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Chapter 5

Food, Fasting, Insulin, and Glycemic Control in the Hospital

Mary Korytkowski, MD,¹ Boris Draznin, MD, PhD,² and Andjela Drincic, MD³

¹Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, PA. ²Division of Endocrinology, Diabetes, and Metabolism, University of Colorado School of Medicine, Aurora, CO. ³Division of Diabetes, Endocrinology and Metabolism, Medical Director, The Nebraska Medical Center Diabetes Center, Omaha, NE.

DOI: 10.2337/9781580406086.05

Introduction

Diabetes treatment in the hospital poses unique challenges that differ from those encountered in the outpatient setting.^1–5 These challenges arise from patient factors that include illness-related variability in insulin sensitivity, as well as system factors related to inconsistency in hospital procedures for insulin dosing and meal delivery, complicating the ability to achieve and maintain desired glycemic goals.^3–7 Despite the demonstrated superiority of scheduled insulin therapy over sliding-scale insulin (SSI) regimens, the latter persists as a fallback strategy for many providers who may be unfamiliar or uncomfortable with basal-plus or basal-bolus insulin (BBI) regimens.^8–13

A major challenge to insulin use in the hospital is related to variability in food intake and carbohydrate exposure, with associated concerns for hypoglycemia when patients are not eating regular meals.^14–16 Appropriate timing of prandial insulin administration can be complicated by lack of coordination in the timing of food tray delivery with point-of-care (POC) measures of capillary blood glucose (BG) and insulin administration, tasks that are performed by personnel from different departments in the hospital setting. Some patients are unable to ingest prescribed calories because of lack of appetite or dislike of hospital meals. Other patients may skip meals and instead consume snacks and meals brought to the hospital by friends or family members without informing nursing personnel of the need for prandial insulin.¹⁴

One of the most frequently encountered scenarios in the care of individuals with diabetes treated with noninsulin or insulin therapy in the hospital is what to do during periods of fasting or inability to take oral nutrition.^3,4,15 Scheduled periods of fasting for diagnostic testing or surgical procedures are frequent occurrences in the inpatient setting. Although there is a general awareness of the need for continuation of some form of glucose-lowering therapy during periods of fasting in patients with diabetes, there is uncertainty about how to modify therapy in a way that prevents both hyperglycemia and hypoglycemia.^7,15,17 Many patients are admitted through same-day surgery units for short outpatient procedures as well as complicated prolonged procedures that require postoperative hospitalization. Therefore, recommendations for adjustments to a glycemic management regimen often begin at home.¹⁵

This chapter will review an approach to adjustments in noninsulin and insulin therapies during periods of fasting and will address the issue of timing of insulin therapy with meals. This section starts with a patient case followed by a discussion of how to modify BBI therapy during a 2-day period of consumption of only clear liquids before a planned surgical procedure. For purposes of this discussion, NPO (nil per os: nothing by mouth) will be used whenever a patient is placed in a fasted state.

Issues to Consider When Writing Consult Notes and Making Recommendations

Patient Case A 64-year-old woman with insulin-treated type 2 diabetes (T2D) is admitted to the hospital for aortic valve replacement. She will be receiving only clear liquids for 2 days before the procedure and will remain NPO after midnight before the procedure. Her admission weight is 76 kg (167 lbs). Her HbA1c 1 month before admission was 8.7%. Her home insulin regimen consists of detemir insulin 40 units at 8 p.m. with fixed doses of 14 units of insulin aspart prior to each meal. She reports home fasting glucose levels of 130–150 mg/dL with daytime values that range between 120 and 260 mg/dL. You are asked to make recommendations regarding her insulin regimen.

Insulin Modifications for Patients on Clear Liquid Diets

Clear liquid diets include the use of fruit juices, sodas (lemon-lime soda and ginger ale), gelatin, popsicles, and broth. Many of these foods are caloric beverages with high sugar content that require doses of nutritional insulin to maintain glycemic control (Table 5.1).

Similar to insulin glargine, detemir is a basal insulin, ideally covering insulin needs in the absence of any food intake.^18,19 In the majority of instances, there is no need to reduce the dose of the basal insulin for a clear liquid diet. The patient in this case was on fixed doses of premeal insulin with wide variability in her glycemic control at home, likely representing variability in her caloric consumption at home.

To determine a premeal insulin dose for a clear liquid diet, calculate the prandial insulin dose according to planned carbohydrate intake (Table 5.1).^16,20 For example, 4 ounces of apple juice or lemon-lime soda contains ~15 g of carbohydrate. The ratio of insulin-to-carbohydrate intake (insulin-to-carbohydrate ratio [ICR]) could be based on the total daily dose (TDD) of basal insulin using one of several published formulas. Of these, the following formulas are the easiest to use:²¹

400/TDD basal insulin (5.1)

2.8 × weight (lb)/TDD basal insulin (5.2)

Although these formulas have been accepted and used in many clinical trials, other authors have proposed dosing formulas that call for higher mealtime insulin delivery.^20,22–26 Caution is advised in using any formula because of differences in patient populations (type 1 diabetes [T1D] vs. type 2 diabetes [T2D]) and insulin delivery devices (subcutaneous injections vs. insulin pumps) used in these prior studies, with some including lean patients with T1D using insulin pump therapy.²⁶

For the patient in this case, consumption of 12 ounces of ginger ale (32 g), 1 cup of gelatin (19 g), and 1 popsicle (17 g) at a meal provides a total carbohydrate intake of 68 g (Table 5.1). Using the first formula (i.e., 400/TDD detemir), her prandial insulin dose would be based on an ICR of 1 unit for each 10 g of carbohydrate or 7 units of insulin aspart. Using the second formula (2.8 × 167 lbs/ TDD detemir), her ICR would be 1 unit for each 12 g of carbohydrate or 6 units of aspart. Both methods provide a dose of aspart that is roughly equivalent to what would be achieved by reducing the current dose of 14 units by 50%. Correction insulin can be used to provide additional aspart insulin for premeal blood glucose above the desired range, with the majority of correction scales beginning at blood glucose levels >140 mg/dL.^20,27

Table 5.2— Guideline for Promoting Appropriate Insulin Administration for Meals on Demand

• Patients are able to order meals within regularly scheduled time intervals

• Nutrition services will call patient for any orders not placed with these intervals

• Personnel distributing meals alert the RN that a meal has been delivered to patient to prompt a BG check and insulin administration

• Prominent note is provided with meal to remind a patient to request a BG check and insulin dose before ingesting a meal

• Avoid administration of meal insulin at intervals of <4 h to avoid insulin stacking

Another option for this patient would be to use a basal-plus-insulin regimen.^28,29 This option continues her current dose of detemir insulin once daily in combination with correction insulin before meals. In one study, this type of regimen was found to have a similar efficacy to BBI in hospitalized patients with T2D.²⁹ Correction insulin can be calculated using a formula of 1,700/TDD of insulin, which would calculate to a correction factor of 21 for the patient in this case.²¹ In the inpatient setting, standardization of correction insulin scales can help prevent errors that occur when too many different algorithms are used.³⁰ Although the calculated correction insulin dose²¹ for this patient is >40 mg/dL, incremental dosing that is made available on many published correction insulin scales, it would be reasonable to use one of the standardized correction scales to avoid confusion and potential medication errors.^30,31 An argument against using a basal-plus regimen for the patient in this case is her requirement for fairly high doses of prandial insulin as an outpatient. This indicates the patient is likely to experience significant hyperglycemia following ingestion of moderate amounts of simple carbohydrates available on a clear liquid diet.

Insulin Regimen Modifications Recommended for Patients Who Become NPO

Once a patient is no longer consuming any caloric foods or liquids, there is no need to provide scheduled nutritional or prandial doses of insulin. Continuation of the basal insulin in combination with correctional insulin for glycemic excursions outside of established goal ranges (i.e., basal plus) is required. Although there is no consensus regarding what percentage of basal insulin to administer to patients who are in the fasting state, there is consensus that insulin-treated patients will require continuation of some portion of basal insulin, often in combination with periodic doses of correctional short- or rapid-acting insulin during a surgical procedure to avoid hyperglycemia.^3–5,7 Withholding insulin in patients with T1D or insulin-treated T2D increases risk for diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) with high risk for perioperative complications.¹⁵

To calculate the percentage of basal insulin to be administered to patients during periods of fasting, consider the degree of preoperative glycemic control as determined from measures of HbA_1c and results of bedside BG monitoring, patient characteristics, type of diabetes, and analysis of their home regimen (physiologic vs. basal heavy). In one study, patients with T1D were given their full dose of basal insulin (glargine) on a day when they were maintained in a fasting state with a low incidence of hypoglycemia.³² Similar studies with detemir or NPH insulin have not been performed. The pharmacokinetics of NPH insulin with a peak time of action at 6–10 h following administration would support reductions in dose of 25–50% of usual doses.^33,34 The pharmacokinetics of detemir can vary from a flat profile at lower doses (<0.3 units/kg/day) to a more pronounced peak action time at higher doses, again supporting recommendations for dose modifications in some patients during periods of fasting.³⁵

One general guideline is to provide 50–75% of the usual basal insulin dose before a surgical procedure.^{3–5,7,15,17} In one study that employed this recommendation in 585 patients with diabetes admitted to a same-day surgical center, 21% of patients arrived at the center with BG >200 mg/dL and 2% had BG <70 mg/dL.¹⁵ This study reveals the wide variability in insulin requirements in patients during periods of fasting. Patients who are under what is considered “tight” glycemic control may require reductions in their doses of basal insulin to avoid hypoglycemia, whereas those who are under fair or poor control may require the full dose to avoid significant hyperglycemia.

Given that the patient in this case was under suboptimal control with BBI as an outpatient, she likely will require the full dose of detemir insulin before surgery. It also is likely that administration of detemir 40 units will not be sufficient to maintain glycemic control during this surgical procedure for which she will receive general anesthesia. General anesthesia is associated with increases in counterregulatory hormones and insulin resistance, often increasing insulin requirements.^7,36,37 This differs from regional or spinal anesthesia in which insulin requirements often remain unchanged.^7,36,37 The responsibility for glucose monitoring with administration of subcutaneous or intravenous (IV), which is preferred, doses of regular or rapid-acting insulin analogs will fall to the anesthesiologist.^15,37,38

Basal-heavy insulin refers to the (usually inappropriate) use of high doses of a single daily injection of basal insulin (glargine, detemir, or NPH) to cover both prandial and basal insulin requirements. Patients on these regimens often receive >0.6 to >1 unit/kg/day of basal insulin each day. Although not recommended by endocrinologists, in reality, this is a fairly common practice. When carbohydrate intake is decreased or eliminated in the NPO state, more aggressive decreases in basal insulin doses of ≥50% are required.

Perioperative Management of Patients Receiving Noninsulin Diabetes Therapy

Evidence is insufficient regarding the best ways to manage patients receiving noninsulin diabetes therapy.^7,15,17 It is generally accepted that on the morning before surgery, although patients are consuming a normal diet, all usual diabetes medications should be continued. For patients on a clear liquid diet such as the patient in this case, or those who are receiving dietary preparation for a colonoscopy, we recommend holding sulfonylurea agents because of the risk of hypoglycemia.³⁹ Short-acting insulin secretogogues such as repaglinide and nateglinide can be continued in reduced doses. Other noninsulin therapies usually can be continued until a patient is in the fasted (NPO) state. On the morning of surgery, we recommend holding all oral and injectable noninsulin diabetes medications.¹⁵

Suboptimal HbA_1c and High-Risk for Postoperative Complications

Although some evidence links preoperative glycemic control with the risk for postoperative complications, available evidence is more suggestive than absolute.^40,41 In the patient in this case, there is no need to delay surgery based on her HbA_1c. Two days in the hospital preoperatively allows time for insulin adjustments and for the institution of a reasonable level of glycemic control, defined as maintaining BG values between 140 and 180 mg/dL.^6,7

For elective procedures (e.g., joint replacement surgery, hernia repair), patients with previous poor diabetes control can be encouraged to improve their metabolic status with the motivating factor being that this will reduce risk for postoperative complications.^40,42 The optimal level of “improved control” is not defined, but the authors of this chapter recommend HbA_1c values of <8.5%, which correspond to a mean BG of <200 mg/dL, the level at which risk for perioperative complications increases most significantly.^43–46

Not all patients will have the ability to achieve this level of glycemic control. In these situations, personal experience and judgment are important. For example, a patient with chronically uncontrolled insulin requiring T2D with HbA_1c values >12% resulting from personal chaos and stress may be encouraged to reduce their HbA_1c to <10% in preparation for elective surgery, but they may have difficulty getting to lower values. In some cases, allowing an elective surgical procedure to take place has the potential to contribute to improved glycemic control by addressing issues such as chronic pain that interfere with self-management. For patients who are unable to achieve desired levels of glycemic control or for whom a procedure is urgent, glycemic control can be achieved rapidly with the use of an IV insulin infusion before, during, and following the surgical procedure.^15,47

Metabolic Effects Associated with NPO Status

Prolonged fasting is associated with reductions in insulin sensitivity in patients with and without diabetes.^48,49 In the absence of diabetes, fasting is associated with a decline in insulin levels and an increase in glucagon, with associated increases in circulating free fatty acids that further impair insulin sensitivity.⁴⁹ Although it is beyond the scope of this chapter, the reader is referred to several recent publications that explore the continued administration of carbohydrates in preparation for surgical procedures as a way to avoid potentially harmful increases in counterregulatory hormones.^49–52

For prolonged procedures, the IV administration of glucose- or dextrose- containing IV fluids may help to limit perioperative changes in insulin sensitivity. Administration of glucose-containing IV fluids contributes to elevated BG. One liter of D5%-containing IV fluid has 50 g of glucose or ~200 calories. If this is infused at a rate of 100 cc/h, this provides 5 g of glucose or 20 calories/h. This calculates to ~1.2 mg/kg/min for an individual who wieghts 70 kg. Although this amount may seem trivial, personal experience indicates that in some cases, this is sufficient to contribute to mild elevations in BG that prompt administration of additional insulin. No published studies have investigated the effect of these low glucose infusion rates on hyperglycemia in hospitalized patients. In one study, glucose infusion rates of ≤4 mg/kg/min were not associated with hyperglycemia in patients without diabetes receiving total parenteral nutrition.⁵³

Preventing Hypoglycemia When NPO Status Is Imposed Abruptly

Some patients may be abruptly placed in the fasting state after full doses of a weight-based BBI regimen has been administered, placing patients at increased risk for hypoglycemia.³⁹ We generally recommend that infusions of D5% or D10% be initiated with more frequent glucose monitoring as a way to reduce this risk.⁵⁴

Patients Who Experience Hypoglycemia while NPO for a Procedure

Little data have addressed the issue of patients who experience hypoglycemia while NPO.⁷ Studies that discuss the benefit of preoperative carbohydrate loading can provide a guide to the safety of ingesting carbohydrate-containing liquids in the event of a hypoglycemic event.^55,56 Our recommendation to patients is to consume 4 ounces of a caloric clear liquid beverage in the event of a hypoglycemic event during the fasting period (Table 5.1).¹⁵ If hypoglycemia persists, this can be repeated as necessary. Patients need to inform personnel in the same-day surgical suite that that this occurred.

Timing of Insulin and Meals

Patient Case The patient in this case eventually will resume eating regular meals within 24–36 h of a surgical procedure. Although food intake may begin while she is in a surgical intensive care unit, she eventually will be transferred to a nursing unit where they will need to coordinate insulin dosing and meal administration.

Hospitalized patients with diabetes depend on hospital personnel to monitor blood glucose levels, administer diabetes medications, and deliver meals in a timely and coordinated manner.^14,16,57 This is a challenge to personnel providing care to inpatients with diabetes in the best of circumstances. This has become even more difficult following the introduction of “meals on demand” or “room service” as part of routine care in many hospitals.¹⁶

Hospitals have responded to the introduction of meals on demand in one of several ways. Some have tried unsuccessfully to disallow this practice in insulin-treated patients, resulting in patient and therefore administrative dissatisfaction. Others have implemented guidelines to help minimize the chaos that leads to poor coordination of the components of administering meal-related insulin (Table 5.2).⁵⁷ One institution introduced a procedure that included posting of signs on the doors of patients scheduled to receive nutritional insulin with the following statement: “Before you eat, please call your nurse for your premeal medication.” Meal servers remove the sign at the time of meal tray delivery and give this to the patient who then calls the nurse to bring their insulin. This resulted in a significant improvement in the percentage of patients receiving meal insulin in a timely manner.⁵⁸

Table 5.2— Guideline for Promoting Appropriate Insulin Administration for Meals on Demand

• Patients are able to order meals within regularly scheduled time intervals

• Nutrition services will call patient for any orders not placed with these intervals

• Personnel distributing meals alert the RN that a meal has been delivered to patient to prompt a BG check and insulin administration

• Prominent note is provided with meal to remind a patient to request a BG check and insulin dose before ingesting a meal

• Avoid administration of meal insulin at intervals of <4 h to avoid insulin stacking

The most important component of promoting the glycemic success (i.e., avoiding hypoglycemia and hyperglycemia) is the need to establish communication among the patient, nurse, and nutrition services. This can be achieved by providing education to nursing and nutrition services personnel regarding the pharmacokinetics of insulin preparations as this relates to meal ingestion.¹⁶ Engaging patients, dietary, and nursing personnel in ensuring timely administration of premeal insulin can facilitate the coordination of activities that promote patient safety in the hospital setting.

Carbohydrate Counting in the Hospital

Even patients with a good appetite who are eating regular meals pose a challenge to diabetes management in the hospital. The decisions as to how and when to cover carbohydrate content of patient meals usually fall under the direction of hospital personnel rather than the patient, even for patients who self-managed their diabetes before admission.^1,3–5 Some hospitals use carbohydrate-controlled diets for all patients with diabetes, which provide a fixed amount of carbohydrate with each meal allowing for more accurate prandial insulin administration.

As outlined previously, many hospitals have introduced programs that allow patients more flexibility in the timing and content of their meals. One justification for this approach is an improvement in patient satisfaction with their care while hospitalized, which has increased their popularity among hospital administrators who are concerned with hospital rankings. As a way to adjust to this variability in the timing of meal delivery for individual patients, some hospitals have adopted the practice of administrating prandial insulin based on carbohydrate intake. This practice requires extensive training and education of nutrition and nursing personnel.

These meal-on-demand practices, in association with insulin dosing based on carbohydrate counting and insulin sensitivity, can allow for more accurate prandial insulin coverage. To date, only one relatively small study had formally examined this issue and has found that a fixed meal dosing strategy provided similar glucose control as flexible meal dosing.²⁰ There were no group differences in mean carbohydrate intake per meal consumed, frequency of hypoglycemia, or overall patient satisfaction. In this study, an inpatient diabetes team provided all diabetes treatment with expertise in glycemic management, a service that is not available in most hospitals. This raises questions about the safety of this practice in hospitals where these teams may not be available.

Timing of Prandial Insulin Administration

There are varying opinions as to the optimal timing of insulin administration in the hospital setting. Some clinicians prefer that insulin be given about 15 min before the meal, which is similar to recommendations for the outpatient setting for rapid-acting insulin administration. Others feel that it is safer to administer prandial doses of insulin following a meal, particularly when there is uncertainty regarding how much food a patient will consume. This latter approach may help reduce risk for hypoglycemia in patients who have a variable appetite or who have difficulty with hospital diets. In these cases, it may be appropriate to administer insulin immediately after each meal. A usual approach is to administer half the dose when a patient consumes half of the meal and to withhold the dose if less than half of the meal is consumed. Although adequate inpatient-based studies on postprandial administration of rapid-acting insulin are lacking, this practice has been evaluated in other patient populations and found to provide satisfactory glycemic control.^59,60

Conclusion

There is an underappreciation of the contribution of nutritional intake, or lack thereof, to glycemic management in the hospital setting. This chapter has provided an approach to the management of patients on clear liquid and regular diets, in which case the issue of matching insulin dosing to the number of carbohydrates consumed is identical. In addition, we have provided a review of the currently available literature describing approaches to use of pharmacologic glycemic-lowering therapy in patients who are in the fasting state in preparation for surgery or other medical procedures. We described the difficulty in making one recommendation for all insulin-treated patients given the number of different regimens that are prescribed in the greater medical community, with some basal-heavy regimens requiring more significant reductions and some basal-appropriate regimens requiring minimal reductions in dosing. Little data have been published to guide the management of these patients. This means that many of the recommendations reflect consensus opinion that incorporates knowledge of the pharmacokinetics of different insulin and oral preparations, published literature, and extensive personal clinical experience.

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