BEATING DIABETES MELLITUS THROUGH MEDICAL INFORMATION MASTERY
DIABETES MELLITUS-THE INCONROVERTIBLE DISEASE
As we have seen
with Obesity and Hypertension (Past
Two Articles for my Family Medicine Rotation and this article for my Jackson Park Rotation in Internal Medicine-attendant
Dr. Murthy, M.D. Hospital Director), it was the little things in life, made as
positive unconscious health habits, which when implemented can reverse
said conditions through a life commitment for health. As you will see,
both obesity and hypertension control are essential elements in
controlling diabetes. However Diabetes and its various types have
genetic or acquired links, receptor damage, cell damage necessary for
the production of prime hormones affecting the insulin and glucagon
worlds, which further complicate concepts of complete cure for even
moderate to severe disease.
Thus, Diabetes Mellitus is presently an
incurable yet in many cases more manageable then
previously (just the last decade) thought disease which is a major cause of premature death and
disability within the United States. As far back as 1997 and for that
year alone, direct medical cost and lost-productivity was measured at
$59 billions per year. And has been rising ever since.
For an alarming example, Diabetes mellitus is on the
rise in the United States in adolescents with an elevated BMI!
A very interesting
Surveillance survey relative to Diabetes Mellitus found for 1990
increased prevalence from prior years of 4.9 to 6.5% increase. During
that period, the sex-age-race adjusted prevalence increased in both
genders, and the largest prevalence increases occurred in the 30-39 age
category and higher education levels. Finally, overall prevalence of
Diabetes Mellitus increased another 6% one year later and was directly
correlated with increased Obesity during the same period.
prevalence for DM has risen dramatically over the past two decades with
the expectation that type 2 DM is expected to rise even more rapidly in
the future because of increasing obesity and reduced activity levels.
Finally DM increases with aging.
first we went through Obesity, then Hypertension which illustrated some
consistent connections between both and understanding disease
ramifications rendering either more controllable.
Now we must understand the various types of diabetes
and the interrelationships between obesity, hypertension, hyperlipidemia
and issues and events which will follow in this series.
However and again, first we must understand Diabetes Mellitus.
non-insulin-dependent DM represents 90% to 95% of all cases.
African-American, Hispanic and native America prevalence for type 2 DM
is 1.3 to 3 times higher than Caucasians. The usual onset for type 2 DM
is in adults over the age of 40 and increases with age over 65. A sub
Variance of type 2 DM, maturity onset diabetes of youth, occurs below
the age of 30 and usually in children. And of course type 1 DM
primarily involves our children.
Defects in insulin
secretion, insulin action or a combination are characterized by
hyperglycemia. Type 1 DM results from an absolute insulin deficiency,
and type 2 DM is characterized by peripheral insulin resistance and
either a relative insulin deficiency or a predominant insulin secretory
defect that leads to hepatic glucose overproduction.
There are three
well understood genetic and autoimmune cell damage that can lead to the
main types of diabetes:
Type 1 Diabetes Mellitus
involves synergistic effects of genetic, environmental, and immunologic
β-cell destruction. If total insulin deficiency is not replaced with
insulin, ketoacidosis, rapid dehydration, coma and death can ensue.
Type 2 Diabetes Mellitus
involves defects in insulin action related to mutations of insulin
receptors. Here there is a progressive increase above normal of fasting
and postprandial glucose levels with higher-than normal insulin levels
caused by insulin resistance. As the insulin resistance and glucose
levels rise, insulin levels decline as β-cells are destroyed. The
process begins five to ten years prior to clinical symptomatology. In
many cases it takes 30 years for the β-cell destruction subsequent to
the clinical symptoms arising.
Maturity onset diabetes of
youth involves β-cell function with impaired insulin secretion in an
Autosomal dominant inheritance with early onset of hyperglycemia. It
must be noted that autoimmune beta cell destructive processes can
develop at any age.
These defects in
insulin action can occur peripherally which affects glucose uptake and
storage in the muscle and/or the liver resulting with increased glucose
production and is thus a vicious cycle with the end result known as
Diabetes Mellitus or glucose intolerance of pregnancy can develop
related to the metabolic changes of late pregnancy which increase s
insulin requirements and may lead to IGT. GDM occurs in approximately
4% of pregnancies in the Unites States with most women reverting back to
normal glucose tolerance post-partum but have a substantial risk (30-60)
of developing DM later in life.
Below is a more
complete listing of causation for Diabetes Mellitus:
Etiologic Classification of Diabetes Mellitus
Type 1 diabetes (β-cell
destruction, usually leading to absolute insulin deficiency)
- Type 2
diabetes (may range from predominantly insulin resistance with
relative insulin deficiency to a predominantly insulin secretory
defect with insulin resistance).
- Other specific
types of diabetes
defects of β-cell function characterized by mutations in:
transcription factor (HNF) 4 α (MODY 1)
Glucokinase (MODY 2)
HNF-1 α (MODY3)
Insulin promoter factor (IPF)
1 (MODY 4)
HNF-1β (MODY 5)
Proinsulin or insulin
B. Genetic defects in insulin
1. Type A insulin resistance
3. Rabson-Mendenhall syndrome
4. Lipodystrophy syndromes
C. Diseases of exocrine pancreases such
as pancreatitis, pancreatectomy, neoplasia, cystic fibrosis,
hemochromatosis, fibrocalculous pancreatopathy.
Endocrinopathies such as
acromegaly, Cushing’s syndrome, glucagonoma, pheochromocytoma,
hyperthyroidism, somatostatinoma, aldosteronoma
Infections such as
congenital rubella, cytomegalovirus, and coxsackie
Uncommon forms of
immune-mediated diabetes – “stiff-man” syndrome, anti-insulin receptor
Other genetic syndromes
sometimes associates with diabetes include Down’s syndrome,
Klinefelter’s syndrome, Turner’s syndrome, wolfram’s syndrome,
Friedreich’s ataxia, Huntington’s Chorea, Laurence-Moon-Biedl syndrome,
myotonic dystrophy, porphyria, and Prader-Willi syndrome.
Gestational diabetes mellitus
The diagnosis of
Diabetes Mellitus can be established if any of three criteria are met.
These criteria follow:
- Presence of
the classic symptoms of diabetes, such as polyuria, polydipsia,
ketonuria, and rapid weight loss, together with gross and
unequivocal elevation of plasma glucose levels ≥ 11.1 mmol/L (200
mg/dL)…where random is defined as without regard to time since the
last meal or
- Fasting plasma
glucose ≥ 7.0 mmol/L (126 mg/dL) where fasting is defined as no
caloric intake for at least 8 hours or
plasma glucose ≥ 11.1 mmol/L (200 mg/dL) during an oral glucose
tolerance test. The test should be performed using a glucose load
containing the equivalent of 75 g anhydrous glucose dissolved n
water; not recommended for routine clinical use.
In the absence of unequivocal
hyperglycemia and acute metabolic decompensation, these criteria should
be confirmed by repeat testing on a different day.
Most patients who
are diabetic according to oral glucose tolerance also have fasting
plasma glucose levels greater than 140 mg/dl. It is wise to test
individual with normal fasting blood glucose if there is a strong
suspicion of diabetes, such as the presence of complications possibly
secondary to diabetes, an extensive family history, or certain genetic
characteristics and conditions. In other words, the diagnosis of
diabetes mellitus should rarely be made in the absence of fasting
Clearly from the
complexity for causation of diabetes, clinical evaluation must include a
thorough history, physical examination, and appropriate diagnostic
testing. With regard to type 2 DM, symptom onset is gradual,
nonspecific, and mild. Approximately one third of people with diabetes
are undiagnosed! It is therefore essential for clinicians to have a
high index of suspicion for risk factors such as family history, along
with the following signs and symptoms:
- General: weight loss, fatigue, chronic malaise, gradually increasing
- Dermatolic; recurrent fungal infections (vaginal, dermatophytic,
intertrigo, etc.), slow healing of skin injuries
- Ophthalmologic: recent visual changes (often requiring a change in
refractive correction), blurred vision (caused by osmotic and fluid
changes in the lens due to hyperglycemia)
- Dental: periodontal disease
- Urinary: nocturnal and polyuria
- Neurologic: burning, tingling, numbness in feet and/or hands
The Elderly patient
with type 2 DM may present acutely with confusion, lethargy,
prostration, hypothermia, dehydration, hypotension/shock, and less
commonly in a nonketotic coma cause by marked hyperglycemia (glucose
level greater than 1,999mg/dL). This syndrome is called hyperglycemic
hyperosmolar nonketotic coma.
Relative to type 1
DM, acute presentation typically occurs during diabetic ketoacidosis.
Patients with type 1 DM, usually children or adolescents, report a rapid
onset of some or all of the classic symptoms of diabetes; polyuria,
polydipsia, polyphagia, weight loss, and fatigue. There is even a
seasonal incidence of type 1 DM which parallels that of viral
infections, with of course more cases presenting in winter and early
Finally no diabetic
history would be complete absent evaluation for risk factors such as
vascular complication. Questioning along these lines would include
smoking habits, previous blood pressure and lipid measurement, physical
activity, and family history of cardiovascular disease. One half of
patients with diabetes have complications at diagnosis, assessment of
current complication should include visual difficulties, periodontal
disease, of course cardiovascular history, sexual dysfunction, and
peripheral neuropathy. Note prior ophthalmologic, dental or podiatric
care. It has been reported that a recent population-based epidemiology
study found that the simple question, “Thinking now of both legs or both
feet, have you had pain or discomfort such as numbness, burning, or
tingling when you are walking in the past 6 months?” was a valuable
predictor of the presence of peripheral neuropathy with a 97%
sensitivity when compared with the gold standard of a formal neurologic
examination by a neurologist.
areas for risk of diabetes have been identified by the American Diabetes
Association and the American ‘Association of Clinical Endocrinologists
and are now guidelines for the initial physical examination of a patient
who is suspected to have diabetes which follow:
- Height and weight
- Blood pressure with ortostatic evaluation
- Ophthalmologic examination
- Oral examination, thyroid palpation
- Cardiac examination
- Evaluation of pulses
- Abdominal examination
- Hand/finger examination
- Feet examination
- Skin examination
- Neurologic examination includes reflexes, vibratory sensation,
touch, and proprioception.
Please note that
both "obesity" and
"hypertension" are horrible risk factors and risk
amplifiers for disease. Obesity is a significant risk factor for type 2
DM as it aggravates insulin resistance. Body Mass Indices >25 and < 30
designate obese. Abdominal adiposity, assessed with waist to hip ratio,
is also an independent risk factor for Diabetes Mellitus hypertension
and ischemic heart disease.
both an independent and co-risk factor for cardiovascular disease in
Diabetes Mellitus patients. Of course measure blood pressure in and out
of the clinical setting to avoid “white coat” hypertension and on
multiple occasions. It has been recommended that blood pressure in
diabetic patients be maintained below 130/85 and, if there is
proteinuria (1 g/24h), below 125/75.
Retinopathy is the
most frequent cause of new cases of blindness among adults between 20
and 74 years of age. Retinopathy is also a microvascular complication
of both type 1 and 2 DM. Thus all patients with DM should have a
retinal screening examination as part of the initial evaluation and
annually thereafter. Examination of the heart, peripheral pulses, feet
and legs, and the peripheral neurologic system as well as dentition
should be meticulously documented at initial evaluation. These organs
are targets of microvascular disease, and should be regularly
For detection of
the propensity to develop foot ulcers, the monofilament foot examination
will identify patients at high risk for subsequent foot ulcer. Compared
with the measurement of pedal pulses, and vibration perception
threshold, the monofilament examination had over 85% reproducibility
between different examiners and different times and was the only test
judged to be satisfactory for such utility.
By the age of 45,
screening for type 2 DM is recommended for individuals at high risk of
DM and, if there are no complications, is repeated at 3-year intervals.
Individuals with significant risk factors such as parents or sibling
with DM, BMI>27, physical inactivity, racial predisposition,
hypertension, elevated lipid levels, and previously identified impaired
fasting glucose (IFG) or impaired glucose tolerance (IGT), and for women
with a history of gestational diabetes or delivery of a baby weighting
greater than 9 lb or who have polycystic ovary syndrome, must have their
laboratory evaluation at much earlier on. Because of the increased
incidence of type 2 DM in youth, over-weight children and adolescents
should be screened at age 19, and every 2 years.
The criteria for
IFG or IGT are as follows:
- IFG: fasting plasma glucose ≥ 110 and < 126 mg/dL (fasting is
defined as no caloric intake for at least 8 hours), or
- IGT: 2-hour postload plasma glucose ≥ 140 and <200 mg/dL (a glucose
load containing the equivalent of 75 g of anhydrous glucose
dissolved n water).
for DM in the non-pregnant adult follows as one of the following
findings must be documented don at least two occasions, on separate
- A 2 hour plasma glucose ≥ 200 mg/dL
- A fasting plasma glucose ≥ 126 mg/dL
- A fasting plasma glucose <126 mg/dL, a high index of suspicion of
DM, and a plasma glucose ≥ 200 performed on a different day.
The development of
baseline levels to establish possible end-organ complications has been
suggested by the American Diabetes Association and American Association
for Clinical endocrinologists through measuring potassium, blood urea
nitrogen, creatinine, and microalbuminuria and creatinine clearance, and
performing both an electrocardiogram and a urinalysis. Dyslipidemia is
determined by the measurement of cholesterol, low-density lipoprotein (LDL)
cholesterol, high-density lipoprotein (HDL) cholesterol), and
differential diagnosis although type 1 DM is most likely when
ketoacidosis is found, patients with severe alcohol and less prevalent
methanol intoxication present with ketosis. Hyperglycemia absent
ketoacidosis can accompany acute pain secondary to trauma, myocardial
ischemia or infarction, or other critical illnesses, steroid us or
Cushing’s disease, hypothyroidism, the infiltrative disease o iron
overload known as hemochromatosis.
Relative to type 2 DM today science and clinical studies have revealed a
MNT or medical nutritional therapy which is a
healthy-eating plan that's naturally rich in
nutrients and low in fat and calories, with
an emphasis on fruits, vegetables and whole grains combined with proper
exercise is the key. In fact, a diabetes diet is the best eating
plan for most folks. The studies reveal that
improper diet for a specific person's physiology
over a life time cause insulin resistance, which begins a cascade of
events leading to the high triglycerides, the high cholesterol, damage
to the blood vessels, high blood pressure, metabolic imbalance
accompanied causing the body to receive poor energy sources akin but not
the same as starvation and being to break down
the muscle glycogen stores, and eventually
80% of glucose comes from
fat breakdown, more specifically from the glycerol backbone of
triglycerides, which enters gluconeogenesis
to create glucose through glyconeogenesis but further fat storage by excess insulin due to insulin
resistance and hence, fat storage around the abdomen but small
extremities due to lack of exercise and proper nutritional proteins and
thus muscle loss. This furthers the metabolic
imbalances leading to the body resisting any weight loss.
If the patient can
become the principal manager of their own diabetes, the primary care
physician and other members of the health care team become partners for
a most successful outcome. In this circumstance, the patient must have
a good understanding of the disease and its complications and then
adhering to the diet, exercise, weight control and/or reduction; self
care that includes dental hygiene, foot care, avoiding tobacco,
increasing physical activity, and modifying alcohol use; glucose
monitoring, and medication compliance albeit
an ideal body weight and an active lifestyle may prevent the onset of
type 2 diabetes while currently there is no way to prevent type 1
approach is required for the care of the diabetic patient. Medical
records reviewed, should allow the visual demonstration of baseline and
follow-up data on glycemic control (Often
times a complete dietary change must commence based on the MNT for that
patient), end organ health, compliance with
lifestyle modifications and medication, and the patient’s continued
understanding of her disease and its management.
requires the team approach to managing diabetes patients. The Diabetes
health care team usually is comprised of the primary care physician,
nurse, dieticians and nutritionists, health educators, metal health counselors, and
medical specialists including the endocrinologist, ophthalmologist,
podiatrist, vascular surgeon, her family or social
supports considered as a central part of the team.
glucose status helps the patient and physician understand the patients
working physiology and live healthfully. Usually diabetic control
measures urine glucose concentrations at various times throughout the
day. The concentration of glucose in the urine depends on the renal
threshold for glucose excretion, the renal blood flow, and the urine
volume. Home blood glucose monitoring, is the method of choice for
monitoring diabetic control. The accurate and routine measurement of
home blood glucose levels by the education/informed patient is an
essential ingredient in any intensive treatment regimen.
of blood glucose is accomplished by checking the glucose content of a
drop of blood. Regular testing tells how well diet, medication, and
exercise are working together to control the diabetes.
The results of
the test can be used to adjust meals, activity, or medications to keep
blood sugar levels in an appropriate range. Testing provides valuable
information for the health care provider and identifies high and low
blood sugar levels before serious problems develop.
Diabetes Association recommends that premeal blood sugar levels fall in
the range of 80 to 120 mg/dL and bedtime blood levels fall in the range
of 100 to 140 mg/dL.
assessment must be taught to the patient by the primary care physician.
The HbA1c is a measure of average blood glucose during the previous two
to three months. It is a very helpful way to monitor a patient's overall
response to diabetes treatment over time. A person without diabetes has
an HbA1c around 5%. People with diabetes should try to keep it below 7%.
is another test that is used in type 1 diabetes. Ketones build up in the
blood when there is not enough insulin in people with type 1 diabetes,
eventually "spilling over" into the urine. The ketone test is done on a
urine sample. High levels of blood ketones may ketoacidosis as
previously discussed. Ketone testing is usually done at the following
When the blood sugar is
higher than 240 mg/dL
During acute illness (for
example, pneumonia, heart attack, or stroke)
When nausea or vomiting
The goals of medical
nutritional therapy are to maintain near-normal blood glucose by
balancing insulin or oral-glucose lowering medications with exercise
and diet; to
achieve optimal serum lipid levels and to maintain reasonable weight
with calories and to prevent acute complications of insulin use and
long-term microvascular and macrovascular complications. It must be
noted that moderate weight loss (10-20lbs) regardless of patient
starting weight, is associated with reduced hyperglycemia, Dyslipidemia,
therapy (MNT) is a term used to describe the optimal coordination of caloric
intake with other aspects of diabetes therapy. For example in patient
with type 2 DM, although weight loss is a concomitant program within
care, the focus of the MNT seeks to modify patient hyperlipidemia and
hypertension. Further glycemic control is also associated with
correct dietary changes concomitant with aerobic
fitness regardless of weight. Weight loss strategies include moderate
reduction of daily caloric intake, 250-500 calories, the appropriate
nutritional intake, reduction of total fat and especially saturate fats,
and increased physical activity. Unless the
patient is tested for food sensitivity which tailors the program to the
individual, and of course has the most success the generalized
daily caloric intake of protein, fat and carbohydrate components
- Protein: 10% to 20%
- Carbohydrates: 50%-60%
- Fat: <30% (saturated fat<10%, polyunsaturated fat<10%,
monounsaturated fat 10-15%).
Patients's with overt nephropathy
should limit protein intake to 10% of total caloric intake. It must be
noted that saturated fats should be <10% of total calories with dietary
cholesterol ≤ 300 mg daily. If LDL is a consideration, saturated fats
should be reduced below 7% and dietary cholesterol below 200 mg/d.
Polyunsaturated fats in the form of the
omega-3 series occurring naturally in fish and other seafood are
acceptable for diabetic patients. It is the total amount of
carbohydrates consumed that is more important than the consumption of
simple versus complex carbohydrates, and again the
first importance is a changed diet away from lab proven sensitivities to
gluten and other elements of the human diet which cause sensitivity
reactions which break down the homeostasis of the patient.
The goal of MNT in
type 1 DM is to coordinate and match the caloric intact, both temporally
and quantitatively, with the appropriate amount of insulin. The goal of MNT in type 2 DM focus on reducing the prevalence of cardiovascular risk
factors such as hypertension, Dyslipidemia, and obesity
as well as the tailored diet away from lab proven food sensitivities.
of these patients are obese, and must be strongly encouraged to make
unconscious good life habit eating and exercise habits. Current protocol
for initial MNT care would emphasize modest caloric reduction, reduced
fat intake, increased physical activity, and reduction of hyperlipidemia
Again soluble dietary fiber may improve glycemic control in
type 2 DM patients but the priority of importance is
to test for and then eliminate discovered food sensitivities.
obese type II DM patients, the aims
of diet management first and foremost which then aids in losing weight and controlling hyperglycemia
(For MNT diet see Beating Obesity Through Medical Information Mastery
and POEMs). The
diet should meet the patient's minimum daily protein requirement (0.9
g/kg) and be designed to induce a gradual and sustained weight loss
(about 2 lb/wk) until ideal body weight is approached and maintained.
Increased physical activity in sedentary obese type II DM patients is
valuable and may decrease insulin resistance over time. Diabetics with
hypertension should be treated with ACE inhibitors, which have been
shown to be more protective against coronary artery disease than Ca
channel blockers, until the dietary changes
concomitant with exercise the lab values to normal or at least a
normalization of Triglycerides, Cholesterol, Blood Pressure, Obesity and
on signs and symptoms of disease that adversely affect the
cardiovascular system, eyes, kidneys, and nervous systems is correlated
with the proposed exercise program individually tailored for the
specific medical condition, age, current condition and taking into
account jarring exercising vs. non-jarring exercises such as swimming.
Exercises which simulate a Valsalva like maneuvers must be avoided in
patient with proliferate retinopathy and overt nephropathy
Regular exercise is especially important for people with
diabetes. It helps with blood sugar control, weight loss, and high blood
pressure. People with diabetes who exercise are less likely to
experience a heart attack or stroke than diabetics who do not exercise
Of course exercise
can be quite a challenge to some patients as not only must they overcome
deconditioining associated with disease, it often feels at first like a
challenge not yet faced. When in reality, it is the very small
repetition of exercise which can lead to longer and increased work
exercise, which eventually will help cardiovascular risk reduction,
reduced blood pressure, maintenance of muscle mass, reduction of body
fat, and weight loss as well as lowering plasma glucose during and
following exercise and increasing insulin sensitivity in both types 1
and 2 DM. Obviously, monitoring of the patients pre, and post exercise
glucose status and when and how much carbohydrate to ingest to prevent
hypoglycemia is mandatory. As the patient is able to self check and
maintain glycemic control, much in the way of disease symptomatology and
manifestations can abate.
diabetes are prone to foot problems because of the likelihood of damage
to blood vessels and nerves and a decreased ability to fight infection.
Problems with blood flow and damage to nerves may cause an injury to the
foot to go unnoticed until infection develops. Death of skin and other
tissue can occur.
untreated, the affected foot may need to be amputated. Diabetes is the
most common condition leading to amputations.
injury to the feet, people with diabetes should adopt a daily routine of
checking and caring for the feet as follows:
Check your feet every
day, and report sores or changes and signs of infection.
Wash your feet every day
with lukewarm water and mild soap, and dry them thoroughly.
Soften dry skin with
lotion or petroleum jelly.
Protect feet with
comfortable, well-fitting shoes.
Exercise daily to promote
See a podiatrist for foot
problems or to have corns or calluses removed.
Remove shoes and socks
during a visit to your health care provider and remind him or her to
examine your feet.
Stop smoking, which
hinders blood flow to the feet
HOW TO TAKE
INSULIN OR ORAL MEDICATION
Human insulin is often preferred in initiating
insulin treatment because it is less antigenic than animal-derived
varieties. However, detectable insulin antibody levels, usually very
low, develop in most insulin-treated patients, including those receiving
human insulin preparations.
Insulin is routinely provided in preparations
containing 100 U/mL (U-100 insulin) and is injected subcutaneously with
disposable insulin syringes. The 1/2-mL syringes are generally preferred
by patients who routinely inject doses of <= 50 U, because they can be
read more easily and facilitate the accurate measurement of smaller
doses. A multiple-dose insulin injection device (NovolinPen), commonly
referred to as an insulin pen, is designed to use a cartridge containing
several days' dosage. Insulin should be refrigerated
but never frozen;
however, most insulin preparations are stable at room temperature for
months, which facilitates their use at work and when traveling.
Insulin preparations are classified as
short-acting (rapid-acting), intermediate-acting, or long-acting.
The critical determinant of the onset and duration of action of an
insulin preparation is the rate of insulin absorption from the injection
Rapid-acting insulins include regular insulin,
which is a preparation of zinc insulin crystals in a suspending
solution; regular insulin is the only insulin preparation that can be
given IV. Lispro, a form of regular insulin that is genetically
engineered with a substitute of one amino acid, provides more rapid
absorption of insulin and therefore may be administered with food.
Semilente insulin is slightly slower rapid-acting insulin, containing
zinc insulin microcrystals in an acetate buffer. Intermediate-acting
insulin includes neutral protamine Hagedorn, which contains a
stoichiometric mixture of regular, and protamine zinc insulin, and
Lente, which contains 30% Semilente insulin and 70% Ultralente insulin
in an acetate buffer. Long-acting protamine zinc insulin contains
insulin that is negatively charged, combined with an excess of
positively charged fish sperm protamine. Ultralente contains large zinc
insulin crystals in an acetate buffer.
Mixtures of insulin preparations with
different onsets and durations of action are frequently given in a
single injection by drawing measured doses of two preparations into the
same syringe immediately before use. The manufacturers recommend that
Semilente be mixed only with Lente or Ultralente to maintain the same
buffer solution. However, individual doses of regular insulin and
neutral protamine Hagedorn or Lente insulin are commonly drawn up into
the same syringe to combine rapid- and intermediate-acting insulin in a
single injection. A preparation that contains a mixture of 70% neutral
protamine Hagedorn and 30% regular human semisynthetic insulin (Novolin
70/30 or Humulin 70/30) is also available, but its fixed ratio of
intermediate- to rapid-acting insulin may restrict its use.
Protamine zinc insulin must always be
injected separately, because it contains
an excess of protamine.
Initiation of insulin therapy in adults:
In DCCT, type I DM patients received an average
total dose of about 40 U insulin a day. Because type II DM patients are
insulin resistant, they require more insulin. Thus, those who are
severely hyperglycemic and obese may be started on about 40 U of insulin
per day. The initial total daily dose may be divided so that 1/2 will be
administered before breakfast, 1/4 before dinner, and 1/4 at bedtime.
Because of severe insulin resistance, type II DM patients may need twice
that much and often more. After the initial dose is selected,
adjustments in the amounts, types, and timing are made based on plasma
glucose determinations. The dose is adjusted to maintain preprandial
plasma glucose between 80 and 150 mg/dL (4.44 and 8.33 mmol/L).
Increments in insulin dose are generally restricted to 10% at a time,
and the effects are assessed over about 3 days before any further
increment is made. More rapid adjustments of regular insulin are
indicated if hypoglycemia threatens.
Initiation of insulin therapy in children:
Children who present at an early stage of type I
DM with moderate hyperglycemia but without ketonuria or acidosis may be
started with a single daily subcutaneous injection of 0.3 to 0.5 U/kg of
intermediate-acting insulin alone. Children who present with both
hyperglycemia and ketonuria but who are not acidotic or dehydrated may
be started on 0.5 to 0.7 U/kg of intermediate-acting insulin and then
supplemented by subcutaneous injections of 0.1 U/kg of regular insulin
at 4- to 6-h intervals. Insulin doses are usually adjusted to maintain
preprandial plasma glucose levels between 80 and 150 mg/dL (4.44 and
8.33 mmol/L) or sometimes between 80 and 120 mg/dL (4.44 and 6.66
The goal of insulin therapy is to control
hyperglycemic surges after meals and to provide baseline levels that
support normal glucose metabolism. Regimens must always be
individualized, and some diabetics will achieve tight control with
highly idiosyncratic schedules. However, the approach should include:
Bedtime intermediate-acting insulin.
This helps control nocturnal hepatic glucose production. Starting
the day with lower morning glucose levels will improve glucose
tolerance throughout the day. Bedtime insulin is associated with
less weight gain than is daytime insulin alone. Bedtime insulin is
also a reasonable way to initiate insulin therapy in type II DM
patients who are not controlled by oral drugs alone.
Before-breakfast mixed insulin.
This often is accomplished with a mixture of about 30% short-acting
and 70% intermediate-acting insulin. Most diabetic patients will
need about half the daily insulin dose before breakfast.
Before-lunch-and-dinner regular insulin.
For tight control, supplemental rapid-acting insulin should be taken
before meals. The dose should be taken 15 to 30 min before a meal
for regular or Semilente and with a meal for Lispro.
subcutaneous insulin injections:
These are designed to maintain normal or
near-normal plasma glucose levels throughout the day in patients with
type I DM. Such treatment may increase the risks for frequent and severe
episodes of hypoglycemia. Patients should be highly motivated, well
educated in DM, informed of the risks and uncertain benefits, competent
in self-monitoring of glucose, and under the supervision of a physician
experienced in its use. In a typical multiple subcutaneous insulin
injection regimen, about 25% of the total daily dose is given as
intermediate-acting insulin at bedtime, with additional doses of
rapid-acting insulin given before each meal (a four-dose regimen). Type
I DM patients may require intermediate- or long-acting insulin in the
morning to give coverage throughout the day. The patient adjusts daily
dosage on the basis of self-monitoring of glucose before each meal and
at bedtime; the plasma glucose level between 2 and 4 am is assessed at
Continuous subcutaneous insulin infusion:
This mode of intensive insulin treatment in
patients with type I DM involves a small battery-powered infusion pump
that provides a continuous subcutaneous infusion of rapid-acting insulin
through a small needle, usually inserted in the abdominal wall. The pump
is programmed to infuse a selected basal rate of insulin, supplemented
by manually triggered or programmed increased rates before each meal.
The patient measures glucose levels several times a day to adjust the
dosage. Control obtainable with this method is superior to that obtained
with multiple injections. Hypoglycemic episodes are common with pump
therapy, especially during the establishment of metabolic control.
However, once metabolic control is established, pumps are not associated
with more hypoglycemia than are multiple injections. Experimental pump
implants and intraperitoneal deliveries of insulin to the portal system
may prove superior. However, the indwelling needle increases the risk of
infections at needle sites.
treatment of brittle diabetes:
Brittle diabetics are type I DM patients who
exhibit frequent, rapid swings in glucose levels without apparent cause.
Brittle diabetes is most common in patients with
no residual insulin secretory capacity. The metabolic processes through
which insulin affects the plasma levels of glucose, albumin-bound free
fatty acids, and ketones are normally regulated by shifts in the balance
between the effects of insulin and the opposing effects of glucagon (in
the liver) and the adrenergic autonomic nervous system. These counter
regulatory mechanisms are independently regulated and normally increased
during fasting, exercise, and other conditions that require protection
against hypoglycemia. Insulin doses must be adequate to deal with a
sudden increase in counter regulatory mechanisms and to prevent rapidly
developing symptomatic hyperglycemia and hyperketonemia, but this
frequently produces transient plasma insulin excess.
Many of these patients improve when switched to a
modified multiple subcutaneous insulin regimen that provides most of the
daily insulin as rapid-acting insulin in daily adjusted dosages before
each meal, with some intermediate-acting insulin in the morning, before
the evening meal, or at bedtime. The aim is not to maintain the diurnal
plasma glucose level in a near-normal range but to stabilize the
fluctuations in a range that prevents symptomatic hyper- and
Complications of insulin treatment:
Hypoglycemia occurs because of an
error in insulin dosage, a small or missed meal, or unplanned exercise
(patients are usually instructed to reduce their insulin dose or to
increase their carbohydrate intake before planned exercise) or without
apparent cause. Patients are taught to recognize symptoms of
hypoglycemia, which usually respond rapidly to the ingestion of sugar.
All diabetics should carry candy, lumps of sugar, or glucose tablets. An
identification card, bracelet, or necklace indicating that the patient
is an insulin-treated diabetic aids in recognizing hypoglycemia in
emergencies. Close family members should be instructed to administer
glucagon with an easy-to-use injection device. Emergency medical
personnel, after confirming the hypoglycemia with a glucostick, should
initiate therapy with a rapid bolus injection of 25 mL of 50% glucose
solution followed by a continuous IV infusion of glucose.
refers to the normal tendency of the plasma glucose to rise in the early
morning hours before breakfast, which is frequently exaggerated in
patients with type I DM and in some patients with type II DM. Fasting
glucose levels rise because of an increase in hepatic glucose
production, which may be secondary to the midnight surge of growth
hormone. In some patients with type I DM, nocturnal hypoglycemia may be
followed by a marked increase in fasting plasma glucose with an increase
in plasma ketones
(Somogyi phenomenon). Thus, both the
dawn and Somogyi phenomena are characterized by morning hyperglycemia,
but the latter is due to rebound (counter regulation) hyperglycemia. The
frequency with which the latter phenomenon actually occurs is disputed.
When it is suspected, the patient should wake between 2 and 4 am to
monitor blood glucose levels. If intermediate insulin is administered at
bedtime, the dawn and Somogyi phenomena can often be prevented.
allergic reactions at the site of
insulin injections are less common with purified porcine and human
insulins. These reactions can produce immediate pain and burning,
followed after several hours by local erythema, pruritus, and induration,
the latter sometimes persisting for days. Most reactions spontaneously
disappear after weeks of continued insulin injection and require no
specific treatment, although antihistamines are sometimes used.
Generalized insulin allergy (usually
to the insulin molecule) is rare but can occur when treatment is
discontinued and restarted after a lapse of months or years. Such
reactions may occur with any type of insulin, including human
biosynthetic insulin. Symptoms usually develop shortly after an
injection and may include urticaria, angioedema, pruritus, bronchospasm,
and, in some cases, circulatory collapse. Treatment with antihistamines
may suffice, but epinephrine and IV glucocorticoids may be required. If
continued insulin treatment is required after the condition stabilizes,
skin testing with a panel of purified insulin preparations and
desensitization should be performed by an experienced physician.
resistance is an increase in insulin
requirement to ≥ 200 U/day and is associated
with marked increases in the plasma insulin-binding capacity. Most
patients treated with insulin for > 6 mo develop antibodies to insulin.
The relative antigenicity of purified insulin preparations is bovine >
porcine > human, but genetic factors also affect individual response.
Circulating insulin-binding antibodies can modify the pharmacokinetics
of free insulin, but treatment usually is not adversely affected. In
patients with insulin resistance, switching to purified porcine or human
insulin may lower the requirement. Remission may be spontaneous or may
be induced in some type II DM patients who can stop insulin treatment
for 1 to 3 mo. Prednisone may decrease insulin requirements within 2 wk;
treatment is usually initiated with about 30 mg bid and is tapered as
the requirements decrease.
fat atrophy or hypertrophy at
injection sites is relatively rare and usually improves by switching to
human insulin and injecting it directly into the affected area. No
specific treatment of local fat hypertrophy is required, but injection
sites should be rotated.
Oral antidiabetic drugs:
These drugs are used for type II DM but not for
type I DM because they cannot prevent symptomatic hyperglycemia or DKA
in such patients. Oral hypoglycemic drugs are the sulfonylureas. Oral
antihyperglycemic drugs are the biguanides, the -glucosidase inhibitors, and the
insulin sensitizers (thiazolidinediones ["glitazones"]).
The sulfonylureas lower plasma glucose primarily
by stimulating insulin secretion. Secondary effects on improving
peripheral and hepatic insulin sensitivity may be due to the decrease in
both glucose toxicity and insulin clearance. Sulfonylureas differ in
potency and duration of action. All of the sulfonylureas are metabolized
in the liver, but only tolbutamide and tolazamide are inactivated
exclusively by the liver. About 30% of chlorpropamide is normally
excreted in the urine, and the principal hepatic metabolite of
acetohexamide is highly active and excreted in urine; both drugs carry
an increased risk of prolonged hypoglycemia in patients with impaired
renal function and in the elderly. The 2nd-generation sulfonylureas
(such as glipizide and glyburide) are about 100 times more potent than
the 1st-generation ones, are absorbed rapidly, and are metabolized
mainly in the liver. Clinically, the 2nd-generation sulfonylureas are
similar in effectiveness.
Allergic reactions and other side effects
(e.g., cholestatic jaundice) are relatively uncommon. Acetohexamide may
be used in patients who are allergic to other sulfonylureas.
Chlorpropamide and acetohexamide should not be used in patients with
impaired renal function. In addition, chlorpropamide should not be used
in elderly patients, because it can potentiate the action of
antidiuretic hormone, often leading to hyponatremia and deterioration in
mental status, which in an elderly patient may often not be recognized
as a drug-induced effect.
initial treatment, many
authorities prefer the shorter-acting sulfonylureas, and most do not
recommend using a combination of different sulfonylureas. Treatment is
started with a low dose, which is adjusted after several days until a
satisfactory response is obtained or the maximum recommended dosage is
reached. About 10 to 20% of patients fail to respond to a trial of
treatment (primary failures), and patients who fail to respond to one
sulfonylurea often fail to respond to others. Of patients who initially
respond, 5 to 10% per year experience secondary failures. In such cases,
insulin may be added to sulfonylurea treatment.
Hypoglycemia is the most important complication of
sulfonylurea treatment. Hypoglycemia can occur in patients treated with
any of the sulfonylureas but occurs most frequently with long-acting
ones (glyburide, chlorpropamide). Sulfonylurea-induced hypoglycemia can
be severe and may last or recur for days after treatment is stopped,
even when it occurs in patients treated with tolbutamide, whose usual
duration of action is 6 to 12 h. A mortality rate of 4.3% in patients
hospitalized with sulfonylurea-induced hypoglycemia has been reported
recently. Therefore, all sulfonylurea-treated patients who develop
hypoglycemia should be hospitalized, because even if they respond
rapidly to initial treatment for hypoglycemia, they must be closely
monitored for 2 to 3 days. Most of these patients may not require
further treatment with sulfonylureas.
has been used as primary therapy in type II DM patients for over 30
years in most of the world. It has been recently approved for use in the
USA. It acts by decreasing hepatic glucose production and may improve
insulin sensitivity in those who lose weight. It is as effective as a
sulfonylurea as monotherapy (when used alone it rarely causes
hypoglycemia) and is synergistic in combination with sulfonylurea
therapy. Metformin also promotes weight loss and decreases lipid levels.
Unlike phenformin, metformin rarely causes severe lactic acidosis. GI
side effects are common, but often transient, and may be prevented if
the drug is taken with meals and if the dosage is gradually increased
(by 500 mg/wk up to 2.5 g). Metformin is contraindicated in patients
with kidney and liver diseases or alcoholism. It is also contraindicated
in patients with lactic acidosis and should be withheld during acute
hospitalization in most patients.
Acarbose is an -glucosidase
inhibitor that competitively inhibits
hydrolysis of oligo- and monosaccharides. This delays carbohydrate
digestion in the small intestine and subsequent absorption, resulting in
less postprandial elevation of blood glucose levels. Because its
mechanism of action differs from that of other oral hypoglycemics, it
can be used in combination therapy with other oral agents. GI side
effects are very common, but often transient. The drug must be taken
with meals, and the dosage should be gradually increased from 25 mg up
to 50 to 100 mg with each meal.
Thiazolidinediones are the
insulin-sensitizer drugs that improve insulin sensitivity in skeletal
muscle and suppress hepatic glucose output. The only such drug available
in the USA is troglitazone. It has been recently approved for use in the
treatment of type II DM patients requiring insulin and has moderate
effects on decreasing plasma glucose and triglyceride levels. This drug
is administered once a day and has potentially idiosyncratic
hepatotoxicity. Patients should be instructed to decrease their daily
insulin dosage with the initiation of therapy.
Diabetes Management during
Diabetic patients admitted to hospitals commonly
have coexisting illnesses that aggravate hyperglycemia, such as an
infection or coronary artery disease. Bed rest and a regular diet may
also aggravate hyperglycemia. Conversely, if the patient is anorectic or
vomits, or if food intake is reduced, continuation of drugs may cause
hypoglycemia. The popular insulin coverage with a sliding scale for
insulin administration should not be the only intervention, because it
is reactive rather than proactive in correcting hyperglycemia. It may
also be inappropriately used when hyperglycemia reflects hepatic
gluconeogenesis in response to previously uncorrected hypoglycemia.
Hospitalized type II DM patients often do well
without any change in drugs. Hypoglycemic drugs may be discontinued
during an acute condition associated with decreased food intake or one
that has a tendency to cause hypoglycemia. Insulin may be added if
plasma glucose levels remain high.
In type I DM patients, intermediate (NPH or Lente)
insulin should be continued at 50 to 70% of the daily dose divided bid
or tid. Supplemental regular insulin can be given on a sliding scale. In
patients receiving total or partial parenteral nutrition, hyperglycemia
may be treated with a continuous IV infusion of insulin or divided doses
of intermediate-acting insulin. Blood glucose should be measured four
times a day before meals.
Diabetes Management during
Surgical procedures (including the prior emotional
stress, the effects of general anesthesia, and the trauma of the
procedure) can markedly increase plasma glucose in diabetics and induce
DKA in type I DM patients. In patients who normally take one or two
daily injections of insulin, 1/3 to 1/2 of the usual morning dose can be
given in the morning before the operation and an IV infusion of 5%
glucose in either 0.9% sodium chloride solution or water at a rate of 1
L (50 g of glucose) over 6 to 8 h started. After the operation, plasma
glucose and the plasma reaction for ketones are checked. Unless a change
in dosage is indicated, the preoperative dose of insulin is repeated
when the patient has recovered from the anesthesia and the glucose
infusion is continued. Plasma glucose and ketones are monitored at 2- to
4-h intervals, and regular insulin is given q 4 to 6 h as needed to
maintain the plasma glucose level between 100 and 250 mg/dL (5.55 and
13.88 mmol/L). This is continued until the patient can be switched to
oral feedings and a one- or two-dose insulin schedule.
Some physicians prefer to withhold subcutaneous
insulin on the day of the operation and to add 6 to 10 U of regular
insulin to 1 L of 5% glucose in 0.9% sodium chloride solution or water
infused initially at 150 mL/h on the morning of the operation based on
the plasma glucose level. This is continued through recovery, with
insulin adjusted based on the plasma glucose levels obtained in the
recovery room and at 2- to 4-h intervals thereafter.
Insulin is not required for diabetics who have
maintained a satisfactory plasma glucose level by diet alone or in
combination with a sulfonylurea before the operation. Sulfonylureas
should be withheld 2 to 4 days before the operation, and plasma glucose
levels should be measured pre- and postoperatively and q 6 h while
patients receive IV fluids.
Diabetes Mellitus is a chronic disease that requires long-term therapy
for successful long-term management. Much akin to hypertension control
over blood pressure and obesity management, it has become clear that
maintenance therapy is important for long-term success with the DM
patient until all food sensitivities have been
eliminated and the patient's own natural system regulation again returns
to normal. This is not always achievable
but more and more research say's its probable for many. Thus reevaluation with their primary care physician or chronic
evaluation ensures the most “spot on” immediate understanding of base
line data and allows flexibility for the patient while offering the
greatest protection against end organ disease, multiple system disease,
and best chance to improve and reverse disease in mild cases. Patients
must regain control over their unconscious health habits which will
reduce or prevent hypertension, obesity, and adult onset related
disease. For those with Diabetes Mellitus, it is now clear that these
very same health habits will help the patient control their disease,
reduce detrimental effects and improve the patients overall life
after the initial treatment plan duration return for Chronic Evaluation
has been proved by the evidence to help the patient maintain their
glucose control, for the best life one can experience while combating
their Diabetes Mellitus.
- Sloane, Philip D et al, Essentials of Family Medicine, 4th
Edition, Lippincott-Williams & Wilkins, pages 453-470
- Andreoli Thomas E et al, Cecil Essentials of Medicine, 4th
Saunders, pages 513-523.
- Kasper Dennis L et al, Harrison’s Principles of Internal Medicine,
16th edition, Mc Graw Hill, pages 2152-2180
- Beers, Mark H et al, The Merc Manual of Diagnosis and Therapy, 17th
Edition, Merck Research Laboratories, pages 165-177
- Brunton Laurence L et al, Goodman & Gilman’s The Pharmacological
Basis of Therapeutics, 11th edition, Mcgraw-Hill, pages
By The Little Guy
October 6th, 2006
"The most acceptable service to God is doing
good to man" Ben