Diabetes Q&A

On the Alpha and the Omega of the Beta Cell (and More)

Kim A. Carmichael, MD, FACP
Paulina Cruz, MD
Volume 54 - Issue 1 - January 2014

Q. When should insulin be started in type 2 diabetes?

A. Based on the 2 main consensus statements from the American Diabetes Association1 and the American Association of Clinical Endocrinologists2, insulin is generally recommended as a second-line therapy when non-insulin agents alone or in combination at maximal tolerated doses fail to achieve glucose targets within a 3 to 6 month period. 

Q. Are there any circumstances to start insulin earlier?

A. Yes, individuals presenting with very high glucose levels (>300 mg/dl), a hemoglobin A1c (A1c) greater than 10%, ketonuria or who are symptomatic are likely to benefit from insulin initially to lower their glucose levels.3 Non-insulin oral or injectable diabetes medications usually only reduce A1c by 0.5% to 1%. 

It is important to consider the duration of the disease. Patients with newly-diagnosed type 2 diabetes are more likely to improve their beta cell function when achieving better glucose control and in some it may later be feasible to transition to oral medications.4 

In general, early initiation of insulin therapy may not reduce long-term complications compared to non-insulin therapy. The ORIGIN trial showed no difference in cardiovascular and microvascular outcomes after 6 years in patients with early diabetes or impaired fasting plasma glucose (IFPG) when adding a daily dose of insulin glargine to achieve normoglycemia compared to standard care.5 As expected, insulin glargine was associated with slightly more weight gain and hypoglycemia and there was a lower incidence of developing new-onset diabetes among those with IFPG. 

Q. How does one start insulin therapy? 

A. Usually patients benefit from long-acting basal insulin like glargine or detemir when they exhibit elevated fasting plasma glucose (FPG) levels while on 1 or 2 non-insulin agents. These are once-daily injections and usually are preferred over neutral protamine Hagedorn, which 

is associated with a greater incidence of hypoglycemia.6 

Among many protocols and algorithms available, patients in the Treat-to-Target trial started with 10 units of insulin glargine at bedtime and were given an algorithm to titrate insulin weekly based on the last 2 days of FPG.6 In this trial, 60% of patients achieved an A1c of less than 7%.

Q. When should one add mealtime insulin?

A. If postprandial glucose levels are elevated despite optimal oral agent therapy, patients may benefit from the mealtime use of one of several rapid-acting insulins—such as aspart, glulisine, or lispro (basal-bolus therapy). These patients should have diabetes education and instruction in carbohydrate counting. Insulin may be titrated on a weekly basis as patients self-monitor blood sugar and carbohydrate intake, adjusting therapy until glycemic targets are achieved. In some patients, pre-mixed insulin combinations may be preferred. 

Q. Should oral antidiabetics be discontinued?

A. Many oral and injectable diabetes medications are approved for use with insulin. If renal function is adequate, metformin is usually continued. Sulfonylureas and glinides are associated with increased risk of hypoglycemia and may be used with caution. Newer drugs are available that carry little additional risk of hypoglycemia, including DDP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors, short-acting bromocriptine, and colvesevelam. When mealtime insulin is added, many of these additional diabetes agents are often discontinued.

Q. What are the barriers to insulin therapy and how can we overcome them?

A. Although commonly overlooked, lifestyle considerations are crucial to achieve success with insulin. Cognitive ability, dexterity problems due to severe arthritis or neuropathy, visual impairment, pain with injections, needle phobia, fear of hypoglycemia, inconsistency in food intake, and disruption of daily routines are a few examples. Use of available self-care resources may be beneficial to increase adherence to insulin therapy and to overcome some of these barriers. 

Team up with a diabetes educator who is knowledgeable in insulin titration to ease your workload. Educate your patients early by regularly explaining the progressive nature of the disease and avoid using insulin as a threat, punishment, or failure. 

A patient-centered approach is best. More stringent A1c targets (eg, less than 7%) are preferred for patients who are motivated, have a short duration of the disease, long life expectancy, and no major complications. This improved control should be achieved without creating a significant risk of hypoglycemia. For high-risk patients, such as those with cardiovascular, cerebrovascular, or advanced renal disease, higher A1c targets should be considered.7,8 ■

PAULINA CRUZ, MD, is a fellow in the department of internal medicine, division of endocrinology, diabetes, and lipid research at Washington University School of Medicine in St Louis, Missouri.

Kim A. Carmichael, MD, is an associate professor of medicine, department of internal medicine, division of endocrinology, diabetes, and lipid research at Washington University School of Medicine in St Louis, Missouri. Dr Carmichael discloses that he is on the speaker’s bureaus for Merck and Janssen.

References:

  1. Garber AJ, Abrahamson MJ, Barzilay JI. AACE comprehensive diabetes algorithm 2013. Endo Pract. 2013;19(2):327-336.
  2. Inzucchi SE, B. R. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position stament of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2013;35 (6):1364-1379.
  3. Hamaty M. Insulin treatment for type 2 diabetes: when to start, which to use. Cleve Clin J Med. 2011;78(5):332-342.
  4. Smiley D, Chandra P, Umpierrez GE. Update on diagnosis, pathogenesis and management of ketosis-prone type 2 diabetes. Diabetes Manag. 2011;1(6):589-600.
  5. ORIGIN trial investigators. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Eng J Med. 2012;367(4):319-328.
  6. Riddle MC, Rosenstock J, Gerich J. The treat-to-target trial. Diabetes Care. 2003;26(11):3080-3086.
  7. The Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-2459.
  8. The ADVANCE Collaborative Group, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560-2572.