One particular type of sugar that has attracted a lot of negative attention is high-fructose corn syrup (HFCS) — and for good reason, as multiple studies suggest HFCS can influence diabetes risk. Some research in people who are overweight and obese, for example, suggests regularly consuming drinks sweetened with either fructose, a byproduct of HFCS, or glucose can lead to weight gain, and drinks with fructose in particular may reduce insulin sensitivity and spike blood sugar levels.
Diet and moderate exercise are the first treatments implemented in diabetes. For many Type II diabetics, weight loss may be an important goal in helping them to control their diabetes. A well-balanced, nutritious diet provides approximately 50-60% of calories from carbohydrates, approximately 10-20% of calories from protein, and less than 30% of calories from fat. The number of calories required by an individual depends on age, weight, and activity level. The calorie intake also needs to be distributed over the course of the entire day so surges of glucose entering the blood system are kept to a minimum.
Complications of diabetes are responsible for considerable morbidity and mortality. The acute complications of diabetes are hypo- and hyperglycemic coma and infections. The chronic complications include microvascular complications such as retinopathy and nephropathy, and the macrovascular complications of heart disease and stroke. Diabetes mellitus is the commonest cause of blindness and renal failure in the UK and the USA. Other common complications include autonomic and peripheral neuropathy. A combination of vascular and neuropathic disturbances results in a high prevalence of impotence in men with diabetes. Peripheral neuropathy causes lack of sensation in the feet which can cause minor injuries to go unnoticed, become infected and, with circulatory problems obstructing healing, ulceration and gangrene are serious risks and amputation is not uncommon. Evidence from meta-analysis of studies of the relationship between glycemic control and microvascular complications (Wang, Lau, & Chalmers, 1993), and from the longitudinal multicenter Diabetes Control and Complications Trial (DCCT) in the USA (DCCT Research Group, 1993), have established a clear relationship between improved blood glucose control and reduction of risk of retinopathy and other microvascular complications in insulin-dependent diabetes mellitus (IDDM). It is likely that there would be similar findings for noninsulin-dependent diabetes mellitus (NIDDM) though the studies did not include NIDDM patients. However, the DCCT included highly selected, well-motivated, well-educated and well-supported patients, cared for by well-staffed diabetes care teams involving educators and psychologists as well as diabetologists and diabetes specialist nurses.
Diabetes mellitus (“diabetes”) and hypertension, which commonly coexist, are global public health issues contributing to an enormous burden of cardiovascular disease, chronic kidney disease, and premature mortality and disability. The presence of both conditions has an amplifying effect on risk for microvascular and macrovascular complications.1 The prevalence of diabetes is rising worldwide (Fig. 37.1). Both diabetes and hypertension disproportionately affect people in middle and low-income countries, and an estimated 70% of all cases of diabetes are found in these countries.2,3 In the United States alone, the total costs of care for diabetes and hypertension in the years 2012 and 2011 were 245 and 46 billion dollars, respectively.4,5 Therefore, there is a great potential for meaningful health and economic gains attached to prevention, detection, and intervention for diabetes and hypertension.

There are two major types of diabetes, called type 1 and type 2. Type 1 diabetes was also formerly called insulin dependent diabetes mellitus (IDDM), or juvenile-onset diabetes mellitus. In type 1 diabetes, the pancreas undergoes an autoimmune attack by the body itself, and is rendered incapable of making insulin. Abnormal antibodies have been found in the majority of patients with type 1 diabetes. Antibodies are proteins in the blood that are part of the body's immune system. The patient with type 1 diabetes must rely on insulin medication for survival.
Most cases of diabetes involve many genes, with each being a small contributor to an increased probability of becoming a type 2 diabetic.[10] If one identical twin has diabetes, the chance of the other developing diabetes within his lifetime is greater than 90%, while the rate for nonidentical siblings is 25–50%.[13] As of 2011, more than 36 genes had been found that contribute to the risk of type 2 diabetes.[37] All of these genes together still only account for 10% of the total heritable component of the disease.[37] The TCF7L2 allele, for example, increases the risk of developing diabetes by 1.5 times and is the greatest risk of the common genetic variants.[13] Most of the genes linked to diabetes are involved in beta cell functions.[13]

Hyperglycemia (ie, random blood glucose concentration of more than 200 mg/dL or 11 mmol/L) results when insulin deficiency leads to uninhibited gluconeogenesis and prevents the use and storage of circulating glucose. The kidneys cannot reabsorb the excess glucose load, causing glycosuria, osmotic diuresis, thirst, and dehydration. Increased fat and protein breakdown leads to ketone production and weight loss. Without insulin, a child with type 1 diabetes mellitus wastes away and eventually dies due to DKA. The effects of insulin deficiency are shown in the image below.


Diabetes mellitus is not a single disorder but a heterogeneous group of disorders. All forms are characterized by hyperglycemia and disturbances of carbohydrate, fat, and protein metabolism which are associated with absolute or relative deficiencies of insulin action and/or insulin secretion. The World Health Organization (WHO) developed a now widely accepted classification of the disorder, largely based on clinical characteristics (see Table 1, WHO, 1985).
According to the Mayo Clinic, your risk of developing type 2 diabetes increases as you age. Your risk goes up after age 45 in particular. However, the incidence of type 2 diabetes is increasing dramatically among children, adolescents, and younger adults. Likely factors include reduced exercise, decreased muscle mass, and weight gain as you age. Type 1 diabetes is usually diagnosed by the age of 30.
Nerve damage (neuropathy). Excess sugar can injure the walls of the tiny blood vessels (capillaries) that nourish your nerves, especially in the legs. This can cause tingling, numbness, burning or pain that usually begins at the tips of the toes or fingers and gradually spreads upward. Poorly controlled blood sugar can eventually cause you to lose all sense of feeling in the affected limbs. Damage to the nerves that control digestion can cause problems with nausea, vomiting, diarrhea or constipation. For men, erectile dysfunction may be an issue.
The good news is that if you have diabetes, you have a great amount of control in managing your disease. Although it can be difficult to manage a disease on a daily basis, the resources and support for people with diabetes is endless. It's important for you to receive as much education as possible so that you can take advantage of all the good information that is out there (and weed out the bad).

Diet, exercise, and education are the cornerstones of treatment of diabetes and often the first recommendations for people with mild diabetes. Weight loss is important for people who are overweight. People who continue to have elevated blood glucose levels despite lifestyle changes, or have very high blood glucose levels and people with type 1 diabetes (no matter their blood glucose levels) also require drugs.

Most cases of diabetes involve many genes, with each being a small contributor to an increased probability of becoming a type 2 diabetic.[10] If one identical twin has diabetes, the chance of the other developing diabetes within his lifetime is greater than 90%, while the rate for nonidentical siblings is 25–50%.[13] As of 2011, more than 36 genes had been found that contribute to the risk of type 2 diabetes.[37] All of these genes together still only account for 10% of the total heritable component of the disease.[37] The TCF7L2 allele, for example, increases the risk of developing diabetes by 1.5 times and is the greatest risk of the common genetic variants.[13] Most of the genes linked to diabetes are involved in beta cell functions.[13]
An article published in November 2012 in the journal Global Public Health found that countries with more access to HFCS tended to have higher rates of the disease. Though it’s likely that these countries’ overall eating habits play a role in their populations’ diabetes risk, a study published in February 2013 in the journal PLoS One found limiting access to HFCS in particular may help reduce rates of the diagnosis.
The levels of glucose in the blood vary normally throughout the day. They rise after a meal and return to pre-meal levels within about 2 hours after eating. Once the levels of glucose in the blood return to premeal levels, insulin production decreases. The variation in blood glucose levels is usually within a narrow range, about 70 to 110 milligrams per deciliter (mg/dL) of blood in healthy people. If people eat a large amount of carbohydrates, the levels may increase more. People older than 65 years tend to have slightly higher levels, especially after eating.
Longer-term, the goals of treatment are to prolong life, reduce symptoms, and prevent diabetes-related complications such as blindness, kidney failure, and amputation of limbs. These goals are accomplished through education, insulin use, meal planning and weight control, exercise, foot care, and careful self-testing of blood glucose levels. Self-testing of blood glucose is accomplished through regular use of a blood glucose monitor (pictured, right). This machine can quickly and easily measure the level of blood glucose based by analysing the level from a small drop of blood that is usually obtained from the tip of a finger. You will also require regular tests for glycated haemoglobin (HbA1c). This measures your overall control over several months.
Large, population-based studies in China, Finland and USA have recently demonstrated the feasibility of preventing, or delaying, the onset of diabetes in overweight subjects with mild glucose intolerance (IGT). The studies suggest that even moderate reduction in weight and only half an hour of walking each day reduced the incidence of diabetes by more than one half.
Type 2 diabetes: Type 2 diabetes affects the way the body uses insulin. While the body still makes insulin, unlike in type I, the cells in the body do not respond to it as effectively as they once did. This is the most common type of diabetes, according to the National Institute of Diabetes and Digestive and Kidney Diseases, and it has strong links with obesity.
Jump up ^ Rubino, F; Nathan, DM; Eckel, RH; Schauer, PR; Alberti, KG; Zimmet, PZ; Del Prato, S; Ji, L; Sadikot, SM; Herman, WH; Amiel, SA; Kaplan, LM; Taroncher-Oldenburg, G; Cummings, DE; Delegates of the 2nd Diabetes Surgery, Summit (June 2016). "Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations". Diabetes Care. 39 (6): 861–77. doi:10.2337/dc16-0236. PMID 27222544.
Findings from the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) have clearly shown that aggressive and intensive control of elevated levels of blood sugar in patients with type 1 and type 2 diabetes decreases the complications of nephropathy, neuropathy, retinopathy, and may reduce the occurrence and severity of large blood vessel diseases. Aggressive control with intensive therapy means achieving fasting glucose levels between 70-120 mg/dl; glucose levels of less than 160 mg/dl after meals; and a near normal hemoglobin A1c levels (see below).
At present, the American Diabetes Association does not recommend general screening of the population for type 1 diabetes, though screening of high risk individuals, such as those with a first degree relative (sibling or parent) with type 1 diabetes should be encouraged. Type 1 diabetes tends to occur in young, lean individuals, usually before 30 years of age; however, older patients do present with this form of diabetes on occasion. This subgroup is referred to as latent autoimmune diabetes in adults (LADA). LADA is a slow, progressive form of type 1 diabetes. Of all the people with diabetes, only approximately 10% have type 1 diabetes and the remaining 90% have type 2 diabetes.
People with these risk factors should be screened for diabetes at least once every three years. Diabetes risk can be estimated using online risk calculators. Doctors may measure fasting blood glucose levels and hemoglobin A1C level, or do an oral glucose tolerance test. If the test results are on the border between normal and abnormal, doctors do the screening tests more often, at least once a year.
Type 2 diabetes is a progressive, chronic disease related to your body's challenges with regulating blood sugar. It is often associated with generalized inflammation. Your pancreas produces the hormone insulin to convert sugar (glucose) to energy that you either use immediately or store. With type 2 diabetes, you are unable to use that insulin efficiently. Although your body produces the hormone, either there isn't enough of it to keep up with the amount of glucose in your system, or the insulin being produced isn't being used as well as it should be, both of which result in high blood sugar levels.
It is recommended that all people with type 2 diabetes get regular eye examination.[13] There is weak evidence suggesting that treating gum disease by scaling and root planing may result in a small short-term improvement in blood sugar levels for people with diabetes.[79] There is no evidence to suggest that this improvement in blood sugar levels is maintained longer than 4 months.[79] There is also not enough evidence to determine if medications to treat gum disease are effective at lowering blood sugar levels.[79]
A study by Mayer-Davis et al indicated that between 2002 and 2012, the incidence of type 1 and type 2 diabetes mellitus saw a significant rise among youths in the United States. According to the report, after the figures were adjusted for age, sex, and race or ethnic group, the incidence of type 1 (in patients aged 0-19 years) and type 2 diabetes mellitus (in patients aged 10-19 years) during this period underwent a relative annual increase of 1.8% and 4.8%, respectively. The greatest increases occurred among minority youths. [29]
Prediabetes is a condition in which blood glucose levels are too high to be considered normal but not high enough to be labeled diabetes. People have prediabetes if their fasting blood glucose level is between 100 mg/dL and 125 mg/dL or if their blood glucose level 2 hours after a glucose tolerance test is between 140 mg/dL and 199 mg/dL. Prediabetes carries a higher risk of future diabetes as well as heart disease. Decreasing body weight by 5 to 10% through diet and exercise can significantly reduce the risk of developing future diabetes.
Rates of diabetes in 1985 were estimated at 30 million, increasing to 135 million in 1995 and 217 million in 2005.[18] This increase is believed to be primarily due to the global population aging, a decrease in exercise, and increasing rates of obesity.[18] The five countries with the greatest number of people with diabetes as of 2000 are India having 31.7 million, China 20.8 million, the United States 17.7 million, Indonesia 8.4 million, and Japan 6.8 million.[109] It is recognized as a global epidemic by the World Health Organization.[1]
Monitoring your caloric intake may be helpful if you’re overweight, but everyone with type 2 diabetes should track how many carbs they’re taking in. That can be tricky because carbs are in many of the common foods you may already eat, but there are both good and bad sources of carbs. Fruits and vegetables, for example, are good sources, while pretzels and cookies are bad sources. (29)
Type 2 diabetes is a progressive, chronic disease related to your body's challenges with regulating blood sugar. It is often associated with generalized inflammation. Your pancreas produces the hormone insulin to convert sugar (glucose) to energy that you either use immediately or store. With type 2 diabetes, you are unable to use that insulin efficiently. Although your body produces the hormone, either there isn't enough of it to keep up with the amount of glucose in your system, or the insulin being produced isn't being used as well as it should be, both of which result in high blood sugar levels.
Diabetes can occur temporarily during pregnancy, and reports suggest that it occurs in 2% to 10% of all pregnancies. Significant hormonal changes during pregnancy can lead to blood sugar elevation in genetically predisposed individuals. Blood sugar elevation during pregnancy is called gestational diabetes. Gestational diabetes usually resolves once the baby is born. However, 35% to 60% of women with gestational diabetes will eventually develop type 2 diabetes over the next 10 to 20 years, especially in those who require insulin during pregnancy and those who remain overweight after their delivery. Women with gestational diabetes are usually asked to undergo an oral glucose tolerance test about six weeks after giving birth to determine if their diabetes has persisted beyond the pregnancy, or if any evidence (such as impaired glucose tolerance) is present that may be a clue to a risk for developing diabetes.
DKA usually follows increasing hyperglycemia and symptoms of osmotic diuresis. Users of insulin pumps, by virtue of absent reservoirs of subcutaneous insulin, may present with ketosis and more normal blood glucose levels. They are more likely to present with nausea, vomiting, and abdominal pain, symptoms similar to food poisoning. DKA may manifest as respiratory distress.
It's not as clear what the rest of the type 1 genes are up to, but researchers are eager to find out. "Even though something accounts for a small part [of the genetic risk], it could have a significant impact," says Stephen Rich, PhD, director of the Center for Public Health Genomics at the University of Virginia School of Medicine. Understanding these genes' role may clue researchers in to less obvious biological pathways involved in type 1 diabetes, and to possible prevention strategies.
“It’s not like you wake up one day and all of a sudden you’re thirsty, hungry, and [going to the bathroom] all the time,” says Melissa Joy Dobbins, RD, a certified diabetes educator in Illinois and a spokesperson for the American Association of Diabetes Educators. “It picks up gradually.” Indeed, “most people are unaware that they have diabetes in its early or even middle phases,” says Aaron Cypess, MD, assistant professor of medicine at Harvard Medical School and staff physician at Joslin Diabetes Center. Just because you’re not keyed in doesn’t mean you’re immune from problems associated with diabetes, he adds. The longer you go without controlling diabetes, the greater your risk for heart disease, kidney disease, amputation, blindness, and other serious complications. “We recommend that people with risk factors for diabetes, such as a family history or being overweight, get evaluated on a regular basis,” Dr. Cypess says. If you’ve been feeling off, talk to your doctor about getting a simple blood test that can diagnose the disease. And pay attention to these subtle signs and symptoms of diabetes.
Supporting evidence for Shulman's theory comes from observations about a rare genetic illness called lipodystrophy. People with lipodystrophy can't make fat tissue, which is where fat should properly be stored. These thin people also develop severe insulin resistance and type 2 diabetes. "They have fat stored in places it doesn't belong," like the liver and muscles, says Shulman. "When we treat them . . . we melt the fat away, reversing insulin resistance and type 2 diabetes." Shulman's theory also suggests why some people who carry extra fat don't get type 2. "There are some individuals who store fat [under the skin] who have relatively normal insulin sensitivity, a so-called fit fat individual," he says. Because of the way their bodies store fat, he believes, they don't get diabetes.
Most pediatric patients with diabetes have type 1 diabetes mellitus (T1DM) and a lifetime dependence on exogenous insulin. Diabetes mellitus (DM) is a chronic metabolic disorder caused by an absolute or relative deficiency of insulin, an anabolic hormone. Insulin is produced by the beta cells of the islets of Langerhans located in the pancreas, and the absence, destruction, or other loss of these cells results in type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]). A possible mechanism for the development of type 1 diabetes is shown in the image below. (See Etiology.)
DM is a strong independent predictor of short- and long-term recurrent ischemic events, including mortality, in acute coronary syndrome (ACS),6,7 including unstable angina and non-ST-elevation MI (NSTEMI),8 ST-elevation MI (STEMI) treated medically,9 and ACS undergoing percutaneous coronary intervention (PCI).10,11 Furthermore, the concomitant presence of cardiovascular risk factors and comorbidities that negatively affect the outcomes of ACS is higher in DM patients.12
Morbidity and mortality stem from the metabolic derangements and from the long-term complications that affect small and large vessels, resulting in retinopathy, nephropathy, neuropathy, ischemic heart disease, and arterial obstruction with gangrene of extremities.2 The acute clinical manifestations can be fully understood in the context of current knowledge of the secretion and action of insulin.3 Genetic and other etiologic considerations implicate autoimmune mechanisms in the evolution of the most common form of childhood diabetes, known as type 1a diabetes.4,5 Genetic defects in insulin secretion are increasingly recognized and understood as defining the causes of monogenic forms of diabetes such as maturity-onset diabetes of youth (MODY) and neonatal DM and contributing to the spectrum of T2DM.6
The earliest surviving work with a detailed reference to diabetes is that of Aretaeus of Cappadocia (2nd or early 3rd century CE). He described the symptoms and the course of the disease, which he attributed to the moisture and coldness, reflecting the beliefs of the "Pneumatic School". He hypothesized a correlation of diabetes with other diseases, and he discussed differential diagnosis from the snakebite which also provokes excessive thirst. His work remained unknown in the West until 1552, when the first Latin edition was published in Venice.[110]
It’s not uncommon for patients to suddenly feel unsteady and immediately need to reach for carbs, says Marjorie Cypress, a nurse practitioner at an endocrinology clinic in Albuquerque, New Mexico, and 2014 president of health care and education for the American Diabetes Association. “When you have high blood sugar, your body has a problem regulating its glucose,” she explains. “If you’ve eaten something high in carbohydrates, your body shoots out a little too much insulin, and your glucose drops quickly. This makes you feel shaky, and you tend to crave carbs or sugar. This can lead to a vicious cycle.” These are the best foods for someone on a diabetic diet.

Patients with type 1 diabetes require life-long treatment with exogenous (artificial) insulin to regulate their blood sugar levels. This insulin may be given through the use of a hypodermic needle (seen right), or other methods such as the use of an insulin pump. Over time, many patients suffer chronic complications: vascular, neurological and organ-specific (such as kidney and eye disease). The frequency and severity of these complications is related to duration that the patient has suffered the disease for, and by how well their blood sugar levels have been controlled. If blood sugar levels, blood pressure and lipids are tightly controlled, many complications of diabetes may be prevented. Some patients may develop the major emergency complication of diabetes, known as ketoacidosis (extremely high blood glucose levels accompanied with extremely low insulin levels), which has a mortality rate of 5-10%.
Merck & Co., Inc., Kenilworth, NJ, USA is a global healthcare leader working to help the world be well. From developing new therapies that treat and prevent disease to helping people in need, we are committed to improving health and well-being around the world. The Merck Manual was first published in 1899 as a service to the community. The legacy of this great resource continues as the Merck Manual in the US and Canada and the MSD Manual outside of North America. Learn more about our commitment to Global Medical Knowledge.
Type 2 diabetes mellitus (non–insulin-dependent diabetes mellitus [NIDDM]) is a heterogeneous disorder. Most patients with type 2 diabetes mellitus have insulin resistance, and their beta cells lack the ability to overcome this resistance. [6] Although this form of diabetes was previously uncommon in children, in some countries, 20% or more of new patients with diabetes in childhood and adolescence have type 2 diabetes mellitus, a change associated with increased rates of obesity. Other patients may have inherited disorders of insulin release, leading to maturity onset diabetes of the young (MODY) or congenital diabetes. [7, 8, 9] This topic addresses only type 1 diabetes mellitus. (See Etiology and Epidemiology.)
Glucagon is a hormone that causes the release of glucose from the liver (for example, it promotes gluconeogenesis). Glucagon can be lifesaving and every patient with diabetes who has a history of hypoglycemia (particularly those on insulin) should have a glucagon kit. Families and friends of those with diabetes need to be taught how to administer glucagon, since obviously the patients will not be able to do it themselves in an emergency situation. Another lifesaving device that should be mentioned is very simple; a medic-alert bracelet should be worn by all patients with diabetes.
A study by Chan et al indicated that in pediatric patients with type 1 diabetes, the presence of hypoglycemia is a sign of decreased insulin sensitivity, while hyperglycemia in these patients, especially overnight, signals improved sensitivity to insulin. In contrast, the investigators found evidence that in pediatric patients with type 2 diabetes, markers of metabolic syndrome and hyperglycemia are associated with reduced insulin sensitivity. Patients in the study were between ages 12 and 19 years. [23]
Most cases (95%) of type 1 diabetes mellitus are the result of environmental factors interacting with a genetically susceptible person. This interaction leads to the development of autoimmune disease directed at the insulin-producing cells of the pancreatic islets of Langerhans. These cells are progressively destroyed, with insulin deficiency usually developing after the destruction of 90% of islet cells.
Diabetic retinopathy is a leading cause of blindness and visual disability. Diabetes mellitus is associated with damage to the small blood vessels in the retina, resulting in loss of vision. Findings, consistent from study to study, make it possible to suggest that, after 15 years of diabetes, approximately 2% of people become blind, while about 10% develop severe visual handicap. Loss of vision due to certain types of glaucoma and cataract may also be more common in people with diabetes than in those without the disease.
FIGURE 19-1 ■. This figure shows the hyperbolic relationship of insulin resistance and beta cell function. On the y-axis is beta cell function as reflected in the first-phase insulin response during intravenous (IV) glucose infusion; on the x-axis is insulin sensitivity and its mirror image resistance. In a subject with normal glucose tolerance (NGT) and beta-cell reserve, an increase in insulin resistance results in increased insulin release and normal glucose tolerance. In an individual for whom the capacity to increase insulin release is compromised, increasing insulin resistance with partial or no beta-cell compensation results in progression from normal glucose tolerance, to impaired glucose tolerance (IGT), and finally to diabetes (T2D). Differences between these categories are small at high insulin sensitivity, which may be maintained by weight reduction, exercise, and certain drugs. At a critical degree of insulin resistance, due to obesity or other listed factors, only a further small increment in resistance requires a large increase in insulin output. Those that can increase insulin secretion to this extent retain normal glucose tolerance; those who cannot achieve this degree of insulin secretion (e.g., due to a mild defect in genes regulating insulin synthesis, insulin secretion, insulin action, or an ongoing immune destruction of beta cells) now unmask varying degrees of carbohydrate intolerance. The product of insulin sensitivity (the reciprocal of insulin resistance) and acute insulin response (a measurement beta-cell function) has been called the “disposition index.” This index remains constant in an individual with normal beta cell compensation in response to changes in insulin resistance. IGT, impaired glucose tolerance; NGT, normal glucose tolerance; T2D, type 2 diabetes.
Type 2 Diabetes: Accounting for 90 to 95 percent of those with diabetes, type 2 is the most common form. Usually, it's diagnosed in adults over age 40 and 80 percent of those with type 2 diabetes are overweight. Because of the increase in obesity, type 2 diabetes is being diagnosed at younger ages, including in children. Initially in type 2 diabetes, insulin is produced, but the insulin doesn't function properly, leading to a condition called insulin resistance. Eventually, most people with type 2 diabetes suffer from decreased insulin production.
×