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Biomedical subjects

F J Service

Publications and source records attributed to F J Service.

At least 37 records · Page 2Linked to original sources
PubMed1994

Proinsulin by immunochemiluminometric assay for the diagnosis of insulinoma.

We used a newly developed immunochemiluminometric assay of proinsulin to determine its relative utility vis-à-vis C-peptide and insulin for the diagnosis of insulinoma. The evaluation was conducted in 20 consecutive patients with histologically confirmed insulinoma and 22 normal subjects who underwent a prolonged fast according to a standard protocol. Patients with insulinoma fasted to the point of demonstrating Whipple's triad; normal subjects fasted to 72 h. At the end of the prolonged fast, when the glucose value was 2.8 mmol/L or less (50 mg/dL), all three hormones had equal sensitivity (100%) in detecting insulinoma with no overlap with the values of normal subjects. When glucose levels were between 2.8 mmol/L (50 mg/dL) and 3.3 mmol/L (60 mg/dL) at the end of the prolonged fast, proinsulin was better than C-peptide and insulin in the diagnosis of insulinoma. The sensitivity was 90% for proinsulin and 85% for both C-peptide and insulin. Therefore, proinsulin not only is useful for the diagnosis of insulinoma, but it may have greater diagnostic accuracy than C-peptide and insulin.

Animals↗
PubMed1993

Non-response bias in studies of diabetic complications: the Rochester Diabetic Neuropathy Study.

Non-response can bias studies of disease conditions but its influence has rarely been evaluated due to limitations of available data on the non-respondents. Because of a detailed medical record review for eligibility, we were able to compare clinical as well as demographic characteristics of respondents and non-respondents in a population-based study of diabetic complications among Rochester, Minnesota residents. Non-respondents were older, less well educated, more likely to be widowed and more often retired. They were much more likely to have cardiovascular disease at baseline, but the prevalence of retinopathy, nephropathy and diabetic neuropathy was similar for respondents and non-respondents, who were also comparable with regard to type of diabetes and diabetic therapy. While these findings indicate that data from the Rochester Diabetic Neuropathy Study can probably be generalized to diabetic residents generally, they reemphasize the potential for non-response bias in epidemiologic studies of clinical conditions, especially cardiovascular disease.

Age Factors↗
PubMed1993

Hypertension and dyslipidemia in patients with insulinoma.

Hyperinsulinemia is alleged to contribute to the pathogenesis of hypertension and dyslipidemia (hypertriglyceridemia) in the setting of insulin resistance. To assess the association among hyperinsulinemia, hypertension, and hypertriglyceridemia in the absence of insulin resistance, we determined their prevalence in a large cohort of patients with insulinoma (N = 250). In this retrospective case-control study, patients with insulinoma were matched by age, gender, race, and year of operation with 217 control patients admitted to the hospital for elective cholecystectomy. Mean preoperative blood pressure measurements were compared between study patients and control patients. In addition, age-, gender-, and race-specific percentiles of blood pressure were compared with data from the National Health and Nutrition Examination Survey I, and those of triglycerides (N = 65) and cholesterol (N = 70) were compared with Mayo Clinic normal reference data. The study group consisted of 105 men and 145 women; the median age was 41 years (range, 8 to 82). The median duration of symptoms before operation was 1.9 years (range, 0.05 to 40 years). After adjustment for body mass index, no statistically significant differences in systolic and diastolic blood pressure were noted between patients with insulinoma and matched control patients (131 +/- 19 versus 128 +/- 18 mm Hg and 81 +/- 11 versus 79 +/- 9 mm Hg, respectively). No relationship was observed between duration of hyperinsulinemia (as long as 40 years) and blood pressure. The age- and gender-specific percentiles of systolic and diastolic blood pressure of the patients with insulinoma did not differ from the age- and gender-specific percentiles for the general white population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

C-peptide during the prolonged fast in insulinoma.

C-Peptide, a marker for insulin secretion, is purported to be elevated in patients with insulinoma but diagnostic criteria have not been established. Thirty-seven patients with histologically confirmed insulinoma studied preoperatively, 19 normal subjects, and 2 patients who subsequently acknowledged self-administration of insulin underwent the prolonged fast (< or = 72 h) according to a standard protocol. Plasma glucose, C-peptide, and insulin were measured every 6 h until plasma glucose was less than or equal to 3.3 mmol, then hourly until Whipple's triad was demonstrated or until 72 h without symptoms was reached. At the termination of the fasts, plasma was analyzed for sulfonylurea. Statistical analysis was by rank sum test. Data are expressed as median (range). The durations of fasts were 20 (2.5-68) h for patients with insulinomas and 72 h for normal subjects. At the end of fasts plasma glucose, C-peptide, and insulin concentrations were 2.2 (1.4-2.9) vs. 3.6 (2.7-5.5) mmol, P < 0.001; 0.60 (0.20-1.92) vs. 0.13 (0.07-0.43) nmol, P < 0.001; and 126 (35-840) vs. 35 (35-126) pmol, P < 0.001, respectively, for insulinoma patients and normal subjects. All plasma samples were negative for sulfonylurea. Insulinoma patients had C-peptide values at the end of the fasts greater than or equal to 0.20 nmol whereas normal subjects and patients with insulin factitial hypoglycemia had C-peptide concentrations less than or equal to 0.10 nmol when plasma glucose was less than or equal to 2.8 mmol. Insulinoma is confirmed in a sulfonylurea negative patient with Whipple's triad during the prolonged fast and a concomitant C-peptide concentration greater than or equal to 0.20 nmol.

Adolescent↗
PubMed1993

Insulin surrogates in insulinoma.

Universally accepted criteria for relative hyperinsulinemia have not been established for the diagnosis of insulinoma. Therefore, we sought measures of insulin action which might act as surrogates for insulin measurements and thereby contribute to the assessment of hyperinsulinemia. Since insulin is antilipolytic, antiketogenic, and glycogenic we measured plasma beta-hydroxybutyrate, FFA, and the response of plasma glucose to iv glucagon at the end of the prolonged fast in 40 patients, later confirmed histologically to have insulinoma and 25 normal persons. Plasma beta-hydroxybutyrate and FFA concentrations were significantly lower in the patients with insulinoma (median, range), (0.3, 0.1-2.7 vs. 4.5, 1.2-7.0 mmol, P < 0.0001, and 1.03, 0.17-1.75 vs. 1.79, 1.17-3.12 mmol, P < 0.001, respectively), whereas the responses of plasma glucose to glucagon were significantly greater (3.0, 1.4-5.4 vs. 0.7, 0.0-1.3 mmol, P < 0.001) than in the normals. For patients with insulinoma (20/40) and normal subjects (13/25) with plasma glucose less than or equal to 3.3 mmol and plasma insulin and C-peptide concentrations in the normal overnight fasting range, conditions in which hyperinsulinemia is most difficult to assess, a clear distinction was provided by plasma glucose response to glucagon and plasma beta-hydroxybutyrate but not by plasma FFA, plasma insulin, nor plasma C-peptide. We conclude that plasma glucose response to iv glucagon greater than or equal to 1.4 mmol and plasma beta-hydroxybutyrate less than or equal to 2.7 mmol, at the end of the prolonged fast are indicative of hyperinsulinemia of insulinoma when the plasma glucose is less than or equal to 3.3 mmol. In this plasma glucose range these insulin surrogates provide better diagnostic accuracy than plasma insulin and C-peptide.

3-Hydroxybutyric Acid↗
PubMed1993

The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study.

The magnitude of the health problem from diabetic neuropathies remains inadequately estimated due to the lack of prospective population-based studies employing standardized and validated assessments of the type and stage of neuropathy as compared with background frequency. All Rochester, Minnesota, residents with diabetes mellitus on January 1, 1986, were invited to participate in a cross-sectional and longitudinal study of diabetic neuropathies (and also of other microvascular and macrovascular complications). Of 64,573 inhabitants on January 1, 1986 in Rochester, 870 (1.3%) had clinically recognized diabetes mellitus (National Diabetes Data Group criteria), of whom 380 were enrolled in the Rochester Diabetic Neuropathy Study. Of these, 102 (26.8%) had insulin-dependent diabetes mellitus (IDDM), and 278 (73.2%) had non-insulin-dependent diabetes mellitus (NIDDM). Approximately 10% of diabetic patients had neurologic deficits attributable to nondiabetic causes. Sixty-six percent of IDDM patients had some form of neuropathy; the frequencies of individual types were as follows: polyneuropathy, 54%; carpal tunnel syndrome, asymptomatic, 22%, and symptomatic, 11%; visceral autonomic neuropathy, 7%, and other varieties, 3%. Among NIDDM patients, 59% had various neuropathies; the individual percentages were 45%, 29%, 6%, 5%, and 3%. Symptomatic degrees of polyneuropathy occurred in only 15% of IDDM and 13% of NIDDM patients. The more severe stage of polyneuropathy, to the point that patients were unable to walk on their heels and also had distal sensory and autonomic deficits (stage 2b) occurred even less frequently--6% of IDDM and 1% of NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Insulinoma in a patient with NIDDM.

OBJECTIVE: To confirm insulinoma as the cause of hypoglycemia in a patient with NIDDM and determine the frequency of the co-occurrence of these two conditions. RESEARCH DESIGN AND METHODS: The patient underwent an in-hospital prolonged fast (< or = 72 h), according to standard protocol, and an ultrasound examination of the pancreas. All cases of histologically confirmed insulinoma at this institution over the period of 1927-1992 were reviewed to determine the prevalence of pre-existent diabetes mellitus. RESULTS: After 10 h of fasting, plasma glucose was low (1.89 mM); plasma insulin (258 pM) and C-peptide (1.39 nM) were elevated in the absence of sulfonylurea in the plasma. An insulinoma detected by ultrasonography was removed surgically with subsequent reoccurrence of insulin-requiring diabetes. Among 313 cases of insulinoma confirmed at this institution, this patient is the only one with pre-existent diabetes mellitus. CONCLUSIONS: Insulinoma occurs extraordinarily rarely in patients with pre-existing NIDDM.

Blood Glucose↗
PubMed1993

Reoperative insulinomas, 1927 to 1992: an institutional experience.

BACKGROUND: Between 1927 and 1992, 313 patients have undergone surgery for insulinoma(s) at our institution, 12% of which were reoperations. We retrospectively reviewed all cases (n = 39) of reoperative surgery for persistent hyperinsulinism to identify changing patterns in surgical approach, morbidity, and outcome and to evaluate the influence of preoperative and intraoperative localization studies. METHODS: The diagnosis of endogenous hyperinsulinism has evolved from satisfying Whipple's triad to documenting concomitant hypoglycemia and endogenous hyperinsulinemia. Thirty-nine patients were divided into two groups for comparison: those treated before localization studies were available (1927 to 1967) (n = 17) and those treated since that time (n = 22). Initial operations were also compared with reoperations among these 39 patients. RESULTS: There were 26 women and 13 men (mean age, 42 years). There was at least one positive preoperative localization study in 16 of 22 patients (73%). Intraoperative ultrasonogram and careful palpation successfully identified 10 of 11 tumors in the reoperative setting. Blind or completion pancreatectomies were common before 1967 (10 of 17 patients). Since 1967, 14 of 22 patients have undergone enucleation of their primary tumor. Operative morbidity increased from 21% to 58% with reoperation but decreased from 65% to 29% (p = 0.026) when comparing the preangiography to the postangiography eras. The development of iatrogenic diabetes mellitus occurred in 13 patients (33%) after reoperation. Forty-one percent had diabetes before 1967 and 27% since that time (p = not significant). Thirty-four of 36 patients (94%) without malignant tumors were cured by reoperation. There was one operative death. Survival for patients who underwent completion or total pancreatectomy was significantly reduced (p = 0.003). CONCLUSIONS: Reoperations for persistent hyperinsulinism can be highly successful in experienced hands. These reoperations, however, are associated with increased morbidity and iatrogenic diabetes. With experience and the use of selected localization studies, first-time failures can be avoided in most cases thus reducing the need for reoperations and its inherent sequelae.

Adolescent↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

Pancreas transplantation at Mayo: III. Multidisciplinary management.

Although pancreas transplantation is a complicated procedure, a good level of success has been achieved because of the introduction of cyclosporine for immunosuppression, improved methods for diagnosing rejection, and a multidisciplinary approach to management. Our immunosuppressive regimen was quadruple therapy with induction by using Minnesota antilymphoblastic globulin. A biopsy technique was instituted in which the pancreas specimens were obtained under cystoscopic direction during episodes of hypoamylasuria. The criteria for rejection episodes were not only biochemical abnormalities but also histologic confirmation and a follow-up to exclude other causes of graft dysfunction. Infectious disease management included use of oral selective bowel decontamination for 3 weeks after transplantation. At the Mayo Clinic between October 1987 and December 1988, 16 patients received pancreaticoduodenal allografts (both kidney and pancreas in 13 and pancreas only in 3 after a prior successful kidney transplantation). In two pancreas and one kidney allograft, function was lost. One patient died of multiorgan failure. The cystoscopically directed biopsy technique was performed 23 times with minimal complications and a 93% success rate. The metabolic results have been excellent; the glycosylated hemoglobulin level was normal 3 to 6 months after transplantation. The quality of life was significantly improved in almost all patients. Nutritional assessment revealed little deterioration after transplantation. With a multidisciplinary approach, the needed answers about the effect of pancreas transplantation on the degenerative complications of diabetes should be forthcoming.

Adult↗
PubMed1990

Lack of effect of gastric inhibitory polypeptide on hepatic and extrahepatic insulin action.

To assess the influence of enteric factors on insulin action, seven lean healthy subjects were studied under conditions of hyperinsulinemic euglycemic glucose clamp, double isotope administration, and enteral vs. parenteral glucose infusion. In random order, glucose and mannitol radiolabeled with [2-3H]glucose were infused intraduodenally for 4 h while the systemic rate of glucose turnover was assessed by [6-14C]glucose. During the final hour of the study, plasma glucose, insulin, C-peptide, glucagon, cholecystokinin, and neurotensin were similar under both experimental conditions. Despite an increase in gastric inhibitory polypeptide concentration during combined enteral and iv glucose infusion to levels that mimicked meal ingestion, total glucose infusion rate, insulin-induced stimulation of glucose uptake, and insulin-induced suppression of hepatic glucose release were comparable to those observed during iv glucose administration. These data indicate that under conditions of modest hyperinsulinemia and euglycemia, gastric inhibitory polypeptide did not influence hepatic or extrahepatic insulin action.

Adult↗
PubMed1990

Meal-related insulin requirements.

Postprandial glycemia correlates with meal size in insulin dependent diabetic and nondiabetic persons. Decline in meal tolerance as the day progresses noted in nondiabetics does not occur in IDDM. Meal size correlates with insulin secretion in nondiabetics and amounts of insulin infused by an artificial endocrine pancreas to IDDM. There is no diurnal change in insulin secretion in nondiabetics or insulin infusion into IDDM but not amounts of insulin secretions by nondiabetics. Sequence of meal ingestion influenced amounts of insulin infused into IDDM. It is unclear to what extent variation in carbohydrate contribution or composition affect postprandial events. More precise quantitative measures of meal-related glucose behavior such as mean indices of meal excursions may be useful. CSII used in IDDM has been shown to normalize postprandial endogenous glucose production.

Blood Glucose↗