Understanding Diabetes: Type 1 vs Type 2 Diagnosis and Treatment

Diagnosing Diabetes

The American Diabetes Association (ADA) and World Health Organization (WHO) have established clear diagnostic criteria for diabetes. A definitive diagnosis requires meeting one of these threshold values:

• Haemoglobin A1C ≥48 mmol/mol
• Fasting plasma glucose ≥7.0 mmol/L (following at least 8 hours without caloric intake)
• 2-hour plasma glucose ≥11.1 mmol/L during an oral glucose tolerance test (OGTT)
• Random plasma glucose ≥11.1 mmol/L in patients exhibiting classic hyperglycaemic symptoms

Clinicians should consider testing for diabetes when patients present with classic symptoms including polyuria (frequent urination), polydipsia (increased thirst), unexplained weight loss, recurrent infections, delayed wound healing, blurred vision, or fatigue.

For asymptomatic patients, diagnosis should never rely on a single abnormal test result. Confirmation requires a second test, either of the same type or a different one, showing values within the diabetic range. When discordant results occur between tests, repeating the abnormal test is recommended, with careful consideration of factors that might affect glucose or A1C measurements.

Diabetes. But, what type?

The distinction between diabetes types is crucial for implementing appropriate treatment strategies. Type 1 diabetes generally requires insulin replacement from diagnosis, while type 2 may initially respond to non-insulin therapies. Figure 1 shows a simple breakdown of the classic clinical features of each type.

As is true of the old adage, ‘’patients don’t always read the textbooks’’ and as such we are often left scratching our head as to the type of diabetes a patient may have. When clinical features don’t clearly point to a specific diabetes type, biomarker testing provides valuable insights:

Islet autoantibody testing is most informative when conducted within three years of diagnosis. Clinicians should test for multiple antibodies including GAD, IA2, and ZnT8, as the presence of multiple positive antibodies strongly supports a type 1 diagnosis. It’s important to note that higher false positive rates occur in older adults, which often necessitates confirmation with C-peptide testing for accurate classification.

C-peptide testing becomes particularly useful when evaluating patients with long-duration diabetes. Very low C-peptide levels (<0.24 ng/mL) strongly indicate type 1 diabetes, while intermediate values (0.6–1.8 ng/mL) require careful clinical correlation as they could represent type 1 diabetes, MODY, or insulin-treated type 2 diabetes. Measurements should be paired with a serum glucose level to aid interpretation.

When interpreting biomarker results, clinicians should consider the complete clinical picture. A patient with negative autoantibodies but persistently low C-peptide levels might still have type 1 diabetes, particularly if the testing was performed many years after diagnosis when autoantibodies may have disappeared. Conversely, a patient with weakly positive single autoantibody but robust C-peptide production likely has type 2 diabetes with a false positive antibody result. This integrated approach to biomarker interpretation helps resolve diagnostic dilemmas in clinically ambiguous presentations.

Generally speaking, if in doubt regarding the underlying cause of diabetes it is safest to err on the side of caution and treat in a way that most reduces potential harm i.e. diabetic ketoacidosis (DKA). In practice this means oftentimes starting insulin on a patient newly diagnosed with diabetes where uncertainty exists between a diagnosis of type 1 of type 2. This is sometimes done while awaiting antibody results and continued until a short interval clinic appointment following hospital discharge. If after several weeks, antibodies have returned negative and the clinical picture more resembles one of type 2 diabetes the insulin can be carefully tapered off or stopped outright and oral medications instituted.

Challenging Clinical Presentations of Diabetes

Type 1 diabetes in older adults presents unique diagnostic challenges. Despite classic presentations with DKA, type 2 diabetes remains significantly more common in older age groups. Negative autoantibody testing in older adults makes type 1 diabetes much less likely, and routine autoantibody screening isn’t necessary if typical type 1 features are absent. For cases with uncertain classification, C-peptide measurement provides valuable confirmation, helping to distinguish late-onset type 1 from insulin-requiring type 2 diabetes, thus guiding appropriate therapeutic approaches.

Indeed, early insulin requirement serves as an important predictive factor for misdiagnosed type 1 diabetes. Patients initially classified as having type 2 diabetes who require insulin therapy within three years of diagnosis likely have slowly progressive type 1 diabetes. These patients should undergo comprehensive biomarker testing, including autoantibody and C-peptide assessment, to confirm the correct diagnosis. Early recognition of misclassified type 1 diabetes helps prevent dangerous gaps in insulin therapy and inappropriate treatment with agents that may have limited efficacy.

Pancreatic cancer should be considered in the differential diagnosis of new-onset diabetes, particularly in specific high-risk scenarios. Clinicians should maintain heightened vigilance when diabetes presents in patients over 50 years old without typical metabolic syndrome features, especially when accompanied by unexplained weight loss, abdominal pain, or jaundice. The relationship works both ways – new-onset diabetes can sometimes be the first detectable sign of pancreatic cancer, presenting months before the cancer becomes clinically apparent through other symptoms. Early imaging studies should be considered for patients with suspicious presentations, particularly when multiple risk factors are present.

Maturity-Onset Diabetes of the Young (MODY) represents several monogenic forms of diabetes that should be considered when patients present with atypical features. These typically include relatively mild hyperglycaemia (A1C <58 mmol/mol at diagnosis), strong multigenerational family history of diabetes, absence of typical autoimmune or insulin resistance markers, and onset at a young age (typically before 25-30 years). Patients with MODY may also display distinctive clinical features suggesting specific genetic variants, such as renal cysts, lipodystrophy, or characteristic patterns of glycemic control such as persistently elevated fasting glucose with normal post-prandial values. Genetic testing provides definitive diagnosis and guides targeted treatment approaches for these patients. Awareness is critical as a MODY diagnosis can dramatically change treatment regimens and reduce burden on patients.

Latent Autoimmune Diabetes in Adults (LADA) presents a particular diagnostic challenge as it initially resembles type 2 diabetes but has an autoimmune pathophysiology similar to type 1. These patients typically appear to have type 2 diabetes but experience a more rapid progression to insulin dependence. GAD autoantibody testing aids identification, and early recognition allows for appropriate treatment planning that accounts for the progressive β -cell failure these patients will experience. Recognizing LADA helps clinicians anticipate the eventual need for insulin therapy rather than persisting with combination oral agents that may prove insufficient.

Modern Diabetes Management: A Practical Guide for Hospital Clinicians

Effective diabetes management requires personalization based on the patient’s age, comorbidities, preferences, and social circumstances. While HbA1c targets of ≤53 mmol/mol suit most adults, consider lower targets for selected patients who can achieve them safely, and more relaxed goals (58-69 mmol/mol) for frail elderly patients.

Type 2 Diabetes Management

Most recent international joint consensus guidelines from the ADA and European Association for the Study of Diabetes (EASD) now emphasise the consideration of cardiorenal protection and weight management alongside glycemic control when devising a medication regimen in type 2 Diabetes.

• Metformin: Remains the first-line pharmacological therapy for most patients with type 2 Diabetes due to its proven efficacy, safety profile, low cost, and extensive clinical experience. Metformin has demonstrated modest cardiovascular benefits, is weight neutral or may promote slight weight loss, and has a low risk of hypoglycaemia. Contraindications include severe renal impairment (eGFR <30 mL/min/1.73m2), and dose adjustment is recommended for moderate renal impairment.
• SGLT2 inhibitors: Consider for patients with established cardiovascular disease (CVD), heart failure, or chronic kidney disease regardless of HbA1c. These reduce heart failure hospitalizations and slow CKD progression, particularly in patients with albuminuria.
• GLP-1 receptor agonists: Offer significant cardiovascular benefits for patients with atherosclerotic disease while providing excellent glycemic control and weight reduction. Tirzepatide (dual GIP/GLP-1 agonist) shows superior efficacy for both glucose management and weight loss compared to earlier GLP-1 RAs. It is now available in Ireland though it’s not yet covered by the long-term illness scheme.
• DPP-4 inhibitors: Provide modest glycemic improvements with minimal hypoglycaemia risk and weight neutrality, making them suitable for elderly patients.
• Traditional agents: Sulfonylureas and insulin remain effective for glucose control but carry increased hypoglycaemia risk and weight gain concerns.

Weight management is crucial—5-10% weight loss improves multiple metabolic parameters, while ≥15% loss can induce diabetes remission in some patients. The availability of GLP-1 RAs have revolutionized pharmacological weight management though recent supply shortages have truncated some patients’ courses and stopped others from accessing the most potent agents. For patients with BMI ≥35 kg/m2 and suboptimal control despite medication, metabolic surgery should be considered though access to this via both the public and private system in Ireland remains difficult and waiting lists are long.

Despite pharmaceutical advances, lifestyle modifications remain fundamental. Recommend individualized nutrition therapy (Mediterranean, plant-based, or moderate low-carbohydrate approaches) and physical activity (≥150 minutes weekly of moderate-intensity activity, resistance training, and reduced sedentary time).

Type 1 Diabetes Management

Person-centred care is essential for type 1 diabetes. Diabetes self-management education and support (DSMES) remains the cornerstone intervention at diagnosis and throughout the patient’s life. The DAFNE (Dose Adjustment For Normal Eating) programme, ideally implemented within 6-12 months of diagnosis, equips patients with carbohydrate counting skills and insulin adjustment strategies.

Continuous glucose monitors (CGMs) represent the preferred monitoring approach, focusing on Time in Range (TIR). Recommend patients aim for >70% of time within 3.9–10.0 mmol/L, while minimizing time below 3.9 mmol/L (<4%, ideally <1% below 3.0 mmol/L).

Insulin therapy options include:

• Multiple daily injections (MDI) with basal-bolus regimens (standard approach)

Continuous subcutaneous insulin infusion (insulin pump therapy)

• Hybrid closed-loop systems (insulin pumps linked to CGM with a software algorithm controlling insulin delivery), which improve outcomes and reduce hypoglycaemia
• Connected insulin pens as intermediate technology, providing dose tracking and decision support

Comprehensive Care Considerations for All Diabetes Types

Beyond glycemic control, address cardiovascular and kidney risk:

• Blood pressure targets: <140/90 mmHg generally, <130/80 mmHg in high-risk patients
• Lipid management: statin therapy for patients >40 years or with additional CVD risk factors. Risk level can be assessed through use of the American College of Cardiology ASCVD risk calculator (Risk Estimator Plus).
• Annual kidney function screening: albuminuria and eGFR
• Regular retinal screening: The National Diabetic Retinal Screening Programme in Ireland facilitates free screening and onward referral to ophthalmology if required.
• Comprehensive foot care: Annual foot examinations to assess skin integrity, vascular status, and neuropathy using monofilament testing and vibration sensation.

The psychological burden of diabetes requires regular screening for diabetes distress, depression, anxiety, and eating disorders. Pay particular attention during care transitions to prevent treatment gaps. Optimal diabetes management requires a multidisciplinary team including endocrinologists, diabetes specialist nurses, dietitians, and psychologists to address the complex biological, technological, and psychosocial aspects of diabetes care.

Key Takeaways for Hospital-Based Clinicians

• Individualise treatment plans considering the whole person, not just their HbA1c
• For type 2 diabetes, select medications based on cardiorenal benefits and weight impacts
• For type 1 diabetes, prioritise education, CGM, and appropriate insulin delivery methods
• Address cardiovascular and kidney risk factors in all patients
• Screen regularly for psychological complications
• Collaborate with a multidisciplinary team for comprehensive care

Guidance taken from:

1. Department of Health (2024), V2. NCEC National Clinical Guideline No. 17 Adult type 1 diabetes mellitus. Available at: http://health.gov.ie/national-patient-safety-office/ncec/
2. Management of Hyperglycaemia in type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 1 November 2022; 45 (11): 2753–2786. https://doi.org/10.2337/dci22-0034
3. The Management of type 1 Diabetes in Adults. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 1 November 2021; 44 (11): 2589–2625. https://doi.org/10.2337/dci21-0043

Written by Professor Derek O’Keeffe, Consultant Physician/ Professor of Medical Device Technology, University Hospital Galway, Ireland/Digital Health Principal Investigator, CURAM Research Ireland Centre for Medical Devices, Ireland, National Clinical Lead Diabetes, HSE.

Dr Lyle McVicker, University Hospital Galway, Endocrinology SPR, Research Physician, University Hospital Galway – As endocrinologists, we frequently encounter diagnostic challenges when differentiating between diabetes types. While both Type 1 and Type 2 diabetes share hyperglycaemia as their hallmark, their underlying pathophysiology, management approaches, and progression significantly differ. This article aims to provide hospital practitioners with practical knowledge on diagnosing diabetes, distinguishing between its main types and effectively managing them.

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