Uncomplicated Type 2 Diabetes Research Articles

Obesity dominates early effects on cardiac structure and arterial stiffness in people with type 2 diabetes.

Type 2 diabetes (T2D) and obesity are global epidemics leading to excess cardiovascular disease (CVD). This study investigates standard and novel cardiac MRI parameters to detect subclinical cardiac and central vascular dysfunction in inactive people with and without T2D. Physically inactive age and BMI-similar premenopausal women and men with ( n = 22) and without [ n = 34, controls with overweight/obesity (CWO)] uncomplicated T2D were compared to an age-similar and sex-similar reference control cohort ( n = 20). Left ventricular (LV) structure, function, and aortic stiffness were assessed by MRI. Global arterial pulse wave velocity (PWV) was assessed using carotid-to-femoral applanation tonometry. Regional PWV was measured via 2D phase-contrast MRI and 4D flow MRI. Global arterial PWV did not differ between CWO and T2D. 2D PC-MRI PWV in the ascending aorta was higher in people with T2D compared with CWOs ( P < 0.01). 4D flow PWV in the thoracic aorta was higher in CWO ( P < 0.01), and T2D ( P < 0.001) compared with RC. End-diastolic volume, end-systolic volume, stroke volume, and cardiac output were lower in CWO and T2D groups compared with reference control. Subclinical changes in arterial stiffening and cardiac remodeling in inactive CWO and T2D compared with reference control support obesity and/or physical inactivity as determinants of incipient CVD complications in uncomplicated T2D. Future studies should determine the mechanistic causes of the CVD complications in greater detail in order to create therapeutic targets. Cardiovascular Mechanisms of Exercise Intolerance in Diabetes and the Role of Sex (NCT03419195).

1633-P: Type 1 Diabetes Induced Alterations in Motor Unit Discharge Rate

Type 1 diabetes (T1D) is a contributing factor in alterations in skeletal muscle health. It has been attributed to accelerated muscle ageing (Monaco et al., 2019), and the molecular alterations in the muscle are also associated with impaired adaptations to physical exercise (Minnock et al., 2022). However, there is no evidence about the consequences of this condition on the behaviour of individual motor units (MUs), despite them being the effectors of the contractile stimulus coming from the nervous system via modulation of their recruitment and discharge activity. This study aimed to investigate whether MUs discharge rate (DR) differs between people living with T1D compared with a control (CON) group of people living without diabetes. Eight people with T1D (4M/4F, 30.50 ± 3.66 years, HbA1c of 8.31 ± 2.40%) without comorbidities and 8 age and sex-matched CON participants undertook the study. MUs DR was evaluated from the vastus lateralis muscle during trapezoidal submaximal isometric contractions with High-Density Electromyography at 20, and 40% of the maximum voluntary contraction (MVC) and DR modulation was defined as the difference between DR at recruitment (i.e., first 3 MUs firings) and DR during the steady-state phase of the contraction. Groups were compared for maximum torque (182.06 ± 47.65 Nm T1D and 171.99 ± 101.97 Nm Non-D). MUs DR was lower for those with T1D at recruitment and during the steady-state phase, both during contractions at 20 and 40% MVC (p&amp;lt;0.05). MUs DR modulation was comparable between the two groups. In conclusion, reductions in MUs DR indicate initial alterations of MUs properties in people living with uncomplicated T1D when compared to CON counterparts. The reduced DR, however, was not accompanied by a reduced range of DR modulation (gain) and was not reflected in reduced force production. These findings suggest that initial alterations of MUs properties are present in people living with uncomplicated T1D and that these alterations are detectable before they become functionally manifest. Disclosure D.Minnock: Employee; Innovation Zed. G.Valli: None. R.Wu: None.

488-P: Subclinical Autonomic Neuropathy in Uncomplicated Type 2 Diabetes

Cardiac autonomic neuropathy (CAN), a common complication of type 2 diabetes (T2D), is often not detected until late in disease progression. Autonomic nervous system (ANS) dysfunction impairs control of heart rate (HR) and vascular dynamics, manifesting as decreased HR variability (HRV) and impaired blood pressure (BP) regulation. We hypothesized that ANS function is impaired in participants with uncomplicated T2D and correlates with cardiac measures. We measured HRV during cycled breathing and Valsalva and postural HR and BP on overweight physically inactive adults aged 22-70 years with (N=53) and without (N=56) T2D. HRV with cycled breathing and Valsalva was lower in participants with T2D (p=0.007 and 0.005, respectively). HRV with respiration was lower with age &amp;gt;50 years (p=0.0001). HRV with respiration correlated with increased age in T2D but not in overweight control participants. There were no significant changes in postural BP or HR with age &amp;gt;50 years or T2D. Significant correlations between ANS measures and cardiac function were only seen in those with T2D. Valsalva ratio was positively correlated with end-diastolic volume (Pearson’s r 0.58, p=0.02) and stroke volume (Pearson’s r 0.55, p=0.03). HRV with respiration was positively correlated with longitudinal, diastolic peak strain rate (SR) (Pearson’s r 0.68, p=0.007). Postural BP was positively correlated with circumferential and longitudinal, systolic peak SR (Pearson’s r =0.45 and 0.48 and p-value=0.05 and 0.04, respectively) and negatively correlated with radial and circumferential peak strain (Pearson’s r =-0.49 and -0.48 and p-value=0.03 and 0.03, respectively). These data suggest subclinical CAN associated with cardiac dysfunction is present in people with otherwise uncomplicated T2D and is exacerbated with age. Detecting CAN changes early may identify people at risk for cardiac disease and inform targeted intervention to restore cardiometabolic health in people with T2D. Disclosure A.Johnston: None. L.A.Abushamat: None. D.Enge: None. A.J.Barker: None. E.W.Clark: None. D.Rafferty: None. J.G.Regensteiner: None. J.E.B.Reusch: Advisory Panel; Medtronic. Funding American Diabetes Association (1-21-CMF-003 to L.A.A.); National Institutes of Health (T32DK120520-01A1); U.S. Department of Veterans Affairs (CX001532)

598-P: No Relationship between Sedentary Behavior Patterns and Peak Oxygen Consumption (VO2peak) among Overweight Individuals With and Without Type 2 Diabetes

Background: Sedentary behavior (SB) has negative effects on health, even in the context of achieving physical activity (PA) guidelines. It is unclear how total volume and patterns of accumulation of SB may vary among overweight/obese adults with and without uncomplicated type 2 diabetes (T2D) and whether SB is related to aerobic capacity. Purpose: To examine SB patterns and their relationship to estimated peak oxygen consumption (VO2peak) among adults with uncomplicated T2D and overweight controls. Methods: This was a secondary analysis of baseline data from VA-MIXED (NCT03419195), a trial in physically inactive, overweight/obese adults aged 30-55 with and without T2D. Daily pattern of PA/SB was assessed via activPAL for 7 days. Participants completed a cycle ergometer graded exercise test to measure maximal workload. VO2peak was estimated using the American College of Sports Medicine metabolic equation. Pearson correlation, two-sample t-tests, and multiple linear regression analyses were used to examine relationships between variables overall and by T2D status. Results: Baseline data were available for 21 participants (8 T2D, 13 overweight controls), mean (SD) age 43.3 (7.6) yrs, BMI 34.6 (5.6) kg/m2. Participants were sedentary (11.7 [2.2] h/day). There were no differences in step count; stepping, standing, or sedentary time; sit-to-stand transitions, and time in SB bouts ≥1 hour by T2D status (all p&amp;gt;0.11). Correlations between SB variables and VO2peak were not significant (all p&amp;gt;0.20). The relationship between total SB and VO2peak did not change when T2D status was included in the model (β −2.22, p=0.39). Discussion: Objectively measured SB patterns were similar between overweight controls and adults with uncomplicated T2D and did not correlate with VO2peak. Future studies should examine these variables in larger cohorts and evaluate if SB patterns are associated with variability in response to exercise. Disclosure M.O.Whipple: None. J.E.B.Reusch: Advisory Panel; Medtronic. A.J.Pinto: None. D.Rafferty: None. R.L.Scalzo: None. L.Abushamat: None. I.E.Schauer: None. A.G.Huebschmann: None. E.Clark: None. J.G.Regensteiner: None. Funding American Diabetes Association (1-21-CMF-003 to L.A.); National Institutes of Health (P50CA244688, P30DK116073, UL1TR001082, R01AG066562, R01DK124344, K12HD057022); Ludeman Family Center for Women’s Health Research; U.S. Department of Veterans Affairs (BX004533, BX002046, CX001532)

Women Have Greater Endothelin-B Receptor Function and Lower Mitochondrial Capacity Compared to Men With Type 1 Diabetes.

Type 1 diabetes (T1D) negatively affects both the endothelin system and muscle oxidative capacity. The endothelin pathway is a critical regulator of microcirculatory function and may exhibit sexual dichotomy by which healthy premenopausal women have greater endothelin-B receptor (ETBR) function compared to men. Moreover, T1D may differentially alter muscle oxidative capacity in men and women; however, whether ETBR function is impaired in women compared to men with T1D and its relationship with muscle oxidative capacity has yet to be explored. The purpose of this investigation was to determine if ETBR-mediated dilation is impaired in women compared to men with T1D and if this is related to their skeletal muscle oxidative capacity. Men (n = 9; glycated hemoglobin A1c [HbA1c] = 7.8 ± 1.0%) and women (N = 10 women; HbA1c = 8.4 ± 1.3%) with uncomplicated T1D were recruited for this investigation. Near-infrared spectroscopy (NIRS) and intradermal microdialysis (750 nM BQ-123 + ET-1 [10-20-10-8 mol/L]) were used to evaluate skeletal muscle oxidative capacity and assess ETBR-mediated vasodilation, respectively. Skeletal muscle oxidative capacity was significantly lower (P = .031) in women compared with men with T1D. However, ETBR-mediated dilation induced a significantly greater (P = .012) vasodilatory response in women compared to men with T1D, and the area under the curve was negatively associated with skeletal muscle oxidative capacity (r = -.620; P = .042). Compared to men with uncomplicated T1D, muscle oxidative capacity was lower and ETBR-mediated vasodilation was higher in women with uncomplicated T1D. ETBR-induced vasodilatory capacity was inversely related to skeletal muscle oxidative capacity, suggesting there may be compensatory mechanisms occurring to preserve microvascular blood flow in women with T1D.

Circulating Ism1 Reduces the Risk of Type 2 Diabetes but not Diabetes-Associated NAFLD.

PurposeTo examine the association of serum Ism1, a new adipokine that can regulate glucose uptake, with type 2 diabetes (T2D) in a Chinese population. Considering high prevalence of Nonalcoholic Fatty Liver Disease in patients with type 2 diabetes and the regulating role of Ism1 on glucose uptake of peripheral tissues, we further explored the association between Ism1 and diabetes-associated nonalcoholic fatty liver disease.MethodsA total of 120 newly diagnosed T2D patients and 60 control subjects with normal glucose were recruited in the case-control study. Serum Ism1 concentrations were determined by ELISA. Multivariate logistic regression analysis was used to evaluate the independent association of serum Ism1 concentration with the risk of T2D. The 120 newly diagnosed T2D patients were divided into uncomplicated T2D group and diabetes-associated NAFLD group according to the FLI score.ResultsThe Ism1 level of normoglycemic controls was higher than that of T2D patients (3.91 ± 0.24 ng/ml vs 3.01 ± 0.16 ng/ml, P=0.001). Based on quartile analysis of Ism1 level, the proportion of high circulating Ism1 levels in the control group increased while T2D group decreased, and the distribution difference was statistically significant (P=0.015). Logistic regression analysis indicated that the serum Ism1 level was an independent protective factor of type 2 diabetes (OR=0.69, 95%CI: 0.54-0.89). The decrease of Ism1 level did not increase the risk of non-alcoholic fatty liver disease in diabetic patients by Binary logistic regression analysis (OR=1.08, 95% CI: 0.69-1.69).ConclusionsThe increase of serum Ism1 was associated with a decreased risk of diabetes, and it did not reduce the risk of non-alcoholic fatty liver disease in diabetic patients.

182-LB: Cardiovascular Response to Exercise in T2D

Type 2 diabetes (T2D) confers a greater likelihood of heart failure (HF) and hospitalization due to HF. Our group has reported sub-clinical cardiac dysfunction and aortic stiffness in youth and adults with uncomplicated T2D. As aortic stiffening is reported to precede HF and is common in people with uncomplicated T2D, we tested the hypothesis that aerobic exercise training will improve cardiac function and central arterial stiffness in people with T2D compared to participants of similar BMI without T2D. Sedentary adults with (n = 18, age 48±7, 45% female) and without (n = 20, age 45±7, 46% female) T2D, underwent MRI for cardiac function and aortic compliance (aortic relative area change [RAC] and pulse wave velocity [PWV]) before and after 15 weeks of aerobic exercise training. At baseline, both cohorts exhibit subclinical diastolic dysfunction, however, those with T2D had lower end-diastolic volume (EDVN,47.2±9.9 vs. 52.3±9.1 mL/m2) and end-systolic volume (ESVN,21.1±5.4 vs. 23.6±5.2 mL/m2), than controls. The T2D group had higher max thickness of the left ventricular (LV) septal wall (LVMTs, 10.5±1.8 vs. 9.3±1.6 mm) and LV lateral wall (LVMTl, 8.4±1.6 vs. 7.6±1.3 mm) than controls. Those with T2D also had lower RAC (12.7±1.6 vs. 20.2±1.6%) and higher PWV (7.4±1.3 vs. 3.9±0.6 m/s) than controls. Preliminary data in a subset post exercise intervention (n=7 with and n=8 without T2D), revealed increased EDVN(42.8±7.9 to 51.5±11.3 mL/m2) and ESVN(19.7±4.0 to 24.3±6.5 mL/m2) and decreased LVMTs(11.35±1.5 to 9.96±1.3 mm) and LVMTl(8.42±0.81 to 7.74±0.89 mm) in the T2D group, but cardiac endpoints were unchanged in controls. Post-intervention in both groups, ascending aorta RAC increased (control: 16.2±4 % to 18.5±1.7 and T2D: 10.6±1.7 % to 19.6±2.2 %) and PWV decreased (control: 6.3±2.0 to 3.4±0.3 and T2D: 8.0±1.4 to 2.9±0.7). Data from this study in progress suggest that adults with T2D have a greater degree of cardiac dysfunction and arterial stiffness than controls of similar BMI, which improve to a greater degree with exercise than in controls. Disclosure D. Enge: None. J.E. Reusch: None. J.G. Regensteiner: None. M. Schäfer: None. K.S. Hunter: None. A.J. Barker: None. K.J. Nadeau: None. R.L. Scalzo: None. I.E. Schauer: None. L. Abushamat: None. M.O. Whipple: None. D. Rafferty: None. Funding U.S. Department of Veterans Affairs (CX001532)

Impact of Self-Reported Sitting Time and Transtheoretical Model Based on Exercise Behavior Change on Glycemic and Weight Control in Japanese Adults with Type 1 Diabetes: A Cross-Sectional Study.

This cross-sectional study aimed to examine the associations among self-reported sitting time (ST), transtheoretical model (TTM) based on exercise behavior change, and glycemic and weight control in Japanese adults with type 1 diabetes (T1D). Forty-two adults (age, 44.0 (33.3–56.8) years) with uncomplicated T1D answered questions regarding their lifestyles, including ST per day, and TTM using self-administered questionnaires. The glycated hemoglobin (HbA1c) level correlated with age and ST (p < 0.05, p < 0.01, respectively), whereas body mass index correlated with duration of T1D and TTM (p < 0.05, p < 0.01, respectively). Logistic regression analysis showed that poor glycemic control (HbA1c, >7%) was associated with ST (odds ratio, 3.53 (95% confidence interval, 1.54–8.11), p < 0.01). In addition, the cut-off points for quartiles of ST were 4.6, 6.0, and 8.0 h/day, and the HbA1c level in the lowest quartile was 15% lower than that in the highest quartile (p < 0.01). Although further studies with larger samples are needed, these results implied that expanded self-reported ST might be related to poor glycemic control in Japanese T1D adults, most of whom were lean, young and middle-aged, regardless of TTM based on exercise behavior change.

Muscle Oxygen Supply and Use in Type 1 Diabetes, From Ambient Air to the Mitochondrial Respiratory Chain: Is There a Limiting Step?

Long before clinical complications of type 1 diabetes (T1D) develop, oxygen supply and use can be altered during activities of daily life. We examined in patients with uncomplicated T1D all steps of the oxygen pathway, from the lungs to the mitochondria, using an integrative ex vivo (muscle biopsies) and in vivo (during exercise) approach. We compared 16 adults with T1D with 16 strictly matched healthy control subjects. We assessed lung diffusion capacity for carbon monoxide and nitric oxide, exercise-induced changes in arterial O2 content (SaO2, PaO2, hemoglobin), muscle blood volume, and O2 extraction (via near-infrared spectroscopy). We analyzed blood samples for metabolic and hormonal vasoactive moieties and factors that are able to shift the O2-hemoglobin dissociation curve. Mitochondrial oxidative capacities were assessed in permeabilized vastus lateralis muscle fibers. Lung diffusion capacity and arterial O2 transport were normal in patients with T1D. However, those patients displayed blunted exercise-induced increases in muscle blood volume, despite higher serum insulin, and in O2 extraction, despite higher erythrocyte 2,3-diphosphoglycerate. Although complex I- and complex II-supported mitochondrial respirations were unaltered, complex IV capacity (relative to complex I capacity) was impaired in patients with T1D, and this was even more apparent in those with long-standing diabetes and high HbA1c. [Formula: see text]O2max was lower in patients with T1D than in the control subjects. Early defects in microvascular delivery of blood to skeletal muscle and in complex IV capacity in the mitochondrial respiratory chain may negatively impact aerobic fitness. These findings are clinically relevant considering the main role of skeletal muscle oxidation in whole-body glucose disposal.

Influence of priming exercise on oxygen uptake and muscle deoxygenation kinetics during moderate-intensity cycling in type 2 diabetes.

The pulmonary oxygen uptake (V̇o2) kinetics during the transition to moderate-intensity exercise is slowed in individuals with type 2 diabetes (T2D), at least in part because of limitations in O2 delivery. The present study tested the hypothesis that a prior heavy-intensity warm-up or "priming" exercise (PE) bout would accelerate V̇o2 kinetics in T2D, because of a better matching of O2 delivery to utilization. Twelve middle-aged individuals with T2D and 12 healthy controls (ND) completed moderate-intensity constant-load cycling bouts either without (Mod A) or with (Mod B) prior PE. The rates of muscle deoxygenation (i.e., deoxygenated hemoglobin and myoglobin concentration, [HHb+Mb]) and oxygenation (i.e., tissue oxygenation index) were continuously measured by near-infrared spectroscopy at the vastus lateralis muscle. The local matching of O2 delivery to O2 utilization was assessed by the Δ[HHb+Mb]-to-ΔV̇o2 ratio. Both groups demonstrated an accelerated V̇O2 kinetics response during Mod B compared with Mod A (T2D, 32 ± 9 vs. 42 ± 12 s; ND, 28 ± 9 vs. 34 ± 8 s; means ± SD) and an elevated muscle oxygenation throughout Mod B, whereas the [HHb+Mb] amplitude was greater during Mod B only in individuals with T2D. The [HHb+Mb] kinetics remained unchanged in both groups. In T2D, Mod B was associated with a decrease in the "overshoot" relative to steady state in the Δ[HHb+Mb]-to-ΔV̇o2 ratio (1.17 ± 0.17 vs. 1.05 ± 0.15), whereas no overshoot was observed in the control group before (1.04 ± 0.12) or after (1.01 ± 0.12) PE. Our findings support a favorable priming-induced acceleration of the V̇o2 kinetics response in middle-aged individuals with uncomplicated T2D attributed to an enhanced matching of microvascular O2 delivery to utilization.NEW & NOTEWORTHY Heavy-intensity "priming" exercise (PE) elicited faster pulmonary oxygen uptake (V̇o2) kinetics during moderate-intensity cycling exercise in middle-aged individuals with type 2 diabetes (T2D). This was accompanied by greater near-infrared spectroscopy-derived muscle deoxygenation (i.e., deoxygenated hemoglobin and myoglobin concentration, [HHb+Mb]) responses and a reduced Δ[HHb+Mb]-to-ΔV̇o2 ratio. This suggests that the PE-induced acceleration in oxidative metabolism in T2D is a result of greater O2 extraction and better matching between O2 delivery and utilization.

Influence of type 2 diabetes on muscle deoxygenation during ramp incremental cycle exercise

We tested the hypothesis that type 2 diabetes (T2D) alters the profile of muscle fractional oxygen (O2) extraction (near-infrared spectroscopy) during incremental cycle exercise. Seventeen middle-aged individuals with uncomplicated T2D and 17 controls performed an upright ramp test to exhaustion. The rate of muscle deoxygenation (i.e. deoxygenated haemoglobin and myoglobin concentration, Δ[HHb+Mb]) profiles of the vastus lateralis muscle were normalised to 100% of the response, plotted against % power output (PO) and fitted with a double linear regression model. Peak oxygen uptake was significantly (P < 0.05) reduced in individuals with T2D. The %Δ[HHb+Mb]/%PO slope of the first linear segment of the double linear regression function was significantly (P < 0.05) steeper in T2D than controls (1.59 (1.14) vs 1.23 (0.51)). Both groups displayed a near-plateau in Δ[HHb+Mb] at an exercise intensity (%PO) not different amongst them. Such findings suggest that a reduced O2 delivery to active muscles is an important underlying cause of exercise intolerance during a maximum graded test in middle-aged individuals with T2D.

735-P: Seasonal Variation in Vascular Function in People with Type 2 Diabetes Who Exercise Regularly

The purpose of this study was to investigate seasonal variation in vascular function in people with type 2 diabetes (T2D) who exercise regularly. Fourteen Japanese adults with uncomplicated T2D (5 men and 9 women, age: 65.9 ± 0.9 years, HbA1c: 7.1 ± 0.1%, mean ± SE). All patients exercised at our hospital for 5 years (January 2010-December 2014). Moderate intensity aerobic exercise using a treadmill or bicycle ergometer was performed for 40 min/day (frequency: ≥ 2 days/week). Vascular function, including flow-mediated dilation (FMD), cardio-ankle vascular index (CAVI), and ankle-brachial pressure index (ABI) in each season (spring: March-May, summer: June-August, fall: September-November, winter: December-February) were compared. Variation in FMD throughout the year was 1.0%, and the level in winter was significantly worse than in spring and summer (winter vs. spring and summer: 3.5 ± 0.1% vs. 4.4 ± 0.1% and 4.6 ± 0.1%; p &amp;lt; 0.01 and p &amp;lt; 0.01, respectively) (Figure). However, CAVI and ABI showed no significant change throughout the year. These results suggested that FMD rather than CAVI and ABI might show seasonal variation, even in people with T2D who exercise regularly. It is important to consider these characteristics when managing T2D. Disclosure H. Honda: None. M. Igaki: None.

Clinical variables and ethnicity may influenced by polymorphism of CAT −262C/T and MnSOD 47C/T antioxidant enzymes in Algerian type1 diabetes without complications

The latest studies in Algeria show that the frequency of type 1 diabetes (T1D) without complications is lower than that with complications and represents a significant burden in terms of cost and treatment. For this reason, we are interested in uncomplicated type1 diabetes and risk factors that are related to polymorphisms of antioxidant enzymes in order to prevent its complications.A total of 260 blood samples of young Algerian adults were examined. The genotypic analysis of Catalase gene (CAT −262C/T, rs1001179) and the superoxide dismutase gene (MnSOD 47C/T, rs4880) was performed by real-time PCR using TaqMan technology.The genotypic distribution of the CAT −262C/T promoter gene's polymorphism showed a significant difference between control and T1D patients for the CC genotype (p = 0.009; OR = 0.30) and for the T allele (p = 0.002; OR = 2.82). In addition, the genotypic distribution of the MnSOD 47C/T gene showed an association with T1D for the CT genotype (p = 0.040; OR = 2.37).Our results revealed that polymorphisms of CAT and MnSOD may be associated with physiopathology causing the onset of T1D. Our data, suggest that the genotypic frequencies of these SNPs appear to be influenced by clinical variables and by the Arab-Berber ethnic origin of the Algerian population.

β-Adrenergic Responsiveness in the Type 2 Diabetic Heart: Effects on Cardiac Reserve.

This study aimed to determine the chronotopic and inotropic response of the type 2 diabetic heart to β-adrenergic stimulation. Eight people with uncomplicated T2D and seven matched controls performed a dual-energy x-ray absorptiometry scan and V˙O2peak test. Plasma catecholamines were determined at rest and during peak exercise. On a second visit, HR and left ventricular contractility were assessed using echocardiography during supine rest, parasympathetic blockade (atropine), and during incremental β-adrenergic stimulation (dobutamine). V˙O2peak and HR reserve were lower in T2D (P < 0.05) as expected. Both groups increased norepinephrine comparably (P = 0.23) during peak exercise; however, epinephrine increased less in the T2D group (P < 0.05). The dobutamine dose required to achieve 85% of age-predicted maximal HR was 36% higher in CON (P < 0.05). Resting HR was higher (P < 0.01) and stroke volume indexed to fat free mass was smaller (P < 0.05) in T2D. During dobutamine infusion the response (% change) in HR, end-diastolic volumeFFM, stroke volume, ejection fraction, and cardiac output were not different between the groups. However, HR was higher (P < 0.01) and end-diastolic volume indexed to fat free mass (P < 0.01), stroke volumeFFM (P < 0.01), ejection fraction (P < 0.05), and stroke work (P < 0.01) were lower in T2D. Although the type 2 diabetic heart worked at smaller volumes, the HR and contractile response to β-adrenergic stimulation were unaffected by diabetes. The reduced cardiac reserve observed in uncomplicated T2D was not explained by impaired myocardial sympathetic responsiveness but may reflect changes in the loading conditions or function of the diabetic left ventricle.

Renal and Vascular Effects of Uric Acid Lowering in Normouricemic Patients With Uncomplicated Type 1 Diabetes.

Higher plasma uric acid (PUA) levels are associated with lower glomerular filtration rate (GFR) and higher blood pressure (BP) in patients with type 1 diabetes (T1D). Our aim was to determine the impact of PUA lowering on renal and vascular function in patients with uncomplicated T1D. T1D patients (n = 49) were studied under euglycemic and hyperglycemic conditions at baseline and after PUA lowering with febuxostat (FBX) for 8 weeks. Healthy control subjects were studied under normoglycemic conditions (n = 24). PUA, GFR (inulin), effective renal plasma flow (para-aminohippurate), BP, and hemodynamic responses to an infusion of angiotensin II (assessment of intrarenal renin-angiotensin-aldosterone system [RAAS]) were measured before and after FBX treatment. Arterial stiffness, flow-mediated dilation (FMD), nitroglycerin-mediated dilation (GMD), urinary nitric oxide (NO), and inflammatory markers were measured before and after FBX treatment. Gomez equations were used to estimate arteriolar afferent resistance, efferent resistance (RE), and glomerular hydrostatic pressure (PGLO). FBX had a modest systolic BP-lowering effect in T1D patients (112 ± 10 to 109 ± 9 mmHg, P = 0.049) without impacting arterial stiffness, FMD, GMD, or NO. FBX enhanced the filtration fraction response to hyperglycemia in T1D patients through larger increases in RE, PGLO, and interleukin-18 but without impacting the RAAS. FBX lowered systolic BP and modulated the renal RE responses to hyperglycemia but without impacting the RAAS or NO levels, suggesting that PUA may augment other hemodynamic or inflammatory mechanisms that control the renal response to hyperglycemia at the efferent arteriole. Ongoing outcome trials will determine cardiorenal outcomes of PUA lowering in patients with T1D.

Resting heart rate variability and exercise capacity in Type 1 diabetes.

People with type 1 diabetes (T1D) have lower exercise capacity (V̇O2max) than their age‐matched nondiabetic counterparts (CON), which might be related to cardiac autonomic dysfunction. We examined whether Heart Rate Variability (HRV; indicator of cardiac autonomic modulation) was associated with exercise capacity in those with and without T1D. Twenty‐three participants with uncomplicated T1D and 17 matched CON were recruited. Heart rate (HR; ECG), blood pressure (BP; finger photo‐plethysmography), and respiratory rate (respiratory belt) were measured during baseline, paced‐breathing and clinical autonomic reflex tests (CARTs); deep breathing, lying‐to‐stand, and Valsalva maneuver. Baseline and paced‐breathing ECG were analyzed for HRV (frequency‐domain). Exercise capacity was determined during an incremental cycle ergometer test while V̇O2, 12‐lead ECG, and BP were measured. In uncomplicated T1D, resting HR was elevated and resting HRV metrics were reduced, indicative of altered cardiac parasympathetic modulation; this was generally undetected by the CARTs. However, BP and plasma catecholamines were not different between groups. In T1D, V̇O2max tended to be lower (P = 0.07) and HR reserve was lower (P < 0.01). Resting Total Power (TP) had stronger positive associations with V̇O2max (R 2 ≥ 0.3) than all other traditional indicators such as age, resting HR, and self‐reported exercise (R 2 = 0.042–0.3) in both T1D and CON. Alterations in cardiac autonomic modulation are an early manifestation of uncomplicated T1D. Total Power was associated with reduced exercise capacity regardless of group, and these associations were generally stronger than traditional indicators.

VO2/PO Relationship In Type 2 Diabetic Subjects.

The ability to perform physical activity of prolonged duration and adequate intensity (i.e. exercise tolerance) is instrumental to obtain the well-known health benefits that are associated with physical training in Type 2 diabetes (T2D). During whole-body physical activity exercise tolerance is compromised as the oxygen cost (VO2) of energy production becomes progressively higher (i.e. “excess” VO2) at power outputs (PO) above the lactate threshold (LT). This loss of muscle efficiency, of which type I fibers fatigue and/or increased type II fibers recruitment are putative causes, impairs exercise tolerance. PURPOSE: We tested the hypothesis that a strength training intervention (ST), by increasing maximal force (Fmax) and reducing the recruitment of high-threshold motor units at a given exercise intensity, will reduce the “excess” VO2 during a cycling incremental exercise. METHODS: 11 male patients (mean±SD age 56±8 yrs, BMI 29±4 kg/m2), with uncomplicated T2D on oral hypoglycemic drugs were tested Pre and Post a 4-months ST intervention (3 times per week, 60 min). VO2/PO relationship during an incremental cycling test to exhaustion was modelled using a double-linear fit: the slopes of the VO2/PO relationship below (S1) and above (S2) the LT were calculated. Parameters were compared with Wilcoxon singed-rank tests. RESULTS: Fmax, VO2max and POmax significantly increased following ST (20±5, 7±7 and 10±10% respectively). No “excess” VO2 was present before (S2 not different from S1: 10.5±1.1 vs 9.9±1.7 mlmin-1W-1) yet it became evident following ST (S2 significantly higher than S1: 14.1±3.1 vs 11.8±4.0 mlmin-1W-1). CONCLUSIONS: Contrarily to our hypothesis, the “excess” VO2, typically displayed by healthy age-matched controls, was absent in our T2D patients. We speculate that this could be due to the acceleration of the age-related selective atrophy of type II muscle fibers that is known to occur in T2D. A 4-months ST that improved muscle Fmax, VO2max and POmax, was associated with the appearance of an “excess” VO2. We speculate that this is the result of the recovered ability to recruit type II muscle fibers towards force production in the heavy-intensity domain of an incremental cycling exercise. The practical implications of the above findings for exercise prescription in T2D require further evaluation.

Sex differences in the effects of type 2 diabetes on exercise performance.

People with uncomplicated type 2 diabetes (T2D) have impaired peak exercise performance compared with that of their nondiabetic counterparts. This impairment may represent the earliest indication of cardiovascular (CV) abnormalities in T2D. Women with T2D are known to have worse CV outcomes than those in men with T2D. We hypothesized that women with diabetes have a greater exercise impairment than that in men with diabetes compared with that in their nondiabetic counterparts. We studied 15 women (premenopausal) and 14 men with T2D as well as their nondiabetic counterparts (22 women and 13 men). Exercise testing was performed. Additional outcomes included measurements of insulin sensitivity, endothelial function, blood flow, and resting cardiac function. Men and women with T2D but not controls had impaired insulin sensitivity. Women with T2D had a lower peak oxygen consumption (V˙O2peak) compared with that of nondiabetic women (24%, P < 0.05) than men with diabetes compared with that in nondiabetic men (16%, P < 0.05) (P value between groups < 0.05). The time constants (phase 2) of the V˙O2 kinetic response tended to be slower in men and women with T2D than those in nondiabetic controls (P = 0.08). There were no differences in resting ventricular function by Doppler echocardiography techniques between groups. Women with T2D had significantly lower flow-mediated dilation and blood flow responses to hyperemia than those in nondiabetic women (both P < 0.05), whereas men with T2D had lower flow-mediated dilation but not lower blood flow than those in nondiabetic men. Although both men and women with uncomplicated T2D had a lower V˙O2peak, the abnormality in women with T2D compared with that in nondiabetic women was greater than that seen in men. Because V˙O2peak has a strong inverse correlation with mortality, sex disparities observed in exercise capacity among people with T2D suggest a possible rationale for the increased CV morbidity and mortality observed in women compared with those observed in men with uncomplicated T2D.

Exercise Effects on Postprandial Glycemia, Mood, and Sympathovagal Balance in Type 2 Diabetes

ObjectivesTo compare the impact of walking with a recreational activity on postprandial glycemia, heart rate variability, and mood state following the dinner meal. DesignParticipants with type 2 diabetes (T2D) participated in 3 trials on different days in random order after ingestion of a standardized dinner meal (300 ± 6 kcals). SettingUniversity clinical testing laboratory. ParticipantsTwelve participants (9 female, 3 male; 58.7 ± 2.4 years) with uncomplicated T2D not taking insulin or beta-blocker medications. InterventionThirty minutes of self-paced walking on a treadmill (TM), 30 minutes of table tennis played continuously against the iPong robot (TT), and 30 minutes of rest (CON) undertaken 30 minutes after the start of ingestion of the same dinner meal on three occasions within a week. MeasurementsBlood glucose was measured at 30-minute intervals through 180 minutes starting immediately prior to the dinner meal. Profile of Mood States was completed before and immediately following exercise or rest. Sympathovagal balance (heart rate variability) was measured prior to eating and 30 minutes after trial completion. ResultsCompared with TT or CON, TM resulted in significantly lower postprandial blood glucose (P < .05), as well as a greater quantity of physical activity than TT (+72%) or rest (+91%; P < .01). Mean heart rate during TM was significantly greater than during TT (+25.9 beats per minute; P < .01). However, neither mood state nor HRV were significantly different among trials. ConclusionsThirty minutes of self-paced walking following the dinner meal may be more effective at lowering postprandial glycemia in T2D than a similar duration of table tennis played continuously against a robot.

Activin a is associated with impaired myocardial glucose metabolism and left ventricular remodeling in patients with uncomplicated type 2 diabetes

BackgroundActivin A released from epicardial adipose tissue has been linked to contractile dysfunction and insulin resistance in cardiomyocytes. This study investigated the role of activin A in clinical diabetic cardiomyopathy by assessing whether circulating activin A levels associate with cardiometabolic parameters in men with uncomplicated type 2 diabetes (T2D), and the effects of treatment with pioglitazone versus metformin on these associations.MethodsSeventy-eight men with uncomplicated T2D and fourteen healthy men with comparable age were included, in this randomized, double-blind, active comparator intervention study. All T2D men were on glimipiride monotherapy, and randomized to a 24-week intervention with either pioglitazone or metformin. Cardiac dimensions and -function were measured using magnetic resonance imaging, whilst myocardial glucose metabolism (MMRglu) was determined using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography during a hyperinsulinemic-euglycemic clamp.ResultsCirculating activin A levels were comparable in T2D men and controls. Activin A levels were independently inversely associated with MMRglu, and positively with left ventricular mass/volume (LVMV)-ratio in T2D men. Intervention with metformin decreased activin A levels, whereas pioglitazone did not alter activin A levels. The changes in plasma activin A levels were not correlated with the changes in MMRglu following either pioglitazone or metformin treatment. A borderline significant correlation (p = 0.051) of changes in plasma activin A levels and changes in LVMV-ratio was observed after pioglitazone treatment.ConclusionsCirculating activin A levels are associated with impaired myocardial glucose metabolism and high LVMV-ratio in patients with uncomplicated T2D, reflecting a potential detrimental role in early human diabetic cardiomyopathy.Trial registration numberCurrent Controlled Trials SRCTN53177482