Type 1 Diabetes Mellitus Differential Diagnoses

Updated: Jul 03, 2023
  • Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: George T Griffing, MD  more...
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Diagnostic Considerations

The following conditions and factors should be taken into account in considering a diagnosis of type 1 diabetes mellitus (DM):

  • Type 2 DM

  • Monogenic DM, [100] previously known as 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, and glucocorticoids

  • Chronic pancreatitis

  • Cystic fibrosis

  • Prader-Willi syndrome - Mental retardation, muscular hypotonia, obesity, short stature, and hypogonadism associated with DM

  • Nondiabetic glycosuria

  • Renal glycosuria - Glucose appears in urine despite normal glucose concentration in blood; this may occur because of an autosomal genetic disorder or dysfunction of the proximal renal tubule (eg, Fanconi syndrome or chronic renal failure), or it may occur during pregnancy as a consequence of the increased glucose load placed on tubules by the elevated glucose filtration rate

  • Peripheral neuropathy from alcohol abuse or vitamin B-12 deficiency

Type 1 versus type 2 diabetes

Determining whether a patient has type 1 or type 2 DM is an important diagnostic and therapeutic concern because patients with type 1 DM depend on continuous exogenous insulin for survival. A patient whose diabetes is controlled with diet or an oral antidiabetic agent clearly has type 2 DM. A lean patient who has had diabetes since childhood, who has always been dependent on insulin, or who has a history of diabetic ketoacidosis (DKA) almost certainly has type 1 DM.

Distinguishing the type of diabetes can be difficult in (1) patients who are treated with insulin and who are younger but clinically appear to have type 2 DM and (2) older patients with late-onset diabetes who nonetheless take insulin and seem to share characteristics of patients with type 1 DM. (This latter group is now said to have latent autoimmune diabetes of the adult [LADA].) It should be noted that for many patients, it will not be possible to fully distinguish type 1 DM from type 2.

When in doubt, treat the patient with insulin and close monitoring of glucose levels. It is not unusual for adolescents or young adults, particularly Hispanic or African-American patients, to present with DKA and subsequently be found to have type 2 DM.

Monogenic diabetes

Although monogenic diabetes syndromes are not very common, representing fewer than 5% of pediatric diabetes cases, it is important to avoid misdiagnosis of monogenic DM as type 1 or type 2 DM. The American Diabetes Association (ADA) advises considering a diagnosis of monogenic diabetes when the following criteria are present [5] :

  • Diabetes is diagnosed within 6 months of birth

  • A strong family history of diabetes is present, without type 2 features (eg, obesity or higher-risk ethnicity)

  • Mild fasting hyperglycemia is observed, especially in young, nonobese children

  • Diabetes is present, but islet cell autoantibodies, obesity, and insulin resistance are absent

If a form of monogenic diabetes is suspected, it is increasingly feasible to obtain a true genetic diagnosis through commercially available genetic testing. For further information about the diagnosis and management of monogenic diabetes, the ADA suggests consulting the 2009 clinical practice consensus guidelines of the International Society for Pediatric and Adolescent Diabetes (ISPAD) at the ISPAD website. [5, 101]

Differential Diagnoses