{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:29:36Z","timestamp":1761895776486},"reference-count":34,"publisher":"American Diabetes Association","issue":"2","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":2786,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,2,1]]},"abstract":"<jats:sec><jats:title>OBJECTIVE<\/jats:title><jats:p>We compared two strategies initiating and intensifying insulin treatment and tested for noninferiority of premixed insulin to basal \u00b1 mealtime insulin analog in patients eating light breakfasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESEARCH DESIGN AND METHODS<\/jats:title><jats:p>This randomized, open-label, 48-week study compared two algorithms. Up to three injections of insulin lispro mix 25 and\/or insulin lispro mix 50 (premix; premixed insulin lispro) or basal insulin glargine plus up to three injections of insulin lispro (basal+; glargine + insulin lispro) were used in type 2 diabetic patients uncontrolled with oral antihyperglycemic medication and consuming &amp;lt;15% daily calories at breakfast. The hypothesis was to test noninferiority of premix to basal+ for glycemic control measured by HbA1c after 48 weeks, assessed using ANCOVA with a 0.4% margin.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Patients (n = 344; 176 [51%] females; mean [SD] age 54.3 [8.8] years; BMI 29.4 [4.6] kg\/m2; baseline HbA1c 9.02 [0.97]%) were randomized to premix (n = 171) or basal+ (n = 173). In the per-protocol analysis (n = 230), least squares means (95% CI) end point HbA1c were 7.40% (7.15\u20137.65) and 7.55% (7.27\u20137.82) in respective arms. Between-treatment difference was \u22120.14% (\u22120.42 to 0.13), with noninferiority met. Significantly more patients in premix achieved HbA1c targets of &amp;lt;7.0% compared with basal+ (48.2 vs. 36.2%; P = 0.024). Self-monitored blood glucose profiles, body weight changes, total insulin doses, and overall hypoglycemia (65 vs. 60%) were similar in premix and basal+ (P = 0.494), except nocturnal episodes (34.3 vs. 23.7%; P = 0.018) were more common in premix.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Both intensive insulin strategies improved glycemic control; however, final HbA1c levels were seen above those achieved in previous treat-to-target trials, likely due to the inadequate insulin titrations and probably due to the complexity of tested insulin regimens. A higher percentage of patients achieved target HbA1c &amp;lt;7% with multiple premixed insulins, but this treatment resulted in more nocturnal hypoglycemia than a basal\u2013bolus regimen.<\/jats:p><\/jats:sec>","DOI":"10.2337\/dc12-2704","type":"journal-article","created":{"date-parts":[[2013,10,30]],"date-time":"2013-10-30T02:53:21Z","timestamp":1383101601000},"page":"372-380","update-policy":"http:\/\/dx.doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":18,"title":["Initiation and Gradual Intensification of Premixed Insulin Lispro Therapy Versus Basal \u00b1 Mealtime Insulin in Patients With Type 2 Diabetes Eating Light Breakfasts"],"prefix":"10.2337","volume":"37","author":[{"given":"Dario","family":"Giugliano","sequence":"first","affiliation":[{"name":"Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy"}]},{"given":"Mariusz","family":"Tracz","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabolic Diseases, Medical University, Warsaw, Poland"}]},{"given":"Sanjiv","family":"Shah","sequence":"additional","affiliation":[{"name":"Diabetes Action Centre, Mumbai, India"}]},{"given":"Alfonso","family":"Calle-Pascual","sequence":"additional","affiliation":[{"name":"Hospital Clinico San Carlos, Servicio Endocrinologia, Madrid, Spain"}]},{"given":"Cristina","family":"Mistodie","sequence":"additional","affiliation":[{"name":"Spitalul Clinic Judetean de Urgenta \u201cSf. Apostol Andrei\u201d Galati, Galati, Romania"}]},{"given":"Rui","family":"Duarte","sequence":"additional","affiliation":[{"name":"Associacao Dos Diabeticos de Portugal, Lisboa, Portugal"}]},{"given":"Ramazan","family":"Sari","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Akdeniz University, Antalya, Turkey"}]},{"given":"Vincent","family":"Woo","sequence":"additional","affiliation":[{"name":"University of Manitoba Health Sciences Center, Winnipeg, Manitoba, Canada"}]},{"given":"Alina O.","family":"Jiletcovici","sequence":"additional","affiliation":[{"name":"Diabetes Medical Affairs Europe, Eli Lilly and Company, Bucharest, Romania"}]},{"given":"J\u00fcrgen","family":"Deinhard","sequence":"additional","affiliation":[{"name":"Accovion GmbH, Eschborn, Germany"}]},{"given":"Simone A.","family":"Wille","sequence":"additional","affiliation":[{"name":"Diabetes Medical Affairs Europe, Eli Lilly and Company, Vienna, Austria"}]},{"given":"Jacek","family":"Kilja\u0144ski","sequence":"additional","affiliation":[{"name":"Diabetes Medical Affairs Europe, Eli Lilly and Company, Warsaw, Poland"}]}],"member":"1167","published-online":{"date-parts":[[2014,1,11]]},"reference":[{"key":"2022031219382151700_B1","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.jada.2005.02.007","article-title":"Breakfast habits, nutritional status, body weight, and academic performance in children and adolescents","volume":"105","author":"Rampersaud","year":"2005","journal-title":"J Am Diet Assoc"},{"key":"2022031219382151700_B2","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.jada.2007.01.011","article-title":"Breakfast: a missed opportunity","volume":"107","author":"Affenito","year":"2007","journal-title":"J Am Diet Assoc"},{"key":"2022031219382151700_B3","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1006\/pmed.2000.0651","article-title":"Differences in food patterns at breakfast by sociodemographic characteristics among a nationally representative sample of adults in the United States","volume":"30","author":"Siega-Riz","year":"2000","journal-title":"Prev Med"},{"key":"2022031219382151700_B4","doi-asserted-by":"crossref","first-page":"407237","DOI":"10.1155\/2011\/407237","article-title":"Overweight and obesity in eastern mediterranean region: prevalence and possible causes","volume":"2011","author":"Musaiger","year":"2011","journal-title":"J Obes"},{"key":"2022031219382151700_B5","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1620\/tjem.218.259","article-title":"The combined unhealthy behaviors of breakfast skipping and smoking are associated with the prevalence of diabetes mellitus","volume":"218","author":"Nishiyama","year":"2009","journal-title":"Tohoku J Exp Med"},{"key":"2022031219382151700_B6","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1177\/147323000803600401","article-title":"Breakfast: a good habit, not a repetitive custom","volume":"36","author":"Giovannini","year":"2008","journal-title":"J Int Med Res"},{"key":"2022031219382151700_B7","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1017\/S0007114508966137","article-title":"Eating behaviours and obesity in the adult population of Spain","volume":"100","author":"Mar\u00edn-Guerrero","year":"2008","journal-title":"Br J Nutr"},{"key":"2022031219382151700_B8","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.diabres.2010.11.007","article-title":"Dose Adjustment for Normal Eating: a qualitative longitudinal exploration of the food and eating practices of type 1 diabetes patients converted to flexible intensive insulin therapy in the UK","volume":"91","author":"Lawton","year":"2011","journal-title":"Diabetes Res Clin Pract"},{"key":"2022031219382151700_B9","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0022-3182(96)70098-5","article-title":"Food choice processes of older adults. A qualitative investigation","volume":"28","author":"Winter Falk","year":"1996","journal-title":"J Nutr Educ"},{"key":"2022031219382151700_B10","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.foodqual.2007.11.002","article-title":"Diversity in the determinants of food choice: a psychological perspective","volume":"20","author":"K\u00f6ster","year":"2009","journal-title":"Food Qual Prefer"},{"key":"2022031219382151700_B11","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1177\/014572179402000410","article-title":"The relationship between eating patterns and metabolic control in patients with non-insulin-dependent diabetes mellitus (NIDDM)","volume":"20","author":"Schmidt","year":"1994","journal-title":"Diabetes Educ"},{"key":"2022031219382151700_B12","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1007\/s10903-010-9428-3","article-title":"Determinants of fasting plasma glucose and glycosylated hemoglobin among low income Latinos with poorly controlled type 2 diabetes","volume":"13","author":"Kollannoor-Samuel","year":"2011","journal-title":"J Immigr Minor Health"},{"key":"2022031219382151700_B13","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1093\/ajcn\/55.3.645","article-title":"The role of breakfast in the treatment of obesity: a randomized clinical trial","volume":"55","author":"Schlundt","year":"1992","journal-title":"Am J Clin Nutr"},{"key":"2022031219382151700_B14","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.diabres.2006.06.025","article-title":"Survey of dietary habits in obese patients with type 2 diabetes treated with either OHA or insulin injections in Japan","volume":"77","author":"Uchigata","year":"2007","journal-title":"Diabetes Res Clin Pract"},{"key":"2022031219382151700_B15","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00592-003-0110-2","article-title":"Importance of premeal injection time in insulin therapy: Humalog Mix25 is convenient for improved post-prandial glycemic control in type 2 diabetic patients with Italian dietary habits","volume":"40","author":"Coscelli","year":"2003","journal-title":"Acta Diabetol"},{"key":"2022031219382151700_B16","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1586\/14737159.8.1.9","article-title":"1,5-anhydroglucitol (GlycoMark) as a marker of short-term glycemic control and glycemic excursions","volume":"8","author":"Dungan","year":"2008","journal-title":"Expert Rev Mol Diagn"},{"key":"2022031219382151700_B17","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.2337\/diacare.28.5.1245","article-title":"Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia","volume":"28","author":"Workgroup on Hypoglycemia, American Diabetes Association","year":"2005","journal-title":"Diabetes Care"},{"key":"2022031219382151700_B18","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0168-8510(96)00822-6","article-title":"EuroQol: the current state of play","volume":"37","author":"Brooks","year":"1996","journal-title":"Health Policy"},{"key":"2022031219382151700_B19","first-page":"111","article-title":"The diabetes treatment satisfaction questionnaire","volume-title":"Handbook of Psychology and Diabetes: A Guide to Psychological Measurement in Diabetes Research and Practice","author":"Bradley","year":"1994"},{"key":"2022031219382151700_B20","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1177\/0145721709345773","article-title":"Barriers to insulin injection therapy: patient and health care provider perspectives","volume":"35","author":"Rubin","year":"2009","journal-title":"Diabetes Educ"},{"key":"2022031219382151700_B21","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.2337\/dc12-0413","article-title":"Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)","volume":"35","author":"Inzucchi","year":"2012","journal-title":"Diabetes Care"},{"key":"2022031219382151700_B22","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1530\/EJE-11-0022","article-title":"Insulin initiation in patients with type 2 diabetes mellitus: treatment guidelines, clinical evidence and patterns of use of basal vs premixed insulin analogues","volume":"166","author":"Vaag","year":"2012","journal-title":"Eur J Endocrinol"},{"key":"2022031219382151700_B23","doi-asserted-by":"crossref","first-page":"510","DOI":"10.2337\/dc10-1710","article-title":"Efficacy of insulin analogs in achieving the hemoglobin A1c target of &lt;7% in type 2 diabetes: meta-analysis of randomized controlled trials","volume":"34","author":"Giugliano","year":"2011","journal-title":"Diabetes Care"},{"key":"2022031219382151700_B24","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1007\/s00125-009-1468-7","article-title":"Optimal insulin regimens in type 2 diabetes mellitus: systematic review and meta-analyses","volume":"52","author":"Lasserson","year":"2009","journal-title":"Diabetologia"},{"key":"2022031219382151700_B25","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.clinthera.2007.07.003","article-title":"Prandial premixed insulin analogue regimens versus basal insulin analogue regimens in the management of type 2 diabetes: an evidence-based comparison","volume":"29","author":"Ilag","year":"2007","journal-title":"Clin Ther"},{"key":"2022031219382151700_B26","doi-asserted-by":"crossref","first-page":"881","DOI":"10.2337\/diacare.26.3.881","article-title":"Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c)","volume":"26","author":"Monnier","year":"2003","journal-title":"Diabetes Care"},{"key":"2022031219382151700_B27","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1111\/j.1463-1326.2008.00967.x","article-title":"Introducing a simplified approach to insulin therapy in type 2 diabetes: a comparison of two single-dose regimens of insulin glulisine plus insulin glargine and oral antidiabetic drugs","volume":"10","author":"Lankisch","year":"2008","journal-title":"Diabetes Obes Metab"},{"key":"2022031219382151700_B28","doi-asserted-by":"crossref","first-page":"395","DOI":"10.4158\/EP10323.OR","article-title":"A stepwise approach to insulin therapy in patients with type 2 diabetes mellitus and basal insulin treatment failure","volume":"17","author":"Davidson","year":"2011","journal-title":"Endocr Pract"},{"key":"2022031219382151700_B29","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1111\/j.1463-1326.2005.00563.x","article-title":"Attainment of glycaemic goals in type 2 diabetes with once-, twice-, or thrice-daily dosing with biphasic insulin aspart 70\/30 (The 1-2-3 study)","volume":"8","author":"Garber","year":"2006","journal-title":"Diabetes Obes Metab"},{"key":"2022031219382151700_B30","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.clinthera.2010.05.001","article-title":"Randomized, open-label, parallel-group evaluations of basal-bolus therapy versus insulin lispro premixed therapy in patients with type 2 diabetes mellitus failing to achieve control with starter insulin treatment and continuing oral antihyperglycemic drugs: a noninferiority intensification substudy of the DURABLE trial","volume":"32","author":"Miser","year":"2010","journal-title":"Clin Ther"},{"key":"2022031219382151700_B31","doi-asserted-by":"crossref","first-page":"20","DOI":"10.2337\/dc07-1122","article-title":"Advancing insulin therapy in type 2 diabetes previously treated with glargine plus oral agents: prandial premixed (insulin lispro protamine suspension\/lispro) versus basal\/bolus (glargine\/lispro) therapy","volume":"31","author":"Rosenstock","year":"2008","journal-title":"Diabetes Care"},{"key":"2022031219382151700_B32","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1111\/j.1463-1326.2010.01287.x","article-title":"Prandial-basal insulin regimens plus oral antihyperglycaemic agents to improve mealtime glycaemia: initiate and progressively advance insulin therapy in type 2 diabetes","volume":"12","author":"Jain","year":"2010","journal-title":"Diabetes Obes Metab"},{"key":"2022031219382151700_B33","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1111\/j.1463-1326.2011.01459.x","article-title":"Effects of initiation and titration of a single pre-prandial dose of insulin glulisine while continuing titrated insulin glargine in type 2 diabetes: a 6-month \u2018proof-of-concept\u2019 study","volume":"13","author":"Owens","year":"2011","journal-title":"Diabetes Obes Metab"},{"key":"2022031219382151700_B34","doi-asserted-by":"crossref","first-page":"727","DOI":"10.4158\/EP10367.OR","article-title":"Comparison of 2 intensification regimens with rapid-acting insulin aspart in type 2 diabetes mellitus inadequately controlled by once-daily insulin detemir and oral antidiabetes drugs: the step-wise randomized study","volume":"17","author":"Meneghini","year":"2011","journal-title":"Endocr Pract"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/37\/2\/372\/620200\/372.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/37\/2\/372\/620200\/372.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,19]],"date-time":"2024-05-19T00:48:14Z","timestamp":1716079694000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/37\/2\/372\/29447\/Initiation-and-Gradual-Intensification-of-Premixed"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,11]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2014,1,11]]},"published-print":{"date-parts":[[2014,2,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc12-2704","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,11]]}}}