Diabetes mellitus (DM) is a group of common metabolic disorders that all share the characteristic feature of chronic hyperglycemia (increased blood glucose levels).

Anatomy & physiology relevant to DM

The hormone that keeps the blood glucose concentration under check is insulin and it is secreted by pancreas an organ situated inside the belly cavity (abdominal cavity).

This hormone secretion is stimulated whenever the glucose concentration in the blood rises or example after food intake and the process digestion is underway. Insulin by various mechanisms helps in pushing the glucose in the blood to inside the body cells and this glucose is used either for energy production or storage as glycogen or fat. Insulin assists in the cell entry of fatty acids and amino acids as well.

So if insulin is absent or deficient then the blood concentration of glucose, fatty acids, amino acids are abnormally elevated and this itself can cause injury to cells & tissues. Also the chronic deprivation of nutrients inside the cells adds up to this insult. There may be other additional mechanism of injuries as not all pathological changes associated with DM can be explained just based on these two above mechanisms.

Classification of DM

DM is generally classifies based on what causes it (etiological factors) ad broadly there are four categories including;

* Type 1 DM (there is beta cell destruction)

Immune mediated
Idiopathic (cause is known)

* Type 2 DM (insulin deficiency and/or insulin resistance)
* Other specific types of DM

A- genetic defects in beta cell function (e.g. maturity onset DM)
B- genetic defect in insulin action (e.g. Type A insulin resistance)
C- Diseases of exocrine pancreas (e.g. pancreatitis)
D- endocrine disorders (e.g. acromegaly)E- chemical or drug induced (e.g. steroid drug induced)
G- infections (e.g. congenital rubella)
G- uncommon forms of immune mediated DM (e.g. stiff-person syndrome)
H- Other genetic syndromes (e.g. myotonic dystrophy)

* Gestational DM (GDM)

What causes DM?

DM is caused by a complex interaction between genetics & environmental factors. The various mechanism involved in resulting hyperglycemia include;

* Absent or reduced insulin secretion
* Insulin resistance & decreased glucose utilization in the cells
* Increased glucose production.

Type 1 DM: There is an interaction among genetic environmental & immunological factors give rise to this DM. These factors ultimately result in the destruction the beta cells of the pancreas.  Type 1 DM is the result of an autoimmune disease in majority of the patients.

Type 2 DM: Although what exactly induces type 2 DM is not precisely known now but it is also thought to be the result of a complex interaction between genetic & environmental factors. There is no evidence for autoimmune injury for type 2 DM. The genetic influence appears to be somewhat more with type 2 as compares to type 1 DM. It starts as insulin resistance and follows with insulin secretory defect.

Risk factors for Type 2 DM;

* History of DM in the family
* Obesity
* Long term physical inactivity
* Race & ethnicity (e.g. Asian American)
* History of GDM or delivery of a baby >4kg
* Hypertension
* Triglycerides >250 mg/dl
* HDL cholesterol < 35 mg/dl)
* Polycystic ovarian syndrome etc.

Complications of DM

Acute complications (short term) include;

* Diabetic ketoacidosis
* HHS (hyperglycemic hyperosmolar state)

Chronic (long term) complications include;

* Micro vascular (small vessel) disease;

Retinal damage (retinopathy)
Nerve damage (neuropathy)
Kidney damage (nephropathy) etc.

* Large vessel disease;

Coronary artery disease (angina, heart attack)
Cerebro vascular disease (stroke)
Peripheral arterial disease etc.

* Other complications;

Infections
Sexual dysfunctions
Cataracts etc.

Clinical manifestations

The symptom of DM can be grouped as either;

* DM related or
* Related with DM complications.

DM related symptoms include;

* Poly-uria (excess passage of urine)
* Poly-dipsia (excess thirst)
* Weight loss
* Fatigue
* Generalized weakness etc.

Related with complications of DM include;

* Retinal damage – blurring of vision, loss of vision etc
* Nerve damage (neuropathy) – numbness, pins & needles, foot drop etc
* Atherosclerosis – strokes, heart attack, angina etc
* Infections – fever etc

Examination findings generally include;

* Retinal changes (diabetic retinopathy)
* Weak peripheral pulses (if atherosclerosis has taken place)
* Diabetic foot-ulcer, gangrene etc.

Diagnosis

The frequent blood investigations ordered to diagnose & mange DM include;

* Random plasma glucose (can be done any time of the day)
* Fasting plasma glucose (no energy intake for at least 8 hours before blood test)
* GTT (glucose tolerance test)
* HBA1c (to check long term blood glucose control) etc.

A diagnosis of DM can be made if one or more criteria are met including;

1) Random plasma glucose ?200 mg/dl with typical DM symptoms like excess thirst, excess passage of urine & weight loss.

2) Fasting plasma glucose ?126 mg/dl.

3) Two-hour plasma glucose ?200 mg/dl during an oral GTT (using 75 g glucose load).

Management

The general managements of diabetic patients include;

* Stabilization of the patient
* Hospitalization if necessary
* Symptomatic treatment (e.g. gabapentin for numbness)
* Treatment of complications like infections, stroke, heart attack etc
* Dietary adjustment (low calorie but nutritious)
* Adequate exercise
* Weight loss for Type 2 DM
* Sugar substitutes like aspartame etc.

Specific treatment for the DM would include

* Oral hypoglycemic agents
* Insulin

Type 2 DM are generally started with oral hypoglycemic agents and some of them may require insulin as well. Type 1 DM is treated with insulin.

The following are some of the most commonly used oral hypoglycemia agents;

* Biguanides:
* Alpha glucosidase inhibitors
* Sulfonylureas
* Meglitinides
* Glitazones etc.

The commonly used drugs under each category are mentioned below.

* Biguanides;

Metformin

* Alpha glucosidase inhibitors;

Miglitol
Acarbose

Sulfonylureas;

Gliclazide
Glimepiride
Glipizide etc.

Sulfonylurea and biguanide combinations;

Gliclazide + Metformin
Glimeperide + metformin
Glipizide + Metformin etc.

Meglitiides;

Tab Repaglinide
Tab Nateglinide

Glitazones;

Rosiglitazone
Pioglitazone

Similar to biguanide and sulfonylurea combination there are combinations available with other drug groups as well.

The insulin preparations are available from various sources including human, animal (bovine & porcine). In addition to the source they are also categorized based on their time for onset of action (OA), duration of action (DA) etc and some important such preparations include;

* Ultra rapid acting (OA 15 minutes, DA 3- 5 hours);

Insulin Lispro
Insulin Aspart etc.

* Rapid acting (OA 30 minutes, DA 6- 8 hours)

Regular human  insulin

* Intermediate acting (OA 2-4 hours, DA 18 – 26 hours)

NPH insulin ( isophane insulin )
Lente Insulin

Long acting (OA 4-8 hours, DA > 36 hours)

Ultra Lente insulin

Some insulin mixtures include;

Huminslin 30/70
Huminsulin 50/50 etc.

A bit about how the thyroid gland works. The thyroid gland consists of closed follicular spaces lined by cells called cuboidal epithelium the spaces themselves being filled with a secretory substance called colloid containing the thyroid hormones. (See Fig-1). The element iodine is required for synthesis of thyroid hormones the deficiency of which causes a disease called goiter which manifests as a swelling in the neck. Iodine is first concentrated in the cells and attached to the newly synthesized molecule thyroglobulin to form the two thyroid hormones.

Once formed the hormones bind with blood proteins and are slowly released to the tissue cells. Where they bind with intracellular proteins starting the transcription of the cellular genes resulting in the synthesis of hundreds of proteins by the cells synthetic machinery. I should remind you that the cellular enzymes which are responsible for making metabolism possible are themselves protein in nature. So in effect the cell’s metabolism is speeded up. That is why we see that thyroid hormone values in growing children is higher than adults as a growing body needs more energy thus a higher rate of metabolism per unit mass.

In children thyroid hormone levels have a great effect on growth. Those who are hypothyroid exhibit stunted growth. The fetal thyroid also secretes thyroid hormone and its deficiency shows up as mental retardation in later life. Such a disease is known as cretinism (See Fig-2).

As such the levels of thyroid hormones are strictly controlled by another hormone secreted from another gland the ‘thyroid stimulating hormone’ or TSH secreted from the anterior pituitary gland. A higher level of thyroid hormone causes the level of TSH to fall thus reducing thyroid hormone synthesis and vice versa. This phenomenon is known as the ‘negative feedback control mechanism’. This TSH is again controlled by another hormone released from a part of the brain known as hypothalamus. This hormone is called throtropin releasing hormone or TRH. This is released with the same negative feedback logic unique to human physiological systems. It has been suggested that TRH acts as a mother controller of the thyroid system. Hormones in the blood are present in very small amounts like a billionth of a milligram per milliliter and can only be measured by a special chemical process developed for that purpose called radioimmunoassay.

Deficiency of thyroid hormone is called myxedema (See Fig-3) or hypothyroidism and can be caused by a number of factors like deficiency of iodine in the diet or decrease in synthesis. The gland in the latter case is impaired or destroyed by the body’s own immune system antibodies a phenomenon called autoimmune disease. Thyroid hormone is given orally as treatment while in the former case elemental iodine is given. In areas where iodine is deficient in diet salt is fortified with iodine and is called iodized salt. Deficiency of iodine produces a swelling of the gland called goiter. Enlarged thyroid gland similar to these is also found in a disease called idiopathic non toxic colloid goiter.
Hypothyroidism manifests itself as extreme lassitude, weight gain and intolerance to cold.

On the other hand hyperthyroid persons (having excess thyroid hormones) are thin, have trembling hands and fingers and have protruded eyeballs a condition called exopthalmos (See Fig-4). The stimulation to the gland comes from antibodies produced by the individuals’ immune system called thyroid stimulating immunoglobulin.

Sometimes hyperthyroidism may develop from a tumor called an adenoma. Hyperthyroidism is tackled by either giving antithyroid drugs or partially destroying the thyroid gland by giving radioactive iodine which destroys the gland by radiation or removing part of the gland surgically by an operation called partial throidectomy.

Thyroid cancer is another disease of the thyroid gland and usually manifests as a nodule which can be felt and shows an increased uptake during a diagnostic process called a thyroid scan. Like other cancers it is treated by surgery, by radiation or by chemicals called chemotherapy.

The thyroid gland also secretes another hormone called calcitonin which is produced by the Para follicular cells or C cells. This has an effect on the plasma ionic calcium concentration.

So dear reader you can realize now the complexity of the thyroid gland, nature’s metabolism regulator having a myriad variety of physiological functions but weighing only 20 grams.

For Type 1 Diabetes, it is usually due to genetic factors. Some children are born with gene defects that may affect the production of insulin which is why symptoms manifest early on in childhood. For Type 2 Diabetes, anyone can get it. Certain risk factors are associated with Type 2 Diabetes including a family history of diabetes, obesity, sedentary lifestyle, hypertension and high cholesterol level. Race is also a risk factor because studies show that Asians, Latinos and Black Americans have a higher risk of developing Diabetes but this risk factor is not as strong as the others previously mentioned.

What Are The Symptoms?

Diabetes can present with a lot of symptoms but the most frequently reported symptoms include persistent thirst and hunger, frequent urinations at night, unexplainable significant weight loss and fatigue. Frequent urinations happen when blood glucose levels are high which is the case in diabetes. When one urinates often, the body interprets it as water lost so the body sends signals to the brain to increase thirst. However, since frequent urination persists, thirst also becomes persistent. Weight loss happens because the body is unable to break down glucose in the blood which is badly needed by the cells in tissues. In effect, the cells use up their stored energy to maintain bodily functions. Imagine the body feeding off itself because it is unable to get glucose from the blood. And since the body’s energy is constantly being depleted to sustain bodily processes, the body adapts by making the person feel fatigued. Fatigue will cause the person to move less which can save the body from using up reserved energy.

How Is It Diagnosed?

People who experience these symptoms must consult a physician. A good medical history is taken, a physical examination is performed and together with lab results, diabetes can be diagnosed. The most cost effective laboratory test that is usually used to diagnose Diabetes Mellitus is the Fasting Blood Sugar (FBS) and Oral Glucose Tolerance Test (OGTT). These tests measure glucose levels in the blood after fasting and after meals respectively. There are normal cut-off values found in Diabetes Guidelines which are used to determine levels that are abnormal. A urinalysis is also routinely performed to detect if sugar is being spilled into the urine.

How Is It Treated?

Diabetes Mellitus is a life-long disorder and cannot be fully treated. However, blood glucose can be controlled with oral and injectable medications. Early diagnosis and immediate treatment is important to delay the progression of diabetes and to prevent complications such as kidney and heart disease.

How Is It Prevented?

Although family history of Diabetes Mellitus is a risk factor, it is still highly preventable. A good lifestyle which includes regular exercise and a low-sugar, low-cholesterol, high fiber diet can prevent Diabetes.

Additional Info & Research
Stem Cell Therapy to Treat Diabetes Mellitus

Hyperthyroidism is the term used to describe the overproduction of thyroid hormones caused by over-activity of the thyroid gland. This gland is situated in the front of the neck. It is not usually noticeable, except when it becomes enlarged (goitre).

The thyroid gland produces two hormones, thyroxine and triiodothyronine, which are both essential for normal body cell functions. If either one or both of these hormones are released in excessive amounts, hyperthyroidism will develop.

The condition is usually associated with a general increase in the size of the gland (when it may be called Graves disease), or with one or more nodules (toxic or hot nodules) appearing on the gland.

What causes Hyperthyroidism?

Graves disease, the most common cause, is an auto-immune disorder in which the body makes antibodies which stimulate cell activity inside the thyroid gland. Another common cause of the condition is when an enlarged thyroid becomes overactive becomes overactive (Toxic modular goitre).

About 1:100 adults develop hyperthyroidism, and women are 5-7 times more likely than men to suffer from this disease. It can occur at many age, but the most common suffers are adults between 30 and 60 years old.

How is hyperthyroidism diagnosed and treated?

The common symptoms of hyperthyroidism are agitation, restlessness and a tremor. There is often loss of weight, despite an increased appetite, and profuse sweating, with a dislike of hot weather. The eyes may protrude. Many people feel weak and lethargic and notice their heart is beating fast. Very occasionally, the hair may steal to fall out.
The doctor will usually make a diagnosis from the symptoms, but occasionally, if the disease develops slowly, it may not be obvious. It will be necessary to carry out blood tests to gauge thyroid function. It may take 2-3 weeks to receive the results of these tests, which measure the level of thyroid hormones in the bloodstream.
There are three main treatments: using drugs, radioactive iodine and surgery.

• Drugs / Medicine
  There are two common anti-thyroid drugs; carbimazole and propylthiouracil (PTU), both of which are taken daily in tablet form and which reduce the gland’s activity. These work quite quickly and are usually taken for up to 18 months. However, there is a risk of relapse after the course of treatment has finished. Drugs known as beta blockers are also given at the start to control the symptoms quickly while waiting for the anti-thyroid drug to work, but these drugs do not cure the underlying problem.
• Radioactive Iodine
  Radioactive iodine treatment is given by mouth and, once the iodine is taken up by the gland, it destroys some of the cells which are producing thyroid hormones. It is often difficult to judge the right dose, and over half those receiving this treatment will swing the other way and develop thyroid under-activity (hypothyroidism) within a few years. On the other hand, a few patients may need a second dose. It is not normally given to women of child-bearing age because of possible risks to the unborn child.
• Surgery
  The last option is surgery. This involves an operation to remove most of the thyroid gland. After surgery about 15% of patients either experience a recurrence of hyperthyroidism or suffer from underactive thyroid.

When should I see my doctor?

You should see your doctor as soon as possible if you think you might have an over-active thyroid gland and if you have some or all of the symptoms listed overleaf. Do not delay or avoid seeking medical help, as the condition will become progressively worse unless it is treated.

What will the doctor do?

Your doctor will check your medical history and will enquire about some of the other symptoms you may be experiencing. You may be weighed and your heart rate may be checked, as it can become irregular as well as fast. A physical examination will include testing nerve reflexes, which typically become abnormally brisk with this condition. The doctor will consider other possible reasons for similar symptoms-these could include an anxiety state or possibly diabetes. The doctor will normally arrange for blood tests to be carried out to check your thyroid function. If hyperthyroidism is suspected, you may be referred to a specialist straightway, without waiting for the results of the blood tests.

What can I do myself?

You cannot help this condition yourself. Occasionally the drugs have side effects, and if you develop a skin rash, joint pains, painful glands, nausea, or vomiting, tell your doctor immediately. If you do have hyperthyroidism and are treated with radioactive iodine or surgery, you could develop thyroid under-activity later. Thyroid tests should be repeated every 1-2 years.

How dangerous is Hyperthyroidism?

If untreated, hyperthyroidism may lead to heart failure. While the condition is not preventable, it is not usually dangerous, provided it is treated.

Symptoms of Hyperthyroidism

- Agitation.
- Restlessness.
- Tremor.
- Loss of weight.
- Sweating.
- Rapid pulse.
- Protruding eyes.

Warning and Precautions

In severe cases, hyperthyroidism can lead to heart failure. Always see your doctor if you think you have any of the symptoms of hyperthyroidism.

Are there any Alternative Treatments for Hyperthyroidism?
The homoeopathic treatment for a hyperactive thyroid is so prescribe Iodum 30, which should be taken twice a day for two weeks.

Other than that, reflexology (massage of zones in the feet) is so said to ease hyperthyroidism.

An ovarian cyst is an abnormal, fluid-filled swelling inside one of the ovaries. These are the almond-shaped glands situated on either side of the uterus, immediately below the entrance to the Fallopian tubes. The ovaries contain follicles, one of which releases an egg during ovulation. The ovaries are also responsible for producing the female sex hormones, oestrogen and progesterone.

Most women will probably have had at least one ovarian cyst without knowing it. They can appear at any age, in any number, and on one or both ovaries. They often disappear on their own without any treatment.

What causes an Ovarian Cyst?

The most common cause of ovarian cysts is a minor upset during ovulation. The follicle, instead of bursting and releasing an egg, continues to grow and accumulates fluid. This causes a functional, or simple cyst, These cysts can grow quite large, sometimes to over 8cm.

Simple cysts can also be caused by endometriosis, a condition in which fragments of the uterine lining travel to other parts of the abdomen. These fragments bleed monthly, as the uterus does (during menstruation) but they can cause blood-filled cysts if they migrate up to the ovaries.

Another type of cyst, a dermoid cyst, accounts for about 10% of all ovarian cysts. Dermoid cysts range in size from just a few millimeters to 10cm or even more. They have a cell structure that is similar to skin and are thought to be made up of the same cells from which an embryo develops. It is quite  common for a dermoid cyst to contain tissues of hair, teeth and bone.

Both simple and dermoid cysts are benign (harmless). However, in some cases an ovarian cyst can be malignant (cancerous) and will have to be surgically removed.

How is an Ovarian Cyst diagnosed and treated?

Since there are usually no symptoms, ovarian cysts are often discovered during a routine pelvic examination. However, abdominal pain, nausea, fever, and abnormally heavy periods can make a doctor suspect a cyst. If this is the case, the doctor will perform an internal examination, and then make a referral to a hospital for ultrasound scanning or a laparascopy (an examination of the abdominal cavity through a viewing tube). Both of these procedures can confirm the diagnosis, as well as determine the size and position of the cyst. They cannot tell whether the cyst is malignant or not.

If a cyst is diagnosed, it will usually be surgically removed, whether the doctor thinks it is malignant or not. This is done in a hospital under a general anaesthetic, and a stay of at least a couple of days is usually needed.

During the operation, a small piece of the cyst may be removed and sent to the laboratory. There, it is quickly examined to find out the nature of the cyst. If it is benign, only the cyst is removed, leaving the ovary in place. The other ovary is also examined, because cysts sometimes occur in both ovaries at the same time.

If the cyst is malignant, the cyst ovary and Fallopian tube are all removed. Again, the second ovary will be examined. If it is affected as well, the second ovary will usually be removed.

What can I do myself?

The pill reduces the risk of benign  ovarian cysts by 90% and reduces the risk of ovarian cancer by 40%. Once a cyst is discovered, it is important to discuss the possibilities and options thoroughly with your doctor before going ahead with any treatment. Find out whether it will be necessary to have both ovaries removed if the cyst is malignant. This is very important if you are still of childbearing age and want to have a family.

If you are of premenopausal age, ask about hormone replacement therapy, because if both the ovaries are removed you will not produce female sex hormones and will start a premature menopause.

When should I see my doctor?

See your doctor immediately if you experience any pain or swelling in the lower abdomen, particularly if you also have some or all of the symptoms listed overleaf.

Are Ovarian Cysts dangerous?

A cancerous cyst that is untreated is dangerous, as the cancer can spread. If the cyst and one ovary are removed, fertility may be slightly reduced but the necessary sex hormones will continue to be produced. Removal of both ovaries results in infertility, and there may be a need for hormone replacement therapy. If the cyst is benign and only the cyst is removed, then there should be no further trouble and it should not affect fertility. There may be a need to be examined more often in the future, in case another cyst develops.

Symptoms of Ovarian Cysts

Ovarian cysts often cause no symptoms, especially when they are small, but signs which may indicate the presence of a cyst include:
-    Abdominal swelling
-    Pain during sexual intercourse
-    Changes in the normal menstrual cycle, including irregular, painful or heavy periods.
-    Frequent urination
-    Difficulty conceiving
-    Abdominal or pelvic pain, nausea and fever if the cyst twists or ruptures

Warning: Any pain or swelling in the lower abdomen should be seen by your doctor. Most ovarian cysts are benign, but delay in getting treatment may lead to problems. Consult your physician as early as possible to avoid complications.

Surgical procedure of removing a swelling ovarian cyst.