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Biomedical subjects

D S Schade

Publications and source records attributed to D S Schade.

At least 19 recordsLinked to original sources
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

A placebo-controlled, randomized study of glimepiride in patients with type 2 diabetes mellitus for whom diet therapy is unsuccessful.

This multicenter, randomized, placebo-controlled study of glimepiride, a new oral sulfonylurea, was conducted in patients with type 2 diabetes for whom dietary treatment was unsuccessful (fasting plasma glucose [FPG] = 151-300 mg/dL) during a 1-week screening period. Patients were randomized to receive glimepiride (n = 123) or placebo (n = 126) once daily for a 10-week dose-titration period, then maintained on an individually determined optimal dose (1-8 mg of glimepiride or placebo) for 12 weeks. Glimepiride lowered FPG by 46 mg/dL, hemoglobin A1C (HbA1C) by 1.4%, and 2-hour postprandial glucose by 72 mg/dL more than placebo. Glimepiride improved postprandial insulin and C-peptide responses without producing clinically meaningful increases in fasting insulin or C-peptide levels. Good glycemic control (HbA1C < or = 7.2%) was achieved by 69% of the patients taking glimepiride versus 32% of those taking placebo. The overall incidence of adverse events was similar in both groups. No clinically noteworthy abnormal laboratory values or hypoglycemia (blood glucose < 60 mg/dL) occurred. Glimepiride is safe and effective for treatment of patients with type 2 diabetes for whom diet therapy is unsuccessful.

Administration, Oral↗
PubMed1998

Prevalences of type 2 diabetes, the insulin resistance syndrome, and coronary heart disease in an elderly, biethnic population.

OBJECTIVE: To compare the prevalences of type 2 diabetes, the various cardiovascular risk factors encompassing the insulin resistance syndrome (IRS), and coronary heart disease (CHD) in elderly Hispanics compared with non-Hispanic whites. RESEARCH DESIGN AND METHODS: Elderly Hispanics (n = 414) and non-Hispanic whites (n = 469), randomly selected from the Medicare rolls of Bernalillo County (Albuquerque, NM; age > or = 65 years), underwent a home interview followed by an interview/examination by a nurse-practitioner, nurse, and nutritionist that included an evaluation of glucose tolerance. Prevalences of total and central obesity, dyslipidemia, hypertension, and microalbuminuria also were determined. History of myocardial infarction, recent angina, and/or coronary bypass graft, and electrocardiograms (ECGs) were used to document CHD. RESULTS: Elderly Hispanics had twice the prevalence of type 2 diabetes compared with non-Hispanic whites, but the prevalence of impaired glucose tolerance was not increased in Hispanics. Mean serum fasting and 2-h post-glucola insulin concentrations, fasting insulin resistance indexes, and HbA1c were higher in Hispanics. Hispanics were shorter, weighed less, and had more total body and central obesity. The higher prevalences of dyslipidemia in Hispanics could be explained by a higher prevalence of diabetes. The prevalences of hypertension and CHD were not different for the two ethnic groups. CONCLUSIONS: Elderly Hispanics had twice the prevalence of diabetes and higher prevalences of cardiovascular risk factors associated with IRS. Prevalences of hypertension and CHD were similar in the two ethnic groups.

Aged↗
PubMed1998

Outcome of recruitment and report on participation rate in the New Mexico Elder Health Survey.

The purpose of this paper is to report on the outcome of recruitment and participation rate in the New Mexico Elder Health Survey. This survey is the first community based epidemiological survey to examine health and health related issues of elderly (65 years or older) Hispanics and non-Hispanic whites in Bernalillo County (Albuquerque), New Mexico. This survey was conducted from May 1993 to September 1995. Subjects (N=2200) were randomly selected from the list of 50,700 Medicare recipients residing in Bernalillo County and stratified by ethnicity and gender. Hispanics were identified using a computer program that selects Hispanic surname patterns and ethnicity was verified by self report. Subjects participated in a home interview, followed by an interview and examination in a senior health clinic. Use of the Medicare list resulted in 75.7% (N=1666) of subjects being contacted. Of the 1666 subjects available, 1130 (67.8%) completed a home interview and 883 (54%) completed the full examination. There were no significant differences in participation by ethnicity, but there were significant differences by gender, with women less likely to participate. The mean age of participants was 74 years, age range 65 to 100. Hispanic elderly demonstrated greater economic poverty and lower levels of formal education. Our survey results show that the elderly and Hispanic elderly can be successfully recruited to participate in a research study. This paper is the first to summarize the details of the survey design, present the results of recruitment and participation, and describe the survey participants.

Age Factors↗
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↗
PubMed1996

Differential effects of physiological versus pathophysiological plasma concentrations of epinephrine and norepinephrine on ketone body metabolism and hepatic portal blood flow in man.

Few studies that have examined the effects of catecholamines on ketogenesis have considered the effects of catecholamines on hepatic portal blood flow. Since hepatic blood flow is a major determinant of hepatic ketogenesis (via modification of free fatty acid availability), interpretation of these studies is difficult. To better define the relative contributions of these variables, we studied the effects of physiological and pathophysiological plasma concentrations of epinephrine and norepinephrine on plasma ketone body concentrations and hepatic portal blood flow in controlled paired studies in young healthy male volunteers. To assess the effects of physiological catecholamine concentrations, each of eight subjects received 60-minute sequential infusions of epinephrine (10 ng/kg/min) and norepinephrine (32.5 ng/kg/min) together with a control infusion of heparin (0.4 U/kg/min) separated by 60-minute washout periods. Similar increments in plasma nonesterified fatty acid ([NEFA] to approximately 1 mmol/L) were observed during each infusion. The ketotic ratios, calculated as the ratio of plasma ketone bodies to fatty acids integrated above baseline for 90 and 120 minutes, respectively, for epinephrine and norepinephrine infusions were both significantly greater (P < .005 for each) than for the heparin control infusion. To assess the effects of pathophysiological plasma catecholamine concentrations, each of eight subjects also received sequential 60-minute infusions of epinephrine 60 ng/kg/min, norepinephrine 80 ng/kg/min (plus heparin 0.1 U/kg/min), and a separate control infusion of heparin with or without Intralipid (KabiVitrum, Alameda, CA). Whereas integrated plasma fatty acid levels were approximately twofold greater than those observed in the physiological protocol, the absolute integrated ketone body response to the pathophysiological concentration of epinephrine was significantly lower than that observed for the physiological dose of the hormone (P < .05). In contrast, the ketotic ratio for norepinephrine was significantly greater (P < .005) than for both epinephrine and the control infusion of heparin with or without Intralipid. Significant (P < .01) increases above baseline fasting levels were observed in plasma glucose and immunoreactive insulin concentrations during infusion of pathophysiological concentrations of epinephrine. Because of the technical difficulties of simultaneously measuring portal blood and sampling blood frequently, studies were repeated in six additional subjects using noninvasive image-guided flowmetry to measure percentage changes in hepatic portal blood flow during catecholamine infusion. Norepinephrine reduced hepatic portal blood flow significantly at the low-physiological concentration by 12% (P < .05) and at the pathophysiological concentration by 18% (P < .05). In summary, (1) both epinephrine and norepinephrine were associated with significant ketotic effects at physiological plasma concentrations; and (2) when infused at pathophysiological concentrations, only norepinephrine exerted a significant additional ketotic effect. Since norepinephrine has a significant simultaneous effect of reducing hepatic portal blood flow, we conclude that previous studies may have underestimated the effect of norepinephrine on hepatic ketogenesis.

Adult↗
PubMed1995

Myocardial atrophy in acquired immunodeficiency syndrome--associated wasting.

This study evaluated the effects of acquired immunodeficiency syndrome wasting syndrome (AWS) on the heart in a population free of overt opportunistic infection or clinical evidence of cardiac disease. Data from 53 patients with AWS and 16 healthy age-matched controls were studied. By echocardiography, a significant reduction in left ventricular mass was found in patients with AWS that remained significantly reduced when corrected for body surface area. Mean ejection fraction was within the normal range in patients with AWS but was significantly less than in controls. End-systolic volume index was slightly elevated in patients with AWS. Although no difference in end-systolic wall stress was seen, the end-systolic wall stress-shortening relation differed significantly. These findings are consistent with myocardial atrophy and subtle left ventricular dysfunction in patients with AWS.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Brittle diabetes: etiology and treatment.

Brittle diabetes is an uncommon complication of type I diabetes. However, the seriousness of the complication and its demands on the health care system warrant aggressive intervention. Studies during the last decade demonstrate that brittle diabetes is always secondary to a specific, identifiable etiology. This etiology is rarely apparent, however, without both extensive metabolic and psychological testing. In the long term, this testing is cost-effective inasmuch as approximately 50% of brittle diabetic patients are amenable to specific therapy. Several important issues have been clarified during the last decade, during which time major attempts have been made to understand the etiology of brittle diabetes. These issues may be summarized as follows: 1. There is always a specific etiology causing the brittle diabetes. 2. There are many different causes of brittle diabetes, but the most common are psychological abnormalities. 3. Therapy should always be directed at correcting the underlying pathogenic factor(s). 4. Empirical therapy and invasive procedures are contraindicated in brittle diabetic patients. 5. Extensive evaluation of a brittle diabetic patient may require referral of the patient to a diabetes center that has the expertise and manpower to appropriately evaluate a brittle diabetic patient. 6. Close follow-up and continued evaluation of therapy are necessary to confirm the suspected etiology and prevent diabetic ketoacidosis from developing. Unfortunately, only 50% of brittle diabetic patients respond to specific etiologic treatment. Research efforts during the next decade will focus on several clinical problems. First, improved psychological interventions are needed for common causes such as manipulative behavior and factitious disease. Second, treatment of severe systemic insulin resistance is still a major therapeutic challenge. Third, impaired glucose counterregulation needs to be better understood so that treatment is possible. The ultimate goal for physicians caring for brittle diabetic patients is to have effective therapy for all causes of brittle diabetes.

Diabetes Mellitus, Type 1↗
PubMed1994

Octreotide: a long-acting inhibitor of endogenous hormone secretion for human metabolic investigations.

Octreotide is a recently available, FDA-approved, long-acting analog of somatostatin. The efficacy and tolerability of octreotide were evaluated in a series of protocols in healthy volunteers to assess its suitability for use in clinical investigations involving short-term inhibition of endogenous hormone secretion. Prolonged (270 minutes) hyperglycemic clamps were used to assess octreotide-mediated suppression of glucose-stimulated endogenous insulin secretion. Compared with a saline-control infusion, octreotide (30 ng/kg/min) suppressed stimulated insulin (P < .0001) and C-peptide (P < .0001) concentrations to basal levels. During insulin-induced hypoglycemia (plasma glucose < 40 mg/dL), octreotide (30 ng/kg/min) effectively suppressed the secretion of glucagon (P < .05) and growth hormone (P < .0005). In islet cell clamp studies, octreotide (30 ng/kg/min) suppressed C-peptide (P < .001), glucagon (P < .01), and growth hormone concentrations to below basal (fasting) levels in all subjects. Subsequent infusion of exogenous insulin, glucagon, and growth hormone resulted in predictable and stable concentrations of each hormone during octreotide-mediated suppression of their endogenous secretion. Consistent with the long half-life of octreotide (approximately 90 minutes), the concentrations of all three hormones remained suppressed below basal levels throughout a 60-minute observation period following the termination of octreotide infusion. In separate high-dose octreotide infusion studies, octreotide (60 ng/kg/min) did not produce any apparent additional metabolic effects, but was associated with an unacceptable degree of gastrointestinal side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Comparative efficacy of a once-daily controlled-release formulation of glipizide and immediate-release glipizide in patients with NIDDM.

OBJECTIVE: To compare the efficacy and safety of controlled-release glipizide (glipizide-GITS [gastrointestinal therapeutic system]) and immediate-release glipizide in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: In a multicenter, open-label, randomized, two-way crossover study, 132 patients with NIDDM received daily doses of 5, 20, or 40 mg of either glipizide-GITS or immediate-release glipizide for 8 weeks followed by 8 weeks of the alternate formulation. Plasma glucose, serum insulin, C-peptide, and plasma glipizide levels were measured at fasting and post-Sustacal challenge at the end of 1 and 8 weeks of each treatment phase. HbA1c was measured at the end of weeks 7 and 8 of each treatment phase. RESULTS: Both formulations of glipizide yielded similar mean HbA1c values. However, mean fasting plasma glucose (FPG) levels were significantly lower with glipizide-GITS treatment than with immediate-release glipizide at the end of week 1 (11.0 vs. 11.6 mmol/l; P < 0.01) and at the end of the 8-week treatment phase (10.9 vs. 11.7 mmol/l; P < 0.001). Fasting insulin and C-peptide levels were lower after 5 mg glipizide-GITS vs. immediate-release glipizide. Glucose responses to Sustacal were similar after both formulations of glipizide; however, serum insulin (P < 0.01) and C-peptide responses (P < 0.05) were lower with glipizide-GITS than with immediate-release glipizide treatment at the end of the 8-week treatment phase. Mean plasma glipizide concentrations were stable by the end of week 1, and the concentrations increased proportionately with dose. Once-daily Glipizide-GITS provided effective mean glipizide concentrations (> 50 ng/ml) 24 h after dosing, even at the lowest (5 mg) dose level. Both formulations were well tolerated. CONCLUSIONS: Glipizide-GITS was significantly more effective than immediate-release glipizide in reducing FPG levels. Both formulations reduced postprandial plasma glucose levels equally; however, glipizide-GITS exerted its control in the presence of lower plasma glipizide concentrations in addition to significantly lower insulin and C-peptide levels. This suggests that glipizide-GITS improves insulin sensitivity.

Administration, Oral↗
PubMed1993

Octreotide reverses hyperinsulinemia and prevents hypoglycemia induced by sulfonylurea overdoses.

Emergency therapy of sulfonylurea overdoses with glucose is often unsatisfactory because glucose stimulates insulin release and initiates a need for escalating quantities of hypertonic glucose to maintain normoglycemia. We tested the hypothesis that octreotide, an analog of somatostatin, would reverse hyperinsulinemia induced by a sulfonylurea overdose. Eight normal subjects received glipizide (1.45 mg/kg) on three occasions. Within 3 h, all subjects became hypoglycemic (< 50 mg/dL) and were initially treated with 50% dextrose followed by 1) dextrose infusion, 2) octreotide (30 ng/kg.min, iv), or 3) diazoxide (300 mg, iv, every 4 h). Euglycemia (85 mg/dL) was maintained with supplementary dextrose in treatment limbs 2 and 3. Insulin concentrations were 4-5 times greater with dextrose alone or in combination with diazoxide than with octreotide (P < 0.01). Dextrose requirements during diazoxide or dextrose alone were not different, but were both greater than those during octreotide treatment (P < 0.0001). All therapies were stopped at 13 h. Glucose levels remained above 3.6 mmol/L (65 mg/dL) in six of eight subjects receiving octreotide for the remaining 4 h. Glucose fell to below 3.6 mmol/L within 1.5 h of stopping either dextrose or diazoxide in each subject. Overall, octreotide reduced and in four of eight subjects entirely eliminated the need for exogenous glucose after a large overdose of glipizide. We conclude that octreotide is safe and effective and should be strongly considered as a logical therapeutic alternative for this metabolic emergency.

Adult↗