous blood samples were taken to measure blood glucose every 10 min and catecholamines, insulin, glucagon, growth hormone, and cortisol every 20 min. Autonomic symptoms first appeared at a plasma glucose level of 2.92 ± 0.21 mmol I−1 with HI vs 2.92 ± 0.48 mmol I−1 with PI (NS). There were no significant differences between the two studies concerning any of the above mentioned clinical parameters or the counterregulatory hormone responses. A differential effect of insulin species on the ability to perceive hypoglycaemia in patients who ascribed diminished perception of hypoglycaemia to the use of HI was thus not observed.

Effects of Thromboxane Synthesis Inhibitor Triflusal on Renal Hemodynamics in Microalbuminuric Diabetic Patients

Triflusal (2-acetoxy-4-trifluormethylbenzoic acid) is a platelet-antiaggregant drug that selectively inhibits thromboxane synthesis with little effect on prostacyclin production. In this study, we evaluated the effect of 5- day administration of 900 mg/day triflusal on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary albumin excretion (UAE), thromboxane B2 (TXB2), 6-ketoprostaglandin F1α (PGF1α), and PGE2 in nine normotensive insulin-dependent diabetic patients with UAE between 30 and 103 fxg/min. Plasma TXB, and plasma renin activity (PRA) were also determined. After administration of triflusal, we observed a reduction in microalbuminuria (59 ± 25 vs. 33 ± 22 μg/min, P < 0.01), an increase in RPF (648 ± 119 vs. 722 ± 134 ml· min−1 · 1.73 m−2, P < 0.01), and a reduction in filtration fraction (0.24 ± 0.04 vs. 0.20 ± 0.03, P < 0.01). Triflusal produced a significant reduction in both plasma TXB2 (130 ± 39 vs. 52 ± 32 pg/ml, P < 0.02) and urine TXB2 (523 ± 249 vs. 312 ± 11 pg/min, P < 0.02), without changes in PRA and UAE of 6-keto-PGF1α and PGE2. Metabolic control and arterial blood pressure did not change during the study. These results suggest that platelet-antiaggregant therapy can reduce microalbuminuria in diabetic patients. This effect could be mediated by a reduction in the transglomerular hydraulic pressure through a vasodilation of efferent arterioles secondary to renal thromboxane synthesis inhibition.

Effects of a short prednisone regime at clinical onset of type 1 diabetes

The effect of corticosteroids on beta cell function and humoral immune response in type 1 diabetes was tested in a 2-month trial conducted on 32 newly diagnosed patients (age 22.8 +/- 1.4 years, mean +/- S.E.M.). Prednisone was administered at immunosuppressive dosage (1 mg.kg-1.day-1) during the initial 10 days and at a maintenance dosage (0.3 mg.kg-1.day-1) for 50 days. Patients (n = 32) were enrolled within 6 weeks after diagnosis and matched in pairs for age, sex, presence of islet cell antibodies (ICA) and glucagon stimulated C-peptide levels. Insulin discontinuation was not contemplated. All the patients who received prednisone became ICA during treatment but in some (4 out of 10) this effect was only transient. Insulin antibodies (IA) were significantly lower in the prednisone group at second and third month (P < 0.05). No patient experienced complete remission but in 10 prednisone and 4 control patients the insulin requirements were below 0.3 IU/kg (P < 0.05). With similar glycemia the fasting C-peptide levels were higher in the treated patients. The profile of the insulin requirements during the follow-up was different in the two groups and at 9 months the prednisone group needed less insulin than the control (P < 0.05). Interestingly, within the prednisone-treated group and after 6 months, the levels of stimulated C-peptide improved significantly among the ICA+ patients while they were steady or declined in ICA- (P < 0.01). The analysis of variance covariance confirmed a positive interaction between ICA and the administration of prednisone on the outcome of beta cell function.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic analysis of seven Mediterranean families with multiple endocrine neoplasia type 2A

OBJECTIVE  Genetic analysis is now essential for the accurate screening of families with multiple endocrine neoplasia type 2 (MEN2). We present the genetic analyses by both haplotype and direct RET proto‐oncogene mutation analysis in seven Mediterranean MEN 2A families and have compared these results with biochemical screening tests and pathological examinations.

Acute water intoxication after intranasal desmopressin in a patient with primary polydispsia

Only a few cases of severe acute water intoxication (AWI) due to intranasal desmopressin have been reported, none of which occurred in patients with primary polydipsia. We describe a case of AWI with semicoma and convulsions, due to intranasal desmopressin, in a 32-year-old patient with dipsogenic diabetes insipidus. Previous reported cases of AWI due to desmopressin are discussed. The importance of ruling out primary polydipsia when this drug is used, not only for central diabetes insipidus but also for other current indications such as classic hemophilia, is stressed.

Late-onset hypocalcemia appearing years after thyroid surgery

We revised four cases of hypocalcemia diagnosed yr after thyroid surgery, including 1 man and 3 women, operated 5–23 yr before the onset of symptoms, which ranged from mild paresthesia to convulsive seizures. Total serum calcium levels ranged from 1.1 to 2.05 mmol/l, and PTH levels were low in the 3 cases in which they were measured. Hypoparathyroidism appearing as late-onset hypocalcemia after extense thyroid surgery is a poorly understood condition, perhaps not as unfrequent as it is considered.

HLA antigens in Spanish type 1 diabetic population. Correlations with clinical, biological and autoimmune markers.

SummaryThe HLA haplotype and its relationships with clinical, biological and immunological parameters were analyzed in a group of 87 Spanish type I diabetic patients at the clinical onset of the disease. The frequency of HLA-B18, DR3 and DR4 antigens was significantly increased whereas DR2, DR5 and DR7 were decreased in comparison with 189 healthy unrelated controls without family history of diabetes. DR3 showed a maximum relative risk for diabetes (5.5) whereas DR4 had a lower one (4.0). HLA-DR4 patients were younger at the time of diagnosis than DR4 negative (16.7vs 21.4 years). We found no statistically significant relationship between HLA antigens and the other variables studied including the presence of islet cell antibodies, complement fixing islet cell antibodies, insulin autoantibodies, organ-specific antibodies, fasting and maximal glucagon stimulated C-peptide levels, initial glycemia and glycosylated hemoglobin.