Ih contributes to increased motoneuron excitability in restless legs syndrome.

KEY POINTS: Restless legs patients complain about sensory and motor symptoms leading to sleep disturbances. Symptoms include painful sensations, an urge to move and involuntary leg movements. The responsible mechanisms of restless legs syndrome are still not known, although current studies indicate an increased neuronal network excitability. Reflex studies indicate the involvement of spinal structures. Peripheral mechanisms have not been investigated so far. In the present study, we provide evidence of increased hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated inward rectification in motor axons. The excitability of sensory axons was not changed. We conclude that, in restless legs syndrome, an increased HCN current in motoneurons may play a pathophysiological role, such that these channels could represent a valuable target for pharmaceutical intervention. ABSTRACT: Restless legs syndrome is a sensorimotor network disorder. So far, the responsible pathophysiological mechanisms are poorly understood. In the present study, we provide evidence that the excitability of peripheral motoneurons contributes to the pathophysiology of restless legs syndrome. In vivo excitability studies on motor and sensory axons of the median nerve were performed on patients with idiopathic restless legs syndrome (iRLS) who were not currently on treatment. The iRLS patients had greater accommodation in motor but not sensory axons to long-lasting hyperpolarization compared to age-matched healthy subjects, indicating greater inward rectification in iRLS. The most reasonable explanation is that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels open at less hyperpolarized membrane potentials, a view supported by mathematical modelling. The half-activation potential for HCN channels (Bq) was the single best parameter that accounted for the difference between normal controls and iRLS data. A 6 mV depolarization of Bq reduced the discrepancy between the normal control model and the iRLS data by 92.1%. Taken together, our results suggest an increase in the excitability of motor units in iRLS that could enhance the likelihood of leg movements. The abnormal axonal properties are consistent with other findings indicating that the peripheral system is part of the network involved in iRLS.

Long-term Remission of Type 2 Diabetes and Patient Survival After Biliopancreatic Diversion with Duodenal Switch.

PURPOSE: This study investigates the long-term effects of biliopancreatic diversion with duodenal switch (BPD-DS) on patients with advanced type 2 diabetes mellitus (T2DM) while paying special attention to preoperative diabetes severity. MATERIALS AND METHODS: A retrospective analysis was conducted using prospective and current data on patients who underwent an open BPD-DS 6-12 years ago. Patients were stratified according to preoperative diabetes severity into 4 groups (group 1: oral antidiabetic drugs only; group 2: insulin < 5 years; group 3: insulin 5-10 years; group 4: insulin > 10 years). The primary endpoint was T2DM remission rate 6-12 years after BPD-DS as a function of preoperative diabetes severity. RESULTS: Ninety-one patients with advanced T2DM were included. Sixty-two patients were available for follow-up (rate of 77%). Follow-up was performed (mean ± SD) 8.9 ± 1.3 years after surgery. Glycated hemoglobin (HbA1c) levels were 9.4 ± 2.0% before surgery and decreased to 5.1 ± 0.8% after 1 year and 5.4 ± 1.0% after 6-12 years. Insulin discontinuation rate after surgery as well as the rate of long-term remission decreased steadily from groups 1 to 4, while long-term mortality increased. T2DM remission rates were 93%, 88%, 45%, and 40% in groups 1, 2, 3, and 4, respectively. Late relapse of T2DM occurred in 3 patients (5%). CONCLUSIONS: BPD-DS causes a rapid and long-lasting normalization of glycemic metabolism in patients with advanced T2DM. T2DM remission rate after 6-12 years varies significantly (from 40% to more than 90%) and is highly dependent on preoperative diabetes severity.

Biliopancreatic diversion with duodenal switch in patients with type 2 diabetes mellitus: is the chance of complete remission dependent on therapy and duration of insulin treatment?

BACKGROUND: Rapid resolution of type 2 diabetes mellitus (T2DM) is a common feature after intestinal bypass surgery bypassing the duodenum and parts of the jejunum. However, the parameters determining the individual chance of remission are imprecisely defined. METHODS: Biliopancreatic diversion with duodenal switch and sleeve gastrectomy (BPD-DS) was performed in n = 86 patients with T2DM (mean age 50 years, range 26-68, 51 females; BMI 47 kg/m(2), range 26-71). The patients were retrospectively divided into 4 groups according to the treatment modality and the duration of insulin treatment preoperatively: n = 18 patients were treated with oral antidiabetic drugs only (group 1); n = 32, n = 24, and n = 12 patients were treated with insulin for less than 5 years, for 5-10 years, and for more than 10 years (groups 2, 3, and 4), respectively. RESULTS: At discharge from hospital, all patients of groups 1 and 2 were free of insulin usage, 30% and 75% of the patients of groups 3 and 4 used up to 48 units of insulin per day (mean 24, n = 16). After 1 year, only 4 patients of group 4 permanently required small amounts of insulin (mean 17 units per day) to keep blood glucose below 200 mg/dl. These 4 patients had been using insulin preoperatively for 13, 15, 22, and 25 years. In 3 of these 4 patients, fasting C-peptide was measured and found to be low (<1.2 ng/ml). The rate of complete remission of diabetes for the whole study population was 91%. CONCLUSION: BPD-DS reliably causes rapid and complete remission of T2DM in all patients on oral antidiabetic drugs and in patients with insulin treatment for less than 5 years. In patients with insulin treatment longer than 5 or 10 years, complete remission rates decline to 88 and 66%, respectively. A low C-peptide preoperatively might be a specific adverse prognostic parameter for the chance of diabetes remission.