Practical Diabetes

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lgorithms for Adjustment of Insulin Dosage by Patients Who Monitor Blood Glucose
JAY S. SKYLER, DENISE L. SKYLER, DEBORAH E. SEIGLER, AND MARY JO O'SULLIVAN

Patient self-monitoring of blood glucose is a useful adjuvant to diabetes therapy that facilitates improved glycemic control when used as part of an intensive diabetes management program that includes careful balancing of food intake, energy expenditure, and insulin dosage. This paper describes an approach by which patient-determined blood glucose measurements may be used to attain and maintain glycemic control. The patient is provided with a set of algorithms by which minor adjustments in a therapeutic routine may be made to achieve the desired control, DIABETES CARE 4-. 3H-318, MARCH- APRIL 1981.
atient self-monitoring of home blood glucose has achieved increased acceptance as a useful technique to monitor diabetic control.1"17 It obviates the vagaries of urine testing and permits documentation of blood glucose levels within the physiologic range, in which glycosuria should not be present. Many physicians and patients have found that self-monitoring of blood glucose facilitates the attainment of improved diabetic control, provided all elements of the treatment plan are intensively applied. For insulin-dependent diabetes mellitus (IDDM), this entails the careful balancing of food intake, serving as an energy source, with energy expenditure in daily activity, and with an insulin dose designed to achieve efficient energy utilization while avoiding the extremes of either hyperglycemia or hypoglycemia. To maintain balance of the three components of therapy food intake, activity, and insulin dosageit is necessary for the patient to respond to alterations in one component by a modification of at least one other component. Since this involves all food intake and all daily activity, the patient must be able to make alterations in his/her treatment regimen whenever appropriate. Measurement of blood glucose by the patient not only permits monitoring of the balance between food, activity, and insulin; it also provides the patient a tool by which he/she may measure the impact of various alterations in the treatment regimen. This article outlines our approach to instructing patients with IDDM in making modifications in their management program, particularly in their insulin dosages. It is an extension of our previously described approach to insulin dosage alterations in patients monitoring balance by urine glucose and ketone determinations and clinical cues.18 The algorithms described herein have been refined from previous versions based on our experience with patients using these regimens. Nevertheless, each may require adaptation to meet the needs of individual patients.
DEFINITIONS

Once balance has been achieved, it should be possible to maintain that balance by keeping food intake, energy expenditure, and insulin dosage relatively constant from day to day. This assumes the absence of intercurrent illness or psychological stress. In such circumstances, the insulin dosage that the patient requires to maintain glycemic control is the basal insulin dose. The basal insulin dose should control the usual postprandial blood glucose excursions in a patient with a stable food and activity pattern. The basal insulin dose may vary during specific times of the week (e.g., with increased activity on weekends), month (e.g., with menses), or year (e.g., summer versus winter); it may also change as the patient's food intake or activity pattern changes. In the attainment of refinements in control, and in response to unexplainable fluctuations in control, it is necessary to make minor changes in the treatment regimen. This is easily accomplished by altering the basal insulin dose. These modifications in the basal insulin dose are termed adjustments. They presuppose that the patient follows a stable food and activity pattern, is in good health, and is free from unusual stress. In contrast to adjustments made in the basal insulin dosage, supplemental insulin ("supplements") is additional insulin used in circumstances in which the food or activity pattern is not stable or when there is intercurrent illness or

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other stress. By definition, then, supplements are temporary insulin doses. We have found it useful to categorize insulin supplements into two types. The first of these types is compensatory supplements, additional insulin used to overcome unusual hyperglycemia that is administered in response to unanticipated blood glucose elevations and during periods of acute loss of control (e.g., with intercurrent illness). The other type is anticipatory supplements, additional insulin used to prevent hyperglycemia. Such anticipatory supplements are administered before expected hyperglycemia (e.g., before an unusually large meal at a dinner party). To aid patients in the use of insulin dose adjustments and supplemental insulin doses, we provide them with a predetermined plan of algorithms, outlining those cues requiring intervention and indicating the appropriate response to such cues.
INTENSIVE CONVENTIONAL THERAPY

-; morning REG

afternoon NPH

evening REG

light NPH

IB

IS

+ H S

FIG. 2. Schematic representation of idealized periods of insulin effect for a split-and-mixed insulin regimen in which the evening intermediate-acting insulin is delayed until bedtime. This results in peak insulin action coinciding with fasting blood glucose, which is measured and which should be the glucose nadir. Algorithms for altering this regimen are outlined in Table I.

The attainment of improved diabetic control requires that all elements of the treatment plan be intensively applied. These include the following: (1) An activity plan should be relatively constant if food and insulin are to be kept constant. Unusual exercise requires appropriate compensatory changes in food intake and/or insulin dosage. Different activity plans (e.g., weekend versus weekday, summer versus winter) may require different food intake and/or insulin dosage. (2) Food intake (basic meal plan) should be relatively consistent from day to day in terms of calories and proportions of nutrients. The meal plan is best derived from a careful dietary history. Timing of meals should be such to avoid hypoglycemia. Rapidly absorbed simple sugars (causing rapid increments in blood glucose) should be omitted from regular meal planning. Deviations from the basic meal plan require appropriate anticipatory or compensatory changes in insulin dosage and/or activity routine. (3) Insulin must be used in a multiple component regimen, so that one component of insulin coincides with each period of the day and each meal. Figures 1-4 depict four multiple component insulin regimens that we have found useful. In all of these regimens, each component of insulin is assumed to have major action during one particular time pemorning REG afternoon NPH evening REG night NPH

riod of the day. Each time period may be monitored by blood glucose determinations 1 or 2 h after the consumption of the meal that initiates the time period, and at the close of that time period (preprandial the next meal). Each insulin component may be altered individually in conjunction with nutritional intake and energy expenditure during the relevant time period. This division of the day into four separate time periods provides both for maximum flexibility and maximum ease of understanding for patient self-regulation. (4) Blood glucose must be regularly measured by the patient to monitor therapy. For labile patients, or during a period of stabilization in any patient, we recommend seven or more blood glucose determinations daily (preprandial, postprandial, bedtime, perhaps during the night). When a relatively stable pattern emerges, the frequency of monitoring may be reduced. Then, we recommend that fasting blood glucose be determined daily with measurement of one to three other samples most days, and measurement of a complete profile (seven or more determinations) at least once weekly. Additional blood glucoses may be desirable surrounding extra food consumption or unusual activity. Figure 5 depicts an example of a flow sheet on which a patient can record the results of these blood glucose measurements, along with insulin dosage and other relevant information. (5) Intensive education and motivation of the patient is necessary to attain improved glycemic control. In addition to standard diabetic education, psychological counseling of the patient and family may be necessary or desirable to lessen stresses that interfere with glycemic control. This may be accomplished in groups, and may be conducted by a knowlmorning REG afternoon REG evening REG night NPH

|B |B L fS HS |B

{L

fS

f HS

|B

FIG. I. Schematic representation of idealized periods of insulin effect for a "split-and-mixed" insulin regimen. Symbols used in Figures 1-4 are: B, breakfast; L, lunch; S, supper; HS, bedtime snack; Arrow, time of insulin injection, 30 min before meal; REG, regular or short-acting insulin effect; and NPH, intermediate-acting insulin effect. Algorithms for altering this regimen are outlined in Table I.

FIG. 3. Schematic representation of idealized periods of insulin effect for a multiple dosage regimen providing four insulin injections daily. Shortacting insulin is given before breakfast, lunch, and supper. Intermediate' acting insulin is given at bedtime to assure duration of action through the night, and so that peak effect coincides with fasting blood glucose. Algorithms for this regimen are not shown, but would be similar to those in Table 1, with "pre-lunch regular" being substituted for "morning NPH" throughout.

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HS

FIG. 4. Schematic representation of idealized periods of insulin effect for a multiple dosage regimen providing preprandial short-acting insulin and basal insulin as long-acting, relatively peakless ultralente insulin. Although the figure depicts the ultralente being mixed with the morning regular insulin, our preference is to provide half of the total ultralente dosage mixed with the pre-supper regular insulin, both to reduce the total volume of injection and to provide smoother action. Algorithms for altering this regimen are outlined in Table 2.

edgeable diabetes unit staff. In all circumstances, the application of intensive conventional therapy will require frequent contact between the patient and diabetes unit staff, particularly during the period of initial stabilization. (6) Glycosylated hemoglobin should be measured every 4 8 wk to document the control attained.19"20
INITIATION OF INTENSIVE CONVENTIONAL THERAPY

he first priority in initiating an intensive conventional regimen of diabetes management is to assure that the patient's routine activity program is relatively constant and to develop a basic meal plan appropriate for usual activity. Once activity and food intake are stable and relatively consistent, an appropriate insulin regimen can be developed. In the interim, the patient's previous insulin regimen may be continued. The patient may begin blood glucose monitoring simultaneous with initiation of review of the activity and food plans, or later. Satisfactory blood glucose monitoring techniques should be assured and verified before beginning patient-initiated alterations in insulin dosage. In most well-controlled IDDM patients within 20% of their ideal body weight, in the absence of intercurrent infection or other periods of instability, insulin dose requirements on a multiple component regimen will approximate 0.5-1.0
HINE AND BLOOD GLUCOSE TESTS BREAKFAST

INSULIU
Until Suppei

EXPLANATIONS Bed I Ounrt

AM B e Ti | K '

U per kg weight per day. During the period of relative remission ("honeymoon" period), requirements may be less. During periods of intercurrent illness, dosage requirement may increase markedly. In starting use of insulin in an intensive conventional therapy program, it is generally safe to use the following total daily doses: (1) 0.5 U/kg/day in newly diagnosed patients, (2) 0.4 U/kg/day during the "honeymoon" period, (3) 0.6 U/kg/day in pregnant patients during the first 20 wk of gestation, and (4) 0.7 U/kg/day in patients with established diabetes previously treated with 0.7-0.9 U/kg/day. For established patients previously treated with less than 0.7 U/kg/day, their previous dose is used, unless it obviously is inadequate. For established patients previously treated with greater than 0.9 U/kg/day, the dose is reduced by at least 2025% at the time of beginning an intensive conventional program with a multiple component insulin regimen. Insulin is initially distributed among the various components of a multiple component regimen arbitrarily, as outlined below. These distributions are empirically derived from the average distribution requirements of other patients. Each patient will then alter the various components individually to attain the desired control. This is accomplished by use of the algorithms described in this paper. For the multiple component regimens depicted in Figures 1-4, we have empirically found the following initial distributions of insulin to be generally useful. For the regimens shown in Figures 1 and 2, we initially use approximately twothirds of the total daily dose in the morning and one-third of the total daily dose in the evening. The morning prebreakfast dose is divided as one-third short-acting insulin and twothirds intermediate-acting insulin. One-half of the evening dose is given as short-acting insulin before supper, and onehalf is given as intermediate-acting insulin either mixed with short-acting insulin before supper (as in Figure 1) or as a separate dose at bedtime (as in Figure 2). For the regimen shown in Figure 3, one-quarter of the total daily dose is given in each of the four injections: short-acting insulin before breakfast, lunch, and supper, and intermediate-acting insulin at bedtime. For the regimen shown in Figure 4, we initially use 40% of the total daily dose as long-acting ultralente insulin, and give short-acting insulin before breakfast, lunch, and supper, given in equal amounts (20% of the total daily dose before each meal).

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Alnr

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w

1
I t t

ADJUSTMENTS OF INSULIN DOSE

Iftailin I

FIG. 5. Example of a flow sheet for patient recording of blood and/or urine glucose results, insulin dosages, alterations in daily routine, and any hypoglycemic episodes. Sugar and acetone may be recorded preprandially if blood glucose determination is not done. Insulin columns include room for recording short-acting dosage (S), intermediate-acting dosage (I), and any supplemental insulin used, at each time interval.

Prerequisites. When glycemic control is outside of the target range selected for the patient, adjustments are made in the basal insulin dose. Adjustments of the basal insulin dose assume the absence of intercurrent illness or other stress. Moreover, before altering the basal insulin dose, the patient should be assured that alterations in food intake or activity regimen cannot explain the blood glucose findings.
Adjustments for hyperglycemia. If the prerequisites have been met, increases in basal insulin dose (i.e., upward adjustments) may be made for hyperglycemia as evidenced by blood glucose levels in excess of the target range (Tables 1

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TABLE 1 Algorithms for adjusting insulin doses using a "split-and-mixed" insulin dosage regimen and patient monitoring of blood glucose Assumptions The morning short-acting regular insulin has major action between breakfast and lunch, and its effect is reflected in the blood glucose test results after breakfast and before lunch. The morning intermediate-acting NPH insulin has major action between lunch and supper, and its effect is reflected in the blood glucose test results after lunch and before supper. The evening short-acting regular insulin has major action between supper and bedtime, and its effect is reflected in the blood glucose test results after supper and at bedtime. The evening or bedtime intermediate-acting NPH insulin has major action overnight, and its effect is reflected in the blood glucose test results on arising the next morning. Blood sugars Ideal Fasting Before meals After meals (1 h) After meals (2 h) 60-90 mg/dl 60-105 mg/dl 140 mg/dl or less 120 mg/dl or less Acceptable 60-130 mg/dl 60-130 mg/dl 180 mg/dl or less 150 mg/dl or less your morning NPH insulin by 1-2 U. If blood glucose 2 h after lunch is consistently greater than 150 mg/dl AND blood glucose before supper is less than 105 mg/dl, consult your doctor or clinician. If blood glucose 2 h after supper is greater than 150 mg/dl, OR if blood glucose at bedtime is greater than 130 mg/dl for 2 days in a row, increase your evening regular insulin by 1 2 U. If blood glucose 2 h after supper is greater than 150 mg/dl, but less than 105 mg/dl before bedtime snack, consult your doctor or clinician. Supplements In addition, if blood glucose on arising OR before supper is greater than 140 mg/dl, take an extra 1-2 U of regular insulin as a supplement at that time. If blood glucose on arising OR before supper is greater than 200 mg/dl, take an extra 2 - 4 U of regular insulin as a supplement at that time. Record the supplement in the supplement column so that you do not accidentally change the basal dose of regular insulin. Hypoglycemia (low blood sugar) not explained by unusual diet/exercise/ insulin Prevent insulin reactions by eating meals and snacks on time. If fasting blood glucose on arising is less than 60 mg/dl, OR if there is evidence of hypoglycemic reactions occurring overnight, reduce your evening NPH insulin by 1-2 U. If blood glucose after breakfast OR before lunch is less than 60 mg/dl, OR if you have a hypoglycemic reaction between breakfast and lunch, reduce your morning regular insulin by 1 2 U. If blood glucose after lunch OR before supper is less than 60 mg/dl, OR if you have a hypoglycemic reaction between lunch and supper, reduce your morning NPH insulin by 1 2 U. If blood glucose after supper OR at bedtime is less than 60 mg/dl, OR if you have a hypoglycemic reaction between supper and bedtime, reduce your evening regular insulin by 1-2 U.

Hyperglycemia (high blood sugar) not explained by unusual diet/exercise/ insulin If fasting blood glucose on arising is greater than 130 mg/dl for 2 days in a row, increase your evening NPH insulin by 1 2 U. If blood glucose 2 h after breakfast is greater than 150 mg/dl OR if blood glucose before lunch is greater than 130 mg/dl for 2 days in a row, increase your morning regular insulin by 1-2 U. If blood sugar 2 h after breakfast is greater than 150 mg/dl, but less than 105 mg/dl before lunch, consult your doctor or clinician. If blood glucose 2 h after lunch is greater than 150 mg/dl, OR if blood glucose before supper is greater than 130 mg/dl for 2 days in a row, increase

and 2). Adjustments may be made if either there is excess postprandial glycemia or if the blood glucose has not returned to the "acceptable" range before the next meal. However, our algorithms preclude the patient making an adjustment on the basis of postprandial excess if the blood glucose value before the next meal is already in the "ideal" range. In that case, we ask that the patient consult his/her physician or clinician. It may be desirable to alter other components of the regimen (i.e., change timing of injection) rather than adjusting the insulin dose, although that may still be the action chosen. In addition, our algorithms provide that hyperglycemia be evident for at least 2 days before an incremental adjustment is made. This helps obviate adjustments being made for random variations in blood glucose. We advise patients to increase only one insulin component at a time. During initial stabilization, this should be the component controlling fasting blood glucose. After fasting hyperglycemia is corrected, the patient can sequentially adjust the other insulin components, starting with the prebreakfast short-acting insulin. The patient should wait 23 days between dose increments. In this manner, glycemic control may gradually be attained.

The magnitude of dose increment, for patients greater than 40 kg in weight, should be approximately 1 U of insulin for every 30-40 mg/dl that glucose differs from the target level up to a maximum of 4 U in one increment. For patients weighing less than 40 kg in weight, dose changes should not exceed 1 U in any increment. Caution must be exerted to avoid inadvertently increasing insulin dosage in response to rebound hyperglycemia that follows hypoglycemia (Somogyi reactions).21"22 Rebound hyperglycemia most often occurs if there is unrecognized, and hence untreated, hypoglycemia, particularly if there are marked excursions in glycemia. Undetected hypoglycemia is most likely with nocturnal hypoglycemia. One advantage of evening intermediate-acting insulin being administered at bedtime (as in Figures 2 and 3) rather than before supper (as in Figure 1) is that peak action then coincides with fasting blood glucose, which is measured, rather than occurring in the middle of the night while the patient sleeps. The essentially peakless ultralente insulin also is unlikely to induce nocturnal hypoglycemia. (Protamine zinc insulin cannot be used in the regimen shown in Figure 4 because it often has a nocturnal peak.)

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TABLE 2 Algorithms for adjusting insulin doses using an ultralente/3-dose regular insulin regimen and patient monitoring of blood glucose Assumptions The ultralente insulin provides a background basal dosage of insulin, and its effect is primarily reflected in the fasting blood glucose. The morning regular insulin has major action between breakfast and lunch, and its effect is reflected in the blood glucose test: results after breakfast and before lunch. The pre-lunch regular insulin has major action between lunch and supper, and its effect is reflected in the blood glucose test results after lunch and before supper. The pre-supper regular insulin has major action between supper and bedtime, and its effect is reflected in the blood glucose test results after supper and at bedtime.
Blood sugars

Ideal Fasting Before meals After meals (1 h) After meals (2 h) 60-90 mg/dl 60-105 mg/dl 140 mg/dl or less 120 mg/dl or less

Acceptable 60-130 mg/dl 60-130 mg/dl 180 mg/dl or less 150 mg/dl or less

If blood glucose 2 h after lunch is consistently greater than 150 mg/dl AND blood glucose before supper is less than 105 mg/dl, consult your doctor or clinician. If blood glucose 2 h after supper is greater than 150 mg/dl, OR if blood glucose at bedtime is greater than 130 mg/dl for 2 days in a row, increase your pre-supper regular insulin by 1-2 U. If blood glucose 2 h after supper is greater than 150 mg/dl, but less than 105 mg/dl before bedtime snack, consult your doctor or clinician. Supplements In addition, if blood glucose on arising OR before supper is greater than 140 mg/dl, take an extra 1-2 U of regular insulin as a supplement at that time. If blood glucose on arising OR before supper is greater than 200 mg/dl, take an extra 24 U of regular insulin as a supplement at that time. Record the supplement in the supplement column so that you do not accidentally change the basal dose of regular insulin. Hypoglycemia (low blood sugar) not explained by unusual diet/exercise/ insulin Prevent insulin reactions by eating meals and snacks on time. If fasting blood glucose on arising is less than 60 mg/dl, OR if there is evidence of hypoglycemic reactions occurring overnight, reduce your ultralente insulin by 1-2 U. If blood glucose after breakfast OR before lunch is less than 60 mg/dl, OR if you have a hypoglycemic reaction between breakfast and lunch, reduce your morning regular insulin by 1-2 U. If blood glucose after lunch OR before supper is less than 60 mg/dl, OR if you have a hypoglycemic reaction between lunch and supper, reduce your prelunch regular insulin by 1-2 U. If blood glucose after supper OR at bedtime is less than 60 mg/dl, OR if you have a hypoglycemic reaction between supper and bedtime, reduce your presupper regular insulin by 1-2 U.

Hyperglycemia (high blood sugar) not explained by unusual diet/exercise/ insulin If fasting blood glucose on arising is greater than 130 mg/dl for 2 days in a row, increase your ultralente insulin by 1-2 U. If blood glucose 2 h after breakfast is greater than 150 mg/dl OR if blood glucose before lunch is greater than 130 mg/dl for 2 days in a row, increase your morning regular insulin by 1-2 U. If blood sugar 2 h after breakfast is greater than 150 mg/dl, but less than 105 mg/dl before lunch, consult your doctor or clinician. If blood glucose 2 h after lunch is greater than 150 mg/dl, OR if blood glucose before supper is greater than 130 mg/dl for 2 days in a row, increase your pre-lunch regular insulin by 1-2 U.

Rebound hyperglycemia after nocturnal hypoglycemia may be suspected by morning ketonuria (ketosis also may occur as a consequence of the counterregulatory surge that follows untreated hypoglycemia) with blood glucose less than 250 mg/dl. Other clues are bad dreams or nightmares, evidence of nocturnal sweating (e.g., soaked bed sheets), morning grumpiness, abdominal pain or headache, and hypothermia. When nocturnal hypoglycemia is suspected, the patient should awaken and obtain blood glucose determinations during the night. This may be done over several nights and may include staggering the timing of these measurements (e.g., 3:00 a.m. one night, 2:00 a.m. the next night, and 4:00 a.m. the third night). When rebound hyperglycemia is suspected after nocturnal hypoglycemia, the overnight insulin component should be decreased. It is generally safer to assume rebound and reduce insulin dosage. If hyperglycemia was indeed a consequence of insulin deficiency, it will be exacerbated and insulin can be adjusted later. It is surprising how rare the rebound phenomenon becomes when an intensive conventional therapy program is used as outlined herein, if one of the regimens shown in Figures 24 is selected, presumably because the magnitude of glycemic excur-

sions is lessened. These regimens also assure sustained insulin availability through the night, thus obviating apparent rebound from occurring as a consequence of cessation of insulin effect.23

djustments for hypoglycemia. In response to hypo-

glycemic symptoms, we recommend that patients try to verify hypoglycemia by determining their blood glucose. This obviates attributing to hypoglycemia symptoms occurring for some other reason (e.g., anxiety). It also helps patients previously uncontrolled to adapt to lower ambient levels of glycemia without imposing additional calories for symptoms triggered by counterregulatory hormone release occurring without true hypoglycemia.24 When hypoglycemia is documented, or if blood glucose determination cannot be obtained and hypoglycemic symptoms occur, the condition should be treated by consumption of rapidly absorbed simple sugar (approximately 10 g). Patients should always have available with them an acceptable source of sugar for this purpose (e.g., sugar cubes wrapped in foil). If meal time is more than 1 h away, additional slowly

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absorbed food (complex carbohydrate and/or protein) should be consumed. If the hypoglycemic episode is not explainable by there having been an alteration in food intake or activity, the patient should decrease the relevant insulin component by 1-2 U the next day, as outlined by the algorithms (Tables 1 and 2). It should be noted, however, that most hypoglycemia episodes are readily explainable by known alterations in food/activity/insulin balance, e.g., delayed meal or unusual activity. In addition to symptomatic hypoglycemia, our algorithms provide for dosage decrements when preprandial blood glucose determinations are below our target range and are not otherwise explainable.
SUPPLEMENTAL INSULIN DOSES

TABLE 3 Algorithms for compensatory insulin supplements during illness During illness, take extra regular insulin according to the following schedule: For blood glucose 120- 150 mg/dl before meals, add U of regular insulin. For blood glucose 150-200 mg/dl before meals or at bedtime, add U of regular insulin. For blood glucose 200-250 mg/dl before meals or at bedtime, add U of regular insulin. For blood glucose of 250-300 mg/dl, add U of regular insulin every 3-4 h. For blood glucose of 300-350 mg/dl, add U of regular insulin every 3-4 h. For blood glucose of 350-400 mg/dl, add U of regular insulin every 3 - 4 h. Check urines for ketones at the time of each blood glucose measurement. If urine ketones are large and blood glucose is 300 or more, double amount of insulin to be taken. After taking two or three supplements, contact the doctor or nurse to let them know you're having a problem. If you are unable to keep food down or are vomiting, call the doctor or nurse immediately. When ill, be sure to drink plenty of fluidsmore than you think you need.

Supplemental insulin may be used either to compensate for unusual hyperglycemia or in anticipation of same. Supplemental insulin doses always consist of short-acting insulin. They may be given several times each day if necessary, although extreme caution should be exercised before giving bedtime supplements in the absence of intercurrent illness. Supplements (or decrements) are temporary changes in insulin and thus should be recorded in the patient's record separate from the basal insulin dose to avoid confusion with same (Figure 5). This helps preclude unintentional incorporation of supplements into the basal dose as a result of misinterpretation of the recorded dosage. Compensatory insulin supplements. As indicated earlier, compensatory insulin supplements are used to overcome unusual hyperglycemia and are administered in response to unanticipated blood glucose elevations and during periods of acute loss of control (e.g., with intercurrent illness). To prevent progressive deterioration of control our algorithms provide for the use of supplemental insulin if the preprandial blood glucose before breakfast or supper exceeds HO mg/dl. In patients greater than 40 kg in weight, we use approximately 1-2 U of insulin for every 30-50 mg/dl that glucose exceeds the target range. For patients less than 40 kg in weight, supplements are proportionately reduced (e.g., 0.5-1.0 U for every 30-50 mg/dl that glucose exceeds the target range). During intercurrent illness, larger and more frequent supplements may be needed (Table 3). Our initial supplements during illness are, again, approximately 1-2 U of insulin for every 30-50 mg/dl that glucose exceeds 120 mg/dl (for patients greater than 40 kg in weight). Supplements may be repeated as often as every 3-4 h, as necessary, if hyperglycemia exceeds 250 mg/dl. The frequency of supplements need only be preprandially if hyperglycemia does not exceed 250 mg/dl. In all circumstances, however, before administration of each supplement, the patient should verify that blood glucose is elevated and calculate the appropriate dosage for the supplement. If glycemia is deteriorating despite the use of supplemental insulin, the magnitude of the supplements should be increased, e.g., doubled. During illness, we also recommend that patients notify their physician if more than two supplements are needed,

since other medical action may be necessary or become necessary. In anticipation of that eventuality, we routinely provide patients with anti-nauseants and with anti-emetic suppositories for use during intercurrent illness. Moreover, patients also need to be aware of the food exchange equivalents of soft foods and liquids that may be desirable if nausea supervenes during illness. They should appreciate the need to continue taking their basal insulin dose throughout illness. Anticipatory insulin supplements. Anticipatory supplements are used to prevent hyperglycemia, and are administered before expected hyperglycemia outside the target range. Such a circumstance may be the consumption of an unusually large meal (e.g., at a dinner party) where there is not expected to be a compensatory increase in activity. There is great individual variation in the quantity of anticipatory supplements, not only between patients but also in a given patient depending on the amount of excess food consumption. The amount will clearly be determined by "trial and error" with a dose selected for a particular amount of excess food, and the outcome monitored by blood glucose determinations before and after the meal for which the anticipatory supplement is taken. A reasonable starting dose for an anticipatory insulin supplement is 5% of the total daily insulin dosage for a "typical" large meal.
COMPENSATIONS FOR UNUSUAL EXERCISE

During activity that is not part of the patient's usual daily routine, we suggest that compensation be made as extra food to provide an energy source for the increased energy expended. Initially, this may be 10-15 g carbohydrate every 30-45 min during activity. Blood glucose should be monitored frequentlybefore, during, and after exerciseto determine the effectiveness of this intervention. Anticipatory

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decrements in insulin dosage should be considered in addition to the dietary supplements. Some patients find hypoglycemia occurs well after exercise (e.g., 12 h after daytime jogging); in this case, the reduction in insulin component should match the period of anticipated hypoglycemia. Finally, patients should recognize that moderately intensive exercise may deplete glycogen stores, resulting in sustained food requirement after cessation of activity to replete those glycogen stores.25
ADAPTING ALGORITHMS FOR SPECIAL CIRCUMSTANCES

that ideal and target blood glucose levels are identical. Moreover, the criteria for implementing a dosage change are lowered. This is illustrated in Table 4, which outlines the algorithms used for the regimens depicted in Figures 1 and 2, and represents a modification of Table 1 for pregnancy. In addition, dose increments may be made at only 2-day intervals, since euglycemia is highly desirable and progressive increased dosage requirements can be expected. During pregnancy, too, fasting urinary ketones are carefully monitored to avoid starvation ketosis.
CONCLUSIONS

lgorithms should be individualized appropriate for the circumstances of any given patient. For example, pregnancy is one circumstance in which meticulous glycemic control is both desirable to lessen fetal morbidity and mortality.10 Such control is attainable with this type of intensive conventional therapy.9"12 During pregnancy, our algorithms are modified so

The disciplined application of an intensive conventional program of diabetes management permits many patients with IDDM to attain excellent glycemic control. The achievement of such control requires careful balancing of food intake, energy expenditure, and insulin dosage, monitored by patient determination of blood glucose on a continuing regu-

TABLE 4 Algorithms for adjusting insulin doses using a "split-and-mixed" insulin dosage regimen and patient monitoring of blood glucose during pregnancy Assumptions The morning short-acting regular insulin has major action between breakfast and lunch, and its effect is reflected in the blood glucose test results after breakfast and before lunch. The morning intermediate-acting NPH insulin has major action between lunch and supper, and its effect is reflected in the blood glucose test results after lunch and before supper. The evening short-acting regular insulin has major action between supper and bedtime, and its effect is reflected in the blood glucose test results after supper and at bedtime. The evening or bedtime intermediate-acting NPH insulin has major action overnight, and its effect is reflected in the blood glucose test results on arising the next morning. Ideal and target blood sugars Fasting 60-90 mg/dl Before meals 60-105 mg/dl After meals (1 h) 140 mg/dl or less After meals (2 h) 120 mg/dl or less Hyperglycemia (high blood sugar) not explained by unusual diet/exercise/ insulin If fasting blood glucose on arising is greater than 90 mg/dl for 2 days in a row, increase your evening NPH insulin by 1-2 U. If blood glucose 2 h after breakfast is greater than 120 mg/dl AND if blood glucose before lunch is greater than 105 mg/dl for 2 days in a row, increase your morning regular insulin by 1-2 U. If blood sugar 2 h after breakfast is greater than 120 mg/dl, but less than 105 mg/dl before lunch, consult your doctor or clinician. If blood glucose 2 h after lunch is greater than 120 mg/dl, AND if blood glucose before supper is greater than 105 mg/dl for 2 days in a row, increase your morning NPH insulin by 1-2 U. If blood glucose 2 h after lunch is consistently greater than 120 mg/dl AND blood glucose before supper is less than 105 mg/dl, consult your doctor or clinician. If blood glucose 2 h after supper is greater than 120 mg/dl, AND if blood glucose at bedtime is greater than 105 mg/dl for 2 days in a row, increase your evening regular insulin by 1-2 U. If blood glucose 2 h after supper is greater than 120 mg/dl, but less than 105 mg/dl before bedtime snack, consult your doctor or clinician. Supplements In addition, if blood glucose on arising OR before supper is greater than 140 mg/dl, take an extra 1-2 U of regular insulin as a supplement at that time. If blood glucose on arising OR before supper is greater than 200 mg/dl, take an extra 2-4 U of regular insulin as a supplement at that time. Record the supplement in the supplement column so that you do not accidentally change the basal dose of regular insulin. Special rules If a blood sugar is greater than 140 mg/dl 2 h after any meal, eliminate 1 fruit or Vi bread from snack. Hypoglycemia (low blood sugar) not explained by unusual diet/exercise/ insulin Prevent insulin reactions by eating meals and snacks on time. If fasting blood glucose on arising is less than 60 mg/dl, OR if there is evidence of hypoglycemic reactions occurring overnight, reduce your evening NPH insulin by 1-2 U. If blood glucose after breakfast OR before lunch is less than 60 mg/dl, OR if you have a hypoglycemic reaction between breakfast and lunch, reduce your morning regular insulin by 1-2 U. If blood glucose after lunch OR before supper is less than 60 mg/dl, OR if you have a hypoglycemic reaction between lunch and supper, reduce your morning NPH by 1-2 U. If blood glucose after supper OR at bedtime is less than 60 mg/dl, OR if you have a hypoglycemic reaction between supper and bedtime, reduce your evening regular insulin by 1 2 U. If you feel a reaction coming on, test your blood and if the blood sugar is between 45 and 60 mg/dl, drink a glass of milk or eat if it is snack or meal time. If blood sugar is very low (45 mg/dl or less) have a fruit and a milk or if it is meal or snack time, eat immediately. Record any acetone in the urine.

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9 Peacock, I., Hunter, J. C , Walford, S., Allison, S. P., Davison, J., Clarke, P., Symonds, E. M., and Tattersall, R. B.: Selfmonitoring of blood glucose in diabetic pregnancy. Br. Med. J. 2: 1333-36, 1979. 10 Mintz, D. H., Skyler, J. S., and Chez, R. A.: Diabetes mellitus and pregnancy. Diabetes Care i: 49-63, 1978. A C K N O W L E D G M E N T S : This work was supported by the Univer11 Jovanovic, L., Peterson, C. M., Saxena, B. B., Dawood, sity of Miami/Southeastern Florida Regional Diabetes Pro- M. Y., and Saudek, C. D.: Feasibility of maintaining normal glugram, funded by a contract with the Health Program Office, cose profiles in insulin-dependent diabetic pregnant women. Am. J. Department of Health and Rehabilitative Services, State of Med. 68: 105-12, 1980. 12 Florida; by the Division of Children's Medical Services, DeSkyler, J. S., O'Sullivan, M. J., Robertson, E. G., Skyler, partment of Health and Rehabilitative Services, State of D. L , Holsinger, K. K., Lasky, I. A., McLeod, A. G. W., Burkett, Florida; by the Diabetes Research Institute Foundation; by G., and Mintz, D. H.: Blood glucose control during pregnancy. DiCare 3: 69-76, 1980. the Ames Company, Elkhart, Indiana; and by Bio-Dyna- abetes 13 Sonksen, P. H.: Home monitoring of blood glucose by diabetic mics/bmc, Indianapolis, Indiana. patients. Acta Endocrinol. (Suppl.) 238: 145-55, 1980. 14 Symposium on home blood glucose monitoring. Diabetes Care From the Departments of Medicine, Pediatrics, and Obstetrics 3: 57-186, 1980. and Gynecology, and the Diabetes-Endocrinology Unit, Univer15 Dupuis, A., Jones, R. L., and Peterson, C. M.: Psychological sity of Miami School of Medicine, Miami, Florida. of blood glucose self-monitoring in diabetic patients. Psychoeffects Address reprint requests to Jay S. Skyler, University of Miami 581-91, 1980. somatics2/: Hospital and Clinics (D-l), 1475 NW 12th Avenue, Miami, Flor16 Shuman, C. R.: Self-monitoring of blood glucose by the diaida 33136. betic patient. Practical Cardiology 6: 50-64, June 1980. 17 Tattersall, R., and Gale, E.: Patient self-monitoring of blood REFERENCES glucose and refinements of conventional insulin treatment. Am. J. 1 Keen, H., and Knight, R. K.: Self sampling for blood sugar. ^ed. 70: 177-82, 1981. 18 Lancet/: 1037-40, 1962. Skyler, J. S., Ellis, G. J., Skyler, D. L , Lasky, I. A., and Le2 Danowski, T. S., and Sunder, J. H.: Jet injection of insulin dur- bovitz, F. L.: Instructing patients in making alterations in insulin ing self-monitoring of blood glucose. Diabetes Care 1: 27-33, 1978. dosage. Diabetes Care 2: 39-45, 1979. 19 3 Bunn, H. F., Gabbay, K. H., and Gallop, P. M.: The glycosylSonksen, P. H., Judd, S. L., and Lowy, C : Home monitoring ation of hemoglobin: reference to diabetes mellitus. Science 200: of blood glucose. Lancet!: 729-32, 1978. 4 Walford, S., Gale, E. A. M., Allison, S. P., and Tattersall, R. 21-27, 1976. 20 Gonen, B., and Rubenstein, A. H.: Hemoglobin Aj and diaB.: Self monitoring of blood glucose. Lancet 1: 732-35, 1978. 5 Skyler, J. S., Lasky, I. A., Skyler, D. L., Robertson, E. G., and betes mellitus. Diabetologia 15: 1-8, 1978. 21 Somogyi, M.: Exacerbation of diabetes by excess insulin action. Mintz, D. H.: Home blood glucose monitoring as an aid in diabetes Am. J. Med. 26: 169-91, 1959. management. Diabetes Care 1: 150-57, 1978. 22 6 Bloom, M . E., Mintz, D . H . , and Field, J. B.: Insulin induced Ikeda, Y., Tajima, N., Nimami, N., Ide, Y., Yoroyama, J., and Abe, M.: Pilot study of self measurement of blood glucose using the post-hypoglycemic hyperglycemia as a cause of "brittle" diabetes. Dextrostix-Eyetone system for juvenile onset diabetes. Diabetologia Am. J. Med. 47: 891-903, 1969. 23 Gale, E. A. M., Kurtz, A. B., and Tattersall, R. B.: In search 15: 91-93, 1978. 7 Peterson, C. M., Jones, R. L., Dupuis, A., Bernstein, R., and of the Somogyi effect. Lancet 2: 279-82, 1980. 24 DeFronzo, R. A., Hendler, R., and Christensen, N.: StimuO'Shea, M.: Feasibility of improved blood glucose control in patients with insulin-dependent diabetes mellitus. Diabetes Care 2: lation of counterregulatory hormonal responses in diabetic man by a fall in glucose concentration. Diabetes 29: 125-31, 1980. 235-39, 1979. 25 8 Wahren, J.: Glucose turnover during exercise in health and in Tattersall, R. B.: Home blood glucose monitoring. Diabetologia diabetes mellitus. Diabetes 28: 82-88, 1979. 15: 71-74, 1979.

lar basis. To accomplish this, patients must be motivated and work in close conjunction with their health care team. This article has outlined the details by which we instruct patients to alter their regimen to attain the desired control.

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