FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 327:1426-1433 November 12, 1992 Number 20 Next

	Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

Abstract

BACKGROUND. Insulin is widely used to improve metabolic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), but there is no consensus about the optimal regimen of insulin treatment. METHODS. We treated 153 patients with NIDDM for three months with five regimens: (1) oral hypoglycemic drug therapy plus NPH insulin given at 7 a.m. (the morning-NPH group), (2) oral hypoglycemic drug therapy plus NPH insulin given at 9 p.m. (the evening-NPH group), (3) NPH and regular insulin (ratio, 70 units to 30 units) given before breakfast and dinner (the two-insulin-injection group), (4) NPH insulin at 9 p.m. and regular insulin before meals (the multiple-insulin-injection group), and (5) continued oral hypoglycemic drug therapy (the control group). RESULTS. The mean (+/- SE) value for glycosylated hemoglobin decreased similarly in all four insulin-treatment groups (1.7 +/- 0.3, 1.9 +/- 0.2, 1.8 +/- 0.3, and 1.6 +/- 0.3 percent, respectively). The decrease was significantly greater in these four groups than in the control group (0.5 +/- 0.2 percent; P < 0.001 vs. all insulin-treated groups). Weight gain was significantly less (1.2 +/- 0.5 kg) in the evening-NPH group than in the other insulin-treatment groups (2.2 +/- 0.5 kg in the morning-NPH group, 1.8 +/- 0.5 kg in the two-insulin-injection group, and 2.9 +/- 0.5 kg in the multiple-injection group; P < 0.05). In addition, the increment in the mean diurnal serum free insulin concentration was 50 to 65 percent smaller in the evening-NPH group than in the other insulin-treatment groups. Subjective well-being improved significantly more in the insulin-treatment groups than in the control group (P < 0.001). CONCLUSIONS. In patients with NIDDM who are receiving oral hypoglycemic drug therapy, the addition of NPH insulin in the evening improves glycemic control in a manner similar to combination therapy with NPH insulin in the morning, a two-insulin-injection regimen, or a multiple-insulin-injection regimen, but induces less weight gain and hyperinsulinemia. The data thus suggest that patients with NIDDM do not benefit from multiple insulin injections and that nocturnal insulin administration appears preferable to daytime administration.

Source Information

Second Department of Medicine, University of Helsinki, Finland.

This article has been cited by other articles:

• Buse, J. B., Wolffenbuttel, B. H.R., Herman, W. H., Shemonsky, N. K., Jiang, H. H., Fahrbach, J. L., Scism-Bacon, J. L., Martin, S. A. (2009). DURAbility of Basal Versus Lispro Mix 75/25 Insulin Efficacy (DURABLE) Trial 24-Week Results: Safety and efficacy of insulin lispro mix 75/25 versus insulin glargine added to oral antihyperglycemic drugs in patients with type 2 diabetes. Diabetes Care 32: 1007-1013 [Abstract] [Full Text]  
• Juurinen, L., Kotronen, A., Graner, M., Yki-Jarvinen, H. (2008). Rosiglitazone Reduces Liver Fat and Insulin Requirements and Improves Hepatic Insulin Sensitivity and Glycemic Control in Patients with Type 2 Diabetes Requiring High Insulin Doses. J. Clin. Endocrinol. Metab. 93: 118-124 [Abstract] [Full Text]  
• Leslie, W.S., Hankey, C.R., Lean, M.E.J. (2007). Weight gain as an adverse effect of some commonly prescribed drugs: a systematic review. QJM 100: 395-404 [Abstract] [Full Text]  
• Yki-Jarvinen, H., Juurinen, L., Alvarsson, M., Bystedt, T., Caldwell, I., Davies, M., Lahdenpera, S., Nijpels, G., Vahatalo, M. (2007). Initiate Insulin by Aggressive Titration and Education (INITIATE): A randomized study to compare initiation of insulin combination therapy in type 2 diabetic patients individually and in groups. Diabetes Care 30: 1364-1369 [Abstract] [Full Text]  
• Juurinen, L., Tiikkainen, M., Hakkinen, A.-M., Hakkarainen, A., Yki-Jarvinen, H. (2007). Effects of insulin therapy on liver fat content and hepatic insulin sensitivity in patients with type 2 diabetes. Am. J. Physiol. Endocrinol. Metab. 292: E829-E835 [Abstract] [Full Text]  
• Janka, H. U., Plewe, G., Riddle, M. C., Kliebe-Frisch, C., Schweitzer, M. A., Yki-Jarvinen, H. (2005). Comparison of Basal Insulin Added to Oral Agents Versus Twice-Daily Premixed Insulin as Initial Insulin Therapy for Type 2 Diabetes. Diabetes Care 28: 254-259 [Abstract] [Full Text]  
• Davidson, M. B. (2005). Starting Insulin Therapy in Type 2 Diabetic Patients: Does it really matter how?. Diabetes Care 28: 494-495 [Full Text]  
• Hirsch, I. B. (2005). Insulin Analogues. NEJM 352: 174-183 [Full Text]  
• Burke, J. (2004). Review: Combination treatment with insulin and oral agents in type 2 diabetes mellitus. British Journal of Diabetes & Vascular Disease 4: 71-76 [Abstract]  
• Daugherty, K. K. (2004). Review of Insulin Therapy. Journal of Pharmacy Practice 17: 10-19 [Abstract]  
• Riddle, M. C., Rosenstock, J., Gerich, J. (2003). The Treat-to-Target Trial: Randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 26: 3080-3086 [Abstract] [Full Text]  
• Weiss, S. R., Cheng, S.-L., Kourides, I. A., Gelfand, R. A., Landschulz, W. H. (2003). Inhaled Insulin Provides Improved Glycemic Control in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Oral Agents: A Randomized Controlled Trial. Arch Intern Med 163: 2277-2282 [Abstract] [Full Text]  
• Fritsche, A., Schweitzer, M. A., Haring, H.-U., the 4001 Study Group*, (2003). Glimepiride Combined with Morning Insulin Glargine, Bedtime Neutral Protamine Hagedorn Insulin, or Bedtime Insulin Glargine in Patients with Type 2 Diabetes: A Randomized, Controlled Trial. ANN INTERN MED 138: 952-959 [Abstract] [Full Text]  
• DeWitt, D. E., Hirsch, I. B. (2003). Outpatient Insulin Therapy in Type 1 and Type 2 Diabetes Mellitus: Scientific Review. JAMA 289: 2254-2264 [Abstract] [Full Text]  
• White, J. R. Jr., Davis, S. N., Cooppan, R., Davidson, M. B., Mulcahy, K., Manko, G. A., Nelinson, D. (2003). Clarifying the Role of Insulin in Type 2 Diabetes Management. Clin. Diabetes 21: 14-21 [Abstract] [Full Text]  
• Seppala-Lindroos, A., Vehkavaara, S., Hakkinen, A.-M., Goto, T., Westerbacka, J., Sovijarvi, A., Halavaara, J., Yki-Jarvinen, H. (2002). Fat Accumulation in the Liver Is Associated with Defects in Insulin Suppression of Glucose Production and Serum Free Fatty Acids Independent of Obesity in Normal Men. J. Clin. Endocrinol. Metab. 87: 3023-3028 [Abstract] [Full Text]  
• Yki-Järvinen, H. (2001). Combination Therapies With Insulin in Type 2 Diabetes. Diabetes Care 24: 758-767 [Full Text]  
• Campbell, S. (2000). Management of Type 2 Diabetes in the Geriatric Patient. Journal of Pharmacy Practice 13: 263-276 [Abstract]  
• DeFronzo, R. A. (1999). Pharmacologic Therapy for Type 2 Diabetes Mellitus. ANN INTERN MED 131: 281-303 [Abstract] [Full Text]  
• Turner, R. C., Cull, C. A., Frighi, V., Holman, R. R., for the UK Prospective Diabetes Study Group, (1999). Glycemic Control With Diet, Sulfonylurea, Metformin, or Insulin in Patients With Type 2 Diabetes Mellitus: Progressive Requirement for Multiple Therapies (UKPDS 49). JAMA 281: 2005-2012 [Abstract] [Full Text]  
• Yki-Jarvinen, H., Ryysy, L., Nikkila, K., Tulokas, T., Vanamo, R., Heikkila, M. (1999). Comparison of Bedtime Insulin Regimens in Patients with Type 2 Diabetes Mellitus: A Randomized, Controlled Trial. ANN INTERN MED 130: 389-396 [Abstract] [Full Text]  
• Wise, S. D., Nielsen, M. F., Cryer, P. E., Rizza, R. A. (1998). Overnight Normalization of Glucose Concentrations Improves Hepatic But Not Extrahepatic Insulin Action in Subjects with Type 2 Diabetes Mellitus. J. Clin. Endocrinol. Metab. 83: 2461-2469 [Abstract] [Full Text]  
• Gaster, B., Hirsch, I. B. (1998). The Effects of Improved Glycemic Control on Complications in Type 2 Diabetes. Arch Intern Med 158: 134-140 [Abstract] [Full Text]  
• Yki-Jarvinen, H., Ryysy, L., Kauppila, M., Kujansuu, E., Lahti, J., Marjanen, T., Niskanen, L., Rajala, S., Salo, S., Seppala, P., Tulokas, T., Viikari, J., Taskinen, M.-R. (1997). Effect of Obesity on the Response to Insulin Therapy in Noninsulin-Dependent Diabetes Mellitus. J. Clin. Endocrinol. Metab. 82: 4037-4043 [Abstract] [Full Text]  
• Dagogo-Jack, S., Santiago, J. V. (1997). Pathophysiology of Type 2 Diabetes and Modes of Action of Therapeutic Interventions. Arch Intern Med 157: 1802-1817 [Abstract]  
• Anderson, J. H. Jr, Brunelle, R. L., Keohane, P., Koivisto, V. A., Trautmann, M. E., Vignati, L., DiMarchi, R. (1997). Mealtime Treatment With Insulin Analog Improves Postprandial Hyperglycemia and Hypoglycemia in Patients With Non-Insulin-Dependent Diabetes Mellitus. Arch Intern Med 157: 1249-1255 [Abstract]  
• Bressler, R., Johnson, D. G. (1997). Pharmacological Regulation of Blood Glucose Levels in Non--Insulin-Department Diabetes Mellitus. Arch Intern Med 157: 836-848 [Abstract]  
• Saudek, C. D., Duckworth, W. C., Giobbie-Hurder, A., Henderson, W. G., Henry, R. R., Kelley, D. E., Edelman, S. V., Zieve, F. J., Adler, R. A., Anderson, J. W., Anderson, R. J., Hamilton, B. P., Donner, T. W., Kirkman, M. S., Morgan, N. A. (1996). Implantable Insulin Pump vs Multiple-Dose Insulin for Non--Insulin-Dependent Diabetes Mellitus: A Randomized Clinical Trial. JAMA 276: 1322-1327 [Abstract]  
• Johnson, J. L., Wolf, S. L., Kabadi, U. M. (1996). Efficacy of Insulin and Sulfonylurea Combination Therapy in Type II Diabetes: A Meta-analysis of the Randomized Placebo-Controlled Trials. Arch Intern Med 156: 259-264 [Abstract]  
• Robert, H. R. (1996). Glucose Control and Insulin Resistance in Non-Insulin-dependent Diabetes Mellitus. ANN INTERN MED 124: 97-103 [Abstract] [Full Text]