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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
PubMed2001

Differential effects of fasting and dehydration in the pathogenesis of diabetic ketoacidosis.

Glycemia varies widely in patients with diabetic ketoacidosis (DKA), with plasma glucose concentrations between 10 to 50 mmol/L commonly encountered. The mechanism of this glycemic variability is uncertain. Our study examined the differential effects of fasting and dehydration on hyperglycemia induced by withdrawal of insulin in type 1 diabetes. To evaluate the respective roles of dehydration and fasting in the pathogenesis of DKA, 25 subjects with type 1 diabetes were studied during 5 hours of insulin withdrawal before (control) and after either 32 hours of fasting (n = 10) or dehydration of 4.1% +/- 2.0% of baseline body weight (n = 15). Samples were obtained every 30 minutes during insulin withdrawal for substrate and counterregulatory hormone levels and rates of glucose production and disposal. Fasting resulted in reduced plasma glucose concentrations compared with the control study, while dehydration resulted in increased plasma glucose concentrations compared with the control study (P < .001). Glucose production and disposal were decreased during the fasting study and increased during the dehydration study compared with the control study. Glucagon concentrations and rates of development of ketosis and metabolic acidosis were increased during both fasting and dehydration compared with control. These data suggest that fasting and dehydration have differential effects on glycemia during insulin deficiency, with dehydration favoring the development of hyperglycemia and fasting resulting in reduced glucose concentrations. This finding is probably attributable to the differing effect of these conditions on endogenous glucose production, as well as to differences in substrate availability and counterregulatory hormone concentrations. The severity of pre-existing fasting and dehydration likely explains much of the variability in plasma glucose concentrations observed in DKA.

Adult↗
PubMed2001

Effect of short-term glucose control on glycemic thresholds for epinephrine and hypoglycemic symptoms.

Hypoglycemia is the principal barrier to achieving target glucose goals in type 2 diabetes. The effect of short-term improvement in glycemic control on plasma glucose thresholds for symptomatic and hormonal responses to hypoglycemia in type 2 diabetes is not known. We hypothesized that the thresholds for these events would be increased by 1 wk of improved glycemic control in elderly patients with type 2 diabetes. Ten elderly patients with type 2 diabetes were admitted for an 8-d inpatient protocol. All subjects underwent insulin-induced hypoglycemia on days 2 (preglucose control) and 8 (postglucose control). Between days 2 and 8, subjects received intensive diabetes management to improve their glycemic control. Timed blood glucose profiles were obtained daily during the week before and during admission. Plasma glucose, counterregulatory hormones, and hypoglycemic symptoms were assessed at baseline and every 10 min during the hypoglycemic studies. Mean blood glucose concentrations were significantly reduced by intensive diabetes management from 9.8 +/- 3.7 mmol/liter to 7.7 +/- 3.3 mmol/liter (P < 0.001). The plasma glucose threshold for epinephrine release during insulin-induced hypoglycemia was significantly increased by intensive management from a glucose concentration of 3.7 +/- 0.5 mmol/liter at baseline to 3.1 +/- 0.3 mmol/liter after intensive management (P < 0.05). The plasma glucose threshold for hypoglycemic symptoms was also increased by intensive therapy from a glucose concentration of 5.3 +/- 1.2 to 3.3 +/- 0.6 mmol/liter (P = 0.003). These rapid changes may increase the risk for severe hypoglycemia in type 2 diabetes and limit the ability of physicians to rapidly correct hyperglycemia in elderly type 2 diabetes patients.

Aged↗
PubMed2001

How low can you go? Chronic hypoglycemia versus normal glucose homeostasis.

BACKGROUND: Set point errors in glucose homeostasis that result in chronic, mild hyperglycemia in the setting of maturity onset diabetes of the young have been described. Similar set point errors may exist that result in chronic, asymptomatic glucopenia. CASE: A healthy 39-year-old female was referred for evaluation of chronic, persistent, and asymptomatic glucopenia that persisted over the prior several years with a record of numerous random plasma glucose concentrations between 35 and 45 mg/dL. She denied ethanol intake and family history of hypoglycemia or diabetes. She was not taking any medications known to cause hypoglycemia, and a urine sulfonylurea screen was negative. Fasting insulin and C-peptide levels were not elevated, and pancreatic imaging studies were normal. We hypothesized that this patient possessed an error in glucose metabolism that resulted in chronic, asymptomatic glucopenia. RESULTS: In a series of clinical studies, we demonstrated a nadir plasma glucose concentration of 35 mg/dL in the absence of symptoms during a 60-hour fast. C-peptide secretion was appropriately suppressed during symptomatic hypoglycemia with exogenous insulin infusion, and counterregulatory hormone secretion was intact during insulin-induced symptomatic hypoglycemia. Finally, the patient demonstrated an incremental increase in insulin concentration in response to minimal increases in plasma glucose during a sequential, stepped infusion of 10% dextrose. CONCLUSIONS: We conclude that this patient exhibits features of a set point error in glucose homeostasis that manifests as chronic, asymptomatic glucopenia. Although the mechanism for this condition remains to be elucidated, such set point errors do exist and should be considered in the differential diagnosis of chronic hypoglycemia.

Adult↗
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↗
PubMed2000

What are the barriers to medical care for patients with newly diagnosed diabetes mellitus?

CONTEXT: Few data are available describing factors that prevent patients with newly diagnosed diabetes from seeking medical care. OBJECTIVE: To identify socioeconomic factors that act as barriers to healthcare among such patients. SETTING: A community-wide diabetes screening programme. PARTICIPANTS: One hundred and eighteen patients with newly identified diabetes mellitus out of 1,824 total screenings. INTERVENTIONS: Each newly identified person with diabetes was instructed to contact a physician for follow-up care. DESIGN: A follow-up survey was obtained from 89 (75%) subjects 9 +/- 7 months after diagnosis. MAIN OUTCOME MEASURE: Whether or not subjects had obtained follow-up care for their diabetes. RESULTS: Of seven variables examined, only lack of health insurance correctly predicted those patients who failed to seek medical care for their diabetes by multivariate analysis. CONCLUSIONS: Lack of health insurance coverage is the primary reason that patients with newly diagnosed diabetes fail to seek medical care.

Age Distribution↗
PubMed2000

Potato-lactulose breath hydrogen testing as a function of gastric motility in diabetes mellitus.

OBJECTIVE: Scintigraphic determination of gastric emptying is the current standard for the assessment of gastric motility and the diagnosis of diabetic gastroparesis. However, such studies are expensive, inconvenient, and involve exposure to radiation. Because the time course of breath hydrogen (H2) excretion after ingestion of lactulose correlates with upper gastrointestinal transit time, we hypothesized that patients with diabetic gastroparesis would exhibit prolonged breath H2 excretion after ingestion of a test meal containing complex carbohydrate and lactulose compared to subjects without diabetes and subjects with diabetes but without gastroparesis. RESEARCH DESIGN AND METHODS: Ten healthy subjects without diabetes, 10 subjects with diabetes but without gastroparesis (gastric emptying T1/2,T1/2 < 90 minutes), and 10 subjects with diabetes and previously diagnosed gastroparesis (T1/2 > 90 minutes) were admitted for a single 24-hour study. Gastric motility agents were withheld 24 hours prior to the study. Euglycemia was established and maintained overnight in subjects with diabetes with continuous intravenous insulin infusion. At 6:00 AM, all subjects ingested a breakfast containing 100 g of cooked potato starch and 20 g lactulose. Breath H2 excretion was monitored at baseline and every 30 minutes for 12 hours after ingestion of the test meal. RESULTS: Twelve hours after ingestion of the test meal, raw and baseline adjusted breath H2 excretion was significantly elevated in the gastroparesis group compared to the unaffected group with diabetes and the group without diabetes (p < 0.001). The baseline and 12-hour data points were adequate to discriminate between normal and delayed gastric emptying. CONCLUSIONS: We conclude that patients with previously diagnosed gastroparesis exhibit prolonged breath H2 excretion after ingestion of a test meal. This test may prove to be a safe, reliable, and affordable outpatient screening test for diabetic gastroparesis.

Adult↗
PubMed2000

Thiazolidinediones: a comparative review of approved uses.

Thiazolidinediones are a powerful and clinically important new class of oral antidiabetic agents that act by improving insulin sensitivity. Troglitazone is the prototype drug in this class but was withdrawn from the market in March 2000 due to its association with idiosyncratic hepatotoxicity. Currently two thiazolidinediones, rosiglitazone and pioglitazone, are U.S. Food and Drug Administration (FDA) approved for treatment of type 2 diabetes. These agents bind to and activate peroxisome proliferator-activator receptor gamma (PPAR-gamma) and work by altering the expression of genes involved in glucose uptake, glucose disposal, and lipid metabolism. The drugs differ in receptor binding and potency due to differences in their side chain moieties. These agents are rapidly absorbed from the gastrointestinal tract and are metabolized mainly in the liver. Rosiglitazone is FDA approved for monotherapy and for use in combination therapy with metformin or sulfonylureas. Pioglitazone is FDA approved for monotherapy as well as for use in combination therapy with metformin, insulin, or sulfonylureas. These drugs may also cause significant changes in plasma lipid concentrations, and improved insulin sensitivity may improve ovulatory function and fertility in women with polycystic ovary syndrome. The most serious side effect of the thiazolidinediones is hepatotoxicity. Although rosiglitazone and pioglitazone were not associated with hepatotoxicity in premarketing clinical trials, there were two recent case reports of idiosyncratic hepatotoxicity in patients treated with rosiglitazone. In addition, these agents may be associated with edema and some hematological changes. The purpose of this review is to provide an overview of the two currently approved thiazolidinediones and to suggest an approach for their safe and rational use.

Blood Glucose↗
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↗