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Background: Lack of time is often cited by persons with type 2 diabetes for non-participation in regular exercise. This highlights the need to explores ways to help persons with type 2 diabetes to engage in an active lifestyle. This study evaluated the effect of a short duration norm intensity exercise on blood glucose and blood pressure in persons with type 2 diabetes., Methods: Twenty persons with type 2 diabetes were randomly assigned to either training group (n = 10) or control group (n = 10). The training group received 4-weeks ambulatory training on a motor-driven treadmill (2 x 20 min per week at 60% target heart rate). The control group received no training. Blood glucose, and systolic and diastolic blood pressures were assessed before and after the 4-weeks training. Repeated measures ANOVA were used to examine training effect., Results: Training significantly improved blood glucose (mean difference = -2.73; p = 0.03). No effects were found for systolic blood pressure (mean difference = -0.30; p = 0.96) and diastolic blood pressure (mean difference = -0.90; p = 0.82)., Conclusion: Training improved blood glucose but not blood pressure. A short-duration ambulatory training is an appropriate exercise mode to elicit beneficial effect, and exercise adoption in persons with type 2 diabetes., Trial Registration: This pilot trial is registered with the Pan African Clinical Trial Registry at pactr.samrc.ac.za (PACTR202306601940612)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Abonie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In the present article, we describe a 3-day experimental workshop on type I diabetes aimed at helping high school students to understand how fundamental research on glycemia regulation contributes to the development of scientific knowledge and therapeutic strategies. The workshop engaged students in open-ended investigations and guided experiments. Each class was divided into three or four groups, with each group working with a trained doctoral student or postdoctoral fellow. During an initial questioning phase, students observed slides depicting the glycemia of individuals in various situations. Students identified hyperglycemic individuals relative to the average glycemia of the displayed population. Students were asked to devise a treatment for these diabetics. They quickly realized that they couldn't experiment on patients and understood the need for laboratory models. Each group gave ideas of experiments to perform. We then explained, taking into account their propositions, the protocols students could execute to address one of the following questions: Which criteria must an animal model of diabetes fulfill? How do pancreatic cells maintain glycemia? Is there a way to produce an insulin protein similar to the one released by human pancreatic cells? We used two different evaluation metrics of the workshop: a questionnaire filled out by the students before and after the workshop and a poster produced by students at the end of the workshop. We found that this educational approach successfully improved student awareness and understanding of the scientific reasoning and research process [ABSTRACT FROM AUTHOR]

In the present article, we describe a 3-day experimental workshop on glycemia regulation and type 1 diabetes that engages students in open-ended investigations and guided experiments leading to results that are not already known to them. After an initial questioning phase during which students observe PowerPoint slides depicting the glycemia (blood glucose levels) of individuals in various situations, students design, execute, and interpret experiments to address one of the following questions: 1) Which criteria must an animal model of diabetes fulfill? 2) How do pancreatic cells maintain glycemia constant? and 3) Is there a way to produce an insulin protein similar to the one released by human pancreatic cells? Students then 1) measure glycemia and glycosuria in control mice and in a mouse model of type 1 diabetes (Alloxan-treated mice), 2) measure the release of insulin by pancreatic β-cells (INS-1 cell line) in response to different concentrations of glucose in the extracellular medium, and 3) transfect Chinese hamster ovary cells with a plasmid coding for green fluorescent protein, observe green fluorescent protein fluorescence of some of the transfected Chinese hamster ovary cells under the microscope, and observe the characteristics of human insulin protein and its three-dimensional conformation using RASMOL software. At the end of the experimental session, students make posters and present their work to researchers. Back at school, they may also present their work to their colleagues. [ABSTRACT FROM AUTHOR]

Background: The current study aimed to reveal the correlation of beta-cell function and insulin sensitivity with glycemic control and weight control before and after medical nutrition therapy (MNT) in patients with newly-diagnosed type 2 diabetes mellitus., Methods: We retrospectively analyzed consecutive 68 patients with newly-diagnosed type 2 diabetes mellitus who started MNT without antihyperglycemic medications and underwent a 75-g oral glucose tolerance test (OGTT) before and after the therapy. Beta-cell function was evaluated by the OGTT-derived disposition index, whereas insulin sensitivity was evaluated by Matsuda's insulin sensitivity index., Results: After 4.0 ± 1.5 months of MNT, mean HbA1c and body mass index significantly decreased from 9.6 ± 1.8% to 7.2 ± 1.0% and from 26.9 ± 4.1 to 25.4 ± 3.7 kg/m 2 (both P < 0.001), while the median disposition index and Matsuda's index significantly increased from 0.34 (0.20-0.68) to 0.88 (0.53-1.52) (P < 0.001) and from 4.70 (2.95-5.93) to 5.17 (3.48-6.89) (P = 0.003), respectively. The disposition index was significantly correlated with HbA1c levels both before and after MNT (r = -0.61 and -0.68; both P < 0.001). The magnitude of the correlation after MNT was not different from that before MNT (P = 0.42). Matsuda's index was correlated not with HbA1c levels but with body mass index, both before (r = 0.07 [P = 0.57] and r = -0.58 [P < 0.001]) and after MNT (r = -0.01 [P = 0.95] and r = -0.52 [P < 0.001])., Conclusions: Beta-cell function was improved in conjunction with glycemic control after MNT in patients with newly-diagnosed type 2 diabetes mellitus. Insulin sensitivity was linked with weight control rather than glycemic control., (© 2022. The Author(s).)

Chickpeas are among the lowest glycaemic index carbohydrate foods eliciting protracted digestion and enhanced satiety responses. In vitro studies suggest that mechanical processing of chickpeas significantly increases starch digestion. However, there is little evidence regarding the impact of processing on postprandial glycaemic response in response to chickpea intake in vivo . Therefore, the aim of this study was to determine the effect of mechanical processing on postprandial interstitial glycaemic and satiety responses in humans. In a randomised crossover design, thirteen normoglycaemic adults attended 4 separate laboratory visits following an overnight fast. On each occasion, one of four test meals, matched for available carbohydrate content and consisting of different physical forms of chickpeas (whole, puree, and pasta) or control (mashed potato), was administered followed by a subsequent standardised lunch meal. Continuous glucose monitoring captured interstitial glucose responses, accompanied by periodic venous blood samples for retrospective analysis of C-peptide, glucagon like peptide-1 (GLP-1), ghrelin, leptin, resistin, and cortisol. Subjective appetite responses were measured by Visual Analogue Scale (VAS). Postprandial glycaemic responses were comparable between chickpea treatments albeit significantly lower than the control ( p < 0.001). Similarly, all chickpea treatments elicited significantly lower C-peptide and GLP-1 responses compared to the control ( p < 0.05), accompanied by enhanced subjective satiety responses ( p < 0.05), whilst no significant differences in satiety hormones were detected among different intervention groups ( p > 0.05). Chickpea consumption elicits low postprandial glycaemic responses and enhanced subjective satiety responses irrespective of processing methods.

Introduction: Blood glucose concentrations are recognized to vary during hemodialysis (HD), with hypoglycemia reported with glucose-free dialysates. As glucose can be converted to lactate, and conversely lactate to glucose, we wished to study factors associated with peri-dialytic changes in blood glucose., Methods: We prospectively collected data including patient profile, dialysis prescription, hemodynamic parameters, medications, dialysis adequacy and monthly blood tests for three consecutive months. All patients used a 100 mg/dl glucose dialysate. Linear mixed model, general estimated equation and binary logistic regression were used for analysis., Results: We studied 157 sessions in 55 patients, median age 67.1 (58.5-72.6) years, 67% male, 71% diabetic, 40% prescribed insulin, dialysis vintage 20.4 (10.7-57.7) months. Mean single pool Kt/Vurea and normalized protein nitrogen appearance rate (nPNA) were 1.70 ± 0.34 and 1.01 ± 0.30 g/kg/day respectively. Hypoglycemia (<70 mg/dl) occurred during 10 sessions (6.4%). 25% of non-diabetes experienced hypoglycemia. The % change in peri-dialytic blood glucose was associated with the % change in lactate (estimate of fixed effect = 0.23 p < 0.001) and pre-HD glucose (estimate of fixed effect = 0.09, p < 0.001). The fall in glucose was not associated with urea clearance, consumption of food, administration of insulin or antidiabetic medications, nPNA, body mass index, or pyridoxine concentrations., Conclusions: Peri-dialytic hypoglycemia cannot simply be explained by dialyzer clearance, as the corresponding fall in lactate would potentially suggest increased gluconeogenesis. Despite using a glucose containing dialysate, asymptomatic hypoglycemia occurred in 6.4% of sessions, suggesting a role for peri-dialytic blood glucose monitoring and avoiding fasting during dialysis., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

The optimal time to bolus insulin for meals is challenging for children and adolescents with type 1 diabetes (T1D). Current guidelines to control glucose excursions do not account for individual differences in glycaemic responses to meals. This study aimed to examine the within- and between-person variability in time to peak (TTP) glycaemic responses after consuming meals under controlled and free-living conditions. Participants aged 8-15 years with T1D ≥ 1 year and using a continuous glucose monitor (CGM) were recruited. Participants consumed a standardised breakfast for six controlled days and maintained their usual daily routine for 14 free-living days. CGM traces were collected after eating. Linear mixed models were used to identify within- and between-person variability in the TTP after each of the controlled breakfasts, free-living breakfasts (FLB), and free-living dinners (FLD) conditions. Thirty participants completed the study (16 females; mean age and standard deviation (SD) 10.5 (1.9)). The TTP variability was greater within a person than the variability between people for all three meal types (between-person vs. within-person SD; controlled breakfast 18.5 vs. 38.9 min; FLB 14.1 vs. 49.6 min; FLD 5.7 vs. 64.5 min). For the first time, the study showed that within-person variability in TTP glycaemic responses is even greater than between-person variability.

Introduction: Type 2 diabetes (T2D) is characterized by a metabolic disorder that elevates blood glucose concentration. Chronic hyperglycemia has been associated with several complications in patients with T2D, one of which is cardiac autonomic dysfunction that can be assessed from heart rate variability (HRV) and heart rate recovery (HRR) response, both associated with many aspects of health and fitness, including severe cardiovascular outcomes., Objective: To evaluate the effects of T2D on cardiac autonomic modulation by means of HRV and HRR measurements., Materials and Methods: This study has an observational with case-control characteristic and involved ninety-three middle-aged adults stratified into two groups (control group - CG, n = 34; diabetes group - DG, n = 59). After signing the free and informed consent form, the patients were submitted to the evaluation protocols, performed biochemical tests to confirm the diagnosis of T2D, collection of R-R intervals for HRV analysis and cardiopulmonary effort test to quantify HRR., Results: At rest, the DG showed a reduction in global HRV (SDNN= 19.31 ± 11.72 vs CG 43.09 ± 12.74, p < 0.0001), lower parasympathetic modulation (RMSSD= 20.49 ± 14.68 vs 52.41 ± 19.50, PNN50 = 4.76 ± 10.53 vs 31.24 ± 19.24, 2VD%= 19.97 ± 10.30 vs 28.81 ± 9.77, p < 0.0001 for both indices) and higher HRrest when compared to CG. After interruption of physical exercise, a slowed heart rate response was observed in the DG when compared to the CG. Finally, a simple linear regression showed that fasting glycemia was able to predict cardiac autonomic involvement in volunteers with T2D., Conclusion: Patients with T2D presented lower parasympathetic modulation at rest and slowed HRR after physical exercise, which may be associated with higher cardiovascular risks. The findings show the glycemic profile as an important predictor of impaired cardiac autonomic modulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Silva, Gentil, Seguro, de Oliveira, Silva, Zamunér, Beltrame and Rebelo.)

Background: To evaluate the impact of oral carbohydrate-rich (Ch-R) supplement taken 2 hours before an elective caesarean delivery (CD) on maternal and neonatal perioperative outcomes., Methods: Ninety pregnant women undergoing elective CD were randomized into the Ch-R group, placebo group and fasting group equally. Participants' blood was drawn at three time points, before intervention, immediately after and 1 day after the surgery to measure maternal and neonatal biochemical indices. Meanwhile women's perioperative symptoms and signs were recorded., Results: Eighty-eight pregnant women were finally included in the study. Women who had drunk Ch-R supplement had lower postoperative insulin level (β = - 3.50, 95% CI - 5.45 to - 1.56), as well as postoperative HOMA-IR index (β = - 0.74, 95% CI - 1.15 to - 0.34), compared with women who had fasted. Additionally, neonates of mothers who were allocated in the Ch-R group also had a higher glucose level, compared with neonates of mothers in the fasting group (β = 0.40, CI 0.17 to 0.62)., Conclusion: Oral Ch-R solution administered 2 hours before an elective CD may not only alleviate maternal postoperative insulin resistance, but also comfort women's preoperative thirst and hunger, compared to fasting. Additionally, it may increase neonatal glucose level as well., Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000033163 . Data of Registration: 2020-5-22., (© 2021. The Author(s).)

Physical activity (PA) is important for individuals living with type 1 diabetes (T1D) due to its various health benefits. Nonetheless, maintaining adequate glycemic control around PA remains a challenge for many individuals living with T1D because of the difficulty in properly managing circulating insulin levels around PA. Although the most common problem is increased incidence of hypoglycemia during and after most types of PA, hyperglycemia can also occur. Accordingly, a large proportion of people living with T1D are sedentary partly due to the fear of PA-associated hypoglycemia. Continuous subcutaneous insulin infusion (CSII) offers a higher precision and flexibility to adjust insulin basal rates and boluses according to the individual's specific needs around PA practice. Indeed, for physically active patients with T1D, CSII can be a preferred option to facilitate glucose regulation. To our knowledge, there are no guidelines to manage exercise-induced hypoglycemia during PA, specifically for individuals living with T1D and using CSII. In this review, we highlight the current state of knowledge on exercise-related glucose variations, especially hypoglycemic risk and its underlying physiology. We also detail the current recommendations for insulin modulations according to the different PA modalities (type, intensity, duration, frequency) in individuals living with T1D using CSII., (Copyright © 2021. Published by Elsevier Inc.)

We investigated the relationship between glycemia and cognitive function, brain structure and incident dementia using bidirectional Mendelian randomization (MR). Data were from the UK Biobank ( n = ∼500,000). Our exposures were genetic instruments for type 2 diabetes (157 variants) and HbA 1c (51 variants) and our outcomes were reaction time (RT), visual memory, hippocampal volume (HV), white matter hyperintensity volume (WMHV), and Alzheimer dementia (AD). We also investigated associations between genetic variants for RT (43 variants) and diabetes and HbA 1c We used conventional inverse-variance-weighted (IVW) MR alongside MR sensitivity analyses. Using IVW, genetic liability to type 2 diabetes was not associated with RT (exponentiated β [expβ] = 1.00 [95% CI 1.00; 1.00]), visual memory (expβ = 1.00 [95% CI 0.99; 1.00]), WMHV (expβ = 0.99 [95% CI 0.97; 1.01]), HV (β-coefficient mm 3 = -2.30 [95% CI -12.39; 7.78]) or AD (odds ratio [OR] 1.15 [95% CI 0.87; 1.52]). HbA 1c was not associated with RT (expβ = 1.00 [95% CI 0.99; 1.02]), visual memory (expβ = 0.99 [95% CI 0.96; 1.02]), WMHV (expβ = 1.03 [95% CI 0.88; 1.22]), HV (β = -21.31 [95% CI -82.96; 40.34]), or risk of AD (OR 1.09 [95% CI 0.42; 2.83]). IVW showed that reaction time was not associated with diabetes risk (OR 0.94 [95% CI 0.54; 1.65]), or with HbA 1c (β-coefficient mmol/mol = -0.88 [95% CI = -1.88; 0.13]) after exclusion of a pleiotropic variant. Overall, we observed little evidence of causal association between genetic instruments for type 2 diabetes or peripheral glycemia and some measures of cognition and brain structure in midlife., (© 2021 by the American Diabetes Association.)

Oestrogens regulate body weight through their action on hypothalamus to modulate food intake and energy expenditure. Hypothalamic de novo ceramide synthesis plays a central role on obesity induced by oestrogen deficiency. Depletion in oestrogens is also known to be associated with glucose intolerance, which favours type 2 diabetes (T2D). However, the implication of hypothalamic ceramide in the regulation of glucose homeostasis by oestrogen is unknown. Here, we studied glucose homeostasis and insulin secretion in ovariectomized (OVX) female rats. OVX induces body weight gain associated with a hypothalamic inflammation and impaired glucose homeostasis. Genetic blockade of ceramide synthesis in the ventromedial nucleus of the hypothalamus (VMH) reverses hypothalamic inflammation and partly restored glucose tolerance induced by OVX. Furthermore, glucose-stimulated insulin secretion (GSIS) is increased in OVX rats due to a raise of insulin secretion second phase, a characteristic of early stage of T2D. In contrast, GSIS from isolated islets of OVX rats is totally blunted. Inhibition of ceramide synthesis in the VMH restores GSIS from isolated OVX islets and represses the second phase of insulin secretion. Stimulation of oestrogen receptor α (ERα) by oestradiol (E2) down-regulates ceramide synthesis in hypothalamic neuronal GT1-7 cells but no in microglial SIM-A9 cells. In contrast, genetic inactivation of ERα in VMH upregulates ceramide synthesis. These results indicate that hypothalamic neuronal de novo ceramide synthesis triggers the OVX-dependent impairment of glucose homeostasis which is partly mediated by a dysregulation of GSIS., (Copyright © 2021 Elsevier Inc. All rights reserved.)

SGLT2 inhibitors have been developed as antidiabetics. Large randomized prospective studies have shown prognostic benefit in patients with heart and/or renal insufficiency regarding cardiovascular and general endpoints - even in absence of type 2 diabetes mellitus. This extends the indication to large groups of multimorbid patients. SGLT2 inhibitors induce ketogenesis comparable to fasting conditions. This may - in presence of additional catabolic factors - deteriorate into life-threatening ketoacidosis - probably due to increased reabsorption of ketone bodies from urine as well as the blockage of SGLT2 receptors on α-cells of the pancreas. Euglycaemic ketoacidosis (eKA) under SGLT2 inhibition occurs in about 2:1000 years of treatment. The diagnosis is challenging: in eKA, blood sugar levels are often normal, and ketone detection in urinalysis can be falsely negative, while glucosuria is excessive compared to euglycemic blood-glucose. The management corresponds to classical diabetic ketoacidosis, but special features of blood glucose target, hydration and potassium management should be considered. SGLT2 inhibitors should be paused if a longer fasting period is expected ("sick-day-break"). Due to the soaring number of prescriptions, a significant increase in the prevalence of eKA is expected. Immediate diagnosis and therapy are essential in emergency and intensive care medicine., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Insulin resistance engenders a compensatory increase in plasma insulin. Inadequate compensation is a primary element in the pathogenesis of type 2 diabetes. The signal that heralds developing insulin resistance and initiates hyperinsulinemic compensation is not known. It has often been assumed to be increased glucose. We tested this assumption by determining whether development of fasting and/or glucose-stimulated hyperinsulinemia with diet-induced insulin resistance occurs because of concomitant elevation of glycemia. Male dogs (n = 58) were fed a hypercaloric, fat-supplemented diet for 6 weeks. Dogs underwent magnetic resonance imaging to quantify total and regional (visceral, subcutaneous) adiposity as well as euglycemic hyperinsulinemic clamps. A subset of animals also underwent an insulin-modified intravenous glucose tolerance test to assess insulin sensitivity, acute insulin response (AIRg), and glucose effectiveness. Fat feeding caused modest weight gain, increased visceral and subcutaneous fat, and insulin resistance at both peripheral and hepatic levels. Hyperinsulinemic compensation was observed in fasting levels as well as increased AIRg. However, we observed absolutely no increase in carefully measured fasting, evening (6 to 8 pm) or nocturnal glycemia (2 to 4 am). Insulin resistance and hyperinsulinemia occurred despite no elevation in 24-hour glucose. Compensatory development of hyperinsulinemia during diet-induced insulin resistance occurs without elevated fasting or 24-hour glycemia. These data refute the idea that glucose itself is a requisite signal for β-cell upregulation. Alternative feedback mechanisms need to be identified., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The study aim was to examine possible correlates of convulsions in children hospitalized for acute gastroenteritis (AGE). Data collected in a prospective study of AGE hospitalizations in children aged 0-59 months in 3 hospitals in Israel during 2008-2015 were analyzed. Stool samples were tested for rotavirus using immunochromatography and stool culture was performed for the detection of Salmonella, Shigella and Campylobacter We compared clinical and demographic characteristics of children hospitalized for AGE who had convulsions (n = 68, cases) with children hospitalized for AGE without convulsions (n = 3505, controls). Age differed between children with and without convulsions (p = 0.005); the former were mostly toddlers aged 12-23 months (51%) compared to 30% of the control group. A higher percentage of cases tested positive for Shigella (11% vs. 4%, p = 0.002), the opposite was found for rotavirus (2% vs. 30% p < 0.001). A multivariable model showed that body temperature (OR 2.91 [95% CI 1.78-4.76], p < 0.001) and high blood glucose level (> 120 mg/dL) (OR 5.71 [95% CI 1.27-25.58] p = 0.023) were positively related to convulsions in children with AGE, while severe AGE (Vesikari score ≥ 11) was inversely related with convulsions (OR 0.09 [95% CI 0.03-0.24], p < 0.001). Conclusion: Elevated body temperature is associated with convulsions in children with AGE, but not severity of AGE, while hyperglycemia might reflect a neuroendocrine stress reaction to convulsions, AGE or both., (© 2021. The Author(s).)

Diabetes mellitus is a complex and multifactorial disease with a global prevalence that exceeds 425 million people. Type 2 diabetes mellitus (T2DM) is characterized by a state of insulin resistance, which leads to metabolic alterations that aggravate the state of health of people. Vitamin D deficiency appears to play an important role in the triggering mechanisms of insulin resistance. In this review, an analysis is made of the biochemical mechanisms associated with the insulin-mimetic effect of vitamin D, its supplementation being a possible nutritional strategy for the T2DM treatment. The current scientific evidence is extensive regarding the dose of vitamin D used for an insulin-mimetic effect. However, clinical trials and systematic reviews show statistical differences on glucose, insulin, and glycated hemoglobin levels of patients with T2DM, associated with activation mechanisms of transcription factors related to genes of the glucide metabolism and the insulin receptor, and the regulation of intracellular Ca2+ insulin concentrations. Likewise, an indirect mechanism associated with antioxidant and anti-inflammatory effects has been shown that also leads to sensitivity to the insulin receptor. The use of a specific dose of vitamin D could be an effective alternative in the T2DM treatment, which would reduce the risk of complications derived from hyperglycemia.

Objective: The intestinal microbiota to immune system crosstalk is a major regulator of metabolism and hence metabolic diseases. An impairment of the chemokine receptor CX3CR1, as a key regulator shaping intestinal microbiota under normal chow feeding, could be one of the early events of dysglycemia., Methods: We studied the gut microbiota ecology by sequencing the gut and tissue microbiota. We studied its role in energy metabolism in CX3CR1-deficent and control mice using various bioassays notably the glycemic regulation during fasting and the respiratory quotient as two highly sensitive physiological features. We used antibiotics and prebiotics treatments, and germ free mouse colonization., Results: We identify that CX3CR1 disruption impairs gut microbiota ecology and identified a specific signature associated to the genotype. The glycemic control during fasting and the respiratory quotient throughout the day are deeply impaired. A selected four-week prebiotic treatment modifies the dysbiotic microbiota and improves the fasting state glycemic control of the CX3CR1-deficent mice and following a glucose tolerance test. A 4 week antibiotic treatment also improves the glycemic control as well. Eventually, germ free mice colonized with the microbiota from CX3CR1-deficent mice developed glucose intolerance., Conclusions: CX3CR1 is a molecular mechanism in the control of the gut microbiota ecology ensuring the maintenance of a steady glycemia and energy metabolism. Its impairment could be an early mechanism leading to gut microbiota dysbiosis and the onset of metabolic disease., (© 2021. Springer-Verlag Italia S.r.l., part of Springer Nature.)

The incretin effect-the amplification of insulin secretion after oral vs intravenous administration of glucose as a mean to improve glucose tolerance-was suspected even before insulin was discovered, and today we know that the effect is due to the secretion of 2 insulinotropic peptides, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). But how important is it? Physiological experiments have shown that, because of the incretin effect, we can ingest increasing amounts of amounts of glucose (carbohydrates) without increasing postprandial glucose excursions, which otherwise might have severe consequences. The mechanism behind this is incretin-stimulated insulin secretion. The availability of antagonists for GLP-1 and most recently also for GIP has made it possible to directly estimate the individual contributions to postprandial insulin secretion of a) glucose itself: 26%; b) GIP: 45%; and c) GLP-1: 29%. Thus, in healthy individuals, GIP is the champion. When the action of both incretins is prevented, glucose tolerance is pathologically impaired. Thus, after 100 years of research, we now know that insulinotropic hormones from the gut are indispensable for normal glucose tolerance. The loss of the incretin effect in type 2 diabetes, therefore, contributes greatly to the impaired postprandial glucose control., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

In humans, food intake and glucose infusion have been reported to increase subcutaneous blood flow. Since local blood flow influences the rate of insulin absorption from the subcutaneous tissue, we hypothesised that an increase in blood glucose levels-occurring as the result of glucose infusion or food intake-could modulate the pharmacokinetic properties of subcutaneously administered insulin. The pharmacokinetic profile of insulin aspart was assessed in 29 domestic pigs that were examined in a fed and fasted state or included in hyperinsulinaemic clamp studies of 4 vs. 10 mmol/L glucose prior to subcutaneous (30 nmol) or intravenous (0.1 nmol/kg) insulin administration. Results showed that food intake compared to fasting accelerated absorption and decreased clearance of insulin aspart (P < 0.05). Furthermore, higher c-peptide but also glucagon levels were observed in fed compared to fasted pigs (P < 0.05). The pharmacokinetic profile of insulin aspart did not differ between pigs clamped at 4 vs. 10 mmol/L glucose. Hence, food intake rather than blood glucose levels within normal range modulates the pharmacokinetic properties of insulin aspart upon subcutaneous and intravenous administration in pigs., (© 2021 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

Obesity and type 2 diabetes are rapidly increasing in the adolescent population. We sought to determine whether adipokines, specifically leptin, C1q/TNF-related proteins 1 (CTRP1) and CTRP9, and the hepatokine fibroblast growth factor 21 (FGF21), are associated with obesity and hyperglycemia in a cohort of lean and obese adolescents, across the spectrum of glycemia. In an observational, longitudinal study of lean and obese adolescents, we measured fasting laboratory tests, oral glucose tolerance tests, and adipokines including leptin, CTRP1, CTRP9, and FGF21. Participants completed baseline and 2-year follow-up study visits and were categorized as lean (LC, lean control; n = 30), obese normoglycemic (ONG; n = 61), and obese hyperglycemic (OHG; n = 31) adolescents at baseline and lean ( n = 8), ONG ( n = 18), and OHG ( n = 4) at follow-up. Groups were compared using ANOVA and regression analysis, and linear mixed effects modeling was used to test for differences in adipokine levels across baseline and follow-up visits. Results showed that at baseline, leptin was higher in all obese groups ( P < 0.001) compared with LC. FGF21 was higher in OHG participants compared with LC ( P < 0.001) and ONG ( P < 0.001) and positively associated with fasting glucose ( P < 0.001), fasting insulin ( P < 0.001), Homeostasis Model Assessment-Insulin Resistance Index (HOMA-IR; P < 0.001), and hemoglobin A1c (HbA1c; P = 0.01). CTRP1 was higher in OHG compared with ONG ( P = 0.03). CTRP9 was not associated with obesity or hyperglycemia in this pediatric cohort. At 2 years, leptin decreased in ONG ( P = 0.003) and FGF21 increased in OHG ( P = 0.02), relative to lean controls. Altered adipokine levels are associated with the inflammatory milieu in obese youth with and without hyperglycemia. In adolescence, the novel adipokine CTRP1 was elevated with hyperglycemia, whereas CTRP9 was unchanged in this cohort. NEW & NOTEWORTHY Leptin is higher in obese adolescents and FGF21 is higher in obese hyperglycemic adolescents. The novel adipokine CTRP1 is higher in obese hyperglycemic adolescents, whereas CTRP9 was unchanged in this adolescent cohort.

The aim of the report was to investigate the impact of soy protein and isoflavones on glucose homeostasis and lipid profile in type 2 diabetes. The studies used in this report were identified by searching through the MEDLINE and EMBASE databases (up to 2020). Meta-regression and subgroup analyses were performed to explore the influence of covariates on net glycemic control and lipid changes. Weighted mean differences and 95% confidence intervals (CI) were calculated by using random-effect models. Changes in the lipid profile showed statistically significant decreases in total cholesterol and LDL-C concentrations: ‒0.21 mmol/L; 95% CI, ‒0.33 to ‒0.09; p = 0.0008 and ‒0.20 mmol/L; 95% CI, ‒0.28 to ‒0.12; p < 0.0001, respectively, as well as in HDL-C (-0.02 mmol/L; 95% CI, -0.05 to 0.01; p = 0.2008 and triacylglycerols (-0.19 mmol/L; 95% CI, -0.48 to 0.09; p = 0.1884). At the same time, a meta-analysis of the included studies revealed statistically insignificant reduction in fasting glucose, insulin, HbA1c, and HOMA-IR (changes in glucose metabolism) after consumption of soy isoflavones. The observed ability of both extracted isoflavone and soy protein with isoflavones to modulate the lipid profile suggests benefits in preventing cardiovascular events in diabetic subjects. Further multicenter studies based on larger and longer duration studies are necessary to determine their beneficial effect on glucose and lipid metabolism.

Hypoglycaemia (blood glucose concentration below the normal range) has been recognised as a complication of insulin treatment from the very first days of the discovery of insulin, and remains a major concern for people with diabetes, their families and healthcare professionals today. Acute hypoglycaemia stimulates a stress response that acts to restore circulating glucose, but plasma glucose concentrations can still fall too low to sustain normal brain function and cardiac rhythm. There are long-term consequences of recurrent hypoglycaemia, which are still not fully understood. This paper reviews our current understanding of the acute and cumulative consequences of hypoglycaemia in insulin-treated diabetes.

The discovery of insulin and its subsequent mass manufacture transformed the lives of people with type 1 and 2 diabetes. Insulin, however, was a drug with a 'dark side'. It brought with it the risk of iatrogenic hypoglycaemia. In this short review, the cellular consequences of recurrent hypoglycaemia, with a particular focus on the brain, are discussed. Using the ventromedial hypothalamus as an exemplar, this review highlights how recurrent hypoglycaemia has an impact on the specialised cells in the brain that are critical to the regulation of glucose homeostasis and the counterregulatory response to hypoglycaemia. In these cells, recurrent hypoglycaemia initiates a series of adaptations that ensure that they are more resilient to subsequent hypoglycaemia, but this leads to impaired hypoglycaemia awareness and a paradoxical increased risk of severe hypoglycaemia. This review also highlights how hypoglycaemia, as an oxidative stressor, may also exacerbate chronic hyperglycaemia-induced increases in oxidative stress and inflammation, leading to damage to vulnerable brain regions (and other end organs) and accelerating cognitive decline. Pre-clinical research indicates that glucose recovery following hypoglycaemia is considered a period where reactive oxygen species generation and oxidative stress are pronounced and can exacerbate the longer-term consequence of chronic hypoglycaemia. It is proposed that prior glycaemic control, hypoglycaemia and the degree of rebound hyperglycaemia interact synergistically to accelerate oxidative stress and inflammation, which may explain why increased glycaemic variability is now increasingly considered a risk factor for the complications of diabetes.

Background: Little is known about whether the influence of glycemic variability on arrhythmia is related to age in type 2 diabetes mellitus (T2DM). Therefore, we aimed to compare the association between glycemic variability and arrhythmia in middle-aged and elderly T2DM patients., Methods: A total of 107 patients were divided into two groups: elderly diabetes mellitus group (EDM, n = 73) and middle-aged diabetes mellitus group (MDM, n = 34). The main clinical data, continuous glucose monitoring (CGM) and dynamic ECG reports were collected. The parameters including standard deviation of blood glucose (SDBG), largest amplitude of glycemic excursions (LAGE), mean amplitude of glycemic excursions (MAGE), absolute means of daily differences (MODD), time in range (TIR), time below range (TBR), time above range (TAR), coefficient of variation (CV) were tested for glycemic variability evaluation., Results: In terms of blood glucose fluctuations, MAGE (5.77 ± 2.16 mmol/L vs 4.63 ± 1.89 mmol/L, P = 0.026), SDBG (2.39 ± 1.00 mmol/L vs 2.00 ± 0.82 mmol/L, P = 0.048), LAGE (9.53 ± 3.37 mmol/L vs 7.84 ± 2.64 mmol/L, P = 0.011) was significantly higher in EDM group than those of MDM group. The incidences of atrial premature beat, couplets of atrial premature beat, atrial tachycardia and ventricular premature beat were significantly higher in EDM group compared with the MDM group (all P < 0.05). Among patients with hypoglycemia events, the incidences of atrial premature beat, couplets of atrial premature beat, atrial tachycardia and ventricular premature beat (all P < 0.05) were significantly higher in the EDM group than those in the MDM group. In EDM group, TIR was negatively correlated with atrial tachycardia in the MAGE1 layer and with atrial tachycardia and ventricular premature beat in the MAGE2 layer, TBR was significantly positively correlated with atrial tachycardia in the MAGE2 layer (all P < 0.05). In MDM group, TAR was positively correlated with ventricular premature beat and atrial tachycardia in the MAGE2 layer (all P < 0.05)., Conclusions: The study demonstrated the elderly patients had greater glycemic variability and were more prone to arrhythmias. Therefore, active control of blood glucose fluctuation in elderly patients will help to reduce the risk of severe arrhythmia.

Plasma glucose and insulin responses following an oral glucose challenge are representative of glucose tolerance and insulin resistance, key indicators of type 2 diabetes mellitus pathophysiology. A large heterogeneity in individuals' challenge test responses has been shown to underlie the effectiveness of lifestyle intervention. Currently, this heterogeneity is overlooked due to a lack of methods to quantify the interconnected dynamics in the glucose and insulin time-courses. Here, a physiology-based mathematical model of the human glucose-insulin system is personalized to elucidate the heterogeneity in individuals' responses using a large population of overweight/obese individuals (n = 738) from the DIOGenes study. The personalized models are derived from population level models through a systematic parameter selection pipeline that may be generalized to other biological systems. The resulting personalized models showed a 4-5 fold decrease in discrepancy between measurements and model simulation compared to population level. The estimated model parameters capture relevant features of individuals' metabolic health such as gastric emptying, endogenous insulin secretion and insulin dependent glucose disposal into tissues, with the latter also showing a significant association with the Insulinogenic index and the Matsuda insulin sensitivity index, respectively., Competing Interests: The authors have declared that no competing interests exist.

Objective: This study aimed to observe the changes in serum vaspin levels in pregnant women after glucose load during oral glucose tolerance test (OGTT) and analyze the effect of blood glucose levels on serum vaspin secretion in pregnant women with gestational diabetes mellitus (GDM)., Methods: It included 30 patients with GDM and 30 age-matched pregnant women with normal glucose tolerance (NGT, control). The blood glucose, insulin, total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), and serum vaspin levels were measured at 24-28 weeks of gestation. The homeostasis model assessment of insulin resistance (HOMA-IR) values were calculated., Results: 1. The levels of fasting plasma glucose (FPG), 1-h PG, 2-h PG, fasting insulin (FINS), HOMA-IR, baseline vaspin, 1-h vaspin, and 2-h vaspin were higher in the GDM group than in the NGT group. 2. The 1-h and 2-h vaspin levels were significantly higher than the baseline levels in the GDM group. The change in the vaspin level after 1 h in the GDM group during the OGTT was significantly greater than that in the NGT group. 3. The vaspin levels in the GDM group positively correlated with 1-h PG and TG, including the baseline vaspin ( r  = 0.494, p  = .006; r  = 0.385, p  = .036), 1-h vaspin ( r  = 0.577, p  = .001; r  = 0.466, p  = .010), and 2-h vaspin ( r  = 0.557, p  = .001; r  = 0.488, p  = .006)., Conclusion: Vaspin might be regulated by the hyperglycemia level and involved in the pathogenesis of GDM and lipid metabolism.

Training with low carbohydrate availability enhances endurance training adaptations but training volume may be compromised. We explored whole-body metabolism and performance with delayed carbohydrate feeding during exercise undertaken following acute sleep-low training. We hypothesised this strategy would not suppress fat oxidation and would maintain exercise performance. The study involved three experimental trials and included 9 men and 1 woman (⩒O 2 peak = 58.8 ± 5.5 mL kg -1 min -1 ). Each trial started in the afternoon with an exhaustive cycling protocol. The following morning 1-h of steady-state cycling (SS) was followed by a time trial (TT). Carbohydrates (CHO) were not ingested in recovery from exhaustive exercise or during next day exercise in the Placebo trial (PLA); CHO were not ingested during recovery but were fed (15 g every ∼15-min) from 30-min into SS and continued during the TT in the delayed feeding trial (DELAY); CHO were provided during recovery (1.2 g/kg/h for 7 h) and next day exercise (as in DELAY) in a third condition (CHO). Exercise metabolism was assessed using indirect calorimetry and blood sampling. Fat oxidation rates during SS were similar in PLA (0.83 ± 0.17 g/min) and DELAY (0.78 ± 0.14 g/min) ( p  > 0.05) and higher than CHO (0.57 ± 0.27 g/min) ( p  < 0.05). There were no significant differences in TT performance (49.1 ± 10.7, 43.4 ± 7.6, 41.0 ± 7.9 min in PLA, DELAY and CHO, respectively; p  > 0.05). Delayed carbohydrate feeding could be a strategy to maintain high-fat oxidation rates typically associated with exercise undertaken after the sleep-low approach to training but the acute performance effects remain inconclusive.

Aims: Nowadays, the ongoing pandemic of COVID-19 caused by the novel coronavirus Syndrome-Coronavirus-2 (SARS-CoV-2) is an emerging, rapidly evolving situation. Complications such as hypertension, diabetes, COPD, cardiovascular disease, and cerebrovascular disease are major risk factors for patients with COVID-19., Methods: No meta-analysis has explored if or not diabetes related to mortality of patients with COVID-19. Therefore, this meta-analysis first aims to explore the possible clinical mortality between diabetes and COVID-19, analyze if diabetes patients infected with SARS-CoV-2 are exposed to the worst clinical prognostic risk, and to evaluate the reliability of the evidence., Results: Our results showed a close relationship between diabetes and mortality of COVID-19, with a pooled OR of 1.75 (95% CI 1.31-2.36; P = 0.0002). The pooled data were calculated with the fixed effects model (FEM) as no heterogeneity appeared in the studies. Sensitivity analysis showed that after omitting any single study or converting a random effect model to FEM, the main results still held., Conclusions: Our meta-analysis showed that diabetes increases the mortality of patients with COVID-19. These results indicated the disturbance of blood glucose in the COVID-19 patients. More importantly, this meta-analysis grades the reliability of evidence for further basic and clinical research into the diabetes dysfunction in COVID-19 patients.

Context: Perturbed inositol physiology in insulin-resistant conditions has led to proposals of inositol supplementation for gestational diabetes (GDM) prevention, but placental inositol biology is poorly understood., Objective: Investigate associations of maternal glycemia with placental inositol content, determine glucose effects on placental expression of inositol enzymes and transporters, and examine relations with birthweight., Design and Participants: Case-control study of placentae from term singleton pregnancies (GDM n = 24, non-GDM n = 26), and culture of another 9 placentae in different concentrations of glucose and myo-inositol for 48 hours., Main Outcome Measures: Placental inositol was quantified by the Megazyme assay. Relative expression of enzymes involved in myo-inositol metabolism and plasma membrane inositol transport was determined by quantitative RT-PCR and immunoblotting. Linear regression analyses were adjusted for maternal age, body mass index, ethnicity, gestational age, and sex., Results: Placental inositol content was 17% lower in GDM compared with non-GDM. Higher maternal mid-gestation glycemia were associated with lower placental inositol. Increasing fasting glycemia was associated with lower protein levels of the myo-inositol synthesis enzyme, IMPA1, and the inositol transporters, SLC5A11 and SLC2A13, the expression of which also correlated with placental inositol content. In vitro, higher glucose concentrations reduced IMPA1 and SLC5A11 mRNA expression. Increasing fasting glycemia positively associated with customized birthweight percentile as expected in cases with low placental inositol, but this association was attenuated with high placental inositol., Conclusion: Glycemia-induced dysregulation of placental inositol synthesis and transport may be implicated in reduced placental inositol content in GDM, and this may in turn be permissive to accelerated fetal growth., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The benefits of self-monitoring of blood glucose (SMBG) on glycemic control among type 2 diabetes (T2DM) patients not receiving insulin remains controversial. This study aimed to examine the association between SMBG and glycemic control in these patients. This retrospective longitudinal study enrolled 4987 eligible patients from a medical center in Taiwan. Data were collected from electronic medical records at 0 (baseline), 3, 6, 9, and 12 (end-point) months after enrollment. Patients were assigned to the early SMBG group or to the non-user group depending on whether they performed SMBG at baseline. Differences in glycated hemoglobin (HbA1c) reduction between groups at each time-point were assessed using SMBG group-by-time interaction in generalized estimating equations models, which were established using backward elimination method for multivariate regression analysis. Subgroup analyses for patients using non-insulin and insulin secretagogues were performed additionally. The estimated maximal difference in HbA1c reduction between groups (early SMBG users vs. non-users) was 0.55% at 3 months. Subgroup analyses showed maximal differences of 0.61% and 0.52% at 3 months in the non-insulin and insulin secretagogues groups, respectively. SMBG group-by-time interaction was statistically significant at 3 months and lasted for 12 months. The finding suggests that performing SMBG at disease onset was positively associated with better glycemic control in newly diagnosed non-insulin-treated T2DM patients, regardless whether non-insulin secretagogues or insulin secretagogues were used.

Importance: Accurate clinical decision support tools are needed to identify patients at risk for iatrogenic hypoglycemia, a potentially serious adverse event, throughout hospitalization., Objective: To predict the risk of iatrogenic hypoglycemia within 24 hours after each blood glucose (BG) measurement during hospitalization using a machine learning model., Design, Setting, and Participants: This retrospective cohort study, conducted at 5 hospitals within the Johns Hopkins Health System, included 54 978 admissions of 35 147 inpatients who had at least 4 BG measurements and received at least 1 U of insulin during hospitalization between December 1, 2014, and July 31, 2018. Data from the largest hospital were split into a 70% training set and 30% test set. A stochastic gradient boosting machine learning model was developed using the training set and validated on internal and external validation., Exposures: A total of 43 clinical predictors of iatrogenic hypoglycemia were extracted from the electronic medical record, including demographic characteristics, diagnoses, procedures, laboratory data, medications, orders, anthropomorphometric data, and vital signs., Main Outcomes and Measures: Iatrogenic hypoglycemia was defined as a BG measurement less than or equal to 70 mg/dL occurring within the pharmacologic duration of action of administered insulin, sulfonylurea, or meglitinide., Results: This cohort study included 54 978 admissions (35 147 inpatients; median [interquartile range] age, 66.0 [56.0-75.0] years; 27 781 [50.5%] male; 30 429 [55.3%] White) from 5 hospitals. Of 1 612 425 index BG measurements, 50 354 (3.1%) were followed by iatrogenic hypoglycemia in the subsequent 24 hours. On internal validation, the model achieved a C statistic of 0.90 (95% CI, 0.89-0.90), a positive predictive value of 0.09 (95% CI, 0.08-0.09), a positive likelihood ratio of 4.67 (95% CI, 4.59-4.74), a negative predictive value of 1.00 (95% CI, 1.00-1.00), and a negative likelihood ratio of 0.22 (95% CI, 0.21-0.23). On external validation, the model achieved C statistics ranging from 0.86 to 0.88, positive predictive values ranging from 0.12 to 0.13, negative predictive values of 0.99, positive likelihood ratios ranging from 3.09 to 3.89, and negative likelihood ratios ranging from 0.23 to 0.25. Basal insulin dose, coefficient of variation of BG, and previous hypoglycemic episodes were the strongest predictors., Conclusions and Relevance: These findings suggest that iatrogenic hypoglycemia can be predicted in a short-term prediction horizon after each BG measurement during hospitalization. Further studies are needed to translate this model into a real-time informatics alert and evaluate its effectiveness in reducing the incidence of inpatient iatrogenic hypoglycemia.

While the chronic effects of certain styles of yoga on cardiometabolic factors have been investigated, little is known about the acute effects of a single yoga session on these outcomes. Moreover, vinyasa yoga's potential to modulate cardiometabolic outcomes has not been established. The purpose of this study is to determine the acute effects of a vinyasa yoga session on arterial stiffness, wave reflection, lipid and glucose concentrations, and mood in adults with prior yoga experience. Thirty yoga practitioners with a minimum of 3 months of practice experience were enrolled into the study. Carotid-femoral pulse wave velocity (cf-PWV), augmentation index (AIx), lipid profile, glucose concentrations, and mood (Positive and Negative Affect Scale) were assessed at baseline and immediately following a 1 -h vinyasa yoga session. After the yoga session, participants had significantly lower AIx (p < 0.001), non-HDL cholesterol (p < 0.05), and negative affect (p < 0.01) compared to baseline. These results highlight the efficacy of a single bout of yoga in altering wave reflection while improving mood and lipid concentrations in healthy adults with a history of yoga practice., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: The prepubertal stage is a critical period of body fat development, in which leptin and insulin re sistance has been associated, however, there are few studies in normal-weight prepubescents. Ob jective: To assess the relationship between leptin and body composition and insulin resistance in a group of normal-weight prepubescents., Patients and Method: Analytical cross-sectional study with 128 healthy prepubescents of normal weight, aged between 6 and 10 years. Height, weight, body mass index (BMI), body fat percentage (BFP), waist circumference (WC), and hip circumference (HC) were measured. Plasma leptin (ng/mL) and insulin (mU/L) were evaluated by immunoassay and glycemia (mmol/L) by enzymatic method. HOMA-IR was calculated. A comparison study and correlation analysis by sex were performed., Results: Females presented higher values than males of leptin (6.8 ± 5 vs 3.3 ± 3.7; p = 0.000), insulin (7.1 ± 4.5 vs 5.2 ± 2.5; p = 0.016), BFP (22.4 ± 4.3 vs 18.6 ± 3.9; p = 0.000), and HC (67 ± 5.7 vs 65.0 ± 4.5; p = 0.019), and a lower waist/hip ratio (0.84 ± 0.04 vs 0.88 ± 0.04; p = 0.000). Leptin correlations with anthropometric variables were significant in both sexes, with greater association in females. The association of HOMA-IR with leptin was similar in both sexes., Conclusions: in normal-weight prepubescents aged between 6-10 years, there are sex differences in adiposity and leptin levels not associated with differences in BMI or insulin resistance. The greater association of leptin with adiposity in girls could be related to a high rate of adipogenesis induced by this hormone.

Aims: Data about the association between periodontal disease or periodontitis (PD), diabetes and hyperglycemia have been reported mostly in patients with type 2 diabetes. Conversely, information about PD in type 1 diabetes (T1DM) is relatively scarce. The aim of this meta-analysis is therefore: (1) to assess the prevalence and severity of PD in patients affected by T1DM in comparison with the general population and (2) to verify the association between severity of PD and glycemic control in type 1 diabetics., Methods: An electronic search was performed on MEDLINE, Cochrane Central Register of Trials and EMBASE, up to October 31, 2019. Estimates of prevalence of PD in T1DM were calculated together with Mantel-Haenszel odds ratios (MH-OR) of the risk of PD associated with T1DM; weighed mean difference in CAL between T1DM and control and weighed mean difference in CAL in patients with T1DM and unsatisfactory glycemic control as compared with those in good glycemic control were also evaluated.., Results: The prevalence of PD in type 1 diabetes was 18.5 [8.0; 37.1] %; the MH-OR for PD is 2.51 (1.32;4.76) in T1DM patients versus general population (p = 0.005). The weighed mean difference in CAL depth between T1DM patients and controls is 0.506 [0.181; 0.832] mm (p < 0.005), and in T1DM patients with good glycemic control CAL depth is - 0.71 [- 1.00; - 0.42] mm less deep than in subjects with HbA1c > 7%., Conclusions: The present data confirm that T1DM is a relevant risk factor for the development of PD. The proportion of patients affected by PD is more than doubled in subjects with T1DM in comparison with non-diabetic individual, and among patients with T1DM, PD seems to be more severe and the differences appear very wide between subjects in optimal and suboptimal glycemic control.

Problem: There are different conclusions about the effects of resistance training on blood sugar levels and pregnancy outcomes in gestational diabetes mellitus (GDM) patients., Background: Resistance training is recommended as an easier and more practical method to exercise for women with GDM due to their growing belly. Although some researchers have explored this notion, there are no consistent conclusions about its effects., Aim: To explore whether resistance training has an effect on blood sugar levels and pregnancy outcomes in patients with GDM in randomized controlled trials., Method: Pubmed, Cochrane Library, CINAHL, Embase, Scopus, Web of Science, Clinical Trials, CKNI, Wanfang Database, VIP Database, and Chinese Biomedical Literature Database were systematically searched since their establishment to April 2019. Relevant meta-analyses, reviews, and eligible literature were also searched. The quality of the included literature was evaluated according to the Cochrane Assessment Manual 5.1.0. Meta-analysis was performed using Revman 5.3 software., Findings: A total of four studies (n = 242 patients) were included. Compared to the control group, there were statistical differences in fasting blood glucose level [MD=-0.37, 95%CI=(-0.65, -0.09), Z = 2.62, P = 0.009], average 2-h post-meal blood glucose level [MD=-0.96, 95%CI=(-1.80, -0.12), Z = 2.25, P = 0.02], insulin dosage [MD=-0.58, 95%CI=(-0.99, -0.17), Z = 2.75, P = 0.006], rate of insulin injection [RR=0.52, 95%CI=(0.31, 0.86), Z = 2.54, P = 0.01], and incidence of macrosomia [RR=0.15, 95%CI=(0.04,0.66), Z = 2.53, P = 0.01] in the intervention group consisting of GDM patients. There were no statistical differences in preterm delivery outcomes [RR=0.44, 95%CI=(0.09, 2.16), Z = 1.01, P = 0.31]., Conclusion: Resistance training can improve blood sugar levels, insulin usage, and some adverse pregnancy outcomes in patients with GDM and is therefore worthy of clinical promotion., Competing Interests: Declaration of Competing Interest All authors report no conflict of interest. This research was funded from Quanzhou science and technology plan project in China and reports no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Objectives: Stroke is one of the leading causes of death, disability, and dementia in developing countries. Our study aimed to evaluate the systemic disorders associated with mortality in patients admitted within 72 hours of the initial stroke event., Setting: The study took place at a tertiary hospital in Kinshasa., Participants: Patients admitted within 72 hours of the initial stroke event., Interventions: This cross-sectional study consisted of a retrospective review of stroke patient records from January 2016 to December 2018. The Pearson-Chi square test and odds ratios were calculated with a threshold of significance of 0.05., Main Outcome Measures: Mortality., Results: We recruited 114 cases. The mean age was 61.8 ± 2.4 years, and the sex ratio was 1.78 in favor of men. Hypertension (76.3%), dyslipidemia (71.1%), and diabetes mellitus (58.8%) were the most frequent comorbidities. Most patients had hypoxia (85.9%), hypertension (82.4%), hyperglycemia (57.8%), and fever (28.1%). We registered thirty-two deaths (28.1%): 20 (62.5%) from the ischemic strokes, and 12 (37.5%) from hemorrhagic strokes. Systemic disorders with the worst prognosis during were arterial hypotension (OR=3.87, p >0.001), and fever (OR =1.56, p = 0.047)., Conclusion: Arterial hypotension and fever adversely affect stroke patient outcomes, and strokes are responsible for high mortality in Congo., Funding: Not applicable., Competing Interests: Conflict of interest: None declared, (Copyright © The Author(s).)

The ongoing pandemic of COVID-19 is now the major issue in global health. Evidence implies that patients with diabetes are at a higher risk of severe disease or death due to COVID-19 than individuals without diabetes. However, the underlying mechanism for this differential effect in individuals with and without diabetes is not clearly understood. We have reviewed the pathophysiological pathways which may facilitate the entry of virus or an increase in its infectivity in host cells in the diabetic milieu. We suggest that the preexisting pathological pathways in patients with poorly controlled diabetes increase the risk of infectivity and are responsible for the higher levels of tissue injury and death in patients with diabetes., Competing Interests: The authors declare to have no conflict of interest in this study., (Copyright © 2020 Habib Yaribeygi et al.)

Aims: To explore associations between multimorbidity condition counts (total; concordant (diabetes-related); discordant (unrelated to diabetes)) and glycaemia (HbA1c; glycaemic variability (GV); time in range (TIR)) using data from a randomised controlled trial examining effectiveness of continuous glucose monitoring (CGM) in people with type 2 diabetes (T2D)., Methods: Cross-sectional study: 279 people with T2D using baseline data from the General Practice Optimising Structured MOnitoring To Improve Clinical outcomes (GP-OSMOTIC) trial from 25 general practices in Australia. Number of long-term conditions (LTCs) in addition to T2D used to quantify total/concordant/discordant multimorbidity counts. GV (measured by coefficient of variation (CV)) and TIR derived from CGM data. Multivariable linear regression models used to examine associations between multimorbidity counts, HbA1c (%), GV and TIR., Results: Mean (SD) age of participants 60.4 (9.9) years; 40.9% female. Multimorbidity was present in 89.2% of participants. Most prevalent comorbid LTCs: hypertension (57.4%), painful conditions (29.8%), coronary heart disease (22.6%) and depression (19.0%). No evidence of associations between multimorbidity counts, HbA1c, GV and TIR., Conclusions: While multimorbidity was common in this T2D cohort, it was not associated with HbA1c, CV or TIR. Future studies should explore factors other than glycaemia that contribute to the increased mortality observed in those with multimorbidity and T2D., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims/hypothesis: Depression is twice as common in individuals with type 2 diabetes as in the general population. However, it remains unclear whether hyperglycaemia and insulin resistance are directly involved in the aetiology of depression. Therefore, we investigated the association of markers of hyperglycaemia and insulin resistance, measured as continuous variables, with incident depressive symptoms over 4 years of follow-up., Methods: We used data from the longitudinal population-based Maastricht Study (n = 2848; mean age 59.9 ± 8.1 years, 48.8% women, 265 incident depression cases, 10,932 person-years of follow-up). We assessed hyperglycaemia by fasting and 2 h post-load OGTT glucose levels, HbA 1c and skin autofluorescence (reflecting AGEs) at baseline. We used the Matsuda insulin sensitivity index and HOMA-IR to calculate insulin resistance at baseline. Depressive symptoms (nine-item Patient Health Questionnaire score ≥10) were assessed at baseline and annually over 4 years. We used Cox regression analyses, and adjusted for demographic, cardiovascular and lifestyle risk factors., Results: Fasting plasma glucose, 2 h post-load glucose and HbA 1c levels were associated with an increased risk for incident depressive symptoms after full adjustment (HR 1.20 [95% CI 1.08, 1.33]; HR 1.25 [1.08, 1.44]; and HR 1.22 [1.09, 1.37] per SD, respectively), while skin autofluorescence, insulin sensitivity index and HOMA-IR were not (HR 0.99 [0.86, 1.13]; HR 1.02 [0.85, 1.25]; and HR 0.93 [0.81, 1.08], per SD, respectively)., Conclusions/interpretation: The observed temporal association between hyperglycaemia and incident depressive symptoms in this study supports the presence of a mechanistic link between hyperglycaemia and the development of depressive symptoms. Graphical abstract.

We present a fully closed-loop design for an artificial pancreas (AP) that regulates the delivery of insulin for the control of Type I diabetes. Our AP controller operates in a fully automated fashion, without requiring any manual interaction with the patient (e.g., in the form of meal announcements). A major obstacle to achieving closed-loop insulin control are the "unknown disturbances" related to various aspects of a patient's daily behavior, especially meals and physical activity. Such disturbances can significantly affect the patient's blood glucose levels. To handle such uncertainties, we present a data-driven, robust, model-predictive control framework in which we capture a wide range of individual meal and exercise patterns using uncertainty sets learned from historical data. These uncertainty sets are then used in the insulin controller to achieve automated, precise, and personalized insulin therapy. We provide an extensive in silico evaluation of our robust AP design, demonstrating the potential of the approach. In particular, without the benefit of explicit meal announcements, our approach can regulate glucose levels for large clusters of meal profiles learned from population-wide survey data and cohorts of virtual patients, even in the presence of high carbohydrate disturbances.

Aims: Diabetes mellitus is a progressive, chronic, systemic, metabolic disease that must be managed effectively. Its prevalence is increasing rapidly. We investigated whether urologists' awareness and recognition of glucosuria contributed to the diagnosis of diabetes and regulation of blood glucose., Methods: A total of 39,053 patients were retrospectively evaluated between January 2018 and February 2019. Of them, 16,211 had undergone urinalysis for varied reasons. Glucosuria was semi-quantitatively measured as (+), (++), (+++), and (++++). Patients were assessed in terms of whether they had been referred to endocrinology or internal medicine departments within the 15 days and the presence/absence of a previous or new diagnosis of diabetes mellitus by measuring blood glucose and HgbA1c levels., Results: Glucosuria was detected in 665 patients (4.1%), of whom 495 were included in the study. 417 (84.2%) had been previously diagnosed with diabetes mellitus, and 56 (11.3%) newly received a diabetes mellitus diagnosis. Blood glucose and HbA1c values were normal in 22 (4.4%) patients with glucosuria. HgbA1c value was determined as 7 or above in 381 (91.3%) of 417 cases with a previous diabetes mellitus diagnosis., Conclusion: Referring all patients detected to have glucosuria in the spot urine test at any time regardless of fasting/non-fasting to the relevant departments can contribute to the diagnosis and treatment of diabetes mellitus disease.

Introduction: Gestational hyperinsulinism is a metabolic disease which is widely concerned at home and abroad. It is a clinical consensus that the embryo implantation ability of patients with hyperinsulinemia is decreased and the abortion rate after implantation is high. The treatment of gestational hyperinsulinism with Multiple dietary fiber diets has been proven. However, due to the lack of evidence, there is no specific method or recommendation, it is necessary to carry out a systematic evaluation of Multiple dietary fiber diet, to provide effective evidence for further research., Methods and Analysis: The following databases will be searched from their inception to August 2020: Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, Nature, Science online, Chinese Biomedical Database WanFang, VIP medicine information, and CNKI. Primary outcomes: Fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance, glycosylated hemoglobin. Additional outcomes: Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), triglycerides (TG), total serum cholesterol (TC). Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews (SR) of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0., Results: The results of this study will systematically evaluate the effectiveness and safety of Multiple dietary fiber diet interventions in the treatment of gestational hyperinsulinism., Conclusion: The SR of this study will summarize the current published evidence of Multiple dietary fiber for the treatment of gestational hyperinsulinism, which can further guide the promotion and application of it., Ethics and Dissemination: This study is a SR, the outcomes are based on the published evidence, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations., Open Science Fra Network (osf) Registration Number: August 19, 2020. osf.io/tbc7z. (https://osf.io/tbc7z).

Aim: To evaluate the association between different degrees of hyperglycaemia and the risk of all-cause mortality among hospitalized patients with COVID-19., Materials and Methods: In a retrospective study conducted from 22 January to 17 March 2020, 453 patients were admitted to Union Hospital in Wuhan, China, with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. Patients were classified into four categories: normal glucose, hyperglycaemia (fasting glucose 5.6-6.9 mmol/L and/or HbA1c 5.7%-6.4%), newly diagnosed diabetes (fasting glucose ≥7 mmol/L and/or HbA1c ≥6.5%) and known diabetes. The major outcomes included in-hospital mortality, intensive care unit (ICU) admission and invasive mechanical ventilation (IMV)., Results: Patients with newly diagnosed diabetes constituted the highest percentage to be admitted to the ICU (11.7%) and require IMV (11.7%), followed by patients with known diabetes (4.1%; 9.2%) and patients with hyperglycaemia (6.2%; 4.7%), compared with patients with normal glucose (1.5%; 2.3%), respectively. The multivariable-adjusted hazard ratios of mortality among COVID-19 patients with normal glucose, hyperglycaemia, newly diagnosed diabetes and known diabetes were 1.00, 3.29 (95% confidence interval [CI] 0.65-16.6), 9.42 (95% CI 2.18-40.7) and 4.63 (95% CI 1.02-21.0), respectively., Conclusion: We showed that COVID-19 patients with newly diagnosed diabetes had the highest risk of all-cause mortality compared with COVID-19 patients with known diabetes, hyperglycaemia and normal glucose. Patients with COVID-19 need to be kept under surveillance for blood glucose screening., (© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)