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Diabetes in Humans
type 1, 2 and 3

Leo Rogier Verberne

7. Long-term diabetes complications

In the present year 2017, there are about 1 million people in the Netherlands with manifest diabetes. Their blood glucose level must be maintained within safe limits by means of self-regulation. The usual target value for that regulation in the Netherlands is HbA1c < 53 mmol/mol (9). But a new criterion < 48 is proposed by an international (American and European) expert committee to prevent long-term diabetes complications (4). However, a majority of the Dutch type 1 diabetics cannot handle even the present HbA1c target: only 20% of them achieves the goal of < 53 mmol/mol (11); children and adolescents score even worse. So the risk of long-term complications is considerable. In type 2 diabetics, the blood glucose level is elevated above normal during many years before discovery (8). Nearly half of these prediabetics already has some degree of diabetic retinopathy at the time that the diabetes diagnose is made (2). All in all, more than half of the 1 million manifest diabetics will experience one or more severe long-term complications later on in life (6).

1. Blood vessels
If the average plasma glucose level exceeds the normal upper limit (HbA1c 42 mmol/mol) for a period of several years, then it damages the inner walls of small and large blood vessels. As a result, untreated and poorly regulated diabetics develop thrombosis more often (2). Subsequently fats (cholesterol) cling to the damaged blood vessel wall, leading to atherosclerosis (‘artery calcification’), that narrows and hardens the blood vessels.

2. Heart
Because of atherosclerosis, untreated prediabetics and poorly regulated manifest diabetics are at twice the risk of experiencing a coronary later on in life (3). If they also suffer from high blood pressure, then coronaries occur eight times more often. And if their cholesterol level is also too high, then the risk is almost twenty times higher than normal (3). As a result, 70% of all diabetics die of heart problems and vascular disease. Their life expectancy is 5 to 10 years lower than on average (16).

A 58-year old man is rushed to the hospital with a heart condition. He is a construction worker, with a sturdy frame and too fat. The blood pressure and cholesterol level are elevated and the coronary arteries appear to be severely affected by atherosclerosis. He undergoes surgery and is given four grafts. Thereafter he is quickly able to go back to work, although he does tire easily. During checkups he is found to be fine. However, his performance is gradually declining and 3 years after the surgery he can hardly function anymore: he spends his days lying on the couch feeling extremely tired. And he suffers a TIA twice. He has gradually started to drink more and more, up to 9 litres of soft drinks a day. When he is finally tested for diabetes, his blood sugar level, non-fasting, is 56 mmol/l (normally < 7.8). So he is admitted to the hospital again. There, he is hooked up to a drip with insulin. Thus his blood glucose level gradually drops to normal. The C-peptide-test is positive, and so his β-cells produce insulin. Because of that, the diagnosis of adult-onset diabetes is posed and accordingly treatment is initiated. In the months to come he loses 15 kg of body-weight and he feels much healthier.

The blood glucose level was excessively high when type 2 diabetes was diagnosed. That was 3 years after the heart surgery. So prior to the coronary his glucose level was probably already too high, as the blood level increases very slowly in type 2 diabetes. It seems likely that this was the cause of atherosclerosis and the coronary. But his blood sugar was not tested. Resulting diabetes treatment accordingly could have prevented clinical problems in the years after the heart surgery.

3. The brain
TIA’s and strokes occur more often at an advanced age in poorly regulated diabetics (14). TIA (transient ischemic attack) and stroke (cerebral infarction) are caused by the obstruction of a blood vessel in the brain, either temporarily or permanently. This is caused by a clot that breaks free from an atherosclerotic plaque in the carotid arteries or in the heart and then becomes lodged in the blood vessels of the brain (6,14). The larger the clot, the greater the loss of functionality. Preventing the development of atherosclerosis reduces the risk. Which is why the HbA1c should be < 48 mmol/mol. Every year, approx. 30,000 people in the Netherlands suffer a stroke and about 120,000 have to live with the consequences (6).

4. Eyes
Diabetic retinopathy develops as a result of chronic hyperglycemia. Moderate retinopathy is already found in about 5% of type 2 diabetic patients at the (Dutch) HbA1c threshold for manifest diabetes (53 mmol/mol) (4), at the moment that the diagnosis of diabetes is made. At this point, nearly half of the patients already have such eye problems to a minor degree (2). This type of retina disorder cannot be corrected; the process can only be slowed down if it is timely detected (7). After a 15 years period of diabetes, more than 80% of the juvenile and adult-onset diabetics suffer from this disorder (6). Its consequence is diminished eyesight or blindness. Thus, diabetes is the main cause of blindness in Europe.

5. Kidneys
Eventually the small blood vessels in the kidneys (glomerular capillaries) are damaged as a result of increased blood glucose concentrations leading to diabetic nephropathy (1). If the deterioration of the kidneys progresses too far, dialysis becomes necessary. Nephropathy occurs at an advanced age in ± 30% of type 1 diabetics, in 25% of type 2 diabetics of European origin and in 50% of African or Indian diabetics (6). Altogether ± 200,000 cases in the Netherlands.

6.Sexual organs
A consequence of poor diabetes regulation is that all organs suffer from a shortage of glucose and switch to the burning of fat as an alternative source of energy. Only the brain and sexual glands (ovaries and testicles) are not capable of such a switch. As a result, fertility becomes disrupted due to a lack of energy. In females, the ovaries come to a standstill and in males it results in poor quality sperm. Besides, men with long lasting poor diabetes regulation often experience erection problems (erectile dysfunction). Of every 10 men with adult-onset diabetes, 7 experience problems in their sexual functioning (5). The cause lies in constriction of blood vessels and neuropathy, both being consequences of increased blood glucose levels over a period of years.

7. Nerves
Another consequence of prolonged blood glucose increase might be that nerves function less adequately, known as diabetic neuropathy. Reduced muscular strength and loss of balance can be consequences, or pain and tingling in the legs and feet (10,12). Abnormal positioning of the foot may develop. The perception of pain may become disrupted: the diabetic can step on a thumbtack, for example, without even noticing. If neuropathy concerns the nerves in and around the stomach, then its movement may be disrupted (gastroparesis). As a result, food is digested too slowly and injected insulin can take effect before the food has been absorbed from the intestinal tract. So that the blood glucose level can drop too much as a result (2).

8. Legs and feet
Besides the possible development of neurologic disorders in feet and legs, the blood supply may also become disrupted as a long-term diabetes complication. A temporary blockage of the arteries in the legs may cause intermittent claudication: a lame walk resulting from pain in (one of) the legs. Permanent blockage causes a diabetic foot. Toes, a foot or lower leg may die off and must be amputated in every 1 out of 15 cases (6). As a result of poor blood supply, wounds can easily begin to fester (2). Such foot problems occur in ± 213,000 diabetics in the Netherlands (6). Not surprisingly, in 70% of them atherosclerosis is found elsewhere in the body.

9. Joints
Chronic hyperglycemia may also damage the connective tissue in the tendons and/or the joints. This may lead to symptoms in the joints, most of the time in the hands. It is called limited joint mobility. An estimated 30% of all people with diabetes experiences this disorder (15). There is an increased risk of carpal tunnel syndrome and a frozen shoulder as long-term diabetes complications (2). The chance of developing a frozen shoulder is approx. 20% higher in diabetics (6).

1. More than half of the ± 1 million people with manifest diabetes in the Netherlands experience one or more severe long-term complications later on in life due to many years of careless regulation.
2. Careful regulation of the blood glucose level prevents the development of long-term diabetes complications; the target value to that end is HbA1c < 48 mmol/mol.
3. Long-term diabetes complications come about as a result of deviations in small and large blood vessels and in certain nerves; and so in fact, all the organs in the body and the limbs are at risk.
4. The life expectancy of people with diabetes is an average of 5 to 10 years lower due to the development of long-term complications.

1. Bilo HJG (2002). Diabetische nefropathie: behandeling is gericht op voorkómen en vertragen. Diabetes, de stille epidemie; Pfizer bv; p 42-53
2. Diabetes.nl (2015). Complicaties van diabetes
3. Guyton AC and Hall JE. Insulin, Glucagon and Diabetes Mellitus. In: Textbook of Medical Physiology 12th ed. (2011); ISBN 978-1-4160-4574-8; p 939-954
4. International Expert Committee (2009). Diabetes Care July 2009; p 1327-1334 Report on the role of the A1C assay in the diagnosis of diabetes.
5. Nijpels G. (2012). De taboe-complicaties. Voordracht Nationale Diabetes-Dag
6. Pinkhof. Diabetes t/m diabetische voet p 300-303; diabetische retinopathie p 985-986; frozen shoulder p 430-431; limited joint mobility p 651; In: Geneeskundig woordenboek 11e druk (2006); ISBN 90-313-4837-6
7. Polak BCP (2002). Elke diabetespatiënt heeft recht op regelmatige oogcontrole. Diabetes, de stille epidemie; Pfizer bv; p 142-155
8. RIVM (2013). Meer dan 800.000 mensen met diabetes in Nederland; toename fors
9. Rutten GEHM, Grauw WJC de, Nijpels G, Houweling ST, van de Laar FA, Bilo HJ, Holleman F, Burgers JS, Wiersma Tj, Janssen PGH. (2013) NHG-Standaard Diabetes mellitus type 2. Derde herziening; Huisarts Wet 2013; DIA 13-43/uit/PJ/ll
10. 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
11. Torren CR vd. en Roep BO (2012). Ned Tijdschr Geneeskd. 2012;156:A4268 Immunotherapie voor diabetes mellitus type 1.
12. Wientjens WHJM (2008). Diabetes … Nou en? Zeventig jaar belevenissen. Novo Nordisk BV; ISBN 978-90-804452-7-7
13. Wikipedia.en (2016) Hyperglycemia
14. Wikipedia.en (2016) Transient ischemic attack
15. Wikipedia.nl (2017) Gewrichten
16. Wolffenbuttel BHR (2002). Cardiovasculaire complicaties belangrijkste doodsoorzaak bij diabetes. Diabetes, de stille epidemie; Pfizer bv; p 156-165

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