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Biomedical subjects

W L Clarke

Publications and source records attributed to W L Clarke.

At least 73 records · Page 4Linked to original sources

Differences in circulating gluconeogenic substrates during short-term fasting in men, women, and children.

To determine whether the differences in fasting glucose responses in men, women and children could be related to differences in glucoregulatory hormone secretion or availability of circulating gluconeogenic substrates, 20 adults (10 men and 10 women) were fasted for 86 hr and 15 children (6.1 +/- 0.8 yr, mean +/- SE) were fasted for 30 hr. Circulating concentrations of glucose, ketone bodies, potential gluconeogenic substrates and glucoregulatory hormones were determined at frequent intervals. In the postprandial state (1-14 hr fasting), substrate and hormone concentrations were similar in all groups with the exception of plasma glutamine concentrations which were higher in men (640 +/- 20 microM) than in women of children (490 +/- 20 microM and 480 +/- 50 microM, respectively, p less than 0.01 for both). Following 30 hr fasting children had the lowest glucose (53 +/- 3 mg/dl) and alanine (167 +/- 17 microM) concentrations and men had the highest (72 +/- 3 mg/dl and 279 +/- 16 microM, respectively) whereas those of women were intermediate (64 +/- 3 mg/dl and 226 +/- 19 microM. respectively). Following 30 hr of fasting betahydroxybutyrate concentrations were highest in children and lowest in men (the children, 3.7 +/- 0.4 mM; women, 1.7 +/- 0.2 mM and men 0.9 +/- 0.2 mM, p less than 0.02 between all groups). An inverse relationship (p less than 0.001 was observed between beta-hydroxybutyrate and glucose concentrations throughout the fast for each group (r greater than 0.92). Although plasma cortisol concentrations were higher in women and children when compared to those of the men, no differences in growth hormone, glucagon, or insulin concentrations were observed among the three groups studied. Differences in plasma substrate responses to fasting among the groups studied may reflect differences in glucose requirements among men, women and children, as well as the relative availability of both gluconeogenic substrate and ketone bodies.

Adult↗

Overnight basal insulin requirements in fasting insulin-dependent diabetics.

Overnight basal insulin requirements to maintain eugycemia were determined in six insulin-requiring diabetic subjects using a feedback-controlled (closed loop) insulin infusion system. Mean hourly insulin infusion rates, required to maintain plasma glucose concentrations at approximately 100 mg/dl, were remarkably stable from 2400 h to 0600 h; however, a twofold to threefold increase in insulin requirements was observed in each subject between 0600 h and 0900 h. This increase in amount of basal insulin required was not associated with increases in plasma glucagon or growth hormone concentrations, but occurred simultaneously with normal diurnal increases in plasma cortisol. These findings suggest that normal diurnal increases in plasma cortisol, independent of the content of the morning meal, contribute to the increased amount of morning insulin required in diabetic subjects. Programs designed for optimal open loop insulin delivery may benefit from modifications designed to coincide with this increase in amount of basal insulin required in the early morning.

Adolescent↗

Studies with a pancreatic beta cell simulator in the third trimester of pregnancies complicated by diabetes.

To determine the potential of an artificial pancreatic beta cell simulator as a therapeutic and research tool we have used the device for short-term monitoring and control of blood glucose concentrations in five pregnant patients with juvenile-onset diabetes (White's Class C) and three pregnant patients with maturity-onset diabetes (Class B). One patient with brittle juvenile-onset diabetes had successful control before, during, and after cesarean section. The other seven patients were studied during the third trimester of pregnancy and at least four weeks before delivery. Blood glucose control with Biostator regulation was excellent (mean, 96 mg. per deciliter; range, 85 to 107). The insulin requirements needed to achieve optimal glucose control with the Biostator were highly variable (range, 20 to 157 U. per 24 hours) but very similar to those previously calculated to provide optimal control by conventional means. Insulin requirements were unrelated to plasma growth hormone, placental lactogen, or glucagon concentrations. The greatest degree of insulin resistance was seen in obese patients with endogenous insulin-secretory capacity. This study indicates that a pancreatic beta cell simulator can normalize glucose concentrations and rapidly estimate daily insulin requirements in pregnant diabetic patients. In addition, the data suggest that exogenous insulin may indirectly suppress endogenous insulin secretion and thus contribute to the "insulin resistance" of obese patients with maturity-onset diabetes.

Adult↗

The effect of hyperglucagonemia on blood glucose concentrations and on insulin requirements in insulin-requiring diabetes mellitus.

The effect of elevated glucagon concentrations on insulin requirements and on blood glucose concentrations was studied in five insulin-requiring diabetic subjects during feedback control of hyperglycemia with an automated glucose-controlled insulin infusion system (artificial endocrine pancreas) for six to eight hours. Two levels of hyperglucagonemia were induced by means of constant intravenous infusion. Raising plasma glucagon concentrations to levels reported in poorly controlled diabetics (450 to 665 pg. per milliliter) did not alter total insulin requirements or blood glucose concentrations. Higher glucagon concentrations (850 to 1,050 pg. per milliliter) caused a modest (26 per cent) increase in insulin requirements and only a slight increase in mean blood glucose concentrations. These studies demonstrate that the degree of hyperglucagonemia found most frequently in insulin-requiring diabetics does not increase insulin requirements or decrease insulin effectiveness in patients given insulin in amounts appropriate to maintain euglycemia.

Adult↗

Glucagon, insulin and glucose response to physiologic testing in normal and massively obese adults.

Ten normal adults and ten nondiabetic massively obese subjects were studied following 4--7 days on identical diets. Intravenous arginine challenge resulted in similar glucose and glucagon responses and threefold greater integrated insulin responses in the obese when compared to the normal subjects. Following oral glucose, glucagon responses were similar, whereas both basal and integrated insulin values were higher in the obese subjects. Basal and integrated insulin concentrations were greater during intravenous glucose testing in the obese subjects, whereas similar glucagon suppression was observed in both groups. Hourly blood samples obtained during a 24-hr period revealed that the obese glucose profile differed significantly from the normals. Insulin values were two- to four-fold higher in the obese subjects, whereas no significant difference was observed in the glucagon concentrations. The nadir and peak glucagon concentrations for both groups occurred at 8:00 a.m. and 8:00 p.m., respectively, and were positively correlated with plasma amino acid values, and were similar in both groups.

Adult↗

Clinical evaluation and preliminary studies on the use of an artificial pancreatic beta cell in juvenile diabetes mellitus.

A newly developed artificial pancreatic beta cell is described and its use in five children with diabetes mellitus is evaluated. This device can be programmed to bring the blood glucose concentration rapidly to a preselected level and normalize glucose tolerance in juvenile diabetic patients with markedly different insulin requirements. It is portable, can be operated by one person, and has been used to regulate the blood glucose concentration before, during, and after surgery requiring general anesthesia. The potential value of the device as an investigational tool is shown by demonstrating that regulation of the blood glucose concentration with insulin for seven to 24 hours does not alter circulating glucagon concentrations in the juvenile diabetic patients studied.

Adolescent↗

The characteristics of a new glucose sensor for use in an artificial pancreatic beta cell.

A new glucose sensor has been developed for the continuous extracorporeal monitoring of blood glucose concentrations in conjunction with an artificial pancreatic beta cell simulator. This sensor has a rapid ninety percent response time (less than 1 min), is stable for periods of up to 140 hours of accumulated use and can be calibrated without the use of a reference glucose analyzer. Its reliability has been confirmed in over 100 clinical studies. A comparison of this sensor to other glucose sensors designed for artificial pancreatic beta cell devices is made and the sensor is shown to be the most advanced glucose sensor presently available for extracorporeal continuous glucose monitoring in man.

Artificial Organs↗

Evaluation of growth hormone release in children using arginine and L-dopa in combination.

L-Dopa in a dose ranging from 125-500 mg and arginine monochloride in a dose of 0.5 gm/kg were given simultaneously to 56 children with short stature (height less than third percentile). Sixteen of these children were subsequently diagnosed as having growth hormone deficiency. The diagnosis of hyposomatotropism was based on clinical findings and on responses to the combination test and to arginine and L-dopa administered as separate tests. All of the remaining 40 children had a normal GH response of greater than 6 ng/ml to the combination test. However, in this group, nine children were identified who responded to the combination test but who failed to respond to arginine and L-dopa in individual tests. The data suggest that a positive response to arginine and L-dopa in combination in children, who do not respond to the usual provocative tests when administered individually, may fail to identify children with partial GH deficiency who would benefit from treatment. The integrated stimulated GH response in the 31 children in whom a normal GH response to all three tests occurred suggests that the effects of L-dopa and arginine are additive.

Adolescent↗

Psychometric properties and normative data for the parent version of the diabetes independence survey.

The parent version of the Diabetes Independence Survey measures parents' perceptions of their children's mastery of 38 diabetes self-care skills. The instrument was administered to 648 parents of 622 children with insulin-dependent diabetes mellitus, ages 3 and 18 years, at seven different pediatric medical centers. Data confirming the internal consistency, interrater reliability, construct validity, and concurrent validity of the instrument are presented in this paper. Age-adjusted normative data for total scores on the instrument as well as item-by-item data on the ages at which mastery of each skill was reported by 25%, 50%, and 75% of parents also are discussed. The Diabetes Independence Survey can be used as a reliable, valid, and efficient research tool for assessing the growth and development of diabetes knowledge and skills among children and adolescents, and as a screening instrument and program evaluation tool for clinical purposes.

Adolescent↗

The relationship between nonroutine use of insulin, food, and exercise and the occurrence of hypoglycemia in adults with IDDM and varying degrees of hypoglycemic awareness and metabolic control.

The purpose of this study was to determine objectively the relationships between changes in the usual amount of insulin injected, food eaten, and exercise performed, and the subsequent occurrence of low blood glucose (< 3.9 mM) in adults with IDDM and varying degrees of hypoglycemic awareness and metabolic control. Subjects used a handheld computer to record whether their most recent insulin, food, and exercise had been omitted or were greater than, less than, or about the same as usual following every measured blood glucose level of < 3.9 mM and > 5.6 mM. Responses for each self-management behavior were compared for the two blood glucose ranges. Food was omitted more frequently prior to a low glucose reading and exercise was omitted more frequently prior to a high glucose reading. More insulin, less food, and more exercise each were associated with low glucose levels. These findings underscore the importance of traditional diabetes education.

Adult↗