Editor’s Note: A correction to this article was published in the July 2013 issue of The Journal of the American Osteopathic Association (2013;113[7]:507). The correction has been incorporated in this online version of the article, Insulin Therapy for Challenging which was posted July 2013. An explanation of the change Patient Cases is available at http://www.jaoa.org/content/113/7/507.2.full. Jay H. Shubrook Jr, DO From the Ohio University Heritage College of Osteopathic Medicine in Athens. This article is based on a continuing medical education symposium held on October 10, 2012, during the American Osteopathic Association’s 2012 annual Osteopathic Medical Conference & Exposition in San Diego, California. This article was developed with assistance from Global Directions in Medicine. The author has approved the article and all of its content. Financial Disclosures: Dr Shubrook receives research support from Eli Lilly and Company and sanofi-aventis US. Address correspondence to Jay H. Shubrook Jr, DO, Ohio University Heritage College of Osteopathic Medicine, Grosvenor Hall, Initiating and advancing insulin therapy in patients with type 2 Athens, OH 45701-2979. diabetes mellitus can be challenging. However, with the avail- E-mail: [email protected] ability of insulin analogs with more physiologic profiles, and with the initiation of simple insulin regimens (eg, the use of basal insulin administered once daily), an opportunity is created to empower patients to self-titrate their insulin. Self-titration can reduce the burden on the physician as well as improve glycemic control in patients. More options for intensifying insulin now exist, including gradually adding prandial insulin (referred to as a basal “plus” strategy) or using premixed insulin analogs for patients with relatively consistent lifestyles and habits. More-concentrated forms of insulin, such as U-500 insulin, may be helpful for patients requiring very large doses of insulin. The key is to match the insulin regimen to the patient; engage in dialogue to understand the patient’s lifestyle, concerns, and skill sets; and develop, through a shared decision-making process, appropriate individualized treatment recommenda- tions. The present review article focuses on the use of insulin replacement therapy in challenging patient cases. J Am Osteopath Assoc. 2013;113(4 suppl 2):S17-S28 [Published correction appears in J Am Osteopath Assoc. 2013;113(7):507.] A Supplement to The Journal of the American Osteopathic Association April 2013 | Vol 113 | No. 4 | Supplement 2 S17 pproximately 26 million cal inertia exists with respect to initiating livery device used.13,14 For most patients people in the United States appropriate insulin therapy in patients whose HbA1c levels are not at goal, the Ahave diabetes, and the vast with T2DM.10 The present article will ex- simplest first step is to start insulin ther- majority have type 2 diabetes mellitus plore some challenging cases for which apy with a single injection of a long-act- (T2DM).1 Even with the establishment the use of insulin is indicated, initiated, ing basal insulin analog.9 Basal insulin of treatment goals and the development and adjusted, albeit not always with im- suppresses hepatic glucose production of considerable advancements in dia- mediate patient acceptance. overnight and between meals. It con- betes treatment,2 inadequate metabolic stitutes approximately 50% of the daily control is pervasive.3-5 The proportion insulin needs of an individual.9 Once- of patients with glycated hemoglobin General Principles daily use of a basal insulin analog (insu- 9 (HbA1c) levels that are at goal is still well Since 2012, treatment algorithms for lin glargine or insulin detemir) offers the below the diabetes indicators discussed the management of patients with T2DM advantages of simple dosing and ease in the Healthy People 2020 initiative.6 have followed the approach to pa- of titration (ie, patients can learn to man- Available data show that many patients tient-centered care established by the age their T2DM with limited training).15-18 with T2DM still have poor glycemic Committee on Quality of Health Care This treatment is highly effective in im- control along with comorbid conditions in America: “providing care that is re- proving glycemic control in patients who that may complicate treatment deci- spectful of and responsive to individual no longer respond to combination oral sions. These conditions include a high patient preferences, needs, and values antidiabetic therapy.13 The goal of basal prevalence of hypertension, heart fail- and ensuring that patient values guide insulin analog therapy is to improve fast- ure, stroke, and nephropathy, as well all clinical decisions.”11 Diabetes man- ing blood glucose levels. Typical starting as other comorbidities associated with agement includes the setting of individu- doses are 10 to 20 U of insulin glargine 7 T2DM. When glycemic control is not alized glucose targets to achieve HbA1c or insulin detemir given once daily (or, optimized, diabetes imposes burden- levels as close to normal as possible in as an alternative, 0.2 U/kg).9 Neutral some care requirements, increased patients who are most likely to benefit protamine Hagedorn (NPH) insulin can health care costs, and a high risk of from good glycemic control (ie, those be a more economical option, but physi- disabling complications.1 These situa- without clinical evidence of macrovas- cians should be aware that NPH insulin tions are especially evident in socioeco- cular complications) while also minimiz- is more of an intermediate-acting insulin nomically disadvantaged and minority ing the possible risks of hypoglycemia. It and that it therefore must be dosed 2 to populations, who are already at higher also includes relaxing targets in patients 3 times per day to serve as a basal in- risk for diabetes. Achieving reductions with limited life expectancy, in patients sulin. Physicians should also be aware in HbA1c levels through a combination with existing diabetes complications or that NPH insulin is associated with a of clinical management and effective longer duration of disease, and in those greater risk of hypoglycemia, especially self-management has demonstrated a for whom there is greater concern about nocturnal hypoglycemia, than are basal reduced risk of microvascular complica- the development of hypoglycemia.10,12 insulin analogs.19 tions.8 More personalized approaches Oral antidiabetic agents are usually to therapy are needed.8 continued when insulin is started, un- Despite the well-documented ben- Initiation of Insulin Therapy less there are specific contraindications efits of both timely glycemic control and When prescribing insulin therapy, the or substantial risks of hypoglycemia (in consensus guidelines that encourage astute osteopathic physician imple- some cases, the dose of sulfonylureas the therapeutic use of insulin earlier in ments the most appropriate form on the may be decreased or discontinued).9 the course of T2DM,9 considerable clini- basis of the insulin type, dose, and de- This continuance of therapy helps pa- S18 A Supplement to The Journal of the American Osteopathic Association April 2013 | Vol 113 | No. 4 | Supplement 2 tients avoid the loss of further glycemic is not currently approved by the US ment are paramount. The body may re- control during the transition to insulin. Food and Drug Administration for use spond to extremely low nocturnal blood The insulin dose should be titrated on with insulin therapy. glucose levels by rebounding with high the basis of a fasting blood glucose tar- blood glucose levels in the morning (re- get. The American Diabetes Association ferred to as the Somogyi effect). This recommends a goal of less than 130 mg/ Proactively Addressing rebound could be incorrectly identified dL.20 A patient should expect an approxi- Hypoglycemia as fasting hyperglycemia. Both the pa- mately 0.5% decrease in the HbA1c level Hypoglycemia has always been the tient and the physician should routinely for each insulin dose increment of 0.1 U/ rate-limiting step in achieving perfect review blood glucose patterns. Patients kg per day. Basal insulins can be self- glycemic control for patients with T2DM. with type 1 diabetes mellitus, as well titrated up to either a target fasting blood Hypoglycemia can be dangerous, and as those with T2DM of long duration, glucose level or an approximate dose assessing patients for this condition is may be at risk of hypoglycemia. With of 0.5 U/kg per day. At higher doses, critically important. For patients, a fear increasing age, the potential reaction the improvement in the decrease in the of hypoglycemia can often have a con- time between awareness and onset of HbA1c level is less substantial, and the siderable negative impact on diabetes symptoms is decreased, contributing risk of hypoglycemia increases.21 If, after management, metabolic control, and to an increased risk for asymptomatic 23 sufficient time, the HbA1c level still has subsequent health outcomes. Not hypoglycemia and greater susceptibility not reached goal with the use of 0.5 U of performing this assessment may result to cognitive impairment.25,26 Recurrent, basal insulin per kilogram per day, then in patients taking such actions as en- unrecognized hypoglycemia can occur attention should be focused on meal- gaging in “defensive” eating or omitting even in patients with T2DM who have time or prandial glucose excursions. If insulin doses to preclude hypoglycemia, well-controlled glycemia.27 Asymptom- excursions are present, consider adding thus thwarting the best efforts of the atic hypoglycemia and nocturnal hy- an agent to target postprandial hyper- physician to help patients achieve gly- poglycemia can interfere with the abil- glycemia, which is the likely cause of cemic control. This behavior becomes ity of patients to recognize subsequent persistent hyperglycemia. This can be particularly dangerous if the physician hypoglycemia, and they can also limit confirmed by having the patient check is titrating insulin regimens. patients’ ability to take appropriate ac- his or her glucose level 2 hours after the Failure to address even mild hypo- tion, thereby exacerbating the situation.