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Biomedical subjects

M R Burge

Publications and source records attributed to M R Burge.

At least 19 recordsLinked to original sources
PubMed2000

Low-dose epinephrine supports plasma glucose in fasted elderly patients with type 2 diabetes.

Recent studies indicate that endogenous epinephrine provides protection against hypoglycemia in fasted elderly patients with type 2 diabetes treated with sulfonylureas. To establish a dose-response relationship and further characterize this hormonal action, 10 subjects with type 2 diabetes aged 67 +/- 1.3 years and receiving glyburide 20 mg daily were studied on 3 separate occasions. Saline placebo, half dose epinephrine ([Epi] 0.375 microg/min), and full dose Epi (0.75 microg/min) were infused during the final 10 hours of a 28-hour fast in a paired, randomized single-blind study to simulate physiologic epinephrine levels. Substrate and hormonal parameters and glucose production (Rd), disposal (Rd), and metabolic clearance rates were determined every 30 minutes. In the placebo study, the mean decline in plasma glucose during the final 10 hours of fasting was -2.7 +/- 0.6 mmol/L, compared with -0.3 +/- 0.3 mmol/L in the half dose Epi study and an actual increase in glucose of 1.0 +/- 0.8 mmol/L in the full dose Epi study (P < .001). There was a similar decline in the glucose Ra in all 3 studies, and the glucose Rd was not significantly different among the 3 study conditions. The baseline-adjusted metabolic clearance rate of glucose was significantly decreased during the epinephrine studies compared with the placebo study (P = .01). The concentration of other counterregulatory hormones did not differ between the studies. We conclude that low physiologic concentrations of epinephrine prevent the progressive decline in plasma glucose observed during fasting in elderly sulfonylurea-treated patients with type 2 diabetes. This finding may be attributable to a relative insulin resistance induced by epinephrine, resulting in a decreased rate of glucose clearance by cells.

Aged↗
PubMed1999

Isolated thyrotropin deficiency secondary to primary empty sella in a patient with differentiated thyroid carcinoma: an indication for recombinant thyrotropin.

The primary empty sella syndrome is a common radiographic finding that is rarely associated with clinical pituitary dysfunction. Studies using dynamic endocrine testing, however, have shown altered pituitary reserve in some patients with the primary empty sella syndrome. We describe a patient with a primary empty sella and an isolated deficiency of thyrotropin reserve. This case is complicated by the presence of an aggressive metastatic papillary epithelial carcinoma of the thyroid. Standard treatment with radioactive iodine was unlikely to be effective in this patient due to the need for adequate thyrotropin (TSH) stimulation of the malignant tissue to optimize uptake of radioactive iodine by the tumor cells. Consequently, this patient was treated with human recombinant TSH before receiving radioactive iodine. The utility of this novel therapeutic agent and a review of hormonal abnormalities associated with the primary empty sella are also discussed.

Carcinoma, Papillary↗
PubMed1999

Optimal administration of lispro insulin in hyperglycemic type 1 diabetes.

OBJECTIVE: Lispro is a new rapidly absorbed insulin analog. At present, there are no recommendations for the optimal injection time of lispro insulin in hyperglycemic patients. In contrast to normoglycemic patients with diabetes, we hypothesized that injection of lispro insulin 15-30 min before meal ingestion would improve postprandial glucose excursion in hyperglycemic diabetic subjects. RESEARCH DESIGN AND METHODS: In 48 randomized overnight studies, 12 healthy adult type 1 diabetic patients received lispro insulin 0.15 U/kg admixed with human ultralente 0.2 U/kg (as background insulin) subcutaneously at minutes (-30, -15, 0, and +15) relative to the ingestion of an American Diabetes Association breakfast of 8.6 kcal/kg. Pre-breakfast hyperglycemia of 10.2 +/- 0.2 mmol/l was established before the study by continuous overnight infusion of intravenous insulin, which was stopped 30 min before lispro insulin injection. Glucose and insulin levels were measured every 30 min for 5 h after breakfast. RESULTS: Results demonstrated that postprandial glucose excursion was reduced when lispro insulin was administered 15 or 30 min before the meal compared with lispro insulin injected at the meal (P < 0.002). The postprandial glucose excursion (millimoles per liter per hour) was -6.4 +/- 3 for the -30-min group, -5.1 +/- 2.9 for the -15-min group, 3.4 +/- 4.1 for the 0-min group, and 5.7 +/- 4.4 for the +15-min group. Although injecting lispro insulin at 30 min before the meal resulted in a significant reduction in postprandial glycemia, it was accompanied by loss of glucose control at 4 h postmeal in two subjects. CONCLUSIONS: Optimization of lispro insulin in hyperglycemic patients requires timing of the insulin injection at least 15 min before the meal.

Adult↗
PubMed1999

Low-dose ethanol predisposes elderly fasted patients with type 2 diabetes to sulfonylurea-induced low blood glucose.

OBJECTIVE: It has previously been demonstrated that the risk of hypoglycemia is low among otherwise healthy elderly fasted patients with type 2 diabetes taking oral sulfonylurea medications. Nevertheless, these agents do cause hypoglycemia in clinical practice, suggesting that accompanying factors must typically be present for hypoglycemia to occur. Ethanol is one putative risk factor that has not been evaluated as a mechanism for low blood glucose among sulfonylurea users. We hypothesized that low concentrations of ethanol would reduce blood glucose concentrations in elderly type 2 diabetic patients receiving sulfonylureas during a short-term fast. RESEARCH DESIGN AND METHODS: A total of 10 type 2 diabetic patients, aged 68 +/- 3 years and receiving 20 mg glyburide daily, participated in a prospective double-blind placebo-controlled in-patient study consisting of two 24-h fasts at least 1 week apart. During hours 14 and 15 of the fasting studies, subjects received intravenous infusions of either 4.35 mmol.kg-1.h-1 ethanol (equivalent to one or two alcoholic beverages) or saline placebo in random order. Ethanol, plasma glucose, insulin, and counterregulatory hormones were assessed very 30-60 min during the final 10 h of the fast. RESULTS: Blood ethanol levels peaked at 17 +/- 2 mmol/l (the lower legal limit of intoxication in New Mexico) during the ethanol study. Plasma glucose concentrations did not differ at baseline (placebo 8.5 +/- 1.8 vs. ethanol 8.7 +/- 1.7 mmol/l; P = 0.50), but nadir plasma glucose was lower after the ethanol infusion compared with placebo (4.4 +/- 1.2 vs. 5.0 +/- 1.4 mmol/l; P = 0.01), and the absolute decline in plasma glucose was also greater during the ethanol study than the placebo study (4.7 +/- 0.9 vs. 3.6 +/- 1.2 mmol/l; P = 0.01). Counterregulatory hormone levels were increased during the ethanol study and nonesterified fatty acid concentrations were suppressed compared with the placebo study. CONCLUSIONS: Low doses of ethanol predispose fasted elderly type 2 diabetic patients to low blood glucose during a short-term fast. This may be one of several mechanisms by which sulfonylurea-induced hypoglycemia occurs in elderly patients.

Administration, Oral↗
PubMed1998

A prospective trial of risk factors for sulfonylurea-induced hypoglycemia in type 2 diabetes mellitus.

CONTEXT: Retrospective studies have identified oral sulfonylureas, age, and fasting as major risk factors for hypoglycemia in patients with type 2 diabetes. Sulfonylureas may be withheld from elderly patients out of concern for hypoglycemia. OBJECTIVE: To evaluate the hypoglycemic effects of maximum doses of once-daily second-generation sulfonylureas administered to fasting elderly patients. DESIGN: A prospective, randomized, double-blind clinical trial. SETTING: The University of New Mexico General Clinical Research Center. PATIENTS: Fifty-two sulfonylurea-treated subjects with type 2 diabetes with a mean (SD) age of 65.1 (5.7) years. INTERVENTIONS: Subjects were randomly assigned to glyburide or glipizide gastrointestinal therapeutic system (GITS). Each subject participated in three 23-hour fasting studies after the sequential administration of 1 week of placebo and 1 week of 10 mg and 1 week of 20 mg of the assigned sulfonylurea. MAIN OUTCOME MEASURES: Occurrence of hypoglycemia (defined as plasma glucose level <3.33 mmol/L [60 mg/dL]) and hormonal parameters during the final 9 hours of the 23-hour fast in patients who had taken sulfonylureas vs placebo. RESULTS: No hypoglycemia was observed during 156 fasting studies. Plasma glucose level was decreased (nadir, 4.9 mmol/L [88 mg/dL] for a 20-mg dose of glyburide vs 8.3 mmol/L [150 mg/dL] for placebo; nadir, 5.8 mmol/L [105 mg/dL] for a 20-mg dose of glipizide GITS vs 8.7 mmol/L [157 mg/dL] for placebo), and serum insulin was increased in the sulfonylurea studies compared with placebo (P<.001). Plasma glucose parameters did not differ between the 2 sulfonylureas, but C peptide concentrations were increased in the glyburide group compared with glipizide GITS in the 20-mg study (P=.05). Concentrations of epinephrine were increased in the sulfonylurea studies compared with placebo (P<.001). Epinephrine secretion increased when glucose concentration fell below the mean (SD) level of 9.10 (2.66) mmol/L (164 [48] mg/dL) in the 10-mg study and 8.77 (2.83) mmol/L (158 [51] mg/ dL) in the 20-mg study. CONCLUSIONS: Fasting was well tolerated among these elderly patients with type 2 diabetes treated with sulfonylureas. Older age should not be considered a contraindication to sulfonylurea treatment for diabetes. Stimulation of epinephrine secretion at normal or elevated plasma glucose levels appears to be the primary mechanism of protection against hypoglycemia in this study.

Age Factors↗
PubMed1998

Risks of complication following thyroidectomy.

OBJECTIVE: Because hypoparathyroidism is a serious complication of thyroidectomy, we attempted to elucidate factors determining the risk of this postoperative outcome. SETTING: Four tertiary care hospitals in Albuquerque, New Mexico. PATIENTS: A retrospective study of 142 patients who underwent total or subtotal thyroidectomy between 1988 and 1995. MEASUREMENTS AND MAIN RESULTS: Permanent hypoparathyroidism was defined as hypocalcemic symptoms plus a requirement for oral vitamin D or calcium 6 months after thyroidectomy. Factors analyzed to determine their contribution to the risk of persistent postoperative hypoparathyroidism were the indication for thyroidectomy, performance of a preoperative thyroid needle biopsy, type of surgery, postoperative pathology, presence and stage of thyroid carcinoma, resident surgeon involvement, and specialty of the surgeon performing the procedure. Surgical specialty and stage of thyroid carcinoma were independent risk factors for persistent postoperative hypoparathyroidism by multivariate analysis. Nine (29%) of 31 patients who had thyroidectomy by otolaryngologists met criteria for permanent hypoparathyroidism, and 6 (5%) of 111 patients who had thyroidectomy by general surgeons met the same criteria (p < .001). Adjustment for the effect of stage did not eliminate the effect of specialty (p = .006), and adjustment for the effect of specialty did not eliminate the effect of stage (p = .02), on the occurrence of postoperative hypoparathyroidism. CONCLUSIONS: We conclude from our data that patients undergoing thyroidectomy by an otolaryngologist may be at a higher risk of permanent postoperative hypoparathyroidism than patients who undergo thyroidectomy by a general surgeon. This may reflect differences in case selection or surgical approach or both.

Administration, Oral↗
PubMed1998

Prospective evaluation of risk factors for exercise-induced hypogonadism in male runners.

Exercise-induced hypogonadotropic hypogonadism is well recognized among female endurance athletes but is less commonly observed in male endurance athletes. We have reported a well-characterized case of severe acquired hypogonadotropic hypogonadism in a male distance runner with osteopenia, stress fracture, and sexual dysfunction. Using this case as an index, we hypothesized that the presence of 1 or more specific risk factors would prospectively identify male endurance athletes with exercise-induced hypogonadotropic hypogonadism. These include a history of stress fracture, sexual dysfunction, or the initiation of endurance exercise before age 18 years. We studied 28 male endurance runners younger than 50 years who ran more than 40 miles per week. Of these runners, 15 had 1 or more of the above risk factors (group 1), and the remaining 13 had none of the putative risk factors (group 2). A group of 10 sedentary control subjects was also studied (group 3). There was no difference between groups 1 and 2 in weekly training mileage. Group 1 was younger than group 2 (32 +/- 10 years versus 39 +/- 6 years, P < .05) and had a lower body mass index (22.4 +/- 1.9 kg per m2 versus 23.9 +/- 2.2 kg per m2, P < .05). By bioelectric impedance, preliminary data showed that group 1 had a reduced body fat content (group 1, 14.5% +/- 2.8%; group 2, 16.9% +/- 2.0%; and group 3, 17.5% +/- 4.1%; P < .05). Fasting morning concentrations of free testosterone (group 1, 45.3 +/- 26.4 pmol/l; group 2, 88.8 +/- 24.3 pmol/l; and group 3, 69.1 +/- 21.5 pmol/l) and luteinizing hormone (group 1, 1.7 +/- 0.7 IU per liter; group 2, 2.0 +/- 1.1 IU per liter; and group 3, 1.9 +/- 0.6 IU per liter) did not differ among the groups (P > .05). One subject with primary hypogonadism was identified in group 1. The presence of the aforementioned risk factors does not predict the occurrence of exercise-induced hypogonadotropic hypogonadism among male endurance runners in this pilot study. A larger sample size or more discriminating risk factors (or both) may be necessary to identify this uncommon but potentially debilitating condition.

Adult↗
PubMed1997

Small cell carcinoma of the vagina causing Cushing's syndrome by ectopic production and secretion of ACTH: a case report.

BACKGROUND: Small cell carcinomas of pulmonary or extrapulmonary origin are neuroendocrine tumors classically associated with ectopic hormone production, particularly ACTH secretion resulting in Cushing's syndrome. However, ectopic Cushing's syndrome has not previously been reported in the setting of small cell carcinoma of the vagina. METHODS: A primary vaginal tumor with hepatic metastases was evaluated with light microscopy. Serum cortisol and plasma ACTH levels were evaluated by radioimmunoassay and immunoradiometric assay, respectively, during a standard high-dose (8 mg) overnight dexamethasone suppression test. RESULTS: Vaginal small cell carcinoma with hepatic metastases was demonstrated. Electrolyte abnormalities, elevated cortisol and ACTH levels, and failure to suppress ACTH secretion during high-dose dexamethasone administration confirmed the diagnosis of ectopic ACTH syndrome. CONCLUSIONS: This case report establishes a clinical association between vaginal small cell carcinoma and ectopic Cushing's syndrome, confirming the neuroendocrine potential of this malignancy and features common to small cell neoplasms originating in other sites.

ACTH Syndrome, Ectopic↗
PubMed1997

Idiopathic hypogonadotropic hypogonadism in a male runner is reversed by clomiphene citrate.

OBJECTIVE: To assess the efficacy of estrogen antagonist therapy on the function of the hypothalamic-pituitary-testicular axis in a young male runner with significant morbidity attributable to idiopathic hypogonadotropic hypogonadism. DESIGN: An uncontrolled case study. SETTING: The outpatient endocrinology clinic of a university tertiary referral center. PATIENT(S): A 29-year-old male who has run 50 to 90 miles per week since 15 years of age and who presented with a pelvic stress fracture, markedly decreased bone mineral density, and symptomatic hypogonadotropic hypogonadism. INTERVENTION(S): Clomiphene citrate (CC) at doses up to 50 mg two times per day over a 5-month period. MAIN OUTCOME MEASURE(S): Serum concentrations of LH, FSH, and T before and after CC therapy, as well as clinical indicators of gonadal function. RESULT(S): Barely detectable levels of LH and FSH associated with hypogonadal levels of T were restored to the normal range with CC therapy. The patient experienced improved erectile function, increased testicular size and sexual hair growth, and an improved sense of well being. CONCLUSION(S): Exercise-induced hypogonadotropic hypogonadism exists as a clinical entity among male endurance athletes, and CC may provide a safe and effective treatment option for males with debilitating hypogonadism related to endurance exercise.

Adult↗
PubMed1997

Insulins.

More than ever before in the history of diabetes therapy, patients and health care providers have the necessary pharmacologic tools available to achieve near-normal blood glucose control. Achievement of this goal, however, requires an in-depth knowledge of the pharmacology and limitations of the currently available insulins. A willingness to try new strategies combined with a creative approach to each patient will result in optimal diabetes management. Continued advances in the development of insulin analogues and investigation into alternative routes of insulin delivery are likely to expand therapeutic options in the near future. Such developments will continue to improve the quality of life and health of patients with diabetes.

Animals↗
PubMed1997

Prolonged efficacy of short acting insulin Lispro in combination with human ultralente in insulin-dependent diabetes mellitus.

Insulin Lispro is a newly FDA approved analog of human insulin that exhibits rapid absorption and a short duration of action after sc injection. Although Lispro insulin improves immediate postprandial glycemia compared to Regular insulin, long term trials of Lispro insulin have not shown improvement in overall glycemic control, as determined by glycosylated hemoglobin. We hypothesize that this lack of improvement is attributable to the development of late postprandial hyperglycemia secondary to a waning of Lispro insulin's effect in conjunction with continued meal absorption. This study was designed to evaluate the duration of Lispro-induced reductions in plasma glucose after a standardized meal when Lispro insulin is incorporated into a regimen typically employed in insulin-dependent diabetes mellitus. After establishment of euglycemia overnight, 12 healthy IDDM patients received human Ultralente insulin (0.2 U/kg) alone and in combination with each of the following treatments in random sequence immediately before ingesting a 750-Cal American Diabetes Association breakfast: 1) 0.15 U/kg human Regular insulin (Regular 0.15 group), 2) 0.15 U/kg Lispro insulin (Lispro 0.15 group), 3) 0.1 U/kg Lispro insulin (Lispro 0.1 group), and 4) an equimolar (1:1) mixture of Lispro and Regular insulins (0.15 U/kg; 1:1 Mix group). Glucose and hormonal parameters were assessed for 8 h after the meal. Peak postprandial glucose was increased in the Regular insulin group compared to that in all groups that incorporated Lispro insulin (P < 0.001). Glucose area under the curve (AUC) was decreased in the Lispro 0.15 group compared to that in the Lispro 0.1 group, and glucose AUC was decreased in the Lispro 0.15 and 1:1 Mix groups compared to that in the group given Regular insulin (P < 0.001). Mean plasma glucose concentrations during the final hour of study were increased in the Ultralente group compared with those in all other treatment groups and were increased in the Lispro 0.1 group compared with those in the Regular, Lispro 0.15, and 1:1 Mix groups (P < 0.05). Insulin AUC was significantly reduced in the Lispro 0.1 group compared to those in all other short acting insulin groups (P < 0.001), and time to peak insulin was more rapid in the two Lispro groups than those in all other treatment groups (P < 0.01). The glucagon response was significantly greater in the Ultralente group compared to those with all other treatments. There was no difference in the development of hypoglycemia between the groups. This study demonstrates that the reductions in plasma glucose effected by Lispro insulin are consistent and stable for 8 h after meal ingestion when Lispro insulin is used in combination with human Ultralente insulin. These findings suggest that improvement in overall glycemia, as assessed by glycosylated hemoglobin, may be achievable with Lispro insulin if adequate doses are administered.

Adult↗
PubMed1997

Meal composition is a determinant of lispro-induced hypoglycemia in IDDM.

OBJECTIVE: Lispro is a newly FDA-approved analog of human insulin that will be widely used in patients with IDDM. This insulin, however, may have an increased potential for hypoglycemia because of its very rapid subcutaneous absorption, especially in a setting of decreased carbohydrate intake. Using a short-term prospective randomized parallel group-study design, we studied the incidence of hypoglycemia when lispro was given before breakfast compared with regular human insulin. Since carbohydrate intake is a determinant of postprandial glycemia, we administered three isocaloric meals characterized by low, average, and high carbohydrate content. RESEARCH DESIGN AND METHODS: Two groups of six IDDM subjects were randomized to receive 0.15 U/kg of lispro or regular human insulin subcutaneously before the ingestion of three 500-kcal breakfast meals of differing carbohydrate content on separate days. Lispro was administered at mealtime, and regular insulin was administered 30 min before mealtime. RESULTS: Postprandial plasma glucose concentrations were decreased in the lispro group compared with the regular-insulin group for all three meal types (P < 0.05), and hypoglycemia developed more frequently and rapidly in the lispro group, compared with the regular-insulin group by survival analysis. Additionally, peak insulin concentrations were higher (P < 0.001) and peaked more rapidly (P < 0.05) in the lispro group, compared with the regular-insulin group. CONCLUSIONS: We conclude that lispro has a tendency for early postprandial hypoglycemia compared with regular insulin in the setting of reduced carbohydrate intake. This fact should be told to patients who decide to switch from regular insulin to lispro. Health care professionals should instruct their IDDM patients to monitor glucose levels frequently after switching to lispro since adjustments in their carbohydrate intake and/or their lispro dosage may be necessary to avoid hypoglycemia.

Adult↗
PubMed1996

Diabetes mellitus: 2. Managing type II disease.

For a large and growing number of people in the United States, too much fatty food, too little activity, and an inherited tendency toward insulin resistance add up to type II diabetes. Improved diet and regular exercise are the ideal therapy. But most patients also require pharmacologic intervention to keep the disorder in check and to ward off microvascular and macrovascular and complications.

Adult↗
PubMed1996

Diabetes mellitus: 1. Improving control in type I disease.

Current consensus stresses intensive insulin therapy, with the goal of bringing blood glucose levels to near normal. Achieving and maintaining that goal involves educating the patient, encouraging regular glucose determinations, and gradually adjusting the dosage and timing of insulin administration to match the patient's glucose levels and lifestyle.

Adult↗