Assessment of ultra low frequency band power of heart rate variability: validation of alternative methods.

UNLABELLED: Alternative methods for assessing ULF spectral power using data from commercial Holter analysers were studied. Different heuristics for ULF calculation were compared with standard research software-based determination of ULF. SETTING: University Hospital. PATIENTS: 43 patients in NYHA classes I-IV heart failure and seven normals of similar ages. METHODS: SDNN, SDANN, ULF, VLF, LF, HF calculated from 24 h Holter monitoring using Oxford scanner software (method 1). ULF power also calculated by subtracting the sum of VLF. LF and HF powers obtained from the Holter scanner from the total variance (method 2) from 2 x ln(SDANN) (method 3), and by performing a standard, research-quality 24-h EFT analysis on the beat files (standard). Results of methods 1-3 were compared with standard using two-way ANOVA with repeated measures, regression analysis and a graphical technique. RESULTS: ULF calculated by method 1 correlated r=0.66 with standard but means differed substantially. In contrast, ULF calculated by method 2 correlated r=0.99 with standard with no significant differences between means. ULF calculated from SDANN (method 3) correlated r=0.983 with standard but means, while similar, were significantly lower (P=0.005). CONCLUSION: ULF reported by commercial HOLTER software is not equivalent to ULF power derived from 24 h FFT analysis. ULF calculated by method 2 can be considered equivalent to the ULF derived by standard 24-h FFT. ULF estimated by method 3 offers direct ULF power estimation from a temporal measure of HRV and can be useful when spectral values are not available.

Retinopathy, but not neuropathy, is influenced by the level of residual endogenous insulin secretion in type 2 diabetes.

The files of 132 patients with Type 2 diabetes were retrospectively studied to characterize the influence of metabolic control and residual insulin secretion on neuropathy and retinopathy, the two most frequent degenerative diabetic complications. Patients were classified according to their metabolic control (mean HbA1C either < or > or = 8%; reference values: 3-6%) and residual endogenous insulin secretion (fasting plasma C-peptide levels either < or > or = 0.600 nmol/l). Neuropathy was more frequent in patients with poor metabolic control (32/64 = 50%) than in those adequately controlled (17/68 = 25%; p < 0.005). In both subgroups, the level of endogenous insulin secretion did not influence the prevalence of neuropathy. Retinopathy was less effected than neuropathy by the degree of metabolic control (37.5% in the subgroup with HbA1C > or = 8% v.s. 25% in the subgroup with HbA1C < 8%; p < 0.10), but was influenced by residual insulin secretion. Indeed, in patients with inadequate metabolic control, the prevalence of retinopathy was significantly increased in those with higher endogenous insulin secretion (51.4 versus 20.6%, p < 0.02) and thus probably higher insulin resistance. Furthermore, higher systolic arterial blood pressure was observed in the subgroups with a higher prevalence of retinopathy. Such conclusions were confirmed using multivariate analysis. Thus, in Type 2 diabetes, neuropathy is essentially affected by the degree of metabolic control, whereas retinopathy is also influenced by the level of residual endogenous insulin secretion and the presence of systolic hypertension.

Postgastroplasty recovery of ideal body weight normalizes glucose and insulin metabolism in obese women.

To study the metabolic effects of normalizing body weight, a frequently sampled iv glucose tolerance test (0.3 g/kg) was performed before [body mass index (BMI), 37.7 +/- 0.5 kg/m2] and 14 +/- 2 months after successful gastroplasty (BMI, 23.7 +/- 0.6 kg/m2) in eight obese women and, for comparison, in eight age- and weight-matched nonobese control women (BMI, 23.6 +/- 0.7 kg/m2). All subjects had normal oral glucose tolerance. The insulin secretion rate (ISR) was derived by deconvolution of plasma C-peptide levels and the insulin MCR (MCRI) by dividing the 0-180 min area under the curve (AUC) of ISR by that of plasma insulin levels (IRI). The insulin sensitivity index (SI) and the glucose effectiveness index (SG) were calculated using Bergman's minimal model. Before gastroplasty, obese subjects showed higher AUC-IRI (P < 0.001) and AUC-ISR (P < 0.02), lower MCRI (P < 0.005) and SI (P < 0.002), but similar SG values, compared to nonobese controls. After gastroplasty, the AUC-IRI dramatically decreased, due to both a reduction of AUC-ISR (from 58,252 +/- 8,437 to 36,675 +/- 4,274 pmol; P < 0.05) and an increase in MCRI (from 658 +/- 117 to 1,299 +/- 127 mL/min.m-2; P < 0.02). SI significantly rose from 4.74 +/- 0.74 to 9.15 +/- 0.96 10(-5) min-1/pmol.L (P < 0.01), whereas SG remained unchanged. All of these parameters became similar to those in nonobese controls (respectively, 32,522 +/- 3,458, 1,180 +/- 101, and 8.48 +/- 1.25; all P = NS). In conclusion, after gastroplasty-induced normalization of body weight, postobese women recover normal insulin secretion, clearance, and action on glucose metabolism.

Measurement of insulin sensitivity by the minimal model method using a simplified intravenous glucose tolerance test: validity and reproducibility.

This study aimed at testing whether 12 rather than 26 plasma glucose and insulin determinations can be used to calculate the indices of insulin sensitivity and of glucose effectiveness using Bergman's minimal model during a simple intravenous glucose tolerance test performed without tolbutamide injection. Two intravenous glucose tolerance tests (separated by 1 week) were performed in 7 lean normal subjects and a single test was performed in 9 severely obese non-diabetic subjects. Intra-subject reproducibility of insulin sensitivity was not significantly different when 26 or 12 time-points were analyzed (CV = 16.8 +/- 3.4 versus 18.9 +/- 3.8% respectively). Compared with the insulin sensitivity of the lean subjects, that of obese subjects was significantly (P < 0.001) and similarly reduced when using 12 (2.14 +/- 0.34 versus 7.97 +/- 1.29 10(-4)min-1/mU.1-1) rather than 26 determinations (2.13 +/- 0.42 versus 6.95 +/- 1.12 10(-4) min-1/mU.1-1) respectively. Glucose effectiveness was less reproducible than insulin sensitivity and was slightly diminished by the reduction of blood samples (relative error: -9.7 +/- 4.4%; P < 0.05). Finally, glucose effectiveness tended to be slightly lower in the morbidly obese subjects than in the lean controls with both modes of calculation. In conclusion, in non-diabetic subjects, the insulin sensitivity index can be accurately measured during a simple intravenous glucose tolerance test, without tolbutamide injection and with only 12 blood samples. The possibility of performing a simplified test should contribute to increase the use of the minimal model method for estimating insulin sensitivity in clinical practice.

Insulin secretion, clearance and action before and after gastroplasty in severely obese subjects.

This study investigated the effects of a drastic weight reduction on insulin secretion rate (ISR), insulin metabolic clearance rate (MCRI) and insulin sensitivity (SI) in severely obese subjects. A frequently sampled intravenous glucose tolerance test (FSIVGTT, 0.3 g/kg) was performed before and 8 +/- 1 months after a vertical ring gastroplasty in 12 overnight-fasted obese non-diabetic subjects; the results were compared to those obtained in 12 lean controls matched for age and sex. ISR was derived by deconvolution of plasma C-peptide levels; MCRI was obtained by dividing the area under the curve (AUC180 min) of ISR by the corresponding AUC of plasma insulin levels (IRI); the SI and the glucose effectiveness index (SG) were calculated by Bergman's minimal model. Before gastroplasty, obese subjects showed significantly higher ISR (P < 0.02), lower MCRI (P < 0.001), lower SI (P < 0.001) but similar SG when compared to lean controls. After gastroplasty (reduction of body weight from 104.8 +/- 3.8 to 73.4 +/- 3.6 kg and of BMI from 37.9 +/- 0.8 to 26.5 +/- 0.9 kg/m2; P < 0.001), ISR only decreased from 53,125 +/- 7968 to 42,302 +/- 3716 pmol/180 min (not significant) while AUC-IRI dramatically fell from 53,626 +/- 6378 to 21,111 +/- 2584 pmol.min/l; P < 0.001); consequently, MCRI markedly increased from 526 +/- 96 to 1257 +/- 150 ml/min/m2; P < 0.01). SI significantly rose from 3.12 +/- 0.45 to 7.10 +/- 1.20 x 10(-4) l/mU/min (P < 0.005) while SG remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin secretion, clearance, and action on glucose metabolism in cirrhotic patients.

To study the mechanisms of glucose intolerance and hyperinsulinism in liver cirrhosis, we compared the plasma glucose, insulin, and C-peptide levels during a frequently sampled i.v. glucose tolerance test (0.3 g glucose/kg BW) in nine compensated cirrhotic patients and nine healthy volunteers well matched for age, sex, and body weight. The insulin secretion rate was derived by the deconvolution of plasma C-peptide levels, insulin sensitivity was calculated using Bergman's minimal model method, and insulin clearance was estimated by dividing the 0-180 min area under the curve of insulin secretion rate by that of peripheral plasma insulin levels. The cirrhotic patients were characterized during the frequently sampled i.v. glucose tolerance test by a 60% greater insulin secretion rate (P < 0.05), a markedly reduced insulin sensitivity index (SI; 2.82 +/- 0.75 vs. 5.86 +/- 0.68 x 10(-4) min/mU.L; P < 0.01) and a 40% reduced insulin clearance (725 +/- 169 vs. 1165 +/- 99 mL/min.m-2; P < 0.05). The reduction of insulin clearance was significantly correlated with the amplitude of the portosystemic shunt, measured using an isotopic method (r = 0.75; P < 0.02). In conclusion, cirrhosis is characterized by an important peripheral hyperinsulinism, resulting from both a higher insulin secretion rate and a reduced insulin hepatic clearance; the severe insulin resistance explains the glucose metabolism alterations.

Isolation of the physiological regulation component of the arterial pressure time variation after postural stresses in by a model of the gravitational and arterial kinking effects.

Prompt active postural manoeuvres induce an immediate arterial pressure variation followed by a period of regulation. For the squatting manoeuvre, initial hypertension was explained by a rise of cardiac filling pressure due to "squeezing blood out of the veins of the legs", leading to an increase in stroke output by Frank-Starling mechanism. For a minor part, it was also explained by "kinking" of the femoral arteries. O'Donnel and Mc Ilroy observed an increase in central blood volume and accepted the idea of a rise of cardiac filling. However, they did not observe so consistent circulatory variations when postural changes were realized in a water tank. Therefore, they concluded that kinking of the arteries and veins of the legs could not be very important. Moreover, the immediate pressure variations, most often appearing in the first beat succeeding the postural manoeuvres cannot be easily explained by the previously invoked modifications of cardiac filling pressures. When Hoffman et al lifted dogs until they stood erect, the right ventricular stroke volume usually fell in the first beat after the postural change, but the left ventricular stroke volume did not fall for another 1-3 beats. When the dogs were rapidly lowered to standing on four legs again, a delay of 2-3 beats was also observed. Thus, another interpretation of immediate hypotension must be added. It should especially take into account the natural gravitational fluid mechanics phenomena imposed to the arterial blood. Besides, to allow the investigation of the orthostatic regulation of arterial blood pressure, it would be necessary to separate the cardiovascular regulation component of the arterial pressure time course from the pressure evolution that would naturally appear in the network without physiological contribution. It is the aim of this study.