Glucose-clamp by artificial pancreas in the study and management of a patient with insulinoma.

Four euglycemic glucose-clamp studies by artificial pancreas (Biostator, Miles) have been performed during prolonged fast before and after pharmacological treatment in a patient with insulinoma. In the basal state a high glucose infusion rate (8.9 g/h) was unable to achieve the preselected blood glucose plateau of 80 mg/100 ml. The plasma insulin levels during this first glucose-clamp were comprised between 18 and 50 microunits/ml. On the first day of diazoxide treatment (300 mg/die),. the glucose infusion rate decreased to 6.4 g/h, without variation in plasma insulin level, thus suggesting a diazoxide effect independent of the inhibition of insulin secretion. After 7 days of diazoxide treatment, a further reduction of glucose infusion (5.8 g/h), together with a lowering of plasma insulin levels (7-18 microunits/ml) was observed. Both in the basal state and during diazoxide treatment a circadian pattern of glucose requirement was noted, with lower glucose need and plasma insulin levels during the night. Surgery was undertaken with glucose-clamp by artificial pancreas; blood glucose level being higher than the preselected value of 80 mg/100 ml, simple monitoring of glycemia was performed. The excision of a single adenoma was followed by a substantial rise in blood glucose 20 min later. An additional glucose-clamp, performed 3 months after surgery showed a dramatic fall of the glucose infusion rate (2.9 g/h) needed to achieve the preselected blood glucose plateau, confirming the completeness of the intervention. This experience shows that glucose-clamp by artificial pancreas may be of great value in the study as well as in the pharmacological and surgical treatment of patients with insulinoma.

Comparison between multi-injection and continuous subcutaneous insulin therapy in insulin-dependent diabetic inpatients.

Circadian blood glucose profiles have been evaluated in 8 insulin-dependent diabetic inpatients on their usual home insulin therapy, on a 3-injection regimen (ultralente in the morning plus 3 injections of regular insulin at meals), on continuous subcutaneous insulin infusion by portable micropumps (Mill Hill 1001) and, again, on a 3-injection regimen at the same insulin dose as during continuous subcutaneous insulin infusion. The 3-injection regimen achieved a mean daily blood glucose level comparable to that obtained by continuous subcutaneous insulin infusion, even if significantly more insulin was needed. At comparable insulin doses, continuous subcutaneous insulin infusion provided a significantly lower mean daily blood glucose. Glycemic control at 0600 and 0800 was better during continuous subcutaneous insulin infusion. Low acceptance by the patients of the home use of portable micropumps was evidenced because of the practical and psychological problems involved.

Clonidine effect on insulin secretion and lipolysis in man.

Clonidine is a hypotensive drug acting as an alpha-mimetic agent in the central nervous system and causing cardiovascular depression. Clonidine administration in animals and man causes slight hyperglycemia and lipid mobilization, as well as an increase in growth hormone levels. We have studied the effect of a 3-day oral treatment (78 microgram three times daily) upon glucose (5 g i.v.)- and tolbutamide (1 g i.v.)-induced insulin release in subjects without metabolic alterations. Acute insulin response (3 min after IVGTT) and insulin release (area between 0 and 10 min) were significantly reduced after clonidine treatment. Blood glucose levels were not affected by clonidine treatment; the insulinogenic index 3 min after the glucose load was significantly reduced by clonidine administration. There was neither an evident effect on tolbutamide-induced insulin release nor a modification of the hypoglycemic effect of tolbutamide. Clonidine did not affect basal lipolysis, evaluated in vitro as glycerol release from human subcutaneous adipose tissue fragments, while norepinephrine-induced lipolysis was slightly reduced. The results presented are compatible with an alpha-mimetic effect of clonidine on pancreatic and adipose tissue.

In vitro effect of insulin on peripheral T-lymphocyte E-rosette function from normal and diabetic subjects.

Juvenile-onset diabetics (JOD) have a significantly low peripheral T-lymphocyte count. In vitro exposure of diabetic lymphocyte cultures to insulin causes a significant T-cells count increase and thereafter no significant difference is detectable among JOD, maturity-onset diabetics (MOD) and normal subjects (NS) T-cells counts. This finding supports the hypothesis that the T-lymphocyte depressed function present in JOD is a secondary phenomenon due to in vivo insulin deficiency. Possible mechanisms of insulin action in restoring E-rosette function are discussed.

Peripheral T-lymphocytes in juvenile-onset diabetics (JOD) and in maternity-onset diabetics (MOD).

The percentage and absolute number per mm.3 of peripheral T-lymphocytes were determined in 11 juvenile-onset diabetics (JOD), in 21 maturity-onset diabetics (MOD), and in 18 normal subjects (NS). The percentage was significantly lower in JOD (38.1) than in MOD (57.2) and NS (56.5). The absolute T-lymphocytes number per mm.3 was significantly lower in JOD (833) than in NS (1,260); this was also true for JOD as against MOD (1,026), even if the difference was not statistically significant. No difference was found between MOD and NS, or between MOD on oral therapy and on insulin treatment. The decrease of peripheral T-lymphocytes in JOD was not related to associated illness or drugs. The data presented suggest the possibility of an altered cell-mediated immunity in juvenile-onset diabetics.