SUMMARY The diagnosis of autonomic neuropathy frequently depends on results of tests which elicit reflex changes in heart rate. Few well-documented normal ranges are available for these tests. The present study was designed to investigate the effect of age upon heart rate variability at rest and in response to a single deep breath, the Valsalva manoeuvre, and standing. A computerised method of measurement of R-R interval variation was used to study heart rate responses in 310 healthy subjects aged 18-85 years. Heart rate variation during each procedure showed a skewed distribution and a statistically significant negative correlation with age. Normal ranges (90% and 95% confidence limits) for subjects aged 20-75 years were calculated for heart rate difference (max-min) and ratio (max/min) and standard deviation (SD). Heart rate responses were less than the 95th centile in at least one of the four procedures in 39 (12-6%) out of the 310 subjects, and were below this limit in two or more tests in five (1 6%) subjects. In view of the decline in heart rate variation with increasing age, normal ranges for tests of autonomic function must be related to the age of the subject.

We measured serum levels of free leptin, bound leptin, and soluble leptin receptor by specific RIA methods in 20 normal and 19 insulin-dependent diabetes mellitus subjects at 20 and 30 weeks gestation and postpartum, and analyzed the data using hierarchical statistical models. Total leptin levels rise from 20-30 weeks gestation (688 +/- 58 to 785 +/- 62 pmol/L, mean +/- SEM; P = 0.009). There is a significant postpartum fall to 445 +/- 47 pmol/L (P < 0.001). This rise is caused by the rise in the bound leptin levels, as there is no significant change in free leptin levels between 20 and 30 weeks (P = 0.17). There is a significant postpartum fall in free leptin levels (P < 0.001). Insulin requirements rise in the third trimester, but despite this there was no significant difference in free or bound leptin levels between the normal and diabetic subjects at any stage [free leptin, 223 +/- 35 and 266 +/- 24, 237 +/- 45 and 223 +/- 27, and 109 +/- 16 and 104 +/- 24 (P = 0.34); bound leptin, 410 +/- 73 and 428 +/- 54, 501 +/- 78 and 562 +/- 71, and 330 +/- 47 and 271 +/- 46 (P = 0.84); for normals and diabetics at 20 and 30 weeks gestation and postpartum, respectively]. Diabetic subjects, however, had significantly higher soluble leptin receptor levels at all stages (P << 0.001), which rose further in the third trimester from 3742 +/- 268 (mean +/- SEM) to 4134 +/- 239 pmol/L, whereas in the normal group there was a fall from 3149 +/- 169 to 2712 +/- 123 (P = 0.05). There is a linear relationship between the soluble leptin receptor levels and the body mass index in the diabetic group only. We conclude that there is no significant difference in free or bound leptin levels between the normal and insulin-dependent diabetic subjects either during pregnancy or postpartum, but female insulin-dependent diabetic subjects have significantly higher soluble leptin receptor levels. We speculate that high soluble leptin receptor levels might be implicated in the development of the leptin resistance in this group.

No abstract

Microalbuminuria is reduced significantly by ramipril treatment in type 1 diabetic patients without hypertension. Although the magnitude of the response was greater, there is no significant difference between responses to 1.25 or 5 mg ramipril. Small but highly significant reductions in systolic and mean arterial pressures occur in ramipril-treated patients. GFR is stable at this stage of the evolution of diabetic nephropathy and is unaffected by ramipril treatment for 2 years.

RBP-4 levels are elevated in women with GDM, but do not correlate with IR indices and correlate negatively with sVCAM-1. The physiological significance of RBP-4 rise in women with GDM remains to be elucidated.