Juvenile, Adult-onset and Monogenic diabetes

diabetes type 1, 2 and 3

Leo Rogier Verberne

3. Diabetes symptoms

Independent of the cause, a series of symptoms develops when the blood glucose level passes the kidney threshold (11.0 mmol/l). This condition is called ‘overt’ or manifest diabetes. In the case of type 2 diabetes, the foregoing ‘silent’ phase or prediabetes can last for 6 or more years until it becomes manifest (2).

Excessive thirst and frequent urination
The classic symptoms of manifest diabetes are excessive thirst and frequent urination of sugary urine (diabetes mellitus means ‘honey-sweet flow’). These symptoms develop as a result of glucose excretion by the kidneys if the blood level rises over 11.0 mmol/l. When this level is 20 mmol/l, approx. 100 grams glucose is excreted per day. In severe cases of diabetes, blood glucose concentrations may possibly exceed 60 mmol/l (5); loss of sugar in the urine is then major and large amounts of urine are produced. This causes thirst, which is why diabetics drink a lot: up to 10 litres per day (and night).

In manifest diabetes, the cause of hyperglycemia is a considerable lack of insulin. Untreated juvenile diabetics have no insulin whatsoever available, as a result of which the organs cannot absorb glucose from the blood. Untreated adult-onset diabetics do not have enough insulin available; as a result an insufficient amount of glucose enters the organs which evokes a rise of the blood glucose level. So juvenile and adult-onset diabetics suffer from a lack of glucose in the organs in different degrees. And glucose is the fuel for bodily functions. Which is why untreated diabetics feel tired all the time. Their organs proceed to burn fat as an alternative supply of energy.

Disturbed brain functions
The human brain only accounts for approx. 2% of the body weight, but for 15% of the total glucose consumption in a state of rest (1). This can double during major brain activity. Unlike other organs, the brain cannot switch to fat combustion in the event of a shortage of glucose. And so a lack of insulin has an immediate effect on brain functions. Shortage of glucose in the brain diminishes the ability of the diabetic to concentrate. In severe cases he has slurred speech or even can’t respond to questions or comments and his coordination becomes disrupted. In the utmost case the failure of glucose in the brain will lead to loss of consciousness, called hyperglycemic coma, after the concurrent high blood glucose level.

A slight lack of glucose in the brain is enough to stimulate the hunger centre and bring about an increased appetite as a reaction. In the case of untreated juvenile diabetics, the lack of glucose in the brain is extreme and they feel incredibly hungry as a result. They therefore eat a lot and their blood sugar subsequently sky-rockets. But because of the lack of insulin, none of the organs can absorb glucose. The subsequent combustion of fat and protein in all organs other than the brain leads to severe loss of weight (illustration 1). As a consequence, juvenile diabetics will die of exhaustion within a few months if not injected with external insulin.

first diabetes patient ever to be treated with insulin - Leonard Thompson

Leonard Thompson, 14 years old, was the first person to be treated with insulin in 1922.
On the right: six months later (5)

Prediabetes is the foregoing, silent phase of manifest diabetes. According to the RIVM, an estimated 750,000 people in the Netherlands had prediabetes on 1 January 2011 (2). Which was about 4% of the Dutch population. And this number is still increasing. In the adult population of North-America, 10-15% has prediabetes (9). Concomitant fasting plasma glucose levels 6.0-7.0 mmol/l do not meet criteria for manifest diabetes, yet are higher than those considered normal, and they point to prediabetes.

Prediabetics are unaware of their disorder because the symptoms of manifest diabetes are (still) lacking. Insulin is available, but to an insufficient degree. Therefore the glucose gates in the organ membranes do not open completely and not enough glucose is absorbed. Which also concerns the brain. As a result, the hunger centre is stimulated and so the appetite of prediabetics is constantly increased. They take in an excess of food and the digested carbohydrates enter the blood as glucose, the surplus of it being stored in the fat depots. And thus prediabetics develop overweight or even obesity.

Overweight is more often observed in those with adult-onset diabetes compared to those who have no diabetes (3). This association (statistic correlation) is generally seen as a causal connection, that is to say, it is generally presumed that overweight causes adult-onset diabetes. That is statistically incorrect: an association demonstrates that a certain observation (overweight) more than coincidentally goes hand in hand with some other observation (adult-onset diabetes). But it does not prove that one causes the other. The same association equally applies the other way round: if adult-onset diabetes causes overweight. The latter interpretation explains why the overweight of diabetics often disappears once the blood glucose level is carefully regulated to normal glycemia.

As a result of a treatment error in the regulation of diabetes an immediate drop in the blood glucose level to under 4 mmol/l can occur. That is referred to as hypoglycemia. Striking is that the symptoms of hypoglycemia largely correspond with symptoms of severe hyperglycemia. How is that possible?
Both, hypo- and severe hyperglycemia, involve a lack of glucose in the brain. In the case of a hypo, because the supply of blood glucose is simply too small; in the case of a hyper, because the insulin level is too low to allow enough blood glucose to enter the brain. Thus in both situations, the brain functions are disrupted due to a lack of glucose. In extreme cases, unconsciousness will occur, both at very low blood sugar levels (hypoglycemic coma) as well as extremely high levels (hyperglycemic coma). So do take care with (treating) an unconscious diabetic!

Alarm reaction
Hypoglycemia generates an alarm reaction in the body. Adrenaline and cortisol are released from the adrenal glands. These hormones mobilize glucose from the reserves in the liver, subsequently increasing the blood sugar level (6). But they also cause paleness, trembling, sweating and heart palpitations. During a severe hypo, the diabetic is no longer able to take in glucose by eating or drinking (6). One of the parents, the partner or a housemate must then administer a glucagon injection while waiting for professional help. It is therefore of vital importance to adequately inform those people involved (4).

After having been at an evening party, a woman is awakened during the night because her partner is twitching in bed. He is sweating all over, talking nonsense and is unresponsive. Yet he was not drunk when they arrived home and they have meanwhile slept for a few hours. She knows that he is a diabetic, but they never discussed the matter in detail. And this has never happened before. She has no idea how to best respond and act on the situation. It is frightening and she calls the emergency number in a panic. Shortly afterwards the twitching subsides and when the ambulance and paramedics arrive fifteen minutes later, her partner can once again speak clearly. He drinks a glass of apple juice and chews on a few dextrose tablets. And with that, the threat of a coma is averted. A glucose drip or glucagon injection is no longer necessary and the ambulance leaves.

Before dinner he had injected his usual dose of insulin, but because they were in a hurry, dinner had been limited to a cup of soup. And he had consumed a few glasses of beer at the party. By not eating as he normally did (no carbohydrates), the dose of insulin had actually been too high in this case; the alcohol then reduced his blood glucose level even further. Ultimately, in the course of the night, the usual evening injection of slow-acting insulin brought him to the verge of a hypoglycemic coma.

Type 1 and type 2
Hypoglycemia occurs more frequently in juvenile diabetes and is more severe than in adult-onset diabetes (3). The explanation for this: in type 1 diabetes the β-cells are shut down and there is no monitoring left of the glucose concentration. When, after injection of too much insulin the blood glucose level drops too far, then this remains undetected and thus there is no response of the α-cells, meaning no production of glucagon. In adult-onset diabetes, β-cells are present but less sensitive as a result of degeneration. However, if the blood glucose level drops too far due to over-medication, then the α-cells are prompted to produce glucagon. Which prevents a hypo if the treatment error is not too severe; or at least it tempers the symptoms by the glucagon that will be released.

Clinical pictures
1. A 10 year old child must leave the school class several times a day to go to the loo; it drinks and eats unusual quantities but nevertheless grows thin. The symptoms have developed in a few weeks and are characteristic of type 1 diabetes.
2. A 50 year old man with a BMI (body mass index) of 30 feels tired all day and has difficulties concentrating; he is constantly thirsty. These problems have existed for many months with increasing intensity. Which is suspicious of type 2 diabetes.
3. In an Aruban family 8 out of 10 children got insulin dependent diabetes at an early age. This seems to be some form of the monogenic type of diabetes (MODY).

1. The classic symptoms of manifest diabetes are excessive thirst with frequent urination of sugary urine and fatigue.
2. Untreated juvenile diabetics are always hungry, but suffer severe weight loss despite the huge amounts of food that they consume.
3. If prediabetics are left untreated, then they have a constant appetite and develop overweight due to excessive eating.
4. Overweight is not the cause of diabetes, but rather prediabetes is the cause of overweight.
5. Symptoms of hypoglycemia and severe hyperglycemia are largely the same as a lack of glucose in the brain occurs in both cases.

1. Guyton AC and Hall JE. Brain metabolism. p 749-750; Insulin, Glucagon and Diabetes Mellitus. p 939-954. In: Textbook of Medical Physiology 12th ed. (2011); ISBN 978-1-4160-4574-8
2. RIVM (2013). Meer dan 800.000 mensen met diabetes in Nederland; toename fors
3. Tack CJ en Stehouwer CDA. Diabetes mellitus. In: Interne geneeskunde. eds. Stehouwer, Koopmans en van der Meer. 14e druk (2010); ISBN 978-90-313-7360-4; p 835-865
4. Wientjes WHJM (2002). Diabeteszorg is onvoldoende, kwantitatief en kwalitatief. Diabetes, de stille epidemie; Pfizer bv; p 8-19
5. Wientjens WHJM (2008). Diabetes … Nou en? zeventig jaar belevenissen. Novo Nordisk BV; ISBN 978-90-804452-7-7; p 15
6. Wikipedia.en (2016) Hypoglycaemia
7. Wikipedia (2016). Impaired glucose tolerance

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© Leo Rogier Verberne
ISBN/EAN: 978-90-825495-0-8

diabetes book Leo Rogier Verberne

Juvenile, Adult-onset and Monogenic diabetes
paperback, 72 pages
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