Biomedical subjects

D Porte

Publications and source records attributed to D Porte.

275 records · Page 16Linked to original sources

PubMedDate not supplied

Pathophysiology of insulin secretion in non-insulin-dependent diabetes mellitus.

The pathogenesis of the abnormal metabolic state in patients with non-insulin-dependent diabetes (NIDDM) is controversial. Even the term NIDDM stirs controversy because of the easily drawn inference that individuals with this form of diabetes do not need insulin treatment. Yet many patients with NIDDM are treated with insulin; some even develop hyperosmolar coma if not given insulin. Ketoacidosis, however, is very infrequent in this syndrome, implying that these patients are not dependent on insulin treatment to prevent mass mobilization of fatty acids and ketone bodies. The phrase noninsulin-dependent is therefore appropriate when used in this restricted fashion but inappropriate when used to imply adequacy of insulin secretion. The evaluation of the adequacy of islet function in this syndrome has been complex, since there is no standard of insulin output that can be defined for normal islets without specifying the physiologic setting under which the assessment has been made. For example, individuals with normal glucose levels but variable degrees of obesity have widely varying insulin secretion rates. Thus, the choice of controls is critical when comparing islet function in NIDDM to normal. In addition, the efficiency of the B-cell response to a challenge (e.g., oral glucose tolerance test) can markedly influence the magnitude of the stimulatory glucose level during the period of testing. For example, a subject with some impairment of insulin output will tend to become more hyperglycemic during the test. The hyperglycemia may then stimulate more insulin secretion so that the overall insulin output may appear equal to or even greater than that of a normal individual. In such a closed-loop system, strict control of input variables is necessary to evaluate whether or not insulin secretion is normal. As will be discussed, control of glucose level and other variables is seldom accomplished in dynamic glucose tolerance tests. As will be presented in this review, the development of appropriately controlled studies of islet function has provided convincing evidence that islet B-cell function is abnormal in patients with NIDDM. Since these studies are based on an understanding of normal islet function, normal islet B-cell physiology is discussed before pathophysiology. Finally, the implications of this analysis for the treatment of NIDDM with diet, hypoglycemic sulfonylureas, and insulin will be discussed.

Administration, Oral↗

PubMedDate not supplied

Attitudes of diabetic men after implantation of a semi-rigid penile prosthesis.

Erectile impotence is a common and distressing problem in diabetic men. In order to examine the impact of a penile prosthesis on the quality of life of the recipients, we mailed a questionnaire to all patients (N = 49) who received a semi-rigid (Small-Carrion) prosthesis at the Seattle VAMC from 1976 to 1981. Fourteen patients with diabetes and 23 without diabetes returned the questionnaire. Direct comparisons showed no statistically significant differences between the responses of the two groups. Based on a scale of 1-7 (1 = worst, 4 = no change, 7 = best), the general effect of the operation on the quality of life of the recipients was 5.7 +/- 0.3 (Mean +/- SEM); the quality of intercourse was 5.1 +/- 0.3; the patient's perception of his partner's response to the prosthesis was 5.2 +/- 0.3; and the patient's perception of postoperative changes in his relationship with his partner was 5.6 +/- 0.3. Eighty-three percent of the patients were satisfied with the performance of the prosthesis. Most of the patients (86%) felt that their preoperative expectations had been fulfilled and would elect to have the procedure if they had it to do over again. However, five patients (14%) stated that they would not elect the operation again because their partners did not appreciate the operation (N = 2); the operation produced severe, prolonged pain (N = 1); or the patient's expectations had not been fulfilled (N = 2). Preoperative counseling should be used to foster realistic patient and partner expectations. This operation, which appears to improve the quality of life for most diabetic patients with erectile impotence, should be considered a part of standard care and not as a cosmetic procedure or extraordinary care.

Coitus↗

PubMedDate not supplied

Correlations among autonomic, sensory, and motor neural function tests in untreated non-insulin-dependent diabetic individuals.

A well-defined group of untreated non-insulin-dependent (NIDD) subjects were evaluated to determine whether involvement of neural function measurements is generalized and symmetrical and to compare the autonomic, sensory, and motor neural measurements. After age adjustment, the sensory and motor neural function measurements were significantly slower in the diabetic group than in normal subjects (P less than 0.01). Similarly, the autonomic nervous system function measurements were also abnormal in the NIDD group (P less than 0.01). Further analysis revealed that each of the specific measurements--median motor nerve conduction velocity (NCV,P less than 0.005), peroneal motor NCV (P less than 0.005), median sensory NCV (P less than 0.005), dark-adapted pupil size after muscarinic blockade (P less than 0.02), pupillary latency time (P less than 0.02), and RR-variation after beta adrenergic blockade (P less than 0.001)--was significantly less by analysis of covariance after age adjustment in the NIDD group than in normal subjects. Thus, there was evidence of motor and sensory neural impairment in the upper and lower extremities as well as evidence of impairment of the reflex arcs involving the parasympathetic nerves to the heart and eye and the sympathetic nerves to the iris. Further analysis revealed that right and left NCV were correlated (P less than 0.01), as were the median motor and median sensory NCV (P less than 0.01), the median motor and peroneal motor NCV (P less than 0.001), and the peroneal motor and median sensory NCV (P less than 0.001). Thus, there was evidence of symmetrical upper and lower limb, as well as motor and sensory proportional involvement of large nerve fiber NCV in this group of NIDD subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Decreased numbers of platelet alpha-adrenergic binding sites in diabetes mellitus.

Eleven men with diabetes mellitus were compared with 45 male controls for platelet alpha-adrenergic binding sites by using [3H]dihydroergocryptine (DHE) as the radioligand antagonist. There was no difference between the two for binding affinity, but the number of sites was 430 +/- 30 (means +/- SEM) for diabetic subjects and 574 +/- 29 for controls (P = .005). Decreased sites were related to increased glycosylated hemoglobin levels (P = .002). There was no relationship between the decreased sites and catecholamine levels, duration of disease, body weight, or fasting blood sugar. Hence, binding sites were inversely related to control, but further studies are needed to define the pathophysiologic significance of this.

Adult↗

PubMedDate not supplied

Acute and chronic effects of sulfonylurea drugs on pancreatic islet function in man.

The pancreatic islet can be viewed as an integrator of nutrient, neural, and hormonal signals. In normal people, glucose directly stimulates insulin release and also plays a key role as a potentiator of nonglucose stimulants of the B-cells. In patients with non-insulin-dependent diabetes mellitus (NIDDM), the direct effect of glucose on insulin secretion is markedly impaired. However, as hyperglycemia develops, basal insulin levels and insulin responses to nonglucose signals are maintained in many NIDD patients by the potentiating effect of hyperglycemia. Both acute and chronic administration of sulfonylurea drugs results in enhanced B-cell sensitivity to the potentiating effect of glucose. During sulfonylurea therapy this effect initially causes an increase in insulin level. However, as the glucose level falls during therapy the insulin level may tend to return toward pretreatment values, thereby masking the improvement of B-cell function. In NIDD patients with mild to moderate hyperglycemia (fasting plasma glucose less than 200 mg/dl), chronic sulfonylurea therapy results in the maintenance of near-normal insulin levels, but at a lower plasma glucose level. In patients with more severely impaired B-cell function, whose insulin levels before therapy are subnormal despite marked hyperglycemia, there is a net absolute increase in insulin levels during chronic sulfonylurea administration. Thus, some NIDD patients may show an increase in basal insulin levels during chronic sulfonylurea therapy while others may not; however, all patients who respond to sulfonylureas demonstrate increased B-cell sensitivity to glucose. Acute and chronic sulfonylurea treatment also results in a suppression of glucagon levels, an effect that may be secondary to the enhancement of B-cell function. The fall of plasma glucose during chronic sulfonylurea therapy is associated with a decrease in hepatic glucose production in NIDD patients. The magnitude of this effect is correlated with the degree of enhancement of basal insulin secretion. Thus, chronic sulfonylurea therapy clearly enhances pancreatic islet function in patients with NIDDM. We postulate that the major antihyperglycemic action of sulfonylurea therapy is mediated by this pancreatic effect.

Chlorpropamide↗