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Biomedical subjects

F J Service

Publications and source records attributed to F J Service.

At least 19 recordsLinked to original sources

C-peptide suppression test: effects of gender, age, and body mass index; implications for the diagnosis of insulinoma.

To assess the effects of gender, age, and body mass index (BMI) on suppression of plasma C-peptide during insulin-induced hypoglycemia, 101 lean and obese, healthy men and women ages 20 to 80 yr underwent infusion of human regular insulin, 0.125 U/kg over 60 min after an overnight fast. Plasma glucose, insulin, and C-peptide were measured every 30 min for 120 min. C-peptide concentrations were influenced by gender at 30 min, by BMI at baseline and both BMI and age at all subsequent time points. Because of variations in baseline plasma C-peptide concentrations, percent decrease in C-peptide was evaluated. Significantly less percent decrease of C-peptide with increased age at 30, 60, and 90 min and with increased BMI at 30 and 60 min were noted with no effect of gender. From stepwise regression analysis using multiple, additional variables only the plasma glucose concentration at 30 min made a significant, albeit small (8%), contribution to the variability in percent decrease in C-peptide at 60 min. When C-peptide responses from eight histologically confirmed insulinoma patients were contrasted to values adjusted for age, gender, and BMI of normal subjects, all insulinoma patients had abnormal responses when percent decrease in C-peptide was used, whereas only four insulinoma patients had abnormal response when actual C-peptide concentrations were used.

Adult

Occult functioning insulinomas: which localizing studies are indicated?

BACKGROUND: An occult insulinoma refers to a biochemically proven tumor with an anatomic site that remains indeterminate before operation. The amount of radiologic localization for such patients is debatable. METHODS: Sixty-five patients with sporadic insulinomas were surgically treated at the Mayo Clinic between January 1980 and December 1990. True occult tumors were present in 31% of these patients (n = 20). Thirty-eight negative preoperative localization studies were performed, with 10 patients undergoing more than one study. A benign adenoma was found in 19 patients when they underwent exploratory operation, whereas one patient had malignant disease with hepatic metastases. Thirteen patients underwent intraoperative ultrasonography with a 7.5 MHz real-time high-resolution transducer. RESULTS: Solitary lesions were successfully removed either by enucleation or by distal pancreatectomy in all 19 patients with benign disease. CONCLUSIONS: This high success rate in the management of occult insulinomas suggests that extensive preoperative radiologic investigation is neither indicated nor cost-effective.

Adolescent

Functioning insulinoma--incidence, recurrence, and long-term survival of patients: a 60-year study.

For the 60-year period from 1927 through 1986, we assessed the incidence, recurrence, and long-term survival among all Mayo Clinic patients with histologically confirmed functioning insulinoma. With use of the complete medical record system at Mayo and the comprehensive epidemiologic data base of residents of Olmsted County, Minnesota, we found 224 patients in whom an initial pancreatic exploration at Mayo had confirmed the presence of insulinoma. The median age (and range) of these patients at surgical diagnosis was 47 (8 to 82) years, and 59% were female patients. During the study period, eight cases of insulinoma occurred among residents of Olmsted County; their age and gender distributions were similar to those of the total cohort. The incidence of insulinoma among residents of Olmsted County increased during the study period to a stable level during the last 2 decades of 4 cases per 1 million person-years. For the total cohort, 7.6% had multiple endocrine neoplasia type I (MEN I), and 5.8% had malignant insulinoma. The risk of recurrence was greater among patients with MEN I (21% at 10 and 20 years) than in those without MEN I (5% at 10 years and 7% at 20 years). Although survival of the total cohort was not significantly impaired, it was significantly worse than expected for patients with malignant insulinoma (29% versus 88% expected at 10 years postoperatively). We conclude that insulinoma is less rare than previously suspected. After successful surgical removal, the long-term risk of recurrent insulinoma is relatively high in patients with MEN I; for patients with benign disease, the long-term survival is normal.

Adolescent

Hypoglycemias.

Low plasma glucose concentrations that may or may not be sufficiently low to result in symptoms can be observed as a concomitant of several diverse diseases. Treatment of the primary underlying disorder usually alleviates the hypoglycemia. For patients whose primary symptom is that of hypoglycemia, it is essential to confirm that the plasma glucose concentration is low during the occurrence of symptoms. Symptoms that occur after meals usually are mild and rarely signify serious disease. With rare exceptions, hypoglycemia resulting in major symptoms occurs in the food-deprived state. Lower concentrations of plasma insulin and C-peptide and a concomitant low plasma glucose are major clues to a correct diagnosis.

Blood Glucose

The surgical aspects of insulinomas.

The clinical diagnosis of insulinoma rests on the demonstration of Whipple's triad (symptoms of hypoglycimia, low circulating glucose and prompt relief of symptoms after glucose administration). Biochemically, the association of an increased value of immunoreactive insulin with a low glucose value is diagnostic of insulin-mediated hypoglycemia. Angiographic localization of these tumors is accomplished in more than 90% of cases. The pathologic changes are usually due to a single adenoma, for which surgical enucleation is the procedure of choice. Malignancy and persistent hypoglycemia occur in slightly less than 10% of cases and can be fairly successfully managed by diazoxide and streptozotocin.

Adenoma, Islet Cell

Effect of intermittent endogenous hyperglucagonemia on glucose homeostasis in normal and diabetic man.

UNLABELLED: Infusion of glucagon causes only a transient increase in glucose production in normal and diabetic man. To assess the effect of intermittent endogenous hyperglucagonemia that might more closely reflect physiologic conditions, arginine (10 g over 30 min) was infused four times to 8 normal subjects and 13 insulin-dependent diabetic subjects (4 of whom were infused concomitantly with somatostatin to examine effects of arginine during prevention of hyperglucagonemia). Each arginine infusion was separated by 60 min. Diabetic subjects were infused throughout the experiments with insulin at rates (0.07-0.48 mU/kg per min) that had normalized base-line plasma glucose and rates of glucose appearance (Ra) and disappearance (Rd). Basal plasma glucagon and arginine-induced hyperglucagonemia were similar in both groups; basal serum insulin in the diabetics (16+/-1 muU/ml, P < 0.05) exceeded those of the normal subjects (10+/-1 muU/ml, P < 0.05) but did not increase with arginine. Serum insulin in normal subjects increased 15-20 muU/ml with each arginine infusion. In both groups each arginine infusion increased plasma glucose and Ra. Increments of Ra in the diabetics exceeded those of normal subjects, (P < 0.02); Rd was similar in both groups. In normal subjects, plasma glucose returned to basal levels after each arginine infusion, whereas in the diabetics hyperglycemia persisted reaching 151+/-15 mg/dl after the last arginine infusion. When glucagon responses were prevented by somatostatin, arginine infusions did not alter plasma glucose or Ra. CONCLUSIONS: Infusion of arginine acutely increases plasma glucose and glucose production in man solely by stimulating glucagon secretion; physiologic increments in plasma glucagon (100-150 pg/ml) can result in sustained hyperglycemia when pancreatic beta cell function is limited.

Adolescent

Pancreatic alpha-cell function in diabetic hemochromatotic subjects.

To clarify further the etiology of the carbohydrate intolerance in idiopathic hemochromatosis, we investigated the glucose, insulin, C-peptide, and glucagon responses to arginine (0.5 g/kg) infused during 30 min in lean normal subjects; in insulin-requiring subjects with hemochromatosis, genetic diabetes, and total pancreatectomy; and in nondiabetic cirrhotic subjects without portosystemic shunting. Serum insulin, C-peptide, and glucagon responses (30K antibody) were determined by RIA, and glucose level was determined by a glucose oxidase technique. Hemochromatotic and genetic diabetic subjects had similar basal glucose (157 +/- 25 vs. 168 +/- 40 mg/dl) and C-peptide (0.73 +/- 0.42 vs. 0.65 +/- 0.22 ng/ml) values, with subnormal C-peptide peak responses to stimulation (1.05 +/- 0.38 and 1.40 +/- 0.83 vs. 3.95 +/- 0.4 ng/ml in normals; P less than 0.05). No glucagon or C-peptide response to arginine was seen in any pancreatectomized subject. Similar but excessive glucagon levels were present in hemochromatosis, diabetes, and cirrhosis under basal conditions (166 +/- 24, 232 +/- 111, and 263 +/- 116 vs. 76 +/- 15 pg/ml; P less than 0.05) and after arginine stimulation (782 +/- 80, 834 +/- 123, and 902 +/- 275 vs. 489 +/- 81 pg/ml; P less than 0.05) when compared with normals. The excessive glucagon levels found in hemochromatosis, diabetes mellitus, and cirrhosis contrast to the absent response in pancreatectomized subjects and indicate that generalized islet cell destruction is not the major factor in diabetic hemochromatotic subjects.

Adult

Calcium homeostasis in diabetes mellitus.

Experimentally diabetic rats have low serum 1,25-dihydroxyvitamin D, intestinal malabsorption of calcium, secondary hyperparathyroidism, and bone loss. To examine the hypothesis that abnormalities similar to those in the diabetic rat might explain human diabetic osteopenia, we studied calcium metabolism in 40 healthy control and 82 diabetic patients aged 18--75 yr [47 untreated: fasting plasma glucose (mean +/- SE), 267 +/- 8 mg/dl; 19 treated but hyperglycemic: glucose 305 +/- 24 mg/dl; 16 treated and in better control: glucose, 146 +/- 8 mg/dl]. Serum total calcium, ionic calcium, immunoreactive parathyroid hormone (Arnaud method, GP-1M and CH-12M antisera), 25-hydroxyvitamin D (Haddad method), and 1,25-dihydroxyvitamin D (Lambert method) concentrations were normal in all 3 groups of diabetics and were not significantly different from values in the control group. We determined absorption of calcium from the intestine by a double isotope method (100 mg Ca carrier; normal range, 40--80%) in 11 control and 13 untreated, uncontrolled diabetics (mean plasma glucose, 285 +/- 17 mg/dl). Absorption of calcium in controls was 60 +/- 3% and in diabetics was 56 +/- 3% (not significantly different). We have found no derangement of calcium metabolism in adults with insulin-requiring juvenile- and adult-onset diabetes regardless of treatment status. The experimental diabetic rat model does not appear to be useful for determining the pathogenesis of adult human diabetic osteopenia.

Adolescent

Renal transplantation in patients with diabetes mellitus--revisited.

Sixty-one patients with end-stage renal failure due to diabetic nephropathy received 68 renal allografts from June 1970 to February 1978. Patient and graft survival results equaled those for nondiabetic patients, as reported by the Human Renal Transplant Registry (HRTR). Renal allografts from siblings or pretreated cadaver donors had a significantly longer survival time than did allografts from nonpretreated cadaver donors. It is concluded that renal transplantation with living related and pretreated cadaver donor kidneys continues to be the treatment of choice and is superior to other forms of treatment in the insulin-dependent diabetic patient with end-stage renal disease.

Adult

Combined deficiency of glucose-6-phosphatase and fructose-1, 6-diphosphatase. Studies of glucagon secretion and fuel utilization.

An adult woman with hypoglycemia, hyperlactatemia, hyperuricemia, hypertriglyceridemia, hyperketonemia and inability to make new glucose from galactose, fructose, glycerol and alanine was found to have no hepatic glucose-6-phosphatase and deficient fructose-1,6-diphosphatase. Nonautonomous hyperglucagonemia was demonstrated and shown to contribute to the hyperlactatemia and hyperketonemia. A paradoxic hyperlactatemic response to glucose and galactose was observed. Studies of substrate utilization showed prompt adaptation to changes in dietary supply of energy which probably accounted for her never having experienced symptoms of hypoglycemia.

Adult

Direct effect of insulin on secretion of insulin, glucagon, gastric inhibitory polypeptide, and gastrin during maintenance of normoglycemia.

The direct effect of insulin on the secretion of insulin (as measured by C-peptide), glucagon, gastric inhibitory polypeptide, and gastrin was studied in normal subjects by infusing insulin while the plasma level of glucose was maintained in the normal fasting range (euglycemic clamp). Insulin-induced hypoglycemia resulted in increases in circulating glucagon and gastric inhibitory polypeptide, a decrease in C-peptide, and no change in gastrin levels. In contrast, during the euglycemic clamp, insulin was found to behave a direct suppressive effect on the secretion of glucagon, C-peptide, and gastrin, but no effect on levels of gastric inhibitory polypeptide.

Blood Glucose

Hypoglycemia.

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Blood Glucose

Normalization of plasma glucose of unstable diabetes: studies under ambulatory, fed conditions with pumped intravenous insulin.

A program using continuously pumped IVI was devised to restore glycemia of unstable diabetes under ambulatory, fed conditions to that of nondiabetic subjects. Five patients with unstable diabetes were studied. The daily regimen consisted of four meals of equal carbohydrate, fat, and protein content taken at 8 A.M., 2 P.M., 8 P.M., and 2 A.M. and 1 hr of standardized exercise in the second postprandial hour (except after the 2 A.M. meal). Confirmation of physiologic replacement of insulin by the IVI program was possible because four patients had low insulin-binding antibodies and minimal distortion of serum IRI. Best glucose control was achieved by increasing the basal flow rate (mean, 0.15 mU/kg/min) 10-fold from 15 to 60 min after daytime meals and from 15 to 105 min after the 2 A.M. meal and doubling the basal rate overnight. Contrasted to the results with SCI, the IVI program significantly improved the mean blood glucose and mean amplitude of glycemic excursions. The IVI program restored the time to glucose peak and postprandial baseline glucose recovery to normal; the amplitude of glucose increase to peak remained somewhat greater than normal.

Adult

Hypoglycemia.

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Adult

C-peptide suppression test for insulinoma.

During hypoglycemia induced by an infusion of porcine insulin, impaired suppression of endogenous insulin secretion as measured by C-peptide was demonstrated in 11 of 12 patients with insulinoma. During hypoglycemia (plasma glucose less than or equal to 40 mg/dl) the mean C-peptide immunoreactivity (CPR) of normal subjects was less than or equal to 1.2 ng/ml, whereas 11 of 12 insulinoma patients had a mean CPR of larger than or equal to 1.9 ng/ml. One patient showed normal CPR suppression by these criteria but may have shown impaired CPR suppression for glucose less than or equal to 30 mg/dl. Impaired CPR suppression during insulin-induced hypoglycemia may prove to be a useful test for insulinoma.

Adenoma, Islet Cell