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Background and aim: The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII). Methods and results: Questionnaires investigating the organisation of diabetes care centres, individuals’ clinical and metabolic features and pump technology and its management were sent to adult and paediatric diabetes centres that use CSII for treatment in Italy. Information on standard clinical variables, demographic data and acute and chronic diabetic complications was derived from local clinical management systems. The sample consisted of 6623 people with diabetes, which was obtained from 93 centres. Of them, 98.8% had type 1 diabetes mellitus, 57.2% were female, 64% used a conventional insulin pump and 36% used a sensor-augmented insulin pump. The median glycated haemoglobin (HbA1c) level was 60 mmol/mol (7.6%). The HbA1c target (i.e. 18 years) was achieved in 43.4% of paediatric and 23% of adult participants. Factors such as advanced pump functions, higher rate of sensor use, pregnancy in the year before the study and longer duration of diabetes were associated with lower HbA1c levels. The most common chronic complications occurring in diabetes were retinopathy, microalbuminuria and hypertension. In the year before the study, 5% of participants reported ≥1 episode of severe hypoglycaemic (SH) episodes (SH) and 2.6% reported ≥1 episode of ketoacidosis. Conclusions: Advanced personal skills and use of sensor-based pump are associated with better metabolic control outcomes in Italian people with diabetes who were treated with CSII. The reduction in SH episodes confirms the positive effect of CSII on hypoglycaemia. Clinical trial registration number: NCT 02620917 (ClinicalTrials.gov).

Italy is dealing with iodine deficiency since ancient times. In 1848 an ad hoc committee appointed by the king of Sardinia, identified extensive areas afflicted by endemic goiter and endemic cretinism in Piedmont, Liguria and Sardinia. Since then many epidemiological studies have been conducted in our country. These showed that iodine deficiency was present not only in mountain areas but also in coastal areas. In 1972 the iodization of salt at 15 mg/kg was allowed by law and iodized salt was distributed on request to selected endemic areas. Five years later the distribution was extended to the whole country. However the sale of iodized salt was not mandatory at that time and only a small fraction of the Italian population started using iodized salt. In 1991 the content of iodine in the salt was raised to 30 mg/kg and in 2005 a nationwide salt iodization program was finally implemented. Some years later a nationwide monitoring program of iodine prophylaxis was also implemented. Since 2005 the sale of iodized salt in Italian supermarkets has increased (34% in 2006, 55% in 2012), although it has been observed that the use of iodized salt is still low in the communal eating areas and in the food industry. These data are coherent with recent epidemiological studies showing that some regions in our country are still characterized by mild iodine deficiency and a high frequency of goiter and other iodine deficiency disorders. This implies that further efforts should be made to successfully correct iodine deficiency in Italy.

OBJECTIVE: To examine the influence of shift work on metabolic and cardiovascular risk factors in subjects working in an industry sited in Apulia, Southern Italy. DESIGN: Cross-sectional study of metabolic effects of shift work in glucose tolerant workers in a chemical industry in southern Italy. SUBJECTS: The subjects included 319 glucose tolerant male individuals, aged 35–60 y. MEASUREMENTS: Anthropometric parameters (body mass index (BMI) and waist-to-hip ratio (WHR)), fasting concentrations of glucose, insulin, and lipids (total cholesterol, HDL-cholesterol, triglycerides), the sum of glucose levels during 75 g-oral glucose tolerance test (Σ-OGTT), and systolic and diastolic blood pressure (SBP and DBP, respectively). RESULTS: The prevalence of obesity was higher among shift workers compared to day workers, whereas body fat distribution was not different between the two groups. Shift workers had higher BMI than day workers, and shift working was associated with BMI, independently of age and work duration. Shift workers had significantly higher SBP levels, which were independently influenced by BMI, but not by shift work, thus suggesting that the difference in SBP may well be mediated by the increased body fatness. CONCLUSION: In workers of an industry sited in Southern Italy, shift work may be directly responsible for increased body fatness and is indirectly associated with higher blood pressure levels and some features of metabolic syndrome.

Purpose: To assess the frequency of retinopathy and vision loss in patients with insulin-dependent diabetes mellitus and their relations to potentially modifiable risk factors. Methods: The authors conducted a multicenter cross-sectional study of diabetic complications and their risk factors using standardized methods of assessment. The sample was comprised of 3250 insulin-dependent diabetic patients (1668 men, 1582 women) aged 15 to 60 years with mean (standard deviation) duration of diabetes of 14.7 (9.3) years from 31 European diabetes centers; 2991 of the patients were eligible for retinal photography. Visual acuity was measured using the Snellen chart. Retinopathy was evaluated by retinal photographs (two fields per eye) graded at a central facility. Glycated hemoglobin (HbA,c), cholesterol, triglyceride, fibrinogen, von Willebrand factor, and urinary albumin excretion rate were assessed at a single location. Results: Corrected visual acuity was greater than or equal to 1.0 in both eyes in 69.7% of patients and less than or equal to 0.1 in the best eye in 2.3%. Factors significantly related to vision loss were age, duration of diabetes, glycated hemoglobin (HbA 1c ), and level of retinopathy. Mild nonproliferative retinopathy was found in 25.8% of the patients, moderate-severe nonproliferative retinopathy in 9.8% of the patients, and proliferative retinopathy in 10.6% of the patients. After adjustment for age, duration of diabetes, HbA 1c , and albumin excretion rate, significant risk factors for moderate-severe nonproliferative retinopathy were blood pressure and triglyceride, and risk factors for proliferative retinopathy were triglyceride and fibrinogen. Conclusion: Vision loss is a common complication of patients with insulin-dependent diabetes, with diabetic retinopathy an important cause. Apart from poor glycemic control, several other potentially modifiable risk factors for retinopathy may be important, including elevated blood pressure, plasma triglyceride, and fibrinogen. In view of the possible barriers to the full implementation of strict glycemic control in this type of diabetes, additional strategies for the prevention and slowing of progression of retinopathy should be investigated, such as blood pressure and lipid lowering therapies.

RIASSUNTO Nonostante gli sforzi per diffondere e implementare le raccomandazioni nutrizionali per il trattamento del diabete, la loro applicazione nella pratica clinica è ancora largamente insufficiente. Tra le possibili ragioni va considerato il fatto che le abitudini alimentari risentono molto delle tradizioni gastronomiche locali. Lo studio si propone di valutare le abitudini alimentari delle persone con diabete in tre macroaree geografiche italiane, nord, centro e sud, per studiare in che misura le tradizioni gastronomiche locali possano influenzare l'adesione alle raccomandazioni nutrizionali. Sono stati studiati 1786 pazienti diabetici di tipo 2; le abitudini alimentari sono state indagate con un questionario alimentare semiquantitativo di frequenza validato (EPIC, European Prospective Investigation on Cancer and Nutrition). L'introito energetico è sovrapponibile nelle 3 macroaree geografiche, ma gli alimenti che contribuiscono alla composizione della dieta sono diversi a seconda della locazione geografica: al nord si osserva un maggiore consumo di carne, salumi e grassi animali; al sud, un maggiore consumo di pane integrale e legumi. Questo si traduce in una differente composizione in nutrienti della dieta: il consumo di grassi totali, grassi saturi e polinsaturi risulta significativamente più basso al sud e al centro rispetto al nord (p < 0,05); il contrario si osserva, invece, per i carboidrati totali e la fibra alimentare (p < 0,05). Infine, la proporzione di pazienti che aderiscono alle raccomandazioni nutrizionali è generalmente scarsa sia per il consumo di fibra, mediamente inferiore rispetto a quanto raccomandato, sia per il consumo di grassi saturi, mediamente superiore ai livelli consigliati. In conclusione, le raccomandazioni nutrizionali sono scarsamente seguite su tutto il territorio nazionale; si osservano, tuttavia, significative differenze geografiche verosimilmente dovute all'influenza delle tradizioni gastronomiche locali che vanno tenute in conto per migliorare l'adesione dei pazienti alle raccomandazioni dietetiche.

OBJECTIVE The aim of the study was to investigate whether the absence of increased 5α-reductase activity explained the absence of hirsutism in premenopausal obese women with increased free testosterone (FT) levels. DESIGN As in hyperandrogenicity there generally exists evidence for increased 5α-reductase activity, we measured, as parameters of 5α-reductase activity, plasma levels of 5α-androstane-3α,17β-diol glucuronlde (ADG) and androsterone glucuronlde (ADTG) as well as their precursor levels in obese women without hirsutlsm, obese hirsute women, non-obese hirsute women, and non-obese, non-hirsute women. PATIENTS Eighty-two premenopausal women (20–45 years old) were studied, in four age matched groups: 39 controls, 18 obese without hirsutism, 11 non-obese hirsute and 14 obese hirsute women. MEASUREMENTS Blood samples were taken between days 5 and 7 of the menstrual cycle. Steroid hormone levels were measured by radioimmunoassay. Free testosterone levels were measured by equilibrium dialysis. RESULTS Compared to controls, mean free testosterone levels were increased (P

Women with upper body obesity are at increased risk for cardiovascular disease (CVD). Several studies have demonstrated a reduced fibrinolytic activity in these patients, mainly due to an enhanced activity of plasminogen activator inhibitor-1 (PAI-1). Since an increase of androgenic activity is a feature of central obesity in women, the present study was aimed at evaluating the possibility of a relationship between androgens and PAI-1 (antigen and activity) in 20 premenopausal women, 10 with upper body obesity and 10 controls. In obese women, PAI-1 antigen showed a positive Pearson correlation with free testosterone (FT), insulin, c-peptide, triglycerides (TG), and waist to hip ratio (WHR) (P less than .01), whereas PAI-1 activity correlated positively only with insulin and WHR (P less than .01). In control women, PAI-1 antigen and activity were positively related only to TG (P less than .01). When we applied the multiple regression model with stepwise backward method to our data, both PAI-1 antigen and activity did not maintain any significant association. However, when the data from both the groups were pooled (n = 20), and PAI-1 antigen was considered as the dependent variable, body weight (Sig T = 0.0001), TG (Sig T = 0.0053), FT (Sig T = 0.013), and luteinizing hormone (LH) (Sig T = 0.0474) met the stepwise criteria, suggesting an independent effect of each of these parameters on PAI-1 antigen. On the other hand, when PAI-1 activity was tested as the dependent variable, only body weight maintained a significant relationship with this parameter (Sig T = 0.0006).(ABSTRACT TRUNCATED AT 250 WORDS)

Gallbladder (GB) volume was monitored by real-time sonography in diabetics (n = 21) and healthy volunteers (n = 55) after a test meal. Seventeen controls and seven diabetics were obese; six patients had both autonomous and somatic neuropathy, and four had somatic neuropathy. Fasting GB volume was similar in controls and diabetics with and without autonomic neuropathy; it was correlated with body mass index (controls, r = 0.43, P less than 0.002; diabetics, r = 0.46, P less than 0.04), and was increased in obese subjects. Post-prandial GB emptying was decreased in diabetics. Those with autonomous neuropathy exhibited larger residual volumes than controls (P less than 0.03). Post-prandial GB emptying was slower and less complete in (non-diabetic) obese subjects and deteriorated further in diabetic obese subjects. GB fasting tone was normal, but GB kinetics were impaired in diabetics; obesity and autonomous neuropathy were correlated with GB hypomotility.

Objective: To verify the occurrence of preferential distribution of vaginally administered progesterone to the uterus compared with extrapelvic regions in vivo and in humans. Design: Prospective clinical study. Setting: University medical school. Patient(s): Twenty postmenopausal women undergoing transabdominal hysterectomy for benign pathologies. Intervention(s): Forty-five minutes before surgery, the women received a single vaginal administration of an oil-based micronized progesterone (100 mg) solution currently available on the market for IM use. During the operation, parallel blood samples were drawn from the uterine and radial arteries. Main Outcome Measure(s): Plasma levels of progesterone were measured by RIA. Result(s): Mean (±SD) plasma levels of progesterone were significantly higher in the uterine artery than in the radial artery (9.75 ± 3.21 vs. 5.12 ± 2.06 ng/mL, respectively). Conclusion(s): Vaginal administration allows a preferential distribution of progesterone to the uterus, which confirms the existence of the so-called "first uterine pass effect."

This study was aimed at investigating the absorption of nasally administered bromocriptine and its effect on serum prolactin level. Fifteen physiologically hyperprolactinemia women who had asked to discontinue breast feeding received a single nasal spray administration of 0.8 mg bromocriptine. Serum prolactin levels were measured by radioimmunoassay at 30 and 15 min before drug administration, at the time of administration and at 15, 30, 60, 120, 240, 480 and 720 min after administration; bromocriptine was radioimmunoassayed in only five of the patients from time 0 to 720 min after administration. Serum bromocriptine levels increased rapidly after administration, reached a maximum at 120 min and thereafter declined slowly over the subsequent 10 h. As the bromocriptine level increased there was a decline in the serum prolactin level. The first significant decline in serum prolactin level compared with the baseline level occurred at 30 min after administration and the level continued to decrease significantly until time 120 min. Four hours after administration the mean serum prolactin level was within the normal assay range. The maximum decline in serum prolactin level was reached at 720 min after administration. Correlation analysis between serum bromocriptine and prolactin concentrations yielded a significant negative value between times 0 and 120 min after administration. There was no significant change in mean orthostatic systolic or diastolic blood pressure or in mean heart rate. Only one patient complained of headache and dizziness; another experienced mild transient nausea, and none had vomiting. Ten patients (66.67%) reported light endonasal burning and an unpleasant taste which subsided after a few minutes; no patient showed nasal irritation at nasal examination. In conclusion, nasal administration of 0.8 mg bromocriptine was effective in reducing the serum prolactin level for more than 12 h after administration without inducing significant side-effects.

To investigate the influence of obesity and body fat distribution on serum levels of ceruloplasmin, a risk factor for myocardial infarction.Fasting concentrations of ceruloplasmin, insulin, glucose, lipid pattern (cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), blood pressure levels, and body fat distribution were determined in a population of non-diabetic subjects.University Hospital Outpatient Clinic.87 consecutive individuals (35 men and 52 women), represented by 27 normal weight (BMI:25.0), 20 overweight (BMI:25.0-30.0) and 40 obese (BMI:30.0) subjects.Serum insulin levels were quantified by radioimmunoassay, plasma glucose and lipid concentrations by enzymatic assays, and serum ceruloplasmin by nephelometry. Intra-abdominal thickness was measured by ultrasound technique.Ceruloplasmin levels were significantly (P0.001) higher in obese (36.5 +/- 8.60 mg/dl) than in overweight (30.4 +/- 6.17 mg/dl) and normal weight (29.3 +/- 8.06 mg/dl) subjects. Of several variables associated with ceruloplasmin (BMI, waist circumference, WHR, intra-abdominal thickness, triglycerides, cholesterol, LDL-cholesterol, insulin), only triglycerides (in both men and women) and ultrasound intra-abdominal thickness (in women) maintained a significantly independent relationship with this protein in multiple stepwise analysis. Moreover, both triglycerides and total cholesterol maintained an independent correlation with ceruloplasmin when the data from both men and women were pooled together.This study indicates that patients with central obesity have characteristically higher ceruloplasmin serum levels, and that ceruloplasmin concentrations are strongly correlated with serum triglyceride and cholesterol levels (in both sexes) and visceral fat accumulation (in women), independently of the other associated cardiovascular risk factors (insulin and blood pressure levels). Since ceruloplasmin has been shown to increase in response to the atherosclerotic inflammatory process, and to promote coronarosclerosis, the determination of serum ceruloplasmin in subjects with central obesity might be a useful tool to identify patients with the highest risk for myocardial infarction.

OBJECTIVE To determine whether the severity of retinopathy is higher in a group of NIDDM patients with sBP ≥ 140 mmHg compared with NIDDM patients with sBP < 140 mmHg. RESEARCH DESIGN AND METHODS Ophthalmoscopy and FAG were conducted among a group of NIDDM patients with either a sBP above (n = 54) or below (n = 55) 140 mmHg. The groups were matched according to diabetes duration, metabolic control (HbA1c), and AER. RESULTS Patients with sBP > 140 mmHg had a higher prevalence of retinopathy, as established according to a rating scale (4.9 ± 3.8 vs. 3.2 ± 3.3, P < 0.02); furthermore, their BMI values were higher (28.1 ± 4.5 vs. 24.9 ± 4.1 kg/m2, P < 0.001). The group of normotensive subjects showed the highest rate of low grading (0–2) values. However, the highest prevalence rates of 8–10 grading values (proliferative retinopathy) were found in the hypertensive group. CONCLUSIONS These data suggest that sBP values ≥ 140 mmHg favor the onset of retinopathy in NIDDM patients during their 1st 10 yr of disease.

Dehydroepiandrosterone (DHEA) has an anti-obesity effect in rodents and reduces body fat in normal men. Therefore, the plasma levels of DHEA were evaluated in nine premenopausal healthy women and in 13 menstrually active nondiabetic obese women, including patients (n = 6) with body mass index (BMI) over 40. In the obese group, a significant inverse correlation between DHEA levels and BMI was found. These results suggest that patients with severe obesity are unable to increase the DHEA adrenal production rate in order to parallel the increase in the hormone metabolic clearance rate (due to enlargement of body fat mass per se). The deficiency of this mechanism might itself contribute to the progressive fat accumulation in severe obesity.

Thermocutaneous, vascular, metabolic and hormonal changes were investigated during 11 hot flashes from 6 postmenopausal women. The first detectable change was an increase in finger blood flow with a concomitant enhancement of skin conductance. The increase in skin conductance was followed rapidly by a sharp rise in finger temperature. The main endocrine-metabolic changes associated with the above phenomena were a sharp increase in plasma free fatty acids (approximately 65%), norepinephrine (approximately 100%) and LH (approximately 20%) levels. Plasma glucose and cortisol tended to be increased but did not reach statistical significance; on the other hand, plasma insulin, glucagon, growth hormone, epinephrine and dopamine remained unchanged.

Enhanced activity of haemodynamic hormones have been reported to be involved in the development of renal lesions of diabetic kidney1,2. Apart from other pressor factors even plasma arginine-vasopressin (AVP) have been found to be increased in uncontrolled diabetic patients very probably reflecting both a hypovolemic status and an increase in “effective” extracellular fluid osmolality; however, high circulating AVP levels have also been observed in certain well controlled diabetic patients thus suggesting that an alteration of mechanisms regulating AVP secretion exists in diabetes mellitus3,4.

381 glucose intake normal curves were studied according to the Diabetes Data Group new classification in healthy persons between 10 and 80 years in order to assess the influence of the age upon the normal glucose tolerance. Such an influence, which was evident in all the subjects, turned out to be more important in women with respect to me. In fact, males showed an increase, per decade, of about 1 mg/dl in fasting glycemic levels, of about 6 mg/dl at 60', of 4 mg/dl at 120', while in females there was an increase of about 2 mg/dl in fasting glicemic values, of about 6 mg/dl at 60' and of about 5 mg/dl at 120'. No meaningful correlation between age and insulinemic values was found at all considered points, either in males or in females. The reasons of the decreased glucose tolerance with aging and of its different behavior in the two sexes are discussed.

The arginine-vasopressin (AVP) response to supine-standing postural change was evaluated in eight healthy subjects and in fourteen diabetic patients. Plasma AVP levels were found to increase in the controls and in nine subjects from the diabetic group. In the controls the increase was 139% 5 min. after standing and 275% 120 min. after standing. In four of the diabetics affected by autonomic neuropathy AVP failed to increase in response to standing, thus suggesting lesions of the neurogenic pathways connecting baroreceptors to neurohypophysis. Consequently, a failure of the afferent limb in the baroregulatory system must be taken into account among other localizations of autonomic neuropathy. On this basis, AVP measurement both in supine and erect positions could represent an additional test for assessing the integrity of the autonomic nervous system.

The effect of PEBG on respiration and oxidative phosphorilation (succinate as substrate) has been studied in liver mitochondria of rat treated with glucagon. The results obtained indicate that, while glucagon, as reported by others, induce a significant increase of respiration rate in state 3 (+ ADP), PEBG, at pharmachological dose, antagonizes this effect. The conclusion is that PEBG exertes its hypoglycemic activity by inhibiting the gluconeogenic reactions promoted by glucagon. This is strongly evident in diabetic or starwed conditions.

20 hirsute women ageing between 13-38 and 10 age matched controls were investigated. Steroid pattern (F, 170HP, T, DHEAS, A, DHT) were evaluated after repetitive ACTH administration (0.25 mg every 45' for 135'). Testosterone was assayed either directly in ether serum extract (T) or after a previous silica-gel thin layer chromatography (Tc). Basal serum values of all steroids under investigation were significantly higher in hirsute women than in controls. T values resulted higher than Tc thus stressing the high degree of cross-reactivity among DHT, DHEAS, A and T in unchromatographed serum steroid RIA. On the other hand ACTH repeated administration elicited an earlier and more significant T value increase in normals than in hirsutes, whereas Tc did not show any significant change in either group. Similarly DHT serum values did not vary after repetitive ACTH administration either in controls or in hirsute women. During ACTH test A serum values enhanced at 45' in both controls and hirsute women without any further increase after ACTH injections, whereas a lower degree of DHEAS enhancement during ACTH test was observed. On the contrary both F and 17-OHP plasma values strongly enhanced at 45' but a further increase of their values after every ACTH stimulus was also observed. Our data seem to confirm the enhanced adrenal steroidogenesis in hirsutism. But the adrenal contribution to enhanced androgen serum pattern of hirsute women appears to be more evident in androstenedione than in the testosterone fraction.

The influence of plasma lipid disorders on red blood cell (RBC) lipid pattern and some related erythrocyte membrane functions, such as glycerol (GLT50) permeability and erythrocyte deformability was studied in diabetes mellitus. Significantly higher red blood cell cholesterol content, GLT50 and erythrocyte filtration time values were found in diabetics. GLT50 values were found closely related to both RBC cholesterol content (r = 0.84, p less than 0.001) and filtration time (r = 0.60, p less than 0.001). Interestingly, six diabetics with retinopathy showed GLT50 values above 60 sec. The RBC Cholesterol/Phospholipids molar ratio was significantly higher in diabetics. The most notable changes of plasma lipid pattern in diabetics were a decrease of both plasma HDL cholesterol, phospholipids and Apolipoprotein A levels with an increase of HDL free cholesterol/phospholipids molar ratio. RBC cholesterol content was found to be inversely related to HDL esterified/free cholesterol molar ratio (r = -0.56, p less than 0.001), while RBC cholesterol/phospholipids molar ratio was significantly related to both HDL free cholesterol/phospholipids (r = 0.51, p. 0.001) and to LDL total cholesterol/phospholipids (r = 0.25, p less than 0.05). Lastly, HDL cholesterol levels were found to inversely relate to glycosylated haemoglobin values (r = -0.54, p less than 0.01).

Catecholamines acutely exert a pronounced insulin-antagonistic effect, which is mediated by beta-adrenergic receptors stimulation. Nevertheless, several patients with pheochromocytoma fail to exhibit an overt diabetic syndrome, in spite of steadily elevated plasma levels of catecholamines. This prompted us to investigate a 16 years old male patient, bearing an extra-adrenal pheochromocytoma, who displayed a slightly impaired glucose tolerance to oral glucose tolerance test, whereas fasting and post-prandial blood glucose, as well as glycaemic response to intravenous glucagon, were in the normal range. Peripheral insulin sensitivity, as evaluated by intravenous insulin tolerance test, was slightly decreased. Supine norepinephrine plasma levels were steadily upon 9 ng/ml; plasma insulin, both fasting and post-prandial, was within the normal range. beta-adrenergic receptors density of peripheral mononuclear cells was strongly reduced when compared to controls (0.97 +/- 0.08 vs 2.82 +/- 0.37 fmol/10(6) cells), without any concomitant change of affinity. Insulin binding to circulating monocytes was reduced as well (2.38 +/- 0.27 vs 5.1 +/- 0.4%/10(7) monocytes); insulin receptor affinity was quite normal (1.7 ng/ml) and total receptor number was 9,200 sites/cell. In desensitization experiments, 1 microM isoproterenol caused only a 20% decrease of beta-adrenergic receptors density in the patient's cells (70% decrease in controls). Six months after surgery, all the above modifications of receptor binding, as well as the mild glucose intolerance, were almost completely reversed. Thus, high levels of norepinephrine were able to induce a decrease of both beta-adrenoceptor and insulin receptor binding, together with a marked reduction of in vitro agonist-induced redistribution of beta-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Pyruvate-dehydrogenase, an enzymatic mitochondrial complex, exists in both inactive and active forms, insulin being the regulating factor of the transformation of a latter into the former. The basal (PDHb) and total (PDHt) activity of this enzyme in adipose tissue mitochondria from obese hyperinsulinemic humans has been found equal to 1014 +/- 459 SD mU respectively. These values are 250% higher than those found in normal subjects (403 +/- 76 SD and 575 +/- 142 SD respectively). Both in normal and obese subjects the PDHb/PDHt percent ratio was equal to about 70. These results show that insulin, undoubtedly hyperactive in obesity, by activating PDH can induce a major synthesis of fat, a high caloric density tissue.

It must be readily understood that the only possibility of fighting obesity is by bringing about a reversal in the energy balance so that inputs are smaller than outputs. At least theoretically, then, obesity's special quality is that it does not present any therapeutic problem. Restriction in food intake is currently the treatment of choice; to be effective, food intake must be cut so that the energy provided is below the obese person's daily consumption, on average below 1200 calories per day, while at the same time holding a comparatively high intake of indispensable elements (proteins, vitamins, certain minerals and oligo-elements). The physician has a choice of various possibilities represented by fasting, a variety of free or controlled diets, protein diets or diets with low carbohydrate content and with a variable fat content; dissociated, zig-zag, one food diets etc. Substantially all these tend to limit the total quantity of glycides and boost the feeling of satiety by increasing the total volume of good while keeping total calories unvaried. It is clear that each of them has specific indications and clear-cut contraindications. The aim is to produce a calory shortfall, not cause denutrition. The diet must therefore be suited to the individual directed during subsequent stages of weight loss in relation to the patient's specific requirements (number of meals, etc.).

The study was designed to determine eventual correlation in diabetes mellitus between reduced erythrocyte deformability and red blood cells (RBC) cholesterol content. Significantly higher RBC cholesterol amount was found in 11 diabetics (IDDM) than in 13 controls of similar age (45 +/- 10 yrs) (1.30 mg ml-1 packed cells -1 +/- 0.15 SD vs 1.19 +/- 0.10 SD, p less than 0.05). Blood filterability values have been found significantly higher (p less than 0.025) in the diabetics (42.2 +/- 11.5 SD ml sec. -1) than in controls (33.5 +/- 6.0). Flow time of RBC filterability, measured in erythrocyte saline buffered suspension (40% Hct) in order to eliminate interferences from plasmatic factors, showed a closely correlation with RBC cholesterol content (r = 0.86 p less than 0.01). A significant inverse correlation between RBC cholesterol content and serum ApoA1-HDL levels was also observed (r = -0.58, p less than 0.05). Moreover ApoA1-HDL serum values were significantly (P less than 0.01) lower in diabetics (111.8 +/- 10.1 mg/dl) than in controls (126 +/- 6.6 mg/dl). Our data underline the possible involvement of augmented erythrocyte cholesterol in impairing the microhemologic competence of RBC in diabetes mellitus. A possible relation with lower ApoA1-HDL and lecithin-cholesterol-acyl-transferase (LCAT) is examined.

Lipoprotein(a) (Lp[a]) is generally considered to be a risk factor for the development of cardiovascular disease, but little is known about the possible influence of obesity on the circulating levels of this lipoprotein. The present study was undertaken to examine this aspect in 136 menstrually active women by comparing the serum concentrations of Lp(a) between 72 obese and 64 age-matched nonobese women. Since an adverse effect of androgens and a protective effect of estrogens have been described for plasma lipoprotein profiles in obese women, the relation between the circulating levels of Lp(a) and those of these other hormones was also investigated in obese patients. In addition, other lipoproteins, anthropometric parameters (body mass index and waist-to-hip ratio), and insulin were evaluated. The levels of Lp(a) were not significantly different (Mann-Whitney U test chi 2, 3.59; p = 0.0582 [NS]) between obese (rank sum, 5,367) and control (rank sum, 3,949) women; in addition, the percentage of patients with high Lp(a) levels (cutoff defined at 30 mg/dL) did not differ between the two groups (obese women, 30%; control, 21.8%; chi 2, 0.90; two-sided p = 0.341 [NS]). Moreover, no correlation was found between Lp(a) and body mass index. Lastly, when the Lp(a) prevalence odds ratio for obesity was examined by adjusting the levels of this lipoprotein for age, triglycerides, total cholesterol, and high density lipoprotein cholesterol, the probability value (0.88) was far from significant. In obese women, no correlation was found between the logarithmically transformed Lp(a) concentrations and all the other variables evaluated in the study. In conclusion, the present study shows that the circulating levels of Lp(a) are not influenced by body weight and cardiovascular risk factors commonly associated with obesity, such as enhanced androgenic activity, hyperinsulinemia, adverse lipoprotein profile, and abdominal fat accumulation.

The effect of D-(—)-β-hydroxybutyrate, at concentrations commonly achieved during ketoacidosis in humans (10 mmol/l), on human fat cell lipolysis in vitro was the aim of this study. The basal lipolysis was not modified and β-hydroxybutyrate did not affect forskolin- or dibutyryl-cAMP-stimulated glycerol release, whereas it markedly inhibited isoproterenol-stimulated lipolysis. In membranes of intact adipocytes exposed to D-(—)-β-hydroxybutyrate for 1 h, we found a decrease in β-adrenoceptor affinity in saturation experiments and a shift to the right of the isoproterenol-mediated radioligand ([125I]-cyanopindolol) displacement curve. These findings suggest that β-hydroxybutyrate inhibits catecholamine-stimulated lipolysis by decreasing β-adrenoceptor affinity. No effect of β-hydroxybutyrate was found on β-adrenoceptor binding of intact mononuclear cells of peripheral blood. In conclusion, the β-adrenoceptor affinity lowering effect of β-hydroxybutyrate is seemingly specific to human fat cells and might represent a feed-back mechanism that prevents an uncontrolled breakdown of triglycerides and indirectly regulates its own production rate.

The influence of lactate on human adipocytes lipolysis and the possible relationship between lactate-induced metabolic effects and beta-adrenoceptor binding sites were investigated. beta-sites were identified in membranes with (125I)-cyanopindolol and in intact cells with (125I)-cyanopindolol and (3H)-CGP 12177. Lactate reduced isoproterenol-induced lipolysis in a dose-response fashion and such inhibition became significant only at 16 mmol/l lactate. Exposure of human fat cells to 16 mmol/l lactate significantly reduced beta-adrenoceptors density on crude membranes. When the binding assay was performed on intact cells using (125I)-cyanopindolol at 37 degrees C, the radioligand identified the same number of receptors, regardless of the presence of lactate in the preincubation medium. When (3H)-CGP 12177 was used, it bound to about 35% less receptors in lactate pre-treated cells than in control. Seemingly, at 37 degrees C, because of its lipophilicity, (125I)-cyanopindolol can cross the plasma membrane and bind to intracellular sites whereas, (3H)-CGP 1277, due to its hydrophilicity, identifies surface receptors only. Thus, the present in vitro study provides evidence that high levels of lactate, similar to the concentrations usually achieved in overt lactic acidosis, are able per se to inhibit human lipolysis and to redistribute beta-adrenoceptors from cell surface to a domain not accessible to hydrophilic ligands.

The oral administration of bromocriptine induces a variety of side-effects in about 50-70% of patients, the most common being nausea and vomiting, probably related to the local gastrointestinal effect of the drug. Nasal administration makes it possible to avoid intestinal and liver metabolism. This study compared the serum concentrations of bromocriptine and prolactin (PRL) in twenty puerperal women who had asked to discontinue breast feeding and were randomized to receive a single oral (2.5 mg) or nasal spray dose (0.8 mg) of bromocriptine. Serum bromocriptine and PRL concentrations were measured at various times before and after drug administration. At 15 min, the circulating concentrations of bromocriptine were about eight times higher after nasal than after oral administration; peak serum concentration (CMax) was reached respectively 45 min and 60 min after administration, and was about three times higher after nasal administration (314 +/- 102 pg/ml vs 112.30 +/- 34.47 pg/ml). The reduction in serum PRL concentrations was also more rapid in the nasally-treated group reaching the normal assay range of < 20 micrograms/l within two as against five hours post-administration. Four orally-treated patients complained of nausea; in the nasally-treated group, six patients reported only a mild endonasal burning that disappeared within a few minutes of administration. Our results suggest that the nasal administration of bromocriptine may lead to a reduction in the required overall dose and fewer gastrointestinal side-effects, and may therefore improve therapy compliance.