Resistance exercise training increases lower limb speed of strength generation during stair ascent and descent in people with diabetic peripheral neuropathy.

AIM: To examine the effects of a 16-week resistance exercise training intervention on the speed of ankle and knee strength generation during stair ascent and descent, in people with neuropathy. METHODS: A total of 43 people: nine with diabetic peripheral neuropathy, 13 with diabetes but no neuropathy and 21 healthy control subjects ascended and descended a custom-built staircase. The speed at which ankle and knee strength were generated, and muscle activation patterns of the ankle and knee extensor muscles were analysed before and after a 16-week intervention period. RESULTS: Ankle and knee strength generation during both stair ascent and descent were significantly higher after the intervention than before the intervention in the people with diabetes who undertook the resistance exercise intervention (P < 0.05). Although muscle activations were altered by the intervention, there were no observable patterns that underpinned the observed changes. CONCLUSIONS: The increased speed of ankle and knee strength generation observed after the intervention would be expected to improve stability during the crucial weight acceptance phase of stair ascent and descent, and ultimately contribute towards reducing the risk of falling. Improvements in muscle strength as a result of the resistance exercise training intervention are likely to be the most influential factor for increasing the speed of strength generation. It is recommended that these exercises could be incorporated into a multi-faceted exercise programme to improve safety in people with diabetes and neuropathy

Mind your step: the effects of mobile phone use on gaze behavior in stair climbing

Stair walking is a hazardous activity and a common cause of fatal and non-fatal falls. Previous studies have assessed the role of eye movements in stair walking by asking people to repeatedly go up and down stairs in quiet and controlled conditions, while the role of peripheral vision was examined by giving participants specific fixation instructions or working memory tasks. We here extend this research to stair walking in a natural environment with other people present on the stairs and a now common secondary task: Using one's mobile phone. Results show that using the mobile phone strongly draws one's attention away from the stairs, but that the distribution of gaze locations away from the phone is little influenced by using one's phone. Phone use also increased the time needed to walk the stairs, but handrail use remained low. These results indicate that limited foveal vision suffices for adequate stair walking in normal environments, but that mobile phone use has a strong influence on attention, which may pose problems when unexpected obstacles are encountered

Contributory Factors to Unsteadiness During Walking Up and Down Stairs in Patients With Diabetic Peripheral Neuropathy

OBJECTIVE Although patients with diabetic peripheral neuropathy (DPN) are more likely to fall than age-matched controls, the underlying causative factors are not yet fully understood. This study examines the effects of diabetes and neuropathy on strength generation and muscle activation patterns during walking up and down stairs, with implications for fall risk. RESEARCH DESIGN AND METHODS Sixty-three participants (21 patients with DPN, 21 diabetic controls, and 21 healthy controls) were examined while walking up and down a custom-built staircase. The speed of strength generation at the ankle and knee and muscle activation patterns of the ankle and knee extensor muscles were analyzed. RESULTS Patients with neuropathy displayed significantly slower ankle and knee strength generation than healthy controls during stair ascent and descent (P < 0.05). During ascent, the ankle and knee extensor muscles were activated significantly later by patients with neuropathy and took longer to reach peak activation (P < 0.05). During descent, neuropathic patients activated the ankle extensors significantly earlier, and the ankle and knee extensors took significantly longer to reach peak activation (P < 0.05). CONCLUSIONS Patients with DPN are slower at generating strength at the ankle and knee than control participants during walking up and down stairs. These changes, which are likely caused by altered activations of the extensor muscles, increase the likelihood of instability and may be important contributory factors for the increased risk of falling. Resistance exercise training may be a potential clinical intervention for improving these aspects and thereby potentially reducing fall risk

Leptin Decreases Gluconeogenesis and Gluconeogenic Substrate Availability in Patients With Lipodystrophy

Context: The effects of leptin, an adipocyte-derived hormone that signals overall energy sufficiency, can only be studied in leptin-deficient conditions. In patients with lipodystrophy, a rare disease and unique model of leptin deficiency, treatment with recombinant leptin (metreleptin) improves glycemia and decreases energy expenditure. We hypothesized that these improvements might be mediated by reduced gluconeogenesis (GNG), an energy-requiring process. Objective: To determine the effects of metreleptin on GNG and GNG substrates. Methods: This was a single-arm prospective study of metreleptin administration in 15 patients with lipodystrophy, 9 of whom had data on GNG (NIH, 2013-2018). We analyzed total GNG, insulin-mediated suppression of GNG, glycerol, palmitate, alanine, lactate, peripheral and hepatic insulin sensitivity, and markers of glycemia (eg, HbA1c, glucose, fasting insulin). Results: Metreleptin administration decreased basal GNG, increased insulin-mediated suppression of GNG, and improved insulin sensitivity and markers of glycemic control. Metreleptin reduced carbon sources for GNG, including plasma alanine and lactate, and rate of appearance (Ra) of glycerol, and decreased Ra of palmitate, a driver of GNG. Glycerol and palmitate Ra correlated with GNG prior to but not during metreleptin administration. Alanine strongly correlated with GNG both before and during metreleptin administration. Conclusions: Metreleptin treatment in patients with lipodystrophy reduced GNG likely through decreased availability of carbon sources for gluconeogenesis, such as alanine, lactate, and glycerol. Associations between alanine and GNG persisted after metreleptin treatment while correlations with glycerol and palmitate Ra did not persist, suggesting reduced importance of lipolysis as a driver of GNG in the leptin-replete state. Trial registration: ClinicalTrials.gov NCT01778556

Meal-Related Changes in Apolipoprotein Particles After Treatment With an Antisense Oligonucleotide to Apolipoprotein CIII

Abstract Background: Lipodystrophy (LD) is defined by partial or complete absence of adipose tissue causing metabolic complications such as high triglycerides (TG). Apolipoprotein CIII (ApoCIII) contributes to high TG by inhibiting lipoprotein lipase (LPL). Measurement of lipoprotein particles using NMR can offer insights into lipid metabolism. Hypothesis: We hypothesized that during a mixed meal test (MMT), clearance of TG-rich lipoprotein particles (TRLP) measured by NMR would increase in LD patients given an antisense oligonucleotide (ASO) to lower ApoCIII. Experimental Design: Five adults with partial LD underwent an MMT (with 18g fat) at week 0 and after 16 weeks (wk) of the ApoCIII ASO. Blood samples were obtained at 0, 30, 60, 120, 180, 240, 300, and 360 minutes (min) and assessed using NMR with the LP4 deconvolution algorithm, which separates TRLPs into 5 size categories: very large (VL), large (L), medium (M), small (S), and very small (VS), all expressed as nmol/L. Major Results: At wk 0, patients had high fasting TG (median 523 mg/dL, IQR 335–1060 mg/dL, normal &amp;lt;150), which decreased after 16wk of ASO[BR([1] (196 mg/dL) Mean TRLP over the 360 min of the MMT was lower after ASO (181.6±14.1 at wk 0, 80.4±2.2 at wk 16). At wk 0, mean L_TRLP during the MMT was 26.8 ± 6.9 and decreased to 9.3±1.3 at wk 16. At wk 0, L_TRLP rose during the MMT to a peak at 180min; at wk 16 there was no rise in L_TRLP during the MMT. Mean S_TRLP during the MMT increased from wk 0 (5.4±3.9) to wk 16 (13.4±10.4). At wk 0, S_TRLP increased minimally during the MMT from 5.2±11.7 at 0 min to 10.9±15.2 at 360 min. At wk 16 there was a more notable rise in S_TRLP in the last 3 hrs of the MMT, from 12.2±15.1 at 0 min to 37.6±28.6 at 360 min. Interpretation of Results and Conclusions: As expected, an ApoCIII ASO lowered fasting and postprandial TG and TRLP. There was minimal rise or fall in any subclass of TRLP during the MMT, either before or after ASO, likely due to the small fat load, which was chosen due to concern for triggering pancreatitis in this at-risk group. The greater post-prandial fluctuation of L_TRLP prior to ASO may represent appearance and disappearance of chylomicron remnants; at wk 16 this was not seen, perhaps due to more rapid clearance of chylomicron remnants by LPL. The larger increase in S_TRLP at the end of the MMT at wk 16 may reflect more rapid lipolysis of L_TRLP by LPL during ASO treatment, thus generating S_TRLP. Next steps include measuring apoB48 and apoB100 during the MMT to distinguish VLDL from chylomicrons, accruing a larger sample size, and collecting MMT data in healthy controls.</jats:p