3. STEPHENSON, HAUG, AND MURPHY 177
and usually disappears when the pregnancy is termi- in diabetics aged 18 to 74 years was 26% in men
nated. 3 The occurrence is most often in the second and 34% in women, while in age-matched nondiabetic
and especially the third trimester. This is a time when males and females it was 13.7% and 19.5%, respec-
resistance to insulin normally develops and carbohy- tively. ~2 The risk of cardiovascular death in a diabetic
drate tolerance declines, secondary to secretion of large person is roughly doubled by the coexistence of hyper-
amounts of insulin antagonistic hormones, including tension. '~'~3 Patients may have manifestations of sys-
human chorionic somatomammatropin, estrogen, and tolic or diastolic hypertension, or both.
progesterone. Up to 50% of gestational diabetics may Neuropathy may be the presenting symptom of dia-
expect to become diabetic in a nonpregnant state within betes mellitus, 6"7 and is generally seen in poorly con-
10 years. 3 Gestational diabetes is associated with peri- trolled diabetics.~ Peripheral neuropathy results in de-
natal risks and fetal mortality. 2'3 creased conduction velocity of nerve impulses. This
usually involves the lower extremities. It sometimes
SECONDARY DIABETES affects motor function, but most often affects sensory
nerves. Clinically, this results in a "stocking-glove"
Secondary diabetes defines a class of patients in distribution of numbness and paresthesia, with muscle
whom hyperglycemia is associated with another sys- wasting leading to foot deformity. Trauma due to di-
temic disease. The clinical phenotype reflects the un- minished sensation may lead to deterioration of joints
derlying disorder. 3 Diabetes secondary to pancreatic (Charcot's joint) and feet, with the ultimate production
disease is type I in characteristics, while diabetes sec- of diabetic foot ulcers. 6'v Mononeuropathy occurs sec-
ondary to hormonal excess (ie, Cushing's disease, ac- ondary to infarcts of a single nerve (simplex) or multi-
romegaly, or glucagonoma) is type II in characteristics. ple single nerves (multiplex). The onset is rapid, with
Drugs such as thiazide diuretics are also associated loss of motor and sensory function. Pain is severe along
with diminished insulin secretion, while drugs such as the distribution of the nerve. Involvement can include
glucocorticoids or oral contraceptives lead to increased cranial nerves, producing Bell's palsy and extraocular
insulin resistance. Finally, a number of diverse genetic muscle palsies. 6
syndromes include diabetes mellitus among their mani- Cutaneous manifestations of diabetes include skin
festations, as illustrated in Table 1. infections, xanthoma diabeticorum, and necrobiosis li-
poidica diabeticorum. Clinically, xanthoma appears as
Clinical Findings a firm, nontender, yellowish nodules that contain lipid-
filled macrophages. Necrobiosis lipoidica diabet-
Polyuria, a common clinical finding, is secondary icorum manifests as a focal necrotic area within the
to hyperglycemia and glycosuria. The increased urine dermis and subcutaneous tissues anywhere on the
osmolarity induces an osmotic diuresis. This occurs at body. Dermatologic infections are the most common
the patient's renal glucose threshold of approximately of the cutaneous manifestations.
180 to 250 md/dL. 2 Obligatory water loss combined
with hyperosmolarity tends to deplete intracellular wa- Diagnostic Modalities
ter and stimulate osmoreceptors in the brain's thirst
center, which manifests as polydipsia. URINE DIPSTICK
Visual disturbances in diabetics may take the form
of retinopathy, cataract formation, or glaucoma. 5 Traditionally, urine glucose testing has been used as
Blindness is 10 times more common in the diabetic an index of prevailing serum glucose concentrations,
population than in the nondiabetic population. 6 Reti- but the relationship between serum and urine glucose
nopathy is the most common form of disturbance and concentrations is indirect. The presence of glucose in
is divided into two categories: background and prolif- the urine occurs because the tubular resorptive capacity
erative. Clinically, background retinopathy produces of glucose has been exceeded. Urine glucose measure-
retinal hemorrhages, retinal exudates, edema, venous ments correlate poorly with plasma glucose levels be-
dilations, microaneurysms, and thickening of retinal cause several physiologic factors affect renal threshold
capillaries (microangiopathy). In proliferative retinop- and, subsequently, urine glucose concentrations. Such
athy, neovascularization is the hallmark clinical find- physiologic factors include high or low glomerular fil-
ing. Proliferative retinopathy is more likely to produce tration and increased or decreased tubular resorption.
blindness; 25% of diabetics with proliferative changes These factors contribute to inadequate reflection of se-
are blind. 6 rum glucose concentration by urine testing. The urine
Hypertension is well documented to be increased in dipstick may have some usefulness in stable, type II
diabetics compared with nondiabetics. At the Joslin diabetics in whom physiologic variables have been ac-
Clinic, in Boston, MA, the prevalence of hypertension counted for or eliminated, and in school-aged children
4. ] 78 MANAGEMENT OF DIABETIC ORAL SURGERY
with diabetes who resist blood testing. ~4 The diagnosis Table 2. Oral Hypoglycemic Agents
of diabetes is not made by urine testing. A positive
Duration Maximal
test for glycosuria must always be confirmed by an
of Starting Daily Doses
elevated plasma glucose before treatment is begun. 3 Action Dose Dosage per
Hypoglycemic Agent (h) (mg) (mg) Day
SERUM GLUCOSE
First-generation agents:
Tolbutamide 6-8 500 3,000 2-3
Home capillary glucose monitoring is the keystone
Acetohexamide 8-12 250 1,500 1-2
of modern diabetes care.14 Capillary glucose monitor- Tolazamide 12-18 100 1,000 1-2
ing is recommended for all patients willing and able Chlorpropamide 24-72 100 500 1
to perform it, but is mandatory for pregnant diabetics, Second-generationagents:
patients on intensive insulin regimens (eg, insulin Glipizide 12-18 2.5 40 1-2
Glyburide 16-24 1.25 20 1-2
pumps), patients with frequent hypoglycemia, and for
those in whom specific problems dictate a switch from
urine testing. 14'15 The consensus is that blood glucose
monitoring is reasonably accurate when correctly per- erythrocyte is exposed] 7 Hemoglobin Alc reflects the
formed. 14 The American Diabetes Association policy degree of hyperglycemia over the previous 8 to 12
statement indicates that capillary glucose monitoring weeks. H Although normal values for this test vary
is preferable to urine testing in any insulin-requiring among laboratories, less than 6.2% is usually consid-
diabetic because it 1) facilitates the prevention of hy- ered normal.~ s
perglycemia that cannot be detected by urine testing,
and 2) facilitates prevention of hypoglycemia, espe- T r e a t m e n t Modalities
cially in episodes of insulin overload. ~5 Capillary glu-
DIET
cose levels can be estimated by visual readings of strips
or reflective meters to gauge the reagent strip's colori- Diet remains the cornerstone in the management of
metric reaction. diabetes mellitus. 19'11 Special diets for patients with
diabetes mellitus have been prescribed for over a cen-
GLUCOSE TOLERANCE TEST tury and a half. 2° The goals of nutritional therapy in
diabetes are to attain and maintain desirable body
This diagnostic modality measures serum glucose weight in adults, maintain normal growth rate in chil-
levels at 30 minutes, 1 hour, and 2 hours after the dren, normalize blood glucose levels to avoid acute
administration of 75 g of glucose to adults (1.75 g&g complications and prevent or delay long-term compli-
in children) in the morning after a fast of 10 to 16 cations, and provide optimum nutrition. 19-21The Amer-
hours. The main deficiency of this test is a lack of ican Diabetes Association recommends a diet con-
reproducibility. A review of 10 literature studies taining 55% to 60% of calories from carbohydrates,
showed a mean difference of 26 mg/dL at 1 hour and 12% of calories from protein, and less than 30% of
20 mg/dL at 2 hours. 3'16 On the basis of the glucose calories from fat. 1~'19-21 Diet regimens with increased
tolerance test, diabetes is defined by the National Dia- fiber content have been shown over the last decade to
betes Data Group as when a 2-hour value and one be of therapeutic value in lowering insulin require-
preceding value exceed 200 mg/dL, while impairment ments, increasing peripheral tissue insulin sensitivity,
of glucose tolerance is defined by a fasting serum glu- and decreasing serum cholesterol and triglyceride val-
cose of 140 mg/dL and one value exceeding 200 mg/ ues. 21'22 A goal of up to 40 g of fiber per day should
dL. One percent to 5% of patients with impaired glu- be achieved.
cose tolerance will become diabetic each year. 16 The most important dietary goal for individuals with
type I diabetes mellitus is the establishment of a regular
GLYCOSYLATED HEMOGLOBIN meal pattern with consistent day-to-day caloric and
carbohydrate intake. The most important dietary and
The measurement of glycosylated hemoglobin in di- therapeutic goal in obese persons with type II diabetes
abetic patients has been available since about 1976 and is weight loss. 22
serves as a determinant of mean serum glucose over
time. Hemoglobin Ale is one of several minor adducts ORAL HYPOGLYCEMICS
of hemoglobin A and is formed by the glycosolution
of the N-terminal valine of one or both of the B chains Oral hypoglycemic agents have been available for
of hemoglobin A. Hemoglobin AIo is formed at a rate the treatment of patients with NIDDM since 195523
dependent on the glucose concentration to which the (Table 2). A sulfonamide derivative, 1-butyl-3-sulfo-
5. STEPHENSON, HAUG, AND MURPHY "179
nylurea (carbutamide), developed to treat pneumonia, produced by a chemical conversion from pork or by
also was found to cause hypoglycemia, and subse- the use of recombinant DNA in Escherichia coli] 5
quently proved effective in treating some diabetic pa- In general, human insulin preparations have a shorter
tients. 24 Oral hypoglycemics promote the release of duration of action than animal preparationsS
insulin from the pancreas, increase the quantity of re- The insulin regimen must be designed to mimic
ceptors on peripheral cell membranes, and correct he- physiologic insulin availability. Physiologic insulin
patic insulin resistanceY -26 Oral hypoglycemic agents regimens have components of insulin action designed
are rapidly absorbed from the gastrointestinal tract to coincide with each major meal and a component
after oral administration and can be measured in the designed to provide sustained insulin availability dur-
plasma 1 hour after ingestion. 26'2s Food does not seem ing the basal state overnight] 5 The initial insulin dos-
to significantly affect bioavailability or onset of action, age is 1 to 2 U per kg per day in children 4 and 0.5 to
with the exception of glipizide, which may have de- 1.5 U per kg per day in adults. 4a9 Regimens may vary
layed absorption. 26 Sulfonylureas are tightly bound to to meet a patient's individual needs, but usually two
plasma albumin (90% to 99%). 24,26All oral hypoglyce- thirds of the total dose can be given in the morning
mics undergo hepatic metabolism and are eliminated and one third in the evening. 4'29 The morning dose
as metabolites or unchanged parent compounds via is divided into one third short-acting and two third
the kidneys. 24 Oral hypoglycemics are categorized into intermediate-acting insulin. One half of the evening
first and second generation compounds (Table 2), dose is given as short-acting and one half as intermedi-
based primarily on potency. Therapy is usually insti- ate-acting insulin before supper. 29 Absorption of insu-
tuted after a trial of diet and exercise that has failed lin can be erratic via the subcutaneous route, and day-
to achieve euglycemia (140 to 180 mg]dL). 1j'28 Oral to-day variation of absorption has been shown to be
hypoglycemics have a spectrum of side effects includ- 25% in individual patients. 27Less variation occurs with
ing hypoglycemia, anorexia, heartburn, occasional short-acting preparations. Thus regimens containing
vomiting, flatulence, abdominal fullness, rashes, syn- greater proportions of regular insulin allow greater pre-
drome of inappropriate antidiuretic hormone, and dictability in insulinemia and glycemia. 27
flushing, diaphoresis, and mild headache associated Regional injection sites for insulin are the thigh,
with alcohol ingestion, depending on which oral hypo- buttocks, arm, and abdomen. The fastest absorption is
glycemic is being u s e d . 23'24'26'28 with the abdomen, followed by the arm, buttocks, and
thigh. 27 Random regional site rotation is not indicated.
INSULIN
Rather, the injection site should be rotated within the
same area to achieve predictable glycemic control. To
treat excessive hyperglycemia, the abdomen should be
Insulin was first discovered in 19214,7 and is used in considered the preferred site when supplemental regu-
specific therapies to normalize plasma glucose levels. lar insulin is administered.
Insulin is initiated in patients with type I diabetes, or
type II diabetics who have not responded to diet, exer- Medical M a n a g e m e n t of the Surgical Patient
cise, and oral hypoglycemics. Insulin is available in
three species types (human, beef, and pork) and is Surgery elicits a response of stress-adaptive hor-
classified according to its duration of action and ab- mones (catecholamines, cortisol, growth hormone, and
sorption characteristics 27 (Table 3). Human insulin is glucagon), which elevates plasma glucose and de-
creases tissue sensitivity to insulin. Therefore, preoper-
ative management of the diabetic patient should be
Table 3. Comparative Action of Different directed toward euglycemia and avoiding hypogly-
Insulin Preparations cemia.
Insulin Onset (h) Peak (h) Duration (h) Accurate physical assessment of complications re-
lated to diabetes is necessary preoperativelyfl° In-
Animal: creased mortality and morbidity in diabetics undergo-
Regular 0.5-2.0 3-4 6-8 ing surgery are related mainly to cardiovascular
NPH 4-6 8-14 20-24
complications, infection, and reduced rates of wound
Lente 4-6 8-14 20-24
Ultralente 8-14 Minimal 24-36 healing. 3°-33 Consequently, the diabetic patient spends
Human: 30% to 50% more time in the hospital than the nondia-
Regular 0.5-1.0 2-3 4-6 betic patient following minor surgery, even if the sur-
NPH 2-4 4-10 14-18 gery proceeds without incident. 32 Adept management
Lente 3-4 4-12 16-20
for this group of patients by the oral and maxillofacial
Ultralente 6-10 12-16 20-30
surgeon is as important as the development of an effec-
6. "180 MANAGEMENT OF DIABETIC ORAL SURGERY
tive liaison between the primary care physician and T a b l e 4. G u i d e l i n e s for Use of an I n s u l i n Drip
anesthesiologist.
Insulin
MINOR [NTRAORAL PROCEDURES Blood Glucose (mg/dL) (U/h) (mL/h)
Minor surgical procedures, including simple extrac- <80 0.0 0.0
tions, biopsies, and placement of implants with local 81-100 0.5 5.0
anesthesia alone or with nitrous oxide analgesia, may 141-180 1.5 15
181-220 2.0 20
be performed in the office for well-controlled diabetics
221-260 2.5 25
regardless of whether they are diet-controlled, on an 261-300 3.0 30
oral hypoglycemic, or using insulin. However, if the 301-340 4.0 40
diabetic patient is symptomatic and/or has fasting >341 5.0 50
blood glucose greater than 140 mg/dL, it is best to
Modified with permission.3v
delay elective procedures until the metabolic condition
is optimum. Management of the diet-controlled, oral
hypoglycemic, and insulin-using patient includes must be performed under a general anesthetic. Gener-
morning food consumption and the usual dose of oral ally, preoperative assessment should include serum
hypoglycemic or insulin. measurements of glucose, sodium, potassium, chloride,
bicarbonate, urea nitrogen, creatinine, and ketones, as
MODERATE INTRAORAL PROCEDURES
well as a complete blood count. 18.35.36Electrocardiogra-
Moderate surgical procedures, such as removal of phy should be done on all diabetic patients preopera-
impacted teeth, requiring intravenous sedation or am- tively and postoperatively for comparison, especially
bulatory general anesthesia are not as benign as might if any unusual surgical stress occurs, because painless
be assumed in the diabetic patient. Some agents used to myocardial infarctions may occur during surgery. 18'36
produce anesthesia can alter carbohydrate metabolism
and, when combined with surgical stress, anesthesia Diet-Controlled Diabetics
has a definite hyperglycemic effect. 34 There is no agent Well-controlled, diet-treated diabetics do not require
specifically contraindicated and none specifically bene- any special treatment before and during surgery. 35 If
ficial in a diabetic patient. Autonomic neuropathy can the fasting plasma glucose is lower than 140 mg/dL,
predispose the patient to orthostatic hypotension, high these patients can be treated initially with close obser-
arrhythmia risk, urinary retention, and gastroparesis. vation. 34'35 Plasma glucose levels should be measured
Renal complications may manifest as electrolyte and hourly intraoperatively. If blood glucose levels in-
fluid disturbances, including hypokalemia. Such hypo- crease rapidly during or after surgery, it may be neces-
kalemia during the induction of anesthesia may be a sary to give insulin] 4 The regimen of exogenous insu-
major factor responsible for the development of cardiac lin given to type I or type II diabetics is appropriate
arrhythmias. 34 The surgical and physiologic needs may for diet-controlled diabetics.
be difficult for the surgeon to manage simultaneously.
Consideration should be given to managing the insulin- Oral Antihyperglycemic-Controlled Diabetics
requiring diabetic patient in the operating room as for
a major procedure. The oral antihyperglycemic-con- Ideally, to achieve metabolic control, it is best to
trolled patient should discontinue oral hypoglycemic admit the patient to the hospital the day before surgery.
therapy the day before surgery. Fasting plasma glucose The patient should have oral hypoglycemic therapy
concentrations should be lower than 140 mg/dL. If discontinued the day before surgery. If the patient is
fasting plasma glucose levels are above 140 mg/dL, taking long-acting agents (glyburide and chlorpro-
and intravenous insulin infusion should be considered pamide), it is important to convert them to short-acting
in an operating room setting. Intraoperative fluids agents (glipizide and tolbutomide) several days before
should consist of 5 % dextrose in normal saline. Postop- admission. 2'37 Type II diabetics will probably require
eratively, these patients resume their oral hypoglyce- temporary use of exogenous insulin because these indi-
mic. The diet-controlled diabetic requires no specific viduals have limited reserves of endogenous insulin,
management considerations. and stress of surgery sometimes may push them into
ketosis. 34 An insulin and glucose regimen should be
MAJOR INTRAORAL/EXTRAORALPROCEDURES administered. This regimen can consist of subcutane-
ous insulin with glucose infusion, combined insulin/
Major surgical procedures, such as trauma manage- glucose infusion, or separate insulin and glucose infu-
ment, joint reconstruction, and infection management, sions, with hourly blood glucose assessments. Postop-
7. STEPHENSON, HAUG, AND MURPHY "18"1
eratively, these patients are resumed on their oral Table 5. Combined Glucose-insulin Infusion
hypoglycemic, but may require several days on a multi-
Treatment Adjustment
ple-dose insulin regimen to regain glycemic con-
trol.32'37
Diet, oral agent, Fasting blood glucose 120-180 mg/dL
or insulin Add 10 U regular human insulin to 1,000 mL
(<50 U/d) 5% dextrose plus 20 mEq potassium chloride
Insulin-Controlled Diabetics Insulin (>50 U/d) Fasting blood glucose 120-180 mg/dL
Add 15 U regular human insulin to 1,000 mL
All patients taking insulin, whether for type I or type 5% dextrose plus 20 mEq potassium
chloride
II diabetes, should receive insulin therapy during the Infuse at a rate of 100 mL/h
surgical procedure. 32 Ideally, these patients should be Check blood glucose hourly:
admitted the day before surgery to obtain metabolic If >180 mg/dL, increase insulin by 5 U
control. The traditional method of management in- If <120 mg/dL, decrease insulin by 5 U
volves subcutaneous injection of 30% to 50% of the
Modified with permission?v
usual morning dose of intermediate insulin NPH or
Lente on the morning o f s u r g e r y , 32'34"37'3s combined
with an intravenous infusion of dextrose (5%) in water
at a rate of 100 mL/h. This approach has several disad- and dosages adjusted as shown in Table 5. If serum
vantages such as variable and unpredictable insulin glucose falls below 80 mg/dL, the same regimen is
absorption, extremes in glucose levels, and lack of followed as previously described. This method lacks
ability to modify effect. Postoperatively, management flexibility, but is acceptable when infusion pumps are
traditionally consists of supplemental schedules of reg- not available and/or when frequent variations in insulin
ular subcutaneous injections, 34'38which results in a roll- needs are not anticipated. Twenty to 40 mEq of potas-
ercoaster-like blood glucose profile. The newer man- sium chloride should be added to the maintenance flu-
agement protocols are using intravenously controlled ids, based on serum potassium determinations.
insulin/glucose infusion regimens, which is perhaps the The success of either of the insulin/glucose infusion
preferable method of managing type I diabetes during regimens is dependent on accurate hourly measure-
surgery. 34'3vThis approach provides flexibility and can ments of blood glucose levels. 32'39Postoperatively, the
be rapidly adjusted depending on the hourly variation infusion is continued until adequate dietary intake is
in blood glucose. The infusions of insulin and glucose tolerated. Once food tolerance is established, the insu-
can continue through the period of anesthesia and into lin-requiring diabetic is returned to the former dosage
the postoperative period. Usually 1 to 2 U of regular or a new basic regimen is established based on the
insulin and 5.0 to 7.5 g of glucose per hour given by previous day's insulin requirement (25% breakfast,
intravenous drip can maintain blood glucose levels in 25% lunch, and 25% dinner as regular insulin, and
the 120 mg/dL to 180 mg/dL range. 32'39 25% at bedtime as N P H ) ] 2 The infusion is terminated
Management with an insulin drip requires the mix- 30 minutes after first subcutaneous injection of short-
acting insulin. 32
ture of 25 U of regular insulin in 250 mL of normal
saline (1 U/10 mL). Perioperative fluids consisting of
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