Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Type 1 Diabetes Mellitus

  • Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: George T Griffing, MD  more...
 
Updated: Jul 06, 2016
 

Practice Essentials

Type 1 diabetes is a chronic illness characterized by the body’s inability to produce insulin due to the autoimmune destruction of the beta cells in the pancreas. Onset most often occurs in childhood, but the disease can also develop in adults in their late 30s and early 40s.[1]

See Clinical Findings in Diabetes Mellitus, a Critical Images slideshow, to help identify various cutaneous, ophthalmologic, vascular, and neurologic manifestations of DM.

Signs and symptoms

The classic symptoms of type 1 diabetes are as follows:

  • Polyuria
  • Polydipsia
  • Polyphagia
  • Unexplained weight loss

Other symptoms may include fatigue, nausea, and blurred vision.

The onset of symptomatic disease may be sudden. It is not unusual for patients with type 1 diabetes to present with diabetic ketoacidosis (DKA).

See Clinical Presentation for more detail.

Diagnosis

Diagnostic criteria by the American Diabetes Association (ADA) include the following[2] :

  • A fasting plasma glucose (FPG) level ≥126 mg/dL (7.0 mmol/L), or
  • A 2-hour plasma glucose level ≥200 mg/dL (11.1 mmol/L) during a 75-g oral glucose tolerance test (OGTT), or
  • A random plasma glucose ≥200 mg/dL (11.1 mmol/L) in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis

Lab studies

A fingerstick glucose test is appropriate for virtually all patients with diabetes. All fingerstick capillary glucose levels must be confirmed in serum or plasma to make the diagnosis. All other laboratory studies should be selected or omitted on the basis of the individual clinical situation.

An international expert committee appointed by the ADA, the European Association for the Study of Diabetes, and the International Diabetes Association recommended the HbA1c assay for diagnosing type 1 diabetes only when the condition is suspected but the classic symptoms are absent.[3]

Screening

Screening for type 1 diabetes in asymptomatic low-risk individuals is not recommended.[2] However, in patients at high risk (eg, those who have first-degree relatives with type 1 diabetes), it may be appropriate to perform annual screening for anti-islet antibodies before the age of 10 years, along with 1 additional screening during adolescence.[4]

See Workup for more detail.

Management

Glycemic control

The ADA recommends using patient age as one consideration in the establishment of glycemic goals, with different targets for preprandial, bedtime/overnight, and hemoglobin A1c (HbA1c) levels in patients aged 0-6, 6-12, and 13-19 years.[5] Benefits of tight glycemic control include not only continued reductions in the rates of microvascular complications but also significant differences in cardiovascular events and overall mortality.

Self-monitoring

Optimal diabetic control requires frequent self-monitoring of blood glucose levels, which allows rational adjustments in insulin doses. All patients with type 1 diabetes should learn how to self-monitor and record their blood glucose levels with home analyzers and adjust their insulin doses accordingly.

Real-time continuous monitoring of glucose—using continuous glucose monitors (CGMs)—can help patients improve glycemic control.[6, 7] CGMs contain subcutaneous sensors that measure interstitial glucose levels every 1-5 minutes, providing alarms when glucose levels are too high or too low or are rapidly rising or falling.

Insulin therapy

Patients with type 1 diabetes require lifelong insulin therapy. Most require 2 or more injections of insulin daily, with doses adjusted on the basis of self-monitoring of blood glucose levels. Insulin replacement is accomplished by giving a basal insulin and a preprandial (premeal) insulin. The basal insulin is either long-acting (glargine or detemir) or intermediate-acting (NPH). The preprandial insulin is either rapid-acting (lispro, aspart, insulin inhaled, or glulisine) or short-acting (regular).

Common insulin regimens include the following:

  • Split or mixed: NPH with rapid-acting (eg, lispro, aspart, or glulisine) or regular insulin before breakfast and supper
  • Split or mixed variant: NPH with rapid-acting or regular insulin before breakfast, rapid-acting or regular insulin before supper, and NPH before bedtime (the idea is to reduce fasting hypoglycemia by giving the NPH later in the evening)
  • Multiple daily injections (MDI): A long-acting insulin (eg, glargine or detemir) once a day in the morning or evening (or twice a day in about 20% of patients) and a rapid-acting insulin before meals or snacks (with the dose adjusted according to the carbohydrate intake and the blood glucose level)
  • Continuous subcutaneous insulin infusion (CSII): Rapid-acting insulin infused continuously 24 hours a day through an insulin pump at 1 or more basal rates, with additional boluses given before each meal and correction doses administered if blood glucose levels exceed target levels

Diet and activity

All patients on insulin should have a comprehensive diet plan, created with the help of a professional dietitian, that includes the following:

  • A daily caloric intake prescription
  • Recommendations for amounts of dietary carbohydrate, fat, and protein
  • Instructions on how to divide calories between meals and snacks

Exercise is also an important aspect of diabetes management. Patients should be encouraged to exercise regularly.

See Treatment and Medication for more detail.

Next

Background

Type 1 diabetes mellitus (DM) is a multisystem disease with both biochemical and anatomic/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.[1] (See Pathophysiology.) (See also Glucose Intolerance.)

Type 1 DM can occur at any age. It is most common in juveniles but can also develop 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 usually are not obese and usually present initially with diabetic ketoacidosis (DKA). The distinguishing characteristic of a patient with type 1 DM is that if his or her insulin is withdrawn, ketosis and eventually ketoacidosis develop. Therefore, these patients are dependent on exogenous insulin. (See Presentation.)

Treatment of type 1 DM requires lifelong insulin therapy. A multidisciplinary approach by the physician, nurse, and dietitian, with regular specialist consultation, is needed to control glycemia, as well as to limit the development of its devastating complications and manage such complications when they do occur. (See Treatmentand Medication.)

Despite the differences between type 1 and type 2 DM, the costs of the 2 conditions are often combined. In a study that focused on type 1 alone, Tao et al estimated that in the United States, type 1 DM is responsible for $14.4 billion in medical costs and lost income each year.[8]

Previous
Next

Pathophysiology

Type 1 DM is the culmination of lymphocytic infiltration and destruction of insulin-secreting beta cells of the islets of Langerhans in the pancreas. As beta-cell mass declines, 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. Patients need exogenous insulin to reverse this catabolic condition, prevent ketosis, decrease hyperglucagonemia, and normalize lipid and protein metabolism.

Currently, autoimmunity is considered the major factor in the pathophysiology of type 1 DM. In a genetically susceptible individual, viral infection may stimulate the production of antibodies against a viral protein that trigger an autoimmune response against antigenically similar beta cell molecules.

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. The most commonly found islet cell antibodies are those directed against glutamic acid decarboxylase (GAD), an enzyme found within pancreatic beta cells.

The prevalence of type 1 DM is increased in patients with other autoimmune diseases, such as Graves disease, Hashimoto thyroiditis, and Addison disease. Pilia et al found a higher prevalence of islet cell antibodies (IA2) and anti-GAD antibodies in patients with autoimmune thyroiditis.[9]

A study by Philippe et al used computed tomography (CT) scans, glucagon stimulation test results, and fecal elastase-1 measurements to confirm reduced pancreatic volume in individuals with DM.[10] This finding, which was equally present in both type 1 and type 2 DM, may also explain the associated exocrine dysfunction that occurs in DM.

Polymorphisms of the class II human leukocyte antigen (HLA) genes that encode DR and DQ are the major genetic determinants of type 1 DM. Approximately 95% of patients with type 1 DM have either HLA-DR3 or HLA-DR4. Heterozygotes for those haplotypes are at significantly greater risk for DM than homozygotes. HLA-DQs are also considered specific markers of type 1 DM susceptibility. In contrast, some haplotypes (eg, HLA-DR2) confer strong protection against type 1 DM.[11]

Sensory and autonomic neuropathy

Sensory and autonomic neuropathy in people with diabetes are caused by axonal degeneration and segmental demyelination. Many factors are involved, including the accumulation of sorbitol in peripheral sensory nerves from sustained hyperglycemia. Motor neuropathy and cranial mononeuropathy result from vascular disease in blood vessels supplying nerves.

Angiopathy

Using nailfold video capillaroscopy, Barchetta et al detected a high prevalence of capillary changes in patients with diabetes, particularly those with retinal damage. This reflects a generalized microvessel involvement in both type 1 and type 2 DM.[12]

Microvascular disease causes multiple pathologic complications in people with diabetes. Hyaline arteriosclerosis, a characteristic pattern of wall thickening of small arterioles and capillaries, is widespread and is responsible for ischemic changes in the kidney, retina, brain, and peripheral nerves.

Atherosclerosis of the main renal arteries and their intrarenal branches causes chronic nephron ischemia. It is a significant component of multiple renal lesions in diabetes.

Vitamin D deficiency is an important independent predictor of development of coronary artery calcification in individuals with type 1 DM.[13] Joergensen et al determined that vitamin D deficiency in type 1 diabetes may predict all causes of mortality but not development of microvascular complications.[14]

Nephropathy

In the kidneys, the characteristic wall thickening of small arterioles and capillaries leads to diabetic nephropathy, which is characterized by proteinuria, glomerular hyalinization (Kimmelstiel-Wilson), and chronic renal failure. Exacerbated expression of cytokines such as tumor growth factor beta 1 is part of the pathophysiology of glomerulosclerosis, which begins early in the course of diabetic nephropathy.

Genetic factors influence the development of diabetic nephropathy. Single-nucleotide polymorphisms affecting the factors involved in its pathogenesis appear to influence the risk for diabetic nephropathy in different people with type 1 DM.[15]

Double diabetes

In areas where rates of type 2 DM and obesity are high, individuals with type 1 DM may share genetic and environmental factors that lead to their exhibiting type 2 features such as reduced insulin sensitivity. This condition is termed double diabetes.

In a study that included 207 patients with type 1 DM, Epstein et al used the estimated glucose disposal rate (eGDR) to assess insulin resistance and found that mean eGDR was significantly lower (and, thus, insulin resistance was higher) in black patients (5.66 mg/kg/min) than in either Hispanic patients (6.70 mg/kg/min) or white patients (7.20 mg/kg/min). In addition, low eGDR was associated with an increased risk of vascular complications of diabetes (eg, cardiovascular disease, diabetic retinopathy, or severe chronic kidney disease).[16, 17]

Previous
Next

Etiology

Type 1A DM results from autoimmune destruction of the beta cells of the pancreas and involves both genetic predisposition and an environmental component.

Genetic factors

Although the genetic aspect of type 1 DM is complex, with multiple genes involved, there is a high sibling relative risk.[18] Whereas dizygotic twins have a 5-6% concordance rate for type 1 DM,[19] monozygotic twins will share the diagnosis more than 50% of the time by the age of 40 years.[20]

For the child of a parent with type 1 DM, the risk varies according to whether the mother or the father has diabetes. Children whose mother has type 1 DM have a 2-3% risk of developing the disease, whereas those whose father has the disease have a 5-6% risk. When both parents are diabetic, the risk rises to almost 30%. In addition, the risk for children of parents with type 1 DM is slightly higher if onset of the disease occurred before age 11 years and slightly lower if the onset occurred after the parent’s 11th birthday.

The genetic contribution to type 1 DM is also reflected in the significant variance in the frequency of the disease among different ethnic populations. Type 1 DM is most prevalent in European populations, with people from northern Europe more often affected than those from Mediterranean regions.[21] The disease is least prevalent in East Asians.[22]

Genome-wide association studies have identified several loci that are associated with type 1 DM, but few causal relations have been established. The genomic region most strongly associated with other autoimmune diseases, the major histocompatibility complex (MHC), is the location of several susceptibility loci for type 1 DM—in particular, class II HLA DR and DQ haplotypes.[23, 24, 25]

A hierarchy of DR-DQ haplotypes associated with increased risk for type 1 DM has been established. The most susceptible haplotypes are as follows[26] :

  • DRB1*0301 - DQA1*0501 - DQB1*0201 (odds ratio [OR] 3.64)
  • DRB1*0405 - DQA1*0301 - DQB1*0302 (OR 11.37)
  • DRB1*0401 - DQA1*0301 - DQB*0302 (OR 8.39)
  • DRB1*0402 - DQA1*0301 - DQB1*0302 (OR 3.63)
  • DRB1*0404 - DQA1*0301 - DQB1*0302 (OR 1.59)
  • DRB1*0801 - DQB1*0401 - DQB1*0402 (OR 1.25)

Other haplotypes appear to offer protection against type 1 DM. These include the following[26] :

  • DRB1*1501 - DQA1*0102 - DQB1*0602 (OR 0.03)
  • DRB1*1401 - DQA1*0101 - DQB1*0503 (OR 0.02)
  • DRB1*0701 - DQA1*0201 - DQB1*0303 (OR 0.02)

From 90% to 95% of young children with type 1 DM carry HLA-DR3 DQB1*0201, HLA-DR4 DQB1*0302, or both. Carriage of both haplotypes (ie, DR3/4 heterozygotes) confers the highest susceptibility.

These high-risk haplotypes are found primarily in people of European descent; other ethnic groups are less well studied. In African Americans, the DRB1*07:01 - DQA1*03:01 -DQB1*02:01g haplotype is associated with increased risk (OR 3.96), whereas the DRB1*07:01-DQA1*02:01 - DQB1*02:01g haplotype appears to be protective (OR 0.34).[27]

The insulin gene (INS), which encodes for the pre-proinsulin peptide, is adjacent to a variable number of tandem repeats (VNTR) polymorphism at chromosome 11p15.5.[28] Different VNTR alleles may promote either resistance or susceptibility to type 1 DM through their effect on INS transcription in the thymus; for example, protective VNTRs are associated with higher INS expression, which may promote deletion of insulin-specific T cells.[29]

Other genes that have been reported to be involved in the mechanism of type 1 DM include CTLA4 (important in T-cell activation), PTPN22 (produces LYP, a negative regulator of T-cell kinase signaling), and IL2RA (encodes for CD25 which is involved with regulating T-cell function). UBASH3A (also known as STS2), may be involved in the increased risk not only of type 1 DM but also of other autoimmune disease and Down syndrome; it is located on locus chromosome 21q22.3.[30]

In addition, genome-wide association studies have implicated numerous other genes, including the following[31] :

  • SH2B3
  • ERBB3
  • CLEC16A
  • IL18RAP
  • PTPN2
  • CCR5

Environmental factors

Extragenetic factors also may contribute. Potential triggers for immunologically mediated destruction of the beta cells include viruses (eg, enterovirus,[32] mumps, rubella, and coxsackievirus B4), toxic chemicals, exposure to cow’s milk in infancy,[33] and cytotoxins.

Combinations of factors may be involved. Lempainen et al found that signs of an enterovirus infection by 12 months of age were associated with the appearance of type 1 DM–related autoimmunity among children who were exposed to cow's milk before 3 months of age. These results suggest an interaction between the 2 factors and provide a possible explanation for the contradictory findings obtained in studies that examined these factors in isolation.[34]

One meta-analysis found a weak but significant linear increase in the risk of childhood type 1 DM with increasing maternal age.[35] However, little evidence supports any substantial increase in childhood type 1 DM risk after pregnancy complicated by preeclampsia.[36]

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 DM.[37] This study was based in Denver, Colorado, and has been following children at increased risk of diabetes since 1993.

Early upper respiratory infection may also be a risk factor for type 1 diabetes. In an analysis of data on 148 children considered genetically at risk for diabetes, upper respiratory infections in the first year of life were associated with an increased risk for type 1 diabetes .[38, 39] All children in the study who developed islet autoimmunity had at least 2 upper respiratory infections in the first year of life and at least 1 infection within 6 months before islet autoantibody seroconversion.

Children with respiratory infections in the first 6 months of life had the greatest increased hazard ratio (HR) for islet autoantibody seroconversion (HR = 2.27), and the risk was also increased in those with respiratory infections at ages 6 to almost 12 months (HR = 1.32).[38, 39] The rate of islet autoantibody seroconversion was highest among children with more than 5 respiratory infections in the first year of year of life. Respiratory infections in the second year of life were not related to increased risk.[38, 39]

Previous
Next

Epidemiology

United States statistics

A 2011 report from the US Centers for Disease Control and Prevention (CDC) estimated that approximately 1 million Americans have type 1 DM.[40] The CDC estimated that each year from 2002 to 2005, type 1 DM was newly diagnosed in 15,600 young people. Among children younger than 10 years, the annual rate of new cases was 19.7 per 100,000 population; among those 10 years or older, the rate was 18.6 per 100,000 population.[40]

Type 1 DM is the most common metabolic disease of childhood. About 1 in every 400-600 children and adolescents has type 1 DM. In adults, type 1 DM constitutes approximately 5% of all diagnosed cases of diabetes.[40]

International statistics

Internationally, rates of type 1 DM are increasing. In Europe, the Middle East, and Australia, rates of type 1 DM are increasing by 2-5% per year.[41] The prevalence of type 1 DM is highest in Scandinavia (ie, approximately 20% of the total number of people with DM) and lowest in China and Japan (ie, fewer than 1% of all people with diabetes). Some of these differences may relate to definitional issues and the completeness of reporting.

Age-related demographics

Previously referred to as 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, appearing fairly abruptly, with the peak incidence of onset at age 11-13 years (ie, in early adolescence and puberty). There is also a relatively high incidence in people in their late 30s and early 40s, in whom the disease tends to present less aggressively (ie, with 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).[40]

The risk of development of antibodies (anti-islet) in relatives of patients with type 1 DM decreases with increasing age. This finding supports annual screening for antibodies in relatives younger than 10 years and 1 additional screening during adolescence.[4]

Sex- and race-related demographics

Type 1 DM is more common in males than in females. In populations of European origin, the male-to-female ratio is greater than 1.5:1.

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

Previous
Next

Prognosis

Type 1 DM is associated with a high morbidity and premature mortality. More than 60% of patients with type 1 DM do not develop serious complications over the long term, but many of the rest experience blindness, end-stage renal disease (ESRD), and, in some cases, early death. The risk of ESRD and proliferative retinopathy is twice as high in men as in women when the onset of diabetes occurred before age 15 years.[42]

Patients with type 1 DM who survive the period 10-20 years after disease onset without fulminant complications have a high probability of maintaining reasonably good health. Other factors affecting long-term outcomes are the patient’s education, awareness, motivation, and intelligence level. The 2012 American Diabetes Association (ADA) standard of care emphasizes the importance of long-term, coordinated care management for improved outcomes and suggests structural changes to existing systems of long-term care delivery.[5]

The morbidity and mortality associated with diabetes are related to the short- and long-term complications. Such complications include the following:

  • Hypoglycemia from management errors
  • Increased risk of infections
  • Microvascular complications (eg, retinopathy and nephropathy)
  • Neuropathic complications
  • Macrovascular disease

These complications result in increased risk for 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 ESRD.

In both diabetic and non-diabetic patients, coronary vasodilator dysfunction is a strong independent predictor of cardiac mortality. In diabetic patients without coronary artery disease, those with impaired coronary flow reserve have event rates similar to those with prior coronary artery disease, while patients with preserved coronary flow reserve have event rates similar to non-diabetic patients.[43]

Type 1 diabetic patients also have a high prevalence of small-fiber neuropathy.[44, 45] In a prospective study of 27 patients who had type 1 diabetes with a mean disease duration of 40 years, almost 60% of the subjects showed signs or symptoms of neuropathy, including sensory neuropathy symptoms (9 patients), pain (3 patients), and carpal-tunnel symptoms (5 patients).[44, 45] Of the 27 patients, 22 were diagnosed with small-fiber dysfunction by means of quantitative sensory testing.

Abnormal results on intraepidermal nerve-fiber density measurement (IENFD) were seen in 19 patients.[45] IENFD was negatively correlated with HbA1c, but this relation was no longer significant after adjustment for age, body mass index, and height. N-ε-(carboxymethyl) lysine (CML), which is linked to painful diabetic neuropathy, remained independently associated with IENFD even after adjustment for these variables. Large-fiber neuropathy was also common, being found in 16 patients.

Although ESRD is one of the most severe complications of type 1 DM, its incidence is relatively low: 2.2% at 20 years after diagnosis and 7.8% at 30 years after diagnosis.[46] A greater risk is that mild diabetic nephropathy in type 1 diabetic persons appears to be associated with an increased likelihood of cardiovascular disease.[47] Moreover, the long-term risk of an impaired glomerular filtration rate (GFR) is lower in persons treated with intense insulin therapy early in the course of disease than in those given conventional therapy.[48]

Although mortality from early-onset type 1 DM (onset age, 0-14 y) has declined, the same may not be true for late-onset type 1 DM (onset age, 15-29 y). One study suggest that women tend to fare worse in both cohorts and that alcohol and drug use account for more than one third of deaths.[49]

Control of blood glucose, hemoglobin A1c (HbA1c), lipids, blood pressure, and weight significantly affects prognosis. Excess weight gain with intensified diabetes treatment is associated with hypertension, insulin resistance, dyslipidemia and extetnsive atherosclerotic cardiovascular disease.[50]

Patients with diabetes face 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, aggressive treatment of hypertension and hyperlipidemia decreases the risk of macrovascular complications.

The benefits of glycemic control and control of comorbidities must be weighed against the risk of hypoglycemia and the short-term costs of providing high-quality preventive care. However, studies have shown cost savings due to a reduction in acute diabetes-related complications within 1-3 years of starting effective preventive care.

Previous
Next

Patient Education

Education is a vital 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 best coordinated by the patient’s long-term care providers.

At every encounter, the clinician should educate the patient—and, in the case of children, the parents—about the disease process, management, goals, and long-term complications. In particular, clinicians should do the following:

  • Make patients aware of the signs and symptoms of hypoglycemia and knowledgeable about ways to manage it
  • Help patients understand and acknowledge 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)
  • Reassure patients about the prognosis in properly managed type 1 DM

ADA guidelines urge that attention be paid to older adolescent patients who may be leaving their home and their current 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.[5] The guidelines identify the National Diabetes Education Program (NDEP) as a source of materials that can help smooth the transition to adult health care.

Education about an appropriate treatment plan and encouragement to follow the plan are especially important in patients with diabetes. 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, an ophthalmologist or podiatrist).

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 fingerstick tests for blood glucose level monitoring.

For patient education information, see the Diabetes Center, as well as Diabetes.

Previous
 
 
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, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus 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, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

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.

References
  1. Aathira R, Jain V. Advances in management of type 1 diabetes mellitus. World J Diabetes. 2014 Oct 15. 5 (5):689-96. [Medline]. [Full Text].

  2. [Guideline] Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010 Jan. 33 Suppl 1:S62-9. [Medline]. [Full Text].

  3. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009 Jul. 32(7):1327-34. [Medline]. [Full Text].

  4. Vehik K, Beam CA, Mahon JL, et al. Development of Autoantibodies in the TrialNet Natural History Study. Diabetes Care. 2011 Sep. 34(9):1897-1901. [Medline]. [Full Text].

  5. [Guideline] American Diabetes Association. Standards of medical care in diabetes--2011. Diabetes Care. 2011 Jan. 34 Suppl 1:S11-61. [Medline]. [Full Text].

  6. Nainggolan L. Continuous Glucose Monitoring: Navigator Beats Rival Devices. Medscape Medical News. January 14, 2013. Available at http://www.medscape.com/viewarticle/777607. Accessed: January 24, 2013.

  7. Damiano ER, El-Khatib FH, Zheng H, Nathan DM, Russell SJ. A Comparative Effectiveness Analysis of Three Continuous Glucose Monitors. Diabetes Care. 2013 Jan 3. [Medline].

  8. 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. PLoS One. 2010 Jul 9. 5(7):e11501. [Medline]. [Full Text].

  9. Pilia S, Casini MR, Cambuli VM, et al. Prevalence of Type 1 diabetes autoantibodies (GAD and IA2) in Sardinian children and adolescents with autoimmune thyroiditis. Diabet Med. 2011 Aug. 28(8):896-9. [Medline].

  10. Philippe MF, Benabadji S, Barbot-Trystram L, et al. Pancreatic volume and endocrine and exocrine functions in patients with diabetes. Pancreas. 2011 Apr. 40(3):359-63. [Medline].

  11. Noble JA, Valdes AM. Genetics of the HLA region in the prediction of type 1 diabetes. Curr Diab Rep. 2011 Dec. 11(6):533-42. [Medline]. [Full Text].

  12. Barchetta I, Riccieri V, Vasile M, et al. High prevalence of capillary abnormalities in patients with diabetes and association with retinopathy. Diabet Med. 2011 Sep. 28(9):1039-44. [Medline].

  13. Young KA, Snell-Bergeon JK, Naik RG, Hokanson JE, Tarullo D, Gottlieb PA, et al. Vitamin D deficiency and coronary artery calcification in subjects with type 1 diabetes. Diabetes Care. 2011 Feb. 34(2):454-8. [Medline]. [Full Text].

  14. Joergensen C, Hovind P, Schmedes A, Parving HH, Rossing P. Vitamin d levels, microvascular complications, and mortality in type 1 diabetes. Diabetes Care. 2011 May. 34(5):1081-5. [Medline].

  15. Zhang D, Efendic S, Brismar K, Gu HF. Effects of MCF2L2, ADIPOQ and SOX2 genetic polymorphisms on the development of nephropathy in type 1 Diabetes Mellitus. BMC Med Genet. 2010 Jul 28. 11:116. [Medline]. [Full Text].

  16. Busko M. Phenomenon of 'double diabetes' common among blacks. Medscape Medical News. April 25, 2013. [Full Text].

  17. Epstein EJ, Osman JL, Cohen HW, Rajpathak SN, Lewis O, Crandall JP. Use of the Estimated Glucose Disposal Rate (eGDR) as a Measure of Insulin Resistance in an Urban Multiethnic Population With Type 1 Diabetes. Diabetes Care. 2013 Apr 17. [Medline].

  18. Davies JL, Kawaguchi Y, Bennett ST, Copeman JB, Cordell HJ, Pritchard LE, et al. A genome-wide search for human type 1 diabetes susceptibility genes. Nature. 1994 Sep 8. 371(6493):130-6. [Medline].

  19. Steck AK, Barriga KJ, Emery LM, Fiallo-Scharer RV, Gottlieb PA, Rewers MJ. Secondary attack rate of type 1 diabetes in Colorado families. Diabetes Care. 2005 Feb. 28(2):296-300. [Medline].

  20. Redondo MJ, Jeffrey J, Fain PR, Eisenbarth GS, Orban T. Concordance for islet autoimmunity among monozygotic twins. N Engl J Med. 2008 Dec 25. 359(26):2849-50. [Medline].

  21. Borchers AT, Uibo R, Gershwin ME. The geoepidemiology of type 1 diabetes. Autoimmun Rev. 2010 Mar. 9(5):A355-65. [Medline].

  22. Diabetes Epidemiology Research International Group. Geographic patterns of childhood insulin-dependent diabetes mellitus. Diabetes Epidemiology Research International Group. Diabetes. 1988 Aug. 37(8):1113-9. [Medline].

  23. Erlich H, Valdes AM, Noble J, Carlson JA, Varney M, Concannon P, et al. HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes. 2008 Apr. 57(4):1084-92. [Medline].

  24. Todd JA, Bell JI, McDevitt HO. HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature. 1987 Oct 15-21. 329(6140):599-604. [Medline].

  25. Corper AL, Stratmann T, Apostolopoulos V, Scott CA, Garcia KC, Kang AS, et al. A structural framework for deciphering the link between I-Ag7 and autoimmune diabetes. Science. 2000 Apr 21. 288(5465):505-11. [Medline].

  26. Erlich H, Valdes AM, Noble J, Carlson JA, Varney M, Concannon P, et al. HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes. 2008 Apr. 57(4):1084-92. [Medline]. [Full Text].

  27. Noble JA, Johnson J, Lane JA, Valdes AM. Race-specific type 1 diabetes risk of HLA-DR7 haplotypes. Tissue Antigens. 2011 Nov. 78(5):348-51. [Medline]. [Full Text].

  28. Rotwein P, Yokoyama S, Didier DK, Chirgwin JM. Genetic analysis of the hypervariable region flanking the human insulin gene. Am J Hum Genet. 1986 Sep. 39(3):291-9. [Medline]. [Full Text].

  29. Pugliese A, Zeller M, Fernandez A Jr, Zalcberg LJ, Bartlett RJ, Ricordi C, et al. The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes. Nat Genet. 1997 Mar. 15(3):293-7. [Medline].

  30. Polychronakos C, Li Q. Understanding type 1 diabetes through genetics: advances and prospects. Nat Rev Genet. 2011 Oct 18. 12(11):781-92. [Medline].

  31. Concannon P, Chen WM, Julier C, Morahan G, Akolkar B, Erlich HA, et al. Genome-wide scan for linkage to type 1 diabetes in 2,496 multiplex families from the Type 1 Diabetes Genetics Consortium. Diabetes. 2009 Apr. 58(4):1018-22. [Medline]. [Full Text].

  32. Yeung WC, Rawlinson WD, Craig ME. Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies. BMJ. 2011 Feb 3. 342:d35. [Medline]. [Full Text].

  33. Paronen J, Knip M, Savilahti E, Virtanen SM, Ilonen J, Akerblom HK, et al. Effect of cow's milk exposure and maternal type 1 diabetes on cellular and humoral immunization to dietary insulin in infants at genetic risk for type 1 diabetes. Finnish Trial to Reduce IDDM in the Genetically at Risk Study Group. Diabetes. 2000 Oct. 49(10):1657-65. [Medline].

  34. Lempainen J, Tauriainen S, Vaarala O, Mäkelä M, Honkanen H, Marttila J, et al. Interaction of enterovirus infection and cow's milk-based formula nutrition in type 1 diabetes-associated autoimmunity. Diabetes Metab Res Rev. 2012 Feb. 28(2):177-85. [Medline].

  35. Cardwell CR, Stene LC, Joner G, Bulsara MK, Cinek O, Rosenbauer J, et al. Maternal age at birth and childhood type 1 diabetes: a pooled analysis of 30 observational studies. Diabetes. 2010 Feb. 59(2):486-94. [Medline]. [Full Text].

  36. Henry EB, Patterson CC, Cardwell CR. A meta-analysis of the association between pre-eclampsia and childhood-onset Type 1 diabetes mellitus. Diabet Med. 2011 Aug. 28(8):900-5. [Medline].

  37. Simpson M, Brady H, Yin X, et al. No association of vitamin D intake or 25-hydroxyvitamin D levels in childhood with risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY). Diabetologia. 2011 Nov. 54(11):2779-88. [Medline].

  38. Melville N. Early Upper-Respiratory Infections Linked to Type 1 Diabetes. Medscape Medical News. Available at http://www.medscape.com/viewarticle/807205. Accessed: July 8, 2013.

  39. Beyerlein A, Wehweck F, Ziegler AG, Pflueger M. Respiratory Infections in Early Life and the Development of Islet Autoimmunity in Children at Increased Type 1 Diabetes Risk: Evidence From the BABYDIET Study. JAMA Pediatr. 2013 Jul 1. [Medline].

  40. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Available at http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed: January 28, 2011.

  41. Imkampe AK, Gulliford MC. Trends in Type 1 diabetes incidence in the UK in 0- to 14-year-olds and in 15- to 34-year-olds, 1991-2008. Diabet Med. 2011 Jul. 28(7):811-4. [Medline].

  42. Harjutsalo V, Maric C, Forsblom C, et al. Sex-related differences in the long-term risk of microvascular complications by age at onset of type 1 diabetes. Diabetologia. 2011 Aug. 54(8):1992-1999. [Medline].

  43. Murthy VL, Naya M, Foster CR, Gaber M, Hainer J, Klein J, et al. Association Between Coronary Vascular Dysfunction and Cardiac Mortality in Patients with and without Diabetes Mellitus. Circulation. 2012 Aug 23. [Medline].

  44. Tucker ME. Small-fiber neuropathy common at 40 years of type 1 diabetes. Medscape Medical News. September 18, 2013. [Full Text].

  45. Sveen KA, Karimé B, Jørum E, Mellgren SI, Fagerland MW, Monnier VM, et al. Small- and Large-Fiber Neuropathy After 40 Years of Type 1 Diabetes: Associations with glycemic control and advanced protein glycation: The Oslo Study. Diabetes Care. 2013 Sep 11. [Medline].

  46. Finne P, Reunanen A, Stenman S, Groop PH, Grönhagen-Riska C. Incidence of end-stage renal disease in patients with type 1 diabetes. JAMA. 2005 Oct 12. 294(14):1782-7. [Medline].

  47. Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005 Dec 22. 353(25):2643-53. [Medline]. [Full Text].

  48. DCCT/EDIC Research Group, de Boer IH, Sun W, Cleary PA, Lachin JM, Molitch ME, et al. Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. N Engl J Med. 2011 Dec 22. 365(25):2366-76. [Medline]. [Full Text].

  49. Harjutsalo V, Forsblom C, Groop PH. Time trends in mortality in patients with type 1 diabetes: nationwide population based cohort study. BMJ. 2011 Sep 8. 343:d5364. [Medline]. [Full Text].

  50. Purnell JQ, Hokanson JE, Cleary PA, Nathan DM, Lachin JM, Zinman B, et al. The Effect of Excess Weight Gain with Intensive Diabetes Treatment on Cardiovascular Disease Risk Factors and Atherosclerosis in Type 1 Diabetes: Results from the Diabetes Control and Complications Trial / Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC) Study. Circulation. 2012 Dec 4. [Medline].

  51. Joshi N, Caputo GM, Weitekamp MR, Karchmer AW. Infections in patients with diabetes mellitus. N Engl J Med. 1999 Dec 16. 341(25):1906-12. [Medline].

  52. Wong VH, Bui BV, Vingrys AJ. Clinical and experimental links between diabetes and glaucoma. Clin Exp Optom. 2011 Jan. 94(1):4-23. [Medline].

  53. Gillespie KM. Type 1 diabetes: pathogenesis and prevention. CMAJ. 2006 Jul 18. 175(2):165-70. [Medline]. [Full Text].

  54. Harris SS. Vitamin D in type 1 diabetes prevention. J Nutr. 2005 Feb. 135(2):323-5. [Medline].

  55. Hammes HP, Kerner W, Hofer S, et al. Diabetic retinopathy in type 1 diabetes-a contemporary analysis of 8,784 patients. Diabetologia. 2011 Aug. 54(8):1977-1984. [Medline].

  56. Julius MC, Schatz DA, Silverstein JH. The prevention of type I diabetes mellitus. Pediatr Ann. 1999 Sep. 28(9):585-8. [Medline].

  57. Vinik AI, Mehrabyan A. Diabetic neuropathies. Med Clin North Am. 2004 Jul. 88(4):947-99, xi. [Medline].

  58. Chou KL, Galetta SL, Liu GT, Volpe NJ, Bennett JL, Asbury AK, et al. Acute ocular motor mononeuropathies: prospective study of the roles of neuroimaging and clinical assessment. J Neurol Sci. 2004 Apr 15. 219(1-2):35-9. [Medline].

  59. Gerstein HC, Islam S, Anand S, et al. Dysglycaemia and the risk of acute myocardial infarction in multiple ethnic groups: an analysis of 15,780 patients from the INTERHEART study. Diabetologia. 2010 Dec. 53(12):2509-17. [Medline].

  60. Falcone C, Nespoli L, Geroldi D, Gazzaruso C, Buzzi MP, Auguadro C, et al. Silent myocardial ischemia in diabetic and nondiabetic patients with coronary artery disease. Int J Cardiol. 2003 Aug. 90(2-3):219-27. [Medline].

  61. [Guideline] Handelsman Y, Mechanick JI, Blonde L, Grunberger G, Bloomgarden ZT, Bray GA, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2011 Mar-Apr. 17 Suppl 2:1-53. [Medline].

  62. [Guideline] Hattersley A, Bruining J, Shield J, Njolstad P, Donaghue KC. The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes. 2009 Sep. 10 Suppl 12:33-42. [Medline].

  63. Hemoglobin A1c and Mean Glucose in Patients With Type 1 Diabetes: Analysis of data from the Juvenile Diabetes Research Foundation continuous glucose monitoring randomized trial. Diabetes Care. 2011 Mar. 34(3):540-4. [Medline]. [Full Text].

  64. Mianowska B, Fendler W, Szadkowska A, Baranowska A, Grzelak-Agaciak E, Sadon J, et al. HbA(1c) levels in schoolchildren with type 1 diabetes are seasonally variable and dependent on weather conditions. Diabetologia. 2011 Apr. 54(4):749-56. [Medline]. [Full Text].

  65. Suzuki S, Koga M, Amamiya S, et al. Glycated albumin but not HbA(1c) reflects glycaemic control in patients with neonatal diabetes mellitus. Diabetologia. 2011 Sep. 54(9):2247-53. [Medline].

  66. McDonald TJ, Colclough K, Brown R, et al. Islet autoantibodies can discriminate maturity-onset diabetes of the young (MODY) from Type 1 diabetes. Diabet Med. 2011 Sep. 28(9):1028-33. [Medline].

  67. [Guideline] Chiang JL, Kirkman MS, Laffel LM, Peters AL. Type 1 Diabetes Through the Life Span: A Position Statement of the American Diabetes Association. Diabetes Care. 2014 Jun 16. [Medline].

  68. Tucker M. First-Ever ADA Guidance Specifically for Type 1 Diabetes. Medscape Medical news. Available at http://www.medscape.com/viewarticle/826854. Accessed: June 20, 2014.

  69. Kielgast U, Holst JJ, Madsbad S. Antidiabetic actions of endogenous and exogenous GLP-1 in type 1 diabetic patients with and without residual ß-cell function. Diabetes. 2011 May. 60(5):1599-607. [Medline].

  70. [Guideline] American Diabetes Association. Standards of Medical Care in Diabetes - 2015: Abridged for Primary Care Providers. Clinical Diabetes. 2015. 33:2:[Full Text].

  71. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993 Sep 30. 329(14):977-86. [Medline].

  72. Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005 Dec 22. 353(25):2643-53. [Medline]. [Full Text].

  73. Genuth S. Insights from the diabetes control and complications trial/epidemiology of diabetes interventions and complications study on the use of intensive glycemic treatment to reduce the risk of complications of type 1 diabetes. Endocr Pract. 2006 Jan-Feb. 12 Suppl 1:34-41. [Medline].

  74. Lind M, Bounias I, Olsson M, et al. Glycaemic control and incidence of heart failure in 20,985 patients with type 1 diabetes: an observational study. Lancet. 2011 Jul 9. 378(9786):140-6. [Medline].

  75. Tomlin A, Dovey S, Tilyard M. Health outcomes for diabetes patients returning for three annual general practice checks. N Z Med J. 2007 Apr 13. 120(1252):U2493. [Medline].

  76. Jacobson AM, Ryan CM, Cleary PA, Waberski BH, Weinger K, Musen G, et al. Biomedical risk factors for decreased cognitive functioning in type 1 diabetes: an 18 year follow-up of the Diabetes Control and Complications Trial (DCCT) cohort. Diabetologia. 2011 Feb. 54(2):245-55. [Medline].

  77. Asvold BO, Sand T, Hestad K, Bjørgaas MR. Cognitive function in type 1 diabetic adults with early exposure to severe hypoglycemia: a 16-year follow-up study. Diabetes Care. 2010 Sep. 33(9):1945-7. [Medline]. [Full Text].

  78. Garg SK, Voelmle MK, Beatson CR, Miller HA, Crew LB, Freson BJ, et al. Use of Continuous Glucose Monitoring in Subjects With Type 1 Diabetes on Multiple Daily Injections Versus Continuous Subcutaneous Insulin Infusion Therapy: A prospective 6-month study. Diabetes Care. 2011 Mar. 34(3):574-9. [Medline]. [Full Text].

  79. Battelino T, Phillip M, Bratina N, Nimri R, Oskarsson P, Bolinder J. Effect of continuous glucose monitoring on hypoglycemia in type 1 diabetes. Diabetes Care. 2011 Apr. 34(4):795-800. [Medline]. [Full Text].

  80. [Guideline] Klonoff DC, Buckingham B, Christiansen JS, et al. Continuous glucose monitoring: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011 Oct. 96(10):2968-79. [Medline].

  81. Medtronic, Inc. Medtronic gains approval of first artificial pancreas device system with threshold suspend automation [press release]. September 27, 2013. Available at http://newsroom.medtronic.com/phoenix.zhtml?c=251324&p=irol-newsArticle&ID=1859361&highlight. Accessed: October 7, 2013.

  82. Tucker ME. FDA OKs insulin pump with low-glucose suspend feature. Medscape Medical News. September 27, 2013. [Full Text].

  83. What is the pancreas? What is an artificial pancreas device system?. US Food and Drug Administration. Available at http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/HomeHealthandConsumer/ConsumerProducts/ArtificialPancreas/ucm259548.htm. May 16, 2016; Accessed: July 6, 2016.

  84. Tucker ME. Coming Soon: 'Artificial Pancreas' Options for Diabetes. Medscape Medical News. June 20, 2016. [Full Text].

  85. Boggs W. Round-the-Clock Closed-Loop Glucose Control Leads to Better Outcomes. Medscape. May 13, 2016. [Full Text].

  86. Renard E, Farret A, Kropff J, et al. Day-and-Night Closed-Loop Glucose Control in Patients With Type 1 Diabetes Under Free-Living Conditions: Results of a Single-Arm 1-Month Experience Compared With a Previously Reported Feasibility Study of Evening and Night at Home. Diabetes Care. 2016 Jul. 39 (7):1151-60. [Medline].

  87. Tucker M. FDA Approves Inhaled Insulin Afrezza for Diabetes. Medscape Medical News. Available at http://www.medscape.com/viewarticle/827539.. Accessed: July 14, 2014.

  88. Afrezza (insulin inhaled) prescribing information [package insert]. Valencia CA, United States: MannKind Corporation. June, 2014. Available at [Full Text].

  89. US Food and Drug Administration. Mixups between Insulin U-100 and U-500 (April 2008). FDA Patient Safety News. Available at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/psn/transcript.cfm?show=79. Accessed: January 28, 2012.

  90. de la Pena A, Riddle M, Morrow LA, et al. Pharmacokinetics and pharmacodynamics of high-dose human regular u-500 insulin versus human regular u-100 insulin in healthy obese subjects. Diabetes Care. 2011 Dec. 34(12):2496-501. [Medline]. [Full Text].

  91. Garg S, Ampudia-Blasco FJ, Pfohl M. Rapid-acting insulin analogues in Basal-bolus regimens in type 1 diabetes mellitus. Endocr Pract. 2010 May-Jun. 16(3):486-505. [Medline].

  92. Birkeland KI, Home PD, Wendisch U, Ratner RE, Johansen T, Endahl LA, et al. Insulin Degludec in Type 1 Diabetes: A randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine. Diabetes Care. 2011 Mar. 34(3):661-5. [Medline]. [Full Text].

  93. Davies MJ, Gross JL, Ono Y, Sasaki T, Bantwal G, Gall MA, et al. Efficacy and safety of insulin degludec given as part of basal-bolus treatment with mealtime insulin aspart in type 1 diabetes: a 26-week randomized, open-label, treat-to-target non-inferiority trial. Diabetes Obes Metab. 2014 Oct. 16 (10):922-30. [Medline]. [Full Text].

  94. Zinman B, DeVries JH, Bode B, Russell-Jones D, Leiter LA, Moses A, et al. Efficacy and safety of insulin degludec three times a week versus insulin glargine once a day in insulin-naive patients with type 2 diabetes: results of two phase 3, 26 week, randomised, open-label, treat-to-target, non-inferiority trials. Lancet Diabetes Endocrinol. 2013 Oct. 1 (2):123-31. [Medline].

  95. Heise T, Pieber TR. Towards peakless, reproducible and long-acting insulins. An assessment of the basal analogues based on isoglycaemic clamp studies. Diabetes Obes Metab. 2007 Sep. 9(5):648-59. [Medline].

  96. Suissa S, Azoulay L, Dell'aniello S, et al. Long-term effects of insulin glargine on the risk of breast cancer. Diabetologia. 2011 Sep. 54(9):2254-62. [Medline].

  97. Johnson JA, Bowker SL, Richardson K, Marra CA. Time-varying incidence of cancer after the onset of type 2 diabetes: evidence of potential detection bias. Diabetologia. 2011 Sep. 54(9):2263-71. [Medline].

  98. Bao J, Gilbertson HR, Gray R, et al. Improving the Estimation of Mealtime Insulin Dose in Adults With Type 1 Diabetes: The Normal Insulin Demand for Dose Adjustment (NIDDA) study. Diabetes Care. 2011 Oct. 34(10):2146-51. [Medline]. [Full Text].

  99. Bergenstal RM, Tamborlane WV, Ahmann A, Buse JB, Dailey G, Davis SN, et al. Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes. N Engl J Med. 2010 Jul 22. 363(4):311-20. [Medline].

  100. Busko M. Insulin pump therapy bests injection therapy in large study. Medscape Medical News. August 19, 2013. [Full Text].

  101. Johnson SR, Cooper MN, Jones TW, Davis EA. Long-term outcome of insulin pump therapy in children with type 1 diabetes assessed in a large population-based case-control study. Diabetologia. 2013 Aug 21. [Medline]. [Full Text].

  102. King BR, Goss PW, Paterson MA, Crock PA, Anderson DG. Changes in Altitude Cause Unintended Insulin Delivery From Insulin Pumps: Mechanisms and implications. Diabetes Care. 2011 Sep. 34(9):1932-3. [Medline]. [Full Text].

  103. Grunberger G, Abelseth JM, Bailey TS, Bode BW, Handelsman Y, Hellman R. Consensus statement by the american association of clinical endocrinologists/american college of endocrinology insulin pump management task force. Endocr Pract. 2014 May 1. 20(5):463-89. [Medline].

  104. Babiker A, Datta V. Lipoatrophy with insulin analogues in type I diabetes. Arch Dis Child. 2011 Jan. 96(1):101-2. [Medline].

  105. Giménez M, Gilabert R, Monteagudo J, Alonso A, Casamitjana R, Paré C, et al. Repeated episodes of hypoglycemia as a potential aggravating factor for preclinical atherosclerosis in subjects with type 1 diabetes. Diabetes Care. 2011 Jan. 34(1):198-203. [Medline]. [Full Text].

  106. Asvold BO, Sand T, Hestad KA, Bjorgaas MR. Quantitative EEG in type 1 diabetic adults with childhood exposure to severe hypoglycaemia: a 16 year follow-up study. Diabetologia. 2011 Sep. 54(9):2404-8. [Medline].

  107. Kacerovsky M, Jones J, Schmid AI, et al. Postprandial and fasting hepatic glucose fluxes in long-standing type 1 diabetes. Diabetes. 2011 Jun. 60(6):1752-8. [Medline]. [Full Text].

  108. Ahmedani MY, Haque MS, Basit A, Fawwad A, Alvi SF. Ramadan Prospective Diabetes Study: the role of drug dosage and timing alteration, active glucose monitoring and patient education. Diabet Med. 2012 Jun. 29(6):709-15. [Medline].

  109. Pannu N, Wiebe N, Tonelli M. Prophylaxis strategies for contrast-induced nephropathy. JAMA. 2006 Jun 21. 295(23):2765-79. [Medline].

  110. Salardi S, Balsamo C, Zucchini S, Maltoni G, Scipione M, Rollo A, et al. High rate of regression from micro-macroalbuminuria to normoalbuminuria in children and adolescents with type 1 diabetes treated or not with enalapril: the influence of HDL cholesterol. Diabetes Care. 2011 Feb. 34(2):424-9. [Medline]. [Full Text].

  111. de Boer IH, Rue TC, Cleary PA, et al. Long-term Renal Outcomes of Patients With Type 1 Diabetes Mellitus and Microalbuminuria: An Analysis of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Cohort. Arch Intern Med. 2011 Mar 14. 171(5):412-420. [Medline]. [Full Text].

  112. Strippoli GF, Bonifati C, Craig M, Navaneethan SD, Craig JC. Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease. Cochrane Database Syst Rev. 2006 Oct 18. CD006257. [Medline].

  113. Vinik AI, Ziegler D. Diabetic cardiovascular autonomic neuropathy. Circulation. 2007 Jan 23. 115(3):387-97. [Medline].

  114. Lipsky BA, Berendt AR, Deery HG, Embil JM, Joseph WS, Karchmer AW, et al. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2004 Oct 1. 39(7):885-910. [Medline].

  115. Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005 Jan 12. 293(2):217-28. [Medline].

  116. Buse JB, Ginsberg HN, Bakris GL, Clark NG, Costa F, Eckel R, et al. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care. 2007 Jan. 30(1):162-72. [Medline].

  117. Margeirsdottir HD, Stensaeth KH, Larsen JR, Brunborg C, Dahl-Jørgensen K. Early signs of atherosclerosis in diabetic children on intensive insulin treatment: a population-based study. Diabetes Care. 2010 Sep. 33(9):2043-8. [Medline]. [Full Text].

  118. van Dieren S, Nöthlings U, van der Schouw YT, Spijkerman AM, Rutten GE, van der A DL, et al. Non-fasting lipids and risk of cardiovascular disease in patients with diabetes mellitus. Diabetologia. 2011 Jan. 54(1):73-7. [Medline]. [Full Text].

  119. Lee SH, Kim JH, Kang MJ, et al. Implications of nocturnal hypertension in children and adolescents with type 1 diabetes. Diabetes Care. 2011 Oct. 34(10):2180-5. [Medline]. [Full Text].

  120. Leiter LA, Lundman P, da Silva PM, et al. Persistent lipid abnormalities in statin-treated patients with diabetes mellitus in Europe and Canada: results of the Dyslipidaemia International Study. Diabet Med. 2011 Nov. 28(11):1343-1351. [Medline].

  121. Lund SS, Tarnow L, Astrup AS, Hovind P, Jacobsen PK, Alibegovic AC, et al. Effect of adjunct metformin treatment on levels of plasma lipids in patients with type 1 diabetes. Diabetes Obes Metab. 2009 Oct. 11(10):966-77. [Medline].

  122. Tucker ME. ACC/AHA statin guidelines, with caveats. WebMD. Available at http://www.medscape.com/viewarticle/837138. Accessed: Dec 24, 2014.

  123. Marks JB. Perioperative management of diabetes. Am Fam Physician. 2003 Jan 1. 67(1):93-100. [Medline].

  124. [Guideline] Qaseem A, Humphrey LL, Chou R, Snow V, Shekelle P. Use of intensive insulin therapy for the management of glycemic control in hospitalized patients: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2011 Feb 15. 154(4):260-7. [Medline].

  125. Kansagara D, Fu R, Freeman M, Wolf F, Helfand M. Intensive insulin therapy in hospitalized patients: a systematic review. Ann Intern Med. 2011 Feb 15. 154(4):268-82. [Medline].

  126. [Guideline] Moghissi ES, Korytkowski MT, DiNardo M, Einhorn D, Hellman R, Hirsch IB, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care. 2009 Jun. 32(6):1119-31. [Medline]. [Full Text].

  127. Vanhorebeek I, Langouche L, Van den Berghe G. Tight blood glucose control: what is the evidence?. Crit Care Med. 2007 Sep. 35(9 Suppl):S496-502. [Medline].

  128. Murphy HR, Steel SA, Roland JM, et al. Obstetric and perinatal outcomes in pregnancies complicated by Type 1 and Type 2 diabetes: influences of glycaemic control, obesity and social disadvantage. Diabet Med. 2011 Sep. 28(9):1060-7. [Medline].

  129. Diabetes Prevention Trial--Type 1 Diabetes Study Group. Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med. 2002 May 30. 346(22):1685-91.

  130. Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med. 2002 May 30. 346(22):1685-91. [Medline].

  131. Gale EA, Bingley PJ, Emmett CL, Collier T. European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes. Lancet. 2004 Mar 20. 363(9413):925-31. [Medline].

  132. Wherrett DK, Bundy B, Becker DJ, et al. Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial. Lancet. 2011 Jul 23. 378(9788):319-27. [Medline].

  133. Sherry N, Hagopian W, Ludvigsson J, et al. Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial. Lancet. 2011 Aug 6. 378(9790):487-97. [Medline].

  134. Orban T, Bundy B, Becker DJ, et al. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet. 2011 Jul 30. 378(9789):412-9. [Medline].

  135. Brooks M. FDA Clears Blood Test to Help Diagnose Type 1 Diabetes. Medscape Medical News. Aug 21 2014. [Full Text].

  136. Hsiao-Chuan L, et al. Enterovirus infection is associated with an increased risk of childhood type 1 diabetes in Taiwan: A nationwide population-based cohort study. Diabetologia. 2014. [Full Text].

  137. Leegaard A, Riis A, Kornum JB, et al. Diabetes, Glycemic Control, and Risk of Tuberculosis: A population-based case-control study. Diabetes Care. 2011 Dec. 34(12):2530-5. [Medline]. [Full Text].

  138. Ludwig J, Sanbonmatsu L, Gennetian L, et al. Neighborhoods, obesity, and diabetes--a randomized social experiment. N Engl J Med. 2011 Oct 20. 365(16):1509-19. [Medline].

  139. Peters A, Laffel L. Diabetes Care for Emerging Adults: Recommendations for Transition From Pediatric to Adult Diabetes Care Systems: A position statement of the American Diabetes Association, with representation by the American College of Osteopathic Family Physicians, the American Academy of Pediatrics, the American Association of Clinical Endocrinologists, the American Osteopathic Association, the Centers for Disease Control and Prevention, Children with Diabetes, The Endocrine Society, the International Socie... Diabetes Care. 2011 Nov. 34(11):2477-2485. [Medline]. [Full Text].

  140. US Food and Drug Administration. Early Communication About Safety of Lantus (Insulin Glargine). Available at http://www.fda.gov/Drugs/DrugSafety/ucm239376.htm. Accessed: May 22, 2012.

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.