Contraception in diabetic women: an Italian study.

Over 1 year, a survey on contraception and obstetric history was performed on a cohort of 667 Caucasian fertile diabetic women (446, type 1 and 201, type 2) living in Italy. RESULTS: Of these women, 30.4% used hormonal contraceptives, 12.0% intra-uterine device (IUD), 10.7% declared they used no contraception, 47.0% only utilised barrier and/or natural methods. However, irrespective of their previous contraceptive strategy, 7.2% of all the studied population was surgically sterilized during caesarean section. HORMONAL CONTRACEPTION: Of these women, 60.4% was prescribed by a gynaecologist, 11.2% by a diabetologist, 15% by both of them and 13.4% by others. The proportion using oral contraception was similar among types 1 and 2 women (29.4% versus 27.8%, chi(2) = ns). SMOKING HABITS: Of women taking hormonal contraception, 30.0% were smokers. EDUCATIONAL LEVEL: University graduates (37.1%), high school leaves (32.2%), secondary school (28.2%) and primary school leaves (15.5%) used oral contraceptives (OC). OBSTETRIC HISTORY: The mean number of deliveries was 1.14 +/- 1.1, of miscarriages was 1.3 +/- 0.7 and of induced abortions 0.17 +/- 0.5. Planning of at least one pregnancy was reported in 29.4% of patients.

A randomized trial of nicotinamide and vitamin E in children with recent onset type 1 diabetes (IMDIAB IX).

OBJECTIVE: Various adjuvant therapies have been introduced along with intensive insulin therapy in patients with recent onset type 1 diabetes. Nicotinamide (NA), administered at diagnosis of the disease, can have beneficial effects on the clinical remission rate, improve metabolic control and preserve or slightly increase beta-cell function, probably by reducing toxicity due to free oxygen radicals. Vitamin E, a known antioxidant, inhibits lipid peroxidation; this can lead to protection of islet beta cells from the combined effects of interleukin 1, tumor necrosis factor and gamma interferon. The aim of the present study was to investigate whether the addition of vitamin E to NA could improve metabolic control and the residual beta-cell function, as measured by C-peptide secretion, in children and adolescents with recent onset type 1 diabetes; patients were followed-up for 2 years after diagnosis. PATIENTS AND STUDY DESIGN: Recent onset type 1 diabetes patients (n=64, mean age 8.8 years) were recruited by participating centres of the IMDIAB group. Thirty-two patients were randomized to NA (25 mg/kg body weight) plus vitamin E (15 mg/kg body weight); 32 patients acted as controls and received NA only at the same dose as above. Intensive insulin therapy was applied to both treatment groups. RESULTS: There were three drop outs during the 2-year follow-up period. Overall, patients assigned to the NA+vitamin E group or the NA group did not significantly differ in terms of glycated hemoglobin (HbA1c) levels, insulin requirement or baseline C-peptide secretion. Patients diagnosed at an age of less than 9 years showed significantly reduced C-peptide levels compared with those aged over 9 years at diagnosis and at the 2-year follow-up but there were no differences between the NA and NA+vitamin E treated groups. However at 6 months, patients over 9 years of age treated with NA+vitamin E showed significantly higher C-peptide compared with the NA group (P<0.003). In both age groups and in the different treatment groups, C-peptide levels found at diagnosis were preserved 2 years later. CONCLUSIONS: The use of NA alone, or in combination with vitamin E, along with intensive insulin therapy is able to preserve baseline C-peptide secretion for up to 2 years after diagnosis. This finding is of particular interest for pre-pubertal children with type 1 diabetes and has never been reported before.

Vitamin E and nicotinamide have similar effects in maintaining residual beta cell function in recent onset insulin-dependent diabetes (the IMDIAB IV study)

OBJECTIVE: Protection of residual beta cell function at the time of diagnosis of insulin-dependent diabetes mellitus (IDDM) by intensive insulin therapy and the addition of nicotinamide (NA) has been established. The objective of this study was to evaluate the effect of a free oxygen radical scavenger such as vitamin E (Vit E) on residual beta cell function and parameters of metabolic control in patients with recent onset IDDM undergoing intensive insulin therapy. DESIGN: The effect of Vit E was compared with that of NA (control group) in a randomized multicentre trial. METHODS: Eighty-four IDDM patients between 5 and 35 years of age (mean age 15.8 +/- 8.4 (s.d.) years) entered a one year prospective study. One group of patients (n = 42) was treated with Vit E (15 mg/kg body weight/day) for one year; the other group (n = 42) received NA for one year (25 mg/kg body weight/day). All patients were under intensive insulin therapy with three to four injections a day. Basal and stimulated (1 mg i.v. glucagon) C-peptide secretion, glycosylated haemoglobin and insulin dose were evaluated at diagnosis and at three-monthly intervals up to one year. RESULTS: Preservation and slight increase of C-peptide levels at one year compared with diagnosis were obtained in the two treated patient groups. No statistically significant differences were observed in basal or stimulated C-peptide levels between the two groups of patients for up to one year after diagnosis. Glycosylated haemoglobin and insulin dose were also similar between the two groups; however patients receiving Vit E under the age of 15 years required significantly more insulin than NA-treated patients one year after diagnosis (P < 0.04). CONCLUSIONS: Our data indicate that Vit E and NA possess similar effects in protecting residual beta cell function in patients with recent onset IDDM. Since their putative mechanism of protection on beta cell cytotoxicity is different, combination of these two vitamins may be envisaged for future trials of intervention at IDDM onset.

Anti-neutrophil cell antibodies in newly diagnosed patients with type-1-diabetes.

Both anti neutrophil cell antibodies and anti endothelial cell antibodies were found in 7 out of 30 newly-diagnosed type-1 diabetic patients. This confirms the abnormal activation of the immunological system in the early stage of type-1 diabetes mellitus.

Carotenoids, retinoids and alpha-tocopherol in human serum: Identification and determination by reversed-phase HPLC.

A rapid, simple and specific high performance liquid chromatographic procedure for assaying alpha- and beta-carotene is described. The method also enables the simultaneous determination of retinol and dl-alpha-tocopherol in human serum. The same chromatographic procedure can be used to assay the major carotenoids in human serum, provided analyses are replicated and the effluent is monitored at 450 nm. The conditions described also enable determination of licopene, cryptoxanthine and lutein with zeaxanthine. An aliquot of 0.5 ml serum is deproteinized with ethanol (0.5 ml) and extracted with petroleum ether (0.75 ml). The petroleum ether extract is evaporated until dry and then redissolved immediately with 0.5 ml of an eluent mixture consisting of methanol-hexane (85:15, v/v). Aliquots of 50 microl are then injected onto a 250 x 4.6 mm column packed with Spherisorb ODS-2. Owing to its good reproducibility, the procedure can be used for assays with external standards. Clinical applications are described for cases of hypercarotinemia associated with endocrine dysfunctions such as hypothyroidism and diabetes.

Factors associated with a rapid normalization of HbA1c in newly diagnosed type 2 diabetes patients seen in a specialist setting.

The time to achieve good metabolic control after diagnosis is essential for type 2 diabetes patients because it can influence long-term prognosis. This study aimed to elucidate the predictive role of several clinical and organization factors in normalizing metabolism within 6 months. A multi-centered, retrospective, observational study on 960 patients, with diabetes duration of 12 months or less, consecutively seen in 123 Italian clinics, was undertaken. Information about clinic's organization, along with data abstracted from medical records at enrollment (first visit) and after 6 months (follow-up visit), was collected. At 6 months, HbA1c dropped by -3.1 ± 2.2 points in those who achieved HbA1c <7 % (responders), whereas in non-responders (HbA1c ≥7 %), the mean reduction was -1.8 ± 1.9. The intervention markedly reduced lipids, blood pressure, BMI, and waist circumference, especially in responders. The presence of a diabetes team correlated with a likelihood of HbA1c normalization (OR 1.94, 1.17-3.22). By contrast, indicators of advanced disease such as previous retinopathy (0.53, 0.29-0.98), use of secretagogues (0.40, 0.25-0.64), high levels of HbA1c at first visit and related insulin use emerged as adverse factors. Early detection of diabetes, along with human resources and organization, was found to play a crucial role in rapidly attaining good metabolic control.

Metabolic factors affecting residual beta cell function assessed by C-peptide secretion in patients with newly diagnosed type 1 diabetes.

BACKGROUND: In recent onset of type 1 diabetes, the residual beta cell function, assessed by baseline and/or stimulated C-peptide secretion, can be a useful parameter to establish the extension of beta cell destruction. How metabolic parameters at diagnosis influence residual C-peptide secretion is not well established. PATIENTS AND METHODS: We analyzed 553 consecutive patients with recent onset (<4 weeks) of type 1 diabetes (250 females and 303 males, mean age 15+/-8 years). Baseline and stimulated C-peptide by i.v. glucagon were evaluated using a highly sensitive radio-immunoassay. Metabolic parameters including blood glucose, HbA1c, insulin dose, and BMI were also evaluated. RESULTS: Baseline and stimulated C-peptide were 0.26+/-0.22 and 0.47+/-0.38 nmol/l and correlated positively with age (p<0.001). There was no significant correlation between C-peptide and blood glucose at diagnosis. BMI was positively correlated with both baseline and stimulated C-peptide secretion (p<0.001). By contrast, HbA1c levels inversely correlated with both baseline and stimulated C-peptide secretion (p<0.001). CONCLUSION: In type 1 diabetes at diagnosis, baseline and stimulated C-peptide are higher in pubertal and young adult patients compared with pre-pubertal patients suggesting that such parameter can be used as an end point marker for studies aimed at protecting and/or restoring beta cells in patients with substantial beta cell function. High levels of HbA1c and lower BMI are dependent variables of C-peptide values.

The effects of calcitriol and nicotinamide on residual pancreatic beta-cell function in patients with recent-onset Type 1 diabetes (IMDIAB XI).

BACKGROUND: A number of recent studies underline the importance of vitamin D in the pathogenesis of Type 1 diabetes (T1D). AIMS: The aim of this study was to investigate whether supplementation with the active form of vitamin D (calcitriol) in subjects with recent-onset T1D protects residual pancreatic beta-cell function and improves glycaemic control (HbA(1c) and insulin requirement). METHODS: In this open-label randomized trial, 70 subjects with recent-onset T1D, mean age 13.6 years +/- 7.6 sd were randomized to calcitriol (0.25 microg on alternate days) or nicotinamide (25 mg/kg daily) and followed up for 1 year. Intensive insulin therapy was implemented with three daily injections of regular insulin + NPH insulin at bedtime. RESULTS: No significant differences were observed between calcitriol and nicotinamide groups in respect of baseline/stimulated C-peptide or HbA1c 1 year after diagnosis, but the insulin dose at 3 and 6 months was significantly reduced in the calcitriol group. CONCLUSIONS: At the dosage used, calcitriol has a modest effect on residual pancreatic beta-cell function and only temporarily reduces the insulin dose.

[Serum content of vitamin A binding proteins (prealbumin and retinol binding proteins) in normal and pathological conditions]. / Contenuto sterico delle proteine vettrici la vitamina A (PA e RBP) in condizioni normali e patologiche.

Blood PA and RBP content were estimated in 100 normal subjects (50 men and 50 women). Mean values of 28.2 and 3.75 mg/dl were ascertained for PA and RBP, respectively. The molar ratio RBP/PA was calculated as 0.31 +/- 0.05. Serum concentrations of PA and RBP are seen to be sex-dependent (20% higher in males). Hyperthyroid subjects exhibit a decrease in the two vitamin A-binding proteins whereas no modification could be revealed for hypothyroid states. In patients on maintenance hemodialysis mean serum PA and RBP concentrations were remarkably higher than normal, whereas liver cirrhotic subjects showed a highly significant depression of mean serum RBP and PA values.

Metabolic abnormalities in first-degree relatives of type 2 diabetics.

Diabetic relatives and obese subjects are at increased risk for development of diabetes mellitus, and therefore are classed as potential abnormality of glucose tolerance (POT-AGT). Disturbances of lipid and purine metabolisms have been reported in diabetic and obese non-diabetic subjects. In obese subjects above alterations are probably due to hyperinsulinemia. This study aimed at verifying whether similar metabolic abnormalities could be found in relatives of non-insulin dependent diabetic patients and whether they could be related to possible glucose intolerance. We have studied 10706 outpatients and 95 hospitalized subjects, aged between 20 and 50 years. We have selected 4 groups according to diabetic relationship and body mass index: A (normal weight subjects), B (obese subjects), C (normal weight NIDDM-relatives), D (overweight NIDDM-relatives). The NIDDM-relatives showed higher prevalence of hyperglycemia, as expected; furthermore the relatives with normal glucose tolerance had higher glucose area during OGTT. Serum levels of uric acid and insulin response to oral glucose were increased in all obese subjects, but abnormalities of lipid metabolism and fasting hyperinsulinemia were found only in obese NIDDM-relatives. These results suggest that family history of diabetes mellitus can be a risk for metabolic disturbance even in absence of glucose intolerance. Furthermore some metabolic disorders observed in obese subjects could be due to an associated and not sufficiently investigated family history of diabetes.

[Changes induced by parturition in serum cholesterol and triglycerides in obese and normal weight women]. / Modificazioni indotte dal parto sul colesterolo e sui trigliceridi sierici in donne obese e normopeso.

It is shown that total cholesterol levels in the blood before and immediately after delivery in obese and normal weighing women remain within normal values. Conversely blood triglycerides levels, higher than normal prior to delivery, are shown to drop back to normal values within three days (p 0.001). This is not thought to be attributable to labor stress.

[Effect of parturition on serum glycerol and non-esterified fatty acids in obese and normal weight women]. / Influenza del parto sul contenuto silrico di glicerolo e di acidi grassi non esterificati in donne obese e normopeso.

Serum glycerol and NEFA content variations are examined before and after labor in obese and normal weighing women (35 subjects). Blood glycerol and NEFA are shown to increase before delivery. Glycerol values are shown to drop to normal immediately after delivery, while NEFA values diminish to a lesser extent. Statistical analysis shown that blood glycerol increase could be pregnancy-dependent in both normal weighing and obese women, but that NEFA increase could be pregnancy-dependent in normal weighing women only. Obesity increases blood glycerol and NEFA concentration considerably, thus masking the effects of pregnancy.

[Oral load test with beta-carotene in normal and dysthyroid subjects]. / La prova da carico per os con beta-carotene nei soggetti normali e distiroidei.

An oral load of beta-carotene (500 mg) was administered to four normal, four hypo and four hyperthyroid subjects. Plasma beta-carotene content was determined at the 2nd, 4th, 6th, 8th, 10th, 12th and 24th hour after administration and at every 24th hour thereafter for 5 consecutive days. Plasma assays were performed by HPLC. No significant differences were revealed by Student's T test for one group to the other. The authors sustain that, as there is no impairment in intestinal uptake of beta-carotene in disthyroid subjects, the elsewhere described increase in carotinemia in hypothyroids is due to other mechanisms.

[Effect of renal and liver failure on blood levels of vitamin A, its precursor (beta-carotene) and its carrier proteins (prealbumin and retinol binding protein)]. / Influenza dell'insufficienza renale ed epatica sul tasso ematico della vitamina A, dei suoi precursori (beta-carotene) e dei suoi vettori proteici (PA e RBP).

Plasma beta-carotene and retinol assay was performed by high pressure liquid chromatography (HPLC) in subjects with chronic renal failure or liver cirrhosis. In the same subjects blood prealbumin (PA) and retinol binding protein (RBP) were determined by immunological technique. A considerable increase of retinol and in a lesser extent of beta-carotene was noted in the blood of patients with renal insufficiency. In cirrhotic patients it was shown a marked decrease both of beta-carotene and retinol plasma concentrations. PA and RBP there were greatly increased in renal failure and decreased in liver cirrhosis. This results suggest that kidney and liver chronic failure interfere with vitamin A metabolism throughout their action on metabolic processes of synthesis and elimination of PA and RBP.

[Behavior of vitamin A, beta-carotene, retinol binding protein and prealbumin in the plasma of hypo- and hyperthyroid subjects]. / Comportamento della vitamina a, dela beta-carotene, della proteina legante il retinolo e della prealbumina nel plasma di soggetti ipo ed ipertiroidei.

Plasma concentrations of beta-carotene and retinol, determined by HPLC, and of transport proteins, ascertained by immunodiffusion technique, in hypo and hyperthyroid subjects are reported. In hypothyroid subject a considerable increase in carotene was noted. This was not the case for retinol. In hyperthyroids both beta-carotene and retinol levels were found to be normal. Transport protein (PA and RBP) levels were found to be lower only in cases of hyperthyroidism but unchanged for hypothyroids. According to the Authors the results show that the alteration in plasma carotene levels to be found in hypothyroid subjects is not the direct consequence of a lack of thyroid hormone in the metabolism of vitamin A but the indirect effect of thyroid disease.

Constipation and obesity: a statistical analysis.

Constipation frequency was investigated among 1897 subjects (874 males and 1023 females), ranging in age from 6 to 70 years, chosen at random between city inhabitants and farmers. Bowel habit was studied in 966 obese patients (390 males and 576 females). The authors followed for the diagnosis of constipation either the commonest and restrictive criterion of the weekly bowel actions or the clinical one which implies also others parameters, like hard or small stools, difficulties of expulsion or feeling of incomplete evacuation after defecation. The statistical analysis showed that constipation frequency is 8.3% in obese patients and 1.5% in normal-weighting, according to weekly bowel actions criterion: the difference is statistically significative (p less than 0.001).