Renal disease in people with insulin-dependent diabetes (IDDM) continues to pose a major health threat. Inhibitors of angiotensin-converting enzyme (ACE) slow the decline of renal function in ...advanced renal disease, but their effects at earlier stages are unclear, and the degree of albuminuria at which treatment should start is not known.
We carried out a randomised, double-blind, placebo-controlled trial of the ACE inhibitor lisinopril in 530 men and women with IDDM aged 20–59 years with normoalbuminuria or microalbuminuria. Patients were recruited from 18 European centres, and were not on medication for hypertension. Resting blood pressure at entry was at least 75 and no more than 90 mm hg diastolic, and no more than 155 mm hg systolic. Urinary albumin excretion rate (AER) was centrally assessed by means of two overnight urine collections at baseline, 6, 12, 18, and 24 months.
There were no differences in baseline characteristics by treatment group; mean AER was 8.0 μg/min in both groups; and prevalence of microalbuminuria was 13% and 17% in the placebo and lisinopril groups, respectively. On intention-to-treat analysis at 2 years, AER was 2.2 μg/min lower in the lisinopril than in the placebo group, a percentage difference of 18.8% (95% CI 2·0–32·7, p=0·03), adjusted for baseline AER and centre, absolute difference 2.2 μg/min. In people with normoalbuminuria, the treatment difference was 1·0 μg/min (12·7% −2·9 to 26·0, p=0·1). In those with microalbuminuria, however, the treatment difference was 34.2 μg/min (49·7% −14·5 to 77·9, p=0·1; for interaction, p=0·04). For patients who completed 24 months on the trial, the final treatment difference in AER was 38·5 μg/min in those with microalbuminuria at baseline (p=0·001), and 0·23 μg/min in those with normoalbuminuria at baseline (p=0·6). There was no treatment difference in hypoglycaemic events or in metabolic control as assessed by glycated haemoglobin.
Lisinopril slows the progression of renal disease in normotensive IDDM patients with little or no albuminuria, though greatest effect was in those with microalbuminuria (AER ≥20 μg/min). Our results show that lisinopril does not increase the risk of hypoglycaemic events in IDDM.
The Eurodiab Insulin Dependent Diabetes (IDDM) Complications Study was a cross-sectional investigation of a stratified random sample of IDDM patients attending 31 clinics in 16 European countries. We ...compared the findings in the only participating Irish centre (Cork Regional Hospital) with those of the study group as a whole. There were fewer episodes of ketosis but severe hypoglycaemia occurred more frequently in Cork patients, when compared to the full study group. There were no significant differences in the prevalence of background retinopathy, proliferative retinopathy, microalbuminuria, macroalbuminuria or peripheral neuropathy, when the two groups were compared. However, autonomic neuropathy was significantly less common in Cork. The prevalence of cardiovascular disease was slightly lower than the Eurodiab average in Cork patients, and cardiovascular risk factors were more favourable. Waist-hip ratio and total plasma cholesterol were significantly lower than in the full study group. The prevalence of hypertension was similar, but there were fewer smokers in Cork than in most other centres.
The concentrations of angiotensin II and aldosterone in plasma were measured in 101 consecutive unselected out-patient diabetic patients and in fifty-three normal controls. The concentration of ...angiotensin II was similar in diabetics without complications and controls, but was significantly lower in patients with hypertension or peripheral neuropathy. In contrast, plasma aldosterone was not reduced in any sub-group. The concentrations of angiotensin II and aldosterone were positively correlated in controls, in diabetes without complications and in hypertensive diabetics, but this relationship was not found in patients with peripheral neuropathy, retinopathy or nephropathy. There was no evidence of overt hypoaldosteronism in any of the diabetic patients. No individual aldosterone concentration was below the range found in controls and no plasma angiotensin II concentration is reduced in patients with specific diabetic complications such as neuropathy, plasma aldosterone may be maintained by factors other than the renin-angiotensin system. This would explain why hypoaldosteronism is rare among unselected diabetics.
On-chip analog self-healing requires low-cost sensors to accurately measure various performance metrics. In this paper we propose a novel approach of indirect performance sensing based upon Bayesian ...model fusion (BMF) to facilitate inexpensive-yet-accurate on-chip performance measurement. A 25GHz differential Colpitts voltage-controlled oscillator (VCO) designed in a 32nm CMOS SOI process is used to validate the proposed indirect performance sensing and self-healing methodology. Our silicon measurement results demonstrate that the parametric yield of the VCO is improved from 0% to 69.17% for a wafer after the proposed self-healing is applied.
We investigated whether or not an increased pressor response to exercise or stress is a feature of the diabetic state per se or a feature of its complications was investigated. Twelve ...insulin-dependent diabetic patients without clinical evidence of complications and with normal albumin excretion rates (less than 20 micrograms/min) were studied together with 12 matched control subjects. Each underwent a study protocol of isometric handgrip exercise at 30% of maximum capacity for four minutes, a cold pressor test with immersion of one hand in ice-cold water for two minutes, and bicycle ergometry at a resistance of 105 watts per minute for six minutes. The tests were undertaken in the same order in all subjects. There was, in both groups, a similar and significant rise in systolic blood pressure and pulse rate in response to each stimulus. Diastolic pressure also rose significantly in response to handgrip exercise and to cold pressor stimulation, but fell slightly during bicycle ergometry in both groups. Mean plasma noradrenaline concentration rose in response to each stimulus but the changes reached conventional significance in both groups only in response to handgrip exercise. Pressor responses to exercise and stress, as tested here, are concluded to be normal in insulin-dependent diabetic patients without complications due to their disease.
Pregnancy is believed to exacerbate diabetes complications, although the degree to which this occurs, and the advice that should be given to women contemplating pregnancy is unclear. We examined 776 ...nulliparous and 582 parous women with Type 1 diabetes from a cross-sectional study performed in 31 European centres. Glycaemic control was better in parous women. Age and duration adjusted prevalence of microalbuminuria was similar in parous and nulliparous women, but macroalbuminuria was lower in parous women (6% versus 10%, p < 0.0001). Prevalence of all retinopathy was lower in parous women (34% in women who had two or more pregnancies, 45% in women who had one), compared with 48% in nulliparous women (chi 2 for trend = 47.1, p < 0.0001). Proliferative retinopathy was lower in parous (8% and 7%, respectively) compared with nulliparous women (16%, chi 2 for trend = 52.2, p < 0.0001). These differences persisted when adjusted for glycaemic control. Excluding referrals for pregnancy, parous women were more likely to have been referred to the diabetes clinic with complications than nulliparous women (p = 0.001). It is unlikely that our findings can be explained by women with complications being advised against pregnancy, or by the better glycaemic control in parous women. Equivalent levels of microalbuminuria and background retinopathy in parous and nulliparous women suggests that pregnancy may not exacerbate these early complications.
Two patients with both primary hyperparathyroidism and primary hyperaldosteronism are described. Each presented with high blood pressure and a history of renal calculi. Mild hypercalcaemia was ...associated with raised plasma parathyroid hormone concentrations and a parathyroid adenoma was excised from each. Both patients also had hypokalaemia, hyperaldosteronism and low plasma renin concentrations. Quadric analysis, adrenal vein plasma aldosterone concentrations, adrenal venography and CT scanning all suggested an adrenal adenoma in each patient. This suspicion was confirmed at operation in one patient; the other patient is unfit for adrenal surgery but her blood pressure and plasma potassium concentration have remained within the normal range during prolonged treatment with either spironolactone or amiloride. Because of this unusual association a search was made for parathyroid hormone excess in patients with primary hyperaldosteronism and for aldosterone excess in primary hyperparathyroidism. None was found.
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