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Biomedical subjects

P Raskin

Publications and source records attributed to P Raskin.

At least 163 records · Page 9Linked to original sources
PubMedDate not supplied

Correlation between erythrocyte aldose reductase activity and the width of skeletal-muscle capillary basement membrane in insulin-dependent diabetes mellitus.

Thickening of capillary basement membrane has been demonstrated in diabetic subjects, and it is considered to be the characteristic pathological lesion of diabetic microvascular disease. There are studies reporting the effects of inhibitors of aldose reductase, the first enzyme of the polyol pathway, on the thickening of the capillary basement membrane. These observations indicate a significant role of the polyol pathway in the development of microvascular disease. However, it is unknown whether or not there is any correlation between the thickness of the capillary basement membrane and the activity of aldose reductase in diabetic patients. To clarify this issue, we measured the width of skeletal-muscle basement membrane and erythrocyte aldose reductase activity in 27 insulin-dependent diabetic and 8 nondiabetic individuals. The results showed that both the aldose reductase activity and the width of capillary basement membrane were increased in diabetic patients as compared to nondiabetic individuals (6.89 +/- 0.38 versus 5.15 +/- 0.60 mL/mU erythrocytes, p < 0.05 and 2257 +/- 166 versus 1136 +/- 69 A, p < 0.0001, respectively) (mean +/- SE), but marked variability was observed in both the enzyme activity and the basement membrane thickness among the diabetic patients. There was a significant correlation between the capillary basement membrane thickness and the activity of erythrocyte aldose reductase (r = 0.51, p < 0.01) in diabetic patients. Our data suggest that the polyol pathway plays an important role in thickening of capillary basement membrane in diabetic individuals, and the variability in aldose reductase activity seen among diabetic patients may result in the varying susceptibility to the development of diabetic microvascular disease.

Adult↗
PubMedDate not supplied

Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of tramadol in a 6-month open extension following a 6-week double-blind randomized trial. RESEARCH DESIGN AND METHODS: Patients with painful diabetic neuropathy who completed the double-blind study were eligible for enrollment in an open extension of up to 6 months. All patients received tramadol 50-400 mg/day. Self-administered pain intensity scores (scale 0-4; none to extreme pain) and pain relief scores (scale -1-4; worse to complete relief) were recorded the first day of the open extension (last day of the double-blind phase) and at 30, 90, and 180 days. RESULTS: A total of 117 patients (56 former tramadol and 61 former placebo) entered the study. On the first day of the study, patients formerly treated with placebo had a significantly higher mean pain intensity score (2. 2+/-1.02 vs. 1.4+/-0.93, P<0.001) and a lower pain relief score (0. 9+/-1.43 vs. 2.2+/-1.27, P<0.001) than former tramadol patients. By Day 90, both groups had mean pain intensity scores of 1.4, which were maintained throughout the study. Mean pain relief scores (2. 4+/-1.09 vs. 2.2+/-1.14) were similar after 30 days in the former placebo and former tramadol groups, respectively and were maintained for the duration of the study. Four patients discontinued therapy due to ineffective pain relief; 13 patients discontinued due to adverse events. The most common adverse events were constipation, nausea, and headache. CONCLUSIONS: Tramadol provides long-term relief of the pain of diabetic neuropathy.

Adult↗
PubMedDate not supplied

Cardiovascular risk in diabetes: a brief review.

Cardiovascular disease (CVD) is the major cause of the morbidity and mortality associated with diabetes in the US. A 2- to 3-fold incidence of CVD occurs in both type 1 and type 2 diabetic individuals over that in age- and gender-matched non-diabetic persons. Recent encouraging data demonstrating a decline in CVD mortality in the general US population do not reflect such a decline in the diabetic population, particularly in women. Increased risk for CVD is related to duration of diabetes and hyperglycemia, as well as hypertension, dyslipidemia, insulin resistance, gender, coagulation abnormalities, and other factors. Health care providers need to advocate for an uncompromising, multi-component attack on all modifiable risk factors for CVD, including glucose control, in the person with diabetes mellitus. This review focuses on known modifiable risk factors for CVD associated with diabetes, potential targets for primary and secondary prevention.

Cardiovascular Diseases↗
PubMedDate not supplied

A comparison of insulin lispro and buffered regular human insulin administered via continuous subcutaneous insulin infusion pump.

This study compared glycemic control achieved with insulin lispro or buffered regular human insulin in patients with Type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) using an external insulin pump. In this 24-week multicenter, randomized, two-way crossover, open-label trial, 58 patients on CSII with adequate glycemic control received either insulin lispro or buffered regular human insulin for 12 weeks, followed by the alternate treatment for another 12 weeks. Efficacy and safety measures included hemoglobin A(1c) (HbA(1c)) at baseline and endpoint, home blood glucose monitoring, hypoglycemia, and frequency of pump catheter occlusion. Patients consumed a standard test meal on three occasions, with determinations of fasting, 1- and 2-h postprandial glucose values. Insulin lispro use was associated with a significantly lower HbA(1c) than was buffered regular human insulin (7.41+/-0.97 vs. 7.65+/-0.85 mmol/l; P=.004). Fasting serum glucose values before the test meal were similar between the two therapies. The 1-h (11.16+/-4.29 vs. 13.20+/-4.68 mmol/l; P=.012) and 2-h (9.64+/-4.10 vs. 12.53+/-4.64 mmol/l; P=.001) postprandial glucose concentrations were significantly lower during treatment with insulin lispro. No differences between treatments were observed in basal or bolus insulin doses, weight gain, or the incidence and rate of hypoglycemia, hyperglycemia, or pump occlusions. When used in external pumps, insulin lispro provides better glycemic control than buffered regular human insulin with a similar adverse event profile.

Adult↗
PubMedDate not supplied

Idiopathic Type 1 diabetes.

The purpose of this article is to review the available pathophysiological and clinical studies of patients with idiopathic Type 1 diabetes. Idiopathic Type 1 diabetes is a common form of diabetes most commonly seen in obese African American individuals living in large urban areas. This type of diabetes usually presents with the typical signs and symptoms of Type 1 diabetes such as diabetic ketoacidosis but its subsequent clinical course often resembles Type 2 diabetes. The natural history and pathogenesis of idiopathic Type 1 diabetes is unknown because most of these studies on these patients were done shortly after diagnosis. For the most part, these patients have been treated as if they had Type 2 diabetes with diet and/or oral agents but recent studies suggest that patients have a very variable response to diet and oral agents. They seem to have better long-term glycemic control with the use of insulin therapy. Although the pathogenesis of this disease is unknown, it may be related to lipotoxicity, glucose toxicity or transcription factors involved in fuel metabolism.

Blood Glucose↗
PubMedDate not supplied

Effects of a large supper on glucose levels the following morning in patients with type 2 diabetes.

Seventeen patients were studied to test the hypothesis that a large evening meal influences the fasting glucose level and glucose tolerance the following morning in patients with type 2 diabetes. Oral hypoglycemic agents were discontinued for 2 weeks. The baseline fasting plasma glucose levels were 12.3 +/- 0.9 mmol/L. Fasting and postprandial (post-Sustacal) glucose, insulin, and C-peptide measurements were performed the morning after the patients received three separate meal protocols spaced 1 week apart. The caloric distribution of the meal protocols was (1) 7 kcal/kg of ideal body weight breakfast and lunch and 14 kcal/kg supper (small supper); (2) 7 kcal/kg breakfast and lunch and 28 kcal/kg for supper (large supper); and (3) 14 kcal/kg breakfast and lunch (no supper). Fasting glucose level were higher the morning after the large supper compared to no supper (13.6 +/- 0.7 versus 12.3 +/- 0.5 mmol/L, p < 0.05) and also to the small supper (13.6 +/- 0.7 versus 12.5 +/- 0.6 mmol/L, p = 0.05). No difference was observed in the fasting glucose levels between the small supper and no supper (p > 0.2). The fasting insulin and C-peptide levels, and the post-Sustacal areas under the curve of glucose, insulin, and C-peptide did not differ among the meals. In patients with type 2 diabetes, a large evening meal is associated with a modest elevation in fasting glucose the following morning.

Blood Glucose↗
PubMedDate not supplied

Initial evaluation of a 290-microm diameter subcutaneous glucose sensor: glucose monitoring with a biocompatible, flexible-wire, enzyme-based amperometric microsensor in diabetic and nondiabetic humans.

Results of the initial clinical evaluation in 20 human subjects of a subcutaneously implanted microsensor-based amperometrically glycemia-monitoring system, carried out between April 1994 and June 1995, are reported. The system was based on the electrical connection ("wiring") of the reaction centers of glucose oxidase to a gold electrode and on elimination of the chemicals that interfere with glucose monitoring through their horseradish peroxidase-catalyzed oxidation by internally generated hydrogen peroxide. The sensor was finer than a 29-gauge needle and had no leachable components. Because of its high selectivity for glucose, the sensor output was virtually nil at zero glucose level. This enables prompt "one-point" in vivo calibration of the sensor with a single blood glucose sample. Microsensors were subcutaneously implanted in ten nondiabetic and ten insulin-dependent diabetes mellitus (IDDM) volunteers. All subjects underwent standard meal tests and intravenous glucose-tolerance tests (IVGTT) in addition to hourly plasma glucose measurements. The sensor signals were continuously recorded, and the glucose concentration estimates were derived by calibrating the sensor using a single blood sample (one-point calibration). Regression analysis revealed that the sensor-estimated glucose concentrations were linearly related to the plasma glucose concentrations (r2 = 0.75) over a wide glucose concentration range (2-28 mmol/L) (sensor estimate = plasma 0.96 + 0.26 mmol/L). The difference between the estimated and actual glucose concentration was -0.13+/-0.23 mmol/L [mean +/-95% confidence interval (CI), n = 546], and 95% of the estimates fell in clinically acceptable zones of the Clarke error grid. The sensing delay time was 10.4+/-2.3 min as measured by the IVGTT. The subjects reported no discomfort associated with wearing the sensors.

Adult↗
PubMedDate not supplied

Association of erythrocyte aldose reductase activity with diabetic complications in type 1 diabetes mellitus.

Erythrocyte aldose reductase was isolated and its activity measured in 72 Type 1 (insulin dependent) diabetic patients and 21 age and sex matched non-diabetic subjects. The diabetic patients were categorized into two groups in terms of presence (n = 29) or absence (n = 43) of severe diabetic complications. Age, sex, duration of diabetes and HbA1c levels were matched between the diabetic groups. Erythrocyte aldose reductase (mean +/- SEM) was increased in patients with Type 1 diabetes compared to the non-diabetic subjects (7.22 +/- 0.24 vs 5.66 +/- 0.19 Ul-erythrocytes-1, < 0.0001). There was a four-fold variation in its activity among the diabetic patients (3.38-12.23 Ul-erythrocytes-1). The enzyme activity was significantly higher in patients with complications than those without (8.17 +/- 0.39 vs 6.58 +/- 0.26 Ul-erythrocytes-1, p < 0.002). When the patients were stratified by duration of the disease, the enzyme activity was highest in patients who had developed complications with a duration of less than 20 years and lowest in those without complications for 20 years or longer (8.54 +/- 0.48 vs 6.46 +/- p +/- 0.33 Ul-erythrocytes-1, p < 0.002). Patients who had an aldose reductase activity greater than the mean +/- 2SD of that seen in non-diabetic controls were four times more likely to have diabetic complications than those whose enzyme activity fell within 2SD of non-diabetic individuals (p < 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Reduction in cardiovascular risk factors with intensive diabetes treatment in insulin-dependent diabetes mellitus.

We measured plasma lipid and lipoprotein levels at baseline and at 6-mo intervals in 47 normolipidemic patients with classic insulin-dependent diabetes mellitus treated either with a conventional (n = 21) or intensive (n = 26) diabetes-treatment program. Patients were followed for a mean of 3 yr (range 1-4 yr). Intensive diabetes treatment resulted in a significant improvement in glycemic control that caused sustained changes in plasma lipid and lipoprotein levels that were not evident with the conventional-treatment program. These changes, which persisted for periods averaging 3 yr, can potentially reduce predicted risk for the development of premature atherosclerosis. Thus, long-term near normoglycemia may have a role in the prevention of atherosclerosis in insulin-dependent diabetic patients.

Adult↗
PubMedDate not supplied

Cutaneous complications of chronic continuous subcutaneous insulin infusion therapy.

The cutaneous complications that can develop with continuous subcutaneous insulin infusion constitutes a significant concern when using this innovative and highly effective form of treatment for type I diabetes. These complications are twofold, the first being infection with abscess formation at the infusion needle site. Proper hygiene and frequent changing of the infusion site are helpful and effective measures. The second complication is the development of local allergic skin reactions, again at the infusion needle site, even with highly purified pork insulin. These may subside after several weeks on their own but switching insulin preparations also may be helpful.

Adolescent↗
PubMedDate not supplied

The effect of continuous subcutaneous insulin infusion on endogenous insulin secretion in type I diabetes.

In an attempt to elucidate possible mechanisms for the success of continuous subcutaneous insulin infusion (CSII), we evaluated the C-peptide response to a standard breakfast in seven type I diabetic patients while they were on conventional insulin treatment and again after 4 wk of near-normal glycemia achieved with CSII. While on conventional therapy their 24-h mean blood glucose level was 211 +/- 12 mg/dl and their glycosylated hemoglobin level was 10.6 +/- 0.6%. After 4 wk of CSII their 24-h mean blood glucose level fell to 95 +/- 7 mg/dl and their glycosylated hemoglobin level fell to 6.5 +/- 0.4%. Plasma C-peptide levels were undetectable in all seven patients both while on conventional therapy and after 4 wk of CSII. We conclude that the success of CSII is related to an improved method of insulin delivery and not to either the selection of type I diabetic patients who have some residual insulin secretory capacity or to some change in endogenous insulin secretion produced by the treatment itself.

Adolescent↗
PubMedDate not supplied

Early diabetic nephropathy: assessment and potential therapeutic interventions.

End-stage renal failure secondary to diabetes has increasingly become a health and socioeconomic issue. Diabetic nephropathy is the major cause of death in type I insulin-dependent diabetic patients and accounts for approximately 25% of all patients beginning hemodialysis in the United States. Once diabetic nephropathy is well established, attempts to modify the relentless downward progression of the disease have been essentially unsuccessful. We focus on the early structural and functional changes that occur as a consequence of diabetic renal disease and examine the evidence for microalbuminuria as an early marker and predictor for future overt diabetic nephropathy. The rationale for different therapeutic interventions to alter the course of early diabetic nephropathy are discussed.

Albuminuria↗
PubMedDate not supplied

From motilin to motilides: a new direction in gastrointestinal endocrinology.

Investigation into gastrointestinal irritation from the use of erythromycin lead to the discovery of the gastrointestinal motor effect of this antibiotic. Erythromycin and gastrointestinal peptide motilin share many similar gastrokinetic activities, and studies indicate that erythromycin mimics the effect of motilin through motilin receptor agonism. Since erythromycin is readily available for clinical use, it may offer an alternative therapeutic approach to gastroparesis and related conditions. Several analogs of erythromycin without antimicrobial activity are also shown to possess similar motor effects, thus termed "motilides". A growing number of motilides may expand our knowledge on gastrointestinal peptides.

Journal Article↗