Since several studies have suggested that a slight increase in urinary albumin excretion (microalbuminuria) is predictive of nephropathy in patients with diabetes mellitus, we studied the relation of albumin excretion to renal structure in patients with insulin-dependent (Type I) diabetes. Renal biopsy specimens were evaluated with light- and electron-microscopical morphometric techniques in 48 patients who had had diabetes for 5 to 40 years and who excreted less than 200 mg of urinary albumin per 24 hours. Patients in Group I (n = 26) had normal urinary albumin excretion, creatinine clearance, and blood pressure; those in Group II (n = 10) had increased urinary albumin excretion but normal creatinine clearance and blood pressure; those in Group III (n = 12) had increased urinary albumin excretion and hypertension, decreased creatinine clearance, or both. Glomerular structure varied similarly, ranging from normal to abnormal in Groups I and II, but was consistently abnormal in Group III. The thickness of the glomerular basement membrane, the fractional volume of the mesangium, and the mesangial volume per glomerulus in Group III exceeded the corresponding values in the other groups significantly. Thus, microalbuminuria, when present with hypertension, decreased creatinine clearance, or both, indicates established abnormalities of glomerular structure. Normal albumin excretion, or microalbuminuria without these other functional abnormalities, does not accurately predict the severity of the underlying glomerular lesions in patients with Type I diabetes.

Fatty acid compositions of phospholipids of heart, liver, kidney, aorta, and serum from rats having streptozotocininduced diabetes were determined and compared with those of nondiabetic controls. Linoleic and dihomo-y-linolenic acids were increased whereas arachidonic acid was decreased in most tissues, suggesting an impairment of A5-desaturase activity. Acids derived from linolenic acid were increased in some diabetic tissues from diabetic animals although the linolenic content was normal, indicating less impairment in the desaturation of the w3 series of fatty acids. Diabetes suppressed all polyunsaturated acids in the whole animal, but the competition between w3 and w6 acids favored the excessive suppression of long-chain w6a acids and an increase in the proportion of w3 acids in lipids of vital tissues. These changes in fatty acid composition of the phospholipids may have significant effects on cellular functions and vasoregulatory control mechanisms in diabetes.Involvement of essential fatty acids (EFA) in diabetes was suggested by the observation that alloxan-induced diabetes accelerated and intensified symptoms of EFA deficiency (1). Changes in fatty acid composition have been reported in both humans (2-4) and animals with diabetes (5)(6)(7)(8). Decreased arachidonic acid in serum is correlated with hyperglycemia (2, 3) and with increased clinical complications. In diabetic rats, decreased arachidonic, palmitoleic, and oleic acids and increased linoleic and docosahexaenoic acids have been found in liver microsomal lipids (8). Conversely, diabetic rats fed an EFA-deficient diet manifest fewer biochemical changes and a higher level of arachidonic acid than do nondiabetic EFA-deficient controls (9). Many changes in fatty acid patterns of diabetic tissues can also result from dietary changes because mammalian cells require exogenous precursors of the long-chain polyunsaturated fatty acids (PUFA) (10, 11). Linoleic acid (18:2w6) § and y-linolenic acid (18:3w3) are the precursors of the w6 and w3 families of PUFA, which are important structural components of tissue lipids, which in turn are precursors of prostaglandins (PGs) and other products of PUFA oxidation important in the regulation of metabolism.This report describes the fatty acid composition of phospholipids (PLs) from several organs of rats made diabetic by streptozotocin, emphasizing the fatty acids of the w6 and w3 series, both known to be essential in humans (11). These two families of PUFA have parallel pathways of metabolism leading to different vasoactive substances (12), which may be related to the pathogenesis of diabetic vascular disease (13,14 In experiment 1, diabetic rats and age-matched nondiabetic controls were fed the chow diet throughout the study to assay whether diabetes influenced the PUFA pattern of rats on a standard rat ration composed of natural feedstuffs. The rats were made diabetic at 49 days of age and killed after 61 days of diabetes. Samples of heart, serum, liver, whole kidney, and abdominal aorta were analyzed.I...

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Overt proteinuria is a hallmark of diabetic nephropathy while microalbuminuria is thought to be a predictor of later onset of diabetic nephropathy. Yet the mechanisms for abnormal urinary protein leak in diabetes have not been defined. We studied 28 patients with type I diabetes for 7 to 33 years. Creatinine clearance, urinary albumin excretion rate (UAE), and multiple blood pressures were obtained in each patient. A renal biopsy was performed in each patient and in 28 normal subjects. Quantitative stereology was used to determine foot process (FP) width, filtration slit length density (FSLV) and filtration slit length/glomerulus (FSLG). FP width was slightly wider than normal in diabetic patients with UAE less than 250 mg/24 hr while FP was significantly wider than both of these groups in diabetics with UAE greater than 250 mg/24 hr. FSLV and FSLG were similar in normals and diabetics with UAE less than 250 mg/24 hr but both were reduced in diabetics with UAE greater than 250 mg/24 hr. UAE correlated with FP width (P less than 0.05), FSLG (P less than 0.01) and most precisely and FSLV (P less than 0.001). Diabetics with microalbuminuria had values for all the structural parameters measured here not different from diabetics with UAE in the normal range. Perturbations of epithelial cell structure are present in diabetes mellitus especially in patients with nephropathy. The exact relationships between albuminuria and epithelial cell structure remains to be elucidated.

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