eMedicine Specialties > Endocrinology > Diabetes Mellitus

Diabetes Mellitus, Type 1: Differential Diagnoses & Workup

Author: Aneela Naureen Hussain, MD, FAAFM, Assistant Professor, Department of Family Medicine, State University of New York Downstate Medical Center; Consulting Staff, Department of Family Medicine, University Hospital of Brooklyn
Coauthor(s): Miriam T Vincent, MD, PhD, Professor and Chair, Department of Family Practice, State University of New York Downstate Medical Center
Contributor Information and Disclosures

Updated: Jul 2, 2009

Differential Diagnoses

Diabetes Mellitus, Type 2
Diabetic Ketoacidosis
Diabetic Nephropathy
Diabetic Ulcers
Insulin Resistance
Lead Nephropathy

Other Problems to Be Considered

Maturity-onset diabetes of youth (MODY), a rare autosomal dominant condition found primarily in whites
Secondary hyperglycemia
Disorders of target tissues (liver, muscles, adipose tissue)
Endocrine disorders - Endocrine tumor causing increased production of growth hormone, glucocorticoids, catecholamines, glucagon, and somatostatin; Addison disease; Graves disease; Hashimoto thyroiditis; acanthosis nigricans (genetic disorders with insulin resistance)

Drugs - Thiazide diuretics, phenytoin, glucocorticoids
Chronic pancreatitis
Cystic fibrosis
Prader-Willi syndrome - Mental retardation, muscular hypotonia, obesity, short stature, and hypogonadism associated with diabetes mellitus (DM)

Nondiabetic glycosuria

Renal glycosuria - Glucose appears in urine despite normal glucose concentration in blood. This glucose may be due to an autosomal genetic disorder or dysfunction of the proximal renal tubule (eg, Fanconi syndrome, chronic renal failure), or it may be due to increased glucose load on tubules by the elevated glucose filtration rate during pregnancy.

Peripheral neuropathy due to alcohol and vitamin B-12 deficiency

Workup

Laboratory Studies

  • Blood glucose: In asymptomatic patients, physicians diagnose diabetes mellitus (DM) using the American Diabetes Association (ADA) recommendation of 2 different fasting plasma glucose levels of greater than 125 mg/dL (ie, >6.99 mmol/L). In symptomatic patients, a random glucose of 200 mg/dL suggests diabetes. All finger stick capillary glucose levels must be confirmed in serum or plasma to make the diagnosis.
  • Serum electrolytes
  • Urinalysis for glucose, ketones, and protein: Urine ketones are not reliable for diagnosing or monitoring DKA. Rather, the plasma acetone, and, specifically, the beta-hydroxybutyrate level, is a reliable indicator of DKA.
  • White blood cell count and blood and urine cultures to rule out infection
  • Glycosylated hemoglobin (Hb) or Hb A1c
    • Hb A1c is the stable product of nonenzymatic irreversible glycosylation of the beta chain of Hb by plasma glucose and is formed at rates that increase with increasing plasma glucose levels.
    • Most physicians periodically determine Hb A1c to estimate plasma glucose control during the preceding 1-3 months.
    • Glycated hemoglobin predicts the progression of diabetic microvascular complications. The reference range for nondiabetic people is 6% in most laboratories.
    • Although elevated Hb A1c often indicates existing diabetes, the determination of Hb A1c levels has not been considered a specific diagnostic test for diabetes. 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 Hb A1c assay for the diagnosis of type 1 and type 2 DM.1 In the case of type 1 DM, however, the committee recommended using the test only when the condition is suspected but the classical symptoms of type 1 DM—polyuria, polydipsia, polyphagia, a random glucose level of 200 mg/dL, and unexplained weight loss—are absent.
    • The committee cited the following advantages of Hb A1c testing over glucose measurement:
      • Captures long-term glucose exposure
      • Has less biologic variability
      • Does not require fasting or timed samples
      • Is currently used to guide management decisions
    • The committee’s recommendation for a diagnosis of DM is an Hb A1c level of 6.5% or higher, with confirmation from repeat testing (unless clinical symptoms are present and the glucose level is >200 mg/dL). Glucose measurement should remain the choice for diagnosing pregnant women or if Hb A1c assay is unavailable.
    • 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 Hb A1c and often is helpful when applying intensive treatment and in short-term clinical trials.
  • Oral glucose tolerance test with insulin levels: Although this test is usually considered unnecessary to make the diagnosis in type 1 DM, with the dramatic increase of type 2 diabetes in the young population, assessment of insulin secretion may become more important.
  • To determine whether the individual has type 1 rather than type 2 DM, an insulin and/or C-peptide level below 5 µU/mL, or 0.6 ng/mL, suggests type 1. C-peptide is formed during conversion of proinsulin to insulin. A high positive titre of glutamic acid decarboxylase antibodies also suggests type 1 DM. An exception is the individual with type 2 DM who presents with a very high glucose, eg, above 300 mg/dL, who temporarily has a low insulin and/or C-peptide level but who will recover insulin production once normal glucose is restored.
  • Islet cell antibodies
  • Thyroxine (T4) and thyroid antibodies

Other Tests

  • Intravenous glucose test for possible early detection of subclinical diabetes
  • HLA typing may be considered.

More on Diabetes Mellitus, Type 1

Overview: Diabetes Mellitus, Type 1
Differential Diagnoses & Workup: Diabetes Mellitus, Type 1
Treatment & Medication: Diabetes Mellitus, Type 1
Follow-up: Diabetes Mellitus, Type 1
References
[ CLOSE WINDOW ]

References

  1. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. Jun 5 2009;[Medline]. [Full Text].

  2. US Food and Drug Administration. Early Communication About Safety of Lantus (Insulin Glargine). July 1, 2009. [Full Text].

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

  4. American Diabetes Association. Clinical practice recommendations 1999. Diabetes Care. Jan 1999;22 Suppl 1:S1-114. [Medline].

  5. American Diabetes Association. Clinical Practice Recommendations 2001. Diabetes Care. Jan 2001;24 Suppl 1:S1-133. [Medline].

  6. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 1998;21 Suppl 1:S54.

  7. American Diabetes Association. Total Prevalence of Diabetes & Pre-diabetes. Available at http://www.diabetes.org/diabetes-statistics/prevalence.jsp.

  8. Bin-Abbas BS, Sakati NA, Al-Ashwal AA. Glycemic control and treatment satisfaction in Saudi diabetic children on insulin pump therapy. Ann Saudi Med. Sep-Oct 2006;26(5):405. [Medline].

  9. Bingley PJ. ENDIT: [Concurrent session: Prevention of type 1 diabetes]. San Diego, Calif: 59th Annual Scientific Sessions of American Diabetes Association; 1999.

  10. Carroll MF, Schade DS. The dawn phenomenon revisited: implications for diabetes therapy. Endocr Pract. Jan-Feb 2005;11(1):55-64. [Medline].

  11. CDC. National Diabetes Fact Sheet. United States. 2003. Available at http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2003.pdf.

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

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

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

  15. Kavey RE, Allada V, Daniels SR, Hayman LL, McCrindle BW, Newburger JW, et al. Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation. Dec 12 2006;114(24):2710-38. [Medline].

  16. Kilpatrick ES, Rigby AS, Atkin SL. Insulin resistance, the metabolic syndrome, and complication risk in type 1 diabetes: "double diabetes" in the Diabetes Control and Complications Trial. Diabetes Care. Mar 2007;30(3):707-12. [Medline].

  17. Leiter LA. Should you put all diabetic patients on statins?. J Fam Pract. Apr 2007;56(4):294-300. [Medline].

  18. Luong K, Nguyen LT, Nguyen DN. The role of vitamin D in protecting type 1 diabetes mellitus. Diabetes Metab Res Rev. Jul-Aug 2005;21(4):338-46. [Medline].

  19. Marre M. Nephropathy in type 1 diabetes. Semin Vasc Med. Feb 2002;2(1):97-107. [Medline].

  20. Mathieu C, Badenhoop K. Vitamin D and type 1 diabetes mellitus: state of the art. Trends Endocrinol Metab. Aug 2005;16(6):261-6. [Medline].

  21. Mathieu C, Gysemans C, Giulietti A, Bouillon R. Vitamin D and diabetes. Diabetologia. Jul 2005;48(7):1247-57. [Medline].

  22. Nelson RG. Advances and emerging opportunities in type 1 diabetes: a strategic plan. Nephrol News Issues. Feb 2007;21(3):28, 31. [Medline].

  23. Orchard TJ, Costacou T, Kretowski A, Nesto RW. Type 1 diabetes and coronary artery disease. Diabetes Care. Nov 2006;29(11):2528-38. [Medline].

  24. Rewers MJ. Future prevention trials [Concurrent session: Prevention of type 1 diabetes]. San Diego, Calif: 59th Annual Scientific Sessions of American Diabetes Association; 1999.

  25. Romero P, Salvat M, Fernández J, Baget M, Martinez I. Renal and retinal microangiopathy after 15 years of follow-up study in a sample of Type 1 diabetes mellitus patients. J Diabetes Complications. Mar-Apr 2007;21(2):93-100. [Medline].

  26. Schatz DA. Diabetes prevention trial - type 1 (DPT-1): rationale and update [Concurrent session: Prevention of type 1 diabetes]. San Diego, Calif: 59th Annual Scientific Sessions of American Diabetes Association; 1999.

  27. Service FJ, O'Brien PC. The effect of glucose variability on the risk of microvascular complications in type 1 diabetes. Diabetes Care. Jan 2007;30(1):186; author reply 187-8. [Medline].

  28. Sibal L, Law HN, Gebbie J, Dashora UK, Agarwal SC, Home P. Predicting the development of macrovascular disease in people with type 1 diabetes: A 9-year follow-up study. Ann N Y Acad Sci. Nov 2006;1084:191-207. [Medline].

  29. Skyler JS. Cellular therapy for type 1 diabetes: has the time come?. JAMA. Apr 11 2007;297(14):1599-600. [Medline].

  30. Skyler JS. Prediction and prevention of type 1 diabetes: progress, problems, and prospects. Clin Pharmacol Ther. May 2007;81(5):768-71. [Medline].

  31. Sosenko JM, Palmer JP, Greenbaum CJ, Mahon J, Cowie C, Krischer JP, et al. Increasing the accuracy of oral glucose tolerance testing and extending its application to individuals with normal glucose tolerance for the prediction of type 1 diabetes: the Diabetes Prevention Trial-Type 1. Diabetes Care. Jan 2007;30(1):38-42. [Medline].

  32. Taylor R, Davison JM. Type 1 diabetes and pregnancy. BMJ. Apr 7 2007;334(7596):742-5. [Medline].

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

  34. Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, et al. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. Apr 11 2007;297(14):1568-76. [Medline].

  35. Zdravkovic V, Hamilton JK, Daneman D, Cummings EA. Pioglitazone as adjunctive therapy in adolescents with type 1 diabetes. J Pediatr. Dec 2006;149(6):845-849. [Medline].

  36. Äkerblom HA. Prevention trials in Finland [Concurrent session: Prevention of type 1 diabetes]. San Diego, Calif: 59th Annual Scientific Sessions of American Diabetes Association; 1999.

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

type 1 DM, type 1 diabetes, type 2 diabetes mellitus, type II diabetes mellitus, autoimmune diabetes mellitus, juvenile-onset diabetes, ketosis-prone diabetes, insulin-dependent diabetes mellitus, IDDM, brittle diabetes mellitus, diabetic ketoacidosis, DKA, maturity-onset diabetes of the young, MODY

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Aneela Naureen Hussain, MD, FAAFM, Assistant Professor, Department of Family Medicine, State University of New York Downstate Medical Center; Consulting Staff, Department of Family Medicine, University Hospital of Brooklyn
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.

Coauthor(s)

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: Merck Honoraria Speaking and teaching; The American Cancer Society Honoraria Speaking and teaching

Medical Editor

Frederick H Ziel, MD, Associate Professor of Medicine, David Geffen School of Medicine at UCLA; 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, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

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.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor 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, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.