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Biomedical subjects

B H Wolffenbuttel

Publications and source records attributed to B H Wolffenbuttel.

At least 19 recordsLinked to original sources
PubMed2004

[Empty sella syndrome as the cause of panhypopituitarism].

In two patients, men aged 78 and 42 years respectively, an empty-sella syndrome was found. The first patient presented with chronic fatigue, in the second the empty sella was the late result of prior neurosurgery followed by external irradiation. Both suffered from panhypopituitarism. In both cases the diagnosis was confirmed following laboratory tests and MRI. Hormone-replacement therapy was found to provide adequate treatment. The course of the empty-sella syndrome is usually benign and with adequate hormone-replacement therapy a good quality of life is maintained.

Adult↗
PubMed2001

Ramipril and the development of diabetes.

CONTEXT: Type 2 diabetes is a growing clinical and public health problem. Preventive efforts related to lifestyle modification are not always successful; therefore, alternative prevention strategies need to be studied. OBJECTIVE: To investigate the effectiveness of ramipril, an angiotensin-converting enzyme inhibitor, in preventing diabetes among high-risk persons. DESIGN, SETTING, AND PARTICIPANTS: The randomized, controlled Heart Outcomes Prevention Evaluation trial of 5720 patients older than 55 years without known diabetes but with vascular disease who were followed up for a mean of 4.5 years. The study included 267 hospitals in 19 countries and was conducted between 1994 and 1999. INTERVENTION: Patients were randomly assigned to receive ramipril, up to 10 mg/d (n = 2837), or placebo (n = 2883). MAIN OUTCOME MEASURE: Diagnosis of diabetes determined from self-report at follow-up visits every 6 months, compared between the 2 groups. RESULTS: One hundred and two individuals (3.6%) in the ramipril group developed diabetes compared with 155 (5.4%) in the placebo group (relative risk [RR], 0.66; 95% confidence interval [CI], 0.51-0.85, P<.001). Similar results were noted when different diagnostic criteria were used; in the ramipril group, the RR for diagnosis of diabetes and hemoglobin A(1c) greater than 110% was 0.60 (95% CI, 0.43-0.85), for initiation of glucose-lowering therapy, 0.56 (95% CI, 0.41-0.77), and for both, 0.51 (95% CI, 0.34-0.76). These effects were also consistently seen in several subgroups examined. CONCLUSIONS: Ramipril is associated with lower rates of new diagnosis of diabetes in high-risk individuals. Because these results have important clinical and public health implications, this hypothesis requires prospective confirmation.

Aged↗
PubMed2001

Effect of atorvastatin on LDL oxidation and antioxidants in normocholesterolemic type 2 diabetic patients.

BACKGROUND: Oxidative stress in diabetes increases lipid peroxidation, which stimulates the development of atherosclerosis. METHODS: We investigated in a 3-month placebo-controlled study with 19 normocholesterolemic type 2 diabetic patients whether treatment with 10-mg atorvastatin influenced antioxidants and reduced LDL oxidizability, assessed by in vitro production of conjugated dienes after copper-induced LDL oxidation. RESULTS: The lag phase, as a measure of the resistance of LDL to oxidation, did not change (62.8+/-8.2 respectively 59.6+/-9.7 min, p=n.s.), while conjugated dienes decreased (512+/-74 respectively 487+/-50 nmol, p=0.012). Plasma alpha-tocopherol and ubiquinol levels decreased, while their ratios to LDL cholesterol remained stable. CONCLUSIONS: Atorvastatin favourably influences some parameters of LDL oxidation. Whether this effect is clinically relevant remains to be determined.

Aged↗
PubMed2001

[Disorders of lipid metabolism in 3 patients with diabetes mellitus type 2].

Three patients with diabetes mellitus (type 2) and cardiovascular disease had disturbed lipid concentrations: two women aged 60 and 73 years and one man aged 47 years. The lipid levels were normalised during the 9-18 years of treatment with medication and in this period the patients experienced no cardiovascular events. Disturbances in plasma lipid levels play a major role in the increased risk of cardiovascular disease in patients with diabetes mellitus (type 2). Cholesterol-lowering treatment should be aggressive and based on the lipid profile. Statins reduce cardiovascular events by lowering the concentration of both the total cholesterol and low-density lipoprotein cholesterol whereas fibrates reduce cardiovascular events by increasing high-density lipoprotein cholesterol concentrations and lowering triglyceride concentrations.

Aged↗
PubMed2001

Clinical experience with Sandostatin LAR in patients with acromegaly.

Patients with acromegaly, who are not cured after transsphenoidal adenomectomy, may be treated with external irradiation and/or octreotide injections. Recently, a long-acting formulation of octreotide (Sandostatin LAR has become available in clinical practice. We assessed the effects of treatment with this long-acting octreotide in 18 consecutive patients with acromegaly treated in our center, who had persistent signs and symptoms of acromegaly despite transsphenoidal surgery with (n=7) or without irradiation (n=11). Twelve had already been treated with regular Sandostatin for a period of 0.5-8 years in dosages of 3 x 50 to 3 x 300 mcg s.c. (median daily dose 300 mcg). All patients started with i.m. injections of 20 mg Sandostatin LAR every 4 weeks. In the patients who started treatment with octreotide for the first time, mean serum IGF-1 levels (measured by IRMA, Nichols Diagnostics) decreased from 634+/-229 to 255+/-88 ng/ml after 3 months, 271+/-81 ng/ml after 1 year and 263+/-97 ng/ml after 2 years (all P<0.05), while random GH levels (DELFIA, Wallac) decreased from 6.6 (range 3.1-67.0) to 2.1 (0.5-3.1) mU/l after 2 years (P<0.05). In the 12 patients who had already been treated with octreotide, mean IGF-1 also fell, from 367+/-193 to 331+/-195 ng/ml (P=0.023) after 3 months, to 342+/-191 ng/ml after 1 year and 277+/-169 ng/ml (P=0.002) after 2 years, while random GH levels decreased from 4.5 (1.1-46) mU/l at baseline to 2.1 (0.4-23.0) after 2 years (P=0.003). Therefore, the average decrease of IGF-1 was 10% after 3 months and 25% after 2 years. One patient had a decrease of less than 5% (but her IGF-1 was normal, 193 ng/ml), and one patient showed no response to both regular and long-acting Sandostatin (ave. IGF-1, 755 ng/ml). No specific side-effects occurred. One patient chose to return to t.i.d. injection of regular octreotide because of slight worsening of her complaints of headache despite normal IGF-1 levels. All other patients favoured continuation of the monthly injections. In six patients, the dose had to be increased to 30-40 mg monthly because the IGF-1 levels still remained elevated. Sandostatin LAR may be considered a great improvement for the treatment of patients with (symptomatic) acromegaly.

Acromegaly↗
PubMed2001

Substitution model with central role for nurse specialist is justified in the care for stable type 2 diabetic outpatients.

AIM OF THE STUDY: Assessment of effects on quality of care, in terms of patient outcomes, when tasks in the care for outpatients with stable type 2 diabetes are transferred from internist to nurse specialist and from outpatient clinic to general practice. BACKGROUND: For the management of chronic diseases with a high prevalence and requiring current monitoring, it is suggested that substitution of care may be an appropriate solution to safeguard high quality care. DESIGN AND METHODS: A 12-month nonequivalent control group design was used. General practitioners (GPs) referring diabetes patients to the University Hospital Maastricht were asked to choose for the traditional model or the nurse specialist model. Informed consent was obtained from patients with stable diabetes type 2 attending these practices. All patients received care according to the model chosen by their GP. Identified outcomes were: clinical status, health status, self-care behaviour, knowledge of diabetes, patient satisfaction, and consultation with care-providers. RESULTS: In the control group (n=47) no patients were treated with oral hypoglycaemic agents (OHA) only. The control group was compared with an intervention subgroup (n=52) also without patients receiving OHA only. Clinical data were available for all patients. Patients without complete data from questionnaires had better mean concentration of HbA1c than patients with complete data (P=0.004). The traditional care model and the nurse specialist model achieved equal outcomes, while glycaemic control of patients in the nurse specialist model improved (from 8.6% to 8.3%) but deteriorated in the traditional model (from 8.6% to 8.8%; P-value between groups=0.001). CONCLUSIONS: The model with nurse specialists taking on roles and tasks beyond those traditionally regarded as their remit as well as new ones, is effective for the care of stable diabetic outpatients.

Aged↗
PubMed2001

Weight reduction and the impaired plasma-derived free fatty acid oxidation in type 2 diabetic subjects.

In a previous study the oxidation of plasma free fatty acids (FFA) under baseline conditions and during exercise was lower in type 2 diabetic subjects compared with weight-matched controls. The present study intended to investigate the effect of weight reduction (very low calorie diet) on plasma FFA oxidation in seven type 2 diabetic male subjects (body fat, 37.4 +/- 1.2%; age, 51.3 +/- 3.4 yr; plasma glucose, 7.45 +/- 0.48 mmol/L). Subjects underwent a 10-week diet period. Body composition and substrate utilization during rest and during bicycle exercise (50% of maximum aerobic capacity) were determined before and after the diet (during weight-stable conditions). FFA metabolism was studied by means of the tracer [U-(13)C]palmitate. Rates of oxidation of plasma FFA were corrected with an acetate recovery factor. Additionally, activities of mitochondrial enzymes and cytosolic fatty acid-binding protein were determined in biopsies from the vastus lateralis muscle before and after the diet. The very low calorie diet resulted in a weight loss of 15.3 kg (110.8 +/- 7.4 vs. 95.5 +/- 5.8 kg; P < 0.01). The basal rates of appearance and disappearance of FFA decreased as a result of diet. The rates of appearance and disappearance of FFA during exercise were not different before and after diet. The oxidation of plasma-derived fatty acids tended to decrease after diet during baseline conditions (P = 0.10), whereas the plasma FFA oxidation during exercise was not different before and after the diet (14.1 +/- 1.9 vs. 14.8 +/- 1.8 micromol/kg fat-free mass.min). Skeletal muscle cytosolic fatty acid-binding protein and the activities of muscle oxidative enzymes did not significantly change as a result of weight loss. In conclusion, considerable weight reduction did not significantly improve plasma-derived FFA oxidation under baseline conditions and during exercise, suggesting that this impairment reflects a primary defect leading to the development of type 2 diabetes mellitus rather than resulting from the type 2 diabetic state.

Arteries↗
PubMed2001

Rosiglitazone.

Type 2 diabetes mellitus is characterised by impaired insulin secretion, diminished peripheral insulin action and increased hepatic glucose production. Clinical trials have indicated that near-normal glucose control may reduce the risk for microvascular and - to a lesser extent - macrovascular complications in Type 2 diabetic patients. Thiazolidinediones improve insulin action by activating a nuclear receptor, PPARgamma. Therefore, these drugs are often referred to as 'insulin sensitisers'. Rosiglitazone is the second compound of this group. Clinical studies with rosiglitazone have shown that it is effective in lowering blood glucose levels in Type 2 diabetic patients treated with either diet alone, sulphonylurea or metformin. Preliminary studies suggest that rosiglitazone also improves glycaemic control in insulin-treated patients while even slightly decreasing insulin dose. The magnitude of the effects is, however, moderate. In diet-treated patients, the reduction of HbA1c levels amounted on average 0.5 - 1.5% and addition to existing sulphonylurea therapy decreased HbA1c by 1.0 - 1.2%. The clinical relevance of additional beneficial effects, i.e., on blood pressure and microalbuminuria, needs to be determined further. Rosiglitazone does not cause hypoglycaemia or gastrointestinal side effects. There is however some concern related to fluid retention, which seems to be an effect of all PPARgamma agonists. In patients treated with rosiglitazone, no severe hepatotoxic side effects have been noticed until now. In the treatment of our patients with Type 2 diabetes, drugs like rosiglitazone which directly reduce insulin resistance are very welcome but more data on its combined use with insulin are needed. Additional studies will also explore its long-term effects in sparing beta-cell function and reducing diabetes-related complications and atherosclerosis.

Animals↗
PubMed2001

From shared care to disease management: key-influencing factors.

BACKGROUND: In order to improve the quality of care of chronically ill patients the traditional boundaries between primary and secondary care are questioned. To demolish these boundaries so-called 'shared care' projects have been initiated in which different ways of substitution of care are applied. When these projects end, disease management may offer a solution to expand the achieved co-operation between primary and secondary care. OBJECTIVE: Answering the question: What key factors influence the development and implementation of shared care projects from a management perspective and how are they linked? THEORY: The theoretical framework is based on the concept of the learning organisation. DESIGN: Reference point is a multiple case study that finally becomes a single case study. Data are collected by means of triangulation. The studied cases concern two interrelated Dutch shared care projects for type 2 diabetic patients, that in the end proceed as one disease management project. RESULTS: In these cases the predominant key-influencing factors appear to be the project management, commitment and local context, respectively. The factor project management directly links the latter two, albeit managing both appear prerequisites to its success. In practice this implies managing the factors' interdependency by the application of change strategies and tactics in a committed and skillful way. CONCLUSION: Project management, as the most important and active key factor, is advised to cope with the interrelationships of the influencing factors in a gradually more fundamental way by using strategies and tactics that enable learning processes. Then small-scale shared care projects may change into a disease management network at a large scale, which may yield the future blueprint to proceed.

Journal Article↗
PubMed2001

Design of a consumer health record for supporting the patient-centered management of chronic diseases.

This paper describes and discusses the design and usage of a shareable consumer health record system to investigate whether these systems can assist in the management of chronic diseases. This web-based system that can be used both by care providers and patients contains medical and patient information, provides access to websites that contain quality information, provides guideline-based advice, allows discussion between patients and allows us to interrogate both patients and care providers on a regular basis in order to get a good impression of the utility of such a consumer record for both chronic patients and the physicians and nurses. A health record system that was developed for the area of Diabetes is presented as an example.

Chronic Disease↗
PubMed2000

Pitfall of the accessory spleen.

Two patients, one with insulinoma and one with Cushing's syndrome, are presented. Biochemical evaluation readily suggested the correct diagnosis. During radiologic imaging, the anatomic abnormality giving rise to these diseases, i.e. a pancreatic islet cell tumor, and an adrenal adenoma, at first were mistakenly interpreted as an accessory spleen on the basis of specific computed tomography and magnetic resonance imaging appearances. The insulinoma was identified as such during laparotomy, whereas additional jodo-cholesterol scintigraphy revealed the real nature of the lesion in the patient with Cushing's syndrome. Both patients were operated successfully.

Adenoma↗
PubMed2000

The ADDITION study: proposed trial of the cost-effectiveness of an intensive multifactorial intervention on morbidity and mortality among people with Type 2 diabetes detected by screening.

OBJECTIVE: The overall aims of the ADDITION study are to evaluate whether screening for prevalent undiagnosed Type 2 diabetes is feasible, and whether subsequent optimised intensive treatment of diabetes, and associated risk factors, is feasible and beneficial. DESIGN: Population-based screening in three European countries followed by an open, randomised controlled trial. SUBJECTS AND METHODS: People aged 40-69 y in the community, without known diabetes, will be offered a random capillary blood glucose screening test by their primary care physicians, followed, if equal to or greater than 5.5 mmol/l, by fasting and 2-h post-glucose-challenge blood glucose measurements. Three thousand newly diagnosed patients will subsequently receive conventional treatment (according to current national guidelines) or intensive multifactorial treatment (lifestyle advice, prescription of aspirin and ACE-inhibitors, in addition to protocol-driven tight control of blood glucose, blood pressure and cholesterol). Patients allocated to intensive treatment will be further randomised to centre-specific interventions to motivate adherence to lifestyle changes and medication. Duration of follow-up is planned for 5 y. Endpoints will include mortality, macrovascular and microvascular complications, patient health status and satisfaction, process-of-care indicators and costs.

Adult↗
PubMed2000

Addition of low-dose rosiglitazone to sulphonylurea therapy improves glycaemic control in Type 2 diabetic patients.

AIMS: This study was designed to test the efficacy and safety of low-dose rosiglitazone, a potent, insulin-sensitizing thiazolidinedione, in combination with sulphonylurea in Type 2 diabetic patients. METHODS: For the intention-to-treat analysis, 574 patients (59% male, mean age 61 years) were available, randomized to receive 26 weeks of twice-daily placebo (n = 192), rosiglitazone 1 mg (n = 199) or rosiglitazone 2 mg (n = 183) in addition to existing sulphonylurea treatment with gliclazide (47.6% of patients), glibenclamide (41.8%) or glipizide (9.4%) (two patients were taking carbutamide or glimepiride). Change in haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fructosamine, insulin, C-peptide, albumin, and lipids were measured, and safety was evaluated. RESULTS: Mean baseline HbA1c was 9.2% and FPG was 11.4 mmol/l. Rosiglitazone at doses of 1 and 2 mg b.d. plus sulphonylurea produced significant decreases, compared with sulphonylurea plus placebo, in HbA1c (-0.59% and -1.03%, respectively; both P<0.0001) and FPG (1.35 mmol/l and 2.44 mmol/l, respectively; both P<0.0001). Both HDL-cholesterol and LDL-cholesterol increased and potentially beneficial decreases in non-esterified fatty acids and gamma glutamyl transpeptidase levels were seen in both rosiglitazone groups. The overall incidence of adverse experiences was similar in all three treatment groups, with no significant cardiac events, hypoglycaemia or hepatotoxicity. CONCLUSIONS: Overall, the combination of rosiglitazone and a sulphonylurea was safe, well tolerated and effective in patients with Type 2 diabetes.

Adult↗
PubMed2000

Plasma FFA utilization and fatty acid-binding protein content are diminished in type 2 diabetic muscle.

In this study, we investigated the hypothesis that impairments in forearm skeletal muscle free fatty acid (FFA) metabolism are present in patients with type 2 diabetes both in the overnight fasted state and during beta-adrenergic stimulation. Eight obese subjects with type 2 diabetes and eight nonobese controls (Con) were studied using the forearm balance technique and indirect calorimetry during infusion of the stable isotope tracer [U-(13)C]palmitate after an overnight fast and during infusion of the nonselective beta-agonist isoprenaline (Iso, 20 ng. kg lean body mass(-1) x min(-1)). Additionally, activities of mitochondrial enzymes and of cytoplasmatic fatty acid-binding protein (FABP) were determined in biopsies from the vastus lateralis muscle. Both during fasting and Iso infusion, the tracer balance data showed that forearm muscle FFA uptake (Con vs. type 2: fast 449+/-69 vs. 258 +/-42 and Iso 715+/-129 vs. 398+/-70 nmol. 100 ml tissue(-1) x min(-1), P<0.05) and FFA release were lower in type 2 diabetes compared with Con. Also, the oxidation of plasma FFA by skeletal muscle was blunted during Iso infusion in type 2 diabetes (Con vs. type 2: Iso 446 +/- 274 vs. 16+/-70 nmol. 100 ml tissue(-1) x min(-1), P<0.05). The net forearm glycerol release was increased in type 2 diabetic subjects (P< 0.05), which points to an increased forearm lipolysis. Additionally, skeletal muscle cytoplasmatic FABP content and the activity of muscle oxidative enzymes were lowered in type 2 diabetes. We conclude that the uptake and oxidation of plasma FFA are impaired in the forearm muscles of type 2 diabetic subjects in the overnight fasted state with and without Iso stimulation.

Acetates↗
PubMed2000

Does the risk of childhood diabetes mellitus require revision of the guideline values for nitrate in drinking water?

In recent years, several studies have addressed a possible relationship between nitrate exposure and childhood type 1 insulin-dependent diabetes mellitus. The present ecologic study describes a possible relation between the incidence of type 1 diabetes and nitrate levels in drinking water in The Netherlands, and evaluates whether the World Health Organization and the European Commission standard for nitrate in drinking water (50 mg/L) is adequate to prevent risk of this disease. During 1993-1995 in The Netherlands, 1,104 cases of type 1 diabetes were diagnosed in children 0-14 years of age. We were able to use 1,064 of these cases in a total of 2,829,020 children in this analysis. We classified mean nitrate levels in drinking water in 3,932 postal code areas in The Netherlands in 1991-1995 into two exposure categories. One category was based on equal numbers of children exposed to different nitrate levels (0.25-2.08, 2.10-6.42, and 6.44-41.19 mg/L nitrate); the other was based on cut-off values of 10 and 25 mg/L nitrate. We determined standardized incidence ratios (SIRs) for type 1 diabetes in subgroups of the 2,829,020 children with respect to both nitrate exposure categories, sex, and age and as compared in univariate analysis using the chi-square test for trend. We compared the incidence rate ratios (IRRs) by multivariate analysis in a Poisson regression model. We found an effect of increasing age of the children on incidence of type 1 diabetes, but we did not find an effect of sex or of nitrate concentration in drinking water using the two exposure categories. For nitrate levels > 25 mg/L, an increased SIR and an increased IRR of 1.46 were observed; however, this increase was not statistically significant, probably because of the small number of cases (15 of 1,064). We concluded that there is no convincing evidence that nitrate in drinking water at current exposure levels is a risk factor for childhood type 1 diabetes mellitus in The Netherlands, although a threshold value > 25 mg/L for the occurrence of this disease can not be excluded.

Adolescent↗
PubMed1999

[Glycemic regulation and management of essential hypertension in diabetics with type 2 diabetes mellitus; the 'United Kingdom prospective diabetes study' of diabetic complications].

Patients with type 2 diabetes mellitus often develop micro- and macrovascular complications. In 25% of them, complications are already present at the time of diagnosis. The principal objective of the United Kingdom prospective diabetes study was to determine if good blood glucose control and adequate treatment of hypertension in patients with type 2 diabetes mellitus can prevent development of diabetes-related complications. The question was also studied if they way in which this blood glucose control was achieved and the way of treating the blood pressure affected the prognosis. Blood glucose control was found to reduce the incidence of--especially--microvascular complications. Oral hypoglycaemic agents and insulin both play an important part in achieving good control. Treatment with metformin reduced mortality due to cardiovascular disease in obese patients. Strict control of the blood pressure reduced development of micro- and macrovascular complications; the mortality from diabetes-related disorders and the numbers of patients suffering a stroke or heart failure. Non of the antihypertensive drugs used (an ACE inhibitor and a beta-blocking agent) offered any advantages over the other.

Adrenergic beta-Antagonists↗