Type 1 Diabetes Mellitus 

  • Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: George T Griffing, MD   more...
 
Updated: Feb 10, 2012
 

Background

Diabetes mellitus (DM) is a multisystem disease with both biochemical and anatomical/structural consequences. It is a chronic disease of carbohydrate, fat, and protein metabolism caused by the lack of insulin, which results from the marked and progressive inability of the pancreas to secrete insulin because of autoimmune destruction of the beta cells. (See Pathophysiology.)

Type 1 DM can occur at any age. It occurs most commonly in juveniles but can also occur in adults, especially in those in their late 30s and early 40s. (See Epidemiology.)

Unlike people with type 2 DM, those with type 1 DM generally are not obese and may present initially with diabetic ketoacidosis (DKA). The distinguishing characteristic of a patient with type 1 diabetes is that if his or her insulin is withdrawn, ketosis and eventually ketoacidosis develop. Therefore, these patients are dependent on exogenous insulin. (See Clinical Presentation.)

Treatment of type 1 DM requires a multidisciplinary approach by physician, nurse, and dietitian. In patients with new-onset type 1 diabetes, lifelong insulin therapy must be started. As a chronic disease, DM requires long-term medical attention both to limit the development of its devastating complications and to manage them when they do occur. (See Treatment and Management and Medication.)

DM is a disproportionately expensive disease; in 2002, the per-capita cost of health care was $13,243 for people with diabetes, while it was $2560 for those without diabetes. The emergency department (ED) utilization rate by people with diabetes is twice that of the unaffected population.[1] Overall, the annual financial cost from diabetes exceeds $100 billion, almost $1 of every $7 dollars of US health expenditures in terms of medical care and loss of productivity.

Go to Diabetes Mellitus, Type 2 and Glucose Intolerance for complete information on these topics.

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Pathophysiology

Type 1 diabetes mellitus (DM) is a catabolic disorder in which circulating insulin is very low or absent, plasma glucagon is elevated, and the pancreatic beta cells fail to respond to all insulin-secretory stimuli. The pancreas shows lymphocytic infiltration and destruction of insulin-secreting cells of the islets of Langerhans, causing insulin deficiency. Patients need exogenous insulin to reverse this catabolic condition, prevent ketosis, decrease hyperglucagonemia, and normalize lipid and protein metabolism.

One theory regarding the etiology of type 1 DM is that it results from damage to pancreatic beta cells from infectious or environmental agents. In a genetically susceptible individual, the immune system is thereby triggered to develop an autoimmune response against altered pancreatic beta cell antigens or molecules in beta cells that resemble a viral protein. Approximately 85% of type 1 DM patients have circulating islet cell antibodies, and the majority also have detectable anti-insulin antibodies before receiving insulin therapy. Most islet cell antibodies are directed against glutamic acid decarboxylase (GAD) within pancreatic beta cells.

A study by Philippe et al used CT scan findings, glucagon stimulation test results, and fecal elastase-1 measurements to confirm reduced pancreatic volume in individuals with diabetes mellitus.[2] This may also explain the associated exocrine dysfunction.

Currently, autoimmunity is considered the major factor in the pathophysiology of type 1 DM. Prevalence is increased in patients with other autoimmune diseases, such as Graves disease, Hashimoto thyroiditis, and Addison disease. Prevalence of type 1 diabetes autoantibodies and newly diagnosed type 1 diabetes is higher in patients with autoimmune thyroiditis.[3]

Approximately 95% of patients with type 1 DM have either human leukocyte antigen (HLA)-DR3 or HLA-DR4. HLA-DQs are considered specific markers of type 1 DM susceptibility.

Amino acid metabolism also plays a key role in the pathogenesis of diabetes. Amino acid profiles could help assess risk of developing diabetes.[4] It might help elucidate further how diabetes evolves.

Recent evidence suggests a role for vitamin D in the pathogenesis and prevention of diabetes mellitus. Vitamin D deficiency is also an important independent predictor of development of coronary artery calcification in individuals with type 1 DM.[5] Joergensen et al determined that vitamin D deficiency in type 1 diabetes may predict all causes of mortality but not development of microvascular complications.[6] The contribution of vitamin D deficiency to mortality must be mediated by nonvascular mechanisms.

However, a study by Simpson et al found that neither vitamin D intake nor 25 hydroxyvitamin D levels throughout childhood were associated with islet autoimmunity or progression to type 1 diabetes.[7]

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Etiology

The etiology of type 1 DM has a strong genetic component. Nevertheless, identical twins have a concordance rate for type 1 DM of less than 50%. In studies of identical twin pairs in which 1 twin has type 1 diabetes, antibodies to the islet cell and to insulin are positive for several years in the nondiabetic twin before overt diabetes develops.

Extragenetic factors also may contribute. Potential triggers for immunologically mediated destruction of the beta cells include viruses (eg, mumps, rubella, coxsackievirus B4), toxic chemicals, exposure to cow’s milk in infancy, and cytotoxins. As beta-cell mass declines with ongoing immunologic destruction, insulin secretion decreases until the available insulin no longer is adequate to maintain normal blood glucose levels. After 80-90% of the beta cells are destroyed, hyperglycemia develops and diabetes may be diagnosed.

A meta-analysis suggests a significant association between enterovirus infection and autoimmune/type 1 DM.[8] The role of enterovirus in development of type 1 DM warrants investigation in larger prospective studies.

Infant weight velocity has a small indirect effect on adult insulin resistance, and this is primarily mediated through its effect on BMI and waist circumference.[9]

Intensive dose statin therapy was associated with increased risk of new onset diabetes compared with moderate dose in a pooled analysis of data from 5 statin trials.[10]

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Epidemiology

United States statistics

About 215,000 people younger 20 years had diabetes (type 1 or type 2) in the United States in 2010.[11]

A 2011 Centers for Disease Control and Prevention (CDC) report estimates that nearly 26 million Americans have diabetes.[11] Additionally, an estimated 79 million Americans have prediabetes. Diabetes affects 8.3% of Americans of all ages and 11.3% of adults aged 20 years and older, according to the National Diabetes Fact Sheet for 2011.[11] About 27% of those with diabetes—7 million Americans—do not know they have the disease. Prediabetes affects 35% of adults aged 20 years and older.

In 2008, the CDC estimated that 23.6 million Americans, or 7.8% of the population, had diabetes and another 57 million adults had prediabetes. The 2001 estimates have increased because of the following reasons:[11] more people are developing diabetes, people with diabetes are living longer (due to improved disease management), and hemoglobin A1c diagnostic tests are now used and previous estimates are not directly comparable.

In 2005, according to the American Diabetes Association (ADA), people with DM were estimated to account for 7% of the US population, or approximately 20.8 million people.[11] Additionally, an estimated 54 million people have prediabetes. Prediabetes, as defined by the ADA, is that state in which blood glucose levels are higher than normal but not high enough to be diagnosed as diabetes. It is presumed that most persons with elevated glucose levels approaching the level needed for the diagnosis of diabetes will subsequently progress to diabetes.

Roughly 5-10% have type 1 diabetes, 90-95% have type 2, and 1-5% have other types. Approximately 1 million Americans have type 1 DM, and physicians diagnose 10,000 new cases every year. Type 1 DM is the most common metabolic disease of childhood, with a yearly incidence of 15 cases per 100,000 people younger than 18 years. About one in every 400-600 children and adolescents has type 1 DM.

A study by Ludwig et al found that neighborhoods with high levels of poverty are associated with increases in the incidence of extreme obesity and diabetes. Although the mechanisms behind this association is unclear, further investigation is warranted.[12]

International statistics

Internationally, rates of type 1 diabetes are increasing. In Europe, the Middle East, and Australia, rates of type 1 diabetes are increasing by 2-5% per year. Scandinavia has the highest prevalence rates for type 1 DM (ie, approximately 20% of the total number of people with DM), while China and Japan have the lowest prevalence rates, with less than 1% of all people with diabetes. Some of these differences may relate to definitional issues and the completeness of reporting.

Prevalence of diabetes by age

Long called juvenile-onset diabetes, type 1 DM is typically diagnosed in childhood, adolescence, or early adulthood. Although the onset of type 1 DM often occurs early in life, 50% of patients with new-onset type 1 DM are older than 20 years of age.

Type 1 DM usually starts in children aged 4 years or older, fairly abruptly, with the peak incidence of onset at age 11-13 years, coinciding with early adolescence and puberty. Also, a relatively high incidence exists in people in their late 30s and early 40s, when the disease tends to present in a less aggressive manner (ie, early hyperglycemia without ketoacidosis and gradual onset of ketosis). This slower-onset adult form of type 1 DM is referred to as latent autoimmune diabetes of the adult (LADA).[11]

The risk of development of antibodies (antiislet) in relatives of patients with type 1 DM decreases with increasing age. This finding supports annual screening for antibodies in children younger than 10 years and one additional screening as adolescent.[13]

Prevalence of diabetes by race

Type 1 DM is more common among non-Hispanic whites, followed by African Americans and Hispanic Americans. It is comparatively uncommon among Asians.

Whites seem to be affected more often than blacks, who have the lowest overall incidence of type 1 diabetes.

Sex distribution for diabetes

Type 1 DM is more common in men than in women. The male-to-female ratio is approximately greater than 1.5:1 in populations of European origin.

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Prognosis

Type 1 DM is associated with a high morbidity and premature mortality. More than 60% of patients with type 1 DM fare reasonably well over the long term. Many of the rest develop blindness, end-stage renal disease, and, in some cases, early death. The risk of end stage renal disease and proliferative retinopathy (PR) in men compared with women doubles when age at onset of diabetes was less than 15 years.[14]

If a patient with type 1 DM survives the period 10-20 years after onset of disease without fulminant complications, he or she has a high probability of reasonably good health. Other factors affecting long-term outcomes are the patient’s education, awareness, motivation, and intelligence level. The 2011 ADA standard of care emphasizes the importance of long-term, coordinated care management for improved outcomes and suggests structural changes to existing systems of chronic care delivery.[15]

The morbidity and mortality associated with diabetes are related to the short- and long-term complications. Such complications include hypoglycemia and hyperglycemia, increased risk of infections, microvascular complications (eg, retinopathy, nephropathy), neuropathic complications, and macrovascular disease. As a result of these complications, people with diabetes have an increased risk of developing ischemic heart disease, cerebral vascular disease, peripheral vascular disease with gangrene of lower limbs, chronic renal disease, reduced visual acuity and blindness, and autonomic and peripheral neuropathy. Diabetes is the major cause of blindness in adults aged 20-74 years, as well as the leading cause of nontraumatic lower-extremity amputation and end-stage renal disease (ESRD).

Although mortality has declined in early onset type 1 DM (onset age, 0-14 y), the same is not true for late onset type 1 DM (onset age, 15-29 y). Women tend to fare worse in both cohorts. Alcohol and drug use accounts for a significant percentage of deaths (39%).[16]

Controlling blood glucose, hemoglobin A1c (HbA1c), lipids, blood pressure, and weight are important prognostic factors. Patients with diabetes have a lifelong challenge to achieve and maintain blood glucose levels as close to the normal range as possible. With appropriate glycemic control, the risk of both microvascular and neuropathic complications is decreased markedly. In addition, if hypertension and hyperlipidemia are treated aggressively, the risk of macrovascular complications decreases as well. The benefits of glycemic control and control of comorbidities are weighed against the risk of hypoglycemia and the short-term costs of providing high-quality preventive care. Studies have shown cost savings due to a reduction in acute diabetes-related complications within 1-3 years of starting effective preventive care.

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Patient Education

Education is the most important aspect of diabetes management. Patients with new-onset type 1 DM require extensive education if they are to manage their disease safely and effectively and to minimize long-term complications. Such education is beyond the scope of ED practice and is best coordinated by the patient’s long-term care providers.

At every encounter, the physician or health care provider should educate the patient—and, in the case of children, the parents—about the disease process, management, goals, and long-term complications. In particular, physicians should make patients aware of the signs and symptoms of hypoglycemia and ways to manage it; should help patients both to acknowledge and to understand the course of diabetes (eg, by teaching patients that they have a chronic condition that requires lifestyle modification and that they are likely to have chronic complications if they do not take control of their disease); and should reassure patients about the prognosis.

Specialized residential and day camps for children with diabetes have gained widespread popularity because they offer a traditional camping experience in a medically safe environment. The camps provide beneficial opportunities for children with diabetes to meet and share their experiences and to learn more about how to self-manage their diabetes. In 2011, the ADA released a position statement on diabetes management at camps for children with diabetes.[17]

The ADA Standards of Medical Care in Diabetes—2011 urges attention to older adolescent patients who may be leaving their home and their existing health care providers. At the transition between pediatric and adult health care, older teens can become detached from the health care system, putting their medical care and their glycemic control at risk.[15] The guideline provides a link to the National Diabetes Education Program (NDEP) and the materials they offer to smooth the transition to adult health care.

It is especially important that patients with diabetes be educated about and encouraged to follow an appropriate treatment plan. Physicians must ensure that the care for each patient with diabetes includes all necessary laboratory tests, examinations (eg, foot and neurologic examinations), and referrals to specialists (eg, ophthalmologist, podiatrist).

The American Association of Clinical Endocrinologists (AACE) produced guidelines in 2011 for developing an individualized comprehensive treatment plan for each patient. The guidelines recommend that such a plan be created for every person with documented diabetes mellitus. Considerations for individualizing the care plan include the patient’s medical history, ethnic and cultural background, age, behaviors, risk factors, and environment.[18]

A dietitian should provide specific diet control education to the patient and family.

A nurse should educate the patient about self–insulin injection and performing finger sticks for blood glucose level monitoring.

Individual attention and education of patients with poorly controlled type 1 DM is superior to group education.[19]

In 2011, the ADA released general guidelines for driving for individuals with diabetes.[20]

For excellent patient education resources, visit eMedicine’s Diabetes Center. Also, see eMedicine’s patient education article Diabetes.

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Contributor Information and Disclosures
Author

Romesh Khardori, MD, PhD, FACP  Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, and Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD  Professor of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Howard A Bessen, MD Professor of Medicine, Department of Emergency Medicine, University of California, Los Angeles, David Geffen School of Medicine; Program Director, Harbor-UCLA Medical Center

Howard A Bessen, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy ofSciences,and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Aneela Naureen Hussain, MD, FAAFM Assistant Professor, Department of Family Medicine, State University of New York Downstate Medical Center; Consulting Staff, Department of Family Medicine, University Hospital of Brooklyn

Aneela Naureen Hussain, MD, FAAFM is a member of the following medical societies: American Academy of Family Physicians, American Medical Association, American Medical Women's Association, Medical Society of the State of New York, and Society of Teachers of Family Medicine

Disclosure: Nothing to disclose.

Anne L Peters, MD, CDE Director of Clinical Diabetes Programs, Professor, Department of Medicine, University of Southern California, Keck School of Medicine, Los Angeles, California, Los Angeles County/University of Southern California Medical Center

Anne L Peters, MD, CDE is a member of the following medical societies: American College of Physicians and American Diabetes Association

Disclosure: Amylin Honoraria Speaking and teaching; AstraZeneca Consulting fee Consulting; Lilly Consulting fee Consulting; Takeda Consulting fee Consulting; Bristol Myers Squibb Honoraria Speaking and teaching; NovoNordisk Consulting fee Consulting; Medtronic Minimed Consulting fee Consulting; Dexcom Honoraria Speaking and teaching; Roche Honoraria Speaking and teaching

Don S Schalch, MD Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics

Don S Schalch, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Central Society for Clinical Research, and Endocrine Society

Disclosure: Nothing to disclose.

Erik D Schraga, MD Staff Physician, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Miriam T Vincent, MD, PhD Professor and Chair, Department of Family Practice, State University of New York Downstate Medical Center

Miriam T Vincent, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Family Physicians, American Association for the Advancement of Science, Medical Society of the State of New York, North American Primary Care Research Group, Sigma Xi, and Society of Teachers of Family Medicine

Disclosure: Joslin Diabetes Group, Harvard Honoraria Speaking and teaching

Scott R Votey, MD Director of Emergency Medicine Residency, Ronald Reagan UCLA Medical Center; Professor of Medicine/Emergency Medicine, University of California, Los Angeles, David Geffen School of Medicine

Scott R Votey, MD is a member of the following medical societies: Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Frederick H Ziel, MD Associate Professor of Medicine, University of California, Los Angeles, David Geffen School of Medicine; Physician-In-Charge, Endocrinology/Diabetes Center, Director of Medical Education, Kaiser Permanente Woodland Hills; Chair of Endocrinology, Co-Chair of Diabetes Complete Care Program, Southern California Permanente Medical Group

Frederick H Ziel, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society for Bone and Mineral Research, California Medical Association, Endocrine Society, andInternational Society for Clinical Densitometry

Disclosure: Nothing to disclose.

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