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Diabetes Mellitus Type 1

Brittle Diabetes Mellitus

Diabetes mellitus type 1 is a class of diabetes that develops secondary to the autoimmune destruction of the pancreatic beta cells, resulting in an insulin deficiency.


Presentation

In patients with a clinical picture suggestive of diabetes, the evaluation consists of a thorough personal and family history including a detailed assessment of risk factors. Furthermore, the comprehensive physical exam should focus on cardiovascular, neurologic, and foot findings. Another key component of the workup includes laboratory studies.

Whether the patient is stable or critically ill, a serum glucose test will provide the definitive diagnosis. In the outpatient setting, the fasting blood glucose test is obtained. In the emergency setting, a finger-stick glucose test is measured promptly followed by a serum level. Also, a urine dipstick may reveal glucose.

Criteria for diagnosis

In the outpatient setting, the workup will meet one of the following criteria: 1) fasting plasma glucose value of at least 126mg/dl, 2) HbA1C equal to or greater than 6.5%, 3) a random plasma glucose level of 200 mg/dL or above, or 4) 2 hour plasma glucose value of 200mg/dL or greater in an oral glucose tolerance test (OGTT) [2].

Differentiation between type 1 and type 2 diabetes

These two are distinguished through autoantibody testing and the C-peptide assay.

DKA

Note that when DKA is suspected, this warrants additional labs for confirmation and management of the condition.

Weight Loss
  • Patients most often present with a few days or weeks of polyuria, polydipsia, weight loss, and weakness. Some patients may present with diabetic ketoacidosis.[us.bestpractice.bmj.com]
  • Patient will present as a young patient with weight loss, increased thirst, and urination. The patient has felt tired and nauseous.[smartypance.com]
  • loss is specific for IDDM; type 2 patients rarely have either Severe fasting hypoglycemia is due to cessation of glycogen storage in fat and muscle Glycosemia causes glycosuria with depletion of water and electrolytes Also: low / absent plasma insulin[pathologyoutlines.com]
  • Weight loss, with no loss of appetite, also is common. The weight loss is due in part to dehydration. Water has weight. Imagine holding a gallon jug of water: it weighs about eight pounds.[drugs.com]
  • loss The main symptoms of type 1 diabetes are often referred to as the 4Ts of type 1 diabetes.[diabetes.co.uk]
Weakness
  • In addition, age has no influence on adiponectin levels. 3) Adiponectin levels are dependent on renal function at a creatinine clearance 45 ml/min. 4) Regression analysis showed a significant, but only weak correlation between BMI and adiponectin in patients[ncbi.nlm.nih.gov]
  • Patients most often present with a few days or weeks of polyuria, polydipsia, weight loss, and weakness. Some patients may present with diabetic ketoacidosis.[us.bestpractice.bmj.com]
  • Symptoms include: Weakness Dizziness Trembling Sudden sweating Headache Confusion Irritability Blurry or double vision Hypoglycemia can lead to coma if it is not corrected by eating or drinking carbohydrates.[drugs.com]
  • […] increased urination) Polydipsia (increased thirst) Polyphagia (Increased appetite) Glycosuria (glucose in urine) Weight loss despite polyphagia Hyperglycemia (increased blood glucose) Ketonuria (ketones in urine) Fruity smelling breath Fatigue Generalized weakness[physio-pedia.com]
  • […] symptoms can appear relatively suddenly and may include: Increased thirst Frequent urination Bed-wetting in children who previously didn't wet the bed during the night Extreme hunger Unintended weight loss Irritability and other mood changes Fatigue and weakness[mayoclinic.org]
Intermittent Claudication
  • Patients with nephropathy showed a faster decrease in PCS (-0.749, P .003), and those with intermittent claudication a faster decrease in EQ-5D (-0.049, P .008).[ncbi.nlm.nih.gov]
Nausea
  • […] around the penis or vagina Blurring of vision (caused by dryness of the eyes) Unexpected cramping Skin infections Emergency diabetes symptoms Seek urgent medical attention if diabetes symptoms combine with any of the following: A serious loss of appetite Nausea[diabetes.co.uk]
  • Signs/symptoms of Diabetic Ketoacidosis: [3] Deep, rapid breathing Fruity breath Dry skin and mouth Flushed face Nausea/vomiting Abdominal pain Hypoglycemia : Blood glucose levels in relation to exercise that a PT should be aware of: 100-250 mg/dL safe[physio-pedia.com]
  • Symptoms include: Nausea and vomiting Abdominal pain Rapid heart rate Rapid breathing rate Dry mouth and skin Fruity breath smell The main treatment is insulin since the body cannot produce it on its own.[symptoma.com]
  • Nerve damage can also cause digestive problems like nausea, vomiting, and diarrhea.[webmd.com]
  • Other common symptoms are weakness, fatigue, confusion, nausea and vomiting. These symptoms can be caused both by dehydration and by a condition called ketoacidosis. Ketoacidosis occurs because cells can't use the glucose they need for energy.[drugs.com]
Vomiting
  • […] or vagina Blurring of vision (caused by dryness of the eyes) Unexpected cramping Skin infections Emergency diabetes symptoms Seek urgent medical attention if diabetes symptoms combine with any of the following: A serious loss of appetite Nausea and vomiting[diabetes.co.uk]
  • Signs/symptoms of Diabetic Ketoacidosis: [3] Deep, rapid breathing Fruity breath Dry skin and mouth Flushed face Nausea/vomiting Abdominal pain Hypoglycemia : Blood glucose levels in relation to exercise that a PT should be aware of: 100-250 mg/dL safe[physio-pedia.com]
  • Symptoms include: Nausea and vomiting Abdominal pain Rapid heart rate Rapid breathing rate Dry mouth and skin Fruity breath smell The main treatment is insulin since the body cannot produce it on its own.[symptoma.com]
  • Nerve damage can also cause digestive problems like nausea, vomiting, and diarrhea.[webmd.com]
  • Other common symptoms are weakness, fatigue, confusion, nausea and vomiting. These symptoms can be caused both by dehydration and by a condition called ketoacidosis. Ketoacidosis occurs because cells can't use the glucose they need for energy.[drugs.com]
Polydipsia
  • Patients most often present with a few days or weeks of polyuria, polydipsia, weight loss, and weakness. Some patients may present with diabetic ketoacidosis.[us.bestpractice.bmj.com]
  • NIDDM patients have autoantibodies but no other features of IDDM Usually chronic (years) Clinical disease when 90% of islet cells are destroyed Clinical features Onset at age 20 years, normal weight (unlike most NIDDM) Characterized by PPP (polyuria, polydipsia[pathologyoutlines.com]
  • Results in hyperglycemia and end-organ complications Features include: Usually rapid onset Absolute insulin dependence Polyphagia, polydipsia, polyuria, and nocturia Ketosis Body habitus: usually normal or thin physique System(s) affected: endocrine/metabolic[unboundmedicine.com]
  • Children with this type of diabetes (formerly known as juvenile-onset diabetes) often develop diabetes symptoms (polydipsia, polyuria, weight loss, hunger) rapidly.[medscape.org]
  • Americans had Diabetes (2012) 1.25 million Americans had Type 1 DM (2012) 208,000 Americans under the age of 20 estimated to have Diabetes, which is 0.25% of the population Characteristics/Clinical Presentation [1] [2] Polyuria (increased urination) Polydipsia[physio-pedia.com]
Diarrhea
  • Damage to the nerves that affect the gastrointestinal tract can cause problems with nausea, vomiting, diarrhea or constipation. For men, erectile dysfunction may be an issue. Kidney damage (nephropathy).[mayoclinic.org]
  • Nerve damage can also cause digestive problems like nausea, vomiting, and diarrhea.[webmd.com]
  • Other signs and symptoms are an unusual odor to the urine, urinary tract infections ( UTIs ), yeast infections, unexplained weight loss, feeling hungry even after meals, stomach pain, diarrhea, fatigue, swollen ankles, darkening skin round the armpits[medicinenet.com]
Abdominal Pain
  • Signs/symptoms of Diabetic Ketoacidosis: [3] Deep, rapid breathing Fruity breath Dry skin and mouth Flushed face Nausea/vomiting Abdominal pain Hypoglycemia : Blood glucose levels in relation to exercise that a PT should be aware of: 100-250 mg/dL safe[physio-pedia.com]
  • Symptoms include: Nausea and vomiting Abdominal pain Rapid heart rate Rapid breathing rate Dry mouth and skin Fruity breath smell The main treatment is insulin since the body cannot produce it on its own.[symptoma.com]
  • Symptoms of type 1 diabetes are frequent urination, excess thirst, weight loss, skin infections, bladder or vaginal infections, and abdominal pain. Sometimes, there are no significant symptoms. Type 1 diabetes is diagnosed by blood tests.[medicinenet.com]
Hepatomegaly
  • Abstract Hepatomegaly and elevated liver enzymes in patients with diabetes are commonly associated with fatty liver disease. However, physicians often forget about another intrinsic substance that can cause a similar clinical picture-glycogen.[ncbi.nlm.nih.gov]
Polyuria
  • Patients most often present with a few days or weeks of polyuria, polydipsia, weight loss, and weakness. Some patients may present with diabetic ketoacidosis.[us.bestpractice.bmj.com]
  • […] antibodies Some NIDDM patients have autoantibodies but no other features of IDDM Usually chronic (years) Clinical disease when 90% of islet cells are destroyed Clinical features Onset at age 20 years, normal weight (unlike most NIDDM) Characterized by PPP (polyuria[pathologyoutlines.com]
  • Results in hyperglycemia and end-organ complications Features include: Usually rapid onset Absolute insulin dependence Polyphagia, polydipsia, polyuria, and nocturia Ketosis Body habitus: usually normal or thin physique System(s) affected: endocrine/metabolic[unboundmedicine.com]
  • Children with this type of diabetes (formerly known as juvenile-onset diabetes) often develop diabetes symptoms (polydipsia, polyuria, weight loss, hunger) rapidly.[medscape.org]
  • […] cases are Type 1 DM 29.1 million Americans had Diabetes (2012) 1.25 million Americans had Type 1 DM (2012) 208,000 Americans under the age of 20 estimated to have Diabetes, which is 0.25% of the population Characteristics/Clinical Presentation [1] [2] Polyuria[physio-pedia.com]
Stroke
  • There are many co-morbidities associated with Type 1 Diabetes Mellitus, including: - Chronic pancreatitis - Cystic fibrosis - Autoimmune disorders - Hyperglycaemia - Heart and blood vessel diseases (MI, Stroke, Atherosclerosis, Hypertension, Angina) -[globenewswire.com]
  • […] which produces ketone bodies (acetoacetic acid and beta hydroxybutyric acid) May get hyperosmotic nonketotic coma - dehydration due to hyperglycemic diuresis with failure to drink enough fluids to compensate, often in an elderly person with diabetes and stroke[pathologyoutlines.com]
  • Patients with uncontrolled diabetes are at marked risk for kidney failure, blindness, myocardial infarction, stroke, and foot amputations.[symptoma.com]
  • It can result in serious vascular complications and neuropathies and can be a major cause of cardiovascular disease and strokes.[physio-pedia.com]
  • Heart and artery disease — People with type 1 diabetes are more likely to have heart disease, strokes and problems related to poor circulation.[drugs.com]
Peripheral Neuropathy
  • This study is for men and women who are experiencing painful diabetic peripheral neuropathy in both lower extremities (legs). The specific events that result ...[centerwatch.com]
  • The former includes peripheral neuropathy, nephropathy, and retinopathy while the latter is comprised of cardiovascular, cerebrovascular, and peripheral vascular disease.[symptoma.com]
  • Damage to nerves in the feet, legs and hands (peripheral neuropathy) is most common. Nerves that control body functions, such as digestion and urination, also can be damaged.[drugs.com]
Forgetful
  • However, physicians often forget about another intrinsic substance that can cause a similar clinical picture-glycogen. Liver stores approximately one third of the total body glycogen and is responsible for blood glucose homeostasis.[ncbi.nlm.nih.gov]
  • If a person takes too much insulin relative to their dietary intake, or if they forget to eat, they can develop dangerous hypoglycemia. If they take too little insulin, or eat too much, they can develop ketoacidosis.[drugs.com]
Headache
  • Symptoms include: Weakness Dizziness Trembling Sudden sweating Headache Confusion Irritability Blurry or double vision Hypoglycemia can lead to coma if it is not corrected by eating or drinking carbohydrates.[drugs.com]
Dysarthria
  • The girl had unstable gait with incoordination of limb movements, impairment of position and vibratory senses, dysarthria, pes cavus, positive Babinski sign and scoliosis.[ncbi.nlm.nih.gov]

Workup

In patients with a clinical picture suggestive of diabetes, the evaluation consists of a thorough personal and family history including a detailed assessment of risk factors. Furthermore, the comprehensive physical exam should focus on cardiovascular, neurologic, and foot findings. Another key component of the workup includes laboratory studies.

Whether the patient is stable or critically ill, a serum glucose test will provide the definitive diagnosis. In the outpatient setting, the fasting blood glucose test is obtained. In the emergency setting, a fingerstick glucose test is measured promptly followed by a serum level. Also, a urine dipstick may reveal glucose.

Criteria for diagnosis

In the outpatient setting, the workup will meet one of the following criteria: 1) fasting plasma glucose value of at least 126mg/dl, 2) HbA1C equal to or greater than 6.5%, 3) a random plasma glucose level of 200 mg/dL or above, or 4) 2 hour plasma glucose value of 200mg/dL or greater in an oral glucose tolerance test (OGTT) [2].

Differentiation between type 1 and type 2 diabetes

These two are distinguished through autoantibody testing and the C-peptide assay.

DKA

Note that when DKA is suspected, this warrants additional labs for confirmation and management of the condition.

Trichophyton Rubrum
  • Thirty-seven (47.4 %) of these patients had positive cultures, particularly for the dermatophyte Trichophyton rubrum (69.2 % of isolates).[ncbi.nlm.nih.gov]

Treatment

The earlier the diagnosis, the sooner the initiation of treatment and hopefully the better the short-term and long-term outcomes. Management of these patients requires a multidisciplinary approach best achieved with a medical team consisting of an internist, nephrologist, neurologist, podiatrist, ophthalmologist, diabetic educator, and nutritionist.

Glycemic control

Insulin replacement is the mainstay therapy. There are different types of insulin analogs, which are categorized according to the duration of action. The rapid-acting are typically injected prior to eating and work for a short amount of time. The other main classes include the short-acting type, which can last up to 8 hours and the long-acting form that may last up to a day or more.

There are a variety of insulin analogs in each category that offers a diversified profile of duration, time of onset, and strength. Hence, the clinician can tailor the regimen for each patient with a combination of these preparations.

The patients should meet with a diabetic nurse who will educate them on how to monitor their glucose levels and adjust their insulin levels accordingly. Patients are also taught to match their levels to the food they consume and the exercise they perform.
Note that some patients may be eligible for different therapies. One of these options utilizes an insulin pump, in which the hormone is continuously injected into the blood through a needle placed beneath the skin. The rate of the pump is managed by the patient. Other alternatives include islet cell transplantation or even pancreas transplantation.

Other

A healthy diet is a fundamental component in glycemic control. This can be achieved with the help of a dietician, who will educate the patients and their family members on appropriate meal planning and further details.

Other important factors are physical exercise and smoking cessation.

Complications

Patients with severe complications such as cardiovascular events, renal failure, retinopathy, and peripheral neuropathy will require treatment and management, typically through consultation with specialists in those areas.

Also, DKA is aggressively managed in the emergency setting with the implementation of specific protocol.

Surveillance

Patients with type 1 diabetes should follow up closely with their physician to ensure good glycemic control. Additionally, they should be surveyed for various complications such as the following [2]:

  • Glycemic control: HbA1C levels should be obtained at certain intervals
  • Cardiovascular disease: blood pressure screening at every visit
  • Nephropathy: annual creatinine measurement and possibly other tests as well
  • Retinopathy: ophthalmic exam within 5 years of diagnosis, followed by annual evaluations
  • Foot care: thorough inspection for ulcers
  • Dyslipidemia: fasting lipid panel annually

Note that the clinician should consult with the diabetic guidelines that provide comprehensive recommendations for all screening.

Prognosis

The prognosis of type I diabetes is based on how well managed the glucose levels are. Patients with uncontrolled diabetes are at marked risk for kidney failure, blindness, myocardial infarction, stroke, and foot amputations. Hence, strict glucose management may reduce the development of microvascular and macrovascular complications in insulin-deficient patients [11]. Moreover, the American Diabetes Association advises nonpregnant patients to achieve and maintain an HbA1c value of less than 7%.

The predominant cause of mortality and morbidity is cardiovascular disease. Furthermore, DKA is a life-threatening condition that occurs in untreated individuals.

Note that there are massive healthcare costs associated with type 1 diabetes in the United States, which is estimated to be $14.4 billion annually due to medical bills and lost income [12].

Etiology

Standard risk factors

There are risk factors associated with type I diabetes, which include 1) body mass index equal to or greater than 25kg/m2, 2) having a first degree relative with this disease, 3) Hispanic, African, Native American, Asian American, or Pacific Islander race or ethnicity, 4) history of cardiovascular disease, 5) women with previous gestational diabetes, 6) hypertension, 7) abnormal lipid profile, 8) females with polycystic ovarian syndrome (PCOS), 8) having conditions linked to insulin resistance, and 9) inadequate physical activity [2].

Other risk factors

The cause of this disease is likely multifactorial. Predisposed individuals may develop the disease in conjunction with environmental interplay. For example, congenital rubella syndrome and human enteroviruses are highly linked to type 1 diabetes [3].

Dietary factors such as vitamin D supplementation in infants could be protective [4] but it is not known whether cow's milk or other dietary modifications elevate the risk of developing the disorder [5].

Additionally, there are particular human leukocyte antigen (HLA) gene polymorphisms that are associated with increased risk or protection from type I diabetes mellitus [5]. Moreover, celiac disease and type I diabetes both share the HLA-DQ2 genotype as the former is frequently observed in cases of type 1 diabetes and vice versa [6].

Epidemiology

Type I diabetes is implicated in 5% to 10% of diabetics. While the actual number of affected individuals worldwide has not been established, researchers estimate that almost 80,000 children develop type 1 diabetes annually [7].

United States

The annual incidence ranges from 8 to 17 cases per population of 100,000. Additionally, there are approximately 1 to 3 million types 1 diabetics [8].

International

The incidence of this disease depends on the geographical location. For example, it occurs more in Europeans as opposed to Asians. Specifically, the Scandinavian region exhibits a yearly incidence of 35 cases per population of 100,000 while this value is 1 individual per 100,000 in China and Japan. Furthermore, children in Finland are at 40 times greater risk to develop type 1 diabetes that those in Japan.

Sex distribution
Age distribution

Pathophysiology

Autoimmune process

Type I diabetes arises from the autoimmune destruction of pancreatic beta-cells in predisposed individuals. A majority of patients possess autoantibodies to at least one of the following: 1) insulin, 2) glutamic acid decarboxylase (GAD), and 3) islet autoantigen-2 (IA-2) [9].

The subclinical phase lasts for months to years and appears as insulitis or inflammation of the beta cells. Furthermore, hyperglycemia emerges when 80% to 90% of pancreatic beta cells have become damaged.

Type I diabetics may have insulin resistance as well, although this is not a pathogenic mechanism in this form of diabetes.

Metabolic dysfunction

Type I diabetics cannot use the glucose available in the adipose tissues and muscles. Regulatory feedback mechanisms cause the release of glucagon, growth hormone, cortisol, and epinephrine, all of which play a role in hepatic gluconeogenesis, glycogenolysis, and ketogenesis. Hence, these patients develop elevated glucose levels and anion gap metabolic acidosis.

Complications

Chronic hyperglycemia produces microvascular and macrovascular diseases. The former includes peripheral neuropathy, nephropathy, and retinopathy while the latter is comprised of cardiovascular, cerebrovascular, and peripheral vascular disease.

The vascular manifestations result from the effects of long-term hyperglycemia on protein glycosylation, sorbitol synthesis, and free radical production. Elevated serum sugar levels also promote the low-density lipoprotein (LDL) deposition into the arterial wall, which then undergoes inflammation and results in the development of atheroma [10].

Prevention

Since the risk factors for type 1 diabetes have been studied thoroughly, this gave rise to the Diabetes Prevention Trial–Type 1 (DPT-1) and European Nicotinamide Diabetes Intervention Trial (ENDIT). However, the results have not been promising.

The DPT-1 study in the United States demonstrated that parenteral insulin did not delay or prevent the development of the disease in patients at risk.

The ENDIT investigation, nicotinamide also failed to delay or prevent type 1 diabetes in individuals with family history.

Summary

Type 1 diabetes mellitus is an autoimmune disease that targets the insulin-producing beta cells in the pancreas. Diabetes affects multiple organs and systems. In fact, untreated cases lead to severe complications particularly in the progression of the disease. For example, acute events include the potentially fatal diabetic ketoacidosis (DKA). Long-term manifestations encompass cardiovascular disease and events, renal failure, peripheral neuropathy, retinopathy, and foot ulcers.

There are risk factors that are predictive of this disease. Ffamily history, certain races and ethnic backgrounds, as well as physical inactivity are some examples. Furthermore, there may be genetic and environmental factors that play a role in the development of the disease. Additionally, the prevalence of type I diabetes varies according to the country and region.

DKA may be the initial presentation of this autoimmune disease. In others, there are the classic symptoms of polydipsia, polyuria, and polyphagia [1]. Early diagnosis and treatment are paramount to the overall well-being of the individual and the prevention of complications.

Treatment consists of the lifelong replacement of the deficient hormone, insulin. Since type 1 diabetes is a complicated and chronic multisystem disorder, consultation with specialists is paramount. Very importantly, the therapeutic goals include glycemic control, prevention or delaying of complications, and management of these sequelae.

Patient Information

Type 1 diabetes mellitus is a chronic disease in which the body destroys the pancreatic cells that are responsible for making insulin. Insulin is a hormone that allows the cells of the body to remove sugar from the blood, and use it for energy. Since the body cannot make enough insulin, patients with this disease will have very high sugar levels in the blood.
The symptoms may develop rapidly. Patients experience the following:

  • Increased thirst
  • Increased hunger
  • Increased urination
  • Fatigue
  • Blurry vision
  • Rapid weight loss in a short amount of time
  • Hunger
  • Neurologic problems such as numbness or no sensation in the feet

Some patients become very ill and develop the life-threatening condition called diabetic ketoacidosis. If not treated, they will fall into a coma and possibly die. Symptoms include:

The main treatment is insulin since the body cannot produce it on its own. This medication is typically self-administered through an injection. Another option is the insulin pump, which can directly release insulin from a device through the bloodstream.

There are different types of insulin medications depending on how quickly and how long they act in the body. The doctor and the patient can develop a regimen together using a combination of these types.

Note that diet and exercise are very important to control the glucose levels and allow the patient to remain healthy. A nutritionist will help the patient develop diabetic friendly meal plans. Also, a diabetic nurse will educate the patient on how to monitor the sugar levels and how to adjust the insulin doses according to what they eat and how they exercise. Also, note that smokers are strongly urged to quit.

The patients should be educated regarding how poor control of sugar levels will cause severe complications such as heart disease, heart attack, stroke, kidney failure, damage to the nerves, skin infections, blindness, high blood pressure, elevated cholesterol, etc. Therefore, patients should follow up with the medical team to manage their sugar levels and prevent these from occurring.

References

Article

  1. Cooke DW, Plotnick L. Type 1 diabetes mellitus in pediatrics. Pediatric Review. 2008; 29(11): 374–84; quiz 385.
  2. American Diabetes Association. Standards of Medical Care in Diabetes—2011. Diabetes Care. 2011;34(Suppl 1):S11-S61. doi:10.2337/dc11-S011.
  3. Devendra D, Liu E, Eisenbarth GS. Type 1 diabetes: recent developments. British Medical Journal. 2004;328(7442):750-754.
  4. Hypponen E, Laara E, Reunanen A, et al. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001;358(9292):1500-1503.
  5. Fronczak CM, Barón AE, Chase HP, et al. In utero dietary exposures and risk of islet autoimmunity in children. Diabetes Care. 2003;26(12):3237-3242.
  6. Ludvigsson JF, Ludvigsson J, Ekbom A, et al. Celiac disease and risk of subsequent type 1 diabetes: a general population cohort study of children and adolescents. Diabetes Care. 2006;29(11):2483-2488.
  7. Chiang, JL, Kirkman MS, Laffel, LMB, Peters AL . Type 1 Diabetes Through the Life Span: A Position Statement of the American Diabetes Association. Diabetes Care. 2014;37(7):2034-54.
  8. Niskanen L, Tuomi T, Karjalainen J, et al. GAD antibodies in NIDDM. Ten-year follow-up from the diagnosis. Diabetes Care. 1995;18(12):1557-1565.
  9. Ziegler AG, Hummel M, Schenker M, et al. Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB study. Diabetes. 1999;48(3):460-468.
  10. Garg R, Chaudhuri A, Munschauer F, et al. Hyperglycemia, insulin, and acute ischemic stroke: a mechanistic justification for a trial of insulin infusion therapy. Stroke. 2006;37(1):267-273.
  11. Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. New England Journal of Medicine. 2005;353(25):2643-2653.
  12. Tao B, Pietropaolo M, Atkinson M, Schatz D, Taylor D. Estimating the cost of type 1 diabetes in the U.S.: a propensity score matching method. Public Library of Science. 2010; 5(7):e11501.

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Last updated: 2018-06-21 22:29