Continuous subcutaneous insulin infusion is more effective than multiple daily insulin injections in preventing albumin excretion rate increase in Type 1 diabetic patients.

AIMS: To compare the effect of continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) on albumin excretion rate (AER) in Type 1 diabetic patients. METHODS: In a 3-year multicentre retrospective observational study, 110 Type 1 diabetic patients treated with CSII were compared with 110 patients treated with MDI matched at baseline for age, sex, diabetes duration and HbA(1c). At entry, 90 patients in each group had normal AER and 20 persistent microalbuminuria. AER, estimated glomerular filtration rate (eGFR), HbA(1c,) lipids and blood pressure were assessed. RESULTS: HbA(1c) was lower in the CSII than in the MDI group (8.1 +/- 0.9 vs. 8.4 +/- 1.3%; P < 0.005 after 3 years). Blood pressure and eGFR were similar during the study. AER [median (95% confidence interval)], similar at baseline [6.0 microg/min (9, 21) in the CSII group vs. 4.4 (8, 16) in the MDI group, NS] was significantly lower in the patients treated with CSII both at year 2 and at year 3 of follow-up [4.7 microg/min (6, 12) vs. 6.4 (13, 29), P < 0.002]. This difference was observed even when normo- and microalbuminuric patients were analysed separately. Nine patients progressed to microalbuminuria in the MDI group and only one in the CSII group. Nine patients regressed to normoalbuminuria in the CSII group, whereas only two regressed to normoalbuminuria in the MDI group. CONCLUSIONS: Despite a small benefit in terms of improved glycaemic control, CSII therapy may be useful in decreasing the progressive increase in AER in Type 1 diabetic patients.

Effect of continuous subcutaneous insulin infusion vs multiple daily insulin injection with glargine as basal insulin: an open parallel long-term study.

Aim of this 1-yr open parallel study was to evaluate the efficacy of two regimens of intensive insulin treatment: continuous s.c. insulin infusion (CSII) and multiple daily insulin injection (MDI) treatment with lispro plus glargine in 48 Type 1 diabetic patients that had been treated with MDI (regular or lispro insulin before each meal plus NPH) for at least 1 yr. Twenty-four patients treated with CSII, receiving lispro at multiple basal infusion rates plus boluses at meal (CSII group), were compared to 24 patients, matched for age, duration of diabetes and metabolic control, treated with MDI with lispro at each meal combined with glargine (glargine group). In the CSII group, compared to traditional MDI treatment, there was a decrease in HbA1c (9.0 +/- 1.3% during traditional MDI vs 8.0 +/- 1.0% during CSII, p<0.001), severe hypoglycaemic episodes (0.42 vs 0.17 per patient/yr, p<0.05), insulin requirement (48 +/- 11.7 vs 35.9 +/- 8.5 U/day, p<0.001). In the glargine group, compared to MDI traditional treatment, there was a decrease in HbA1c (8.6 +/- 1.1 vs 7.9 +/- 1.2%, p<0.001) and severe hypoglycaemic episodes (0.46 vs 0.21 per patient/yr, p<0.05). No significant difference between the CSII group and the glargine group was present in the degree of improvement in HbA1c and severe hypoglycaemic episodes. However, in the CSII group there was a significantly greater reduction in mean amplitude of glycaemic excursions (MAGE) and insulin requirement than in the glargine group. In conclusion, despite a similar improvement in metabolic control, CSII improves blood glucose variability when compared to MDI with glargine as basal insulin.

Glycaemic control and microvascular complications in a large cohort of Italian Type 1 diabetic out-patients.

The purpose of this cross-sectional study was to evaluate the degree of metabolic control, the prevalence of microvascular complications (nephropathy, retinopathy, and peripheral neuropathy) and their association with risk factors for cardiovascular diseases in all adult Type 1 diabetic out-patients attending 2 Diabetes Clinics of Northern Italy over 12 months. A total of 458 patients (mean age 37 +/- 12 yr, duration of diabetes 15.3 +/- 10.6 yr, BMI 23.2 +/- 3.1 kg/m2) were studied. Clinical characteristics and microvascular complications were evaluated. The proportion of patients with a good glycaemic control (HbA1c < 7%) was 14.7%. Nephropathy was observed in 24.4%, retinopathy in 41%, peripheral neuropathy in 23.7%. The prevalence of hypertension was 30.3%. Microvascular complications were associated with age, duration of diabetes, systolic blood pressure, creatinine, triglycerides and cholesterol plasma levels. Mean HbA1c was 8.5 +/- 1.6. Patients with HbA1c levels < 7% presented a lower prevalence of complications and lower levels of cholesterol, triglycerides, systolic blood pressure than patients with HbA1c > 9%. Our study indicates that an acceptable metabolic control is achieved in a too low proportion of Type 1 diabetic patients, even under multiple insulin injections. The association of poor metabolic control and microalbuminuria identifies a group of patients at higher risk of diabetic complications.

Safety, efficacy, acceptability of a pre-filled insulin pen in diabetic patients over 60 years old.

The aim of the study was to evaluate safety, efficacy and acceptability of a pre-filled insulin pen device (NovoLet) in diabetic patients over 60 years old already treated with insulin administered with conventional syringes. After a run-in period of 2 weeks, 60 patients participated in a randomized cross-over study with two 6-week treatment periods using the insulin pen or conventional syringes. Insulin regimens did not change during the study. Hypoglycaemic episodes did not differ significantly between both kinds of treatment and no severe hypoglycaemia was registered. HbAlc (%) was (mean +/- S.D.) 7.7 +/- 1.2 and 7.9 +/- 1.1 during pen and syringe treatment, respectively. Blood glucose profiles were similar during both treatment modalities except for pre-lunch blood glucose values (mmol/l) lower during pen treatment (8.7 +/- 2.9 vs. 9.2 +/- 2.7, P < 0.01). The insulin dose (U/day) was 31.9 +/- 8.9 (pen) and 32.3 +/- 9 (syringe). 54 patients found the functioning of the insulin pen easy to understand and preferred it for future treatment because the conditions of insulin administration are faster and easier than with conventional syringes. We concluded that the pre-filled insulin pen is safe, efficacious and is highly accepted in over 60 years old diabetic patients.

[Use of omega-3 in diabetic patients]. / Impiego degli omega-3 nel paziente diabetico.

The use of omega-3 fatty acids for diabetic patients is based on well confirmed observations concerning the presence of cardiovascular risk factors in these patients. Changes of lipid metabolism, reduced erythrocyte deformability, increased platelet aggregation, and high blood pressure often found in subjects with diabetes mellitus are all favourably influenced by the administration of eicosapentanoic and docosahexanoic acid. In non insulin dependent subjects, these fatty acids may bring about a rapid reversible deterioration of blood glucose balance while in insulin dependent patients there is no relevant interference. Therefore, omega-3 administration would appear advisable in insulin dependent diabetics with increased cardiovascular risk factors.

The effect of various blood glucose levels on post-glucagon C-peptide secretion in type 2 (non insulin-dependent) diabetes.

We investigated how different plasma glucose concentrations could significantly modify the C-peptide response to glucagon. Twenty poorly-controlled (HbA1c 10.2 +/- 1.5%) non insulin-dependent (NIDDM) subjects (body mass index 27 +/- 1.8), 2 treated with diet alone and 18 with oral hypoglycemic agents were studied. The first day glucagon (1 mg iv) was injected, patients being fasting and untreated. Mean plasma glucose levels were 11.4 +/- 1.2 mM. On a second non consecutive day, after an overnight fast, the same patients were connected to a closed-loop insulin infusion system (Betalike, Genoa), their blood glucose concentrations were stabilized within a normoglycemic range (5-5.5 mM) for 2 h and insulin infusion was stopped. The glucagon test was repeated 30 min later. Blood samples were taken 0, 6, 10, 20 min after glucagon injection. In the second test, basal, and 6, 10 and 20 min post-glucagon glucose levels were significantly lower (p less than 0.001); similarly C-peptide concentrations were significantly reduced both in basal conditions (0.55 +/- 0.04 vs 0.37 +/- 0.04 nM; p less than 0.001) and 6 (0.92 +/- 0.06 vs 0.6 +/- 0.06; p less than 0.001), 10 (0.79 +/- 0.06 vs 0.56 +/- 0.06; p less than 0.001) and 20 min (0.64 +/- 0.05 vs 0.44 +/- 0.04; p less than 0.001) after stimulation. The C-peptide secretion area showed the same trend (49.5 +/- 4.8 vs 32.1 +/- 5.8; p less than 0.001). In conclusion, our data confirms that blood glucose levels modulate the pancreatic insulin secretion; glycemic normalization significantly reduced both basal and post-glucagon C-peptide release.

[The complex relation of pregnancy and diabetes mellitus]. / I complessi rapporti tra gravidanza e diabete.

A glucose metabolism impairment occurs in about 2-3% of all pregnancies. Two different groups of women are involved: diabetic women who become pregnant and healthy women developing gestational diabetes or glucose intolerance during pregnancy. Due to therapeutic improvements and new techniques of fetal monitoring, maternal and perinatal mortality now approaches that of normal pregnancies. On the contrary, congenital anomalies are still four times more frequent. A good control of the mother metabolism is necessary to reduce complications in fetal development, especially during the first six weeks, a crucial period for the early cell division. Fetal monitoring is very important not only to control the normality of the growth and the well-being of the fetus, but also for early identification of possible anomalies.

[Bodily experiences and sexuality in obese women. A clinical study]. / Il vissuto corporeo e la sessualità nella donna obesa. Uno studio clinico.

The aim of the study was to investigate the centralized impulsive dynamics of 21 obese women in comparison with 21 normal ones, with particular reference to the unconscious bodily experiences and sexuality. Two tests comparing areas of unconscious experience and body organs and classes of feelings, and emotional self-assessment questionnaire and a colour choice test, were given. The statistical analysis of the results showed significant differences between the two groups studied, the obese women being immature, dependent, hypersensitive and introverted with great oral requirements and low autonomous control and with some confusion between food and affection. Their sexuality is pervaded with great aggressiveness and has little connection with its maternal and relational function. Finally, some psychotherapeutic strategies are mentioned.

Effects of a somatostatin derivative (SMS 201-995) on postprandial hyperglycemia in insulin-dependent diabetics studied by means of a closed-loop device.

We studied the effects of a premeal sc injection of an analog of somatostatin (SMS 201-995, Sandoz) on the postprandial glycemic excursions, insulin requirement and hormone profiles (GH, glucagon and C-peptide) in 8 IDDM patients (diabetes duration 14.0 +/- 6.5 yr, daily insulin requirement 36 +/- 6.4 U) maintained normoglycemic by connecting them to a closed-loop insulin infusion system (Betalike, Genoa). The morning of the test the patients were connected to the Betalike and their glucose levels stabilized for at least 4 h. At 13:00 h the study was begun with a sc injection of 50 micrograms of SMS 201-995 or placebo (randomly) and a standardized mixed meal (800 Kcal) was given. Blood samples were obtained 0, 15, 30, 60, 120 and 180 min after the injection. Each patient was tested both with SMS 201-995 and placebo. Postmeal glycemic peaks were decreased after SMS 201-995 (119.6 +/- 5.4 mg/dl vs 149.1 +/- 4.2; p less than 0.05) as well as insulin requirements (3.2 +/- 0.8 U vs 13.3 +/- 1.9; p less than 0.01) for the 180 min postprandial period. Similarly, glucagon level was reduced 30 min postprandially (24 +/- 6 pg/ml vs 59 +/- 24; p less than 0.05) and so GH level only 180 min after lunch (p less than 0.05). The premeal injection of SMS decreases postprandial glycemic excursions and the corresponding insulin requirement. The action of SMS 201-995 may be mainly mediated by the suppression of postprandial glucagon peak.

Inhibition of ticlopidine of platelet adhesion to human venous subendothelium in patients with diabetes.

To elucidate the bleeding tendency that follows the administration of ticlopidine, we investigated the skin bleeding time and some ex vivo functions of platelets from nine patients with insulin-dependent diabetes before and 2 weeks after daily doses of 500 mg ticlopidine. Ticlopidine significantly prolonged bleeding time and reduced platelet reactivity to fixed, relatively high concentrations of aggregating agents, without interfering with thromboxane B2 formation. We used a rotating probe device at a relatively low shear rate (570 sec-1) to measure platelet adhesion to human subendothelium. This system was able to detect an impairment of platelet adhesion dependent on glycoprotein (GP) Ib defect (Bernard Soulier syndrome) or on low platelet von Willebrand factor content, but was insensitive to platelet GPIIb-IIIa defect (Glanzmann's thrombasthenia). In our patients, platelet adhesion was consistently reduced after the administration of ticlopidine. We conclude that ticlopidine is an inhibitor of platelet function that modulates the interaction between platelets. The drug also appears to interfere with mechanisms that modulate platelet-subendothelium interaction at relatively low shear rates. This double action could be relevant in the prevention of vasculopathy in patients with diabetes.

Empty sella syndrome and growth deficiency in childhood.

We describe four cases of empty sella syndrome in childhood associated with growth and neuroendocrine disorders. We note that empty sella syndrome probably presents with endocrine disorders more often in childhood than in adults and that its frequency seems to be underestimated.

[Effects of a vagolytic substance on the circadian rhythm of the ACTH-secreting system in man]. / Variations circadiennes des effets d'une substance vagolytique sur le système ACTH-secrétant chez l'homme.

The circadian rhythm of plasma cortisol and urinary 17-hydroxy-corticosteroids has been studied in 6 normal volunteers both in basal conditions and after the administration of a single dose of 30 mg of a banthine derivative (the beta methyl-beta-isopropylaminoethyl ester bromide of xantene-9-carbonic acid, "Pervagal") given orally once a day at different hours (midnight, 4 AM, 8 AM, noon, 4 PM, 8 PM). The vagolytic drug inhibits the cortisol secretion only when administered at 4 PM, 8 PM or midnight, whereas it is ineffective when given at different hours. If don't exist circadian variations of the bio-availability of the drug employed, our results suggest that also in human beings as well as in experimental animals, the cholinergic mechanisms are effective, over all if not exclusively, in starting the circadian activation of the hypothalamo-pituitary-adrenal system.