A Review on Diabetes Mellitus

Diabetes is a life-long disease that affects the way your body handles glucose, a kind of sugar, in your blood. It is often referred as Diabetes Mellitus (DM) by doctors which describes a group of metabolic diseases resulting in high blood glucose, either due to inadequate production of insulin or because the body’s cells do not respond well to insulin or both. Normally, the pancreas releases insulin to help your body store and use the sugar and fat from the food you eat. Diabetes can occur when the pancreas produces very little or no insulin, or when the body does not respond appropriately to insulin. In 2014 it was estimated that over 422 million people throughout the world had diabetes. The most common diabetes symptoms include frequent urination, intense thirst and hunger, weight gain, unusual weight loss, fatigue, cuts and bruises that do not heal, male sexual dysfunction, numbness and tingling in hands and feet. According to health day reporter, Steve Reinberg in September 2018, 30 million Americans now have diabetes. 1 in 7 Americans has diabetes, and many don’t even know they have high blood glucose disease. According to the U.S. centers for disease control and prevention, 14% of U.S adults have diabetes of which 10% know it and over 4% are undiagnosed. According to the American Diabetes Association, 95% of the diabetes cases are type 2, which is often tied to overweight or obesity. About 5 % of diabetes cases are type 1, which can arise early in life and is not linked with lifestyle factors. According to the report, nearly 16% of men and 12% of women have diabetes and the risk of developing both diagnosed and undiagnosed diabetes increases with age. In terms of population, diabetes is more common among Hispanics (20%), and blacks (18%), than whites (12%). The research found that overweight and obese are more likely to develop diabetes. Only 6% of underweight or normal weight adults had the disease, while 12% of overweight adults and 21% of obese adults had diabetes. Diabetes cannot be cured but treatment modalities include lifestyle modifications, treatment of obesity, and oral hypoglycemic agents like iguanids, sulfonylurea, thiazolidinedione’s, alpha glucosidase inhibitors, dipeptidyl peptidase-IV inhibitors and insulin.

Diabetes Mellitus (DM) is an endocrinological disorder which is a group of metabolic or heterogeneous affliction resulting from an irregularity in insulin secretions and insulin actions or both. It is one of the oldest diseases known to man. It was first reported in Egyptian manuscript about 3000 years ago. It is also referred as black-death from the 14th century. Patients with diabetes have been classified into two main categories: type-1 diabetes mellitus (T1DM), characterized by a near-absolute deficiency of insulin secretion and type-2 diabetes mellitus (T2DM) where the cause is a combination of insulin resistance and an insulin secretory defect. In 1936, the distinction between type 1 and type 2 diabetes mellitus was clearly made. Type 2 diabetes mellitus was first described as a component of metabolic syndrome in 1988. The presence of DM shows increased risk of many complications such as cardiovascular diseases, peripheral vascular diseases, stroke, neuropathy, renal failure, retinopathy, blindness, amputations, etc. People living with type 2 DM are more vulnerable to various forms of both short and long term complications, which often lead to their premature death. Drugs are used primarily to save life and alleviate symptoms. Secondary aims are to prevent long-term diabetic complications and, by eliminating various risk factors, to increase longevity.

Figure 1: Illustration of an artery with normal blood glucose level and an artery with high blood glucose levels. (Image source: foodnurish.com.

Figure 2: (Image source: babygest.com).

Figure 3: (Image source: thermofisher.com).

Figure 4: (Image source: danii.org.au).

Globally, the number of people with diabetes mellitus has quadrupled in the past three decades, and diabetes mellitus is the ninth major cause of death. Most patients with T2DM have at least one complication, and cardiovascular complications are the leading cause of morbidity and mortality in these patients. The number of people (20-79 years) living with diabetes in 2017 was estimated to be 424.9 million. This value is further estimated to be 628.6 million by 2045. The largest number of people (20-79 years) with diabetes are in China, India and United States in 2017. Diabetes in people older than 65 years was estimated to be 122.8 million in 2017, which is further estimated to be 253.4 million in 2045. It was estimated that globally as many as 212.4 million people or half (50.0%) of all people 20-79 years with diabetes were unaware of their disease in 2017. In low income countries like Africa, the proportion of undiagnosed diabetes is 69.2% while in high income countries, this value contributes to 37.3%. Asia is a major area of the rapidly emerging T2DMglobal epidemic, with China and India the top two epicenters.

Earlier Diabetes was classified mainly into two types as Type 1 or Insulin-Dependent Diabetes Mellitus (IDDM) and Type 2 or Non-Insulin-Dependent Diabetes Mellitus (NIDDM) which were proposed by WHO in 1980 and 1985. In recent years, the traditional way of classifying DM has been replaced by new classification which includes mainly four types of DM.

?. Type 1 Diabetes Mellitus

A.      Autoimmune

B.      Idiopathic

?. Type 2 Diabetes Mellitus

It ranges from relative insulin deficiency to disorders of insulin secretion and insulin resistance.

III. Gestational Diabetes Mellitus (Occurs in Pregnant woman)

IV. Other specific types of Diabetes Mellitus

A.      Genetic defects in ?-cell function

1.       Chromosome 12, HNF-1? (MODY 3)

2.       Chromosome 7, glycosidase (MODY 2)

3.       Chromosome 20, HNF-4? (MODY 1)

4.       Mitochondrial DNA

5.       Monogenic Diabetes

B.      Genetic defects in insulin action

1.       Type A insulin resistance

2.       Leprechaunism

3.       Rabson-Mendenhall syndrome

4.       Lipotrophic diabetes

C.      Disease of the exocrine pancreas

1.       Pancreatitis

2.       Pancreatectomy/trauma

3.       Neoplasia

4.       Cystic fibrosis

5.       Hemochromatosis

6.       Fibrocalcificpancreatopathy

D.      Endocrinopathies

1.       Acromegaly

2.       Cushing’s syndrome

3.       Glucagonoma

4.       Pheochromocytoma

5.       Hyperthyroidism

6.       Somatostatinoma

7.       Aldosteronoma

E.        Pharmacologically or chemically induced

1.       Vacor

2.       Pentamidine

3.       Nicotinic acid

4.       Glucocorticoids

5.       Thyroid hormones

6.       Diazoxide

7.       ?-adrenergic agonists

8.       Thiazides

9.       Dilantin (phenytoin)

10.    ?-interferon

F.       Others 

1.       Infections

1.       Congenital rubella

2.       Cytomegalovirus

3.       Others

2.       Infrequent forms of autoimmune diabetes

1.       Stiff-man syndrome

2.       Antibodies against insulin receptors

3.       Others

3.       Other syndromes occasionally associated with diabetes

1.       Down’s syndrome

2.       Klinefelter’s syndrome

3.       Turner’s syndrome

4.       Wolfram’s syndrome

5.       Friedreich’s ataxia

6.       Huntington’s chorea

7.       Lawrence-Moon-Biedel syndrome

8.       Myotonic dystrophy

9.       Porphyria

10.    Prader-Willi syndrome

G.      Post-Transplant

Table 4: Types of Oral antidiabetics.

It is also known as pregnancy induced diabetes. It is a temporary condition in which the blood glucose levels increase during third trimester of pregnancy but usually return to normal after delivery. According to Centers of Disease Control and Prevention (CDC), between 2 – 10% pregnancies each year results in gestational diabetes. Women with gestational diabetes are at an increased risk of complications during pregnancy and at delivery. These women and their children are possibly at an increased risk of type 2 diabetes in the future. According to CDC report, around 50% of people with gestational diabetes will later develop type 2 diabetes.

Complications associated with Gestational diabetes

Uncontrolled or untreated blood sugar levels can cause problems to babies as well as their mother. Most women with gestational diabetes deliver healthy babies if proper treatment is given.

Complications in baby can be of the following types.

·   Low blood sugar: Babies may be hypoglycemic shortly after their birth because their own insulin production is high.

·  Premature birth: Gestational diabetes increases the risk of mothers giving premature birth.Excess growth: High glucose levels in mother can cross the placenta which can trigger the baby’s pancreas to make extra insulin. This in turn, can cause the baby to grow too large. As a result of this, it may require a C-section.

·   Death: If the gestational diabetes is left untreated, it may result in the death of the baby before delivery or shortly after delivery.

·   Type 2 Diabetes later in life: Mothers with gestational diabetes are at a higher risk of developing type 2 diabetes later in their life. The same applies to their babies.

Following activities are advised in case of gestational diabetes.

·         Proper diet plan (Dietician or doctors can advise about meal plan)

·         Regular exercise

·         Staying active

·         Monitoring blood sugar levels

·         Monitoring the growth and development of the fetus

·         Keeping weight gain under control

·         Taking oral medications or insulin as per doctor’s advice to control blood sugar level

Diabetes and Prediabetes can be diagnosed by several methods by a doctor or a registered healthcare practitioner. Doctors general recommend different tests depending on whether the patient has any symptoms or not, or if the patient is pregnant. Diagnosis at an early stage can be accomplished through relatively inexpensive blood glucose test. The blood test may be repeated on a second day to diagnose diabetes on recommendation of a doctor. However, if your blood glucose level is very high, or if you have classic symptoms of hyperglycemia in addition to one positive test, second test may not be required by the doctor to diagnose diabetes (Tables 1-5) (Figures 1-4).

1.    Fasting Plasma Glucose Test (FPG): In this test, the patient should not eat or drink anything except water for at least 8 hours. The patient is advised to have a normal dinner and then undergo fasting overnight. The test is done next day in the morning before having breakfast.

2.   A1C Test: In this test, the average blood glucose for the past two to three months is measured. This test is also called hemoglobin A1C, HbA1C, glycated hemoglobin, and glycosylated hemoglobin test. This test has an advantage over other tests because the patient does not have to undergo fasting or drink glucose before test.

3.    Oral Glucose Tolerance Test (OGTT): You will have to fast for at least 8 hours before this test. Blood sample is taken to measure the glucose level after fasting and then you are allowed to drink a liquid which is high in sugar. After 2 hours of drinking the liquid, another blood sample is withdrawn to check the glucose level in blood.

4    Random plasma glucose test: In this test, blood glucose can be tested anytime of the day without fasting.

5.  Glucose challenge test: This test is done to check gestational diabetes in pregnant woman. Fasting is not required for this test. The patient is given a sweet liquid containing glucose to drink. Blood sample is taken after one hour of drinking sweet liquid to measure the blood glucose content. If the blood sugar level is too high, oral glucose tolerance test after fasting will be done to confirm gestational diabetes.

There is a guideline developed by American Diabetes Association (ADA) which recommends screening of following people for diabetes.

·  Anyone with a BMI (Body Mass Index) higher than 25 (23 for Asian Americans), regardless of age, if they have any additional risk factors like sedentary lifestyle, high blood pressure, high cholesterol level, a history of polycystic ovary syndrome, heart disease or family history of diabetes.

·    Any person older than 35 years of age should have their blood sugar tested. If the results are normal, screening can be done every 3 years after that.

·    Women with gestational diabetes should be screened for diabetes every 3 years.

·  Anyone who has been diagnosed with prediabetes should undergo screening every year.

·   HIV positive patients are advised to go for regular screening

Prevention of Diabetes

Diabetes can be prevented by certain lifestyle changes. We can easily prevent or delay the onset of type 2 diabetes by following ways.

·         Maintain a healthy body weight as per body mass index.

·         Regular physical exercise for 30 minutes daily.

·         Avoid junk food, sugar and saturated fat. Eat a healthy diet.

·         Quit smoking

·         Manage stress and anxiety.

·      Monitor and keep your blood pressure and cholesterol within normal range.

·         Regular screening for diabetes.

Treatment of Diabetes

Managing diabetes is important to live a long and healthy life. Depending on type of diabetes, blood sugar monitoring, insulin and oral drugs may be taken for the treatment. Early treatment in people with prediabetes can also return their blood glucose levels to normal range.

1.   Treatment for type 1 diabetes: Patients with type 1 diabetes are required to take insulin injections or insulin pump as a lifelong insulin therapy. Patients are advised to self-monitor their glucose level at home using glucose test strips. Depending on the glucose level, 2 or more injections of insulin may be advised by the doctor. Some of the patients may also be required to undergo pancreas transplant or islet cell transplant depending on the severity and on the recommendation of a doctor.

2.   Treatment of type 2 diabetes: Oral anti diabetic drugs or insulin or both may be required to treat type 2 diabetes mellitus along with a healthy lifestyle, regular physical exercise and proper diet plan. Some of the oral antidiabetic drugs work by increasing the release of insulin by pancreas while some of them prevent the production and release of glucose by the liver. There are many different types of oral antidiabetic drugs having their own mechanism of action to reduce the blood sugar level. For example; metformin, glimepiride, sitagliptin, voglibose, dapagliflozin, etc.

It is advised that patients with diabetes mellitus either type 1 or type 2 should monitor their blood glucose concentrations periodically at home using a glucometer. Glucometer is a simple device to measure the blood sugar level at home. Whenever the patient have the symptoms of hypoglycemia, this device is very helpful in such conditions. The patient can prick their finger with the needle provided with the device and a drop of blood is enough to measure the blood sugar level using this device [1-17].

·         The number of people with diabetes increased from 108 million in 1980 to 422 million in 2014. Prevalence has been rising more rapidly in low and middle income countries than in high income countries.

·         Diabetes is a major cause of blindness, kidney failure, heart attacks, stroke and lower limb amputation.

·         Between 2000 and 2019, there was a 3% increase in diabetes mortality rates by age.

·         In 2019, diabetes and kidney disease due to diabetes caused an estimated 2 million deaths.

·         A healthy diet, regular physical activity, maintaining a normal body weight and avoiding tobacco use are ways to prevent or delay the onset of type 2 diabetes.

·         Diabetes can be treated and its consequences avoided or delayed with diet, physical activity, medication and regular screening and treatment for complications.

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