Diabetes Mellitus: The Things You Should Know
Diabetes is a common problem nowadays. In a family at least one person is suffering from diabetes. It has become a common problem in this modern era
Diabetes mellitus is a group of metabolic disorders of fat, carbohydrate, and protein metabolism resulting from defects in insulin secretion, insulin sensitivity action or both characterized by hyperglycemia. So, it is the term given to a syndrome which has as its most prominent feature elevation of the blood glucose & is a chronic condition caused by an absolute lack of insulin or relative lack of insulin as a result of impaired insulin secretion and action
Diabetes is seen from very early times. In an Egyptian papyrus dating from 1550 BC a polyuric state was described. Clearly recognizable description of type 1 diabetes mellitus in the 2nd century AD was given by Aretaeus of Cappadocia. Aretaeus was the first to use the term “diabetes” from the Greek word for a siphon. He described, “It’s because the fluid does not remain in the body. It uses the man’s body as a channel whereby to leave it”
The Hindu physicians, Charak and Sushrut, between 400 and 500 BC, were probably the first to recognize the sweetness of diabetic urine. Indeed, the diagnosis was made by tasting the urine or they noticed that ants congregated round it. Charak and Sushrut noted that the disease was most prevalent in those who were indolent, overweight, and gluttonous, and who indulged in sweet and fatty foods. The crucial fact that from the 9–11th centuries AD, diabetic urine tasted sweet was also emphasized by Arabic medical texts notably in the medical encyclopedia which was written by Avicenna (980–1037)
In Europe, during the 17th century diabetes was neglected until Thomas Willis (1621–1675) wrote Diabetes addressing as the Pissing Evil. According to him, “diabetes was a disease so rare among the ancients that many famous physicians made no mention of it, but in our age, given to good fellowship and guzzling down of unallayed wine, we meet with examples and instances enough, I may say daily, of this disease.” He described the urine as being “wonderfully sweet like sugar or honey” but did not consider that this phenomenon might be because it contained sugar.
In 1776 by Matthew Dobson (1735–1784) descripted hyperglycemia was published in a paper of Liverpool. He found that the serum & so is the urine also of his patient Peter Dickonson (who passed 28 pints of urine per day) tasted sweet. Moreover, he heated those urine and found “a white cake which smelled sweet like brown sugar, neither could it by the taste be distinguished from sugar.” Dobson concluded that the kidneys excreted sugar and that it was not “formed in the secretory organ but previously existed in the serum of the blood.”
The Edinburgh-trained surgeon named John Rollo (d. 1809) was the first to apply the term “mellitus” from the Latin word meaning “honey”. Moreover, In 1815, the French chemist Michel Chevreul (1786–1889) proved that the sugar in diabetic urine was glucose. In June 1889, the concept of “internal secretions” had been publicized by the well-known physiologist Charles-Édouard Brown-Séquard (1817–1894), who claimed to have rejuvenated himself by injections of testicular extract. It was given further credence in 1891, when Murray reported that myxedema could be cured by sheep thyroid extract by injection or orally.
Eduard von Jaeger (1818–1884) gave the first description of diabetic retinopathy, in his beautiful Atlas of Diseases of the Ocular Fundus. Surprisingly, Kidney disease was known to be relatively common in diabetes. In 1859, Wilhelm Griesinger (1817–1868) reported 64 autopsies in adults, half of whom had renal changes which he attributed to hypertension and atherosclerosis. However, the histologic features of diabetic kidney disease and the importance of renal complications were not reported until the 1930s.
“Insulin” was first produced by Macleod but he didn’t know about de Meyer’s earlier suggestion of insuline. News of its miraculous effects spread rapidly In 1922. There were only 19 references in world literature to “insulin” or equivalent terms like “pancreatic extract” by the end of 1923. During the 1st 6 months of 1924, there were 320 new reports and a further 317 were published newly. By October 1923, insulin was sufficiently available throughout North America and Europe. International recognition followed rapidly for its inventors and the 1923 Nobel Prize for Physiology or Medicine was awarded jointly to Banting and Macleod. Banting was angered by the decision and so he announced publicly that he would share his prize with Best, where Macleod decided to do the same with Collip.
The “insulin clamp” technique which was raised in the 1970s by Ralph DeFronzo in the USA and it was the first to measure rigorously the hypoglycemic action of insulin. he by himself led to countless studies of insulin resistance and its relationship to type 2 diabetes and vascular disease as well as various groups, including DeFronzo’s, have helped to clarify the role of β-cell failure in type 2 diabetes and how this relates to insulin resistance. Maturity-onset diabetes of the young (MODY) was recognized in 1974 by Robert Tattersall (1943). Clearly, a variety of different molecular defects have been identified in the following condition dominantly inherited subset of type 2 diabetes since 1993
There are usually 2 types of diabetes mellitus
- Type 1 Diabetes
- Type 2 Diabetes
But others can be found like,
- Gestational Diabetes Mellitus
- Other specific types
- Genetic defects
- MODY 3 (Chromosome 12, HNF-1α)
- MODY 1 (Chromosome 20, HNF-4α)
- MODY 2 (Chromosome 7, glucokinase)
- Other very rare forms of MODY (e.g. MODY 4: Chromosome 13, insulin promoter factor-1; MODY 6: Chromosome 2, NeuroDl MODY 7: Chromosome 9, carboxyl ester lipase)
- Transient neonatal diabetes (most commonly ZAC/HYAMI imprinting defect on 6q24)
- Permanent neonatal diabetes (most commonly KCNJ11 gene encoding Kir6.2 subunit of (β-cell KATP channel)
- Mitochondrial DNA
- Genetic defects in insulin action
- Type A insulin resistance
- Rabson–Mendenhall syndrome
- Lipoatrophic diabetes and
- Diseases of the exocrine pancreas
- Cystic fibrosis
- Fibrocalculous pancreatopathy and
- Cushing’s syndrome
- Aldosteronoma and
- Congenital rubella, Cytomegalovirus, and others
- Uncommon forms of immune-mediated diabetes
- Stiff-man syndrome
- Anti-insulin receptor antibodies and
- Drug- or chemical-induced
- Nicotinic acid
- Thyroid hormone
- β-Adrenergic agonists
- Thiazides Dilantin
- γ-Interferon and
- Other genetic syndromes sometimes associated with diabetes
- Down syndrome
- Klinefelter syndrome
- Turner syndrome
- Wolfram syndrome
- Friedreich ataxia
- Huntington chorea
- Laurence–Moon–Biedl syndrome
- Myotonic dystrophy
- Prader–Willi syndrome and Others
- Genetic defects
A. Type 1 Diabetes Mellitus
- It is said that type 1 diabetes mellitus is called insulin dependent. It is because we have to rely on external sources of insulin.
- Normally our cells contain 2 types of hormones for maintaining blood glucose level. One is Insulin and the other one is glucagon. Insulin helps blood glucose level decrease and so cells can take glucose for their use. Glucagon does the exact opposite by increasing blood glucose level. During type 1 diabetes mellitus there is lack of insulin.
- Our Pancreas contains Islets of Langerhens cells which contain these 2 hormones. But it is an immune mediated disorder where a person’”s own T-cell attacks the pancreas, specifically β-cell. That”s why there is disturbance of production of Insulin.
- Type 1 Diabetes is idiopathic. But it is thought that it has genetic causes associated with the HLA (Human Leukocyte Antigen) system. In chromosome 6 MHC (major Histocompatibility Complex) recognizes foreign molecules as well as maintaining self tolerance. Not everyone develops type 1 diabetes having basically same HLA ; HLA-DR3 and HLA-DR4
- Here insulin is produced sufficiently but tissues themselves don’t respond to the insulin receptor. The exact reason is still being studied.
- In our body the insulin receptor causes the vesicles containing glucose transporters to fuse with our cell membrane when muscle tissue and adipose tissue activate them. But during type 2 diabetes the glucose transporters are not moved and as a result the receptors don’t work. Here the situation is like the cells resist insulin which is termed as Insulin Resistance.
- Although the causes are not definitely known, research shows that excess amounts of adipose tissue release free fatty acid and adipokines. Together they cause inflammation and result in insulin resistance.
- Pancreas make a lot more insulin to decrease the same blood glucose level. So, the β-cells have hyperplasia(increase number of cells) & hypertrophy(increase size of cells) just to produce more insulin. But Pancreas secretes amylin that creates amyloid deposits and aggregates to make β-cell exhausted resulting in fatigue and disfunctionable. So, atrophy (decrease cell size and number) occurs, causing cell death. So insulin resistance happens and causes type 2 diabetes.
Commonly diabetes mellitus shows some common symptoms:-
- Poly means a lot & Phagia means eating
- Our cells need energy but our adipose tissue & muscle tissues need glucose. Due to destruction of β-cells glucose cannot enter the cells so the cells starve for energy. As a result, adipose tissues begin to breakdown fat which is called lipolysis and muscle tissue breakdown to protein and they both result in weight loss. It’s a catabolic or breakdown process which makes people hungry. When they get hungry there creates a tendency to eat a lot
- Glycos means glucose and Uria represents urea
- Due to the presence of glucose in our blood, they are excreted by urine through our kidneys
- Polyuria means excessive amount of urination
- So, our body excretes glucose which is osmotically active and can drain more water. It results in more urine excretion
- Polydipsia means excessive thirsty
- As a lot of water is excreted from our body, it’ll make us thirsty
There are more symptoms to be observed such as:-
- Tingling of the hands
- Different types of infection
- Slow healing of lesions
- Difficulty in concentrating
- Muscle wasting
- Blurry vision
- Mood change
- Erectile Dysfunction
When adipose tissues have lipolysis and break into fatty acids that go to the liver & produce ketone bodies. They increase the acidity of blood. Being acidic the protons exchange themselves with potassiums. This results in the protons entering into the cell & exiting of potassiums. This causes hyperkalemia and leads to paralysis, dehydration, acute starvation and so on. Interestingly, ketone bodies break down into acetone & makes the gas breathe like a sweet fruity smell.
There can be 2 types of neuropathic complications seen in diabetes mellitus.
- Acute:- It is seen during or sometimes after a period of poor diabetic control. A variety of neuropathic syndromes seen affecting both motor and sensory nerves of the both limbs. There can be seen:-
- mononeuritis multiple
- Bilateral ulnar nerve palsy
- Diabetic amyotrophy(caused by y a proximal radiculopathy)
- Wasting of proximal limb muscles, particularly the thighs
- lsolated cranial nerve palsy usually 3rd nerve occur
- Prayer sign
- Argyll Robertson pupil
- Fatty infiltration of liver
- Skin xanthoma
- Balanitis(vulvitis in women)
- Postural hypotension and hypertension
- Charcot joint
- lnsulin atrophy or hypertrophy
- Loss of tendon jerks
- Neuropathic ulcers
The renal complications are much uncertain. Though there could be-
- necrotising papillitis
- Kimmelstiel Wilson Syndrome raised by diabetic glomerulosclerosis
- nephrotic syndrome
Retinopathic complications get higher in diabetes. Glaucoma, Cataract, Disturbances of visual acuity. Moreover lesions caused by retinopathy:-
- Venous changes consisting initially of generalized dilation of veins
- Arterial changes consisting of hyalinization and narrowing of the arteries
- Cotton wool spots
- Macular disease
- Proliferative retinopathy
- Vitreous hemorrhage
Diabetes increases different coronary diseases. MI, Angina pectoris, Infraction etc develops without any doubt. Also form Hyaline arteriosclerosis in which hyaline deposits in arteries making them strong and inflexible. Also makes the basement membrane thickened resulting in hypoxia. Oxygen cannot enter the tissues due to thickened basement membrane. Most commonly atherosclerosis form in arteries which leads to stroke, heart attack and so on.
It is shortly known as HbA1c. The HbA1c assay is an accurate and precise measure of chronic glycaemic levels. It helps to correlate well with the risk of diabetes complications. It is produced by the glycosylation of hemoglobin. Mainly it is the proportion of hemoglobin with glucose stuck to it. When glucose is increased in blood vessels it tends to stick with our red blood cells. The measurement helps monitoring the management of diabetes. It shows the index of risk for developing diabetes.
Less than 100 mg/dL or 5.6 mmol/L is generally seen in normal people
Non-fasting Glucose/ Random
Oral Glucose Tolerance
≥ 126 mg/dL
≥ 200 mg/dL
≥ 200 mg/dL
- In fasting glucose, a person doesn’t take food or drink for 8 hours and test blood. Here if fasting blood glucose level is 100 to 125 mg/dL or 5.6-6.9 mmol/L, is considered as pre-diabetes. But if the fasting blood glucose level is equal or more than 126 mg/dL or 7.0 mmol/L it is considered as diabetes.
- In non-fasting glucose or random glucose, sample can be taken anytime. If sample shows 200 mg/dL or 11.1 mmol/L, it is considered as diabetes
- In OGTT or Oral Glucose Tolerance Test,the patient is given glucose and measured at the intervals. Usually it is taken 2 hours after glucose load. If sample shows 140-199 mg/dL or 7.7 mmol/L, it is considered as pre-diabetes,whether if it is equal or more than 200 mg/dL or 11.1 mmol/L it is considered as diabetes.
During pregnancy if a mother develops diabetes recognized as gestational diabetes. Thus pregnant women have increased blood glucose level, usually in the 3rd trimester. The mechanism of diabetes is similar to type 2 diabetes, as there are insulin enough but sadly the insulin receptors don’t work
Obese people are in high risk
Β-cell becomes dysfunctional with age
People of South Asian or Afro-Caribbean origin are at high risk. Hispanic and South Asian children may also develop type 2 diabetes
- Family history
- Western Lifestyle
- Dyslipidemia (↑TG, ↓HDL)
- Polycystic ovary syndrome (PCOS)
- Sedentery lifestyle
Insulin is the choice of drugs and given parenterally which is given in type 1 diabetes. Lifelong insulin therapy is given. It is because there is no sufficient insulin present. That’s why insulin is needed. Insulin is produced from sheep or pork which creates less sensitivity and acts as antigen.
Oral hypoglycemic drugs are used orally for type 2 diabetes mellitus. There are many oral drugs.
- Sulfonylureas: Gliclazide, Glimepiride, Glibenclamide, Glipizide, Glyburide are the 2nd generation drugs.They increase endogenous insulin production
- Generally well tolerated
- Highly effective at reducing HbA1c and blood glucose in symptomatic patients
- Risk of hypoglycaemia
- Weight gain
- Biguanides: Metformin, Phenformin, Buformin are the drugs. They reduce hepatic gluconeogenesis, increases insulin sensitivity, reduces carbohydrate absorption from the GI tract
- Weight neutral
- No risk of hypoglycaemia
- Possible cardiovascular benefits beyond hypoglycaemic effects
- Gastrointestinal side effects limit its usefulness
- Alpha-glucosidase inhibitors: Miglitol, Acarbose. They delay the digestion and absorption of ingested carbohydrate
- Reduces postprandial hyperglycemia
- Weight neutral
- Poorly tolerated due to gastrointestinal side effects including flatulence
- Meglitinides: Repaglinide, Nateglinide. They stimulate the release of preformed endogenous insulin.
- Specifically aimed at postprandial hyperglycemia
- Rapid action
- Multiple doses required – before each meal
- DPP-4 Inhibitors: Sitagliptin, Vildagliptin. They delay the clearance of natural incretins
- Weight neutral
- Sitagliptin can be used as triple therapy with metformin and a sulphonylureas
- Relatively expensive
- Not always effective enough at reducing HbA1c
Diabetes is a disease that cannot be cured rather it can be controlled and managed. Proper medicines are useful to control this diabetes.
- Medicines: A diabetic patient should take his/her medicine properly and regularly to control. It cannot be cured. But medicine will help not to worsen the situation of patients.
- Diet: A healthy diet can prevent diabetes. Even after diabetes a proper diet can decrease the risk factors and symptoms easily. Control of food diet and having vegetables and fruits can lead a diabetic free life
- Insulin Injection: For insulin deficiency, Insulin injection is the best treatment for diabetic patients. Insulin injection can decrease blood glucose level in vessels and cells can get enough glucose to maintain the body
- Alcohol control: Consumption of alcohol plays a major role in diabetes. So it must be stopped to control unwanted diabetes
- Smoking: Just like alcohol, smoking is also a factor for diabetes. It increases the risk of diabetes. A person who doesn’t smoke has least chance to have diabetes
- Obesity: Obese patients have the higher risk of getting diabetes. Not all obese patients are suffering from it. Although it’s not a fact, certain cases show obesity increases the chances for diabetes. So controlling food & keeping BMI (Body Mass Index) control can gift one a happy healthy diabetic free life
Changing life-style to increase physical activities and a diet with modest calorie restriction, less saturated fat and more dietary fibre can significantly reduce the rate at which impaired glucose tolerance progresses to type 2 diabetes. It has been observed that even older people can successfully undertake the lifestyle programmes required. Patients present with an insulin-resistant diabetes often with marked hypertriglyceridaemia can be a risk factor for pancreatitis and should be managed with a low fat diet and lipid-lowering medication. Strategy for a diabetic patient can be added like:
- Keep total dietary intake of fat to ≤30% of total energy intake
- Keep intake of saturated fats to ≤10% of total fat intake
- Keep intake of dietary cholesterol to <300 mg/day
- Replace saturated fats by an increased intake of monounsaturated fats
- Increase intake of fresh fruit and vegetables to at least five portions per day
- Regular intake of fish and other sources of omega-3 fatty acids
- Limit alcohol intake
- Limit intake of salt to <100 mmol/l day (<6 g of sodium chloride or <2.4 g of sodium per day