Summary
To determine whether sustained control of hyperglycaemia in Type 2 (non-insulin-dependent) diabetic patients would diminish proteinuria, the effect of hypocaloric diet therapy (500 kcal/day) on proteinuria was assessed in obese, Type 2 diabetic patients (n=24) and compared with results obtained for obese subjects with normal glucose tolerance (n=7) and impaired glucose tolerance (n=6). Diet therapy of similar mean duration resulted in similar percentage weight loss (mean percentage of original weight ±SEM) in diabetic (13.6±1.6%), glucose intolerant (16.4±3.3%) and obese nondiabetic (11.0±1.0%) subjects. Following therapy, plasma glucose concentrations 2h after an oral glucose load declined in the diabetic (18.34±0.81 to 10.67±0.50 mmol/1, mean ±SEM; p<0.001) and in the glucose intolerant subjects (10.2±0.3 to 7.3±0.4 mmol/l, p<0.01) while remaining unchanged in the obese non-diabetic subjects (7.09±0.23 to 6.77±0.32 mmol/l, NS). Concentrations of total protein of plasma origin and albumin in 24-h urine collections were quantified by a sensitive immunonephelometric assay using specific antisera. Initially, 24-h excretion of total protein and albumin were elevated in the diabetic [mg protein/24 h; (median±95% confidence limits): 63 (42–138), p<0.05; albumin: 26 (14–56), p<0.05] and glucose intolerant subjects [protein:52 (13–92), NS; albumin: 24 (3–61), NS] compared with the non-diabetic subjects [protein: 20 (5–38); albumin: 6.2 (3.5–9.5)]. Following diet therapy, both total protein and albumin excretion were reduced significantly in diabetic subjects (p<0.001) and similar decreases were observed in clearance rates of protein and albumin. Initially, 11 out of the 24 diabetic subjects had 24-h albumin excretion in the subclinical range (>30, < 500 mg/24h), whereas following diet therapy, only three out of the 11 had subclinical albuminuria. For all subjects, the decrease in albumin excretion following diet therapy was significantly correlated with the initial albumin excretion (r=0.63, p<0.0001). In one diabetic subject, whose glucose tolerance and albumin excretion were sequentially monitored for 14 months, the decreases in glycaemia and proteinuria observed in the first month of therapy persisted after discontinuation of diet therapy. Thus, metabolic control of Type2 diabetes by a hypocaloric diet produced significant sustained reductions in proteinuria. The question remains whether or not this retards the development of clinical nephropathy or end stage renal disease.
Article PDF
Similar content being viewed by others
References
Tchobroutsky G (1978) Relation of diabetic control to development of microvascular complications. Diabetologia 15: 143–152
Skyler JS (1979) Complications of diabetes mellitus: relationship to metabolic dysfunction. Diabetes Care 2: 499–509
Brownlee M, Cahill GF (1979) Diabetic control and vascular complications. Atheroscl Rev 4: 29–70
Service FJ, Molnar GD, Rosevear JW, Ackerman E, Gatewood LC, Taylor WF (1970) Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes 19: 644–655
Raskin P (1978) Diabetic regulation and its relationship to microangiopathy. Metabolism 27: 235–252
Felig P, Tamborlane WV (1980) Insulin delivery devices. Ann Int Med 93: 627–629
Knowles HC Jr. (1971) Long term juvenile diabetes treated with unmeasured diet. Trans Assoc Am Physicians 84: 95–101
Deckert T, Poulson JE, Larsen M (1978) Prognosis of diabetes with diabetes onset before the age of thirty-one. Diabetologia 14: 363–370
Knowler WC, Bennett PH, Ballintine EJ (1980) Increased incidence of retinopathy in diabetes with elevated blood pressure. New Eng J Med 302: 645–50
Viberti GC, Jarrett RJ, Mahmud LL, Hill RD, Argyropoulus A, Keen H (1981) Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet 1: 1430–1432
Parving HH, Noer I, Deckert T, Eurin PE, Nielsen SL, Lyngsoe J, Mogensen CE, Rorth M, Svendsen PA, Trap-Jensen J, Lassen NA (1976) The effect of metabolic regulation on microvascular permeability to small and large molecules in short-term juvenile diabetics. Diabetologia 12: 161–166
Viberti GC, Pickup JC, Jarrett RJ, Keen H (1979) Effect of control of blood glucose on urinary excretion of albumin and microglobulin in insulin dependent diabetes. N Eng J Med 300: 638–641
Savage PJ, Bennion LJ, Flock EV, Nagulesparan M, Mott D, Roth J, Unger RH, Bennett PH (1979) Diet-induced improvement of abnormalities in insulin and glucagon secretion and in insulin receptor binding in diabetes mellitus. J Clin Endocrinol Metab 48: 999–1007
Rendell M, Zarriello J, Drew HM, Dranbauer B, Wilson G, Ward J, Ross D (1981) Recovery from decompensated non-insulin dependent diabetes mellitus: studies of C-peptide secretion. Diabetes Care 4: 354–359
Keen H, Chlouverakis C (1963) An immunoassay for urinary albumin at low concentrations. Lancet 2: 913–914
Killingsworth LM, Britain CE, Woodard LL (1975) Automated immunochemical method for determination of urinary protein of plasma origin. Clin Chem 21: 1465–1468
Savage PJ, Bennion LJ, Bennett PH (1979) Normalization of insulin and glucagon secretion in ketosis-resistant diabetes mellitus with prolonged therapy. J Clin Endocrinol Metab 49: 830–833
Hollander M, Wolfe D (1973) Non-parametric statistical methods. J Wiley & Sons, New York
Hemmingsen I, Skaarup P (1975) The 24-hour excretion of plasma proteins in the urine of apparently health subjects. Scand J Clin Lab Invest 35: 347–353
Williamson JR, Kilo C (1977) Current status of capillary basement membrane disease in diabetes mellitus. Diabetes 26: 65–73
Lee SM, Bressler R (1981) Prevention of diabetic nephropathy by diet control in the db/db mouse. Diabetes 30: 106–111
Mogensen CE (1971) Urinary albumin excretion in early and longterm juvenile diabetes. Scan J Clin Lab Invest 28: 183–193
Tamborlane WV, Puklin JE, Bergman M, Verdonk C, Rudolf MC, Feiig P, Genel M and Sherwin R (1982) Long-term improvement of metabolic control with the insulin pump does not reverse diabetic microangiopathy. Diabetes Care 5 (Suppl 1): 58–63
Viberti GC, Bilous RW, Mackintosh D, Bendiny JJ and Keen H (1983) Long-term correction of hyperglycaemia and progression of renal failure in insulin-dependent diabetes. Br Med J 286: 598–602
Pettitt DJ, Knowler WC, Lisse JR, Bennett PH (1980) Development of retinopathy and proteinuria in relation to plasma glucose concentrations in Pima Indians. Lancet 2: 1050–1052
Hostetter TH, Helmut GR, Brenner BM (1982) The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies. Am J Med 72: 375–380
Mogensen CE (1971) Kidney function and glomerular permeability to macromolecules in early juvenile diabetes. Scand J Clin Lab Invest 28: 91–100
Mogensen CE (1976) Renal function changes in diabetes. Diabetes 25: 872–879
Christiansen JS, Frandsem M, Parving HH (1981) The effect of intravenous insulin infusion on kidney function in insulin-dependent diabetes mellitus. Diabetologia 20: 199–204
Aronoff SL, Schnider S, Smeltzer J, Mackay W, Tchou P, Rush forth Miller M, Bennett PH (1981) Urinary excretion and renal clearance of specific plasma proteins in diabetes of short and long duration. Diabetes 30: 656–663
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Vasquez, B., Flock, E.V., Savage, P.J. et al. Sustained reduction of proteinuria in Type 2 (non-insulin-dependent) diabetes following diet-induced reduction of hyperglycaemia. Diabetologia 26, 127–133 (1984). https://doi.org/10.1007/BF00281119
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00281119