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Treatment of Non-Insulin-Dependent Diabetes Mellitus and its Complications

A State of the Art Review

  • Review Article
  • Drug Therapy
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Summary

Non-insulin-dependent diabetes mellitus (NIDDM) is a major health problem which occurs predominantly in the older population; 16.8% of persons over age 65 years have NIDDM. The total health costs of NIDDM are in excess of $US20 billion annually.

The primary objective in the treatment of NIDDM is to achieve normoglycaemia, without aggravating coexisting abnormalities. Common abnormalities include obesity, hypertension, retinopathy, nephropathy and neuropathies.

Diet, and consequent bodyweight reduction, is the cornerstone of therapy for NIDDM. Total calorie intake should be limited, while the percentage of calories from carbohydrates should be increased and that from fats and cholesterol should be decreased. Exercise may also help to reduce bodyweight.

Sulphonylurea drugs stimulate insulin secretion from β-cells, and may be a useful adjunct to nonpharmacological therapy. Failure to respond to sulphonylurea drugs may be primary (25 to 30% of initially treated patients) or secondary (5 to 10% per year). It is not clear which is the most effective pharmacological intervention in such cases. Options include switching to or combining therapy with insulin, a biguanide, or other insulin-sparing antihyperglycaemic agents, e.g. α-glucosidase inhibitors, thiazolidinediones, chloroquine or hydroxychloroquine, or fibric acid derivatives such as clofibrate. Other experimental agents include the fatty acid oxidation inhibitors and dichloroacetate.

Specific agents, such as antihypertensives, lipid lowering agents and sorbitol inhibitors, may be needed to prevent the complications arising from the spectrum of clinical and metabolic abnormalities which arise from insulin resistance.

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References

  • Alberti K, Griss F (Eds). Management of NIDDM in Europe: a consensus view. Diabetic Medicine 5: 275–278, 1988

    Google Scholar 

  • American Diabetes Association. Consensus Statement. Role of cardiovascular risk factors in prevention and treatment of macrovascular disease in diabetes. Diabetes Care 15 (Suppl. 2): 68–74, 1992

    Google Scholar 

  • Anderson S. Do low protein diets delay renal insufficiency in patients with early diabetic nephropathy: 40th Annual Advanced Postgraduate Course Syllabus, pp. 25–26, 1993

  • Arauz-Pacheco C, Ramirez LC, Rios J, et al. Hypoglycemia induced by angiotensin-converting-enzyme inhibitors in non-insulin-dependent diabetic patients on sulfonylurea therapy. American Journal of Medicine 89: 811–813, 1990

    PubMed  CAS  Google Scholar 

  • Arauz C, Ramirez L, Pruneda L, Sanborn G, Rosenstock J, et al. The effect of aldose reductase inhibitor, Ponalrestat, on the progression of diabetic retinopathy. Journal of Diabetic Complications 6: 131–137, 1992

    Google Scholar 

  • Assman G, Schulte H. The Prospective Cardiovascular Münster (PROCAM): Prevalence of hyperlipidaemia in persons with hypertension and/or diabetes mellitus and their relationship to coronary heart disease. American Heart Journal 116: 1713–1724, 1988

    Google Scholar 

  • Bailey CJ. Metformin revisited: its actions and indications for use. Diabetic Medicine 5: 315–320, 1988

    PubMed  CAS  Google Scholar 

  • Bailey CJ. Biguanides and NIDDM. Diabetes Care 15: 755–772, 1992

    PubMed  CAS  Google Scholar 

  • Bailey CJ, Puah JA. Effect of metformin on glucose metabolism in mouse soleus muscle. Diabetes and Metabolism 12: 212–218, 1986

    CAS  Google Scholar 

  • Barrett-Connor E, Crique MH, Klauser MR, Holdbrook M. Diabetes and hypertension in a community of older adults. American Journal of Epidemiology 113: 276–286, 1981

    Google Scholar 

  • Barrett-Connor E, Wingard PL. Sex differential in ischemic heart disease mortality in diabetics: a prospective population-based study. American Journal of Preventive Medicine 3: 206, 1987

    PubMed  CAS  Google Scholar 

  • Beck-Nielsen H, Vaag A, Damsbo P, Handberg A, Nielsen OH, et al. Resistance in skeletal muscles in patients with NIDDM. Diabetes Care 15: 418–429, 1992

    PubMed  CAS  Google Scholar 

  • Bingham PR, Riddle MC. Combined insulin-sulfonylurea treatment of type II diabetes. Diabetes Educator 15: 450–455, 1989

    PubMed  CAS  Google Scholar 

  • Bistrian BR, Blackman GL, Flatt JP, et al. Nitrogen metabolism and insulin requirements in obese diabetic adults on a protein-sparing modified fast. Diabetes 25: 494–504, 1976

    PubMed  CAS  Google Scholar 

  • Bjorntorp P. Obesity and adipose tissue distribution as risk factors for the development of disease. Infusionstherapie 17: 24–27, 1990

    PubMed  CAS  Google Scholar 

  • Blankenship GW, Machemer R. Long-term diabetic vitrectomy results. Report of 10-year follow-up. Ophthalmology 92: 503–506, 1985

    PubMed  CAS  Google Scholar 

  • Botterman P, Classen M. Diabetes mellitus and arterial hypertension. Zeitschrift Fuer Die Gesamte Innere Medizin Und Ihre Grenzgebiete 46: 558–562, 1991

    Google Scholar 

  • Bruns W. New knowledge of diet therapy of type 2 (non-insulin-dependent) diabetes. Zeitschrift Fuer Die Gesamte Innere Medizin Und Ihre Grenzgebiete 45: 290–294, 1990

    CAS  Google Scholar 

  • Bruns W. Treatment of type 2 (non-insulin-dependent) diabetes and the metabolic syndrome with diet. Zetschrift Fuer Die Gesamte Innere Medizin Und Ihre Grenzgebiete 46: 563–567, 1991

    CAS  Google Scholar 

  • Burgi U. Late-onset diabetes 1989. Schweizerische Medizinische Wochenschriff-Journal Suisse de Medecine 120: 809–816, 1990

    CAS  Google Scholar 

  • Campbell DB, Lavielle R, Nathan C. The mode of action and clinical pharmacology of gliclazide: a review. Diabetes Research and Clinical Practice 14 (Suppl. 2): S21-S36, 1991

    Google Scholar 

  • Campbell IW. Sulphonylureas and metformin: efficacy and inadequacy. In Bailey et al. (Eds) New antidiabetic drugs, pp. 33–51, Smith-Gordon, Nishimura, London, 1990

    Google Scholar 

  • Campbell IW, Menzies DG, McBain AM, Brown IRF. Effects of metformin on blood pressure and microalbuminuria in diabetes mellitus. Diabetes and Metabolism 14: 613–617, 1988

    Google Scholar 

  • Cerutti F, Sacchetti C, Vigo A, Dianzani I, Baratone S, et al. Course of retinopathy in children and adolescents with insulin-dependent diabetes mellitus: a ten-year study. Ophthalomologica 198: 116–123, 1989

    CAS  Google Scholar 

  • Chait A, Robertson T, Brunzell JD. Chylomicronemia syndrome in diabetes mellitus. Diabetes Care 4: 343–348, 1981

    PubMed  CAS  Google Scholar 

  • Chakrabarti R, Hicking ED, Fearneley GR. Fibrinolytic effect of metformin in coronary artery disease. Lancet 2: 256–259, 1965

    PubMed  CAS  Google Scholar 

  • Cigolini M, Zancanaro C, Benati D, Cavallo E, Bosell O, et al. Metformin enhances insulin binding to in vitro down-regulated human fat cells. Diabetes and Metabolism 13: 20–22, 1987

    CAS  Google Scholar 

  • Clissold SP, Edwards C. Acarbose: A preliminary review of its phar-macodynamic and pharmacokinetic properties and therapeutic potential. Drugs 35: 214–243, 1988

    PubMed  CAS  Google Scholar 

  • Cohen RD. The relative risks of different biguanides in the causation of lactic acidosis. Research and Clinical Forums 1: 125–134, 1979

    Google Scholar 

  • Cohen KL, Harris S. Efficacy of glyburide in diabetics poorly controlled on first-generation oral hypoglycemics. Diabetes Care 10: 555–557, 1987

    PubMed  CAS  Google Scholar 

  • Colca JR, Morton DR. In Bailey (Eds) Antihyperglycemic thiazolidinediones. Antidiabetic Drugs, pp. 255-261, Smith-Gordon, London, 1990

    Google Scholar 

  • Consoli A. Role of liver in pathophysiology of NIDDM. Diabetes Care 15: 430–441, 1992

    PubMed  CAS  Google Scholar 

  • Crouse JR. Hypertriglyceridemia: A contraindication to the use of bile-acid binding resins. American Journal of Medicine 83: 243–248, 1987

    PubMed  Google Scholar 

  • DAMAD Study Group. Effect of aspirin alone and aspirin plus dipyridamole in early diabetic retinopathy. A multicenter randomized controlled clinical trial. Diabetes 38: 491–498, 1989

    Google Scholar 

  • De Fronzo RA. The effect of insulin on renal sodium metabolism. A review with clinical implications. Diabetologia 21: 165–171, 1981

    Google Scholar 

  • DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM. A balanced overview. Diabetes Care 15: 318–368, 1992

    PubMed  CAS  Google Scholar 

  • De Fronzo RA, Ferrannini E. Insulin resistance- a multi-faceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14: 173–194, 1991

    Google Scholar 

  • Diabetes Control and Complications Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. New England Journal of Medicine 329: 977–986, 1993

    Google Scholar 

  • Doft BH, Blankenship G. Retinopathy risk factor regression after laser panretinal photocoagulation for proliferative diabetic retinopathy. Ophthalmology 91: 1453–1457, 1984

    PubMed  CAS  Google Scholar 

  • Dunn FL. Management of hyperlipidemia in diabetes mellitus. Endocrinology and Metabolism Clinics of North America 21: 395–414, 1992

    PubMed  CAS  Google Scholar 

  • Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular adema. Early treatment diabetic retinopathy study report number 1. Archives of Ophthalmology 103: 1796–1806, 1985

    Google Scholar 

  • Engerman R, Bloodworm Jr JM, Nelson S. Relationship of microvascular disease in diabetes to metabolic control. Diabetes 26: 760–769, 1977

    PubMed  CAS  Google Scholar 

  • Epstein M, Sowers JR. Diabetes mellitus and hypertension. Hypertension 19: 403–418, 1992

    PubMed  CAS  Google Scholar 

  • Fantus IG, Brosseau R. Mechanism of action of metformin: insulin receptor and post-receptor effects in vitro and in vivo. Journal of Clinical Endocrinology and Metabolism 63: 898–905, 1986

    PubMed  CAS  Google Scholar 

  • Feher MD. Doxazosin therapy in the treatment of diabetic hypertension. American Heart Journal 121 (4 Pt 2): 1294–1301, 1991

    PubMed  CAS  Google Scholar 

  • Fernandez-Soto ML, Gonzalez-Jimenez A, Lopez-Cozar LN, Lobon-Hernandez JA, Aguirre-Zamorano MA, et al. Diet & NIDDM: historic and current perspectives. Revista Clinica Espanola 186: 131–133, 1990

    PubMed  CAS  Google Scholar 

  • Ferrannini E, De Fronzo RA. The association of hypertension, diabetes, and obesity: A review. Journal of Nephrology 1: 3–15, 1991

    Google Scholar 

  • Feruglio FS, Calabrese S, Giansante C, Cattin L. Metformin and platelet aggregation. Research and Clinical Forums 1: 105–112, 1979

    Google Scholar 

  • Firth RG. Insulin: Either alone or combined with oral hypoglycemia agents. Primary Care 15: 665–683, 1988

    PubMed  CAS  Google Scholar 

  • Foley JE. Rationale and application of fatty acid oxidation inhibitors in treatment of diabetes mellitus. Diabetes Care 15: 773–784, 1992

    PubMed  CAS  Google Scholar 

  • Frayn KN, Adnitt PI. Effects of metformin on glucose uptake by isolated diaphragm from normal and diabetic rats. Biochemical Pharmacology 21: 3153–3162, 1972

    PubMed  CAS  Google Scholar 

  • Galloway JA. Treatment of NIDDM with insulin agonists or substitutes. Diabetes Care 72: 1209–1239, 1990

    Google Scholar 

  • Garg A, Grundy SM. Lovastatin for lowering cholesterol levels in non-insulin-dependent diabetes mellitus. New England Journal of Medicine 318: 81–86, 1988

    PubMed  CAS  Google Scholar 

  • Garg A, Bonanome A, Grundy SM, et al. Comparison of a high-carbohydrate diet with a high-monounsaturated fat diet in patients with NIDDM. New England Journal of Medicine 319: 829–834, 1988

    PubMed  CAS  Google Scholar 

  • Garg A, Grundy SM. Nicotinic acid may not be first-line therapy for dyslipidemia in NIDDM. Abstract. Clinical Research 37: 449A, 1989

    Google Scholar 

  • Garg A, Grundy SM. Management of dyslipidemia in NIDDM. Diabetes Care 13: 153–169, 1990

    PubMed  CAS  Google Scholar 

  • Genuth S. Management of the adult onset diabetic with sulfonylurea drug failure. Endocrinology and Metabolism Clinics of North America 21: 351–370, 1992

    PubMed  CAS  Google Scholar 

  • Genuth S, Mortin P. Control of hyperglycemia in adult diabetes by pulsed insulin delivery. Diabetes 26: 571–581, 1977

    PubMed  CAS  Google Scholar 

  • Gin H, Slama G, Weissbrodt P, Poynard T, Vexiau P, et al. Metformin reduces postprandial insulin needs in type I (insulin-dependent) diabetic patients: assessment by the artificial pancreas. Diabetologia 23: 34–36, 1982

    PubMed  CAS  Google Scholar 

  • Goldberg AP, Coon PJ. Non-insulin-dependent diabetes mellitus in the elderly. Influence of obesity and physical inactivity. Endocrinology and Metabolism Clinics of North America 16: 843–865, 1987

    PubMed  CAS  Google Scholar 

  • Granner RK, O’Brien RM. Molecular physiology and genetics of NIDDM. Importance of metabolic staging. Diabetes Care 15: 369–395, 1992

    PubMed  CAS  Google Scholar 

  • Greene DA. Pathophysiology and results in new clinical studies with aldose reductase inhibitors. ADA: 40th Annual Advanced Postgraduate Course Syllabus, pp. 3–5, 1993

    Google Scholar 

  • Greene DA, Bochenek W, Harati Y, Sima AAF, Hohman T, et al. Tolrestat study group: Biochemical and morphometric response to tolrestat in human diabetic nerve. Presented at the European Association for the Study of Diabetes. Copenhagen. Diabetologia 33: A92, 1990a

    Google Scholar 

  • Greene DA, Sima AAF, Pfeifer MA, Albers JW. Diabetic neuropathy. Annual Review of Medicine 41: 303–317, 1990b

    PubMed  CAS  Google Scholar 

  • Groop L. Sulfonylureas in NIDDM. Diabetes Care 18: 737–754, 1992

    Google Scholar 

  • Groop L, Harno K. Diurnal pattern of plasma insulin and blood glucose during glibenclamide and glipizide therapy in elderly diabetics. Acta Endocrinologica 94 (Suppl.): 44–52, 1980

    Google Scholar 

  • Groop L, Luzi L, Melander A, Groop PH, Patheiser K, et al. Different effects of glyburide and glipizide on insulin secretion and hepatic glucose production in normal and NIDDM subjects. Diabetes 36: 1320–1328, 1987

    PubMed  CAS  Google Scholar 

  • Groop L, Wahkin-Boll E, Groop P-H, Totterman K-J, Melander A, et al. Pharmacokinetics and metabolic effects of glibenclamide and glipizide in type 2 diabetics. European Journal of Clinical Pharmacology 28: 697–704, 1985

    PubMed  CAS  Google Scholar 

  • Groop LC, Barzilai N, Ratheiser K, Luzi G, Wahlin-Boll E, et al. Dose-dependent effects of glyburide on insulin secretion and glucose uptake in humans. Diabetes Care 14: 724–727, 1991a

    PubMed  CAS  Google Scholar 

  • Groop LC, Ratheiser K, Luzi L, Melander A, Simonson DC, et al. Effect of sulfonylurea on glucose-stimulated insulin secretion in healthy and non-insulin-dependent diabetic subjects: a dose-response study. Acta Diabetologica 28: 162–168, 1991b

    PubMed  CAS  Google Scholar 

  • Grundy SM. Dietary therapy in diabetes mellitus. Is there a single best diet? Diabetes Care 14: 796–801, 1991

    PubMed  CAS  Google Scholar 

  • Gustafson A, Bjorntorp P, Fahler M. Metformin administration in hyperlipidemic states. Acta Medica Scandinavica 190: 491–494, 1991

    Google Scholar 

  • Haffner SM, Fong D, Stern MP, Pugh JA, Hazuda HP, et al. Diabetic retinopathy in Mexican-Americans and non-Hispanic whites. Diabetes 27: 878–884, 1988

    Google Scholar 

  • Heine RJ. Insulin treatment of NIDDM. Balliere’s Clinical Endocrinology and Metabolism 2: 477–492, 1988

    CAS  Google Scholar 

  • Helms RB. Implications of population growth on prevalence of diabetes: A look at the future. Diabetes Care 15 (Suppl. 1): 6–9, 1992

    PubMed  Google Scholar 

  • Henry RR, Gumbinier B. Benefits and limitations of very-low-calorie diet therapy in obese NIDDM. Diabetes Care 14: 802–823, 1991

    PubMed  CAS  Google Scholar 

  • Hermann LS. Metformin: A review of its pharmacological properties and therapeutic use. Diabetes Metabolism Reviews 5: 233–245, 1979

    CAS  Google Scholar 

  • Hermann LS. Biguanides and sulfonylureas as combination therapy in NIDDM. Diabetes Care 13 (Suppl. 3): 37–41, 1990

    PubMed  Google Scholar 

  • Hillfrisch J. Dietary sugars and carbohydrate metabolism in Type II diabetes. Journal of the American College of Nutrition 6: 385–396, 1987

    Google Scholar 

  • Hiramatsu K, Arimori S. Increased Superoxide production by mononuclear cells of patients with hypertriglyceridemia and diabetes. Diabetes 37: 832–837, 1988

    PubMed  CAS  Google Scholar 

  • Hocking ED, Chakrabarti R, Evans J, Fearnley GR. Effect of biguanides and atromid on fibrinolysis. Journal of Atherosclerosis 7: 121–130, 1967

    CAS  Google Scholar 

  • Hollander E, Szekely A. The effect of fiber-rich diet on the postprandial blood sugar level in diabetics. Orvosi Hetilap 13: 1209–1214, 1989

    Google Scholar 

  • Holle A, Mangels W, Dreyer M, Kuhnau J, Rudiger HW. Biguanide treatment increases the number of insulin-receptor sites on human erythrocytes. New England Journal of Medicine 305: 563–566, 1981

    PubMed  CAS  Google Scholar 

  • Holman PR, Steemson J, Turner RC. Sulphonylurea failure in type 2 diabetes: treatment with a basal insulin supplement. Diabetic Medicine 4: 457–462, 1987

    PubMed  CAS  Google Scholar 

  • Horii S, Fukase H, Matsuo T, Kameda Y, Asano N, et al. Synthesis and alpha-D-glucosidase inhibitory activity of N-substituted valiolamine derivatives as potential oral antidiabetic agents. Journal of Medicinal Chemistry 29: 1038–1046, 1986

    PubMed  CAS  Google Scholar 

  • Horton ES. Exercise in the treatment of NIDDM. Diabetes 40 (Suppl. 2): 175–178, 1991

    PubMed  Google Scholar 

  • Horton ES. Role of environmental factors in the development of non-insulin-dependent diabetes mellitus. American Journal of Medicine 75: 32–40, 1983

    PubMed  CAS  Google Scholar 

  • Houston MC. Treatment of hypertension in diabetes mellitus. American Heart Journal 118: 819–829, 1989

    PubMed  CAS  Google Scholar 

  • Howard BV, Knowler WC, Vasquez B, et al. Plasma and lipoprotein cholesterol and triglyceride in the Pima Indian population. Comparison of diabetics and non-diabetics. Arteriosclerosis 4: 462–471, 1984

    PubMed  CAS  Google Scholar 

  • Howard-Williams J, Hillson RM, Bron A, Awdey P, Mann JI, et al. Retinopathy is associated with higher glycemia in maturity-onset type diabetes. Diabetologia 27: 198–202, 1984

    PubMed  CAS  Google Scholar 

  • Hsueh WA. Effect of the renin-angiotensin system in the vascular diasease of type 2 diabetes mellitus. American Journal of Medicine 92 (4B): 13S–14S, 1992

    PubMed  CAS  Google Scholar 

  • Huth K, Burkard M, Goebel T. Dyslipoproteinemia and diabetes mellitus in a metabolic syndrome. Fortschritte Der Medizin 11: 200–204, 1992

    Google Scholar 

  • Jacobs DB, Hayes GR, Truglia JA, Lockwood DH. Effects of metformin on insulin receptor tyrosine kinase activity in rat adipocytes. Diabetologia 29: 798–801, 1986

    PubMed  CAS  Google Scholar 

  • Jarrett RJ, Al Sayegh H. Impaired glucose tolerance: defining those at risk of diabetic complications. Diabetologia 15: 243–248, 1978

    Google Scholar 

  • Johnson KH, O’Brien TD, Betsholtz C, Westermark P. Islet amyloid polypeptide and diabetes mellitus. New England Journal of Medicine 321: 513–518, 1989

    PubMed  CAS  Google Scholar 

  • Johnson PC, Doll SC, Cromey DW. Pathogenesis of diabetic neuropathy. Annals of Neurology 19: 450–457, 1986

    PubMed  CAS  Google Scholar 

  • Jones IR, Swai A, Taylor R, et al. Lowering of plasma glucose concentrations with bezafibrate in patients with moderately controlled NIDDM. Diabetes Care 13: 855–863, 1990

    PubMed  CAS  Google Scholar 

  • Kahn SE, Beard JE, Schwartz MW, et al. Increased beta-cell secretory capacity as mechanism for islet adaptation to nicotinic acidinduced insulin resistance. Diabetes 38: 562–568, 1989

    PubMed  CAS  Google Scholar 

  • Karam JH. Type II diabetes and syndrome X. Pathogenesis and glycemic management. Endocrinology and Metabolism Clinics of North America 21: 329–350, 1992

    PubMed  CAS  Google Scholar 

  • Karam JH, Salber PR, Forsham PH. Pancreatic Hormones and Diabetes Mellitus. In Greenspan (Ed.) Basic and clinical endocrinology, pp. 592–650, Appleton and Lange, Connecticut, 1991

    Google Scholar 

  • Kasiske BL, Kalil RSN, Ma JZ, Keane WF. Effect of antihypertensive therapy on the kidney in patients with diabetes: a meta-regression analysis. Annals of Internal Medicine 118: 129–138, 1993

    PubMed  CAS  Google Scholar 

  • Kaufman SC, Ferris FL, Siegel DG, Davis MD, DeMets DL. DRS research group. Factors associated with visual outcome after photocoagulation for diabetic retinopathy. Diabetic Retinopathy Study report #13. Investigative Ophthalmology and Visual Science 30: 23–28, 1989

    PubMed  CAS  Google Scholar 

  • Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin Epidemiologic study of diabetic retinopathy: II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. Archives of Ophthalmology 102: 520–526, 1984a

    PubMed  CAS  Google Scholar 

  • Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy: III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Archives of Ophthalmology 102: 527–532, 1984b

    PubMed  CAS  Google Scholar 

  • Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy: IV. Diabetic macular edema. Ophthalmology 91: 1464–1474, 1984c

    PubMed  CAS  Google Scholar 

  • Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. Is blood pressure a predictor of the incidence or progression of diabetic retinopathy? Archives of Internal Medicine 149: 2427–2432, 1989a

    PubMed  CAS  Google Scholar 

  • Klein R, Klein BE, Moss S, DeMets DL. Proteinuria in diabetes. Archives of Internal Medicine 148: 181–186, 1989b

    Google Scholar 

  • Klip A, Sarabia V, Ramlal T, Bilan PJ, Leiter LA. Glucose transport in human muscle cells in culture: stimulation by insulin and metformin. Diabetes (Suppl. 1): 82A, 1990

    Google Scholar 

  • Knuiman MW, Welborn TA, McCann VJ, Danton KG, Constable IJ. Prevalence of diabetic complications in relation to risk factors. Diabetes 35: 1332–1339, 1986

    PubMed  CAS  Google Scholar 

  • Kobayashi M, Shigeta Y, Hirata Y, et al. Improvement of glucose tolerance in NIDDM by clofibrate: randomized double-blind study. Diabetes Care 11: 495–499, 1988

    PubMed  CAS  Google Scholar 

  • Kohner M, Caldwell G, Plehwe WE, Brown R, Rosen E. Ponalrestat in early diabetic retinopathy. Diabetes 39 (Suppl. 1): 62A, 1990

    Google Scholar 

  • Kolterman OG. Glyburide in NIDDM: an update. Clinical Therapeutics 14: 196–213, 1992

    PubMed  CAS  Google Scholar 

  • Koschinsky T, Banting CE, Rutter R, Gries FA. Influence of metformin on vascular cell proliferation. Diabetes and Metabolism 14: 566–570, 1988

    Google Scholar 

  • Krall LP. The treatments of NIDDM in the decade of 90’s. Diabetes Research and Clinical Practice 14 (Suppl. 2): S15–S19, 1991

    PubMed  Google Scholar 

  • Krosnick A. Economic impact of Type II diabetes mellitus. Primary Care: Clinics in Office Practice 15: 423–432, 1988

    PubMed  CAS  Google Scholar 

  • Kunnel WB, McGee DL. Diabetics and cardiovascular disease. The Framingham Study. Journal of the American Medical Association 241: 2035–2038, 1979

    Google Scholar 

  • Lampman RM, Schteingart DE. Effects of exercise training on glucose control, lipid metabolism, and insulin sensitivity in hypertriglyceridemia and non-insulin-dependent diabetes mellitus. Medicine and Science in Sports and Exercise 23: 703–712, 1991

    PubMed  CAS  Google Scholar 

  • Landry GL, Allen DB. Diabetes mellitus and exercise. Clinics In Sports Medicine 11: 403–418, 1992

    PubMed  CAS  Google Scholar 

  • Lebovitz HE. Are oral hypoglycemic agents likely to benefit NIDDM patients? Hospital Practice 27 (Suppl. 1): 26–31, 1992

    PubMed  Google Scholar 

  • Lebovitz HE, Pasmantier R. Combination insulin-sulfonylurea therapy. Diabetes Care 13: 667–675, 1990

    PubMed  CAS  Google Scholar 

  • Levey AS, Beck GJ, Caggeula AW, Greene T, Hunsicker LG, et al. A hypothesis for the results of the Modification of Diet in Renal Disease (MDRD) study. Journal of the American Society of Nephrology 4 (3): 253, 1993

    Google Scholar 

  • Lewis EJ, Hunsicker LG, Bain RP, Rohde RD, Collaborative Study Group. The effect of angiotensin-converting enzyme inhibition on diabetic nephropathy. New England Journal of Medicine 329: 1456–1462, 1993

    PubMed  CAS  Google Scholar 

  • Lintott CJ, Scott RS. HMG-CoA reducatase inhibitor use in the aged. A review of clinical experience. Drugs & Aging 2: 518–529, 1992

    CAS  Google Scholar 

  • Lintott CJ, Scott RS, Sutherland WHF, Bremer JM, Shand BI, et al. Comparison of simvastatin vs gemfibrozil therapy on lipid, glycaemic, and haemorheological parameters in type II diabetes mellitus. Diabetes, Nutrition & Metabolism 5: 183–189, 1992

    Google Scholar 

  • Lopez-Virella MF, Klein RL, Lyons TJ, et al. Glycosylation of lowdensity lipoprotein enhances cholesteryl ester synthesis in human monocyte-derived macrophages. Diabetes 37: 550–557, 1988

    Google Scholar 

  • Lord JM, Atkins TW, Bailey CJ. Effect of metformin on hepatocyte insulin receptor binding in normal streptozotocin diabetic and genetically obese diabetic (ob/ob) mice. Diabetologia 25: 108–113, 1983a

    PubMed  CAS  Google Scholar 

  • Lord JM, White SI, Bailey CJ, Atkins TW, Fletcher RF, et al. Effect of metformin on insulin receptor binding and glycemic control on type 2 diabetes. British Medical Journal 286: 830–831, 1983b

    PubMed  CAS  Google Scholar 

  • Lotz N. Combination therapy with sulfonylurea plus insulin in ‘secondary failure’ of type 2 diabetes. Therapetische Umschau 47: 49–54, 1990

    CAS  Google Scholar 

  • Lucas CP, Estigarribia JA, Darga LL, Reaven GM. Insulin and blood pressure in obesity. Hypertension 7: 809–817, 1985

    Google Scholar 

  • Lucis OJ. The status of metformin in Canada. Canadian Medical Association Journal 128: 24–26, 1983

    PubMed  CAS  Google Scholar 

  • Malaisse WJ, Malaisse-Lagae F, Mayhew DA, Wright PH. Effects of sulfonylureas upon insulin secretion by the rat pancreas. Amsterdam Ecerpta Med 149: 49–60, 1967

    Google Scholar 

  • Maldonato A, Iavicoli M, Falluca F. When to start an NIDDM patient on insulin: Which insulin could be recommended? Diabetes Research and Clinical Practice 4 (Suppl. 1): 29–34, 1988

    PubMed  Google Scholar 

  • Marchetti P, Giannarelli R, di Carlo A, Navalesi R. Pharmacokinetic optimisation of oral hypoglycemic therapy. Clinical Pharmacokinetics 21: 308–317, 1991

    PubMed  CAS  Google Scholar 

  • Mathiesen ER, Hommel E, Giese J, Parving HH. Efficacy of captopril in postponing nephropathy in normotensive insulin-dependent diabetic patients with microalbuminemia. British Medical Journal 303: 81–87, 1991

    PubMed  CAS  Google Scholar 

  • Melander A, Bitzen PO, Sarton G, Schersten B, Wahlin-Boll E. Will sulfonylurea treatment of impaired glucose tolerance delay development and complications of NIDDM? Diabetes Care 13 (Suppl. 3): 53–58, 1990

    PubMed  Google Scholar 

  • Melander A, Bitzen PO, Faber O, Groop L. Sulphonylurea anti-diabetic drugs. An update of their clinical pharmacology and rational therapeutic use. Drugs 37: 58–72, 1989

    PubMed  CAS  Google Scholar 

  • Meyer TW, Lawrence WE, Brenner BM. Dietary protein and the progression of renal disease. Kidney International 24 (Suppl. 16): S243–S247, 1983

    Google Scholar 

  • Mitch WE. The influence of the diet on the progression of renal insufficiency. Annual Review of Medicine 35: 249–264, 1989

    Google Scholar 

  • Modan M, Hallain H, Almog S, Lusky A, Eshkil A, et al. Hyperinsulinemia: A link between hypertension, obesity, and glucose intolerance. Journal of Clinical Investigation 75: 809–817, 1985

    PubMed  CAS  Google Scholar 

  • Moloney JB, Drury MI. The effect of pregnancy on the natural course of diabetic retinopathy. American Journal of Ophthalmology 93: 745–756, 1982

    PubMed  CAS  Google Scholar 

  • Montaguti U, Celin D, Ceredi C, Descovich GC. Efficacy of the long-term administration of metformin in hyperlipidemic patients. Research and Clinical Forums 1: 95–103, 1979

    Google Scholar 

  • Morgado A, Schneider SH. Sports medicine for the diabetic athlete. New Jersey Medicine 88: 651–654, 1991

    PubMed  CAS  Google Scholar 

  • Morgensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. New England Journal of Medicine 310: 356–360, 1984

    Google Scholar 

  • Morley JE, Perry III HM. The management of diabetes mellitus in older individuals. Drugs 41: 548–565, 1991

    PubMed  CAS  Google Scholar 

  • Murphy MB, Lewis PJ, Kohner E, Schumer B, Dollery CT. Glucose intolerance in hypertensive patients treated with diuretics. A fourteen-year follow-up. Lancet 2: 1293–1295, 1982

    PubMed  CAS  Google Scholar 

  • Nestel PJ. Fish oil attenuates the cholesterol-induced rise in lipoprotein cholesterol. American Journal of Clinical Nutrition 43: 752–757, 1986

    PubMed  CAS  Google Scholar 

  • Nestel PJ, Connor WE, Reardon MF, et al. Suppression by diets rich in fish oil of very low density lipoprotein production in man. Journal of Clinical Investigation 74: 82–89, 1984

    PubMed  CAS  Google Scholar 

  • Norell SA, Ahlbom A, Feychting M, et al. Fish consumption and mortality from coronary heart disease. British Medical Journal 293: 426, 1986

    PubMed  CAS  Google Scholar 

  • Pagano G, Tagliaferro V, Carta Q, Caselle MT, Bozzo C, et al. Metformin reduces insulin requirement in Type I (insulin-dependent) diabetes. Diabetologia 24: 351–354, 1983

    PubMed  CAS  Google Scholar 

  • Pan XR, Salden CE, Warnick GR, et al. Comparison of plasma lipoproteins and apoproteins in Chinese and American non-insulin-dependent subjects and controls. Diabetes Care 9: 395–400, 1986

    PubMed  CAS  Google Scholar 

  • Pederson O. Insulin resistance — a physiopathological condition with numerous sequelae: non-insulin-dependent diabetes mellitus (NIDDM), android obesity, essential hypertension, dyslipidemia, and atherosclerosis. Ugeskrift for Laeger 154: 1411–1418, 1992

    Google Scholar 

  • Pederson O, Hermansen K, Palvig B, Pedersen SE, Sondergaard K. Dietary treatment of diabetes mellitus. Background and rationale for recommendations in the 1990’s. Ugeskrist For Laeger 154: 910–916, 1992

    Google Scholar 

  • Penicaud L, Hitier Y, Ferr P, Girard J. Hypoglycemic effect of metformin in genetically obese (fa/fa) rats results from an increased utilization of blood glucose by the intestine. Biochemical Journal 262: 881–885, 1989

    PubMed  CAS  Google Scholar 

  • Pezzini V, Trischitta V, Purrello F, Vigneri R. Effect of metformin on insulin binding to receptors in cultured human lymphocytes and cancer cells. Diabetologia 23: 131–135, 1982

    Google Scholar 

  • Pfeifer MA, Bruzell JD, Best JD, et al. The response of plasma triglyceride, cholesterol, and lipoprotein lipase to treatment in non-insulin-dependent diabetic subjects without familial hypertriglyceridemia. Diabetes 32: 525–531, 1983

    PubMed  CAS  Google Scholar 

  • Phillipson BE, Rothrock DW, Connor WE, et al. Reduction of plasma lipids, lipoproteins and apoproteins by dietary fish oils in patients with hypertriglyceridemia. New England Journal of Medicine 312: 1210–1216, 1985

    PubMed  CAS  Google Scholar 

  • Pierce LR, Wyskowski DK, Gross TP. Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy. Journal of the American Medical Association 264: 71–75, 1990

    PubMed  CAS  Google Scholar 

  • Pollare T, Sithell H, Selnius I, et al. Application of prazosin is associated with an increase of insulin sensitivity in obese patients with hypertension. Diabetologia 31: 415–420, 1988

    PubMed  CAS  Google Scholar 

  • Quatraro A, Consoli G, Ceriello A, et al. Combined insulin and sulfonylurea therapy in non-insulin-dependent diabetics with secondary failure to oral drugs. Diabetes Medicine 12: 315–318, 1986

    CAS  Google Scholar 

  • Raskin P, Arauz-Pacheco C. The treatment of diabetic retinopathy: A view for the internist. Annals of Internal Medicine 117: 226–233, 1992

    PubMed  CAS  Google Scholar 

  • Reaven GM, Lardinois CK, Greenfield MS, et al. Effect of acarbose on carbohydrate and lipid metabolism in NIDDM patients poorly controlled by sulfonylureas. Diabetes Care 13 (Suppl. 2): 32–36, 1990

    PubMed  Google Scholar 

  • Reaven GM. Role of insulin resistance in human disease. Diabetes 37: 1595–1606, 1988

    PubMed  CAS  Google Scholar 

  • Reichard P, Nilsson BY, Rosenqvist U. The effect of long-term intensified insulin treatment on the deveopment of microvascular complications of diabetes mellitus. New England Journal of Medicine 329: 304–309, 1993

    PubMed  CAS  Google Scholar 

  • Rossetti L, Shulman GI, Zawalich W, DeFronzo RA. Effect of chronic hyperglycemia on in vivo insulin secretion in partially pancreatectomized rats. Journal of Clinical Investigation 80: 1037–1040, 1987

    PubMed  CAS  Google Scholar 

  • Rushforth NB, Miller M, Bennett PH. Fasting and two-hour postload glucose levels for the diagnosis of diabetes: The relationship between glucose levels and complications of diabetes in the Pima Indians. Diabetologia 16: 373–379, 1979

    PubMed  CAS  Google Scholar 

  • Salo S, Groop L. Combination of two sulfonylureas. Does it make sense? Diabetes Care 11: 751–753, 1988

    PubMed  CAS  Google Scholar 

  • Samanta A, Burden AC, Jones GR, et al. The effect of short-term intensive insulin therapy in non-insulin-dependent diabetes who had failed on sulfonylurea therapy. Diabetes Research 3: 269–271, 1986

    PubMed  CAS  Google Scholar 

  • Sane T, Mustajoki P, Valimaki M. Insulin therapy in maturity-onset diabetes. Annals of Medicine 23: 13–19, 1991

    PubMed  CAS  Google Scholar 

  • Schnack C, Prager RJF, Winkler J, et al. Effects of 8-wk. alpha-glucosidase inhibition on metabolic control, C-peptide secretion, hepatic glucose output and peripheral insulin sensitivity in poorly controlled type 2 diabetic patients. Diabetes Care 12: 537–543, 1989

    PubMed  CAS  Google Scholar 

  • Singer DE, Nathan DM, Fogel HA, Schachat AP. Screening for diabetic retinopathy. Annals of Internal Medicine 116: 660–671, 1992

    PubMed  CAS  Google Scholar 

  • Sirtori CR, Franceshini G, Gianfranschi G, Sirtori M, Montanari G, et al. Metformin improve peripheral vascular flow in non-hyperlipidemic patients with areterial disease. Journal of Cardiovascular Pharmacology 6: 914–923, 1984

    PubMed  CAS  Google Scholar 

  • Sirtori CR, Tremoli E, Sirtori M, Conti F, Paoletti R, et al. Treatment of hypertriglyceridemia with metformin. Atherosclerosis 26: 853–862, 1977

    Google Scholar 

  • Smith GD, Amos TAS, Mahler R, et al. Effect of chloroquine on insulin and glucose homeostasis in normal subjects and patients with NIDDM. British Medical Journal 294: 465–467, 1987

    PubMed  CAS  Google Scholar 

  • Sorbinil Retinopathy Trial Research Group. A randomized trial of sorbinil, an aldose reductase inhibitor, in diabetic retinopathy. Archives of Ophthalmology 108: 1234–1244, 1990

    Google Scholar 

  • Sowers JR, Khoury S, Standley P, et al. Mechanisms of hypertension in diabetes. American Journal of Hypertension 4: 177–182, 1991

    PubMed  CAS  Google Scholar 

  • Stacpoole PW, Greene YJ. Dichloroacetate. Diabetes Care 15: 785–791, 1992

    PubMed  CAS  Google Scholar 

  • Stenman S, Groop PH, Lakkonen K, Wahlin-Boll E, Melander A. Relationship between sulfonylurea dose and metabolic effect. Diabetes 39 (Suppl. 1): 108A, 1990

    Google Scholar 

  • Stern MP, Haffner SM. Dyslipidemia in type II diabetes. Implications for therapeutic intervention. Diabetes Care 14: 1144–1159, 1991

    PubMed  CAS  Google Scholar 

  • Stolar MW. Atherosclerosis in diabetes: the role of hyperinsulinemia. Metabolism 37 (Suppl. 1): 1–9, 1988

    PubMed  CAS  Google Scholar 

  • Stout R. Overview of association between insulin and atherosclerosis. Metabolism 34 (Suppl. 1): 7–12, 1985

    PubMed  CAS  Google Scholar 

  • Struthers AD, Murphy MB, Dolery CT. Glucose tolerance during antihypertensive therapy in patients with diabetes mellitus. Hypertension 7 (6 Pt 2): 95–101, 1985

    Google Scholar 

  • Sumpio BE, Hayslett JP. Renal handling of proteins in normal and disease states. Quarterly Journal of Medicine 57: 611–635, 1985

    PubMed  CAS  Google Scholar 

  • Suter SL, Nolan JJ, Wallace P, et al. Metabolic effects of a new oral hypoglycemic agent CS-045 in NIDDM subjects. Diabetes Care 15: 193–203, 1992

    PubMed  CAS  Google Scholar 

  • Suzuki N, Oikawa S, Hori S, et al. Appearance of multi-disperse low density lipoprotein and altered lipoprotein composition in non-insulin-dependent diabetes with type 2 and hyperlipoproteinemia. Metabolism 38: 224–291, 1989

    PubMed  CAS  Google Scholar 

  • Swenson MR. Diabetic neuropathy: Recent concepts and potential treatments. The Endocrine Society: 43rd Postgraduate Assembly Syllabus, pp. 483–496, 1991

    Google Scholar 

  • Taskinen MR, Kuusi T, Helve E, Nikiila EA, Yki-Jarvinen H. Insulin therapy induce anti-atherogenic changes of serum lipoproteins in non-insulin-dependent diabetes. Arteriosclerosis 8: 168–177, 1988

    PubMed  CAS  Google Scholar 

  • Tattersal RB, Scott AR. When to use insulin in the maturity-onset diabetic. Postgraduate Medicine Journal 63: 859–864, 1987

    Google Scholar 

  • Taylor R. Aetiology of non-insulin-dependent diabetes. British Medical Bulletin 45: 73–91, 1989

    PubMed  CAS  Google Scholar 

  • TIMAD Study Group. Ticlopidine treatment reduces the progression of non-proliferative retinopathy. Archives of Ophthalmology 108: 1577–1584, 1990

    Google Scholar 

  • Toeller M. Diet therapy for diabetes mellitus. Firtschritte Der Medizin 109: 41–45, 1991

    CAS  Google Scholar 

  • Trischitta V, Gullo D, Pezzino V, Vigneri R. Metformin normalizes insulin binding to monocytes from obese non-diabetic subjects and obese type 2 diabetic patients. Journal of Clinical Endocrinology and Metabolism 57: 713–718, 1983

    PubMed  CAS  Google Scholar 

  • Tuck ML, Corry DB. Pathophysiology and management of hypertension in diabetes. Annual Review of Medicine 42: 533–548, 1991

    PubMed  CAS  Google Scholar 

  • Tuck ML, Sowers JR, Dornfeld L, Whitfield L, Maxwell M. Reductions in plasma catecholamines and blood pressure during weight loss in obese subjects. Acta Endocrinologica 102: 252–257, 1983

    PubMed  CAS  Google Scholar 

  • Turner RC, Holman RR. Insulin use in NIDDM: Rationale based on pathophysiology of disease. Diabetes Care 13: 1011–1020, 1990

    PubMed  CAS  Google Scholar 

  • Turner RC, Phillips MA, Ward EA. Ultralente-based insulin regimens — clinical applications, advantages, and disadvantages. Acta Medica Scandinavica 671 (Suppl.): 75–86, 1986

    Google Scholar 

  • Tyms AS, Berrie EM, Ryder TA, Nash RJ, Hegarty M, et al. Castanospermine and other plant alkaloid inhibitors of glucosidase activity block the growth of HIV. Lancet 2: 1025–1026, 1987

    PubMed  CAS  Google Scholar 

  • Vague P, Juhan-Vague I, Alessi MC, Badier C, Valadier J. Metformin decreases the high plasminogen activitor capacity, plasma insulin, and triglyceride levels in non-diabetic obese subjects. Thrombosis and Haemostasis 57: 326–328, 1987

    PubMed  CAS  Google Scholar 

  • Van Gaal LF, Vansant GA, De Leeuw IH. Upper body adiposity and the risk for atherosclerosis. Journal of the American College of Nutrition 8: 504–514, 1989

    PubMed  Google Scholar 

  • Vinik AI. New treatment modalities for diabetic neuropathy. ADA: 40th Annual Advanced Postgraduate Course Syllabus, pp. 9–12, 1993

    Google Scholar 

  • Vinik AI, Wing R. The Good, the bad, and the ugly in diabetic diets. Endocrinology and Metabolism Clinics in North America. 21: 237–279, 1992

    CAS  Google Scholar 

  • Vora JP, Anderson S. Diabetic renal disease: An overview with therapeutic implications. The Endocrinologist 2: 223–230, 1992

    Google Scholar 

  • Wahlin-Boll E, Sartor G, Melander A, Schersten B. Impaired effect of sulfonylurea following increased dosage. European Journal of Clinical Pharmacology 22: 21–25, 1982

    PubMed  CAS  Google Scholar 

  • Waldhausl W. Pathophysiology of insulin secretion in diabetes. Recenti Progressi in Medicina 81: 67–71, 1990

    PubMed  CAS  Google Scholar 

  • West KM, Ahuja MMS, Bennett PH, et al. The role of circulating glucose and triglyceride concentrations and their interactions with other ‘risk factors’ as determinants of arterial disease in nine diabetic population samples from the WHO multinational study. Diabetes Care 6: 361–369, 1983

    PubMed  CAS  Google Scholar 

  • Wiegmann TB. Microalbuminuria in diabetic nephropathy. ADA: 40th Annual Advanced Postgraduate Course Syllabus, pp. 15–17, 1993

    Google Scholar 

  • Wolffenbuttel BH, Weber RF, Weeks L, et al. Twice daily insulin therpay in patients with type 2 diabetes and secondary failure to sulphonylureas. Diabetes Research Clinical and Experimental 13: 79–84, 1990

    CAS  Google Scholar 

  • Wu MS, Johnston P, Sheu WHH, Hollenbeck CB, Jeng CY, et al. Effect of metformin on carbohydrate lipoprotein metabolism in NIDDM patients. Diabetes Care 13: 1–8, 1990

    PubMed  CAS  Google Scholar 

  • Yagi S, Takata S, Kiyokawa H. Effects of insulin on vasoconstrictive responses to norepinephrine and angiotensin II in rabbit femoral artery and vein. Diabetes 37: 1064–1067, 1988

    PubMed  CAS  Google Scholar 

  • Yki-Jarvinen H. Acute and chronic effects of hyperglycemia on glucose metabolism. Diabetologia 33: 579–585, 1990

    PubMed  CAS  Google Scholar 

  • Yki-Jarvinen H, Esko N, Eero H, Marja-Riitta T. Clinical benefits and mechanisms of a sustained response to intermittent insulin therapy in type 2 diabetes with secondary drug failure. American Journal of Medicine 84: 185–192, 1988

    PubMed  CAS  Google Scholar 

  • Yki-Jarvinen H, Taskinen MR. Interrelationships among insulin’s antilipolytic and glucoregulatory effects on plasma triglycerides in nondiabetic and diabetic patients with endogenous hypertriglyceridemia. Diabetes 37: 1271–1278, 1988

    PubMed  CAS  Google Scholar 

  • Yoshino G, Kazumi T, Iwai M, Matsushita M, Matsuba K, et al. Long-term treatment of hypercholesterolemic non-insulin dependent diabetics (NIDDM) with pravastatin (CS-514). Atherosclerosis 75: 67–72, 1989

    PubMed  CAS  Google Scholar 

  • Ziegler O, Drouin P. Hemobiological activity of gliclazide in diabetes mellitus. Diabetes Research and Clinical Practice 14 (Suppl. 2): 583–589, 1991

    Google Scholar 

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Ilarde, A., Tuck, M. Treatment of Non-Insulin-Dependent Diabetes Mellitus and its Complications. Drugs & Aging 4, 470–491 (1994). https://doi.org/10.2165/00002512-199404060-00004

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