Impact of an Okinawa/Nordic based diet on endocrinological and periodontal conditions in individuals with type 2 diabetes. A randomized case-control study.

OBJECTIVES: To assess if the results following intake of a diet using an Okinawan-based Nordic diet (OBND) over one month differs in endocrinological, periodontal clinical outcome, and serum cytokine levels compared to a standard hospital care diet in individuals with diabetes type 2 (T2D) (control group). BACKGROUND: Scientific evidence suggests that the use of diet for individuals with T2D may be beneficial. METHODS: Participating individuals with T2D were randomly assigned to a test (OBND) (n = 14), or control group (n = 16). Anthropometric data, blood glucose levels, HbA1c levels, lipids, serum inflammation markers (CRP, and a routine panel of 24 cytokines), blood pressure, gingival bleeding on probing (BOP), probing pocket depths (PPD), and clinical attachment levels (CAL) were studied. RESULTS: Statistical analyses of baseline study data failed to demonstrate study group differences. The mean weight reduction was greater in the OBND group (4.1 kg) versus the control group (1.3 kg) (p < 0.01). The reduction in BMI was 1.4 kg/m2 in OBND (p < 0.001) and 0.5 kg/m2 in the control group, respectively (p < 0.01). Diastolic and systolic blood pressure reductions were greater in the OBND group than in the control group (p < 0.01). Periodontal study parameters (BOP % scores) and (PPD values) decreased (p < 0.001) overall with no between group differences. The OBND resulted in reduction of serum levels of IFNγ, Eotaxin IL-9, IP10,IL17a, MCP-1,m and PDFBB compared to the control diet. CONCLUSIONS: A strict T2D- diet provides an association between reduction in serum HbA1c and BOP scores. Serum levels decreases in IFNγ, Eotaxin IL-9, IP-10, IL17a. MCP-1, and PDFBB were only found in the test group.

Development and prevention of ischemic contracture ("stone heart") in the pig heart.

Stone heart (ischemic contracture) is a rare and serious condition observed in the heart after periods of warm ischemia. The underlying mechanisms are largely unknown and treatment options are lacking. In view of the possibilities for cardiac donation after circulatory death (DCD), introducing risks for ischemic damage, we have investigated stone heart in pigs. Following cessation of ventilation, circulatory death (systolic pressure <8 mmHg) occurred within 13.1 ± 1.2 min; and a stone heart, manifested with asystole, increased left ventricular wall thickness and stiffness, established after a further 17 ± 6 min. Adenosine triphosphate and phosphocreatine levels decreased by about 50% in the stone heart. Electron microscopy showed deteriorated structure with contraction bands, Z-line streaming and swollen mitochondria. Synchrotron based small angle X-ray scattering of trabecular samples from stone hearts revealed attachment of myosin to actin, without volume changes in the sarcomeres. Ca2+ sensitivity, determined in permeabilized muscle, was increased in stone heart samples. An in vitro model for stone heart, using isolated trabecular muscle exposed to hypoxia/zero glucose, exhibited the main characteristics of stone heart in whole animals, with a fall in high-energy phosphates and development of muscle contracture. The stone heart condition in vitro was significantly attenuated by the myosin inhibitor MYK-461 (Mavacamten). In conclusion, the stone heart is a hypercontracted state associated with myosin binding to actin and increased Ca2+ sensitivity. The hypercontractile state, once developed, is poorly reversible. The myosin inhibitor MYK-461, which is clinically approved for other indications, could be a promising venue for prevention.

Excitation and contraction of cardiac muscle and coronary arteries of brain-dead pigs.

Excitability and contraction of cardiac muscle from brain-dead donors critically influence the success of heart transplantation. Membrane physiology, Ca2+-handling, and force production of cardiac muscle and the contractile properties of coronary arteries were studied in hearts of brain-dead pigs. Cardiac muscle and vascular function after 12 h brain death (decapitation between C2 and C3) were compared with properties of fresh tissue. In both isolated cardiomyocytes (whole-cell patch clamp) and trabecular muscle (conventional microelectrodes), action potential duration was shorter in brain dead, compared to controls. Cellular shortening and Ca2+ transients were attenuated in the brain dead, and linked to lower mRNA expression of L-type calcium channels and a slightly lower ICa,L, current, as well as to a lower expression of phospholamban. The current-voltage relationship and the current above the equilibrium potential of the inward K+ (IK1) channel were altered in the brain-dead group, associated with lower mRNA expression of the Kir2.2 channel. Delayed K+ currents were detected (IKr, IKs) and were not different between groups. The transient outward K+ current (Ito) was not observed in the pig heart. Coronary arteries exhibited increased contractility and sensitivity to the thromboxane analogue (U46619), and unaltered endothelial relaxation. In conclusion, brain death involves changes in cardiac cellular excitation which might lower contractility after transplantation. Changes in the inward rectifier K+ channel can be associated with an increased risk for arrhythmia. Increased reactivity of coronary arteries may lead to increased risk of vascular spasm, although endothelial relaxant function was well preserved.

Intact coronary and myocardial functions after 24 hours of non-ischemic heart preservation.

Objectives. The aim of this study was to investigate endothelium dependent relaxation (EDR) in coronary artery and the myocardial contractility after 24 h of non-ischemic heart preservation (NIHP). Design. Explanted cardioplegic hearts from six pigs were preserved by NIHP for 24 h. The perfusion medium consisted of an albumin containing hyperoncotic cardioplegic nutrition-hormone solution with erythrocytes to a hematocrit of 10%. Coronary artery ring segments were then studied in organ baths. Thromboxane A2 was used for vasocontraction and Substance P to elicit endothelium dependent relaxation. A heart trabecula from the right ventricle was mounted in an organ bath and a special stimulation protocol was used to characterize myocardial contractility. Fresh cardioplegic hearts from 11 pigs were used as controls. The water content of the hearts was calculated. Results. There was no significant difference between NIHP and fresh controls regarding EDR (91.2 ± 1.2% vs 93.1 ± 1.8%). The contraction force, potentiation and calcium recirculation fraction did not differ between the groups. The water content of the myocardium was 79.3 ± 0.2% for NIHP and 79.5 ± 0.2% for controls. Conclusions. NIHP for 24 h keeps coronary artery EDR and myocardial contractility intact and causes no edema.

Improved General and Oral Health in Diabetic Patients by an Okinawan-Based Nordic Diet: A Pilot Study.

Periodontal disease, periodontitis as well as the preceding gingivitis, has been associated with both obesity and diabetes. Studies have shown that diet changes can lead to a lower incidence of such inflammation. The aim of the present case series over four weeks was to study the effects on medical and dental conditions in patients with type 2 diabetes of the consumption of the Okinawan-based Nordic Diet (OBND®). Medical and dental examinations were performed to estimate the general health and gingivitis/periodontitis. Serum cytokine levels were assessed using Luminex technology. Eight of ten study participants completed the study. All participants lost weight (p = 0.012). Six out of seven that were treated with insulin could reduce their insulin intake after two weeks with OBND®. The reduction was about 16 units which corresponds to a 34% relative reduction compared to the starting point (range 15­63%). Fasting blood glucose values fell (p = 0.035). Hemoglobin A1c (HbA1c) (p = 0.01), triglycerides (p = 0.05), and low-density lipoprotein (LDL) (p = 0.05) were also reduced. Bleeding on probing changed from ~28% before any dietary changes to ~13% after two weeks with OBND® (p = 0.01). The reduction in gingival bleeding was as substantial as might be expected from one session of professional tooth cleaning. Markers of inflammation were also reduced. The OBND® thus showed significant promise in alleviating the impact of diabetes on dental as well as general health.

An Okinawan-based Nordic diet improves anthropometry, metabolic control, and health-related quality of life in Scandinavian patients with type 2 diabetes: a pilot trial.

BACKGROUND: Our hypothesis was that a modified diet would improve blood glucose control with beneficial impact on weight management and overall health in established diabetes. OBJECTIVE: This prospective interventional study investigated the clinical effect of an Okinawan-based Nordic diet on anthropometry, metabolic control, and health-related quality of life (HRQoL) in Scandinavian type 2 diabetes patients. DESIGN: Food was prepared and delivered to 30 type 2 diabetes patients. Clinical information along with data on HRQoL, blood samples, and urine samples were collected during 12 weeks of diet interventions, with follow-up 16 weeks after diet completion. RESULTS: After 12 weeks of dietary intervention, a reduction in body weight (7%) (p<0.001), body mass index (p<0.001), and waist circumference (7.0 cm) (p<0.001) was seen. Improved levels of proinsulin (p=0.005), insulin (p=0.011), and fasting plasma glucose (p<0.001) were found already after 2 weeks; these improved levels remained after 12 weeks when lowered levels of C-peptide (p=0.015), triglycerides (p=0.009), total cholesterol (p=0.001), and low-density lipoprotein-cholesterol (p=0.041) were also observed. Insulin resistance homeostasis model assessment for insulin resistance was lowered throughout the study, with a 20% reduction in hemoglobin A1c levels (p<0.001) at week 12, despite reduced anti-diabetes treatment. Lowered systolic blood pressure (9.6 mmHg) (p<0.001), diastolic blood pressure (2.7 mmHg) (p<0.001), and heart and respiratory rates (p<0.001) were accompanied by decreased cortisol levels (p=0.015) and improvement in HRQoL. At follow-up, increased levels of high-density lipoprotein-cholesterol were found (p=0.003). CONCLUSION: This interventional study demonstrates a considerable improvement of anthropometric and metabolic parameters and HRQoL in Scandinavian type 2 diabetes patients when introducing a modified Okinawan-based Nordic diet, independently of exercise or other interventions. Through these dietary changes, anti-diabetes treatment could be decreased or cancelled.

Plasma ANP and BNP during exercise in patients with major depressive disorder and in healthy controls.

BACKGROUND: Increased levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) have been shown to reduce the hormones in the HPA axis. In this study we addressed the question whether patients with unmedicated major depressive disorder (MDD) might have altered baseline levels of these natriuretic peptides and an altered response to acute exercise. METHODS: An incremental exercise test was performed in 18 patients with MDD and in 18 healthy controls. Plasma concentrations of ANP and BNP were determined at rest, during the exercise test and 30 min post exercise using immunoradiometric assays. RESULTS: During the exercise test the concentrations of ANP and BNP increased significantly in both groups. The MDD group showed significantly lower levels of ANP than the controls at rest, at maximal work rate and post exercise and of BNP at rest and at maximal work rate. The dynamic changes of both ANP and BNP, respectively, from baseline to maximal work rate were significantly lower in the MDD group. A slightly lower (non-significant) maximal work rate was observed in the MDD group compared with the controls. LIMITATIONS: Group sizes are relatively limited. CONCLUSION: Lower concentrations of ANP and BNP during rest and exercise were observed in the MDD patients together with a decreased dynamic response to maximal exercise. Hypothetically, the reduced ANP and BNP concentration contributes to the high hormone levels in the HPA system seen in depressive disorders. Of interest for future research is whether physical training might increase the levels of ANP and BNP and thereby diminish depressive symptoms.

Manual versus mechanical cardiopulmonary resuscitation. An experimental study in pigs.

BACKGROUND: Optimal manual closed chest compressions are difficult to give. A mechanical compression/decompression device, named LUCAS, is programmed to give compression according to the latest international guidelines (2005) for cardiopulmonary resuscitation (CPR). The aim of the present study was to compare manual CPR with LUCAS-CPR. METHODS: 30 kg pigs were anesthetized and intubated. After a base-line period and five minutes of ventricular fibrillation, manual CPR (n = 8) or LUCAS-CPR (n = 8) was started and run for 20 minutes. Professional paramedics gave manual chest compression's alternating in 2-minute periods. Ventilation, one breath for each 10 compressions, was given to all animals. Defibrillation and, if needed, adrenaline were given to obtain a return of spontaneous circulation (ROSC). RESULTS: The mean coronary perfusion pressure was significantly (p < 0.01) higher in the mechanical group, around 20 mmHg, compared to around 5 mmHg in the manual group. In the manual group 54 rib fractures occurred compared to 33 in the LUCAS group (p < 0.01). In the manual group one severe liver injury and one pressure pneumothorax were also seen. All 8 pigs in the mechanical group achieved ROSC, as compared with 3 pigs in the manual group. CONCLUSIONS: LUCAS-CPR gave significantly higher coronary perfusion pressure and significantly fewer rib fractures than manual CPR in this porcine model.

The acute response of plasma brain-derived neurotrophic factor as a result of exercise in major depressive disorder.

Brain-derived neurotrophic factor (BDNF) and other neurotrophins are believed to play an important role in affective disorders. In this study we investigated plasma-BDNF response during an incremental exercise test in 18 patients suffering from moderate major depressive disorder (MDD) and 18 controls. The patients were not treated with antidepressants or neuroleptics. Possible associations between plasma plasma-BDNF levels, dexamethasone suppression test cortisol levels and Montgomery-Asberg Depression Rating Scale (MADRS) scores were also tested. No difference in basal BDNF levels between patients and controls was found. BDNF increased significantly during exercise in both male and female patients as well as in male controls, with no significant differences between the groups. BDNF levels declined after exercise, but after 60 min of rest BDNF levels showed tendencies to increase again in male patients. No correlation between BDNF and cortisol or MADRS scores was found. We conclude that unmedicated patients with moderate depression and normal activity of the hypothalamic-pituitary-adrenal axis do not have a disturbed peripheral BDNF release during exercise. The BDNF increase 60 min after interruption of exercise in male patients might indicate up-regulated BDNF synthesis, but this needs to be further investigated in future studies.

Working capacity and well-being after radical cystectomy with continent cutaneous diversion.

OBJECTIVES: The primary aim was to compare the working capacity in patients with continent urinary diversion with a control group. Secondary aims were to assess the changes in electrolyte and acid-base homeostasis and the functional status during strenuous physical activity, and finally, the well-being in the two groups. METHODS: Eleven patients who had undergone radical cystectomy and continent cutaneous diversion using an ileocolonic segment participated. The control group consisted of 12 men, matched for age and activity level. Working capacity was assessed by ergospirometry on an exercise bicycle. Venous blood samples were taken before the test, when the expiratory exchange ratio (RER) was about 1.0 and immediately after completion of the test. SF-36 was used to evaluate the subject's functional status and well-being. RESULTS: The median working capacity in the patient group was 155 (85-190) W and 155 (125-215) W in the control group (n.s.) corresponding to 72 (43-97) % and 80 (59-97) % respectively of predicted values. Peak oxygen uptake was somewhat low in both groups when compared to P-O Astrands norms. Blood tests revealed that patients developed a slight metabolic hyperchloremic acidosis, not seen in the control group. There were no differences between the groups as assessed with SF-36. CONCLUSION: Patients with a continent urinary diversion have a working capacity equal to a control group despite a slight metabolic hyperchloremic acidosis. Quality of life was similar in the two groups and corresponded well with the norms for the general Swedish population aged 65 to 74.

The beat-to-beat decay of cardiac contractility from highly potentiated levels is bi-exponential.

In order to determine the mode of beat-to-beat decay of contractility from very high levels, we studied the beat-by-beat decay of cardiac contractility following potentiation. Such decay curves are normally analysed using a mono-exponential decay function, which assumes that a fixed fraction of activator calcium ions is recirculated from one beat to the next. We postulated that there might be deviations from such a mono-exponential expression at high levels of contractility. In single sucrose-gap voltage clamp experiments of isolated ferret papillary muscle, we obtained very high contractility by potentiation due to prolonged depolarisations. We found a bi-exponential decay in 9 of 11 muscles studied, in which the initial decay is much faster than the subsequent slower decay, as judged by residual variance of least-squares exponential fitting and by analysis of covariance using a linear equation (force of beat versus force of previous beat), p = 0.0089. In the slower decay period (physiological range), the decay was identical to that following post-extrasystolic potentiation in the same muscles studied with conventional stimulation.

Aerobic and functional capacity in a group of healthy women: reference values and repeatability.

Twenty-five randomly selected, low or moderately fit and healthy women (22-44 years) rated their perceived physical capacity and performed an incremental cycle exercise test with respiratory gas analysis. The aerobic and functional capacity did not decrease with age. However, tauVo(2) increased with age. The mean value of the perceived physical capacity was 10 metabolic equivalents and that of Vo(2max) 2075 ml min(-1). The increasing anaerobic metabolism was determined at three points DX (where the rate of Vco(2) increase just exceeds the rate of Vo(2) increase), PX (where Vco(2)/Vo(2) = 1.0) and PQ (where ventilation increase disproportionately in relation to Vco(2)). The mean Vo(2) (% of Vo(2max)) at DX, PX and PQ were 1263 (63%), 1528 (73%) and 1620 (78%) ml min(-1), respectively. The mean value of deltaVo(2)/deltaW was 10.2 ml min(-1) W(-1) while that of tauVo(2) was 0.578 (age) + 15.6. Ten women performed a test and re-test on two consecutive days, and eight of these performed another re-test 4 weeks later. The repeatability was analysed and the variations were expressed as 2 SD of the differences between the tests. The variation was greater for the 4-week re-test than the day-to-day re-test regarding Vo(2max), o(2) at DX, PX and PQ, deltaVo(2)/deltaW and HR. The variation in Vo(2max), PX and deltaVo(2)/deltaW for the 4-week re-test was more than twice that of the previously reported 4-week variation for men. The considerable variation, especially for 4-week re-testing for women should be considered when evaluating the effects of exercise and rehabilitation.

Determination of both the time constant of vO2 and DeltavO2/DeltaW from a single incremental exercise test: validation and repeatability.

A single incremental cycle exercise test including a steady-state load, combined with respiratory gas exchange, was performed with the objective of determining the time constant (tauVO(2)) and the amount of oxygen required at each load (DeltaVO(2)/DeltaW) by using a novel equation. The protocol was validated using four exercise tests at different constant loads and conventionally fitted mono-exponential functions to determine tauVO(2), and interpolation of VO(2) versus load to determine DeltaVO(2)/DeltaW. No significant differences were seen between the means of either tauVO(2) or DeltaVO(2)/DeltaW determined with the two protocols. The correlation coefficient was 0.62 for tauVO(2) and 0.48 for DeltaVO(2)/DeltaW. The absolute differences (2 SD) were 11.6 s for tauVO(2) and 1.1 ml min(-1) W(-1) for DeltaVO(2)/DeltaW. The equations were compared in the same steady-state test and good agreement of tauVO(2) was obtained (R = 0.99). The 5-6-week repeatability (incremental test) was evaluated. No statistical differences were seen between the mean of the repeated tests. The difference between the tests (2 SD) were 20 s for tauVO(2) and 1.2 ml min(-1) W(-1) for DeltaVO(2)/DeltaW. In conclusion, tauVO(2) and DeltaVO(2)/DeltaW can be determined from a single incremental test. The validation showed an acceptable agreement, although the variations in absolute values were not negligible. This could partly be explained by the natural day-to-day variation and fluctuations in incoming raw data. The test-retest variation in absolute values was considerable, which must be taken into account when using tauVO(2) and DeltaVO(2)/DeltaW for evaluation of aerobic function.

A refined technique for determining the respiratory gas exchange responses to anaerobic metabolism during progressive exercise - repeatability in a group of healthy men.

The respiratory gas exchange and ventilation during an incremental cycle exercise test were analysed in a group of 19 healthy, moderately fit men. Different computer algorithms were used to estimate the VO2 values where: (i) the rate of VCO(2) increase just exceeds the rate of VO(2) increase (DX, derivative crossing), (ii) VCO(2)/VO(2) = 1.00 (PX, point of crossing) and (iii) ventilation (VE) increases disproportionately in relation to VCO(2) (PQ, point of VCO(2) equivalent rise). The DX and PQ measurements were analysed using a new approach employing polynomial regression and the value of PX was determined following low-pass filtration of raw data. The repeatability of the measurements was evaluated with a 5-6 week interval between the tests. The correlations between tests were 0.75 at DX, 0.85 at PX and 0.62 at PQ. The mean differences between the repeated tests were not statistically significant. The repeatability of VO2, in absolute values expressed as +/-2 SD of the differences between the tests, had values of 5.0, 6.1 and 9.5 ml min(-1) kg(-1) for DX, PX and PQ, respectively. The mean value of VO(2) for each measurement point expressed as a percentage of VO(2 max) was 54% at DX, 68% at PX and 70% at PQ. The most common sequence of the measured values was DX < PX < PQ, but the sequence DX < PQ < PX was also observed. It is concluded that the gas exchange responses to developing anaerobic metabolism during progressive exercise can be characterized by a series of thresholds. However, the considerable variation in absolute values in the two testing occasions requires further attention.

Reference values for the physical work capacity on a bicycle ergometer for men -- a comparison with a previous study on women.

The aim of the study was to collect new reference values for the clinical ramp exercise test on bicycle, because in our experience, the commonly used values were too low. A group of healthy men (n = 81, 20-80 years) was randomly selected from the local municipal register to achieve an even distribution in age. Data were compared with those obtained in a similar, previous study on women (n = 87). The subjects were encouraged to cycle until exhaustion (19 on the Borg scale) when maximal load, heart rate and systolic blood pressure were recorded. Maximal load (W(max)) was related to age (years) and height (m) using a non-linear function: W(max) = (244.6 x height - 92.1)/[1 + exp[0.038 x (age - 77.3)]]. Maximal heart rate (HRmax) was described by a similar function: HRmax = 203.7/[1 + exp[0.033 x (age - 104.3)]]. The maximal systolic blood pressure (BP(max)) was described by a linear function based on age: BP(max) = 0.505 x age + 192. Similar functions for the women are also given. It is suggested that 80-120% of the predicted maximal load can be taken as a reference interval for both men and women and similarly 90-110% of the maximal heart rate. In this study, 84% of the men reached a maximal load within the reference interval and 93% maximal heart rate within the reference interval. The reported values for maximal load were 104-132% of the reference values published by others.

Repeatability of measurements of oxygen consumption, heart rate and Borg's scale in men during ergometer cycling.

The coefficient of repeatability (COR), expressed as 2-SD of differences, was calculated between two measurements of oxygen consumption (V O2), heart rate (HR) and rating of perceived exertion (RPE) during ergometer cycling by men. The two sets of measurements were performed 5 to 6 weeks apart. Nineteen healthy men performed an incremental maximal exercise test on an ergometer cycle. The load started at 50 W and increased by 5 W 20 s-1 until exhaustion was reached. At 40% of the individual maximum load of the pretest, the load was kept constant for 4 min in order to reach steady state. Gas measurements were recorded continuously by computerized instrumentation. The HR was monitored with electrocardiography (ECG) and the perceived exertion was evaluated using Borg's scale. The COR of V O2 at sub-maximal load was 14% and at maximum load 11%. The values in absolute figures were 209 and 332 ml min-1. The corresponding COR of the HR was 16% at sub-maximum load and 6% at maximum load, and an evaluation of the perceived exertion yielded CORs in absolute values of 4.8 and 1.3, respectively. The COR for V O2, HR and ratings of perceived exertion when cycling on an ergometer cycle thus indicate a better agreement between the measurements at maximum load. The COR of the heart at sub-maximal loads must be kept in mind when using HR for estimation of V O2max. The reported findings should be considered when using tests on an ergometer cycle for evaluating exercise capacity.

A novel rating scale to predict maximal exercise capacity.

To predict maximal exercise capacity, we have developed the rating of perceived capacity (RPC) scale, based on metabolic equivalents (METs). MET values from 1 to 20 were listed on a progressive scale and linked to physical activities. Test subjects rated their perceived capacity by choosing the most strenuous activity and the corresponding MET value that they could sustain for 30 min. In order to validate the RPC, 87 healthy women participated in the study (age range 21-79 years). The capacity rated from the scale (MET(RPC)) was compared with the actual work capacity in a maximal incremental ramp cycle test. The maximal load achieved at the cycle test (in W), was transformed into the unit MET (MET(test)). The mean difference between MET(RPC) and MET(test) was -1.4 (3.18) (2SD). Multiple linear regression showed that MET(test) depended significantly on MET(RPC) and age. Extended regression analysis suggested that a nonlinear correction was most appropriate in order to improve the prediction. The maximal predicted capacity was given by: MET(pred) = (5.08 + 0.70 x MET(RPC))/[1+(e(0.059 (age-87.2)))]. After this correction, the mean difference between MET(pred) and MET(test) was reduced to 0.0 (2.62) (2SD). Reference values for MET(pred) and MET(test) were also obtained. In conclusion, the RPC combined with an age correction was shown to predict accurately maximal exercise capacity; it is also quick and easy to use. Thus, RPC may be a valuable tool in the prescription of exercise and in monitoring the effects of exercise and rehabilitation.