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In a previous study, we observed an impairment of the theophylline-induced suppressive system in recent onset IDDM patients, and demonstrated also a correlation with metabolic derangement. The aim of this study was to better investigate the relationship between theophylline sensitivity (ThS) and blood glucose/plasma insulin levels in recent onset IDDM patients subjected to preprogrammed variations by an insulin/glucose clamp with artificial pancreas. Eight patients were studied within 8 weeks from the onset of IDDM. ThS was evaluated as the ability of theophylline to inhibit blastogenic response of peripheral blood lymphocytes (PBL) to Concanavalin A (ConA), after 120 min preincubation of the cells. All patients were connected to an artificial pancreas. Through i.v. continuous insulin infusion (0.02 U/kg/h) and/or i.v. continuous glucose and saline infusion, the following experimental conditions, lasting at least 1h, were obtained: T1: relative euglycemia and normal insulinemia; T2: relative euglycemia and hyperinsulinemia; T3: hyperglycemia and normal insulinemia; T4: hyperglycemia and hyperinsulinemia. ThS was maintained in 6/8 patients at T1 and in 8/8 patients at T4. ThS was lost in 4/8 patients at T2 and T3. These data suggest that the loss of ThS induced by hyperglycemia can be corrected by hyperinsulinemia, and that it is maintained when euglycemia is accompained by hypoinsulinemia. It is lost when these two parameters lose their interrelationship. [ABSTRACT FROM AUTHOR]

The genetic background seems to be involved in the development of type I diabetes and it might also be involved in the development of diabetic complications, but studies carried out so far have yielded conflicting results. The aim of this study was to evaluate the influence of some genetic markers and metabolic factors in the development of late diabetic complications. One hundred and twenty-seven patients (69 males, 58 females) with type I diabetes were evaluated for ABO and Rh blood groups, chlorpropamide alcohol flush (CPAF) and acetylator phenotype (AP) as well as for life-habits (smoking, alcohol use, diet and drug compliance), metabolic indexes (M-value, HbA, cholesterol and triglyceride levels) and late complications of diabetes [coronary heart disease (CHD), arterial hypertension (AH), retinopathy and nephropathy]. Diabetic patients were more frequently fast acetylators and CPAF positive than controls and CPAF was more frequent among females than among males. None of the genetic markers used in this study appeared as a risk factor for the development of diabetic complications. At multiple logistic analysis different risk factors appeared for each microangiopathic complication. For retinopathy: female sex, duration of disease and triglyceride levels; for nephropathy: male sex, cholesterol levels and hypertension. These risk factors have already been recognized in previous studies, while the genetic markers evaluated in our study do not identify a greater or smaller risk for the development of late complications. [ABSTRACT FROM AUTHOR]

Different prevalences of chlorpropamide alcohol flushing (CPAF) have been reported by different authors in either type I or type II diabetics or in normal subjects and this could be due to different methodological approaches or to different criteria of evaluation of CPAF. Previous studies in small series of patients have also suggested the existence of an association between type I diabetes and the fast acetylator phenotype (AP). The first aim of this study was to find reliable criteria for the assessment of CPAF. The second was to evaluate the prevalence of CPAF and of AP in a large series of type I and type II diabetics; and the third was to evaluate possible associations of CPAF and AP. AP and CPAF were evaluated separately in 256 diabetics (110 with type I and 146 with type II diabetes) and in 183 diabetics (74 with type I and 109 with type II diabetes), respectively. In 156 of these subjects, the two markers were evaluated together. The occurrence of CPAF was studied by subjective and objective assessment and by thermographic recording; CPAF was quantified by the differential value of skin temperature increase [Δ T(C-P)] and by the value of differential speed of ascent, expressed in angle-degrees [Δ a(C-P)], after treatment with placebo and with chlorpropamide. The fast AP was more frequent in type I than in type II diabetics, was not related to family history of diabetes, sex of the patients, age at onset and duration of diabetes or metabolic control. The most reliable assessment of CPAF was represented by thermographic recording of speed of ascent of skin temperature. CPAF was more frequent in females than in males, more frequent in diabetics than in healthy controls, similarly frequent in type I and in type II diabetes and showed no relationship with family history of diabetes, age at onset, duration of diabetes or metabolic control. An association between fast AP and CPAF was found in type II, but not in type I diabetics: fast acetylators were more frequently CPAF-positive, while slow acetylators were more frequently CPAF-negative. In addition, a linear relationship was found between rate of acetylation and speed of ascent of facial skin temperature after chlorpropamide and alcohol in type II diabetics, not in type I diabetics. The meaning of this association is not clear and deserves further investigations. [ABSTRACT FROM AUTHOR]

Intranasal administration of glucagon, 1 mg, plus sodium glycocholate 15 mg as a surfactant, raised blood glucose levels and plasma levels of immunoreactive glucagon (IRG) and immunoreactive insulin (IRI). Spray solutions were more effective than drops, and neither the surfactant alone nor glucagon alone had any effect. Blood glucose levels were similarly affected by intravenous glucagon, while intramuscular glucagon was slightly more effective. The highest IRG concentrations were reached after intravenous administration, while intramuscular injection of glucagon was accompanied by the highest IRI release. These data indicate that intranasal administration of glucagon exerts metabolic effects similar to intramuscular and intravenous administrations. Further studies are needed to improve bioavailability and efficacy of intranasally administered glucagon. [ABSTRACT FROM AUTHOR]

The aim of the present paper was to evaluate the prevalence of the chlorpropamide-alcohol-flush (CPAF) in patients with type 2 and with type 1 diabetes. Ninety-seven patients with type 2 diabetes and 33 with type 1 diabetes drank 40 ml vermouth 12 h after placebo and again 12 h after 1 tablet of chlorpropamide (250 mg) or 12 h after the last of repeated administrations of chlorpropamide (250 mg b.i.d. for 2 days). Skin temperature was recorded in all patients by a thermocouple probe connected to the left cheek. In 47 patients serum concentrations of chlorpropamide and of its metabolite CBSU were also determined. The prevalence of CPAF was similar in type 1 and type 2 diabetes, was greater in women than in men, and was significantly greater after repeated administrations than after one single administration of chlorpropamide. The increase of skin temperature during a 30-min period was significantly higher in patients with CPAF than in patients without CPAF. Serum concentrations of chlorpropamide and of its metabolite CBSU were more elevated after 4 than after 1 tablet of chlorpropamide, but were not significantly different in patients with and without CPAF. These data indicate that both genetic factors and the amount of chlorpropamide used affect the appearance of CPAF. To assess the possible role of serotonin and of dopamine in the CPAF, some patients with CPAF were tested again after treatment with metergoline, an antiserotonin agent, or with bromocriptine, a dopamine-agonist. Neither drug influenced the CPAF, indicating that the two neurotransmitters are not involved in the CPAF. [ABSTRACT FROM AUTHOR]

Clofibrate, 3 g/die for 10 consecutive days, significantly reduced arginine-induced IRI release in chemical diabetics and in normal controls, whether of normal body weight or obese. Blood glucose levels were not affected by clofibrate. In agreement with previous findings, it would appear that clofibrate, administered for short periods, does not lead to a decrease in glucose tolerance. However, studies relating to the effect of chronic clofibrate administration in chemical diabetes are needed in order to be sure that prolonged inhibition of IRI secretion does not lead to overt diabetes. [ABSTRACT FROM AUTHOR]

Glucose tolerance is considered to decrease with ageing. In order to assess the role of insulin and growth hormone (GH) in this process, insulin and GH response to arginine infusion were evaluated in 42 subjects with a normal glucose tolerance test, divided according to age into three groups (20-39, 40-59 and 60-80 years). In 6 subjects of each age group, insulin response to oral glucose was also evaluated. Blood glucose levels following the two stimuli were higher in older subjects. Insulin response tended towards higher values in older subjects. GH secretion did not vary in the three age groups. These data indicate that the deterioration of glucose tolerance is not due to diminished insulin secretion or to enhanced GH secretion. The cause of the higher glucose levels in response to arginine in the elderly remains to clarified. [ABSTRACT FROM AUTHOR]