Biomedical subjects

A Pfützner

Publications and source records attributed to A Pfützner.

At least 37 records · Page 2Linked to original sources

PubMed2003

Pilot study with technosphere/PTH(1-34)--a new approach for effective pulmonary delivery of parathyroid hormone (1-34).

Sequential subcutaneous PTH injection therapy (repeated 14 days of PTH administration and a subsequent treatment pause for a few weeks) is known to increase bone mineral density in patients with osteopenic disorders. Alternative methods of drug delivery may be beneficial in increasing compliance. A pilot study was performed in 10 healthy volunteers (4 female/6-male, age: 25.6 +/- 3.5 years, BMI: 22.3 +/- 2.4 kg/m 2, mean +/- SD) to assess the pharmacokinetic profiles of 1600 IU of PTH(1 - 34) using the pulmonary Technosphere drug delivery system in comparison to a subcutaneous injection of 400 IU. The treatments were administered in the morning after an overnight fast and blood samples for measurement of PTH(1 - 34), PTH(1 - 84), and calcium and calcitonin were taken over a period of 6 hours. Both injection and pulmonary application of PTH(1 - 34) were well tolerated. After pulmonary administration of Technosphere/PTH(1 - 34), PTH(1 - 34) appeared in the serum with a faster concentration increase (T max: pulmonary 10 +/- 5 min vs. subcutaneous 28 +/- 8 min, p < 0.001) and with higher maximal concentrations (C max : pulmonary 309 +/- 215 pmol/l vs. subcutaneous 102 +/- 45 pmol/l, p < 0.05) as compared to the subcutaneous injection. The relative bioavailability of pulmonary Technosphere/PTH(1 - 34) was calculated to be 48 %. No differences were seen between pulmonary and subcutaneous application with regard to the PTH(1 - 84), calcitonin and calcium concentrations. In conclusion, pulmonary application of Technosphere/PTH(1 - 34) appears to be an effective and thus attractive candidate for PTH substitution therapy in osteoporosis and other conditions leading to a decrease in bone mineral density.

Adult↗

PubMed2003

Investigation on the accuracy of the blood glucose monitoring device Prestige IQ.

The aim of this study was to investigate the accuracy and reliability of the blood glucose self-monitoring system Prestige IQ (Home Diagnostics, Inc., Ft. Lauderdale, USA) in comparison to an established blood glucose reference method and four commercially available blood glucose self-monitoring devices. Over a 3-month period, 61 patients with Type 1 (T1DM) and Type 2 diabetes mellitus (T2DM) participated in this study. The patients entered the study clinic for two visits. Each visit consisted of 7 glucose determinations in samples of capillary whole blood drawn from the fingertip. The first and last measurements were determined using the laboratory reference and the mean of both readings was used as the reference value for statistical analysis. The 5 remaining glucose measurements were performed in randomized order using the 5 commercially available blood glucose devices. One hundred twenty-one data sets were generated and used to evaluate accuracy. Prestige IQ blood glucose results obtained from the fingertip agreed well with the laboratory reference (linear regression analysis: slope = 1.016; intercept = 0.4 mg/dl; SD = 13.555 mg/dl; correlation r = 0.972) and were comparable to the results generated using the other four blood glucose devices. Bland-Altman analysis for reliability confirmed that 119 out of 121 Prestige IQ results (98.3%) exhibited acceptable accuracy as defined in the new ISO/DIS guideline 15197.2 (85.1-99.2% in this area for the other devices). Error-grid-analysis shows all Prestige IQ glucose results in clinically acceptable zones A and B (95.9% in zone A and 4.1% in zone B). In conclusion, Prestige IQ showed excellent performance with clinically acceptable accuracy and reliability as compared to both the laboratory reference and the four commercially available self-monitoring blood glucose systems.

Aged↗

PubMed2002

The influence of local capsaicin treatment on small nerve fibre function and neurovascular control in symptomatic diabetic neuropathy.

Topical treatment with capsaicin cream has been shown to be successful in the treatment of different symptomatic nerve disorders like diabetic neuropathy. Conflicting data exist on the effect of capsaicin on nerve function and neurovascular control especially in patients with diabetic neuropathy. The aim of this pilot study was to investigate the impact of topical capsaicin application on small nerve fibre function and neurovascular control. Capsaicin cream was applied to the feet of 13 patients with symptomatic diabetic neuropathy over a period of 8 weeks. Before and during the treatment period, we investigated the total symptoms score, the vibration, thermal (heat and cold) and pain perception thresholds, and the neurovascular responses to heat and acetylcholine stimuli. In addition, the serum plasma levels of substance P, a neurotransmitter of nociceptor C-fibres, were measured. A significant improvement in total symptoms score was observed during topical capsaicin treatment (18.3+/-3.2 vs. 14.3+/-3.3; p<0.05). An improvement in the heat perception threshold was also found (12.7+/-0.4 degrees C vs. 11.4+/-0.7 degrees C: p<0.05), while other sensory nerve fibre functions remained unchanged. No significant change in neurovascular control was observed, neither after mild thermal injury nor after stimulation with acetylcholine. Serum substance P levels increased after initiation of topical capsaicin treatment (72.9+/-5.8 pg/ml vs. 81.7+/-5.0 pg/ml; p<0.05), but returned to baseline levels during further treatment (77.4+/-8.3 pg/ml: n.s.). In conclusion, topical treatment with capsaicin cream over a period of 8 weeks in patients with symptomatic diabetic neuropathy is effective without adverse effects on nerve fibre function or neurovascular control.

Administration, Topical↗

PubMed2002

Technosphere/Insulin--proof of concept study with a new insulin formulation for pulmonary delivery.

Summary.Technosphere/Insulin (TI) is a formulation of regular human insulin and Technosphere, a new drug delivery system for pulmonary administration. The formulation is designed for efficient transport of insulin across the intact respiratory epithelium into the systemic circulation. We have investigated the pharmacodynamic and pharmacokinetic properties of Technosphere/Insulin in five healthy, non-smoking volunteers. In an open, randomized, three-way crossover study, subjects received 5 IU regular human insulin (HI) intravenously, 10 IU HI subcutaneously; and 100 IU TI via inhalation using a small commercially available asthma inhaler. The time action profiles of all three insulin formulations were assessed by the euglycemic glucose clamp technique on three different study days. Glucose infusion rates were monitored from 2 h before until 6 h after insulin administration. Other study measures were serum insulin, serum C-peptide concentrations, and safety parameters. The inhalation of TI was well tolerated. The time to peak action was significantly shorter with both i.v. injection and inhalation, as compared to s.c. (14 +/- 6 min and 39 +/- 36 min vs. 163 +/- 25 min; p < 0.0002 and p < 0.007 (mean +/- SD)). The metabolic effect during the first 3 h after insulin administration was higher with inhaled TI than with HI s.c. (AUC0-180 for glucose infusion rate: 1.94 +/- 0.77 mg/kg * min vs. 1.15 +/- 0.50 mg/kg * min; p < 0.04). Relative and absolute bioavailability for the first 3 h were 26 +/- 12% and 15 +/- 5% respectively (6 h: 16 +/- 8 and 16 +/- 6%). We conclude that inhalation of TI leads to a rapid onset of metabolic action resembling the effect observed with i.v. administration of regular HI. Despite the use of a common asthma inhaler, bioavailability over the three hour prandial period was substantially greater than with other reported pulmonary systems. Therefore, inhalation of Technosphere/Insulin may become a suitable and attractive alternative for prandial insulin delivery, especially for patients with type 2 diabetes mellitus.

Adult↗

PubMed2001

The influence of isolated small nerve fibre dysfunction on microvascular control in patients with diabetes mellitus.

AIM: The aim of the study was to investigate the influence of isolated small nerve fibre dysfunction on microvascular skin blood flow and transcutaneous oxygen tension in patients with diabetes mellitus. METHODS: Small nerve fibre dysfunction was assessed by the measurement of thermal and pain perception thresholds. Patients with evidence of large fibre disturbances as evaluated by means of vibration perception threshold were excluded from the study. Microvascular blood flow was investigated with laser-Doppler-fluxmetry (LDF) following stimulation with acetylcholine and mild thermal injury. RESULTS: Diabetic patients with small nerve fibre injury showed a significantly reduced increase in the laser-Doppler-flux signal following the application of acetylcholine compared with patients without neuropathy or healthy control subjects (2.8 arbitrary units (AU) (1.3-5.5) vs. 7.2 AU (4.1-25.5); P = 0.007 and vs. 8.5 AU (3.0-17.0), P = 0.02, respectively). The increase in LDF following thermal injury was also diminished in patients with small nerve fibre dysfunction compared with patients without neuropathy or the control group (29.8 AU (17.2-46.5) vs. 51.2 AU (29.5-93.5); P = 0.02 and vs. 54.6 AU (39.7-97.7); P = 0.004, respectively). In addition, they showed a significantly reduced transcutaneous oxygen tension compared with the other groups (42.9 mmHg (41.6-55.5) vs. 56.1 mmHg (49.2-60.8); P = 0.04 and vs. 59.0 mmHg (54.6-80.3), P = 0.03, respectively). CONCLUSIONS: Our study confirms an association between small nerve fibre injury and skin microvascular dysfunction. It further underlines the concept of neurovascular disturbances in the pathogenesis of neurotrophic foot ulceration. Diabet. Med. 18, 489-494 (2001)

Acetylcholine↗

PubMed2001

Alternative routes of administration as an approach to improve insulin therapy: update on dermal, oral, nasal and pulmonary insulin delivery.

For the past 75 years subcutaneous injections have been the only route of delivery of insulin therapy to diabetic patients. During this time, numerous attempts have been made to explore alternative routes for systemic insulin administration. However, thus far, no feasible other way of non-invasive insulin delivery has been developed. Dermal insulin application does not result in a reproducible and sufficient transfer of insulin across the highly efficient skin barrier. The dream of an "insulin tablet" has also not become a reality, the main problem being digestion and a lack of a specific peptide carrier system in the gut. Nasal insulin application was considered for a number of years as a potential method, because of the rapid absorption of insulin across the nasal mucosa. However, relative bioavailability was low and required use of absorption enhancers and more importantly, the metabolic effect lasted too short to be of clinical usefulness. To date the most promising alternative route of insulin administration, is the pulmonary delivery of insulin by inhalation which will likely lead to a practically usable system within the next few years. For maximal rate of absorption insulin must be applied deep into the lung, i.e., into the alveoli. A considerable number of inhalers (in combination with appropriate insulin formulations), which are ask to generate insulin particles with an appropriate size for pulmonary delivery, are currently in the clinical phase of development. The pharmaco dynamic effects of insulin formulations administered via the lung are comparable to, or even faster than, those of s.c. injected regular insulin or rapid-acting insulin analogues. The relative biopotency of inhaled insulin in most cases is approximately 10%, i.e., the dose of insulin administered must be 10-fold higher than with s.c. application. The published results of clinical trials thus far, indicate that metabolic control is comparable to that of s.c. insulin therapy. As of to date no serious side effects have been reported from these human trials. In summary, it appear that after several decades of research, for the first time a feasible alternative route for insulin administration is within reach.

Administration, Cutaneous↗

PubMed2001

Impact of diabetic nephropathy on pharmacodynamic and Pharmacokinetic properties of insulin in type 1 diabetic patients.

OBJECTIVE: To quantify pharmacokinetic and pharmacodynamic properties of regular insulin and insulin lispro in type 1 diabetic patients with and without overt diabetic nephropathy. RESEARCH DESIGN AND METHODS: In this double-blind, two-way cross-over, euglycemic (5 mmol/l) glucose clamp study, we investigated the metabolic response to subcutaneous injections of regular insulin and insulin lispro (0.2 U/kg) in 12 type 1 diabetic patients with overt diabetic nephropathy (proteinuria >500 mg/24 h and/or serum creatinine >1.5 mg/dl; NP group) and in a control group of 12 type 1 diabetic patients with normal renal function (DC group). RESULTS: Peak plasma free insulin levels with insulin lispro (359 [NP] vs. 254 pmol/l [DC]) were higher and time to maximal insulin concentrations (85 [NP] vs. 99 min [DC]) shorter than with regular insulin (213 [NP] vs. 144 pmol/l [DC]; 118 [NP] vs. 153 min [DC]) in both patient groups. Overall insulin levels for regular insulin and for insulin lispro were higher in patients with overt diabetic nephropathy compared with control patients. Time to maximal metabolic effect was shorter with insulin lispro than with regular insulin in both patient groups (102 vs. 191 min [NP]; 105 vs. 172 min [DC]). The overall metabolic effect of regular insulin but not of insulin lispro was lower in patients with diabetic nephropathy than in diabetic control patients (967 vs. 1,510 mg/kg, respectively). CONCLUSIONS: Although insulin levels are higher in patients with overt diabetic nephropathy, the metabolic response to regular insulin is reduced. Insulin lispro maintains its characteristic pharmacokinetic and pharmacodynamic properties in patients with overt diabetic nephropathy.

Adult↗

PubMed2001

Evaluation of a systemic antibiotic treatment of toxic puerperal metritis in dairy cows.

The objective of this study was to evaluate the efficacy and economic efficiency of a systemic treatment of toxic puerperal metritis in dairy cows with ceftiofur. Cows with abnormal vaginal discharge at a postpartum examination (d 4 to 6 after calving) and a rectal temperature > or = 39.5 degrees C were assigned to three treatment groups. Cows in group 1 (n = 70) received 600 mg of ceftiofur intramuscularly (i.m.) on 3 consecutive days. Cows in group 2 (n = 79) received an intrauterine treatment with antibiotic pills consisting of 2500 mg of ampicillin and 2500 mg of cloxacillin and an additional 6000 mg (i.m.) of ampicillin. This treatment was performed on 3 consecutive days. Cows in group 3 (n = 78) received the same intrauterine treatment as in group 2. In addition, 600 mg of ceftiofur was administered i.m. on 3 consecutive days. Body temperature was recorded daily for 6 d after first treatment. There were no significant differences among the groups regarding clinical efficacy at d 6 after first treatment. The cure rates based on rectal temperatures declining to below 39.5 degrees C on d 6 after treatment were 82.9, 84.8, and 84.6% for groups 1, 2, and 3, respectively. Reproductive performance did not differ significantly between group 1 and groups 2 and 3 for any of the measures tested. A financial analysis with 87 different cost scenarios demonstrated that a systemic treatment of toxic puerperal metritis in cattle with ceftiofur is an effective alternative to the combination of local and systemic treatments.

Ampicillin↗

PubMed2000

[Present role of continuous subcutaneous insulin infusion (CSII) by insulin pump in the treatment of diabetes mellitus].

Since the publication of the DCCT results, intensive insulin treatment, including continuous subcutaneous insulin infusion (CSII), has been considered one of the best methods for near-normal insulin delivery. The development of new, robust and easily programmable insulin pumps has led to readier acceptance of this therapy by physicians and patients. In clinical trials, CSII was found to be superior to multiple daily injection regimens in many cases. Patients with unsatisfactory glucose control, frequent hypoglycaemic events, and otherwise uncontrollable morning rises of blood glucose may in particular benefit from insulin pump therapy. Glucose control can even be improved in CSII if insulin lispro is used instead of regular human insulin, as demonstrated in many clinical investigations. Possible side effects of CSII are increased risk of ketoacidosis (e.g. in the case of catheter occlusion) and side effects at the infusion site. Since the successful development of devices for continuous glucose monitoring, the development of closed-loop systems has become more and more the focus of current clinical and technological research.

Blood Glucose↗

PubMed2000

[Predictive genetic investigations. Individualization of diagnosis and treatment in families with multiple endocrine neoplasia type II].

BACKGROUND AND OBJECTIVE: When multiple endocrine neoplasia type 2 (MEN2) is suspected, genetic tests are at the centre of screening procedures. It was the aim of this study to compare the diagnostic value of molecular biological investigations with that of conventional biochemical tests. PATIENTS AND METHODS: The study cohort consisted of all 144 patients cared for in our department since 1990 with the suspected diagnosis of MEN2 (evidence of a medullary thyroid carcinoma [MTC]), coexistence of two MEN2 tumours or a family history of MEN2. 14 of the 144 patients (from 12 families) were already known to have an hereditary MTC, while the remaining 130 had been referred for further diagnostic investigations. RESULTS: An hereditary MTC was diagnosed in 22 of the 130 patients, a sporadic MTC in 32, while no definitive classification was possible in 20 MTC patients without a positive family history and on whom no mutation analysis had been performed. MEN2 was excluded in 56 family members. All 22 patients with newly diagnosed MTC had abnormally high calcitonin levels. A germ-line mutation in the RET proto-oncogene was found in 8 of the 9 families who had undergone molecular biological tests. The investigate results led to a thyroidectomy in 19 of the 22 patients with hereditary MTC; in all of them the surgical specimen showed C-cell hyperplasia and/o MTC. CONCLUSION: These results emphasize the importance of genetic tests in family screening. Preoperative measurement of calcitonin remains essential in MEN2 families in whom a germ-line mutation is not known. The choice of the appropriate diagnostic test must be individualized to the particular patients so that optimal results are obtained.

Adolescent↗

PubMed2000

Serum levels of substance P are decreased in patients with type 1 diabetes.

Morphological and immunohistochemical studies in diabetic subjects have shown a depletion of the neuropeptide substance P (SP) in the central and peripheral nervous system. This is the first study investigating serum levels of substance P in type 1 diabetes patients (n=50) and controls (n=75) by means of an enzyme immunoassay. The serum level of SP was significantly decreased in the diabetic group compared to the control group (10.12+/-0.29 vs. 12.25+/-0.38 pg/ml; p<0.0001). In diabetic patients, there was no correlation of substance P levels with age, serum creatinine, albuminuria, total cholesterol, HDL- or LDL-cholesterol, triglycerides, HbA1c, type or duration of diabetes and gender. Furthermore, there was no difference in serum levels of SP in patients with or without retinopathy, but SP was significantly decreased in patients with neuropathy (9.59+/-0.48 vs. 10.78+/-0.83 pg/ml; p=0.04). These data show that SP is decreased in serum of type 1 diabetes patients, especially in those with diabetic neuropathy. Subsequent and already ongoing prospective studies in well validated diabetic patients with neuropathy may characterize the impact of this neurogenic marker in the course of diabetic neuropathy.

Adolescent↗

PubMed2000

Improved diagnostic methods in the follow-up of medullary thyroid carcinoma by highly specific calcitonin measurements.

Calcitonin (CT) is an important tumor marker for medullary thyroid carcinoma (MTC). Recent CT assays chiefly recognize the monomeric form of CT (mCT). It was the objective of this study to examine the consequences of the higher specificity of the assay for interpretation of the postoperative CT values in MTC patients. The postoperative mCT concentration was measured in 214 patients with differentiated thyroid carcinoma (MTC excepted; non-MTC patients) to determine a reference range of mCT in totally thyroidectomized patients. Monomeric CT was also determined with a two-site chemiluminescence immunoassay (Nichols) in 94 healthy subjects and in 68 MTC patients. The mCT concentrations were below the detection limit in all examined completely thyroidectomized non-MTC patients. Basal and stimulated mCT values were also below the detection limit in 32 of the 68 MTC patients. The biochemical and imaging diagnosis of the latter patients did not give any indication of tumor recurrence. We conclude that completely thyroidectomized patients with non-MTC do not show any measurable mCT concentrations. In comparison with an unspecific CT-RIA, the more specific mCT determination by immunoluminometric assay permits a more precise differentiation between postoperative normal and pathological values and an earlier diagnosis of recurrent MTC.

Adult↗

PubMed2000

Effects of proinsulin C-peptide on nitric oxide, microvascular blood flow and erythrocyte Na+,K+-ATPase activity in diabetes mellitus type I.

This study was conducted to evaluate the influence of proinsulin C-peptide on erythrocyte Na(+),K(+)-ATPase and endothelial nitric oxide synthase activities in patients with type I diabetes. In a randomized double-blind study design, ten patients with type I diabetes received intravenous infusions of either human C-peptide or physiological saline on two different occasions. C-peptide was infused at a rate of 3 pmol.min(-1).kg(-1) for 60 min, and thereafter at 10 pmol.min(-1).kg(-1) for 60 min. At baseline and after 60 and 120 min, laser Doppler flow (LDF) was measured following acetylcholine iontophoresis or mild thermal stimulation (44 degrees C), and venous blood samples were collected to determine plasma cGMP levels and erythrocyte membrane Na(+),K(+)-ATPase activity. The LDF response to acetylcholine increased during C-peptide infusion and decreased during saline infusion [18.6+/-19.2 and -13.2+/-9.4 arbitrary units respectively; mean+/-S.E.M.; P<0.05). No significant change in LDF was observed after thermal stimulation. The baseline plasma concentration of cGMP was 5.5+/-0.6 nmol.l(-1); this rose to 6.8+/-0.9 nmol.l(-1) during C-peptide infusion (P<0.05). Erythrocyte Na(+),K(+)-ATPase activity increased from 140+/-29 nmol of P(i).h(-1).mg(-1) in the basal state to 287+/-5 nmol of P(i). h(-1).mg(-1) during C-peptide infusion (P<0.01). There was a significant linear relationship between plasma C-peptide levels and erythrocyte Na(+),K(+)-ATPase activity during the C-peptide infusion (r=0.46, P<0.01). No significant changes in plasma cGMP levels or Na(+),K(+)-ATPase activity were observed during saline infusion. This study demonstrates an effect of human proinsulin C-peptide on microvascular function, which might be mediated by an increase in NO production and an activation of the erythrocyte Na(+),K(+)-ATPase. These mechanisms are compatible with the previous observed microvascular effects of C-peptide in patients with type I diabetes.

Acetylcholine↗

PubMed2000

Comparison of immunoassays for the detection of anti-GAD65 autoantibodies in patients with diabetes mellitus.

Recent studies have demonstrated that a combination of GAD-antibody assays and IA-2 autoantibody assays show a high diagnostic specificity for Type 1 diabetes. For this reason there is increasing interest in the use of GAD-antibody measurement for Type 1 risk assessment. Since a number of different assays have been published and documented in the literature, the aim of this study was to evaluate four different anti-GAD test systems that are commercially available in Germany. We tested the anti-GAD prevalences in five patient groups with the different immunoassays and compared them with the values obtained by an immunoprecipitation test (IP-Test). All assays correlated well with the IP-test and showed high sensitivity and specificity in the group of patients with recent onset Type 1 diabetes and the control group. The groups tested consisted of 20 subjects with recent onset Type 1 diabetes (< 6 weeks) (sensitivity 70-90%), nine subjects with a Type 1 duration of more than 2 years (sensitivity 11-33%), 21 patients with pluriglandular insufficiency (sensitivity 28.5-47.5%), 10 patients with Type 2 (specificity: 90-100%), and 14 healthy control subjects (specificity: 93-100%). Our data show a high level of sensitivity and specificity of the tested, commercially available, assays. Since almost every laboratory should be able to establish one of these assays, this may facilitate the possibility of further large scale population studies with the aim of investigating GAD-antibody prevalences in screening for Type 1 diabetes. Increased measurement of the diabetes-associated antibodies will be helpful in the differential diagnosis of gestational diabetes mellitus (GDM) and latent autoimmune diabetes of the adult (LADA).

Adolescent↗

PubMed1999

The effect of human proinsulin C-peptide on erythrocyte deformability in patients with Type I diabetes mellitus.

AIMS/HYPOTHESIS: In recent years, evidence has arisen that proinsulin C-peptide exerts biological effects especially on microcirculation, e.g. C-peptide has been shown to increase skin microcirculation in patients with Type I (insulin-dependent) diabetes mellitus and to activate endothelial nitric oxide synthase. This study aimed to investigate the influence of pro-insulin C-peptide on erythrocyte deformability which was assessed by means of laser diffractoscopy. METHODS: Blood samples from healthy control subjects (n = 10) and Type I diabetic patients (n = 15) completely deficient of C-peptide were analysed at shear stresses ranging from 0.3 to 30 Pa. RESULTS: Erythrocyte deformability was lower in the group of Type I diabetic patients than in the control subjects. Preincubation of the diabetic blood samples with various concentrations of human proinsulin C-peptide for 8 h restored the deformability of erythrocytes, almost reaching the values of control samples. In contrast, proinsulin C-peptide did not modify the erythrocyte deformability of control subjects. CONCLUSION/INTERPRETATION: We conclude that proinsulin C-peptide is able to ameliorate the impaired deformability of erythrocytes in Type I diabetic patients and we hypothesise that this effect is mediated by restoration of Na(+)-K(+)-ATPase activity, which is known to be attenuated in diabetic patients.

C-Peptide↗

PubMed1999

Serum leptin is associated with serum uric acid concentrations in humans.

This cross-sectional study aimed to evaluate the relationship between leptin and the cluster of abnormalities often referred to as the metabolic syndrome. The serum leptin concentration, body mass index (BMI), percent body fat, total fat mass (FM), waist and hip circumference, waist to hip ratio (WHR), prevalence of hypertension, and triglyceride (TG), lipoprotein, and uric acid concentration were determined in 86 type 2 diabetic (n = 59) and healthy (n = 27) subjects. Multiple regression analyses showed that the estimates of total body obesity (BMI, percent body fat, and total FM), sex, and serum uric acid concentration are independently associated with the serum leptin concentration. The finding of a positive correlation between serum leptin and uric acid levels suggests that leptin could be a pathogenic factor responsible for hyperuricemia in obesity.

Adipose Tissue↗

PubMed1999

Elevated serum leptin concentrations in type 2 diabetic patients with microalbuminuria and macroalbuminuria.

Leptin levels are elevated in end-stage renal disease, suggesting an impairment of renal leptin degradation. The present study aimed to determine whether leptin levels are also elevated in patients with earlier stages of renal disease, ie, microalbuminuric and macroalbuminuric nephropathy. A total of 60 subjects were assigned to two study groups. Group A contained 10 type 2 diabetics with macroalbuminuria, 10 type 2 diabetics with normoalbuminuria, and 10 healthy control subjects. Group B contained 10 type 2 diabetics with microalbuminuria, 10 type 2 diabetics with normoalbuminuria, and 10 healthy controls. The subgroups of both study groups were matched for sex and body fatness. In group A, macroalbuminuric diabetic patients had higher serum leptin levels than the normoalbuminuric diabetics (11.90 +/- 2.98 v 4.13 +/- 0.92 ng/mL, P < .002) and control subjects (4.78 +/- 1.37 ng/mL, P < .006). In group B, microalbuminuric diabetics had higher serum leptin levels than the normoalbuminuric diabetics (21.16 +/- 5.80 v8.74 +/- 1.89 ng/mL, P < .04) and control subjects (10.06 + 3.00 ng/mL, P < .06). In both groups A and B, creatinine clearance was inversely correlated with the serum leptin level after adjusting for body fat. In conclusion, serum leptin levels are elevated in type 2 diabetic patients with microalbuminuria and macroalbuminuria, suggesting that renal leptin degradation is already impaired in the early stages of renal disease.

Adipose Tissue↗

PubMed1999

Binding of monocytes from normolipidemic hyperglycemic patients with type 1 diabetes to endothelial cells is increased in vitro.

Increased endothelial binding and emigration of monocytes play a dominant role in the pathogenesis of atherosclerosis in diabetes mellitus. Previous studies revealed that hyperlipidemia correlates with monocyte binding in vitro. The aim of this study was to characterize the monocyte-endothelial interaction of leucocytes of hyperglycemic patients with type 1 diabetes but lacking hyperlipidemia. We isolated monocytes from healthy controls and normolipidemic type 1 diabetes patients with elevated levels of HbA1c and quantified monocyte binding by an immunoilluminometric cell adhesion assay. Purity of isolated monocytes was at least 98%. Endothelial binding of monocytes from patients with type 1 diabetes was found to be significantly increased compared to controls (19.2 +/- 3.9% vs. 14.9 +/- 3.5%). This difference of monocyte binding remained unchanged if the endothelial cells were stimulated with 27.7 mmol/l glucose for seven days prior to adhesion studies (31.5 +/- 4.9% in diabetes patients vs. 25.8 +/- 4.1% in controls) whereby monocyte binding markedly increased under these hyperglycemic conditions. Furthermore, an increased CD11b expression could be demonstrated on monocytes of normolipidemic hyperglycemic type 1 diabetes patients. Thus, we suggest that hyperglycemia per se may contribute to increased monocyte binding to endothelial cells by promoting leucocyte integrin expression. Recently performed studies of our group strengthen the hypothesis that this monocyte activation is mediated by stimulation of the beta-isoform of proteinkinase C.

Adult↗