A study designed to determine the most effective timing of rapid-acting insulin analog (Novorapid®) with CSII in children with type 1 diabetes reported that glucose levels 3 h after the meal were lower when the prandial insulin was administered 15 min or immediately before the meal, rather than after the meal (Scaramuzza 2010). Also demonstrated was a significant difference in 1-h postprandial glucose levels, which were significantly higher when the prandial insulin was given after the meal and lowest when the insulin was administered 15 min before the meal. This result occurred even if the blood glucose was in the hypoglycemic range before eating.
Subjects with type 1 diabetes using CSII participated in a crossover study consisting of three treatment arms: delivering rapid-acting insulin analog (glulisine) 20 min before a meal, immediately before the meal, and 20 min after the meal initiation (Cobry 2010). At both 60 and 120 min after meal initiation, the 20-min before-meal insulin arm showed significantly lower glycemic excursions than when the prandial insulin was given immediately before the meal. Glycemic area under the curve was significantly less in the before-meal insulin group than in both the immediately before- or after-meal initiation groups. The authors concluded that although delivering the prandial dose of insulin 20 min before the meal may be inconvenient, it is an important strategy that can result in a reduction of postprandial glucose levels over 180 mg/dL.
Another trial assessed the effect of the rapid-acting insulin analog (aspart) timing on postprandial glucose levels in subjects with type 1 diabetes using CSII when the prandial insulin was administered at 30, 15, or 0 min before mealtime (Luijf 2010). The administration of the prandial insulin 15 min before mealtime resulted in lower postprandial glucose excursions and more time spent in desirable ranges without an increase in hypoglycemia.
Data from these three small studies argue for administration of rapid-acting insulin analogs 15–20 min before the start of the meal. However, larger trials outside the clinical research center are needed to confirm these findings. Tridgell and colleagues proposed progressively longer lag times for rapid-acting prandial and correction dose insulin depending on the degree of hyperglycemia (Tridgell 2010) (see Table 5.4 for lag times for prandial insulin).
Table 5.4 Recommended Insulin Lag Times for Rapid-Acting Insulin Based on Degree of Preprandial Hyperglycemia
When recommending preprandial times, clinical judgment is required in specific patient populations such as young children or the elderly, who do not have predictable food intake (Tridgell 2010). It may be appropriate to give these individuals the dose of prandial insulin during the meal or immediately after the meal to reduce the risk of hypoglycemia. In addition, individuals with delayed gastric emptying may benefit from administration of rapid-acting insulin at the end of the meal or the use of regular insulin 30 min before the start of the meal (see Chapter 18, Nutrition Therapy for Diabetic Gastropathy).
If hypoglycemia is determined before the start of a meal, the individual should treat the low glucose level with a carbohydrate food, inject the prandial insulin, and then eat (Scaramuzza 2010). Others have suggested treating the hypoglycemia and delaying the prandial injection for a brief time (Trigdell 2010). On the basis of clinical experience, the individual could additionally be advised to reduce the prandial insulin dose or instructed to increase carbohydrate food consumed at the meal.
Postprandial Glycemic Control and Diabetes Complications
Diabetes management decisions have traditionally been made using fasting and premeal blood glucose measurements as well as A1C test results. This approach has left many people with diabetes with suboptimal glycemic control because of inadequate control of postprandial hyperglycemia. Postprandial glucose excursions and postprandial hyperglycemia occur frequently in people with diabetes, even when A1C may be <7%, and this result may convey increased risk of cardiovascular morbidity and mortality (Ceriello 2005; Home 2005). Advocates of postprandial monitoring propose that it is critical to the establishment of good glycemic control (Hirsch 2005b; Tridgell 2010), whereas others are not convinced that postprandial SMBG is essential (Buse 2003).
Some surrogate measures of vascular pathology, such as endothelial dysfunction, are negatively affected by postprandial hyperglycemia (American Diabetes Association [ADA] 2012; Ceriello 2002). The mechanisms through which postprandial hyperglycemia exerts its effects may be related to the production of free radicals, which in turn can induce endothelial dysfunction and inflammation (Ceriello 2006).
It has been proposed that dysglycemia of patients with diabetes is the sum of the two following disorders: 1) sustained chronic elevations of glucose and 2) glycemic variability with its main component of postprandial excursions (Monnier 2003). Glucose variability not only includes upward acute fluctuations (postprandial excursions), but also includes downward changes (i.e., decreases from either baseline or interprandial concentrations to glucose nadirs) and is also associated with activation of oxidative stress, one of the main mechanisms leading to diabetes complications (Brownlee 2006). It is therefore suggested that both glycemic variability and postprandial excursions should be monitored and managed in people with diabetes.
In addition, in people with type 2 diabetes, it was reported that there is a progressive shift in the respective contributions of fasting and postprandial hyperglycemia when patients progress from moderate to high hyperglycemia, with the contribution of postprandial glucose excursions being predominant in patients with moderate diabetes. In addition, the contribution of fasting hyperglycemia increases with worsening diabetes (Monnier 2003). The results of the Monnier study suggest that as the patient gets closer to A1C goals of 7%, more attention must be given to reducing postprandial hyperglycemia. Therefore, effective management of diabetes must also include control of postprandial glucose levels, with current guidelines recommending postprandial blood glucose levels <180 mg/dL (ADA 2012).
Other Diabetes Medications for Treating Postprandial Hyperglycemia
People with type 2 as well as type 1 diabetes may have significant postprandial hyperglycemia because of a rapid influx of glucose from the gut (resulting from increased gastric motility), impaired insulin release, excess hepatic glucose production (from inappropriate elevations in glucagon), and insulin resistance (Sudhir 2002). Nine distinct classes of medications are now available for treatment of diabetes in the U.S. and six specifically affect postprandial hyperglycemia: meglitinides, a-glucosidase inhibitors, incretin mimetics, an amylin analog, dipeptidyl peptidase-4 inhibitors, and insulin. Two of these classes of medications, the incretin mimetics (exenatide and liraglutide) and the amylin analog (pramlintide), in addition to their ability to treat these numerous abnormalities, are also associated with modest weight loss (Garber 2011; Nathan 2009).
NUTRITION THERAPY FOR TYPE 1 DIABETES AND INSULIN-REQUIRING TYPE 2 DIABETES
The ADA published nutrition recommendations and interventions in 2008 (ADA 2008). These recommendations are integrated into their annual standards of medical care and updated as new evidence becomes available (ADA 2012). In addition, in 2008, the Academy of Nutrition and Dietetics (formerly the American Dietetic Association) (Acad Nutr Diet) published evidence-based nutrition practice guidelines (EBNPG) for adults with type 1 and type 2 diabetes in the Acad Nut Diet Evidence Analysis Library (EAL) (Acad Nutr Diet 2008). Subsequently, a review of the research leading to the EBNPG and a summary of the research published after the completion of the EAL (through 1 September 2009) were published (Franz 2010).
To update this chapter, a literature search was conducted using PubMed MEDLINE for research published after 2009 on nutrition therapy for insulin-requiring adult patients. Search criteria included the following: carbohydrate counting, medical nutrition therapy, dietary therapy, healthy eating, nutrition counseling, nutrition education, glycemic index, glycemic load or treatment research in human subjects with type 1 diabetes, and English language articles. Study design preferences were randomized controlled trials, clinical controlled studies, large nonrandomized observational