Impaired Glycemic Control Research Articles

LBSUN151 The Impact Of The COVID-19 Pandemic On Diabetes & Weight Management

Abstract COVID-19 was declared a pandemic on 03/11/2020 by the WHO and the State of Minnesota issued a stay-at-home mandate on 03/27/2020. While individuals with diabetes mellitus (DM) and severe obesity were identified as more likely to be infected and at higher risk of complications from COVID-19, access to outpatient clinics was limited during this time, with a shift towards telemedicine. In June 2020, the WHO reported that in 49% of 155 surveyed countries, diabetes treatment was disrupted. However, the impact on diabetes care in the US was poorly characterized, particularly among underserved groups. Aim To study the impact of the pandemic and telemedicine on medical treatment of patients with DM at Hennepin County Medical Center (HCMC), a teaching hospital in Minneapolis, Minnesota serving a diverse inner-city population. Methods Retrospective cohort study design with 710 participants. We compared A1C and weight changes before and after the pandemic. The study group (n=344) included patients, 18 years of age or older, with DM Type 1 or Type 2 who presented for an HCMC diabetes clinic visit between 12/2019-02/2020 and a follow up visit between 6/2020 -10/2020. The control group (n=366) included patients with DM who presented for an HCMC diabetes clinic visit between 12/2018 - 02/2019 and a follow up visit between 6/2019 - 10/2019. Results There was a significantly lower A1C reduction in the cases as compared to the control group (-0.34 [CI -0.59, -0. 09] p value 0. 007), adjusted for inpatient admission, continuous glucose monitor use, diabetes type 1, insurance status, insulin use, GLP-1 agonist use, smoking status and hypertension. Weight reduction during the pandemic was lower as compared to the control but did not achieve statistical significance (-0.96 [CI -3. 02, 1. 09] p value 0.36). Telemedicine use among the study group resulted in an insignificant A1c reduction of -0.24 (p value 0.23). There was statistically significant weight gain of 0.42 among the group who used telemedicine, while nonusers had weight loss of -3.24 (p value 0. 04). Telemedicine users had higher insulin utilization (92.6% vs 83.3%, p value 0. 017) and lower self-pay and Medicaid enrollment (1.7% vs 5.9% and 33.8% vs 40.6% respectively, p value 0. 011) as compared to nonusers. Conclusion The COVID-19 pandemic led to a significant deterioration of glycemic control but had no effect on weight. Telemedicine use led to A1c reduction but did not reach statistical significance potentially due to the small sample size and short duration of follow up. Significant weight gain was observed in telemedicine users influenced by greater insulin use and insurance coverage as compared to weight loss amongst nonusers which may be attributed to socioeconomic barriers such as food scarcity among those without the means to access telemedicine. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Parasympathetic tonus in type 2 diabetes and pre-diabetes and its clinical implications

Autonomic imbalance reflected by higher resting heart rate and reduced parasympathetic tone may be driven by low-grade inflammation (LGI) and impaired glycemic control in type 2 diabetes mellitus (T2DM) and pre-diabetes. We examined the interaction of parasympathetic components of heart rate variability (HRV), variables of LGI, and glucose metabolism in people with T2DM, pre-diabetes, and normal glucose metabolism (NGM). We recorded HRV by Holter (48 h) in 633 community-dwelling people of whom T2DM n = 131, pre-diabetes n = 372, and NGM n = 130 and mean HbA1c of 7.2, 6.0 and 5.3%, respectively. Age was 55–75 years and all were without known cardiovascular disease except from hypertension. Fasting plasma glucose, fasting insulin, HOMA-IR, HbA1c and LGI (CRP, Interleukin-18 (IL-18), and white blood cells) were measured. Root-mean-square-of-normal-to-normal-beats (RMSSD), and proportion of normal-to-normal complexes differing by more than 50 ms (pNN50) are accepted measures of parasympathetic activity. In univariate analyses, RMSSD and pNN50 were significantly inversely correlated with level of HbA1c and CRP among people with T2DM and pre-diabetes, but not among NGM. RMSSD and pNN50 remained significantly inversely associated with level of HbA1c after adjusting for age, sex, smoking, and BMI among people with T2DM (β = − 0.22) and pre-diabetes (β = − 0.11); adjustment for LGI, HOMA-IR, and FPG did not attenuate these associations. In backward elimination models, age and level of HbA1c remained associated with RMSSD and pNN50. In people with well controlled diabetes and pre-diabetes, a lower parasympathetic activity was more related to age and HbA1c than to markers of LGI. Thus, this study shows that the driver of parasympathetic tonus may be more the level of glycemic control than inflammation in people with prediabetes and well controlled diabetes.

Functional and biochemical characteristics of the muscle system in children with type I diabetes

Background. The purpose of the study was to determine possible markers of skeletal muscle damage in children with type 1 diabetes mellitus (T1DM) and their relationship with the features of disease course. Materials and methods. The observation group consisted of 98 children with type 1 diabetes mellitus: the first group included 22 people without disorders of the muscular system; the second — 42 patients with dynapenia; the third — 34 children with diabetic myopathy. Control group — 30 relatively healthy children. Assessment of the static endurance of skeletal muscles, determination of the level of creatine kinase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, periostin and cardiotrophin-1 in blood serum were performed in all patients. Results. The conducted studies demonstrate that children with diabetes, regardless of the structural and functional state of their muscular system, have signs of skeletal muscle damage, which were most expressed in diabetic myopathy and progressed with maximal deterioration of glycemic control. It was found that the highest content of alkaline phosphatase was characteristic of children from group 1, while in patients with diabetic myopathy its serum content was not statistically different from that of controls. These disorders occurred against the background of changes in alkaline phosphatase activity, the level of which was highest in children from group 1, while in patients with diabetic myopathy, its serum content was not statistically different from that of controls. At the same time, during the course of diabetic myopathy in children with T1DM, there was an increase in lactate dehydrogenase activity by 1.2 times (p < 0.01) and cardiotrophin-1 by 300 times (p < 0.01) compared to the corresponding indicator of the control group. Serum periostin level was increased in all patients with T1DM. Its maximum values were determined in group 1, whose periostin concentration exceeded control indicators by 103 times (p < 0.01). With deterioration of skeletal muscle state, there was a gradual decrease in periostin serum level, but in patients with dynapenia, it was 35.5 times higher than in the control group (p < 0.05) and 19.2 times higher in those with diabetic myopathy (p < 0.05). Conclusions. The course of type 1 diabetes in children is accompanied by skeletal muscle damage, the first clinical sign of which is a decrease in the static muscle endurance against the background of worsening disease course. Alkaline phosphatase, lactate dehydrogenase, periostin, and cardiotrophin-1 are biochemical markers of skeletal muscle damage in children with type 1 diabetes. A common feature of the changes in the specified indicators is their increase; however, each clinical condition of the skeletal muscles corresponds to its own configuration of changes in the abovementioned markers.

ISPAD Clinical Practice Consensus Guidelines 2022: Diabetes in adolescence.

ISPAD Clinical Practice Consensus Guidelines 2022: Diabetes in adolescence.

Impact of high-intensity statin therapy on glycemic control post-acute coronary syndrome using real-world data

Abstract Background Statins use has been linked with increased risk of new onset diabetes and impaired glycemic control in the JUPITER trial and meta-analyses of randomized controlled trials. Nevertheless, the evidence is scarce in the real-world clinical settings, particularly among those receiving high-intensity statin post-acute coronary syndrome (ACS). Methods We conducted a retrospective observational study to determine the impact of statin use post-ACS on glycosylated hemoglobin (HbA1c) and the incidence of diabetes. The study included adults admitted with ACS between January 1, 2017 and December 31, 2018 and newly started on a high-intensity statin (rosuvastatin or atorvastatin). The outcomes assessed within 12 months of statin initiation were: (a) HbA1c before and after statin use among diabetic and non-diabetic patients; (b) incidence of diabetes. Paired sample t-test was used to compare HbA1c values pre and post statin use. Results Of the 1,253 patients included, 627 received rosuvastatin and 626 received atorvastatin following ACS. Most of the patients were Asian (77.3%), male (95.8%) with a median age of 51 years. The baseline HbA1c was 7.2±2.2% and 45% of the study population were diabetic at baseline. Among non-diabetic patients, statin use resulted in HbA1c increase from 5.7±0.7% to 6.0±0.8%, p<0.001, while among diabetic patients who were receiving treatment for diabetes, HbA1c decreased from 8.8±1.9% to 7.8±1.9%, p<0.001. New onset diabetes occurred in 41 (6%) of the non-diabetic patients, of whom 13 (1.9%) were receiving atorvastatin, while 28 (4.1%) were on rosuvastatin, p-value = 0.032. The use of both statins resulted in a significant increase of HbA1c among non-diabetic patients as demonstrated in Figure 1. Conclusion High intensity statin post-ACS was associated with increased HbA1c among non-diabetic patients. In particular, rosuvastatin significantly increased the new onset of diabetes compared to atorvastatin which might provide preference of atorvastatin use over rosuvastatin among non-diabetic patients post-acute coronary syndrome. Funding Acknowledgement Type of funding sources: None.

Postprandial glycemic responses to a high-protein dairy snack and energy-enriched berry snacks in older adults.

We have previously shown that regular consumption of high-protein dairy- and energy-enriched berry-based products consumed as snacks improved nutritional status, functional status, and quality of life among vulnerable older people. These products contain protein, sugar and other components which may have acute effects on glycemic control. The aim of the present study was to determine the effects of these snack products on postprandial glycemic responses in older adults. In a randomized, single-blinded crossover design, 25 subjects aged 71.4±4.6 years consumed either a high-protein dairy drink or one of the two energy-enriched berry purées, as well as corresponding reference products, as mid-morning snacks, each containing 25g of available carbohydrates. Baseline and postprandial blood samples for measurements of glucose, insulin, and non-esterified fatty acids (NEFA) were collected at regular intervals up to 3h. In comparison with a protein-free reference, consumption of the dairy product resulted in a remarkably high insulin response, a fall in glucose concentration and suppression of late postprandial NEFA rebound. In comparison with a low-berry reference, both berry products led to significantly lower glucose, insulin and NEFA responses. The high-protein dairy product which induces short-term hyperinsulinemia, accompanied with reduced glycemia, may help to improve muscle protein and energy metabolism. The energy-enriched berry products maintain balanced postprandial glycemia. These are beneficial effects in older adults who may suffer from impaired muscle performance or glycemic control. NCT04175353.

Clinical parameters correlated with the psoas muscle index in Japanese individuals with type 2 diabetes mellitus.

Muscle atrophy is a diabetic complication, which results in a deterioration in glycemic control in type 2 diabetes mellitus (T2DM) individuals. The psoas muscle mass index (PMI) is a reliable indicator for estimating whole-body muscle mass. We aimed to examine the relationship between clinical parameters and the PMI to clarify the mechanism underlying muscle atrophy in diabetes. This retrospective, cross-sectional study examined 51 patients (31 men and 20 women) with T2DM and a mean HbA1c value of 9.9 ± 1.7%. These patients were admitted to Aichi Medical University Hospital and underwent abdominal computed tomography imaging from July 2020 to April 2021. Multiple clinical parameters were assessed with the PMI. In a multiple regression analysis adjusted for age and sex, the PMI was correlated with body weight, body mass index, serum concentrations of corrected calcium, aspartate aminotransferase, alanine aminotransferase, creatine kinase, thyroid-stimulating hormone (TSH), urinary C-peptide concentrations, the free triiodothyronine/free thyroxine (FT3/FT4) ratio, and the young adult mean score at the femur neck. Receiver operating characteristic curves were created using TSH concentrations and the FT3/FT4 ratio for diagnosing a low PMI. The area under the curve was 0.593 and 0.699, respectively. The cut-off value with maximum accuracy for TSH concentrations was 1.491μIU/mL, sensitivity was 56.1%, and specificity was 80.0%. Corresponding values for the FT3/FT4 ratio were 1.723, 78.0, and 66.7%, respectively. TSH concentrations and the FT3/FT4 ratio are correlated with the PMI, and their thresholds may help prevent muscle mass loss in Japanese individuals with T2DM.

Discordance In Fasting And Postprandial Indices Of Glycemic Dysregulation In Individuals With Spinal Cord Injury

Fasting levels of glucose and insulin are routine clinical measures used to diagnose type-2 diabetes. However, individuals with spinal cord injury (SCI) often present with clinically normal fasting glucose but have impaired postprandial responses to a meal challenge. PURPOSE: We aimed to characterize the postprandial glycemic responses and assess the prevalence of glycemic dysregulation using fasting and postprandial indices in individuals with SCI. METHODS: Sixteen men with chronic SCI reported to the laboratory after an overnight fast to undergo either a 2-hour: oral glucose tolerance test (OGTT) using a 75-g (~300 kcal) glucose load (n = 8) or; a mixed meal tolerance test (MMTT, (1037 ± 148 kcal: 45% CHO, 37% fat, 18% PRO) (n = 8). Serial measurements of systemic glucose and insulin concentrations at baseline and in response to the OGTT/MMTT were converted into summary statistics: Insulin Resistance was estimated by the Homeostasis Model Assessment of Insulin Resistance (HOMA2-IR); whole body Insulin Sensitivity Index was estimated using methods described by Matsuda (ISIMatsuda). RESULTS: There were no differences between groups in age (p = 1.0), body mass index (p = 0.87), cardiorespiratory fitness (p = 0.26), fasting glucose (p = 0.53) or insulin (p = 0.19). In the MMTT group, 3 (38%) individuals were identified as prediabetic (fasting plasma glucose (FPG), 7.3 ± 0.9 mmol/L) and 0 individuals had impaired insulin resistance (HOMA2-IR, 1.05 ± 0.6). However, 5 (63%) individuals had impaired postprandial insulin sensitivity (ISIMatsuida, 2.2 ± 0.4). In the OGTT group, 2 (25%) individuals were prediabetic (FPG, 6.2 ± 0.2 mmol/L), 2 (25%) different individuals had impaired insulin resistance (HOMA2-IR, 3.2 ± 0.9), but 7 (88%) individuals had impaired postprandial insulin sensitivity (ISIMatsuida, 2.3 ± 0.9). CONCLUSIONS: In this small study, an OGTT identified more SCI participants with glucose dysregulation than MMTT. Postprandial measures of insulin sensitivity identified a greater proportion of SCI participants with impaired glycemic control and may have preferred utility in identifying individuals at high risk of diabetes. Future studies should compare and contrast the specificity and sensitivity of fasting and postprandial methods in this high-risk population.

Hyperglycaemia at hospital discharge is associated with worse cardiovascular outcomes after hospitalization for acute decompensated heart failure.

Impaired glycaemic control is common in hospitalized patients, and hyperglycaemia is associated with poor clinical outcomes including increased length of stay, hospital readmission, and mortality.1 Acute hyperglycaemia is associated with adverse outcomes following acute coronary syndromes.2,3 There are limited data regarding the association between impaired glycaemic control on outcomes after acute decompensated heart failure (ADHF). We aimed to evaluate the association between discharge hyperglycaemia and adverse outcomes after ADHF. We performed a retrospective analysis of all patients admitted for ADHF from July to December 2019 on a high-acuity cardiovascular ward. Patients with acute coronary syndromes and cardiogenic shock were excluded. Patients were analyzed for clinical characteristics and discharge fasting plasma glucose (DG). We used Kaplan–Meier analysis and the log-rank test to assess the incidence of the primary outcome of ADHF readmission or cardiovascular death at 90 days. We constructed Cox hazards models to compare the primary outcome by tertile of DG, adjusting for factors previously associated with ADHF readmission. The final model adjusted for age, sex, body mass index, Charlson comorbidity index, left ventricular ejection fraction (LVEF), discharge systolic blood pressure, discharge creatinine, B-type natriuretic peptide level, and discharge loop diuretic requirement in furosemide equivalents. We also adjusted for number of HF medications (beta-blocker, renin-angiotensin-aldosterone system inhibitor, mineralocorticoid antagonist) at discharge in patients with reduced LVEF. We additionally adjusted for A1c and number of diabetes mellitus (DM)-directed medications (insulin and oral agents) at discharge in diabetics. Statistical analysis was performed with SPSS (version 27.0, IBM Corp., Armonk, NY, USA).

Development of High Fat Diet-Induced Hyperinsulinemia in Mice Is Enhanced by Co-treatment With a TLR7 Agonist.

Metabolic syndrome (MetS) is common in Systemic Lupus Erythematosus (SLE) patients and is associated with increased cardio-renal risk. Toll-like receptor 7 (TLR7) stimulation promotes the development of SLE through mechanisms including activating type I Interferon (IFN) and autoreactive B cells. The current study tested whether combined TLR7 agonist treatment and exposure to a high fat, high sucrose “Western diet” intervention affects the early-stage development of SLE or MetS features. Female C57BL/6 mice were untreated or treated with the TLR7 agonist imiquimod (IMQ) and fed a high-fat diet (HFD; fat 42% kcal, sucrose 34% kcal) or control diet (fat 12.6% kcal, sucrose 34% kcal) for 6 weeks. Supporting early-stage induction of autoimmunity, spleen weights were significantly increased and anti-nuclear antibody (ANA) positivity was detected in IMQ-treated mice. Increased body weight, gonadal fat pad mass, and plasma leptin levels were observed between HFD and control animals for both IMQ and untreated mice. However, the increase in these parameters with HFD was slightly but significantly diminished in IMQ-treated mice. Both the HFD and IMQ treatments significantly increased fasting blood glucose levels. Notably, IMQ treatment affected fasting insulin concentrations in a diet-dependent manner, with hyperinsulinemia observed in IMQ-HFD treated mice. Together, this indicates that the IMQ model of SLE is associated with metabolic alterations, impaired glycemic control, and hyperinsulinemia under HFD conditions. This model may be helpful in further investigating the relationship between MetS and SLE, and supports a role of TLR7 signaling in promoting or accelerating the development of dysglycemia and hyperinsulinemia.

Diabetes und Psyche

Both type 1 and type 2 diabetes mellitus (DM) are associated with mental disorders, e.g., eating disorders and depression. Comorbid mental disorders are associated with impaired glycemic control, a higher risk of diabetes complications, and even a higher mortality. Mental problems can also negatively influence adherence to the necessary medical regimens. Regarding psychopharmacological treatment, the choice of drug is essential because many antidepressants and antipsychotics can cause substantial weight gain, which exerts a negative influence on glycemic control. Cognitive behavioral approaches have been shown to successfully reduce mental comorbidity and to also positively influence glycemic control. In their 2022 guidelines, the American Diabetes Association thus recommends that psychosocial care should be integrated into a collaborative, patient-centered approach and be provided to all people with DM, with the goal to optimize health outcomes and health-related quality of life.

The coexistence of autoimmune diabetes and maturity-onset diabetes of the young (MODY): a case series.

SummaryThe coexistence of autoimmune diabetes and maturity-onset diabetes (MODY) is rare. The absence of pancreatic autoantibodies is a key factor prompting MODY genetic testing. In this study, we report three cases of young-onset diabetes with progressive beta-cell dysfunction, strongly positive glutamic acid decarboxylase (GAD) antibodies, and genetic confirmation of pathogenic gene variants of HNF-1A, HNF-4A, and ABCC8-MODY. The first case is a woman diagnosed with HNF-1A-MODY diabetes more than 30 years after her diagnosis of adult-onset diabetes at 25 years. She required insulin after her fourth pregnancy. She became ketotic on oral hypoglycaemic agents (OHAs) and subsequently, her GAD antibodies tested positive. The second case is a woman diagnosed with diabetes at 17 years who was subsequently diagnosed with HNF-4A-MODY after many hypoglycaemic episodes on low-dose insulin. GAD antibodies were strongly positive. The last case is a man diagnosed with diabetes at 26 years who was well controlled on OHAs and required insulin years later due to sudden deterioration in glycaemic control. His ABCC8-MODY was diagnosed upon realisation of strong family history and his GAD antibodies tested positive. All subjects are now treated with insulin. Less than 1% of subjects with MODY have positive autoantibodies. These cases highlight individuals who may have two different types of diabetes simultaneously or consecutively. Deterioration of glycaemic control in subjects with MODY diabetes should highlight the need to look for the emergence of autoantibodies. At each clinic visit, one should update the family history as MODY was diagnosed in each case after the development of diabetes in their offspring.Learning pointsThese cases highlight the rare coexistence of autoimmune diabetes and MODY.Deterioration of glycaemic control in subjects with MODY diabetes should highlight the emergence of autoantibodies.One should revise and update the family history as the diagnosis of MODY was made after the development of diabetes in offspring.Understanding the spectrum of diabetes allows for precision medicine.

Impact of stopping smoking on metabolic parameters in diabetes mellitus: A scoping review.

The purpose of this scoping review is to create a single narrative that describes the impact of smoking cessation on metabolic parameters in people with diabetes. It is generally well accepted that smoking enhances the harmful effects of elevated blood glucose levels, accelerating the vascular damage seen in patients with diabetes. Smoking cessation has clear benefits in terms of reducing cardiovascular morbidity and mortality. However, there is less evidence for the impact of smoking cessation on other diabetes-related complications. Studies in people with diabetes have shown improvement as well as temporary deterioration in glycemic control after ceasing smoking. Only a few studies have described the effect of quitting smoking on insulin resistance and lipid parameters, however, their results have been inconclusive. In this situation, healthcare professionals should not assume that cessation of smoking will improve metabolic parameters in patients with diabetes. It seems they should, first of all, emphasize the prevention of weight gain that may be associated with quitting smoking. The lack of data regarding the metabolic effects of smoking and smoking cessation in diabetes is very disappointing and this area needs to be addressed.

690-P: Deterioration in Glycemic Control on School Days among School-Aged Children with Type 1 Diabetes: A Continuous Glucose Monitoring–Based Study

Background: Children with type 1 diabetes (T1D) spend more time in school when they turn school age. The impact of such transition on glycemic control remains unclear. We aimed to investigate the impact of school life by comparing the glycemic control between holidays and schooldays in school-aged children with T1D. Methods: This observational study collected data from school aged T1D children with continuous glucose monitoring (CGM) data from September 20to July 2021. Eligible datasets should include CGM records for at least 3 schooldays and 3 holidays. Data providers’ demographic and lifestyle-related information were collected via questionnaires. We compared the CGM metrics between schooldays and holidays using paired T-test. Results: A total of 78 school aged children with T1D were included (40 boys, median age 9.75 years, median diabetes duration 2.20 years) . 142,945 hours of CGM data were analyzed. Overall, time in range (3.9-7.8 mmol/L, TIR) was better on holidays than that during schooldays [57.0% (SD 15.0%) vs. 55.9% (SD 15.1%) , p = 0.039] and time above range (>7.8mmol/L, TAR) was lower on holidays [35.8% (SD 15.5%) vs. 36.9% (SD 15.5%) , p = 0.085]. No significant difference was observed in time spent <3.9mmol/L or numbers of hypoglycemia events per week. Nocturnal glycemic deterioration could be attributed to a significantly longer nighttime (0am to 6am) TIR [60.4% (SD 17.1%) vs. 56.9% (SD 18.1%) , p = 0.001] and a shorter nighttime TAR [31.8% (SD 17.5%) vs. 35.6% (SD 18.5%) , p = 0.001] on holidays compared with those on schooldays, with no difference in daytime metrics. Stratified analysis revealed the nocturnal difference was more prone to children aged 6 to years, girls, and insulin pump users, while bedtime and midnight snacks had no impact. Conclusion: Among school-aged children with T1D, deterioration in nocturnal glycemic control was found in schooldays and active adjustment in treatment is needed to improve schooldays glycemia. Disclosure X.Wu: None. W.Zhang: None. Y.Ding: None. X.Zheng: None. J.Weng: None. S.Luo: None.

193-OR: Chronotherapy with the Glucokinase Activator AZD1656 Greatly Affects Its Ability to Improve Metabolism in Obese Zucker Rats

Circadian rhythms play critical roles in regulating metabolism, including daily feeding/fasting periods and oscillating expressions of certain genes. Glucokinase (Gck) , expressed in the liver and pancreas, is central for whole-body glucose homeostasis by acting as a glucose sensor and regulating metabolism according to prevailing glucose levels. Gck expression has also been shown to follow a circadian rhythm. Gck activators (GKAs) effectively reduce hyperglycemia, however, adverse events have also involved hypoglycemia, hyperlipidemia, and hepatic steatosis. Given the circadian rhythmicity and natural postprandial activation of Gck, we hypothesized that GKA treatment would benefit from being timed specifically during feeding periods. We compared the metabolic effects following differentially timed administrations of the GKA AZD1656 in the obese, insulin resistant Zucker rat. Four weeks of continuous treatment significantly improved glycemic control; however, hepatic steatosis and inflammation manifested. In contrast, a robust reduction in hepatic steatosis and inflammation on top of improved glycemia, was observed when AZD1656 administration was timed to feeding periods only. When AZD1656 was timed to fasting periods, detrimental metabolic effects were observed, including impaired glycemic control, severe liver steatosis and elevated inflammation. Mechanistically, timing AZD1656 administration to feeding periods was found to divert de novo lipogenesis-derived lipids away from hepatic storage towards VLDL synthesis and secretion, without affecting plasma triglyceride levels. In conclusion, intermittent AZD1656 dosing timed to feeding periods promotes glucose disposal when needed the most, while the daily drug holiday allows for maintained metabolic flexibility and avoids hepatic steatosis. Chronotherapeutic approaches should be considered for the development of GKAs and other drugs acting on metabolic targets. Disclosure T. Kroon: Employee; AstraZeneca. I. Alexandersson: Employee; AstraZeneca. A. Ferm: Employee; AstraZeneca. M. Petersson: Employee; AstraZeneca. S. Maurer: Employee; AstraZeneca, Merck Sharp & Dohme Corp. B. Zarrouki: Employee; AstraZeneca. K. Wallenius: Employee; AstraZeneca. N.D. Oakes: Employee; AstraZeneca. J. Boucher: Employee; AstraZeneca, Evotec International GmbH.

Cholecystectomy is associated with dysglycaemia: Cross‐sectional and prospective analyses

Cholecystectomy has been reported to be associated with increased risk of diabetes in cross‐sectional studies. In the current study, we performed both cross‐sectional and prospective analyses to examine the association between cholecystectomy and dysglycaemia in Chinese community‐dwelling adults. A total of 1612 participants (n = 1564 without cholecystectomy and n = 48 with cholecystectomy) were evaluated for glycaemic status (according to the World Health Organization (WHO) 1999 criteria) and then followed up over ~3.2 years. Percent changes (Δ) in fasting blood glucose and HbA1c from baseline at the follow‐up visit were calculated to define glycaemic control as stable (−10% ≤ Δ < 10%), improved (Δ < −10%), or worsened (Δ ≥ 10%). The baseline cross‐sectional analyses indicated that cholecystectomy was associated with an increased risk of both prediabetes and diabetes, while the prospective analysis indicated that cholecystectomy was also associated with a greater risk of deterioration in glycaemic control (ΔFPG ≥10% and ΔHbA1c ≥10%) (P < 0.05 for each, both before and after adjusting for potential confounding covariates). These observations suggest that individuals in the Chinese community‐dwelling population who have undergone cholecystectomy are at increased risk of dysglycaemia. Further studies are warranted to both delineate the underlying mechanisms and to clarify whether more intense surveillance for future development of diabetes is needed in this group.

Association between glycemic control and the outcome in hospitalized patients with COVID-19.

PurposeCoronavirus disease 2019 (COVID-19) clinical outcome and disease severity affected by several factors; deterioration of glycemic control is one of them. Therefore, achieving optimum blood glucose parameters is hypothesized for better consequences of COVID-19. However, varying data supporting this hypothesis is available in literature. The intention of this study was to investigate the role of glycemic management on the prognosis of hospitalized COVID-19 patients with varying degrees of severity.MethodsFrom April 2020 to January 2021, we carried this retrospective cohort in a clinical care facility in Pakistan.ResultsMortality was lowest in patients with HbA1c of less than 7% (53 mmol/mol) (p < 0.001). Similarly, mortality was found lowest in patients with fasting blood glucose less than 126 mg/dl and random blood glucose less than 160 mg/dl (p < 0.001 in each). In contrast, need for admission in critical care was found highest in patients with HbA1c between 7 and 10% (53–86 mmol/mol) (p 0.002). However, participants with blood glucose levels during fasting greater than 200 mg/dl and random blood glucose levels greater than 250 mg/dl were found to have a greater need for invasive mechanical ventilation. Cox regression hazard showed no difference in risk of death and invasive mechanical ventilation based on previous glycemic control.ConclusionEffective diabetic management is correlated with a considerably lower risk of mortality and invasive mechanical ventilation in COVID-19 cases.

Symptoms and Glycemic Control in Young People With Type 1 Diabetes Following SARS-CoV-2 Infection: An Observational Study.

Context Data is needed regarding the effect of SARS-CoV-19 infection on young people with established type 1 diabetes. Identifying the disease outcomes, short and long-term sequelae may help to establish an evidence-based prevention and education policy for sick days management and DKA prevention.Objective This work aims to describe clinical manifestations of SARS-CoV-2 infection in children, adolescents, and young adults with established type 1 diabetes (T1D) and explore the effects of COVID-19 on glycemic control and disease course.MethodsAn observational study was conducted at 3 pediatric diabetes clinics in Israel between mid-March 2020 and mid-March 2021. Included were young people with established T1D, age younger than 30 years, who tested positive for SARS-CoV-2 (quantitative real-time polymerase chain reaction). Data were collected from medical files, diabetes devices, and COVID-19 questionnaire. Outcome measures were analyzed by the presence/absence of clinical symptoms (symptomatic/asymptomatic) and by age group (pediatric, < 19 years/young adults, 19-30 years).ResultsOf 132 patients, mean age 16.9 ± 5.3years, with COVID-19–confirmed infection, 103 (78%) had related symptoms; the most common were headaches, fatigue, fever, and loss of sense of smell. All had a mild disease course, but 4 required hospitalization and 2 cases were directly related to COVID-19 infection (pleuropneumonia in a patient with immunodeficiency syndrome, 1 case of diabetic ketoacidosis). Logistic regression analysis showed that age (odds ratio [OR] = 1.11; 95% CI, 1.01-1.23; P = .033), elevated glucose levels (OR = 5.23; 95% CI, 1.12-24.41; P = .035), and comorbidities (OR = 8.21; 95% CI, 1.00-67.51; P = .050) were positively associated with symptomatic infection. Persistent symptoms occurred in 16.5% of the cohort over a median of 6.7 months; age (OR = 1.14; 95% CI, 1.01-1.29; P = .030) and elevated glucose levels (OR = 3.42; 95% CI, 1.12-10.40; P = .031) were positively associated with persistent symptoms. Usually, no change was reported in glucose levels (64%) except for a temporary deterioration in glycemic control during the short infection period.ConclusionYoung people with established T1D experience mild COVID-19 infection. Elevated glucose levels during COVID-19 infection and older age were associated with prolonged disease course.

The effect of intentional underestimation of the food carbohydrate content and other diet-related negligence on glycaemic patterns in patient utilizing the loop-based do-it-yourself artificial pancreas systems

Artificial pancreas systems (APS) are supposed to minimize the workload of managing type 1 diabetes mellitus for patients, but even APS users are still supposed to count carbohydrates and announce meals to achieve the best control. Here, we present the effect of intentional underestimation of food carbohydrate content and other diet-related negligence on glycaemic patterns in patients utilizing a loop-based APS. Since the patient started using the “Loop”, his glycaemic control has been satisfactory (glycated haemoglobin: 6.7% (50 mmol/mol) to 6.4% (46 mmol/mol). The problems with glycaemic control occurred when the patient went on holiday. During this period, the patient deliberately underestimated his carbohydrate meal content announced to the APS. He also used the “override” function (set to 70–80% of normal insulin requirements), which reduced the amount of insulin delivered. The patient tended to consume more alcohol and routinely consumed high glycaemic index products during this period of time. The food bolus was delivered either just before or even during meals. No loop system settings were modified. An intentional underestimation of food carbohydrate content led to the deterioration of glycaemic control in the user of the loop-based APS; however, one can speculate that with some dietary modifications (e.g. limiting carbohydrate intake) the patient could achieve better glycaemic patterns.

The Impact of Removal of Exercise for 3 Days on Glycemic Control in Older Active Adults

Postprandial glycemia (PPG) predicts cardiovascular disease, and 3 days of physical inactivity impairs PPG in young, active adults. Whether this occurs in older, active adults who may be more prone to bouts of inactivity is unknown. This study determined if PPG was impaired in active older adults (old) following a 3 day removal of exercise compared to active young adults. In this randomized, crossover study, 10 older (73.0 ± 1.9 yrs) and 9 young (32.8 ± 1.8 yrs) habitually active (≥90 min/week of exercise) adults completed a 3 day period of exercise removal (NOEX) and a 3 day period of normal exercise maintenance (EX), separated by ≥ 1 week. Diet was standardized across phases. Glycemic control (GC) (2 hour PPG, peak glucose values, and standard deviation (STDEV) of blood glucose values) was assessed via continuous glucose monitoring (IPro2, Enlite Sensors, Medtronic Inc., Northridge, CA) during both phases. No differences in body mass index (Old: 26.5 ± 1.3, Young: 24.8 ± 1.0 kg/m2, p&gt;0.05) existed between groups. Both groups had a similar reduction in activity during NOEX (Old: ‐64.6% ± 6.2, Young: ‐55.7% ± 4.9, p&gt;0.05). There were significant main effects (p&lt;0.05) in PPG of age (Old: 116±1.2 mg/dL, Young: 106 ± 1.3 mg/dL), phase (Inactive: 113 ± 1.3 mg/dL, Active: 109 ± 1.2 mg/dL), and time (0 min: 99 ± 2.0, 30 min: 118 ± 2.0, 60 min: 117 ± 2.0, 90 min: 112 ± 2.0, 120 min: 108 ± 2.0 mg/dL), but no interaction (p&gt;0.05). Further, a trend (p=0.06) for significant main effect of age (Old: 149±5.6, Young: 133±5.9 mg/dL) and phase (p&lt;0.05; Inactive: 145±4.4, Active: 136±4.4 mg/dL) were found for peak glucose values. Significant main effects (p&lt;0.05) exist for age (Old: 15.3±1.2, Young: 11.3±1.2) and phase (Inactive: 14.4±0.97, Active: 12.2±0.97) for blood glucose STDEV. These results indicate that older adults have impaired GC compared to young adults and that removal of exercise impairs GC. Yet, the impairment in GC with exercise removal is not different between old and young adults when the decrease in daily physical activity is similar.