The present study was aimed at investigating the effect of calcitonin on plasma glucose, C-peptide, glucagon and growth hormone (GH) responses to arginine in insulin-dependent diabetic subjects. For this purpose, 6 insulin-requiring diabetics were submitted to an arginine tolerance test twice, in basal conditions and during the simultaneous infusion of salmon calcitonin (100 MRC) plus arginine in random order. Calcitonin caused a clear inhibition of the plasma glucose rise triggered by the amino acid, without significant modifications of the plasma C-peptide and glucagon responses. A significant rebound of plasma glucose was seen after calcitonin was stopped. Plasma GH rise following arginine administration was significantly inhibited by calcitonin. These findings suggest some positive interferences of calcitonin with the arginine-induced plasma glucose increase in insulin-dependent diabetes.

Adolescent↗

PubMedDate not supplied

Is the common presence of glucose intolerance in old age a reliable index for the subsequent occurrence of fasting hyperglycemia?

The aim of the present study was to verify the validity of diagnostic criteria developed by the NDDG for the diagnosis of diabetes mellitus in old age. One hundred and fifty-one ambulatory old (range: 66-77 years) subjects (group A) underwent OGTT showing the following results: 33% normal, 12% non-diagnostic, 23% impaired glucose tolerance (IGT), 32% diabetic-type tolerance (DT). In addition, 84 subjects (group B) selected from 1978 to 1982 (42 aged 51-60 years, 30 aged 61-70, and 12 aged 71-80) with abnormalities of glucose tolerance during OGTT (IGT or DT) were asked to control their fasting plasma glucose every month during 1984. In group B a significant correlation between DT and subsequent development of fasting hyperglycemia was observed only in the subjects of the 6th and 7th decades of age. On the contrary, no subjects aged 71-80 years developed fasting hyperglycemia. The authors suggest that a high prevalence of abnormalities in glucose tolerance according to NDDG exists in old age which cannot be considered evidence of a true diabetes mellitus being unpredictive of a progression towards fasting hyperglycemia.

Aged↗

PubMedDate not supplied

Increased alpha 2-macroglobulin in diabetes: a hyperglycemia related phenomenon associated with reduced antithrombin III activity.

Increased alpha 2-macroglobulin (alpha 2M) activity and concentration, and decreased antithrombin III (ATIII) plasma concentration are reported in diabetic subjects. In diabetes an inverse correlation between ATIII activity and blood glucose, HbA1, alpha 2M activity and alpha 2M concentration, and a direct correlation between both alpha 2M activity and alpha 2M concentration with blood glucose and HbA1 are found. Moreover, a direct correlation between alpha 2M activity and alpha 2M concentration fails. In both diabetic and normal subjects induced hyperglycemia increases alpha 2M activity and alpha 2M concentration reduces ATIII activity, while ATIII concentration is not affected. These data which show that hyperglycemia may increase alpha 2M molecule levels while altering only the biological function of ATIII, provide evidence that hyperglycemia may decrease, directly, the biological function of some proteins and may condition the levels of some risk factors for the development of diabetic complications such as alpha 2M.

Adult↗

PubMedDate not supplied

Pathophysiological study of the non-insulin-dependent phase of type I diabetes mellitus.

The usual practice of considering type I diabetes synonymous with insulin-dependent diabetes has been criticized. Since type I diabetes can have a non-insulin-dependent phase (pre-type I diabetes and/or honeymoon) the differentiation of two main types of diabetes according to insulin-dependency is not absolute. We studied the insulin, C-peptide and glucagon responses to various tests (OGTT, IVGTT, glibenclamide test, mixed meal tolerance test and ITT) performed during the non-insulin-dependent phase of 3 young patients (range 8-18 years) who developed ketosis 12-24 months after the discovery of fasting hyperglycemia, and in 6 patients (age 15-23 years) who presented a remission phase 4-6 months after the sudden clinical onset of type I diabetes. An insignificant insulin and C-peptide increase following i.v. glucose was observed in all patients, whereas the B-cell response to both oral glucose and other secretagogues was preserved, although at a subnormal level. In the three hyperglycemic and preketoacidotic patients the basal levels of glucagon were low and no significant increase after secretagogues was seen. Sensitivity to exogenous insulin in all patients was good. Thus, B-cell response in our patients was reminiscent of the differential responsiveness to various stimulants in the early stage of type II (non-insulin-dependent) diabetes. These results suggest that type I and type II diabetes can be characterized by the same functional B-cell defect during a period of their natural history.

Adolescent↗

PubMedDate not supplied

Somatostatin and insulin secretion in man. II. The effect of theophylline.

This study was aimed at evaluating the effect of theophylline, a drug that increases the intracellular concentrations of cAMP by inhibiting phosphodiesterase activity, on somatostatin (SRIF)-mediated inhibition of insulin secretion in man. Acute insulin response (AIR) to i.v. glucose (mean change 3-10 min) was almost totally suppressed by SRIF (500 micrograms/h) and glucose utilization was reduced (p less than 0.0001). These SRIF-induced decreases failed to be eliminated by a concurrent infusion of theophylline (100 mg as a loading dose followed by a constant infusion of 5 mg/min). Theophylline alone resulted in a significant increase in both AIR (p less than 0.01) and glucose removal rates (p less than 0.05). Thus, our data disprove the involvement of the phosphodiesterase enzymes in the inhibitory action of SRIF on glucose-induced insulin secretion in man.

Adult↗

PubMedDate not supplied

A comparative study of metabolic and hormonal responses to somatostatin and propranolol in man.

The aim of this study was to compare the metabolic and hormonal effects of somatostatin to those of propranolol, a beta-adrenergic blocking agent known to reduce basal insulin secretion. For this purpose, 6 normal subjects received somatostatin (4 microgram/min) per 60 min and 6 subjects were infused with propranolol (0.08 mg/min). Somatostatin resulted in a significant decrease of basal insulin (p less than 0.05) and glucagon (p less than 0.01) and raised plasma FFA levels from a mean basal value of 417 +/- 24 muEq/1 (x +/- SEM) to 600 +/- 46 muEq/1 at 60 min (p less than 0.01). Propranolol significantly decreased basal insulin (p less than 0.05) and glucagon (p less than 0.05); FFA levels rose slightly at the end of propranolol administration (p less than 0.05). The levels of FFA which were significantly higher (p less than 0.025) during somatostatin as compared to those observed during propranolol, seem to suggest a role for this tetradecapeptide in lipid metabolism independent of its inhibiting action on islet hormone release.

Adult↗

PubMedDate not supplied

Glycemic control with an artificial pancreas improves insulin responses to both oral and glucose in nonobese noninsulin-dependent diabetic subjects.

Insulin secretory responses to both oral and intravenous glucose were investigated in 12 nonobese noninsulin-dependent diabetic subjects before and after strict metabolic control of blood glucose levels without weight loss. Glycemic control was achieved by applying an artificial pancreas to all diabetics for 2 or 3 days, which led to restoration of normal fasting blood glucose levels and to significant reduction of fasting plasma insulin (p less than 0.01) and C-peptide (p less than 0.05) levels. Initially, the insulin response to oral glucose was weak and delayed, but increased significantly after treatment (p less than 0.01), although none of the diabetic subjects achieved completely normal glucose tolerance. The i.v. glucose tolerance test (0.33 g/kg) revealed that all diabetics lacked acute insulin response in the basal state with low glucose disappearance rates (0.37 +/- 0.07 %/min). After 48h of normoglycemia, these figures did not change significantly, although the insulinogenic index (insulin area/glucose area) was significantly increased (p less than 0.05). A marked increase in both phases of insulin secretion was evident when a larger intravenous glucose pulse (0.66 g/kg) was used in some diabetics in order to raise the blood glucose concentrations of the post-treatment test to those of the pre-treatment test. In absolute terms, the insulin responses of the post-treatment tests were not significantly different from those of sex-, age- and weight-matched control subjects, but were significantly lower if related to the corresponding plasma glucose responses (insulinogenic index lower than that of controls). These studies in nonobese noninsulin-dependent diabetic subjects indicate that glycemic control with an artificial pancreas improves insulin response to glucose, suggesting that chronic hyperglycemia may stress the impaired B-cell secretory capacity of diabetes.

Administration, Oral↗

PubMedDate not supplied

In vivo and in vitro experiments on relationships between PGA1 and glucose utilization.

The in vivo and in vitro effects of PGA1 on glucose utilization were investigated in normal rats and in rats with alloxan-diabetes (50 mg/kg i.v. administered 48 hrs before experiment). The animals were divided into two groups. The first group -- which included both normal and diabetic animals -- was submitted to an IVGIT after a 12-h fast and during a sodium chloride infusion. In the second group -- which equally included normal and diabetic rats -- the same GTT was performed during a sodium chloride infusion in which PGA1 had been diluted, so that a dose of 0.5 g/kg/min was administered. This dose is devoid of any effect on cardiovascular activity. For in vitro experiments, glucose utilization was studied in the rat diaphragm incubated with insulin (200 muU/ml) and PGA1 (10 and 100 ng): results demonstrated that PGA1 enhances the insulin effect on glucose utilization and the enhancement is dose-dependent. The same results were observed also in the in vivo experiments: in normal rats PGA1 really improves glucose utilization without any interference with insulin secretion from B-cells. On the other hand, PGA1 has no effect on this utilization in diabetic rats. From our experiments it can therefore be concluded that PGA1 improves glucose utilization, showing a synergic action with the increased quantity of insulin secreted in response to a glucose load. No effect is noted when insulin secretion from B-cells is reduced or absent.

Animals↗

PubMedDate not supplied

The oxygen-release capacity of red blood cells in insulin-dependent diabetics after artificial pancreas.

Oxygen-release capacity of the red blood cells was investigated in non-acidotic insulin-dependent diabetics before and after the achievement of strict metabolic control with the aid of the artificial pancreas. P50std (oxygen tension at 50% oxygen saturation) values were low in basal condition and returned to normal after the 24-h treatment period. No significant changes were observed in the content of red cell 2,3-diphosphoglycerate nor in the acid-base balance. Only the labile form of glycosylated hemoglobin showed significant decreases after treatment. These results suggest that insulin-dependent diabetics may have a state of relative tissue hypoxia which can be easily overcome by the achievement of strict metabolic control.

Adolescent↗

PubMedDate not supplied

Sodium salicylate restores the impaired insulin response to glucose and improves glucose tolerance in heroin addicts.

Plasma glucose, insulin, C-peptide, glucagon and growth hormone responses to intravenous glucose were evaluated in 10 heroin addicts in the basal state and during an infusion of sodium salicylate, an inhibitor of endogenous prostaglandin synthesis. Ten normal subjects, matched for age, sex and weight served as controls. In the basal state, the heroin addicts had markedly reduced insulin responses to intravenous glucose and low glucose disappearance rates (p less than 0.01 vs controls). The infusion of sodium salicylate caused a striking increase of the acute insulin response to intravenous glucose (from 14.5 +/- 4 microU/ml to 88 +/- 11 microU/ml, p less than 0.001) and restored to normal the reduced glucose tolerance (KG from 1.10 +/- 0.1% min-1 to 2.04 +/- 0.19% min-1). Hypoglycemic values were found in all addicts at the end of the test during salicylate infusion. Indomethacin pretreatment in five additional addicts also caused normalization of the impaired insulin responses to the intravenous glucose challenge and restored to normal the reduced glucose disappearance rate. Plasma glucagon and growth hormone levels were normally suppressed by glucose in addicts in basal conditions; sodium salicylate infusion completely overturned these hormonal responses which became positive in the first 15 min following the glucose challenge. These results demonstrate that the two prostaglandin synthesis inhibitors can restore the impaired B-cell response to glucose in heroin addicts to normal, indicating that this response is not lost but is inhibited by heroin itself or by other substances, perhaps by the endogenous prostaglandins.

Adolescent↗

PubMedDate not supplied

[Non-insulin-dependent diabetes mellitus associated with nonalcoholic liver cirrhosis: an evaluation of treatment with the intestinal alpha-glucosidase inhibitor acarbose].

Non-insulin-dependent diabetes mellitus not responding to diet only in patients with non-alcoholic liver cirrhosis is characterized by high post-prandial hyperglycemia. The aim of this study was to evaluate the safety and efficacy of 24 weeks of treatment with 300 mg acarbose per day in 76 consecutive outpatients affected by type 2 diabetes and well-compensated liver cirrhosis. The study design was double-blind cross-over vs placebo. All patients tolerated both treatments well, and no significant variations in liver function tests were observed (< 5% vs pre-treatment). A significant reduction of several parameters was observed only after acarbose: fasting glycemia (19 +/- 6 vs 2 +/- 0.5%; p < 0.01), post-prandial glycemia (41 +/- 9 vs 3 +/- 0.6%; p < 0.01), mean glycemia (30 +/- 8 vs 14 +/- 5%; p < 0.01), daily glycemic variation (52 +/- 8 vs 8 +/- 1%; p < 0.01), HbA1c (16 +/- 1 vs 2 +/- 0.5; p < 0.05), incremental area of C-peptide after a standard meal (80 +/- 19 vs 200 +/- 36 ng/mL/300 min; p < 0.01). After acarbose a significant increase of intestinal voiding/week (98 vs 28%; p < 0.01) and a parallel reduction of blood ammonia levels (52 +/- 9 vs 9 +/- 5%; p < 0.01) were observed. Results clearly document the good tolerability and the absence of toxic effects of acarbose on the liver, due to a theoretic absence of both absorption by the gut and hepatic metabolism of the drug. In fact, acarbose increases peristaltic movement of the gut, stimulates the proliferation of saccharolytic bacteria and simultaneously reduces proteolytic bacterial proliferation, thus actively reducing blood ammonia levels. These unexpected effects of acarbose may be used to advantage for the treatment of type 2 diabetes mellitus in patients with well-compensated liver cirrhosis.

Acarbose↗

PubMedDate not supplied

Restoration of sensitivity to sulfonylurea after strict glycaemic control with insulin in non-obese type 2 diabetic subjects.

Ten non-obese type 2 diabetic patients with secondary failure to sulfonylureas received an intensive insulin therapy (four doses schedule) for 90 days. The glycaemic control was poor at entry (HbA1c = 11.7 +/- 1.2%) and ameliorated significantly after insulin (HbA1c = 7.1 +/- 0.7%, p less than 0.01). The reintroduction of the sulfonylurea after insulin withdrawal resulted in a persistent satisfactory long-term control (300 days) in all, but two diabetics responded no more after about 3 and 4 months of clinical remission (good control on sulfonylurea). Both basal and stimulated (iv glucagon and mixed meal) beta-cell secretory activity increased significantly at 3 months and declined thereafter without falling below baseline values. Three months of strict metabolic control seem to restore the sensitivity to sulfonylurea by enhancing beta-cell secretory activity in non-obese type 2 diabetic patients.

Blood Glucose↗

PubMedDate not supplied

Sensorimotor evaluation of ano-rectal complex in diabetes mellitus.

To evaluate the status of ano-rectal complex in diabetic patients, 20 patients with no fecal incontinence and/or local ano-rectal disorders and 18 normal subjects underwent to: 1) ano-rectal manometry; 2) defecography; and 3) rectal sensation tests. In all subjects, the five classic cardiovascular reflexes tests were performed to detect autonomic neuropathy. No significant difference between diabetic patients and controls was found in length, maximum resting pressure and strength of phasic external anal sphincter or anal canal at ano-rectal manometry; similarly, no significant difference between diabetic and normal subjects was found by the same technique in threshold and amplitude of ano-rectal inhibitory reflex. Ano-rectal angle of diabetic patients was not significantly different from normals both at resting and during straining at defecographic study. By rectal sensation testing, it was possible to demonstrate a significant difference between diabetic and normal subjects in perception of rectal distension (87.5 +/- 27.5 vs 39.2 +/- 6.5 ml, p less than 0.05; mean +/- SEM) and of stimulus of defecation (147.0 +/- 56.3 vs 52.9 +/- 18.5 ml, p less than 0.001) but not in perception of maximum tolerable volume (343.5 +/- 69.9 vs 322.0 +/- 48.5 ml, p = NS). No relationship was found between these results and the score of autonomic neuropathy and/or duration of diabetic disease. These data suggest that an early involvement of only sensory parasympathetic fibers of ano-rectal complex occurs in diabetic patients without gastrointestinal symptoms.

Adolescent↗