Effects of the stress hyperglycemia ratio on long-term mortality in patients with triple-vessel disease and acute coronary syndrome.

AIMS: Risk assessment for triple-vessel disease (TVD) remain challenging. Stress hyperglycemia represents the regulation of glucose metabolism in response to stress, and stress hyperglycemia ratio (SHR) is recently found to reflect true acute hyperglycemic status. This study aimed to evaluate the prognostic value of SHR and its role in risk stratification in TVD patients with acute coronary syndrome (ACS). METHODS: A total of 3812 TVD patients with ACS with available baseline SHR measurement were enrolled from two independent centers. The endpoint was cardiovascular mortality. Cox regression was used to evaluate the association between SHR and cardiovascular mortality. The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) II (SSII) was used as the reference model in the model improvement analysis. RESULTS: During a median follow-up of 5.1 years, 219 (5.8%) TVD patients with ACS suffered cardiovascular mortality. TVD patients with ACS with high SHR had an increased risk of cardiovascular mortality after robust adjustment for confounding (high vs. median SHR: adjusted hazard ratio 1.809, 95% confidence interval 1.160-2.822, P = 0.009), which was fitted as a J-shaped pattern. The prognostic value of the SHR was found exclusively among patients with diabetes instead of those without diabetes. Moreover, addition of SHR improved the reclassification abilities of the SSII model for predicting cardiovascular mortality in TVD patients with ACS. CONCLUSIONS: The high level of SHR is associated with the long-term risk of cardiovascular mortality in TVD patients with ACS, and is confirmed to have incremental prediction value beyond standard SSII. Assessment of SHR may help to improve the risk stratification strategy in TVD patients who are under acute stress.

Adropin as a potential protective factor of metabolic complications in obese pregnant women with hyperglycaemia diagnosed in early pregnancy.

Adropin is a hormone which increases insulin sensitivity. It enhances the oxygenation of glucose in the muscles. The 91 obese pregnant women (BMI >30 kg/m2) with gestational diabetes mellitus (GDM) diagnosed in the first half of pregnancy has been recruited to the study group. The control group consisted of 10 age matched and homogeneous pregnant women with BMI <25 kg/m2. Blood samples were collected on visit V1 - between the 28th and 32nd week and on visit V2 - between the 37th and 39th week of gestation. The ELISA test was used to measure the adropin level. The results in the study group and the control group were compared. Blood samples were collected at the same visits. The median concentration of adropin was 442.2 pg/ml on V1 and 453.1 pg/ml on V2. The increase was significant (p<0.05). Results were significantly lower in the control group's patients, i.e. 57.0 pg/ml (p<0.001) on V1 and 107.9 pg/ml on V2 (p<0.001). The higher adropin level on the V1 and V2 visits were related to patients' lower BMI and better metabolic control. The increase in the adropin level in the third trimester may have been involved in the weight gain reduction, whereas better dietary adherence might have had a compensatory effect on increasing insulin resistance. However, the small control group is a limitation of this study.

Effects of Endocrine Metabolic Factors on Hemocyte Parameters, Tumor Markers, and Blood Electrolytes in Patients with Hyperglycemia.

Objective: This study was designed to investigate the effect of endocrine metabolic factors on hemocyte parameters, tumor markers, and blood electrolytes in patients with hyperglycemia. Methods: In this study, 1791 patients with hyperglycemia were recruited and grouped according to different testing indexes, and their medical records and laboratory indexes were recorded and analyzed. Results: In adult patients with hyperglycemia, we found that high-density lipoprotein cholesterol (HDL-C) was negatively correlated with white blood cell (WBC) and could exert an effect on WBC; triglyceride (TG) level was positively associated with lymphocyte (LYM#); age, TG, and P affected the level of LYM#; and uric acid (UA) level was positively related to eosinophil (EO#). Besides, age was positively correlated with red blood cell distribution width-coefficient of variation (RDW-CV) level; fasting blood glucose (FBG) and serum phosphorus (P) were negatively correlated with RDW-CV level; and age, creatinine (Cre), FBG, HDL-C, and P were influencing factors of RDW-CV level in adult hyperglycemic patients. HDL-C was negatively correlated with fibrinogen (Fib) level, and age, HDL-C, serum kalium (K), serum sodium (Na), and body mass index (BMI) were the influencing factors of Fib levels. TG was positively associated with neuron-specific enolase (NSE) level and affected the NSE level. Serum magnesium (Mg) was negatively related to carcinoembryonic antigen (CEA) level, and sex, age, FBG, Mg, and BMI could have an effect on CEA level. As well, age and FBG were positively associated with carbohydrate antigen 50 (CA50) levels, UA was negatively correlated with CA50 levels, and age, aspartate aminotransferase (AST), UA, and FBG were the influencing factors of CA50 levels. FBG was negatively related to Mg levels; K, serum zinc (Zn), and fasting C-peptide (C-P) were positively correlated with Mg levels; and FBG, K, Zn, and C-P had an effect on Mg levels. Conclusion: Endocrine metabolic factors are closely related to hemocyte parameters, tumor markers, and blood electrolytes in patients with hyperglycemia.

Lower versus Higher Glycemic Criteria for Diagnosis of Gestational Diabetes.

BACKGROUND: Treatment of gestational diabetes improves maternal and infant health, although diagnostic criteria remain unclear. METHODS: We randomly assigned women at 24 to 32 weeks' gestation in a 1:1 ratio to be evaluated for gestational diabetes with the use of lower or higher glycemic criteria for diagnosis. The lower glycemic criterion was a fasting plasma glucose level of at least 92 mg per deciliter (≥5.1 mmol per liter), a 1-hour level of at least 180 mg per deciliter (≥10.0 mmol per liter), or a 2-hour level of at least 153 mg per deciliter (≥8.5 mmol per liter). The higher glycemic criterion was a fasting plasma glucose level of at least 99 mg per deciliter (≥5.5 mmol per liter) or a 2-hour level of at least 162 mg per deciliter (≥9.0 mmol per liter). The primary outcome was the birth of an infant who was large for gestational age (defined as a birth weight above the 90th percentile according to Fenton-World Health Organization standards). Secondary outcomes were maternal and infant health. RESULTS: A total of 4061 women underwent randomization. Gestational diabetes was diagnosed in 310 of 2022 women (15.3%) in the lower-glycemic-criteria group and in 124 of 2039 women (6.1%) in the higher-glycemic-criteria group. Among 2019 infants born to women in the lower-glycemic-criteria group, 178 (8.8%) were large for gestational age, and among 2031 infants born to women in the higher-glycemic-criteria group, 181 (8.9%) were large for gestational age (adjusted relative risk, 0.98; 95% confidence interval, 0.80 to 1.19; P = 0.82). Induction of labor, use of health services, use of pharmacologic agents, and neonatal hypoglycemia were more common in the lower-glycemic-criteria group than in the higher-glycemic-criteria group. The results for the other secondary outcomes were similar in the two trial groups, and there were no substantial between-group differences in adverse events. Among the women in both groups who had glucose test results that fell between the lower and higher glycemic criteria, those who were treated for gestational diabetes (195 women), as compared with those who were not (178 women), had maternal and infant health benefits, including fewer large-for-gestational-age infants. CONCLUSIONS: The use of lower glycemic criteria for the diagnosis of gestational diabetes did not result in a lower risk of a large-for-gestational-age infant than the use of higher glycemic criteria. (Funded by the Health Research Council of New Zealand and others; GEMS Australian New Zealand Clinical Trials Registry number, ACTRN12615000290594.).

Impact of prolonged requirement for insulin on 90-day mortality in critically ill patients without previous diabetic treatments: a post hoc analysis of the CONTROLING randomized control trial.

BACKGROUND: Stress hyperglycemia can persist during an intensive care unit (ICU) stay and result in prolonged requirement for insulin (PRI). The impact of PRI on ICU patient outcomes is not known. We evaluated the relationship between PRI and Day 90 mortality in ICU patients without previous diabetic treatments. METHODS: This is a post hoc analysis of the CONTROLING trial, involving 12 French ICUs. Patients in the personalized glucose control arm with an ICU length of stay ≥ 5 days and who had never previously received diabetic treatments (oral drugs or insulin) were included. Personalized blood glucose targets were estimated on their preadmission usual glycemia as estimated by their glycated A1c hemoglobin (HbA1C). PRI was defined by insulin requirement. The relationship between PRI on Day 5 and 90-day mortality was assessed by Cox survival models with inverse probability of treatment weighting (IPTW). Glycemic control was defined as at least one blood glucose value below the blood glucose target value on Day 5. RESULTS: A total of 476 patients were included, of whom 62.4% were male, with a median age of 66 (54-76) years. Median values for SAPS II and HbA1C were 50 (37.5-64) and 5.7 (5.4-6.1)%, respectively. PRI was observed in 364/476 (72.5%) patients on Day 5. 90-day mortality was 23.1% in the whole cohort, 25.3% in the PRI group and 16.1% in the non-PRI group (p < 0.01). IPTW analysis showed that PRI on Day 5 was not associated with Day 90 mortality (IPTWHR = 1.22; CI 95% 0.84-1.75; p = 0.29), whereas PRI without glycemic control was associated with an increased risk of death at Day 90 (IPTWHR = 3.34; CI 95% 1.26-8.83; p < 0.01). CONCLUSION: In ICU patients without previous diabetic treatments, only PRI without glycemic control on Day 5 was associated with an increased risk of death. Additional studies are required to determine the factors contributing to these results.

Efficacy of Glucocorticoids and Glucocorticoid-Induced Hyperglycaemia in Renal Disease: A Meta-Analysis of Randomized Controlled Trials.

Background: Glucocorticoids are the most effective anti-inflammatory and immunosuppressive drugs used to treat patients with renal disease. This study pooled the current evidence of the efficacy of Glucocorticoids and Glucocorticoid-induced hyperglycaemia in renal disease. Methods: We conducted a systematic literature search on PubMed, Cochrane Central, and Web of Science for relevant randomized controlled trials (RCTs) up to September 1, 2021. The meta-analysis, sensitivity analysis and bias analysis were performed using Review Manager 5. 3. Results: In this study, seven RCTs with 797 patients were included in our analysis. The analysis revealed that glucocorticoids had a certain alleviating effect on the reduction of renal function. (risk ratio [RR] 0.49 95% confidence interval [Cl] 0. 28 to 0.85, p =0.01) and reduction of proteinuria (weight mean difference [WMD] -0.43; 95% CI -0.57 to-0.28) when compared with the control group. Patients receiving glucocorticoids therapy did not have an increased risk of developing new-onset diabetes mellitus or impaired glucose tolerance. (RR 3.76 95% CI 0.54 to 26.10, p =0.18). For other safety outcomes, glucocorticoids therapy did not increase risk of respiratory infections (RR 1.63, 95% CI 0. 69to3. 89, p =0.27) and Gastrointestinal SAEs is relatively controversial (RR 1.10, 95% CI 0.32 to 3.79, p =0.88). Discussion. In conclusion, current clinical evidence indicates that glucocorticoids is efficacious and safe to renal disease compared with control. Further research comparing long-term glucocorticoids use is needed.

GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia.

Severe cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with elevated blood glucose levels and metabolic complications. However, the molecular mechanisms for how SARS-CoV-2 infection alters glycometabolic control are incompletely understood. Here, we connect the circulating protein GP73 with enhanced hepatic gluconeogenesis during SARS-CoV-2 infection. We first demonstrate that GP73 secretion is induced in multiple tissues upon fasting and that GP73 stimulates hepatic gluconeogenesis through the cAMP/PKA signaling pathway. We further show that GP73 secretion is increased in cultured cells infected with SARS-CoV-2, after overexpression of SARS-CoV-2 nucleocapsid and spike proteins and in lungs and livers of mice infected with a mouse-adapted SARS-CoV-2 strain. GP73 blockade with an antibody inhibits excessive glucogenesis stimulated by SARS-CoV-2 in vitro and lowers elevated fasting blood glucose levels in infected mice. In patients with COVID-19, plasma GP73 levels are elevated and positively correlate with blood glucose levels. Our data suggest that GP73 is a glucogenic hormone that likely contributes to SARS-CoV-2-induced abnormalities in systemic glucose metabolism.

Admission Hyperglycemia in Acute Type A Aortic Dissection Predicts for a Prolonged Duration of Mechanical Ventilation.

Previous studies have demonstrated that admission hyperglycemia is a predictor of mortality and poor prognosis in patients with cardiovascular diseases, such as acute myocardial infarction. However, the prognostic value of admission hyperglycemia in patients with acute type A aortic dissection (AAAD) has never been explored. To clarify the association between hyperglycemia and in-hospital outcomes, we retrospectively analyzed 734 patients with AAAD. The interest endpoints were in-hospital mortality rate, the duration of intensive care unit and hospital stays, the occurrence of prolonged mechanical ventilation (PMV), and other complications. All patients were divided into the normal blood glucose group (≤ 140 mg/dL) and hyperglycemia group (> 140 mg/dL), to compare the in-hospital outcomes rate in the two groups. There were 531 (72.3%) patients with normal blood glucose levels and 203 (27.7%) patients with hyperglycemia. The in-hospital mortality rate was 21.1%, and no statistically significant differences were found between the two groups (20.3% versus 23.2%, P = 0.403). PMV is the most frequent postoperative complication, the incidence of which was significantly higher in the hyperglycemia group than in the normal blood glucose group (59.6% versus 50.8%, P = 0.040). The logistic regression analysis revealed that hyperglycemia (odds ratio (OR): 1.492; 95% CI: 1.014 to 2.197; P = 0.042) was an independent risk factor for PMV after adjusting for confounding factors. Age (OR: 1.021; 95% CI: 1.006-1.037; P = 0.007) and body mass index (OR: 1.101; 95% CI: 1.051-1.153; P < 0.001) were also associated with PMV. In conclusion, our study showed for the first time that a strong correlation between admission hyperglycemia and increased postoperative PMV in patients with AAAD, but not with in-hospital mortality rate.

Serum levels of 4-hydroxynonenal adducts and responding autoantibodies correlate with the pathogenesis from hyperglycemia to Alzheimer's disease.

OBJECTIVE: Hyperglycemia leads to lipid peroxidation, producing 4-hydroxynonenal (HNE) adducts which correlate with the production of amyloid-beta (Aß), one of the hallmarks of Alzheimer's disease (AD). This study is to investigate the interactions of Aß, HNE adducts and responding autoantibodies during the pathogenesis from hyperglycemia to AD. METHODS: A total of 239 Taiwanese serum samples from a healthy control group and patients with hyperglycemia, and AD with and without hyperglycemia were analyzed. Aß was immunoprecipitated from randomly pooled serum in each group and immunoblotted. Synthetic Aß1-16 and Aß17-28 peptides were modified with HNE in vitro and verified with LC-MS/MS. The levels of Aß, HNE adducts, and autoantibody isotypes IgG and IgM against either native or HNE-modified Aß were determined with ELISA. The diagnostic power of potential biomarkers was evaluated. RESULTS: Increased fasting glucose and decreased high-density-lipoprotein cholesterol in AD groups indicated abnormal metabolism in the pathogenesis progression from hyperglycemia to AD. Indeed, serum Aß, HNE adducts and most of the autoantibodies recognizing either native or HNE-modified Aß were increased in the diseased groups. However, HNE adducts had better diagnostic performances than Aß for both hyperglycemia and AD. Additionally, HNE-Aß peptide levels were increased, and the responding autoantibodies (most notably IgM) were decreased in hyperglycemic AD group compared to the hyperglycemia only group, suggesting an immunity disturbance in the pathogenesis progression from hyperglycemia to AD. CONCLUSION: Hyperglycemia increases the level of HNE adducts which may be neutralized by responding autoantibodies. Depletion of these autoantibodies promotes AD-like pathogenesis. Thus, levels of a patient's HNE adducts and associated responding autoantibodies are potential biomarkers for AD with diabetes.

Gain of Function of Malate Dehydrogenase 2 and Familial Hyperglycemia.

CONTEXT: Genes causing familial forms of diabetes mellitus are only partially known. OBJECTIVE: We set out to identify the genetic cause of hyperglycemia in multigenerational families with an apparent autosomal dominant form of adult-onset diabetes not due to mutations in known monogenic diabetes genes. METHODS: Existing whole-exome sequencing (WES) data were used to identify exonic variants segregating with diabetes in 60 families from the United States and Italy. Functional studies were carried out in vitro (transduced MIN6-K8 cells) and in vivo (Caenorhabditis elegans) to assess the diabetogenic potential of 2 variants in the malate dehydrogenase 2 (MDH2) gene linked with hyperglycemia in 2 of the families. RESULTS: A very rare mutation (p.Arg52Cys) in MDH2 strongly segregated with hyperglycemia in 1 family from the United States. An infrequent MDH2 missense variant (p.Val160Met) also showed disease cosegregation in a family from Italy, although with reduced penetrance. In silico, both Arg52Cys and Val160Met were shown to affect MDH2 protein structure and function. In transfected HepG2 cells, both variants significantly increased MDH2 enzymatic activity, thereby decreasing the NAD+/NADH ratio-a change known to affect insulin signaling and secretion. Stable expression of human wild-type MDH2 in MIN6-K8 cell lines enhanced glucose- and GLP-1-stimulated insulin secretion. This effect was blunted by the Cys52 or Met160 substitutions. Nematodes carrying equivalent changes at the orthologous positions of the mdh-2 gene showed impaired glucose-stimulated insulin secretion. CONCLUSION: Our findings suggest a central role of MDH2 in human glucose homeostasis and indicate that gain of function variants in this gene may be involved in the etiology of familial forms of diabetes.

The performance of glycated albumin as a biomarker of hyperglycemia and cardiometabolic risk in children and adolescents in the United States.

OBJECTIVE: Diabetes and prediabetes are growing concerns among US youth. Fasting glucose (FG) and HbA1c are standard diabetes screening tests, but HbA1c may be unreliable in some settings and fasting is burdensome in children. Glycated albumin (GA) is a non-fasting test that was recently cleared for clinical use in the United States, but studies in youth without diabetes are limited. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional analysis in 6826 youth without diabetes aged 8-19 years in the 1999-2004 National Health and Nutrition Examination Survey. We evaluated the associations of GA with HbA1c, FG, and cardiometabolic risk factors. RESULTS: GA was poorly correlated with HbA1c (ρ = 0.074) and FG (ρ = -0.047) and was negatively associated with body mass index (BMI) and cardiometabolic risk factors. Compared to youth in the highest tertile of GA (≥13.5%), those in the lowest GA tertile (<12.4%) had a higher prevalence of obesity (29.9% vs. 7.6%), low high-density lipoprotein cholesterol (29.7% vs. 16.5%), and hypertensive blood pressure (4.0% vs. 2.7%). These inverse associations persisted after adjustment for age, sex, race/ethnicity, serum albumin, and C-reactive protein. CONCLUSIONS: GA was poorly correlated with traditional markers of hyperglycemia in youth without diabetes. Counterintuitively, there was a negative association between GA and BMI. Among youth without diabetes, GA does not identify youth at high cardiometabolic risk, and it does not appear to be an appropriate biomarker for screening of hyperglycemia.

Variations in Sleep Characteristics and Glucose Regulation in Young Adults With Type 1 Diabetes.

CONTEXT: Short sleep duration and sleep disruptions are associated with impaired glucoregulation in type 1 diabetes (T1D). However, the mechanistic pathways between sleep and glucose variability remain unclear. OBJECTIVE: To determine within- and between-person associations between objective sleep-wake characteristics and glucose variability indices. METHODS: Multilevel models were used to analyze concurrent sleep and glucose patterns over 7 days in 42 young adults with T1D in their natural home environment. Young adults with T1D (mean age 22.2 ± 3.0 years, HbA1c 7.2%, 32.6% male) for at least 6 months with no other medical or major psychiatric comorbidity were included. Sleep-wake characteristics were measured via wrist actigraphy and glucose variability indices via a continuous glucose monitor (CGM). RESULTS: Lower sleep efficiency predicted higher glucose variability (less time in range ß = 0.011 and more time in hyperglycemia ß = -0.011) within-person. A longer wake after sleep onset and more sleep disruptions were associated with higher glucose variability between persons (ß = 0.28 and 0.31). Higher glucose variability predicted poorer sleep within-person (delayed bedtime, waketime, mid-sleep time, and lower sleep efficiency), while higher glucose variability was associated with poorer sleep and more sleep disruptions between persons (lower sleep efficiency, longer wake after sleep onset, and a higher sleep fragmentation index). CONCLUSION: Clinicians can address the reciprocal nature of the sleep-glucose relationship by optimizing sleep and targeting efforts toward a euglycemic range overnight. Sleep habits are a modifiable personal target in diabetes care.

A high-fat diet catalyzes progression to hyperglycemia in mice with selective impairment of insulin action in Glut4-expressing tissues.

Insulin resistance impairs postprandial glucose uptake through glucose transporter type 4 (GLUT4) and is the primary defect preceding type 2 diabetes. We previously generated an insulin-resistant mouse model with human GLUT4 promoter-driven insulin receptor knockout (GIRKO) in the muscle, adipose, and neuronal subpopulations. However, the rate of diabetes in GIRKO mice remained low prior to 6 months of age on normal chow diet (NCD), suggesting that additional factors/mechanisms are responsible for adverse metabolic effects driving the ultimate progression of overt diabetes. In this study, we characterized the metabolic phenotypes of the adult GIRKO mice acutely switched to high-fat diet (HFD) feeding in order to identify additional metabolic challenges required for disease progression. Distinct from other diet-induced obesity (DIO) and genetic models (e.g., db/db mice), GIRKO mice remained leaner on HFD feeding, but developed other cardinal features of insulin resistance syndrome. GIRKO mice rapidly developed hyperglycemia despite compensatory increases in ß-cell mass and hyperinsulinemia. Furthermore, GIRKO mice also had impaired oral glucose tolerance and a limited glucose-lowering benefit from exendin-4, suggesting that the blunted incretin effect contributed to hyperglycemia. Secondly, GIRKO mice manifested severe dyslipidemia while on HFD due to elevated hepatic lipid secretion, serum triglyceride concentration, and lipid droplet accumulation in hepatocytes. Thirdly, GIRKO mice on HFD had increased inflammatory cues in the gut, which were associated with the HFD-induced microbiome alterations and increased serum lipopolysaccharide (LPS). In conclusion, our studies identified important gene/diet interactions contributing to diabetes progression, which might be leveraged to develop more efficacious therapies.

The mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus.

The most common complication during pregnancy, gestational diabetes mellitus (GDM), can cause adverse pregnancy outcomes and result in the mother and infant having a higher risk of developing type 2 diabetes after pregnancy. However, existing therapies for GDM remain scant, with the most common being lifestyle intervention and appropriate insulin treatment. MOTS-c, a mitochondrial-derived peptide, can target skeletal muscle and enhance glucose metabolism. Here, we demonstrate that MOTS-c can be an effective treatment for GDM. A GDM mouse model was established by short term high-fat diet combined with low-dose streptozotocin (STZ) treatment while MOTS-c was administrated daily during pregnancy. GDM symptoms such as blood glucose and insulin levels, glucose and insulin tolerance, as well as reproductive outcomes were investigated. MOTS-c significantly alleviated hyperglycemia, improved insulin sensitivity and glucose tolerance, and reduced birth weight and the death of offspring induced by GDM. Similar to a previous study, MOTS-c also could activate insulin sensitivity in the skeletal muscle of GDM mice and elevate glucose uptake in vitro. In addition, we found that MOTS-c protects pancreatic ß-cell from STZ-mediated injury. Taken together, our findings demonstrate that MOTS-c could be a promising strategy for the treatment of GDM.

Does introduction of continuous glucose monitoring at diagnosis of type 1 diabetes increase uptake in children and adolescents?

OBJECTIVE: To assess whether introduction of continuous glucose monitoring (CGM) at diagnosis of type 1 diabetes (T1D), leads to greater uptake and continuation at 12 and 24 months, in a population-based pediatric diabetes clinic. RESEARCH DESIGN AND METHODS: All T1D children and adolescents diagnosed in the 12 months following full government subsidization of CGM were offered CGM from diagnosis at Women's and Children's Hospital, SA (Cohort 1). Uptake and continuation of CGM was compared to those diagnosed in the preceding year, who were started on CGM after diagnosis, but otherwise had identical diabetes management (Cohort 2). Demographic and clinical data were collected prospectively. The primary outcome variable was CGM wear >75% of the time at 12 and 24 months. RESULTS: In Cohort 1, 84% were started on CGM at diagnosis. 88% had commenced CGM by 12 months and 90% by 24 months. In Cohort 2, CGM was started on average 10 months after diagnosis (range 1-25 months), with 81% started on CGM within 24 months of subsidization. At 24 months, 78% of Cohort 1 and 66% of Cohort 2 were wearing CGM >75% of the time (p = 0.26), higher than the WCH Clinic as a whole (58%). There was no difference in HbA1c between cohorts. CONCLUSION: Starting CGM at diagnosis of T1D is feasible and well received by families, with high uptake across all ages. Although CGM continuation (wearing CGM >75% of the time) was slightly higher in Cohort 1 than Cohort 2, this did not reach statistical significance.

Effects of Dietary Fat and Protein on Glucoregulatory Hormones in Adolescents and Young Adults With Type 1 Diabetes.

CONTEXT: Dietary fat and protein impact postprandial hyperglycemia in people with type 1 diabetes, but the underlying mechanisms are poorly understood. Glucoregulatory hormones are also known to modulate gastric emptying and may contribute to this effect. OBJECTIVE: Investigate the effects of fat and protein on glucagon-like peptide (GLP-1), glucagon-dependent insulinotropic polypeptide (GIP) and glucagon secretion. METHODS: 2 crossover euglycemic insulin clamp clinical trials at 2 Australian pediatric diabetes centers. Participants were 12-21 years (n = 21) with type 1 diabetes for ≥1 year. Participants consumed a low-protein (LP) or high-protein (HP) meal in Study 1, and low-protein/low-fat (LPLF) or high-protein/high-fat (HPHF) meal in Study 2, all containing 30 g of carbohydrate. An insulin clamp was used to maintain postprandial euglycemia and plasma glucoregulatory hormones were measured every 30 minutes for 5 hours. Data from both cohorts (n = 11, 10) were analyzed separately. The main outcome measure was area under the curve of GLP-1, GIP, and glucagon. RESULTS: Meals low in fat and protein had minimal effect on GLP-1, while there was sustained elevation after HP (80.3 ± 16.8 pmol/L) vs LP (56.9 ± 18.6), P = .016, and HPHF (103.0 ± 26.9) vs LPLF (69.5 ± 31.9) meals, P = .002. The prompt rise in GIP after all meals was greater after HP (190.2 ± 35.7 pmol/L) vs LP (152.3 ± 23.3), P = .003, and HPHF (258.6 ± 31.0) vs LPLF (151.7 ± 29.4), P < .001. A rise in glucagon was also seen in response to protein, and HP (292.5 ± 88.1 pg/mL) vs LP (182.8 ± 48.5), P = .010. CONCLUSION: The impact of fat and protein on postprandial glucose excursions may be mediated by the differential secretion of glucoregulatory hormones. Further studies to better understand these mechanisms may lead to improved personalized postprandial glucose management.

Vitamin D Levels Are Associated With Blood Glucose and BMI in COVID-19 Patients, Predicting Disease Severity.

CONTEXT: A high prevalence of vitamin D (VD) deficiency in COVID-19 patients has been reported and hypothesized to increase COVID-19 severity likely because of its negative impact on immune and inflammatory responses. Furthermore, clear associations between hypovitaminosis D and fat body mass excess and diabetes, factors associated with COVID-19 severity, have been widely recognized. OBJECTIVE: The aim of this study was to evaluate in COVID-19 patients the relationship between VD levels and inflammatory response, body mass index (BMI), blood glucose (GLU), and disease severity. METHODS: Patients admitted to San Raffaele-Hospital for COVID-19 were enrolled in this study, excluding those with comorbidities and therapies influencing VD metabolism. 25-Hydroxyvitamin D levels, plasma GLU levels, BMI, and inflammatory parameters were evaluated at admission. RESULTS: A total of 88 patients were included. Median VD level was 16.3 ng/mL and VD deficiency was found in 68.2% of patients. VD deficiency was found more frequently in male patients and in those affected by severe COVID-19. Regression analyses showed a positive correlation between VD and PaO2/FiO2 ratio, and negative correlations between VD and plasma GLU, BMI, neutrophil/lymphocyte ratio, C-reactive protein, and interleukin 6. Patients with both hypovitaminosis D and diabetes mellitus, as well those with hypovitaminosis D and overweight, were more frequently affected by a severe disease with worse inflammatory response and respiratory parameters, compared to those without or just one of these conditions. CONCLUSION: We showed, for the first-time, a strict association of VD levels with blood GLU and BMI in COVID-19 patients. VD deficiency might be a novel common pathophysiological mechanism involved in the detrimental effect of hyperglycemia and adiposity on disease severity.

Characterization and risk factors of hyperglycaemia during treatment of childhood hematologic malignancies.

BACKGROUND: Secondary forms of diabetes are often understudied and underdiagnosed in children and adolescents with cancer. The objectives of our cohort study were to study the incidence and risk factors for hyperglycaemia in leukaemia and lymphoma patients. METHODS: We retrospectively collected 15 years of data from paediatric patients treated for acute lymphoblastic leukaemia (ALL), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL) immediately at cancer diagnosis. We studied risk factors for hyperglycaemia in univariate and multivariate analyses. RESULTS: Our study cohort included 267 patients corresponding to 179 patients with ALL, 48 with NHL and 40 with HL. Eighteen per cent of ALL patients (32/179) and 17% of NHL patients (8/48) developed hyperglycaemia, with more than 61% developing hyperglycaemia within the first month of treatment. No hyperglycaemia was observed in HL patients. Multivariate analysis showed the following hyperglycaemia risk factors for ALL patients: overweight or obesity (OR 3.793) and pubertal onset (OR 4.269) at cancer diagnosis, steroid-resistant disease (OR 3.445) and hematopoietic stem cell transplant (HSCT) (OR 4.754). CONCLUSION: In our cohort, 18% of patients with ALL or NHL developed early-onset hyperglycaemia after chemotherapy/radiotherapy. Patients with ALL with increased hyperglycaemia risk can be readily identified by measuring BMI and puberty stage at cancer diagnosis. Also, glucose monitoring should be reinforced when patients show steroid-resistant disease and/or require HSCT.