Group visits improve metabolic control in type 2 diabetes: a 2-year follow-up.

OBJECTIVE: To evaluate whether group visits, delivered as routine diabetes care and structured according to a systemic education approach, are more effective than individual consultations in improving metabolic control in non-insulin-treated type 2 diabetes. RESEARCH DESIGN AND METHODS: In a randomized controlled clinical trial of 112 patients, 56 patients were allocated to groups of 9 or 10 individuals who participated in group consultations, and 56 patients (considered control subjects) underwent individual visits plus support education. All visits were scheduled every 3 months. RESULTS: After 2 years, HbA(1c) levels were lower in patients seen in groups than in control subjects (P < 0.002). Levels of HDL cholesterol had increased in patients seen in groups but had not increased in control subjects (P = 0.045). BMI (P = 0.06) and fasting triglyceride level (P = 0.053) were lower. Patients participating in group visits had improved knowledge of diabetes (P < 0.001) and quality of life (P < 0.001) and experienced more appropriate health behaviors (P < 0.001). Physicians spent less time seeing 9-10 patients as a group rather than individually, but patients had longer interaction with health care providers. CONCLUSIONS: Group consultations may improve metabolic control in the medium term by inducing more appropriate health behaviors. They are feasible in everyday clinical practice without increasing working hours.

Benfotiamine is similar to thiamine in correcting endothelial cell defects induced by high glucose.

We investigated the hypothesis that benfotiamine, a lipophilic derivative of thiamine, affects replication delay and generation of advanced glycosylation end-products (AGE) in human umbilical vein endothelial cells cultured in the presence of high glucose. Cells were grown in physiological (5.6 mM) and high (28.0 mM) concentrations of D-glucose, with and without 150 microM thiamine or benfotiamine. Cell proliferation was measured by mitochondrial dehydrogenase activity. AGE generation after 20 days was assessed fluorimetrically. Cell replication was impaired by high glucose (72.3%+/-5.1% of that in physiological glucose, p=0.001). This was corrected by the addition of either thiamine (80.6%+/-2.4%, p=0.005) or benfotiamine (87.5%+/-8.9%, p=0.006), although it not was completely normalized (p=0.001 and p=0.008, respectively) to that in physiological glucose. Increased AGE production in high glucose (159.7%+/-38.9% of fluorescence in physiological glucose, p=0.003) was reduced by thiamine (113.2%+/-16.3%, p=0.008 vs. high glucose alone) or benfotiamine (135.6%+/-49.8%, p=0.03 vs. high glucose alone) to levels similar to those observed in physiological glucose. Benfotiamine, a derivative of thiamine with better bioavailability, corrects defective replication and increased AGE generation in endothelial cells cultured in high glucose, to a similar extent as thiamine. These effects may result from normalization of accelerated glycolysis and the consequent decrease in metabolites that are extremely active in generating nonenzymatic protein glycation. The potential role of thiamine administration in the prevention or treatment of vascular complications of diabetes deserves further investigation.

Evidence for a positive correlation between serum cortisol levels and IL-1beta production by peripheral mononuclear cells in anorexia nervosa.

A hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in anorexia nervosa (AN), together with some immunological abnormalities, involving citokine - and particularly Tumor Necrosis-Factor-alpha (TNF-alpha) - production by polymorphonuclear cells. The ability of pro-inflammatory cytokines to activate the HPA axis is well known; however, there are no data demonstrating an interdependence between immunological and endocrine response in AN. To investigate the presence of a correlation between immune response and pituitary-adrenal function, plasma ACTH and serum cortisol concentrations were measured in 13 AN patients and in the same number of controls. TNF-alpha and interleukin (IL)-1beta production by ex-vivo unstimulated and LPS-stimulated peripheral mononuclear cells was also assessed. Circulating cortisol concentrations were higher (p<0.01) in AN (156.7 +/- 45.1 microg/l, mean +/- SD) than in controls (105.9 +/- 25.7 microg/l). Unstimulated IL-1beta release in supernatants of mononuclear cell cultures was slightly but not significantly higher in AN than in controls, while TNF-alpha release was similar in the two groups. A positive correlation was found between IL-1beta concentrations in unstimulated culture supranatants and serum cortisol levels in AN (r=0.782, p=0.002), while in normal subjects there was a trend toward a negative correlation; a slight positive correlation, while not significant, between IL-1beta and plasma ACTH, as well as between TNF-alpha and serum cortisol was also found in AN. These data suggest that the normal relationship between pro-inflammatory cytokines release, particularly IL-1beta, and cortisol secretion is deranged in AN.

Bone metabolism in type 2 diabetes mellitus.

Several conditions have been described to cause osteoporosis, including diabetes mellitus. While the relationship between type 1 diabetes and osteopenia is well documented in the literature, data on the presence of this complication in type 2 diabetes have not been well established. We studied a population composed of 66 post-menopausal women with type 2 diabetes and a control population. We examined bone mineral density with the dual-energy X-ray absorptiometry (DXA) technique at the lumbar and femoral levels and, in a subgroup of patients, we also measured the levels of markers of bone remodelling. We found significantly higher levels of bone mineral density at the femoral (but not lumbar) level in the diabetic subjects compared with the control population in all the examined subregions, except Ward's triangle. Moreover, we found higher levels of some markers of bone resorption (urinary calcium and hydroxyproline, telopeptide) in the patients with diabetes, while urinary crosslinks were higher in the controls. On the basis of these results, we suggest that osteoporosis cannot be considered a complication of type 2 diabetes and that, from a metabolic point of view, bone resorption is greater in diabetic patients than in normal subjects, as suggested by the high levels of most of the markers of osteoclastic activity.

Comparison of the cost-effectiveness of three approaches to screening for and treating sight-threatening diabetic retinopathy.

The purpose of this study was to analyse and compare the costs involved in screening for and treating sight-threatening diabetic retinopathy in three different clinical settings. In the first setting, diabetologists screened using ophthalmoscopy and color photography, according to the St. Vincent Declaration guidelines, and selected patients for further assessment by a visiting ophthalmologist and for treatment in another hospital. In the second setting, all patients were regularly referred to ophthalmologists, either in the same hospital or elsewhere, for all aspects of eye care. In the third setting, screening was done again with ophthalmoscopy alone by diabetologists who followed the St. Vincent Declaration guidelines; however, further assessment and treatment were carried out in the eye department of the same hospital. Costs to the Italian National Health Service and to patients were calculated per screening performed and per patient subjected to laser treatment as a result of screening. A sensitivity analysis was then performed to simulate the costs of standardised patient populations going through the three different settings. It is concluded that absolute costs would be lower, both for the Italian National Health Service and for patients, if screening, assessment and treatment were all carried out in the same hospital. Equipping a diabetic clinic specially for screening would not be more expensive than delegating eye care to external parties, even for a hospital without an eye department. Moreover, delegating eye care more than doubles costs for patients. Screening for, assessing and treating sight-threatening diabetic retinopathy may be a cost-effective procedure for society as a whole in Italy.

[Increased body mass index increase and insulin resistance parameters in dyslipidemia. Risk and positive correlation in essential obesity]. / Aumento del BMI e parametri di insulino-resistenza e di dislipidemia. Riscontro di correlazioni positive nell'obesità essenziale.

BACKGROUND: Obesity is frequently characterized by hyperinsulinemia with insulin-resistance, tendency to impaired glucose tolerance and by impaired lipidic picture. The relationship existing between some obesity parameters i.e. BMI and weight excess (EP) regarding ideal weight calculated according Lorenz's formula and main parameters both of insulin-resistance and lipidic picture can be interesting. METHODS: 58 obese subject (10 M e 48 F) age 38 +/- 6.2 years (mean +/- DS) with BMI 34.3 +/- 5.3 and EP 33.7 +/- 15; they didn't suffer from hypertension and diabetes; they was subjected to an OGTT and evaluation of glycemia and insulinemia after 0', 60', 90', 120', 150', 180'. Moreover an assessment of lipidic state (cholesterol, triglyceride, HDL, LDL) was carried out. Glycemia and insulinemia with respective areas under curve (AUC glyc. e AUC ins.) and increases (AUCI glyc. e AUCI ins.) were compared with BMI and EP for searching relationship. The same was done for lipidic state. RESULTS: BMI was found positively related with glycemia after 0' (r = 0.3043, p < 0.05) 60' (r = 0.3465, p < 0.05) 120' (r = 0.2895, p < 0.05) with AUC glyc. (r = 0411, p < 0.01) and AUCI glyc. (r = 0.276, p < 0.05), with insulinemia after 0' (r = 0.365, p < 0.01) 60' (r = 0.350, p < 0.01) and with AUC ins. (r = 0.272, p < 0.05). HDL is negatively (r = -0.307, p < 0.05) instead of triglyceride positive related (r = 0.338, p < 0.05) with BMI. EP is positively related with glycemia after 0' (r = 0.376, p < 0.01), 60' (r = 0.362, p < 0.01), 120' (r = 0.290, p < 0.05), with AUC glyc. (r = 0.422, p < 0.01), with insulinemia after 0' (r = 0.512, p < 0.01), 60' (r = 0.473, p < 0.01) with AUC ins. (r = 0.420, p < 0.01) and AUCI ins. (r = 0.354, p < 0.01). Triglyceride was positively related (r = 0.365 p < 0.01) with EP. CONCLUSIONS: These relationships suggest that BMI and EP can be considered as indicators not only of obesity degree, but also of hyperinsulinemia and, to a lesser extent, dyslipidemia severity.

[Primary hyperaldosteronism. Update on a topic of physiopathology and clinical features]. / L'iperaldosteronismo primitivo. Attualità in tema di fisiopatologia e clinica.

The authors examine the various forms of primary hyperaldosteronism, outlining the most recent acquisitions in terms of etiopathogenesis and physiopathology. While Conn's original description of primary hyperaldosteronism is a syndrome based on corticoadrenal aldosteronesecreting adenoma, it was later seen that this condition could recognise other anatomic substrates, such as carcinoma and in particular bilateral corticoadrenal hyperplasia. A peculiar form of the latter can be suppressed with glucocorticoids sustained by an anomalous recombination of aldosterone-synthase and 11-beta-hydroxylase. The main focus in this paper is on clinical management, in particular the current diagnostic criteria which show that primary hyperaldosteronism affects a higher percentage of the hypertense population that was estimated in the past. Above all, the significance of the aldosterone/PRA (ARR) ratio in screening for this condition is discussed, above all in normokalemic forms, together with the role of molecular biology in identifying glucocorticoid-suppressible forms. Lastly, the principles of medical and surgical management are outlined, emphasising the role of laparoscopic surgery.

Evidence for an interaction between alpha-MSH and opioids in the regulation of gonadotropin secretion in man.

Gonadotropin secretion is inhibited by the endogenous opioids and stimulated by their antagonist naloxone. LH secretion is stimulated by alpha-MSH, a tridecapeptide derived from the post-translational processing of POMC. The possibility that alpha-MSH interacts with the opioids, as suggested by the experimental evidence, was investigated in 7 normal males aged 24-29 through the performance of seven tests: naloxone (0.8 mg i.v. bolus, followed by infusion of 1.6 mg/h for 120'); alpha-MSH (2.5 mg i.v. bolus); naloxone + alpha-MSH (2.5 mg i.v. 15' after commencement of the naloxone infusion); naloxone + GnRH (100 micrograms i.v. 15' after commencement of the naloxone infusion); alpha-MSH + GnRH (respectively 2.5 mg and 100 micrograms at time 0), GnRH alone (100 micrograms at time 0), placebo (150 nmol/l NaCl solution). The LH AUCs during both naloxone (30.3 +/- 2.7 mIU/ml.min-1) and alpha-MSH test (32.9 +/- 4.6 mIU/ml.min-1) were significantly greater (p < 0.005) than that observed during placebo (16.9 +/- 3.6 mIU/ml.min-1). The LH AUC during alpha-MSH + naloxone (37.6 +/- 2.6 mIU/ml.min-1) was not significantly different from that recorded during their separate administration. GnRH injected alone, during the naloxone infusion and with alpha-MSH produced similar increases in LH, that were significantly higher than that observed during the other tests (AUCs: GnRH 89.4 +/- 10.6, GnRH + naloxone 100.5 +/- 9.1, GnRH + alpha-MSH 94.6 +/- 7.9 mIU/ml.min-1, p < 0.001). Significant increase in FSH (p < 0.001) was only observed during GnRH, GnRH + naloxone and GnRH + aMSH tests (AUCs: placebo 13.3 +/- 1.7; naloxone 14.7 +/- 2.5; alpha-MSH 15.5 +/- 2.3; alpha-MSH + naloxone 16.9 +/- 1.9; GnRH 19.1 +/- 1.1; GnRH + alpha-MSH 20.7 +/- 1.3; GnRH + naloxone 21.2 +/- 1.8 mIU/ml.min-1). These results are in line with the possibility of an interaction between alpha-MSH and the opioids in the regulation of gonadotropin secretion, perhaps with opposing effects on a final common pathway.

Hypertension and oedema caused by cortexone hyperproduction and cured by monolateral adrenalectomy. Case report.

Excess 11-deoxycorticosterone (DOC) production, mostly due to an enzyme defect 11-beta-hydroxylase, is a rare cause of secondary hypertension. Even rarer are those forms due to an adrenal adenoma or to a bilateral hyperplasia. In this paper we report the case of 23-year-old woman with excess DOC production, presenting with arterial hypertension and oedema, whom we first observed in 1961. Complete clinical remission, persisting more than 30 years later, was obtained by monolateral adrenalectomy. The literature reports of DOC-induced hypertension due to adrenal adenoma or hyperplasia are reviewed and the possible pathogenetic mechanisms are discussed.

Thiamine corrects delayed replication and decreases production of lactate and advanced glycation end-products in bovine retinal and human umbilical vein endothelial cells cultured under high glucose conditions.

This study aimed at verifying whether thiamine, a co-enzyme which decreases intracellular glycolysis metabolites by allowing pyruvate and glyceraldheyde 3-phosphate to enter the Krebs cycle and the pentose-phosphate shunt, respectively, corrects delayed replication caused by high glucose concentrations in cultured human umbilical vein (HUVEC) and bovine retinal endothelial cells (BREC). After incubation in physiological (5.6 mmol/l) or high (28.0 mmol/l) glucose with or without 150 mumol/l thiamine, cells were counted and proliferation assessed by mitochondrial dehydrogenase activity. Lactate was measured in both cell types as an index of glycolytic activity and fluorescent advanced glycosylation end-products (AGE) concentration was determined in the HUVEC lysate. Both cell counts and proliferation assays in either of the cell types confirmed the impairment to cell replication induced by high glucose. When thiamine was added to cells kept under high glucose conditions, the number of surviving cells was significantly increased and the reduced cell proliferation appeared to be corrected. Lactate assays confirmed the increased production of this metabolite by BREC and HUVEC in high glucose, which was reduced by thiamine. Fluorescent AGE determination showed that thiamine may prevent non-enzymatic glycation in HUVEC. Thiamine restores cell replication, decreases the glycolytic flux and prevents fluorescent AGE formation in endothelial cells cultured in high glucose, suggesting that abnormal levels of glycolytic metabolite(s) may damage cells.

Altered adrenocorticotropin and cortisol response to corticotropin-releasing hormone in HIV-1 infection.

Alterations of the hypothalamic-pituitary-adrenal (HPA) axis are common in HIV infection. To characterize further the site of these derangements and their possible causes, eight male drug addicts with symptomatic HIV infection (stage IV C2) underwent the following investigations: repeated baseline determinations of cortisol, adrenocorticotropin (ACTH), interleukin 1 beta (IL-1 beta), IL-6 and interferon alpha (IFN-alpha); and ovine corticotropin-releasing hormone (CRH) test (100 micrograms IV) for ACTH and cortisol determinations. Baseline cortisol levels were either normal or elevated in all patients. A significant linear correlation was found between baseline levels of cortisol and both IL-6 (r = 0.955; p < 0.001) and IL-1 beta (r = 0.863; p < 0.005), but not between cortisol and ACTH or between ACTH and circulating cytokines. Both ACTH and cortisol responses to CRH were nearly absent in six out of eight patients, and delayed in the others. The areas under the curves of both ACTH and cortisol after CRH were significantly lower in HIV patients than in a group of eight healthy control subjects (p = 0.0157 for ACTH and p = 0.046 for cortisol). Out data suggest the possibility of an inappropriate stimulation of the HPA axis in symptomatic HIV infection by HIV-induced release of cytokines, with a blunted pituitary and adrenal response to CRH.

Diabetic retinopathy as a cause of blindness in the province of Turin, north-west Italy, in 1967-1991.

Diabetes is known to be a major contributor to blindness in industrialized countries but few data are available on the situation in Italy. As an introductory step to the implementation of permanent screening for diabetic retinopathy, a search was carried out on the causes of visual loss in the provincial territory surrounding Turin, the main city of North-West Italy. The case notes of all 4549 residents in the province who were certified blind between 1967 and 1991 were examined with regard to cause, age at onset, and year of onset of visual acuity < or = 1/20. Diabetic retinopathy was the second commonest cause of bilateral blindness (13.1% of cases), preceded by cataract (26.7%) and followed by myopia (11.1%), optic atrophy (8.9%), glaucoma (8.9%), retinitis pigmentosa (7.2%), and senile macular degeneration (4.1%). Diabetic retinopathy was the commonest eye disease among those who became blind between the ages of 50 and 70 and remained the leading cause of visual loss when the age groups 20 to 70 were pooled together. The incidence of diabetic retinopathy-related blindness did not show any trend to decrease over the 25 years investigated. It is concluded that, in spite of widespread availability of facilities for its assessment and treatment, diabetic retinopathy remains a leading cause of blindness in North-West Italy. This fully justifies the implementation of screening programmes and efficient referral chains for the early detection and prompt treatment of this complication of diabetes.

Treatment of Cushing's disease by interstitial pituitary irradiation: short- and long-term follow-up.

Trans-sphenoidal intrasellar implantation of radioactive rods was employed to treat Cushing's disease in our Institution between 1958 and 1981. The patients were followed at regular intervals after the procedure. The aim of this work is to assess retrospectively the results, comparing the short- (1 year) and long-term (average 21.8 years) effects of this treatment. Seventy-six patients received pituitary implantation of 90Y- and one of 198Au-labelled rods, delivering a dose of 100-150,000 rad. Complete remission was obtained in a few weeks to months in 57/76 patients (5 of whom required a second implantation); 2 patients died of meningoencephalitis and 3 of cardiovascular complications associated with hypercortisolism 1 to 2 months after surgery. In 12 patients bilateral adrenalectomy or external pituitary irradiation were required to achieve remission; one of them developed Nelson's syndrome 15 years after implantation. Two were lost at follow-up. Long-term follow-up was possible in 41 patients of the initial series. Of these, 40 were cured of the disease, with hypoadrenalism developing in 25, while recurrence was observed only in the patient treated with 198Au. The incidence of hypothyroidism was 50%, and that of hypogonadism 54%. Permanent diabetes insipidus developed in 1 subject. GH deficiency resulting in retarded growth was found in the youngest patient, who had been operated at the age of 14. In conclusion, interstitial irradiation of pituitary adenomas was a safe and effective procedure for the treatment of Cushing's disease.

Metabolic markers for the early diagnosis of postmenopausal osteoporosis.

We performed a cross-sectional study in 147 women, 41 in premenopausal age and 106 in menopause for 1-5 years: bone mineral density (BMD) at the distal radius and annual bone loss (as shown by plasma alkaline phosphatase and osteocalcin levels, and by calcium/creatinine and hydroxyproline/creatinine in the second urine of the morning) were evaluated. A significant reduction of BMD with a significant increase of bone loss was observed with increasing duration of menopause. Furthermore, when the women were subdivided into two groups according to annual bone loss (over or under 1.7%), significant differences were found between bone mineral density in the second and third years of menopause. As this is a cross-sectional and not a longitudinal study, it confirms that, in the presence of a higher bone loss, the BMD levels are lower and consequently the theoretical definition of this parameter can allow useful information on the presumable behavior of BMD.

Alpha-melanocyte-stimulating hormone antagonizes the inhibitory effect of corticotropin-releasing hormone on luteinizing hormone secretion during the luteal phase in normal women.

CRH inhibits the secretion of gonadotropins by activating endogenous opioids, whereas alpha MSH, which displays various behavioral and neuroendocrine effects contrary to those of the opioids, stimulates their release. To evaluate the possible interaction of CRH and alpha MSH, eight women in the luteal phase underwent the following tests: 1) ovine CRH infused at 100 micrograms/h for 3 h, 2) alpha MSH (2.5 mg as an iv bolus 60 min after the start of saline infusion), 3) CRH plus alpha MSH (injected 60 min after the start of CRH infusion), and 4) placebo. LH, FSH, PRL, ACTH, and cortisol were determined every 15 min for 180 min. CRH significantly (P < 0.001) reduced serum LH. alpha MSH alone significantly (P < 0.001) increased LH to a peak within 15-30 min (baseline, 3.3 +/- 0.7 mIU/mL; maximum increase, 3.5 +/- 0.9 mIU/mL) and induced an even greater rise when injected during the CRH infusion (baseline, 2.8 +/- 03 mIU/mL; maximum increase 7.5 +/- 1.6 mIU/mL; P < 0.05 vs. alpha MSH alone). FSH was always unaffected. ACTH and cortisol increased (P < 0.001) during the CRH infusion and fell significantly (P < 0.001) during the placebo infusion. alpha MSH had no effect on these changes. PRL fell during the placebo infusion (P < 0.001). No changes were induced by CRH or alpha MSH. In conclusion, alpha MSH antagonizes CRH inhibition of LH secretion. This finding lends support to the view that differential posttranslational processing of POMC contributes to the regulation of LH secretion. Further investigation is needed to clarify the mechanism of the antagonism between alpha MSH and CRH.

[Male fertility in the elderly]. / La fertilità maschile nella terza età.

Fertility in the elderly is still a less known argument. We report some news about seminal parameters (SP) and testicular hystological parameters (THP) in this age. About SP: the volume of the ejaculate, the number and the motility of spermatozoa are reduced. The morphology is typical: spermatozoa with coiled tails are common. About THP: some testes show a normal hystological architecture; others show a reduced volume and some aspects of hypospermatogenesis or maturative arrest; others show a very reduced volume, thickness of the tubular basal membrane and other signs of cellular regression. These signs are dependent upon the vascular insufficiency and the hormonal alterations which may occur in the elderly.

[Role of the endothelium in the control of vascular motility: physiologic aspects and physiopathologic implications in cardiovascular diseases]. / Ruolo dell'endotelio nel controllo della motilità vascolare: aspetti fisiologici ed implicazioni fisiopatologiche nelle malattie cardiovascolari.

It was recently demonstrated that vascular endothelium produces many substances which modulate the vascular tone by acting locally (endothelium derived relaxing factor, angiotensin II, endothelin, prostacyclin). The authors review the physiological regulatory role of these substances and their involvement in cardiovascular diseases. They also consider the interaction between the endothelium derived factors and some cardiovascular drugs (such as calcium antagonists and ACE-inhibitors) and also the mechanisms of the possible protective action of these drugs on the vascular wall.

[Virilization in women. Clinical and therapeutic aspects]. / L'androgenizzazione nella donna. Aspetti clinici e terapeutici.

Androgenization in women can be divided, from a clinical standpoint, in two groups: a major form (with hirsutism, seborrhea, acne, hair loss, menstrual irregularities, masculinization of muscles and voice, mammary atrophy) and a minor one, with skin changes only (in particular hirsutism) with or without menstrual problems. The different clinical presentations are reviewed here: virilizing tumours of adrenal glands and ovaries, adrenogenital congenital syndromes, Cushing's syndrome and disease, iatrogenic forms, simple or idiopathic hirsutism, late onset enzymatic defects of adrenal steroidogenesis, polycystic ovary syndrome). The relevant therapeutic options are discussed. Special attention is devoted to the treatment of simple cutaneous androgenization, a problem affecting about 10% of women, by antiandrogenic drugs, mostly cyproterone acetate and spironolactone. These compounds compete with dehydrotestosterone for androgen cutaneous receptors, and have obtained good results, although not permanent. The indications, use and side-effects are also discussed.