 PRACTICE GUIDELINES GUIDELINE
ISSUED: APRIL 1998
UPDATE: FEBRUARY 2000 CLINICAL
PRACTICE GUIDELINE for
MANAGEMENT of DIABETES MELLITUS ENDORSED
BY: CHIEFS OF
ENDOCRINOLOGY
CHIEFS OF
MEDICINE INTRODUCTION
This is an update of the
Clinical Practice Guidelines
for the Management of Diabetes Mellitus intended to incorporate the
results of clinical trials
that have been published since the April 1998 release of the guideline.
Additional
issues important to the management of
diabetes
mellitus are thoroughly discussed in the April 1998 guideline.
These include: management of
type I diabetes, patient education and behavior change, psychosocial
issues, nutrition, physical
activity, aspirin prophylaxis, lower extremity complications,
adverse outcomes of pregnancy,
and psychiatric complications. For more detailed information see the
Kaiser Permanente Northern
California Clinical Practice Guidelines for the management of Diabetes
Mellitus, April 1998. Key
points * Glycemic control, regardless of the way it is
achieved,
will reduce microvascular complications
in patients with
type 2 diabetes. The therapeutic
goal for glycemic control is a HbAlc of < 7.0%. *Monotherapy and
combination drug therapies have
changed (both standard and optional therapies). * Blood pressure (BP) control
reduces macrovascular and
microvascular morbidity and mortality.
The target blood
pressure should be < 130/85
mm Hg for all patients with diabetes mellitus. If there are early
signs of nephropathy, the
patient with diabetes should have a target BP of 125/75 mm Hg or lower,
if tolerated. *
Hyperlipidemia is a common
comorbidity associated with
diabetes. For a given level of cholesterol, patients with
diabetes have a much greater
frequency of cardiovascular events; therefore, aggressive therapy
of diabetic dyslipidemia
is indicated. Goals:
LDL < 100 mg/dL
with vascular disease; LDL
< 130 mg/dL no vascular disease: HDL > 50 mg/dL;
triglycerides < 200 mg/dL. SCREENING
& DIAGNOSIS A
fasting plasma glucose (no food or beverage for
at least
8 hours prior to the test) remains the test of choice for diagnosing
diabetes mellitus. While glycosylated
hemoglobin (HbAlc) has proven to be a very valuable tool for
monitoring treatment, further
studies continue to discourage its use for screening or diagnosis. This
is due to both the lack
of standardization as well as poor reproducibility in healthy
adult populations. One meta-analysis
concluded that a HbAlc level of 7 % or higher (or > 1 %
above upper limit assay) has
sufficiently high sensitivity for identifying diabetes that requires
treatment. Unfortunately, at this
level, cases of impaired fasting glucose (IFG) or impaired glucose
tolerance (IGT), as well as
some cases of diabetes will be missed. The
prevalence of IGT and type 2 diabetes in women
with
polycystic ovarian syndrome (PCOS) is substantially higher than
expected when compared with
age and weight matched populations of women without PCOS. There is
also a higher conversion
from IGT or IFG to type 2 diabetes each year. It is estimated that 35%
of PCOS patients have
IGT, and 10% will be diagnosed with diabetes before reaching the fourth
decade. Therefore, this group
of women should be included as a high-risk group that is appropriate for
diabetes screening. Blood
pressure and lipids should be aggressively managed in this group. Recommendations
* Screening for type I diabetes, outside of a
research
environment, is not recommended. Community screening
in the general population for
type 2 diabetes is not recommended due to its low yield. * Screening of high-risk
groups for type 2 diabetes is
reasonable based on current evidence.
The major risk
factors for type 2 diabetes
are <>
Obesity
(>120% of desired body weight or a BMI
>27 kg/m) 0
<>A first degree
relative with diabetes <>
African-American, Hispanic, Native American, Pacific
Islander <>
Delivery of a
baby > 9 pounds or a previousdiagnosis
of gestational diabetes <>
Hypertension
(³140/90
mm Hg) <>
HDL-C
£ 35 mg/dL
or a triglyceride >250mg/dL <> History of
impaired glucose tolerance (IGT) or
impaired fasting glucose (IFG) <> Women with
polycystic ovarian syndrome (PCOS) The
available data are currently insufficient to
make
an evidence-based recommendation concerning optimal screening
intervals among high-risk
groups; however, it is the consensus
of the Diabetes Guidelines
Team that annual screening
by fasting blood glucose level of patients with a history of
gestational diabetes, IGT,
and PCOS should be done. For
additional information on screening and
diagnosis,
see pages 5-6 in the Kaiser Permanente Northern California Clinical
Practice Guidelines for
the Management of Diabetes Mellitus,
April 1998.
MANAGEMENT OF TYPE 2 DIABETES Glycemic Control The
United Kingdom Prospective Diabetes Study
(UKPDS)
evaluated 3867 patients with newly diagnosed type 2
diabetes over 10 years. Tighter
glucose control with insulin, metformin or sulfonylureas was
compared to conventional
treatment. Average HbAlc over 10 years was 7% in the
intensively treated group and
7.9% in the conventionally treated group.
Despite this minimal
difference, there were fewer microvascular
complications and a trend towards
reduced macrovascular
diabetes complications
in the intensively treated patients. HIGHLIGHTS
OF THE UKPDS *Type
2 diabetes is
progressive and additional oral medication
and/or insulin are likely needed
to maintain adequate
glycemic control. *No
advantage or disadvantage was observed with
any particular
agent in attaining glycemic
control. * Obese patients taking metformin had
fewer diabetes-related
complications along with less weight gain and fewer
hypoglycemic episodes. Mortality
and stroke in these
obese patients were decreased
in the intensive therapy group who received metformin. For
these reasons, it is the
consensus of the Diabetes Guideline Team that metformin
is the drug of choice in most
overweight type 2 diabetes patients without
contraindications (e.g., heart failure, renal
or hepatic insufficiency, or hypoxic states).
*
Even small decreases in average blood glucose
resulted
in decreased microvascular complications.
GLYCEMIC CONTROL MEASURES
The recommendation of the
Diabetes Guideline Team is
that the therapeutic goal for glycemic control is < 7.0% (see
table below) based on the results
of the UKPDS and the recommendation of the American Diabetes
Association. However, at this
point, this value differs from the goals set for glycemic control using the
Quality Indicators for
the APC Population Management Diabetes Management Program and for
HEDIS. The Quality Indicators
for the APC Diabetes Management Program measures good control
as HbAlc < 8.0 and fair
control as HbAlc < 10.0% (in 2001, HbAlc <
9.5%). In contrast, HEDIS
does not have a measure for good glycemic control, but does set a
measure for poorly controlled
diabetes as HbAlc of >9.5%. CLINICAL
CONSIDERATIONS
*
After a new drug is initiated or when the dosage of
a medication is adjusted, follow up (e.g.,
by telephone appointment visit [TAV]) with the
patient. Ask about glycemic control and
hvpoglycemic symptoms. *
Consider one of the following if glycemic
control is
suboptimal or unstable before concluding that drug therapy
has failed: <>
Occult
infections (e.g., urinary tract infections) <> New onset
endocrinopathy (e.g., hyper- or hypothyroidism,
Cushing's Syndrome, adrenal
insufficiency) <>
Overeating to
compensate for hypoglycemia <>
Dosing
intervals and dosages may need adjusting
regularly, using self-monitoring of blood glucose as well as
symptom monitoring. *
When adding an insulin sensitizer (e.g.,
metformin or
thiazolidinediones), watch for hypoglycemia. Reducing the
dose of insulin or sulfonylurea
is a desired effect of adding the insulin sensitizers.
Warning patients of hypoglycemia
and having an action plan can improve compliance. SELF-MONITORING
OF BLOOD GLUCOSE (SMBG) Frequency
and timing of SMBG
in Type I and Type 2 patients
should be a collaborative decision between the provider
and the patient, based
on the patient's individual needs, intensity of management and goals of
treatment plan to help patient
adjust therapy. The
frequency of testing should be adjusted to
both motivate
patients and enhance their glycemic
control and
lifestyle. Patients who do not adjust
their insulin dosage based on their blood glucose readings may not
benefit from as frequent
testing. Suggested minimal frequency and timing of SMBG in
diabetes
can be viewed online in the Regional
Diabetes Mellitus CPG
section on the Kaiser
Permanente Northern California intranet website at http://cl.kp.org
IMMUNIZATIONS INFLUENZA - all patients with
diabetes should be immunized
for influenza annually, if no contraindications exist. PNEUMOCOCCAL VACCINE - current
CDC recommendations are *All
people with
diabetes above the age of two
should be immunized with pneumococcal vaccine. * Revaccinate patients
³
65 years of age, if the person received his/her first vaccination
before age 65 and if more than
5 years have elapsed since
the first dose.
 MEDICATION
FOOTNOTES
'Sulfonylureas Sulfonylurcas
remain a cost
effective and successful
treatment for many Type 2 diabetes patients. The UKPDS has
alienated concerns about long-term
cardiovascular safety. Sulfonylureas have been used in combination
therapies with synergistic
effects on blood glucose lowering. 2Biguanides
Metformin
(Glucophage®)
continues to be the only drug in this class currently available in the
United States. A subgroup of
overweight diabetes patients
in the UKPDS treated with metformin had fewer macrovascular
complications, and its use was associated
with less weight gain and fewer hypoglycemic attacks. For
these reasons, it is the consensus
of the Diabetes Guideline Team that metformin is the drug of
choice in most overweight Type
2 diabetes patients without contraindications
(e.g., heart
failure, renal or hepatic
insufficient or hypoxic states). 3Insulin
Protocols for insulin
adiustment can be viewed online
in the Regional Diabetes Mellitus CPG section on the Kaiser
Permanente Northern California
intranet website at http://cl.kp.org Lispro
insulin (Humalog®)
is designed for very rapid release and shorter duration of action. This
insulin can be useful in
multi-dose regimens to provide
more intensive control of blood sugar with less hypoglycemia. 4Thiazolidinediones
Two new medications in this
class have recently been
released in the United States - rosiglitazone (Avandia®,
non-formulary) and pioglitazone (Actos®).
Both appear to have a better safety profile than troglitazone
(Rezulin®,
non-formulary), with similar effectiveness. The new
medications currently require
bimonthly monitoring of
liver function for the first year, and periodic monitoring
thereafter. Rosiglitazone is dosed
at 4 and 8 mg daily, while pioglitazone is dosed at 15,30, and 43 mg
daily. It may take 4 - 6 weeks
before a glycemic effect is seen. Expect some weight gain and volume
expansion with these medications.
Allow one week "washout" when switching from troglitazone to
the newer medications. 5Alpha-Glucosidase
Inhibitors Two preparations
are currently
available in the United
States - acarbose (Precose®,
non- formulary)
and miglitol
(Glyset®).
The two medications are similar in action, effectiveness,
and side effects. However,
miglitol has near-complete
absorption after oral doses, and is excreted unchanged in the
urine. In clinical trials,
miglitol was not associated with elevations in
serum transaminase levels.
Unlike acarbose, routine monitoring
of liver enzymes is not recommended
with miglitol
therapy. Although there has
been some suggestion for avoidance of miglitol in renal
insufficiency, no systemic toxicity
has been demonstrated. However, avoid using miglitol or acarbose if serum
creatinine > 2.0 mg/dL.
There are more drug interactions with miglitol than with acarbose.
The consensus of the Guideline
Team is that these drugs should not be used as first-line therapy.
They should be considered
for the subgroup of patients with high postprandial glucose levels.
6Repaglinide
(non-formulary) Repaglinide
(Prandin®)
lowers blood glucose levels by stimulating the release of insulin from
the pancreas in patients with
Type 2 diabetes. Repaglinide
is taken before meals to lower the postprandial increase in blood
glucose. The consensus
of the Guideline Team is that this drug should not to be used as first
line therapy. It should
be considered for the subgroup of patients with
high postprandial glucose
levels or those who have genuine
sulfonylurea allergies. Medication
tables can be viewed online in the
Regional
Diabetes Mellitus CPG section on the Kaiser Permanente Northern
California intranet website
at http://cl.kp.org PREVENTION AND
TREATMENT OF COMPLICATIONS
Beneficial Effects of ACE Inhibitors ACE
inhibitors decrease
mortality in post-MI patients
and heart failure patients. Retinopathy
and nephropathy
may be delayed. Recent evidence
in the HOPE study suggests
that the ACE
inhibitor, ramipril, has beneficial
effects on cardiovascular endpoints
in patients with
diabetes who are over the
age of 55. Current evidence is still insufficient to recommend
universal use of these agents
in patients with diabetes. Hypertension Blood pressure
control reduces macrovascular and microvascular
morbidity and
mortality in patients with diabetes.
Hypertension
markedly increases the risk of
macrovascular
complications (MI, stroke, and
peripheral vascular
disease) and microvascular complications
(retinopathy and
nephropathy) in patients
with diabetes. Prompt and
continuous control of blood pressure
decreases the risk of
these complications. The
target blood pressure should
be < 130/85 mm
Hg for all patients with diabetes
mellitus. If there are early signs of nephropathy
(albumin/creatinine ratio > 30 mcg/mg
Cr), the patient with diabetes
should have a target
BP of 125/75 mm Hg or lower,
if tolerated. In
the Hypertension Optimal Treatment (HOT) study,
patients
were randomized to one
of three groups (diastolic
BP <80 or <85or<90mmHg).
A long-acting calcium
channel blocker was
used as initial therapy:
beta-blockers, ACE inhibitors and diuretics were added as
needed. Cardiovascular events
and mortality were decreased
with lower blood
pressure in patients with
diabetes, with further improvements
in patients with
target diastolic blood
pressure < 80 mm Hg. Decreases
in cardiovascular
events and mortality were
proportional to reductions in diastolic blood pressure.
The
United Kingdom Prospective Diabetes Study
(UKPDS)
showed that tight control of BP (144/82) with either
captopril or atenolol reduced
the risk of heart failure by 56%, stroke by 44%, and death
from diabetes by 32% compared
to patients with BP 154/87.
The risk of renal
damage and progression of retinopathy
also was decreased
by improved BP
control. Previous studies (SHEP
and HDS) had shown improvements
in outcome with
diuretics as first-line
treatment. With reduction of macrovascular and microvascular
complications
of Type 2 diabetes as the goal,
it appears that lowering the
blood pressure is more important than the
choice of antihypertensive medication
used. For
additional
information on the treatment of hypertension
in patients with diabetes, see pages 28 - 29 in the
Kaiser Permanente Northern California
Clinical Practice Guidelines for the
Management of Diabetes Mellitus,
April 1998 and page 5 in the Kaiser Permanente Northern
California Clinical Practice Guideline
for Screening, Evaluation and Management of
Adult Hypertension, January-1999. Lipids Hyperlipidemia is a
common comorbidity associated
with diabetes. For a given level of cholesterol,
patients with diabetes have a much
greater frequency of cardiovascular events: therefore,
aggressive therapy of diabetic
dyslipidemia is indicated. A common abnormal lipid
pattern in Type 2 diabetes is
increased triglyceride/very-low-density lipoprotein (VLDL), decreased
HDL, and an LDL fraction
that contains a greater proportion
of small, dense
atherogenic LDL particles.
Initial therapy for all diabetes patients, regardless of lipid
levels, should include
a low-fat, low-cholesterol diet, regular physical activity, and
optimal glycemic control. Initial
drug therapy for the majority of people
with
diabetes and hyperlipidemia is a HMG CoA
reductase inhibitor [e.g., lovastatin
(Mevacor®), simvastatin
(Zocor®)].
Higher doses or combination therapy may be needed to achieve goals.
With these changes,
additional monitoring for side
effects (e.g., rhabdomyolysis) is needed. Drug
therapy should be directed first at lowering
LDL.
For diabetes patients with pre- existing vascular disease, the
goal is to
reduceLDL to < 100 mg/dL. For diabetes
patients without
known vascular disease, the goal
for LDL is < 130
mg/dL. Some experts recommend
that all patients with diabetes have an LDL < 100
because of their risk for increased
cardiovascular events, especially those with additional risk
factors such as tobacco use,
hypertension, or microalbuminuria.
Further
reductions of LDL below 100
lead to reduction of atherosclerotic
plaque.
Isolated low HDLs (< 50) also
should be treated aggressively. For
additional information on the treatment of
hyperlipidemia
in diabetes, see pages 30 - 31
in the Kaiser Pemianente
Northern California Clinical
Practice Guidelines for the
Management of Diabetes
Mellitus, April 1998. and
page 12 in the Kaiser Permanente Northern California Clinical
Practice Guidelines for
Adult Cholesterol Management,
November 1998. Peripheral
Neuropathy Control of pain in
diabetic
peripheral neuropathy continues
to be challenging. A recent
randomized control
trial showed that gabapenlin
(Neurontin®) (titrated
from 900 to 3600
mg/day or maximum
tolerated dosage) appeared
to be efficacious. Limiting side
effects included
dizziness, somnolence, abdominal
pain, and memory loss. Gabapentin
is not FDA approved
for this use. A
separate Veterans Administration Hospital study
concluded
that gabapentin may be an alternative
for treating
diabetic peripheral neuropathy
pain, yet does not appear to offer considerable advantage
over amitriptyline and is
more expensive. Autonomic
Neuropathy
GASTROINTESTINAL MANIFESTATIONS Dietary
modifications include
reductions in fat (<40
gm) and fiber. Four to six small meals are recommended. The use
of agents that may slow
gastric emptying such as calcium
channel blockers,
tricyclic antidepressants,
anticholinergic agents should
be minimized.
Optimization of glucose control
will further improve gastric motility. Prokinetic
agents include erythromycin,
metoclopromide,
or cisapride. Intravenous metoclopramide
(Reglan®)
10 mg IV qid for up to 10 days or erythromycin (3 mg/kg
IV q8 hours) may be used for
patients who cannot tolerate
oral medications. Cisapride
(Propulsid®)
10-20 mg po may be used 30 minutes before each meal and at
bedtime. Important changes
have been made in the cisapride
labeling. These changes
include
recommendations for performing diagnostic
tests prior to any use of cisapride. There have been
continuing reports of heart
rhythm disorders and deaths associated
mostly in people
who are either taking certain
other medications or who have
certain underlying
conditions that are known risk
factors. Review the new information
prior to starting
cisapride. Domperidone
remains investigational. MALE
IMPOTENCE |