Glycaemic Monitoring in Diabetic Kidney Disease – Is HbA1c Reliable?

Diabetic kidney disease (DKD) is a known complication of diabetes mellitus that increases patients’ risks of developing end-stage renal failure requiring dialysis treatment and vulnerability of fatal outcomes resulted from cardiovascular events. Therefore, a good diabetic control among patients with DKD is essential. Nevertheless, monitoring glycaemia in DKD is very challenging. The use of the gold standard glycaemic marker, haemoglobin A1c (HbA1c), is complicated by many hindrances associated with both biochemical and physiological derangements of DKD. Despite the constraints, the Kidney Disease Improving Global Outcome has recommended the use of HbA1c as a reliable glycaemic marker in DKD patients, whose estimated glomerular filtration rate is down to 30 millilitres/minute per 1.73 meter2 . In this article, we discuss the reliability and limitations of HbA1c as an advocated glycaemic marker in DKD. Considering that the reliability of HbA1c is highly dependent on the interpretation of the results, we also highlighted the common potential factors that can affect HbA1c interpretation in patients with DKD. The article also discusses the issues related to the utility of glycated albumin and serum fructosamine as alternative glycaemic biomarkers, and continuous glucose monitoring as a complementary marker to HbA1c in clinical practice. Understanding the HbA1c values and their limitations is important to ensure accurate interpretation of glycaemic status and to achieve optimal diabetic control in patients with DKD.

Diabetes mellitus remission in a cat with hyperadrenocorticism after cabergoline treatment

Case summary A 7-year-old spayed female domestic shorthair cat weighing 5 kg was referred with polyuria, polydipsia, lethargy, abdominal distension and dermatologic abnormalities. Diabetes mellitus was diagnosed and treatment was started with a diet for diabetic cats and insulin glargine (1 IU q12h SC). Hyperadrenocorticism (HAC) was suspected and diagnosed based on clinical signs, increased urinary cortisol:creatinine ratio, lack of suppression on low-dose dexamethasone suppression test and abdominal ultrasonography demonstrating bilateral adrenal enlargement. Oral cabergoline (10 μg/kg every other day) was initiated. After the second administration of cabergoline, the cat suffered from clinical hypoglycemia and no longer required insulin. One month after insulin withdrawal, blood work and urine analysis results showed normoglycemia, a normal serum fructosamine concentration (244 μmol/l) and normal urine analysis without glycosuria. Diabetic remission persisted until its death 7 months later. In addition, cabergoline treatment was associated with improvement in clinical signs such as lethargy, seborrhea, alopecia and abdominal distension. Relevance and novel information To our knowledge, this is the first reported case of the use of cabergoline in a cat with HAC, as well as the first reported case of diabetic remission in a cat with HAC after cabergoline treatment. Cabergoline could be an alternative treatment for diabetic cats with pituitary-dependent HAC. Further work should focus on different protocols with greater number of cases.

Insulin glargine 300 U/ml for the treatment of feline diabetes mellitus

Objectives The study aimed to evaluate the efficacy and safety of insulin glargine 300 U/ml (IGla-U300) in cats with variable duration of diabetes mellitus (DM). Methods Thirteen client-owned cats with DM completed a prospective clinical trial. Four cats were highly suspected of hypersomatotropism and excluded from the insulin efficacy evaluation. All cats were treated with IGla-U300 SC at a starting dosage of 0.5 U/kg q12h and fed with a low carbohydrate diet. Cats were monitored for 8 weeks with a once-weekly at-home 16 h blood glucose curve (BGC) and a questionnaire evaluating the presence of DM-related clinical signs. In-clinic evaluations, including serum fructosamine measurement, were scheduled within 3 days of the first, third, sixth and eighth BGC. Glycemic variability was assessed by calculating the SD of each BGC. Results Excluding four cats suspected of hypersomatotropism, at the time of the eighth BGC, improved or absent polyuria, polydipsia, polyphagia, weight loss, lethargy and improved or normal general demeanor were reported in 8/9 (88%), 8/9 (88%), 7/9 (77%), 7/9 (77%), 7/9 (77%) and 8/9 (88%) cats, respectively. Two cats achieved remission after 29 and 53 days. Another two cats went into remission after the end of the study (days 82 and 96). All cats that achieved remission were newly diagnosed diabetics. Median (range) serum fructosamine concentration significantly decreased when comparing the time of enrollment (604 [457–683] µmol/l) with the eighth week of treatment (366 [220–738] µmol/l) ( P = 0.02). In all 13 cats, biochemical hypoglycemia (blood glucose <60 mg/dl; <3.3 mmol/l) was detected in 13/104 (12.5%) BGCs, while clinical signs suggesting hypoglycemic episodes were not reported. Glycemic variability was significantly lower at the fifth BGC when comparing cats that achieved remission with cats that did not achieve remission ( P = 0.02). Conclusions and relevance IGla-U300 seems effective and safe for the treatment of feline diabetes, but more long- term and comparative clinical trials are needed.

Serum fructosamine targeting the treatment of gestational diabetes mellitus

Background: Currently,the blood glucose control in women with gestational diabetes (GDM) in Vietnam has been still based on the criteria applied for non-pregnant diabetic patients, while these GDM patients require more specific criteria in order to get a better care of the women and the good delivery outcome. Objective: To determine serum fructosamine target as a supporting test for the treatment and follow-up of GDM. Methodology: A prospective study was done in 451women with GDM at Cho Ray Hospital from August 2016 to March 2019.At least 2 of 3 tests (Go, G2 and HbA1c) and serum fructosamine were determined every 2-3 week-up until delivery. Result: The target fructosamine reference value at Cho Ray Hospital was 188.5±42.3µmol/L. Conclusion: The specific target of serum fructosamine in GDM treatment at Cho Ray hospital should be £188.5 ± 42.3mmol/L.

Salivary Fructosamine as a Noninvasive Glycemic Biomarker: A Systematic Review

Background: Standard diagnostic and monitoring methods for glycemic status involve invasive sample collection through venous puncture or fingerstick. Recent attention has been focused on exploring noninvasive methods through oral biofluids. Specifically, serum fructosamine has been established as a short-term (2- to 3-wk) marker of disease status in patients with diabetes. Fructosamine measured through noninvasive means such as saliva has shown promise, but its clinical applicability is unknown. Objective: Evaluate the available evidence on using salivary fructosamine as a reliable noninvasive marker to screen and diagnose patients with diabetes mellitus in the clinical setting. A comparative analysis of the correlative accuracy of salivary fructosamine measurements with established blood glycemic biomarkers such as serum fructosamine, blood glucose, and HbA1c will be conducted. Methods: Six electronic databases (PubMed, PubMed Central, MEDLINE, EMBASE, Scopus, Cochrane Library) were searched for original research papers (clinical and animal studies) that were relevant to the objective of this systematic review. The search was initiated on May 28, 2020. The systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Bias risk assessment, overall quality, and level of evidence were based on the Oxford Centre for Evidence-Based Medicine, Appraisal Tool for Cross-Sectional Studies, and Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies tool. Heterogeneity was assessed using the National Institutes of Health quality assessment tool for cross-sectional studies. Results: A total of 174 records were identified. Full-text articles screened for eligibility (n = 21) identified only 6 original research articles relevant to the research question and were thus included in the systematic review. The types of studies identified were cross-sectional and in vivo studies. Three studies (3/6) showed positive correlation of salivary fructosamine with blood glucose levels, while 1 study (1/6) demonstrated a positive correlation with glycated hemoglobin (HbA1c). Limitations related to sample size and selection were identified along with a fair level of interstudy heterogeneity. Conclusion: Based on the evidence evaluated, the utility of salivary fructosamine as a noninvasive marker to screen and diagnose patients with diabetes is doubtful. The overall level of evidence was low (IIIB) and the risk of bias was determined to be high. Knowledge Transfer Statement: Further evidence in the form of large-scale well-controlled studies is needed prior to recommending salivary fructosamine as a noninvasive diagnostic tool for glycemic status in patients with diabetes mellitus.