Clinical presentation
Type 1 diabetes can be diagnosed at any age, with a peak around 10 to 14 years.[18]Norris JM, Johnson RK, Stene LC. Type 1 diabetes-early life origins and changing epidemiology. Lancet Diabetes Endocrinol. 2020 Mar;8(3):226-38.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332108
http://www.ncbi.nlm.nih.gov/pubmed/31999944?tool=bestpractice.com
It commonly presents with polyuria, polydipsia, weight loss, and generalized weakness.[40]Usher-Smith JA, Thompson MJ, Zhu H, et al. The pathway to diagnosis of type 1 diabetes in children: a questionnaire study. BMJ Open. 2015 Mar 17;5(3):e006470.
https://bmjopen.bmj.com/content/5/3/e006470.long
http://www.ncbi.nlm.nih.gov/pubmed/25783422?tool=bestpractice.com
Other symptoms, such as blurred vision, may occur.[40]Usher-Smith JA, Thompson MJ, Zhu H, et al. The pathway to diagnosis of type 1 diabetes in children: a questionnaire study. BMJ Open. 2015 Mar 17;5(3):e006470.
https://bmjopen.bmj.com/content/5/3/e006470.long
http://www.ncbi.nlm.nih.gov/pubmed/25783422?tool=bestpractice.com
Many patients present with diabetic ketoacidosis, an acute complication of type 1 diabetes.[41]Cherubini V, Grimsmann JM, Åkesson K, et al. Temporal trends in diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes between 2006 and 2016: results from 13 countries in three continents. Diabetologia. 2020 Aug;63(8):1530-41.
https://link.springer.com/article/10.1007%2Fs00125-020-05152-1
http://www.ncbi.nlm.nih.gov/pubmed/32382815?tool=bestpractice.com
[42]Usher-Smith JA, Thompson MJ, Sharp SJ, et al. Factors associated with the presence of diabetic ketoacidosis at diagnosis of diabetes in children and young adults: a systematic review. BMJ. 2011 Jul 7;343:d4092.
https://www.doi.org/10.1136/bmj.d4092
http://www.ncbi.nlm.nih.gov/pubmed/21737470?tool=bestpractice.com
[43]Fayfman M, Pasquel FJ, Umpierrez GE. Management of hyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar state. Med Clin North Am. 2017 May;101(3):587-606.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535398
http://www.ncbi.nlm.nih.gov/pubmed/28372715?tool=bestpractice.com
These patients have symptoms of dehydration and acidosis such as nausea, vomiting, abdominal pain, tachypnea, tachycardia, lethargy, and altered mental status.[41]Cherubini V, Grimsmann JM, Åkesson K, et al. Temporal trends in diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes between 2006 and 2016: results from 13 countries in three continents. Diabetologia. 2020 Aug;63(8):1530-41.
https://link.springer.com/article/10.1007%2Fs00125-020-05152-1
http://www.ncbi.nlm.nih.gov/pubmed/32382815?tool=bestpractice.com
[42]Usher-Smith JA, Thompson MJ, Sharp SJ, et al. Factors associated with the presence of diabetic ketoacidosis at diagnosis of diabetes in children and young adults: a systematic review. BMJ. 2011 Jul 7;343:d4092.
https://www.doi.org/10.1136/bmj.d4092
http://www.ncbi.nlm.nih.gov/pubmed/21737470?tool=bestpractice.com
[43]Fayfman M, Pasquel FJ, Umpierrez GE. Management of hyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar state. Med Clin North Am. 2017 May;101(3):587-606.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535398
http://www.ncbi.nlm.nih.gov/pubmed/28372715?tool=bestpractice.com
When the initial presentation of type 1 diabetes occurs in adulthood, it is known as latent autoimmune diabetes in adults (LADA).[44]O'Neal KS, Johnson JL, Panak RL. Recognizing and appropriately treating latent autoimmune diabetes in adults. Diabetes Spectr. 2016 Nov;29(4):249-52.
http://spectrum.diabetesjournals.org/content/29/4/249
http://www.ncbi.nlm.nih.gov/pubmed/27899877?tool=bestpractice.com
It is important to distinguish LADA from type 2 diabetes, as treatment with insulin is required.[6]Pieralice S, Pozzilli P. Latent autoimmune diabetes in adults: a review on clinical implications and management. Diabetes Metab J. 2018 Dec;42(6):451-64.
https://e-dmj.org/journal/view.php?doi=10.4093/dmj.2018.0190
http://www.ncbi.nlm.nih.gov/pubmed/30565440?tool=bestpractice.com
Rarely, a patient is diagnosed with type 1 diabetes during routine blood tests. The condition is diagnosed long before its chronic complications have developed.
Diagnosis
Diagnosis of diabetes can be made on the basis of any of the following:[1]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care. 2024 Jan;47(1):S1-321.
https://diabetesjournals.org/care/issue/47/Supplement_1
Glycosylated hemoglobin (HbA1c) ≥6.5% (≥48 mmol/mol); OR
Fasting plasma glucose ≥126 mg/dL (≥7.0 mmol/L); OR
Plasma glucose ≥200 mg/dL (≥11.1 mmol/L) 2 hours after 75 g oral glucose; OR
Random plasma glucose of ≥200 mg/dL (≥11.1 mmol/L) in the presence of symptoms of hyperglycemia or hyperglycemic crisis.
In an asymptomatic patient, results should be confirmed by ensuring that two tests (e.g., HbA1c and fasting glucose) are abnormal at the same time, or by repeating the abnormal test (or performing an additional test) at a different time point.[1]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care. 2024 Jan;47(1):S1-321.
https://diabetesjournals.org/care/issue/47/Supplement_1
In symptomatic patients, a random plasma glucose value of ≥200 mg/dL (≥11.1 mmol/L) is sufficient to diagnose diabetes.[1]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care. 2024 Jan;47(1):S1-321.
https://diabetesjournals.org/care/issue/47/Supplement_1
Diabetes is the overall diagnostic term applied to people satisfying these criteria, with type 1 and type 2 being further classified based on clinical and/or laboratory criteria.[45]Gale EA. The discovery of type 1 diabetes. Diabetes. 2001 Feb;50(2):217-26.
http://www.ncbi.nlm.nih.gov/pubmed/11272129?tool=bestpractice.com
The diagnosis of type 1 diabetes is often obvious from the clinical presentation, but can be confirmed through additional testing. Low C-peptide levels and presence of one or more autoimmune markers are consistent with a diagnosis of type 1 diabetes.[46]Chiang JL, Maahs DM, Garvey KC, et al. Type 1 diabetes in children and adolescents: a position statement by the American Diabetes Association. Diabetes Care. 2018 Aug 9;41(9):2026-44.
http://care.diabetesjournals.org/content/41/9/2026.long
http://www.ncbi.nlm.nih.gov/pubmed/30093549?tool=bestpractice.com
Autoimmune markers include autoantibodies to glutamic acid decarboxylase (GAD), insulin, islet cells, islet antigens (IA2 and IA2-beta), and the zinc transporter ZnT8.
Elevated plasma or urine ketones in the presence of hyperglycemia suggests type 1 diabetes, but can occasionally be seen at presentation in a patient with type 2 diabetes. As an example, when a teenager with obesity and a positive family history of type 2 diabetes is found to have high plasma glucose levels on routine blood tests, the diagnosis of type 1 versus type 2 diabetes may not be clear. If C-peptide levels are very low or undetectable relative to the plasma glucose, and anti-GAD antibodies are positive in such a patient, a diagnosis of type 1 diabetes can be made.
It is important that people with diabetes are classified appropriately to ensure provision of optimal and individualized management.[1]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care. 2024 Jan;47(1):S1-321.
https://diabetesjournals.org/care/issue/47/Supplement_1
When type 1 diabetes is suspected, it is important to consider the possibility of monogenic diabetes as a differential, since this accounts for up to 4% of pediatric diabetes, and insulin treatment may be inappropriate in these cases.[1]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care. 2024 Jan;47(1):S1-321.
https://diabetesjournals.org/care/issue/47/Supplement_1
[46]Chiang JL, Maahs DM, Garvey KC, et al. Type 1 diabetes in children and adolescents: a position statement by the American Diabetes Association. Diabetes Care. 2018 Aug 9;41(9):2026-44.
http://care.diabetesjournals.org/content/41/9/2026.long
http://www.ncbi.nlm.nih.gov/pubmed/30093549?tool=bestpractice.com
The two main forms of monogenic diabetes are maturity-onset diabetes of the young (MODY) and neonatal diabetes.[1]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care. 2024 Jan;47(1):S1-321.
https://diabetesjournals.org/care/issue/47/Supplement_1
Suspicion for monogenic diabetes should be higher in autoantibody-negative pediatric and younger adult patients (<35 years) who do not display the typical signs of type 1 or type 2 diabetes, and who have a family history of diabetes in successive generations.[1]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care. 2024 Jan;47(1):S1-321.
https://diabetesjournals.org/care/issue/47/Supplement_1
The American Diabetes Association (ADA) recommends genetic testing for MODY in these patients.[1]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care. 2024 Jan;47(1):S1-321.
https://diabetesjournals.org/care/issue/47/Supplement_1
They also recommend that all individuals (regardless of current age) that have been diagnosed with diabetes in the first 6 months of life should have genetic testing for neonatal diabetes.[1]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care. 2024 Jan;47(1):S1-321.
https://diabetesjournals.org/care/issue/47/Supplement_1
HbA1c <7.5% (<58 mmol/mol) at diagnosis is another feature suggestive of monogenic diabetes, and the person may have additional features of a specific monogenic cause (e.g., renal cysts, partial lipodystrophy).[1]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care. 2024 Jan;47(1):S1-321.
https://diabetesjournals.org/care/issue/47/Supplement_1
Genetic testing is definitive and can be used to counsel the patient and family members.[1]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care. 2024 Jan;47(1):S1-321.
https://diabetesjournals.org/care/issue/47/Supplement_1
C-peptide testing can also be used when there is uncertainty about the diagnosis to help identify people who should have genetic testing.[1]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care. 2024 Jan;47(1):S1-321.
https://diabetesjournals.org/care/issue/47/Supplement_1