FAQs in Diabetes Rajeev Chawla, Aastha Chawla
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Diabetes: An OverviewChapter 1

Question: What is diabetes mellitus?
Diabetes mellitus has been defined by the American Diabetes Association (ADA) as a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Deficient action of insulin on target tissues forms the basis of the abnormalities in carbohydrate, fat, and protein metabolism in diabetes. This could result from inadequate insulin secretion and/or diminished tissue responses to insulin at one or more points in the complex pathways of hormone action. Impairment of insulin secretion and defects in insulin action frequently coexist in the same patient, and it is often unclear which abnormality, if either alone, is the primary cause of the hyperglycemia.
The chronic hyperglycemia is associated with long-term damage, dysfunction, and failure of different organs, especially the eyes, kidneys, nerves, heart, and blood vessels.
Question: What are the common types of diabetes?
Based on the etiopathogenesis, diabetes can be categorized into two broad types. In type 1 diabetes mellitus (T1DM), there is an absolute deficiency of insulin secretion. Individuals at increased risk of developing this type of diabetes often have serological evidence of an autoimmune pathologic process occurring in the pancreatic islets and by genetic markers.
Type 2 diabetes mellitus (T2DM), the more prevalent category, is a result of combination of resistance to insulin action and an inadequate compensatory insulin secretory response. In the latter category, a degree of hyperglycemia sufficient to cause pathologic and functional changes in various target tissues is present without clinical symptoms. This may be present for a long period of time before diabetes is detected. During this asymptomatic period, it is possible to demonstrate an abnormality in carbohydrate metabolism by measurement of plasma glucose in the fasting state or after a challenge with an oral glucose load or by glycosylated hemoglobin (HbA1c).2
Sometimes, categorizing an individual to a type of diabetes depends on the circumstances present at the time of diagnosis, and many diabetic individuals do not easily fit into a single class. Women developing diabetes during pregnancy are classified as having gestational diabetes mellitus (GDM). Other uncommon and diverse types apart from these, also exist, and are caused by plethora of factors, such as infections, drugs, endocrinopathies, destruction of pancreas, and genetic defects (Box 1).
Women with GDM may continue to be hyperglycemic after delivery and may be determined to have, in fact, T2DM. Individuals with diabetes because of large doses of exogenous steroids may become normoglycemic once the glucocorticoids are discontinued, but may develop diabetes many years later after recurrent episodes of pancreatitis. Similarly, those treated with thiazides develop diabetes years later. Since, thiazides seldom cause severe hyperglycemia, such individuals probably have T2DM that is exacerbated by the drug. Thus, for the clinician and patient, it is less important to label the particular type of diabetes than it is to understand the pathogenesis of the hyperglycemia and to treat it effectively.
Question: What are the symptoms of diabetes?
The primary pathogenic abnormality in diabetes is hyperglycemia. Symptoms of marked hyperglycemia include polyuria, polydipsia, weight loss, sometimes with polyphagia, and blurred vision. Chronic hyperglycemia may sometimes be accompanied by impairment of growth and susceptibility to certain infections.
Acute, life-threatening complications of uncontrolled diabetes are hyperglycemia with ketoacidosis or the nonketotic hyperosmolar syndrome.
Long-term consequences of diabetes include retinopathy with potential loss of vision, nephropathy leading to renal failure, peripheral neuropathy 3with risk of foot ulcers, amputations, and Charcot joints, and autonomic neuropathy causing gastrointestinal, genitourinary, and cardiovascular symptoms, and sexual dysfunction. Patients with diabetes have an increased incidence of atherosclerotic cardiovascular, peripheral arterial, and cerebrovascular disease. Hypertension and abnormalities of lipoprotein metabolism are often seen in patients with diabetes.
Question: What causes diabetes?
Several pathogenic mechanisms are involved in the development of diabetes. T1DM results from destruction of pancreatic β-cells usually leading to absolute insulin deficiency. Two major subtypes have been recognized:
  • Type 1A diabetes mellitus: It occurs as a result of autoimmune destruction of the insulin-producing β-cells in the islets of Langerhans. Previously known as insulin-dependent diabetes or juvenile onset diabetes, it results from a cellular mediated autoimmune destruction of the β-cells of the pancreas. Autoimmune destruction of β-cells has multiple genetic predispositions and is probably triggered by environmental factors that are still poorly defined. These patients are also prone to other autoimmune disorders.
  • Type 1B diabetes mellitus: This refers to a non-autoimmune or idiopathic destruction of the islet cells, leading to deficiency of insulin.
Type 2 diabetes mellitus is caused by defects in the insulin action or secretion leading to glucose intolerance and an eventual progression to full-blown disease. There is progressive increase in resistance to insulin action in muscles or adipose tissue causing pancreatic β-cells hyperstimulation to overcome the tissue resistance. This progression continues till β-cells can compensate for insulin resistance, but eventually the β-cells get gradually exhausted, resulting in a corresponding increase in the glucose level.
Question: What are the risk factors for diabetes?
Although the exact cause for diabetes remains undetermined, there are several factors that increase the risk of diabetes.
Risk factors for type 1 diabetes mellitus
  • Genetics and family history
  • Diseases of the pancreas
  • Infection or illness.
Risk factors for type 2 diabetes mellitus
  • Insulin resistance
  • Prediabetes4
  • African-American, Hispanic, Native American or Asian-American race or ethnic background
  • Obesity
  • High blood pressure
  • Low level of high density lipoprotein (HDL) cholesterol
  • High blood levels of triglycerides
  • Physical inactivity
  • Family history
  • History of GDM
  • Polycystic ovary syndrome
  • Metabolic syndrome
  • Age, older than 45 years.
Risk factors for gestational diabetes mellitus
  • Obesity
  • Previous glucose intolerance
  • Family history
  • Age.
Question: When and how was diabetes discovered in the history of mankind?
Diabetes was first described in the literature in 1500 BCE mentioning “too great emptying of the urine.” Around the same time, Sushruta, an Indian physician described the disease and named it as madhumeha or honey urine noting that the urine would attract ants. The term "diabetes" or "to pass through" was first used in 250 BCE by the Greek Apollonius Of Memphis. Sushruta and Charaka in 400-500 CE identified type 1 and type 2 diabetes mellitus as separate conditions with T1DM associated with youth and T2DM with obesity. The term "mellitus" or "from honey" was added by Thomas Willis in the late 1600s to separate the condition from diabetes insipidus which is also associated with frequent urination. The first complete clinical description of diabetes was given by the ancient Greek physician Aretaeus of Cappadocia (1st century CE), who also noted the excessive amount of urine which passed through the kidneys.
Although diabetes has been described since the ancient times, pathogenesis of diabetes has only been understood experimentally since about 1900. An effective treatment was only developed after Frederick Banting and Charles Best first used insulin in 1921 and 1922.
Paul Langerhans, an anatomist first discovered the islets of Langerhans in 1869 and identified the cells in the pancreas which produce the main substance that controls glucose levels in the body. Sir Edward Albert Sharpey-Schafer, in 1910, proposed a single chemical was deficient in diabetics and this was normally produced by the pancreas. He suggested the name insulin 5for this substance, from the Latin insula, meaning island, in reference to the insulin-producing islets of Langerhans in the pancreas.
Banting, Best, and colleagues (especially the chemist Collip) then purified insulin from bovine pancreas that led to the availability of an effective treatment, insulin injections, and the first patient was treated in 1922. This discovery revolutionized the treatment of once dreaded disease and was followed by other landmark discoveries.
Question: What is the prevalence of diabetes?
Once considered a mild disease seen in elderly population, diabetes now is an important cause of mortality and morbidity. The number of people with diabetes is increasing exponentially due to growth, aging, urbanization, and increasing prevalence of obesity and physical inactivity. More alarming is the fact that one out of two people with diabetes do not know that they have the disease. Quantifying the prevalence of diabetes is, therefore, important to allow rational planning and allocation of resources.
Globally, it is estimated that 382 million people suffer from diabetes (a prevalence of 8.3%). All types of diabetes, in particular T2DM, are on increase. It has been predicted that the global burden of diabetes will increase by 55% by 2035 (Fig. 1). Almost half of all adults with diabetes are between the ages of 40 and 59 years. There is little gender difference in the global numbers of people with diabetes for 2013 or 2035.
Additionally, another 21 million cases of high blood glucose in pregnancy are estimated to contribute to diabetes cases worldwide. That is equivalent to 17% of live births to women in 2013 that had some form of high blood glucose in pregnancy. Considering the diabetes burden in human as well as financial terms, an enormous number of 5.1 million deaths that consume about USD 548 billion dollars in health spending (11% of the total spent worldwide), was reported in 2013.
Question: Is there any difference in the geographical distribution of the disease?
Although diabetes is a global phenomenon, different regions are affected to widely different degrees. Western Pacific region accounts for the maximum number of diabetics in the world.
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FIGURE 1: Prevalence of type 2 diabetes mellitus in the year 2013 and prediction for the year 2035
With more than 138 million people affected, its prevalence is 8.6% that is close to the prevalence of the world. At the other end of the spectrum, Africa reports the smallest diabetes population among the regions. However, this is set to double by 2035, and, ominously for Africa's capacity to develop, more than three-quarters of deaths from diabetes in 2013 occurred in people under 60.
Similar worrisome scenario is seen in South and Central America, where the diabetes population is projected to increase by 60% by 2035. Fast pace development has led to a rapidly growing epidemic. Rapid development has driven a fast-growing epidemic of diabetes in South East Asia, accounting for close to one-fifth of all cases worldwide. The outlook is similar in Middle East and North Africa where development has led to high proportions of diabetes, where one in ten adults in the region have the disease.
It is interesting to note that 35 out of 219 countries (16% of the total) have very high prevalence of diabetes, over 12%. These countries are located mainly in Western Pacific, and Middle East and North Africa regions.
A prevalence of 8.5% has been reported in Europe, with Turkey in upper extreme of prevalence of diabetes with 14.9%, followed by Montenegro with 10.1% of prevalence.
In North America and Caribbean, Belize (15.9%), Guyana (15.8%), and Curacao (14.5%) are the top three countries with the higher prevalence of diabetes. At the same time, this region presents the highest values of prevalence of impaired glucose tolerance (IGT) with a median of 12%.
No countries are escaping the diabetes epidemic, and in states and territories worldwide, it is the poor and disadvantaged who are suffering the most. More than 80% of diabetics are living in low and middle income countries. Indigenous communities are among those especially vulnerable to diabetes (Fig. 2).
Question: What is the scenario of diabetes in India?
Diabetes is rapidly achieving the status of a potential epidemic in India with more than 62 million diabetic individuals currently diagnosed with the disease. In the previous decade (2000), India (31.7 million) dominated the world with the highest number of people with diabetes mellitus followed by China (20.8 million) with the United States (17.7 million) in second and third place, respectively. The investigators have predicted that the prevalence of diabetes will double globally from 171 million in 2000 to 366 million in 2030 with a maximum increase in India. It has also been predicted that by 2030, diabetes mellitus may afflict up to 79.4 million individuals in India, while China (42.3 million) and the United States (30.3 million) will also see significant increases in those affected by the disease.
In addition to an increasing prevalence of diabetes in India, there is also an alarmingly high prevalence of undiagnosed diabetes. This group is separate from the one with IGT and adds up to the disease burden as well as morbidity and mortality due to diabetes and its complications.7
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FIGURE 2: Top 10 countries/territories of number of people with diabetes (20–79 years), 2013
Presently, India faces an uncertain future in relation to the potential burden that diabetes may inflict upon the country, posing significant healthcare burden on both the individual and the society. There is, therefore, a need for appropriate government interventions and combined efforts from all the strata of the society.
Government policies may aid in developing guidelines on diabetes management, funding community programs for public awareness about the diabetes risk reduction, availability of medications and diagnostic services to all sections of community. Clinicians may assist in implementation of screening and early detection programs, diabetes prevention, self-management counseling, and therapeutic management of diabetes in accordance with the appropriate local guidelines. Continuing education programs for general practitioners would be helpful to initiate program adherence, and may be a major step in achieving target glycemic levels and the prevention of disease complications. Aggressive clinical measures in terms of early insulin initiation combined with optimal doses of oral hypoglycemic agents and appropriate lifestyle modification would surely have long-term favorable effects in disease management.8
Question: Is there any regional difference in the prevalence of diabetes in India?
There is definitely difference in the prevalence of diabetes related to the geographical distribution of diabetes in India. Epidemiological studies indicate that the prevalence of diabetes in rural population is one-quarter of that of urban population for India. Similar data has also been noted for other Indian sub-continent countries, such as Bangladesh, Nepal, Bhutan, and Sri Lanka.
A large community study by the Indian Council of Medical research reported a lower prevalence of diabetes in the states of North India (Chandigarh 0.12 million, Jharkhand 0.96 million) as compared to Maharashtra (9.2 million) and Tamil Nadu (4.8 million). The National Urban Survey conducted across the metropolitan cities of India reported similar trend: 11.7% in Kolkata (East India), 6.1% in Kashmir valley (North India), 11.6% in New Delhi (North India), and 9.3% in West India (Mumbai) compared with 13.5% in Chennai (South India), 16.6% in Hyderabad (South India), and 12.4% in Bangalore (South India).
A possible explanation for this regional difference could be that north Indians are migrant Asian populations and south Indians are the host populations. However, this has not been corroborated through further research. Therefore, more studies are needed in India to highlight cultural and ethnic trends and provide a more complete understanding of the differences in diabetes etiology between Indian and other ethnic groups within India.
Indian population experiences a disproportionate allocation of health resources between urban and rural areas. In addition to the poverty, rural areas also face problems of food insecurity, illiteracy, poor sanitation, and dominance of communicable diseases. Lack of adequate infrastructure and poor aged care facilities also contribute to disparity in the diabetes management compared with their urban counterparts, with these populations more likely to suffer from diabetic complications. More steps are needed to address the rural-urban inequality in diabetes intervention.
Question: What are the causes of poor glycemic control in Indians?
Indians are genetically predisposed for developing diabetes and its complications at an earlier age. A unique combination of clinical and biochemical parameters have been identified and labeled as “Asian Indian phenotype.” A variety of other factors, such as lifestyle changes, increased longevity, poor diabetic control, migration, and certain environmental factors are also responsible for poor glycemic control in Indians.
Obesity, a major risk factor for diabetes has been little studied in India. India has a higher prevalence of diabetes compared to western countries, 9suggesting that diabetes may occur at a much lower body mass index (BMI) in Indians compared with Europeans. Therefore, relatively lean Indian adults with a lower BMI may be at equal risk as those who are obese. Furthermore, Indians are genetically predisposed to the development of coronary artery disease due to dyslipidemia and low levels of HDL; these determinants make Indians more prone to development of the complications of diabetes at an early age (20–40 years) compared with Caucasians (>50 years) and indicate that diabetes must be carefully screened and monitored regardless of patient age in India.
Question: What is impaired glucose tolerance and impaired fasting glucose?
In 1997 and 2003, the Expert Committee on Diagnosis and Classification of Diabetes Mellitus identified an intermediate group of individuals whose glucose levels were higher than the normal and yet failed to meet the criteria for diabetes. The committee defined them as impaired fasting glucose (IFG) or IGT (Box 2).
This intermediate group of individuals was referred to as having prediabetes or considered at a relatively higher risk for the future development of diabetes. IFG and IGT should not be viewed as clinical entities in their own right but rather risk factors for diabetes as well as cardiovascular disease (CVD). IFG and IGT are also associated with obesity (especially abdominal or visceral obesity), dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertension.
As compared to diabetes (8.3%), the global prevalence of IGT is around 6.9% and is predicted to increase to 8.0% by 2035 with approximately 471 million individuals (age group 20–79 years) afftected by the disease.
Therapeutic measures delaying the development of diabetes in individuals with prediabetes include lifestyle modifications aimed at increasing physical activity and producing 5–10% loss of body weight, and use of certain pharmacological agents. However, the possible effect of these interventions on the reduction in mortality or the incidence of CVD has not been demonstrated to date. It is important to note that the 2003 ADA Expert Committee reported a reduced lower fasting plasma glucose cutoff point to define IFG from 110 mg/dL (6.1 mmol/L) to 100 mg/dL (5.6 mmol/L), in part to ensure that prevalence of IFG was similar to that of IGT.
10However, the World Health Organization and many other diabetes organizations did not adopt this change in the definition of IFG.
Facts about diabetes
  • 387 million people have diabetes; by the year 2035, this will rise to 592 million
  • The number of people with T2DM is increasing in every country
  • A majority (77%) of diabetics live in low and middle-income countries
  • The greatest number of people with diabetes fall in the age group of 40–59 years
  • About 179 million people with diabetes are undiagnosed
  • Diabetes caused 4.9 million deaths in the year 2014
  • Every 7 seconds, a person dies from diabetes
  • More than 79,000 children developed T1DM in the year 2013
  • More than 21 million live births were affected by diabetes during pregnancy in the year 2013.
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