Download Diabetes mellitus, an overview

Diabetes mellitus, an overview
By Erik Hagman, MD, Family Physician
I have chosen diabetes mellitus (DM) as the topic for today’s lecture, with an emphasis on
type-1 diabetes, as this seems to be a less well known disease entity in these quarters. But as
we all know, we recently lost two patients in this hospital, due to diabetic keto-acidosis and
coma, which is the most feared and disastrous acute complication of type-1 DM. Their lives
might have been spared, had only insulin and potassium for i.v. use been available. But they
were not.
DM is an important disease. It has been calculated that world-wide, close to 300 mios of
people are afflicted with diabetes, and the number is ever increasing. 90% of these people
have DM type-2, while the rest have DM type-1. Fortunately, Africa lags behind in this
epidemic, but with rising standard of living, the number of diabetics in this part of the world
will increase as well. DM type-2 is considered a life-style related disease, linked to obesity
and a sedentary life-style, and as a matter of fact, 80% of type-2 diabetics are obese.
DM is important also because of its long-term complications. Most diabetics die from the
cardio-vascular complications of the disease, and DM is a leading cause of blindness, renal
failure and gangrene of the lower limbs.
History
DM has been known for ages. The first written account of this disease is from ancient Egypt,
where the main features of DM – thirst, increased urinary output, hunger and wasting - are
described. The difference between type-1 and type-2 diabetes has also been recognized for
centuries.
The word ’diabetes’ comes from the Greek language, meaning ’running through’, or
’streaming through’, as it seems that ingested fluid just ’runs through’ the body. ’Mellitus’ is
derived from Latin, where the word ’mellis’ means honey. In earlier days it was common
practise that when examining the patient, the doctor would taste the urine of the patient. As
diabetic urine contains a lot of sugar, it had a sweet taste – it tasted of honey. Hence
’mellitus’. Fortunately, medical practice has changed, and we are no longer expected to take a
sip of the patient’s urine.
The first crude determinations of blood sugar were introduced in the 1860’s, and it was
found that the blood sugar levels of diabetic patients far exceeded that of healthy people.
Experimental pathology gave a contribution to the understanding of the pathophysiology of
diabetes in the 1890’s, when German doctors von Mehring and Minkovsky were able to
demonstratet that surgical removal of the pancreas of dogs resulted in prompt development of
diabetes in the animals.
The real breakthrough in diabetic care came in the early 1920’s, when Canadian doctors
Banting and Best succeded in extracting a substance from pancreatic tissue, which, when
administered parenterally, could reverse the symptoms of diabetes. As it became obvious that
this new substance was produced in the so-called islets of Langerhans, the discovery was
named insulin. ’Insula’ is the Latin word for island, or islet.
In my student days, in the 1960’s, we were taught that there were two types of DM:
juvenile, or childhood diabetes, and adult, or late-onset diabetes. Later, it has been
demonstrated that there is overlapping between these two types, and today, we talk about
type-1, or insulin-dependent diabetes, and type-2, or non-insulin dependent diabetes.
Differences and similarities between type-1 and type-2 diabetes
So what are the differences and similarities between these two types of DM?
The presenting symptoms are pretty similar: intense thirst, which makes the patient drink
copious amounts of fluid; and accordingly, a huge output of urine. There is hunger, but in
spite of adequate food intake, the body weight goes down. Fatigue, and general malaise are
also part of the picture.
The differences are striking. Type-1 DM is a disease of rapid onset and progression – left
untreated it will kill the patient within weeks. Type-2 DM has an insidious course, developing
in a matter of months, or even years. Most type-1 diabetics fall ill at a young age, even as
babies – as it happens, Finland is the world leader in the incidense of early-onset DM-1.
While type-2 DM usually starts at middle or late age, and, as said, the victims are mostly
obese. Obesity is not a feature of type-1 DM.
Common to both types is a raised blood sugar level. But the pathophysiology is different:
Type-1 DM is a disease of insuline deficiency. For some reason or another, the insulin
producing beta cells of the pancreatic islets of Langerhans are destructed, but why this
happens is largely a matter of speculation. It seems that this is an auto-immune process, i.e.
something in the body’s immune defence goes wrong, and the beta-cells are ’killed by
mistake’. Genetic factors may be involved, and viral infections have been suspected, but we
don’t really know. Dietary factors have been extensively scrutinised, but there is very little
solid evidence that a particular diet would be diabetogenic.
Type-2 DM, on the other hand, is another type of disease. Insulin levels in the blood are
mostly normal, or in some cases, even above normal. We talk of ’insulin resistance’.
Insulin has a number of different functions in the body, but the main one is to keep the
blood sugar level at an equilibrium. When carbohydrates are absorbed from the gut after
meals, the blood sugar level increases. The pancreas responds to this with release of insulin,
which targets the so-called insulin receptors in the muscles and the liver. When insulin
receptors are stimulated, the gates are opened, and sugar enters the muscles and the liver,
where it is stored as glycogen. Sugar is then released when needed to satisfy the energy
requirements of the body.
In type-2 DM, the insulin receptors have been ’numbed’, and the uptake of sugar is thus
blocked in muscles and the liver. Why this happens is not clear, but as weight reduction has
been shown to reverse (at least in part) DM-2, there is obviously a link between obesity and
insulin resistance.
In a Finnish study some years back it was shown that sound eating and exercise habits
could prevent, or at least delay, the onset of type-2 DM. So, if you want to ward off DM-2,
keep slim, and take some exercise!
There are a number of sophisticated lab tests to differentiate between these two types of
DM, but the one most employed is the determination of C-peptide in the blood. Insulin
consists of two parallel chains of amino acids, called chain-A and chain-B, and they are united
by a short third chain, called chain-C, or C-peptide. Determining the level of C-peptide is
fairly simple, and correlates to the insulin levels in the blood.
Treatment
The treatment of both types of DM rests on three pillars: diet, excercise and drugs.
The optimal diet for diabetics is probably not established yet, but anyway, it should be a
balanced diet, with a reasonable share of carbohydrates, proteins and fats. Unfortunately for
you, the local diet here in Tanzania is heavily skewed towards carbohydrates – maize,
potatoes, cereals – which is unfavourable for the metabolism in diabetic patients. More meat
(chicken, pork, beef), more fat (vegetable oil in particular), less ugali! But who can afford
that...
Exercise is no problem here – hard work in the fields provides exercise enough, you don’t
need to visit gyms, or resort to jogging, as we do in Europe.
Drugs: DM-1 is a disease of insulin deficiency, and insulin substitution is life-saving. In
Europe, we worry a lot about blood-pressure and cholesterol, but I don’t think this is much of
a concern in your country today. But may be one day in the future?
For DM-2 there is a wide range of drugs today. Unfortunately, financial constraints make
many of them unavailable here. But here, as in the Western world, metformin should be the
number one drug in DM-2. It is safe, it is cheap, it prolongs life, and it has even a weightreducing capacity. Sulfonylureas, such as glimeperide, or glibenclamide are useful – BUT
THEY SHOULD NOT BE USED IN DM-1!
Diabetic keto-acidosis and coma
If not treated with insulin substitution, DM type-1 will inevitably lead to keto-acidosis and
coma, and ultimately, the patient will perish. Keto-acidosis is the end-result of seriously
impaired glucose metabolism, with deleterious consequences for the fluid and electrolyte
balance.
How do we recognise diabetic keto-acidosis?
When a patient in dehydrated and semi-comatouse or comatouse state is brought to the ER,
diabetic keto-acidosis should be suspected if the patient is a known diabetic. The skin is dry
and hot, the patient is breathing fast, may be complaining of abdominal pain sometimes so
severe that a perforated ulcer may be suspected. A dip-stick urine test will react for glucose,
and the blood sugar level is grossly elevated, to 30-40 mmols per liter, or above. There may
be a sweet odour in the breath of the patient, and the mental state is often clouded.
How does this come about?
When the blood sugar rises, the kidneys try to get rid of the excess by excreting sugar into
the urine. This makes the urine hyper-osmolar, and ’sucks’ fluid from the body. The fluid
deficit may be many liters in a few hours, and if not corrected, will lead to hypovolemic
shock.
As there are no energy deposits in the muscles and the liver, the body tries to compensate
for the energy deficit by burning fat. This may sound innocent, but unfortunately, burning fat
results in toxic waste, i.e. so-called ketone bodies. In particular, 2-hydroxy butyric acid is a
sinister compound. Ketone bodies make the blood acid, and as a compensatory measure, the
respiratory system tries to balance this by excreting more carbon dioxide, which also
contributes to the blood acidity. Thus the rapid breathing. This is far from enough, however,
and the mix of dehydration and acidosis is a lethal one.
The restoration of fluid and electrolyte balance in the blood requires i.v. fluids, insulin and
i.v. potassium, but how to manage diabetic keto-acidosis and coma would require a separate
lecture, so I will conclude my talk here.