Summary
We examined the impact of hypertension and microalbuminuria on insulin sensitivity in patients with Type 2 (non-insulin-dependent) diabetes mellitus using the euglycaemic insulin clamp technique in 52 Type 2 diabetic patients and in 19 healthy control subjects. Twenty-five diabetic patients had hypertension and 19 had microalbuminuria. Hypertension per se was associated with a 27% reduction in the rate of total glucose metabolism and a 40% reduction in the rate of non-oxidative glucose metabolism compared with normotensive Type 2 diabetic patients (both p<0.001). Glucose metabolism was also impaired in normotensive microalbuminuric patients compared with normotensive normoalbuminuric patients (29.4±2.2 vs 40.5±2.8 μmol · kg lean body mass−1 · min−1; p=0.012), primarily due to a reduction in non-oxidative glucose metabolism (12.7±2.9 vs 21.1±2.6 μmol · kg lean body mass−1 ·min−1; p=0.06). In a factorial ANOVA design, however, only hypertension (p=0.008) and the combination of hypertension and microalbuminuria (p=0.030) were significantly associated with the rate of glucose metabolism. The highest triglyceride and lowest HDL cholesterol concentrations were observed in Type 2 diabetic patients with both hypertension and microalbuminuria. Of note, glucose metabolism was indistinguishable from that in control subjects in Type 2 diabetic patients without hypertension and microalbuminuria (40.5±2.8 vs 44.4±2.8 μmol · kg lean body mass−1 · min−1). We conclude that insulin resistance in Type 2 diabetes is predominantly associated with either hypertension or microalbuminuria or with both.
Article PDF
Similar content being viewed by others
References
DeFronzo RA (1988) The triumvirate: β-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37: 667–687
Reaven GM (1988) Role of insulin resistance in human disease. Diabetes 37: 1595–1607
Groop L, Bonadonna R, Del Prato S et al. (1989) Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. J Clin Invest 84: 205–213
Ferrannini E, Buzzigoli G, Bonadonna R et al. (1987) Insulin resistance in essential hypertension. N Engl J Med 317: 350–357
Laakso M, Sarlund H, Mykkänen L (1989) Essential hypertension and insulin resistance in non-insulin-dependent diabetes. Eur J Clin Invest 19: 518–526
Viberti GC, Hill RD, Jarrett RJ, Argyropoulus A, Mahmud U, Keen H (1982) Microalbuminuria as a predictor of clinical nephropathy in insulin dependent diabetes mellitus. Lancet I: 1430–1432
Mogensen CE, Christensen CK (1984) Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311: 89–93
Mogensen CE (1984) Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 310: 356–360
Jarrett RJ, Viberti GC, Argyropoulus A, Hill RD, Mahmud U, Murrells TJ (1984) Microalbuminuria predicts mortality in non-insulin-dependent diabetes. Diabetic Med 1: 17–19
Schmitz A, Vaeth M (1988) Microalbuminuria: a major risk factor in non-insulin-dependent diabetes. A 10-year follow-up study of 503 patients. Diabetic Med 5: 126–134
Mattock MB, Keen H, Viberti GC et al. (1988) Coronary heart disease and urinary albumin excretion rate in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 31: 82–87
Niskanen L, Uusitupa M, Sarlund H et al. (1990) Microalbuminuria predicts the development of serum lipoprotein abnormalities favouring atherogenesis in newly diagnosed type 2 (non-insulin-dependent) diabetic patients. Diabetologia 33: 237–243
DeFronzo RA, Tobin JD, Anders R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237: E214-E223
Ferrannini E (1988) The theoretical basis of indirect calorimetry: a review. Metabolism 37: 287–301
Coleman TG, Manning RD Jr, Norman RA Jr, Guyton AC (1972) Dynamics of water-isotope distribution. Am J Physiol 223: 1371–1375
Teppo AM, Groop L (1985) Urinary excretion of plasma proteins in diabetic subjects. Increased excretion of kappa light chains in diabetic patients with and without proliferative retinopathy. Diabetes 34: 589–594
Radziuk J, Norwich KH, Vranic M (1978) Experimental validation of measurements of glucose turnover in non-steady state. Am J Physiol 234: E84-E93
Shulman GI, Rothman DL, Jue T, Stein P, DeFronzo RA, Shulman RG (1990) Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Engl J Med 322: 223–228
Shen D-C, Shieh S-M, Fuh MM-T, Wu D-A, Chen Y-DI, Reaven GM (1988) Resistance to insulin-stimulated-glucose uptake in patients with hypertension. J Clin Endocrinol Metab 66: 580–583
Forsblom C, Ekstrand A, Eriksson J et al. (1992) Microalbuminuria in non-diabetic first degree relatives of type 2 diabetic patients. Diabetologia 35 [Suppl 1]: A 61 (Abstract)
Tötterman K, Groop L, Groop P-H, Kala R, Tolppanen E-M, Fyhrqvist F (1984) Effect of beta-blocking drugs on beta-cell function and insulin sensitivity in hypertensive non-diabetic patients. Eur J Clin Pharmacol 26: 13–17
Pollare T, Lithell H, Berne C (1989) A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension. N Engl J Med 321: 868–873
Morales PA, Mitchell BD, Valdez RA, Hazuda HP, Stern MP, Haffner SM (1993) Incidence of NIDDM and impaired glucose tolerance in hypertensive subjects. The San Antonio Heart Study. Diabetes 42: 154–161
Stehouwer CDA, Nauta JJP, Zeldenrust GC et al. (1992) Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin dependent diabetes mellitus. Lancet 340: 319–323
Jensen T, Bjerre-Knudsen J, Feldt-Rasmussen B, Deckert T (1989) Features of endothelial dysfunction in early diabetic nephropathy. Lancet I: 461–463
Nörgaard K, Jensen T, Feldt-Rasmussen B (1993) Transcapillary escape rate of albumin in hypertensive patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 36: 57–61
Haffner SM, Stern MP, Kozlowski Gruber MK, Hazuda HP, Mitchell BD, Patterson JK (1990) Microalbuminuria. Potential marker for increased cardiovascular risk factors in non-diabetic subjects? Arteriosclerosis 10: 727–731
Lopes De Faria JB, Jones SL, MacDonald F, Chambers J, Mattock MB, Viberti GC (1992) Sodium-lithium countertransport activity and insulin resistance in normotensive IDDM patients. Diabetes 41: 610–615
Catalano C, Winocour PH, Thomas TH et al. (1993) Erythrocyte sodium-lithium countertransport activity and total body insulin-mediated glucose disposal in normoalbuminuric normotensive type 1 (insulin-dependent) diabetic patients. Diabetologia 36: 52–56
Borkman M, Storlien LH, Pan DA, Jenkins AB, Chisholm DJ, Campbell LV (1993) The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids. N Engl J Med 328: 238–244
Resnick LM (1989) Hypertension and abnormal glucose homeostasis. Possible role of divalent ion metabolism. Am J Med 87 [Suppl 6A]: 17S-22S
Solini A, Muollo B, Frigato F et al. (1992) Abnormalities in extrahepatic insulin sensitivity are a peculiar feature of non-insulin dependent diabetic patients with but not without hypertension and/or microalbuminuria. Diabetologia 35 [Suppl 1]: A 96 (Abstract)
Arner P, Pollare T, Lithell H (1991) Different aetiologies of type 2 (non-insulin dependent) diabetes mellitus in obese and non-obese subjects. Diabetologia 34: 483–487
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Groop, L., Ekstrand, A., Forsblom, C. et al. Insulin resistance, hypertension and microalbuminuria in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 36, 642–647 (1993). https://doi.org/10.1007/BF00404074
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00404074