eMedicine Specialties > Endocrinology > Diabetes Mellitus

Diabetes Mellitus, Type 1

Author: 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
Coauthor(s): Miriam T Vincent, MD, PhD, Professor and Chair, Department of Family Practice, State University of New York Downstate Medical Center
Contributor Information and Disclosures

Updated: Feb 4, 2010

Introduction

Background

Diabetes mellitus (DM) is a multisystem disease with both biochemical and anatomical consequences. It is a chronic disease of carbohydrate, fat, and protein metabolism caused by the lack of insulin. In type 1 diabetes, insulin is functionally absent because of the destruction of the beta cells of the pancreas. Type 1 DM occurs most commonly in juveniles but can occur in adults, especially in those in their late 30s and early 40s. Unlike people with type 2 DM, those with type 1 DM generally are not obese and may present initially with diabetic ketoacidosis (DKA).

Pathophysiology

Type 1 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. Patients need exogenous insulin to reverse this catabolic condition, prevent ketosis, decrease hyperglucagonemia, and normalize lipid and protein metabolism.

Type 1 DM is an autoimmune disease. The pancreas shows lymphocytic infiltration and destruction of insulin-secreting cells of the islets of Langerhans, causing insulin deficiency. Approximately 85% of 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 B cells.

One theory regarding the etiology of type 1 DM is that it results from damage to pancreatic beta cells from an infectious or environmental agent. It triggers the immune system in a genetically susceptible individual to develop an autoimmune response against altered pancreatic beta cell antigens or molecules in beta cells that resemble a viral protein. 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. 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.

Environmental agents that have been hypothesized to induce an attack on beta cell function include viruses (eg, mumps, rubella, Coxsackie B4), toxic chemicals, exposure to cow's milk in infancy, and cytotoxins.

Recent evidence suggests a role for vitamin D in the pathogenesis and prevention of diabetes mellitus.

Frequency

United States

Roughly 5-15% of all cases of diabetes are type 1 DM. It is the most common metabolic disease of childhood, with a yearly incidence of 15 cases per 100,000 people younger than 18 years. Approximately 1 million Americans have type 1 DM, and physicians diagnose 10,000 new cases every year.

According to the American Diabetes Association, there are 20.8 million children and adults in the United States, or 7% of the population, who have diabetes. While an estimated 14.6 million have been diagnosed, unfortunately, 6.2 million people (or nearly one-third) are undiagnosed. Fifty-four million people are prediabetes status. In people younger than 20 years, 176,500 cases, or 0.22% of all people in this age group, have diabetes. About one in every 400-600 children and adolescents has type 1 DM. Two million adolescents (or 1 in 6 overweight adolescents) aged 12-19 years have prediabetes status. In people aged 20 years or older, 1.5 million new cases of diabetes were diagnosed  in 2005.

International

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.

Mortality/Morbidity

Type 1 DM is associated with a high morbidity and premature mortality due to complications. The annual financial cost from diabetes overall exceeds $100 billion, almost $1 of every $7 dollars of US health expenditures in terms of medical care and loss of productivity. Advances in treatment that permit tight glycemic control and control of comorbidities (hyperlipidemia) can greatly reduce the incidence of microvascular and macrovascular complications.

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.

Race

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

Sex

Type 1 DM is more common in men than in women.

Age

Type 1 DM usually starts in children aged 4 years or older, 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 it tends to present in a less aggressive manner, ie, early hyperglycemia without ketoacidosis and gradual onset of ketosis.

Clinical

History

The most common symptoms of type 1 diabetes mellitus (DM) are polyuria, polydipsia, and polyphagia, along with lassitude, nausea, and blurred vision, all of which are due to the hyperglycemia itself. The disease onset may be sudden, with the presentation of an infection. It is not unusual for type 1 DM to present with ketoacidosis; it may occur de novo or develop with the stress of illness or surgery. An explosive onset of symptoms in a young lean patient with ketoacidosis always has been considered diagnostic of type 1 DM.

• Polyuria and thirst: Polyuria is due to osmotic diuresis secondary to hyperglycemia. Thirst is due to the hyperosmolar state and dehydration.
• Polyphagia with weight loss: The weight loss with a normal or increased appetite is due to depletion of water and a catabolic state with reduced glycogen, proteins, and triglycerides.
• Fatigue and weakness: This may be due to muscle wasting from the catabolic state of insulin deficiency, hypovolemia, and hypokalemia.
• Muscle cramps: This is due to electrolyte imbalance.
• Nocturnal enuresis: Severe enuresis secondary to polyuria can be an indication of onset of diabetes in young children.
• Blurred vision: This also is due to the effect of the hyperosmolar state on the lens and vitreous humor. Glucose and its metabolites cause dilation of the lens, altering its normal focal length.
• Gastrointestinal symptoms: Nausea, abdominal discomfort or pain, and change in bowel movements may accompany acute DKA. Acute fatty liver may lead to distention of the hepatic capsule, causing right upper quadrant pain. Persistent abdominal pain may indicate another serious abdominal cause of DKA, eg, pancreatitis. Chronic gastrointestinal symptoms in the later stage of diabetes are due to visceral autonomic neuropathy.
• Patients may maintain their normal weight or exhibit wasting, depending on the interval between the onset of the disease and initiation of treatment.
• Peripheral neuropathy: This presents as numbness and tingling in both hands and feet, in a glove and stocking pattern. It is bilateral, symmetric, and ascending neuropathy, which results from many factors, including the accumulation of sorbitol in peripheral sensory nerves due to sustained hyperglycemia.
• Symptoms at the time of the first clinical presentation can usually be traced back several days to several weeks; however, beta cell destruction may have started months, or even years, before the onset of clinical symptoms.

Physical

In new cases of diabetes, physical examination findings are usually normal, except in DKA, wherein signs of Kussmaul respiration, dehydration, hypotension, and, in some cases, altered mental status are present.

In established cases, patients should be examined every 3 months for macrovascular and microvascular complications. They should have funduscopic examination for retinopathy and monofilament testing for peripheral neuropathy.

Causes

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%. Extragenetic factors also may contribute, which are discussed in Pathophysiology.

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