Biomedical subjects

H Kolb

Publications and source records attributed to H Kolb.

At least 19 recordsLinked to original sources

PubMed2006

The metabolic syndrome sensitizes leukocytes for glucose-induced immune gene expression.

Definitions of the metabolic syndrome (MetS) include obesity, dyslipidemia, elevated levels of fasting blood glucose, and blood pressure as criteria, but it is also known that the MetS is associated with chronic, subclinical inflammation. Hyperglycemia (fasting and postprandial) may be important in exacerbating this proinflammatory state. We aimed to assess the impact of oral glucose challenge and in vitro glucose-stimulation on gene expression and secretion of inflammatory parameters in peripheral blood leukocytes and to investigate whether presence of the MetS could "prime" leukocytes to up-regulate proinflammatory markers in response to glucose. Using quantitative real-time PCR, we could show that the expression of intercellular adhesion molecule 1 (ICAM-1), tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) significantly increased in peripheral blood leukocytes from "MetS" subjects (n=39) compared to "no MetS" subjects (n=35) 2 h after an oral glucose tolerance test (ICAM-1 +52%, TNF-alpha +107%, and IL-6 +38%) and also in vitro after 72 h cultivation in high-glucose medium (ICAM-1 +74%, TNF-alpha +71%, and IL-6 +44%). Using ELISA and Luminex technique, we further observed a trend towards increased immune mediator concentrations in the corresponding cell culture supernatants from MetS patients (ICAM-1 +21%, TNF-alpha +31%, and IL-6 +175%). Thus, the MetS may support peripheral inflammation by sensitizing leukocytes to up-regulate proinflammatory markers in response to glucose, which in turn increases the risk for type-2 diabetes mellitus and cardiovascular disease.

Gene Expression Regulation↗

PubMed2006

Constitutive and regulated expression and secretion of interferon-gamma-inducible protein 10 (IP-10/CXCL10) in human adipocytes.

OBJECTIVE: Chemokine secretion by adipocytes has been postulated to initiate leukocyte infiltration in adipose tissue and might mediate an important step in the establishment of obesity-related chronic immune activation. The chemokine interferon (IFN)gamma-inducible protein-10 (IP-10/CXCL10) is a chemoattractant for various leukocyte subsets and has been implicated in the pathogenesis of atherosclerosis. This study investigates whether IP-10 is expressed in human adipocytes and whether its release is regulated by body mass index (BMI) or immunological stimuli. METHODS: In cultures of human mature adipocytes and in vitro differentiated adipocytes, IP-10 expression under basal conditions and in the presence of IFNgamma, lipopolysaccharide (LPS) or interleukin (IL)-4 was characterized by reverse transcriptase-polymerase chain reaction, Luminex technology and immunofluorescence. RESULTS: IP-10 was expressed and secreted constitutively in most cultures of mature adipocytes from omental and subcutaneous (s.c.) depots. The association between IP-10 release and donor BMI was not significant. In in vitro differentiated adipocytes from s.c. and mammary depots and in mature s.c. adipocytes, IP-10 secretion was strongly upregulated by IFNgamma, whereas LPS or IL-4 did not affect IP-10 expression in s.c. mature adipocytes. Immunofluorescence confirmed IP-10 expression in adipocytes with abundant lipid droplets. CONCLUSION: Mature human adipocytes express and secrete the chemokine IP-10 and are thus identified as a novel cellular source of this disease-related immune mediator. IP-10 expression could be significantly induced by IFNgamma, but not by LPS, which points to both similar reactivities and functional differences between adipocytes and innate immune cells.

Adipocytes↗

PubMed2006

Chemokines as risk factors for type 2 diabetes: results from the MONICA/KORA Augsburg study, 1984-2002.

AIMS/HYPOTHESIS: The chemokines monocyte chemoattractant protein-1 (MCP-1), IL-8 and interferon-gamma-inducible protein-10 (IP-10) are released by adipocytes and appear to be involved in atherosclerosis. We hypothesised that these chemokines may be risk factors for the development of type 2 diabetes. SUBJECTS AND METHODS: Using a case-cohort design based on data from the population-based Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Kooperative Gesundheitsforschung in der Region Augsburg/Cooperative Health Research in the Region of Augsburg (KORA Augsburg) study, chemokine levels at baseline were analysed in 526 individuals with and 1,695 individuals without incident type 2 diabetes. The mean follow-up time was 10.8 years. RESULTS: MCP-1 was associated with type 2 diabetes, largely independently of classic risk factors, whereas various clinical and metabolic parameters as well as lifestyle factors were major confounders of the association of IL-8 and IP-10 with type 2 diabetes. Further adjustment for C-reactive protein (CRP) and IL-6 had no impact on the observed associations. The hazard ratio (HR) for subjects with systemic concentrations of all three chemokines (MCP-1, IL-8 and IP-10) above the respective median compared with those with all chemokines below or equal to the median was 1.79 (95% CI 1.18-2.72) and was comparable with the HR for elevated CRP and IL-6 together (adjusted for age, sex, survey, BMI, systolic blood pressure, total cholesterol:HDL cholesterol ratio, physical activity, alcohol intake, smoking and parental history of diabetes). CONCLUSIONS/INTERPRETATION: Elevated concentrations of MCP-1, IL-8 and IP-10 are associated with incident type 2 diabetes. Whereas the association of IL-8 and IP-10 with diabetes was attenuated by multivariable adjustment, high MCP-1 levels contributed to diabetes risk independently of previously described clinical, metabolic and immunological risk factors.

Blood Pressure↗

PubMed2006

Association of interferon-gamma and interleukin 10 genotypes and serum levels with partial clinical remission in type 1 diabetes.

We studied whether serum interferon (IFN)-gamma or interleukin (IL)-10 levels and their corresponding functional polymorphic genotypes are associated with partial remission of type 1 diabetes (T1D). A multi-centre study was undertaken in patients with newly diagnosed T1D and matched controls. T1D patients were followed for 3 months and characterized for remission status. Partial clinical remission was defined as a daily insulin dose <or= 0.38 units/kg/24 h with an HbA1c <or= 7.5%. Thirty-three patients and 32 controls were phenotyped for serum concentrations of IFN-gamma and IL-10 and genotyped for functional polymorphisms of the IFN-gamma and IL-10 genes. Sixteen of 25 informative patients (63%) remitted. Serum IFN-gamma concentrations were significantly decreased in remitters but increased in non-remitters compared to controls, and did not change over time in any group. IFN-gamma genotypes corresponded with serum levels in controls and non-remitters, but not in remitters who displayed the lowest serum IFN-gamma levels despite more often carrying high-producing IFN-gamma genotypes. Neither the frequency of IL-10 genotypes nor serum IL-10 concentration differed between patients and controls. The combination of high-producing IFN-gamma genotype together with low serum IFN-gamma concentration at the time of diagnosis provided a strong positive predictive value for remission. Serum IFN-gamma concentrations predicted by genotype and observed serum levels were discordant in remitters, suggestive of regulation overruling genetic predisposition. Although high-producing genotypes were less frequent in remitters, they were predictive of remission in combination with low serum IFN-gamma levels. These data imply that remission is partially immune-mediated and involves regulation of IFN-gamma transcription.

Analysis of Variance↗

PubMed2006

Altered chemokine levels in individuals at risk of Type 1 diabetes mellitus.

AIMS: The hypothesis was tested in an exploratory study that individuals at high risk of developing Type 1 diabetes mellitus have altered systemic levels of cytokines and chemokines. SUBJECTS AND METHODS: Forty-two non-diabetic first-degree relatives of patients with Type 1 diabetes mellitus were recruited. Of these, 18 had multiple islet autoantibodies (islet cell antibody, glutamic acid decarboxylase antibody, IA-2 antibody). Follow-up for 9-11 years confirmed high vs. moderate diabetes risk in islet autoantibody-positive vs. -negative relatives. Cytokines and chemokines were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum concentrations of classic Th1-associated cytokines (IFN-gamma, IL-12, IL-18) or Th2/Treg-associated cytokines (IL-5, IL-10, IL-13) did not significantly differ in high vs. moderate diabetes risk group. However, of six chemokines analysed, levels of CCL3 and CCL4 were increased (P = 0.0442 and P = 0.0334) while CCL2 was decreased (P = 0.0318) in the multiple islet autoantibody-positive group. No significant differences were seen for CCL5, CCL11, CXCL10. There was a significant correlation between the two closely related chemokines CCL3 and CCL4 in individuals at risk (r = 0.84, P = 0.00005), but not in the autoantibody-negative group. CONCLUSION: Relatives at high risk of developing Type 1 diabetes mellitus have abnormal cellular immune regulation at the level of systemic chemokines. The up-regulation of CCL3 and CCL4 vs. down-regulation of CCL2 suggests opposed functions of these chemokines in the disease process. These findings need to be confirmed by independent studies.

Autoantibodies↗

PubMed2005

Self-monitoring of blood glucose in type 2 diabetes and long-term outcome: an epidemiological cohort study.

AIMS/HYPOTHESIS: The aim of this study was to obtain epidemiological data on self-monitoring of blood glucose (SMBG) in type 2 diabetes and to investigate the relationship of SMBG with disease-related morbidity and mortality. METHODS: The German multicentre Retrolective Study 'Self-monitoring of Blood Glucose and Outcome in Patients with Type 2 Diabetes' (ROSSO) followed 3,268 patients from diagnosis of type 2 diabetes between 1995 and 1999 until the end of 2003. Endpoints were diabetes-related morbidity (non-fatal myocardial infarction, stroke, foot amputation, blindness or haemodialysis) and all-cause mortality. SMBG was defined as self-measurement of blood glucose for at least 1 year. RESULTS: During a mean follow-up period of 6.5 years, 1,479 patients (45.3%) began SMBG prior to an endpoint and an additional 64 patients started SMBG after a non-fatal endpoint. Interestingly, many patients used SMBG while being treated with diet or oral hypoglycaemic drugs (808 of 2,515, 32%). At baseline, the SMBG cohort had higher mean fasting blood glucose levels than the non-SMBG cohort (p<0.001), suggesting that insufficient metabolic control was one reason for initiating SMBG. This was associated with a higher rate of microvascular endpoints. However, the total rate of non-fatal events, micro- and macrovascular, was lower in the SMBG group than in the non-SMBG group (7.2 vs 10.4%, p=0.002). A similar difference was found for the rate of fatal events (2.7 vs 4.6%, p=0.004). Cox regression analysis identified SMBG as an independent predictor of morbidity and mortality, with adjusted hazard ratios of 0.68 (95% CI 0.51-0.91, p=0.009) and 0.49 (95% CI 0.31-0.78, p=0.003), respectively. A better outcome for both endpoints was also observed in the SMBG cohort when only those patients who were not receiving insulin were analysed. CONCLUSIONS/INTERPRETATION: SMBG was associated with decreased diabetes-related morbidity and all-cause mortality in type 2 diabetes, and this association remained in a subgroup of patients who were not receiving insulin therapy. SMBG may be associated with a healthier lifestyle and/or better disease management.

Aged↗

PubMed2005

An immune origin of type 2 diabetes?

Subclinical, low-grade systemic inflammation has been observed in patients with type 2 diabetes and in those at increased risk of the disease. This may be more than an epiphenomenon. Alleles of genes encoding immune/inflammatory mediators are associated with the disease, and the two major environmental factors the contribute to the risk of type 2 diabetes-diet and physical activity-have a direct impact on levels of systemic immune mediators. In animal models, targeting of immune genes enhanced or suppressed the development of obesity or diabetes. Obesity is associated with the infiltration and proinflammatory activity of macrophages in adipose tissue, and immune mediators may be important regulators of insulin resistance, mitochondrial function, ectopic lipid storage and beta cell dysfunction or death. Intervention studies targeting these pathways would help to determine the contribution of an activated innate immune system to the development of type 2 diabetes.

Adipose Tissue↗

PubMed2005

Helicobacter pylori seropositive subjects do not show a pronounced systemic inflammatory response even in the presence of the interleukin-1 receptor antagonist gene polymorphism.

The aim of this analysis was to evaluate the effects of the presence of the IL-1RA gene polymorphism and H. pylori infection on markers of a systemic inflammatory response taking into account virulence markers of this infection. Serum concentrations of interleukin (IL)-6, IL-8, and tumour-necrosis factor (TNF)-alpha of 479 occasional blood donors were not statistically significantly higher in subjects having antibodies against H. pylori, or more specifically against CagA and VacA, and being homozygous for the pro-inflammatory IL-1RN*2 allele compared to others after adjustment for covariates. The findings suggest that the possible pro-inflammatory effect of the IL-1RN*2 allele in combination with H. pylori infection is limited to the mucosal level.

Adult↗

PubMed2005

The diabetes epidemic in the elderly population in Western Europe: data from population-based studies.

Valid epidemiologic data on type 2 diabetes in the elderly population are scarce in the European Region despite its enormous human and economic burden. The aim was to assess population-based data on type 2 diabetes and impaired glucose regulation (IGR) from surveys carried out in Western Europe since 1990 using oral glucose tolerance tests, and to discuss the possible impact of risk factors on geographic variation, in particular, obesity and physical activity. In the decade below 60 years of age, about 10 % of the population had known or newly diagnosed diabetes in European surveys. In the age group 70 to 79 years, average total diabetes prevalence was about one quarter. IGR prevalences also increased with age, reaching a maximum of 25 % (men) to 30 % (women) above 70 years of age. There was a wide variation of total diabetes prevalence in the elderly population in Western European countries, however, without clear geographical pattern. Whereas age- and sex-specific prevalences for total diabetes in the German KORA Survey S4 (1999/2001) (Augsburg) were comparable to the European average, IGR prevalences were higher in Augsburg (60-69 years: KORA: men: 30.2 %, women: 22.4 % Europe: men: 21.2 %, women: 19.0 %). Thus, there is a huge reservoir for future diabetes cases in the elderly population in Germany. Differences at the population level were found for obesity, nutrition, and sedentary lifestyle in Western Europe. Comparative studies on the predictive values of obesity, physical activity, and nutrition and possible interactions with genetic markers in European populations are of interest in the future.

Age Distribution↗

PubMed2005

Inflammation and type 2 diabetes: results from KORA Augsburg.

Type 2 diabetes is associated with a systemic low-grade inflammation. First data provided by cross-sectional studies from as early as the 1960s demonstrated elevated systemic levels of glycoproteins and acute-phase reactants and increased leukocyte counts in type 2 diabetes patients. Subsequently, prospective studies showed that elevated concentrations of several acute-phase proteins and cytokines are predictive of later type 2 diabetes. Immune gene variants in man and in animal models were found to affect insulin resistance and diabetes incidence. Antidiabetic treatment by medication, diet or physical activity results in a significant decrease of systemic immune mediator concentrations. Immunological analyses of the KORA Survey S4 (1999/2001) allowed us to show that levels of circulating acute-phase proteins like CRP and of IL-6 are highly correlated and associated not only with overt type 2 diabetes, but already with impaired glucose tolerance (IGT) pointing out a role of these mediators in the pathogenesis of type 2 diabetes. On the contrary, TNFalpha was neither coregulated with CRP nor associated with diabetes status. Our study therefore shows that type 2 diabetes is accompanied by a non-random and differential upregulation of components of the innate immunity and suggests that this inflammatory condition is involved in the aetiology of the disease. Future work will extend the range of analysed immune mediators to chemokines and will also investigate the association of immune markers with indices of obesity to elucidate the relevance of this traditional risk factor for low-grade inflammation.

Acute-Phase Proteins↗

PubMed2005

Genetics of type 2 diabetes: impact of interleukin-6 gene variants.

The KORA studies serve as a powerful tool for the genetic analysis of complex diseases like type 2 diabetes or the metabolic syndrome. These studies include more than 2,000 prevalent and incident type 2 diabetes cases. DNA of these patients is available to be used in genetic studies. Up to now the analyses have focussed on genes coding for proteins being involved in the inflammatory response. Interleukin-6 (IL-6) as the key mediator of the acute phase reaction is of interest. Elevated protein concentrations of IL-6 in the blood have been shown to predict type 2 diabetes. We investigated the association of the IL-6 single nucleotide polymorphism (SNP) C-174G with type 2 diabetes in a case-control study of 704 elderly participants of the KORA Survey S4 (1999/2001). When BMI, HDL cholesterol, physical activity, hypertension, hormone replacement therapy and smoking were considered as covariables the SNP C-174G showed a trend for association with type 2 diabetes (- 174G: OR 1.20, 95 % CI 0.90 - 1.59, p = 0.21).

Adult↗

PubMed2005

Association of humoral immunity to human Hsp60 with the IL-6 gene polymorphism C-174G in patients with type 2 diabetes and controls.

The relationship between humoral immunity to hsp60 and type 2 diabetes along with other relevant metabolic, inflammatory and immunogenetic variables was studied in 76 non-diabetic and 74 diabetic persons aged 55-74 years selected from the population-based KORA Survey 2000. Antibodies to human hsp60 were measured in serum samples by ELISA. Hsp60 antibodies were detected in all but two individuals in a considerable range of titres (22-1,856 AU/ml). There was no significant association to age and sex, or to key clinical or metabolic parameters (BMI, WHR, HbA1c, total cholesterol, LDL cholesterol, HDL cholesterol, systolic and diastolic blood pressure, albumin, uric acid) or immunological parameters (CRP, IL-6, sIL-6R, TNFalpha, sTNFalpha R60, sTNFalpha R80). Analysis of antibody-positive individuals revealed an association between hsp60 antibodies and diabetes at borderline significance (p = 0.047), which was lost when the two antibody-negative individuals were included. Genetic analyses indicated that this association was significant in carriers of the C allele of the IL-6 promoter region polymorphism at nucleotide -174 (p = 0.02), but not in GG genotype carriers. We conclude that humoral immunity to human hsp60 may be enhanced in those diabetic patients carrying the -174C allele of the IL-6 gene. This finding may contribute to an understanding of the relationship between the -174C allele and increased risk of atherosclerosis.

Aged↗

PubMed2004

Identification of pancreatic exocrinopathy in non-obese diabetic mice by gene subtraction analysis.

Type 1 diabetes is an immune-mediated disease with pancreatic infiltration and subsequent beta cell destruction. In this study pancreatic exocrinopathy in non-obese diabetic mice (NOD) was identified using gene subtraction methods (SSH) and macroarray analysis. Female NOD mice were treated with cyclophosphamide for acceleration and synchronization of the disease process at 70 d of age and analysed 10 d later, before the onset of overt diabetes. Extraction of total RNA of pancreas was followed by subtraction using the SSH technique. Pools of cDNA were generated using total RNA from treated and untreated NOD mice. Subtraction of cDNA pools of cyclophosphamide treated mice from cDNA pools of untreated mice resulted in a cDNA library, from which 480 clones were randomly selected. The clones were hybridized against labelled cDNA-probes generated from cyclophosphamide-treated and control NOD mice. Fifty-three clones (11 %) revealed at least twofold differential gene expression after cyclophosphamide treatment. Three of the downregulated genes (amylase, carboxypeptidase and preprotrypsin) were selected for evaluation of macroarray data by quantitative real-time PCR. Analysis of real-time PCR data confirmed suppression of gene expression with highest fold change for amylase (4.68-fold) followed by carboxypeptidase (2.79-fold) and preprotrypsin (2.14-fold). These results lead to the conclusion that inflammation in this animal model of type 1 diabetes is not restricted to pancreatic islets and that subtraction followed by macroarray analysis is capable of identifying genes responsible associated with disease progression.

Amylases↗

PubMed2004

Prolonged stenting does not prevent obstruction after TIP repair when the glans was deeply incised.

PURPOSE: To evaluate whether prolonged postoperative stenting may reduce the risk of obstruction of the neourethra after TIP repair with deep glanular incision. METHODS: In a 1-year period 27 patients were operated for penile hypospadias using the TIP technique described by Snodgrass. In contrast to a previous study with 8 - 10 days of postoperative catheter drainage, the indwelling transurethral catheter was kept in place for 12 - 14 days. Deep incision of the urethral plate up to the tip of the glans is the most remarkable surgical detail, resulting in a meatus on top of the glans but in a defect on the dorsal rim of the neomeatus as well. After 3 - 6 months 22 patients were re-investigated during an outpatient visit using a scheme to describe the position of the neomeatus. Uroflowmetry was also performed. Information in three toddlers was gained by phone and 2 patients were lost to follow-up. RESULTS: Two patients returned with significant obstruction including an urethrocutaneous fistula in one. In contrast to the good assessment by parents and compared to the early appearance after catheter removal a change in meatal position was observed in the majority of patients. Only 6 patients presented with an unchanged meatal position whereas in 16 patients the meatus lost its oval or slit-like shape as well as its position on the tip of the glans. However, despite one obstructive meatus in the coronal position 15 patients showed a sufficient size and position of the meatus underneath the tip of the glans. Uroflowmetry revealed reduced peak-flow values (mean: 8.1 ml/s) in some of the 9 patients evaluated. CONCLUSIONS: Our data indicate that prolonged stenting does not give better results in those TIP repairs, in whom the urethral plate was incised across the rim of the neomeatus. The early excellent aspect of the glans after stent removal is often impaired by partial closure of the glans incision with a short-term change in size and position of the meatus. To prevent this, the rim of the meatus during reconstruction should be kept completely epithelialised.

Child↗

PubMed2004

Multiple organ failure due to 5-fluorouracil chemotherapy in a patient with a rare dihydropyrimidine dehydrogenase gene variant.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the metabolism of the chemotherapeutic drug 5-fluorouracil (5-FU). Application of 5-FU is restricted by a narrow therapeutic index because of severe toxicity of WHO grades III-IV. The exon 14-skipping mutation (c.1905+1G>A) accounts for approximately a quarter of all severely toxic cases. However, numerous other polymorphisms have been identified within the DPYD gene in affected patients, and the pathophysiological significance of most of them is unclear. PATIENT AND METHODS: We report a patient with advanced caecum cancer who twice received 950 mg 5-FU and 45 mg folinic acid as adjuvant by bolus injection. 2 days after onset of chemotherapy, the patient developed a multiple organ dysfunction exhibiting a cardiogenic shock with severe left ventricular insufficiency, marked reduction of renal function, and beginning hepatic encephalopathy with somnolence, myoclonus, and a seizure. In order to investigate a possible defect within the DPYD gene direct sequencing of all 23 exons was carried out. RESULTS: Genotyping revealed a rare c.1601G>A polymorphism which causes a change in the protein sequence (S534N). Data regarding the clinical relevance are ambiguous. The polymorphism has been detected together with an intronic mutation and both polymorphisms have consistently been reported with reduced enzyme activity. CONCLUSION: The present case provides further evidence of an etiologic role of the c.1601G>A mutation for DPD deficiency and the occurrence of severe 5-FU-related toxicity and underlines the value of comprehensive pharmakogenetic diagnostics with respect to the dihydropyrimidine dehydrogenase.

Adenocarcinoma↗

PubMed2004

Significant association of the interleukin-6 gene polymorphisms C-174G and A-598G with type 2 diabetes.

Elevated blood concentrations of IL-6 have been shown to predict type 2 diabetes. Because the impact of IL-6 gene polymorphisms on diabetes status, parameters of the metabolic syndrome, and low-grade systemic inflammation has not been analyzed in a population-based study, we investigated the association of the IL-6 single nucleotide polymorphisms C-174G and A-598G on these parameters in 704 elderly participants of the Kooperative Gesundheitsforschung im Raum Augsburg/Cooperative Research in the Region of Augsburg (KORA) Survey 2000. Both -174G and -598G alleles were significantly associated with type 2 diabetes (-174G: odds ratio = 1.51, 95% confidence interval = 1.11-2.07, P = 0.0096; -598G: odds ratio = 1.56, 95% confidence interval = 1.13-2.15, P = 0.0069) but not with impaired glucose tolerance. In subgroup analyses, the association reached statistical significance in men and in leaner subjects (body mass index <or= 28.7 kg/m(2), i.e. study median) but not in women or more obese persons. Circulating IL-6 levels were not associated with the IL-6 polymorphisms, but significantly elevated levels of the chemokine monocyte chemoattractant protein-1/CC chemokine ligand 2 in carriers of the protective genotypes indicated an indirect effect of these single nucleotide polymorphisms on the innate immune system. Our findings confirm that immune gene polymorphisms can be considered as independent risk factors in the etiology of type 2 diabetes and suggest that their contribution may be indirect, by influencing the levels of other immune mediators like monocyte chemoattractant protein-1.

Adult↗

PubMed2003

Change in patients' body weight after 12 months of treatment with glimepiride or glibenclamide in Type 2 diabetes: a multicentre retrospective cohort study.

AIMS/HYPOTHESIS: Our study compared the effects of glimepiride or glibenclamide treatment on body weight over 12 months of treatment in patients with Type 2 diabetes in routine outpatient practice. METHODS: This new retrospective study design used data from physicians in a restricted manner (retrolective). Data from case report forms from 520 patients from 91 randomly selected centres were assessed and covariance analysis performed. RESULTS: The influence of practice and patient characteristics on treatment assignment was low, reflecting the design of randomised controlled trials. Mean weight loss and reduction in body mass index from baseline to study endpoint were greater with glimepiride than with glibenclamide (-2.04+/-3.99 kg vs -0.58+/-3.65 kg, p<0.001; -0.71+/-1.38 kg/m(2) vs -0.20+/-1.28 kg/m(2), p<0.001). Duration of treatment at baseline influenced treatment outcome, but propensity score, sex, age and fasting blood glucose at baseline did not. Both glimepiride and glibenclamide led to decreases in fasting blood glucose (-2.43+/-0.24 mmol/l vs -3.03+/-0.24 mmol/l; p<0.001 vs baseline) and HbA(1c) (-1.23+/-0.09% vs -1.26+/-0.09%; p<0.001 vs baseline). Both treatments were associated with a decrease in serum total cholesterol and low density lipoprotein cholesterol. Triglycerides were lower in the glibenclamide group and high density lipoprotein cholesterol was higher in the glimepiride group only. CONCLUSIONS/INTERPRETATION: Initial treatment of Type 2 diabetes with glimepiride was associated with a significantly greater decrease in body weight and body mass index than treatment with glibenclamide, while providing equivalent glycaemic control.

Blood Glucose↗

PubMed2003

Diagnosis and classification of inguinal hernias.

BACKGROUND: The aim of this prospective clinical study was to determine whether the presence of a hernia, its size, and its type can be established preoperatively by clinical and ultrasound, examination. METHODS: The study population comprised 220 consecutive patients referred to our department for the surgical management of an inguinal hernia. On admission, both inguinal regions were examined clinically and by ultrasound. All patients were operated on laparoscopically. RESULTS: In regard to the intraoperative findings for both inguinal regions, clinical and ultrasound examination for the diagnosis of inguinal hernia yielded a high total rate of accuracy of 93% respective 94%. However, when the same methods were used to differentiate between lateral and medial hernia, the total rate of accuracy fell to only 54% respective 62%. In the determination of inguinal hernia size, it was even lower: 50% respective 53%. CONCLUSIONS: Although a diagnosis of inguinal hernia can be established reliably by clinical and ultrasound examination, only an approximate classification is possible by these methods.

Adult↗