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.

Protocol for a randomized controlled trial of medically tailored meals compared to usual care among individuals with type 2 diabetes in Australia.

BACKGROUND: 'Food is medicine' strategies aim to integrate food-based nutrition interventions into healthcare systems and are of growing interest to healthcare providers and policy makers. 'Medically Tailored Meals' (MTM) is one such intervention, which involves the 'prescription' by healthcare providers of subsidized, pre-prepared meals for individuals to prevent or manage chronic conditions, combined with nutrition education. OBJECTIVE: This study will test the efficacy of an MTM program in Australia among participants with type 2 diabetes (T2D) and hyperglycemia, who experience difficulties accessing and eating nutritious food. METHODS: This study will be a two-arm parallel trial (goal n = 212) with individuals randomized in a 1:1 ratio to a MTM intervention group or a control group (106 per arm). Over 26 weeks, the intervention group will be prescribed 20 MTM per fortnight and up to 3 sessions with an accredited dietitian. Controls will continue with their usual care. The primary outcome is glycated hemoglobin (HbA1c, %) and secondary outcomes include differences in blood pressure, blood lipids and weight, all measured at 26 weeks. Process and economic data will be analyzed to assess the feasibility, acceptability, scalability, and cost-effectiveness of the intervention. Recruitment commenced in the first quarter of 2023, with analyses and results anticipated to be available by March 2025. DISCUSSION: Few randomized controlled trials have assessed the impact of MTM on clinical outcomes. This Australian-first trial will generate robust data to inform the case for sustained, large-scale implementation of MTM to improve the management of T2D among vulnerable populations. ANZCTR: ACTRN12622000852752. PROTOCOL VERSION: Version 1.1, July 2023.

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.

ISPAD Clinical Practice Consensus Guidelines 2022: Type 2 diabetes in children and adolescents.

Since the 2018 ISPAD guidelines on this topic, follow-up of large cohorts from around the globe have continued informing the current incidence and prevalence of co-morbidities and complications in young adults with youth-onset type 2 diabetes (T2D). This chapter focuses on the risk factors, diagnosis and presentation of youth-onset T2D, the initial and subsequent management of youth-onset T2D, and management of co-morbidities and complications. We include key updates from the observational phase of the multi-center Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial, the SEARCH for Diabetes in Youth (SEARCH) study and new data from the Restoring Insulin Secretion (RISE) study, a head-to-head comparison of youth onset vs adult-onset T2D. We also include an expanded section on risk factors associated with T2D, algorithms and tables for treatment, management, and assessment of co-morbidities and complications, and sections on recently approved pharmacologic therapies for the treatment of youth-onset T2D, social determinants of health, and settings of care given COVID-19 pandemic.

Myocardial fibrosis in Type 2 Diabetes is associated with functional and metabolomic parameters.

AIMS: To identify biomarkers of cardiomyopathy in patients with type 2 diabetes mellitus (T2DM) using cardiovascular magnetic resonance (CMR) and to identify associations between functional status, metabolomic profile and myocardial fibrosis. METHODS: In this prospective case control study, patients (n = 49) with T2DM without significant coronary artery disease, and matched controls (n = 18) underwent CMR, cardiopulmonary exercise testing, and plasma metabolomic analyses. RESULTS: Patients with T2DM (n = 49, median [interquartile range] age 61 [56-63] years, 61% male, diabetes duration 11 [7-20] years), historical HbA1c 7.6% (60 mmol/mol) (6.9-8.6) and matched controls (n = 18) were examined. Study patients had increased myocardial extracellular volume (ECV) (26.9 [23.8-30.0] vs 23.4 [22.4-25.5) %, p < 0.001). Increased ECV was associated with male sex (p = 0.04), time with T2DM (p = 0.02), reduced peak VO2 (R2 = 0.48, p = 0.01), increased circulating choline (p = 0.002) and cysteamine (p = 0.002) both of which were also associated with reduced peak VO2 (p < 0.025 and 0.014 respectively). CONCLUSIONS: Patients with well-controlled T2DM without significant coronary disease exhibit focal and diffuse myocardial fibrosis and diffuse myocardial fibrosis is associated with reduced exercise tolerance and metabolites. Plasma metabolites may provide mechanistic insights into diffuse myocardial fibrosis, and cardiopulmonary fitness.

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.

A Clinical Update on Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) traditionally refers to abnormal glucose tolerance with onset or first recognition during pregnancy. GDM has long been associated with obstetric and neonatal complications primarily relating to higher infant birthweight and is increasingly recognized as a risk factor for future maternal and offspring cardiometabolic disease. The prevalence of GDM continues to rise internationally due to epidemiological factors including the increase in background rates of obesity in women of reproductive age and rising maternal age and the implementation of the revised International Association of the Diabetes and Pregnancy Study Groups' criteria and diagnostic procedures for GDM. The current lack of international consensus for the diagnosis of GDM reflects its complex historical evolution and pragmatic antenatal resource considerations given GDM is now 1 of the most common complications of pregnancy. Regardless, the contemporary clinical approach to GDM should be informed not only by its short-term complications but also by its longer term prognosis. Recent data demonstrate the effect of early in utero exposure to maternal hyperglycemia, with evidence for fetal overgrowth present prior to the traditional diagnosis of GDM from 24 weeks' gestation, as well as the durable adverse impact of maternal hyperglycemia on child and adolescent metabolism. The major contribution of GDM to the global epidemic of intergenerational cardiometabolic disease highlights the importance of identifying GDM as an early risk factor for type 2 diabetes and cardiovascular disease, broadening the prevailing clinical approach to address longer term maternal and offspring complications following a diagnosis of GDM.

Ramadan and gestational diabetes: maternal and neonatal outcomes.

AIMS: The impact of Ramadan exposure to Gestational Diabetes Mellitus (GDM) pregnancies is not known. We therefore aimed to assess the association of Ramadan with maternal and neonatal outcomes among pregnant women with GDM. METHODS: Retrospective cohort study of 345 Muslim women with singleton pregnancies who attended a major Sydney teaching hospital during the period 1989-2010, was undertaken. Exposure to Ramadan was stratified by the: (1) total pregnancy days exposed to Ramadan, (2) duration (hours) of daily fasting and (3) trimester of exposure. Maternal and neonatal outcomes were examined by exposure status, and never exposed pregnancies were comparator in all three analyses. Fasting status was not recorded. RESULTS: We found no significant effect of Ramadan exposure on mean birthweight, macrosomia and maternal outcomes. However, we found a significant trend for increased neonatal hyperbilirubinemia with increasing Ramadan days exposure and later trimester exposure (ptrend ≤ 0.02 for both), with adjusted OR 3.9 (p=0.03) for those with ≥ 21 days exposure to Ramadan and adjusted OR 4.3 (p=0.04) for third trimester exposure. Conversely longer Ramadan exposure and late trimester exposure were independently associated with a lower prevalence of neonatal hypoglycaemia (adjusted OR 0.4 and 0.3 for ≥ 21 days and third trimester exposure, respectively). Furthermore, neonatal hypoglycaemia decreased for the fasting period of > 15 h group (adjusted OR 0.2, p = 0.01). CONCLUSIONS: Ramadan exposure is associated with reduced neonatal hypoglycaemia, with no effect on birthweight, implying more favourable glycaemic control. However, the fourfold excess of neonatal hyperbilirubinemia indicates a need for further study of Ramadan and GDM.

Physicians' Perception About Use of Vitamin B12 in the Treatment or Prevention of Diabetic Neuropathy: A Cross-sectional Survey in Saudi Arabia.

BACKGROUND: Diabetic neuropathy is a condition that is prevalent among type 2 diabetic patients. Some physicians prescribe vitamin B12 or vitamin B complex supplements to improve symptoms, but studies have shown that there is little to no evidence of vitamin B12 being an effective treatment for diabetic neuropathy. Thus, this study aims to investigate local physicians' knowledge and tendency to prescribe vitamin B12 or vitamin B complex for the treatment or prevention of diabetic peripheral neuropathy. METHODS: It was a cross-sectional study, conducted between May and November of 2019, in several primary healthcare centers in different cities of Saudi Arabia. A total of 412 physicians with a minimum of three years of experience answered a three-part questionnaire on their demographic information, prescribing behavior, and knowledge of the relationship between vitamin B12 or vitamin B complex and diabetic neuropathy. RESULTS: The study found that only 42% of the physicians believed that vitamin B12 supplementation did not prevent diabetic neuropathy, while only 52.7% found it to be an ineffective treatment for this condition. Moreover, 58.7% stated that they had certainly prescribed vitamin B12 or multivitamins as a form of treatment or prevention of diabetic neuropathy. 47.8% of the patients requested a vitamin B12 prescription 1-6 times from their physicians, while 31.6% of them requested it ≥ 7 times, with 42.5% of physicians agreeing that their prescriptions of vitamin B12 had been a result of patient demand more than clinical justification. Likewise, 43% of respondents were aware that vitamin B12 levels should be tested annually. Furthermore, a higher proportion of consultants chose not to prescribe vitamin B12 to prevent or treat diabetic neuropathy than any other rank. CONCLUSION: The findings of this study indicate a tendency of unnecessarily prescribing vitamin B12 supplementation for the prevention or treatment of diabetic neuropathy as well as a lack of knowledge on the matter among doctors in primary care hospitals in Saudi Arabia. The study has also shown that there are patients who often request this prescription, adding pressure on their physicians to comply. Future studies should investigate most of the hospitals in Saudi cities and include less experienced residents and medical students.

Comparison of a subcutaneous versus intravenous insulin protocol for managing hyperglycemia following antenatal betamethasone in women with diabetes: a pilot randomized controlled trial.

INTRODUCTION: Evaluate the safety and efficacy of a subcutaneous insulin (SC-I) versus intravenous insulin (IV-I) protocol for optimizing maternal blood glucose levels (BGLs) post-betamethasone administration. METHODS: Randomized controlled in-patient pilot study in pregnant women with diabetes, excluding type 1 diabetes, receiving betamethasone ≥24 weeks' gestation. Interventions were stratified SC-I and IV-I protocols, titrated to hourly BGLs (IV-I) or predicted maternal hyperglycemia and 2-4 hourly BGLs (SC-I). Primary outcome was percentage at-target BGL 4.0-8.0 mmol/L over 48 h post-betamethasone. Secondary outcomes were rates of maternal hyperglycemia (>8.0 mmol/L), hypoglycemia (<4.0 mmol/L) and neonatal hypoglycemia (≤2.5 mmol/L). RESULTS: 19 women (3 with type 2 diabetes [T2DM], 4 with gestational diabetes [GDM]-diet, 12 GDM-insulin) were randomized to a SC-I (n = 13) or IV-I (n = 6) protocol in a 9-month period. There was a non-significant trend for higher mean percentage at-target BGLs with SC-I vs IV-I (87% vs 81%; p = .055); this was significant when the cohort was restricted to women with GDM (89% vs 81%; p = .04). Maternal hyperglycemia (85% vs 100%; p = .31) and hypoglycemia (54% vs 33%; p = .41) were not significantly different, but there were no BGLs <3.8 mmol/L with IV-I (vs 4 women with SC-I; p = .13). The rate of neonatal hypoglycemia was not different between groups. CONCLUSION: A SC-I or IV-I protocol controls maternal BGLs following betamethasone, but SC-I appears safe and minimizes labor intensive IV-I in GDM. An adequately powered RCT to assess superiority of SC-I is planned.

Testing the Feasibility and Dietary Impact of a "Produce Prescription" Program for Adults with Undermanaged Type 2 Diabetes and Food Insecurity in Australia.

BACKGROUND: There is growing interest in Food is Medicine programs that incorporate food-based interventions into health care for patients with diet-related conditions. OBJECTIVES: We aimed to test the feasibility of a "produce prescription" program and its impact on diet quality for people with type 2 diabetes (T2D) experiencing food insecurity in Australia. METHODS: We conducted a pre-post intervention study in n = 50 adults experiencing food insecurity with T2D and glycated hemoglobin (HbA1c) ≥8%. Once enrolled, participants received healthy food boxes weekly free of charge, with the contents sufficient to create 2 meals/d, 5 d/wk for the entire household, over 12 wk. Participants were also provided with tailored recipes and behavioral change support. The primary outcome was change in diet quality assessed by 24-h diet recalls. Secondary outcomes included differences in cardiovascular disease risk factors; blood micronutrients; and feasibility indicators. Differences in the baseline and 12-wk mean primary and secondary outcomes were assessed by paired t tests. RESULTS: Participants were older adults with mean ± SD age 63 ± 9 y (range: 40-87 y), HbA1c 9.8% ± 1.5%, and 46% were female. Overall, 92% completed the final study follow-up for the primary outcome. Compared with baseline, diet quality improved at week 12, with an increase in the mean overall diet quality (Alternate Healthy Eating Index score) of 12.9 (95% CI: 8.7, 17.1; P < 0.001), driven by significant improvements in vegetables, fruits, whole grains, red/processed meat, trans fat, sodium, and alcohol consumption. Blood lipids also improved (total:HDL cholesterol: -0.48; 95% CI: -0.72, -0.24; P < 0.001), and there was significant weight loss (-1.74 kg; 95% CI: -2.80, -0.68 kg, P = 0.002), but no changes in other clinical outcomes. Participants reported high levels of satisfaction with the program. CONCLUSIONS: These findings provide strong support for an adequately powered randomized trial to assess effects of produce prescription as an innovative approach to improve clinical management among individuals with T2D experiencing food insecurity. This trial was registered at https://anzctr.org.au/ as ACTRN12621000404820.

Young adult onset type 2 diabetes versus type 1 diabetes: Progression to and survival on renal replacement therapy.

BACKGROUND: Young-onset type 2 diabetes is an aggressive disease characterized by development of diabetic complications, including nephropathy, early in the disease course. However, within the cohort of young-onset type 1 and type 2 diabetes there are limited comparative data regarding progression to ESKD requiring renal replacement therapy or renal-related death (RRT/RRD). METHODS: Probabilistic linkage of data from the RPAH Diabetes Centre, National Death Index and Australian and New Zealand Dialysis and Transplant Registry was undertaken. Cumulative Incidence Competing Risk and Cox Proportional Hazards Modelling approaches were utilized to examine progression to ESKD in young-onset type 1 and type 2 diabetes (age of diagnosis 15-35 years). FINDINGS: Unadjusted incidence rates (95% CI) of RRT/RRD in young-onset type 1 and type 2 diabetes were 3.1 (2.3-4.0) and 4.6 (3.7-5.7) per 1000 person years respectively. After adjustment for gender, ethnicity and duration of diabetes, the HR (95% CI) of RRT/RRD in young-onset type 2 diabetes was 2.0 (1.4-2.9). The HR remained higher after further adjustment for first available cholesterol, HbA1c and systolic blood pressure but not BMI. For those who progressed to RRT, prognosis was similar irrespective of diabetes type; cumulative incidence of mortality was 40% in both young-onset type 1 and type 2 diabetes after 6 years of dialysis. INTERPRETATION: Progression to RRT/RRD is greater in young-onset type 2 diabetes than in young-onset type 1 diabetes. The increased progression is associated with increased BMI. However, once ESKD is reached, individuals with young-onset type 1 and type 2 diabetes do equally poorly.

An Enhanced SMS Text Message-Based Support and Reminder Program for Young Adults With Type 2 Diabetes (TEXT2U): Randomized Controlled Trial.

BACKGROUND: Clinic attendance, metabolic control, engagement in self-management, and psychological health are suboptimal in young-onset (age of onset <40 years) type 2 diabetes. OBJECTIVE: We examined the effectiveness of an enhanced SMS text message-based support and reminder program in improving clinic attendance, metabolic control, engagement in self-management, and psychological health in young-onset type 2 diabetes. METHODS: A 12-month, parallel-arm, randomized controlled trial comparing an enhanced, semipersonalized SMS text message-based intervention (incorporating 1-8 supportive and/or informative text messages per month) against standard care was conducted in a specialized clinic for young adult type 2 diabetes. The primary outcome was maintenance of 100% attendance at scheduled quarterly clinical appointments. Secondary outcomes included (1) metabolic indices, (2) pathology and self-monitored blood glucose (SMBG) data availability, and (3) psychosocial well-being. RESULTS: A total of 40 participants were randomized, and 32 completed their 12-month study visit. The average participant age was 32.7 (SD 5.1) years, 50% (20/40) were male, and baseline glycated hemoglobin A1c (HbA1c) was 7.3% (SD 1.9%) (56 mmol/mol, SD 20). A higher proportion of the intervention group achieved 100% attendance (12/21, 57%, vs 5/19, 26%, for the control group); Kaplan-Meier analysis demonstrated significantly greater cumulative attendance in the intervention group (P=.04). There were no between-group differences in HbA1c, BMI, lipids, or availability of pathology and SMBG data. Odds of recording an improvement in the Diabetes Empowerment Scale-Short Form score were higher in the intervention group at 6 months (odds ratio [OR] 4.3, 95% CI 1.1-17), with attenuation of this effect at study end (OR 3.1, 95% CI 0.9-11). Program acceptability was high; >90% of participants would recommend the program to new patients. CONCLUSIONS: An enhanced SMS text message-based support and reminder program doubled scheduled clinic attendance rates for patients with young-onset type 2 diabetes. The program was highly acceptable and provided early support for patient empowerment but had no significant effect on measures of metabolic control or self-management. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12618000479202); https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373579.

Monocyte phenotype as a predictive marker for wound healing in diabetes-related foot ulcers.

AIMS: Delayed healing of diabetes-related foot ulcers (DRFUs) is associated with increased macrophage and matrix metalloproteinases (MMPs) at the wound site. Whether circulating monocyte phenotype and/or MMPs are altered in association with wound healing outcome is unknown, and was investigated in this study. METHODS: Blood was obtained from 21 participants with DRFU, at initial visit (V1), week-4 (V2), and week-8 (V3) for measurement of monocyte number (CD14+), phenotype (CD16, CD163) and chemokine receptors (CCRs) by flow cytometry, and circulating MMPs and TIMP-1 by ELISA. RESULTS: Six wounds healed during the study. At V1, non-classical CD16++ monocytes and MMP-3 were higher in healed vs unhealed (both p < 0.05). At V3, the increased %CD16++ persisted and %CCR2+ was decreased in healed, but no other monocyte markers nor MMP/TIMP differed between groups. Increased wound closure rate (WCR) at V3 correlated with increased %CD16++ monocytes and decreased MMP-2 at V1 or V1 + V2. Receiver operating characteristic (ROC) curves yielded an area-under-the-curve of %CD16++ at V1 of 0.78 to predict ulcer healing at V3. CONCLUSIONS: These results indicate that circulating monocyte phenotype and MMPs alter as DRFUs heal. The relationship of %CD16++ monocytes with WCR and ROC curve suggest a predictive role of %CD16++ monocytes for ulcer healing.

Impact of age at type 2 diabetes mellitus diagnosis on mortality and vascular complications: systematic review and meta-analyses.

AIMS/HYPOTHESIS: Few studies examine the association between age at diagnosis and subsequent complications from type 2 diabetes. This paper aims to summarise the risk of mortality, macrovascular complications and microvascular complications associated with age at diagnosis of type 2 diabetes. METHODS: Data were sourced from MEDLINE and All EBM (Evidence Based Medicine) databases from inception to July 2018. Observational studies, investigating the effect of age at diabetes diagnosis on macrovascular and microvascular diabetes complications in adults with type 2 diabetes were selected according to pre-specified criteria. Two investigators independently extracted data and evaluated all studies. If data were not reported in a comparable format, data were obtained from authors, presented as minimally adjusted ORs (and 95% CIs) per 1 year increase in age at diabetes diagnosis, adjusted for current age for each outcome of interest. The study protocol was recorded with PROSPERO International Prospective Register of Systematic Reviews (CRD42016043593). RESULTS: Data from 26 observational studies comprising 1,325,493 individuals from 30 countries were included. Random-effects meta-analyses with inverse variance weighting were used to obtain the pooled ORs. Age at diabetes diagnosis was inversely associated with risk of all-cause mortality and macrovascular and microvascular disease (all p < 0.001). Each 1 year increase in age at diabetes diagnosis was associated with a 4%, 3% and 5% decreased risk of all-cause mortality, macrovascular disease and microvascular disease, respectively, adjusted for current age. The effects were consistent for the individual components of the composite outcomes (all p < 0.001). CONCLUSIONS/INTERPRETATION: Younger, rather than older, age at diabetes diagnosis was associated with higher risk of mortality and vascular disease. Early and sustained interventions to delay type 2 diabetes onset and improve blood glucose levels and cardiovascular risk profiles of those already diagnosed are essential to reduce morbidity and mortality. Graphical abstract.

The Safety and Efficacy of Second-Generation Basal Insulin Analogues in Adults with Type 2 Diabetes at Risk of Hypoglycemia and Use in Other Special Populations: A Narrative Review.

Hypoglycemia is a major barrier impeding glycemic control in persons with type 2 diabetes mellitus and creates a substantial burden on the healthcare system. Certain populations that require special attention, such as older adults and individuals with renal impairment, a longer duration of diabetes or those who have experienced prior hypoglycemia, may be at a higher risk of hypoglycemia, particularly with insulin treatment. Second-generation basal insulin analogues (insulin glargine 300 U/mL and degludec) have demonstrated reductions in hypoglycemia compared with insulin glargine 100 U/mL although evidence of this benefit across specific populations is less clear. In this review we summarize the literature with respect to the efficacy and safety data for second-generation basal insulin analogues in adults with type 2 diabetes mellitus who are at risk of hypoglycemia or who require special attention. Randomized controlled trials, meta-analyses and real-world evidence demonstrate that the use of second-generation basal insulin analogues is associated with less hypoglycemia compared with insulin glargine 100 U/mL without compromising glycated hemoglobin control. A reduced risk of hypoglycemia with second-generation basal insulin analogues was evident in older adults and in individuals with obesity, renal impairment, a history of cardiovascular disease or a long duration of insulin use. Further studies are needed in other populations, including those with more severe renal impairment or hepatic dysfunction, the hospitalized population and those with cognitive impairment. Overall, less hypoglycemia associated with second-generation basal insulin analogues may help reduce barriers for insulin use, improve adherence and offset the costs of hypoglycemia-related healthcare resource utilization.

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.

Screening, assessment and management of type 2 diabetes mellitus in children and adolescents: Australasian Paediatric Endocrine Group guidelines.

INTRODUCTION: The incidence of type 2 diabetes mellitus has increased in children and adolescents due largely to the obesity epidemic, particularly in high risk ethnic groups. ß-Cell function declines faster and diabetes complications develop earlier in paediatric type 2 diabetes compared with adult-onset type 2 diabetes. There are no consensus guidelines in Australasia for assessment and management of type 2 diabetes in paediatric populations and health professionals have had to refer to adult guidelines. Recent international paediatric guidelines did not address adaptations to care for patients from Indigenous backgrounds. MAIN RECOMMENDATIONS: This guideline provides advice on paediatric type 2 diabetes in relation to screening, diagnosis, diabetes education, monitoring including targets, multicomponent healthy lifestyle, pharmacotherapy, assessment and management of complications and comorbidities, and transition. There is also a dedicated section on considerations of care for children and adolescents from Indigenous background in Australia and New Zealand. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINES: Published international guidelines currently exist, but the challenges and specifics to care for children and adolescents with type 2 diabetes which should apply to Australasia have not been addressed to date. These include: recommendations regarding care of children and adolescents from Indigenous backgrounds in Australia and New Zealand including screening and management; tighter diabetes targets (glycated haemoglobin, ≤ 48 mmol/mol [≤ 6.5%]) for all children and adolescents; considering the use of newer medications approved for adults with type 2 diabetes under the guidance of a paediatric endocrinologist; and the need to transition adolescents with type 2 diabetes to a diabetes multidisciplinary care team including an adult endocrinologist for their ongoing care.

Secular Trends in Information Communications Technology: Access, Use, and Attitudes of Young and Older Patients With Diabetes.

BACKGROUND: Advances in information communications technology (ICT) provide opportunities for enhanced diabetes care. Knowledge of the more acceptable communication modalities in patients of different ages will help to inform the direction of future innovations. METHODS: An anonymous ICT survey (examining access and use of mobile phones, computers, tablets, and the Internet and attitudes toward e-mail, Web-based consultations, and online peer-support) was conducted at the Royal Prince Alfred Hospital Diabetes Centre in Sydney, Australia. Survey deployment occurred during 4-month periods in 2012 and 2017. Respondents were stratified by current age (<40 or ≥40 years). RESULTS: A total of 614 unselected patients (20% with type 1 diabetes, 55% with type 2 diabetes, 13% with gestational diabetes mellitus, and 12% with an undisclosed type of diabetes) completed the survey. Access to ICT increased from 89% in 2012 to 97% in 2017. The most commonly owned device was a mobile phone (87% ownership in 2017). Increase in mobile Internet usage in the <40 years of age subgroup was significant (P = 0.04). Significant increases in Internet access and smartphone feature use were observed in patients aged ≥40 years (P ≤0.001 for all). Overall use of short message service (SMS, or text messaging) was high (90 and 80% for ages <40 and ≥40 years, respectively). Use of digital applications was low, even among the young (45% in 2017). Comfort with online consultations (40%) and support groups (32%) was also low. CONCLUSION: Access to and acceptance and use of ICT is high, especially in those <40 years of age; however, the greatest increases were seen in those aged ≥40 years. High penetrance of mobile phones and text messaging in all age-groups would suggest that innovations involving an SMS platform have the greatest potential to enhance diabetes care.