title: The Barmer study: impact of standardized warming of the injection site to enhance insulin absorption and reduce prandial insulin requirements and hypoglycemia in obese patients with diabetes mellitus.
abstract: BACKGROUND
  The primary objective of this prospective controlled study was to investigate the impact of standardized injection-site warming on prandial rapid acting insulin dose and glycemic control when studied under real-world conditions.
  
  
  METHODS
  All 145 participating patients (51 female, 94 male, 13 type 1 and 132 type 2 patients, age: 61.6 ± 8.4 yrs, HbA1c: 7.19 ± 0.50%) were treated with intensive insulin glargine and short-acting insulin analog therapy. After a 4 week treatment optimization run-in period, patients were randomized to continue therapy for three months without (control) or with a local injection-site warming device (InsuPad * ). Observation parameters included HbA1c, insulin dose, frequency of hypoglycemia, body weight and adverse events.
  
  
  RESULTS
  HbA1c improved in both arms until study end (control group: 6.3 ± 0.5%; injection-site warming device: 6.3 ± 0.5%; both p < 0.001 vs. baseline). To achieve this good control, patients in the control group needed to increase the daily prandial insulin dose by 8.1% (from 66 ± 31 U to 71 ± 38 U, p < 0.05) with stable basal insulin requirements. Patients who used the injection-site warming device required less prandial insulin (70 ± 43 U to 55 ± 34 U; -19%, p < 0.001) and slightly more basal insulin (+3.9%). Total daily insulin dose increased in the control group (+3.7%) and decreased with warming device use (-8.6%, p < 0.001). The number of hypoglycemic events (<63 mg/dL) during the observation period was higher in the control group (6.2 ± 9.9/patient vs. injection-site warming device: 3.3 ± 4.8/patient, p < 0.05). Main study limitations can be seen in the open label design reliability of the collected dose information and the very obese patient cohort.
  
  
  CONCLUSIONS
  When treating obese patients to target with insulin therapy, use of an injection-site warming device for 3 months resulted in a lower frequency of hypoglycemic events and a reduction in prandial insulin analog requirements. If these results are confirmed in other patient populations, an injection-site warming device may be useful in achieving treatment targets with a safer and more efficient basal bolus therapy in insulin-treated patients with type 1 and type 2 diabetes.
authors.affiliation: IKFE Services - Institute of Clinical Research and Development , Mainz , Germany.
authors.forename: A
authors.initials: A
authors.lastname: Pfützner
authors.forename: N
authors.initials: N
authors.lastname: Hermanns
authors.forename: K
authors.initials: K
authors.lastname: Funke
authors.forename: T
authors.initials: T
authors.lastname: Forst
authors.forename: T
authors.initials: T
authors.lastname: Behnke
authors.forename: G
authors.initials: G
authors.lastname: Bitton
authors.forename: R
authors.initials: R
authors.lastname: Nagar
authors.forename: I
authors.initials: I
authors.lastname: Raz
authors.forename: T
authors.initials: T
authors.lastname: Haak
mesh_terms: D000042:Absorption; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007003:Hypoglycemia / Q000097:blood / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000378:metabolism; D019518:Postprandial Period; D011446:Prospective Studies
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine