Diabetes, major depressive disorder (MDD), and generalised anxiety disorder (GAD) frequently co-exist, and their interaction can significantly affect HbA1c — the key measure of long-term blood glucose control. When depression or anxiety accompanies diabetes, self-management often suffers and hormonal stress responses can directly raise blood sugar levels, creating a challenging cycle that is difficult to break. This article explores how MDD and GAD influence glycaemic outcomes, what the evidence says about HbA1c in people with comorbid mental health conditions, and how NICE-recommended treatments and NHS services can help address both conditions effectively.

How Depression and Anxiety Affect Blood Sugar Control in Diabetes

Depression and anxiety impair blood sugar control through both behavioural lapses in self-care and physiological mechanisms, including elevated cortisol and sympathetic nervous system activation, which reduce insulin sensitivity and raise blood glucose.

Living with diabetes is a demanding condition that requires consistent self-management, and the psychological burden it places on individuals is well recognised. When mental health conditions such as major depressive disorder (MDD) or generalised anxiety disorder (GAD) are present alongside diabetes, the ability to maintain stable blood sugar levels can be significantly compromised. Understanding how these conditions interact is an important step towards better overall health.

Depression and anxiety affect blood sugar control through both behavioural and physiological pathways. From a behavioural perspective, individuals experiencing low mood or persistent worry may find it harder to:

• Adhere to prescribed medication regimens

• Follow dietary recommendations

• Engage in regular physical activity

• Attend routine diabetes monitoring appointments

These lapses in self-care can directly contribute to elevated blood glucose levels over time.

Physiologically, MDD in particular — and to a lesser extent GAD — is associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to elevated cortisol levels. Cortisol is a stress hormone that promotes gluconeogenesis in the liver and reduces insulin sensitivity in peripheral tissues, effectively raising blood glucose. Activation of the sympathetic nervous system during anxiety states also releases adrenaline and noradrenaline, which can further antagonise insulin action. These hormonal changes are plausible contributors to poorer glycaemic control, though the precise mechanisms remain an area of ongoing research.

It is important to note that the relationship between mental health and blood glucose is bidirectional and complex. Poor glycaemic control may itself contribute to low mood or anxiety through neurobiological and quality-of-life mechanisms, and factors such as illness severity, treatment burden, and social circumstances can confound the association. The evidence linking depression to glycaemic outcomes is more consistent than that for GAD, where findings across studies are more heterogeneous. Recognising this complexity is essential for clinicians and patients alike, and is reflected in guidance from NICE (NG28, NG222, CG113) and NHS resources on diabetes and mental wellbeing.

Understanding HbA1c and Its Role in Monitoring Diabetes

HbA1c measures average blood glucose over 2–3 months; in the UK, 48 mmol/mol or above confirms type 2 diabetes, and NICE NG28 recommends monitoring every 3–6 months when targets are unmet.

HbA1c — glycated haemoglobin — is the cornerstone laboratory measure used to assess long-term blood glucose control in people with diabetes. It reflects the average blood glucose concentration over the preceding two to three months, corresponding to the lifespan of red blood cells. Unlike a single fasting glucose reading, HbA1c provides a broader picture of glycaemic trends, making it an invaluable tool for both diagnosis and ongoing management.

In the UK, HbA1c is expressed in millimoles per mole (mmol/mol) following adoption of the IFCC standardisation. Key reference values include:

• Below 42 mmol/mol: Generally considered within the non-diabetic range

• 42–47 mmol/mol: Non-diabetic hyperglycaemia (sometimes referred to as 'prediabetes'); indicates increased risk and warrants monitoring and lifestyle advice

• 48 mmol/mol or above: The diagnostic threshold for type 2 diabetes (when confirmed on repeat testing in the absence of symptoms)

• Target for most adults with type 2 diabetes: 48–53 mmol/mol, as per NICE guideline NG28

• Individualised targets: May be set higher (e.g., 58–64 mmol/mol) for those at risk of hypoglycaemia, with complex needs, or limited life expectancy

As recommended in NICE NG28, HbA1c should be measured every three to six months when treatment is being adjusted or targets have not been met, and every six months once stable. It is important to note that HbA1c can be unreliable or is not the appropriate measure in certain circumstances, including:

• Haemoglobinopathies (e.g., sickle cell disease, thalassaemia)

• Haemolytic anaemia or recent blood transfusion

• Iron deficiency anaemia, which can falsely raise HbA1c

• Pregnancy (where fasting plasma glucose or oral glucose tolerance test is preferred)

• Children and young people with type 1 diabetes (where additional monitoring metrics apply)

• Acute illness or rapid changes in glycaemic status

In these situations, alternative assessments such as fructosamine, fasting plasma glucose, oral glucose tolerance testing, or continuous glucose monitoring (CGM) metrics may be used. For people managing both diabetes and mental health conditions, HbA1c monitoring takes on added significance, as psychological factors can silently drive deterioration in glycaemic control without the individual being fully aware. Further information is available from the NHS HbA1c test page and Diabetes UK.

The Link Between MDD, GAD, and Poorer Glycaemic Outcomes

Comorbid MDD in diabetes is associated with HbA1c increases of approximately 3–5 mmol/mol; evidence for GAD's independent effect is less consistent and may be confounded by comorbid depression.

A substantial body of evidence demonstrates that people with diabetes who also have MDD are more likely to have elevated HbA1c levels compared to those without comorbid depression. Meta-analyses (including work by de Groot and colleagues) suggest that depression in diabetes is associated with a modest increase in HbA1c — estimates vary across studies, with pooled differences often in the range of approximately 0.3–0.5 percentage points (roughly 3–5 mmol/mol), though some analyses report wider ranges depending on population and methodology. This is a clinically meaningful difference that may increase the risk of long-term complications. The evidence for GAD's independent impact on HbA1c is less consistent and more heterogeneous; findings may be confounded by comorbid depression, illness severity, and other factors, and should be interpreted with caution.

The mechanisms underpinning this association are multifactorial and, in part, hypothesised rather than definitively proven. Chronic psychological distress is associated with elevated pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), which may impair insulin receptor signalling. This low-grade systemic inflammation, observed in both MDD and GAD, could compound the metabolic dysfunction already present in diabetes, though causality has not been firmly established.

Furthermore, diabetes distress — a specific form of emotional burden related to living with diabetes — is distinct from clinical depression but frequently co-occurs with it. Diabetes distress is associated with reduced motivation for self-care and is an independent predictor of poorer HbA1c outcomes. Validated tools such as the Problem Areas in Diabetes (PAID) scale or the Diabetes Distress Scale (DDS) can help identify this in clinical practice.

Given the bidirectional nature of the relationship — where poor glycaemic control may itself contribute to depressive symptoms — clinicians should consider screening for mental health conditions whenever HbA1c remains persistently above target despite apparent adherence to treatment, using validated measures where appropriate (see NICE NG222 and CG113).

NICE Guidance on Managing Mental Health Conditions Alongside Diabetes

NICE guidelines NG28, NG222, and CG113 recommend integrated stepped care — including validated screening, CBT, and NHS Talking Therapies — for people with comorbid diabetes and mental health conditions.

NICE provides clear guidance on the integrated management of mental health and long-term physical conditions. NICE guideline NG28 (Type 2 Diabetes in Adults) recommends that healthcare professionals consider the psychological and social aspects of living with diabetes as part of routine care. NICE guideline NG222 (Depression in Adults: Treatment and Management, which supersedes the earlier CG90) and NICE guideline CG113 (Generalised Anxiety Disorder and Panic Disorder in Adults) outline evidence-based treatment pathways applicable to individuals with comorbid physical health conditions.

Key recommendations relevant to this population include:

• Psychological screening using validated tools: NICE advises using validated measures — such as the PHQ-9 or PHQ-2 for depression, and the GAD-7 or GAD-2 for anxiety — where appropriate in people with long-term conditions, including diabetes. NICE does not universally mandate specific instruments; the choice of tool should be guided by clinical context and local protocols

• Collaborative care models: Integrated approaches where diabetes nurses, GPs, and mental health practitioners work together are supported as more effective than siloed management, though availability varies across NHS settings

• Stepped care: Both NG222 and CG113 advocate a stepped-care model, beginning with low-intensity interventions (such as guided self-help or computerised CBT) and escalating to high-intensity psychological therapy or pharmacotherapy as needed

• Avoiding therapeutic nihilism: NICE explicitly cautions against under-treating mental health conditions in people with physical illness, as this worsens outcomes for both conditions

The NHS Long Term Plan highlights the importance of NHS Talking Therapies (formerly Improving Access to Psychological Therapies, IAPT) for people with long-term physical health conditions, including diabetes. Referral to these services should be considered proactively. Importantly, self-referral is available in many areas — patients can refer themselves directly without needing to go through their GP first, via the NHS Talking Therapies service finder at nhs.uk/mental-health/talking-therapies-medicine-treatments/talking-therapies-and-counselling/nhs-talking-therapies.

Treatment Approaches That Address Both Mood Disorders and HbA1c

CBT is first-line for MDD and GAD in diabetes; SSRIs are commonly used pharmacologically, but some — particularly fluoxetine — can cause hypoglycaemia, requiring closer blood glucose monitoring.

Effective management of MDD and GAD in the context of diabetes requires a carefully considered approach, as some treatments can influence glycaemic control directly. The goal is to improve psychological wellbeing whilst supporting — rather than undermining — HbA1c targets.

Psychological therapies are generally the first-line approach and carry no metabolic risk. Cognitive behavioural therapy (CBT) has the strongest evidence base for both MDD and GAD and has been shown in some studies to modestly improve HbA1c alongside mood outcomes, though effect sizes vary. Diabetes-specific psychological interventions, such as those addressing diabetes distress, can also be beneficial.

When pharmacotherapy is indicated, selective serotonin reuptake inhibitors (SSRIs) such as sertraline or fluoxetine are commonly used. The metabolic effects of SSRIs in diabetes are variable and agent-dependent:

• Some SSRIs may cause modest weight loss initially, which could benefit glycaemic control in some individuals

• Others, particularly paroxetine and mirtazapine, are associated with weight gain and increased appetite over longer-term use

• Certain SSRIs — most notably fluoxetine — have been associated with hypoglycaemic effects in some individuals. This risk is particularly relevant for those taking insulin or sulfonylureas, who should be advised to monitor their blood glucose more closely when starting or changing antidepressant treatment. Prescribers should consult the relevant Summary of Product Characteristics (SmPC) via the Electronic Medicines Compendium (EMC) and the BNF for agent-specific guidance

Tricyclic antidepressants (TCAs) and some antipsychotics used in treatment-resistant depression are generally less preferred in diabetes due to their propensity to cause weight gain and worsen insulin resistance. Where these agents are used, baseline and ongoing metabolic monitoring — including weight, blood glucose or HbA1c, lipids, and blood pressure — is advisable, and the decision should involve shared decision-making between the patient and prescriber, with reference to NICE NG222 and BNF guidance.

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Lifestyle interventions — including structured physical activity programmes — have dual benefits, improving both mood and insulin sensitivity. In line with the UK Chief Medical Officers' Physical Activity Guidelines, adults are advised to aim for at least 150 minutes of moderate-intensity aerobic activity per week, alongside muscle-strengthening activities on two or more days per week. Even modest increases in activity can meaningfully reduce HbA1c. Multidisciplinary team involvement, including dietitians and diabetes specialist nurses, is valuable in coordinating care across both domains.

If you experience any suspected side effects from a new or existing medicine, you can report these to the MHRA via the Yellow Card Scheme at yellowcard.mhra.gov.uk or through the Yellow Card app.

When to Seek Further Support From Your GP or Diabetes Team

Seek GP or diabetes team support promptly if low mood, excessive worry, or neglect of diabetes self-care persists beyond two weeks, or if HbA1c remains consistently above target despite adherence.

Knowing when to seek additional help is an important aspect of self-management for anyone living with diabetes and a mental health condition. Many people delay seeking support due to stigma, uncertainty about what constitutes a significant problem, or feeling that their concerns may not be taken seriously. However, early intervention consistently leads to better outcomes for both mental health and glycaemic control.

Contact your GP or diabetes team promptly if you notice:

• Persistent low mood, tearfulness, or loss of interest in activities lasting more than two weeks

• Excessive or uncontrollable worry that is interfering with daily life

• Difficulty sleeping, significant changes in appetite, or unexplained fatigue

• Neglecting diabetes self-care tasks such as taking medication, monitoring blood glucose, or attending appointments

• HbA1c results that are consistently above your agreed target despite your best efforts

• Thoughts of self-harm or hopelessness — seek urgent help immediately (see below)

If you are in crisis or having thoughts of self-harm:

• Call 999 if you or someone else is in immediate danger

• Contact your GP or call NHS 111 for urgent advice

• Call the Samaritans on 116 123 (free, 24 hours a day, 7 days a week)

• Attend your nearest A&E if you need immediate support

• Your local NHS urgent mental health helpline can also provide same-day support — details are available via NHS 111 or your GP practice

Your GP can arrange a formal mental health assessment, initiate a referral to NHS Talking Therapies, or liaise with your diabetes specialist team to review your overall management plan. In many areas, you can also self-refer directly to NHS Talking Therapies without needing a GP referral — visit nhs.uk to find your local service. Many GP practices also have access to social prescribing link workers who can connect you with community support.

It is worth remembering that experiencing depression or anxiety alongside diabetes is common and is not a sign of personal failure. Both conditions are recognised medical diagnoses with effective treatments available. Open, honest communication with your healthcare team is the most important step you can take towards improving both your mental wellbeing and your long-term diabetes outcomes.

Frequently Asked Questions