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Biomedical subjects

M Hanefeld

Publications and source records attributed to M Hanefeld.

At least 19 recordsLinked to original sources
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↗
PubMed2001

[Intima-media thickness in healthy probands without risk factors for arteriosclerosis].

BACKGROUND AND OBJECTIVE: Ultrasound examination of the intima-media thickness (IMT) is a well accepted, highly reproducible method for the evaluation of early atherosclerosis. However, for the exact interpretation of these measurements reference values for IMT should be determined. The present work provides for the first time normal values for IMT of the common carotid artery and the arteries of the lower limbs (common femoral, superficial and popliteal arteries) in a German population of healthy subjects without risk factors. SUBJECTS AND METHODS: A total of 112 subjects (50 men, 62 women), aged 40 to 70, were examined, according to the following inclusion criteria: no diabetes or marked elevation of postprandial plasma glucose; non-smokers; no hypertension, obesity, dys/hyperlipidaemia or albuminuria; no history of coronary heart disease, stroke and peripheral arterial occlusion. IMT was measured and standardized by the method of Pignoli. Total cholesterol, triglycerides, HDL-cholesterol, HbA1c, plasma glucose (fasting and postprandial) and albuminuria were examined by routine methods. RESULTS: The mean values of double measurements bilaterally in the distal part of the common carotid artery in men were 0.79 (0.73 ... 0.84) mm (40-54 years) and 0.87 (0.81 ... 0.93) mm (55-70 years). In women the values were: -0.70 (0.67 ... 0.75) mm and 0.82 (0.75 ... 0.90) mm, resp. In the group aged 40-54 years the men showed significantly higher IMT of all examined vessels in comparison to the women. In the group aged 55-70 years somewhat higher IMT of the common carotid artery and significantly higher IMT of the arteries of the lower extremity were observed in men. In multivariate analysis age was found to be a significant determinant of IMT of all examined vessels. CONCLUSION: Intima-media thickening of the common carotid artery in men aged 40-70 years is to be accepted if a single measurement of IMT exceeds > or = 1 mm. For women, aged 40-54 years, IMT is defined as pathological if one IMT is above 0.85 mm, and for those aged 55-70 years if IMT exceeds 1 mm.

Adult↗
PubMed2001

[Hyperlipidemia and fibrates with special reference to diabetes].

The lipid triad: hypertriglyceridemia, low HDL, small dense LDL represents a high risk group for excessive cardiovascular morbidity and mortality in type 2 diabetes. In poorly controlled diabetes LDL are increasingly oxydized and glycosylated whereas HDL degradation is accelerated. The high lipid risk in coincidence with the diseases of the metabolic syndrome leads to the conclusion that diabetes today is a cardiovascular disease demanding an aggressive correction of the lipid triad. The benefit of lipid lowering treatment has been proven not only for statins but there is more and more evidence also in favour of fibrates. Fibrates are particularly useful in the treatment of hypertriglyceridemia/low HDL. This also leads to a reduction in small dense LDL. In the case of insufficient correction of LDL a combination with a low dose of a statin is recommended. A definite answer with respect to the benefit/risk ratio of fibrates should be provided by large ongoing studies with these drugs in representative groups of diabetes patients (LDS, TrUMPET, FIELD).

Cholesterol, HDL↗
PubMed2001

Improved glycaemic control with miglitol in inadequately-controlled type 2 diabetics.

OBJECTIVE: The study compared the long-term efficacy and safety of miglitol to placebo in Type 2 diabetic outpatients inadequately controlled on combination therapy of diet, glibenclamide and metformin. METHODS: Type 2 diabetic patients (n = 154) receiving glibenclamide 7-20 mg/day and at least one 500-850 mg tablet metformin per day were randomized to receive additional miglitol or placebo for 24 weeks, titrated up stepwise from 25 to 100 mg trice daily. RESULTS: Addition of miglitol to sulphonylureas and metformin (per protocol analysis) produced a statistically, significantly greater reduction in HbA1c (-0.55%, P = 0.04) and postprandial glucose (-2.6 mmol/l, P = 0.0009) from baseline to endpoint than placebo (-0.2% and -0.6 mol/l, respectively). Reduction in fasting blood glucose was greater with miglitol than placebo, and there was a possible difference in favor of miglitol for fasting and postprandial triglyceride levels, but these did not reach statistical significance. Flatulence and diarrhea were reported by statistically, significantly more patients receiving miglitol than placebo, but adverse events overall were reported by only 10% more patients in the miglitol group. No cases of hypoglycaemia were reported. CONCLUSIONS: Miglitol can safely and effectively be added to long-term combination therapy in people with Type 2 diabetes inadequately controlled with glibenclamide plus metformin.

1-Deoxynojirimycin↗
PubMed2001

Search for mitochondrial DNA mutation at position 3243 in German patients with a positive family history of maternal diabetes mellitus.

Mitochondrial diabetes is one of the most common monogenetic forms of diabetes mellitus. However, variable prevalences have been reported by different investigators. Therefore, the aim of our study was to investigate the prevalence of the most prevalent mitochondrial DNA mutation at position 3243 (A --> G) in german patients with a positive family history of maternally inherited diabetes mellitus and/or hearing loss. We screened 1460 patients with diabetes mellitus by a questionnaire and identified 122 patients with a positive family history of maternal diabetes mellitus. Seven of the 122 patients suffered from hearing loss in addition. An EDTA blood sample of each patient was examined by polymerase chain reaction followed by a digestion with Bsp120I. In addition all samples were further examined by denaturing gradient gel electrophoresis to increase the detection limit for heteroplasmy. Only one mt DNA mutation at position 3243 could be detected in the 122 patients. The detection limit of denaturing gradient gel electrophoresis (DGGE) for heteroplasmy was 3%. We detected one new polymorphism at position 3333 (C --> T) of the mitochondrial genome (0.8% of the patients), and a known polymorphism at position 3197 (T --> C) in 10.6% of the patients. We therefore conclude that the frequency of the A3243G mutation is much lower in the investigated study population, mostly originating from Saxonia, than in asian populations.

Adult↗
PubMed2001

Pharmacokinetics and clinical efficacy of pioglitazone.

Pioglitazone is a thiazolidinedione that increases insulin sensitivity in target tissues. It is well-absorbed, with a mean absolute bioavailability of 83% and reaching maximum concentrations in around 1.5 hours. It is metabolised by the hepatic cytochrome P450 enzyme system. However, unlike troglitazone, studies have provided no evidence to suggest that pioglitazone administration leads to inhibition or induction of any of the P450 isoenzymes involved in drug metabolism. Therefore pioglitazone may have lower potential for drug interaction. The half-life is about 9 hours but two active metabolites mainly contribute to the extended glucose-lowering effects. It is administered once daily without regard to meals. The pharmacokinetics are not significantly altered in Type 2 diabetes, renal or hepatic insufficiency or in the elderly. In placebo-controlled clinical studies, pioglitazone effectively improved glycaemic control in people with Type 2 diabetes as evidenced by significant reductions in HbA1c and fasting plasma glucose, whether used as monotherapy or in combination with sulphonylurea, metformin or insulin. Pioglitazone also had a beneficial effect on the abnormal lipid profile seen in Type 2 diabetes. Compared with placebo, pioglitazone significantly reduced serum triglycerides and increased high density lipoprotein cholesterol with no change in low density lipoprotein or total cholesterol.

Diabetes Mellitus, Type 2↗
PubMed2001

Safety profile of pioglitazone.

The safety profile of pioglitazone has been evaluated in trials including over 5,400 subjects, of whom over 3,500 received active treatment resulting in over 2,500 patient-years of exposure. Since its launch, over 1.4 million patients have been prescribed pioglitazone. This paper will examine the clinical trial tolerability and safety data available for pioglitazone. Safety was evaluated both as monotherapy and in combination with other antihyperglycaemic drugs. All studies had a placebo-controlled, double-blind, randomised, parallel-group, multi-centre design, in which pioglitazone was administered once daily over a period of 16-24 weeks. Most trials also had a long-term open label extension. In these trials, adverse events were recorded, as were details of laboratory blood values, urine analysis, vital signs and electrocardiograms. In addition, specific studies were conducted to examine any effects of pioglitazone on cardiac structure and function, and body composition. This paper will also briefly review data available from post-marketing surveillance.

Cardiovascular System↗
PubMed2000

Impaired glucose tolerance (IGT) is not associated with disturbed homocysteine metabolism.

Elevated plasma total homocysteine (tHcy) has been suggested to be an additional risk factor for cardiovascular disease in subjects with impaired glucose tolerance (IGT) and Type 2 diabetes (T2D). In order to investigate whether an insulin resistant/chronic hyperinsulinemic situation in male diabetic and prediabetic subjects directly influences the tHcy metabolism, fasting tHcy and post-methionine load tHcy plasma levels (PML-tHcy) were determined in 15 men with IGT, 13 men with newly diagnosed T2D, and 16 normoglycemic controls (NGT). Fasting tHcy (IGT, 13.1 +/- 4.6; T2D, 12.8 +/- 4.0; NGT, 10.7 +/- 4.4 micromol/L) and PML-tHcy (IGT, 46.5 +/-17.39; T2D, 41.1 +/- 6.8; NGT, 38.0 +/- 9.7 micromol/L) showed no differences between the groups. Fasting tHcy and PML-tHcy correlated with fasting proinsulin (r = 0.395, p < 0.05; r = 0.386, p< 0.05) and creatinine (r = 0.489, p < 0.01; r = 0.339, p < 0.05), resp. Multiple regression analysis showed only a relationship between fasting tHcy and creatinine. No relationships have been found between fasting tHcy and PML-tHcy, resp., and indicators of an insulin resistant state, e.g., insulin and proinsulin, as well as serum cobalamin and folate concentrations. In conclusion, our data suggest that the degree of glucose intolerance has no direct impact on the metabolism of homocysteine. However, tHcy levels tend to be elevated with the development of nephropathy, indicating an association between tHcy and renal function in these subjects.

Blood Glucose↗
PubMed2000

Post-challenge hyperglycaemia relates more strongly than fasting hyperglycaemia with carotid intima-media thickness: the RIAD Study. Risk Factors in Impaired Glucose Tolerance for Atherosclerosis and Diabetes.

AIMS: Only scarce information exists on the distribution and atherosclerosis risk in different types of hyperglycaemia at diabetes detection. This study aimed to analyse the occurrence of isolated fasting (IFH), isolated post-challenge (IPH) and combined hyperglycaemia (FH/PH) among subjects detected to have diabetes and the association of these types of hyperglycaemia with cardiovascular risk factors and carotid intima-media thickness (IMT). METHODS: A total of 785 middle-aged subjects of the Risk Factors in Impaired Glucose Tolerance (IGT) for Atherosclerosis and Diabetes (RIAD) study underwent a 75-g oral glucose tolerance test and examination of various atherosclerosis risk factors. IMT was measured by B-mode ultrasound. RESULTS: One hundred and nineteen (15.2%) asymptomatic diabetic subjects were detected: of these, 35.3% with IFH, 26% with IPH and 38.7% with FH/PH. The level of risk factors was higher in diabetic vs. non-diabetic subjects. HbA1c and cardiovascular risk factors were in the same range for IFH and IPH except for active plasminogen activator inhibitor (PAI)-1 which was significantly higher in IFH. A higher risk burden was found in the FH/PH group vs. both IFH and IPH. IMT was as follows: non-diabetic subjects 0.85 +/- 0.18 mm, IFH 0.91 +/- 0.20 mm, IPH 0.94 +/- 0.18 mm, FH/PH 0.98 +/- 0.17 mm (P < 0.05 vs. non-diabetes). 2 h post-challenge glucose (2hPG) correlated more closely (r = 0.23, P < 0.001) to IMT than fasting plasma glucose (FPG) (r = 0.14, P = 0.004). The importance of 2hPG was confirmed by the direct comparison of FPG and 2hPG in a three dimensional analysis. A significant increase of IMT was only observed in the subgroups with abnormal post-challenge hyperglycaemia for both combinations with normal FPG and IFG. FPG category did not significantly add to IMT in either group of post-challenge hyperglycaemia. Regression analysis in the whole sample revealed 2hPG but not FPG as a significant determinant of IMT. Further significant risk factors were age, male sex, total cholesterol, HDL-cholesterol and hypertension. CONCLUSIONS: The RIAD study population at high risk for Type 2 diabetes mellitus, post-challenge hyperglycaemia was found to relate more strongly than fasting hyperglycaemia with carotid IMT.

Adult↗
PubMed2000

Prevalence and atherosclerosis risk in different types of non-diabetic hyperglycemia. Is mild hyperglycemia an underestimated evil?

So far little is known about the importance of different types of non-diabetic hyperglycemia for the development of macrovascular disease. The aim of this work was to examine the intima-media thickness (IMT) of the common carotid artery (CCA), a well-accepted marker of atherosclerosis, as well as various risk factors for atherosclerosis in non-diabetic subjects with isolated fasting (IFH; n=67), isolated postchallenge (IPH; n=82) and combined hyperglycemia (CH; n=88) in comparison to normoglycemic (NG; n=265) controls. Subjects were participants of the RIAD study (Risk Factors in IGT for Atherosclerosis and Diabetes). IMT in the IPH (IMTmean: 0.89+/-0.02 mm; IMTmax: 1.01+/-0.02 mm; mean+/-SEM) and CH group (IMTmean: 0.91+/-0.02 mm; IMTmax: 1.03+/-0.02 mm) was significantly increased vs. the NG (IMTmean: 0.82+/-0.01 mm; IMTmax: 0.94+/-0.01 mm) and IFH group (IMTmean: 0.81+/-0.02 mm; IMTmax: 0.90+/-0.03 mm). IMT of the IFH group was similar to the normoglycemic controls. Subjects in the first and second tertile for postchallenge plasma glucose have similar carotid IMT irrespective of the level of fasting plasma glucose. The individuals of the third tertile for 2 h plasma glucose, whether in the first, second or third tertile of fasting plasma glucose, showed the same carotid IMT, which was significantly higher than all other groups, except for the one with lowest tertile for fasting and postchallenge plasma glucose. Except for total cholesterol and von Willebrand factor the levels of all other risk parameters were significantly higher in the hyperglycemic groups in comparison to the normoglycemic controls. Among the hyperglycemic subjects the CH group was at the highest risk for atherosclerosis with significantly increased levels of plasma triglycerides, fibrinogen, PAI-1, albuminuria, HDL-triglycerides, free fatty acids, insulin and proinsulin, and significantly reduced HDL-cholesterol in comparison to the normoglycemic controls. In summary, postchallenge hyperglycemia within the non-diabetic range is associated with atherosclerosis, as measured by the increased intima-media thickness of the common carotid artery. Furthermore, cardiovascular risk factors are significantly raised in all types of non-diabetic hyperglycemia.

Albuminuria↗
PubMed2000

Metabolic diseases and their possible link to risk indicators of periodontitis.

BACKGROUND: During the last few years, risk assessment has become one of the main topics of periodontal research. Therefore, the aim of this study was to determine whether a predisposition to metabolic disorders such as diabetes mellitus (in the absence of diagnosed diabetic disease) or hyperlipidemia may be risk indicators for periodontitis. METHODS: One hundred patients ranging in age from 40 to 70 years were examined. The patients were classified as having impaired glucose tolerance (IGT) but no manifest diabetes (56 patients), hyperlipidemia (17 patients, HL), or normal metabolic status (27 control patients). Probing depth (PD), attachment level (AL), plaque index (PI), and gingival bleeding on probing (BOP) were recorded. Serum antibody titers (SAT) to A. actinomycetemcomitans (A.a.), P. intermedia (P.i.), and P. gingivalis (P.g.) were determined by enzyme-linked immunosorbent assay (ELISA). Pooled subgingival plaque samples were analyzed using indirect immunofluorescence to detect the same organisms. In addition, respiratory burst activity of peripheral polymorphonuclear leukocytes (PMN) was evaluated by chemiluminescence (CL). RESULTS: No significant differences were observed between the IGT group and normal controls in the following parameters: 1) percentage of sites exhibiting BOP; 2) mean PI; 3) mean PD and AL; 4) percentage of periodontal microorganisms; and 5) increased SAT. The IGT probands exhibited a significantly higher mean serum level of triglycerides, as well as higher formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated PMN chemiluminescence than the control group. Patients with hyperlipidemia (HL) showed a significantly higher number of sextants with increased PD (73.4%) than the control group (50.6%). Similar results were obtained when comparing the percentage of all sites with increased PD (HL = 16.7%, control 12.3%). The mean FMLP-stimulated CL in patients with hyperlipidemia was significantly higher than the control group. When looking at all patients, there was a small but statistically significant correlation between PD and lipid levels. In addition, a significant correlation was observed between lipid serum levels and the FMLP-stimulated chemiluminescence. CONCLUSIONS: These findings suggest that abnormal glucose tolerance, which is a predisposing factor for diabetes mellitus, does not appear to be a risk indicator for periodontal disease. On the other hand, impaired lipid metabolism does seem to be a risk indicator for periodontitis.

Adult↗
PubMed2000

Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level.

OBJECTIVE: To observe the relationship of fasting plasma glucose (FPG), postchallenge plasma glucose (PG) (30, 60, 90, and 120 min during an oral glucose tolerance test [OGTT], as well as maximal PG during an OGTT, postchallenge glucose spikes [PGS], and glucose under the OGTT curve), and HbA1c to intima-media thickness (IMT) as a marker of atherosclerosis. RESEARCH DESIGN AND METHODS: OGTT, ultrasound measurement of carotid IMT, and various atherosclerosis risk factors, such as family history of diabetes, obesity, and/or hyperlipoproteinemia, but without known diabetes, were analyzed in 582 individuals aged 40-70 years and at risk for type 2 diabetes. RESULTS: In univariate analysis, all examined glycemic parameters were significantly correlated to IMT. The 2-h postchallenge plasma glucose showed the strongest odds ratio (OR) of 1.88 (1.34-2.63) in relation to abnormal IMT. All PG variables, except for 30-min glucose in OGTT, showed a significant OR, whereas the OR for HbA1c and FPG was not significant. In logistic regression analysis, 2-h PG was identified as the strongest determinant of IMT from all glycemic parameters. The 2-h PG and PGS, but not FPG, were associated with a significant rise of IMT in tertiles of HbA1c. Glycemic parameters were strongly related to each other and to many atherosclerosis risk factors. In multivariate analysis including a variety of atherosclerosis risk factors, 2-h PG was a significant independent determinant of IMT. CONCLUSIONS: PG and PGS are more strongly associated with carotid IMT than FPG and HbA1c level and modify substantially the risk for atherosclerosis, estimated by HbA1c alone, in a cohort at risk for diabetes and in the early diabetes stage.

Adult↗
PubMed2000

Rapid and short-acting mealtime insulin secretion with nateglinide controls both prandial and mean glycemia.

OBJECTIVE: The objective of the study was to assess the efficacy and safety of four fixed doses of nateglinide compared with placebo in the treatment of patients with type 2 diabetes with focus on the prandial state. RESEARCH DESIGN AND METHODS: This randomized double-blind placebo-controlled multicenter study was conducted in 289 patients who received either nateglinide at doses of 30 mg (n = 51), 60 mg (n = 58), 120 mg (n = 63), or 180 mg (n = 57) or placebo (n = 60) before three main meals for 12 weeks. Levels of HbA1c, fasting plasma glucose (FPG), fructosamine, and plasma lipids were measured at predetermined intervals, and the effects of nateglinide on prandial glucose insulin, C-peptide, and triglyceride levels were measured after a liquid standard meal (Sustacal; Mead Johnson, Evansville, IN). Adverse events and hypoglycemic episodes were recorded. RESULTS: After a liquid meal challenge, nateglinide rapidly increased mealtime insulin levels within 30 min of drug intake and reduced mealtime glucose excursions without affecting triglyceride levels. At study end point, reduction of HbA1c levels was statistically significantly greater with nateglinide at doses of 60, 120, and 180 mg than placebo (-0.45, -0.62, and -0.64%, respectively; P<0.05). The mean level of FPG was significantly reduced versus placebo in the nateglinide 120-mg group only (-1.14 mmol/l P<0.01). Overall, nateglinide was well tolerated. CONCLUSIONS: This study demonstrated that nateglinide improves mealtime and mean glycemic control in a dose-dependent manner by restoring early insulin secretion phase. Nateglinide was well tolerated and is suitable for the treatment of patients with type 2 diabetes.

Adult↗