[Physiopathology of non-insulin-dependent diabetes].
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Diabetes Mellitus, Type 2↗
Biomedical subjects
J Lubetzki
Publications and source records attributed to J Lubetzki.
[Dysthyroidism in patients treated with interferon alpha].
In addition to their initially recognized antiviral activity, interferons are known to have a number of effects on the immune system. The role of alpha-interferon (alpha-IFN) has been evaluated in 8 studies, including 573 patients, aimed at determining the prevalence, clinical course and predictive factors of autoimmune dysthyroidism in patients treated with alpha-IFN. Two major categories of patients were treated with alpha-IFN: those with cancer and those with chronic viral hepatitis. Two types of interferon were used: human leukocyte IFN and recombinant IFN. Among the 542 patients in which thyroid function was evaluated, 47 (8.7%) had clinical or biological dysthyroidism: hypothyroidism in 25 (53%), hyperthyroidism in 13 (28%) and biphasic hyper-hypothyroidism in 9 (19%). The delay to onset was known in 44 patients (mean 9 months, range 1.5 to 23 months). Dysthyroidism was temporary in certain patients and did not require treatment, but antithyroid drugs were required in others. The prevalence of antithyroglobulin and/or antimicrosomal antibodies varied from 0 to 20% (mean 13.7%). The prevalence of antithyroid stimulating hormone receptor antibodies appeared to be lower than that of antithyroid antibodies. The pathogenic mechanism of dysthyroidism in patients given alpha-IFN remains unknown, but could result from the induction of antithyroid antibodies or an increase in pre-existing levels. Abherent expression of HLA-DR antigens on the surface of the thyrocytes has been proposed as a possible factor, although gamma-IFN and not alpha-IFN leads to the expression of class II antigens. It has also been shown that alpha-IFN induces the expression of class I antigens on thyrocytes, indicating that the observed dysthyroidism might result from an over-expression of class I antigens which would facilitate direct activation of cytotoxic T cells. In summary, alpha-IFN can induce dysthyroidism in about 1 out of 10 patients, probably by the induction or stimulation of autoimmune phenomena. The positive predictive value of antithyroid antibodies is modest, about 60%, but the negative predictive value is high at 93%. Thyroid function should be monitored closely in patients given alpha-interferon.
Breast Neoplasms↗
Remission of proteinuria following correction of hyperlipidemia in NIDDM patients with nondiabetic glomerulopathy.
OBJECTIVE: Animal studies suggest that hyperlipidemia may play a direct role in glomerular damage. In patients with non-insulin-dependent diabetes mellitus (NIDDM), dyslipidemia occurs early in the course of nephropathy and may be involved in the progression of renal disease. CASES: We report on two young NIDDM patients with marked hyperlipidemia and proteinuria, in whom renal biopsy demonstrated nondiabetic glomerulopathy. In both cases, the decrease in blood lipid levels was associated with a major decrease in proteinuria. Episodes of hyperlipidemia were associated with a resumption of heavy proteinuria in one patient with serum triglyceride levels and proteinuria being closely correlated. CONCLUSIONS: These two cases suggest that hyperlipidemia has an important role in the pathogenesis of glomerular disease.
Adult↗
[Diabetic thoracoabdominal neuropathy. Clinical and electrophysiological study with evaluation of the autonomic nervous system].
We report on eight patients with diabetic thoracoabdominal neuropathy in whom careful evaluation of peripheral and autonomic nervous system function was performed. All patients had non insulin-dependent diabetes mellitus of 10.5 +/- 6.7 years mean (+/- SD) known duration with poor glycemic control. Thoracic (n = 7) or abdominal (n = 1) pain of sudden onset involved several adjacent dermatomal segments and was bilateral and asymmetrical in 7/8 patients. Four patients had hypoesthesia in the painful zone and six presented with significant weight loss (6.2 +/- 4.3 kg) which reversed after the relief of pain. Truncal electromyogram was abnormal in 7/7 patients. Nerve damage was not limited to thoracic nerves since electrophysiological studies evidenced distal polyneuropathy in all patients. The autonomic nervous system was also involved. Sympathetic skin response was abnormal in 7/7 patients and autonomic cardiovascular function tests demonstrated cardiac denervation in 5/5 patients. In 4/4 patients a marked relief of pain was noted within one week with amitriptyline treatment. This report confirms the characteristic clinical presentation of diabetic thoracoabdominal neuropathy. Moreover, it suggests that this neuropathy is part of a diffuse damage that also involves peripheral nerves of the limbs and autonomic nervous system.
Abdominal Pain↗
Non-responsiveness of serum gonadotropins and testosterone to pulsatile GnRH in hemochromatosis suggesting a pituitary defect.
We investigated the potential pituitary origin of gonadal insufficiency in hemochromatosis. Gonadotropin secretion was studied in seven patients with hemochromatosis and hypogonadism, before and after chronic pulsatile GnRH therapy. Pulsatile LH secretion was studied before (sampling every 10 min for 6 h) and after 15-30 days of chronic pulsatile GnRH therapy (10-12 micrograms per pulse). Prior to GnRH therapy, all the patients had low serum testosterone, FSH and LH levels. LH secretion was non-pulsatile in four patients, while a single pulse was detected in the remaining three. Chronic pulsatile GnRH administration did not increase serum testosterone levels; similarly, serum LH levels remained low: neither pulse frequency nor pulse amplitude was modified. We conclude that hypogonadism in hemochromatosis is due to pituitary lesions.
Adolescent↗
Effects of octreotide on lipid metabolism in acromegaly.
Hypertriglyceridemia is the most frequent modification of lipid metabolism observed in acromegaly. The somatostatin analog, octreotide (Sandostatin), widely used in the treatment of acromegaly, is able to produce a decrease in levels of growth hormone (GH), insulin, and Insulin-like Growth Factor 1 (IGF1). We have attempted to evaluate the influence of this treatment on the lipid status of acromegalic patients. Seventeen patients with active acromegaly were treated with octreotide, 100 to 500 micrograms/injection subcutaneously three times daily. The levels of fasting serum triglycerides (TG), total cholesterol, High Density Lipoprotein (HDL) cholesterol and IGF1, as well as mean plasma GH and insulin levels during a diurnal profile, were evaluated before and after three months of octreotide therapy. GH, insulin and IGF1 decreased by 61%, 42% and 36% respectively (p less than 0.05). Mean levels (+/- SEM) of TG and total cholesterol fell from 2.2 +/- 0.4 mmol/l to 1.6 +/- 0.3 mmol/l (p less than 0.05) and 6.4 +/- 0.39 mmol/l to 5.6 +/- 0.27 mmol/l (p greater than 0.05), respectively. There was no correlation between triglyceride decrease and hormonal changes or clinical status (BMI, age, sex). In conclusion, the administration of octreotide over a three month period to acromegalic patients is associated with a decrease in TG levels.
Acromegaly↗
Lipoprotein(a) in diabetic patients with and without chronic renal failure.
OBJECTIVE: To examine the distribution of Lp(a) plasma levels in patients with IDDM and NIDDM, and in nondiabetic and IDDM patients with chronic renal failure. RESEARCH DESIGN AND METHODS: Cross-sectional study of Lp(a) plasma levels in a population of diabetic patients with stable metabolic control, with simultaneous determination of plasma lipids, fasting plasma glucose, and HbA1. Thirty-six patients with IDDM, 90 with NIDDM, and 41 with chronic renal failure (20 IDDM, 21 nondiabetic) were compared with 78 control subjects. RESULTS: Lp(a) plasma levels were significantly higher in IDDM and NIDDM patients, as well as in nondiabetic and IDDM patients with chronic renal failure compared with control subjects. No correlation was observed between Lp(a) and lipid plasma levels, fasting plasma glucose, and HbA1. CONCLUSIONS: Lp(a) may contribute to the increased prevalence of atherosclerotic disease in diabetic patients and patients with chronic renal failure, especially in IDDM patients whose lipoprotein pattern was not different from that of the control group.
Adult↗
Short-term continuous infusion of octreotide in acromegaly. Pharmacokinetics and prediction of the response to long-term treatment.
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Acromegaly↗
Effect of the new dopaminergic agonist CV 205-502 on plasma prolactin levels and tumour size in bromocriptine-resistant prolactinomas.
Bromocriptine is currently and successfully used for the treatment of pituitary prolactinomas. However, bromocriptine appears unable to normalize plasma prolactin levels in about 10% and to reduce tumour size in one-third of cases. The lack of normalization of plasma prolactin levels in spite of a daily dose of bromocriptine equal to or higher than 15 mg suggests a bromocriptine resistance. We compared the long-term effects of bromocriptine and CV 205-502 (a non-ergot derivative D2 dopamine agonist) on plasma prolactin levels and tumour size in seven bromocriptine-resistant prolactinomas. Bromocriptine reduced significantly (P less than 0.001) plasma prolactin levels (from 2307 +/- 518 to 568 +/- 279 micrograms/l) (conversion to Sl units: 1 microgram/l = 20 mU/l). Visual field defects observed in five patients improved in four. However, CT scan analysis showed a decrease in tumour size in only three patients. Except for transient and minor side-effects at the beginning of the treatment, CV 205-502 was well tolerated in five of seven patients. In the remaining two patients nausea and vertigo occurred with high dosages of CV 205-502 and it was necessary to reduce the daily dose. CV 205-502 lowered plasma prolactin to levels similar to those obtained after bromocriptine therapy in four cases. In the three remaining patients, CV 205-502 was more potent than bromocriptine as demonstrated by the further 90% reduction in plasma levels obtained in one case and by the normalization of plasma prolactin levels in the two other cases. One woman became pregnant during CV 205-502 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Decreased bronchial response to methacholine in IDDM patients with autonomic neuropathy.
This study was designed to evaluate the involvement of airways innervation during diabetic autonomic neuropathy. Bronchial response to methacholine was assessed by inhalation of serially doubling doses in 22 insulin-dependent diabetes mellitus (IDDM) patients and 11 nondiabetic control subjects selected for their nonsmoking habits. Cardiovascular autonomic control was studied by four standardized tests, i.e., blood pressure and heart-rate variations during orthostatism, heart-rate variation during Valsalva maneuver, and deep breathing. Magnitude and time-course of response to methacholine were similar in nondiabetic subjects and IDDM patients without any abnormal result on cardiovascular tests. Conversely, bronchial response to methacholine was markedly reduced in IDDM patients with one or more abnormal results by cardiovascular assessment of autonomic control. In the IDDM patients, bronchial response to methacholine was significantly correlated to indexes of cardiovascular autonomic control. These results suggest that, during diabetic neuropathy, innervation of the airways likewise involves cardiac autonomic control and leads to impairment of defense reflexes of the airways.
Adult↗
[Isolated corticotropin insufficiency, disclosed by hyponatremia, and associated with hypothyroidism].
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Adrenocorticotropic Hormone↗
Cardiovascular effects of the somatostatin analog octreotide in acromegaly.
OBJECTIVE: To determine the cardiovascular effects of the somatostatin analog octreotide in patients with acromegaly. DESIGN: Prospective nonrandomized study. SETTING: Referral-based endocrinology clinic. PATIENTS: Seven patients with active acromegaly, three of whom had refractory congestive heart failure. The other four patients were free of symptoms associated with heart failure. INTERVENTIONS: All patients were treated with octreotide, 100 to 500 micrograms subcutaneously three times daily. The three patients with heart failure continued to receive cardiovascular therapy (angiotensin converting enzyme inhibitors, digitalis, diuretics). MEASUREMENTS AND MAIN RESULTS: During octreotide therapy, patients showed a rapid decrease in growth hormone and insulin-like growth factor 1 (IGF-1): Mean levels (+/- SD) fell from 28.1 +/- 32.7 micrograms/L to 5.2 +/- 8.3 micrograms/L and 740 +/- 126 micrograms/L to 372 +/- 64 micrograms/L, respectively (P less than 0.025). Plasma volume returned to normal and heart rate decreased significantly. In the four patients without heart failure, right-heart catheterization done before and after 3 months of octreotide therapy showed an 18.3% +/- 11% reduction in stroke volume and a return to normal of the cardiac index. The three patients with congestive heart failure, evaluated before and after 40 days and up to 2 years of therapy, showed a dramatic clinical improvement that was associated with an increase in stroke volume (by 24% to 51%). In these patients, the cardiac index remained in the normal range, filling pressures were markedly decreased, and pulmonary wedge pressure returned to normal. This improvement was sustained for up to 3 years in the two patients with heart failure who were receiving long-term treatment. CONCLUSION: The rapid and sustained cardiac improvement seen in our patients shows that octreotide therapy for patients with acromegaly may be highly beneficial, even in those patients with advanced cardiac failure.
Acromegaly↗
Atrial natriuretic factor in patients with acromegaly.
In acromegaly the plasma volume is chronically elevated and it returns to normal when the disease is successfully treated. To define the role of ANF in such a chronic disorder of extracellular fluid volume homeostasis the plasma level was assayed in 37 acromegalic patients with active or inactive (successfully treated) disease. Five patients were studied before and after therapy. The effects of acute change in sodium-fluid status on plasma ANF levels was examined in 7 active and 4 inactive acromegalic patients and in 7 healthy subjects. As compared to 14 patients with inactive acromegaly, 23 patients with active acromegaly had an expanded plasma volume (n = 12; 50.1 vs 37.6 ml.kg-1 BW) and an increased blood concentration of growth hormone (n = 23; 22.5 vs 2.1 ng.ml-1). Plasma ANF concentrations in active and inactive acromegalic patients (33.2 and 26.6 pg.ml-1, respectively) did not differ significantly from one another or from the level in the controls (26.9 pg.ml-1). In those patients there was no correlation between plasma volume and ANF level. Infusion of 21 isotonic saline in 2 h led to a similar, significant increase in ANF levels in active (from 26.2 to 72.4 pg.ml-1) and in inactive acromegalic patients (from 33.6 to 96.7 pg.ml-1) as well as in healthy subjects (from 21 to 70.6 pg.ml-1). Successful treatment reduced the plasma volume (from 49.2 to 35.8 ml.kg-1 BW) and growth hormone level (from 10.1 to 2.6 pg.ml-1), while the ANF level remained unchanged (from 33.8 to 35.5 pg.ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Acromegaly↗
Pituitary granuloma and pyoderma gangrenosum.
Pyoderma gangrenosum is a rare chronic and recurrent skin disease characterized by progressing lesions from papulopustules to large necrotic sterile ulcers. Its definite etiology remains unknown. In a 40-year-old woman with typical pyoderma gangrenosum an intrasellar mass with suprasellar extension was diagnosed and removed by transsphenoidal surgery. Histopathological features of the lesion were those of a nonspecific granulomatous hypophysitis. Five months postoperatively the patient experienced visual defects and hypopituitarism demonstrated by endocrine evaluation. Computerized tomography showed the recurrence of the intrasellar expanding mass. Extensive and repeated evaluation failed to find any evidence of sarcoidosis, tuberculosis or histiocytosis. Corticosteroid therapy was preferred to surgery and 80 mg daily prednisone produced a dramatic shrinkage of the pituitary pseudotumor. Long-term follow-up studies did not disclose any recurrence of the pituitary granulomatous process nor objective evidence of underlying disease even after steroid dosage has been tapered. The hypothesis of a pituitary localization of pyoderma gangrenosum is suggested by the similarity between the histopathologic findings of the two conditions and the excellent response to steroid therapy.
Adult↗
Effects of chronic growth hormone hypersecretion on intrinsic contractility, energetics, isomyosin pattern, and myosin adenosine triphosphatase activity of rat left ventricle.
We studied papillary muscle mechanics and energetics, myosin phenotype, and ATPase activities in left ventricles from rats bearing a growth hormone (GH)--secreting tumor. 18 wk after tumor induction, animals exhibited a dramatic increase in body weight (+101% vs. controls) but no change in the ventricular weight/body weight ratio. The maximum isometric force of papillary muscles normalized per cross-sectional area rose markedly (+42%, P less than 0.05 vs. controls), whereas the maximum unloaded shortening velocity did not change. This was observed despite a marked isomyosin shift towards V3 (32 +/- 5% vs. 8 +/- 2% in controls, P less than 0.001). Increased curvature of the force-velocity relationship (+64%, P less than 0.05 vs. controls) indicated that the muscles contracted more economically, suggesting the involvement of V3 myosin. Total calcium- and actin-activated myosin ATPase activities assayed on quickly frozen left ventricular sections were similar in tumor-bearing rats and in controls. After alkaline preincubation, these activities only decreased in tumor-bearing rats, demonstrating that V3 enzymatic sites were involved in total ATPase activity. These data demonstrate that chronic GH hypersecretion in the rat leads to a unique pattern of myocardial adaptation which allows the muscle to improve its contractile performance and economy simultaneously, thanks to myosin phenoconversion and an increase in the number of active enzymatic sites.
Actomyosin↗
Comparison of HbA1 and fructosamine in diagnosis of glucose-tolerance abnormalities.
Total glycosylated hemoglobin (HbA1) and fructosamine were evaluated as screening tools for detection of glucose-tolerance abnormalities in 144 asymptomatic subjects undergoing a 75-g oral glucose tolerance test. Subjects were classified according to World Health Organization criteria as having normal (n = 78), impaired (n = 40), or diabetic (n = 26) glucose tolerance. We found good specificity for HbA1 and fructosamine (100 and 97%, respectively) but low sensitivity (15 and 19%, respectively). At the intersection of the curves of sensitivity and specificity drawn from various thresholds of normality, both sensitivity and specificity were 75% for HbA1 and 55% for fructosamine. Thus, neither HbA1 nor fructosamine seems to be suitable for the diagnosis of mild abnormalities in glucose tolerance.
Blood Glucose↗
Comparison of fructosamine with glycated hemoglobin as an index of glycemic control in diabetic patients.
Fasting and postprandial (or post-glucose load) plasma glucose, total HbA1 and fructosamine (F) were simultaneously assessed in 371 diabetic patients (125 insulin dependent and 246 non-insulin dependent) and in 122 nondiabetic subjects, (98 with normal glucose tolerance and 24 with impaired glucose tolerance). Fructosamine yielded nearly similar information as HbA1 about glycemic control, since similar relationships were observed between plasma glucose values and HbA1 or fructosamine levels in the different groups. A longitudinal study performed during a three-month follow-up in 74 diabetic patients and extended to six months in 19 of them, without any modification of treatment, indicated that reproducibility of HbA1 and fructosamine was nearly the same with a slight advantage for HbA1. The only clinically significant difference results from the longer half-life of hemoglobin when compared to serum proteins. Fructosamine assay should be proposed as a complement of HbA1 in the management of diabetic patients when detection of recent metabolic changes is needed.
Adult↗
[Increase of circulating levels of thymulin in hyperprolactinemia and acromegaly].
The production of thymulin by the thymic epithelium is under complex control involving the endocrine system. Experimental models have suggested that prolactin (PRL) and growth hormone (GH) participate in this regulation but this has not been documented in humans. Using a bioassay we measured circulating thymulin levels in patients with hyperprolactinemia (n = 21), acromegaly (n = 15), or both (n = 6). Thymulin was elevated in these three groups of patients compared with normal subjects or with patients with pituitary disease but no excess in PRL or GH. Contrasting with observations in control groups, thymulin did not decrease as a function of age in patients. No correlation between thymulin and PRL or GH levels was observed while thymulin and insulin-like growth factor 1 levels were correlated. A new radioimmunoassay used in some patients for thymulin determination yielded similar results. Overall these data demonstrate that PRL and GH are involved in the hormonal control of thymulin production by the thymic epithelium in the human.
Acromegaly↗