Are insulin pumps underutilized in type 1 diabetes? No.
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Diabetes Mellitus, Type 1↗
Biomedical subjects
David S Schade
Publications and source records attributed to David S Schade.
Timing of antioxidant vitamin ingestion alters postprandial proatherogenic serum markers.
BACKGROUND: This study was designed to determine the optimal timing of vitamins E and C to prevent oxidative stress induced by a high-fat evening meal in type 2 diabetes. METHODS AND RESULTS: Eleven subjects were admitted on 4 occasions. Euglycemia was maintained for 24 hours by insulin infusion. Participants were fed a high-fat test supper equivalent to a McDonald's Big Mac Meal. Blood was drawn for measurement of C-reactive protein (CRP), interleukin 6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), malonyldialdehyde (MDA), and total radical antioxidant parameter (TRAP) before and during the 4 hours after the test meal. Studies were performed in random sequence with vitamin E 800 IU and vitamin C 1 g given either before breakfast or before supper in a double-blind manner on the day of the test meal. Control studies were performed with no vitamins and no test meal administered. There was a significant rise in CRP and PAI-1 after the test supper (P<0.05 compared with "no meal"). Either presupper or prebreakfast vitamins E and C prevented the meal-induced rise in CRP (P=0.03), although presupper vitamins were more effective (P=0.03 compared with prebreakfast vitamins). Only prebreakfast vitamins prevented the meal-induced rise in PAI-1 (P=0.006). There were no significant meal-related changes in the concentrations of IL-6, MDA, or TRAP. CONCLUSIONS: The timing of administration of antioxidant vitamins has variable effects on markers of meal-induced inflammation and fibrinolysis. This observation may be one reason why cardiovascular disease prevention trials using these vitamins have reported conflicting results.
Administration, Oral↗
A practical approach to hypercalcemia.
Hypercalcemia is a disorder commonly encountered by primary care physicians. The diagnosis often is made incidentally in asymptomatic patients. Clinical manifestations affect the neuromuscular, gastrointestinal, renal, skeletal, and cardiovascular systems. The most common causes of hypercalcemia are primary hyperparathyroidism and malignancy. Some other important causes of hypercalcemia are medications and familial hypocalciuric hypercalcemia. An initial diagnostic work-up should include measurement of intact parathyroid hormone, and any medications that are likely to be causative should be discontinued. Parathyroid hormone is suppressed in malignancy-associated hypercalcemia and elevated in primary hyperparathyroidism. It is essential to exclude other causes before considering parathyroid surgery, and patients should be referred for parathyroidectomy only if they meet certain criteria. Many patients with primary hyperparathyroidism have a benign course and do not need surgery. Hypercalcemic crisis is a life-threatening emergency. Aggressive intravenous rehydration is the mainstay of management in severe hypercalcemia, and antiresorptive agents, such as calcitonin and bisphosphonates, frequently can alleviate the clinical manifestations of hypercalcemic disorders.
Diagnosis, Differential↗
Severe hypoglycemia in adults.
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Acute Disease↗
Impact of subclinical hypothyroidism on serum total homocysteine concentrations, the prevalence of coronary heart disease (CHD), and CHD risk factors in the New Mexico Elder Health Survey.
The serum/plasma total homocysteine (tHcy) concentration, now recognized as an independent risk factor for accelerated atherosclerotic disease, is increased in overtly hypothyroid patients, and it decreases with thyroid replacement therapy. Whether or not individuals with subclinical hypothyroidism also increase their tHcy concentrations, and whether this elevation might help to explain the increased prevalence of the atherosclerotic diseases observed in this condition, remains unclear. If individuals with subclinical hypothyroidism have higher tHcy concentrations than euthyroid subjects, there would be added incentive to treat this condition earlier. In this cross-sectional study (New Mexico Elder Health Survey) of a randomly selected sample of Medicare recipients (age > or =65 years), no significant difference in serum tHcy concentrations could be detected between the 112 participants with subclinical hypothyroidism (Groups 2 and 3) and the 643 participants with thyrotropin (TSH) values < or =4.6 microU/mL (Group 1) after adjusting for differences in gender, ethnicity, age, and serum concentrations of folate, vitamin B(12), and creatinine. Only those participants with the highest TSH levels (>10 microU/mL) (Group 3) had a significantly higher prevalence of coronary heart disease (CHD) when compared against Group 1 participants (p = 0.007). No consistent significant differences in the prevalences of CHD or in the CHD risk factors examined were observed when all participants with subclinical hypothyroidism (Groups 2 and 3 combined) were compared against Group 1 participants.
Aged↗
Targeting postprandial hyperglycemia: a comparative study of insulinotropic agents in type 2 diabetes.
This study was designed to compare the efficacy of three insulinotropic agents in the control of postprandial hyperglycemia in type 2 diabetes. Fifteen subjects with noninsulin-requiring type 2 diabetes were admitted to the General Clinical Research Center on four separate occasions. During the control study and following 7-10 d on each study medication, daylong glucose profiles were performed to investigate the effects of the assigned medication on postprandial hyperglycemia. During each admission, placebo or study medications were administered before three isocaloric meals as follows: immediate-release glipizide 30 min before breakfast and 30 min before supper, glipizide gastrointestinal therapeutic system (GITS) 30 min before breakfast, or nateglinide 120 mg 10 min before breakfast, before lunch, and before supper. Blood was drawn for analysis of glucose, insulin, and C-peptide at -0.05, 0, 0.25, 0.5, 1, 2, 3, and 4 h relative to each test meal. Immediate-release glipizide, nateglinide, or glipizide GITS administration resulted in significantly lower integrated daylong (glucose area under the curve) and peak glucose levels, compared with placebo. There were no significant differences in the daylong integrated glucose levels among the three study medications. The peak postbreakfast glucose level (but not glucose area under the curve) was lower with nateglinide, compared with either immediate-release glipizide or glipizide GITS. Postlunch and postdinner integrated glucose levels were significantly lower with immediate-release glipizide or glipizide GITS, compared with nateglinide. C-peptide levels were significantly higher with immediate-release glipizide, compared with glipizide GITS. Insulin levels did not differ among the three study medications. Once-daily glipizide GITS, twice-daily immediate-release glipizide, or three-times-a-day administration of nateglinide results in equivalent control of postmeal hyperglycemia in type 2 diabetes. The decision to prescribe one of these three insulinotropic agents should be based on factors such as the patient's ability to comply with complex dosing regimens, the need to control fasting hyperglycemia, the risk of interprandial hypoglycemia, and pharmacoeconomic considerations, rather than postprandial glucose-lowering efficacy.
Adult↗
The mechanism of glucose-induced catecholamine stimulation.
Catecholamines are important hormones for maintaining homeostasis and may be secreted in response to several different stimuli. A report by Robertson and Porte in 1974 made the unexpected observation that acute administration of hypertonic glucose stimulates catecholamine secretion. Our study reassessed this observation by measuring individual catecholamines, explored its potential mechanism, and quantitated it relative to exercise and hypoglycemia-stimulated catecholamine secretion. We hypothesized that the mechanism of glucose-induced catecholamine secretion was related to an acute increase in plasma osmolality, which we tested with the nonmetabolizable hexose mannitol. In 56 studies, 14 normal adults underwent 4 partially randomized studies. The 4 study conditions consisted of the following: (1) rapid intravenous injection of 20 g of glucose; (2) rapid intravenous injection of 20 g of mannitol; (3) acute exercise (80 J/kg); and (4) insulin-induced hypoglycemia. Our results demonstrate that a significant increase in plasma catecholamine concentration occurs following each of the above stimuli, but its composition differs relative to the magnitude of epinephrine versus norepinephrine secretion. We conclude that the mechanism of glucose-induced catecholamine stimulation is the acute elevation in plasma osmolality induced by glucose, and that its stimulation is less than that which occurs following exercise for norepinephrine and less than that which occurs following hypoglycemia for epinephrine.
Adult↗
Frequency of the dawn phenomenon in type 2 diabetes: implications for diabetes therapy.
This study was designed to assess the frequency of the dawn phenomenon in patients with type 2 diabetes. A secondary aim was to examine the influence of varying treatment regimens on the frequency of the dawn phenomenon. The dawn phenomenon was defined as a rise in plasma glucose levels of > or = 0.5 mmol/L (10 mg/dL) between 0500 and 0900 h occurring after a growth hormone surge of > or = 5 microg/L. Sixteen subjects (six men, 10 women) with type 2 diabetes were studied overnight on their current mode of therapy in the General Clinical Research Center. Additionally, six of these subjects were restudied in random order after each of the following three therapeutic regimens: (1) 6 weeks of glipizide, (2) 6 weeks of bedtime NPH insulin, and (3) 3 days of intensive insulin therapy with multiple injections of regular insulin followed by assessment during overnight intravenous infusion of insulin. Thus, a total of 34 overnight studies were performed under various treatment conditions to provide an approximate frequency of the dawn phenomenon in type 2 diabetes. Blood was drawn every 30 min between midnight and 0800 h for measurement of glucose, insulin, C-peptide, and growth hormone levels. Additional counterregulatory hormone levels were determined during 24 of the studies, and the integrity of growth hormone secretion in response to insulin-induced hypoglycemia was assessed in 12 of the 16 patients. The subjects were aged 51 +/- 15 years with a body mass index of 31 +/- 5 kg/m(2) and a mean glycosylated hemoglobin of 8.1 +/- 1.2%. The dawn phenomenon occurred in only one of 34 (3%) studies. Moreover, the four different treatment regimens did not affect the frequency of occurrence of the dawn phenomenon. Ten of the 12 patients tested failed to secrete growth hormone in response to insulin-induced hypoglycemia. These data suggest that the dawn phenomenon is unusual in type 2 diabetes. Previously reported high prevalence rates in studies using similar sample size may be attributable to a Biostator-induced artifact. Decisions regarding therapies for type 2 diabetes should not be based on the assumption that the dawn phenomenon routinely causes early morning hyperglycemia.
Blood Glucose↗
Effect of smoking on hemoglobin A1c and body mass index in patients with type 2 diabetes mellitus.
BACKGROUND: Smoking is associated with a decrease in body weight in patients without diabetes mellitus and an increase in insulin resistance and hemoglobin A1c (HbA1c) levels in patients with type 1 diabetes mellitus. Whether smoking is associated with an increase in HbA1c and/or a decrease in body mass index (BMI) in type 2 diabetes mellitus is unresolved, however. Therefore, the objective of this study was to determine the effect of smoking on HbA1c levels and BMI in a cross-section of outpatients with type 2 diabetes mellitus. METHODS: A questionnaire was completed by 102 sequential outpatients (32 men, 70 women) with type 2 diabetes mellitus to assess age, sex, duration of diabetes mellitus, medications, exposure to nicotine, medical complications as a result of type 2 diabetes mellitus, and BMI In addition, a urine sample was obtained from each patient to assess the microalbumin-creatinine and cotinine-creatinine ratios. HbA1c level were also obtained from each volunteer as a measure of glucose control. RESULTS: Smokers had significantly higher cotinine-creatinine ratios than nonsmokers. Smokers and nonsmokers did not differ significantly with regard to HbA1c level, BMI, or duration of diabetes mellitus. Smokers were younger than nonsmokers. Smokers and nonsmokers did not differ significantly in terms of microalbumin-creatinine ratio, amount of diabetic medications, or medical complications. CONCLUSION: The results of this study suggest that smoking does not have a significant direct effect on BMI or HbA1c in patients with type 2 diabetes mellitus. This conclusion suggests that the relationship between these factors is much more complex than in people without diabetes or in patients with type 1 diabetes mellitus.
Adult↗
To pump or not to pump.
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Costs and Cost Analysis↗
Control of postprandial hyperglycemia: optimal use of short-acting insulin secretagogues.
OBJECTIVE: This study was designed to compare the efficacy of acute premeal administration of glipizide versus nateglinide in controlling postprandial hyperglycemia in subjects with non-insulin-requiring type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 20 subjects (10 female, 10 male) with non-insulin-requiring type 2 diabetes were admitted overnight to the General Clinical Research Center on four occasions. In random order, 10 mg glipizide (30 min premeal), 120 mg nateglinide (15 min premeal), 10 mg glipizide plus nateglinide (30 and 15 min premeal, respectively), or placebo pills (30 and 15 min premeal) were administered in a double-blind fashion before a standardized breakfast. Blood was drawn for analysis of glucose, insulin, and C-peptide at -0.05, 0, 0.5, 1, 2, 3, and 4 h relative to the meal. RESULTS: The subjects were aged 56 +/- 2 years and were moderately obese (BMI 31 +/- 1 kg/m(2)), with a mean HbA(1c) of 7.4 +/- 0.4%. The peak postprandial glucose excursion above baseline was higher with placebo (6.1 +/- 0.5 mmol/l) than glipizide (4.3 +/- 0.6 mmol/l, P = 0.002), nateglinide (4.2 +/- 0.4 mmol/l, P = 0.001), or glipizide plus nateglinide (4.1 +/- 0.5 mmol/l, P = 0.001). The area under the curve for the glucose excursion above baseline was also higher with placebo (14.1 +/- 1.8 mmol/h. l) compared with glipizide (6.9 +/- 2.4 mmol/h. l, P = 0.002), nateglinide (9.7 +/- 2 mmol/h. l, P = 0.004), or glipizide plus nateglinide (5.6 +/- 2.2 mmol/h. l, P < 0.001). Peak and integrated glucose excursions did not differ significantly between glipizide and nateglinide. However, by 4 h postmeal, plasma glucose levels were significantly higher with nateglinide (9 +/- 0.9 mmol/l) compared with the premeal baseline (7.8 +/- 0.6 mmol/l, P = 0.04) and compared with the 4-h postprandial glucose level after administration of glipizide (7.6 +/- 0.6 mmol/l, P = 0.02). Integrated postprandial insulin levels were higher with glipizide (1,556 +/- 349 pmol/h. l) than nateglinide (1,364 +/- 231 pmol/h. l; P = 0.03). Early insulin secretion, as measured by insulin levels at 30 min postmeal, did not differ between glipizide and nateglinide. CONCLUSIONS: Acute premeal administration of nateglinide or glipizide has equal efficacy in controlling postbreakfast hyperglycemia in type 2 diabetes when each drug is administered at the optimum time before the meal. Glipizide causes a more pronounced and sustained postmeal insulin secretory response compared with nateglinide. Glipizide facilitates the return to near-fasting glucose levels at 4 h postmeal, but with the possible risk of increased frequency of postmeal hypoglycemia in drug-naive patients. The clinical decision to use glipizide versus nateglinide should be based on factors other than the control of postprandial hyperglycemia in type 2 diabetes.
C-Peptide↗
Fasting hyperglycemia predicts the magnitude of postprandial hyperglycemia: implications for diabetes therapy.
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Administration, Oral↗
The dawn phenomenon revisited: implications for diabetes therapy.
OBJECTIVE: To summarize current data on the magnitude, prevalence, variability, pathogenesis, and management of the dawn phenomenon in patients with diabetes mellitus. METHODS: On the basis of the pertinent available literature and clinical experience, we propose a quantitative definition of the dawn phenomenon, discuss potential pathogenic mechanisms, and suggest management options. RESULTS: The "dawn phenomenon" is a term used to describe hyperglycemia or an increase in the amount of insulin needed to maintain normoglycemia, occurring in the absence of antecedent hypoglycemia or waning insulin levels, during the early morning hours. To be clinically relevant, the magnitude of the dawn increase in blood glucose level should be more than 10 mg/dL or the increase in insulin requirement should be at least 20% from the overnight nadir. Controversy exists regarding the frequency, reproducibility, and pathogenesis of the dawn phenomenon. Approximately 54% of patients with type 1 diabetes and 55% of patients with type 2 diabetes experience the dawn phenomenon when the foregoing quantitative definition is used. The most likely pathogenic mechanism underlying the dawn phenomenon is growth hormone-mediated impairment of insulin sensitivity at the liver and muscles. The exact biochemical pathways involved are unknown. Therapeutic decisions aimed at correcting fasting hyperglycemia should take into account the variability and magnitude of the dawn phenomenon within individual patients. Successful insulinization appears to minimize the effects of the dawn phenomenon. Currently, no subcutaneous depot preparation of insulin exists that is capable of mimicking the basal insulinsecretion of the healthy pancreas. CONCLUSION: Increases in the bedtime doses of hypoglycemic agents with nighttime peaks in action may correct early morning hyperglycemia but be associated with undesirable nocturnal hypoglycemia. Targeted continuous subcutaneous insulin infusion programming can facilitate the prevention of early morning hyperglycemia in selected patients.
Circadian Rhythm↗
Randomized, double-blind, placebo-controlled trial of orlistat for weight loss in adolescents.
OBJECTIVE: To evaluate the efficacy of orlistat to enhance weight loss in obese adolescents. METHODS: The study was a 6-month randomized, double-blind, placebo-controlled trial to compare the effects of orlistat (120 mg orally 3 times a day) and placebo on reduction of body mass index (BMI). Forty adolescents between 14 and 18 years of age with a mean BMI of 40 kg/m2 entered the protocol between December 2002 and February 2003. Study subjects stayed overnight in the General Clinical Research Center, during which dietary records were reviewed and lifestyle recommendations were given. The study participants received either orlistat (120 mg orally 3 times a day) or placebo and were assessed monthly for 6 months. At 0, 3, and 6 months, fasting laboratory tests were performed. The primary end point was the change in BMI from baseline to 6 months. Secondary outcomes included changes in weight, lean body mass, and results of blood chemistry studies. RESULTS: No statistically significant difference was noted between the 2 study groups for decrease in BMI from baseline to 6 months (P = 0.39). The decrease in BMI within the orlistat group (-1.3 +/- 1.6 kg/m2; P = 0.04) and within the placebo group (-0.8 +/- 3.0 kg/m2; P = 0.02), however, was statistically significant. Laboratory measurements did not differ between the 2 groups. In comparison with the placebo group, the orlistat group had increased adverse events, primarily gastrointestinal symptoms and findings. CONCLUSION: In this study of obese adolescents, orlistat did not significantly reduce BMI in comparison with placebo at 6 months.
Adolescent↗
Vitamin E in humans: an explanation of clinical trial failure.
OBJECTIVE: To describe the potential benefits and hazards of vitamin E supplementation and present a rational basis for understanding the conflicting results among randomized clinical trials, epidemiologic investigations, and animal studies on the use of vitamin E to prevent atherosclerosis. METHODS: We conducted a retrospective review of the pertinent literature found in PubMed from 1981 through August 2005. The published data are analyzed and summarized. RESULTS: The possible factors implicated for failure of vitamin E therapy include the following: (1) the inclusion of patients without biochemical evidence of increased oxidative stress, (2) the relatively short duration of treatment, (3) the use of suboptimal dosages of vitamin E, (4) the suppression of gamma-tocopherol by alpha-tocopherol, (5) the use of vitamin E supplementation without the concurrent use of vitamin C, (6) the lack of inclusion of biochemical markers of oxidative stress and markers of vascular response, (7) the inappropriate administration of vitamins relative to meal ingestion, and (8) the poor patient compliance and the lack of monitoring of vitamin E levels. CONCLUSION: Large, randomized clinical trials have not yet substantiated a beneficial effect of use of vitamin E to reduce atherosclerotic risk in humans, despite demonstration of antioxidant effects in vitro and in animals. Only in subsets of patients at high risk for atherosclerosis has a beneficial effect been suggested. Before additional large, randomized clinical trials of vitamin E are performed, the specific biologic and surrogate marker effects of vitamin E in each target population must be defined more carefully. This approach will save resources, minimize untoward side effects, and identify the patients who will benefit the most.
Anti-Inflammatory Agents↗