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Summary: A 20-year-old South Asian male presented with polyuria, polydipsia, HbA1c 81 mmol/mol, BMI 28.8 and family history of both type 1 and type 2 diabetes mellitus. As autoantibody testing was negative and c-peptide level demonstrated significant endogenous insulin secretion, type 1 diabetes was excluded. Given his age and family history, the differential diagnosis included maturity-onset diabetes of the young (MODY), a rare form of diabetes caused by a single-gene variant. A high probability of MODY was calculated and he was subsequently referred for genetic testing. Although a useful tool, the pre-test probability calculator for MODY is only validated in White Europeans. A heterogenous variant of unknown clinical significance of the NEUROD1 gene was detected, leading to gliclazide use with poor response. The patient responded well to metformin. Type 2 diabetes was considered the most likely diagnosis. This case highlights the diagnostic challenges in young patients of Asian ethnicity and the importance of interpreting genetic results of unknown significance within the clinical context. Ethnicity-specific BMI thresholds should be used when classifying patients as overweight or obese. Learning points: Variants of unknown significance detected by genetic sequencing should be interpreted within the context of the patient's other clinical parameters. It is important to use ethnicity-specific BMI thresholds for obesity. Diagnosis of type 2 diabetes mellitus at younger ages is becoming increasingly common. The pre-test probability calculator for MODY is only validated in White Europeans; although a useful guide, results should be interpreted with caution in patients of other ethnicities.
RESUMO
BACKGROUND: Advanced heart failure patients suffer with breathlessness and peripheral oedema, which are frequently treated with parenteral diuretics despite limited evidence. AIM: To analyse the effectiveness of parenteral diuretics on breathlessness and peripheral oedema in advanced heart failure patients. METHODS: We searched Embase, MEDLINE(R), PsycINFO, CINAHL and CENTRAL from their respective inceptions to 2021, and performed handsearching, citation searching and grey literature search; limited to English publications. Selection criteria included parenteral (intravenous/subcutaneous) diuretic administration in advanced heart failure patients (New York Heart Association class III-IV). Two authors independently assessed articles for inclusion; one author extracted data. Data were synthesised through narrative synthesis or meta-analysed as appropriate. RESULTS: 4646 records were screened; 6 trials (384 participants) were included. All were randomised controlled trials (RCTs) comparing intravenous continuous furosemide infusion (CFI) versus intravenous bolus furosemide infusion (BFI). Improvement in breathlessness and peripheral oedema (two studies, n=161, OR 2.80, 95% CI 1.45 to 5.40; I2=0%), and increase in urine output (four studies, n=234, mean difference, MD 344.76, 95% CI 132.87 to 556.64; I2=44%), were statistically significant in favour of CFI. Significantly lower serum potassium was found in BFI compared with CFI (three studies, n=194, MD -0.20, 95% CI -0.38 to -0.01; I2=0%). There was no difference between CFI and BFI on reduction in weight, renal function or length of hospital stay. CONCLUSIONS: CFI appears to improve congestion in advanced heart failure patients in the short term. Available data came from small trials. Larger, prospective RCTs are recommended to address the evidence gap.