pmc logo image
Logo of cmajCMAJ Information for AuthorsCMAJ Home Page

Formats:

CMAJ. 1991 December 15; 145(12): 1571–1581.
PMCID: PMC1336077
Non-insulin-dependent (type II) diabetes mellitus.
W Rodger
Lawson Diabetes Centre, St. Joseph's Health Centre, London, Ont.
Abstract
Non-insulin-dependent (type II) diabetes mellitus is an inherited metabolic disorder characterized by hyperglycemia with resistance to ketosis. The onset is usually after age 40 years. Patients are variably symptomatic and frequently obese, hyperlipidemic and hypertensive. Clinical, pathological and biochemical evidence suggests that the disease is caused by a combined defect of insulin secretion and insulin resistance. Goals in the treatment of hyperglycemia, dyslipidemia and hypertension should be appropriate to the patient's age, the status of diabetic complications and the safety of the regimen. Nonpharmacologic management includes meal planning to achieve a suitable weight, such that carbohydrates supply 50% to 60% of the daily energy intake, with limitation of saturated fats, cholesterol and salt when indicated, and physical activity appropriate to the patient's age and cardiovascular status. Follow-up should include regular visits with the physician, access to diabetes education, self-monitoring of the blood or urine glucose level and laboratory-based measurement of the plasma levels of glucose and glycated hemoglobin. If unacceptably high plasma glucose levels (e.g., 8 mmol/L or more before meals) persist the use of orally given hypoglycemic agents (a sulfonylurea agent or metformin or both) is indicated. Temporary insulin therapy may be needed during intercurrent illness, surgery or pregnancy. Long-term insulin therapy is recommended in patients with continuing symptoms or hyperglycemia despite treatment with diet modification and orally given hypoglycemic agents. The risk of pancreatitis may be reduced by treating severe hypertriglyceridemia (fasting serum level greater than 10 mmol/L) and atherosclerotic disease through dietary and, if necessary, pharmacologic management of dyslipidemia. Antihypertensive agents are available that have fewer adverse metabolic effects than thiazides and beta-adrenergic receptor blockers. New drugs are being developed that will enhance effective insulin secretion and action and inhibit the progress of complications.
Full text
Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.8M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
  • Melander A, Lebovitz HE, Faber OK. Sulfonylureas. Why, which, and how? Diabetes Care. 1990 Aug;13 Suppl 3:18–25. [PubMed]
  • Waldhäusl WK. The physiological basis of insulin treatment--clinical aspects. Diabetologia. 1986 Dec;29(12):837–849. [PubMed]
  • Gerich JE. Oral hypoglycemic agents. N Engl J Med. 1989 Nov 2;321(18):1231–1245. [PubMed]
  • Hamet P, Kalant N, Ross SA, Wilson TW, Leenen FH, Haynes RB. Recommendations from the Canadian Hypertension Society Consensus Conference on Hypertension and Diabetes. CMAJ. 1988 Dec 1;139(11):1059–1062. [PubMed]
  • Barnett AH, Eff C, Leslie RD, Pyke DA. Diabetes in identical twins. A study of 200 pairs. Diabetologia. 1981 Feb;20(2):87–93. [PubMed]
  • DeFronzo RA. Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes. 1988 Jun;37(6):667–687. [PubMed]
  • Olefsky JM. The insulin receptor. A multifunctional protein. Diabetes. 1990 Sep;39(9):1009–1016. [PubMed]
  • Warram JH, Martin BC, Krolewski AS, Soeldner JS, Kahn CR. Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. Ann Intern Med. 1990 Dec 15;113(12):909–915. [PubMed]
  • Johnson JH, Ogawa A, Chen L, Orci L, Newgard CB, Alam T, Unger RH. Underexpression of beta cell high Km glucose transporters in noninsulin-dependent diabetes. Science. 1990 Oct 26;250(4980):546–549. [PubMed]
  • Temple RC, Carrington CA, Luzio SD, Owens DR, Schneider AE, Sobey WJ, Hales CN. Insulin deficiency in non-insulin-dependent diabetes. Lancet. 1989 Feb 11;1(8633):293–295. [PubMed]
  • Reaven GM, Chen YD, Golay A, Swislocki AL, Jaspan JB. Documentation of hyperglucagonemia throughout the day in nonobese and obese patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1987 Jan;64(1):106–110. [PubMed]
  • Rossetti L, Giaccari A, DeFronzo RA. Glucose toxicity. Diabetes Care. 1990 Jun;13(6):610–630. [PubMed]
  • Zimmerman BR, Service FJ. Management of noninsulin-dependent diabetes mellitus. Med Clin North Am. 1988 Nov;72(6):1355–1364. [PubMed]
  • Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. Glycosylated hemoglobin predicts the incidence and progression of diabetic retinopathy. JAMA. 1988 Nov 18;260(19):2864–2871. [PubMed]
  • Kannel WB, D'Agostino RB, Wilson PW, Belanger AJ, Gagnon DR. Diabetes, fibrinogen, and risk of cardiovascular disease: the Framingham experience. Am Heart J. 1990 Sep;120(3):672–676. [PubMed]
  • Westphal SA, Goetz FC. Current approaches to continuous insulin replacement for insulin-dependent diabetes: pancreas transplantation and pumps. Adv Intern Med. 1990;35:107–137. [PubMed]
  • Miettinen TA, Huttunen JK, Naukkarinen V, Strandberg T, Mattila S, Kumlin T, Sarna S. Multifactorial primary prevention of cardiovascular diseases in middle-aged men. Risk factor changes, incidence, and mortality. JAMA. 1985 Oct 18;254(15):2097–2102. [PubMed]
  • Siperstein MD. Diabetic microangiopathy, genetics, environment, and treatment. Am J Med. 1988 Nov 28;85(5A):119–130. [PubMed]
  • Stern MP, Patterson JK, Haffner SM, Hazuda HP, Mitchell BD. Lack of awareness and treatment of hyperlipidemia in type II diabetes in a community survey. JAMA. 1989 Jul 21;262(3):360–364. [PubMed]
  • Dunn FL. Treatment of lipid disorders in diabetes mellitus. Med Clin North Am. 1988 Nov;72(6):1379–1398. [PubMed]
  • Teuscher A, Egger M, Herman JB. Diabetes and hypertension. Blood pressure in clinical diabetic patients and a control population. Arch Intern Med. 1989 Sep;149(9):1942–1945. [PubMed]
  • Larochelle P, Bass MJ, Birkett NJ, De Champlain J, Myers MG. Recommendations from the Consensus Conference on Hypertension in the Elderly. CMAJ. 1986 Oct 1;135(7):741–745. [PubMed]
  • Mogensen CE. Management of diabetic renal involvement and disease. Lancet. 1988 Apr 16;1(8590):867–870. [PubMed]
  • Watkins JD, Williams TF, Martin DA, Hogan MD, Anderson E. A study of diabetic patients at home. Am J Public Health Nations Health. 1967 Mar;57(3):452–459. [PubMed]
  • Henry RR, Scheaffer L, Olefsky JM. Glycemic effects of intensive caloric restriction and isocaloric refeeding in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1985 Nov;61(5):917–925. [PubMed]
  • Souney PF, Cyr DA, Chang JT, Kaul AF. Sugar content of selected pharmaceuticals. Diabetes Care. 1983 May–Jun;6(3):231–240. [PubMed]
  • Chockalingam A, Abbott D, Bass M, Battista R, Cameron R, de Champlain J, Evans CE, Laidlaw J, Lee BL, Leiter L, et al. Recommendations of the Canadian Consensus Conference on Non-Pharmacological Approaches to the Management of High Blood Pressure, Mar. 21-23, 1989, Halifax, Nova Scotia. CMAJ. 1990 Jun 15;142(12):1397–1409. [PubMed]
  • McInnes GT, Brodie MJ. Drug interactions that matter. A critical reappraisal. Drugs. 1988 Jul;36(1):83–110. [PubMed]
  • Walsh CH, Soler NG, James H, Fitzgerald MG, Malins JM. Studies on whole-body potassium in non-ketoacidotic diabetics before and after treatment. Br Med J. 1974 Dec 28;4(5947):738–740. [PubMed]
  • Bogardus C, Ravussin E, Robbins DC, Wolfe RR, Horton ES, Sims EA. Effects of physical training and diet therapy on carbohydrate metabolism in patients with glucose intolerance and non-insulin-dependent diabetes mellitus. Diabetes. 1984 Apr;33(4):311–318. [PubMed]
  • Rönnemaa T, Marniemi J, Puukka P, Kuusi T. Effects of long-term physical exercise on serum lipids, lipoproteins and lipid metabolizing enzymes in type 2 (non-insulin-dependent) diabetic patients. Diabetes Res. 1988 Feb;7(2):79–84. [PubMed]
  • Wing RR, Epstein LH, Paternostro-Bayles M, Kriska A, Nowalk MP, Gooding W. Exercise in a behavioural weight control programme for obese patients with Type 2 (non-insulin-dependent) diabetes. Diabetologia. 1988 Dec;31(12):902–909. [PubMed]
  • West KM. Diet therapy of diabetes: an analysis of failure. Ann Intern Med. 1973 Sep;79(3):425–434. [PubMed]
  • Simonson DC. Effects of glyburide on in vivo insulin-mediated glucose disposal. Am J Med. 1990 Aug 20;89(2A):44S–53S. [PubMed]
  • Kennedy DL, Piper JM, Baum C. Trends in use of oral hypoglycemic agents 1964-1986. Diabetes Care. 1988 Jul–Aug;11(7):558–562. [PubMed]
  • Balant L. Clinical pharmacokinetics of sulphonylurea hypoglycaemic drugs. Clin Pharmacokinet. 1981 May–Jun;6(3):215–241. [PubMed]
  • Groop LC, Pelkonen R, Koskimies S, Bottazzo GF, Doniach D. Secondary failure to treatment with oral antidiabetic agents in non-insulin-dependent diabetes. Diabetes Care. 1986 Mar–Apr;9(2):129–133. [PubMed]
  • Jennings AM, Wilson RM, Ward JD. Symptomatic hypoglycemia in NIDDM patients treated with oral hypoglycemic agents. Diabetes Care. 1989 Mar;12(3):203–208. [PubMed]
  • Campbell IW. Metformin and the sulphonylureas: the comparative risk. Horm Metab Res Suppl. 1985;15:105–111. [PubMed]
  • Seltzer HS. Drug-induced hypoglycemia. A review of 1418 cases. Endocrinol Metab Clin North Am. 1989 Mar;18(1):163–183. [PubMed]
  • Meinert CL, Knatterud GL, Prout TE, Klimt CR. A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II. Mortality results. Diabetes. 1970;19(Suppl):789–830. [PubMed]
  • Kilo C, Miller JP, Williamson JR. The Achilles heel of the University Group Diabetes Program. JAMA. 1980 Feb 1;243(5):450–457. [PubMed]
  • Bailey CJ. Metformin revisited: its actions and indications for use. Diabet Med. 1988 May–Jun;5(4):315–320. [PubMed]
  • Klip A, Leiter LA. Cellular mechanism of action of metformin. Diabetes Care. 1990 Jun;13(6):696–704. [PubMed]
  • Vigneri R, Goldfine ID. Role of metformin in treatment of diabetes mellitus. Diabetes Care. 1987 Jan–Feb;10(1):118–122. [PubMed]
  • Alberti KG, Gries FA. Management of non-insulin-dependent diabetes mellitus in Europe: a concensus view. Diabet Med. 1988 Apr;5(3):275–281. [PubMed]
  • Hermann LS. Biguanides and sulfonylureas as combination therapy in NIDDM. Diabetes Care. 1990 Aug;13 Suppl 3:37–41. [PubMed]
  • Groop L, Widén E, Franssila-Kallunki A, Ekstrand A, Saloranta C, Schalin C, Eriksson J. Different effects of insulin and oral antidiabetic agents on glucose and energy metabolism in type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia. 1989 Aug;32(8):599–605. [PubMed]
  • Rains SG, Wilson GA, Richmond W, Elkeles RS. The effect of glibenclamide and metformin on serum lipoproteins in type 2 diabetes. Diabet Med. 1988 Oct;5(7):653–658. [PubMed]
  • Nathan DM, Roussell A, Godine JE. Glyburide or insulin for metabolic control in non-insulin-dependent diabetes mellitus. A randomized, double-blind study. Ann Intern Med. 1988 Mar;108(3):334–340. [PubMed]
  • Peacock I, Tattersall RB. The difficult choice of treatment for poorly controlled maturity onset diabetes: tablets or insulin? Br Med J (Clin Res Ed). 1984 Jun 30;288(6435):1956–1959. [PubMed]
  • Selam JL, Charles MA. Devices for insulin administration. Diabetes Care. 1990 Sep;13(9):955–979. [PubMed]
  • Sonnenberg GE, Berger M. Human insulin: much ado about one amino acid? Diabetologia. 1983 Dec;25(6):457–459. [PubMed]
  • Clark AJ, Adeniyi-Jones RO, Knight G, Leiper JM, Wiles PG, Jones RH, Keen H, MacCuish AC, Ward JD, Watkins PJ, Cauldwell JM, Glynne A, Scotton JB. Biosynthetic human insulin in the treatment of diabetes. A double-blind crossover trial in established diabetic patients. Lancet. 1982 Aug 14;2(8294):354–357. [PubMed]
  • Genuth S. Insulin use in NIDDM. Diabetes Care. 1990 Dec;13(12):1240–1264. [PubMed]
  • Heller SR, Macdonald IA, Tattersall RB. Counterregulation in type 2 (non-insulin-dependent) diabetes mellitus. Normal endocrine and glycaemic responses, up to ten years after diagnosis. Diabetologia. 1987 Dec;30(12):924–929. [PubMed]
  • Scarlett JA, Gray RS, Griffin J, Olefsky JM, Kolterman OG. Insulin treatment reverses the insulin resistance of type II diabetes mellitus. Diabetes Care. 1982 Jul–Aug;5(4):353–363. [PubMed]
  • Welle S, Nair KS, Lockwood D. Effect of a sulfonylurea and insulin on energy expenditure in type II diabetes mellitus. J Clin Endocrinol Metab. 1988 Mar;66(3):593–597. [PubMed]
  • SHIPP JC, CUNNINGHAM RW, RUSSELL RO, MARBLE A. INSULIN RESISTANCE: CLINICAL FEATURES, NATURAL COURSE AND EFFECTS OF ADRENAL STEROID TREATMENT. Medicine (Baltimore). 1965 Mar;44:165–186. [PubMed]
  • Ryan NT, George BC, Egdahl DH, Egdahl RH. Chronic tissue insulin resistance following hemorrhagic shock. Ann Surg. 1974 Oct;180(4):402–407. [PubMed]
  • Lundholm K, Holm G, Scherstén T. Insulin resistance in patients with cancer. Cancer Res. 1978 Dec;38(12):4665–4670. [PubMed]
  • Bergenstal RM, Dupre J, Lawson PM, Rizza RA, Rubenstein AH. Observations on C-peptide and free insulin in the blood during continuous subcutaneous insulin infusion and conventional insulin therapy. Diabetes. 1985 Aug;34 Suppl 3:31–36. [PubMed]
  • Shumak SL. Insulin treatment, NIDDM and atherosclerosis. CMAJ. 1991 Jul 15;145(2):134. [PubMed]
  • Wing RR, Epstein LH, Nowalk MP, Scott N, Koeske R, Hagg S. Does self-monitoring of blood glucose levels improve dietary compliance for obese patients with type II diabetes? Am J Med. 1986 Nov;81(5):830–836. [PubMed]
  • Garg A, Grundy SM. Management of dyslipidemia in NIDDM. Diabetes Care. 1990 Feb;13(2):153–169. [PubMed]
  • Hoeg JM, Gregg RE, Brewer HB., Jr An approach to the management of hyperlipoproteinemia. JAMA. 1986 Jan 24;255(4):512–521. [PubMed]
  • Glauber H, Wallace P, Griver K, Brechtel G. Adverse metabolic effect of omega-3 fatty acids in non-insulin-dependent diabetes mellitus. Ann Intern Med. 1988 May;108(5):663–668. [PubMed]
  • Porter JM, Cutler BS, Lee BY, Reich T, Reichle FA, Scogin JT, Strandness DE. Pentoxifylline efficacy in the treatment of intermittent claudication: multicenter controlled double-blind trial with objective assessment of chronic occlusive arterial disease patients. Am Heart J. 1982 Jul;104(1):66–72. [PubMed]
  • Colwell JA, Bingham SF, Abraira C, Anderson JW, Comstock JP, Kwaan HC, Nuttall F. Veterans Administration Cooperative Study on antiplatelet agents in diabetic patients after amputation for gangrene: II. Effects of aspirin and dipyridamole on atherosclerotic vascular disease rates. Diabetes Care. 1986 Mar–Apr;9(2):140–148. [PubMed]
  • Myers MG, Carruthers SG, Leenen FH, Haynes RB. Recommendations from the Canadian Hypertension Society Consensus Conference on the Pharmacologic Treatment of Hypertension. CMAJ. 1989 May 15;140(10):1141–1146. [PubMed]
  • Brass EP. Effects of antihypertensive drugs on endocrine function. Drugs. 1984 May;27(5):447–458. [PubMed]
  • Brogden RN, Todd PA, Sorkin EM. Captopril. An update of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure. Drugs. 1988 Nov;36(5):540–600. [PubMed]
  • Greene DA, Sima AF, Pfeifer MA, Albers JW. Diabetic neuropathy. Annu Rev Med. 1990;41:303–317. [PubMed]
  • McCallum RW, Prakash C, Campoli-Richards DM, Goa KL. Cisapride. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use as a prokinetic agent in gastrointestinal motility disorders. Drugs. 1988 Dec;36(6):652–681. [PubMed]
  • Ogbonnaya KI, Arem R. Diabetic diarrhea. Pathophysiology, diagnosis, and management. Arch Intern Med. 1990 Feb;150(2):262–267. [PubMed]
  • Lardinois CK, Greenfield MS, Schwartz HC, Vreman HJ, Reaven GM. Acarbose treatment of non-insulin-dependent diabetes mellitus. Arch Intern Med. 1984 Feb;144(2):345–347. [PubMed]
  • Pontiroli AE, Alberetto M, Secchi A, Dossi G, Bosi I, Pozza G. Insulin given intranasally induces hypoglycaemia in normal and diabetic subjects. Br Med J (Clin Res Ed). 1982 Jan 30;284(6312):303–306. [PubMed]
  • Kinoshita JH, Nishimura C. The involvement of aldose reductase in diabetic complications. Diabetes Metab Rev. 1988 Jun;4(4):323–337. [PubMed]
  • Boulton AJ, Levin S, Comstock J. A multicentre trial of the aldose-reductase inhibitor, tolrestat, in patients with symptomatic diabetic neuropathy. Diabetologia. 1990 Jul;33(7):431–437. [PubMed]
  • Parving HH, Hommel E, Damkjaer Nielsen M, Giese J. Effect of captopril on blood pressure and kidney function in normotensive insulin dependent diabetics with nephropathy. BMJ. 1989 Aug 26;299(6698):533–536. [PubMed]