in Patients with NIDDM

1
( ) in Patients with NIDDM ( ). How should L.H.
be switched from oral agents ( ?) Is it
reasonable to use insulin in combination with
oral sulfonylurea therapy? Some have suggested
that the addition of basal insulin doses (evening
NPH or long-acting insulins) may bring patients
who are poorly controlled on oral agents under
control.293, 294 They recommend day-time dosing
of the oral sulfonylureas in conjunction with
ultralente in the evening or NPH at bedtime to
suppress hepatic glucose output during the
post-absorptive state (BIDSBedtime Insulin
Day-time Sulfonylureas).
2
However, it is common clinical practice to treat
patients who have responded poorly to the oral
agents with insulin alone. The switch may be made
abruptly, but one should be aware of the
prolonged action of chlorpropamide and glyburide
in patients taking these agents and use more
conservative doses initially.
3
Since tolazamide has an intermediate duration of
action, it is unlikely that any residual effects
will remain be-j-ond one day. Even if they do,
L.H. is in such poor control that any effect is
unlikely to be clinically impor- tant.
Therefore, L.H. can be instructed to discontinue
her tolazamide immediately and begin
insulin therapy. In- sulin dosing
procedures are the same as those described
for patients with IDDM in Questions 5 and 15
through 15, except that L.H.'s total
daily dose of insulin may be
4
higher on a unit/kg basis due to insulin tissue
resis- tance.284 (See Table 69.12.) One
should be aware, that when high doses of
insulin are used, patients have difficulty
losing weight. This is secondary to the anabolic
effects of insulin and hunger that can
occur in associa- tion with low glucose
concentrations. There is also concern
about the potential atherogenic consequences of
chronically-elevated insulin
levels.S9930'
5
Combined Use of Oral Sulfonyt ureas and J\A.
Insulin. Over a period of six weeks, L.H. is
moderately-well controlled on twice daily doses
of NPH and regular insulin 45 U NPH/15 U Reg in
the a.m. and 20 UNPH/10 U Reg in the p.m. She now
uses HBGM fasting blood glucose concentrations
range from 140 to 160 mg/dL and pre-prandial
blood glucose concentrations range from 120 to
200 mg/dL. Despite what she considers earnest
attempts to comply with her diabetic diet, she
has gained five pounds since her Jast visit four
weeks ago. Is it rational to add oral
sujfonylureas to L.H.'s therapy? Several
investigators have explored the beneficial
effects of sulfonylureas used in combination with
insulin. Combined therapy is based on the
hypothesis that less exogenously administered
insulin may be required if an oral agent can
stimulate at least some endogenous insulin
release and, in particular, increase insulin
tissue sensitivity.
6
Most studies demonstrate that the addition of
sulfonylureas to insulin therapy in.patients
with true IDDM (i.e., no C-peptide) has no effect
on glucose control.3Q2'30S Placebo-controlled3'0"3
14 and uncontrolled215-517 studies indicate that
in some patients with NIDDM who have failed
treatment with sulfonylureas alone, the addition
of sulfonylureas to insulin therapy may improve
fasting plasma glucose concentrations and
glycosylated hemoglobin values modestly (40 to
50 mg/uL and 1 to 2, respective! gt Tiut may
or may not be accompanied bv h