Insulin therapy in type II diabetes
Who needs it, how much of it, and for how long?
Jay S. Skyler, MD
VOL 101 / NO 2 / FEBRUARY 1997 / POSTGRADUATE MEDICINE
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This is the third of three articles on insulin therapy
Preview: Patients with type II diabetes mellitus are usually not dependent on insulin for
prevention of ketosis or maintenance of life. However, they often benefit from insulin
therapy to control symptoms or correct disordered metabolism, and a temporary course
may be used to adjust glucose control. In this article, Dr Skyler discusses underlying
concepts that direct insulin therapy in type II diabetes. He also summarizes the present
state of combination therapy in which insulin is paired with another glucose-lowering
agent.
Although type II diabetes may rarely make its appearance as early as adolescence, it
usually begins after the age of 40 (which accounts for its previously used name, maturityonset diabetes). Prevalence is increased in older persons, particularly those who are
overweight or sedentary, which is not surprising considering that age brings a progressive
decrease in insulin sensitivity and that insulin resistance is induced by adiposity and
inactivity. Moreover, hyperglycemia can further impair both beta-cell function and
insulin action, thus creating a vicious circle that aggravates hyperglycemia.
Type II diabetes is characterized by altered insulin secretory dynamics with retention of
endogenous pancreatic insulin secretion, absence of ketosis (accounting for another of its
names, ketosis-resistant diabetes), and insulin resistance due to diminished target-cell
action of insulin. Although type II diabetes is heterogeneous, both of the major
pathogenetic mechanisms (ie, impaired islet beta-cell function [impaired insulin
secretion] and impaired insulin action [insulin resistance or decreased insulin sensitivity])
(1-4) are operative in variable degrees in most patients. Current thinking is that separate
genetic defects are responsible for the predominance of one mechanism over the other. In
addition, environmental factors create further insulin resistance.
Therapeutic objectives
The beneficial effects of glucose control on chronic complications (retinopathy,
nephropathy, and neuropathy) in type I diabetes have been firmly established (5-7), and a
study from Japan has shown similar results in type II diabetes (8). Moreover, results of
analyses suggest that similar relationships exist between glucose control and other
diabetic complications for both type I and type II diabetes (9,10).
Since glucose control is clearly important and should be sought in all patients with
diabetes, the American Diabetes Association has suggested indexes of control for type II
diabetes (table 1) (11,12). Minimum treatment goals are correction of fasting and
preprandial hyperglycemia to below 140 mg/dL, which is the threshold for diagnosis of
diabetes based on fasting hyperglycemia alone; the ideal to strive for is a normal fasting
glucose level (<115 mg/dL). Minimizing excessive postprandial hyperglycemia and
obviating glycosuria, as reflected by a normal or near-normal level of glycosylated
hemoglobin (HbA1c or HbA1), are also important goals.
Table 1. Indexes of glucose control in type II diabetes
Index
Typical level in
Goal in type
nondiabetic persons II diabetics
Level at which therapy
is recommended
Fasting and
preprandial plasma
glucose
<115 mg/dL
80-120 mg/dL
<80 or >140 mg/dL
Bedtime plasma
glucose
<120 mg/dL
100-140
mg/dL
<100 or >160 mg/dL
Hemoglobin A1c*
<6%
<7%
>8%
*Nondiabetic reference range, 4% to 6%.
Adapted from the American Diabetes Association (11,12).
Progressive use of various methods until targeted glucose-control goals are attained (ie,
goal-based therapy) is the basis for contemporary management of type II diabetes (13).
Another variable that requires attention is atherosclerotic risk, which is substantial. Lipid
levels and blood pressure need meticulous control. In addition, a nutritional plan and
promotion of physical activity are cornerstones of management. Attaining and
maintaining weight as close to ideal as possible is as crucial as controlling glucose levels
in obese patients with type II diabetes, since successful weight control often leads to
successful glucose control. A final objective is smoking cessation.
Indications for and choice of insulin
The need for insulin therapy in patients with type II diabetes depends on the severity of
the disease and whether glucose-control goals have been met with other means. Most
patients require some type of pharmacologic therapy, and most of them as well as their
physicians prefer to try other pharmacologic approaches before starting insulin therapy.
Some investigators have argued that insulin therapy is not effective in type II diabetes
because insulin deficiency is not the primary defect. However, with insulin therapy it is
possible to overcome insulin resistance and provide adequate insulin even in the presence
of islet beta-cell dysfunction (14,15); almost invariably, with use of enough insulin,
glucose levels can be regulated.
Against the backdrop of these differing opinions, guidelines for therapy of type II
diabetes are evolving, namely, that insulin should be considered in the presence of any of
the following conditions:









Hyperglycemia despite maximum doses of oral agents
Decompensation due to an intercurrent event (eg, infection, acute injury, stress)
Severe hyperglycemia with ketonemia or ketonuria
Uncontrolled weight loss
Upcoming surgery
Pregnancy
Renal disease
Allergy or other serious reaction to oral agents
A preference for insulin therapy by the patient or physician
Since insulin therapy may be interrupted in type II diabetes, choosing the least
immunogenic insulin available is a good idea. Therefore, highly purified human insulin
preparations should be used and animal insulins avoided. For a short-acting insulin, either
human regular insulin or the insulin analogue lispro (Humalog) may be given. Lispro
insulin has a more rapid onset and shorter duration of action than regular insulin. These
characteristics may offer advantages, since prolonged postprandial hyperglycemia occurs
often in type II diabetes and is minimized with use of lispro.
Glucose toxicity
Glucose toxicity has been shown to contribute to development of insulin resistance and
impaired insulin secretion in animal models of diabetes (16,17), and data suggest that
hyperglycemia is responsible for some of the resistance and some of the impairment in
beta-cell function.
In humans with type II diabetes, a considerable body of evidence indicates that chronic
elevation in plasma glucose concentration leads to progressive impairment in insulin
secretion as well as aggravation of insulin resistance due to downregulation of the
glucose-transport system. Thus, impairments in insulin secretory response and insulin
action are the result of dynamic processes. Chronic hyperglycemia may, of itself,
aggravate the defects. Most important, in patients with poorly controlled diabetes,
improved glucose control results in improved insulin secretion and amelioration of some
of the insulin resistance.
Therefore, insulin therapy can be used to overcome glucose toxicity and restore the
potential effectiveness of other therapeutic methods, making the improved metabolic
state easier to maintain. Such a "feed-forward" system explains the clinical aphorism that
it is much easier to maintain than to attain glucose control. The relationship between
insulin and glucose toxicity explains the rationale behind temporary insulin therapy to
initially attain glucose control and re-regulate decompensated patients as well as that
behind discontinuation of insulin therapy in some patients.
Temporary insulin therapy
In patients with severe type II diabetes, temporary insulin therapy is an important method
of initially attaining glucose control, overcoming glucose toxicity, and restoring
regulation in decompensated patients (18,19). In fact, type II diabetes may be considered
a disease of periodic decompensation that requires re-regulation, usually with insulin
therapy. For this reason, all patients with type II diabetes should learn insulin
administration techniques and be prepared to initiate therapy in the face of periodic
decompensation, which occurs spontaneously or, more often, as a result of intercurrent
illness or stress. Unfortunately, however, temporary use of insulin is one of the more
neglected principles of management in type II diabetes.
The hypothesis that short-term insulin therapy may induce long-lasting metabolic
improvements in patients with type II diabetes has been tested; the degree of success has
varied with the stage of the disease. The approach works extraordinarily well in early
disease to attain initial glucose control and re-regulate decompensated patients with
intercurrent illness or stress.
Short-term insulin therapy has also been used in patients with long-standing disease in
whom other methods have failed to adequately control glucose levels. (Such patients
probably have progressive pancreatic beta-cell failure, which is unrelated to glucose
toxicity.) In these patients, temporary insulin therapy has had variable results (19). After
insulin withdrawal, improved glucose control continues in some patients, whereas in
others, blood glucose levels increase but usually remain below pretreatment levels. In this
situation, after 4 weeks of insulin therapy, ambient blood glucose levels and basal
glucose production are decreased and insulin secretory response and insulin action (rate
of in vivo glucose disposal) are improved. Improvements in insulin secretory response
and insulin action persist after cessation of insulin therapy; unfortunately, however, these
improvements may not be sufficient to achieve desired glucose target levels, and longterm insulin therapy may be required.
For initial glucose control, vigorous insulin therapy may be needed to overcome insulin
resistance and glucose toxicity. Insulin is part of a program of "sequential therapy," in
which glucose control is attained with insulin and subsequently maintained with use of
basal insulin, oral agents, or diet and exercise.
For re-regulation of decompensated patients with intercurrent illness, insulin can often be
added to existing oral therapy. Often, it is used for only a few days to a few weeks.
Insulin may be administered as a supplement, with the amount based on the prevailing
glucose level before meals (eg, 1 to 2 U of short-acting insulin for every 50 mg/dL above
the preprandial target level). Another option is to add a relatively small total daily dose
(eg, 0.2 to 0.3 U/kg) of intermediate-acting insulin or a combination of intermediate- and
short-acting insulin to existing therapy.
Discontinuation of insulin
With correction of glucose toxicity in patients with type II diabetes, both endogenous
insulin secretion and insulin sensitivity are improved and discontinuation of exogenous
insulin therapy may be possible. Candidates are patients whose clinical condition,
including body weight, is stable and whose glucose target levels are being met.
I use the following guidelines for discontinuing insulin therapy:
1. Reduce the dose by 10% to 15% of the total daily dose, while carefully
monitoring blood glucose level to be sure there is no deterioration in glucose
control.
2. If the blood glucose level rises, restore the initial dose. If the level does not rise,
reduce the dose about 10% to 15% every 1 to 2 weeks.
3. When the daily dose has been reduced to less than 0.3 to 0.4 U/kg, consider
discontinuing insulin and replacing it with a sulfonylurea alone or combined with
metformin hydrochloride (Glucophage). I usually use glipizide by GITS delivery
(Glucotrol XL) or glimepiride (Amaryl) as the sulfonylurea.
4. If the glucose level is nearly normal and only a low daily dose (about 0.25 to 0.3
U/kg) is required at the time of insulin replacement, it is often possible to use a
sulfonylurea alone, albeit at a fairly high dose. Since a sulfonylurea has
immediate effect, insulin may be discontinued after the first dose.
If the glucose level is not quite normal or the required daily insulin dose is a little higher
(about 0.3 to 0.4 U/kg), a sulfonylurea plus metformin is usually desirable. Metformin
requires 3 to 6 weeks to reach its full effect, so some insulin (usually about half of the
earlier dose) should be continued for this period.
Basal insulin therapy
The fasting (basal) glucose level is crucial in type II diabetes, because it is the level
above which glucose levels oscillate in a given patient. Fasting hyperglycemia is a
consequence of increased hepatic glucose production, and adequate overnight insulinemia
is important in prevention. Basal insulin therapy dates back to the earliest use of
sustained-action insulin and is designed to correct fasting hyperglycemia (18,20,21). In
some cases, it may be used alone to correct fasting hyperglycemia when endogenous
insulin secretion is adequate to control meal-related glucose excursions.
Basal insulin therapy reduces overnight hepatic glucose production by inhibiting
gluconeogenesis from lactate (22). It can suppress high nocturnal concentrations of free
fatty acids in type II diabetes, which may contribute to hepatic insensitivity to insulin and
fasting hyperglycemia (23). Moreover, basal insulin therapy can control overnight
waning of insulinization, which is responsible for the dawn phenomenon in type II
diabetes (24,25). Therefore, adequate basal insulin levels are an essential component of
diabetes management.
Several regimens of basal insulin therapy have been proposed for type II diabetes. It can
be provided as a bedtime dose of intermediate-acting insulin (eg, NPH or lente), as a
long-acting (ultralente) supplement to basal insulin secretion, or as a continuous insulin
infusion. Unfortunately, marketing surveys by US insulin manufacturers suggest that
more than 60% of insulin is prescribed as a single morning dose of an intermediate-acting
form. Such treatment fails to provide adequate basal insulin levels and may result in
daytime hypoglycemia. Morning insulin is prescribed for convenience and because of
fear of nocturnal hypoglycemia. However, several studies have shown that a bedtime
dose of intermediate-acting insulin is superior to a morning dose in patients with type II
diabetes (26-30). Basal insulin therapy provides better glucose control, with less weight
gain and lower ambient levels of circulating insulin.
The concept of bedtime insulin has also been applied in studies of combination insulin
and sulfonylurea therapy (31-38), discussed later.
Ongoing insulin therapy
In most patients, type II diabetes can be controlled with insulin if adequate doses are
given and if the patient follows an appropriate diet and activity program, which facilitates
insulin action. Failure to follow an appropriate diet may countermand the effects of
insulin and lead to a vicious circle of progressive increases in insulin doses yet failure to
control glucose levels.
Classification and treatment by disease severity
For clinical purposes, type II diabetes may be classified as mild, moderate, severe, or
very severe (table 2) (18). The fasting (basal) plasma glucose level is the principal
determinant because it is relatively constant from day to day when patients are on a stable
program of diet and activity. The postprandial glucose response is also used to determine
classification. Although type II diabetes is characterized by prolonged postprandial
hyperglycemia, typically, the endogenous insulin response to meals is sufficiently intact
to restore glucose level (within 20 to 25 mg/dL) to basal readings within 4 to 5 hours
after meal consumption. The exception is very severe type II diabetes, in which the
postprandial glucose level does not return to the basal level within this time period.
Table 2. Classification of type II diabetes
Category
Fasting (basal) plasma
glucose level (mg/dL)*
Mild
<140
Moderate
140-250
Severe
>250
Very
severe**
>250-300
*In patients following a consistent diet
and activity program.
**Glucose level is not restored to
within 20-25 mg/dL of basal level
within 4-5 hr after meals.
Adapted from Skyler (18).
Insulin therapy for type II diabetes depends on the severity of the disease (table 3). In all
four classifications, adequate therapy may improve islet beta-cell function and peripheral
insulin action at target cells sufficiently to improve glucose homeostasis. In such cases,
patients may be reclassified to a less severe category, and glucose control may be
maintained with a treatment program typical for that category. For example, improved
glucose control may permit patients initially treated with insulin to be maintained using
diet and activity alone or oral hypoglycemic agents. Downward adjustment of the insulin
dose to less than 0.3 to 0.4 U/day suggests that maintenance therapy with an oral
hypoglycemic agent may be attempted.
Table 3. Approaches to attaining glucose
control in type II diabetes based on
severity of disease
Mild
Insulin virtually never needed
Moderate
Basal insulin therapy usually
sufficient

Bedtime dose of intermediateacting insulin (NPH or lente)
or

Use of long-acting (ultralente)
insulin supplement
or

Continuous insulin infusion
Endogenous insulin controls mealrelated glucose excursions
Severe
Around-the-clock insulinization
needed

Twice-daily intermediateacting insulin (NPH or lente)
or

Use of long-acting insulin
or

Continuous insulin infusion
For patients who require more
intensive therapy, a short-acting
insulin (regular or lispro [Humalog])
may be added
Very severe
Treat akin to type I diabetes
Mild: Patients with mild type II diabetes have a fasting plasma glucose level below the
diagnostic threshold (ie, <140 mg/dL). These patients sometimes respond to a diet and
activity program with no pharmacologic intervention. If such a program proves
inadequate, addition of a sulfonylurea or metformin may be beneficial. Patients with mild
type II diabetes almost never require insulin therapy.
Moderate: Patients with moderate type II diabetes have a fasting plasma glucose level of
140 to 250 mg/dL. They almost invariably require pharmacologic intervention in addition
to modifications in diet and activity. Fasting hyperglycemia can often be corrected by
basal insulin therapy; endogenous insulin secretion is usually adequate to control mealrelated glucose excursions. Basal insulin therapy may be provided as described earlier.
Required daily doses are usually in the range of 0.3 to 0.6 U/kg. When intermediateacting insulin is administered at bedtime, its peak effect 8 to 10 hours later coincides with
the pre-breakfast period, thus controlling fasting glucose levels.
Severe: Patients with severe type II diabetes have a fasting plasma glucose level of more
than 250 mg/dL, but within 5 hours of meals, the glucose level is restored to basal
readings. Glucose control can be attained most readily with insulin therapy providing
around-the-clock insulinization. Thus, a bedtime dose of intermediate-acting insulin
cannot be used (although a twice-daily regimen of intermediate-acting insulin can).
Most patients require an intensive insulin program (with addition of short-acting insulin,
either regular or lispro) to attain glucose control. Required daily doses are usually
between 0.5 and 1.2 U/kg. However, large daily doses, even in excess of 1.5 U/kg, may
be needed, at least initially, to overcome prevailing insulin resistance.
Such high-dose therapy may be necessary only to attain control. Subsequent, long-term
control may be maintainable with lower doses, a basal insulin program, or a sulfonylurea
alone or with metformin. Often, insulin therapy is continued at daily doses of 0.3 to 1
U/kg. The use of premixed insulin preparations (eg, 70% NPH and 30% regular insulin,
or 70/30) may facilitate implementation of such maintenance programs.
Another option is to attain glucose control with use of continuous insulin infusion and
then achieve maintenance with one of the methods mentioned.
Very severe: Patients with very severe type II diabetes usually have a fasting plasma
glucose level above 250 mg/dL; it can reach 300 mg/dL or even more. Most important,
the endogenous insulin response to meals is nonintact. Insulin deficiency is so profound
that initially it may be difficult to distinguish these patients from those with type I
diabetes (although, in general, they do not manifest ketosis). In fact, initially, it is best to
administer the same treatment as in type I patients.
The need for progressive therapy
Type II diabetes is a progressive disease. Over time, in spite of maximum doses of
various therapeutic agents, glucose control may deteriorate.
In patients with type II diabetes in whom standard therapy with oral agents has failed to
achieve adequate glucose control, insulin therapy becomes necessary. When initial basal
insulin therapy fails to achieve adequate glucose control, the regimen should be
intensified to combination therapy using the following stepwise approach: addition of a
sulfonylurea during the day, administration of insulin twice daily and, ultimately,
administration of insulin three or four times daily (8,39).
However, as a consequence of progressive beta-cell failure, near-normal glucose levels
cannot be sustained indefinitely. In a multicenter, controlled trial of more than 4,000
patients with type II diabetes followed for more than 9 years (40,41), even insulin therapy
did not achieve the therapeutic goal of near-normal glucose levels, owing to the difficulty
of treating marked hyperglycemia and the risk of hypoglycemic episodes.
Latent autoimmune diabetes in adults
A subtype of type II diabetes, which appears to be a slowly evolving variant of type I
diabetes, has been termed latent autoimmune diabetes in adults (42). It should be
suspected in patients with type II diabetes who have onset of disease in the third or fourth
decade of life and who are thin (although the disease may present at any age and in
persons who are not thin). A family history of type I diabetes or autoimmune endocrine
disease favors the diagnosis. Antibodies directed against islet-cell antigens establish the
diagnosis. The condition should always be treated with insulin, given as for type I
diabetes, because insulin may slow progression of the autoimmune process and because
actively secreting beta cells are more prone to autoimmune attack. Sulfonylurea therapy
may hasten beta-cell failure in these patients.
Considerations in elderly patients
Insulin therapy is often used in elderly patients with type II diabetes as a last resort, after
dietary management and maximum doses of oral hypoglycemic agents have failed. The
aim of therapy in the elderly is to relieve symptoms and prevent both hypoglycemia and
acute complications of uncontrolled diabetes (eg, hyperosmolar states). Insulin-injection
schedules should be kept as simple as possible and premixed insulins used when feasible,
because self-administration is often difficult and dosage errors are not uncommon.
Combination therapy
Sulfonylureas, biguanides, alpha-glucosidase inhibitors, and thiozolidinediones
(glitazones) have been added to insulin therapy. The usefulness of these combination
therapies has varied, and all require further study.
Sulfonylureas
Sulfonylureas enhance endogenous insulin secretion (43). They lower ambient glucose
levels and overcome glucose toxicity, resulting in improved insulin action.
Meta-analyses of randomized trials have suggested that addition of a sulfonylurea to
insulin therapy reduces hyperglycemia, insulin dose, or both (44-46). However, some
investigators (44,45) believed that benefits were quantitatively marginal and were not
demonstrated conclusively over the long term. Other investigators (46) endorsed the
combination more strongly. Part of the controversy exists because different subject
groups were studied using different treatment programs. In any case, the findings failed
to provide consistent conclusions.
Nevertheless, interest in insulin-sulfonylurea combination therapy has been rekindled
(21), partly because many studies have used bedtime administration of intermediateacting insulin and daytime administration of a sulfonylurea (31-38). (This method is often
called BIDS therapy, for bedtime insulin, daytime sulfonylurea.) The bedtime
intermediate-acting insulin decreases hepatic glucose production and thus controls fasting
hyperglycemia, and the preprandial sulfonylurea stimulates pancreatic insulin secretory
response to meals. BIDS therapy should be considered in the following patients:


Those who are already taking the maximum dose of sulfonylurea but whose
fasting plasma glucose level continues to rise
Those in whom bedtime intermediate-acting insulin results in adequate control of
fasting plasma glucose levels but loss of glucose control after meals and
throughout the day
Biguanides
Biguanides (eg, metformin) decrease hepatic glucose production and thus reduce fasting
glucose levels (47). They may also have a secondary effect of improving insulin action.
The strategy of combining a biguanide with insulin therapy was considered because the
agents are active in the presence of insulin and thus might facilitate its effects (48).
Several studies in both type I and type II diabetes have examined the possible synergistic
effect of the combination therapy. Although some of these studies have shown that
insulin requirements were decreased during administration of a biguanide, they were not
rigorously controlled and are generally unimpressive. What little effect occurs seems to
be maximal shortly after administration of the biguanide. Some investigators have
claimed that use of a biguanide reduces glucose excursions, but other researchers refute
this claim.
Since the only alleged benefit of adding a biguanide to insulin is a decrease in insulin
requirements and most studies to date have been inadequate, this combination cannot be
recommended with much enthusiasm at present.
Alpha-glucosidase inhibitors
Another possible strategy is to combine an alpha-glucosidase inhibitor (eg, acarbose
[Precose]) with insulin therapy. The alpha-glucosidase inhibitor decreases postprandial
glycemia by inhibiting digestion of complex carbohydrates and disaccharides, thus
retarding gastrointestinal glucose absorption (49). Since postprandial hyperglycemia
remains a problem in both type I and type II diabetes, even in insulin-treated patients, this
approach is logical, and there are reports of improved control with the addition of the oral
agent. Unfortunately, data are inadequate as yet to draw firm conclusions, and findings
that exist at present have been drawn mostly from relatively short-term studies.
Nevertheless, the approach is sound theoretically and it must therefore be given some
consideration.
Thiozolidinediones
The primary mechanism of action of thiozolidinediones is correction of insulin resistance
and improvement of target-cell insulin action through insulin sensitization (50). Since
thiozolidinediones improve insulin action, combining one with insulin would seem to be
a logical therapeutic option for type II diabetes. Studies exploring this combination
therapy are in progress but have not yet been reported. The thiozolidinedione troglitazone
will become available in the United States in 1997.
Insulin resistance
The insulin-resistance syndrome is a cluster of metabolic disorders that includes type II
diabetes, central obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular
disease (51). The resistance to insulin action engenders compensatory hyperinsulinemia,
so in epidemiologic studies, hyperinsulinemia has been associated with hypertension,
dyslipidemia, and cardiovascular disease.
Some researchers criticize using insulin therapy in type II diabetes on the grounds that
insulin may have atherogenic effects and that relative hyperinsulinemia is already present
in this insulin-resistant state. Yet, the state of cellular resistance to insulin action subtends
the observed hyperinsulinemia. In fact, patients with moderate to severe hyperglycemia
have reduced endogenous insulin secretion, which provides a logical basis for insulin
administration. Moreover, sufficient insulin doses can overcome any insulin resistance
that is present.
There is substantial evidence that it is insulin resistance rather than hyperinsulinemia that
accounts for both hypertension and dyslipidemia in the insulin-resistance syndrome (52).
For example, vasodilation is one of insulin's effects (53). Therefore, impaired insulinmediated vasodilation could contribute to the hypertension found in the insulin-resistance
syndrome (52,53). Inhibition of lipolysis is another of insulin's effects, so impaired
insulin inhibition of lipolysis could lead to elevated plasma free fatty acid concentrations.
These greater concentrations provide increased substrate and thus enhance very-lowdensity lipoprotein synthesis, leading to hypertriglyceridemia and the dyslipidemia found
in the insulin-resistance syndrome (54).
In an important study of the metabolic effects of intensive insulin therapy in type II
diabetes (55), glucose control was markedly improved with little hypoglycemia.
Concomitantly, dyslipidemia was dramatically improved, although the average weight
gain was substantial (19 lb [8.7 kg]). The improved lipid profile with insulin therapy is
consistent with findings of other studies (56,57). It and the improved glucose levels
achieved with vigorous insulin therapy can be sustained for 2 to 3 years (58).
Insulin pump use
Studies demonstrate that continuous subcutaneous insulin infusion (ie, insulin-pump
delivery) is a viable method in patients with type II diabetes. In one study comparing
insulin pump and conventional insulin therapy (59), glucose control improved in both
groups. However, a much higher proportion of patients using an insulin pump achieved
the established glucose target level, and they also had greater improvement in serum
triglyceride levels. A similarly designed study (60) also found greater improvement in
glucose control in the insulin-pump group, even though no preprandial boluses were
used.
A recent 1-year study of intensive insulin therapy for type II diabetes (61) compared use
of an implantable insulin pump with multiple daily insulin injections. The approaches
improved control of blood glucose levels equally. However, the implantable insulin pump
also reduced glycemic variability, clinical hypoglycemia, and weight gain while
improving quality of life. Although implantation of an insulin pump may be too extreme
to be considered routine practice, it may be useful in special circumstances or in research
studies.
Summary
Insulin therapy can control glucose levels in patients with type II diabetes. Because of
insulin resistance, high doses may be required initially to attain satisfactory control;
however, also because of insulin resistance, hypoglycemia with insulin therapy is much
less common among patients with type II diabetes than among those with type I diabetes.
Insulin therapy need not be permanent. In some cases, temporary worsening of disease is
the result of glucose toxicity and insulin can be discontinued or doses reduced when
disease severity subsides. On the other hand, beta-cell failure is progressive, and with
long duration of diabetes, permanent insulin therapy may be necessary to achieve
satisfactory glucose control.
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Dr Skyler is professor of medicine, pediatrics, and psychology; division of
endocrinology; University of Miami School of Medicine. Jay S. Skyler, MD, University
of Miami School of Medicine, Jackson Medical Towers (D-110), 1500 NW 12th Ave,
Suite 1012 E, Miami, FL 33136. E-mail: jskyler@mednet.med.miami.edu.
Symposium Index
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

Introduction
Insulin Analogues: New agents for improving glycemic control by John R.
White Jr, PharmD, R. Keith Campbell, RPh, CDE, Irl Hirsch, MD
Benefits of Lispro Insulin: Control of postprandial glucose levels is within
reach by Nancy J. V. Bohannon, MD
Insulin Therapy in Type II Diabetes: Who needs it, how much of it, and for
how long? by Jay S. Skyler, MD
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