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M Hanefeld

Publications and source records attributed to M Hanefeld.

At least 19 recordsLinked to original sources
PubMed2007

[History and definition(s) of metabolic syndrome].

Metabolic syndrome--a cluster of metabolic diseases and hypertension--is not a new disease. It has been present in the upper classes of all highly developed cultures suffering from over-nutrition and limited physical activity. In the medical literature, it can be found in Renaissance and Baroque times. We are presently experiencing a global tsunami of this syndrome as over-nutrition and lack of movement are typical for large groups of the population. The current definition of metabolic syndrome of the American Heart Association/National Heart, Lung and Blood Institute and the International Diabetes Federation incorporates the quartet central obesity, hypertension, increased blood sugar and dyslipidemia (hypertriglyceridemia, low HDL cholesterol). Thus, simple, collective diagnostics and therapy for this finely meshed group of diseases together with its risk factors is possible.

Cardiovascular Diseases↗
PubMed2006

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus.

AIMS/HYPOTHESIS: The aim of this study was to assess the efficacy and safety of sitagliptin (MK-0431) as monotherapy in patients with type 2 diabetes mellitus and inadequate glycaemic control (HbA(1c) > or =7% and < or =10%) on exercise and diet. METHODS: A total of 521 patients aged 27-76 years with a mean baseline HbA(1c) of 8.1% were randomised in a 1:2:2 ratio to treatment with placebo, sitagliptin 100 mg once daily, or sitagliptin 200 mg once daily, for 18 weeks. The efficacy analysis was based on an all-patients-treated population using an analysis of covariance, excluding data obtained after glycaemic rescue. RESULTS: After 18 weeks, HbA(1c) was significantly reduced with sitagliptin 100 mg and 200 mg compared with placebo (placebo-subtracted HbA(1c) reduction: -0.60% and -0.48%, respectively). Sitagliptin also significantly decreased fasting plasma glucose relative to placebo. Patients with higher baseline HbA(1c) (> or =9%) experienced greater placebo-subtracted HbA(1c) reductions with sitagliptin (-1.20% for 100 mg and -1.04% for 200 mg) than those with HbA(1c) <8% (-0.44% and -0.33%, respectively) or > or =8% to 8.9% (-0.61% and -0.39%, respectively). Homeostasis model assessment beta cell function index and fasting proinsulin:insulin ratio, markers of insulin secretion and beta cell function, were significantly improved with sitagliptin. The incidence of hypoglycaemia and gastrointestinal adverse experiences was not significantly different between sitagliptin and placebo. Sitagliptin had a neutral effect on body weight. CONCLUSIONS/INTERPRETATION: Sitagliptin significantly improved glycaemic control and was well tolerated in patients with type 2 diabetes mellitus who had inadequate glycaemic control on exercise and diet.

Adenosine Deaminase Inhibitors↗
PubMed2006

Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial.

BACKGROUND: Rosiglitazone is a thiazolidinedione that reduces insulin resistance and might preserve insulin secretion. The aim of this study was to assess prospectively the drug's ability to prevent type 2 diabetes in individuals at high risk of developing the condition. METHODS: 5269 adults aged 30 years or more with impaired fasting glucose or impaired glucose tolerance, or both, and no previous cardiovascular disease were recruited from 191 sites in 21 countries and randomly assigned to receive rosiglitazone (8 mg daily; n=2365) or placebo (2634) and followed for a median of 3 years. The primary outcome was a composite of incident diabetes or death. Analyses were done by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00095654. FINDINGS: At the end of study, 59 individuals had dropped out from the rosiglitazone group and 46 from the placebo group. 306 (11.6%) individuals given rosiglitazone and 686 (26.0%) given placebo developed the composite primary outcome (hazard ratio 0.40, 95% CI 0.35-0.46; p<0.0001); 1330 (50.5%) individuals in the rosiglitazone group and 798 (30.3%) in the placebo group became normoglycaemic (1.71, 1.57-1.87; p<0.0001). Cardiovascular event rates were much the same in both groups, although 14 (0.5%) participants in the rosiglitazone group and two (0.1%) in the placebo group developed heart failure (p=0.01). INTERPRETATION: Rosiglitazone at 8 mg daily for 3 years substantially reduces incident type 2 diabetes and increases the likelihood of regression to normoglycaemia in adults with impaired fasting glucose or impaired glucose tolerance, or both.

Adult↗
PubMed2006

Relationship between diurnal glucose levels and HbA1c in type 2 diabetes.

AIMS AND METHODS: Study results still conflict on the contribution of diurnal blood glucose (BG) values to Hb (A1c) in type 2 diabetes. We investigated the relationship between Hb (A1c) and diurnal BG obtained under standardized conditions - before breakfast, two hours after breakfast, before lunch, two hours after lunch, before dinner, two hours after dinner, and at 10 PM, 12 midnight and 3 AM in 68 type 2 diabetic patients before and after optimizing glycemic control. The areas under the curve above fasting BG (AUC1) and above 5.6 mmol/l (AUC2) were calculated for further evaluation. Hb (A1c) was measured at baseline and after a mean of 89 (74 to 108) days. RESULTS: Each BG value at baseline and after treatment optimization significantly correlated with baseline and follow-up Hb (A1c), respectively. The pre-breakfast BG showed the closest correlation with Hb (A1c). The relative contribution of postprandial BG concentrations (AUC1) to overall hyperglycemia (AUC2) decreased with poorer glycemic control. However, treatment optimization mainly resulted in improved blood glucose values in patients with the poorest glycemic control at baseline. Multiple regression analysis demonstrated that fasting (AUC2-AUC1) and postprandial (AUC1) hyperglycemia independently determined Hb (A1c) or the change in Hb (A1c) after treatment optimization. CONCLUSIONS: Our findings indicate that intensive blood glucose monitoring during fasting and postprandial states is important for glycemic control, and is therefore an essential part of good clinical practice.

Blood Glucose↗
PubMed2006

[The metabolic syndrome: where are we going and for what benefits?].

The metabolic syndrome is found in 25-30 % of the German population over the age of 40 years. The concept of metabolic syndrome makes possible an all-inclusive diagnosis and treatment of a bundle of diseases. Prevention of this syndrome is essential if a further rise in the incidence of type 2 diabetes mellitus and coronary heart disease is to be prevented. Building on a "common soil" for the disease components, optimal treatment can be provided and side effect as well as costs reduced.

Cardiovascular Diseases↗
PubMed2006

Glycemic control and treatment failure with pioglitazone versus glibenclamide in type 2 diabetes mellitus: a 42-month, open-label, observational, primary care study.

BACKGROUND: Insulin resistance and declining beta-cell function are the core defects in type 2 diabetes mellitus. It has been suggested that deteriorating glycemic control is related to baseline hemoglobin A(1c) (HbA(1c)) values and remaining beta-cell function. PATIENTS AND METHODS: We report glycemic data from a 3.5-year, open-label, observational, primary care study comparing 30 mg/day pioglitazone with 3.5 mg/day glibenclamide add-on to stable metformin monotherapy in 500 patients with type 2 diabetes. Insulin commencement was considered for patients with HbA(1c) > or = 8.0% or when vascular complications occurred. The change in HbA(1c) compared with baseline and the difference in time to failure to maintain glycemic control were calculated. RESULTS: At endpoint, HbA(1c) had decreased by 1.0% in the pioglitazone group (p < 0.005) and by 0.6% in the glibenclamide group (p < 0.05). Annual progression rates to insulin treatment were 6.6% (pioglitazone) and 16.4% (glibenclamide; p < 0.001 between-group difference). Mean weight increases of 3.5 +/- 0.42 kg in the pioglitazone group and 3.3 +/- 0.38 kg in the glibenclamide group were noted. Overall, both treatments were well tolerated. CONCLUSIONS: Pioglitazone add-on to metformin revealed significant benefits in long-term glycemic control compared with glibenclamide. This difference may be explained by a large between-group difference in HOMA-S, which was shown to correlate significantly to the change in HbA(1c). This suggests that a strategy to reduce insulin resistance to lower the burden of the beta-cell is superior to treatment with glibenclamide.

Aged↗
PubMed2005

Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD): study design and protocol.

AIMS/HYPOTHESIS: Studies suggest that in addition to blood glucose concentrations, thiazolidinediones such as rosiglitazone improve some cardiovascular (CV) risk factors and surrogate markers, that are abnormal in type 2 diabetes. However, fluid retention might lead to cardiac failure in a minority of people. The aim of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) study is to evaluate the long-term impact of these effects on CV outcomes, as well as on long-term glycaemic control, in people with type 2 diabetes. MATERIALS AND METHODS: RECORD is a 6-year, randomised, open-label study in type 2 diabetic patients with inadequate blood glucose control (HbA1c 7.1-9.0%) on metformin or sulphonylurea alone. The study is being performed in 327 centres in Europe and Australasia. After a 4-week run-in, participants were randomised by current treatment stratum to add-on rosiglitazone, metformin or sulphonylurea, with dose titration to a target HbA1c of < or = 7.0%. If confirmed HbA1c rises to > or = 8.5%, either a third glucose-lowering drug is added (rosiglitazone-treated group) or insulin is started (non-rosiglitazone group). The same criterion for failure of triple oral drug therapy in the rosiglitazone-treated group is used for starting insulin in this group. The primary endpoint is the time to first CV hospitalisation or death, blindly adjudicated by a central endpoints committee. The study aim is to evaluate non-inferiority of the rosiglitazone group vs the non-rosiglitazone group with respect to CV outcomes. Safety, tolerability and study conduct are monitored by an independent board. All CV endpoint and safety data are held and analysed by a clinical trials organisation, and are not available to the study investigators while data collection is open. RESULTS: Over a 2-year period a total of 7,428 people were screened in 25 countries. Of these, 4,458 were randomised; 2,228 on background metformin, 2,230 on background sulphonylurea. Approximately half of the participants are male (52%) and almost all are Caucasian (99%). CONCLUSIONS/INTERPRETATION: The RECORD study should provide robust data on the extent to which rosiglitazone, in combination with metformin or sulphonylurea therapy, affects CV outcomes and progression of diabetes in the long term.

Blood Glucose↗
PubMed2005

Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this analysis was to examine the long-term effects of pioglitazone or gliclazide addition to failing metformin monotherapy and pioglitazone or metformin addition to failing sulphonylurea monotherapy in patients with type 2 diabetes. METHODS: Two 2-year, randomised, multicentre trials were performed in patients with inadequately controlled type 2 diabetes (HbA1c 7.5-11% inclusive), who were receiving either metformin or a sulphonylurea at > or = 50% of the maximum recommended dose or at the maximum tolerated dose. In the first study, patients on metformin received add-on therapy with pioglitazone (15-45 mg/day, n = 317) or gliclazide (80-320 mg/day, n = 313). In the second study, patients on sulphonylurea therapy were randomised to receive add-on therapy with either pioglitazone (15-45 mg/day, n = 319) or metformin (850-2,550 mg/day, n = 320). HbA(1)c, fasting plasma glucose, insulin and lipids were investigated. RESULTS: At week 104, the mean reduction from baseline in HbA(1)c was 0.89% for pioglitazone and 0.77% for gliclazide addition to metformin (p = 0.200). There was a statistically significant between-group difference for the change in mean fasting plasma glucose at week 104 (-1.8 mmol/l for pioglitazone vs -1.1 mmol/l for gliclazide, p < 0.001). There were no significant differences in changes from baseline in glycaemic parameters for pioglitazone compared with metformin addition to sulphonylurea therapy. Whether added to metformin or sulphonylurea, pioglitazone caused significantly greater decreases in triglycerides and significantly greater increases in HDL cholesterol than the comparator regimens (p < or = 0.001). There were decreases in LDL cholesterol in the comparator groups and these were significantly different from the small changes observed with pioglitazone (p < 0.001). All treatment regimens were well tolerated. There were weight increases of 2.5 kg and 3.7 kg in the pioglitazone and 1.2 kg in the gliclazide add-on groups, and there was a mean decrease of 1.7 kg in the metformin add-on group. CONCLUSIONS/INTERPRETATION: As add-on therapy to existing sulphonylurea or metformin therapy, pioglitazone improved glycaemic control and this improvement was sustained over 2 years. Furthermore, there were potential benefits in terms of improvements in specific lipid abnormalities. This could offer an advantage over the addition of other oral agents in the long-term treatment of diabetes.

Adult↗
PubMed2005

[Glucose-independent impact of the glitazones on the cardiovascular outcome].

Insulin resistance is a major intermediate link between disordered glucose metabolism and macrovascular complications. The glitazones (pioglitazone, rosiglitazone) impact directly and selectively on the key problem of insulin resistance. In the meantime, much evidence has accumulated for a vessel-protective effect of the glitazone class of substances. Currently, major endpoint studies are investigating the extent to which, and under what conditions, a glitazone actually does influence the cardiovascular morbidity and mortality. The first results from the PROactive study--the design of which, together with the data at study begin have already been published--are expected to become available by the end of 2005.

Body Mass Index↗
PubMed2005

A long-term comparison of pioglitazone and gliclazide in patients with Type 2 diabetes mellitus: a randomized, double-blind, parallel-group comparison trial.

AIMS: This study compared the effects of pioglitazone and gliclazide on metabolic control in drug-naive patients with Type 2 diabetes mellitus. METHODS: A total of 1270 patients with Type 2 diabetes were randomized in a parallel-group, double-dummy, double-blind study. Patients with poorly controlled Type 2 diabetes (HbA1c 7.5-11%), despite dietary advice, received either pioglitazone up to 45 mg once daily or gliclazide up to 160 mg two times daily. Primary efficacy endpoint was change in HbA1c from baseline to the end of the study. Secondary efficacy endpoints included change in fasting plasma glucose, fasting plasma insulin and plasma lipids. At selected centres, oral glucose tolerance tests were performed and C-peptide and pro-insulin levels were measured. RESULTS: Mean HbA1c values decreased by the same amount in the two treatment groups from baseline to week 52 [pioglitazone: -1.4%; gliclazide: -1.4%; (90% CI: -0.18 to 0.02)]. A significantly greater mean reduction in fasting plasma glucose was observed in the pioglitazone group (2.4 mmol/l) than in the gliclazide group [2.0 mmol/l; treatment difference -0.4 mmol/l in favour of pioglitazone; P = 0.002; (95% CI: -0.7 to -0.1)]. Improvements in high-density lipoprotein cholesterol (HDL-C) and total cholesterol/HDL-C were greater with pioglitazone than with gliclazide (P < 0.001). The frequencies of adverse events were comparable between the two treatment groups, but more hypoglycaemic events were reported for gliclazide, whereas twice as many patients reported oedema with pioglitazone than with gliclazide. CONCLUSIONS: Pioglitazone monotherapy was equivalent to gliclazide in reducing HbA1c, with specific differences between treatments in terms of mechanism of action, plasma lipids and adverse events.

Adult↗
PubMed2005

Outcome studies in type 2 diabetes.

BACKGROUND: Outcome studies are used to measure clinically meaningful primary end points, such as mortality and cardiovascular morbidity. However, few outcome trials have been conducted exclusively in people with diabetes; the majority of conventional diabetes trials use surrogate end points that may or may not translate into clinical benefits. Our current knowledge of the effects of pharmacotherapies on cardiovascular risk in patients with diabetes has been gained from subgroups included in large-scale studies. Several trials with lipid-modifying, antiplatelet and/or antihypertensive therapy, for example the recent Collaborative AtoRvastatin Diabetes Study, have included sufficient numbers of patients with diabetes to indicate that effective management can reduce cardio vascular risk in this patient population. The United Kingdom Diabetes Study and the Diabetes Control and Complications Trial provide important, but inconclusive data on the impact of glucose-lowering therapy on the incidence of cardiovascular complications in diabetes. Thiazolidinediones have only become available during the past few years, thus their effects were not assessed in these landmark trials. Ongoing studies in diabetic populations at high risk for further macrovascular events, such as the PROspective pioglitAzone Clinical Trial In macroVascular Events, have been designed to assess the effect of thiazolidinediones on cardiovascular outcome in patients with diabetes and should help to reinforce the importance of broad-based treatment of the multiple metabolic risk factors for cardiovascular disease in people with diabetes. SCOPE: This paper (based upon MEDLINE and EMBASE literature searches in the year range 1990-2005) reviews what we have learned from outcome studies up to the end of 2004 and looks at what we hope to learn from ongoing studies.

Cardiovascular Agents↗
PubMed2004

[Hyperglycemia and cardiovascular events].

Besides classical, modifiable risk factors (hypercholesterolemia, hypertension, smoking) abnormalities of the glucose metabolism (diabetes mellitus, impaired glucose tolerance) are strong emerging cardiovascular risk factors. Epidemiological data indicate that 8 % of the population and up to 60 % of patients with coronary artery disease have abnormalities of glucose metabolism. The prevalence of these abnormalities will increase as the population ages and the mean body weight increases. An abnormal glucose concentration damages the endothelium in several ways: increased oxidative stress, inflammatory processes and an activation of procoagulant factors all impair endothelial function. A blood glucose normalising therapy is thought to decrease the incidence of cardiovascular events in these patients. In patients with an acute myocardial infarction and diabetes mellitus an early intensive insulin therapy improves the outcome of these patients. In summary, the early detection and treatment of abnormalities of glucose metabolism reduces cardiac events.

Cardiovascular Diseases↗
PubMed2004

[Screening, prevention and early therapy of type 2 diabetics].

For each known diabetic at least one new patient is diagnosed when the 75-g OGTT is used for screening. For early diagnosis in high risk groups, the oral glucose tolerance test is indispensable since ca. 30% of the asymptomatic diabetes cases are identified on the basis of a 2-hour postchallenge glucose value of > 11.1 mmol/l. In controlled studies on persons with IGT, every second diabetes case could be prevented through lifestyle modifications beginning in childhood. Three-year studies showed that the incidence of diabetes could be reduced by about one-third with the medications acarbose, metformin and orlistat. The observation that statins, ACE inhibitors and AT1 blockers also contributed to a reduction of new diabetes cases was made in studies on the prevention of coronary heart diseases.

Age Factors↗
PubMed2004

Acarbose for the prevention of Type 2 diabetes, hypertension and cardiovascular disease in subjects with impaired glucose tolerance: facts and interpretations concerning the critical analysis of the STOP-NIDDM Trial data.

The STOP-NIDDM Trial has shown that acarbose treatment in subjects with impaired glucose tolerance is associated with a significant risk reduction in the development of diabetes, hypertension and cardiovascular complications. Kaiser and Sawicki have accused the investigators of the STOP-NIDDM Trial of major biases in the conduct of the study, of manipulating the data and of conflict of interest. The aim of this paper is to present data and explanations refuting these allegations. In the STOP-NIDDM Trial, 61 subjects were excluded from the efficacy analysis before unblinding for legitimate reasons: failure to satisfy major entry criteria (n=17) and lack of post-randomisation data (n=44). Blinding and randomisation were carried out by an independent biostatistician. Titration of placebo/acarbose is well described in the protocol and in the study design paper. Of the study population, 9.3% had a fasting plasma glucose of > or =7.0 mmol/l at screening and could have been diabetic according to the new diagnostic criteria. However, even if these subjects are excluded, patients having acarbose treatment still saw a significant risk reduction in the development of diabetes (p=0.0027). The changes in weight are consistent in different publications and are related to different times of follow-up and assessment. Weight change does have an effect on the development of diabetes, but acarbose treatment is still effective even after adjusting for this (p=0.0063). The cardiovascular endpoints were a clearly designated assessment in the original protocol, and only those defined in the protocol and ascertained by the independent Cardiovascular Event Adjudication Committee were used in the analysis. Hypertension was defined according to the most recent diagnostic criteria. The STOP-NIDDM Trial results are scientifically sound and credible. The investigators stand strongly behind these results demonstrating that acarbose treatment is associated with a delay in the development of diabetes, hypertension and cardiovascular complications in a high-risk population with IGT.

Acarbose↗
PubMed2004

Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies.

AIMS: To assess if treatment with the alpha-glucosidase inhibitor acarbose can reduce cardiovascular events in type 2 diabetic patients. METHODS AND RESULTS: This meta-analysis included seven randomized, double-blind, placebo-controlled acarbose studies with a minimum treatment duration of 52 weeks. Type 2 diabetic patients valid for safety were randomized to either acarbose (n=1248) or placebo (n=932). The primary outcome measure was the time to develop a cardiovascular event. Primary analysis was conducted using Cox regression analysis. The effect of acarbose on metabolic parameters was also investigated. Acarbose therapy showed favourable trends towards risk reduction for all selected cardiovascular event categories. The treatment significantly reduced the risk for "myocardial infarction" (hazards ratio=0.36 [95% Cl 0.16-0.80], P=0.0120) and "any cardiovascular event" (0.65 [95% Cl 0.48-0.88], P=0.0061). Glycaemic control, triglyceride levels, body weight and systolic blood pressure also improved significantly during acarbose treatment. CONCLUSION: Intervention with acarbose can prevent myocardial infarction and cardiovascular disease in type 2 diabetic patients while most of them are already on intensive concomitant cardiovascular medication.

Acarbose↗
PubMed2004

The lipid triad in type 2 diabetes - prevalence and relevance of hypertriglyceridaemia/low high-density lipoprotein syndrome in type 2 diabetes.

Cardiovascular disease is the major cause of morbidity and mortality in type 2 diabetes mellitus. Among the established risk factors, the lipid triad (elevated triglycerides, decreased high-density lipoprotein cholesterol, and small dense low-density lipoprotein cholesterol) is a powerful risk factor for atherosclerosis in type 2 diabetes. The prevalence of hypertriglyceridaemia (HTG) in type 2 diabetes is two to three times higher than in non-diabetics. The Copenhagen Male study, the AMORIS study, and several other trials showed hypertriglyceridaemia to be an independent predictor of coronary heart disease (CHD). HTG may promote risk both directly and indirectly through association with alterations of lipoprotein size and composition. The Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT) demonstrated that raising high-density lipoprotein cholesterol (HDL-C) in patients with low (HDL-C) and low-density lipoprotein cholesterol (LDL-C) is associated with a significant reduction in CHD risk. It was shown in the Diabetes Intervention Study, AFCAPS/TexCAPS, and PROCAM studies that decreased HDL-C and elevated triglycerides are independent risk factors for atherosclerosis, particularly in patients with diabetes mellitus. Several epidemiological studies demonstrated that total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratios or low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratios could be better predictors of atherosclerosis than any single lipid parameter. Intima-media thickness (IMT), a well established marker of early atherosclerosis, is associated with HTG/low HDL-cholesterol. In the Risk factors in IGT for Atherosclerosis and Diabetes (RIAD) study total and HDL-cholesterol were independent determinants of IMT in subjects at risk for type 2 diabetes. Postprandial HTG was also shown to be correlated with increased IMT in type 2 diabetic patients.

Arteriosclerosis↗