[Diabetes mellitus and periodontitis. Bidirectional relationship and clinical implications. A consensus document]. / Diabetes mellitus und Parodontitis. Wechselbeziehung und klinische Implikationen. Ein Konsensuspapier.

Diabetes and periodontitis are chronic diseases with an increasing prevalence in the German population. There is a bi-directional relationship between both diseases. Diabetes promotes the occurrence, the progression and the severity of periodontitis. Periodontitis complicates the glycemic control of diabetes, increases the risk of diabetes-associated complications and possibly even of its onset. In view of the existing evidence, that is still not sufficiently communicated within the medical community, an expert panel consisting of four diabetologists and four periodontists has addressed the following questions: What is the effect of diabetes mellitus on periodontitis and on periodontal therapy? What is the effect of periodontitis on diabetes mellitus? What are the practical consequences, that result for interdisciplinary treatment strategies? The treatment of periodontal infections should become an integral part of the management of diabetes, whereas glycemic control is a prerequisite for successful periodontal therapy.

[Challenge in diabetes therapy: effects of glitazones beyond blood glucose control]. / Herausforderung Diabetestherapie: Effekte der Glitazone jenseits der Blutzuckerkontrolle.

Not just since the results of ACCORD, ADVANCE and VADT were published, it is clear that lowering blood glucose alone does not reduce the cardiovascular risk of patients with type 2 diabetes. In fact, many studies also indicate that some treatment strategies may even have adverse effects. To treat type 2 diabetes appropriately, the co-morbidities such as diabetic dyslipidaemia, hypertension or nephropathy must also be taken into account. Thiazolidinediones reduce insulin resistance thus allowing to direct the treatment of type 2 diabetes towards its pathophysiologic origin. Due to their mechanism of action, thiazolidinediones not only lower blood glucose but have also beneficial effects on inflammatory and atherogenic parameters, blood pressure and microalbuminuria. Furthermore pioglitazone improves dyslipidaemia and reduces mortality, myocardial infarction and stroke in high risk patients. Effects of rosiglitazone on the cardiovascular risk are yet unclear. Numerous studies document the efficacy and safety of thiazolidinediones and provide a basis for an evidence-based therapeutic approach beyond blood glucose control.

Long-term treatment experience in a subject with Dunnigan-type familial partial lipodystrophy: efficacy of rosiglitazone.

Dunnigan-type familial partial lipodystrophy (FPLD) is caused by mutations in LMNA, the gene that encodes nuclear lamins A and C. FPLD is characterized by peripheral fat loss, excess central adiposity, insulin resistance, and hyperlipidaemia, which are difficult to treat. We present our 2 years' experience of treatment with rosiglitazone in a subject with FPLD. Insulin requirement decreased significantly from 240 IU/day to 76 IU/day (range 20-240 IU/day) and serum triglyceride concentration was lowered from 13.7 +/- 14.4 mmol/l to 4.5 +/- 4.3 mmol/l and remained stable. Mean HbA(1c) prior to rosiglitazone therapy was 9.4 +/- 1.32% and decreased to 7.4 +/- 0.6% during therapy with rosiglitazone. This case demonstrates the benefits of PPARgamma-agonists on glycaemic control and dyslipidaemia in a patient with FPLD. This in turn implies that PPARgamma may play a pathophysiological role in FPLD.

Initiating oral glucose-lowering therapy with metformin in type 2 diabetic patients: an evidence-based strategy to reduce the burden of late-developing diabetes complications.

A major aim of glucose-lowering therapy in people with diabetes is to delay or prevent the late-developing complications of diabetes that threaten the quality and duration of life. While intensive interventions to control hyperglycaemia may impair well-being to some extent, the balance of quality of life is usually highly positive. Diet and exercise therapy remains the cornerstone of management, and should usually be given a trial alone first. However, the magnitude and duration of benefit from this intervention is insufficient for most people. More frequent, early, use of metformin is an evidence-based strategy for reducing the risk of adverse outcomes of diabetes in people with type 2 diabetes with sub-optimal glucose control on lifestyle measures alone. This has been recognised in recent evidenced-based guidelines from the UK National Institute for Clinical Excellence and from Diabetes UK, which now support the use of metformin as initial pharmacological therapy for all people without contraindications to the drug. Other national and local guideline committees should consider updating their recommendations on diabetes management in line with these findings.

[Delaying and preventing type 2 diabetes mellitus]. / Typ 2 Diabetes: Verzögerte Manifestation und Prävention.

In recent years, numerous studies have been concerned with delaying the manifestation of, or preventing, type 2 diabetes. In this connection, changes in lifestyle (weight reduction, physical activity) have proved to be particularly successful. Good results have, however, also been obtained with oral antidiabetics and/or ramipril. A striking finding has been the positive impact of acarbose on parameters of macroangiopathy.

Metformin, the rebirth of a biguanide: mechanism of action and place in the prevention and treatment of insulin resistance.

Metformin should be regarded as a first-choice therapy of type 2 diabetes, showing an especially good efficacy in obese patients with hyperinsulinaemia. Reduction of blood glucose without hyperinsulinaemia and without hypoglycaemia, favourable influence on the lipid profile and inhibition of coagulation factors lead to an antidiabetic and antiatherogenic effect. Not only are these characteristics relevant to judging the value of the drug, but also the strict observation of contraindications is needed to avoid the dangerous complication of lactic acidosis.

Alpha-lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials.

Diabetic neuropathy represents a major health problem, as it is responsible for substantial morbidity, increased mortality, and impaired quality of life. Near-normoglycaemia is now generally accepted as the primary approach to prevention of diabetic neuropathy, but is not achievable in a considerable number of patients. In the past two decades several medical treatments that exert their effects despite hyperglycaemia have been derived from the experimental pathogenetic concepts of diabetic neuropathy. Such compounds have been designed to improve or slow the progression of the neuropathic process and are being evaluated in clinical trials, but with the exception of alpha-lipoic acid (thioctic acid) which is available in Germany, none of these drugs is currently available in clinical practice. Here we review the current evidence from the clinical trials that assessed the therapeutic efficacy and safety of thioctic acid in diabetic polyneuropathy. Thus far, 15 clinical trials have been completed using different study designs, durations of treatment, doses, sample sizes, and patient populations. Within this variety of clinical trials, those with beneficial effects of thioctic acid on either neuropathic symptoms and deficits due to polyneuropathy or reduced heart rate variability resulting from cardiac autonomic neuropathy used doses of at least 600 mg per day. The following conclusions can be drawn from the recent controlled clinical trials. 1.) Short-term treatment for 3 weeks using 600 mg of thioctic acid i.v. per day appears to reduce the chief symptoms of diabetic polyneuropathy. A 3-week pilot study of 1800 mg per day given orally indicates that the therapeutic effect may be independent of the route of administration, but this needs to be confirmed in a larger sample size. 2.) The effect on symptoms is accompanied by an improvement of neuropathic deficits. 3.) Oral treatment for 4-7 months tends to reduce neuropathic deficits and improves cardiac autonomic neuropathy. 4.) Preliminary data over 2 years indicate possible long-term improvement in motor and sensory nerve conduction in the lower limbs. 5.) Clinical and postmarketing surveillance studies have revealed a highly favourable safety profile of the drug. Based on these findings, a pivotal long-term multicenter trial of oral treatment with thioctic acid (NATHAN I Study) is being conducted in North America and Europe aimed at slowing the progression of diabetic polyneuropathy using a clinically meaningful and reliable primary outcome measure that combines clinical and neurophysiological assessment.

Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy.

Short-term trials with the antioxidant thioctic acid (TA) appear to improve neuropathic symptoms in diabetic patients, but the long-term response remains to be established. Therefore, Type 1 and Type 2 diabetic patients with symptomatic polyneuropathy were randomly assigned to three treatment regimens: (1) 2 x 600(mg of TA (TA 1200), (2) 600)mg of TA plus placebo (PLA) (TA 600) or (3) placebo and placebo (PLA). A trometamol salt solution of TA of 1200 or 600 mg or PLA was intravenously administered once daily for five consecutive days before enrolling the patients in the oral treatment phase. The study was prospective, PLA-controlled, randomized, double-blind and conducted for two years. Severity of diabetic neuropathy was assessed by the Neuropathy Disability Score (NDS) and electrophysiological attributes of the sural (sensory nerve conduction velocity (SNCV), sensory nerve action potential (SNAP)) and the tibial (motor nerve conduction velocity (MNCV), motor nerve distal latency (MNDL)) nerve. Statistical analysis was performed after independent reviewers excluded all patients with highly variable data allowing a final analysis of 65 patients (TA 1200: n = 18, TA 600: n = 27; PLA: n = 20). At baseline no significant differences were noted between the groups regarding the demographic variables and peripheral nerve function parameters for these 65 patients. Statistically significant changes after 24 months between TA and PLA were observed (mean +/- SD) for sural SNCV: +3.8 +/- 4.2 m/s in TA 1200, +3.0+/-3.0m/s in TA 600, -0.1+/-4.8m/s in PLA (p < 0.05 for TA 1200 and TA 600 vs. PLA); sural SNAP: +0.6+/-2.5 microV in TA 1200, +0.3+/-1.4 microV in TA 600, -0.7 +/- 1.5 microV in PLA (p = 0.076 for TA 1200 vs. PLA and p < 0.05 for TA 600 vs. PLA), and in tibial MNCV: +/- 1.2 +/- 3.8 m/s in TA 1200, -0.3 +/- 5.2 m/s in TA 600, 1.5 +/- 2.9 m/s in PLA (p < 0.05 for TA 1200 vs. PLA). No significant differences between the groups after 24 months were noted regarding the tibial MNDL and the NDS. We conclude that in a subgroup of patients after exclusion of patients with excessive test variability throughout the trial, TA appeared to have a beneficial effect on several attributes of nerve conduction.

Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy.

AIMS: To evaluate the efficacy and safety of short-term oral treatment with the antioxidant thioctic acid (TA) on neuropathic symptoms and deficits in patients with Type 2 diabetes mellitus with symptomatic polyneuropathy. METHODS: Patients were randomly assigned to oral treatment with 600 mg of TA t.i.d. (n = 12) or placebo (n = 12) for 3 weeks. Neuropathic symptoms (pain, burning, paraesthesiae, and numbness) in the feet were scored at weekly intervals and summarized as a Total Symptom Score (TSS). The Hamburg Pain Adjective List (HPAL) and the Neuropathy Disability Score (NDS) were assessed at baseline and day 19. RESULTS: At baseline the TSS, HPAL, and NDS were not significantly different between the groups. The TSS in the foot decreased from baseline to day 19 by -3.75 +/- 1.88 points (-47%) in the TA group and by -1.94 +/- 1.50 points (-24%) in the placebo group (P= 0.021 for TA vs. placebo). The total HPAL score decreased from baseline to day 19 by -2.20 +/- 1.65 points (-60%) in the TA group and by -0.96 +/- 1.32 points (-29%) in the placebo group (P = 0.072 for TA vs. placebo). The NDS decreased by -0.27 +/- 0.47 points in the TA group, whereas it slightly increased by +0.18 +/- 0.4 points in the placebo group (P = 0.025 for TA vs. placebo). No differences between the groups were noted regarding the rates of adverse events. CONCLUSIONS: These preliminary findings indicate that oral treatment with 600 mg of TA t.i.d. for 3 weeks may improve symptoms and deficits resulting from polyneuropathy in Type 2 diabetic patients, without causing significant adverse reactions.

[Current insulin therapy--avoidable errors]. / Aktuelle Insulintherapie--vermeidbare Fehler.

Since its introduction in 1922, insulin therapy has undergone constant development and improvement. Today, the spectrum ranges from short- to very long-acting depot insulins, and "human" insulins. Further stages in the development of this form of treatment have been intensive insulin therapy, self-measurement of blood sugar, development of insulin-analogues and the use of insulin pumps or pens, to mention but a few. As a reflection of how widespread insulin therapy in the doctor's office has become and what the frontiers are, the present paper lists a range of 15 errors, and discusses how they can be avoided and insulin treatment thus further optimized.

New aspects of insulin resistance in hypertension.

Primary hypertension is a frequent polygenic disease with strong genetic and environmental components. During the last decade, evidence has been increasing that insulin resistance as a marker of increased risk for Type 2 diabetes and cardiovascular atherosclerotic disease is present not only in individuals with obesity, Type 2 diabetes and impaired glucose tolerance, but also in the majority of the hypertensive population. Insulin resistance describes a tissue- and pathway-specific defect of glucose metabolism present in the so called 'metabolic syndrome'. Hyperinsulinaemia compensates for insulin resistance, leading to a cluster of undesirable processes predisposing to diabetes, atheroma and, directly or indirectly, hypertension. Candidate mechanisms whereby this metabolic syndrome might lead to hypertension include renal sodium retention, vascular hyperresponsiveness, arteriolar smooth muscle cell proliferation, altered cellular electrolyte transport and composition, stimulation of sympatho-adrenergic activity and growth promoting effects. Insulin per se does not appear to be the cause of elevated blood pressure as frequently seen in insulin-resistant states, but it may act with other factors to promote hypertension and atherosclerotic cardiovascular disease.