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Biomedical subjects

A Frid

Publications and source records attributed to A Frid.

18 recordsLinked to original sources

Glycaemic and nonglycaemic effects of pioglitazone in triple oral therapy of patients with type 2 diabetes.

OBJECTIVES: To examine pioglitazone as add-on to metformin and insulin secretagogues in patients with type 2 diabetes and inadequate glycaemic control and its effect on glycaemic control, surrogate measures of insulin sensitivity (adiponectin) and beta-cell function (proinsulin/insulin) and fluid retention. DESIGN AND SETTING: Prospective open-label study of 54 patients with type 2 diabetes and HbA1c>or=6.5% admitted to outpatient unit at Malmö University Hospital. The patients received 30-45 mg pioglitazone daily during 26 weeks in addition to their existing antidiabetic medication. After 26 weeks, one-third of patients were followed for 3 months without pioglitazone. RESULTS: HbA1c decreased (7.8+/-0.9-6.3+/-0.9%, P<0.001) with 61% of patients achieving levels<6.5%. However, in the group followed for another 3 months HbA1c increased (6.1+/-0.73-7.1+/-0.9, n=18, P<0.001) after pioglitazone withdrawal. Adiponectin increased (6.1+/-2.8-13.2+/-5.8 microg mL-1, P<0.001) and the proinsulin to insulin ratio decreased (0.89+/-0.66-0.66+/-0.53, P<0.001). Nt-proBNP increased from 487.3+/-252.2 to 657.8+/-392.1 pmol L-1 (P<0.001). CONCLUSIONS: Pioglitazone is effective in achieving glycaemic targets and reducing risk factors involved in atherosclerosis and improving beta-cell function when used as part of triple oral therapy in patients with type 2 diabetes and secondary drug failure. Nt-proBNP increase with concomitant decrease in haemoglobin suggests a subclinical sign of fluid retention.

Adiponectin↗

Impaired glucose tolerance associated with adverse pregnancy outcome: a population-based study in southern Sweden.

OBJECTIVE: We conducted a population-based study of maternal and neonatal characteristics and delivery complications in relation to the outcome of a 75-g, 2-hour oral glucose tolerance test at 25 to 30 weeks' gestation. STUDY DESIGN: An oral glucose tolerance test was offered to pregnant women in a geographically defined population. Pregnancy outcome was analyzed according to the test result. RESULTS: Among women delivered at Lund Hospital, we identified 4526 women with an oral glucose tolerance value of <7.8 mmol/L (<140 mg/dL), 131 women with a value of 7.8 to 8.9 mmol/L (140-162 mg/dL), and 116 women with gestational diabetes (> or =9.0 mmol/L [> or =162 mg/dL]). A further 28 cases of gestational diabetes were identified, giving a prevalence of 1.2%. An increased rate of cesarean delivery and infant macrosomia was observed in the group with a glucose tolerance value of 7.8 to 8.9 mmol/L (140-162 mg/dL) and in the gestational diabetes group. Advanced maternal age and high body mass index were risk factors for increased oral glucose tolerance values in 12,657 screened women in the area. CONCLUSION: The study stresses the significance of moderately increased oral glucose tolerance values.

Adolescent↗

Influence of bisphosphonate on the negative erythropoietic effects of uranyl nitrate.

Uranium salts, such as uranyl nitrate, induce severe renal dysfunction and tubular necrosis and a significant impairment of both oxygen dependent erythropoietin production and response to recombinant human erythropoietin. All effects are transient and reach maximal severity on the 7th day post injection. We investigated the effects of ethane 1-hydroxy-1, 1-bisphosphonate, which counteracts the inhibitory effect of uranyl nitrate on bone formation, on the negative erythropoietic effects of uranyl nitrate. Adult female Wistar rats received 1 mg/kg body weight of uranyl acetate by the i.v. route. Ethane 1-hydroxy-1,1-bisphosphonate was injected simultaneously at a dose of 7.5 mg/kg by the same route. Seven days after drug injections, plasma erythropoietin was estimated after hypobaric hypoxemia or cobalt chloride administration. The response to exogenous erythropoietin was also measured in uranyl nitrate- and/or ethane 1-hydroxy-1,1-bisphosphonate-injected rats made polycythemic by transfusion. The erythroid response was quantitated in terms of red blood cell 59iron uptake. Ethane 1-hydroxy-1, 1-bisphosphonate counteracted the effect of uranyl nitrate on oxygen-dependent and cobalt-dependent erythropoietin production, but did not correct the right shift of the dose-response relationship for exogenous erythropoietin induced by uranyl nitrate in the polycythemic rat.

Animals↗

The thigh may not be suitable as an injection site for patients self-injecting sumatriptan.

The objective of our study was to evaluate the differences between injection sites in the midthigh and the upper lateral quadrant of the gluteal area regarding the effect, depth of subcutaneous tissue, side effects, and patient preference in patients with cluster headache who self-inject 6 mg (0.5 ml) of sumatriptan. Our open, prospective clinical study was performed at the outpatient department of a Swedish university clinic. There were 19 male and one female subjects, 34 to 68 years old, suffering from cluster headache. We measured the subcutaneous tissue depth by ultrasound. Subjects performed four self-injections of sumatriptan, two in the thigh and two in the gluteal area. We evaluated the subcutaneous tissue depth from the skin surface to the muscle fascia, the effect on headache, side effects, and patient preference regarding the injection site. Subcutaneous tissue depth laterally in the thigh was 2 to 12 mm (median, 4 mm) and in the gluteal area was 34 to 68 mm (median, 45 mm). The needle of the self-injector protrudes 5 to 6 mm. Forty thigh and 39 gluteal injections were recorded. The effect on headache was equal. Following injection in thigh the patients experienced more bleeding (p < 0.001, chi 2); local pain (p < 0.05, chi 2); and a feeling of oppression in the head, neck, and chest area (p < 0.05, chi 2); compared with injections in the gluteal area. Fifteen patients preferred the gluteal area as the injection site after the study, two patients had no preference, and three preferred the thigh. When using the self-injector in the lateral aspect of the thigh, intramuscular injection is liable to occur frequently in male patients. This may explain the differences in local and general side effects observed in this study. The upper lateral quadrant of the gluteal area is a more suitable injection site for male, and some female, patients when using the sumatriptan self-injector.

Adult↗

Unchanged insulin absorption after 4 days' use of subcutaneous indwelling catheters for insulin injections.

OBJECTIVE: Since 1985, we have used indwelling catheters (Insuflon, Maersk Medical, Lynge, Denmark; Chronimed, Minnetonka, MN) to lessen pain when injecting insulin. However, some patients experience a rise in blood glucose after using indwelling catheters for a few days. We therefore studied the absorption of 125I-labeled insulin when using indwelling catheters. RESEARCH DESIGN AND METHODS: Five men and five women participated (age 18-25 years, C-peptide negative, HbA1c 9.0 +/- 1.0% [mean +/- SD, DCA-2000 method], diabetes duration 5-21 [median 9.5] years). After thyroid blockage with potassium iodide, we injected 5IU of 125I-labeled short-acting insulin subcutaneously in the abdomen ("ordinary injection") and 5 IU on the contralateral side through an indwelling catheter ("catheter injection"). The injection/insertion area was free of lipohyper- and lipohypotrophies. Disappearance rate was measured for 180 min with a gamma camera. The patients injected all premeal injections of short-acting insulin through the same indwelling catheter in the following 4 days. The investigation procedure was repeated day 3 and 5. RESULTS: We found no statistically or clinically (95% CI) significant difference in residual activity of 125I-insulin after 60 min or in time for 50% of the injected depot to disappear (T-50%) among catheter injections on day 1, 3, and 5; ordinary injections on days 1, 3, and 5; or catheter and ordinary injections on days 1, 3, and 5, respectively. HbA1c correlated both to T-50% (r = 0.73, P = 0.016) and residual activity of 125I-insulin after 60 min (r = 0.69, P = 0.028), indicating that patients with a slower absorption will have a less ideal metabolic control when using premeal bolus injections. CONCLUSIONS: We conclude that using indwelling subcutaneous catheters for insulin injections for up to 4 days does not affect the absorption of short-acting insulin.

Absorption↗

Depressed eruption dental rate in rats with hemodynamically-mediated acute renal failure.

The effects of acute renal failure on the impeded (IER) and unimpeded (UER) eruption dental rate and attrition rate (AR) were investigated. Adult female Wistar rats were injected with 125 mg/kg b.w of human methemoglobin (M-Hb) in order to induce a first episode of hemodynamically-mediated acute renal failure (H-ARF). Ten days after the injection of M-Hb, other groups of rats received another equal dose of the drug in order to induce a second episode of H-ARF. A group of six animals was pair-fed daily and individually with rats of M-Hb groups. Evaluation of renal function, histopathology studies, IER, UER, food intake (FI), AR and body weight gains was performed at different times after the first and second injections, of M-Hb. Treatment induced transient increases in plasma urea concentration and urine volume, and significant depression in urine osmolality, body weight gains, IER, UER and AR. In every case, the maximal effect of the first injection of M-Hb on the individual parameters was always greater than that of the second injection. Histologic sections showed interstitial cellular infiltration, desquamation of the proximal tubular epithelium and collapse or dilation of the tubular lumen. The functional values of kidney, histologic findings, IER, UER and AR of the pair-fed rats were not significantly different from control values. The results of the present study indicate that dental eruption rate (IER and UER) is relatively low in uremic rats with kidney tubule lesions and that both parameters are related.

Acute Kidney Injury↗

Intraregional differences in the absorption of unmodified insulin from the abdominal wall.

Absorption of subcutaneously injected unmodified human 125I-insulin (5 U; 100 U ml-1) was studied concurrently from three areas of the abdominal wall (120 mm above, 120 mm lateral to, and 40 mm below the umbilicus), and one area of the thigh (upper midline), in nine Type 1 diabetic patients of normal body weight, and from deep (2 mm above muscle fascia) and superficial (3 mm beneath skin surface) sites in abdominal wall and thigh in 11 Type 1 diabetic patients. The absorption rates were followed continuously for 3 h with the patient in the supine position. Whereas 125I-insulin disappeared considerably faster from the site above the umbilicus than from sites below or lateral to the umbilicus or from the thigh (residual radioactivities after 175 min: 36 +/- 4 vs 49 +/- 5, 54 +/- 2, and 62 +/- 4 (+/- SE)%, respectively; p less than 0.05 or better), no significant differences were found between deep and superficial sites in either abdominal wall or thigh. The results suggest that insulin absorption rates from subcutaneous injection sites within the abdominal wall differ sufficiently for this to be of clinical importance.

Abdominal Muscles↗

Growth of the skeletal units of the rat mandible in acute renal failure experimental model.

A study of the effect of acute renal failure (ARF) on the growth of the skeletal units of the mandible was performed. Male Wistar rats weighing 35-40 g were assigned to three groups. One of the groups received a basal choline-deficient diet ad libitum. A second group was pair-fed with the first one and was given a basal diet supplemented with 0.35 g choline chloride/100 g of diet. The third group was fed a basal diet plus 0.35 g choline chloride/100 g of diet ad libitum and used as the normal control. Body length, renal function parameters and measurements of the mandible were recorded at the end of a 12-day period on the different diets. Food intake and body weight were recorded every day. Plasma urea and creatinine concentrations markedly increased over the first 12 days of exposure to a choline-deficient diet. Significant increases in urine volume and significant depressions in urine osmolality were also observed. The average body weight and body length gains for rats given the choline-deficient diet were lower than those of control rats. There were no significant differences between the average body weight and body length of pair-fed and normal rats. All skeletal measurements of the mandible of the choline-deficient group differed significantly from those of the control group. These differences varied between 7% and 30%. The skeletal units of the mandible of the pair-fed group did not differ significantly from ad libitum controls. This study suggests that this rat model can be used for the investigation of the different alterations observed in uremia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Hypoglycemia risk during exercise after intramuscular injection of insulin in thigh in IDDM.

The influence of bicycle exercise (60% of W170 [working capacity at a pulse rate of 170 beats/min]; 40 min) on the absorption of 125I-labeled fast-acting insulin (10 U; Actrapid human insulin) after intramuscular compared with subcutaneous injection in the thigh was studied on 2 consecutive days in 10 insulin-dependent diabetes mellitus (IDDM) patients. Insulin absorption was measured as disappearance of radioactivity (1st-order elimination rate constants) by continuous external monitoring and as appearance of plasma free immunoreactive insulin (IRI). Subcutaneous adipose tissue blood flow (ATBF) and skeletal muscle blood flow (MF) were measured concomitantly in the contralateral thigh with the 133Xe wash-out technique. Plasma glucose was determined intermittently. The rate constant for 125I-insulin increased during exercise from 0.46 +/- 0.08 to 1.17 +/- 0.14%/min after intramuscular injection (P less than 0.001) and from 0.31 +/- 0.05 to 0.45 +/- 0.09%/min (NS) after subcutaneous injection. The rate constant of 125I-insulin from muscle remained elevated during the 80-min recovery period. The peak plasma free-IRI value was 39 mU/L higher, the area under the IRI curve was approximately 80% greater, and the decrease in plasma glucose was approximately 2 mM greater after intramuscular injection. Whereas MF increased fivefold, ATBF did not rise significantly during exercise. The results demonstrate that intramuscular compared with subcutaneous thigh injection of insulin followed by bicycle exercise induces a marked increase in insulin absorption and a substantial fall in plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Depressed plasma erythropoietin levels in rats with hemodynamically-mediated acute renal failure.

Adult female Wistar rats were injected with 125 mg/kg b.w. of human methemoglobin (M-Hb) in order to induce a first episode of hemodynamically-mediated acute renal failure (HMARF). Eleven days after the injection of M-Hb, other groups of rats received another equal dose of the drug in order to induce a second episode of HMARF. Evaluation of renal function, histopathology studies, and determinations of plasma and kidney erythropoietin (Epo) titers by radioimmunoassay in normoxic and hypoxic conditions were performed 1, 2, 3, 5 and 10 days after M-Hb administration. Treatment induced transient increases in plasma urea concentration, fractional sodium excretion, and urine volume, and significant depression in urine osmolality. In every case, the maximal effect of the first injection of M-Hb on the individual parameters was always greater than that of the second injection, and observed on the 5th post-injection day. Histologic sections showed interstitial cellular infiltration, desquamation of the proximal tubular epithelium and collapse or dilation of the tubular lumen. Treatment with M-Hb depressed Epo titers in both kidney homogenates and plasma in normoxic as well as hypoxic rats. Here again, the effect of the first injection of the drug was higher than that of the second one. These observations indicate that there is a negative correlation between kidney tubule injury and Epo production in normoxic and hypoxic conditions. The findings give support to the concept that Epo production is related to proximal tubular function.

Acute Kidney Injury↗

Effects of accidental intramuscular injection on insulin absorption in IDDM.

Recent studies have shown that with the injection technique presently recommended to diabetic patients, accidental intramuscular injection of insulin is liable to occur quite frequently. In this study, the simultaneous absorption of 125I-labeled soluble human insulin (5 U) from subcutaneous and intramuscular injection sites in the thigh and abdomen was measured for 3 h in 10 insulin-dependent diabetic subjects to evaluate the importance of accidental intramuscular injection for insulin absorption in the resting state. Injection sites were located with computed tomography of the thigh and abdomen. From a superficial part of the thigh musculature, the absorption rate was at least 50% higher than from the adjacent subcutaneous tissue, the time until 50% of the initial activity remained (t1/2) being 123 +/- 14 and greater than 180 min, respectively (P less than .001). No difference in absorption rates was found between the two tissues in the abdomen (t1/2 84 +/- 6 vs. 93 +/- 7 min, NS). The results suggest that in the thigh, accidental intramuscular injections will considerably increase the variability of insulin absorption and may impair glycemic control in insulin-dependent diabetic patients. Furthermore, the influence of accidental intramuscular injection on insulin absorption seems to vary among injection regions.

Abdomen↗

Clinically important differences in insulin absorption from abdomen in IDDM.

The absorption of radiolabeled soluble insulin ([125I]Actrapid Human; 10 U) from subcutaneous injection sites above (120 mm) and below (40 mm) the umbilicus was studied on 2 consecutive days in nine IDDM patients during 180 min. Insulin absorption was measured as disappearance of radioactivity by continuous external monitoring and as appearance of plasma immunoreactive free insulin (IRI). Adipose tissue blood flow (ATBF) was measured concomitantly by the 133Xe-washout technique. Plasma glucose was determined. Prior to the injections the depth of the subcutaneous fat tissue was determined using ultrasound. Significantly less radioactivity remained at the upper site, 42 +/- 5 vs. 60 +/- 6% after 180 min (P < 0.001). In accordance with this, injection into the site above vs. below the umbilicus resulted in a greater area under curve for plasma insulin, 3306 +/- 493 vs. 2357 +/- 466 mU/l per min (0-180 min; P < 0.01), and a more pronounced plasma glucose-lowering effect (P < 0.05). However, ATBF did not differ significantly between the two sites. These data suggest that there are clinically relevant differences in insulin absorption within the abdomen. Thus, insulin injection into the epigastric area causes more rapid insulin absorption resulting in an enhanced plasma glucose-lowering effect than injection into the more conventional site close beneath the umbilicus.

Abdomen↗