Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Beta-adrenoceptors desensitization may modulate catecholamine induced insulin resistance in human pheochromocytoma

Catecholamines acutely exert a pronounced insulin-antagonistic effect, which is mediated by beta-adrenergic receptors stimulation. Nevertheless, several patients with pheochromocytoma fail to exhibit an overt diabetic syndrome, in spite of steadily elevated plasma levels of catecholamines. This prompted us to investigate a 16 years old male patient, bearing an extra-adrenal pheochromocytoma, who displayed a slightly impaired glucose tolerance to oral glucose tolerance test, whereas fasting and post-prandial blood glucose, as well as glycaemic response to intravenous glucagon, were in the normal range. Peripheral insulin sensitivity, as evaluated by intravenous insulin tolerance test, was slightly decreased. Supine norepinephrine plasma levels were steadily upon 9 ng/ml; plasma insulin, both fasting and post-prandial, was within the normal range. beta-adrenergic receptors density of peripheral mononuclear cells was strongly reduced when compared to controls (0.97 +/- 0.08 vs 2.82 +/- 0.37 fmol/10(6) cells), without any concomitant change of affinity. Insulin binding to circulating monocytes was reduced as well (2.38 +/- 0.27 vs 5.1 +/- 0.4%/10(7) monocytes); insulin receptor affinity was quite normal (1.7 ng/ml) and total receptor number was 9,200 sites/cell. In desensitization experiments, 1 microM isoproterenol caused only a 20% decrease of beta-adrenergic receptors density in the patient's cells (70% decrease in controls). Six months after surgery, all the above modifications of receptor binding, as well as the mild glucose intolerance, were almost completely reversed. Thus, high levels of norepinephrine were able to induce a decrease of both beta-adrenoceptor and insulin receptor binding, together with a marked reduction of in vitro agonist-induced redistribution of beta-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS