Glycemic Changes Research Articles

Sleep behaviours and associated habits and the progression of pre-diabetes to type 2 diabetes mellitus in adults: A systematic review and meta-analysis.

IntroductionCertain sleep behaviours increase risk of type 2 diabetes mellitus (T2DM) in the general population, but whether they contribute to the progression from pre-diabetes to T2DM is uncertain. We conducted a systematic review to assess this.MethodsStructured searches were performed on bibliographic databases (MEDLINE, EMBASE and CINAHL) from inception to 26/04/2021 for longitudinal studies/trials consisting of adults⩾18 years with pre-diabetes and sleep behaviours (short or long sleep duration (SD), late chronotype, insomnia, obstructive sleep apnoea, daytime napping and/or night-shift employment) that reported on incident T2DM or glycaemic changes. The Newcastle-Ottawa Scale was used for quality assessment.ResultsSix studies were included. Meta-analysis of three studies (n = 20,139) demonstrated that short SD was associated with greater risk of progression to T2DM, hazard ratio (HR) 1.59 (95% CI 1.29-1.97), I2 heterogeneity score 0%, p < 0.0001, but not for long SD, HR 1.50 (0.86–2.62), I2 heterogeneity 77%, p = 0.15. The systematic review showed insomnia and night-shift duty were associated with higher progression to T2DM. Studies were rated as moderate-to-high quality.ConclusionsProgression from pre-diabetes to T2DM increases with short SD, but only limited data exists for insomnia and night-shift duty. Whether manipulating sleep could reduce progression from pre-diabetes to T2DM needs to be examined.

Accounting for concurrent antihyperglycemic medication changes in dietary and physical activity interventions: A focused literature review.

AimsTo summarize methods used to account for antihyperglycemic medication changes in randomized controlled trials evaluating the effect of dietary and physical activity interventions on glycemia among adults with diabetes.MethodsUsing studies included in two recently published systematic reviews of randomized controlled trials examining the glycemic effects of dietary and physical activity interventions, we evaluated how each study accounted for antihyperglycemic medication changes. Data were analyzed using summary statistics, stratified by the type of intervention studied, and each was assigned a score from 0 to 6 reflecting the strength of medication controls employed.ResultsWe evaluated 22 physical activity focused and 27 dietary focused articles. Our scoring system yielded a mean concurrent medication adjustment score of 3.9/6 for the physical activity studies and a score of 1.7/6 (p < 0.001) for the dietary studies.ConclusionsWe found that randomized controlled trials included in recent systematic reviews of physical activity and dietary interventions did not robustly account or control for changes in antihyperglycemic medications, with physical activity interventions doing so more robustly than dietary interventions. This is a threat to the validity of study findings, as observed glycemic changes may in fact be attributable to imbalances in concurrent medication adjustments between groups.

To Determine the Mean Glycemic Changes after Vitamin D3 Supplement in Children with Type I Diabetes Mellitus and Vitamin D Deficiency Presenting at a Tertiary Care Hospital in Karachi

Introduction: Glucose Homeostasis can potentially be affected by Vitamin D. Vitamin D deficiency has been identified as a global problem with an estimated one billion people worldwide suffering from vitamin D deficiency or insufficiency. Vitamin D deficiency (VDD) is a global health issue and is on the rise in Pakistani pediatric population. Type 1 diabetes (T1D) also negatively impacts bone health and is associated with a modest reduction in bone mineral density (BMD) and strength (7,8) Given the negative impact of vitamin D inadequacy and T1D on bone health, Adolescent with both conditions have multiple risk factors for increased skeletal fragility. In this study we evaluated glycemic changes after vitamin D3 supplement in patients with type I diabetes mellitus and vitamin D deficiency.&#x0D; Objective: To determine the mean glycemic changes after vitamin D3 supplement in children with type I diabetes mellitus and vitamin D deficiency presenting at a tertiary care hospital in Karachi.&#x0D; Methodology: A quasi experimental study design was conducted on 40 children who were presenting in OPD of NICH Karachi for six months. All patients were subjected to demographics and detailed history for Type 1 Diabetes and Vitamin D deficiency. Immunoturbidometry for HbA1C and ELISA for 25OHD was performed. Vitamin D3 supplement was advised as per operational definition. Insulin dose was recorded by parents for three months. 25OHD and HbA1C levels were measured following Vitamin D3 supplements. Statistical analysis was performed to analyze the significance.&#x0D; Results: We observed a significant difference in mean HbA1c level at pre-treatment and post treatment was 9.89±2.04 and 8.42±1.87 respectively with Vitamin D3 supplements, with p-value 0.001.&#x0D; Conclusion: Vitamin D3 supplement improves HbA1C in patients with type I diabetes and vitamin D deficiency.

Characterization of glucose metabolism in youth with vs. without cystic fibrosis liver disease: A pilot study

BackgroundDiabetes and liver disease are life-threatening complications of cystic fibrosis (CF). CF-liver disease is a risk factor for CF related diabetes (CFRD) development, but the underlying mechanisms linking the two co-morbidities are not known. The objective of this pilot study was to characterize glucose metabolism in youth with CF with and without liver disease. MethodsIn this two-center cross-sectional study, 20 youth with CF with and without liver disease underwent a 3-hour oral glucose tolerance test. Subjects were categorized by liver disease (LD) status [no LD, mild LD, severe LD] and diabetes status. Measures of glucose excursion, islet cell secretory responses, insulin sensitivity and clearance were obtained. ResultsParticipants with severe LD had the highest fasting, peak, and glucose area under the curve over 3 h (AUC3h) among individuals with CFRD (interaction p < 0.05). In parallel with glycemic changes, prandial β-cell secretory response (AUC C-peptide 3h) was lower in those with severe LD compared to mild or no LD (p < 0.01). There was a trend of higher HOMA-IR in those with severe LD (p = 0.1) as well as lower fasting insulin clearance in those with mild and severe LD compared to no LD (p = 0.06) and lower prandial insulin clearance in severe LD among those with CFRD (interaction p = 0.1). ConclusionIn this small cohort, subjects with severe LD tended to have more impaired glycemia, insulin secretion, insulin sensitivity and clearance. Larger studies are imperative to define the pathogenesis to inform clinical care guidelines in terms of CFRD screening, diagnosis, and treatment options.

Serum Metabolomics of Incident Diabetes and Glycemic Changes in a Population With High Diabetes Burden: The Hispanic Community Health Study/Study of Latinos.

Metabolomic signatures of incident diabetes remain largely unclear for the U.S. Hispanic/Latino population, a group with high diabetes burden. We evaluated the associations of 624 known serum metabolites (measured by a global, untargeted approach) with incident diabetes in a subsample (n = 2,010) of the Hispanic Community Health Study/Study of Latinos without diabetes and cardiovascular disease at baseline (2008-2011). Based on the significant metabolites associated with incident diabetes, metabolite modules were detected using topological network analysis, and their associations with incident diabetes and longitudinal changes in cardiometabolic traits were further examined. There were 224 incident cases of diabetes after an average 6 years of follow-up. After adjustment for sociodemographic, behavioral, and clinical factors, 134 metabolites were associated with incident diabetes (false discovery rate-adjusted P < 0.05). We identified 10 metabolite modules, including modules comprising previously reported diabetes-related metabolites (e.g., sphingolipids, phospholipids, branched-chain and aromatic amino acids, glycine), and 2 reflecting potentially novel metabolite groups (e.g., threonate, N-methylproline, oxalate, and tartarate in a plant food metabolite module and androstenediol sulfates in an androgenic steroid metabolite module). The plant food metabolite module and its components were associated with higher diet quality (especially higher intakes of healthy plant-based foods), lower risk of diabetes, and favorable longitudinal changes in HOMA for insulin resistance. The androgenic steroid module and its component metabolites decreased with increasing age and were associated with a higher risk of diabetes and greater increases in 2-h glucose over time. We replicated the associations of both modules with incident diabetes in a U.S. cohort of non-Hispanic Black and White adults (n = 1,754). Among U.S. Hispanic/Latino adults, we identified metabolites across various biological pathways, including those reflecting androgenic steroids and plant-derived foods, associated with incident diabetes and changes in glycemic traits, highlighting the importance of hormones and dietary intake in the pathogenesis of diabetes.

Prolonged Glycemic Adaptation Following Transition From a Low- to High-Carbohydrate Diet: A Randomized Controlled Feeding Trial.

OBJECTIVEConsuming ≥150 g/day carbohydrate is recommended for 3 days before an oral glucose tolerance test (OGTT) for diabetes diagnosis. For evaluation of this recommendation, time courses of glycemic changes following transition from a very-low-carbohydrate (VLC) to high-carbohydrate diet were assessed with continuous glucose monitoring (CGM).RESEARCH DESIGN AND METHODSAfter achieving a weight loss target of 15% (±3%) on the run-in VLC diet, participants (18–50 years old, BMI ≥27 kg/m2) were randomly assigned for 10 weeks to one of three isoenergetic diets: VLC (5% carbohydrate and 77% fat); high carbohydrate, high starch (HC-Starch) (57% carbohydrate and 25% fat, including 20% refined grains); and high carbohydrate, high sugar (HC-Sugar) (57% carbohydrate and 25% fat, including 20% sugar). CGM was done throughout the trial (n = 64) and OGTT at start and end (n = 41). All food was prepared in a metabolic kitchen and consumed under observation.RESULTSGlucose metrics continued to decline after week 1 in the HC-Starch and HC-Sugar groups (P < 0.05) but not VLC. During weeks 2–5, fasting and 2-h glucose (millimoles per liter per week) decreased in HC-Starch (fasting −0.10, P = 0.001; 2 h −0.10, P = 0.04). During weeks 6–9, 2-h glucose decreased in HC-Starch (−0.07, P = 0.01) and fasting and 2-h glucose decreased in HC-Sugar (fasting −0.09, P = 0.001; 2 h −0.09, P = 0.003). The number of participants with abnormal glucose tolerance by OGTT remained 10 (of 16) in VLC at start and end but decreased from 17 to 9 (of 25) in both high-carbohydrate groups.CONCLUSIONSPhysiological adaptation from a low- to high-carbohydrate diet may require many weeks, with implications for the accuracy of diabetes tests, interpretation of macronutrient trials, and risks of periodic planned deviations from a VLC diet.

Blood DNA methylation at TXNIP and glycemic changes in response to weight-loss diet interventions: the POUNDS lost trial.

Background:Thioredoxin Interacting Protein (TXNIP) functions as a master regulator for glucose homeostasis. Hypomethylation at the 5’-cytosine-phosphate-guanine-3’ (CpG) site cg19693031 of TXNIP has been consistently related to islet dysfunction, hyperglycemia, and type 2 diabetes. DNA methylation (DNAm) may reveal the missing mechanistic link between obesity and type 2 diabetes. We hypothesize that baseline DNAm level at TXNIP in blood may be associated with glycemic traits and their changes in response to weight-loss diet interventions.Methods:We included 639 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss diet intervention. Baseline blood DNAm levels were profiled by high-resolution methylC-capture sequencing. We defined the regional DNAm level of TXNIP as the average methylation level over CpGs within 500 bp of cg19693031. Generalized linear regression models were used for main analyses.Results:We found that higher regional DNAm at TXNIP was significantly correlated with lower fasting glucose, HbA1c, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at baseline (P<0.05 for all). Significant interactions were observed between dietary protein intake and DNAm on changes in insulin (P-interaction=0.007) and HOMA-IR (P-interaction=0.009) at 6 months. In participants with the highest tertile of regional DNAm at TXNIP, average protein (15%) intake was associated with a greater reduction in insulin (β: −0.14; 95% CI: −0.24, −0.03; P=0.011) and HOMA-IR (β: −0.15; 95% CI: −0.26, −0.03; P=0.014) than high protein (25%) intake, whereas no significant associations were found in those with the lower tertiles (P>0.05). The interaction was attenuated to be non-significant at 2 years, presumably related to decreasing adherence to the diet intervention.Conclusions:Our data indicate that higher regional DNAm level at TXNIP was significantly associated with better fasting glucose, HbA1c, and HOMA-IR; and people with higher regional DNAm levels benefited more in insulin and HOMA-IR improvement by taking the average-protein weight-loss diet.

Quantifying the impact of physical activity on future glucose trends using machine learning

SummaryPrevention of hypoglycemia (glucose <70 mg/dL) during aerobic exercise is a major challenge in type 1 diabetes. Providing predictions of glycemic changes during and following exercise can help people with type 1 diabetes avoid hypoglycemia. A unique dataset representing 320 days and 50,000 + time points of glycemic measurements was collected in adults with type 1 diabetes who participated in a 4-arm crossover study evaluating insulin-pump therapies, whereby each participant performed eight identically designed in-clinic exercise studies. We demonstrate that even under highly controlled conditions, there is considerable intra-participant and inter-participant variability in glucose outcomes during and following exercise. Participants with higher aerobic fitness exhibited significantly lower minimum glucose and steeper glucose declines during exercise. Adaptive, personalized machine learning (ML) algorithms were designed to predict exercise-related glucose changes. These algorithms achieved high accuracy in predicting the minimum glucose and hypoglycemia during and following exercise sessions, for all fitness levels.

Bempedoic acid in patients with type 2 diabetes mellitus, prediabetes, and normoglycaemia: A post hoc analysis of efficacy and glycaemic control using pooled data from phase 3 clinical trials.

AimTo evaluate the effect of bempedoic acid on glycaemic and lipid variables in patients with hypercholesterolaemia.MethodsA patient‐level pooled analysis of four phase 3, randomized, double‐blind, placebo‐controlled trials evaluated changes in glycaemia, change from baseline in LDL‐C, and adverse events. Patients (N = 3621) on maximally tolerated statins were randomized 2:1 to oral bempedoic acid 180 mg or placebo once daily for 12 to 52 weeks with the results analysed by baseline glycaemic status (diabetes, prediabetes, or normoglycaemia).ResultsThe annual rate of new‐onset diabetes for bempedoic acid versus placebo in patients with normoglycaemia at baseline (n = 618) was 0.3% versus 0.8%, and for patients with prediabetes at baseline (n = 1868) it was 4.7% versus 5.9%. In patients with diabetes or prediabetes, bempedoic acid significantly (P < .0001) reduced HbA1c by −0.12% and −0.06%, respectively, and did not worsen fasting glucose versus placebo. Bempedoic acid significantly and consistently lowered LDL‐C levels versus placebo, regardless of baseline glycaemic status (placebo‐corrected difference range, −17.2% to −29.6%; P < .001 for each stratum). The safety of bempedoic acid was comparable with placebo and similar across glycaemic strata.ConclusionsBempedoic acid significantly lowered LDL‐C across glycaemic strata and did not worsen glycaemic variables or increase the incidence of new‐onset diabetes versus placebo over a median follow‐up of 1 year.

Does gender affect the driving performance of young patients with diabetes?

Recent evidence suggests that poor glycemic control among young patients with type 1 diabetes mellitus (T1DM) has negative cognitive and physical effects, whose extent is gender-dependent. For example, female patients with diabetes present more physical and cognitive limitations than male patients in terms of cognitive adjustment, quality of decision making, and functioning. Studies about traffic safety report that diabetic drivers are at increased risk of being involved in road crashes, especially when driving in a state of hypoglycemia under which their blood glucose level is too low. We have recently demonstrated that acute hyperglycemia (when the blood glucose level is too high) can also lead to poor driving performance among T1DM young adult patients. Against this background, the objective of the present study was to find out whether gender affects the driving performance of young drivers with diabetes. Twenty-six T1DM drivers participated in a counterbalanced crossover experiment. While being monitored by an eye tracker, they drove a driving simulator and twice navigated through the nine hazardous scenarios: once under a normal blood glucose (euglycemia) level and once high blood glucose (hyperglycemia) level. The first main result is that young female drivers are more affected by diabetes than young male drivers, regardless of momentary glycemic changes. The second main result is that poor glycemic control substantially deteriorates hazard perception and driving performance of young males with diabetes. Thus, it is argued that an uncontrolled state of a high blood glucose level may be more hazardous for young males with diabetes since it negatively impacts their driving performance.

Does a high dietary intake of resistant starch affect glycaemic control and alter the gut microbiome in women with gestational diabetes? A randomised control trial protocol

BackgroundGestational Diabetes Mellitus (GDM) is prevalent with lasting health implications for the mother and offspring. Medical nutrition therapy is the foundation of GDM management yet achieving optimal glycaemic control often requires treatment with medications, like insulin. New dietary strategies to improve GDM management and outcomes are required.Gut dysbiosis is a feature of GDM pregnancies, therefore, dietary manipulation of the gut microbiota may offer a new avenue for management. Resistant starch is a fermentable dietary fibre known to alter the gut microbiota and enhance production of short-chain fatty acids. Evidence suggests that short-chain fatty acids improve glycaemia via multiple mechanisms, however, this has not been evaluated in GDM.MethodsAn open-label, parallel-group design study will investigate whether a high dietary resistant starch intake or resistant starch supplement improves glycaemic control and changes the gut microbiome compared with standard dietary advice in women with newly diagnosed GDM. Ninety women will be randomised to one of three groups - standard dietary treatment for GDM (Control), a high resistant starch diet or a high resistant starch diet plus a 16 g resistant starch supplement. Measurements taken at Baseline (24 to 30-weeks’ gestation), Day 10 and Day 56 (approximately 36 weeks’ gestation) will include fasting plasma glucose levels, microbial composition and short-chain fatty acid concentrations in stool, 3-day dietary intake records and bowel symptoms questionnaires. One-week post-natal data collection will include microbial composition and short-chain fatty acid concentrations of maternal and neonatal stools, microbial composition of breastmilk, birthweight, maternal and neonatal outcomes. Mixed model analysis of variance will assess change in glycaemia and permutation-based multivariate analysis of variance will assess changes in microbial composition within and between intervention groups. Distance-based linear modelling will identify correlation between change in stool microbiota, short-chain fatty acids and measures of glycaemia.DiscussionTo improve outcomes for GDM dyads, evaluation of a high dietary intake of resistant starch to improve glycaemia through the gut microbiome needs to be established. This will expand the dietary interventions available to manage GDM without medication.Trial registrationAustralian New Zealand Clinical Trial Registry, ACTRN12620000968976p. Registered 28 September 2020

Suprachiasmatic nucleus-mediated glucose entry into the arcuate nucleus determines the daily rhythm in blood glycemia

Glycemia is maintained within very narrow boundaries with less than 5% variation at a given time of the day. However, over the circadian cycle, glycemia changes with almost 50% difference. How the suprachiasmatic nucleus, the biological clock, maintains these day-night variations with such tiny disparities remains obscure. We show that via vasopressin release at the beginning of the sleep phase, the suprachiasmatic nucleus increases the glucose transporter GLUT1 in tanycytes. Hereby GLUT1 promotes glucose entrance into the arcuate nucleus, thereby lowering peripheral glycemia. Conversely, blocking vasopressin activity or the GLUT1 transporter at the daily trough of glycemia increases circulating glucose levels usually seen at thepeak of the rhythm. Thus, biological clock-controlled mechanisms promoting glucose entry into the arcuate nucleus explain why peripheral blood glucose is low before sleep onset.

CATAMENIAL DIABETIC KETOACIDOSIS.

Diabetic ketoacidosis (DKA) is a common medical emergency situation. In rare cases, glycemic changes associated with the menstrual cycle may create a predisposing factor for DKA. In the absence of facilitating factors that may cause DKA, catamenial DKA should be considered. In the patients with catamenial DKA, increasing the insulin dose 1-2 days before menstruation may prevent the development of hyperglycemia or DKA associated with menstrual cycle. In this study, we present a 21-year-old female with type 1 diabetes mellitus (DM) that recurrently applied to our hospital due to DKA a few days prior to menstrual bleeding.

Sex-specific impact of major depressive disorder on 12-year change in glycaemic status: Results from a nationwide cohort study of adults without diabetes in Germany.

There is evidence for an increased type 2 diabetes (T2D) risk associated with depression, but its role for diabetes prevention remains unclear. This study aimed to add insight by investigating the impact of major depressive disorder (MDD) on prospective glycaemic changes. The study was based on a cohort of n=1,766 adults without diabetes (776men, 990 women; 18-65years of age) who participated in the mental health supplement of the German National Health Interview and Examination Survey (GNHIES98-MHS, 1997-1999) and in a follow-up survey (DEGS1, 2008-2011). Glycaemic status was defined as normoglycaemia [HbA1c < 39mmol/mol (<5.7%)], prediabetes [39 ≤ HbA1c<48mmol/mol (5.7-6.4%)] and diabetes [HbA1c ≥ 48mmol/mol (≥ 6.5%), diagnosed diabetes, or antidiabetic medication], and glycaemic changes categorized as 'remission', 'stability' and 'progression'. Baseline MDD was assessed via a modified German version of the WHO Composite International Diagnostic Interview. Multivariable logistic regressions were applied to analyse the association of MDD with glycaemic changes and incident T2D, adjusting for socio-demographics, lifestyle conditions, chronic diseases, antidepressant use and mental health care. MDD prevalence was 21.4% for women and 8.9% for men. Among women, MDD was associated with a lower chance for remission (RRR 0.43; 95% CI 0.23, 0.82). Among men, MDD was not significantly related to glycaemic changes. MDD had no significant effect on incident T2D (men: OR 1.58; 0.55, 4.52; women: OR 0.76; 0.37, 1.58). Findings of the current study highlight the role of depression in T2D prevention, particularly among women.

Targeting the Pancreatic α-Cell to Prevent Hypoglycemia in Type 1 Diabetes.

Life-threatening hypoglycemia is a limiting factor in the management of type 1 diabetes. People with diabetes are prone to develop hypoglycemia because they lose physiological mechanisms that prevent plasma glucose levels from falling. Among these so-called counterregulatory responses, secretion of glucagon from pancreatic α-cells is preeminent. Glucagon, a hormone secreted in response to a lowering in glucose concentration, counteracts a further drop in glycemia by promoting gluconeogenesis and glycogenolysis in target tissues. In diabetes, however, α-cells do not respond appropriately to changes in glycemia and, thus, cannot mount a counterregulatory response. If the α-cell could be targeted therapeutically to restore its ability to prevent hypoglycemia, type 1 diabetes could be managed more efficiently and safely. Unfortunately, the mechanisms that allow the α-cell to respond to hypoglycemia have not been fully elucidated. We know even less about the pathophysiological mechanisms that cause α-cell dysfunction in diabetes. Based on published findings and unpublished observations, and taking into account its electrophysiological properties, we propose here a model of α-cell function that could explain its impairment in diabetes. Within this frame, we emphasize those elements that could be targeted pharmacologically with repurposed U.S. Food and Drug Administration-approved drugs to rescue α-cell function and restore glucose counterregulation in people with diabetes.

Dexamethasone and postoperative analgesia in minimally invasive thoracic surgery: a retrospective cohort study

BackgroundDexamethasone is commonly used for the prevention of postoperative nausea and vomiting (PONV), and recent reviews suggest a role for dexamethasone in postoperative analgesia. The aim of this study is to evaluate the efficacy of dexamethasone as an analgesic adjuvant in minimally invasive thoracic surgery. Primary outcome was morphine consumption 24 h after surgery; secondary outcomes were pain control, measured as numeric rating scale (NRS), glycemic changes, PONV, and surgical wound infection.ResultsWe performed a retrospective cohort study considering 70 patients who underwent elective lobectomy, segmentectomy, or wedge resection surgery with a mini-thoracotomy approach or video-assisted thoracoscopic surgery (VATS). All patients received the same locoregional techniques and short-acting opioids during surgery; 46 patients received dexamethasone at induction. There were no significant differences in morphine consumption at 24 h (p = 0.09) and in postoperative pain scores. Nevertheless, a higher frequency of rescue therapy (p = 0.01) and a tendency for a higher attempted-PCA pushes count were observed in patients who did not receive dexamethasone. No cases of surgical wound infections were detected, and the incidence of PONV was similar in the two groups. Postoperative glycemia was transiently higher in the dexamethasone group (p = 0.004), but the need of hypoglycemic therapy was not significantly different.ConclusionsPreoperative administration of dexamethasone did not cause a significant reduction in morphine consumption, but appears to be safe and plays a role in a multimodal anesthesia approach for patients undergoing elective minimally invasive thoracic surgery.

Selective targeting of angiopoietin-like 3 (ANGPTL3) with vupanorsen for the treatment of patients with familial partial lipodystrophy (FPLD): results of a proof-of-concept study

BackgroundFamilial partial lipodystrophy (FPLD) is a rare disease characterized by selective loss of peripheral subcutaneous fat, associated with dyslipidemia and diabetes mellitus. Reductions in circulating levels of ANGPTL3 are associated with lower triglyceride and other atherogenic lipids, making it an attractive target for treatment of FPLD patients. This proof-of-concept study was conducted to assess the efficacy and safety of targeting ANGPTL3 with vupanorsen in patients with FPLD.MethodsThis was an open-label study. Four patients with FPLD (two with pathogenic variants in LMNA gene, and two with no causative genetic variant), diabetes (HbA1c ≥ 7.0 % and ≤ 12 %), hypertriglyceridemia (≥ 500 mg/dL), and hepatic steatosis (hepatic fat fraction, HFF ≥ 6.4 %) were included. Patients received vupanorsen subcutaneously at a dose of 20 mg weekly for 26 weeks. The primary endpoint was the percent change from baseline in fasting triglycerides at Week 27. Other endpoints analyzed at the same time point included changes in ANGPTL3, fasting lipids and lipoproteins, insulin secretion/sensitivity, postprandial lipids, and glycemic changes in response to a mixed meal test, HFF measured by MRI, and body composition measured by dual-energy absorptiometry (DEXA).ResultsBaseline mean ± SD fasting triglyceride level was 9.24 ± 4.9 mmol/L (817.8 ± 431.9 mg/dL). Treatment resulted in reduction in fasting levels of triglycerides by 59.9 %, ANGPTL3 by 54.7 %, and in several other lipoproteins/lipids, including very low-density lipoprotein cholesterol by 53.5 %, non-high-density lipoprotein cholesterol by 20.9 %, and free fatty acids (FFA) by 41.7 %. The area under the curve for postprandial triglycerides, FFA, and glucose was reduced by 60 %, 32 %, and 14 %, respectively. Treatment with vupanorsen also resulted in 55 % reduction in adipose tissue insulin resistance index, while other insulin sensitivity indices and HbA1c levels were not changed. Additional investigations into HFF and DEXA parameters suggested dynamic changes in fat partitioning during treatment. Adverse events observed were related to common serious complications associated with diabetes and FPLD. Vupanorsen was well tolerated, and there was no effect on platelet count.ConclusionsAlthough limited, these results suggest that targeting ANGPTL3 with vupanorsen could address several metabolic abnormalities in patients with FPLD.

Does Preoperative Glycemic Control Restore Immune Defense Against Implant-related Infection in Mice With Diabetes?

Does Preoperative Glycemic Control Restore Immune Defense Against Implant-related Infection in Mice With Diabetes?

Abstract 10659: Blood DNA Methylation at TXNIP and Glycemic Changes in Response to Weight-Loss Diet Interventions: The POUNDS Lost Trial

Introduction: Thioredoxin Interacting Protein ( TXNIP ) functions as a master regulator for glucose homeostasis. Hypomethylation at the 5'-cytosine-phosphate-guanine-3' (CpG) site cg19693031 of TXNIP has been consistently related to islet dysfunction, hyperglycemia, and type 2 diabetes. DNA methylation (DNAm) may reveal the missing mechanistic link between obesity and type 2 diabetes; however, little is known about whether the DNAm level at TXNIP in blood is associated with glycemic changes in response to weight-loss diet interventions. Hypothesis: We hypothesized that participants with varying DNAm level of TXNIP responded differentially to weight-loss diet interventions on glycemic changes. Method: We included 639 overweight and obese participants from Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial, who were randomly assigned to 1 of 4 weight-loss diets varying in macronutrient contents. Blood DNAm levels were profiled by a high-resolution methylC-capture sequencing at baseline. We defined regional methylation level of TXNIP as average methylation level over CpGs within 500 bp of cg19693031. Results: Higher regional methylation level at TXNIP was correlated with lower fasting glucose, HbA1c, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at baseline (p&lt;0.05 for all). Participants with distinct regional methylation level of TXNIP showed significantly different changes in fasting insulin (p-interaction=0.007) and HOMA-IR (p-interaction=0.009) in response to average- vs. high-protein diet intervention at 6 months, independent of weight loss. Among participants with an average-protein diet, higher regional methylation level at TXNIP was associated with a greater reduction of fasting insulin and HOMA-IR at 6 months, while an opposite association was found among those with a high-protein diet. Such difference was attenuated to be nonsignificant at 2 years. Conclusions: DNAm level at TXNIP in blood may modify the effects of diet interventions on changes in glycemic traits, independent of weight loss. Overweight and obese individuals with higher methylation level at TXNIP may benefit more in improving insulin and HOMA-IR by consuming an average-protein diet than a high-protein diet.

Resistant Starch Consumption Effects on Glycemic Control and Glycemic Variability in Patients with Type 2 Diabetes: A Randomized Crossover Study.

We previously observed beneficial effects of native banana starch (NBS) with a high resistant starch (RS) content on glycemic response in lean and obese participants. Here, we aimed to determine the effects of NBS and high-amylose maize starch (HMS) on glycemic control (GC) and glycemic variability (GV) in patients with type 2 diabetes (T2D) when treatments were matched for digestible starch content. In a randomized, crossover study, continuous glucose monitoring (CGM) was performed in 17 participants (aged 28–65 years, BMI ≥ 25 kg/m2, both genders) consuming HMS, NBS, or digestible maize starch (DMS) for 4 days. HMS and NBS induced an increase in 24 h mean blood glucose during days 2 to 4 (p < 0.05). CONGA, GRADE, and J-index values were higher in HMS compared with DMS only at day 4 (p < 0.05). Yet, NBS intake provoked a reduction in fasting glycemia changes from baseline compared with DMS (p = 0.0074). In conclusion, under the experimental conditions, RS from two sources did not improve GC or GV. Future longer studies are needed to determine whether these findings were affected by a different baseline microbiota or other environmental factors.