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A female patient in her early sixties had problems of recurrent syncopal attacks and panic attacks over the last 5 years. She had been initially managed for an anxiety disorder with psychiatric medications. During one of those episodes, she was brought to our hospital in an unconscious state with a low blood sugar level of 43 mg/dL. She was suspected to have a neuroendocrine tumour and diagnosis was established by supervised fasting up to 72 hours and imaging. Her recorded blood sugar during fasting was 37 mg/dL. She underwent surgery and presently remains asymptomatic. Physicians should have a high suspicion of insulinoma in patients presenting with repeated episodes of hypoglycaemic symptoms in the absence of any cognizable cause.

Objectives: The purpose of the study is to investigate body awareness and body image perception of patients with type 2 diabetes mellitus (T2DM) and to explore the association between clinical parameters and body awareness. Methods: A total of 92 participants with T2DM (38 women and 54 men) aged 36–76 years were recruited. Biochemical measurements, including fasting blood glucose, postprandial blood glucose and hemoglobin A1c (HbA1c), were obtained from the patients’ blood sample records. The Body Awareness Questionnaire (BAQ), Body Cathexis Scale (BCS) and Awareness Body Chart (ABC) were filled in by all subjects. Results: Most participants had an above-average BAQ (81.5%) and BCS (87%) score. There was a significant correlation between body mass index and ABC pain subscale. HbA1c was significantly associated with the duration of diabetes and sleep-wake cycle, process domains and total BAQ score. The body awareness score for the lower leg and foot regions (ABC parts) was negatively correlated with fasting blood glucose and HbA1c levels, while body awareness in the foot region was negatively correlated with the duration of diabetes. There was no association between BCS and any clinical parameters. Conclusion: This study showed that body awareness is associated with diabetes-related clinical parameters, such as fasting blood glucose and HbA1c levels, and duration of diabetes in patients with T2DM. Following diabetes progression and an increase in blood glucose levels, body awareness tended to decrease, particularly in the lower leg and foot regions. These findings highlighted the importance of evaluating body awareness in patients with T2DM. © 2023 Elsevier Ltd

In this paper, we provide an overview of the evolution of the definition of hyperglycemia during the past century and the alterations in glucose dynamics that cause fasting and postprandial hyperglycemia. We discuss how extensive mechanistic, physiological research into the factors and pathways that regulate the appearance of glucose in the circulation and its uptake and metabolism by tissues and organs has contributed knowledge that has advanced our understanding of different types of hyperglycemia, namely prediabetes and diabetes and their subtypes (impaired fasting plasma glucose, impaired glucose tolerance, combined impaired fasting plasma glucose, impaired glucose tolerance, type 1 diabetes, type 2 diabetes, gestational diabetes mellitus), their relationships with medical complications, and how to prevent and treat hyperglycemia.

Several aspects of diabetes pathophysiology and complications result from hyperglycemia-induced alterations in the structure and function of plasma proteins. Furthermore, insulin has a significant influence on protein metabolism by affecting both the synthesis and degradation of proteins in various tissues. To understand the role of progressive hyperglycemia on plasma proteins, in this study, we measured the turnover rates of high-density lipoprotein (HDL)-associated proteins in control (chow diet), prediabetic [a high-fat diet (HFD) for 8 wk] or diabetic [HFD for 8 wk with low-dose streptozotocin (HFD + STZ) in

Cypermethrin (CYP), a prototypical synthetic pyrethroid, reportedly causes metabolic disruption, while its stereoselective impact remains elusive. This study initially revealed that only α-CYP caused significant weight loss at 8.5 mg/(kg•day) in rats. All three CYP isomers caused the accumulation of hepatic glycogen, and hyperlipemia phenotype as the increment of total triglyceride. Rats treated with α-CYP had markedly high blood glucose levels and homeostasis model assessment of insulin resistance index. The systematic inflammation of θ-CYP group rats was evidenced by high lipopolysaccharide-binding protein levels and abnormalities of leukocytes indices. By examining the gut microbiome, we found that α-CYP-treated rats had low contents of Firmicutes and high levels of Verrucomicrobia while Elusimicrobia was enriched in the β-CYP group. The increasing alpha diversity in the θ-CYP group may be due to the dominance of pathogenic bacteria and the increase of probiotics to counteract adverse effects. Exclusively, the α-CYP group enriched total short-chain fatty acids (SCFAs), whereas most SCFAs depleted in the θ-CYP group. The correlation analysis further found Firmicutes, an energy storage modulator, was positive to body weight (BW), while SCFAs exerted the opposite, confirming the low BW in α-CYP. Blood glucose that correlated well with SCFAs and Verrucomicrobia can be accounted for the discrepancy between α-CYP and θ-CYP. Overall, the three isomers exerted stereoselective glycolipid disruption in rats, and gut homeostasis acted as vital indicators.

OBJECTIVE: The aim of this study was to investigate glucose tolerance, glucagon response, and beta cell function during a 1-year maintenance period with either exercise, the glucagon-like peptide-1 receptor agonist liraglutide, or the combination after diet-induced weight loss.METHODS: In this randomized placebo-controlled trial, adults with obesity (BMI: 32-43 kg/m 2 ) without diabetes underwent an 8-week low-calorie diet (800 kcal/d) and were randomized to 52 weeks of aerobic exercise, liraglutide 3.0 mg/d, exercise and liraglutide combined, or placebo. Change in glucose and glucagon response to a 3-hour mixed meal test and disposition index, as a measure of beta cell function, were measured. RESULTS: A total of 195 participants were randomized. After 1 year of treatment, the combination group had decreased postprandial glucose response by -9% (95% CI: -14% to -3%; p = 0.002), improved beta cell function by 49% (95% CI: 16% to 93%; p = 0.002), and decreased glucagon response by -18% (95% CI: -34% to -3%; p = 0.024) compared with placebo. Compared with placebo, liraglutide alone improved postprandial glucose response by -7% (95% CI: -12% to -1%; p = 0.018), but not beta cell function or glucagon. Exercise alone had similar postprandial glucose response, beta cell function, and glucagon response as placebo.CONCLUSIONS: Only the combination of exercise and liraglutide improved glucose tolerance, beta cell function, and glucagon responses after weight loss.

The Medtronic advanced hybrid closed-loop (AHCL) and MiniMed™ 670G hybrid closed-loop (HCL) systems provide the option to temporarily increase the glucose target to 150 mg/dL (8.3 mmol/L). This analysis investigated the efficacy of the AHCL compared with that of the HCL after the use of this setting. Data from 60 participants in the Fuzzy Logic Automated Insulin Regulation (FLAIR) study were used to compare the AHCL and HCL systems after the use of the temporary target (TT), and during analogous periods where this setting was not used. Differences in time in range 70-180 mg/dL between the systems were similar after the use of the TT setting and during analogous non-TT periods (interaction

Repeated hypoglycemia exposure leads to impaired awareness of hypoglycemia (IAH) and the development of defective counterregulatory responses. To date, only pancreas or islet transplantation has demonstrated normalization of hypoglycemia awareness and the endogenous glucose production (EGP) response to defend against insulin-induced hypoglycemia in long-standing type 1 diabetes (T1D). This study aims to validate clinical metrics of IAH (Clarke score), hypoglycemia severity (HYPO score), glycemic lability (lability index), and continuous glucose monitoring (CGM) as predictors of absent autonomic symptom (AS) recognition and defective glucose counterregulation during insulin-induced hypoglycemia, thus enabling early identification of individuals with compromised physiologic defense against clinically significant hypoglycemia. Forty-three subjects with mean ± standard deviation age 43 ± 13 years and T1D duration 28 ± 13 years, including 32 with IAH and 11 with hypoglycemia awareness (Aware), and 12 nondiabetic control subjects, underwent single-blinded randomized-paired hyperinsulinemic-euglycemic and hypoglycemic clamp experiments. Receiver operating characteristic (ROC) curves and sensitivity analyses were performed to assess metric prediction of absent AS recognition and defective EGP responses to hypoglycemia. Clarke score and CGM measures of hypoglycemia exposure demonstrated good ability to predict absent AS recognition (area under the curve ≥0.80). A composite threshold of IAH-Clarke ≥4 with ROC curve-derived thresholds for CGM measures of hypoglycemia exposure showed high specificity and predictive value in identifying an absent AS response during the hypoglycemic clamp. Metrics demonstrated poor ability to predict defective glucose counterregulation by the EGP response, which was impaired even in the Aware group. Screening for IAH alongside assessment of CGM data can increase the specificity for identifying individuals with absent hypoglycemia symptom recognition who may benefit from further intervention.

Clozapine is an atypical antipsychotic used in refractory schizophrenia, also efficient in alleviating dyskinesia in Parkinson’s disease. Despite its potency, this drug is associated with severe metabolic side effects, including increased risk for diabetes. We report the case of a 45-year-old overweight woman with Parkinson’s disease who presented with rapid-onset hyperglycaemia within 2 months after starting clozapine for refractory dyskinaesia. She had a history of gestational diabetes. At presentation, her blood glucose level was 505 mg/dL and glycated haemoglobin 12.4%, with no catabolic symptoms. Clozapine was suspended and metformin was started, but adequate glycaemic control was achieved only with insulin therapy, along with exenatide and empagliflozin afterwards. We assume that clozapine acted as a trigger for rapid deterioration of glycaemic control through direct pathophysiological mechanisms, rather than an indirect slowly evolving weight gain-related metabolic syndrome pathway. Clinicians should be aware of this complication, enabling timely diagnosis and proper treatment.

Glucose control in patients after total pancreatectomy is problematic because of the complete absence of α- and β-cells, leading to impaired quality of life. A novel, bihormonal artificial pancreas (BIHAP), using both insulin and glucagon, may improve glucose control, but studies in this setting are lacking.To assess the efficacy and safety of the BIHAP in patients after total pancreatectomy.This randomized crossover clinical trial compared the fully closed-loop BIHAP with current diabetes care (ie, insulin pump or pen therapy) in 12 adult outpatients after total pancreatectomy. Patients were recruited between August 21 and November 16, 2020. This first-in-patient study began with a feasibility phase in 2 patients. Subsequently, 12 patients were randomly assigned to 7-day treatment with the BIHAP (preceded by a 5-day training period) followed by 7-day treatment with current diabetes care, or the same treatments in reverse order. Statistical analysis was by Wilcoxon signed rank and Mann-Whitney U tests, with significance set at a 2-sided P.05.The primary outcome was the percentage of time spent in euglycemia (70-180 mg/dL [3.9-10 mmol/L]) as assessed by continuous glucose monitoring.In total, 12 patients (7 men and 3 women; median [IQR] age, 62.5 [43.1-74.0] years) were randomly assigned, of whom 3 did not complete the BIHAP phase and 1 was replaced. The time spent in euglycemia was significantly higher during treatment with the BIHAP (median, 78.30%; IQR, 71.05%-82.61%) than current diabetes care (median, 57.38%; IQR, 52.38%-81.35%; P = .03). In addition, the time spent in hypoglycemia (70 mg/dL [3.9 mmol/L]) was lower with the BIHAP (median, 0.00% [IQR, 0.00%-0.07%] vs 1.61% [IQR, 0.80%-3.81%]; P = .004). No serious adverse events occurred.Patients using the BIHAP after total pancreatectomy experienced an increased percentage of time in euglycemia and a reduced percentage of time in hypoglycemia compared with current diabetes care, without apparent safety risks. Larger randomized trials, including longer periods of treatment and an assessment of quality of life, should confirm these findings.trialregister.nl Identifier: NL8871.

This study examined the dynamic, real-time associations between partner involvement in diabetes self-care and continuous glucose monitor (CGM) metrics in adults with type 2 diabetes.For 1 week, 63 participants wore Dexcom G4 CGMs and provided momentary reports of partner involvement in diabetes self-care five times per day. Dynamic structural equation models were used to estimate the reciprocal lagged effects of partner involvement on next-hour CGM metrics (and vice versa).Partner involvement predicted improved next-hour glucose control for five of six CGM metrics in analyses adjusted for time-varying covariates. The hour after partner involvement, the model predicted a 26.34 mg/dl decrease in glucose level (standardized β = -0.19), 30% greater odds of meeting target time in target range ( β = 0.07), 48% higher odds of target time below target range (TBR; β = 0.04; the only nonsignificant effect), 47% greater odds of target time above target range (β = 0.11), a 4.20 unit decrease in glucose standard deviation ( β = -0.19), and a 0.01 unit decrease in glucose coefficient of variation ( β = -0.08; all p values.05). There was less consistent support for the reverse pathway, with only two metrics significantly related to next-hour partner involvement: glucose level ( β = 0.15) and TBR ( β = 0.21), such that having higher levels and meeting target TBR were significantly predictive of next-hour partner involvement.This is the first study showing that partner involvement in daily diabetes management predicts short-term glucose control. More research is needed to understand how partners influence glycemic control and evaluate interventions that promote their involvement in diabetes care.

Herbal preparations, often promoted as being natural and completely safe, are gaining popularity in the management of diabetes mellitus, despite lack of scientific data to confirm their efficacy and safety claims. This study investigated efficacy and safety of eight commercial antidiabetic herbal products. Antidiabetic activities were investigated in streptozotocin-induced diabetic rats at doses based on their labelled recommended dosages using metformin as reference drug. Body weights, blood glucose level (BGL), haematogical and biochemical parameters as well as histopathology of the kidney and lungs were assessed by standard procedures. All the samples demonstrated weight reduction (p

Large amount of people having diabetics in the world, and it is increasing very rapidly. Diabetics should to check their blood glucose level at least four times a day. When controls are not done regularly, risk of hypoglycemia and hyperglycemia may arise. There are ongoing researches for developing non-invasive methods as an alternative to finger piercing, which is the most commonly used and painful method for patients. In this study, although a physical glucometer design has not been completed yet, it has been demonstrated which wavelength ranges and which parameters can be used for non-invasive device. Most importantly an empirical relationship has been established between the level of blood sugar and de-polarization disturbance seen in circularly polarized light. The proposed equation can estimate the blood glucose level based on de-polarization information with an average error rate of 1%.

Objectives Investigating empirical relationships among laboratory measures in children with diabetic ketoacidosis (DKA) can provide insights into physiological alterations occurring during DKA. We determined whether alterations in laboratory measures during DKA conform to theoretical predictions. Methods We used Pearson correlation statistics and linear regression to investigate correlations between blood glucose, electrolytes, pH and PCO2 at emergency department presentation in 1,681 pediatric DKA episodes. Among children with repeat DKA episodes, we also assessed correlations between laboratory measures at the first vs. second episode. Results pH and bicarbonate levels were strongly correlated (r=0.64), however, pH and PCO2 were only loosely correlated (r=0.17). Glucose levels were correlated with indicators of dehydration and kidney function (blood urea nitrogen (BUN), r=0.44; creatinine, r=0.42; glucose-corrected sodium, r=0.32). Among children with repeat DKA episodes, PCO2 levels tended to be similar at the first vs. second episode (r=0.34), although pH levels were only loosely correlated (r=0.19). Conclusions Elevated glucose levels at DKA presentation largely reflect alterations in glomerular filtration rate. pH and PCO2 are weakly correlated suggesting that respiratory responses to acidosis vary among individuals and may be influenced by pulmonary and central nervous system effects of DKA.

The aim of this study was to perform a comprehensive literature review regarding the relevant hormonal and histologic changes observed after Roux-en-Y gastric bypass (RYGB). We aimed to describe the relevant hormonal (glucagon-like peptides 1 and 2 [GLP-1 and GLP-2], peptide YY [PYY], oxyntomodulin [OXM], bile acids [BA], cholecystokinin [CCK], ghrelin, glucagon, gastric inhibitory polypeptide [GIP], and amylin) profiles, as well as the histologic (mucosal cellular) adaptations happening after patients undergo RYGB. Our review compiles the current evidence and furthers the understanding of the rationale behind the food intake regulatory adaptations occurring after RYGB surgery. We identify gaps in the literature where the potential for future investigations and therapeutics may lie. We performed a comprehensive database search without language restrictions looking for RYGB bariatric surgery outcomes in patients with pre- and postoperative blood work hormonal profiling and/or gut mucosal biopsies. We gathered the relevant study results and describe them in this review. Where human findings were lacking, we included animal model studies. The amalgamation of physiologic, metabolic, and cellular adaptations following RYGB is yet to be fully characterized. This constitutes a fundamental aspiration for enhancing and individualizing obesity therapy.

Slow, deep breathing (SDB) lowers blood pressure (BP) though the underlying mechanisms are unknown. Redox improvements could facilitate hemodynamic adjustments with SDB though this has not been investigated. The purpose of this randomized, sham-controlled trial was to examine the acute effects of SDB on oxidative stress and endothelial function during a physiological perturbation (high-fat meal) known to induce oxidative stress.Seventeen males (ages 18-35 years) were enrolled, and anthropometric measurements and 7-day physical activity monitoring were completed. Testing sessions consisted of 24-h diet recalls (ASA24), blood sample collection for superoxide dismutase (SOD) and thiobarbituric acid reactive substances (TBARS) analysis, and flow-mediated dilation (FMD). High-fat meals were ingested and 2-min breathing exercises (SDB or sham control breathing) were completed every 15 min during the 4-h postprandial phase. Blood sample collection and FMD were repeated 1-, 2-, and 4-h post meal consumption. Mean body mass index and step counts were 25.6 ± 4.3 kg/mFindings from the current investigation suggest that SDB alters postprandial redox in the absence of changes in endothelial function in young, healthy males.NCT04864184.NCT04864184.

Type 1 Diabetes (T1D) is an autoimmune disease that affects millions of people worldwide. A critical issue in T1D patients is the managing of Postprandial Glucose Response (PGR), through the dosing of the insulin bolus to inject before meals. The Artificial Pancreas (AP), combining autonomous insulin delivery and blood glucose monitoring, is a promising solution. However, state-of-the-art APs require several information for bolus delivery, such as the estimated carbohydrate intake over the meals. This is mainly related to the limited knowledge of the determinants of PGR. Although meal carbohydrates are mostly considered as the major factor into, uencing PGR, other food components play a relevant role in PGRs, and thus, should be taken into account. Based on these considerations, a study to determine the effect of nutritional factors (i.e., carbohydrates, proteins, lipids, fibers, and energy intake) in the short and middle term on Blood Glucose Levels (BGLs) prediction was conducted by Machine Learning (ML) methods. A ML model able to predict the BGLs after 15, 30, 45, and 60 minutes from the meal leveraging on insulin doses, blood glucose, and nutritional factors in T1D patients on AP systems was implemented. More specifically, to investigate the impact of the nutritional factors on the model predictions, a Feed-Forward Neural Network, was fed with several dispositions of BGLs, insulin, and nutritional factors. Both public and self-produced data were used to validate the proposal. The results suggest that patient-specific information about nutritional factors can be significant for middle term postprandial BGLs predictions.

Blood gas analyzers employing glucose-oxidase biosensors under-recover glucose when pOWhole blood specimens were tested by GEM®Premier™ 4000 (GEM 4000) and 5000 (GEM 5000). Specimens with an incalculable ("incalc") error code for glucose result or that had a glucose ≥ 20 mmol/L were retested on a second analyzer of the same type within 5 min over the course of 30 months in 5 hospitals in Calgary, Alberta. Discordant retests were defined as either: 1) paired numeric results with a difference 10 %, or 2) an "incalc" code that yielded a numeric result upon retesting. Glucose recovery in relation to pOOf 1,776 glucose tests repeated on the GEM 5000 or 1,544 on GEM 4000, 10% were discordant. GEM 5000 produced twice as many discordant numeric retests versus the GEM 4000 [5.9% (98/1,651) vs 2.7% (38/1,391)]. The majority of "incalc" error codes repeated with a numeric glucose result on both GEM analyzers [(79.7% (122/153) vs 75.2% (94/125)]. Among specimens experimentally depleted of pOThe algorithm in the GEM®Premier

Treatment of hyperkalemia using intravenous insulin can result in severe hypoglycemia, but regular blood glucose monitoring is not standardized. This study aimed to (i) explore the demographics of adult patients receiving hyperkalemia treatment and (ii) identify the incidence rate of hypoglycemia and associated demographic or clinical characteristics.A descriptive design with prospective data collection was used. This study recruited 135 patients who received hyperkalemia treatment in the emergency department. Structured blood glucose monitoring was conducted at 1, 2, 4, and 6 hours after receiving intravenous insulin. Univariate analyses of association between demographic and clinical variables and hypoglycemia outcome were performed.There were 31 hypoglycemic events, with 11.9%, 7.4%, 2.2%, and 1.5% occurring at the 1, 2, 4, and 6 hours after treatment. The logit regression showed no significantly increased risk of hypoglycemia in terms of the demographic and clinical variables.The variation in blood glucose response observed in this study combined with the high incidences of hypolycaemia indicated the need for frequent and longer duration of monitoring for patients who were being treated for hyperkalaemia with IDT.

Background: Adipose tissue-derived mesenchymal stem cells (AD-MSCs) were proved to differentiate into insulin-producing cells (IPCs), but the amount of insulin secreted was relatively low compared to the insulin secreted by mature pancreatic islets. Enrichment of MSCs culture with melatonin (MT) was detected to promote cartilage matrix synthesis, osteogenic and neuronal differentiation. Therefore, the present study was conducted to evaluate the potential role of MT pre-treated AD-MSCs in enhancing the treatment and regeneration of the islet cells of Langerhans in diabetic rats induced by streptozotocin ( STZ). Materials and Methods: Forty adult male Sprague Dawley albino rats were divided equally into groups; group I (control group), group II (STZ group), group III (STZ+AD-MSCs) and group IV (STZ+MT pre-treated AD-MSCs ) . Biochemical studies were implemented including measurements of the body weight, fasting blood glucose and serum insulin levels, Interleukin 17 (IL-17) and IL-10. Samples of the pancreas were taken and prepared for light, fluorescent microscopic examination, PCNA and caspase-3 immunohistochemical studies and histomorphometric analysis. Results: The present study confirmed the regenerative and therapeutic effects of AD-MSCs on the pancreatic cells. Concomitant supply of MT to the culture of AD-MSCs, in group IV, was shown to retain the normal architecture of the islet cells of Langerhans. They appeared well-defined and lightly stained, surrounded by classical pancreatic acini and contained a large number of islet cells with vesicular nuclei and prominent nucleoli. Improvements of all the biochemical parameters, in the same group, was demonstrated by increased body weight and serum insulin levels with a decrease in the fasting blood glucose levels. Significant decrease in the pro-inflammatory cytokine; IL-17 and increase in the anti-inflammatory cytokine; IL-10, compared to the STZ group, were also discovered. Significant increase in the PCNA proliferation index, decrease in caspase-3 and increase in PKH26 labeled MSCs area percent was recorded in the group of AD-MSCs enriched with MT compared to the group of AD-MSCs without MT. Conclusions: The present study confirmed the potential therapeutic and protective role of MT pre-treated AD-MSCs against the STZ-induced pancreatic islet cells’ damage. Further studies were recommended to investigate the efficacy of MT and AD-MSCs over longer experimental durations.

OBJECTIVE High cereal fiber and low-glycemic index (GI) diets are associated with reduced cardiovascular disease (CVD) risk in cohort studies. Clinical trial evidence on event incidence is lacking. Therefore, to make trial outcomes more directly relevant to CVD, we compared the effect on carotid plaque development in diabetes of a low-GI diet versus a whole-grain wheat-fiber diet. RESEARCH DESIGN AND METHODS The study randomized 169 men and women with well-controlled type 2 diabetes to counseling on a low GI-diet or whole-grain wheat-fiber diet for 3 years. Change in carotid vessel wall volume (VWV) (prespecified primary end point) was assessed by MRI as an indication of arterial damage. RESULTS Of 169 randomized participants, 134 completed the study. No treatment differences were seen in VWV. However, on the whole-grain wheat-fiber diet, VWV increased significantly from baseline, 23 mm3 (95% CI 4, 41; P = 0.016), but not on the low-GI diet, 8 mm3 (95% CI −10, 26; P = 0.381). The low-GI diet resulted in preservation of renal function, as estimated glomerular filtration rate, compared with the reduction following the wheat-fiber diet. HbA1c was modestly reduced over the first 9 months in the intention-to-treat analysis and extended with greater compliance to 15 months in the per-protocol analysis. CONCLUSIONS Since the low-GI diet was similar to the whole-grain wheat-fiber diet recommended for cardiovascular risk reduction, the low-GI diet may also be effective for CVD risk reduction.

Hyperglycemia is a symptom of type 2 diabetes mellitus, a chronic metabolic disease characterized by elevated blood glucose concentrations. Antidiabetic drugs are common treatments for this metabolic disorder; however, they may have unpleasant side effects. This study hypothesized that probiotic fermented products could preserve nutritional value, maintain metabolic homeostasis, and attenuate the inflammatory response associated with diabetes while reducing side effects. Lactobacillus plantarum KU985438 and Lactobacillus rhamnosus KU985439 showed the lowest alfa-amylase enzyme (α-amylase) activity among 8 lactobacilli tested. These 2 strains were used to develop functional fermented milk products, and their antidiabetic efficacy was tested in induced diabetic Wistar rats. The treatment of diabetic rats with L. plantarum KU985438 or L. rhamnosus KU985439 fermented yogurt resulted in a considerable reduction in blood glucose concentrations (136.79% and 145.17%, respectively) and α-amylase concentrations (56.84% and 56.84%, respectively) compared with conventional treatments. Diabetes relief began after 4 days of yogurt consumption compared with drug-based treatment. Significant improvements in both liver and kidney enzyme concentrations were also observed, in addition to a significant increase in high-density lipoprotein cholesterol concentrations and improved lipid profiles. Inhibition in nuclear factor κB and an increase in Bcl-2 concentrations were also detected. Histopathological examination of both hepatic and pancreatic cells revealed the positive effects of the studied treatment compared with standard treatment. Therefore, the selected Lactobacilli, which has hypoglycemic potential, could be used to produce functional nutraceutical antidiabetic supplements.

Bariatric surgery is evolving as a successful tool for managing morbid obesity and T2DM. This study aimed to identify predictors of diabetes remission after two types of bariatric procedures.This prospective study enrolled 172 patients with morbid obesity associated with T2DM scheduled for bariatric surgery. Two laparoscopic bariatric procedures were done; single anastomosis gastric bypass (SAGB, n = 83) and sleeve gastrectomy (LSG, n = 68). Lipid accumulation product index (LAP) and quantitative insulin sensitivity check index (QUICKI) were used to evaluate lipid profile and insulin sensitivity. Two years after surgery condition of DM was evaluated as complete remission (CR), partial remission (PR), or improvement. The primary outcome measure was predictors of diabetes remission.Two years after surgery, 151 patients were available for evaluation, where 75 patients (49.7%) achieved CR, while PR was found in 36 (23.8%). CR was significantly associated with younger age, shorter duration of DM (p 0.001, for both), higher C-peptide and GLP-1 levels (p 0.001 and p = 0.002, respectively), and bypass surgery (p = 0.027). On multivariate analysis, shorter duration of DM, lower BMI, and higher C-peptide levels were the independent factors predicting CR.Complete remission of T2DM can be achieved in nearly half of the patients two years after SG or SAGB. The duration of diabetes and preoperative BMI and C-peptide levels are the independent factors predicting complete remissions.

The BETTER (BEhaviors, Therapies, TEchnologies and hypoglycemic Risk in Type 1 diabetes) registry is a type 1 diabetes population surveillance system codeveloped with patient partners to address the burden of hypoglycemia and assess the impact of new therapies and technologies. The aim of this report was to describe the baseline characteristics of the BETTER registry cohort.A cross-sectional baseline evaluation was performed of a Canadian clinical cohort established after distribution of an online questionnaire. Participants were recruited through clinics, public foundations, advertising and social media. As of February 2021, 1,430 persons ≥14 years of age and living with type 1 diabetes or latent-autoimmune diabetes (LADA) were enrolled. The trial was registered on ClinicalTrials.gov (NCT03720197).Participants were (mean ± standard deviation) 41.2±15.7 years old with a diabetes duration of 22.0±14.7 years, 62.0% female, 92.1% Caucasian and 7.8% self-reporting as LADA, with 40.9% using a continuous subcutaneous insulin infusion (CSII) system and 78.0% using a continuous glucose monitoring (CGM) system. The most recent glycated hemoglobin ≤7% was reported by 29.7% of participants. At least 1 episode of hypoglycemia3.0 mmol/L (level 2-H) in the last month was reported by 78.4% of participants, with a median (interquartile range) of 5 (3, 10) episodes. The occurrence of severe hypoglycemia (level 3-H) in the last 12 months was reported by 13.3% of participants. Among these, the median number of episodes was 2 (1, 3).We have established the first surveillance registry for people living with type 1 diabetes in Canada relying on patient-reported outcomes and experiences. Hypoglycemia is a highly prevalent burden despite a relatively wide adoption of CSII and CGM use.

Introduction: Acromegaly is a rare disease that results from growth hormone (GH) excess. Diabetes mellitus, hypertension,cardiomyopathy, and obstructive sleep apnoea syndrome( OSAS) are frequent complications. Aim of the study: Identify a useful system to obtain a reliable remote monitoring of glucose and the most important vital parameters in the acromegalic subjects. Patients and Methods: Sixteen acromegalic patients (from 30 to 73 years old) were enrolled. We provided health monitor devices to the patients for continuous acquisition of physiological signals including twelve-lead electrocardiography (EKG) and nocturnal SpO2. At the same time, we applied on the same patients the blinded continuous glucose monitoring system(CGMS). Results: The lowest saturation peaks at night ( Conclusion: The health monitor device associated with CGM may be a new useful and versatile tool for fragile patients who can self-manage remote monitoring, and for physicians who can obtain real-time information for the clinical and therapeutic management of patients. It is also a useful tool for the follow-up of patients with OSAS. Moreover, once the interference of the OSAS is excluded, the CGM allows us to obtain a more reliable and accurate diagnosis of DM.

Achieving glycemic targets in youth and young adults with type 1 diabetes (T1D) is challenging. Diabetes devices, including continuous glucose monitors (CGM) may impact glycemic control. We analyzed the proportion of CGM use in youth and young adults with T1D at nine U.S. T1D Exchange Quality Improvement (T1DX-QI) Collaborative centers and 402 European diabetes prospective follow-up registry (Diabetes-Patienten-Verlaufsdokumentation [DPV]) sites from 2017 to 2020 and examined the association of CGM use to glycemic control as measured by hemoglobin A1c (HbA1c). CGM use increased each year from 2017 to 2020 across all age ranges (6, 6-12, 12-18, 18-25 years) in both registries and lower mean HbA1c was observed in CGM users compared with nonusers regardless of insulin delivery method for all years analyzed. CGM use appeared to increase more so in the European DPV than the U.S. T1DX-QI, which may be due to transatlantic differences in health care systems, insurance coverage, and prescriber habits.

Premature pubarche (PP) is a risk factor for metabolic syndrome (MS). The aim was to evaluate if glucose-insulin metabolism, cardiovascular risk factors, familial cardiovascular risk factors (FCVRF) created a risk for insulin resistance (IR) and if PP was a risk factor alone for MS in normal weight prepubertal girls with PP.Thirty-five prepubertal, non-obese girls with PP with normal birth weight and 35 age-matched control girls were evaluated for FCVRF, anthropometric measurements, blood pressure, lipid profile, fasting blood glucose-insulin, hemoglobin A1c (HbA1c), sex hormone binding globulin (SHBG), leptin, adiponectin, tumor necrosis factor-alpha (TNF-α), androgen levels, and bone age. Oral glucose tolerance test was performed in PP participants. Homeostasis model of assessment of IR (HOMA-IR), fasting glucose/insulin ratio, atherogenic index (AI), and free androgen index (FAI) were calculated. PP participants were further stratified by FCVRF.HbA1c, lipid profile, testosterone, leptin, adiponectin, TNF-α, HOMA-IR, glucose/insulin ratio, AI, and fasting glucose-insulin levels were similar. In the PP group FAI was significantly higher (p=0.001), whereas SHBG was significantly lower (p=0.010) than the control group. Leptin levels of FCVRF+ and FCVRF- subgroups were 15.2±9.1 and 9.7±7.2 ng/mL, respectively and the difference was significant (p=0.016).As PP does not appear to be a risk factor alone for impaired glucose metabolism and IR in prepubertal non-obese girls with normal birth weight, it is our opinion that it is unnecessary to examine in detail such cases before puberty. Low SHBG levels in the PP group and high leptin levels in FCVRF+ subgroup might suggest that these may be predictive for MS in the future.

Insulin resistance in the vasculature is a hallmark of type 2 diabetes (T2D), and blunting of insulin-induced vasodilation is its primary consequence. Individuals with T2D exhibit a marked impairment in insulin-induced dilation in resistance arteries across vascular beds. Importantly, reduced insulin-stimulated vasodilation and blood flow to skeletal muscle limits glucose uptake and contributes to impaired glucose control in T2D. The study of mechanisms responsible for the suppressed vasodilatory effects of insulin has been a growing topic of interest for not only its association with glucose control and extension to T2D but also its relationship with cardiovascular disease development and progression. In this mini-review, we integrate findings from recent studies by our group with the existing literature focused on the mechanisms underlying endothelial insulin resistance in T2D.

Serum lipids, glucose and uric acid are well-known risk factors for metabolic syndrome and cardiovascular diseases; however, how serum uric acid levels are associated with fasting glucose and lipid levels remains to be evaluated.A cross-sectional study was performed in 104,328 males and 74,916 females. Quantile regression analyses were adopted to optimally fit the associations between levels of uric acid, lipids and glucose. Fasting high-density lipoprotein cholesterol (HDL-C) levels were negatively associated with serum uric acid levels; the associations remained stable in males but strengthened in females with increasing uric acid concentrations. Non-HDL-C and triglyceride (TG) levels were positively associated with serum uric acid levels; the associations also strengthened across deciles of uric acid levels from low to high. Fasting glucose levels were positively associated with uric acid levels in both sexes except in males in the 1st and 2nd deciles of uric acid concentrations; the association coefficients for females were higher than coefficients in males in each decile of uric acid levels. All associations had distinguishable patterns by sex except non-HDL-C, which was associated with uric acid levels with relatively similar trends between sexes. Adjustment for known confounding factors only slightly altered the above associations.Fasting serum uric acid levels are associated with fasting levels of HDL-C, non-HDL-C, TG and glucose; the associations strengthened with the deciles of uric acid increase and displayed non-negligible sex differences.

Hypoglycaemia caused by malignant tumours other than insulinoma is referred to as non-islet cell tumour hypoglycaemia (NICTH), which may be caused by hepatocellular carcinoma (HCC) and leiomyosarcoma (LMS) in veterinary medicine. However, the pathogenetic mechanism of NICTH remains unclear. Therefore, this study aimed to evaluate the gene-expression levels of glucoregulatory factors in canine HCC and LMS accompanied by hypoglycaemia.Four patients (three with HCC and one with LMS) exhibiting hypoglycemia were included in the hypoglycemic (H) group, whereas ten patients not exhibiting hypoglycemia were in the non-hypoglycaemia (NH) group. The preoperative and postoperative blood glucose and serum insulin-like growth factor-2 (IGF-2) levels, as well as the expression of genes involved regulating blood glucose levels were analysed.Compared with the NH group, the H group exhibited significantly decreased blood-glucose levels, which increased to normal values after surgery. Compared with the NH group, the H group exhibited significantly increased gene expression of insulin-like growth factor 1, IGF-2, and insulin-like growth factor binding protein 3 in the tumours. Conversely, expression of genes encoding glucoregulatory factors including insulin, gastric inhibitory polypeptide and glucagon was not observed. Serum IGF-2 levels were significantly higher in the H group compared with that in the control group (healthy dogs) and NH group. In two cases in the H group, serum IGF-2 levels decreased after tumour resection.These results suggest that NICTH development in dogs with HCC and LMS is mechanistically associated with IGF-2 overexpression and elevated serum IGF-2 levels.

Intestinal electrical stimulation (IES) has been proposed for treating diabetes; however, its parameters need to be further systematically optimized. This study aimed to optimize the parameters of IES and investigate its possible mechanisms involving glucagon-like peptide-1 (GLP-1) in diabetic rats.Thirty-six high-fat diet-induced diabetic rats were chronically implanted with a pair of bipolar electrodes at the duodenum for IES. The oral glucose tolerance test (OGTT) was performed in a number of sessions with IES using different parameters and biphasic charge-balanced waveforms to derive the best values for train on-time, pulse frequency, and pulse width. Incretin hormones such as GLP-1 were assessed and the GLP-1 antagonist Exendin 9-39 was used to assess the role of GLP-1 in the ameliorating effect of IES on hyperglycemia.The most effective IES parameters in reducing blood glucose (BG) during the OGTT were derived: 1.2 sec on, 0.3 sec off, 80 Hz, 3 msec. IES with these parameters reduced BG level by at least 29% from 15 min to 180 min (p 0.05 for all points, N = 10). IES with these stimulation parameters increased plasma GLP-1 level at 30 min, 60 min, 90 min and gastric inhibitory peptide (GIP) level at 30 min (N = 8). Exendin 9-39 blocked the inhibitory effect of IES on BG (p 0.05, IES + Exendin 9-39 vs sham-IES, N = 8).IES with the most effective parameters derived in this study improves hyperglycemia in diabetic rats. The ameliorating effect of IES on hyperglycemia is attributed to the enhanced release of GLP-1. IES has great potential for treating diabetes.

Clinical trials have shown that bariatric surgery (BS) is associated with better glycemic control and diabetes remission in patients with type 2 diabetes (T2D) compared with routine care.We conducted a real-world population-based study examining the impact of BS on glycemic control and medications in patients with T2D.This was a retrospective, matched, controlled cohort study conducted between January 1, 1990, and January 31, 2018, using IQVIA Medical Research Data, a primary care electronic records database. Adults with body mass index (BMI) ≥30 kg/mA total of 1126 patients in the surgical group and 2219 patients in the control group were analyzed. Mean (standard deviation) age was 50.0 (9.3) years, 67.6% were women, baseline glycocylated hemoglobin (HbA1C) was 7.8% (1.7 mmol/mol), and diabetes duration was 4.7 years (range, 2.0-8.4 years). Over a median (interquartile range) follow-up of 3.6 years (1.7-5.9 years), a higher proportion of patients in the surgical group achieved an HbA1C of ≤6.0% than the control group (65.8% versus 22.8%). The surgical group showed a decrease in mean HbA1C of 1.5% (95% confidence interval [CI]: 1.4%-1.7%), 1.4% (1.2%-1.5%), and 1.3% (1.1%-1.5%) at 1-, 2-, and 3-year follow-up, respectively, whereas HbA1C increased in the control group. The proportion of patients receiving glucose-lowering medications decreased in the surgical group (92.2% to 66.5%) but increased in the control group (85.3% to 90.2%).BS is associated with significant improvement in glycemic control, achievement of normal HbA1C levels, and reduced need for glucose-lowering therapy in patients with T2D.

White bread is widely consumed in many countries despite being a high-glycemic index (GI) food. It has been shown that the "food matrix effect" may help with diabetes and obesity management through lowering GI and appetite. This study aimed at investigating the effects of dough kneading time and flour particle size on white bread structure, glycemic response, and aspects of appetite.A two-phase randomized cross-over design was used in 10 healthy subjects over the course of 2 h. In phase 1, Texture Profile Analysis (TPA) attributes, Scanning Electron Microscope (SEM) image, glycemic response, and appetite aspects of white bread made with a 15-min dough kneading time (K15) were compared with white bread made with a 10-min dough kneading time (K10). In phase 2, TPA, SEM image, glycemic response, and satiety score of white bread made with coarse flour (CF) were compared to white bread made with fine flour (FF).With increasing hardness (force required to compress a food between the molars to a given deformation), total blood glucose IAUC in K15 (IAUC = 119 ± 12; GI = 66) was significantly (p 0.05) lower than in K10 (IAUC = 154 ± 10; GI = 81). No marked difference was observed between K15 and K10 on aspects of appetite except for hunger. There was no significant (p 0.05) difference in glycemic response between CF (IAUC = 126 ± 18; GI = 64) and FF (IAUC = 147 ± 12; GI = 81). Similarly, no discernible difference in satiety between CF and FF.Changes in processing conditions can improve blood glucose response relalated to white bread consumption.

Highlights • Mean HBA1c in diabetic patients increased by 0.51% in immediate post lock down period due to COVID 19. • Increased mean HBA1c may significantly increase the annual incidences of complications related to diabetes. • With early identification and multidisciplinary approach which is patient centric good glycemic control can be achieved back. • By achieving good glycemic control, the predicted annual percentage increase in complication rate can be reduced., Background and aims Diabetes is a chronic metabolic condition characterized by hyperglycemia and is associated with several complications. Prevalence of Diabetes in adult population in India ranges from 10.9 to 14.2% in urban area and 3.0–7.8% in rural area. Glycemic control is an important factor in preventing the complications associated with diabetes. HBA1c is the indicator of long-term glycemic control and slight variation in it significantly alters the risk of diabetic complications. Thus, the aim of this study was to study the change in HBA1c levels due to lock down in patients with diabetes. Methods 307 patients with diabetes who had attended our endocrine OPD in last 3 months before nationwide 68 days lockdown from 24 March 2020 to 31 May 2020, and had recent HBA1c report in past and willing to participate were included in the study after informed consent from 2nd June 2020 to 14th June 2020 when first phase of Unlock started, to identify the change in HBA1c levels during the lockdown period in our patients with diabetes. Results The patients were aged between 25–69 years and male to female ratio was 181:126 (1.44: 1). The mean age and mean duration of diabetes in our patients was 55.68 years and 7.95 years respectively. Increment of 0.51% was seen in mean HBA1c levels in our patient from 7.92% mean pre-lockdown HBA1c to mean of 8.43% after release of lock down. Conclusion Glycemic control got deranged during lockdown period with significant increase of mean HBA1c by 0.51% in immediate post lock down period which may significantly increase the annual incidence of complications related to diabetes.

As a complication of obesity, type 2 diabetes (T2D) is a chronic disease that is difficult to manage. However, bariatric surgery makes it possible to alleviate T2D. While the existing generic index glycosylated hemoglobin (HbA1c) is a powerful tool for examining overall blood glucose levels, it still has some limitations as a daily measure of blood glucose levels and as a judge of the effectiveness of bariatric surgery. Using the time-in-range (TIR) measurement and its derivatives is a better way to evaluate short-term blood glucose fluctuations and can be used as a supplement to HbA1c. In this article, we discuss the utility and limitations of HbA1c and other indicators used during surgery. In addition, we mentioned TIR as a novel metric that can act as an accurate predictor of the risk of T2D complications and an index of preoperative risk assessment in bariatric surgery. In contrast to previous indicators, TIR has the advantage that it cannot be affected by caloric restriction to better reflect the patient's glucose level and the level of pancreatic islet function. On this basis, TIR is a promising indicator for both the diagnosis of diabetes and the preoperative and postoperative prediction and evaluation.

Nocturnal blood glucose regulation was one of the key challenges in diabetic treatments. However, development of the smart insulin complexes with mild and glucose-responsive delivering performances was mostly relied on experience of the senior researchers and numerous confirmation experiments. In this work, a series of bioinspired fatty-acid-modified glucose-responsive insulin-delivering polymeric nanoparticles were designed. The molecular docking technique was utilized to efficiently screen the fatty-acid-derived functional groups. The results provided the basis for polymer functionalization and simplified the optimization experiments. For the optimized formulation (C10MS), insulin-loaded C10MS successfully fulfilled the nocturnal-glycemic-controlling requirement of the diabetic rats with lower occurrence of hypoglycemia than the conventional insulin injection schemes. Such formulation also possessed good biocompatibility with the moderate elimination kinetics in vivo, which matched the demand of bio-safety in the daily treatments. Overall, this work opened up a new path for efficient design of functional polymeric materials.

Induction of diabetes mellitus by streptozotocin (STZ) in rats at birth is of high mortality and low success rate when male puppies are separated from females, prioritizing females breastfeeding. Cross-parental care of the entire litter and SZT-induced diabetes up to 12 h post-birth become with high success rate, low animal death, and females with glycaemia140 mg/dL on the 90 postnatal day. Cross-parental care is more effective in STZ-induction of diabetes, which is maintained during pregnancy (diabetes in pregnancy), than the conventional protocol of male separation at birth.

Background: Insulin-treated patients with long duration of type 2 diabetes mellitus (T2DM) are at increased risk of ketoacidosis related to sodium-glucose co-transporter 2 inhibitor (SGLT2i). The extent of circulating ketone elevation in these patients remains unknown. We conducted this study to compare the serum ketone response between dapagliflozin, an SGLT2i, and sitagliptin, a dipeptidyl peptidase-4 inhibitor, among insulin-treated T2DM patients.Methods: This was a randomized, open-label, active comparator-controlled study involving 60 insulin-treated T2DM patients. Participants were randomized 1:1 for 24-week of dapagliflozin 10 mg daily or sitagliptin 100 mg daily. Serum β-hydroxybutyrate (BHB) levels were measured at baseline, 12 and 24 weeks after intervention. Comprehensive cardiometabolic assessments were performed with measurements of high-density lipoprotein cholesterol (HDL-C) cholesterol efflux capacity (CEC), vibration-controlled transient elastography and echocardiography.Results: Among these 60 insulin-treated participants (mean age 58.8 years, diabetes duration 18.2 years, glycosylated hemoglobin 8.87%), as compared with sitagliptin, serum BHB levels increased significantly after 24 weeks of dapagliflozin (P=0.045), with a median of 27% increase from baseline. Change in serum BHB levels correlated significantly with change in free fatty acid levels. Despite similar glucose lowering, dapagliflozin led to significant improvements in body weight (P=0.006), waist circumference (P=0.028), HDL-C (P=0.041), CEC (P=0.045), controlled attenuation parameter (P=0.007), and liver stiffness (P=0.022). Average E/e’, an echocardiographic index of left ventricular diastolic dysfunction, was also significantly lower at 24 weeks in participants treated with dapagliflozin (P=0.037).Conclusion: Among insulin-treated T2DM patients with long diabetes duration, compared to sitagliptin, dapagliflozin modestly increased ketone levels and was associated with cardiometabolic benefits.

Background: We investigated whether fasting glucose (FG) variability could predict the risk of dementia.Methods: This cohort study analyzed data from Koreans with diabetes after at least three health examinations by the Korean National Health Insurance Corporation between 2005 and 2010, which included at least one examination between 2009 and 2010. A total of 769,554 individuals were included, excluding those aged

Type 2 DM (T2DM) is associated with inflammation and vascular dysfunction which impact hemostasis. Thromboelastography (TEG) as a hemostasis assessment method, is not routinely applied in T2DM. We aimed to detect hemostasis abnormalities by using the TEG method in association with glycemic levels and type of therapy among T2DM patients.A cross-sectional study was conducted among T2DM patients attending the Endocrinology Clinic of Saiful Anwar Hospital, Indonesia. Glycemic profiles were determined using fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2hPPG), and glycosylated hemoglobin (HbA1c). Therapy for T2DM was classified into insulin and non-insulin regimens. The primary and secondary hemostasis profile were examined using TEG and was classified as hypo- hyper- and normo-coagulable states.A total of 57 T2DM patients were included. Kruskal-Wallis test did not reveal a significant association between glycemic profiles and groups of hemostasis. However, the median HbA1c was higher in the hypercoagulable group of primary hemostasis and fibrinolysis. The median FPG and 2hPPG were higher in the normo-coagulable group of secondary hemostasis. Logistic regression did not indicate a significant association between type of therapy for diabetes and hemostasis profile.This study did not find significant associations between glycemic levels and type of DM therapy with hemostasis profiles using the TEG method in patients with T2DM.

This study described and compared glycaemic changes with the use of the following Continuous Glucose Monitoring (CGM) metrics: time in range, time in hyperglycaemia and time in hypoglycaemia from retrospective CGM data among children and adolescents with Type 1 Diabetes Mellitus (T1DM), before and during Ramadan to better understand the impact of fasting during this season.This study was conducted in 2 tertiary centres: Hospital Putrajaya (HPJ) and Hospital Universiti Sains Malaysia (HUSM) from February to May 2020. Muslim T1DM patients between ages 8 to18 who intended to fast during Ramadan were given Ramadan-focused education. CGM iPro2Of the 32 patients, only 24 (12 female) were analysed. Mean age was 13.6 ± 3.1 years old, mean HbAlc was 9.6 ± 1.9% and mean duration of illness was 5.4 ± 3.4 years. Majority (91.7%) were on multiple dose injections (MDI) while only 8.3% were on continuous subcutaneous insulin infusion (CSII). All fasted in Ramadan without acute complications. Retrospective CGM analysis revealed similar results in time in range (TIR), time in hyperglycaemia and time in hypoglycaemia before and during Ramadan, indicating no increased hypoglycaemic or hyperglycaemic events related to fasting. Glycaemic variability before Ramadan as measured by the LBGI, HBGI and MAG, were similar to values during Ramadan.Ramadan fasting among T1DM children and adolescents, by itself, is not associated with short-term glycaemic deterioration. T1DM youths can fast safely in Ramadan with the provision of focused education and regular SMBG.