Impact of high-intensity interval training and sprint interval training on peripheral markers of glycemic control in metabolic syndrome and type 2 diabetes

Glycemic control is essential to reduce the risk of complications associated with metabolic syndrome (MetS) and type 2 diabetes (T2D). Aerobic and resistance exercise performed alone or in combination improve glycemic control in both conditions. However, perceived lack of time and commitment are considered principal barriers to performing exercise regularly. High intensity interval training (HIIT) and sprint interval training (SIT) can be performed in a fraction of the time required for continuous aerobic exercise. A substantial scientific evidence indicates that HIIT/SIT improve glycemic control to a similar or greater extent than aerobic exercise in populations without MetS or T2D. Likewise, growing evidence suggest that HIIT/SIT improve the glycemic control during MetS and T2D. The aim of this review is to discuss the effects of interval training protocols on peripheral markers of glucose metabolism in patients with MetS and T2D.     

Human skeletal muscle fiber type alteration with high-intensity intermittent training

The response of muscle fiber type proportions and fiber areas to 15 weeks of strenuous high-intensity intermittent training was investigated in twenty-four carefully ascertained sedentary (14 women and 10 men) and 10 control (4 women and 6 men) subjects. The supervised training program consisted mainly of series of supramaximal exercise lasting 15 s to 90 s on a cycle ergometer. Proportions of muscle fiber type and areas of the fibers were determined from a biopsy of the vastus lateralis before and after the training program. No significant change was observed for any of the histochemical characteristics in the control group. Training significantly increased the proportion of type I and decreased type IIb fibers, the proportion of type IIa remained unchanged. Areas of type I and IIb fibers increased significantly with training. These results suggest that high-intensity intermittent training in humans may alter the proportion of type I and the area of type I and IIb fibers and in consequence that fiber type composition in human vastus lateralis muscle is not determined solely by genetic factors.     

Six sessions of sprint interval training increases muscle oxidative potential and cycle endurance capacity in humans.

Parra et al. (Acta Physiol. Scand 169: 157-165, 2000) showed that 2 wk of daily sprint interval training (SIT) increased citrate synthase (CS) maximal activity but did not change "anaerobic" work capacity, possibly because of chronic fatigue induced by daily training. The effect of fewer SIT sessions on muscle oxidative potential is unknown, and aside from changes in peak oxygen uptake (Vo(2 peak)), no study has examined the effect of SIT on "aerobic" exercise capacity. We tested the hypothesis that six sessions of SIT, performed over 2 wk with 1-2 days rest between sessions to promote recovery, would increase CS maximal activity and endurance capacity during cycling at approximately 80% Vo(2 peak). Eight recreationally active subjects [age = 22 +/- 1 yr; Vo(2 peak) = 45 +/- 3 ml.kg(-1).min(-1) (mean +/- SE)] were studied before and 3 days after SIT. Each training session consisted of four to seven "all-out" 30-s Wingate tests with 4 min of recovery. After SIT, CS maximal activity increased by 38% (5.5 +/- 1.0 vs. 4.0 +/- 0.7 mmol.kg protein(-1).h(-1)) and resting muscle glycogen content increased by 26% (614 +/- 39 vs. 489 +/- 57 mmol/kg dry wt) (both P < 0.05). Most strikingly, cycle endurance capacity increased by 100% after SIT (51 +/- 11 vs. 26 +/- 5 min; P < 0.05), despite no change in Vo(2 peak). The coefficient of variation for the cycle test was 12.0%, and a control group (n = 8) showed no change in performance when tested approximately 2 wk apart without SIT. We conclude that short sprint interval training (approximately 15 min of intense exercise over 2 wk) increased muscle oxidative potential and doubled endurance capacity during intense aerobic cycling in recreationally active individuals.     

Effect of high-intensity interval training on muscle remodeling in rheumatoid arthritis compared to prediabetes

Background

Sarcopenic obesity, associated with greater risk of cardiovascular disease (CVD) and mortality in rheumatoid arthritis (RA), may be related to dysregulated muscle remodeling. To determine whether exercise training could improve remodeling, we measured changes in inter-relationships of plasma galectin-3, skeletal muscle cytokines, and muscle myostatin in patients with RA and prediabetes before and after a high-intensity interval training (HIIT) program.

Methods

Previously sedentary persons with either RA (n = 12) or prediabetes (n = 9) completed a 10-week supervised HIIT program. At baseline and after training, participants underwent body composition (Bod Pod^®) and cardiopulmonary exercise testing, plasma collection, and vastus lateralis biopsies. Plasma galectin-3, muscle cytokines, muscle interleukin-1 beta (mIL-1β), mIL-6, mIL-8, muscle tumor necrosis factor-alpha (mTNF-α), mIL-10, and muscle myostatin were measured via enzyme-linked immunosorbent assays. An independent cohort of patients with RA (n = 47) and age-, gender-, and body mass index (BMI)-matched non-RA controls (n = 23) were used for additional analyses of galectin-3 inter-relationships.

Results

Exercise training did not reduce mean concentration of galectin-3, muscle cytokines, or muscle myostatin in persons with either RA or prediabetes. However, training-induced alterations varied among individuals and were associated with cardiorespiratory fitness and body composition changes. Improved cardiorespiratory fitness (increased absolute peak maximal oxygen consumption, or VO₂) correlated with reductions in galectin-3 (r = ?0.57, P = 0.05 in RA; r = ?0.48, P = 0.23 in prediabetes). Training-induced improvements in body composition were related to reductions in muscle IL-6 and TNF-α (r < ?0.60 and P <0.05 for all). However, the association between increased lean mass and decreased muscle IL-6 association was stronger in prediabetes compared with RA (Fisher r-to-z P = 0.0004); in prediabetes but not RA, lean mass increases occurred in conjunction with reductions in muscle myostatin (r = ?0.92; P <0.05; Fisher r-to-z P = 0.026). Subjects who received TNF inhibitors (n = 4) or hydroxychloroquine (n = 4) did not improve body composition with exercise training.

Conclusion

Exercise responses in muscle myostatin, cytokines, and body composition were significantly greater in prediabetes than in RA, consistent with impaired muscle remodeling in RA. To maximize physiologic improvements with exercise training in RA, a better understanding is needed of skeletal muscle and physiologic responses to exercise training and their modulation by RA disease–specific features or pharmacologic agents or both.

Trial registration

ClinicalTrials.gov Identifier: NCT02528344. Registered on August 19, 2015.

     

Folate supplementation reduces serum hsp70 levels in patients with type 2 diabetes

Type 2 diabetes patients are subject to oxidative stress as a result of hyperglycemia. The aim of this study was to determine whether administration of the antioxidant folic acid, previously shown to reduce homocysteine levels, would reduce circulating levels of Hsp70 while improving the condition of type 2 diabetes patients with microalbuminuria. Plasma homocysteine fell from pretreatment values of 12.9 to 10.3 microM (P < 0.0001). The urine albumin-creatinine ratio fell from 12.4 to 10.4 mg/mM (P = 0.38). Pretreatment Hsp70 levels were higher in patients not taking insulin (5.32 ng/mL) compared with those on insulin (2.44 ng/mL) (P = 0.012). Folic acid supplementation resulted in a significant fall in Hsp70 (5.32 to 2.05 ng/mL) (P = 0.004). There was no change in Hsp70 in those receiving insulin. Folic acid supplementation in non-insulin-treated type 2 diabetes patients, therefore, resulted in a fall in Hsp70, reflecting an improvement in oxidative stress. The data shows that improvement in homocysteine status can lead to a reduction in Hsp70, indicating the possibility of its use as a marker for severity of disease.     

Tetrahydrobiopterin increases insulin sensitivity in patients with type 2 diabetes and coronary heart disease

Tetrahydrobiopterin (BH(4)) is an essential cofactor of nitric oxide synthase that improves endothelial function in diabetics, smokers, and patients with hypercholesterolemia. Insulin resistance has been suggested as a contributing factor in the development of endothelial dysfunction via an abnormal pteridine metabolism. We hypothesized that BH(4) would restore flow-mediated vasodilation (FMD, endothelial-dependent vasodilation), which may affect insulin resistance in type 2 diabetic patients. Thirty-two subjects (12 type 2 diabetic subjects, 10 matched nondiabetic subjects, and 10 healthy unmatched subjects) underwent infusion of BH(4) or saline in a random crossover study. Insulin sensitivity index (S(I)) was measured by hyperinsulinemic isoglycemic clamp. FMD was measured using ultrasonography. BH(4) significantly increased S(I) in the type 2 diabetics [3.6 +/- 0.6 vs. 4.9 +/- 0.7 x 10(-4) dl.kg(-1).min(-1)/(microU/ml), P < 0.05], while having no effects in nondiabetics [8.9 +/- 1.1 vs. 9.0 +/- 0.9 x 10(-4) dl.kg(-1).min(-1)/(microU/ml), P = 0.92] or in healthy subjects [17.5 +/- 1.6 vs. 18 +/- 1.8 x 10(-4) dl.kg(-1).min(-1)/(microU/ml), P = 0.87]. BH(4) did not affect the relative changes in brachial artery diameter from baseline FMD (%) in type 2 diabetic subjects (2.3 +/- 0.8 vs. 1.8 +/- 1.0%, P = 0.42), nondiabetic subjects (5.3 +/- 1.1 vs. 6.6 +/- 0.9%, P = 0.32), or healthy subjects (11.9 +/- 0.6 vs. 11.0 +/- 1.0%, P = 0.48). In conclusion, BH(4) significantly increases insulin sensitivity in type 2 diabetic patients without any discernible improvement in endothelial function.     

Inflammatory,antioxidant and glycemic status to different mode of high-intensity training in type 2 diabetes mellitus

Molecular Biology Reports - Exercise has traditionally been used and prescribed as an effective and suitable way to treat type 2 diabetics Mellitus (T2DM). In this regard, we compared inflammatory,...     

Metabolic adaptations to training precede changes in muscle mitochondrial capacity.

To determine whether increases in muscle mitochondrial capacity are necessary for the characteristic lower exercise glycogen loss and lactate concentration observed during exercise in the trained state, we have employed a short-term training model involving 2 h of cycling per day at 67% maximal O2 uptake (VO2max) for 5-7 consecutive days. Before and after training, biopsies were extracted from the vastus lateralis of nine male subjects during a continuous exercise challenge consisting of 30 min of work at 67% VO2max followed by 30 min at 76% VO2max. Analysis of samples at 0, 15, 20, and 60 min indicated a pronounced reduction (P less than 0.05) in glycogen utilization after training. Reductions in glycogen utilization were accompanied by reductions (P less than 0.05) in muscle lactate concentration (mmol/kg dry wt) at 15 min [37.4 +/- 9.3 (SE) vs. 20.2 +/- 5.3], 30 min (30.5 +/- 6.9 vs. 17.6 +/- 3.8), and 60 min (26.5 +/- 5.8 vs. 17.8 +/- 3.5) of exercise. Maximal aerobic power, VO2max (l/min) was unaffected by the training (3.99 +/- 0.21 vs. 4.05 +/- 0.26). Measurements of maximal activities of enzymes representative of the citric acid cycle (succinic dehydrogenase and citrate synthase) were similar before and after the training. It is concluded that, in the voluntary exercising human, altered metabolic events are an early adaptive response to training and need not be accompanied by changes in muscle mitochondrial capacity.     

Cardioprotective effects of high-intensity interval training are mediated through microRNA regulation of mitochondrial and oxidative stress pathways

Human studies have shown high-intensity interval training (HIIT) has beneficial cardiovascular effects and is typically more time-efficient compared with traditional endurance exercise. The main goal of this study is to show the potential molecular and functional cardiovascular benefits of HIIT compared with endurance training (ET). Three groups of mice were used including sedentary-control, ET mice, and HIIT mice groups. Results indicated ejection fraction was increased in HIIT compared with ET while fractional shortening was increased in the HIIT group compared with both groups. Blood flow of the abdominal aorta was increased in both exercise groups compared with control. Increases in cross-sectional area and mitochondrial and antioxidative markers in HIIT compared with control were observed, along with several microRNAs. These findings indicate HIIT has specific cardiac-protective effects and may be a viable alternative to traditional ET as a cardiovascular preventative medicine intervention.     

Fiber type changes in rat skeletal muscle after intense interval training

Summary Female Sprague-Dawley rats were subjected to a ten week training program to determine the influence of intense interval running on the fiber type composition of selected hindlimb muscles; soleus (S), plantaris (P), deep vastus lateralis (DVL), and superficial vastus lateralis (SVL). The muscles of one hindlimb were used for histochemical ATPase analysis to determine the distribution of fiber types and those of the contralateral hindlimb were assayed biochemically for citrate synthase activity (an aerobic marker). Training induced a significant increase in citrate synthase activity in each muscle section. The largest absolute increase occurred in the DVL and the largest relative increase occurred in the SVL. The distribution of fiber types within the S (85% slow-twitch) and SVL (100% fast-twitch) remained unchanged with training. However, significant increases in the percentage of type I (slow-twitch) fibers in both the P (2-fold) and DVL (3-fold) were observed with concomitant decreases in the type II (fast-twitch) population. In addition, training induced significant changes in the fast-twitch subtype populations of the DVL (IIBIIA). These data suggest exercise-induced fiber type transformations occurring both within the fast-twitch population and between fast-twitch and slow-twitch fibers in certain hindlimb muscles of the rat following a high intensity interval training program.     

Fiber type changes in rat skeletal muscle after intense interval training

Female Sprague-Dawley rats were subjected to a ten week training program to determine the influence of intense interval running on the fiber type composition of selected hindlimb muscles; soleus (S), plantaris (P), deep vastus lateralis (DVL), and superficial vastus lateralis (SVL). The muscles of one hindlimb were used for histochemical ATPase analysis to determine the distribution of fiber types and those of the contralateral hindlimb were assayed biochemically for citrate synthase activity (an aerobic marker). Training induced a significant increase in citrate synthase activity in each muscle section. The largest absolute increase occurred in the DVL and the largest relative increase occurred in the SVL. The distribution of fiber types within the S (85% slow-twitch) and SVL (100% fast-twitch) remained unchanged with training. However, significant increases in the percentage of type I (slow-twitch) fibers in both the P (2-fold) and DVL (3-fold) were observed with concomitant decreases in the type II (fast-twitch) population. In addition, training induced significant changes in the fast-twitch subtype populations of the DVL (IIB----IIA). These data suggest exercise-induced fiber type transformations occurring both within the fast-twitch population and between fast-twitch and slow-twitch fibers in certain hindlimb muscles of the rat following a high intensity interval training program.     

Blood glucose discrimination training in patients with type II diabetes

This study was designed to determine whether patients with Type II diabetes could be taught to discriminate blood glucose after experiencing a variety of blood glucose levels and receiving feedback on the accuracy of their estimates. Thirty-six subjects (18 on oral agents and 18 on insulin) were randomly assigned to one of two feedback conditions: (1) current feedback, which received accurate information regarding their blood glucose levels, (2) noncurrent feedback, which received blood glucose levels from the preceding session. Subjects were exposed to a wide range of blood glucose values in six training sessions by ingesting drinks with three different caloric loads. In pre/post comparisons using several indices of accuracy, both groups showed significant improvement in estimating blood glucose levels. However, feedback on current blood glucose levels did not produce greater improvement than noncurrent. Accuracy was unrelated to the degree to which subjects reported associating internal sensations to their estimates. Failure to find differences between the two feedback conditions may have been due to the noncurrent feedback group's receiving fairly accurate information, to the difficulty of the discrimination task, and to the limited number of training trials.     

Determination of metabolic equivalents during low- and high-intensity resistance exercise in healthy young subjects and patients with type 2 diabetes

The purpose of this study was to quantify the metabolic equivalents (METs) of resistance exercise in obese patients with type 2 diabetes (T2DM) and healthy young subjects and to evaluate whether there were differences between sessions executed at low- versus high-intensity resistance exercise. Twenty obese patients with T2DM (62.9±6.1 years) and 22 young subjects (22.6±1.9 years) performed two training sessions: one at vigorous intensity (80% of 1-repetition maximum (1RM)) and one at moderate intensity (60% of 1RM). Both groups carried out three strength exercises with a 2-day recovery between sessions. Oxygen consumption was continuously measured 15 min before, during and after each training session. Obese T2DM patients showed lower METs values compared with young healthy participants at the baseline phase (F= 2043.86; P<0.01), during training (F=1140.59; P<0.01) and in the post-exercise phase (F=1012.71; P<0.01). No effects were detected in the group x intensity analysis of covariance. In this study, at both light-moderate and vigorous resistance exercise intensities, the METs value that best represented both sessions was 3 METs for the obese elderly T2DM patients and 5 METs for young subjects.     

Similar health benefits of endurance and high-intensity interval training in obese children

Purpose

To compare two modalities of exercise training (i.e., Endurance Training [ET] and High-Intensity Interval Training [HIT]) on health-related parameters in obese children aged between 8 and 12 years.

Methods

Thirty obese children were randomly allocated into either the ET or HIT group. The ET group performed a 30 to 60-minute continuous exercise at 80% of the peak heart rate (HR). The HIT group training performed 3 to 6 sets of 60-s sprint at 100% of the peak velocity interspersed by a 3-min active recovery period at 50% of the exercise velocity. HIT sessions last ∼70% less than ET sessions. At baseline and after 12 weeks of intervention, aerobic fitness, body composition and metabolic parameters were assessed.

Results

Both the absolute (ET: 26.0%; HIT: 19.0%) and the relative VO₂ peak (ET: 13.1%; HIT: 14.6%) were significantly increased in both groups after the intervention. Additionally, the total time of exercise (ET: 19.5%; HIT: 16.4%) and the peak velocity during the maximal graded cardiorespiratory test (ET: 16.9%; HIT: 13.4%) were significantly improved across interventions. Insulinemia (ET: 29.4%; HIT: 30.5%) and HOMA-index (ET: 42.8%; HIT: 37.0%) were significantly lower for both groups at POST when compared to PRE. Body mass was significantly reduced in the HIT (2.6%), but not in the ET group (1.2%). A significant reduction in BMI was observed for both groups after the intervention (ET: 3.0%; HIT: 5.0%). The responsiveness analysis revealed a very similar pattern of the most responsive variables among groups.

Conclusion

HIT and ET were equally effective in improving important health related parameters in obese youth.     

Astilbe thunbergii reduces postprandial hyperglycemia in a type 2 diabetes rat model via pancreatic alpha-amylase inhibition by highly condensed procyanidins

Type 2 diabetes mellitus (T2DM) is a common global health problem. Prevention of this disease is an important task, and functional food supplements are considered an effective method. We found potent pancreatic α-amylase inhibition in Astilbe thunbergii root extract (AT) and confirmed that AT treatment in a T2DM rat model reduces post-starch administration blood glucose levels. Activity-guided isolation revealed procyanidin (AT-P) as the α-amylase inhibitory component with IC₅₀ = 1.7 μg/mL against porcine pancreatic α-amylase. Structure analysis of AT-P revealed it is a B-type procyanidin comprised of four types of flavan-3-ols, some with a galloyl group, and catechin attached as the terminal unit. The abundant AT-P content and its comparable α-amylase inhibition to acarbose, the anti-diabetic medicine, suggest that AT is a promising food supplement for diabetes prevention.     

Acute glucose fluctuations and chronic sustained hyperglycemia as risk factors for cardiovascular diseases in patients with type 2 diabetes.

Chronic hyperglycemia, usually assessed from HbA1c determinations, results in excessive glycation and generation of oxidative stress. As a consequence, chronic hyperglycemia has been identified as a risk factor for diabetes complications leading to accelerated atherosclerosis. Both fasting and postprandial hyperglycemia contribute to this process. However the acute glucose fluctuations that occur in diabetes have been recently described as an additional factor that activates the oxidative stress. As a consequence, acute glucose swings, including upward (postprandial) and downward (interprandial) fluctuations can be considered as risk factors for cardiovascular events and should be included in the "dysglycemia" of diabetes in combination with fasting and postprandial hyperglycemia. As postprandial glucose is a contributor of both acute glucose fluctuations and chronic sustained hyperglycemia, it remains difficult to know whether these 2 mechanisms are equivalent or not equivalent risk factors for cardiovascular disease.     

Postprandial hyperglycemia and endothelial function in type 2 diabetes: focus on mitiglinide

ABSTRACT: The risk of cardiovascular complication in a diabetes patient is similar to that in a nondiabetic patient with a history of myocardial infarction. Although intensive control of glycemia achieved by conventional antidiabetic agents decreases microvascular complications such as retinopathy and nephropathy, no marked effect has been reported on macrovascular complications or all-cause mortality. Evidence from VADT, ACCORD, and ADVANCE would suggest that glycemic control has little effect on macrovascular outcomes. Moreover, in the case of ACCORD, intensive glycemic control may be associated with an increased risk of mortality. There is sufficient evidence that suggests that postprandial hyperglycemia may be an independent risk factor for cardiovascular disease in diabetes patients. However, there are no prospective clinical trials supporting the recommendation that lowering postprandial blood glucose leads to lower risk of cardiovascular outcomes. Mitiglinide is a short-acting insulinotropic agent used in type 2 diabetes treatment. It has a rapid stimulatory effect on insulin secretion and reduces postprandial plasma glucose level in patients with type 2 diabetes. Because of its short action time, it is unlikely to exert adverse effects related to hypoglycemia early in the morning and between meals. Mitiglinide reduces excess oxidative stress and inflammation, plays a cardioprotective role, and improves postprandial metabolic disorders. Moreover, mitiglinide add-on therapy with pioglitazone favorably affects the vascular endothelial function in type 2 diabetes patients. These data suggest that mitiglinide plays a potentially beneficial role in the improvement of postprandial hyperglycemia in type 2 diabetes patients and can be used to prevent cardiovascular diseases. Although the results of long-term, randomized, placebo-controlled trials for determining the cardiovascular effects of mitiglinide on clinical outcomes are awaited, this review is aimed at summarizing substantial insights into this topic.