Definition

Diabetes Mellitus (DM) is a heterogeneous clinical syndrome marked elevation of blood glucose level
(hyperglycemia) chronicles a result deficiency insulin, relative or absolute, and / or
hiperglukagonemia. Due to insulin deficiency will interference arising in carbohydrate metabolism
(carbohydrate substance, KH), fat and protein

Clasifikation 
According to the PB. PERKENI (2002), based on the DM can etiology classified as follows:
1. Type 1 DM 
Type 1 DM caused destructs beta cells, generally to insulin deficiency absolute and can be autoimmune
or idiopathic
2. Type 2 DM 
Type 2 DM have type vary, particularly dominant start of insulin resistance with relative insulin
deficiency, until a particularly defek sekresi insulin with insulin resistance.
3. DM Type Other 
Other Type of DM may be a genetic defek beta cell function, insulin defek genetic work, exocrine
pancreas disease, endokrinopati, because drugs or chemical substances, infection, immunology for a
rare, genetic syndrome or other related to the DM.
4. DM Gestational 
DM Gestational glucose tolerance is a disturbance of various degrees
found at the time of first pregnancy, without discriminating whether sufferer 
need insulin therapy or not.

Diagnosis 
According to the PB. PERKENI (2002), diagnostic criteria of DM and glucose Disturbance Tolerance is as
follows:
1. When blood glucose level (plasma vena) ≥ 200 mg / dl
2. Fasting blood glucose value (plasma vena) ≥ 126 mg / dl
3. Measure plasma glucose ≥ 200 mg / dl at 2 hours post-glucose loading
75 grams on Tolerance Test Oral glucose (TTGO).

Diagnostic criteria should be re-confirmed on the other, except for special circumstances
hyperglycemia with dekompensasi metabolic weight, such as ketoasidosis, and the classic symptoms:
poliuri, polidipsi, polifagi and body weight decreased rapidly.

The incidence of diabetes is on the rise, in both the developed

and developing worlds. Klaus Dugi, Professor of Medicine at
the University of Heidelberg, Germany, discusses the causes,
symptoms and treatment of diabetes.
 
 Structure of insulin
 
Translated from ancient Greek, diabetes mellitus means ‘honey sweet flow’ and stems from a
time in which tasting a patient’s urine was still part of the physician’s diagnostic repertoire.  By
the sweet taste of the urine, diabetes mellitus could be distinguished from diabetes insipidus,
another disease with increased urinary output.  The term diabetes mellitus covers several disease
states with underlying causes that are characterized by an abnormal increase in blood sugar
(glucose) levels.
 
Classification
In 1997, the World Health Organization and the American Diabetes Association agreed on a new
classification for diabetes mellitus.  The most frequent diabetes forms are Type 1 diabetes and
Type 2 diabetes.  Type 1 diabetes typically manifests during childhood or adolescence, but it has
recently become apparent that adults can also develop this form, in some cases as late as in their
forties or fifties.  Type 2 diabetes is mainly a disease of the elderly, but as rates of obesity
increase, more and more young adults, and even adolescents, are being diagnosed with this form
of the disease.  Other forms of diabetes include gestational diabetes (pregnancy diabetes),
diabetes after operative resection of the pancreas, and rare forms of genetic diabetes.
 
Epidemiology
About 90% of patients with diabetes mellitus have Type 2 diabetes.  An estimated 150 million
people worldwide have Type 2 diabetes, and this number is expected to double within the next
20 years.  Most of the increase will stem from developing and threshold countries such as India
and China. In the USA, where the prevalence of diabetes is high, it is estimated that one in three
people will develop Type 2 diabetes.
 
Pathophysiology.  Normal situation
The body derives glucose from several sources.  Firstly, it is taken up from food in the gut, either
directly as glucose or after more complex carbohydrates have been digested into glucose and
other simple sugars.  Secondly, glucose is synthesized from other energy sources, mainly in the
liver, in a process known as gluconeogenesis.  Thirdly, glucose is stored in the liver, muscles,
and other tissues in the form of glycogen.  On demand, glycogen is broken down into glucose
and secreted into the bloodstream.  Glucose is transported via the blood, whence it is absorbed by
tissues needing glucose.  After a meal, about 80% of the uptake of blood sugar is by muscle
cells.  During fasting, however, over 50% of glucose uptake is by the brain.  This imbalance is
probably because the sole source of energy for the brain is glucose , and the body needs to
safeguard the brain’s glucose supply.  If the blood sugar level falls too low (hypoglycaemia), the
brain malfunctions, causing such symptoms as lack of concentration, dizziness and faintness, or,
in severe cases, convulsions, coma and death.
 
The processes of glucose uptake and release are tightly regulated by hormones.  The most
important hormone is insulin, because it is the only hormone that can lower blood sugar levels.
Insulin is synthesised and secreted only in the beta or islet cells of the pancreas. It lowers the
blood glucose level by facilitating the uptake of glucose from blood by all cell types, reducing
gluconeogenesis, and encouraging the storage of glucose in the form of glycogen.  Several other
hormones, such as adrenaline, glucagon, thyroid hormone and growth hormone, are involved in
increasing the blood sugar level.
 
 Glucose regulation
 
Insulin resistance
The vast majority of patients with Type 2 diabetes or pre-diabetes are characterised by insulin
resistance.  Despite normal or even elevated blood levels of insulin, insulin has less effect than in
normal individuals.  Peripheral insulin resistance means that insulin is less effective at mediating
the uptake of blood glucose by muscle cells.  In the liver, insulin fails to suppress the production
of new glucose and the breakdown of glycogen.  Thus, insulin resistance tips the glucose
homeostasis towards high blood sugar levels (hyperglycaemia).
 
Type 1 diabetes
Type 1 diabetes is an autoimmune disease.  In genetically susceptible individuals, an
inflammation of pancreatic beta cells is triggered, most likely by a viral infection.  Because beta
cells are the only ones able to produce and secrete insulin, complete insulin deficiency ensues.
As a result, all Type 1 diabetic patients require insulin replacement therapy.  The only exception
is during the ‘honeymoon period’ that some patients experience shortly after diagnosis and initial
treatment, owing to some residual insulin secretion early in the progress of the disease.
 
Type 2 diabetes
Type 2 diabetes is a prime example of a disease caused by a combination of genetic and
environmental factors.  The genetic influence is greater than for Type 1 diabetes: the identical
twin of a Type 2 diabetic patient is almost certain to develop the disease.  On the other hand,
lifestyle factors such as diet and exercise are also important determinants; in times of scarce food
supply, for instance, the incidence of Type 2 diabetes is very low.
 

Structure of the pancreas

 
A good example of the interplay of genetics and lifestyle are the Pima Indians.  Those living in
Mexico have a diabetes prevalence of about 8%, whereas those who have emigrated to the USA,
where the lifestyle is more sedentary and access to energy dense (fatty) food is easier, have a
diabetes prevalence of about 50%.  The most important risk factor for Type 2 diabetes is
obesity.  Epidemiological studies have shown that, compared to lean individuals, very obese men
and women (body mass index >35) have a 60- and 90- fold increased probability of developing
Type 2 diabetes, respectively (see figure).
 
 Incidence of diabetes among Pima Indians: gene-environment interaction
 
In terms of genetics, Type 2 diabetes is a multifactorial disease for which no single gene is
responsible. In contrast to patients with overt Type 2 diabetes, patients with pre-diabetes
(characterised by insulin resistance) do not exhibit hyperglycaemia when fasting.  However, after
a challenge like an oral glucose tolerance test (oGTT), during which 75 grams of glucose are
ingested, patients exhibit pathologically high glucose levels (see Table 1).
 

Table 1: Diagnostic criteria for Type 2 diabetes

 
These patients, therefore, are characterised as having impaired glucose tolerance.  For a limited
period, pancreatic beta cells are able to produce enough insulin to overcome the insulin
resistance, so many pre-diabetic patients actually have elevated plasma insulin levels.  However,
in most patients, the rate of beta-cell death exceeds that of beta-cell formation in the
pancreas, resulting in fewer insulin-producing beta cells.  When the insulin-producing capacity
of the pancreas is overtakenby the increased demand caused by insulin resistance, the patient
develops overt Type 2 diabetes.
 
Three main factors contribute to hyperglycaemia:
1. Insulin resistance in the muscle tissue, causing the muscles to take up less glucose from the
blood.
2. Impaired insulin secretion by the pancreas.
3. Increased glucose production by the liver as a consequence of hepatic insulin resistance.  In
the last few years, it has been demonstrated that adipose (fat) tissue and the central nervous
system also play important roles in the pathogenesis of Type 2 diabetes.
 
Diagnosis.  Symptoms
Unspecific early symptoms of diabetes include fatigue, a lack of general well-being, or an
increased tendency towards infections, e.g. bladder infections.  When hyperglycaemia becomes
more pronounced, patients lose glucose via the urine, and produce more urine.  This leads to the
symptoms of overt diabetes, which are typically the initial symptoms of Type 1 diabetes:
increased frequency of urination leading to increased thirst, and subsequently to dehydration and
weight loss.
 
Screening
In the early stages of Type 2 diabetes, patients have few or no symptoms, and often go
undiagnosed for many years.  Unfortunately, diabetic complications (see below) frequently
develop during this time.  Therefore, it is important to screen those at risk of developing Type 2
diabetes, such as obese people, those with a family history of diabetes, and women who
previously experienced gestational diabetes.  Screening can be done either by measuring the
blood glucose levels while the individual is fasting, or by performing an oGTT (see above).  The
most important criteria for diagnosing diabetes are shown in Table 1.  The most important
measure for monitoring the course of diabetes is glycosylated haemoglobin (HbA1c).  The higher
the blood glucose value over time, the more non-enzymatic glycosylation of haemoglobin will
occur.  Because haemoglobin is transported in red blood cells, which have a mean lifespan of
about 120 days, the HbA1c value is a reflection of the glucose control over the previous three
months.  In most assays, an HbA1c value of <6.1% is considered normal.  The target value for
diabetic patients is an HbA1c of <7.0%, or even <6.5%.
 
Treatment
The basis of diabetes treatment is educating patients about the pathogenesis of the disease,
diabetic complications, dietary and drug treatment, and other aspects of the disease.  All diabetic
patients need to be instructed about the appropriate diet and exercise, and the necessity, in most
cases, of losing weight.  Those Type 2 diabetic patients who manage to radically change their
lifestyle and lose significant amounts of weight have a very good chance of ridding themselves
of the disease.  Unfortunately, only a very small minority of patients manage this.  If the HbA1c
value stays above 7.0% despite improved diet and exercise, drug treatment is warranted.  Several
oral anti-diabetic drugs are currently on the market which target different causes of
hyperglycaemia.  Metformin reduces hepatic glucose output, sulfonylurea drugs increase
pancreatic insulin secretion, and the glitazones reduce peripheral insulin resistance.
 
If the HbA1c value stays above 7.0% despite treatment with several oral anti-diabetic drugs,
insulin therapy is indicated.  The first step is often to treat with long-acting insulin at bedtime. 
Eventually, many Type 2 diabetic patients will, like Type 1 diabetic patients, require full insulin
therapy.  This will be either a fixed twice-daily regimen of mixed insulin containing a short-
acting and a long acting insulin, or an intensive regimen with injection of a long-acting insulin at
bedtime and/or in the morning, and injections of short-acting insulin with meals.  Insulin dose
and food intake must be closely matched to prevent either hyper- or hypoglycaemia.  Due to the
high risk of cardiovascular problems (see below), it is important to treat not only the glucose
disturbances, but also other risk factors of cardiovascular disease such as high blood pressure and
high cholesterol levels.
 
Complications
Due to a high frequency of complications, diabetes significantly reduces life expectancy. 
Because of complications with the small blood vessels (microvascular disease), Type 2 diabetes
is currently the most frequent cause of adult-onset loss of vision (diabetic retinopathy), renal
failure (diabetic nephropathy), and amputation (diabetic foot) in the industrialised world.  The
most frequent microvascular complication is diabetic neuropathy, usually a disease of the distal
sensory nerves, which impairs the perception of vibration, temperature, and pain in feet and
hands.  In later stages, diabetic neuropathy can be characterised by severe pain.  In addition,
Type 2 diabetes is associated with complications of the large blood vessels (macrovascular
disease), and a two- to five-fold increased risk of cardiovascular disease, mainly myocardial
infarctions (heart attack) and strokes.
 
Outlook
New application methods of insulin – inhaled and oral – are currently being tested in clinical
trials, along with drugs with improved efficacy and reduced side-effect profiles.  More important,
however, would be preventive measures to tackle the worldwide increase in obesity and diabetes,
especially in developing countries in which most of the predicted new cases of diabetes will
occur.
 

Obesity as a risk factor for Type 2 diabetes: relative risk for Type 2 diabetes (age corrected)
 

This article is suitable for updating secondary school biology teachers on diabetes mellitus, an
issue of general interest and social relevance.  This disease is becoming more and more common
in industrialised countries and even in developing countries.  The text, which is divided into
paragraphs to make information retrieval easy, takes into account every aspect of the disease, is
written in a plain style, and explains technical terms clearly.  I recommend the use of this
material for the teacher as a basis for classroom activities on human physiology and health
education.  Upper secondary school students would also benefit from using the article as a source
of information to work autonomously.

Insulin Resistance
 Insulin Resistance and the Metabolic Syndrome

For a type 2 diabetic the term “insulin resistance” in and of itself does not mean that
your pancreas doesn’t make enough insulin (as is the case with type  1 diabetics). It means
that, for some reason, your body’s cells aren’t able to make use of the insulin that your
pancreas secretes. In fact, if you are insulin resistant, your pancreas is very likely
secreting too much insulin in an attempt to overcome your cells’ resistance. This over-
supply of insulin is what causes the problem we’ll talk about below, the Metabolic
Syndrome orSyndrome X.

What is the primary cause of insulin resistance? There are several hypotheses. Each
hypothesis is based on different premises. One hypothesis (see path #  1 in the diagram
above) is called resistin-mediated insulin resistance . This idea was put forth by Dr.
Mitchell Lazar, an endocrinologist at the University of Pennsylvania, in the journal Nature
in January of 2001. Dr. Lazar and his team discovered a hormone they call resistin which
is produced by the fat cells that make up intra-abdominal fat (not the fat cells of
subcutaneous fat). Like insulin, resistin is probably necessary for the body’s well-being in
small amounts – organisms usually have a constructive use for everything they make. But
too much intra-abdominal fat means too much resistin. The excess resistin seems to
prevent insulin from binding to cell membranes (the “skin” around each cell). It may do
this by attaching to the same receptor molecules on the cell membrane that insulin is
supposed to attach to. Since the cell can’t bind enough insulin to its membrane, glucose
can’t enter the cell in sufficient amounts and the excluded glucose accumulates in the
blood. This causes your blood sugar to start creeping up. You start to develop the
condition that doctors call “impaired glucose tolerance’” or – a more popular term now –
“prediabetes.” This hypothesis, production (or over-production) of the
hormone resistin by intra-abdominal fat cells, is indicated by the pathway marked
number 1 in the diagram above.

Another hypothesis is called  free fatty acid (FFA)-mediated insulin resistance ,

and this one is under investigation in many laboratories right now. (See path # 2 in the
diagram above). This hypothesis states that insulin resistance is the direct result of too
many free fatty acids (FFAs) that have been released into the bloodstream by masses of
excessive intra-abdominal fat. It appears that, in our muscles, FFAs interfere with
insulin metabolism by putting an extra phosphorous molecule on a substance called
insulin receptor substrate 1 (IRS1). When IRS1 is phosphorylated it can’t bind insulin to a
muscle cell’s membrane and the cell is then insulin resistant and it can’t get enough
glucose to supply the energy it needs. High blood sugar levels are due, for the most part, to
the inability of muscle cells to take in glucose. You can see that IRS1 is very important.
FFAs also go to the liver and, by interfering with insulin metabolism there, cause that
organ to spew too much glucose into the blood, again raising blood glucose levels. In the
pancreas, FFAs cause the B-cells (the ones that secrete insulin) to over-secrete. So, all
together, a person's blood sugar and insulin levels will climb. In people who have type
2 diabetes, high serum levels of FFAs seem to account for 50% of their insulin
resistance. The hormone resistin, also produced by intra-abdominal fat, may
account for much of the other half.

The Metabolic Syndrome (Syndrome X)

The condition I call Syndrome X is also referred to as the Metabolic Syndrome. In

medical parlance, a “syndrome” (SIN-drum) is a related collection of symptoms or diseases
that usually occur together. A person with Syndrome X may have hypertension (high blood
pressure), high triglycerides, high cholesterol, gout, liver spots (“age spots”) and benign
skin tumors (“skin tags”) and insulin resistance – all at the same time! Many indicators
point to a prolonged prior period of high insulin levels (hyperinsulinemia) as the
underlying cause of Syndrome X.
          Syndrome X was discovered and named by Dr. Charles Reaven of Stanford
University in 1988. After hyperinsulinemia was identified as the causal factor, it was
renamed the Metabolic Syndrome. By whatever name it’s called, Syndrome X is a
deadly condition. If no remedial steps are taken, it will almost certainly progress
into Type 2 diabetes.

          Just as high blood insulin levels are known to precede Syndrome X, so is obesity

(excess amounts of intra-abdominal fat) known to precede hyperinsulinemia. There is a
chain of causation that stretches unbroken from our sedentary, overfed lifestyle to obesity
to hyperinsulinemia to Syndrome X to Type 2 diabetes and finally to heart disease and
stroke. If an afflicted person is to survive, he or she must break this pernicious chain and
the place to start is at the beginning: excess intra-abdominal fat. That is what getting back
to the pre-industrial lifestyle I mentioned earlier may help you to accomplish.

Jakarta, 29 Dec 2009

Insulin resistance
INSULIN RESISTANCE 

Introduction 
What is it?

Insulin resistance (IR) is the condition in which normal amounts of insulin are inadequate to produce a normal insulin
response from fat, muscle and liver cells. Insulin resistance in fat cells reduces the effects of insulin and results in elevated
hydrolysis of stored triglycerides in the absence of measures which either increase insulin sensitivity or which provide
additional insulin. Increased mobilization of stored lipids in these cells elevates free fatty acids in the blood plasma. Insulin
resistance in muscle cells reduces glucose uptake (and so local storage of glucose as glycogen), whereas insulin resistance
in liver cells results in impaired glycogen synthesis and a failure to suppress glucose production. Elevated blood fatty-acid
concentrations (associated with insulin resistance and diabetes mellitus Type 2), reduced muscle glucose uptake, and
increased liver glucose production all contribute to elevated blood glucose concentration. Unlike type 1 diabetes mellitus,
insulin resistance is generally "post-receptor", meaning it is a problem with the cells that respond to insulin rather than a
problem with the production of insulin. High plasma levels of insulin and glucose due to insulin resistance are believed to be
the origin of metabolic syndrome and type 2 diabetes, including its complications.

What cause it?

There are several conditions causing insulin resistance.

Pathophysiology

In a person with normal metabolism, insulin is released from the beta (ß) cells of the Islets of Langerhans located in the
pancreas after eating ("postprandial"), and it signals insulin-sensitive tissues in the body (e.g., muscle, adipose) to absorb
glucose. This lowers blood glucose levels. The beta cells reduce their insulin output as blood glucose levels fall, with the
result that blood glucose is maintained at approximately 5 mmol/L (mM) (90 mg/dL). In an insulin-resistant person, normal
levels of insulin do not have the same effect on muscle and adipose cells, with the result that glucose levels stay higher
than normal. To compensate for this, the pancreas in an insulin-resistant individual is stimulated to release more insulin.
The elevated insulin levels have additional effects (see insulin) which cause further biological effects throughout the body.

The most common type of insulin resistance is associated with a collection of symptoms known as metabolic syndrome.
Insulin resistance can progress to full Type 2 diabetes mellitus (T2DM). This is often seen when hyperglycemia develops
after a meal, when pancreatic ß-cells are unable to produce sufficient insulin to maintain normal blood sugar levels
(euglycemia). The inability of the ß-cells to produce sufficient insulin in a condition of hyperglycemia is what characterizes
the transition from insulin resistance to Type 2 diabetes mellitus. [1]

Various disease states make the body tissues more resistant to the actions of insulin. Examples include infection (mediated
by the cytokine TNFa) and acidosis. Recent research is investigating the roles of adipokines (the cytokines produced by
adipose tissue) in insulin resistance. Certain drugs may also be associated with insulin resistance (e.g., glucocorticoids).

Insulin itself can lead to insulin resistance; every time a cell is exposed to insulin, the production of GLUT4 (type four
glucose receptors) on the cell's membrane is decreased. [2] This leads to a greater need for insulin, which again leads to
fewer glucose receptors. Exercise reverses this process in muscle tissue, [3] but if left unchecked, it can spiral into insulin
resistance.

Elevated blood levels of glucose — regardless of cause — leads to increased glycation of proteins with changes (only a few
of which are understood in any detail) in protein function throughout the body.

Insulin resistance is often found in people with visceral adiposity (i.e., a high degree of fatty tissue underneath the
abdominal muscle wall - as distinct from subcutaneous adiposity or fat between the skin and the muscle wall, especially
elsewhere on the body, such as hips or thighs), hypertension, hyperglycemia and dyslipidemia involving elevated
triglycerides, small dense low-density lipoprotein (sdLDL) particles, and decreased HDL cholesterol levels. With respect to
visceral adiposity, a great deal of evidence suggests two strong links with insulin resistance. First, unlike subcutaneous
adipose tissue, visceral adipose cells produce significant amounts of proinflammatory cytokines such as tumor necrosis
factor-alpha (TNF-a), and Interleukins-1 and -6, etc. In numerous experimental models, these proinflammatory cytokines
profoundly disrupt normal insulin action in fat and muscle cells, and may be a major factor in causing the whole-body insulin
resistance observed in patients with visceral adiposity. A great deal of attention into the production of proinflammatory
cytokines has focused on the IKK-beta/NF-kappa-B pathway, a protein network that enhances transcription of cytokine
genes. Second, visceral adiposity is related to an accumulation of fat in the liver, a condition known as nonalcoholic fatty
liver disease (NAFLD). The result of NAFLD is an excessive release of free fatty acids into the bloodstream (due to increased
lipolysis), and an increase in hepatic glucose production, both of which have the effect of exacerbating peripheral insulin
resistance and increasing the likelihood of Type 2 diabetes mellitus. [4]

Insulin resistance is also often associated with a hypercoagulable state (impaired fibrinolysis) and increased inflammatory
cytokine levels.

Insulin resistance is also occasionally found in patients who use insulin. In this case, the production of antibodies against
insulin leads to lower-than-expected glucose level reductions (glycemia) after a specific dose of insulin. With the
development of human insulin and analogues in the 1980s and the decline in the use of animal insulins (e.g., pork, beef),
this type of insulin resistance has become uncommon.

Magnesium (Mg) is present in living cells and its plasma concentration is remarkably constant in healthy subjects. Plasma
and intracellular Mg concentrations are tightly regulated by several factors. Among them, insulin seems to be one of the
most important. In vitro and in vivo studies have demonstrated that insulin may modulate the shift of Mg from extracellular
to intracellular space. Intracellular Mg concentration has also been shown to be effective in modulating insulin action
(mainly oxidative glucose metabolism), offset calcium-related excitation-contraction coupling, and decrease smooth cell
responsiveness to depolarizing stimuli. Poor intracellular Mg concentrations, as found in Type 2 diabetes mellitus and in
hypertensive patients, may result in a defective tyrosine-kinase activity at the insulin receptor level and exaggerated
intracellular calcium concentration. Both events are responsible for the impairment in insulin action and a worsening of
insulin resistance in noninsulin-dependent diabetic and hypertensive patients. By contrast, in T2DM patients daily Mg
administration, restoring a more appropriate intracellular Mg concentration, contributes to improve insulin-mediated glucose
uptake. The benefits deriving- from daily Mg supplementation in T2DM patients are further supported by epidemiological
studies showing that high daily Mg intake are predictive of a lower incidence of T2DM. [5,6]

How to detect/ measure insulin resistance?

Serum insulin  concentration is seldom measured in clinical practice. For research purposes, there are various methods of
measurement. Among others, the simplest ways of detecting insulin resistance are as follows [7] :

1.HOMA (homeostatic model assessment), using formula:

                  Io x Go
                    405
                   where

 Io =fasting insulin level ( µU/ml)

 Go=fasting glucose level (mg/dl)
 Normal value 100%
        

2.G/I ratio.  Ratio < 4.5 indicates the presence of  IR

3.Fasting serum insulin (Io). Normal upper limit of fasting serum insulin is 60 pmol/L or 8.6  µU/ml. 
Concentration above  20 µU/ml confirms the presence of  IR
ACUTE INSULIN RESISTANCE
Insulin resistance that occurs in chronic diseases, such as Type 2 diabetes, obesity and
hypertension, normally takes months, years or even decades to develop. Hyperglycemia and insulin
resistance in critically ill patients is characterized by rapid onset, developing in minutes, hours or days,
and is thus termed acute insulin resistance. [8] Major Surgical stress/trauma, sepsis and inflammation as
well as acute stroke may result in acute insulin resistance. Therefore, it is not suprising to observe
hyperglycemia in patients with those conditions without history of pre-existing  diabetes.

Insulin resistance as a marker of surgical stress

Elective surgery causes a marked transient reduction in insulin sensitivity. The degree of the reduction is
related to the magnitude of the operation and type of anaesthesia/ analgesia. It is not clear which
mediators are the most important for the development of IR after surgery. Nevertheless, marked insulin
resistance can develop after elective surgery without concomitant elevations in cortisol, cathecolamines
or glucagon. The main sites for insulin resistance seem to be extrahepatic tissues, probably skeletal
muscle, where preliminary data suggest that glucose transporting system is involved. [9]
A novel approach to minimise insulin resistance after surgery suggests that simply pretreating patient
with sufficient amounts of carbohydrates orally or parenterally instead of fasting can significantly reduce
postoperative insulin resistance.  In addition, postoperatively, provision of  400-600 kcal per day for first
few days (1000-1500 ml glucose and amino acids containing maintenance solutions, such as Aminofluid) 
seems to be a logical approach.