Diabetes Mellitus, Type 1

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.


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