People with Type 2 Diabetes on Premixed Insulin Therapy: How is the Daily Insulin Dose Partitioned and are there Effects on the Metabolic Control?

Abstract

Aim: To investigate the correctness of the recommendation for dose distribution in premixed insulin therapy, with two thirds of daily insulin dose before breakfast and one third of daily insulin dose before dinner.

Methods: The individual insulin dose distribution and metabolic control of people with Type 2 diabetes treated with premixed insulin therapy were studied in a cross sectional study involving 199 patients in a university outpatient department and 2 general practices in 2010.

Results: All 199 patients were treated with premixed human insulin. The mean pre-breakfast dose was 57% (min. 32%, max. 83%) and the mean pre-dinner dose 43% (17–67%) of the total daily insulin. A pre-breakfast dose of exactly two thirds of total daily insulin was used by 6.5% (n=13), about two thirds, i. e., 60–70%, was injected by 27.6% of the patients. The diurnal insulin distribution<60%, 60% up to 70% and > 70% pre-breakfast insulin did not make any difference in HbA1c, which was 7.3% (56 mmol/mol) each.

Conclusion: The quite common recommendation in German and Austrian medical textbooks, that premixed insulin therapy should consists of a dose distribution with two thirds before breakfast and one third before dinner, is not observed in daily practice. Diurnal insulin dose distribution and HbA1c are not associated in this cohort.

Novelty statement: The circadian insulin dose distribution of 2/3 before breakfast and 1/3 before dinner could not be confirmed for patients with diabetes type 2 and conventional insulin therapy. No correlation between metabolic control and insulin circadian insulin dose distribution was detected.

Key words

type 2 diabetes mellitus - hemoglobin A1c protein - human mixed insulins - metabolic diseases - primary health care - chronic disease

• References

• 1 Matthaei S, Bierwirth R, Fritsche A et al. for the German Diabetes Association . Medical antihyperglycaemic treatment of type 2 diabetes mellitus: update of the evidence based guideline of the German Diabetes Association. Exp Clin Endocrinol Diabetes 2009; 117: 522-557
• 2 Mühlhauser I, Spraul M, Berger M. Insulinsubstitutionstherapie incl. Insulinpumpentherapie (Insulin supplemention therapy including insulin pump). Berger M. Hrsg Diabetes mellitus. Urban und Schwarzenberg; 1995: 259
• 3 Mehnert H, Standl E, Usadel K et al. Behandlung mit Insulin (Treatment with insulin). Mehnert H. Hrsg Diabetologie in Klinik und Praxis. Thieme Verlag; 2003: 324
• 4 Braun J, Dormann Arno J, Braun J Hrsg Klinikleitfaden Innere Medizin (Clinical guidelines Internal Medicine). Urban & Fischer; 2009: 656
• 5 Gesenhues S, Ziesché R. Stoffwechsel und Hormonerkrankungen. Gesenhues S. Hrsg Praxisleitfaden Allgemeinmedizin (Guidelines for General Practise). Urban & Fischer; 2010: 966
• 6 Herold G. Diabetes mellitus. Herold G. Hrsg Lehrbuch Innere Medizin. Gerd Herold Verlag; 2014: 719-747
• 7 Holman RR, Thorne KI, Farmer AJ et al. for the 4-T Study Group . Addition of Biphasic, Prandial, or Basal Insulin to Oral Therapy in Type 2 Diabetes. N Engl J Med 2007; 357: 1716-1730
• 8 Kloos C, Sämann A, Lehmann T et al. Flexible, intensive vs. conventional insulin therapy in insulin-naive adults with type 2 diabetes - an open-label, randomized controlled cross-over clinical trial of metabolic control and patient preference. Diabetes Care 2007; 30: 3031-3032
• 9 Ohkubo Y, Kishikawa H, Araki E et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin dependent diabetes mellitus: a randomized prospective 5-year study. Diab Res Clin Pract 1995; 28: 103-117
• 10 Gerstein HC, Miller ME, Byington RP et al. Action to Control Cardiovascular Risk in Diabetes Study Group – Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358: 2545-2559
• 11 Patel A, MacMahon S, Chalmers J et al. ADVANCE Collaborative Group . Intensive blood glucose control and vascular outcomes in patients with Type 2 diabetes. N Engl J Med 2008; 358: 2560-2572
• 12 Nationale VersorgungsLeitlinie (national treatment guidelinei), Therapie des Typ 2 Diabetes (treatment of Type 2 diabetes), Langfassung (long version), 1. Auflage, August 2013. http://www.versorgungsleitlinien.de/themen/diabetes2/dm2_therapie/pdf/NVL-DM2-Ther-lang-2.pdf Accessed 16.09.2013
• 13 Heller T, Kloos C, Keßler D et al. Use of snacks in insulin-treated people with diabetes mellitus and association with HbA1c, weight and quality of life: a cross sectional study. Diabet Med 2015; 32: 353-358
• 14 Kalfhaus J, Berger M. Insulin treatment with preprandial injections of regular insulin in middle aged type 2 diabetic patients. A two years observational study. Diabetes Metab 2000; 26: 197-201
• 15 Grüsser M, Bott U, Ellermann P et al. Evaluation of a structured treatment and teaching program for non-insulin-treated type-II-diabetic outpatients in Germany after the nationwide introduction of reimbursment policy for physicians. Diabetes Care 1993; 16: 1268-1275
• 16 Reise K, Hartung V, Kloos C et al. Inzidenz nicht schwerer Unterzuckerungen bei insulinbehandelten Patienten mit Diabetes mellitus Typ 2 in Abhängigkeit von der Therapieform. (Incidence of non-severe hypoglycaemia in patients with Type 2 Diabetes and Insulin treatment in regard to insulin-regimes). Diab Stoffw 2011; 6 – P155
• 17 Beluchin E, Bäz L, Müller N et al. Frequency of self-adjustment of insulin dose and metabolic control in Type 2 diabetes – is there an association?. Diabet Med 2013; 30 e91–e94
• 18 Kloos C, Weimer D, Müller UA. Ernährung bei Patienten mit Diabetes mellitus Typ 2 unter konventioneller (CIT) Therapie mit Mischinsulin und intensivierter Therapie (MIT) mit präprandialem Normalinsulin – eine strukturierte Befragung von nicht selektierten Patienten in einer Hochschulambulanz (FSU Jena) 2004 (Nutrition in patients with Type 2 diabetes with conventional treatment with premixed insulin and intensive treatment with normal insulin – a structured survey of not randomized patients in a university outpatient department (FSU Jena) 2004). Diab Stoffw 2005; 14 Suppl: 61
• 19 Inzucchi SE, Bergenstal RM, Buse JB et al. Management of hyperglycaemia in type 2 diabetes: a patientcentered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2012;
• 20 Müller UA, Müller R, Starrach A et al. Should insulin therapy in type II diabetic patients be started on an out- or inpatient basis? Results of a prospective controlled trial using the same treatment and teaching programme in ambulatory care and in a University hospital. Diab Metab (Paris) 1998; 24: 251-255