Plasma glucose control and arterial pressure were assessed in 28 Type 1 (insulin-dependent) diabetic patients with different degrees of micro-albuminuria. They were divided into two groups according to their urinary albumin excretion rate: a low micro-albuminuria group (n = 16) with albumin excretion ranging between 12.1 and 28.9 micrograms/min and a high micro-albuminuria group (n = 12) with albumin excretion between 32.4 and 91.3 micrograms/min. The groups were matched for age, sex and duration of diabetes with the same number of normo-albuminuric (2.0-10.4 micrograms/min) diabetic control subjects. Both the low and high micro-albuminuria groups had significantly higher glycosylated haemoglobin levels and mean plasma glucose concentrations during a 24-h profile than their respective normo-albuminuric control subjects. A correlation between glycosylated haemoglobin level and urinary albumin excretion rate was found in the whole study group (r = 0.48; p less than 0.001). Arterial pressure (both systolic and diastolic) was significantly higher in the high micro-albuminuria group than in either the control group or the low micro-albuminuria group. A significant correlation was found between arterial pressure and albumin excretion rate in the whole study population (r = 0.49; p less than 0.001) as well as in the pooled micro-albuminuria groups (r = 0.43; p less than 0.05). Multiple regression analysis showed that glycosylated haemoglobin and arterial pressure levels were independently correlated with albumin excretion rates. Diabetic patients with micro-albuminuria of any degree have worse glycaemic control than normo-albuminuric patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Background:The combination of the reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib with gemcitabine obtained FDA approval for treating patients with pancreatic cancer. However, duration of response is often limited and there is currently no reliable predictive marker.Methods:We determined the sensitivity of a panel of human pancreatic tumour cell lines to treatment with afatinib, erlotinib, monoclonal antibody (mAb) ICR62, and gemcitabine, using the Sulforhodamine B colorimetric assay. The effect of these agents on cell signalling and cell-cycle distribution was determined by western blot and flow cytometry, respectively.Results:At 200 n, ICR62 had no effect on growth of these tumour cells with the exception of BxPC-3 cells. BxPC-3 cells were also sensitive to treatment with afatinib and erlotinib with respective IC50 values of 11 and 1200 n. Compared with erlotinib, afatinib was also more effective in inhibiting the growth of the other human pancreatic tumour cell lines and in blocking the EGF-induced phosphorylation of tyrosine, EGFR, MAPK, and AKT. When tested in BxPC-3 xenografts, afatinib induced significant delay in tumour growth.Conclusion:The superiority of afatinib in this study encourages further investigation on the therapeutic potential of afatinib as a single agent or in combination with gemcitabine in pancreatic cancer.
The effect of long term correction of hyperglycaemia on the rate of deterioration of renal function was studied in six insulin dependent diabetics with proteinuria due to diabetic nephropathy.
The excretion rates of albumin, IgG and beta 2-microglobulin were studied in insulin-dependent diabetic patients with (Albustix positive) and without (Albustix negative) clinical proteinuria and in a group of nondiabetic controls. In patients negative for clinical proteinuria, the mean excretion rate of albumin and IgG was increased but that of beta 2-microglobulin was normal. HbA1, a measure of excess glycemia, was positively correlated with both albumin and IgG urinary excretion rates. Vigorous correction of glycemic control significantly reduced IgG excretion in nine patients. In patients positive for clinical proteinuria, albumin and IgG clearances were inversely correlated with GFR, the filtration of IgG increasing relatively more than that of albumin as GFR declined. A negative hyperbolic correlation was found between GFR and beta 2-micro-globulin excretion. In this group HbA1 was unrelated to excretion rates or clearances of albumin and IgG. In clinically proteinuric patients, long-term correction of hyperglycemia by continuous subcutaneous insulin infusion failed to check the increasing albumin and IgG filtration. The microproteinuria of diabetes is glomerular in origin, is influenced by prevailing glycemia, and is reversible by vigorous glycemic control. In the clinically proteinuric phase, by contrast, selectivity is progressively lost and, as GFR falls, proteinuria becomes of a mixed glomerular and tubular origin. There is no evident association with prevailing glycemia, and metabolic near-normalization dose not appear to affect progression over the period of observation considered. This study suggests that clinical proteinuria denotes the installation of a self-maintaining process, largely independent of the diabetic metabolic disturbance which gave rise to it. Prevention of clinical diabetic nephropathy by metabolic correction may be achievable only in the phase of early microproteinuria.
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