Plasma concentrations of lipoproteins and risk of lower-limb peripheral artery disease in people with type 2 diabetes: the SURDIAGENE study.

AIMS/HYPOTHESIS: The lipid profile has not been fully investigated in individuals with peripheral artery disease (PAD). We aimed to evaluate the relationship between plasma concentrations of lipoproteins and the prevalence of lower-limb PAD at baseline and its incidence during follow-up in people with type 2 diabetes. METHODS: Plasma concentrations of total cholesterol, HDL-cholesterol, triacylglycerol and apolipoprotein (Apo) A-I, ApoA-II, ApoB-100 and Apo(a) were measured at baseline using colorimetric or MS methods in the SURDIAGENE cohort. Total cholesterol/HDL-cholesterol ratio, non-HDL-cholesterol and LDL-cholesterol were estimated using computation formulas. Logistic and Cox proportional hazard regression models were fitted to estimate OR or HR, with related 95% CI, for baseline prevalence or incidence of major PAD (lower-limb amputation or requirement of revascularisation) during follow-up by increasing lipoprotein tertiles, after adjustment for key confounders. RESULTS: Among 1468 participants (women 42%, mean ± SD age 65 ± 11 years, duration of diabetes 14 ± 10 years at baseline), 129 (8.8%) had a baseline history of major PAD. Major PAD was less prevalent at baseline in the highest (vs lowest) tertile of HDL-cholesterol (OR 0.42 [95% CI 0.26, 0.71], p = 0.001) and ApoA-I (OR 0.39 [95% CI 0.23, 0.67], p = 0.0007), and more frequent in the highest tertile of total cholesterol/HDL-cholesterol ratio (OR 1.95 [95% CI 1.18, 3.24], p = 0.01). Among 1339 participants without a history of PAD at baseline, incident PAD occurred in 97 (7.2%) during a median (25th-75th percentile) duration of follow-up of 7.1 (4.4-10.7) years, corresponding to 9685 person-years and an incidence rate of 9.8 (95% CI 8.0, 12.0) per 1000 person-years. The risk of incident PAD was lower in the top (vs bottom) tertile of HDL-cholesterol (HR 0.54 [95% CI 0.30, 0.95], p = 0.03) or ApoA-I (HR 0.50 [95% CI 0.28, 0.86], p = 0.01) and higher in the top tertile of total cholesterol/HDL-cholesterol ratio (HR 2.81 [95% CI 1.61, 5.04], p = 0.0002) and non-HDL-cholesterol (HR 1.80 [95% CI 1.06, 3.12], p = 0.03). CONCLUSIONS/INTERPRETATION: We reported independent associations between HDL-cholesterol, ApoA-I, total cholesterol/HDL-cholesterol ratio or non-HDL-cholesterol and the prevalence or the incidence of major PAD in people with type 2 diabetes. Our findings provide a picture of lipoprotein profile in people with type 2 diabetes. Graphical abstract.

Plantar flexor muscle-tendon unit length and stiffness do not influence neuromuscular fatigue in boys and men.

PURPOSE: The twofold purpose of this study was (1) to compare differences in development and etiology of neuromuscular fatigue at different plantar flexor (PF) muscle-tendon unit (MTU) lengths between boys and men, and (2) to examine the relationship between musculotendinous stiffness and peripheral fatigue. METHODS: Nineteen pre-pubertal boys and 23 men performed three intermittent fatigue protocols at different PF MTU lengths (short: S, neutral: N and long: L), consisting of repeating maximal voluntary isometric contractions (MVIC) until the torque reached 60% of the initial value of MVIC. The etiology of the neuromuscular fatigue and the gastrocnemius medialis aponeuroses and tendon stiffness (KGM) were investigated using non-invasive methods. RESULT: The number of repetitions did not differ between men and boys, regardless of the PF MTU length (S: 16.5 ± 5.4 and 17.6 ± 5.8; N: 15.8 ± 4.5 and 13.3 ± 3.6; L: 13.6 ± 4.8 and 12.6 ± 4.6, respectively). Boys displayed a lower decrement of potentiated twitch torque (Qtwpot; p < 0.001) and greater decrease of voluntary activation level than men (p < 0.001). Although boys showed lower KGM values than men at S, no significant correlation was found between KGM and Qtwpot. CONCLUSION: PF MTU length had no effect on differences in the development and etiology of neuromuscular fatigue between boys and men. Although both groups displayed similar development of fatigue, central mechanisms mainly accounted for fatigue in boys and peripheral mechanisms were mainly involved in men. Additionally, musculotendinous stiffness did not account for difference in peripheral fatigue between children and adults.

Characteristics of motor unit recruitment in boys and men at maximal and submaximal force levels.

The aim of this study was to compare voluntary activation (VA) and motor units (MU) recruitment patterns between boys and men at different contraction levels of the knee extensor muscles. We hypothesized that boys and men would display similar VA and MU recruitment patterns at low submaximal force levels, but that boys would display a lower utilization of their higher-threshold MU and a lower VA at near-maximal and maximal force levels than men. 11 prepubertal boys and 13 men were tested at the optimal knee angle. Next, VA was assessed using the twitch interpolation technique during maximal (MVC) and submaximal isometric voluntary contractions. Mean firing rate (MFR), recruitment threshold (RT) and motor unit action potential size (MUAPSIZE) were extracted to characterize neural strategies. No significant difference between groups was found for VA at every contraction level. Similarly, no significant difference was found for the MFR vs. RT relationship parameters between groups. For the vastus lateralis (VL) muscle, the MUAPSIZE vs. RT relationship differed between boys and men independent of the contraction level (p < 0.05). Boys also displayed a different MFR vs. MUAPSIZE relationship on the VL muscle independent of the contraction level (p < 0.05). To conclude, no difference between boys and men was found for VA regardless of the contraction level investigated. Differences in motor unit recruitment parameters between boys and men seem to be explained by different muscle dimensions between groups.

M-wave and H-reflex recruitment curves in boys and men.

The aim of the present study was to check whether the M-wave and H-reflex recruitment curves differ between prepubertal boys and men. Eleven boys (9-11 yr) and eleven men (18-35 yr) were magnetically stimulated at the tibial nerve in a prone position. M-wave and H-reflex maximal amplitudes (Hmax; Mmax ; Hmax /Mmax ), thresholds, regression slopes (Hslp ; Mslp ; Hslp /Mslp ) were extracted from M-wave and H-reflex recruitment curves and compared between the two age groups. Overall, no significant difference in M-wave and H-reflex recruitment curve parameters was found between the two populations. Nevertheless, the size of the M-wave associated with maximal H-reflex amplitude was lower in boys as compared to men when expressed relative to maximal M-wave amplitude (MHmax /Mmax : 0.18 ± 0.06 vs. 0.31 ± 0.13; p < .05). This result suggests that the development of peripheral nerve was completed in 9 to 11-year-old boys and did not affect the M-wave and H-reflex recruitment curves parameters. In neuromuscular function studies, it implies that Hmax /Mmax and Hslp /Mslp could be used indifferently to compare spinal motoneuron excitability between 9-11-year-old boys and men. Conversely, evoking H-reflexes at a given percentage of Mmax may bias the comparison between boys and men.

In Amateur Athletes With Type 1 Diabetes, a 9-Day Period of Cycling at Moderate-to-Vigorous Intensity Unexpectedly Increased the Time Spent in Hyperglycemia, Which Was Associated With Impairment in Heart Rate Variability.

OBJECTIVE: In type 1 diabetes, autonomic dysfunction may occur early as a decrease in heart rate variability (HRV). In populations without diabetes, the positive effects of exercise training on HRV are well-documented. However, exercise in individuals with type 1 diabetes, particularly if strenuous and prolonged, can lead to sharp glycemic variations, which can negatively impact HRV. This study explores the impact of a 9-day cycling tour on HRV in this population, with a focus on exercise-induced glycemic excursions. RESEARCH DESIGN AND METHODS: Twenty amateur athletes with uncomplicated type 1 diabetes cycled 1,500 km. HRV and glycemic variability were measured by heart rate and continuous glucose monitoring. Linear mixed models were used to test the effects of exercise on HRV, with concomitant glycemic excursions and subject characteristics considered as covariates. RESULTS: Nighttime HRV tended to decrease with the daily distance traveled. The more time the subjects spent in hyperglycemia, the lower the parasympathetic tone was. This result is striking given that hyperglycemic excursions progressively increased throughout the 9 days of the tour, and to a greater degree on the days a longer distance was traveled, while time spent in hypoglycemia surprisingly decreased. This phenomenon occurred despite no changes in insulin administration and a decrease in carbohydrate intake from snacks. CONCLUSIONS: In sports enthusiasts with type 1 diabetes, multiday prolonged exercise at moderate-to-vigorous intensity worsened hyperglycemia, with hyperglycemia negatively associated with parasympathetic cardiac tone. Considering the putative deleterious consequences on cardiac risks, future work should focus on understanding and managing exercise-induced hyperglycemia.

Children Exhibit a More Comparable Neuromuscular Fatigue Profile to Endurance Athletes Than Untrained Adults.

The present study compared neuromuscular fatigue profiles between children, untrained adults and adult endurance athletes during repeated maximal muscle contractions. Eighteen prepubertal boys, 19 untrained men and 13 endurance male athletes performed 5-s maximal voluntary isometric knee extensor contractions (MVICs) interspersed with 5-s recovery until MVIC reached 60% of its initial value. Single and doublet magnetic stimulations were delivered to the femoral nerve to quantify the time course of potentiated twitch amplitude (Ttw,pot), high-frequency torque (T100 Hz) and the low-to-high frequency torque ratio (T10 Hz/T100 Hz), i.e., indicators of peripheral fatigue. M-wave-normalized EMG amplitudes (EMG/M) and the maximal voluntary activation level (VA) were calculated to quantify central fatigue. Adults (15.9 ± 3.9 repetitions) performed fewer MVICs than children (40.4 ± 19.7) and endurance athletes (51.7 ± 19.6), however, no difference was observed between children and athletes (P = 0.13). Ttw,pot (∼52%, P < 0.001), T100 Hz (∼39%, P < 0.001) and T10 Hz/T100 Hz (∼23%, P < 0.001) decreased only in adults. Similar decrements in vastus medialis and vastus lateralis EMG/M were observed in children and endurance athletes (range: 40-50%), and these were greater than in adults (∼15%). Whilst VA decreased more in children (-38.4 ± 22.5%, P < 0.001) than endurance athletes (-20.3 ± 10.1%, P < 0.001), it did not change in adults. Thus, children fatigued more slowly than adults and as much as endurance athletes. They developed less peripheral and more central fatigue than adults and, although central fatigue appeared somewhat higher in children than endurance athletes, both children and endurance athletes experienced greater decrements than adults. Therefore, children exhibit a more comparable neuromuscular fatigue profile to endurance athletes than adults.

Effect of Muscle-Tendon Unit Length on Child-Adult Difference in Neuromuscular Fatigue.

PURPOSE: The purpose of this study was to compare the development and etiology of neuromuscular fatigue of the knee extensor muscles at different muscle-tendon unit (MTU) lengths during repeated maximal voluntary isometric contractions (MVIC) between boys and men. METHODS: Twenty-two prepubertal boys (9-11 yr) and 22 men (18-30 yr) performed three knee extensor fatigue protocols at short (SHORT), optimal (OPT), and long (LONG) MTU lengths, consisting of repeating 5-s MVIC interspersed with 5-s passive recovery periods until torque reached 60% of the initial MVIC torque. The etiology of neuromuscular fatigue was identified using noninvasive methods such as surface electromyography, near-infrared spectroscopy, magnetic nerve stimulation and twitch interpolation technique. RESULTS: The number of repetitions was significantly lower in men at OPT (14.8 ± 3.2) and LONG (15.8 ± 5.8) than boys (39.7 ± 18.4 and 29.5 ± 10.2, respectively; P < 0.001), whereas no difference was found at SHORT between both age groups (boys, 33.7 ± 15.4; men, 40.9 ± 14.2). At OPT and LONG boys showed a lower reduction in the single potentiated twitch (Qtwpot) and a greater decrease in the voluntary activation level than men. At SHORT, both populations displayed a moderate Qtwpot decrement and a significant voluntary activation reduction (P < 0.001). The differences in maximal torque between boys and men were almost twice greater at OPT (223.9 N·m) than at SHORT (123.3 N·m) and LONG (136.5 N·m). CONCLUSIONS: The differences in neuromuscular fatigue between children and adults are dependent on MTU length. Differences in maximal torque could underpin differences in neuromuscular fatigue between children and adults at OPT and SHORT. However, at LONG these differences do not seem to be explained by differences in maximal torque. The origins of this specific effect of MTU length remain to be determined.

Child-adult differences in neuromuscular fatigue are muscle dependent.

The aim of the present study was to compare the development and etiology of neuromuscular fatigue of the knee extensor (KE) and plantar flexor (PF) muscles during repeated maximal voluntary isometric contractions (MVICs) between children and adults. Prepubertal boys (n = 21; 9-11 yr) and men (n = 24; 18-30 yr) performed two fatigue protocols consisting of a repetition of 5-s isometric MVIC of the KE or PF muscles interspersed with 5-s passive recovery periods until MVIC reached 60% of its initial value. The etiology of neuromuscular fatigue of the KE and PF muscles was investigated by means of noninvasive methods, such as the surface electromyography, single and doublet magnetic stimulation, twitch interpolation technique, and near-infrared spectroscopy. The number of repetitions performed was significantly lower in men (15.4 ± 3.8) than boys (38.7 ± 18.8) for the KE fatigue test. In contrast, no significant difference was found for the PF muscles between boys and men (12.1 ± 4.9 and 13.8 ± 4.9 repetitions, respectively). Boys displayed a lower reduction in potentiated twitch torque, low-frequency fatigue, and muscle oxygenation than men whatever the muscle group considered. In contrast, voluntary activation level and normalized electromyography data decreased to a greater extent in boys than men for both muscle groups. To conclude, boys experienced less peripheral and more central fatigue during repeated MVICs than men whatever the muscle group considered. However, child-adult differences in neuromuscular fatigue were muscle-dependent since boys fatigued similarly to men with the PF muscles and to a lower extent with the KE muscles.NEW & NOTEWORTHY Child-adult differences in neuromuscular fatigue during repeated maximal voluntary contractions are specific to the muscle group since children fatigue similarly to adults with the plantar flexor muscles and to a lower extent with the knee extensor muscles. Children experience less peripheral fatigue and more central fatigue than adults, regardless of the muscle group considered.