Plasma Glucose Concentrations Research Articles

THU265 A U-Shaped Relationship Between Undiagnosed Diabetes And Thyroid Function

Abstract Disclosure: Z.Z. Alvi: None. R. Karnchanasorn: None. H. Ou: None. L. Chuang: None. A.G. Gianoukakis: None. K.C. Chiu: None. Thyroid dysfunction is present in about 20 million people in the United States, with about 60% percent unaware of their condition. Thyroid hormone is one of the key hormone regulators of energy metabolism, while diabetes mellitus (DM) is a disorder of dysregulated fuel metabolism. Thus, thyroid hormone can affect glucose metabolism. Unfortunately, this area has received little attention over the past few decades. This study investigates the rate of undiagnosed DM in relation to thyroid function. A representative and noninstitutionalized US adult (aged 20 years or older with BMI available) population from the National Health and Nutrition Examination Survey 2007-2012 was used for this study. Subjects with known thyroid diseases and/or diabetes were excluded. This study only included subjects with available TSH, free T4 (FT4), and free T3 (FT3) levels and the defined status of glucose tolerance by HbA1c, fasting, and/or 2-hour post-challenge plasma glucose concentrations (n=6,843). The rates of previously undiagnosed DM were determined for each quintile of TSH, FT4, and FT3 with sample-weighted analysis. The adjusted odds ratio (AOD) with a 95% confidence interval (95%CI) for DM was calculated with the lowest quintile as a reference after consideration of age, gender, BMI, and racial/ethnic groups. Amongst 6,834 subjects in this study, DM was found in 488 subjects. The rates of DM from quintile 1 to quintile 5 were 3.37%, 3.95%, 3.84%, 6.42%, and 7.26 % for TSH quintiles (P<0.0001 by ANOVA); 5.69%, 4.27%, 5.05%, 4.74%, and 6.46% for FT4 quintiles (P<0.0001 by ANOVA); and 4.82%, 4.63%, 5.33%, 5.33%, and 4.93% for FT3 quintiles (P<0.0001 by ANOVA). Although the correlations were imperfect among TSH, FT4, and FT3 quintiles, the U-shaped relationship of DM with thyroid function was confirmed by the lowest AOD of 0.80 (95%CI: 0.80 - 0.80, P<0.0001) for the 3rd quintile of TSH (TSH: 1.321 - 1.771 mIU/L). The association of DM with low thyroid function was confirmed by the AOD of 1.31 (95%CI: 1.30 - 1.32, P<0.0001) for the 5th quintile of TSH (TSH: 2.519 - 80.968 mIU/L). The association of DM with high thyroid function was confirmed by AOD of 2.45 (95%CI: 2.44 - 2.46, P<0.0001) for the 5th quintile of FT3 (FT3: 3.51 - 28.82 pg/mL). FT4 confirmed the U-shaped relationship with the highest AOD of 1.07 (95%CI: 1.07 - 1.08, P<0.0001) for the 5th quintile of FT4 (FT4: 0.91 - 4.80 ng/mL) and the lowest AOD of 0.82 (95%CI: 0.82 - 0.82, P<0.001) for the 2nd quintile of FT4 (FT4: 0.91 - 4.80 ng/mL). Our study revealed a U-shaped relationship between the rates of undiagnosed DM with thyroid function in a representative and noninstitutionalized US adult population without a prior diagnosis of thyroid dysfunction and diabetes. Different underlying mechanisms may be responsible for the association of DM with high and low thyroid function. Further studies are required to elucidate the underlying mechanisms. Presentation: Thursday, June 15, 2023

FRI364 A Case Of Carcinoid Syndrome Symptoms Masked By Niacin Use

Abstract Disclosure: S. Yang: None. R. Sharag Eldin: None. D. Teves Qualler: None. Case Presentation: A 72 male presented with worsening of facial flushing and diarrhea for 10 years. The patient described episodic feeling of hotness in the face associated with red- purplish discoloration of his facial skin lasting for 2 to 3 minutes. He has had 5 to 6 episodes per day. The patient reported the use of Niacin in the past and it was believed that it was the cause of his flushing episodes despite its persistence for years after stopping it. The patient also suffered from long standing diarrhea which started around the same time of the flushing. Diarrhea has been watery or loose and he has 5 to 6 bowel movements a day. His symptoms were concerning for Carcinoid syndrome and a 24-hour urine collection for HIAA showed elevated HIAA to 108.7 mg/24 hour (<6 mg/24 hour). A CT scan of the abdomen revealed a 1.8 cm wall thickness in the cecum and a 3.6 cm spiculated mesenteric mass with central calcification with multiple hypervascular masses in the liver concerning for a metastatic neuroendocrine tumor. Core biopsy of one of the liver masses showed a well differentiated neuroendocrine tumor. He was also found to have tricuspid valve regurgitation as well as a Glycohemoglobin of 9%. The patient was treated medically with octreotide rather than surgery due to the significant disease burden. Interestingly, he was initially started on Lanreotide but developed foreign body granulomas at the injection sites. Discussion: Carcinoid-syndrome is a category of well-differentiated neuroendocrine neoplasms. The overproduction of serotonin is most used to assess the presence of carcinoid syndrome via its breakdown product 5- HIAA in the urine. Symptoms from niacin supplementation are variable and may include flushing and constipation. Patient’s flushing presented for years after discontinuing niacin supplementation. However, clinicians continued to attribute it to its use despite typical resolution of symptoms within 3 hours of discontinuing use. Niacin exposure may have been a mimicker of his underlying neuro endocrine neoplasia (NEN) as diarrhea is also an overlapping feature as seen in our patient’s presentation. DM as seen in our patient is not well documented in relation to carcinoid syndrome. One study (n=10) of the patients with functionally active NENs, 70% had borderline to diabetic-level blood glucose. Of the patients with carcinoid syndrome, there was no significant difference in fasting plasma glucose concentration or fasting plasma insulin concentration when compared to age-matched normal volunteers. Conclusion: Clinicians should have low level of suspicion in diagnosing carcinoid syndrome in the presence of typical symptoms of flushing and diarrhea. Due to the past use of niacin, our patient’s diagnosis was delayed despite the persistence of flushing years after stopping it. Presentation: Friday, June 16, 2023

SAT175 Noninsulinoma Pancreatogenous Hypoglycemia Syndrome As A Complication Of Nissen Fundoplication

Abstract Disclosure: R. Rinn: None. S. Lacount: None. J. Muuse: None. Hypoglycemia is a common condition that is typically diagnosed with Whipple’s Triad (hypoglycemic symptoms, low blood glucose, resolution of symptoms with treatment). It is important to recognize and treat early as it has the potential for lethal outcomes. Dumping syndrome is a rare presentation after Nissen’s fundoplication and predominantly reported in children. Here we present a case of an adult with persistent postprandial hypoglycemia after Nissen Fundoplication. A 79-year-old male with a recent Nissen’s fundoplication presented with repeated episodes of extreme fatigue and diaphoresis after eating. Other complaints included weakness and significant weight loss. Finger stick glucose on multiple checks were found to be in 40s. He was hospitalized and underwent extensive workup with Endocrinology and Gastroenterology. Important labs revealed elevated insulin 10.2, C-peptide level at 7.3 and pro-insulin at 27.7, negative insulin antibodies, a normal Insulin like growth factor (IGF-1) at 74, Beta-hydroxybutyrate level 0.1, and a negative screen for sulfonylureas. He was discharged home on a low carbohydrate diet but continued having repeated Whipple’s triad positive hypoglycemic episodes. In terms of imaging, CT of the abdomen did not reveal a mass, other localization studies were deferred since the episodes were mostly post-prandial concerning for NIPHS than insulinoma. For management, he had minimal response to octreotide and verapamil. His symptoms are currently being managed on acarbose and diazoxide with dietary modifications consisting of high protein and limited complex carbohydrates. Postprandial hypoglycemia as a complication of Nissen’s fundoplication is thought to be secondary to dumping syndrome (DS). DS is divided into two stages- early/osmotic stage and late/ hypoglycemic stage. Both types are caused by a large amount of gastric contents emptying into the duodenum, resulting in vasomotor symptoms from changes in blood pressure, pulse and glucose levels, as well as gastrointestinal symptoms. Glucagon like peptide-1 is responsible for the second phase and the levels are directly related to gastric emptying and inversely related to plasma glucose concentration. Accelerated gastric emptying causes increased GLP-1 levels leading to exaggerated insulin response resulting in rebound severe hypoglycemia. It is important to realize that diet plays an important role in symptom management. After Nissen’s fundoplication, a decrease occurs in the storage capacity of the fundus and gastric distensibility, which causes increased gastric motility with rapid emptying. Dietary modifications include reduction of carbohydrate intake and supplementation of dietary fibers with meals greatly help relieve symptoms associated with dumping syndrome in addition to drug therapy. Presentation: Saturday, June 17, 2023

Multiparity increases the risk of diabetes by impairing the proliferative capacity of pancreatic β cells

Pregnancy imposes a substantial metabolic burden on women, but little is known about whether or how multiple pregnancies increase the risk of maternal postpartum diabetes. In this study, we assessed the metabolic impact of multiple pregnancies in humans and in a rodent model. Mice that underwent multiple pregnancies had increased adiposity, but their glucose tolerance was initially improved compared to those of age-matched virgin mice. Later, however, insulin resistance developed over time, but insulin secretory function and compensatory pancreatic β cell proliferation were impaired in multiparous mice. The β cells of multiparous mice exhibited aging features, including telomere shortening and increased expression of Cdkn2a. Single-cell RNA-seq analysis revealed that the β cells of multiparous mice exhibited upregulation of stress-related pathways and downregulation of cellular respiration- and oxidative phosphorylation-related pathways. In humans, women who delivered more than three times were more obese, and their plasma glucose concentrations were elevated compared to women who had delivered three or fewer times, as assessed at 2 months postpartum. The disposition index, which is a measure of the insulin secretory function of β cells, decreased when women with higher parity gained body weight after delivery. Taken together, our findings indicate that multiple pregnancies induce cellular stress and aging features in β cells, which impair their proliferative capacity to compensate for insulin resistance.

Oral glucose sensing in cephalic phase insulin release

Oral stimulation with foods or food components elicits cephalic phase insulin release (CPIR), which limits postprandial hyperglycemia. Despite its physiological importance, the specific gustatory mechanisms that elicit CPIR have not been clearly defined. While most studies point to glucose and glucose-containing saccharides (e.g., sucrose, maltodextrins) as being the most consistent elicitors, it is not apparent whether this is due to the detection of glucose per se, or to the perceived taste cues associated with these stimuli (e.g., sweetness, starchiness). This study investigated potential sensory mechanisms involved with eliciting CPIR in humans, focusing on the role of oral glucose detection and associated taste. Four stimulus conditions possessing different carbohydrate and taste profiles were designed: 1) glucose alone; 2) glucose mixed with lactisole, a sweet taste inhibitor; 3) maltodextrin, which is digested to starchy- and sweet-tasting products during oral processing; and 4) maltodextrin mixed with lactisole and acarbose, an oral digestion inhibitor. Healthy adults (N = 22) attended four sessions where blood samples were drawn before and after oral stimulation with one of the target stimuli. Plasma c-peptide, insulin, and glucose concentrations were then analyzed. Whereas glucose alone elicited CPIR (one-sample t-test, p < 0.05), it did not stimulate the response in the presence of lactisole. Likewise, maltodextrin alone stimulated CPIR (p < 0.05), but maltodextrin with lactisole and acarbose did not. Together, these findings indicate that glucose is an effective CPIR stimulus, but that an associated taste sensation also serves as an important cue for triggering this response in humans.

Dental Correction Does Not Alter Postprandial Nutrient Concentrations in Healthy Mares

Irregular wear patterns are theorized to cause poor feed digestion and weight loss in the horse. The objective of this study was to test the hypothesis that dental correction would increase postprandial nutrient concentrations and reduce fecal particle size (FPS) in clinically healthy mares. The study was conducted in 16 mares of mature age (4–17) who had not received dental care in the previous year. A diet consisting of ad libitum Coastal Bermudagrass hay and 1.36 kg of a pelleted feed was fed daily prior to and during the study. Eight mares received dental work and eight served as untreated controls. While the consumption of a concentrate meal increased plasma concentrations of glucose and amino acids at 90 minutes postfeeding (P < .001), dental correction did not have an influence on plasma nutrient concentrations (P > .1). On day 56, untreated control horses had a larger percent of large FPS than horses having received dental correction (14.7 ± 0.1 vs. 12.5 ± 0.1; P = .028). Dental correction may improve mechanical digestion of feed, but this does not translate to altered postprandial plasma nutrient concentrations following the consumption of a concentrate meal.

Correlation between neutrophil-to-lymphocyte ratio and contrast-induced acute kidney injury and the establishment of machine-learning-based predictive models

Objective To explore the correlation between neutrophil-to-lymphocyte ratio (NLR) and contrast-induced acute kidney injury (CI-AKI). To develop machine-learning (ML) methods based on NLR and other relevant high-risk factors to establish new and effective predictive models of CI-AKI. Methods: The data of 2230 patients, who underwent elective vascular intervention, coronary angiography and percutaneous coronary intervention were retrospectively collected. The patients were divided into a CI-AKI group and a non-CI-AKI group. Logistic regression was used to analyze the correlation of NLR with CI-AKI and high-risk factors for CI-AKI, and logistic regression (LR), random forest (RF), gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and naïve Bayes (NB) models based on NLR and the high-risk factors were established. Results A high NLR(>2.844) was an independent risk factor for CI-AKI (odds ratio = 2.304, p < 0.001). The area under the ROC curve (AUC) of the NB model was the largest (0.774), indicating that it had the best performance. NLR, serum creatinine concentration, fasting plasma glucose concentration, and use of β-blocker all accounted for a large proportion of the predictive performance of each model and were the four most important factors affecting the occurrence of CI-AKI. Conclusions There was a significant correlation between NLR and CI-AKI The NB model exhibited the best predictive performance out of the five ML models based on NLR exhibited the best predictive performance out of the five ML models.

Suppression of Endogenous Insulin Secretion by Euglycemic Hyperinsulinemia.

The impact of insulin, particularly exogenous hyperinsulinemia, on insulin secretion in humans is debated. We assessed the effects of exogenous hyperinsulinemia on insulin secretion and whether the response is altered in insulin resistance associated with obesity. Insulin secretion rates (ISRs) during euglycemic hyperinsulinemic clamp studies (52 volunteers) were calculated using a model that employs plasma C-peptide concentrations. One study involved a 2-step insulin clamp and the other study was a single step insulin clamp. For both studies the goal was to achieve plasma glucose concentrations of 95 mg/dL during the clamp irrespective of fasting glucose concentrations. The percent change in ISR from fasting to the end of the insulin clamp interval was the main outcome. Linear regression and analysis of covariance were used to test for the effects of insulin on ISR and to test for group differences. ISR was greater in obese volunteers (P < .001) under fasting and hyperinsulinemic clamp conditions. The change in plasma glucose from baseline to the end of the insulin clamp interval was highly correlated with the change in ISR (r = 0.61, P < .001). From baseline to the end of the clamp we observed a 27% (SD 20) suppression of ISR. The participants who underwent a 2-step insulin clamp had greater suppression of ISR during the second step than the first step (P < .001). The proportional suppression of ISR during euglycemic hyperinsulinemia was not different between nonobese and obese groups (P = .19). Hyperinsulinemia suppresses endogenous insulin secretion and the relative change in insulin secretion produced by exogenous insulin did not differ between nonobese and obese people.

Effects of Supplementation of Saviotan Feed (Chestnut Tannin) on Blood Parameters and Yolk Cholesterol Concentration in Japanese Quails (Coturnix japonica)

Tannins are secondary metabolites and active compounds widely present in plants. Tannins have several properties, such as astringent, antiparasitic, anti-diarrheal, anti-bacterial, and antioxidant. Hence, plants containing tannins are a major study subject for a natural alternative to in-feed antibiotics or antioxidants. The functions of tannin extracted from chestnut wood, namely Saviotan Feed (SF) in poultry, especially in quails, have not yet been fully understood. The current study aimed to examine the effect of SF supplementation on some plasma metabolites, including glucose (GLU), triglyceride (TG), total cholesterol (TCHO) concentration, and yolk cholesterol in quails (Coturnix japonica). A total of 100 unsexed quails were divided into 4 groups, with 25 quails in each group. These quails were then placed into 20 experimental pens, with 5 quails per pen. Each treatment was replicated 5 times, and the quails were fed a commercial rations diet supplemented with different SF doses of 0% (control), 0.1%, 0.2%, and 0.3%. Quails were provided with SF supplementation from 14 to 56 days of age. A sample of 40 plasma and eggs were randomly collected and analyzed for GLU, TG, and TCHO. The results indicated no significant effects of SF on plasma GLU and TG concentration, but a significant effect was found regarding TCHO. Moreover, supplementation of SF from 0.1 to 0.3% significantly decreased TCHO concentration in the yolk. In conclusion, it has been determined that supplementation of SF may play a significant role in decreasing TCHO in yolk eggs in quails.

Possible role of corticosterone on behavioral, physiological, and immune responses in chicks

Glucocorticoids are one of steroid hormone and have a variety of functions including stress response, carbohydrate metabolism, and modulation of immune system in vertebrates. Corticosterone is the main glucocorticoid in birds, although the precise role of the glucocorticoid during immune challenge is not fully understood. Therefore, the purpose of the present study was to determine if a single subcutaneous injection of corticosterone could affect inflammation-related gene expressions in the spleen and liver of chicks (Gallus gallus). In addition, the effects of corticosterone injection on the food intake, cloacal temperature, formation of conditioned visual aversion, and plasma constituents were also measured. Corticosterone did not affect the food intake or cloacal temperature and did not cause conditioned visual aversion in chicks. The corticosterone injection was associated with a significant decrease in gene expression of several pro-inflammatory cytokines including inducible nitric oxide synthase and cyclooxygenase-2 in the spleen and liver at 1 and 3 h post-injection. Corticosterone increased the plasma glucose and uric acid concentrations and the antioxidant capacity. In summary, the present study suggests that corticosterone is likely not associated with food intake, cloacal temperature or the development of aversive sensation, but suppresses the synthesis of inflammation-associated bioactive molecules and increases the antioxidant capacity in chicks.

Association of shift work with oxidative stress and alteration of fasting plasma glucose level in Chinese adults.

This study aimed to assess the association of shift work with blood glucose and the mediating role of oxidative stress. Fasting plasma glucose (FPG) and urinary concentrations of oxidative stress biomarkers (8-hydroxy-2'-deoxyguanosine [8-OHdG], 4-hydroxy-2-nonenal-mercapturic acid, and 8-iso-prostaglandin F2α [8-isoPGF2α ]) were measured among 831 participants. Positive dose-response relationships amongshift work duration, FPG (ptrend < 0.001), and abnormal glucose regulation (AGR; ptrend = 0.035) were found. Compared with participants without shift work, three-shift work was associated with a higher level of FPG (percentage change: 6.49%, 95% CI: 4.21%-8.83%) and a higher prevalence of impaired fasting glucose (odds ratio: 1.886, 95% CI: 1.114-3.192) and AGR (odds ratio: 1.929, 95% CI: 1.197-3.111). A dose-response relationship was found between shift work duration and 8-OHdG (ptrend = 0.002) and 8-isoPGF2α (ptrend = 0.019). Urinary 8-OHdG and 8-isoPGF2α partially mediated the association between shift work duration and FPG levels and the prevalence of impaired fasting glucose and AGR, with mediating proportions ranging from 4.77% to 20.76%. These findings suggest that shift work is positively associated with blood glucose, and the association ispartially mediated by oxidative stress.

Pharmacokinetic and pharmacodynamic properties of once-weekly insulin icodec in individuals with type 2 diabetes.

To characterize the pharmacokinetic and pharmacodynamic properties of once-weekly insulin icodec in type 2 diabetes (T2D). In an open-label trial, 46 individuals with T2D (18-75 years; body mass index 18.0-38.0 kg/m2 ; glycated haemoglobin ≤75 mmol/mol [≤9%]; basal insulin-treated) received subcutaneous once-weekly icodec for ≥8 weeks at individualized doses, aiming at a pre-breakfast plasma glucose concentration of 4.4 to 7.0 mmol/L (80-126 mg/dL) on the last three mornings of each weekly dosing interval. Frequent blood sampling to assess total serum icodec concentration (ie, albumin-bound and unbound) occurred from first icodec dose until 35 days after last dose. Icodec trough concentrations following initiation of once-weekly dosing were predicted by pharmacokinetic modelling. During the final 3 weeks of icodec treatment, while at steady state, the icodec glucose-lowering effect was assessed in three glucose clamps (target 7.5 mmol/L [135 mg/dL]): 0 to 36, 40 to 64 and 144 to 168 h post-dose, thus covering the initial, middle and last part of the 1-week dosing interval. Glucose-lowering effect during a complete dosing interval was predicted by pharmacokinetic-pharmacodynamic modelling. Model-predicted icodec steady state was attained after 3 to 4 weeks. At steady state, model-predicted daily proportions of glucose-lowering effect on days 1 to 7 of the 1-week dosing interval were 14.1%, 16.1%, 15.8%, 15.0%, 14.0%, 13.0% and 12.0%, respectively. Icodec duration of action was at least 1 week in all participants. Once-weekly icodec was overall safe and well tolerated in the current trial. The pharmacokinetic and pharmacodynamic characteristics of icodec in individuals with T2D support its potential as a once-weekly basal insulin.

Robust μ-Controller for Automatic Glucose Regulation for Type I Diabetes Mellitus

Type I diabetes mellitus is a serious autoimmune condition impacting a large population around the world that need a daily infusion of insulin substitutes to regulate blood glucose levels within healthy limits. The purpose of the study was to design a robust μ-controller based on an uncertain linear-time invariant (LTI) representation of the Hovorka model for glucose–insulin metabolism. The model set was obtained using linearization around an equilibrium point and adding parametric uncertainty to account for the time delay variation between plasma glucose concentration and its subcutaneous measurement. As a result, the robust stability and performance of the closed loop were proved using the structured singular value μ. The performance of the designed controller was also checked with a numerical simulation in connection with the nonlinear model.

The Triglyceride-Glucose Index is Independently Associated with Chronic Kidney Disease in the Geriatric Population, Regardless of Obesity and Sex.

Insulin resistance (IR) negatively affects several risk factors of chronic kidney disease (CKD). This cross-sectional study investigated whether the triglyceride-glucose (TyG) index, which reflects IR, was independently associated with CKD in a geriatric population, regardless of obesity and sex. The analysis included 7,326 individuals (2,864 males and 4,462 females) aged ≥60 years. Non-obesity or obesity was evaluated using a body mass index cutoff of 25 kg/m2. The TyG index was calculated as ln [triglyceride concentration (mg/dL)×fasting plasma glucose concentration (mg/dL)]/2. All participants were categorized into three groups according to TyG tertiles. Moderate-to-severe CKD (MSCKD) was defined as an estimated glomerular filtration rate (eGFR) of <45.0 mL/min/1.73 m2. In males and females with or without obesity, a trend test showed a decreasing tendency in the eGFR from the lowest to highest TyG tertiles. Males without obesity and females with obesity in the middle and highest tertiles of the TyG index were 2.342 and 2.393, and were 2.313 and 3.516 times more likely to have MSCKD, respectively. Those with or without obesity in the highest tertile of the TyG index were 1.736 and 2.374 times more likely to have MSCKD, respectively. Geriatric populations with an increased TyG index have a high risk of MSCKD regardless of obesity and sex. Our findings suggest that increased IR is associated with CKD in the geriatric population independent of obesity and sex.

Sensitivity, specificity, and diagnostic accuracy of WHO 2013 criteria for diagnosis of gestational diabetes mellitus in low risk early pregnancies: international, prospective, multicentre cohort study

ObjectiveTo evaluate the predictability of gestational diabetes mellitus wth a 75 g oral glucose tolerance test (OGTT) in early pregnancy, based on the 2013 criteria of the World Health Organization,...

Measuring capillary blood glucose concentration: Is the first blood drop really the right blood drop?

BackgroundCapillary blood glucose (CBG) is fundamental for diabetes mellitus management. However, it is still unclear whether the first or the subsequent blood drops most accurately reflect patients’ blood glucose levels. Methods128 healthy volunteers were included in this prospective cohort study from November 2021 to December 2021. Capillary blood glucose concentrations of the first four blood drops, measured using glucose meters were compared with venous blood concentrations of the respective donors, measured using an in-lab hexokinase method. ANOVA, the Spearman correlation coefficient and Bland-Altman plots were used to analyze the data. ResultsThe mean plasma glucose concentration was 90.46 mg/dl with an SD of ± 14.416 (5.02 ± 0.8 mmol/l). There were statistically strong correlations among the glucose concentrations of all capillary blood drops (correlation coefficients of r > 0.8). The first capillary blood drops showed the lowest mean difference to plasma blood glucose concentrations (+4.92 mg/dl; +0.27 mmol/l), followed by the third drop (+7.28 mg/dl; +0.4 mmol/l), second drop (+7.30 mg/dl; +0.4 mmol/l) and fourth drop (+8.87 mg/dl; +0.49 mmol/l). ConclusionThere is a strong correlation and good agreement between the different capillary blood drops, making all blood drops equally suitable for blood glucose monitoring. In practice, the given setting (clinical or patient self-monitoring) should be considered upon choosing a specific blood drop.

Influence of general anaesthesia on circulating biomarkers of glucose metabolism in pigs.

Pigs are widely used in metabolic research with procedures often requiring general anaesthesia. The aim was to investigate the effect of four different anaesthetic protocols: 1) isoflurane inhalation, 2) propofol infusion, 3) a mixture of tiletamine, zolazepam, medetomidine, ketamine and butorphanol (TZMKB)) and 4) ketamine combined with midazolam and xylazine (KMX)) on selected biomarkers during basal and glucose stimulated conditions. Eight domestic pigs were included in a cross-over design. Plasma concentrations of glucose, insulin, C-peptide, glucagon, cortisol, triglycerides, total cholesterol, aspartate amino transferase and alanine amino transferase, creatinine, urea, fructosamine, albumin, free fatty acids (FFAs) and glycerol were measured at baseline, during 2 h of anaesthesia and during 1 h of recovery. Intravenous glucose tolerance test (IVGTT, 0.5 g glucose/kg) was performed after 1 h of anaesthesia. Glucose disappearance rate and areas under the insulin, C-peptide and glucagon curves from the IVGTT were calculated. All four anaesthetic protocols affected glucose metabolism parameters significantly compared with un-anaesthetised pigs, which was particularly evident during IVGTT and for TZMKB and KMX anaesthesia. Propofol additionally influenced the plasma concentrations of triglycerides, FFAs and glycerol significantly. The remaining circulating biomarkers were largely unaffected by anaesthesia. These data underline the importance of considering the anaesthetic protocol in porcine studies of circulating metabolic biomarkers.

The effects of Mediterranean diets with low or high glycemic index on plasma glucose and insulin profiles are different in adult men and women: Data from MEDGI-Carb randomized clinical trial

Recent evidence suggests that the ability to regulate glucose and insulin homeostasis is different in men and women. Against this background, it has been hypothesized that the impact on daily plasma glucose and insulin profiles of the glycemic index (GI) of the habitual diet may differ according to sex. The aim of this study is to evaluate whether 8-h average plasma glucose and insulin profiles during a low- or a high-GI diet in individuals at high risk of developing type 2 diabetes are influenced by sex. We conducted a randomized, controlled, parallel group dietary intervention, comparing high-versus low-GI diets in a multi-national (Italy, Sweden, and the United States) sample of 156 adults at risk for type 2 diabetes. For 12 weeks, 82 vs 74 participants consumed either a low-GI or high-GI Mediterranean diet, respectively. The two experimental diets contained the same quantity of available carbohydrate (270g/d) and fiber (35g/d) and the same foods and beverages, except for the major sources of starch that was specific to the low-GI and high-GI groups (pasta, brown rice, flatbread, all bran, and wheat bread plus rye and seeds, vs jasmine rice, potato, couscous, wholegrain bread, and rusks). At baseline and after the intervention plasma glucose and insulin profiles were evaluated for 8h in the two intervention groups - separately for men and women - with both breakfast and lunch resembling food choices of the assigned diet. One hundred fifty-six adults (82 women, 74 men) with at least two traits of the metabolic syndrome completed the intervention. In women, the high-GI induced significantly higher (23%, p<0.05) 8-h average plasma glucose concentrations in comparison to the low-GI dietalready on the first day of the intervention; the difference increased up to 37% (p<0.05) after 12 weeks of diet. Conversely, there were no significant differences between the two diets in men. These results were confirmed by the two-way analysis of variance showing a statistically significant interaction between the effects of sex and diet on the glucose profile after breakfast and lunch (F=7.887, p=0.006). The results of our intervention show that women, compared to men, are more sensitive to the metabolic effects of the dietary GI. This has a strong clinical and scientific relevance and, if confirmed in further studies, it might have important implications for dietary strategies for diabetes and cardiovascular disease prevention in the context of personalized nutrition. Clinicaltrials.gov n. NCT03410719.

Adding fasting-mimicking diet to first-line carboplatin-based chemotherapy is associated with better overall survival in advanced triple-negative breast cancer patients: A subanalysis of the NCT03340935 trial.

Severe calorie restriction, in the form of cyclic fasting or fasting-mimicking diets (FMDs), boosts the antitumor activity of cytotoxic chemotherapy in mouse models of triple-negative breast cancer (TNBC). This effect is mostly mediated by fasting/FMD-induced reduction of plasma glucose concentration and by a boost in antitumor immunity. However, clinical evidence that cyclic FMD may impact on the outcomes of advanced TNBC (aTNBC) patients is lacking. We compared the overall survival (OS) of 14 aTNBC patients receiving first-line carboplatin-gemcitabine plus cyclic FMD in the context of the NCT03340935 trial with the OS of 76 consecutive aTNBC patients treated with carboplatin-based chemotherapy alone at Fondazione IRCCS Istituto Nazionale dei Tumori. Multivariable Cox regression models were used to adjust the prognostic impact of FMD for other prognostic variables. Patients undergoing cyclic FMD in combination with carboplatin-gemcitabine had better OS when compared to patients receiving chemotherapy alone (median OS 30.3 months, 95% CI 18-NR, vs 17.2 months, 95% CI 15.3-25.1, log-rank P value .041). Multivariable analysis confirmed an association between FMD use and better OS (HR: 0.40; 95% CI: 0.19-0.86; P = .019) also after propensity score-based matching according to patient ECOG PS and the presence of de novo metastatic disease (HR: 0.41; 95% CI: 0.21-0.83; P = .013). Cyclic FMD in combination with first-line chemotherapy may improve clinical outcomes in aTNBC patients. Our study paves the way for conducting phase II trials to investigate if cyclic FMD can increase the antitumor activity/efficacy of chemotherapy or chemoimmunotherapy in patients with early-stage TNBC or aTNBC.

Insulinoma in a thin Lean Indian male

Insulinoma is a tumor that secretes insulin, leading to hypoglycemia as a result of excessive insulin release. The diagnosis of insulinoma is based on the presence of Whipple’s triad, which includes the following criteria: symptoms of hypoglycemia such as tremor, sweating, irritability, uneasiness, and weakness; a plasma glucose concentration of less than 55 mg/dL (3.0 mmol/L); and resolution of symptoms upon administration of glucose. A 30-year-old male presented with recurrent episodes of palpitations, sweating, dizziness, and vision difficulty, primarily occurring in a fasting state and relieved by food ingestion. Investigations revealed hypoglycemia during an episode, along with endogenous hyperinsulinism. Imaging studies showed a hyperenhancing lesion in the pancreatic body, which was confirmed as a neuroendocrine tumor on histology and immunohistochemistry. The patient underwent enucleation of the lesion, resulting in the normalization of plasma glucose levels postoperatively.