Maria L. Zonderland

Insulin Secretion in Normal Glucose-Tolerant Relatives of Type 2 Diabetic Subjects: Assessments using hyperglycemic glucose clamps and oral glucose tolerance tests

OBJECTIVE To assess insulin secretion in normal glucose-tolerant Caucasian first-degree relatives of type 2 diabetes subjects and in matched normal glucose-tolerant control subjects and to compare insulin secretion as assessed using a hyperglycemic glucose clamp with insulin secretion as assessed using an oral glucose tolerance test (OGTT). RESEARCH DESIGN AND METHODS Twenty-one first-degree relatives of type 2 diabetic subjects and 21 control subjects without a family history of type 2 diabetes, who were matched for sex, age, BM1, waist-to-hip ratio, and aerobic capacity, underwent a hyperglycemic glucose clamp (10 mmol/1, 180 min). An OGTT (75 g glucose in 300 ml water) was also performed. RESULTS First-phase insulin release (plasma insulin, 0–10 min) was not different (multiple analysis of variance [MANOVA]: F = 2.63, P = 0.11). Second-phase insulin release was lower (MANOVA: F = 4.18, P = 0.047). Separate analyses of variance showed decreased plasma insulin levels from 120 min onward (all P < 0.05), decreasing to geometric mean (95% CI) levels of 330 (270–402) and 462 (366–582) pmol/1 at 180 min in relatives and control subjects, respectively. The insulin sensitivity index (ISI) as assessed using a hyperglycemic clamp was not different between the two groups. Mean ± SE ISI during the 3rd hour was 27.5 ± 2.2 and 30.5 ± 3.0 μg · kg−1 · min−1 · pmol−1 · l−1 in relatives and control subjects, respectively (P > 0.20). At 90 min after the OGTT, log plasma insulin levels correlated significantly with secondphase insulin release as assessed using the hyperglycemic glucose clamp. CONCLUSIONS Normal glucose-tolerant first-degree relatives of type 2 diabetic subjects have a decreased second-phase insulin release, compared with matched control subjects. After an OGTT, 90-min values of log plasma insulin and 90-min values of the ratio of log plasma insulin to blood glucose may be good indicators of insulin secretory properties in normal glucose-tolerant family members of type 2 diabetic subjects.

Skeletal muscle metabolic recovery following submaximal exercise in chronic heart failure is limited more by O2 delivery than O2 utilization

CHF (chronic heart failure) is associated with a prolonged recovery of skeletal muscle energy stores following submaximal exercise, limiting the ability to perform repetitive daily activities.However, the pathophysiological background of this impairment is not well established. The aim of the present study was to investigate whether muscle metabolic recovery following submaximal exercise in patients with CHF is limited by O2 delivery or O2 utilization. A total of 13 stable CHF patients (New York Heart Association classes II-III) and eight healthy subjects, matched for age and BMI (body mass index), were included. All subjects performed repetitive submaximal dynamic single leg extensions in the supine position. Post-exercise PCr (phosphocreatine) resynthesis was assessed by 31P-MRS (magnetic resonance spectroscopy). NIRS (near-IR spectroscopy) was applied simultaneously, using the rate of decrease in HHb (deoxygenated haemoglobin) as an index of post-exercise muscle re-oxygenation. As expected, PCr recovery was slower in CHF patients than in control subjects (time constant, 47+/-10 compared with 35+/-12 s respectively; P=0.04). HHb recovery kinetics were also prolonged in CHF patients (mean response time, 74+/-41 compared with 44+/-17 s respectively; P=0.04). In the patient group, HHb recovery kinetics were slower than PCr recovery kinetics (P=0.02), whereas no difference existed in the control group(P=0.32). In conclusion, prolonged metabolic recovery in CHF patients is associated with an even slower muscle tissue re-oxygenation, indicating a lower O(2) delivery relative to metabolic demands. Therefore we postulate that the impaired ability to perform repetitive daily activities in these patients depends more on a reduced muscle blood flow than on limitations in O(2) utilization.

Are oxygen uptake kinetics in chronic heart failure limited by oxygen delivery or oxygen utilization

BACKGROUND The delay in O(2) uptake kinetics during and after submaximal physical activity (O(2) onset and recovery kinetics, respectively) correlates well with the functional capacity of patients with chronic heart failure (CHF). This study examined the physiological background of this delay in moderately impaired CHF patients by comparing kinetics of cardiac output (Q) and O(2) uptake (V(O(2))). METHODS Fourteen stable CHF patients (New York Heart Association class II-III) and 8 healthy subjects, matched for age and body mass index, were included. All subjects performed a submaximal constant-load exercise test to assess O(2) uptake kinetics. Furthermore, in 10 CHF patients Q was measured by a radial artery pulse contour analysis method, which enabled the simultaneous modelling of exercise-related kinetics of Q and V(O(2)). RESULTS Both O(2) onset and recovery kinetics were delayed in the patient group. There were no significant differences between the time constants of Q and V(O(2)) during exercise-onset (62+/-25 s versus 59+/-28 s, p=0.51) or recovery (61+/-25 s versus 57+/-20 s, p=0.38) in the patient group, indicating that O(2) delivery was not in excess of the metabolic demands in these patients. CONCLUSION The delay in O(2) onset and recovery kinetics in moderately impaired CHF patients is suggested to be due to limitations in O(2) delivery. Therefore, strategies aimed at improving exercise performance of these patients should focus more on improvements of O(2) delivery than on O(2) utilization.

Predicting Effects of Exercise Training in Patients With Heart Failure Secondary to Ischemic or Idiopathic Dilated Cardiomyopathy

The purpose of this study was to investigate which patient characteristics may predict training effects on maximal and submaximal exercise performance in patients with heart failure. Together with commonly used clinical and performance-related variables, oxygen uptake kinetics during exercise recovery were included as possible predictors. Fifty patients with heart failure (New York Heart Association class II or III) performed a 12-week training program (cycle interval and resistance training). Training effects were expressed as changes in peak oxygen uptake (Vo(2)), Vo(2) at ventilatory threshold (VT), and the time constant of Vo(2) recovery after submaximal exercise (tau-rec). After training, peak Vo(2), Vo(2) at VT, and tau-rec improved significantly, with a wide variety in training responses. Changes in peak Vo(2) were related to changes in VT (r = 0.79, p <0.001), but both changes were not related to changes in tau-rec. Using multivariate regression analyses, post-training changes in peak Vo(2) could be predicted by recovery halftime of peak Vo(2) (T1/2), peak Vo(2) (percentage of predicted), and peak respiratory exchange ratio (R(2) = 36%). Post-training changes in VT could be predicted by T1/2 and VT (predicted) (R(2) = 29%), whereas changes in tau-rec could be predicted only by tau-rec at baseline (R(2) = 34%). In conclusion, oxygen recovery kinetics after maximal and submaximal exercise substantially add to the prediction of training effects in patients with heart failure, presumably because of their relations with, respectively, central and peripheral impairments of exercise capacity. However, the explained variance in training effects is not sufficient to make a definite distinction between training responders and nonresponders.

Does physical training increase insulin sensitivity in chronic heart failure patients

To determine the effect of training on insulin sensitivity (IS) and how this relates to peak V(.)O(2) (peak oxygen uptake) in CHF (chronic heart failure), 77 CHF patients (New York Heart Association class, II/III; men/women, 59/18; age, 60+/-9 years; body mass index, 26.7+/-3.9 kg/m(2); left ventricular ejection fraction, 26.9+/-8.1%; expressed as means+/-S.D.) participated in the study. Patients were randomly assigned to a training or control group (TrG or CG respectively). Sixty-one patients completed the study. Patients participated in training (combined strength and endurance exercises) four times per week, two times supervised and two times at home. Before and after intervention, anthropometry, IS (euglycaemic hyperinsulinaemic clamp) and peak V(.)O(2) (incremental cycle ergometry) were assessed. Intervention did not affect IS significantly, even though IS increased by 20% in TrG and 11% in CG (not significant). Peak V(.)O(2) increased as a result of training (6% increase in TrG; 2% decrease in CG; P <0.05). In both groups (TrG and CG), the change in IS correlated positively with the change in peak V(.)O(2) ( r =0.30, P <0.05). Training resulted in an increase in peak V(.)O(2), but not in IS. Whether physical training actually increases IS in CHF patients remains unclear.

Oxygen uptake kinetics in chronic heart failure: clinical and physiological aspects

One of the hallmark symptoms of patients with chronic heart failure (CHF) is exercise intolerance. Therefore, exercise testing has become an important tool for the evaluation and monitoring of heart failure. Whereas the maximal aerobic capacity (peak VO2) is a reliable indicator of the severity and prognosis of heart failure, submaximal exercise parameters may be more closely related to the ability to perform daily activities. As such, oxygen (O2) uptake kinetics, describing the rate change of O2 uptake during onset or recovery of submaximal constant-load exercise (O2 onset and recovery kinetics, respectively), have been shown to be useful parameters for objectively evaluating the functional capacity of CHF patients. However, their evaluation in this population is not a routine part of daily clinical practice. Possible reasons for this include a lack of standardisation of the assessment methodology and a limited number of studies evaluating the clinical use of O2 uptake kinetics in CHF patients. In addition, the pathophysiological mechanisms underlying the delay in O2 uptake kinetics in these patients are not completely understood. This review discusses the current literature on the clinical potency and physiological determinants of O2 uptake kinetics in CHF patients and provides directions for future research. (Neth Heart J 2009;17:238–44.)

Determinants of insulin sensitivity in chronic heart failure.

To describe the determinants of insulin sensitivity (IS) in chronic heart failure (CHF), we created a model in which the influence of lifestyle factors and etiology of heart failure on IS were incorporated concomitantly with age, left ventricular ejection fraction (LVEF) and parameters of body composition.

Determinants of maximal exercise performance in chronic heart failure.

Background Chronic heart failure (CHF) is characterized by symptoms like fatigue, dyspnoea and limited exercise performance. It has been postulated that maximal exercise performance (Wmax) is predominantly limited by skeletal muscle function and less by heart function. Aim To study the interrelation between most relevant muscle and anthropometrical variables and Wmax in CHF patients in order to develop a model that describes the impact of these variables for maximal exercise performance. Design In 77 patients with CHF Wmax was assessed by incremental cycle ergometry until exhaustion (20 Watt/3 min). Peak torque (strength) and total work (endurance) for the quadriceps and hamstrings were assessed by isokinetic dynamometry. Isometric strength was measured by hand dynamometry. Relevant muscle areas were calculated by computerized tomography scan. Results Significant correlations between Wmax and isokinetic muscle parameters (peak torque and total work) ranged from 0.41-0.65 (P<0.01). Other significant relationships (P<0.01) with Wmax were obtained for age (r = −0.22), gender (r = 0.45), fat free mass (FFM) (r = 0.51), quadriceps muscle area (r = 0.73), hamstrings muscle area (r = 0.50), upper leg muscle function (i.e., a combination of muscle strength and muscle endurance) (r = 0.71) and isometric strength (r = 0.63). Multiple regression analysis showed that upper leg muscle function and quadriceps muscle area could predict 57% of the variance in Wmax. Conclusion Muscle strength and muscle endurance, combined with quadriceps muscle area are the main predictors of maximal exercise performance in patients with CHF.

Bewegen en chronisch hartfalen

Hartfalen wordt gedefinieerd als een complex van klachten en verschijnselen tengevolge van een tekortschietende pompfunctie van het hart.1 Er zijn verschillende manieren om patienten met hartfalen in te delen. De New York Heart Association-indeling (nyha-indeling) is een veelgebruikte methode en loopt van nyha-klasse I (geen klachten; behandeld hartfalen) tot aan klasse IV (patient heeft klachten in rust, ondanks behandeling). Zoals beschreven in hoofdstuk 3 is het nadeel van de nyha-indeling dat hij erg subjectief is en dat het lastig differentieren is tussen klasse II- en klasse III-patienten. Een andere veelgebruikte indeling, die bovendien objectiever is dan de nyha-indeling, is de indeling volgens Weber.2 In tabel 9.1 zijn de meest gebruikte indelingen voor patienten met hartfalen samengevat.