DISTINGUISHING TYPE 1 FROM TYPE 2 DIABETES
With the explosion of diabetes worldwide, it has become increasingly difficult to distinguish type 1 from atypical presentations of type 2 diabetes. Patients with type 1 diabetes may have at presentation or develop over time an absolute requirement for insulin therapy. However, many patients with type 2 diabetes lose beta cell function over time and require insulin for glucose management. Thus, need for insulin per se does not distinguish between type 1 and type 2 diabetes. As noted above, diabetic ketoacidosis (DKA) cannot be relied upon as an absolute indicator that the patient has type 1 diabetes or that long-term insulin therapy will be required. (See “Syndromes of ketosis-prone diabetes mellitus”.)
Patients with type 1 diabetes may coincidentally have pathophysiologic elements of type 2 diabetes. In the past, poor metabolic control of type 1 diabetes prevented most of these patients from gaining weight. Intensive therapy now commonly used to manage type 1 diabetes has resulted in an increasingly similar prevalence of overweight and obesity in the type 1 diabetes population as in the nondiabetic population. Insulin resistance and other features of type 2 diabetes may be exhibited in such patients with type 1 diabetes, especially those who also have a family history of type 2 diabetes [18].
●When to perform islet autoantibody testing – Given the overlap of type 1 and type 2 diabetes and the emergence of many atypical forms of diabetes, clinicians should have a low threshold for islet autoantibody testing in adults with any form of diabetes that is not easily classifiable.
We measure autoantibodies when the diagnosis of type 1 or type 2 diabetes is uncertain by clinical presentation:
•Patients who have a subtherapeutic response to initial therapy with sulfonylureas or metformin, particularly those without overweight or obesity
•Individuals with a personal or family history of autoimmune disease
•Young adults (age <35 years)
•Adults age ≥35 years who present with unintentional weight loss or ketoacidosis at the time of diagnosis
Based upon a review of clinical features in 102 adult patients with diabetes who did not initially require insulin but who were positive for glutamic acid decarboxylase 65 (GAD65) autoantibodies, a screening tool was developed to identify adult patients with newly diagnosed diabetes who should be considered for antibody testing [19]. These features included: age of onset <50 years, acute symptoms, body mass index (BMI) <25 kg/m2, and personal or family history of autoimmune disease. The presence of two or more criteria had a 90 percent sensitivity and 71 percent specificity for identifying patients positive for anti-GAD antibodies. (See “Prediction of type 1 diabetes mellitus”, section on 'Immunologic markers'.)
●Which islet autoantibodies should be measured? – Two (ie, islet cell antibodies [ICA] and GAD65) or a panel (insulin-associated antibodies [IAA], GAD65, insulinoma-associated protein 2 [IA-2], and zinc transporter [ZnT8]) antibodies can be measured. Measuring more than one antibody will increase the likelihood of a positive value, but it is also more costly.
Insulin antibodies generally should not be measured for diagnostic purposes if the patient has received insulin therapy for ≥2 weeks because some insulins can generate anti-insulin antibody formation. Nonetheless, this phenomenon is less common with human or analog insulins, which are the predominant insulins in clinical use.
If one or more of the antibodies is present, and especially if two or more are positive, the patient should be presumed to have type 1 diabetes and should be treated promptly with insulin replacement therapy, as these patients respond poorly to diet and oral hypoglycemic drug therapy. In addition, during early stages in the development of type 1 diabetes, intensive insulin therapy prolongs beta cell function [20].
The presence of antibodies to GAD, islet cell, insulin, the tyrosine phosphatases (IA-2 and IA-2 beta), and ZnT8 in patients with presumed type 2 diabetes can identify patients who may have latent autoimmune diabetes in adults [LADA]) and are more likely to require insulin [3,7-9,21].
Given the risk of DKA, insulin should also be started in any patient (regardless of whether they are thought to have type 1 or type 2 diabetes) who is catabolic (weight loss or dehydration in the setting of hyperglycemia), or who has evidence of increased ketogenesis (ketonuria or acidosis).
source = up to date juli 2023