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DIABETES MELLITUS
Dara P. Schuster, MD, and Vani Duvuuri, MD

DEFINITION OF DIABETES MELLITUS

Diabetes mellitus is a group of metabolic diseases characterized by

hyperglycemia resulting from defects in insulin secretion, insulin action,
or both. The chronic hyperglycemia of diabetes mellitus is associated
with long-term damage, dysfunction, and failure of various organs espe-
cially the eyes, kidneys, nerves, heart, and blood vessels.4 This article
briefly reviews the definition, classification, diagnostic criteria, manage-
ment, and acute and chronic complications of diabetes mellitus.

INCIDENCE AND PREVALENCE

Based on the National Health Interview Survey (NHIS), in 1993

approximately 7.8 million people in United States had been diagnosed
with diabetes mellitus, of whom 90% to 95% seemed to have type 2
(non-insulin dependent) diabetes mellitus. Prevalence rates of type 2
diabetes were 1.3% between the ages of 18 to 44 years, 6.2% at age 45 to
64 years, and 10.4% at ages above 65 years. The number of cases of
type 1 (insulin-dependent) diabetes mellitus in the United States is
approximately 300,000 to 5000,000. Approximately 625,000 new cases of
diabetes mellitus are diagnosed annually in the United States.30

From the Division of Endocrinology, Department of Internal Medicine, The Ohio State
University, Columbus, Ohio

CLINICS IN PODIATRIC MEDICINE AND SURGERY

VOLUME 19 • NUMBER 1 • JANUARY 2002 79

80 SCHUSTER & DUVUURI

CLASSIFICATION AND DIAGNOSIS

The National Diabetes Data Group (NDDG) in the United States

developed the current diagnostic criteria and classification of diabetes
mellitus, which were published in 1979. Based upon these data and on
the rationale which was accepted in 1979, along with the research find-
ings of the past 18 years, the Expert Committee of the American Diabetic
Association has developed new criteria for the etiologic classification of
diabetes mellitus4:
Etiologic classification of diabetes mellitus
1. Type I diabetes (beta-cell destruction, usually leading to absolute
deficiency)
a. Immune-mediated
Classic autoimmune diabetes presenting with ketosis
Late autoimmune diabetes of adults (LADA)
b. Idiopathic
2. Type 2 diabetes (insulin resistance and relative insulin deficiency)
3. Other specific types
a. Genetic defects of beta-cell function
Maturity onset of diabetes of youth (MODY) types 1 to 5
Mitochondrial DNA mutation
b. Genetic defects in insulin action
Type A insulin resistance
Rabson-Mendenhall syndrome
Lipoatrophic diabetes
Others
c. Disease of exocrine pancreas
Pancreatitis
Trauma or pancreatectomy
Neoplasia
Cystic fibrosis
Hematochromatosis
Fibrocalculous pancreatopathy
Others
d. Endocrinopathies
Acromegaly
Cushing’s syndrome
Glucagonoma
Hyperthyroidism
Somatostatinoma
Aldosteronoma
Pheochromocytoma
Others
 DIABETES MELLITUS 81

e. Drug or chemically induced

Vacor
Pentamidine
Nicotinic acid
Glucocorticoids
Thyroid hormone
Diazoxide
Beta adrenergic agonists
Thiazides
Dilantin
Alfa-interferon
Others
f. Infections
Congenital rubella
Cytomegalo virus
Others
g. Uncommon forms of immune-mediated diabetes
Stiff man syndrome
Anti-insulin receptor antibodies
Others
h. Other genetic syndromes sometimes associated with diabetes
Down syndrome
Kliefelter’s syndrome
Turner syndrome
Wolfram’s syndrome
Friedreich’s ataxia
Huntington’s chorea
Laurece-Moon-Biedl syndrome
Mytonic dystrophy
Porphyria
Prader-Willi syndrome
Others
4. Gestational diabetes mellitus

TYPE 1 DIABETES MELLITUS

Type 1 diabetes mellitus results from cellular autoimmune beta-cell

destruction of the pancreas, leading to absolute insulin deficiency.7 Type
1 diabetes mellitus previously has been known as insulin-dependent
diabetes mellitus, juvenile-onset diabetes, ketosis-prone diabetes, and
brittle diabetes of youth. Type 1 diabetes mellitus most commonly occurs
in childhood, but it can occur at any age, even in the eighth and ninth
decades of life. The onset of type 1 diabetes mellitus is quite variable,
82 SCHUSTER & DUVUURI

usually rapid in infants and children and slow in adults. Some children
and adolescents may present with ketoacidosis as the first manifestation
of the disease, whereas others have modest fasting hyperglycemia that
can rapidly change to severe hyperglycemia and ketoacidosis in the
presence of infection or stress. Others, particularly adults, may retain
residual beta-cell function sufficient to prevent ketoacidosis for many
years.56 Many individuals with this form of type 1 diabetes mellitus
eventually become dependent on insulin for survival and are at risk of
ketoacidosis. At this latter stage, there is little or no insulin, as noted by
low or undetectable levels of C peptide. Although insulin secretion is
severely decreased in type 1 diabetes mellitus, short periods of normal
glucose homeostasis and insulin release may be seen in the type 1
diabetic patient shortly after diagnosis. This period is termed the honey-
moon phase and can occur for as long as 6 to 12 months after diagnosis.

Pathogenesis of Type 1 Diabetes Mellitus

Genetics of Type 1 Diabetes Mellitus

The lifelong risk of type 1 diabetes mellitus for a close relatives of
patients with type 1 diabetes mellitus averages 6% in offspring, 5% in
siblings, and 30% in identical twins. The risk of type 1 diabetes mellitus
for persons with no family history is 0.4%.7, 40, 36 A monozygotic twin of
a patient with type 1 diabetes mellitus is at higher risk than a dizygotic
twin, the risk for dizygotic twins of a patient with type 1 diabetes is
similar to that in other siblings.36 The major susceptibility locus for type
1 diabetes mellitus is on the short arm of chromosome 6 in the HLA
class II region. This locus provides 40% to 50% of the inheritable diabetic
risk.15, 22 The histocompatibility antigens most commonly associated with
type 1 diabetes mellitus are DR3, DR4, B8, and B15.22 The HLA alleles are
thought to be associated through linkage disequilibrium to the immune
response (or self-recognition) genes. In contrast, the DQA1*102,DQB1*-
602 heterodimer found on HLA-DR2 haplotypes confers dominant pro-
tection from the development of type 1 diabetes mellitus.

Environmental Factors
Viruses that have been implicated in the ultimate destruction of
beta cells in type 1 diabetes mellitus include cocksackie B, mumps, and
cytomegalovirus. Viruses can trigger beta-cell destruction by any of three
mechanisms: (1) direct cellular destruction, (2) generation of cytokines
that damage beta cells, or (3) molecular mimicry.42 Following beta-cell
injury in type 1 diabetes mellitus, an immune response is associated with
 DIABETES MELLITUS 83

the release of beta-cell antigens into the circulation with the subsequent
formation of islet-cell antibodies. The markers of the immune destruction
of the beta cell include islet-cell autoantibodies (ICA), autoantibodies to
insulin (IAA), autoantibodies to glutamic decarboxylase (GAD65), and
autoantibodies to tyrosinephosphatases (IA-2).6 Titers of these antibodies
predict the risk of type 1 diabetes mellitus and are present within first
year of onset. The antibodies generally decrease in time (20% after 5
years). The cell-mediated immune response (killer T lymphocytes or NK
cells) may also be involved in the pathogenesis of type 1 diabetes
mellitus. Other autoimmune disorders such as Grave’s disease, Hashi-
moto’s thyroiditis, Addison’s disease, vitiligo, pernicious anemia, and
celiac disease have been associated with type 1 diabetes mellitus.22

TYPE 2 DIABETES MELLITUS

Type 2 diabetes mellitus (relative insulin deficiency or insulin resis-

tance) is also referred to as noninsulin-dependent diabetes mellitus or
adult-onset diabetes mellitus. Early insulin resistance and hyperinsuli-
nemia characterize type 2 diabetes mellitus in the prediabetic phase,
which is followed by subsequent failure of insulin secretion with resul-
tant hyperglycemia and overt diabetes mellitus.

Pathogenesis of Type 2 Diabetes Mellitus

Understanding the pathogenesis of type 2 diabetes mellitus is com-

plicated by several factors. Individuals may present with insulin resis-
tance, insulin deficiency, or a combination of both. The clinical features
can arise from genetic and environmental factors, making it difficult to
determine the exact cause in an individual patient.

Impaired Insulin Secretion and Insulin Resistance

It is uncertain whether insulin resistance causes insulin deficiency
or whether both are necessary to cause overt type 2 diabetes mellitus.33, 52
In most type 2 diabetic patients, insulin resistance precipitates a relative
insulin deficiency, which then leads to hyperglycemia. In a normal
individual who develops insulin resistance, insulin secretion is appropri-
ately increased to overcome the insulin resistance, and normal glucose
metabolism is maintained. In individuals with the genetic predisposition
to develop type 2 diabetes mellitus, both insulin resistance and impaired
insulin secretion contribute to the development of hyperglycemia. A
small percentage of type 2 diabetics have no insulin resistance and have
84 SCHUSTER & DUVUURI

a marked beta-cell deficiency. In contrast, some type 2 diabetics have

severe insulin resistance and only a minor deficiency in insulin secretion.

Impaired Insulin Processing

In normal individuals, insulin is produced from cleavage of proinsu-
lin. Ten percent to 15% of the insulin secreted is proinsulin. The pro-
cessing of proinsulin to insulin in the beta cells is impaired in type 2
diabetics. The percentage of proinsulin is elevated to 40% in patients
with the type 2 diabetes mellitus.41

Role of Islet Amyloid Polypeptide

Islet amyloid polypeptide is stored in insulin-secreting granules in
the pancreatic beta cells. It is cosecreted with insulin, resulting in serum
concentration of insulin/islet amyloid peptide of about 1/10 and is
increased in patients with type 2 diabetes mellitus. A high concentration
of amylin decreases glucose uptake and inhibits endogenous insulin
secretion; this finding suggests that amylin may be involved directly in
the pathogenesis of type 2 diabetes mellitus.28 The causative role of
amylin in type 2 diabetes mellitus is unclear, and there is no apparent
association between the amylin gene and type 2 diabetes mellitus.

Impaired Hepatic Glucose Production

The maintenance of normal glucose tolerance after glucose ingestion
depends on the following mechanisms16:
• stimulation of insulin by hyperglycemia
• suppression of hepatic glucose production by the resultant hyper-
insulinemia and hyperglycemia
• stimulation of glucose uptake by peripheral tissues, primarily by
muscle, in response to hyperinsulinemia and hyperglycemia
In type 2 diabetics with established fasting hyperglycemia above
140 mg/dL, there is excessive hepatic glucose production even though
insulin levels are increased by two- to four-fold. Recent studies have
shown that accelerated gluconeogenesis is the major abnormality respon-
sible for the increased rate of basal hepatic glucose production.16

Genetics of Type 2 Diabetes Mellitus

The genetic predisposition for type 2 diabetes is stronger than that
for type 1 diabetes mellitus.36 The genetics of type 2 diabetes mellitus
are complex, however, and are not clearly defined. The risk of type 2
 DIABETES MELLITUS 85

diabetes mellitus in a monozygotic twin of an affected person is 60% to

90%.8 The lifetime risk of type 2 diabetes mellitus for a first-degree
relative of a person with type 2 diabetes mellitus is 5 to 10 times higher
than for age- and weight-matched persons without a family history.
Thirty-nine percent of patients with type 2 diabetes mellitus have at
least one parent with the disease.

Genetic Defects of Beta Cells

Maturity-onset diabetes mellitus of the young is characterized by
impaired insulin secretion and is associated with monogenetic defects in
beta-cell function. Three abnormal genetic loci have been identified on
different chromosomes. The most common is associated with mutations
on chromosome 12 in a hepatic transcription factor referred to as hepato-
cyte nuclear factor (HNF)–1␣.47 A second form, MODY 2, is associated
with mutations in the glucokinase gene on chromosome 7p. The defect
in the glucokinase gene requires increased plasma levels of glucose to
elicit normal levels of insulin secretion and results in a defective glucoki-
nase molecule.10

Genetic Defects in Insulin Action

The first step in insulin action involves binding of the hormone to
a specific insulin receptor that is present in many cells throughout the
body. In persons with type 2 diabetes, both the number of insulin
receptors on the cell surface and the binding affinity of insulin to its
receptor are diminished.40
There are five glucose transport units.17 The insulin-stimulated glu-
cose transporter (GLUT4) is in the muscle. The GLUT4 transporter is
inserted into the cell membrane and activated in response to insulin.
Glucose enters the cell and then is either phosphorylated into glucose-
6-phosphate by hexokinase and subsequently converted into glycogen
or is oxidized.
Multiple intracellular defects have been identified in type 2 diabetes
mellitus. The first intracellular defect is an inability of insulin to activate
the insulin receptor by stimulating tyrosine phosphorylation by the
insulin receptor. The ability of insulin to phosphorylate IRS-1 (insulin
recepter substrate-1) and PI-3 (insulin recepter substrate-1) kinase are
impaired. The defects in muscle glucose phosphorylation by hexokinase
11, glycogen synthase, and pyurvate dehydrogenase have been well
described in type 2 diabetes mellitus. Which of these intracellular defects
are primary and which are secondary to diabetes mellitus remains to be
elucidated.
86 SCHUSTER & DUVUURI

Environmental Factors
Role of Obesity. The mechanism by which obesity induces insulin
resistance is poorly understood, but a high concentration of plasma free
fatty acid and the pattern of fat distribution are important factors.
Plasma free fatty acids are high in obese patients. Increased plasma
concentrations of free fatty acid cause insulin resistance by decreasing
insulin-mediated glucose transport into the cell.12, 38 Most studies suggest
that visceral adiposity rather than subcutaneous or total adiposity is the
significant determinant of insulin resistance. Mutation of the gene for ␤-
3 adrenergic receptor is associated with obesity and type 2 diabetes
mellitus.53

GESTATIONAL DIABETES MELLITUS

Gestational diabetes mellitus (GDM) is defined as carbohydrate

intolerance of variable severity with onset or first recognition during the
current pregnancy. The overall prevalence of gestational diabetes melli-
tus in the United States is 2% to 5%.4

Screening for Gestational Diabetes Mellitus

It was previously recommended that screening for gestational diabe-

tes mellitus be performed in all pregnancies. This approach is not cost-
effective. Certain factors place women at low risk for the development
of glucose intolerance during pregnancy31:
• age less than 25 years
• normal body weight
• no first-degree relatives with diabetes
• no abnormal history of glucose metabolism or poor obstretic out-
come
• not a member of an ethnic or racial group with a high prevalence
of diabetes (Hispanic American, Native American, African-Ameri-
can, Pacific Islander)
Table 1 summarizes the criteria for the diagnosis of gestational diabetes
mellitus.4

NEW CRITERIA FOR DIAGNOSIS

OF DIABETES MELLITUS

The diagnostic criteria for diabetes mellitus are based upon the new
American Diabetes Association recommendations published in 1997.
 DIABETES MELLITUS 87

Table 1. CRITERIA FOR DIAGNOSIS OF GESTATIONAL DIABETES MELLITUS BASED

ON 100-GRAM OR 75-GRAM GLUCOSE LOAD

100-gram Glucose Load 75-gram Glucose Load

fasting 95 mg/dL 95 mg/dL
1 hour 180 mg/dL 180 mg/dL
2 hours 155 mg/dL 155 mg/dL
3 hours 140 mg/dL* —

*There are two criteria based on results of the 3 hour glucose tolerance test. According to the
participants of the Fourth International Workshop Conference on GDM, GDM is present if two or more
of the plasma glucose values are exceeded. These values are lower than those proposed by the NDDG
group, which used cutoff values of 105, 190, 160, and 145 mg/dL.
GDM  gestational diabetes mellitus; NDDG  National Diabetes Data Group

There are three ways to diagnose diabetes mellitus, and unless the
patient experiences unequivocal hyperglycemia with acute metabolic
decompensation, each must be confirmed on a subsequent day:
1. Symptoms of diabetes plus casual plasma glucose concentration
above 200 mg/dL (11.1 mmol/L). (Casual is defined as occurring
at any time of day, without regard to time elapsed since the
last meal. The classic symptoms of diabetes include polyuria,
polydipsia, and unexplained weight loss.)
or
2. Fasting plasma glucose (FPG) above 126 mg/dL (Fasting is de-
fined as no calorie intake for at least 8 hours.)
or
3. 2-hour plasma glucose above 200 mg/dL (11.1 mmol/L) during
an oral glucose tolerance test (OGTT). The test should be per-
formed in accordance with World Health Organization (WHO)
criteria using a glucose load containing the equivalent of 75 g
of anhydrous glucose dissolved in water. This measure is not
recommended for routine clinical use.
These criteria for the diagnosis of diabetes mellitus with fasting
plasma sugars above 126 mg/dL are based on epidemiologic studies.
The long-term prospective studies demonstrate that 10% to 15% of
individuals with fasting plasma glucose levels above 126 mg/dL de-
velop diabetic retinopathy within 10 years.

Other Definitions

The Expert Committee of the American Diabetes Association (ADA)

recognizes an intermediate group of persons who do not meet the
criteria for diabetes mellitus but whose glucose levels are too high to be
88 SCHUSTER & DUVUURI

Table 2. DIAGNOSTIC CRITERIA FOR INTERMEDIATE GROUPS–ADA

RECOMMENDATIONS, 1997

2-Hour Plasma Glucose

FPG (mg/dL) (mg/dL)
Normal glucose tolerance ⬍ 110 ⬍ 140
Impaired fasting plasma glucose 110–125 —
Impaired glucose tolerance 140–199
Diabetes mellitus ⬎ 126 ⬎ 200

ADA  American Diabetes Association; FPG  fasting plasma glucose

considered normal. Table 2 summarizes the diagnostic criteria for the

intermediate groups.4

SCREENING CRITERIA FOR TESTING FOR DIABETES

MELLITUS IN ASYMPTOMATIC, UNDIAGNOSED
INDIVIDUALS: RECOMMENDATIONS OF THE
AMERICAN DIABETES ASSOCIATION

Testing for diabetes mellitus should be considered in all individuals

at age 45 years and above. If results are normal, testing should be
repeated at 3-year intervals.4 Testing should be considered at a younger
age or be carried out more frequently in individuals who
• are obese (who weigh more than 120% of their desirable body
weight or have a body mass index (BMI) above 27 kg/m2)
• have a first-degree relative with diabetes mellitus
• are members of a high-risk ethnic population (e.g., African-Ameri-
can, Hispanic American, Native american, Asian American, Pacific
Islander)
• have delivered a baby weighing more than 9 pounds or have been
diagnosed with gestational diabetes mellitus
• are hypertensive (blood pressure above 140/90 mm Hg)
• have a high-density lipoprotein (HDL) cholesterol level above 35
mg/dL and triglyceride levels above 250 mg/dL
• on previous testing had IGT OR IFG

Fasting plasma glucose or an oral glucose tolerance test (OGTT)

may be used for diagnosis of diabetes mellitus, but fasting plasma
glucose levels are greatly preferred in the clinical setting because of their
convenience, lower cost, acceptability, and ease of administration.
 DIABETES MELLITUS 89

MANAGEMENT OF DIABETES MELLITUS

Diabetes mellitus is a chronic illness that requires continuing medi-

cal care and education to prevent acute complications and to reduce the
risk of long-term complications. Diabetes mellitus care should be pro-
vided by a physician-coordinated team that includes physicians, nurses,
dietitians, and mental health professionals with expertise and a special
interest in diabetes mellitus. As summarized in Table 3, lowering blood
glucose to normal or nearly normal levels has proven benefits for pa-
tients with diabetes mellitus.5
• The decompensation caused by diabetic ketoacidosis or hyperos-
molar hyperglycemic nonketotic syndrome and associated mor-
bidity and mortality are reduced markedly.
• The symptoms of blurred vision and the risk of polyuria, polydip-
sia, fatigue, weight loss with polyphagia, and vaginitis may be
decreased.
• The risks of development or progression of diabetic retinopathy,
nephropathy, and neuropathy all are greatly decreased.
• Near-normalization of blood glucose level has been associated
with a less-atherogenic lipid profile.

Specific Goals of Treatment

Type 1 Diabetes Mellitus

The glycemic target goals are based on prospective, randomized
clinical trials, most notably the Diabetes Control and Complications Trial
(DCCT).43 This trial demonstrated, in patients with type 1 diabetes
mellitus, a 50% to 70% reduction in the risk of development or progres-
sion of retinopathy, nephropathy, and neuropathy by intensive treatment
regimens when compared with conventional treatment regimens.17

Table 3. EFFECT OF GOOD GLYCEMIC CONTROL ON INCIDENCE OF

COMPLICATIONS IN PATIENTS WITH DIABETES

DCCT UKPDS
HbA1c reduction 9%–7% 8%–7%
Retinopathy 63% 17–21%
Nephropathy 63% 24–33%
Neuropathy 54% —
Macrovascular disease — 16%

HbA1c  hemoglobin A1c ; DCCT  Diabetes Control and Complications Trial; UKPDS  United
Kingdom Prospective Diabetes Study
90 SCHUSTER & DUVUURI

Achieving nearly normal glucose levels with intensive insulin treat-

ment to prevent complications requires15
• frequent self-monitoring of blood glucose (SMBG) (at least 3 to 4
times/day)
• medical nutrition therapy
• patient education in self-management and problem solving
Other factors that may increase the risk or decrease the benefit of
intensive treatment are advanced cardiovascular disease or cerebrovas-
cular disease, advanced age, and coexisting disease that shortens life
expectancy.

Type 2 Diabetes Mellitus

The goals of glycemic control in type 2 diabetes mellitus are the
same as those for type 1 diabetes mellitus, whether treated with insulin,
hypoglycemic agents, or both, as outlined in Table 4. In type 2 diabetes
mellitus, the United Kingdom Prospective Study (UKPDS) has shown a
relationship between hyperglycemia and microvascular disease similar
to that shown in the DCCT trials in type 1 diabetes mellitus. Analysis
of the UKPDS data has shown45–48 that
• Improved blood glucose control is associated with reduced risk
of developing retinopathy, nephropathy, and possibly reduced
neuropathy.
• The overall microvascular complication rate was decreased by
25% in patients receiving intensive therapy versus conventional
therapy.
• There is a continuous relationship between the risk of microvascu-
lar complications and glycemia: for every percentage-point de-
crease in hemoglobin A1C (HbA1C) there is a 35% reduction in
microvascular complications.

Table 4. GOALS OF GLYCEMIC CONTROL FOR PEOPLE WITH DIABETES

Glucose Values (mg/dL) Normal Goal Action Suggested

Whole Blood
Preprandial glucose ⬍100 80–120 ⬍80/⬎140
Bedtime glucose ⬍110 100–140 ⬍100/160
Plasma Values
Preprandial glucose ⬍110 90–130 ⬍90/⬎150
Bedtime glucose ⬍120 110–150 ⬍110/⬎180
HbA1c (%) ⬍6 ⬍7 ⬎8

HbA1c  hemoglobin A1c

 DIABETES MELLITUS 91

• Aggressive control of blood pressure, consistent with ADA recom-

mendations, significantly reduces strokes, diabetes-related deaths,
heart failure, microvascular complications, and visual loss.

Treatment of type 2 diabetes mellitus should emphasize manage-

ment of multiple risk factors. Such treatment should include medical
nutrition therapy, exercise, weight reduction when indicated, and use of
oral glucose-lowering agents or insulin. Attention should be given to
cardiovascular risk factors, including hypertension, smoking, dyslipide-
mia, and family history.5

History and Physical Examination

The history should include symptoms of hyperglycemia, nutrition

history, exercise history, frequency and severity of acute complications
(e.g., diabetic ketoacidosis (DKA), nonketotic hyphosmolar coma
[NKHS]), symptoms of chronic complications, family history of diabetes
mellitus, risk factors for atherosclerosis, smoking, hypertension, hyper-
lipidemia, and so forth.5
The physical examination should focus on detection of complica-
tions of diabetes mellitus that affect eye, nerve, kidney, foot, skin, car-
diac, and vascular systems.

Laboratory Evaluation

The following tests should be performed to determine the degree of

glycemic control and to define associated complications and risk factors:
FPG, HbA1C, fasting lipids profile, total cholesterol, HDL cholesterol,
low-density lipoprotein (LDL) cholesterol, and triglyceride levels. The
urinalysis should be examined for glucose, protein, ketones, and sedi-
ment, and urine culture should be performed if sediment is abnormal
or symptoms are present. The serum creatinine level should be followed
in adults and in children if proteinuria is present. A test should be
performed for microalbuminuria (timed-specimen or the albumin/creati-
nine ratio) in pubertal and postpubertal patients with type 1 diabetes
mellitus who have had diabetes for at least 5 years and in all patients
with type 2 diabetes mellitus. Thyroid-stimulating hormone should be
checked in all type 1 patients on a yearly basis, and adults should have
a baseline electrocardiogram.5
92 SCHUSTER & DUVUURI

Health Maintenance

Health-maintenance measures recommended by the ADA5 for dia-

betic patients are for comprehensive annual dilated eye and visual
examinations by an ophthalmologist or optometrist for all patients aged
10 years and older who have had diabetes mellitus for 3 to 5 years, for
all patients diagnosed after age 30 years, and for any patient with visual
symptoms or abnormalities
• dental hygiene
• influenza vaccination annually; pneumococcal vaccination
• foot examination in patients at risk at least once a year to identify
high-risk conditions. This examination should include an assess-
ment of protective sensation, foot structure, biomechanics, vascu-
lar status, and skin integrity. Persons with neuropathy should
have visual inspection of their feet at every contact with a health
care professional.
• quarterly HbA1C evaluation if treatment changes or the patient is
not meeting goals; twice-yearly evaluation if stable
• fasting lipid profile annually
• urinalysis for protein annually
• microalbumin measurement annually (if urinalysis is negative for
protein)
Treatment regimens of diabetes mellitus include diet, exercise, and
oral glucose-lowering agents or insulin

Diet

A proper diet is a fundamental element of therapy in all patients

with diabetes mellitus. Adherence to nutrition therapy is one of the most
challenging aspects of diabetes care. The reasons include complexity of
dietary instructions and poor understanding of the dietary control by
the physician and the patient. Because of the complexity of nutritional
issues, it is recommended that a registered dietitian who is knowledge-
able and skilled in implementing the diabetic’s medical nutrition therapy
be the team member providing nutrition care and education. Today
there is no single diabetic or ADA diet. The recommended diet can only
be defined as a nutrition prescription based on assessment and treatment
goals and outcomes.2

Nutrition Therapy and Type 1 Diabetes Mellitus

A meal plan based on an individual’s food intake should be deter-
mined and used as the basis for integrating insulin therapy into the
 DIABETES MELLITUS 93

usual eating and exercise patterns. Individuals using insulin therapy

should eat at consistent times synchronized with the action-time of the
insulin preparation used. Intensified therapy involving multiple daily
injections or continuous subcutaneous insulin infusion (CSII) allows
more flexibility in the timing of meals and snacks and in the amount of
food eaten.

Nutrition Therapy and Type 2 Diabetes Mellitus

The primary medical nutrition therapy goals for individuals with
type 2 diabetes mellitus are to achieve and maintain glucose, lipid, and
blood pressure target goals. Hypocaloric diets and weight loss usually
improve short-term glycemic levels and have the potential to improve
long-term metabolic control. Traditional dietary strategies and even low-
calorie diets cannot achieve long-term weight loss, however. The reason
is unclear.
A moderate caloric restriction (200–500 calories less than the average
daily intake) and nutritionally adequate meal plans with a reduction of
total fat (especially saturated fat), accompanied by an increase in physi-
cal activity, should be recommended. A hypocaloric diet, independent
of weight loss, is associated with increased sensitivity to insulin and
improvement of blood glucose levels. A moderate weight loss of 5 to 9
kg, irrespective of starting weight, has been shown to reduce hyperglyce-
mia, dyslipidemia, and hypertension.
Spacing of meals (spreading nutrient and particularly carbohydrate
intake) throughout the day is another strategy that can be adopted. Oral
glucose-lowering agents or insulin may be added to medical nutrition
therapy if metabolic control has not improved.

Protein
Protein requirements for people with diabetes mellitus are the same
as for the general population, that is, 10% to 20% of daily caloric intake.
With the onset of overt nephropathy, a lower intake of protein (0.8 g/
kg/day) should be considered. It has been suggested that once the
glomerular filtration rate begins to fall, further restriction to 0.6 kg/day
may prove useful in slowing the decline.26

Total Fat
For people with diabetes mellitus, 25% to 30% of total calories
should be contributed by fat. The distribution of calories from fat and
carbohydrate can vary and can be individualized based on the nutrition
94 SCHUSTER & DUVUURI

assessment and treatment goals. Cholesterol intake should be less than

300 mg, and less than 10% of total calories should be from saturated fat.

Fiber
Daily consumption of a diet containing 20 to 35 g of soluble and
insoluble dietary fiber from a wide variety of food sources is recom-
mended.

Alcohol
The ADA dietary guidelines recommend no more than two drinks/
day for men and no more than one drink/day for women.2 The effect of
alcohol on blood glucose levels depends on the amount of alcohol
ingested and on the relationship to food intake. Alcohol is not metabo-
lized to glucose and inhibits gluconeogenesis; therefore, if persons
treated with insulin or oral glucose-lowering agents consume alcohol
without food, hypoglycemia can result. Hypoglycemia can occur at
blood alcohol levels that do not exceed mild intoxication.

Exercise

Exercise improves insulin sensitivity, lowers blood glucose levels,

reduces cardiovascular morbidity, and may prevent the development of
type 2 diabetes mellitus in high-risk groups.50, 51, 57 For type 1 diabetes,
exercise, although necessary and beneficial, can be somewhat problem-
atic. The counter-regulatory hormonal adaptations are lost in patients
with type 1 diabetes mellitus. As a consequence, when such individuals
have too little insulin in circulation because of inadequate therapy, an
excessive release of counterregulatory hormones may aggravate already
high levels of glucose and ketones and can even precipitate ketoacidosis.
The presence of high levels of insulin caused by exogenous insulin
administration can attenuate or prevent the mobilization of glucose and
other substrates induced by exercise. As a result, hypoglycemia may
ensue. In patients with type 2 diabetes mellitus treated with an oral
hypoglycemic drug, exercise tends to lower blood glucose concentration.
This effect may depend on the timing of the patient’s meal. Hypoglyce-
mia tends to be less of a problem in patients with type 2 diabetes
mellitus.1

Recommendations
Regular exercise is likely to be beneficial in most diabetics, even in
those with advanced, long-standing disease. The patient needs to be
 DIABETES MELLITUS 95

enthusiastic and realistic. For those over 35 years of age, with diabetes
duration of more than 10 years, any risk factor for coronary artery
disease, the presence of microvascular disease, or peripheral vascular
disease requires a complete physical examination and exercise stress test
before beginning an exercise program.1

Prevention of Type 2 Diabetes Mellitus

Preliminary studies have shown that physical activity of moderate

intensity reduces the incidence of new cases of type 2 diabetes mellitus
and the progression to overt type 2 diabetes mellitus. This finding led
to the hypothesis that exercise may be useful in preventing or delaying
the onset of type 2 diabetes mellitus. The National Institutes of Health
is currently sponsoring a large, prospective, multicenter trial in the
United States to clarify the feasibility of this approach.37, 44, 50

Oral Glucose-Lowering Agents

Pharmacologic treatment with oral agents is indicated in patients

with type 2 diabetes mellitus when diet and exercise fail to achieve
acceptable glycemic control (HbA1C ⬎ 7%). Five classes of oral diabetic
agents currently are approved for the treatment of type 2 diabetes
mellitus in the United States. The goal of therapy is to reduce the HbA1C
to less than 7%. Combination therapy in type 2 diabetes mellitus is
indicated when plasma glucose levels are in excess of 180 to 200mg/dL
and response with monotherapy is inadequate after 4 to 8 weeks.39
Table 5 illustrates the mechanism of action, dosing schedule, and
side effects of the antidiabetic drugs.

Indications for Insulin Therapy

Insulin is indicated for

• patients with type 1 diabetes mellitus
• patients with long-standing type 2 diabetes mellitus when combi-
nations of two different classes of oral agents fail to achieve
glycemic goals
• pregnant patients
• treating acute complications of diabetes mellitus, DKA, and NKHS
96

Table 5. ORAL GLUCOSE-LOWERING AGENTS

Effects on
Glycemia
Units
Mechanism Dose Range (mg/day) FPG앗 HbA1c앗% Side Effects
Insulin Secretagogues (Close KATP Channel in Beta Cell)
Sulfonylureas
Glipizide (Glucotrol, Stimulates pancreatic insulin 5 to 20 before meals once 50–75 1.5–2.5 Hypoglycemia
Glucotrol XL ) secretion or twice a day
Glyburide (DiaBeta, Stimulates pancreatic insulin 1.25 to 20 (0.75 to 12 for Hypoglycemia
Micronase, Glynase) secretion Glynase only) with
meals once daily b.i.d.
or t.i.d.
Glimepiride (Amaryl) Stimulates pancreatic insulin 1 to 4 (maximum 8) once Hypoglycemia
secretion, increases tissue daily with meal
sensitivity to insulin
Meglitinides
Repaglinide (Prandin) Increases pancreatic insulin 1.5 to 12 (maximum 16) 50–78 1.5–2.5 Hypoglycemia
secretion and requires taken only with meals
presence of glucose for its (no more than 30 min
action before first bite), t.i.d.
or q.i.d.
Nateglinide (Starlix) Increases pancreatic insulin
secretion and requires
presence of glucose for its
action
 a-Glucosidase Inhibitors (Delay Digestion and Absorption of Complex Carbohydrates)
Acarbose (Precose) Delays glucose absorption 75 to 150 (maximum 300) 20–30 0.5–1 Elevated serum transaminases (AST or ALT),
by inhibiting pancreatic a- with first bite of each flatuence, diarrhea, abdominal pain, may
glucosidase enzymes meal, t.i.d. increase the hypoglycemic potential of
sulfonylureas
Miglitol (Glyset) Delays glucose absorption 150 to 300
(Bayer Corporation, by inhibiting pancreatic a-
West Haven, CT) glucosidase enzymes
Biguanides (Insulin Sensitizers)
Metformin Decreases hepatic glucose 1000 to 2500 with meals, 50–75 1.5–2.5 Lactic acidosis, diarrhea, nausea, vomiting,
(Glucophage) production, increases b.i.d. or t.i.d. abdominal bloating, anorexia
(Bristol–Mayers Squibb, peripheral glucose uptake WARNING: Contraindicated in patients with
Princeton, NJ) and use renal insufficiency (creatinine ⱖ 1.5 if
male, ⱖ 1.4 if female)
Thiazolidinediones (Insulin Sensitizers)
Rosiglitazone (Avandia) Improves insulin sensitivity 4 to 8 once daily, or may ⬃70 1.5 Edema, decreased hematocrit
(Smith, Kline, Beecham, in muscle and adipose be divided b.i.d. Rosaglitazone and pioglitazone are
Pittsburgh, PA) tissue, decreases hepatic contraindicated in patients with active
Pioglitazone (Actos) gluconeogenesis liver disease or ALT ⬎2.5 times the upper
(Jakeda Pharmaceuitials, 15 to 45 limit of normal. Because of the association
Linconshire, IL) of hepatocellular injury with the
thiazolidinedione class (troglitazone),
current manufacturer recommendation is
transaminase assessment every other
month for the first 12 months of therapy,
and periodically thereafter.

FPG  fasting plasma glucose; HbA1c  hemoglobin A1c ; KATP  potassium channels; AST  aspartate aminotransferase; ALT  alanine aminotransferase; b.i.d. 
two times/day; t.i.d.  three times/day
97
98 SCHUSTER & DUVUURI

Table 6 summarizes the different types of insulin, onset and peak

of action, and adverse effects.33

COMPLICATIONS OF DIABETES MELLITUS

Acute Complications

Diabetic ketoacidosis and NKHS are the two most serious acute
metabolic complications of diabetes mellitus. These disorders can occur
in both type 1 and type 2 diabetes mellitus. The mortality rate in
patients with diabetic ketoacidosis is less than 5% in experienced centers,
whereas the mortality rate in patients with hyperosmolar hyperglycemic
state still remains high, at approximately 15%.

Diabetic Ketoacidosis and Nonketotic

Hyperosmolar State

Diabetic ketoacidosis occurs as a result of severe insulin deficiency

and an excess of counterregulatory hormones such as glucagon, catechol-
amines, cortisol, and growth hormone. The combination of insulin defi-
ciency and increased counterregulatory hormones in DKA leads to the
release of free fatty acids into the circulation from adipose tissue and
hepatic fatty acid oxidation to ketone bodies (beta-hydroxybutyrate and
acetoacetate), with resulting ketonemia and metabolic acidosis. The
NKHS syndrome occurs predominantly in patients with type 2 diabetes
mellitus and is caused by a plasma insulin concentration that is inade-
quate to facilitate glucose use by insulin-sensitive tissues but is adequate
to prevent lipolysis and subsequent ketogenesis. Diabetic ketoacidosis
and NKHS are associated with glycosuria, leading to osmotic diuresis
with loss of water, sodium, potassium, and other electrolytes.32

Precipitating Factors
The most common precipitating factor in the development of DKA
is infection. Other precipitating factors include cerebrovascular accident,
alcohol abuse, pancreatitis, myocardial infarction, trauma, and drugs (␤-
blockers, thiazide, glucocorticoids, phenytoin, didanosine, and somato-
statin). In addition, new-onset type 1 diabetes mellitus or discontinuation
of or inadequate insulin in established type 1 diabetes mellitus com-
monly leads to the development of DKA. Elderly individuals with new-
onset diabetes or individuals with known diabetes mellitus who are
 Table 6. TYPES OF INSULIN, ONSET, AND PEAK OF ACTION, AND ADVERSE EFFECTS
Onset of Peak Action Duration of
Insulin Type Action (hrs) Action (hrs) Adverse Effects Remarks

Rapid-acting
Insulin lispro (Humalog) 5–15 min 1–2 4–5 Hypoglycemia, Insulin lispro injection, whether alone or mixed with a longer-acting
Lilly lipodystrophy insulin, must be timed immediately within 15 min before the
beginning of a meal.
Short-acting
Regular human insulin (Humulin R, Lilly) 30–60 min 2–4 6–8 Hypoglycemia, Regular human insulin is also appropriate for intravenous use in the
(Novdin R, Nova Noodisk) lipodystrophy hospital setting. With intravenous use, the onset and peak effect
(30–90 min) will be earlier than with subcutaneous injection.
Intermediate-acting
NPH, human insulin isophane suspension 1–3 hrs 5–7 13–18 Hypoglycemia,
(Humulin N, Lilly) lipodystrophy
Indianopdis, IN
Lente human insulin 1–3 hrs 4–8 13–20 Hypoglycemia, Lente insulin should not be mixed with NPH insulin. Mixing of
Insulin zinc suspension (Humulin L, Lilly) lipodystrophy regular and Lente insulins is not recommended except for patients
(Novolin L Nova Noodisk, already well controlled on this combination, because this admixture
Princeton,NJ) may delay the onset of the short-acting insulin
Long-acting
Ultralente (extended insulin zinc 2–4 hrs 8–14 18–24 Same as above Typical duration of effect: up to 28 hours after injection
suspension) (Humulin U, Lilly)
(Lantus Coecombinart
DNA oogin, Aventis Pharmaceuticals,
Bridgeport, NJ)
Insulin glargine 1–3 hrs 3–24 24–48 Availability anticipated
Premixed Insulin
70/30 (70% Human insulin isophane Same as above Mixtures of NPH and Regular/Lispro Human Insulin are available
suspension (NPH); 30% Buffered regular commercially and may be used if appropriate for a given patient’s
human insulin coecombinant DNA insulin requirements. Commonly used preparations involve 70% or
oogin) (Humulin 70/30-Lilly- 75% NPH and 30% Regular or 25% Lispro or 50% of NPH and 50%
Indianapolis, IN. Novolin 70/30-Novo Regular
Nordisk, Princeton NJ),
50/50 (50% Human insulin isophane
suspension (NPH); 50% Regular human
insulin injection (Recombinant DNA
orgin)
75/25 (75% Insulin lispro protamine
suspension; 25% Insulin lispro injection
(Recombinant DNA orgin) (Humalog
75/25 mix) Lilly, Indianopolis, IN)
99
100 SCHUSTER & DUVUURI

unaware of hyperglycemia or are unable to take fluids when necessary

are at risk for NKHS.

History and Physical Examination

The initial evaluation should include a brief history and physical

examination. The classic clinical picture includes a history of polyuria,
polydipsia, polyphagia, weight loss, vomiting, abdominal pain, dehydra-
tion, weakness, clouding of sensorium, and finally coma. Physical find-
ings include poor skin turgor, Kussmaul’s respiration, tachycardia, hypo-
tension, altered mental status, shock, and coma. Hypothermia, if present,
is a poor prognostic sign.

Laboratory Findings

Laboratory evaluation in DKA reveals metabolic acidosis with an

elevated anion gap and the presence of serum ketones. Plasma glucose
concentration is always elevated. Other laboratory findings may include
hyponatremia, hyperkalemia, increased serum urea nitrogen (BUN) and
creatinine levels, hyperosmolality, and an elevation of serum amylase
unrelated to pancreatic disease. Laboratory evaluations in NKHS are
similar to those for DKA and should reveal hyperglycemia (often greater
than 600 mg/dL), absence of ketonemia or mild ketonemia, and plasma
osmolarity greater than 320 mOsm/L, arterial pH above 7.3, and bicar-
bonate above 15 mEq/L. Associated findings include severe azotemia
and lactic acidosis.

Treatment

Successful treatment of DKA and NKHS requires correction of dehy-

dration with fluids, correction of hyperglycemia with insulin, correction
of electrolyte imbalances, identification of comorbid precipitating events,
and frequent monitoring.

Complications

The most common complications of DKA include hyperglycemia

caused by overzealous treatment with insulin, hypokalemia caused by
insulin administration and treatment of acidosis with bicarbonate, and
hyperglycemia resulting from the interruption or discontinuation of
 DIABETES MELLITUS 101

intravenous insulin therapy after recovery without coverage with subcu-

taneous insulin. Cerebral edema may occur during therapy for DKA,
manifested by headache, altered mental status, and papilledema. A
computed tomographic (CT) scan of the head can establish the diagno-
sis.19 Hypoxemia and noncardiogenic pulmonary edema may complicate
the treatment of DKA and NKHS.

Chronic Complications

Hyperglycemia is key in the development of microvascular compli-

cations in both type 1 and type 2 diabetes mellitus. Diabetes mellitus
also is associated with premature macrovascular disease. The prevention
or delay of the development or progression of the chronic complications
of diabetes mellitus depends on the degree to which the metabolic
abnormalities are chronically controlled. See Table 3, which summarizes
the decreased incidence of chronic complications with good glycemic
control.

Macrovascular Complications
Coronary artery disease, stroke, and myocardial infarction occur
with increased frequency in diabetes mellitus. Heart disease should be
suspected when dyspnea or unexplained hyperglycemia occur, even
when angina is atypical or absent. Diabetes mellitus also is associated
with cardiomyopathy characterized by heart failure in the absence of
identifiable organic heart disease and normal coronary arteries. Athero-
sclerosis is extensive in diabetes mellitus and occurs earlier than in the
general population. The cause of the accelerated course is not known.
Atherosclerosis occurs in many sites. Peripheral deposits may cause
intermittent claudication, and gangrene and impotence in men occur as
a result of vascular disease or diabetic neuropathy.34
Diabetes mellitus is associated with increased platelet adhesiveness,
add elevated levels of factor VIII, von Willebrand’s factors, and tissue-
type plasminogen activator (PA) inhibitor type 1.

Microvascular Complications
Retinopathy. Diabetic retinopathy is the major cause of blindness
among adults between the ages of 20 and 74 years in the United States.
Blindness in diabetes occurs as a result of proliferative retinopathy and
also because of an increased rate of cataracts and glaucoma.34
Diabetic retinopathy includes nonproliferative retinopathy (simple
or background), which is limited to the retina (microaneurysms, retinal
102 SCHUSTER & DUVUURI

infarcts) and proliferative retinopathy (neovascularization), extended an-

teriorly to the retina, obscuring underlying retinal details. Macular
edema should be suspected when glasses do not correct the loss of visual
acuity. Ophthalmologic consultation should be sought early, because the
vision may be spared with laser therapy of macular edema. The two
serious complications of retinopathy are vitreous hemorrhage and retinal
detachment, manifest by sudden loss of vision.21
Treatment of diabetic retinopathy is photocoagulation. Prevention
of diabetic retinopathy can be achieved by maintaining target glycemic
and blood pressure goals. An annual examination by an ophthalmologist
is recommended beginning at 5 years following the onset of type 1
diabetes mellitus (or at puberty) and at the time of diagnosis in type 2
diabetes mellitus or the onset of diabetes mellitus in patients 30 years or
older. For pregnant patients with preexisting diabetes, eye examination is
recommended before conception and during the first trimester.5
Diabetic Nephropathy. Diabetes mellitus is the leading cause of
end-stage renal disease (ESRD) in the United States. About 20% to 30%
of patients with type 1 or type 2 diabetes mellitus develop evidence of
nephropathy, but a smaller percentage of patients with type 2 diabetes
progress to end-stage renal disease. The four approaches to the preven-
tion of diabetic renal disease are (1) control of glycemia, (2) treatment of
hypertension, (3) restriction of protein, and (4) avoidance of nephrotoxic
drugs. Glycemic control resulting from pancreas transplantation does
not ameliorate advanced nephropathy, but it delays the progression of
nephropathy in donor kidneys. Angiotensin-converting enzyme (ACE)
inhibitors delay the onset and progression of diabetic nephropathy and
also have a specific renoprotective effect. The use of ACE inhibitors
prevents the progression of renal disease in patients with diabetes melli-
tus, even in the absence of hypertension. The calcium-channel blocks,
diltiazem and nicardipine, decrease albuminuria and should be consid-
ered as alternative therapy when ACE inhibitors are contraindicated
(in patients with renal artery stenosis or hyperkalemia).20 The ADA
recommends testing for microalbuminuria (timed-specimen or albumin/
creatinine ratio) in pubertal and postpubertal patients with type 1 diabe-
tes mellitus who have had diabetes mellitus for at least 5 years and in
all patients with type 2 diabetes mellitus. Because of the variability in
urinary albumin excretion, 2 or 3 specimens collected within a 3 to 6
month period should be abnormal before a patient should be considered
as having crossed one of these diagnostic thresholds. Exercise within 24
hours, infection, fever, congestive heart failure, marked hyperglycemia,
and marked hypertension may elevate urinary albumin excretion over
baseline values.5
Diabetic Neuropathy. Diabetic neuropathies are one of the most
common and least recognized complications of diabetes mellitus. In a
 DIABETES MELLITUS 103

DCCT trial, intensive treatment decreased the neuropathy by 60%. The

diabetic neuropathies occur as sensorimotor peripheral neuropathies and
autonomic neuropathies. Mononeuropathies commonly involve the third
and sixth cranial nerves. The onset is sudden, and resolution is spontane-
ous. Diabetic amyotrophy, which manifests as wasting disease, resolves
in 6 to 12 months of intensified glycemic control and physical therapy.
The most common picture is peripheral neuropathy (sensorimotor neu-
ropathy) which presents as severe dysesthesias, anorexia, and weight
loss. There is no effective specific treatment. Treatment is symptomatic
with antidepressants, and analgesics are occasionally effective. Resolu-
tion of symptoms is slow.
Autonomic neuropathy may cause postural hypotension, persistent
tachycardia, neurogenic bladder, gastroparesis, diarrhea, and impotence.
Impaired visceral pain sensation can obscure symptoms of angina and
myocardial infarction.14
Diabetic Foot Problems. Diabetic foot problems are the major cause
of lower-limb amputations in diabetic individuals. Diabetic foot is a major
manifestation of chronic neuropathy aggravated by vascular insuffi-
ciency and infection. The foot ulcers and infection result from a combina-
tion of anatomic deformities, sensory neuropathy that reduces pain and
pressure perception, and vascular insufficiency. Specialized treatment is
necessary to prevent and manage foot disease. Preventive foot care
includes risk identification, foot examination, and prevention of high-
risk conditions. The risk of ulcers or amputations is increased in people
who have had diabetes mellitus 10 years, are male, have poor glucose
control, or have cardiovascular, retinal, or renal complications. The foot-
related conditions associated with increased risk of amputation are pe-
ripheral neuropathy with loss of protective function, altered biomecha-
nics (bony deformity, callus), peripheral vascular disease, history of ulcer
or amputation, and severe nail pathology.3
The foot examination includes assessment of protective function,
foot structure, biomechanics, vascular status, and skin integrity. All
individuals should receive an annual foot examination. Persons with
neuropathy should have a visual inspection of their feet at every visit to
a health care professional. Controlling glucose to nearly normal levels is
the most effective means of preventing neuropathy. Smoking cessation
should be recommended to reduce the risk of vascular disease.

Management of High-Risk Conditions

People with neuropathy or evidence of increased plantar pressure
may be managed with well-fitted walking shoes or athletic shoes. Pa-
tients should be educated on ways to substitute other sensory modalities
(hand palpation, visual inspection) for surveillance of early problems.
104 SCHUSTER & DUVUURI

Symptoms of claudication require further vascular assessment. Ulcers

should be evaluated for underlying pathology. Minor conditions such as
dry skin and tinea pedis should be treated to prevent the development
of a serious condition.

Skin Lesions in Diabetes Mellitus

Diabetic dermopathy (shin spots) are small, round plaques with
raised borders, located at the anterior tibial surface. They crust at the
edge and ulcerate centrally. Necrobiosis lipoid diabeticorum is a
plaquelike lesion with a central yellowish area surrounded by a brown
border. It is usually found over the anterior aspects of the legs. Infesta-
tion of skin with Candida and dermatophytes are common.

SUMMARY

Diabetes mellitus is a group of metabolic diseases characterized by

hyperglycemia resulting from defects in insulin secretion, insulin action,
or both. The chronic hyperglycemia of diabetes mellitus is associated
with long-term damage, dysfunction, and failure of various organs,
especially the eyes, kidneys, nerves, heart, and blood vessels. The man-
agement of this disease process is complicated. Good diabetic control
depends on diligence in blood glucose monitoring, frequent adjustment
of medications, adherence to a regular diet and exercise plan, and
treatment of comorbid conditions such as hypertension and hyperlipid-
emia.

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Address reprint requests to

Dara P. Schuster
Division of Endocrinology
The Ohio State University Hospitals
491 McCampbell Hall
1581 Dodd Drive
Columbus, OH 43205–2696
e-mail: [email protected]