The Damping Parameters Cye (Curb Your Enthusiasm) and Dsp (Downscale Pre-Emptively) for Basal Insulin Therapy

Abstract

When glycemic targets are not met, treatment intensification for type 2 diabetes may consist of the introduction of long-acting insulin analogue therapy, in combination with noninsulin therapies ( 1. Riddle M.C. Rosenstock J. Gerich J. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003; 26: 3080-3086 Crossref PubMed Scopus (1393) Google Scholar ). For those who do not achieve control, basal-bolus therapy may be the most efficacious insulin analogue regimen for reaching glycated hemoglobin (A1c) goals ( 2. Giugliano D. Maiorino M.I. Bellastella G. Chiodini P. Ceriello A. Esposito K. Efficacy of insulin analogs in achieving the hemoglobin A1c target of <7% in type 2 diabetes: meta-analysis of randomized controlled trials. Diabetes Care. 2011; 34: 510-517 Crossref PubMed Scopus (114) Google Scholar , 3. Handelsman Y. Bloomgarden Z.T. Grunberger G. et al. American Association of Clinical Endocrinologists and American College of Endocrinology - clinical practice guidelines for developing a diabetes mellitus comprehensive care plan - 2015. Endocr Pract. 2015; 21: 1-87 Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar ). However, it is commonly supposed, for those patients having persistence of first morning fasting blood glucose (BG) elevation, that persistence of A1c elevation indicates need for further dosage increments of long-acting insulin analogue. The scenario is addressed in this issue of Endocrine Practice by Shaefer and colleagues ( 4. Shaefer C. Reid T. Vlajnic A. Zhou R. DiGenio A. Fasting versus postprandial hyperglycemia as a treatment target to lower elevated hemoglobin A1c. Endocr Pract. 2015; 21: 1323-1332 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar ) and in the accompanying commentary by Gerich ( 5. Gerich J.G. Commentary. Endocr Pract. 2015; 21: 1439-1441 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ). Shaefer and colleagues extracted data from studies of patients who were not at goal with respect to A1c after treatment for 24 weeks with glargine insulin intended to deliver “optimized basal insulin therapy” for treatment of type 2 diabetes, under a strategy identified by Gerich as “fix the fasting first.” Judging by group averages of 7-point BG monitoring as shown in Figure 1B of the paper by Shaefer et al ( 4. Shaefer C. Reid T. Vlajnic A. Zhou R. DiGenio A. Fasting versus postprandial hyperglycemia as a treatment target to lower elevated hemoglobin A1c. Endocr Pract. 2015; 21: 1323-1332 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar ), the long-acting insulin analogue therapy was providing more than physiologic basal insulin coverage. For the 340 patients having A1c ≥7.0% and postprandial BG ≥180 mg/dL at 2 hours after any meal and at a mean dose of 0.47 IU/kg of glargine insulin, estimations of the authors suggested substantial unaddressed prandial contribution to hyperglycemic exposure, regardless of subgroup assignment by fasting plasma glucose <130 or ≥130 mg/dL ( 4. Shaefer C. Reid T. Vlajnic A. Zhou R. DiGenio A. Fasting versus postprandial hyperglycemia as a treatment target to lower elevated hemoglobin A1c. Endocr Pract. 2015; 21: 1323-1332 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar ). Although the event rate per patient-year for hypoglycemia was greatest in those not having fasting hyperglycemia, still hypoglycemia was observed in 32.7% of those with fasting hyperglycemia. The study could be used to generate the hypothesis that pharmacologic intervention relying upon prandial coverage would be safer and more effective than further forced titration of basal insulin, even for those having fasting hyperglycemia. As pointed out by the commentator, to prove such a hypothesis, there would need to be a randomized trial ( 5. Gerich J.G. Commentary. Endocr Pract. 2015; 21: 1439-1441 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ).