Diabetic ketoacidosis in an adult with beta-ketothiolase deficiency (BKD) involving a novel ACAT1 variant : first report of established diabetes in BKD and a review of the literature.

BACKGROUND: Diabetes presenting in young adults is often challenging to classify. Diabetic ketoacidosis is typically seen in autoimmune type 1 diabetes mellitus and more rarely in young onset type 2 diabetes mellitus. Beta-ketothiolase deficiency (BKD) is a rare autosomal recessive condition affecting isoleucine catabolism and ketone body metabolism. BKD typically manifests in childhood as recurrent episodes of ketoacidosis, the frequency of which tends to reduce with age. There is a paucity of data with respect to the co-existence of persistent dysglycemia with BKD. CASE PRESENTATION AND LITERATURE REVIEW: We present a novel case of diabetes presenting as diabetic ketoacidosis in a 34-year-old man with BKD, with genetically confirmed compound heterozygosity for variants in ACAT1, including a novel ACAT1 c.481T>C, p.(Tyr161His) variant. Diabetes in people with BKD presents unique diagnostic and management challenges. To further contextualize our findings, we conducted a comprehensive narrative review of the existing literature with respect to dysglycemia in those with BKD, especially in adulthood. There are no existing reports describing diabetes in adults with BKD. Stress hyperglycemia is not uncommon when children with BKD are acutely unwell, with several pediatric case reports describing short-lived hyperglycemia but normal HbA1c measurements during metabolic crises (indicating the absence of persistent hyperglycemia). CONCLUSIONS: This is the first report of diabetic ketoacidosis in an adult with BKD, with an elevated HbA1c consistent with persistent hyperglycemia. This case highlights the importance of checking HbA1c in people with BKD and hyperglycemia in order to uncover potential coexisting diabetes, facilitating timely management and preventing complications. Increased reporting on the longitudinal outcomes of those with rare metabolic disorders is essential for identifying potential associations with conditions like diabetes.

Circulating soluble CD163 as a potential biomarker of diabetes complications.

AIMS: To investigate whether soluble CD163 (sCD163) is altered in those with diabetes and various subtypes of complications and non-alcoholic fatty liver disease (NAFLD), and whether it can assess disease complications and severity in people with diabetes. METHODS: Adults with diabetes (n = 101) were recruited and assessed for the presence of any complications (D+Comps). Liver steatosis presence was determined by ultrasound and liver stiffness measurement (LSM) by transient elastography. Liver pathology other than non-alcoholic steatohepatitis (NASH) was excluded. Plasma sCD163 was measured by ELISA. RESULTS: sCD163 was higher in D+Comps (n = 59) compared to D-comps (n = 42) in those with microvascular complications (n = 56; 1.3-fold), including a 1.4-fold increase in chronic kidney disease (CKD) (n = 42). sCD163 correlated positively with HbA1c and urinary albumin-creatinine ratio and negatively with HDL-c in D+Comps. sCD163 was increased 1.7-fold in those with advanced NASH fibrosis (LSM ≥ 10.3 kPa, n = 19) compared to those without (LSM < 10.3 kPa, n = 80). The AUC-ROC-curve was 0.64 for sCD163 to detect CKD and 0.74 to detect advanced NASH fibrosis. CONCLUSIONS: In this study, the elevated circulating sCD163 occurred in people with diabetes who had microvascular complications or advanced NASH fibrosis, suggesting sCD163 may have clinical utility as a biomarker in certain diabetes complications and disease severity in NAFLD.

Asia-Pacific consensus recommendations for application of continuous glucose monitoring in diabetes management.

Glucose monitoring has evolved from self-monitoring of blood glucose to glycated hemoglobin, and the latest continuous glucose monitoring (CGM). A key challenge to adoption of CGM for management of diabetes in Asia is the lack of regional CGM recommendations. Hence, thirteen diabetes-specialists from eight Asia-Pacific (APAC) countries/regions convened to formulate evidence-based, APAC-specific CGM recommendations for individuals with diabetes. We defined CGM metrics/targets and developed 13 guiding-statements on use of CGM in: (1) people with diabetes on intensive insulin therapy, and (2) people with type 2 diabetes on basal insulin with/without glucose lowering drugs. Continual use of CGM is recommended in individuals with diabetes on intensive insulin therapy and suboptimal glycemic control, or at high risk of problematic hypoglycemia. Continual/intermittent CGM may also be considered in individuals with type 2 diabetes on basal insulin regimen and with suboptimal glycemic control. In this paper, we provided guidance for optimizing CGM in special populations/situations, including elderly, pregnancy, Ramadan-fasting, newly diagnosed type 1 diabetes, and comorbid renal disease. Statements on remote CGM, and stepwise interpretation of CGM data were also developed. Two Delphi surveys were conducted to rate the agreement on statements. The current APAC-specific CGM recommendations provide useful guidance for optimizing use of CGM in the region.

Management of type 2 diabetes in young adults aged 18-30 years: ADS/ADEA/APEG consensus statement.

INTRODUCTION: Type 2 diabetes in young adults (nominally, 18-30 years of age) is a more aggressive condition than that seen in older age, with a greater risk of major morbidity and early mortality. This first Australian consensus statement on the management of type 2 diabetes in young adults considers areas where existing type 2 diabetes guidance, directed mainly towards older adults, may not be appropriate or relevant for the young adult population. Where applicable, recommendations are harmonised with current national guidance for type 2 diabetes in children and adolescents (aged < 18 years). The full statement is available at https://www.diabetessociety.com.au, https://www.adea.com.au and https://www.apeg.org.au. MAIN RECOMMENDATIONS: Advice is provided on important aspects of care including screening, diabetes type, psychological care, lifestyle, glycaemic targets, pharmacological agents, cardiovascular disease risk management, comorbidity assessment, contraception and pregnancy planning, and patient-centred education. Special considerations for Aboriginal and Torres Strait Islander Australians are highlighted separately. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: Management recommendations for young adults, which differ from those for adults, include: ▪screening for diabetes in young adults with overweight or obesity and additional risk factors, including in utero exposure to type 2 diabetes or gestational diabetes mellitus; ▪more stringent glucose targets (glycated haemoglobin ≤ 6.5% [≤ 48 mmol/mol]); ▪in the context of obesity or higher cardio-renal risk, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors are preferred second line agents; ▪ß-cell decline is more rapid, so frequent review, early treatment intensification and avoidance of therapeutic inertia are indicated; ▪a blood pressure target of < 130/80 mmHg, as the adult target of ≤ 140/90 mmHg is too high; ▪absolute cardiovascular disease risk calculators are not likely to be accurate in this age group; early statin use should therefore be considered; and ▪a multidisciplinary model of care including an endocrinologist and a certified diabetes educator.

Effect of High-Intensity Interval Training on Glycemic Control in Adults With Type 1 Diabetes and Overweight or Obesity: A Randomized Controlled Trial With Partial Crossover.

OBJECTIVE: To study the effect of 12 weeks of high-intensity interval training (HIIT) on glycemic control in adults with type 1 diabetes and overweight or obesity. RESEARCH DESIGN AND METHODS: Thirty inactive adults with type 1 diabetes who had BMI ≥25 kg/m2 and HbA1c ≥7.5% were randomized to 12 weeks of either HIIT exercise intervention consisting of 4 × 4-min HIIT (85-95% peak heart rate) performed thrice weekly or usual care control. In a partial crossover design, the control group subsequently performed the 12-week HIIT intervention. The primary end point was the change in HbA1c from baseline to 12 weeks. Glycemic and cardiometabolic outcomes were measured at 0, 12, and 24 weeks. RESULTS: Participants were aged 44 ± 10 years with diabetes duration 19 ± 11 years and BMI 30.1 ± 3.1 kg/m2. HbA1c decreased from 8.63 ± 0.66% at baseline to 8.10 ± 1.04% at 12 weeks in the HIIT intervention group (P = 0.01); however, this change was not significantly different from the control group (HIIT -0.53 ± 0.61%, control -0.14 ± 0.48%, P = 0.08). In participants who undertook at least 50% of the prescribed HIIT intervention, the HbA1c reduction was significantly greater than control (HIIT -0.64 ± 0.64% [n = 9], control -0.14 ± 0.48% [n = 15], P = 0.04). There were no differences in insulin dose, hypoglycemia on continuous glucose monitoring, blood pressure, blood lipids, body weight, or body composition between groups. CONCLUSIONS: Overall, there was no significant reduction in HbA1c with a 12-week HIIT intervention in adults with type 1 diabetes. However, glycemic control may improve for people who undertake HIIT with greater adherence.

An on-line support tool to reduce exercise-related hypoglycaemia and improve confidence to exercise in type 1 diabetes.

OBJECTIVE: Hypoglycaemia related to exercise and lack of confidence to exercise, are common in T1DM. An online educational exercise tool (ExT1D) was tested to determine whether these parameters can be improved. RESEARCH DESIGN AND METHODS: Thirty two adults with T1DM (50%M, age 35.8 ±â€¯9.5 yr diabetes duration 12.3 ±â€¯9.9 yr, median HbA1c 7.1%[ICR 6.4-7.7] NGSPU) exercising ≥ 60 min/week enrolled in a RCT utilising ExT1D, with partial cross-over design. The primary end-point was Exercise-related hypoglycaemia (ErH) number corrected for exercise session number, with ErH defined as CGM episodes < 4.0 mM occurring within 24 h of exercise. Secondary RCT endpoints were total ErH duration, and ErH duration/episode. A pre-defined longitudinal analysis with each subject compared with their baseline was also undertaken, for the three ErH parameters, and using fear of hypoglycaemia questionnaires. RESEARCH: In the RCT a 50% lower median ErH number (P = 0.6) (37% lower ErH number per exercise session (P = 0.06, NS primary endpoint) occurred in the Intervention vs Control group. A 49% lower ErH duration per episode (P = 0.2), and 80% less ErH duration (P = 0.3), were also observed in the Intervention vs Control group. In the longitudinal study, ErH number reduced by 43% (P = 0.088), ErH duration per episode by 52% (P = 0.157) and total duration of ErH fell by 71% (P = 0.015). Confidence to prevent glucose lowering by exercise also improved (P = 0.039). Post-hoc analysis showed those with the greatest ErH events at baseline benefited most. Fructosamine and HbA1c levels were unchanged from baseline. CONCLUSIONS: ExT1D can reduce exercise-related hypoglycaemia and provide greater confidence to exercise.