Silent Killer: Diabetes

 

Silent Killers

Whenever we think of a disease, we imagine a person who is sick, lethargic, and bedridden. But there are few diseases which can show no specific symptoms for a very long time i.e. they remain silent. The person seems to be normal but if these conditions are not diagnosed early then they have the potential to kill a person by many complications. So, these conditions are logically called Silent Killers.  Two of the most common silent killers are:

1.     Diabetes

2.     Hypertension

In this blog I will be focusing on Diabetes, making hypertension the topic of upcoming blog.

What is diabetes?

Image Credit: diabetes.co.uk

In Greek, the word Diabetes means ‘fountain’. The condition in human is logically named Diabetes because it causes frequent urination of large volume of urine (Polyuria). Polyuria is caused by Diabetes mellitus and Diabetes insipidus. Though these two diseases have similar name and similar symptoms, they have completely different pathophysiology. In this blog I will be writing about Diabetes mellitus. But before proceeding ahead, let’s differentiate Diabetes mellitus from Diabetes insipidus. Diabetes mellitus is a condition where there is Polyuria with chronically elevated blood glucose; urine also contains glucose (the Latin meaning of mellitus is sweet).  Diabetes insipidus on other hand doesn’t involve elevated glucose level and has completely different mechanism (Latin meaning of insipidus is lacking flavor).

How do I know if I have Diabetes Mellitus?

1.     Diabetes is usually asymptomatic until complications develop. However, we can notice Polyuria (frequent urination with large volume of urine), Polydipsia (increase thirst). If these symptoms are seen and the blood glucose level is measured more than 200 mg/dl then it is Diabetes.

2.     Since symptoms may not be seen until very late, so screening is necessary. If you are asymptomatic then you can have your fasting blood glucose level tested. Test the blood glucose after 8 hours of fasting

                        Less than 100 mg/dl : Normal

                        100 to 125 mg/dl: Pre-Diabetes

                        More than 126mg/dl : Diabetes

3.     Since glucose level is very high, Hemoglobin(Hb) in the RBC combines with glucose by the process called glycosylation forming glycated hemoglobin (HbA1C). This process does not even require a catalyst (enzyme).

HbA1C less than 5.7% : Normal

HbA1C between 5.7 to 6.4% : Pre-Diabetes

HbA1C greater than 6.5%: Diabetes

Since RBC lives for 120 days. This test shows the glucose level in blood for past 3-4 months and is used to monitor therapy in Diabetic patient undergoing treatment.

How does Diabetes develop?

To explain Diabetes mellitus, I want to introduce the hormone insulin. Pancreas is an exocrine as well as endocrine organ in our body. Exocrine portion secrete digestive enzymes. Endocrine portion secrete hormones. Alpha cell of endocrine pancreas secretes the hormone glucagon and beta cell of endocrine pancreas secrete hormone insulin. Glucagon raises blood glucose level whereas Insulin decreases blood glucose level. In Diabetes there is chronically elevated blood glucose because of deficiency of Insulin; deficiency in either amount of Insulin (Type I Diabetes) or the deficiency in effect of insulin (Type II Diabetes Mellitus).

Type I Diabetes Mellitus

It is an autoimmune disorder where our own T lymphocytes mediates destruction of beta cell of pancreas. This results in loss of insulin. It is mostly a childhood disorder. Since there is lack of insulin, we can treat it using insulin.

One of the main complications of Diabetes Mellitus Type I is Diabetic Ketoacidosis. There is increase in glucose and ketone bodies in the urine and blood. Since ketones have acidic properties, it leads to anion gap metabolic acidosis. Acidosis leads to increase in plasma potassium and this can cause abnormal rhythm of heart (arrhythmias). To manage increasing acidic environment inside the body our body tries to eliminate acidic gas (CO₂) from the body. For this reason, the breathing rate increases (hyperventilation). A special type of deep, labored breathing is seen known as Kussmaul breathing. Ketones has fruity odor so we can smell fruity odor in breath.  

To manage acidosis (H⁺), phosphate (PO₄^3-) shifts into ECF (extra cellular fluid) but is excreted in urine with osmotic diuresis. Because we lose phosphate, we can’t generate enough ATP (Adenosine triphosphate). Due to loss of ATP, there can be muscle weakness. Respiratory muscle can get weak leading to difficulty in respiration.

Note: Although there is increase in potassium level in blood, total potassium in the body decreases because we are constantly losing potassium with frequent urination. When we start insulin therapy, insulin shifts potassium backs to the cell from the blood. This can cause decrease in potassium in the blood and we may need to administer potassium as well along with insulin.

Type II Diabetes Mellitus

This is the most common form of Diabetes. It is more common in adults however incidence is increasing in children also. This is caused due to deficiency of effect of insulin. The receptor on which insulin binds to show its effect is abnormal and resistant to insulin in this case. There is not any problem with pancreas initially. Pancreas produce enough insulin required for our body physiology but since insulin can’t exert its effect pancreas is tricked into thinking that there is deficiency of insulin in the body and produces more insulin but since insulin receptor is resistant to insulin it still can’t exert its effect. Pancreas again produces more insulin and the cycle goes on till pancreas gets overwhelmed and fail to function properly. When this happens insulin level gets low. This shows that in Type II Diabetes mellitus, the level of insulin is initially high but eventually low.

How does insulin resistance develop?

This is not well understood but there are many studies suggesting that the resistance is related to obesity. Fat cells (Adipocytes) secrete TNF alpha. TNF alpha may activate an enzyme serine threonine kinase. For insulin to show its action, its Tyrosine Kinase that has to be activated.

Resistance also shows positive association with family history. Genetic predisposition is seen more in Type II Diabetes mellitus than Type I Diabetes Mellitus. First degree relatives are at 2-3 times greater risk of developing diabetes mellitus.

Complications of Diabetes Mellitus Type II

The complications are related to one of two mechanism.

1.     Amino acids in the protein combine with glucose forming crosslinked protein known as “Advanced Glycosylation End Products” (AGEs). This does not require an enzyme. AGE can cause damage to large and small blood vessels.

2.     The excess glucose in the blood can be converted to Sorbitol by the enzyme Aldose reductase. Sorbitol being an osmotic agent draws in fluid and causes osmotic damage in the areas it is deposited.

Diabetic Macroangiopathy (macro= large, Angio= blood vessel, Pathy= diseases)

AGE causes atherosclerosis in the large vessel of heart, brain and legs. This leads to Coronary artery diseases like Myocardial infarction and Angina pectoris. It can also cause Stroke. Because of blocking of peripheral vessel in the leg, it can cause pain in the leg and poor wound healing.

Image Credit: Britannica.com

Diabetic Microangiopathy (micro= small)

It commonly occurs in kidney of Diabetics. AGE cause hyaline arteriosclerosis (thickening of arterioles) in afferent as well as efferent arteriole of nephron (functional unit of kidney). Arteriosclerosis of afferent arteriole is also seen in hypertension. Arteriosclerosis of efferent arteriole is rarely seen except in diabetes. If afferent arteriole is involved, blood can’t enter kidney, and this can cause renal failure. If efferent arteriole is involved, blood cannot leave kidney easily. This leads to hyperfiltration and filtration of protein as well. We can find protein in the urine in this case which is normally absent.

 

Cataracts

Some tissues in the body like muscles and adipose tissue do not uptake glucose from blood without signals from insulin. However other tissues may uptake glucose without insulin. Lens of eye, Schwann cells of peripheral nervous system and pericyte of retina are few important tissues for our discussion here which do not require insulin signal. Lens uptake glucose and converts to sorbitol. Sorbitol draws water into the lens. This opacifies over time leading to cataract.

Image Credit: myeyesspecialist.com.sg

Neuropathy

Sorbitol accumulates in the Schwann cells and cause osmotic damage to Schwann cells which are the myelinating cells of peripheral nerves. This leads to sensory loss- loss of vibration sense and proprioception. There is impairment in the sense of pain, light touch, temperature.

As we discussed earlier that AGE can block peripheral vessel leading to delayed wound healing. If neuropathy is added to that then we cant properly sense touch and pain especially in the long nerves (nerves supplying legs). If there is infection in the leg, patient may remain unaware and by the time it come to attention there can be ulcer development in the leg and amputation as well in some case. This is described as diabetic foot disease. For this reason, for diabetics regular foot exam is recommended as a prevention.

Note: In Diabetic neuropathy the condition is worse distally and better proximally. In Neuropathy due to Vitamin B12 deficiency, both extremities are equally affected.

Image Credit: pristyncare.com

Retinopathy

AGE can deposit in capillary basement membrane causing hyaline arteriosclerosis.

Sorbitol can deposit in pericyte (cell that wrap capillaries). This cause pericyte degeneration. This increase chance of microaneurysms in the retina. These aneurysms can rupture and cause blindness.

Image Credit: 2020vision4nh.org

Acanthosis nigricans

This is hyper-pigmented plaques on skin classically seen in neck and axillae.

Image Credit: mbbch.com

 

Prevention and Management Of Diabetes

Diabetes can’t be completely cured. However it can be managed and prevented. Some of the important measures for this are:

1.     Maintain normal weight: Obesity is the main risk factor for Diabetes. So, it is recommended to modify your lifestyle to reduce your weight. One of my friends asked me that he has gained some weight and was concerned about obesity. So I want to further elaborate this. Obesity can’t be determined by weight alone. It requires height as well so that we can measure body mass index (BMI)

BMI = Weight (in Kg)

            (Height)² (in meter)

By calculating BMI you can know where you stand.

 

Image Credit: everydayhealth.com

Exercise: Regular exercise improves body’s use of insulin and helps to reduce fat as well.

Relaxation: Stress can raise blood pressure as well as blood sugar. To manage this you can practice relaxation technique like deep breathing and meditation.

Medications: There are many oral and subcutaneous medications available to manage diabetes.

Test blood sugar time to time: If you are prediabetic then it can be cured by lifestyle modification and diet planning. If you are diabetic and on continuous therapy, then your glucose level may go down due to excessive use of insulin. This can be fatal. So, blood glucose test is recommended.

In these ways Diabetes can be managed. For furthermore drop a comment or concern your doctor. I hope this was useful.