Glomerular function in Pima Indians with noninsulin-dependent diabetes mellitus of recent onset.

Abstract

Differential solute clearances were used to characterize glomerular function in 20 Pima Indians with noninsulin-dependent diabetes mellitus (NIDDM) of < 3 yr duration. 28 Pima Indians with normal glucose tolerance served as controls. In the diabetic group, the glomerular filtration rate (GFR, iothalamate clearance) exceeded the control value by 15% (140±6 vs. 122±5 ml/min, P < 0.01). A corresponding 12% increase in renal plasma flow (RPF) was not statistically significant and did not account fully for the observed hyperfiltration, suggesting a concomitant elevation of the ultrafiltration pressure or coefficient. The median albumin excretion ratio in NIDDM exceeded control by almost twofold (10.1 vs. 5.8 mg/g creatinine), a trend which just failed to achieve statistical significance (P = 0.06). Fractional clearances of dextrans of broad size distribution were also elevated in diabetic subjects, significantly so for larger dextrans of between 48 and 60 A radius. A theoretical analysis of dextran transport through a heteroporous membrane revealed glomerular pores in NIDDM to be uniformly shifted towards pores of larger size than in controls. We conclude that an impairment of barrier size selectivity combined with high GFR elevates the filtered protein load in NIDDM of recent onset. We propose that enhanced transglomerular trafficking of protein may predispose to sclerosis of glomeruli in those Pima Indians with NIDDM who ultimately develop diabetic nephropathy. (J. Clin. Invest. 1991. 88:524-530.) Key words: hyperfiltration * barrier size-selectivity * transmembrane protein shunting. heteroporous membrane models Introduction Considerable evidence in experimental animals and some indirect evidence in humans suggests that the development ofinsu-

Glomerular size-and charge selectivity in Type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy

“…In Pima Indians with duration of Type 2 diabetes less than 3 years and slightly increased urinary albumin-to-creatinine ratio, fractional clearance of dextran of broad size (48-60 A) was significantly elevated compared to non-diabetic control subjects, suggesting a defect in barrier size selectivity in Type 2 diabetes of recent onset [24]. At present, no studies on dextran clearances in albuminuric Type 2 diabetic patients with diabetic glomerulosclerosis are available.…”

Renal hyperfiltration in type 2 diabetes: effect of age-related decline in glomerular filtration rate

“…Previous reports suggest that the prevalence of hyperfiltration is higher in certain ethnic groups, such as Pima Indians, African-Americans, Asians and Polynesians, than in Caucasians [1,2,8,10,28,29]. However, in these ethnic groups diabetes occurs at an earlier age, and the prevalence rates may be affected by the age-unadjusted definition of hyperfiltration as discussed below.…”

Early Renal Function Decline in Type 2 Diabetes

“…Although the appearance of RFD before the onset of macroalbuminuria could reflect the initiation of progressive kidney disease in some patients, it could also represent a purely functional change in renal vasomotion associated with improvement in diabetes control or simply the intrinsic variability in GFR in the absence of significant histopathological changes (11). Enhanced glomerular perfusion in diabetes is the consequence of a vasomotor disturbance often reflected by an increase in GFR (22,23). The magnitude of this disturbance is variable and can be influenced by various factors, such as age, treatment with renin-angiotensin system blockers, changes in glycemic control, or modifications of dietary protein intake.…”