Monogenic diabetes and the role of the diabetes nurse
DOI:
https://doi.org/10.1002/edn.242Keywords:
diabetes specialist nurse, monogenic diabetes, maturity onset diabetes of the young (MODY), neonatal diabetes, genetic testingAbstract
AbstractDiabetes specialist nurses are ideally placed to identify patients with monogenic diabetes but may lack knowledge of the key features and fail to recognise potential cases. Once the diagnosis of diabetes has been made this may not be revisited and may be assumed to be correct. However, increasing knowledge and awareness of monogenic diabetes will allow health care professionals to question the diagnosis of their patients where appropriate and lead to greater recognition and correct treatment of monogenic diabetes.
Maturity onset diabetes of the young (MODY) is typically detected in individuals diagnosed with diabetes before the age of 25 years who also have a parent with diabetes. They are non-insulin dependent but are often mistaken to have type 1 diabetes and are insulin treated. Patients meeting these criteria should be considered for further investigation to ensure their diagnosis is correct. Neonatal diabetes can also be caused by a single genetic change, and patients diagnosed with diabetes within the first six months of life should be referred for genetic testing whatever their current age.
This paper highlights three useful means of aiding differential diagnosis: urinary C-peptide creatinine ratio (UCPCR), pancreatic autoantibodies, and use of the online MODY probability calculator. Case studies are used to illustrate the key diagnostic features of MODY and indicate how awareness of family history and other features raised suspicion of an alternative cause of diabetes in these families. Treatment change following a positive molecular genetic diagnosis is also described.
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References
Hammersley S, et al Prevalence of non-type 1 diabetes in paediatric diabetes. Diabet Med 2013;30 (Suppl 1) :24 (A67).
Hudson MM, et al. A population-based approach to genetic testing defines the preva-lence of maturity onset diabetes of the young (MODY) in patients with diabetes diagnosed under 30 years as 3%. Diabet Med 2013; 30(Suppl 1) :24 (A68).
Shepherd M, et al A genetic diagnosis of HNFlA diabetes alters treatment and improves glycaemic control in the majority of insulin treated patients. Diabet Med 2009;26:437–41.
Pearson ER, et al. Sensitivity to sulphony-lureas in patients with HNFlA mutations: evi-dence for pharmacogenetics in diabetes. Diabet Med 2000;17:543–5.
Shepherd M, et al No deterioration in gly-caemic control in HNF-1 alpha MODYfollow-ing transfer from long-term insulin to sulpho-nylureas. Diabetes Care 2003;26:3191–2.
Shepherd M. 'I'm amazed I've been able to come off injections': Patients' perceptions of genetic testing in diabetes. Report of the 2003 Janet Kinson Lecture. Prad Diabetes Int 2003;20:338–43.
Pearson ER, et al. Genetic cause of hypergly-caemia and response to treatment in dia-betes. Lancet 2003;362:1275–81.
Stride A, et al. Cross-sectional and longitudinal studies suggest pharmacological treatment used in patients with glucokinase muta-tions does not alter glycaemia. Diabetologia 2014; 57: 54–6. [Epub 2013 Oct 4.]
Murphy R, et al Clinical implications of a molecular genetic classification of mono-genic beta-cell diabetes. Nat Clin Pract Endocrinol Metab 2008;4:200–13.
Shields BM, et al. Maturity-onset diabetes of the young (MODY) in the UK; how many cases are we missing? Diabetologia 2010; 53:2504–8.
Stride A, Hattersley AT. Different genes dif-ferent diabetes: lessons from maturity-onset diabetes of the young. Ann Med 2002; 34:207–16.
Edghill EL, et al Permanent neonatal dia-betes due to activating mutations in ABCC8 and KCNJ11. Rev Endocr Metab Disord 2010; 11:193–8.
Flanagan SE, et al. Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by geno-type. Diabetologia 2006;49:1190–7.
Gloyn AL, et al Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med 2004; 350:1838–49. Erratum in: N Engif Med 2004; 351: 1470.
McDonald TJ, et al Stability and repro-ducibility of a single sample urinary Gpep-tide/creatinine ratio and its correlation with 24-h urinary C-peptide. Clin Chem 2009; 55:2035–9.
Besser REJ, et al. Urinary C-peptide creatinine ratio (UCPCR) is a practical outpatient tool for identifying HNF1A/HNF4A MODY from long duration type 1 diabetes. Diabetes Care 2011;34:286–91.
Bowman P, et al. Validation of a single-sample urinary C-peptide creatinine ratio as a reproducible alternative to serum C-peptide in patients with type 2 diabetes. Diabet Med 2012;29:90–3.
Besser RE, et al. Urine Gpeptide creatinine ratio is a noninvasive alternative to the mixed-meal tolerance test in children and adults with type 1 diabetes. Diabetes Care 2011;34:607–9.
McDonald TJ, et al. Islet autoantibodies can discriminate maturity onset diabetes of the young (MODY) from type 1 diabetes. Diabet Med 2011;28:1028–33.
Sabbah E, et al. Genetic, autoimmune, and clinical characteristics of childhood- and adult-onset type 1 diabetes. Diabetes Care 2000;23:1326–32.
Shields BM, et al. The development and validation of a clinical prediction model to determine the probability of MODY in patients with young-onset diabetes. Diabetologia 2012;55:1265–72.
Shepherd M, et al. Differential diagnosis: Identifying people with monogenic diabetes. J Diabetes Nurs 2010;14:342–7.
Stride A, et al. Beta-cell dysfunction, insulin sensitivity, and glycosuria precede diabetes in hepatocyte nuclear factor-lalpha mutation carriers. Diabetes Care 2005;28:1751–6.
Steele AM, et al. Increased all-cause and cardiovascular mortality in monogenic dia-betes as a result of mutations in the HNFlA gene. Diabet Med 2010;27:157–61.
Pearson ER, et al. Macrosomia and hyperin-sulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med 2007;4(4) :e118.
Pearson ER, et al. Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4 mutations in a large European collection. Diabetologia 2005;48:878–85.
Steele AM, et al. Low prevalence of diabetes complications after 48 years of mild hyper-glycaemia in patients with glucokinase muta-tions supports current glycaemic targets for diabetes management. Diabet Med 2013; 30(Suppl 1):A70.
Steele AM, et al. Use of HbAk in the identifi-cation of patients with hyperglycaemia caused by a glucokinase mutation: observa-tional case control studies. PLoS One 2012; 8(6) :e65326.
Ellard S, et al. A high prevalence of glucoki-nase mutations in gestational diabetic sub-jects selected by clinical criteria. Diabetologia 2000;43:250–3.
Shepherd M, et al. Dimensions of personal loss and gain associated with a rare genetic type of diabetes. Illness, Crisis and Loss 2003;11:362–76.
Bingham C, et al. Abnormal nephron devel-opment associated with a frameshift muta-tion in the transcription factor hepatocyte nuclear factor-113. Kidney Int 2000;57: 898–907.
Bingham C, Hattersley AT. Renal cysts and diabetes syndrome resulting from mutations in hepatocyte nuclear factor-113. Nephrol Dial Transplant 2004;19:2703–8.
Bellanné-Chantelot C, et al. Clinical spectrum associated with hepatocyte nuclear factor-lbeta mutations. Ann Intern Med 2004; 140:510–7.
Shepherd M. Transforming lives: transferring patients with neonatal diabetes from insulin to sulphonylureas. Eur Diabetes Nurs 2006; 3:137–42.
Hattersley AT, Ashcroft FM. Activating muta-tions in Kir6.2 and neonatal diabetes: new clinical syndromes, new scientific insights, and new therapy. Diabetes 2005;54:2503–13.
Proks P, et al. A heterozygous activating muta-tion in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes. Hum Mol Genet 2006;15:1793–800.
Gloyn AL, et al. KCNJ11 activating mutations are associated with developmental delay, epilepsy and neonatal diabetes syndrome and other neurological features. Eur J Hum Genet 2006;14:824–30.
Pearson ER, et al.; Neonatal Diabetes International Collaborative Group. Switch-ing from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 muta-tions. N Engl J Med 2006;355:467–77.
Sagen JV, et al. Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy. Diabetes 2004;53:2713–8.
Slingerland AS, Hattersley AT. Mutations in the Kir6.2 subunit of the KATP channel and permanent neonatal diabetes: new insights and new treatment. Ann Med 2005;37:186–95.
Slingerland AS, et al. Sulphonylurea therapy improves cognition in a patient with the V59M KCNJ11 mutation. Diabet Med 2008; 25:277–81.
Slingerland AS, et al. Improved motor devel-opment and good long-term glycaemic con-trol with sulfonylurea treatment in a patient with the syndrome of intermediate develop-mental delay, early-onset generalised epilepsy and neonatal diabetes associated with the V59M mutation in the KCNJ11 gene. Diabetologia 2006;49:2559–63.
Edghill EL, et al. Origin of de novo KCNJ11 mutations and risk of neonatal diabetes for subsequent siblings. J Clin Enclocrinol Metab 2007;92:1773–7.
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