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Biomedical subjects

M Hanefeld

Publications and source records attributed to M Hanefeld.

At least 37 records · Page 2Linked to original sources
PubMed2004

Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial.

Pioglitazone increases the insulin sensitivity of peripheral tissues and may provide an alternative first-line treatment for type 2 diabetes. This study compared metabolic control in drug-naive type 2 diabetes patients given either pioglitazone or metformin. Eleven hundred and ninety-nine patients with poorly controlled type 2 diabetes mellitus [glycosylated hemoglobin (HbA1c), 7.5-11%; normal, 4.3-6.1%] were randomized to receive either pioglitazone (< or =45 mg/d) or metformin (< or =850 mg, three times daily). HbA1c, fasting plasma glucose (FPG), insulin levels, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol, triglycerides, free fatty acids, and urinary albumin/creatinine ratio were measured. Mean HbA1c decreased in both treatment groups from baseline to wk 52 (-1.4% and -1.5%). Significantly greater mean reductions in FPG were observed in the pioglitazone group (-45.0 mg/dl; -2.5 mmol/liter) than in the metformin (-39.6 mg/dl; -2.2 mmol/liter) group (P = 0.016). Favorable changes in triglycerides and HDL-C were more pronounced with pioglitazone. Although low density lipoprotein cholesterol and TC levels increased with pioglitazone, TC/HDL-C ratios decreased similarly with both treatments. The urinary albumin/creatinine ratio was reduced by 19% with pioglitazone treatment, but remained unchanged with metformin therapy (-1%; P = 0.002). There was an increase in body weight of 1.9 kg in the pioglitazone group and a decrease of 2.5 kg in the metformin group. The overall frequency of adverse events was similar between treatment groups, but adverse event profiles were different between treatment groups. HbA1c reduction is similar after pioglitazone and metformin monotherapies, but differences in FPG, plasma lipids, and adverse effects between the two compounds may influence decision-making in individual prescribers.

Adult↗
PubMed2003

[Significance of triglycerides for other metabolic parameters in the familial metabolic syndrome].

BACKGROUND: The relationship between the various degrees of glucose tolerance and metabolic parameters have already been examined in various studies. Whether and to what extent the triglycerides (TG) affect other metabolic parameters in the different degrees of glucose tolerance is not certain. We therefore studied the importance of the triglycerides within a defined glycemic state in patients with an elevated familial risk for metabolic diseases. METHODS: We examined 866 patients (380 men, 486 women, mean age 44,4 years) in the "Familial Metabolic Syndrome Study" (FAMES). The patients were assigned to various degrees of glucose tolerance, according to the result of an oral glucose tolerance test. All degrees were divided into subgroups in respect of the triglyceride level (TG < 1,7 or TG >/= 1,7 mmol/l). In these subgroups we measured various metabolic parameters like fasting glucose, insulin resistance, insulin and proinsulin levels, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), uric acid, HbA (1c), and free fatty acids (FFA). RESULTS: In patients with normal glucose tolerance the hypertriglyceridemia is already associated with other components of the metabolic syndrome like elevated HbA (1c), free fatty acids, proinsulin and insulin levels, worsened insulin sensitivity, elevated uric acid and LDL-C levels as well as a lowered HDL-C level. The patients with diabetes and hypertriglyceridemia also showed higher levels of FFA, proinsulin and insulin, a lower HDL-C level and a more prominent insulin resistance. CONCLUSION: Hypertriglyceridemia is an indicator for insulin resistance and elevated levels of other components of the metabolic syndrome within the various degrees of glucose tolerance.

Adult↗
PubMed2003

[Therapy decision based on the glucose triad. Drug treatment of type 2 diabetes].

For the treatment of type 2 diabetes we now have available a wide spectrum of oral antidiabetic agents and insulins that make it possible to offer the patient an individualized, pathophysiologically oriented therapy. Such treatment should be oriented to the two basic defects--insulin resistance and impaired early secretion of insulin--which can be assessed on the basis of fasting and postprandial blood sugar. Since monotherapy rarely suffices to correct the complex dysregulation, when close-to normalization of the glucose triad fasting blood glucose, postprandial blood glucose and HbA1C fails, early application of complementary combinations offer advantages, with preference being given to metformin in the overweight patient. This also applies to the combination with insulin.

1-Deoxynojirimycin↗
PubMed2003

Influence of treatment with acarbose or glibenclamide on insulin sensitivity in type 2 diabetic patients.

AIM: The aim of our double-blind, placebo-controlled study was to compare the effect of acarbose and glibenclamide on the insulin sensitivity in type 2 diabetes. METHODS: We investigated 77 patients (mean age 58.7 years, mean BMI 27.3 kg/m2), treated by diet alone for at least 4 weeks. The subjects were randomized into three treatment groups for 16 weeks: 100 mg t.i.d. acarbose (n = 25) or 1 mg t.i.d. glibenclamide (n = 27) or one t.i.d. placebo (n = 25). Before and after therapy, the levels of fasting plasma glucose, glycosylated haemoglobin, fasting insulin, plasma glucose and insulin 1 h after a standardized breakfast were measured and insulin sensitivity determined by euglycaemic hyperinsulinaemic clamp test. RESULTS: After the treatment period, BMI in the acarbose and placebo group decreased significantly, whereas in the glibenclamide group a significant increase was observed. Fasting plasma glucose was only significant reduced under glibenclamide. The postprandial glucose decreased significantly after acarbose (13.8 vs. 11.4 mmol/l, p < 0.05) and glibenclamide treatment (14.6 vs. 11.4 mmol/l, p < 0.05) and was unchanged under placebo (13.8 vs. 13.7 mmol/l). The fasting insulin levels remained unchanged in all three groups, whereas postprandial insulin values increased significantly under glibenclamide. Neither acarbose nor glibenclamide significantly changed insulin sensitivity [acarbose: glucose disposal rate before treatment 2.3 mg/kg body weight/min/insulin, after treatment 3.2; glibenclamide 2.2 vs. 2.1; placebo 2.6 vs. 3.0]. CONCLUSIONS: Our results show a more substantial improvement of glucose control under glibenclamide than under acarbose which, however, was not associated with an increase of insulin sensitivity.

Acarbose↗
PubMed2002

[Predictors of abnormal glucose tolerance in persons at risk of type 2 diabetes: the RIAD study].

BACKGROUND AND OBJECTIVE: Early detection of glucose intolerance is an important issue in diabetes care. In the metabolic syndrome it is associated with an increased incidence of cardiovascular events. So far it is not clear which anthropometric and metabolic/hormonal parameters are of importance in the conversion of normal to impaired glucose tolerance. PATIENTS AND METHODS: The participants of the RIAD (Risk factors in IGT for Atherosclerosis and Diabetes) study had to meet the following criteria: related to type 2 diabetic patients, obesity and/or dyslipidaemia. A total of 358 subjects (age: 40-70 years) with normal glucose tolerance (NGT) in an oral glucose tolerance test (OGTT, 75 g glucose), were examined after a follow-up of 2.90 +/- 0.47 years. 284 of them remained with normal glucose tolerance, while 64 developed an impaired glucose tolerance (IGT) and ten type 2 diabetes (T2DM). The data of the initial screening examination were analysed in three groups (NGT-NGT; NGT-IGT; NGT-T2DM). Plasma glucose (PG), insulin, C-peptide and proinsulin were measured in the fasting state, as well as every 30 minutes during an OGTT, and also basal plasminogen activator inhibitor (PAI) and inflammatory parameters. RESULTS: Subjects who converted to IGT or diabetes show, already in the stage of normal glucose tolerance, clear tendency for the development of the metabolic syndrome. They were more obese and had higher fasting and 2 hPG values. The early phase insulin secretion, calculated as a ratio of DeltaInsulin 30'/DeltaPG 30', was lower in the IGT and the diabetes groups (n. s.). Both groups showed a significantly increased insulin resistance. Both converter groups revealed significantly higher PAI (Plasminogen-Activator-Inhibitor) levels and a striking but not significant increase in inflammatory parameters. CONCLUSIONS: Subjects who develop IGT and type 2 diabetes, will already in the stage of NGT show an impairment of insulin secretion and higher insulin resistance. Both processes seem to develop parallel to each other and determine the progress of the glucose intolerance. Fasting and 2h post-challenge glucose were the most important predictors of subsequent glucose intolerance.

Adult↗
PubMed2002

Insulin-resistant patients with type 2 diabetes mellitus have higher serum leptin levels independently of body fat mass.

In obese people, an increase of plasma leptin levels is well-known and is seen as a consequence of the increased body fat mass. Moreover, a relationship between fasting concentrations of leptin and insulin has been described. Hyperinsulinemia is considered to be indicative of insulin resistance. We aimed at elucidating the interrelations between leptin, insulin and insulin resistance in type 2 diabetic patients. Under metabolic ward conditions, we investigated 21 moderately overweight men with type 2 diabetes. The patients had a mean age of 49.1 years, a mean body mass index (BMI) of 26.8 kg/m(2), and a mean diabetes duration of 82.5 months. All patients were treated with diet alone. We measured fasting leptin and insulin levels, body composition by determination of total body water, and insulin resistance by euglycemic hyperinsulinemic clamp technique. At univariate analysis, fasting leptin level significantly and positively correlated with BMI (r=0.49, p=0.02) and with fasting insulin (r=0.69, p=0.001), while it negatively correlated with the glucose disposal rate (r=-0.62, p=0.002). Furthermore, leptin was inversely correlated with HDL-cholesterol (r=-0.45, p=0.04). When excluding the influence of body fat mass or of BMI in partial correlation analysis, the correlations between leptin and insulin or insulin sensitivity remained significant. The relationship between insulin resistance (as measured directly in the clamp experiments) and leptin concentrations was also shown by subdividing the diabetic patients according to tertiles of insulin sensitivity. The highest fasting leptin levels were observed in those patients with the most expressed insulin resistance. Our data point to a functional relationship between insulin resistance and leptin concentrations in insulin-resistant type 2 diabetic men, independently of body composition. This relationship is believed to be mediated by insulin.

Adipose Tissue↗
PubMed2002

Different effects of acarbose and glibenclamide on proinsulin and insulin profiles in people with Type 2 diabetes.

AIM: In a double-blind, placebo-controlled study, we compared the effect of acarbose (A) and glibenclamide (G) on post-prandial (pp) and 24-h profiles of proinsulin and insulin. METHODS: Twenty-seven patients with Type 2 diabetes mellitus insufficiently controlled with diet alone were randomised to receive acarbose, 100 mg thrice daily, glibenclamide, 1 mg thrice daily, or placebo. Before and after 16 weeks of treatment, 24-h profiles of proinsulin, insulin and glucose (fasting, 1 h after breakfast and every 3-h for a 24-h period) were measured under metabolic ward conditions with standardised meals. RESULTS: With acarbose, a reduced 24-h level of proinsulin was observed compared with glibenclamide (AUC 1096 +/- 118 vs. 1604 +/- 174 pmol/l per h, P<0.05) at 16 weeks. The breakfast increment of proinsulin was lower with acarbose than glibenclamide (6.8 vs. 19.3 pmol/l, P<0.05) as was the level at that time (37.3 +/- 5.3 vs. 56.4 +/- 7.5 pmol/l, P<0.05). A lower AUC of insulin after treatment was also observed with acarbose than glibenclamide (7.9 +/- 0.9 vs. 14.8 +/- 4.5 nmol/l per h, P<0.05), as also for 1-h increment (81 +/- 26, vs. 380 +/- 120 pmol/l, P<0.01) and 1-h level (325 +/- 30 vs. 621 +/- 132 pmol/l, P<0.01). Acarbose reduced 1-h breakfast glucose increment (baseline 6.3 +/- 0.6, 16-week 3.5 +/- 0.6 mmol/l, P<0.01) and 1-h glucose level (18.1 +/- 1.1 and 14.5 +/- 1.3 mmol/l, P<0.01), whereas glibenclamide did not (6.6 +/- 0.7 vs. 5.4 +/- 0.6 mmol/l and 18.9 +/- 1.5 vs. 15.3 +/- 1.3 mmol/l). CONCLUSIONS: Measurement of circadian excursions of proinsulin and insulin reveals distinct differences in meal-time proinsulin and insulin increment and level between acarbose and glibenclamide whereas fasting levels of these insulin fractions remained unaffected.

Acarbose↗
PubMed2002

Insulin resistance and metabolic parameters in type 2 diabetic patients.

Background: The importance of insulin resistance in type 2 diabetes mellitus has been generally accepted. Only very few data about the degree of insulin resistance in a representative group of type 2 diabetic patients are available. The aim of this study was to ascertain the degree of insulin resistance and its relation to metabolic parameters in type 2 diabetic patients. Methods: We studied 96 type 2 diabetic patients. The inclusion criteria were type 2 diabetes according to WHO criteria and HbA(1c) between 6.8% and 10.5%. Insulin resistance was estimated in a euglycemic hyperinsulinemic clamp. Blood parameters like lipids, insulin, glucose, fatty acids, and leukocytes were also studied. Results: The insulin sensitivity of 71 of the type 2 diabetic patients was markedly lower than that of the controls. Twenty-five diabetic patients had an M(c) value within the range of the controls. The M(c) values, as a measure of insulin resistance, of the diabetic patients were between 0.3 and 5.2 mg/(kg min insulin), whereas the M(c) range of the controls was from 2.6 to 10.8 mg/(kg min insulin). Conclusions: Approximately 75% of the type 2 diabetic patients were insulin-resistant. Hence, type 2 diabetes mellitus was not equivalent to insulin resistance in every case.

Journal Article↗
PubMed2002

[Differential type 2 diabetes therapy based on pathophysiological aspects].

Type 2 Diabetes is characterized by a deficit in early insulin secretion and increased insulin resistance. Based on the measurement of fasting and 2 h postprandial blood glucose a simple typing of hyperglycemia is possible in isolated fasting hyperglycemia (IFH), isolated postprandial hyperglycemia (IPH) and combined hyperglycemia (CH). IFH is predominantly associated with insulin resistance whereas in IPH a more pronounced insulin deficit is found. This and other simple parameters such as BMI, comorbidities and age are the basis of differential therapy with OAD if best efforts with life style modification fail to reach the target values of the lipid triad. Patients with IFH profit particularly from metformin and long acting sulfonylureas (glimepiride, glibenclamide). Patients with IPH are candidates for prandial antidiabetics (AGI, nateglinide, repaglinide). Antihyperglycemic agents such as metformin and AGI bear no risk of hyperglycemia and reduce body weight. Prandial insulin secretagogues have lower risk of weight gain and hypoglycemia than long acting sulfonylureas. They are therefore beneficial in obese patients and the elderly. The same principles are valid for combination treatment. With exception of insulin secretagogues all OAD can be combined if monotherapy fails to reach the target levels of the gluco-triad. Instead of a stepwise treatment algorithm an individualized therapy based on pathophysiology and comorbidities taking into account the global risk seems to be beneficial.

Blood Glucose Self-Monitoring↗
PubMed2002

The effects of orlistat on body weight and glycaemic control in overweight patients with type 2 diabetes: a randomized, placebo-controlled trial.

AIM: To assess the long-term effects of orlistat on body weight, glycaemic control and cardiovascular risk factors in overweight patients with type 2 diabetes. METHODS: This was a multicentre, randomized, placebo-controlled study with a 4-week placebo plus diet lead-in period and a 48-week, double-blind treatment period. Overweight or obese adults [body mass index (BMI) >or= 28 kg/m2] with HbA1c of 6.5-11% and clinical type 2 diabetes were randomized to orlistat (120 mg t.i.d. n = 189) or placebo (n = 180) in conjunction with a low-calorie diet. Patients had either received sulphonylurea therapy for at least 2 months before the study or were not receiving any antidiabetic medication (the majority of which were drug-naïve). RESULTS: After 1 year, patients in the orlistat group lost significantly more weight than patients in the placebo group (-5.4% vs. -3.6%; p = 0.006). Moreover, significantly more patients achieved weight loss of >or= 5% with orlistat compared with placebo (51.3% vs. 31.6%; p = 0.0001). Patients treated with orlistat also had significantly greater improvements than placebo-treated patients in HbA1c (-0.9% vs. -0.4%; p < 0.001), fasting glucose (-1.6 vs.-0.7 mmol/l; p = 0.004) and post-prandial glucose (-1.8 vs. -0.5 mmol/l; p = 0.003). In addition, orlistat-treated patients had a significantly greater reduction in LDL cholesterol compared with placebo. Overall, orlistat had a similar safety profile to placebo, with the exception of a higher incidence of generally mild and transient gastrointestinal events known to be associated with the mode of action of orlistat. CONCLUSIONS: Treatment with orlistat plus diet resulted in significant weight loss, improved glycaemic control and cardiovascular risk factor profile in overweight patients with type 2 diabetes.

Adolescent↗
PubMed2002

Subclinical inflammation is strongly related to insulin resistance but not to impaired insulin secretion in a high risk population for diabetes.

Subclinical inflammation was shown to be a strong predictor of cardiovascular events and was suggested to be a part of the metabolic syndrome (MS). The aim of the present study was to investigate the relationship of the inflammatory parameters-leukocyte count, C-reactive protein (CRP), and fibrinogen level-to insulin resistance and insulin secretion, as well as to other components of the MS in a population at risk for diabetes. A total of 396 subjects (142 men and 254 women) were analyzed from the follow-up of the Risk Factors in Impaired Glucose tolerance (IGT) for Atherosclerosis and Diabetes (RIAD) study, who were at risk for type 2 diabetes, such as family history of diabetes, obesity, and/or hyper/dyslipoproteinemia. Subjects under lipid-lowering treatment or with acute infections were not eligible. A variety of risk factors within the MS were examined: lipids, glycemic parameters, coagulation, insulin fractions. and microalbuminuria. CRP was determined by a highly sensitive method, using an immunological agglutination test, and fibrinogen was measured by the method of Clauss. Insulin resistance was evaluated by the homeostasis model assessment (HOMA) and insulin secretion by HOMA and by insulin areas under curve in an oral glucose tolerance test (OGTT), insulin increment at 30 mnutes of OGTT, and insulin increment/glucose increment at 30 minutes of OGTT. By univariate analysis, fibrinogen level (r = 0.180, P <.001), leukocyte count (r = 0.162, P =.001), and CRP (r = 0.251, P <.001) were all highly significantly correlated to insulin resistance, but not to insulin secretion. A significant rise was found for the majority of the components of the MS in quartiles of the examined inflammatory parameters. In multivariate analysis of all analyzed metabolic parameters, including age, sex, physical activity, and smoking, body mass index (BMI) was found a strong independent determinant of all inflammatory markers examined. Thus, in a population at risk for type 2 diabetes we demonstrate that subclinical inflammation underlies the metabolic syndrome, through association to one of its primary anomalies-insulin resistance, whereas no association was found to impaired insulin secretion.

Blood Glucose↗
PubMed2002

Intima-media thickness and atherosclerotic plaques in familial defective apolipoprotein B-100 and familial hypercholesterolemia.

Familial defective apolipoprotein B-100 (FDB) is a genetic disorder characterized by a decreased binding of low-density lipoprotein (LDL) particles to the LDL receptor due to defective apo B-100. Impaired LDL clearance could also be due to defects of the LDL receptor (familial hypercholesterolemia, FH). FDB was suggested to be clinically indistinguishable from classical FH. The measurement of the intima-media thickness (IMT) is an accepted method for the direct evaluation of early atherosclerosis. Thus, the aim of this study was to examine the IMT in patients with FDB in comparison to FH. Our data indicate that IMT in FDB does not differ from IMT in FH.

Adult↗
PubMed2002

Impaired glucose tolerance is not associated with lipid intolerance.

Post-prandial (pp) hypertriglyceridaemia (HTG) has an important role in the development of atherosclerosis in Type 2 diabetes. Impaired glucose tolerance (IGT) is associated with an increased risk of atherosclerosis and increased level of fasting triglycerides (TG). The aim of this study was to analyse pp HTG and the composition of TG-rich lipoproteins in carefully selected subjects with IGT in comparison to controls with normal glucose tolerance (NGT). Fifteen men with IGT and 27 men with NGT, aged 44 to 70 yr, were examined. All study participants were non-smokers and had fasting TG <4.6 mmol/l. The subjects underwent an oral glucose tolerance test (75 g glucose) and a lipid-glucose tolerance test (LGTT; 92 g fat, 126 g carbohydrate), that allowed the assessment of lipid and glucose tolerance in one test. HbA1C, plasma glucose and lipids were measured by routine methods. Lipoprotein subfraction analysis of VLDL (VLDL1: Sf60-400 and VLDL2: Sf20-60) was conducted in a fasting state, as well as 4 hr after the LGTT using a density gradient ultracentrifugation with a subsequent compositional analysis. No significant difference was found either for fasting or pp TG, or for area under curve (AUC) -TG (12.21 +/- 4.27 mmol/l x 6 hr vs 13.95 +/- 6.74 mmol/l x 6 hr; p>0.05) between the IGT and NGT. A highly significant correlation was found between the fasting TG and the AUC-TG (r=0.925; p<0.01). To avoid bias by differences in fasting plasma TG known to affect lipid tolerance we investigated 11 matched pairs for fasting TG. Also, the matched-pairs evaluation pp TG course did not differ significantly from the IGT and NGT. No significant difference for fasting or pp levels of VLDL1 and VLDL2, or for the TG content of chylomicron, VLDL1 and VLDL2 and for the percentage of TG in VLDL1 and VLDL2 was found between the IGT and NGT group. In conclusion, IGT subjects with a similar level of fasting TG do not exhibit lipid intolerance. Our data suggest that glucose intolerance should precede lipid intolerance.

Adult↗
PubMed2002

Control of post-prandial hyperglycemia--an essential part of good diabetes treatment and prevention of cardiovascular complications.

AIM: This article reviews the relationship between the control of post-prandial hyperglycemia and diabetes-related complications. DATA SYNTHESIS: Hyperglycemia is a modifiable risk factor that has a deleterious effect on the development and progression of microvascular and macrovascular complications in patients with type 2 diabetes. The UK Prospective Diabetes Study revealed how reductions in hemoglobin A1c (HbA1c) correlate with a significant reduction in all-cause mortality and the incidence of myocardial infarction. The Diabetes Intervention Study showed that poor control of fasting glycemia does not increase the risk of myocardial infarction or mortality, whereas poor control of post-prandial glucose is associated with a high all-cause mortality rate. HbA1c is the standard measure for metabolic control and therapeutic efficacy, but does not reflect fluctuations in glycemic control. Plasma glucose concentrations in healthy subjects remain within a narrow range, which suggests that the fluctuations in glucose levels caused by inappropriate treatment may have negative consequences. These fluctuations have been associated with acute adverse effects (particularly excessive post-prandial hyperglycemia, pre-meal hypoglycemia and weight gain) that counteract the positive effect of lowering fasting plasma glucose and HbA1c. Post-prandial hyperglycemia and spikes also have deleterious effects on insulin secretion and sensitivity. Prandial oral antidiabetic agents such as alpha-glucosidase inhibitors (acarbose, miglitol) and rapidly acting insulin secretagogues (nateglinide, repaglinide) have recently been introduced to improve the control of post-prandial hyperglycemia. CONCLUSION: Near-normal post-prandial glycemic control is associated with lower rates of cardiovascular and all-cause mortality than excessive post-challenge hyperglycemia. In addition to the aggressive control of HbA1c and fasting plasma glucose, the strict normalisation of postprandial hyperglycemia is an essential part of good diabetes treatment. There is growing evidence from epidemiological and clinical studies that this also reduces the risk of cardiovascular complications.

Blood Glucose↗
PubMed2001

[The new oral antidiabetics. Type 2 diabetes under control only with tablets?].

The new oral antidiabetics have expanded our possibilities of treating type 2 diabetes and associated diseases. AGIs and insulin sensitizers represent new principles of action. The insulinotropic substances improve the dynamics of insulin secretion. They enable pathophysiologically-oriented treatment that takes account of the patient's need for simple, low-stress management. This improves the quality of life, in particular of the elderly and disabled patient. However, this fact does not justify delaying treatment with insulin, which is always needed when the goals of treatment cannot be achieved with oral preparations.

Administration, Oral↗