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Biomedical subjects

S V Edelman

Publications and source records attributed to S V Edelman.

32 records · Page 2Linked to original sources
PubMed1990

Use of a variable tracer infusion method to determine glucose turnover in humans.

The single-compartment pool fraction model, when used with the hyperinsulinemic glucose clamp technique to measure rates of glucose turnover, sometimes underestimates true rates of glucose appearance (Ra) resulting in negative values for hepatic glucose output (HGO). We focused our attention on isotope discrimination and model error as possible explanations for this underestimation. We found no difference in [3-3H] glucose specific activity in samples obtained simultaneously from the femoral artery and vein (2,400 +/- 455 vs. 2,454 +/- 522 dpm/mg) in 6 men during a hyperinsulinemic euglycemic clamp study where insulin was infused at 40 mU.m-2.min-1 for 3 h; therefore, isotope discrimination did not occur. We compared the ability of a constant (0.6 microCi/min) vs. variable tracer infusion method (tracer added to the glucose infusate) to measure non-steady-state Ra during hyperinsulinemic clamp studies. Plasma specific activity fell during the constant tracer infusion studies but did not change from base line during the variable tracer infusion studies. By maintaining a constant plasma specific activity the variable tracer infusion method eliminates uncertainty about changes in glucose pool size. This overcame modeling error and more accurately measures non-steady-state Ra (P less than 0.001 by analysis of variance vs. constant infusion method). In conclusion, underestimation of Ra determined isotopically during hyperinsulinemic clamp studies is largely due to modeling error that can be overcome by use of the variable tracer infusion method. This method allows more accurate determination of Ra and HGO under non-steady-state conditions.

Blood Glucose↗
PubMed1990

Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance.

Obesity is characterized by decreased rates of skeletal muscle insulin-mediated glucose uptake (IMGU). Since IMGU equals the product of the arteriovenous glucose difference (AVGd) across muscle and blood flow into muscle, reduced blood flow and/or tissue activity (AVGd) can lead to decreased IMGU. To examine this issue, we studied six lean (weight 68 +/- 3 kg, mean +/- SEM) and six obese (94 +/- 3 kg) men. The insulin dose-response curves for whole body and leg IMGU were constructed using the euglycemic clamp and leg balance techniques over a large range of serum insulin concentrations. In lean and obese subjects, whole body IMGU, AVGd, blood flow, and leg IMGU increased in a dose dependent fashion and maximal rates of all parameters were reduced in obese subjects compared to lean subjects. The dose-response curves for whole body IMGU, leg IMGU, and AVGd were right-shifted in obese subjects with an ED50 two- to threefold higher than that of lean subjects for each parameter. Leg blood flow increased approximately twofold from basal 2.7 +/- 0.2 to 4.4 +/- 0.2 dl/min in lean, P less than 0.01, and from 2.5 +/- 0.3 to 4.4 +/- 0.4 dl/min in obese subjects, P less than 0.01. The ED50 for insulin's effect to increase leg blood flow was about fourfold higher for obese (957 pmol/liter) than lean subjects (266 pmol/liter), P less than 0.01. Therefore, decreased insulin sensitivity in human obesity is not only due to lower glucose extraction in insulin-sensitive tissues but also to lower blood flow to these tissues. Thus, in vivo insulin resistance can be due to a defect in insulin action at the tissue level and/or a defect in insulin's hemodynamic action to increase blood flow to insulin sensitive tissues.

Adult↗
PubMed1990

Reduced postprandial skeletal muscle blood flow contributes to glucose intolerance in human obesity.

While it is well accepted that the disposal of an oral glucose load (OGL) occurs primarily in skeletal muscle, the mechanisms by which this occurs are not completely elucidated. Glucose uptake (GU) in skeletal muscle follows the Fick principal, such that GU equals the products of the arteriovenous glucose difference (AVGd) across and the blood flow (BF) into muscle. It is widely believed that in the postprandial period both insulin and glucose increase GU by increasing the AVGd; however, a role for increments in BF in the disposal and tolerance of an OGL has not been established. To investigate this issue, whole body GU (isotope dilution), leg GU (leg balance technique), leg BF, and cardiac index (CI) were measured after an overnight fast and over 180 min after an OGL (1 g/kg) in 8 lean (ln) and 8 obese (ob) subjects [mean +/- SEM age, 36 +/- 2 vs. 37 +/- 2 yr (P = NS) and 60 +/- 1 vs. 99 +/- 5 kg (P less than 0.01), respectively]. Serum glucose levels were higher in the ob than in the ln subjects between 100 and 160 min, indicating reduced glucose tolerance. Fasting and post-OGL serum insulin levels were 2- to 3-fold higher in ob vs. ln at all times, indicating insulin resistance. Peak (40-80 min) incremental whole body GU above baseline was 32% lower in ob vs. ln, (P less than 0.05). Peak femoral AVGd was not different between ob and ln (0.55 +/- 0.16 vs. 0.66 +/- 0.14 mmol/L; P = NS). Peak leg BF increased 36% over baseline in ln (0.328 +/- 0.052 to 0.449 +/- 0.073 L/min; P less than 0.05), while ob subjects displayed no change in leg BF from baseline. Consequently, peak leg GU was 44% lower in ob vs. ln (P less than 0.05). CI increased 24% from baseline at 60 min in ln (P less than 0.05), but was unchanged in ob. In summary, after an OGL 1) femoral AVGd increases in both ln and ob subjects, but skeletal muscle BF and CI increase in ln only; 2) since peak femoral AVGd values were similar in ln and ob, differences in peak leg GU and (by inference) whole body GU are largely due to reduced BF to insulin-sensitive tissues; and 3) hemodynamics play an important role in the physiological disposal of an OGL, and therefore, hemodynamic defects can potentially contribute to reduced glucose tolerance and insulin resistance.

Adult↗
PubMed1990

Kinetics of insulin-mediated and non-insulin-mediated glucose uptake in humans.

The kinetics of insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU) in humans have not been well defined. We used the glucose-clamp technique to measure rates of whole-body and leg muscle glucose uptake in six healthy lean men during hyperinsulinemia (approximately 460 pM) to study IMGU and during somatostatin-induced insulinopenia to study NIMGU at four glucose levels (4.5, 9, 12, and 21 mM). To measure leg glucose uptake, the femoral artery and vein were catheterized, and blood flow was measured by thermodilution (leg glucose uptake = arteriovenous glucose difference [A-VG] x blood flow). With this approach, we found that, during hyperinsulinemia, both whole-body and leg glucose uptake increased in a curvilinear fashion at every glucose level, the highest glucose uptake values obtained being 139 +/- 17 mumol.kg-1.min-1 and 3656 +/- 931 mumol.min-1.leg-1, respectively. Leg blood flow increased twofold from 6.0 +/- 1.7 to 11.7 +/- 3.1 dl/min (P less than 0.01) over the range of glucose and was correlated with whole-body glucose uptake (r = 0.55, P less than 0.005). Leg muscle glucose extraction, independent of changes in blood flow, which is reflected by the A-VG, saturated over the range of glucose (1.28 +/- 0.12, 2.22 +/- 0.30, 2.92 +/- 0.42, 3.02 +/- 0.41 mM, NS between last 2 values) with a half-maximal effective glucose concentration (EG50) of 5.3 +/- 0.4 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Kinetics of in vivo muscle insulin-mediated glucose uptake in human obesity.

The kinetics of in vivo insulin-mediated glucose uptake in human obesity have not been previously studied. To examine this, we used the glucose-clamp technique to measure whole-body and leg muscle glucose uptake in seven lean and six obese men during hyperinsulinemia (approximately 2000 pM) at four glucose levels (approximately 4.5, approximately 8.3, approximately 13.5, and approximately 23.5 mM). To measure leg glucose uptake, the femoral artery and vein were catheterized, and blood flow was measured by thermodilution (leg glucose uptake = arteriovenous glucose difference x blood flow). With this approach, we found that rates of whole-body and leg glucose uptake were significantly lower in obese than in lean subjects at each glucose plateau. Leg blood flow rates increased from 4.3 +/- 0.4 to 6.5 +/- 0.8 dl/min over the range of glucose in lean subjects (P less than 0.05) but remained unchanged in obese subjects. The apparent maximal capacity (Vmax), based on whole-body and leg glucose uptake, was reduced in obese compared with lean subjects, but the apparent Km was similar in the lean and obese subjects (6-9 mM, NS). To assess the affinity of muscle for glucose extraction independent of changes in muscle plasma flow, we determined the mean half-maximal effective glucose concentration (EG50) and found it was similar in the lean and obese subjects (6.0 +/- 0.3 vs. 6.0 +/- 0.8 mM, NS). We conclude that 1) the kinetics of in vivo insulin-mediated glucose uptake in skeletal muscle in human obesity are characterized by reduced Vmax but normal Km; 2) the EG50 for insulin-mediated glucose extraction in skeletal muscle was 6 mM in both lean and obese subjects, consistent with a Km characteristic of the glucose-transport system; 3) obese subjects were unable to generate increases in blood flow in response to hyperglycemia under hyperinsulinemic conditions, and this contributed significantly to lower rates of leg and whole-body glucose uptake.

Adult↗
PubMed1989

Effects of free fatty acids and ketone bodies on in vivo non-insulin-mediated glucose utilization and production in humans.

The current study was undertaken to examine the effect of an acute elevation of serum levels of free fatty acids (FFA) and ketone bodies (KB) on non-insulin-mediated glucose uptake (NIMGU) in humans. The study group consisted of 11 healthy men, mean age (+/- SD) 30 (+/- 7) years and mean weight (+/- SD) 72 (+/- 7) kg. To examine the effects of FFA levels on NIMGU and insulin-mediated glucose uptake (IMGU), glucose uptake was measured isotopically (3H-3-glucose) in six subjects on four separate days during saline infusion or lipid + heparin infusion with concomitant infusions of somatostatin (SHIF, 0.16 micrograms/kg/min) with or without insulin infusion (40 mU/m2/min) while the serum glucose level was clamped at approximately 11 mmol/L. To examine the effect of KB on NIMGU, saline or sodium acetoacetate (20 mumol/kg/min) was infused in five subjects on separate days during SRIF-induced insulinopenia while the serum glucose level was clamped sequentially at euglycemia and at approximately 11 mmol/L. During insulinopenia basal FFA levels rose twofold during saline infusion and sixfold during infusion of lipid + heparin. Rates of NIMGU were 2.49 +/- 0.27 v 2.41 +/- 0.14 mg/kg/min during saline and lipid infusion, respectively (P = NS). Rates of IMGU were decreased by 55% during lipid + heparin infusion. During insulinopenia basal beta-hydroxybutyrate (BOB) levels rose twofold during saline and approximately 11-fold during sodium acetoacetate infusion. Rates of NIMGU were unchanged by the sodium acetoacetate infusion at euglycemia and hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetoacetates↗
PubMed1988

Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans.

In vivo glucose uptake can occur via two mechanisms, namely, insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU). Although the principal tissue sites for IMGU are skeletal muscle, the tissue sites for NIMGU at a given serum glucose concentration are not known. To examine this issue, rates of whole body glucose uptake (Rd) were measured at basal and during glucose clamp studies performed at euglycemia (approximately 90 mg/dl) and hyperglycemia (approximately 220 mg/dl) in six lean healthy men. Studies were performed during hyperinsulinemia (approximately 70 microU/ml) and during somatostatin-induced insulinopenia to measure IMGU and NIMGU, respectively. During each study, leg glucose balance (arteriovenous catheter technique) was also measured. With this approach, rates of whole body skeletal muscle IMGU and NIMGU can be estimated, and the difference between overall Rd and skeletal muscle glucose uptake represents non-skeletal muscle Rd. The results indicate that approximately 20% of basal Rd is into skeletal muscle. During insulinopenia approximately 86% of body NIMGU occurs in non-skeletal muscle tissues at euglycemia. When hyperglycemia was created, whole body NIMGU increased from 128 +/- 6 to 213 +/- 18 mg/min (P less than 0.01); NIMGU into non-skeletal muscle tissues was 134 +/- 11 and 111 +/- 6 mg/min at hyperglycemia and euglycemia, respectively, P = NS. Therefore, virtually all the hyperglycemia induced increment in NIMGU occurred in skeletal muscle. During hyperinsulinemia, IMGU in skeletal muscle represented 75 and 95% of body Rd, at euglycemia and hyperglycemia, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Fasting decreases rates of noninsulin-mediated glucose uptake in man.

Although fasting decreases insulin-mediated glucose uptake (IMGU), its effect on noninsulin-mediated glucose uptake (NIMGU) is not known. To examine this issue we studied seven obese men [mean (+/- SD) age, 36 +/- 5 yr; weight, 91 +/- 13 kg] after an overnight fast (day 0) and 3 days (day 4) and 9 days (day 10) of total fasting and six normal weight men (age, 32 +/- 4 yr; weight, 73 +/- 6 kg) after an overnight and 3 days of fasting. To study NIMGU, somatostatin (0.16 micrograms/kg.min) was infused to create severe insulin deficiency and [3H]3-glucose to measure glucose disappearance (Rd), while serum glucose was sequentially clamped at a level of about 4.7 mmol/L for 180 min and about 11 mmol/L for an additional 100 min. The results from the last 60 min of each glycemic plateau were used for analysis. Under these conditions insulin action is absent and Rd = NIMGU. Since under conditions of euglycemic insulinopenia, NIMGU into noncentral nervous system tissues is negligible, and central nervous system (CNS) glucose uptake saturates at physiological glucose concentrations, it follows that at a glucose level of about 4.7 mmol/L, NIMGU reflects CNS glucose uptake and at about 11 mmol/L, NIMGU reflect CNS plus non-CNS tissues. Thus, non-CNS NIMGU = NIMGU at 11 mmol/L - NIMGU at about 4.7 mmol/L. The obese subjects' mean weight fell to 88 +/- 5 kg on day 4 and 85 +/- 5 kg on day 10 (P less than 0.001 between all values). The mean basal serum glucose level fell from 5.3 +/- 0.1 on day 0 to 4.2 +/- 0.2 and 3.8 +/- 0.2 mmol/L on days 4 and 10, respectively (P less than 0.01 between all values). During insulinopenia plasma FFA and serum beta-hydroxybutyrate levels on day 10 were 3- and 30-fold higher than the basal prefast levels, respectively. Noninsulin-mediated glucose clearance at about 4.7 mmol/L did not change during fasting [0.0016 +/- 0.0001 (day 0) vs. 0.0016 +/- 0.0001 (day 4) and 0.0014 +/- 0.0001 L/kg.min (day 10); P = NS between all values]; at about 11 mmol/L noninsulin-mediated glucose clearance fell from 0.0016 +/- 0.0001 on day 0 to 0.0001 +/- 0.0001 dL/kg.min on day 10 (P less than 0.001). Results in the lean group were similar to those in the obese group after a 3-day fast.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Neuro-osteoarthropathy (Charcot's joint) in diabetes mellitus following revascularization surgery. Three case reports and a review of the literature.

The initial primary defect in the development of neuro-osteoarthropathy is neuropathy. Our case reports and a review of the literature strongly implicate a neurally initiated vascular reflex leading to increased blood flow. This may play a pivotal role in the development of Charcot's joint in the neuropathic limb. Mechanical trauma in an insensitive foot is contributory, but it is probably a secondary mechanism.

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

New orally administered antihyperglycemic agents for the management of patients with type ii diabetes and the syndrome of insulin resistance.

OBJECTIVE: To describe several newly developed orally administered antidiabetic drugs, which are effective for type II diabetes. METHODS: Detailed clinical information about three types of antihyperglycemic agents--carbohydrase inhibitors, biguanides, and thiazolidinediones--is presented. RESULTS: Miglitol and acarbose, two a-glucosidase inhibitors, effectively reduce postprandial blood glucose values and do not cause hypoglycemia. The biguanide metformin has been shown to suppress hepatic glucose production, augment glucose uptake, and enhance insulin action in peripheral tissues. Metformin is effective alone or in combination with other orally administered antidiabetic agents or insulin. A new class of antidiabetic agents called the thiazolidinediones (not yet available for clinical use) apparently works by mainly reducing insulin resistance in skeletal muscle. The most extensively studied drug in this category is troglitazone. Carbohydrase inhibitors as well as biguanides may be useful in patients with the insulin resistance syndrome, especially those with obesity, hypertension, and hyperinsulinemia. CONCLUSION: Because of the development of new antihyperglycemic agents for oral administration, the need for insulin injections in patients with type II diabetes will be minimized, and the clinical management of such patients will be improved.

Journal Article↗
PubMedDate not supplied

Home testing of fructosamine improves glycemic control in patients with diabetes.

OBJECTIVE: To determine whether weekly fructosamine testing at home by patients with type 2 diabetes, combined with therapeutic intervention when necessary on the basis of the results, would lead to improved glycemic control in comparison with usual care during a 3-month period. METHODS: In a prospective study, 25 patients with glycosylated hemoglobin (HbA1c) values above 8.0% were randomized into 2 groups. Both groups, a glucose-only testing group (14 patients with an initial mean HbA1c of 9.4 +/- 0.9%) and a combined glucose plus fructosamine testing group (11 patients with an initial mean HbA1c of 9.2 +/- 0.7%), received therapeutic intervention at the time of randomization. Both groups were instructed to perform blood glucose testing up to four times per day. The combined glucose plus fructosamine testing group was also instructed to perform weekly fructosamine testing in addition to the glucose testing and to telephone the investigator if their home-testing fructosamine value exceeded 350 mmol/L (approximately equivalent to HbA1c of 7.8%), whereupon the investigator implemented further interventions. Both groups returned in 3 months, at which time HbA1c testing was repeated in order to determine whether glycemic control had changed. RESULTS: The study results after 3 months showed that the HbA1c values in the combined glucose plus fructosamine testing group decreased from 9.2 +/- 0.7% to 8.0 +/- 0.5% (P<0.0001). In contrast, the HbA1c values in the glucose-only testing group declined from 9.4 +/- 0.9% to 9.1 +/- 1.3%, a difference that was not significant. CONCLUSION: In the 3 months after a change in therapy for type 2 diabetes, weekly home testing of fructosamine, combined with therapeutic interventions based on the results, led to a more rapid and significant improvement in glycemic control than did the usual regimen of glucose-only testing.

Blood Glucose Self-Monitoring↗
PubMedDate not supplied

Implantable insulin pump vs multiple-dose insulin for non-insulin-dependent diabetes mellitus: a randomized clinical trial. Department of Veterans Affairs Implantable Insulin Pump Study Group.

OBJECTIVE: To determine whether implantable insulin pump (IIP) therapy and multiple daily insulin (MDI) injections could equally attain improved blood glucose control, and to compare the 2 treatments with respect to reducing daily blood glucose fluctuations, reducing serious hypoglycemic insulin reactions, and improving patients' quality of life. DESIGN: Randomized clinical trial. SETTING: Seven Veterans Affairs medical centers. PATIENTS: One hundred twenty-one male type II diabetic patients between the ages of 40 and 69 years, receiving at least 1 injection of insulin per day and having hemoglobin A1c (HbA1c) levels of 8% or above. INTERVENTION: Intensive therapy (IIP or MDI) for 1 year. MAIN OUTCOME MEASURES: Hemoglobin A1c and blood glucose levels. RESULTS: Blood glucose levels declined to 7.96+/-1.08 mmol/L (143.4+/-19.5 mg/dL) and 8.30+/-1.52 mmol/L (149.6+/-27.4 mg/dL) (mean +/- SD) for IIP and MDI, respectively (P=.57). Hemoglobin A1c levels improved in both groups (time effect P<.001), to means of 7.54%+/-0.83% (MDI) vs 7.34%+/-0.79% (IIP). IIP reduced blood glucose fluctuations compared with MDI (P<.001), and reduced the incidence of mild clinical hypoglycemia by 68% (P<.001); IIP also eliminated the weight gain associated with MDI therapy and yielded better overall quality-of-life (P=.03) and impact-of-disease subscale scores (P=.05). Adverse events included 25% of subjects with episodes of insulin underdelivery due to microprecipitates of insulin within the pump. CONCLUSIONS: Intensive insulin therapy with IIP and MDI is effective in controlling non-insulin-dependent diabetes mellitus. IIP has significant advantages in reducing glycemic variability, clinical hypoglycemia, and weight gain, while improving aspects of quality of life.

Adult↗