Type 1 Diabetes Mellitus Workup
- Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: George T Griffing, MD more...
Patients with type 1 diabetes mellitus (DM) typically present with symptoms of uncontrolled hyperglycemia (eg, polyuria, polydipsia, polyphagia). In such cases, the diagnosis of DM can be confirmed with a random (nonfasting) plasma glucose concentration of 200 mg/dL or a fasting plasma glucose concentration of 126 mg/dL (6.99 mmol/L) or higher.[2, 61]
A fingerstick glucose test is appropriate in the emergency department (ED) 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. Intravenous (IV) glucose testing may be considered for possible early detection of subclinical diabetes.
Individually measured glucose levels may differ considerably from estimated glucose averages calculated from measured hemoglobin A1c (HbA1c) levels. Therefore, caution is urged when the decision is made to estimate rather than actually measure glucose concentration; the difference between the 2 has a potential impact on decision making.
HbA<SUB1C< sub>1c is the stable product of nonenzymatic irreversible glycation of the beta chain of hemoglobin by plasma glucose and is formed at rates that increase with increasing plasma glucose levels. HbA1c levels provide an estimate of plasma glucose levels during the preceding 1-3 months. The reference range for nondiabetic people is 6% in most laboratories. Glycated hemoglobin levels also predict the progression of diabetic microvascular complications.
American Diabetes Association (ADA) guidelines recommend measuring HbA1c at least every 6 months in patients with diabetes who are meeting treatment goals and who have stable glycemic control. For patients whose therapy has changed or who are not meeting glycemic goals, the guidelines recommend HbA1c testing every 3 months.
In the past, HbA1c measurements were not considered useful for the diagnosis of DM. Drawbacks included a lack of international standardization and insensitivity for the detection of milder forms of glucose intolerance.
In a 2009 report, however, 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 and type 2 DM. In the case of type 1 DM, however, the committee recommended using the test only when the condition is suspected but the classic symptoms of type 1 DM—polyuria, polydipsia, polyphagia, a random glucose level of 200 mg/dL, and unexplained weight loss—are absent.
The committee noted the improvement in standardization and cited the following advantages of HbA1c testing over glucose measurement:
Ability to capture long-term glucose exposure
Less biologic variability
No requirement for fasting or timed samples
Current use in guiding management decisions
Consequently, since 2010 the ADA has included an HbA1c level of 6.5% or higher as a criterion for diabetes diagnosis, with confirmation from repeat testing (unless clinical symptoms are present and the glucose level exceeds 200 mg/dL). HbA1c testing cannot be used in patients with abnormal red blood cell (RBC) turnover (as in hemolytic or iron-deficiency anemia). In children with rapidly evolving type 1 DM, HbA1c may not be significantly elevated despite frank diabetes.
One study found seasonal variability in HbA1c levels of school-age children with higher levels (0.44%) coinciding with colder outdoor temperatures, fewer hours of sunlight, and lower levels of solar irradiance. This effect was seen in school-aged children but not preschoolers and may hold importance for studies using HbA1c as a primary endpoint and HbA1c -based diagnosis of diabetes.
HbA1c cannot be used as an indicator of glycemic control in patients with neonatal diabetes mellitus (NDM) because of the high levels of fetal hemoglobin (HbF) remaining in the blood. A study by Suzuki et al found that glycated albumin, which is not affected by HbF levels, more strongly correlated with 1-month average postprandial blood glucose and was therefore a better marker of diabetes in neonates. This finding is important to neonatologist and those caring for newborns.
ADA guidelines recommend measuring HbA1c at least every 6 months year in patients who are meeting treatment goals and who have stable glycemic control. For patients whose therapy has changed or who are not meeting glycemic goals, the guidelines recommend HbA1c testing every 3 months.
Other laboratory studies
Fructosamine levels also test for glucose levels. Fructosamine is formed by a chemical reaction of glucose with plasma protein and reflects glucose control in the previous 1-3 weeks. This assay, therefore, may show a change in control before HbA1c and often is helpful when applying intensive treatment and in short-term clinical trials.
Urine ketones are not reliable for diagnosing or monitoring diabetic ketoacidosis (DKA), although they may be useful in screening to see whether a hyperglycemic individual may have some degree of ketonemia. The plasma acetone level—specifically, the beta-hydroxybutyrate level—is a more reliable indicator of DKA, along with measurement of plasma bicarbonate or arterial pH as clinically required. (See the Medscape Reference Laboratory Medicine article Ketones.)
Screening for type 1 DM in asymptomatic low-risk individuals is not recommended. However, in patients at high risk (eg, those who have first-degree relatives with type 1 DM), it may be appropriate to perform annual screening for anti-islet antibodies before the age 10 years, along with 1 additional screening during adolescence.
Tests to Differentiate Type 1 from Type 2 Diabetes
Although the oral glucose tolerance test with insulin levels is usually considered unnecessary for diagnosing type 1 DM, the dramatic increase of type 2 DM in the young suggests that assessment of insulin secretion may become more important. The 2011 American Association of Clinical Endocrinologists (AACE) guidelines note that to help distinguish between the 2 types in children, physicians should measure insulin and C-peptide levels and immune markers (eg, glutamic acid decarboxylase [GAD] autoantibodies), as well as obtain a detailed family history.
C-peptide is formed during conversion of proinsulin to insulin. An insulin or C-peptide level below 5 µU/mL (0.6 ng/mL) suggests type 1 DM; a fasting C-peptide level greater than 1 ng/dL in a patient who has had diabetes for more than 1-2 years is suggestive of type 2 (ie, residual beta-cell function). An exception is the individual with type 2 DM who presents with a very high glucose level (eg, >300 mg/dL) and a temporarily low insulin or C-peptide level but who will recover insulin production once normal glucose is restored.
Most patients who present with undiagnosed type 1 DM have the classic symptoms of uncontrolled hyperglycemia, including polyuria, polydipsia, nocturia, fatigue, and weight loss. In these patients, a confirmatory random plasma glucose level of greater than 200 mg/dL is adequate to establish the diagnosis of DM. On occasion, a patient who is ultimately found to have type 1 DM presents with subtle symptoms because of residual insulin secretion.
Islet-cell (IA2), anti-GAD65, and anti-insulin autoantibodies can be present in early type 1 but not type 2 DM. Measurements of IA2 autoantibodies within 6 months of diagnosis can help differentiate between type 1 and type 2 DM. These titers decrease after 6 months. Anti-GAD65 antibodies can be present at diagnosis of type 1 DM and are persistently positive over time. (See also Type 2 Diabetes Mellitus.)
Testing for islet autoantibodies can substitute for expensive genetic testing in those patients suspected of having maturity-onset diabetes of the young (MODY). The prevalence of these antibodies is the same in patients with MODY as in the healthy population. A positive test for positive islet autoantibodies makes MODY highly unlikely.
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.
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].
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].
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].
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].
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].
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].
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].
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].
Busko M. Phenomenon of 'double diabetes' common among blacks. Medscape Medical News. April 25, 2013. [Full Text].
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].
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].
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].
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].
Borchers AT, Uibo R, Gershwin ME. The geoepidemiology of type 1 diabetes. Autoimmun Rev. 2010 Mar. 9(5):A355-65. [Medline].
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].
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].
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].
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].
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].
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].
Polychronakos C, Li Q. Understanding type 1 diabetes through genetics: advances and prospects. Nat Rev Genet. 2011 Oct 18. 12(11):781-92. [Medline].
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].
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].
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].
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].
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].
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].
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].
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.
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].
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.
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].
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].
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].
Tucker ME. Small-fiber neuropathy common at 40 years of type 1 diabetes. Medscape Medical News. September 18, 2013. [Full Text].
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].
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].
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].
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].
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].
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].
Wong VH, Bui BV, Vingrys AJ. Clinical and experimental links between diabetes and glaucoma. Clin Exp Optom. 2011 Jan. 94(1):4-23. [Medline].
Harris SS. Vitamin D in type 1 diabetes prevention. J Nutr. 2005 Feb. 135(2):323-5. [Medline].
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].
Julius MC, Schatz DA, Silverstein JH. The prevention of type I diabetes mellitus. Pediatr Ann. 1999 Sep. 28(9):585-8. [Medline].
Vinik AI, Mehrabyan A. Diabetic neuropathies. Med Clin North Am. 2004 Jul. 88(4):947-99, xi. [Medline].
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].
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].
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].
[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].
[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].
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].
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].
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].
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].
[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].
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.
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].
[Guideline] American Diabetes Association. Standards of Medical Care in Diabetes - 2015: Abridged for Primary Care Providers. Clinical Diabetes. 2015. 33:2:[Full Text].
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].
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].
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].
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].
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].
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].
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].
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].
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].
[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].
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.
Tucker ME. FDA OKs insulin pump with low-glucose suspend feature. Medscape Medical News. September 27, 2013. [Full Text].
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.
Tucker ME. Coming Soon: 'Artificial Pancreas' Options for Diabetes. Medscape Medical News. June 20, 2016. [Full Text].
Boggs W. Round-the-Clock Closed-Loop Glucose Control Leads to Better Outcomes. Medscape. May 13, 2016. [Full Text].
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].
Tucker M. FDA Approves Inhaled Insulin Afrezza for Diabetes. Medscape Medical News. Available at http://www.medscape.com/viewarticle/827539.. Accessed: July 14, 2014.
Afrezza (insulin inhaled) prescribing information [package insert]. Valencia CA, United States: MannKind Corporation. June, 2014. Available at [Full Text].
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.
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
Busko M. Insulin pump therapy bests injection therapy in large study. Medscape Medical News. August 19, 2013. [Full Text].
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].
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].
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].
Babiker A, Datta V. Lipoatrophy with insulin analogues in type I diabetes. Arch Dis Child. 2011 Jan. 96(1):101-2. [Medline].
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].
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].
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].
Pannu N, Wiebe N, Tonelli M. Prophylaxis strategies for contrast-induced nephropathy. JAMA. 2006 Jun 21. 295(23):2765-79. [Medline].
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].
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].
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].
Vinik AI, Ziegler D. Diabetic cardiovascular autonomic neuropathy. Circulation. 2007 Jan 23. 115(3):387-97. [Medline].
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].
Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005 Jan 12. 293(2):217-28. [Medline].
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].
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].
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].
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].
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].
Tucker ME. ACC/AHA statin guidelines, with caveats. WebMD. Available at http://www.medscape.com/viewarticle/837138. Accessed: Dec 24, 2014.
Marks JB. Perioperative management of diabetes. Am Fam Physician. 2003 Jan 1. 67(1):93-100. [Medline].
[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].
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].
[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].
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].
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].
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.
Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med. 2002 May 30. 346(22):1685-91. [Medline].
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].
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].
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].
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].
Brooks M. FDA Clears Blood Test to Help Diagnose Type 1 Diabetes. Medscape Medical News. Aug 21 2014. [Full Text].
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].
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].
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].
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.