Lower Glucose Research Articles

Dapagliflozin improves diabetic cognitive impairment via indirectly modulating the mitochondria homeostasis of hippocampus in diabetic mice.

Cognitive impairment is increasingly recognized as an important comorbidity of diabetes progression; however, the underlying molecular mechanism is unclear. Dapagliflozin, an inhibitor of sodium-glucose co-transporter 2 (SGLT2), has shown promising effects against diabetes in rodent experiments and human clinical assays. This study aimed to determine the underlying mechanism and examine the effect of dapagliflozin on diabetic cognitive impairment. To create an in vivo model of diabetic cognitive impairment, streptozotocin (STZ)-induced diabetic mice were used. Dapagliflozin was administered to mice for 8 weeks. The context fear condition and Morris water maze test was used to evaluate mice's behavioral change. Western blotting was used to evaluate protein expression. Hematoxylin and eosin (HE) and Nissl staining were applied to monitor morphological and structural changes. Congo red staining was performed to identify the formation of senile plaques. Mitochondria morphology was examined using a transmission electron microscope, and blood flow in the mouse cerebral cortex was measured using a laser Doppler imaging assay. Comparison to the diabetes mellitus (DM) group, the dapagliflozin group had lower glucose levels. Behavioral studies have shown that dapagliflozin can restore memory deficits in diabetic mice. The murky cell membrane edges and Nissl bodies more difficult to identify in the DM group were revealed by HE and Nissl staining, which were both improved by dapagliflozin treatment. Dapagliflozin inhibited the progression of Aβ generation and the reduced cerebral blood flow in the DM group was rescued. After dapagliflozin treatment, damaged mitochondria and lack of SGLT2 in the hippocampus and cortex of diabetic mice were repaired. Diabetes-induced cognitive dysfunction was attenuated by dapagliflozin and the effect was indirect rather than direct.

Associations between avocado intake and measures of glucose and insulin homeostasis in Hispanic individuals with and without type 2 diabetes: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Background and AimsTo investigate associations between avocado intake and glycemia in adults with Hispanic/Latino ancestry. Methods and ResultsThe associations of avocado intake with measures of insulin and glucose homeostasis were evaluated in a cross-sectional analysis of up to 14,591 Hispanic/Latino adults, using measures of: average glucose levels (hemoglobin A1c; HbA1c), fasting glucose and insulin, glucose and insulin levels after an oral glucose tolerance test (OGTT), and calculated measures of insulin resistance (HOMA-IR, and HOMA-%β), and insulinogenic index. Associations were assessed using multivariable linear regression models, which controlled for sociodemographic factors and health behaviors, and which were stratified by dysglycemia status.In those with normoglycemia, avocado intake was associated with a higher insulinogenic index (β = 0.17 ± 0.07, P = 0.02). In those with T2D (treated and untreated), avocado intake was associated with lower hemoglobin A1c (HbA1c; β = −0.36 ± 0.21, P = 0.02), and lower fasting glucose (β = −0.27 ± 0.12, P = 0.02). In the those with untreated T2D, avocado intake was additionally associated with HOMA-%β (β = 0.39 ± 0.19, P = 0.04), higher insulin values 2-h after an oral glucose load (β = 0.62 ± 0.23, P = 0.01), and a higher insulinogenic index (β = 0.42 ± 0.18, P = 0.02). No associations were observed in participants with prediabetes. ConclusionsWe observed an association of avocado intake with better glucose/insulin homeostasis, especially in those with T2D.

Low glomerular filtration rate values are associated with higher TSH in an elderly population at high cardiovascular disease risk.

Hypothyroidism is associated with impaired glomerular filtration rate (GFR), a recognized cardiovascular disease (CVD), and mortality risk factor. In older adults, this association remains unexplored. We aimed to determine the relationship of elevated TSH with GFR in an elderly population at high CVD risk. Older adults (age>65ys) with high CVD risk defined by two or more CVD risk factors: smoking (S), high blood pressure (HBP), high total cholesterol, low HDL cholesterol, diabetes (DM), metabolic syndrome or previous cardiovascular event, were prospectively included at our ambulatory Endocrine Clinic. Patients under levothyroxine or thyroid disease were excluded. TSH> 6mU/l defined subclinical hypothyroidism (ScH) with normal free T4 levels. Estimated GFR was calculated by the Berlin-Initiative Study (BIS)-1 formula for elderly population. Urinary albumin to creatinine ratio (uACR), IL-6 and TNF-α, and Carotid intima-media thickness (CIMT) were also determined. The U Mann-Whitney test, the Spearman test, and multiple linear regression were used as statistical tests. Finally 246 patients (68% females) were included and 20 (8%) had ScH. This group, was older (median, Q1-Q3: 77,72-78; 72,68-77 years, p=0.01) and DM was less frequent than in the euthyroid group (35 vs 58%, p=0.039). Lower fasting glucose (-20%,p=0.01), GFR (-14%,p=0.01) and freeT4 (-10%,p<0.001) were found compared to euthyroid patients. A higher prevalence of Kidney failure was found in ScH (80 vs. 46%, p=0.003) vs. euthyroid individuals. Significant correlations with GFR were detected: age (r-0.482,p<0.001), TSH (r-0.172,p=0.004), IL-6 (r-0.150,p=0.047), TNF-α (r-0.274,p<0.001), uACR (r-0.170,p=0.009) and CIMT(r-0.189,p=0.004). By multiple linear regression, in a model adjusted by age, sex, BMI, uACR, S, DM, TNF-α and HBP, TSH (Bst -0.14, p=0.023, R2 = 0.25) was found an independent predictor of GFR. In older adults with high CVD risk, ScH is associated with lower renal function, and this relationship is present regardless of other cardiometabolic risk factors. These results suggest that ScH could contribute to low GFR and excess CVD risk, although this hypothesis should be addressed in longitudinal studies.

Long-term Follow-up 15 Years After Duodenal Switch or Gastric Bypass for Super Obesity: a Randomized Controlled Trial

BackgroundIn super obesity, Roux-en-Y gastric bypass (RYGB) may be insufficient why some surgeons advocate biliopancreatic diversion with duodenal switch (BPD/DS), a more malabsorptive procedure. There is a paucity of evidence regarding results beyond 10 years, especially after BPD/DS. The aim of this randomized controlled trial was to compare the long-term outcome of BPD/DS, and RYGB in patients with super obesity, i.e., body mass index (BMI) > 50 kg/m2.MethodsThis is a 13- to 17-year follow-up study of a single-center, single-blinded randomized trial in which 47 patients (BMI > 48 and eligible for bariatric surgery) were randomized 1:1 to BPD/DS and RYGB (25 men, 24 BPD/DS, 39.1 ± 9.9 years, BMI 54.5 ± 6.1 kg/m2). The primary outcome was weight loss. The study was financed by Swedish governmental funding of clinical research (ALF). Trial registration number: ISRCTN10940791.ResultsThirty-four (18 BPD/DS) of the living 42 patients (81.0%) participated. BPD/DS resulted in higher BMI loss (20.4 ± 7.9 vs. 12.4 ± 8.6, p = .008) and higher percent of total body weight loss (37.5% ± 12.2 vs. 22.8% ± 14.8, p = .004). BPD/DS was associated with lower fasting glucose, glycated hemoglobin (HbA1c), and low-density lipoprotein (LDL) as well as lower hemoglobin. Adverse events were more common after BPD/DS (2.7 vs. 0.9 per patient, p = .004). The global assessment tool BAROS (Bariatric Analysis and Reporting Outcome System) demonstrated superior scores for BPD/DS (p = .047).ConclusionWhen compared to RYGB, BPD/DS results in superior weight loss and metabolic control as well as superior BAROS score, however, at the cost of more adverse events.Graphical

Effects of Quinine on the Glycaemic Response to, and Gastric Emptying of, a Mixed-Nutrient Drink in Females and Males.

Intraduodenal quinine, in the dose of 600 mg, stimulates glucagon-like peptide-1 (GLP-1), cholecystokinin and insulin; slows gastric emptying (GE); and lowers post-meal glucose in men. Oral sensitivity to bitter substances may be greater in women than men. We, accordingly, evaluated the dose-related effects of quinine on GE, and the glycaemic responses to, a mixed-nutrient drink in females, and compared the effects of the higher dose with those in males. A total of 13 female and 13 male healthy volunteers received quinine-hydrochloride (600 mg ('QHCl-600') or 300 mg ('QHCl-300', females only) or control ('C'), intraduodenally (10 mL bolus) 30 min before a drink (500 kcal, 74 g carbohydrates). Plasma glucose, insulin, C-peptide, GLP-1, glucose-dependent insulinotropic polypeptide (GIP) and cholecystokinin were measured at baseline, for 30 min after quinine alone, and then for 2 h post-drink. GE was measured by 13C-acetate breath-test. QHCl-600 alone stimulated insulin, C-peptide and GLP-1 secretion compared to C. Post-drink, QHCl-600 reduced plasma glucose, stimulated C-peptide and GLP-1, and increased the C-peptide/glucose ratio and oral disposition index, while cholecystokinin and GIP were less, in females and males. QHCl-600 also slowed GE compared to C in males and compared to QHCl-300 in females (p < 0.05). QHCl-300 reduced post-meal glucose concentrations and increased the C-peptide/glucose ratio, compared to C (p < 0.05). Magnitudes of glucose lowering and increase in C-peptide/glucose ratio by QHCl-600 were greater in females than males (p < 0.05). We conclude that quinine modulates glucoregulatory functions, associated with glucose lowering in healthy males and females. However, glucose lowering appears to be greater in females than males, without apparent differential effects on GI functions.

The role of weight control in the management of type 2 diabetes mellitus: Perspectives on semaglutide

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used to address multiple aspects of type 2 diabetes mellitus (T2DM) management, including glycaemic control, weight loss, and cardiovascular risk reduction. Semaglutide, a well-established GLP-1 RA approved for T2DM treatment and weight management, demonstrates marked efficacy in achieving these clinically important goals. The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) consensus report emphasizes the importance of a holistic approach to T2DM treatment, with weight control as a key component for improving patient outcomes. Notably, semaglutide is mentioned in the consensus report as having 'very high' efficacy for both glucose lowering and weight loss in T2DM treatment. Nevertheless, as has been observed with other weight-lowering drugs, weight loss observed with semaglutide appears less profound in individuals with T2DM than in those with obesity without T2DM, a phenomenon requiring further investigation. The semaglutide safety and tolerability profiles are well established, and it is approved in some countries to reduce cardiovascular risk in certain populations with T2DM. Thus, semaglutide offers a well-established therapeutic option that aligns well with guideline recommendations for T2DM management, emphasizing the high importance of weight control and amelioration of other cardiometabolic risk factors.

Glucose levels are not the same for everyone: a real-world big data study evaluating fasting serum glucose levels by sex and age among children.

Understanding the normal range of laboratory values as pertained to different age groups and males or females is paramount in health care delivery. We aimed to assess the distribution of morning fasting serum glucose levels by age and sex in the general population of children using a large-scale population-based cohort. A retrospective study with real-world de-identified data from a large, state mandated health fund in Israel among children aged 2-18 years old between 2006 and 2019. Age, sex, and BMI differences in mean glucose levels were evaluated. Study included 130,170 venous blood samples from 117,411 children, 53.3 % were female. After adjusting for age boys had higher fasting serum glucose levels than girls, with a mean of 89.21±8.66 mg/dL vs. 87.59±8.35 (p<0.001) [4.95±0.48 mmol/L vs. 4.86±0.46]. Compared to the 15 to 18 year-olds (88.49±7.63 mg/dL) [4.92±0.42 mmol/L], 2 to 5 year-olds had lower glucose levels (84.19±10.65, [4.68±0.59] (p<0.001)), 11 to 14 year-olds had higher glucose (90.40±7.42 [5.02±0.41], (p<0.001)) and 6 to 10 year-olds showed no difference (88.45±8.25) [4.91±0.46]. 33.0 % (n=42,991) had a BMI percentile record the same year as their glucose test result. There was a weak yet significant positive association between blood glucose levels and BMI. Our large cohort indicates that boys have slightly higher fasting serum glucose levels than girls, as do adolescents compared to younger children. This finding is important for the delivery of adequate health care, screening for illness and avoiding unnecessary investigations and tests.

Beyond body condition: Experimental evidence that plasma metabolites improve nutritional state measurements in a free-living seabird

The ability to efficiently measure the health and nutritional status of wild populations in situ is a valuable tool, as many methods of evaluating animal physiology do not occur in real-time, limiting the possibilities for direct intervention. This study investigates the use of blood plasma metabolite concentrations, measured via point-of-care devices or a simple plate reader assay, as indicators of nutritional state in free-living seabirds. We experimentally manipulated the energy expenditure of wild black-legged kittiwakes on Middleton Island, Alaska, and measured the plasma concentrations of glucose, cholesterol, B-hydroxybutyrate, and triglycerides throughout the breeding season, along with measures of body condition (size-corrected mass [SCM] and muscle depth). Supplemental feeding improved the nutritional state of kittiwakes by increasing feeding rate (higher glucose and triglycerides, lower cholesterol), and flight-handicapping caused a slight nutritional decline (lower glucose and triglycerides, higher cholesterol and B-hydroxybutyrate). Glucose and triglycerides were the best indicators of nutritional state when used alongside SCM, and improved upon commonly used metrics for measuring individual condition (i.e. SCM or mass alone). Metabolite concentrations varied across the breeding period, suggesting that the pre-laying stage, when feeding rates tend to be lower, was the most nutritionally challenging period for kittiwakes (low glucose, high cholesterol). Muscle depth also varied by treatment and breeding stage, but differed from other nutritional indices, suggesting that muscle depth is an indicator of exercise and activity level rather than nutrition. Here we demonstrate potential for the use of blood plasma metabolites measured via point-of-care devices as proxies for evaluating individual health, population health, and environmental food availability.

Associations between Metabolomic Biomarkers of Avocado Intake and Glycemia in the Multi-Ethnic Study of Atherosclerosis

BackgroundAvocado consumption is linked to better glucose homeostasis, but small associations suggest potential population heterogeneity. Metabolomic data capture the effects of food intake after digestion and metabolism, thus accounting for individual differences in these processes. ObjectivesTo identify metabolomic biomarkers of avocado intake and to examine their associations with glycemia. MethodsBaseline data from 6224 multi-ethnic older adults (62% female) included self-reported avocado intake, fasting glucose and insulin, and untargeted plasma proton nuclear magnetic resonance metabolomic features (metabolomic data were available for a randomly selected subset; N = 3438). Subsequently, incident type 2 diabetes (T2D) was assessed over an ∼18 y follow-up period. A metabolome-wide association study of avocado consumption status (consumer compared with nonconsumer) was conducted, and the relationship of these features with glycemia via cross-sectional associations with fasting insulin and glucose and longitudinal associations with incident T2D was examined. ResultsThree highly-correlated spectral features were associated with avocado intake at metabolome-wide significance levels (P < 5.3 ∗ 10–7) and combined into a single biomarker. We did not find evidence that these features were additionally associated with overall dietary quality, nor with any of 47 other food groups (all P > 0.001), supporting their suitability as a biomarker of avocado intake. Avocado intake showed a modest association only with lower fasting insulin (β = –0.07 +/- 0.03, P = 0.03), an association that was attenuated to nonsignificance when additionally controlling for body mass index (kg/m2). However, our biomarker of avocado intake was strongly associated with lower fasting glucose (β = –0.22 +/- 0.02, P < 2.0 ∗ 10–16), lower fasting insulin (β = –0.17 +/- 0.02, P < 2.0 ∗ 10–16), and a lower incidence of T2D (hazard ratio: 0.68; 0.63–074, P < 2.0 ∗ 10–16), even when adjusting for BMI. ConclusionsHighly significant associations between glycemia and avocado-related metabolomic features, which serve as biomarkers of the physiological impact of dietary intake after digestion and absorption, compared to modest relationships between glycemia and avocado consumption, highlights the importance of considering individual differences in metabolism when considering diet-health relationships.

Design of a Dual Agonist of Exendin-4 and FGF21 as a Potential Treatment for Type 2 Diabetes Mellitus and Obesity.

Fibroblast growth factor 21 (FGF21) is a metabolic, endocrine hormone regulating insulin sensitivity, energy expenditure, and lipid metabolism. It has significant potential as a therapeutic drug for treating type 2 diabetes and obesity. However, the clinical efficacy of FGF21 analogs is limited due to their instability and short half-life. Glucagon-like peptide 1 (GLP-1) receptor agonists have been recognized as effective medications for type 2 diabetes mellitus and obesity over the past two decades. This study designed a new long-acting dual-agonist, exendin-4/FGF21, utilizing albumin-binding-designed ankyrin repeat proteins (DARPins) as carriers. The purified fusion proteins were subcutaneously injected into mice for pharmacokinetic and biological activity studies. Ex-DARP-FGF21 had a high binding affinity for human serum albumin (HSA) in vitro and a prolonged half-life of 27.6 hours in vivo. Bioactivity results reveal that Ex-DARP-FGF21 significantly reduced blood glucose levels in healthy mice. Moreover, compared to Ex-DARP alone, the Ex-DARP-FGF21 dual agonist displayed enhanced blood glucose lowering bioactivity and superior body weight management in the diet-induced obesity (DIO) mouse model. These results indicate that the long-acting dual agonist of exendin-4 and FGF21 holds considerable potential as a treatment for type 2 diabetes mellitus (T2DM) and obesity in the future.

Genetic Evidence Strongly Supports Managing Weight and Blood Pressure in Addition to Glycemic Control in Preventing Vascular Complications in People With Type 2 Diabetes.

To investigate the causal association of type 2 diabetes and its components with risk of vascular complications independent of shared risk factors obesity and hypertension and to identify the main driver of this risk. We conducted Mendelian randomization (MR) using independent genetic variants previously associated with type 2 diabetes, fasting glucose, HbA1c, fasting insulin, BMI, and systolic blood pressure as instrumental variables. We obtained summary-level data for 18 vascular diseases (15 for type 2 diabetes) from FinnGen and publicly available genome-wide association studies as our outcomes. We conducted univariable and multivariable MR, in addition to sensitivity tests to detect and minimize pleiotropic effects. Univariable MR analysis showed that type 2 diabetes was associated with 9 of 15 outcomes; BMI and systolic blood pressure were associated with 13 and 15 of 18 vascular outcomes, respectively; and fasting insulin was associated with 4 and fasting glucose with 2. No robust association was found for HbA1c instruments. With adjustment for correlated traits in the multivariable test, BMI and systolic blood pressure, consistent causal effects were maintained, while five associations with type 2 diabetes (chronic kidney disease, ischemic heart disease, heart failure, subarachnoid hemorrhage, and intracerebral hemorrhage) were attenuated to null. Our findings add strong evidence to support the importance of BMI and systolic blood pressure in the development of vascular complications in people with type 2 diabetes. Such findings strongly support the need for better weight and blood pressure management in type 2 diabetes, independent of glucose lowering, to limit important complications.

Dietary supplementation of pyridoxine can enhance the growth performance and improve the protein, lipid utilization efficiency of mandarin fish (Siniperca chuatsi).

This study aimed to assess the effect of pyridoxine supplementation in the mandarin fish diet on growth performance, protein and lipid metabolism, and liver and intestinal histology. Mandarin fish were fed six diets with different levels of pyridoxine (2.67 mg/kg (control), 4.41 mg/kg, 6.57 mg/kg, 10.25 mg/kg, 17.93 mg/kg, 33.12 mg/kg diet) for 8 weeks, and samples were collected for analysis. The findings demonstrated that feeding mandarin fish a diet with 6.57 mg/kg pyridoxine led to a significant increase in weight gain rate (WGR), protein efficiency ratio (PER), whole-body crude protein, whole-body crude lipid, serum protein, cholesterol (CHO), triacylglycerol (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and alkaline phosphatase (ALP), as well as significantly lower serum glucose (GLU) and feed conversion ratio (FCR), compared to the control group (P < 0.05). Furthermore, we found a significant upregulation of the relative expression of genes associated with hepatic lipid oxidation and synthesis (hl, lpl, pparα, cpt1, cs, srebp1, and fas) and proteolysis (ast, alt, and gdh) in fish fed a diet containing 6.57 mg/kg pyridoxine (P < 0.05). Regarding the histological analysis, we observed a notable decrease in the quantity of intestinal mucus-secreting cells when the fish fed a diet containing 10.25 mg/kg pyridoxine (P < 0.05). These findings suggest that dietary pyridoxine supplementation promotes mandarin fish growth by improving the efficiency of protein and lipid utilization. Additionally, we used a broken-line regression analysis to estimate the optimal dietary pyridoxine requirement for mandarin fish in the range of 6.17-6.41 mg/kg based on WGR, FCR, and PER.

Glycemic variability and hypoglycemia before and after Roux-en-Y Gastric Bypass and Sleeve Gastrectomy – A cohort study of females without diabetes

BackgroundRoux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) lead to lower fasting glucose concentrations, but might cause higher glycemic variability (GV) and increased risk of hypoglycemia. However, it has been sparsely studied in patients without preoperative diabetes under normal living conditions. ObjectivesTo study 24-hour interstitial glucose (IG) concentrations, GV, the occurrence of hypoglycemia and dietary intake before and after laparoscopic RYGB and SG in females without diabetes. SettingOutpatient bariatric units at a community and a university hospital. MethodsContinuous glucose monitoring and open-ended food recording over 4 days in 4 study periods: at baseline, during the preoperative low-energy diet (LED) regimen, and at 6 and 12 months postoperatively. ResultsOf 47 patients included at baseline, 83%, 81%, and 79% completed the remaining 3 study periods. The mean 24-hour IG concentration was similar during the preoperative LED regimen and after surgery and significantly lower compared to baseline in both surgical groups. GV was significantly increased 6 and 12 months after surgery compared to baseline. The self-reported carbohydrate intake was positively associated with GV after surgery. IG concentrations below 3.9 mmol/L were observed in 14/25 (56%) of RYGB- and 9/12 (75%) of SG-treated patients 12 months after surgery. About 70% of patients with low IG concentrations also reported hypoglycemic symptoms. ConclusionsThe lower IG concentration in combination with the higher GV after surgery, might create a lower margin to hypoglycemia. This could help explain the increased occurrence of hypoglycemic episodes after RYGB and SG.

Intermittent scanning continuous glucose monitoring is safe and useful in postsurgical glucose monitoring after pancreatoduodenectomy

AimsIntermittently scanned continuous glucose monitoring (isCGM) systems have not been thoroughly evaluated during in-hospital stay, and there are concerns about accuracy during various conditions. Patients undergoing pancreatoduodenectomy have an increased risk of hyperglycaemia after surgery which is aggravated by parenteral nutrition therapy. This study aims to evaluate glycaemic control and safety during insulin infusion in a surgical non-ICU ward, using a hybrid glucose monitoring approach with isCMG and periodic point-of-care (POC) testing.MethodsWe prospectively included 100 patients with a resectable pancreatic tumour. After surgery, continuous insulin infusion was initiated when POC glucose was > 7 mmol/l and titrated to maintain glucose between 7 and 10 mmol/l. Glucose was monitored with isCGM together with intermittent POC, every 3–6 h. Median absolute relative difference (MARD) and hypoglycaemic events were evaluated. Mean glucose was compared with a historic control (n = 100) treated with multiple subcutaneously insulin injections, monitored with POC only.ResultsThe intervention group (isCGM/POC) had significantly lower POC glucose compared with the historic control group (8.8 ± 2.2 vs. 10.4 ± 3.4 mmol/l, p < 0.001). MARD was 17.8% (IQR 10.2–26.7). isCGM readings were higher than POC measurements in 91% of the paired cases, and isCGM did not miss any hypoglycaemic event. About 4.5% of all isCGM readings were < 3.9 mmol/l, but only six events were confirmed with POC, and none was < 3.0 mmol/l.ConclusionsA hybrid approach with isCGM/POC is a safe and effective treatment option in a non-ICU setting after pancreatoduodenectomy.

Gestational Glucose Intolerance and Birth Weight-Related Complications.

To evaluate the risks of large-for-gestational-age birth weight (LGA) and birth weight-related complications in pregnant individuals with gestational glucose intolerance, an abnormal screening glucose loading test result without meeting gestational diabetes mellitus (GDM) criteria. In a retrospective cohort study of 46,989 individuals with singleton pregnancies who delivered after 28 weeks of gestation, those with glucose loading test results less than 140 mg/dL were classified as having normal glucose tolerance. Those with glucose loading test results of 140 mg/dL or higher and fewer than two abnormal values on a 3-hour 100-g oral glucose tolerance test (OGTT) were classified as having gestational glucose intolerance. Those with two or more abnormal OGTT values were classified as having GDM. We hypothesized that gestational glucose intolerance would be associated with higher odds of LGA (birth weight greater than the 90th percentile for gestational age and sex). We used generalized estimating equations to examine the odds of LGA in pregnant individuals with gestational glucose intolerance compared with those with normal glucose tolerance, after adjustment for age, body mass index, parity, health insurance, race and ethnicity, and marital status. In addition, we investigated differences in birth weight-related adverse pregnancy outcomes. Large for gestational age was present in 7.8% of 39,685 pregnant individuals with normal glucose tolerance, 9.5% of 4,155 pregnant individuals with gestational glucose intolerance and normal OGTT, 14.5% of 1,438 pregnant individuals with gestational glucose intolerance and one abnormal OGTT value, and 16.0% of 1,711 pregnant individuals with GDM. The adjusted odds of LGA were higher in pregnant individuals with gestational glucose intolerance than in those with normal glucose tolerance overall (adjusted odds ratio [aOR] 1.35, 95% CI 1.23-1.49, P <.001). When compared separately with pregnant individuals with normal glucose tolerance, those with either gestational glucose intolerance subtype had higher adjusted LGA odds (gestational glucose intolerance with normal OGTT aOR 1.21, 95% CI 1.08-1.35, P <.001; gestational glucose intolerance with one abnormal OGTT value aOR 1.77, 95% CI 1.52-2.08, P <.001). The odds of birth weight-related adverse outcomes (including cesarean delivery, severe perineal lacerations, and shoulder dystocia or clavicular fracture) were higher in pregnant individuals with gestational glucose intolerance with one abnormal OGTT value than in those with normal glucose tolerance. Gestational glucose intolerance in pregnancy is associated with birth weight-related adverse pregnancy outcomes. Glucose lowering should be investigated as a strategy for lowering the risk of these outcomes in this group.

Integrating metabolic expenditure information from wearable fitness sensors into an AI-augmented automated insulin delivery system: a randomised clinical trial

Exercise can rapidly drop glucose in people with type 1 diabetes. Ubiquitous wearable fitness sensors are not integrated into automated insulin delivery (AID) systems. We hypothesised that an AID can automate insulin adjustments using real-time wearable fitness data to reduce hypoglycaemia during exercise and free-living conditions compared with an AID not automating use of fitness data. Our study population comprised of individuals (aged 21-50 years) with type 1 diabetes from from the Harold Schnitzer Diabetes Health Center clinic at Oregon Health and Science University, OR, USA, who were enrolled into a 76 h single-centre, two-arm randomised (4-block randomisation), non-blinded crossover study to use (1) an AID that detects exercise, prompts the user, and shuts off insulin during exercise using an exercise-aware adaptive proportional derivative (exAPD) algorithm or (2) an AID that automates insulin adjustments using fitness data in real-time through an exercise-aware model predictive control (exMPC) algorithm. Both algorithms ran on iPancreas comprising commercial glucose sensors, insulin pumps, and smartwatches. Participants executed 1 week run-in on usual therapy followed by exAPD or exMPC for one 12 h primary in-clinic session involving meals, exercise, and activities of daily living, and 2 free-living out-patient days. Primary outcome was time below range (<3·9 mmol/L) during the primary in-clinic session. Secondary outcome measures included mean glucose and time in range (3·9-10 mmol/L). This trial is registered with ClinicalTrials.gov, NCT04771403. Between April 13, 2021, and Oct 3, 2022, 27 participants (18 females) were enrolled into the study. There was no significant difference between exMPC (n=24) versus exAPD (n=22) in time below range (mean [SD] 1·3% [2·9] vs 2·5% [7·0]) or time in range (63·2% [23·9] vs 59·4% [23·1]) during the primary in-clinic session. In the 2 h period after start of in-clinic exercise, exMPC had significantly lower mean glucose (7·3 [1·6] vs 8·0 [1·7] mmol/L, p=0·023) and comparable time below range (1·4% [4·2] vs 4·9% [14·4]). Across the 76 h study, both algorithms achieved clinical time in range targets (71·2% [16] and 75·5% [11]) and time below range (1·0% [1·2] and 1·3% [2·2]), significantly lower than run-in period (2·4% [2·4], p=0·0004 vs exMPC; p=0·012 vs exAPD). No adverse events occurred. AIDs can integrate exercise data from smartwatches to inform insulin dosing and limit hypoglycaemia while improving glucose outcomes. Future AID systems that integrate exercise metrics from wearable fitness sensors may help people living with type 1 diabetes exercise safely by limiting hypoglycaemia. JDRF Foundation and the Leona M and Harry B Helmsley Charitable Trust, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.

The anti-inflammatory and immunological properties of SGLT-2 inhibitors.

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are antidiabetic oral drugs that act on proximal renal tubules promoting renal glucose excretion. Although SGLT-2i belong to the class of hypoglycemic agents, in the last years great interest has emerged in studying their pleiotropic effects, beyond their ability to lower glucose levels. In this review we are describing the anti-inflammatory and immunological properties of SGLT-2i; furthermore, we are addressing how the mechanisms associated with the aforementioned anti-inflammatory properties may contribute to the beneficial effects of SGLT-2i in diabetes. A systematic search was undertaken for studies related the properties of SGLT-2i in reducing the inflammatory milieu of acute and chronic disease by acting on the immune system, independently by glycemia. Recently, some data described the anti-inflammatory and immunological properties of SGLT-2 in both pre-clinical and clinical studies. Numerous data confirmed the cardio- and -renal protective effects of SGLT-2i in patients with heart failure and kidney diseases, with or without diabetes. SGLT-2i are promising drugs with anti-inflammatory and immunological properties. Despite the mechanism of action of SGLT-2i is not fully understood, these drugs demonstrated anti-inflammatory effects, which may help in keeping under control the variety of complications associated with diabetes.

Residual β-Cell Function Is Associated With Longer Time in Range in Individuals With Type 1 Diabetes.

Little is known about the influence of residual islet function on glycemic control in type 1 diabetes (T1D). We investigated the associations between residual β-cell function and metrics of continuous glucose monitoring (CGM) in individuals with T1D. In this cross-sectional cohort comprising 489 individuals (64% female, age 41.0 ± 14.0 years), T1D duration was 15.0 (interquartile range [IQR] 6.0-29.0) years. Individuals had a time in range (TIR) of 66% (IQR 52-80%) and a urinary C-peptide-to-creatinine ratio (UCPCR) of 0.01 (IQR 0.00-0.41) nmol/mmol. To assess β-cell function, we measured UCPCR (detectable >0.01 nmol/mmol), and to assess α-cell function, fasting plasma glucagon/glucose ratios were measured. CGM was used to record TIR (3.9-10 mmol/L), time below range (TBR) (<3.9 mmol/L), time above range (TAR) (>10 mmol/L), and glucose coefficient of variance (CV). For CGM, 74.7% used FreeStyle Libre 2, 13.8% Medtronic Guardian, and 11.5% Dexcom G6 as their device. The percentage of patients with T1D who had a detectable UCPCR was 49.4%. A higher UCPCR correlated with higher TIR (r = 0.330, P < 0.05), lower TBR (r = -0.237, P < 0.05), lower TAR (r = -0.302, P < 0.05), and lower glucose CV (r = -0.356, P < 0.05). A higher UCPCR correlated negatively with HbA1c levels (r = -0.183, P < 0.05) and total daily insulin dose (r = -0.183, P < 0.05). Glucagon/glucose ratios correlated with longer TIR (r = 0.234, P < 0.05). Significantly longer TIR, shorter TBR and TAR, and lower CV were observed in individuals with greater UCPCR-assessed β-cell function. Therefore, better CGM-derived metrics in individuals with preserved β-cell function may be a contributor to a lower risk of developing long-term complications.

Perioperative glycaemic control for people with diabetes undergoing surgery.

Perioperative glycaemic control for people with diabetes undergoing surgery.

Comparative effectiveness of second line glucose lowering drug treatments using real world data: emulation of a target trial

ObjectiveTo build on the recently completed GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) randomised trial examining the comparative effectiveness of second line glucose lowering drugs in achieving...