OBJECTIVE -To determine the prevalence and characteristics of patients with type 2 diabetes who have impaired renal function, defined as a glomerular filtration rate (GFR) Ͻ60 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 , and normoalbuminuria. RESEARCH DESIGN AND METHODS-A cross-sectional survey of 301 outpatients attending a single tertiary referral center using the plasma disappearance of isotopic 99m Tcdiethylene-triamine-penta-acetic acid to measure GFR and at least two measurements of urinary albumin excretion rate (AER) over 24 h to determine albuminuria.RESULTS -A total of 109 patients (36%) had a GFR Ͻ60 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 . The overall prevalence of normo-, micro-, and macroalbuminuria was 43 of 109 (39%), 38 of 109 (35%), and 28 of 109 (26%), respectively. Compared with patients with macroalbuminuria, those with normoalbuminuria were more likely to be older and female. After excluding patients whose normoalbuminuric status was possibly related to the initiation of a renin-angiotensin system (RAS) inhibitor before the start of the study, the prevalence of a GFR Ͻ60 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2and normoalbuminuria was 23%. Temporal changes in GFR in a subset of 34 of 109 (32%) unselected patients with impaired renal function were available for comparison over a 3-to 10-year period. The rates of decline in GFR (ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 ⅐ year Ϫ1 ) of Ϫ4.6 Ϯ 1.0, Ϫ2.8 Ϯ 1.0, and Ϫ3.0 Ϯ 07 were not significantly different for normo-(n ϭ 12), micro-(n ϭ 12), and macroalbuminuric (n ϭ 10) patients, respectively.CONCLUSIONS -These results suggest that patients with type 2 diabetes can commonly progress to a significant degree of renal impairment while remaining normoalbuminuric. Diabetes Care 27:195-200, 2004A reduced glomerular filtration rate (GFR), mainly estimated from creatinine clearance measurements, has been reported to occur in some longstanding normoalbuminuric type 1 diabetic patients (1,2). Work from our group has suggested that this phenomenon can also occur in both type 1 or type 2 diabetes and that it may be more common in type 2 diabetes (3). Furthermore, in comparison to patients with type 1 diabetes, albuminuric patients with type 2 diabetes have a great deal of renal ultrastructural heterogeneity (4,5). This structural heterogeneity raises the possibility that different GFR and AER relationships are seen in patients with type 2 compared with those with type 1 diabetes. We have therefore further investigated the association between GFR and AER in patients with type 2 diabetes. In particular, we determined the prevalence and characteristics of patients with impaired renal function, defined as a GFR Ͻ60 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 , and an AER within the normoalbuminuric range. RESEARCH DESIGN ANDMETHODS -A total of 625 patients attending the diabetes clinic at Austin Health, a tertiary referral center and teaching hospital of The University of Melbourne, Victoria, Australia, were studied between 1990 and 2001 as part of an ongoing project investigating the pathogenesis of diabetic renal disease. Isotopic estimations o...

Experiments to determine the site of slow-wave origin and the mechanism of propagation were performed on muscles of the canine proximal colon. Cells along the submucosal border of the circular layer had resting membrane potentials (RMP) averaging -78 mV, and slow waves, 40 mV in amplitude. The RMP of cells through the thickness of the circular layer decreased exponentially with distance from the submucosal border, such that RMPs of circular cells at the myenteric border were only -43 mV. Slow waves decreased in amplitude through the thickness such that slow waves could not be detected adjacent to the myenteric border. When a thin strip of muscle along the submucosal border was removed, slow waves were not recorded from the bulk of the circular layer and could not be evoked by acetylcholine. Slow waves were still present in the excised strip. Experiments to determine the rate of slow-wave propagation were also performed. Two cells were impaled, one at the submucosal surface, and another at some distance through the circular layer. Slow waves occurred nearly simultaneously at both sites. What latency was observed could be explained on the basis of electrotonic conduction. The results support the hypothesis that in the canine proximal colon slow waves are generated at the extreme submucosal surface of the circular layer. The bulk of the circular layer does not possess either pacemaker or regenerative mechanisms, and slow waves propagate passively toward the myenteric border. The cable properties of the circular muscle syncytium furnish a barrier to invasion of the longitudinal layer by the slow wave event.

Experiments were conducted to evaluate the potential for dietary garlic to influence egg yolk cholesterol concentrations and overall performance in different layer strains. Thirty-six, 28-wk-old, Hisex Brown,Isa Brown, Lohmann, Starcross, Babcock, and Starcross-579 strains (six hens per strain) were fed diets supplemented with 0 (control), 2, 4, 6, 8, or 10% sun-dried garlic paste for 6 wk. There were no differences (P > 0.05) among diets or strains in egg weight, egg mass, feed consumption, feed efficiency, and BW gain as averaged over 6 wk. Yolk weight, however, responded quadratically with increasing levels of dietary garlic and differed among strains (P < 0.05). Egg production and yolk weights were significantly higher in the Babcock strain in comparison with other strains. Serum and egg yolk cholesterol concentrations decreased linearly (P < 0.05) with increasing levels of dietary garlic. Serum and egg yolk cholesterol concentrations also differed among different strains (P < 0.05). It was concluded that garlic paste in the diets of laying hens reduced serum and yolk cholesterol concentrations. It was also concluded that dietary garlic paste had no adverse effects on layer performance.

The effects on morphologically and electrophysiologically characterized myenteric neurons of activation of intestinal reflex pathways were examined in vitro. Opened segments of guinea pig small intestine were pinned serosa down in an organ bath that had two balloons set into its base. A 5-10-mm-wide strip of myenteric plexus between the balloons was exposed from the mucosal side, and neurons were impaled with microelectrodes. Reflex pathways were stimulated by inflation of the balloons to distend the intestinal wall, and by deforming the exposed mucosal villi with a brush. Impaled neurons were classified electrophysiologically as AH-neurons or S-neurons (Hirst et al., 1974) and were injected with biocytin to determine their shapes and projections. None of the 58 AH-neurons responded to distension. In contrast, 63 of 131 S-neurons responded to distension with a burst of fast EPSPs; about one-third of the responding S-neurons received input from ascending reflex pathways, one-third received input from descending reflex pathways, and one-third received input from both ascending and descending pathways. Most neurons in this last group supplied extensive varicose branches to the tertiary plexus and were probably longitudinal muscle motor neurons. Neurons receiving input from only one pathway usually projected in the direction of that pathway; many of these were circular muscle motor neurons. Almost all neurons responding to distension were also excited by deforming the villi. Responses evoked by distension or deforming the mucosa declined when stimuli were repeated at intervals less than 10 sec. This was seen in ascending and descending pathways but was more prominent in the former. Deforming the mucosa evoked a normal response even when the response to repeated distensions had disappeared. It is concluded that distension and deforming the mucosa excite separate populations of sensory neurons to activate reflex pathways that converge onto common motor neurons and probably onto common interneurons.

Aims/hypothesis: We compared the predictive performance of a GFR based on serum cystatin C levels with commonly used creatinine-based methods in subjects with diabetes.