Microalbuminuria in diabetes: relationships between urinary albumin excretion and diabetes-related variables

A single observer reviewed 842 of the 917 known diabetic patients registered with 40 GPs in the Poole area. Fifty-nine per cent (493) of those reviewed submitted a timed overnight urine collection to measure albumin excretion rate (AER) and overnight albumin/creatinine ratio (ON-Alb/Creat); 43 samples were excluded because of urinary tract infection and/or proteinuria. A random urine sample was obtained in 607 diabetic patients to measure the random albumin/creatinine ratio (R-Alb/Creat); 68 specimens were excluded because of infection and/or proteinuria, and in a further 10 samples urinary creatinine was not measured. Stepwise multiple regression analyses found significant associations with the following variables: for AER, blood glucose (p = 0.001), smoking category (p = 0.002), sex (p = 0.034), and systolic blood pressure (p = 0.035); for R-Alb/Creat, blood glucose (p = 0.001), retinopathy (p = 0.004), systolic blood pressure (p = 0.004), diastolic blood pressure (p = 0.015), coronary artery disease (p = 0.02), sex (p = 0.034), and vibration sense (p = 0.038). Interestingly, glycosylated haemoglobin was not a significant determinant of albuminuria in either analysis.     

Multiple Cerebral Haematomata and Peripheral Nerve Palsies Associated with a Case of Juvenile Diabetic Ketoacidosis

A 15-year-old girl presented de novo in diabetic ketoacidosis having been comatose for 24 h (day 1). A CT scan and lumbar puncture performed on admission were normal and her conscious level slowly improved over several days. On day 7 she had central neurological signs of bilateral knee clonus and an extensor plantar response. In addition, she had developed lower motor neurological signs of an ulnar nerve palsy of the left forearm, and ulnar, median, and radial nerve palsies of the right forearm. Magnetic resonance imaging (MRI), performed on day 12, showed multiple small cerebral haematomata with appearances at least several days of age. The scattered lesions were localized particularly to the parieto-occipital region, with sparing of the basal ganglia and without cerebral oedema, a novel feature not previously described in juvenile ketoacidosis. Four months later there was minimal residual disability of her right arm. The clinical findings together with the MRI images suggested that the peripheral nerve and central lesions were temporally related, suggesting a common aetiology. However, it is likely that MRI showed cerebral lesions which may have been missed by the conventional CT scanning performed initially.     

Heart rate fluctuations in diabetic patients with cardiac vagal dysfunction: a spectral analysis

The autonomic nervous control of cardiac function during active orthostatic load has been studied by measuring the power spectrum of heart rate fluctuations in 16 insulin-dependent diabetic patients and 14 age-matched control subjects. The patients were subdivided into two groups: 8 with normal respiratory sinus dysrhythmia (RSA+) and 8 with reduced respiratory sinus dysrhythmia (RSA-). In RSA- patients the total power (0.01-0.50 Hz) was significantly reduced compared with control subjects (4.7 versus 15.5 min-2, 2p less than 0.05) and the pattern of heart rate fluctuations was characterized by a relative increase in the low-frequency component (0.01-0.05 Hz) as compared with RSA+ patients and control subjects (45% versus 24% and 27%, both 2p less than 0.01). There was also a significant reduction in the high-frequency component (0.15-0.50 Hz) as compared with RSA+ patients and control subjects (17% versus 36% and 33%, both 2p less than 0.05). During standing, a significant increase in total power was found only in control subjects (2p less than 0.01) and the difference between control subjects, and RSA+ and RSA- patients reached significance (32.2 versus 15.1 and 12.7 min-2, 2p less than 0.02 and 2p less than 0.01). The pattern of heart rate fluctuations in RSA- patients showed no significant change on standing. These results suggest that the reduced overall heart rate variability in diabetic patients with cardiac autonomic neuropathy is associated with a typical heart rate fluctuation pattern.     

Abnormal Digital Pressure Measurements in Diabetic Neuropathic Foot Ulceration

The diabetic neuropathic ulcer is typically slow to heal and recurrent. Macrovascular insufficiency is usually excluded as foot pulses are present and ankle:brachial pressure ratios are not decreased. These assessments cannot however exclude more distal vascular disease. Digital pressure measurements enable a reliable assessment of the distal peripheral vascular status to be made. The aim of this study was therefore to use toe pressures to assess the contribution of distal ischaemia in the pathogenesis of the neuropathic ulcer. Sixteen diabetic patients with recurrent neuropathic foot ulceration had their toe pressures compared to 10 neuropathic patients without a history of foot ulceration, 10 diabetic control subjects, and 11 normal subjects. Four non-diabetic patients with neuropathy and foot ulceration were also assessed. All subjects had ankle:brachial pressure indices ≧ 1. Toe pressure was assessed using laser Doppler flowmetry to record the return of skin blood flow. The toe:brachial pressure index (TBI) was then calculated. The diabetic patients with a history of recurrent neuropathic ulceration, had the lowest mean TBI, 0.63 ± 0.14 (SD), compared to the non-ulcerated diabetic neuropathy patients, the diabetic control subjects, and the normal subjects. 0.84 ± 0.11, 0.82 ± 0.1, and 0.81 ± 0.07, p < 0.01, respectively. Three of the four non-diabetic patients with neuropathic foot ulceration also had an abnormally low TBI. Reduced toe pressure measurements are thus found to be associated with neuropathic foot ulceration. The contribution of distal ischaemia in the pathogenesis of the diabetic neuropathic foot ulcer needs to be evaluated. One hundred and eight non-insulin-dependent diabetic patients who had been tested for autonomic dysfunction in 1984/85 were re-evaluated 5 years later. Autonomic function was assessed by means of four cardiovascular tests (heart rate variation during deep breathing and standing, and blood pressure variation after standing and sustained handgrip). Eighteen subjects were lost to follow-up; in the 90 patients who completed the study, both the deep breathing and the handgrip test significantly worsened (respectively from 13.7 ± 7.8 to 11.6 ± 6.3 beats min^?1 p < 0.01, and from 16.9 ± 8.2 to 12.7 ± 7.1 mmHg, p < 0.001), whereas both the 30:15 ratio and the variation of blood pressure on standing did not change. The impairment of a comprehensive evaluation score (from 2.5 ± 1.7 to 3.0 ± 1.5; p < 0.05) also confirmed the gradual deterioration of autonomic function over the study period.     

Dietary factors and progression of diabetic nephropathy

The role of dietary factors in patients with type 1 (insulin-dependent) diabetes is reviewed by examining three different aspects: the effect of an acute protein load, the effect of dietary protein restriction on the progression of nephropathy and the metabolic effects of low-protein diets. After an acute protein load some impairment of the renal functional reserve may be observed only in patients with type 1 diabetes and overt nephropathy. However, the renal functional reserve is not able to give useful indications of the extent of renal damage and the prognosis of the disease. Both short-term and long-term dietary protein restriction are followed by a significant decrease in glomerular filtration rate (GFR) and albuminuria in type 1 diabetics with incipient nephropathy. In patients with overt nephropathy the long-term administration of a low-protein diet is followed by significant reductions in the rate of decline of GFR and in urinary protein excretion only when started at GFR values higher than 45 ml/min. The rate of functional deterioration when dietary treatment is prescribed seems critical in modulating the effects of a low-protein diet. In addition, low-protein diets may exert important metabolic and clinical effects beyond their supposed effect on progression. Clearly, an adequate dietary regimen is only part of the medical treatment in patients with diabetic nephropathy.     

Genomic structure and eight novel exonic polymorphisms of the human N-cadherin gene

 Analysis of the detailed genomic structure of human N-cadherin revealed that the 16-exon gene is more than 72 kb in length and that it consists of a mosaic of exons. Five repeated cadherin domains, a transmembrane domain, and a cytoplasmic domain are encoded by exons 4 to 13, 13 and 14, and 14 to 16, respectively. A search for molecular variants in the entire coding region in 96 Japanese individuals resulted in the identification of eight sequence polymorphisms including three CCT- or GCC-type trinucleotide repeat polymorphisms adjacent to the initiation codon and five other novel single-nucleoticle polymorphisms (SNPs) in the coding region. Three of the five SNPs accompanied an amino acid substitution: Ala118Thr, Ala826Thr, and Asn845Ser. Knowlege of the fine gene structure and eight novel polymorphisms will be useful for the genetic study of the role of N-cadherin in diseases involving cell adhesion in the brain and in cardiomyocytes. Received: January 23, 2002 / Accepted: March 12, 2002