14th September 2024

Type 1 diabetes

Type 1 Diabetes Mellitus (T1DM) is primarily an autoimmune disorder (90% of cases), leading to the destruction of insulin-producing beta cells in the pancreas, resulting in an absolute deficiency of insulin and subsequent hyperglycaemia. In some patients, there may be no evidence of autoimmune destruction; this is referred to as idiopathic T1DM. T1DM is a polygenic heritable disease that arises when environmental factors trigger autoimmunity in genetically susceptible individuals (HLA-DR3 > DR4 haplotypes).

Diagnosis

T1DM is diagnosed when persistent hyperglycaemia (random plasma glucose > 11 mmol/L) is observed, caused by absolute insulin deficiency, a family history, and other symptoms traditionally associated with diabetes, such as fatigue, polyuria, polydipsia, and rapid weight loss. Older adults may present atypically. Diagnosis is confirmed by measuring C-peptide levels and/or diabetes-specific antibody titres.

Numerous antibodies are associated with a higher risk of developing T1DM, although their presence is not part of the diagnostic criteria. These autoantibodies include islet cell antibodies (ICA), glutamic acid decarboxylase (GAD), islet tyrosine phosphatase (IA-2), and zinc transporter 8 (ZnT8).

Management

Patients with T1DM fundamentally require insulin replacement. NICE favours starting with basal bolus regimens (twice daily long acting detemir). These patients need structured education on how to adjust insulin doses for the carbohydrate quantity of meals (DAFNE courses). Cardiovascular risk factors, as with T2DM, are important prognostically and should not be neglected. Metformin can be added if the patient has a BMI of above 25, but equally insulin can be uptitrated. Patients should measure their glucose levels 4 times a day. Sometimes, it is appropriate to measure more often (10 times a day), for instance, in acute illness, exercise, or when HbA1c targets are not met (aim for less than 6.5%/48mmol/mol). Poor glucose control can lead to Impaired hypoglycaemic awareness, which is a state that occurs when hypoglycaemia recurs so often that patients stop getting hypoglycaemic symptoms. Continuous glucose monitoring devices (Libre) measure glucose levels in the interstitium and are increasingly used. Blood glucose targets should not be increased to avoid hypo episodes. Continuous subcutaneous insulin infusions can be used in impaired hypo awareness or in patients with persistently high HbA1c levels.

Diabetic ketoacidosis

The combination of hyperglycaemia (>11 mmol/l), acidosis (bicarbonate <15 mmol/L; pH <7.3) and ketosis (blood ketones <3 mmol/l, urine ketones ≥++) leads to the diagnosis of DKA, which can often be the first presentation of T1DM. Alternatively, it can be provoked by infection or myocardial ischemia. Note that it is possible for “ketosis-prone” type 2 diabetics to develop DKA. Euglycaemic ketoacidosis can also occur with normal blood sugar levels, as a side effect of SGLT2 inhibitors (e.g., dapagliflozin). Management of DKA consists of fixed rate insulin infusion (FRII) at 0.1 units/kg/hr and rehydration. Basal insulin and insulin pumps should continue at all times. DKA patients are considerably dehydrated and potassium depleted. For potassium levels between 3.5 and 5.5 mmol/l, use 40 mmol KCl in addition to saline. Resolution of DKA occurs when serum ketones are <0.6 mmol/l and pH >7.3. When DKA resolves, switch the patient to their normal insulin regimen (if they are eating) or to a variable-rate insulin infusion (if not eating).

Hypoglycaemia

Hypoglycaemia is associated with all forms of diabetes, particularly when insulin is used. It is defined as a glucose level of <3.5 mmol/l and is more prone to occur in those with illnesses, diabetic patients on insulin therapy, medications with hypoglycemia risk such as sulfonylureas, missed meals or being nil by mouth, insulin dose errors, renal impairment in patients on insulin, recent changes to diet or weight while on insulin, Addison’s and coeliac disease (which can co-occur with T1DM), gastroparesis (a complication of diabetes and hyperglycemia, which can be treated with erythromycin/metoclopramide), liver disease, alcohol, and insulinomas. Symptoms of hypoglycemia include tremors, sweating, fatigue, and palpitations. This can progress to syncope, convulsions, and death. Impaired awareness is, therefore, exceedingly dangerous and is an indication for continuous subcutaneous insulin infusions. If refractory to treatment, impaired awareness can ultimately be treated with islet or pancreatic transplantation.

Other complications

The complications of persistent hyperglycemia are divided into macrovascular and microvascular. Macrovascular complications encompass the increased risk of stroke, MI, and peripheral arterial disease. Microvascular complications encompass neuropathy, nephropathy, and retinopathy. Retinopathy starts as early non-proliferative (aneurysms, exudates, and small haemorrhages) and progresses to proliferative, which can result in retinal detachment and vitreous haemorrhage (diabetes is the most common cause of acquired blindness in the UK). Nephropathy manifests as albuminuria initially and progresses to CKD. Neuropathy can be sensorimotor or autonomic (gastroparesis, erectile dysfunction, silent myocardial infarction).

DVLA

For Group 1 (cars and motorcycles) and Group 2 (large vehicles and lorries) licences, patients must inform the DVLA if they begin long-term insulin treatment. Episodes of severe hypoglycaemia (those that the patient cannot treat without assistance) can lead to the licence being revoked. For Group 1 licences, more than one episode of severe hypoglycaemia will result in the licence being revoked. For Group 2 licences, only one episode is required for revocation. Any single episode of severe hypoglycaemia while driving will result in the licence being revoked.

References

• NICE CKS (2020) Type 1 Diabetes Guidelines, Available at: https://cks.nice.org.uk/topics/diabetes-type-1/
• Driver and Vehicle Licensing Agency. Assessing fitness to drive – a guide for medical professionals. https://www.gov.uk/government/publications/assessing-fitness-to-drive-a-guide-for-medical-professionals
• Sinclair AJ, Dunning T, Dhatariya K; an International Group of Experts. Clinical guidelines for type 1 diabetes mellitus with an emphasis on older adults: an Executive Summary. Diabet Med. 2020 Jan;37(1):53-70. doi: 10.1111/dme.14135. Epub 2019 Sep 23. PMID: 31498912.BMJ 2012 (Mobile App)
• Dhatariya KK; Joint British Diabetes Societies for Inpatient Care. The management of diabetic ketoacidosis in adults-An updated guideline from the Joint British Diabetes Society for Inpatient Care. Diabet Med. 2022 Jun;39(6):e14788. doi: 10.1111/dme.14788. Epub 2022 Feb 27. PMID: 35224769.
• Aune D et al (2015); “. Physical activity and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis”.. Eur J Epidemiol. 2015 Jul;30(7):529-42. doi: 10.1007/s10654-015-0056-z. Epub 2015 Jun 20. PMID: 26092138.
• Misra S, Oliver NS. Diabetic ketoacidosis in adults. BMJ. 2015 Oct 28;351:h5660. doi: 10.1136/bmj.h5660. Erratum in: BMJ. 2015;351:h5866. PMID: 26510442.
• Polly J. Bingley, Clinical Applications of Diabetes Antibody Testing, The Journal of Clinical Endocrinology & Metabolism, Volume 95, Issue 1, 1 January 2010, Pages 25–33, https://doi.org/10.1210/jc.2009-1365
• Plewa MC, Bryant M, King-Thiele R. Euglycemic Diabetic Ketoacidosis. [Updated 2023 Jan 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554570/
• Joint Formulary Committee. British National Formulary (online) London: BMJ and Pharmaceutical Press <http://www.medicinescomplete.com; https://bnf.nice.org.uk/treatment-summaries/diabetic-hyperglycaemic-emergencies/
• Katsarou, A., Gudbjörnsdottir, S., Rawshani, A. et al. Type 1 diabetes mellitus. Nat Rev Dis Primers 3, 17016 (2017). https://doi.org/10.1038/nrdp.2017.16
• The Hospital Management of Hypoglycaemia in Adults with Diabetes Mellitus; Joint British Diabetes Societies for inpatient care 4th Edition; January 2020; Esther Walden; Debbie Stanisstreet; Alex Graveling
• Type 1 diabetes in adults: diagnosis and Management; Nice guidance; August 2022; https://www.nice.org.uk/guidance/ng17/chapter/Recommendations
• Driving and diabetes; Diabetes UK; Found at: Driving when you have diabetes | Diabetes UK