The Syndrome of Hyperglycaemia without Glycosuria - An Overview
Asian Journal of Research in Nephrology,
The importance of hyperglycaemia without glycosuria, seems to have been under played, as evidenced by the paucity of reports about the same, in the literature. Ralph H. Major et al.  observed in JAMA, on review of literature till then, that there was no reported case as such, in the literature before. CF. Davidson et al.  reported in the Journal of Endocrinology, that between 1932 t0 1937 inclusive, not even a single case of hyperglycaemia without glycosuria was reported in the literature. Hardly there are not even a handful of cases reported till this date, as observed by this author. The awareness appears to be low, as regards to the significance of this syndrome. With the dispensing off, of urine glucose testing, consequent to the advent of home monitoring of the blood sugar with glucometer, there is a every chance of missing this entity. The complacency, that this is just as sequel to the increased renal threshold /tubular maximum that occurs in the natural history of long standing DM2, could also be contributory for not taking this syndrome seriously. This fatalistic attitude, might under score the underlying structural and functional damage of the kidneys. This article aims to shift the emphasis to renal glomerular than tubular pathology, leading to the syndrome of hyperglycaemia without glycosuria.DM2, being the leading cause of the end stage renal disease (ESRD),focus on this syndrome is expected to create awareness among the patients of DM2,about the underlying serious structural and functional damage, to their kidneys. This syndrome is hoped to serve as a biomarker of DKD (diabetic kidney disease) progressing to ESRD, which helps the diabetic patient to seek nephrologist's consultation/ intervention earlier than otherwise. It could serve as a prelude for ordering other tests like estimated glomerular filtration rate (eGFR) and protein –creatinine (PCR) ratio etc. The necessary pathophysiological basis is provided for proper understanding of this syndrome along with review of literature and emphasis on its importance in the early recognition and prevention of ESRD, are focussed in this article.
- Diabetic nephropathy
- KW syndrome
- glomerular nodulosclerosis
- renal threshold
- transport maximum
- end stage renal disease
How to Cite
Davidson CF. Hyperglycemia without Glycosuria, Endocrinology. 1938;22(4):493 –496.
Wright M, Hirayama BA, Loo DF. Active sugar transport in health and disease J Intern Med. 2007;261:32-43.
Fine J. Glucose content of normal urine. Br Med J. 1965;1:1209–214.
Davidson JK, Delcher HK, Hall WD. Glucosuria and ketonuria in Clinical Methods, 2nd Edition, Hurst JW, ed. 535] 1978;1035–1039.
Xiao-Dan Yue, Jing-Yu. Characteristics and impact factors of renal threshold for glucose excretion in patients with type 2. Diabetes Mellitus Med Sci. 2017;32(4): 62[1–627.
Feingold KF. The danger of a changing renal threshold for glucose. Diabetes Care. 1980;3:570–571.
Hieshima K, Sugiyama S, Yoshida A, Kurinami N, Suzuki T, et al. High eRTg is associated with low GIR and high HbA1c, elevation of the renal threshold for glucose is associated with insulin resistance and higher glycated hemoglobin levels. J Diabetes Investig. 2020;11(3): 617-6255.
Valenta CL. Urine testing and home blood-glucose monitoring in Nurs Clin North. Am Vol. 1983;645–659.
Gupta RC, Goyal A, Ghosh R, Punjabi M, Singh PP. Normal range for glucose in uri ne: Age-related changes. Clin Chem. 1982; 28:2335.
Robertson JA, Gray CH. Mechanism of lowered renal threshold for glucose in diabetes. Lancet. 1953;2:12–15.
Johansen K, Svendsen PA, Lorup B. Variations in renal threshold for glucose in type I (insulin-dependent) diabetes mellitus. Diabetologia. 1984;26:180–182.
Moe OW, Wright SH, Palac M. Renal handling of organic solute Brenner BM, Rector FC (Eds.), Brenner & Rector’s the kidney (8th edn.), Saunders Elsevier, Phila delphia. 2008;214-247.
Vallon V, Platt KA, Cunard R, et al. SGLT2 mediates glucose reabsorption in the early proximal tubule. J Am Soc Nephrol. 2011; 22:104–112.
Wilding JP. The role of the kidneys in glucose homeostasis in type 2 diabetes: Clinical implications and therapeutic significance through sodium glucose co-transporter 2 inhibitors. Metabolism. 2014; 63:1228–1237.
Davidson MB. The case for routinely testing the first-voided urine speci men. Diabetes Care. 1981;4:443–444.
Lawrence RD. Renal threshold for glucose: Normal and in diabetics. Br Med J. 1940; 1:766–68.
Sidon A. Blood sugar versus urine sugar. JAMA. 1939;112:2503–2508.
Marsenic O. Glucose control by the kidney: An emerging target in diabetes. Am J Kidney Dis. 2009;53:875.
Wilding JP. The role of the kidneys in glucose homeostasis in type 2 diabetes: Clinical implications and therapeutic significance through sodium glucose co-transporter inhibitors. Metabolism. 2014; 63:1228–1237.
Walford S, Page MMcB, Allison SP. The influence of renal threshold on the interpretation of urine tests for glucose in diabetic patients. Diabetes Care. 1980;3: 672–674.
Davidson MB. The case for routinely testing the first-voided urine specimen. Diabetes Care. 1981;4:443–444.
Rose Burton, Rennke, Helmut. Renal pathophysiology – the essentials (1st ed.). Philadelphia: Lippincott Williams & Wilkins. 1994;194.
Charles T. Stone, hyperglycemia without glycosuria in one thousand diabetic patients. JAMA. 1926;87(6):388-390.
Perry Mcullagh E, William N. Fewel Corona Del Mar et al. Significance of hyperglycaemia without glycosuria: Ten to twenty eight year study. JAMA. 1954; 156(10):925-929.
Greene SA, Dalton RN, Turner C, Haycock GB, Chantler C. Hyperglycaemia without glycosuria: Effect on inulin and para-amino hippocrates clearance. Kidneyint. 1987; 32(6):896-9.
Rahmoune H, Thompson PW, Ward JM, Smith CD, Hong G, Brown J. Gucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin- dependent diabetes. Diabetes. 2005;54:3427–34.
Aukland K. Myogenic mechanisms in the kidney. J Hypertens Suppl. 1989;7(4):S71-6; discussion S77.
Remuzzi G, Perico N, Macia M, Ruggenenti P. The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease. Kidney Int Suppl. 2005;(99):S57-65.
Reutens AT. Epidemiology of diabetic kidney disease. Medical Clinics of North America. 2013;97(1):1–18.
Mechanistic insights from gene-manipulated mice. kidney Int. 2008;74: 418–26.
Najafian B, Alpers CE, Fogo AB. Pathology of human diabetic nephropathy. Contrib Nephrol. 2011;170:36-47.
Vallon V, Thomson SC. Renal function in diabetic disease models: The tubular system in the pathophysiology of the diabetic kidney. Annu Rev Physiol. 2012; 74:351–375.
The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The diabetes control and complications trial research group. The New England Journal of Medicine. 1993;329(14):977–986.
Effect of intensive blood-glucose control with metformin on complications in over weight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group,” The Lancet, 1998; 352(9131):854–865.
Ritz E, Rychlik I, Locatelli F, Halimi S. End-stage renal failure in type 2 diabetes: A medical catastrophe of worldwide dimensions. Am J Kidney Dis. 1999;34: 795.
Centers for disease control and prevention. Chronic Kidney Disease in the United States, Atlanta, GA: US. Department of Health and Human Services, Centers for Disease Control and Prevention; 2019.
Gobe GC, Johnson DW. Distal tubular epithelial cells of the kidney: Potential support for proximal tubular cell survival after renal injury. Int J Biochem Cell Biol. 2007;39:1551–1561.
Vaughan M, Quaggin S. How Do Mesangial and Endothelial Cells Form the Glomerular Tuft? Journal of the American Society of Nephrology. 2008;19(1):24–33.
Guyton AC, Hall JE. Chapter 27: Urine formation by the kidneys: II Tubular processing of the Glomerular Filtrate. In: Textbook Of Medical Physiology (11th Edition). Guyton AC, Hall JE (Eds). Elsevier Saunders, Philadelphia, Pennsy lvania. 2006;327–347.
Schlondorff D, Banas B. The mesangial cell revisited: No cell is an Island. Journal of the American Society of Nephrology. 2009;20(6):1179–1187.
Ren Y, Carretero O, Garvin J. Role of mesangial cells j tubuloglomerular feedback. Kidney International. 2002; 62(2):525–531.
Ayo SH, Radnik RA, Garoni JA, Glass WF, Kreisberg JI. High glucose causes an increase in extracellular matrix proteins in cultured mesangial cells. American Journal of Pathology. 1990;136(6):1339–1348.
Miner JH. Renal basement membrane components. Kidney International. 1999; 56(6):2016–2024.
Mason RM, Wahab NA. Extracellular matrix metabolism in diabetic nephropathy. Journal of the American Society of Nephrology. 2003;14(5):1358–1373.
Ziyadeh FN. Renal tubular basement membrane and collagen type IV in diabetes mellitus. Kidney International. 1993;43(1):114–120.
Nerlich A, Schleicher E. Immunohisto chemical localization of extracellular matrix components in human diabetic glomerular lesions. American Journal of Pathology, 1991;139(4):889–899.
Bright R. Original papers of richard bright on renal disease. London: Oxford Univer sity Press; 1937.
Rosenbaum JL, Mikail M, Wiedmann F. Further correlation of renal function with kidney biopsy in chronic renal disease. Am J Med Sci. 1967;254:156–160.
Chevalier L et al. The proximal tubule is the primary target of injury and progression of kidney disease: Role of the glomeru lotubular junction .Am J Physiol Renal Physiol. 2016;311(1): F145–F161.
Kriz W, LeHir M. Pathways to nephron loss starting from glomerular diseases - Insights from animal models. Kidney Int. 2005;67:404–419.
Hall AM, Unwin RJ, Parker N, Duchen MR. Multiphoton imaging reveals differen ces in mitochondrial function between nephron segments. J Am Soc Nephrol. 2009; 20:1293–1302.
Alicic RZ, Tuttle KR. Novel therapies for diabetic kidney disease. Advances in Chronic Kidney Disease. 2014;21(2):121–133.
Schwartz MM, Lewis EJ, Leonard-Martin T et al. Renal pathology patterns in type II diabetes mellitus: Relationship with retinopathy. Nephrology Dialysis Transplantation. 1998;13(10):2547–2552.
MacIsaac RJ, Tsalamandris C, Panagioto poulos S, Smith TJ, McNeil KJ, Jerums G. Nonalbuminuric renal insufficien cy in type 2 diabetes. Diabetes Care. 2004;27(1): 195–200.
Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013; 3:1-150.9911x.
Athologic classification of diabetic nephropathy. J Am Soc Nephrol. 2010; 21(4):556-63.
Futrakul N, Futrakul P. Biomarker for early renal microvascular and diabetic kidney diseases. Ren Fail. 2017;39(1):505-511.
Abstract View: 407 times
PDF Download: 333 times