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FAMILY PRACTICE BOARD REVIEW MANUAL
PUBLISHING STAFF
PRESIDENT, PUBLISHER
Type 2 Diabetes Mellitus
Bruce M.White
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Debra Dreger
SENIOR EDITOR
Miranda J. Hughes, PhD
EDITOR
Series Editor and Contributing Author:
Miriam T. Vincent, MD
Associate Professor, Interim Chair, Department of Family Medicine,
State University of New York, Health Science Center at Brooklyn,
Brooklyn, NY
Becky Krumm
ASSISTANT EDITOR
Contributing Author: Daisy A. Arce G., MD
Barclay Cunningham
Clinical Assistant Instructor, Department of Family Medicine,
State University of New York, Health Science Center at Brooklyn,
Brooklyn, NY
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Melissa Frederick
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Table of Contents
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NOTE FROM THE PUBLISHER:
This publication has been developed without involvement of or review by the
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endorses HOSPITAL PHYSICIAN for the purpose of presenting the latest developments in
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Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Case Presentation. . . . . . . . . . . . . . . . . . . . . . . . 2
Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Complications. . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Ambulatory Care Monitoring . . . . . . . . . . . . . . 10
Board Review Questions . . . . . . . . . . . . . . . . . 11
Answers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Suggested Readings . . . . . . . . . . . . . . . . . . . . . 12
Cover Illustration by Vanessa Ray
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Family Practice Volume 3, Part 1 1
®
FAMILY PRACTICE BOARD REVIEW MANUAL
Type 2 Diabetes Mellitus
Series Editor and Contributing Author:
Miriam T. Vincent, MD
Contributing Author:
Daisy A. Arce G., MD
Interim Chair
Department of Family Medicine
State University of New York
Health Science Center at Brooklyn
Brooklyn, NY
Clinical Assistant Instructor
Department of Family Medicine
State University of New York
Health Science Center at Brooklyn
Brooklyn, NY
I. INTRODUCTION
Diabetes mellitus is a syndrome of metabolic disorders
characterized by hyperglycemia that results from an absolute or a functional deficiency of insulin. In addition to
hyperglycemia, this syndrome includes abnormalities of
carbohydrate, lipid, and protein metabolism. Acute complications of diabetes include diabetic ketoacidosis, hyperosmolar coma, and hypoglycemia. Chronic complications
include microvascular disease (retinopathy, neuropathy,
and nephropathy) and macrovascular disease (coronary
artery, cerebrovascular, and peripheral vascular).
Diabetes mellitus is a chronic and pervasive disease
that is increasing in prevalence. By the year 2000, 20 million people in the United States will have a form of diabetes mellitus.1 By the year 2010, the number of people
with diabetes worldwide will double.1 The increased
prevalence of diabetes mellitus in the United States stems
largely from an increase in type 2 diabetes, which is a
result of an aging population, an increasing prevalence
of obesity, and a more sedentary population. In the
United States, it has been estimated that $100 billion, or
1 out of every 7 health care dollars, is spent on patients
with diabetes.1
Diabetes mellitus is classified on the basis of pathogenesis, and most cases fall into 1 of 4 categories (Table 1).2
Type 1 diabetes mellitus represents 5% to 10% of the diabetic population in the United States. It usually has an
2 Hospital Physician Board Review Manual
acute onset and is characterized by poorly functioning or
nonfunctioning pancreatic beta cells, leading to hypoinsulinemia and resultant hyperglycemia and acidosis.
Most diabetics (90% to 95%) have type 2 diabetes mellitus. Type 2 disease is a heterogeneous disorder that
develops gradually. It is characterized by decreased insulin
sensitivity, defective beta cell insulin secretion, and increased glucose output by the liver. Insulin resistance in
type 2 disease is thought to precede insulin secretory deficiency. Early stages of the disease (ie, during the first
10 years) are often characterized by hyperinsulinemia. It
has recently been understood that many patients with
type 2 disease, especially those with long-standing disease,
have decreased beta cell function together with insulin
insensitivity. The prevalence of type 2 diabetes has not
been well evaluated.
II. CASE PRESENTATION
A 38-year-old African-American woman who has
been a patient of yours for many years calls your office
with complaints of vaginal itching and burning, dysuria,
and urinary frequency for the previous 18 hours. She
has polycystic ovarian disease and visits your office periodically for ongoing evaluation of her condition. She
states that she cannot wait until her next appointment
to be evaluated because of her severe discomfort. She
denies sexual promiscuity, use of steroids, pelvic pain,
Type 2 Diabetes Mellitus
and vaginal discharge. She admits to polyuria, polydipsia, occasional dizziness, and generalized weakness.
On physical examination, she is pleasant, and her
vital signs are stable. She is 5 ft 3 in tall and weighs 167 lb,
reflecting a loss of 23 lb since her last visit 2 months ago.
Her family history is significant for a mother with asthma, chronic obstructive pulmonary disease, and diabetes. The patient does not smoke cigarettes or use alcohol or other drugs. Her HEENT (head, ears, eyes, nose,
throat) examination is unremarkable except for mild
oral mucosal dryness. There are no skin lesions present.
Neurologically, she has decreased sensation to soft touch
in both feet. She now admits to intermittent numbness
and tingling in both her hands and feet for the past
3 weeks. On pelvic examination, you note a scant white,
cheesy vaginal discharge with accompanying urethral
and vaginal erythema and no exudate. On wet mount,
results of microscopic evaluation of the discharge are
positive for budding yeast on potassium hydroxide preparation and negative for Trichomonas vaginalis on normal saline evaluation. There are 2 to 3 leukocytes per
high-power field with a paucity of lactobacilli.
Vaginal cultures are sent for bacterial evaluation (including gonorrhea and chlamydia) and fungal evaluation. Blood and urine samples are collected for laboratory analysis, and urine is sent for culture. Complete
blood count is within normal limits, and blood chemistry analysis reveals a plasma glucose level of 463 mg/dL
(not a fasting sample); low-density lipoprotein (LDL)
cholesterol, 158 mg/dL; blood urea nitrogen,
17 mg/dL; and creatinine, 0.9 mg/dL. Results of liver
function tests are within normal parameters. Serum levels of magnesium, phosphates, calcium, and all other
electrolytes fall within normal parameters. Urinalysis is
+4 for glucose and +1 for protein and blood. Candida is
noted to be present in the urine.
III. DIAGNOSIS
• What is the diagnosis for the case patient?
• Should the case patient’s adolescent daughter be
screened for diabetes?
DIAGNOSTIC CRITERIA
Diabetes Mellitus
Diagnostic criteria for diabetes mellitus, which have
recently been revised,2 are presented in Table 2. In general, a diagnosis of diabetes is made when the fasting
serum glucose level is greater than 126 mg/dL or
2-hour postprandial levels exceed 200 mg/dL.
Table 1. American Diabetes Association Etiologic
Classification of Diabetes Mellitus
Type 1 diabetes
Autoimmune
Idiopathic
Type 2 diabetes
Other specific types with known causes*
Gestational diabetes mellitus
*For example, genetic defects, endocrinopathies, infection, chemical
exposure.
Based on American Diabetes Association: clinical practice recommendations 1999. Diabetes Care 1999; 22(suppl 1): S1–S114.
The patient presented in the case study meets the
first set of criteria listed in Table 2 and is diagnosed with
type 2 diabetes.
Impaired Glucose Tolerance
Patients whose serum glucose levels are elevated but
are below the levels required for a diagnosis of diabetes
are considered to have impaired glucose tolerance
(IGT). These patients have insulin resistance with an
increased compensatory beta cell hyperfunction and
hyperinsulinemia. Relatively normal glucose levels are
maintained in this population by the increased production of insulin by the pancreas. With no intervention
and the continuation of dietary indiscretion and sedentary lifestyle, beta cells cannot continue to compensate
for the increased insulin required, and overt type 2 diabetes mellitus will develop.
SCREENING OF AT-RISK PATIENTS
Risk factors for developing type 2 diabetes mellitus
are listed in Table 3. Patients with the risk factors indicated should be screened with a fasting glucose test
annually. Patients without risk factors should be
screened at age 45 years, and if blood glucose levels
are normal, testing should be repeated at 3-year intervals.
IV. TREATMENT
• What will be your initial approach to the treatment of
the case patient?
• Does the fact that the case patient has coexistent polycystic ovarian disease affect the treatment approach?
Family Practice Volume 3, Part 1 3
Type 2 Diabetes Mellitus
Table 2. American Diabetes Association Diagnostic Criteria
for Diabetes Mellitus and Impaired Glucose Tolerance
Table 3. Risk Factors for Development of Type 2
Diabetes Mellitus
Diagnosis
Obesity
Criteria
Diabetes mellitus* 1. Symptoms of diabetes plus casual†
PG concentration ≥ 200 mg/dL or
African-American, Native American, Hispanic,
Asian-American, or Pacific Islander ethnicity
2. Fasting PG ≥ 126 mg/dL or
Age > 45 years
3. Two-hour PG ≥ 200 mg/dL during an
oral glucose tolerance test
In women, a history of gestational diabetes or of having
delivered a baby weighing more than 9 lbs
Impaired glucose
tolerance
Two-hour PG ≥ 140 mg/dL and < 200 mg/dL
Truncal obesity
Impaired fasting
glucose
Fasting PG ≥ 110 mg/dL and < 126 mg/dL
Family history of diabetes mellitus type 2
PG = plasma glucose.
*For the diagnosis of diabetes mellitus in the absence of unequivocal
hyperglycemia with acute metabolic decompensation, the criteria
should be confirmed by repeated testing on a different day.
†Casual is defined as any time of day without regard to time since the
last meal.
Based on American Diabetes Association: Report of the expert committee on the diagnosis and classification of diabetes mellitus. In Clinical
Practice Recommendations 1999. Diabetes Care 1999;22(suppl 1):S5–S19.
GOALS OF TREATMENT
The major goals of treatment in patients with type 2
diabetes mellitus are presented in Table 4. Intensive
therapy geared toward maintaining normal glycemic
control has been demonstrated to reduce the risk of
long-term microvascular complications of diabetes mellitus by 50% to 70%.3
COMPONENTS OF A TREATMENT PLAN
The optimal treatment plan is one that is individualized and effective. It should take into consideration the
patient’s age, socioeconomic status, family, home support, and access to health care. Coexisting medical conditions, especially those that add to the complications of
diabetes, must be managed in an integrative manner
with a goal of not further increasing insulin resistance
(eg, avoiding treatment of hypertension with diuretics
and of hyperlipidemia with niacin). The acute complications of diabetes must be avoided, detected early, and
minimized (see Section V.). A recommended sequence
of interventions for obese, early diagnosed patients with
type 2 diabetes mellitus (eg, the case patient presented)
is shown in Figure 1.
Patient education and nutritional counseling are
integral components of the treatment plan. A team
4 Hospital Physician Board Review Manual
Sedentary lifestyle
Hypertension (blood pressure ≥ 140/90 mm Hg)
Hyperlipidemia (HDL cholesterol level ≤ 35 mg/dL and/or
triglyceride level ≥ 250 mg/dL)
IFG or IGT
HDL = high-density lipoprotein; IFG = impaired fasting glucose; IGT =
impaired glucose tolerance.
Based on American Diabetes Association: Screening for type 2 diabetes. In
Clinical Practice Recommendations 1999. Diabetes Care 1999;22(suppl 1):
S20–S23.
approach involving the patient, the primary care provider, a dietitian, appropriate specialist(s), and, ideally, a
diabetes educator should be used. Self-monitoring of
blood glucose (SMBG) must be taught, reinforced, and
monitored. Reports of SMBG should be brought to
each visit. Patients and their families must be made
aware of the high and low glucose values that should
elicit concern and immediate evaluation or require
changes in treatment.
Patients should understand and be invested in the
achievement of short- and long-term goals. They should
take responsibility for the care of their disease and appropriately use the results of SMBG to adjust their nutritional intake and level of activity. Patients should know
the names and dosages of their medications and understand how they work. The importance of eye, foot, and
dental monitoring must be appreciated.
LIFESTYLE CHANGES
The initial therapy for type 2 diabetes mellitus includes nutritional therapy, exercise, and a program designed to encourage weight loss.
Weight Loss
Eighty percent to 90% of patients with type 2 diabetes mellitus are overweight.4 Weight loss in these
patients reduces the degree of elevation of glucose
Type 2 Diabetes Mellitus
Table 4. Goals of Treatment of Type 2 Diabetes Mellitus
Maintain normal glycemic control at all times*
Reduce weight to ideal body mass
Reduce low-density lipoprotein cholesterol level to
< 120 mg/dL
Normalize blood pressures (systolic < 130 mm Hg, diastolic
< 85 mm Hg)
Reduce hemoglobin A1C level to < 7.2%
Control associated risk factors for microvascular and
macrovascular disease without adversely affecting
glycemic control†
*Target serum glucose levels: postprandial, 100 to 120 mg/dL; preprandial, 80 to 120 mg/dL.
†Such risk factors include hypertension, hyperlipidemia, cigarette
smoking, and obesity.
Insulin
α-Glucosidase inhibitors
Insulin secretagogues
Insulin sensitizers
Diet, exercise, education, SMBG
Figure 1. Treatment plan for obese, early diagnosed patients
with type 2 diabetes mellitus. SMBG = self-monitoring of blood
glucose.
• Maintenance of blood glucose levels to as close
to normal as possible, by balancing food intake
with insulin or oral hypoglycemic medications
and physical activity
• Achievement of optimal serum lipid levels
hepatic output, increases peripheral insulin sensitivity,
and improves insulin secretion. Even a weight loss of
10 to 20 lb has been demonstrated to improve
glycemic control.4 Every 2 lb of weight loss in the diabetic patient results in an increase of 3 to 4 months in
life expectancy.5
Exercise
In patients with type 2 diabetes, regular exercise
(20 minutes, 4 times weekly) increases insulin sensitivity and may improve glycemic control, aid in weight loss,
and help to control hypertension and hyperlipidemia,
while providing an enhanced quality of life and sense of
control for patients. Studies indicate that a 6-week regimen of regular exercise has the potential to decrease
hemoglobin A1c levels by 1% to 1.5%.6
It is critical that exercise be prescribed with the evaluation and care that one uses in prescribing medication. Pre-exercise evaluation for hypertension, neuropathy, nephropathy, retinopathy, and silent ischemic
disease permits the physician to decide on an individualized, safe, and effective regimen. A “start low and go
slow” progressive approach has the greatest potential
for effectiveness without adverse effects.
Nutritional Therapy
Medical nutritional therapy (MNT) for patients with
diabetes should be individualized, with consideration
given to usual eating habits and other lifestyle factors.
The overall goal of MNT is to assist people with diabetes
in making changes in nutrition and exercise habits
leading to improved metabolic control. Additional
goals include the following:
• Provision of adequate calories for maintaining
reasonable weights for adults
• Prevention and treatment of the acute and
chronic complications of diabetes
• Improvement of overall health through optimal
nutrition
A moderate caloric restriction (250 to 500 calories
less than the average daily intake, as calculated from a
food history) and a nutritionally adequate meal plan
with a reduction of total fat, especially saturated fat,
accompanied by an increase in physical activity should
be recommended. Recommended protein intake is
approximately 10% to 20% of daily caloric intake for
people with diabetes, but with onset of nephropathy
lower intakes of protein should be considered.
PHARMACOLOGIC TREATMENT
Weight loss and exercise form the foundation of therapy for type 2 diabetes mellitus; however, fewer than 10%
of patients will be able to maintain long-term goals of
glycemic control with nonpharmacologic therapy alone.
Medication should be viewed as a supplement to, and not
a substitute for, diet and exercise. The pharmacologic therapies presented here may be used alone or in combination to achieve the treatment goals previously described.
Insulin Sensitizers
Insulin sensitizers (eg, metformin, troglitazone) improve insulin sensitivity and are a first-line pharmacologic treatment for type 2 disease. Metformin acts primarily
on the liver to reduce hepatic glucose output, with secondary effects on skeletal muscle. Metformin is not a
Family Practice Volume 3, Part 1 5
Type 2 Diabetes Mellitus
hypoglycemic agent but rather an antihyperinsulinemic
agent. It is the ideal agent for the treatment of type 2 diabetes in a patient with polycystic ovarian disease.7 It carries a risk of lactic acidosis and must not be administered
to patients with renal dysfunction, hepatic dysfunction,
alcoholism, acute cardiovascular collapse (eg, myocardial
infarction, septicemia), or who require diagnostic evaluation necessitating iodinated contrast. Metformin also
helps reduce serum lipid levels and promotes weight loss.
Troglitazone acts primarily on adipose tissue and skeletal muscle to increase glucose uptake by binding to peroxisome proliferator–activated receptors, resulting in the
stimulation of insulin-sensitizing enzymes. Troglitazone
has beneficial effects on serum lipid levels (ie, decreases
triglycerides, increases high-density lipoprotein [HDL]
cholesterol).8 Liver function tests must be monitored
closely and regularly in patients receiving troglitazone
because it can cause hepatic dysfunction and, rarely,
severe hepatotoxicity.
Insulin Secretagogues
Insulin secretagogues (eg, sulfonylureas, repaglinide)
are hypoglycemic agents that act directly on beta cells,
binding to a receptor on the cell surface and stimulating
the production of insulin. Repaglinide stimulates the first
phase of insulin secretion (short burst; most effective for
postprandial hyperglycemia). Sulfonylureas stimulate the
second (sustained) phase of insulin secretion. Currently,
40% of patients with type 2 diabetes mellitus use sulfonylureas to treat their condition.9
Patients likely to respond to sulfonylureas include
those diagnosed with type 2 diabetes mellitus within the
past 5 years, patients who are older than 40 years at diagnosis, obese patients (body mass index > 30 kg/m2),
and patients with poor glycemic control who are already using diet and exercise. Hypoglycemia and
weight gain are the major side effects of sulfonylureas.
All of these agents undergo hepatic metabolism and
must be used cautiously in patients with hepatic disease.
α-Glucosidase Inhibitors
α-Glucosidase inhibitors (eg, acarbose) reduce postprandial hyperglycemia by reversibly inhibiting αglucosidase enzymes located in the brush border of the
small intestine, resulting in delayed carbohydrate absorption and reduced postprandial serum glucose. Gastrointestinal side effects of these agents include abdominal discomfort and bloating. They should not be prescribed for
patients with inflammatory bowel disease.
Insulin
Insulin remains the mainstay of therapy, with 61% of
6 Hospital Physician Board Review Manual
patients with type 2 disease taking insulin.10 This therapy
may accelerate the progression of macrovascular complications if the patient is already hyperinsulinemic and can
result in weight gain and increase the risk of hypoglycemia.
TREATMENT OF CASE PATIENT
The ideal treatment plan is the one that works for the
patient. The patient described in this case is referred to
a dietitian for nutritional counseling and is given guidance regarding exercise, foot care, and SMBG. She is
referred for an electrocardiogram prior to initiating a
new exercise regimen.
The best pharmacologic agent to treat the case patient, who has polycystic ovarian disease concomitant
with type 2 diabetes mellitus, would be metformin. The
patient is put on metformin but experiences intolerable
gastrointestinal side effects and is switched to troglitazone. Over the following 6 months, her hemoglobin A1C
drops from 11% to 6.8% with diet, exercise, and troglitazone, and her LDL cholesterol level drops to 98 mg/dL.
V. COMPLICATIONS
ACUTE COMPLICATIONS
Acute complications of diabetes mellitus include diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic
nonketotic syndrome (HHNKS), and severe or frequent
hypoglycemia. DKA and HHNKS represent decompensation in diabetic control and require immediate treatment. Intravenous insulin is usually required for treatment of both conditions. The primary care provider
should refer all suspected cases of DKA or HHNKS for
emergency department evaluation and treatment.
Diabetic Ketoacidosis
DKA is a medical emergency. Although it is usually
associated with type 1 diabetes, DKA does occur rarely
in patients with type 2 disease. DKA should be suspected in adolescent patients and in any patient with type 1
diabetes who withholds insulin.
Symptoms most commonly seen in patients with
DKA include polyuria, polydipsia, and vomiting with or
without abdominal pain and weakness. DKA is manifested clinically by severe dehydration and alterations in
the sensorium. Coma and changes in mental status may
occur. Laboratory testing reveals hyperglycemia (serum
glucose level generally greater than 300 mg/dL), leukocytosis, hypertriglyceridemia, and anion gap acidosis. A
serum pH of 7.25 or lower and the presence of serum
ketones are typical criteria for diagnosis of DKA.11
Type 2 Diabetes Mellitus
The patient should be carefully evaluated for associated or precipitating events (eg, infection, medications,
vascular events), and associated problems must be treated appropriately.
Hyperosmolar Hyperglycemic Nonketotic Syndrome
HHNKS occurs predominantly in patients with type 2
diabetes. Laboratory testing reveals hyperglycemia
(serum glucose levels often exceed 600 mg/dL), the
absence of serum ketones, and dehydration, as evidenced by weight loss and, often, azotemia. As with DKA,
coma and changes in mental status can occur.
Etiology includes infection, stress (eg, myocardial
infarction, trauma), reduction or omission of diabetic
medications, administration of drugs with hyperglycemic effects (eg, phenytoin, diazoxide, diuretics, steroids), and new or previously unrecognized diabetes
(30%).
Severe or Frequent Hypoglycemia
A variety of conditions may increase the risk of hypoglycemia in diabetic patients. Patients with autonomic
neuropathy or who are taking β-blockers may have
hypoglycemic unawareness. Delayed gastric emptying
(gastroparesis) and extensive gastrointestinal surgery
can increase the risk of hypoglycemia by changing the
absorption of nutrients from the gut. Pancreatic damage interferes with glucagon production, thus preventing the body’s efforts at counterregulation in response
to low blood sugar levels. Hypoglycemia may also result
from insulin dose errors, as an adverse reaction to sulfonylurea, or from other drug-related effects. It may
also be associated with excessive alcohol intake.
Hypoglycemia may be a consequence of the therapeutic regimen and always requires evaluation of both
the management plan and its execution by the patient.
Family members and close associates of the patient who
uses insulin should be taught to use glucagon. Patients
should be instructed to keep a record of whenever a
hypoglycemic event occurs, including time of occurrence, relation to meals or snacks, exercise, sleep, and
the last medication dosage and amount taken.11
CHRONIC COMPLICATIONS
Although macrovascular complications result in
most excess mortality among patients with diabetes, the
microvascular complications of diabetes are considerable in terms of incidence, cost, and patient disability. A
number of recent studies have found that most diabetic complications are the result of prolonged hyperglycemia. Good glycemic control is the most powerful
tool we have to prevent the complications of diabetes.
Microvascular Disease
Diabetes is a leading cause of blindness, renal failure,
and peripheral neuropathy. The Diabetes Control and
Complications Trial (DCCT) followed 1441 patients
with type 1 diabetes for 9 years3 and the Kumamoto
study followed 110 Japanese patients with type 2 diabetes for 6 years.12 Both studies established that
improved glycemic control reduces the risk of microvascular complications.
Retinopathy. Retinopathy is one of the earliest signs
of the effects of sustained hyperglycemia on the microvasculature. Vision-threatening retinopathy virtually
never appears in type 1 patients in the first 3 to 5 years
of diabetes or before puberty. Over the subsequent
2 decades, however, nearly all patients with type 1 disease
develop retinopathy. It has recently been found that up
to 21% of patients with type 2 diabetes have retinopathy
at the time that their diabetes is diagnosed.13
The retinal complications of diabetes are best detected by indirect ophthalmoscopic examination through
dilated pupils. (The early stages of retinopathy are
detectable through undilated pupils in only approximately 50% of cases.) Currently, the American Diabetes
Association (ADA) recommends annual dilated eye
examinations by an ophthalmologist or licensed
optometrist skilled in assessing the retinas of diabetic
patients.14
In general, the progression of retinopathy is orderly.
It initially consists of mild, nonproliferative abnormalities characterized by increased vascular permeability
manifested by retinal microaneurysms, occasional blot
hemorrhages, and a few cotton-wool spots. It progresses to moderate and severe nonproliferative diabetic
retinopathy, characterized by vascular closure manifested by venous beading, significant areas of large retinal
blot hemorrhages, and multiple cotton-wool spots. The
last stage, proliferative diabetic retinopathy, is characterized by the growth of blood vessels on the retina and
posterior surface of the vitreous body; this is followed by
fibrous tissue proliferation and retinal traction, tears, or
detachment. Treatment options for diabetic retinopathy are listed in Table 5.
Nephropathy. Diabetes has become the most common single cause of end-stage renal disease (ESRD) in
the United States and Europe. The earliest clinical evidence of nephropathy is microalbuminuria (ie, low but
abnormal levels of albumin in the urine [> 30 mg/day or
20 µg/min]). Without any specific intervention, 80% of
subjects with type 1 diabetes progress to the stage of overt
nephropathy or clinical albuminuria (> 300 mg/day
or ~ 200 µg/min) over a period of 10 to 15 years, with
hypertension developing concurrently. In patients with
Family Practice Volume 3, Part 1 7
Type 2 Diabetes Mellitus
Table 5. Initial Treatment Options for Diabetic
Retinopathy
Table 6. Clinical Manifestations of Diabetic Neuropathy
Peripheral sensory neuropathy
Retinal Complication
Usual Initial Treatment
“Pins and needles” in extremities
High-risk proliferative
retinopathy
Scatter (panretinal)
photocoagulation
Loss of sensation
Macular edema
Focal laser photocoagulation
Autonomic neuropathy
Vitreous hemorrhage
Observation or vitrectomy
Bladder and bowel dysfunction
Retinal detachment
Vitrectomy
Impotence
Reduced ability to feel pain
Gastroparesis
Constipation and diarrhea, often occurring alternately
type 2 diabetes, microalbuminuria occurs at an earlier
point following diagnosis than in type 1 diabetes and may
even be present at diagnosis. This may be because diabetes has gone undetected for several years or because of
the concomitant presence of hypertension, which hastens progression of nephropathy. Without specific interventions, 20% to 40% of type 2 diabetes patients with
microalbuminuria progress to overt nephropathy and
20% to ESRD.15
In addition to being the earliest manifestation of
nephropathy, albuminuria is a marker of greatly increased
cardiovascular morbidity and mortality for patients with
either type 1 or type 2 diabetes. Microalbuminuria is an
indication to screen for possible vascular disease and to
apply an aggressive interventional strategy to reduce all
cardiovascular risk factors.
The ADA recommends annual screening for microalbuminuria in diabetic patients, which can be performed by any 1 of 3 methods:15
(1) Measurement of the albumin-to-creatinine
ratio in a random spot collection
(2) 24-hour collection with creatinine, allowing
the simultaneous measurement of creatinine
clearance
(3) Timed (eg, 4-hour or overnight) collection
Diabetic retinopathy almost always precedes the
development of microalbuminuria. If microalbuminuria is detected, a dilated eye examination should be
performed as soon as possible. If there is no evidence of
retinopathy, other causes of microalbuminuria should
be suspected.
The DCCT Research Group (1993)3 showed that optimal control of blood glucose levels can prevent or delay
progression of nephropathy in type 1 diabetes. Alzaid16
reported that in type 2 disease, higher levels of glucose
and glycohemoglobin are most strongly associated with
microalbuminuria. Control of hypertension will also
slow the rate of development of both nephropathy and
8 Hospital Physician Board Review Manual
Change in blood pressure, including hypotension
retinopathy. In patients with diabetes, maintaining
blood pressure as close to 120/80 mm Hg as possible is
ideal; keeping pressure below 130/85 mm Hg is recommended.
Angiotensin-converting enzyme (ACE) inhibitors
have been shown to have renal protective effects independent of their action in lowering blood pressure.
ACE inhibitors reduce microalbuminuria and proteinuria and delay or retard diabetic nephropathy in normotensive or hypertensive people with diabetes. ACE
inhibitors have been shown to decrease progression
from microalbuminuria to clinical proteinuria in patients with hypertension and type 2 diabetes.17 The
drugs have no activity detrimental to glycemic control
or lipid profile and can improve insulin sensitivity. The
most common side effect of ACE inhibitors is cough;
secondary side effects include angioedema, hyperkalemia, rash, loss of taste, and leukopenia. These drugs
are contraindicated in women of childbearing age. The
new angiotensin II receptor blockers, which do not
cause cough, are being studied in humans with regard
to renal protective effects.
α-Blockers, calcium channel antagonists, and diuretics in low doses can also be used to control blood pressure in hypertensive diabetic patients because these
agents have few adverse effects on glucose homeostasis
and renal function.
High protein intake increases the glomerular filtration rate and renal workload, thereby aggravating proteinuria. A low-protein diet is often recommended for
patients with diabetes and nephropathy.
Neuropathy. Allen et al18 reported that nerves degenerate in the presence of persistent hyperglycemia,
with findings in both motor conduction and peripheral
sensory pathways. Clinical manifestations of neuropathy
in diabetics are listed in Table 6.
Type 2 Diabetes Mellitus
Table 7. Components of the Initial Evaluation of
Patients with Type 2 Diabetes Mellitus
Table 8. Components of Management Plan for
Patients with Type 2 Diabetes Mellitus
Medical history
Short- and long-term goals
Symptoms, laboratory results related to diagnosis
Medications
Prior glycohemoglobin records
Medical nutrition therapy
Nutritional assessment, weight history
Lifestyle changes
Previous and present treatment plans
Self-management education
Current treatment of diabetes
Monitoring instructions
Exercise history and medical nutrition therapy
Annual referral to ophthalmologist
Acute complications
History of infections
Chronic diabetic complications
Consultation for podiatry services (as indicated)
Specialty consultations (as indicated)
Agreement on continuing support/follow-up
Other medications that may affect blood glucose levels
Risk factors for atherosclerosis (eg, smoking, hypertension,
obesity, dyslipidemia)
Family history
Gestational history
Psychosocial/economic factors
Physical examination
Height and weight
Sexual maturation (if peripubertal)
Blood pressure
Ophthalmoscopic examination
Oral examination, include dentition
Thyroid palpation
Cardiac examination
Abdominal examination
Evaluation of pulses
Hand/finger examination
Foot examination
Skin examination
Neurologic examination
Laboratory evaluation
Fasting plasma glucose level (optional)
Glycohemoglobin level
Fasting lipid profile
Serum creatinine level
Urinalysis
Urine culture (if indicated)
Thyroid function tests (if indicated)
Electrocardiogram (adults)
Peripheral neuropathy is common in diabetes; patients should be instructed to regularly examine their
feet for dryness, calluses, corns, ulcers, and deformities.
A monofilament wand has been developed to test point
sensation in the feet. The filament delivers a standardized 10-g force when touched to specific areas of the
foot. Patients who cannot sense pressure from the filament have lost protective sensation and are at increased
risk of developing foot ulcers. Family physicians must
include a careful examination of the feet at each visit
for diabetic patients.
Macrovascular Complications
Macrovascular complications include cardiovascular,
cerebrovascular, and peripheral vascular diseases.
These complications are strongly associated with the
hyperinsulinemia secondary to insulin resistance.
Coronary artery disease is the most prevalent of the
macrovascular complications of diabetes. Its incidence is
55% in adults with type 2 disease, compared with 2% to
4% in persons without diabetes. The risk of death from
coronary artery disease is 6-fold greater in men with diabetes and 4-fold greater in women with diabetes compared with the general population.19 A Danish study 20 reported that stroke was 4 to 10 times more common,
amputation 20 times as common, and peripheral vascular
disease 2 to 6 times more common among persons with
diabetes.
Chronic hyperglycemia results in the modification of
proteins by the nonenzymatic addition of glucose, which
leads to the formation of advanced glycosylation end
products that have been shown to play a major role in the
development of both microvascular and macrovascular
complications of diabetes. Insulin-mediated biochemical
pathways lead to enhanced vascular smooth muscle proliferation, platelet adhesiveness, and vasoconstriction, all
Family Practice Volume 3, Part 1 9
Type 2 Diabetes Mellitus
Table 9. Components of Routine Follow-up Visits for
Patients with Type 2 Diabetes Mellitus*
Table 10. Components of Annual Follow-up Visits for
Patients with Type 2 Diabetes Mellitus*
Physical examination
Physical examination
Weight
Comprehensive examination (see Table 7)
Blood pressure
Dilated eye examination
Foot examination
Laboratory evaluation
Evaluation of abnormalities found on previous examinations
Fasting lipid profile
Laboratory evaluation
Urinalysis for protein
Glycohemoglobin (hemoglobin A1c)
Urine albumin level (if urinalysis for protein is negative)
Fasting plasma glucose (optional)
Fasting plasma glucose (optional)
History/assessment of treatment regimen
Evaluate patient’s knowledge of diabetes
Frequency and severity of hypo/hyperglycemia
Evaluate patient’s self-management skills
SMBG results
Medications
*Components listed should be performed in addition to the components of a routine follow-up visit (see Table 9).
Patient’s regimen adjustments
Adherence problems
Symptoms of complications
Other medical illnesses
Lifestyle changes
Psychosocial issues
Review of management plan
Short- and long-term goals
Blood glucose levels
Control of dyslipidemia
Blood pressure
Weight
Medical nutrition therapy
Exercise regimen
pulses, carotid bruits, electrocardiogram abnormalities)
requires efforts to correct contributing risk factors in addition to the specific treatment of the cardiovascular problem. Daily intake of aspirin has been shown to reduce cardiovascular events in patients with diabetes.
A number of trials have identified elevated levels of
LDL cholesterol and triglycerides and reduced levels of
HDL cholesterol as being predictive of macrovascular
complications for diabetic patients. According to the
National Cholesterol Education Program, patients with
diabetes, like those with established cardiovascular disease, should have a goal of reducing LDL cholesterol to
below 100 mg/dL.21
Adherence to self-management training
Follow-up of referrals
VI. AMBULATORY CARE MONITORING
Psychosocial adjustment
SMBG = self-monitoring of blood glucose.
*Routine follow-up visits should occur quarterly for patients who are
not meeting their goals and semiannually for other patients.
of which play a significant role in the development of
macrovascular complications in diabetes.
Risk factors for cardiovascular disease in patients with
type 2 diabetes include the duration of disease and the
development of increased urinary protein excretion
and/or retinopathy. Contributing risk factors include
obesity, smoking, hypertension, sedentary lifestyle, dyslipidemia, and poorly regulated diabetes. Evidence of cardiovascular disease (eg, angina, claudication, decreased
10 Hospital Physician Board Review Manual
The ADA has published specific guidelines for the
office management of diabetes and its complications.14
The goal should be to help the patient to develop an
individualized and effective self-management plan.
INITIAL OFFICE VISIT
The initial office visit of a patient with diabetes should
include a thorough history, physical examination, and
laboratory evaluation (Table 7). A management plan
should be discussed with the patient (Table 8).
FOLLOW-UP VISITS
Patients who are meeting their treatment goals should
have routine follow-up visits twice yearly, and those who
are not should be seen quarterly. The components of a
Type 2 Diabetes Mellitus
routine follow-up visit for a patient with diabetes are
shown in Table 9. A more comprehensive visit should
occur annually (Table 10).
In addition, patients who are beginning insulin treatment or whose insulin regimen has been changed
should be evaluated daily. Patients beginning or changing a regimen of oral glucose-lowering agent(s) should
be evaluated weekly.
5.
Which one of the following is the pharmacologic
treatment of choice for a female diabetic patient
with polycystic ovarian disease?
A) Repaglinide
B) Insulin
C) Metformin
D) Sulfonylurea
6.
The hemoglobin A1c level of a patient with diabetes
should be below which one of the following values
to reduce the risk of developing microvascular and
macrovascular complications?
A) 3.5%
B) 5%
C) 7.2%
D) 9%
E) 10%
7.
A 50-year-old white man with a history of type 2 diabetes mellitus and microalbuminuria is found to
have hypertension. Which one of the following
would be the preferred antihypertensive medication for this patient?
A) Captopril
B) Hydrochlorothiazide
C) Terazosin
D) Propranolol
E) Nifedipine
8.
All of the following are proven risk factors for cardiovascular disease in patients with type 2 diabetes
EXCEPT:
A) Development of peripheral neuropathy
B) Duration of diabetes
C) Increased urinary protein excretion
D) Development of retinopathy
E) Dyslipidemia
9.
In the management of diabetes mellitus, which of the
following low-density lipoprotein cholesterol levels is
an appropriate target for preventing macrovascular
complications?
A) < 200 mg/dL
B) < 160 mg/dL
C) < 130 mg/dL
D) < 120 mg/dL
BOARD REVIEW QUESTIONS
Choose the single best answer for each question.
1.
2.
3.
4.
Which one of the following is a diagnostic criterion
for diabetes according to the most recent guidelines of the American Diabetes Association (ADA)?
A) Fasting glucose level ≥ 140 mg/dL
B) Fasting glucose level ≥ 126 mg/dL
C) Fasting glucose level ≥ 110 mg/dL
C) Glucose level ≥ 126 mg/dL in a 2-hour oral
glucose tolerance test
E) Glucose level ≥ 140 mg/dL in a 2-hour oral
glucose tolerance test
The pathophysiology of type 2 diabetes is associated with all of the following factors EXCEPT:
A) Increase of insulin resistance
B) Decrease of serum insulin levels
C) Abnormal glucagon secretion
D) Decrease in beta cell mass, abnormal function
of beta cells, or both
E) Increase in glucose output by the liver
All of the following are effects of exercise in diabetic
patients EXCEPT:
A) Increased insulin levels
B) Increased insulin sensitivity
C) Improved glucose metabolism
D) Reduced hemoglobin A1c level
E) Heightened sense of well-being
Which one of the following statements regarding
sulfonylureas is correct?
A) They cannot be administered safely in conjunction with metformin
B) They cannot be administered safely during
pregnancy
C) They can cause severe hypoglycemia resulting
in altered mental status
D) They cannot be administered safely in conjunction with troglitazone or insulin
10. Annual evaluation of patients with type 2 diabetes,
as suggested by the ADA, includes all of the following EXCEPT:
A) Eye examination
B) Oral glucose tolerance test
C) Urinalysis for protein
D) Hemoglobin A1c level
E) Fasting lipid profile
Family Practice Volume 3, Part 1 11
Type 2 Diabetes Mellitus
lar complications in Japanese patients with non-insulindependent diabetes mellitus: a randomized prospective
6-year study. Diabetes Res Clin Pract 1995;28:103–117.
ANSWERS
1.
2.
3.
4.
5.
B
B
A
C
C
6.
7.
8.
9.
10.
C
A
A
D
B
REFERENCES
1. Rubin RJ, Altman WM, Mendelson DN: Health care
expenditures for people with diabetes mellitus, 1992.
J Clin Endocrinol Metab 1994;78:809A–809F.
2. American Diabetes Association: Report of the expert
committee on the diagnosis and classification of diabetes
mellitus. In Clinical Practice Recommendations 1999.
Diabetes Care 1999;22(suppl 1):S5–S19.
3. The Diabetes Control and Complications Trial Research
Group: The effect of intensive treatment of diabetes on
the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J
Med 1993;329:977–986.
4. Wing RR, Koeske R, Epstein LH, et al: Long-term effects
of modest weight loss in type II diabetic patients. Arch Int
Med 1987;147:1749–1753.
5. Williams G: Management of non–insulin-dependent diabetes mellitus. Lancet 1994;343:95–100.
6. Ruderman N, Apelian AZ, Schneider SH: Exercise in
therapy and prevention of type II diabetes: implication
for blacks. Diabetes Care 1990;13:1163–1168.
7. Bailey CJ, Turner RC: Metformin. N Engl J Med 1996;334:
574–579.
8. Petrie J, Small M, Connell J: “Glitazones,” a prospect for
non-insulin-dependent diabetes. Lancet 1997;349:70–71.
9. Tal A: Oral hypoglycemic agents in the treatment of type
II diabetes. Am Fam Physician 1993;48:1089–1095.
10. Lebovitz HE: Stepwise and combination drug therapy for
the treatment of NIDDM. Diabetes Care 1994;17:1542–1544.
11. Green-Hernandez C: Diabetes mellitus. In Primary Care.
Singleton JK, Sandowski S, Green-Hernandez C, et al,
eds. Philadelphia: Lippincott, 1999:195–223.
12. Ohkubo Y, Kishikawa H, Araki E, et al: Intensive insulin
therapy prevents the progression of diabetic microvascu-
13. American Diabetes Association: Diabetic retinopathy. In
Clinical Practice Recommendations 1999. Diabetes Care
1999;22(suppl 1):S70–S73.
14. American Diabetes Association: Standards of medical care
for patients with diabetes mellitus. In Clinical Practice
Recommendations 1999. Diabetes Care 1999;22(suppl 1):
S32–S41.
15. American Diabetes Association: Diabetic nephropathy.
In Clinical Practice Recommendations 1999. Diabetes
Care 1999;22(suppl 1):S66–S69.
16. Alzaid AA: Microalbuminuria in patients with NIDDM:
an overview. Diabetes Care 1996;19:79–89.
17. Lebovitz HE, Wiegmann TB, Cnaan A., et al: Renal protective effects of enalapril in hypertensive NIDDM: role of
baseline albuminuria. Kidney Int Suppl 1994;45:S150–S155.
18. Allen C, Shen G, Palta M, et al: Long-term hyperglycemia
is related to peripheral nerve changes at a diabetes duration of 4 years. The Wisconsin Diabetes Registry. Diabetes
Care 1997;20:1154–1158.
19. Sobel BE: Complications of diabetes: macrovascular disease. In Current Approaches to the Management of Type 2
Diabetes. Olefsky JM, ed. Secaucus, NJ: Professional Postgraduate Services, 1997.
20. Beck-Nielsen H, Damsgaard EM, Faber O, et al: Noninsulin-dependent diabetes mellitus: diagnosis and treatment. An interpretation [in Danish]. Ugeskr Laeger 1990;
152:2–10.
21. Florence JA, Yeager BF: Treatment of type 2 diabetes mellitus. Am Fam Physician 1999;59:2835–2844,2849–2850.
SUGGESTED READINGS
Haffner SM: Risk factors for non-insulin-dependent diabetes
mellitus. J Hypertens Suppl 1995;13:S73–S76.
Tan GH, Nelson RL: Pharmacologic treatment options for
non-insulin-dependent diabetes mellitus. Mayo Clin Proc 1996;
71:763–768.
White JR Jr: The pharmacologic management of patients with
type II diabetes mellitus in the era of new oral agents and insulin
analogs. Diabetes Spectrum 1996;9:227–234.
Copyright 1999 by Turner White Communications Inc., Wayne, PA. All rights reserved.
12 Hospital Physician Board Review Manual