Overnight Glucose Research Articles

Increasing particle size of oat flours decreases postprandial glycemia and increases appetite in healthy adults

Consumption of oats is associated with lowered risks of type 2 diabetes and obesity. However, many oat-based products (e.g., breakfast cereals) use finely milled flours but are associated with health claims based on oats of larger particle sizes. The objective of this study was to test the hypothesis that increasing oat flour particle size will result in lower postprandial glycemia and appetite. Using a randomized-controlled, crossover design, 20 participants (10 males, 10 females; age: 25.3 ± 1.0 years; body mass index: 23.2 ± 0.6 kg/m2) consumed a serving of porridge made using 40 g of coarse (675.7 ± 19.6 µm), whole (443.3 ± 36.2 µm), fine (96.0 ± 2.1 µm), or a commercial (375.9 ± 14.8 µm) oat flour unmatched in available carbohydrate, protein, and dietary fiber content. After a 12-hour overnight fast, blood glucose, insulin, and appetite were measured at 15 to 30-minute intervals over 120 minutes posttreatment consumption. Coarse and whole flours led to lower blood glucose between 30 and 60 minutes (P < .02). Blood glucose area under the curve (AUC) was lower after coarse than fine and commercial oat flours (P < 0.03), and after whole than fine oat flour (P < .002). Both coarse and whole oat flours resulted in lower insulin AUC than finer flours (P < .05). Appetite AUC was lower after the commercial than coarse flour (P < .007). Controlling milling to produce coarser oat flour to add to common foods may have health benefits. This study was registered at ClinicalTrials.gov (NCT05291351).

A probabilistic computation framework to estimate the dawn phenomenon in type 2 diabetes using continuous glucose monitoring.

In type 2 diabetes (T2D), the dawn phenomenon is an overnight glucose rise recognized to contribute to overall glycemia and is a potential target for therapeutic intervention. Existing CGM-based approaches do not account for sensor error, which can mask the true extent of the dawn phenomenon. To address this challenge, we developed a probabilistic framework that incorporates sensor error to assign a probability to the occurrence of dawn phenomenon. In contrast, the current approaches label glucose fluctuations as dawn phenomena as a binary yes/no. We compared the proposed probabilistic model with a standard binary model on CGM data from 173 participants (71% female, 87% Hispanic/Latino, 54 ± 12years, with either a diagnosis of T2D for six months or with an elevated risk of T2D) stratified by HbA1c levels into normal but at risk for T2D, with pre-T2D, or with non-insulin-treated T2D. The probabilistic model revealed a higher dawn phenomenon frequency in T2D [49% (95% CI 37-63%)] compared to pre-T2D [36% (95% CI 31-48%), p = 0.01] and at-risk participants [34% (95% CI 27-39%), p < 0.0001]. While these trends were also found using the binary approach, the probabilistic model identified significantly greater dawn phenomenon frequency than the traditional binary model across all three HbA1c sub-groups (p < 0.0001), indicating its potential to detect the dawn phenomenon earlier across diabetes risk categories.

93-OR: Hepatic Acyl-Protein Thioesterases Prevent Insulin Resistance

Elevated fatty acids in the context of metabolic disease are associated with insulin resistance. Fatty acids covalently and reversibly modify proteins through a process known as palmitoylation. We hypothesized that depalmitoylation by acyl-protein thioesterases 1 and 2 (APT1 and APT2) in the liver regulates glucose metabolism. The hepatic roles of APT1 and APT2 are unknown. We deleted APT1 and/or APT2 from the livers of mice, followed by high-fat diet (HFD) feeding. We performed acyl resin-assisted capture (acyl-RAC) to isolate palmitoylated proteins from APT KO livers followed by mass spectrometry. APT1 primarily depalmitoylated proteins linked to mitochondrial function and amino acid metabolism, including glutamine and branched-chain amino acid metabolism. To identify direct substrates of APT1 and APT2, we determined the protein-protein proximity network of each APT by fusing each enzyme to the highly efficient biotin ligase, miniTurbo (mT). We expressed these APT-mT constructs in human hepatocellular carcinoma HepG2 cells, followed by purification of biotin-labeled proteins and analysis by mass spectrometry. The APT proximity networks demonstrated that both APT1 and APT2 interact with mitochondrial proteins. APT1 and APT2 were also proximal to several glutamine transporters including Slc1a5 (also known as ASCT2), the only glutamine transporter known to localize to mitochondria. Male mice with dual but not single deletion of APT1 and APT2 from the liver (DLKO mice) had impaired insulin sensitivity independent of p-Akt levels or expression of Pck1 and G6pc. Elevated overnight fasting glucose in DLKO mice was associated with increased glutamine-driven gluconeogenesis and decreased liver mass. These data suggest that APT1 and APT2 regulate hepatic glucose metabolism, insulin signaling, and amino acid flux in a functionally redundant manner. These novel findings are the first to illustrate the hepatic depalmitoylation substrates and protein-protein proximity networks of APT1 and APT2. Disclosure S.L.Speck: None. Q.Zhang: None. D.P.Bhatt: None. S.Adak: None. G.Dong: None. X.Wei: None. C.F.Semenkovich: Consultant; Alnylam Pharmaceuticals. Funding National Institutes of Health (T32GM007200, F30DK131830, R01HL157154, P30DK020579)

Effects of acute changes in fasting glucose and free fatty acid concentrations on indices of β-cell function and glucose metabolism in subjects without diabetes.

Elevated fasting free fatty acids (FFAs) and fasting glucose are additively associated with impaired glucose tolerance (IGT) and decreased β-cell function [quantified as disposition index (DI)]. We sought to examine how changes in fasting FFA and glucose alter islet function. We studied 10 subjects with normal fasting glucose (NFG) and normal glucose tolerance (NGT) on two occasions. On one occasion, Intralipid and glucose were infused overnight to mimic conditions present in IFG/IGT. In addition, we studied seven subjects with IFG/IGT on two occasions. On one occasion, insulin was infused to lower overnight FFA and glucose concentrations to those observed in people with NFG/NGT. The following morning, a labeled mixed meal was used to measure postprandial glucose metabolism and β-cell function. Elevation of overnight fasting FFA and glucose in NFG/NGT did not alter peak or integrated glucose concentrations (2.0 ± 0.1 vs. 2.0 ± 0.1 Mol per 5 h, Saline vs. Intralipid/glucose, P = 0.55). Although overall β-cell function quantified by the Disposition Index was unchanged, the dynamic component of β-cell responsivity (ϕd) was decreased by Intralipid and glucose infusion (9 ± 1 vs. 16 ± 3 10-9, P = 0.02). In people with IFG/IGT, insulin did not alter postprandial glucose concentrations or indices of β-cell function. Endogenous glucose production and glucose disappearance were also unchanged in both groups. We conclude that acute, overnight changes in FFA, and glucose concentrations do not alter islet function or glucose metabolism in prediabetes.NEW & NOTEWORTHY This experiment studied the effect of changes in overnight concentrations of free fatty acids (FFAs) and glucose on β-cell function and glucose metabolism. In response to elevation of these metabolites, the dynamic component of the β-cell response to glucose was impaired. This suggests that in health overnight hyperglycemia and FFA elevation can deplete preformed insulin granules in the β-cell.

Corncob bedding alters fasting blood glucose and vascular function in mice

Rodent husbandry requires careful consideration of environmental factors that may impact colony performance and subsequent physiological studies. Of note, recent reports have suggested corncob bedding is potentially a confounding variable affecting a broad range of organ systems. As corncob bedding may contain digestible hemicelluloses, trace sugars, and fiber, we hypothesized that corncob bedding impacts murine vascular function and overnight fasting blood glucose. Here, we compared mice housed on corncob bedding, which were then fasted overnight on either corncob or ALPHA-dri bedding, a paper cellulose alternative. Male and female mice were used from two non-induced, endothelial-specific conditional knock-out strains (Cadherin 5-CreERT2, floxed hemoglobin alpha 1 [Hba1] or Cadherin 5-CreERT2, floxed cytochrome B5 reductase 3 [CyB5R3]) on a C57BL/6J genetic background. After fasting overnight, initial blood glucose was measured, and mice were anesthetized with isoflurane for measurement of blood perfusion via laser speckle contrast analysis using a PeriMed PeriCam PSI NR system. After a 15-minute equilibration, the mice were injected intraperitoneally with phenylephrine (5 mg/kg) or saline and monitored for changes in blood perfusion. After a 15-minute response period, blood glucose was remeasured post-procedure. Consistently, mice fasted on corncob bedding had higher blood glucose than the ALPHA-dri group. In the CyB5R3 strain, corncob bedding caused a reduction in phenylephrine-mediated vasoconstriction. In the Hba1 strain, phenylephrine-induced vasoconstriction was more variable in the corncob group. Altogether, this work suggests that corncob bedding could be a confounding variable for vascular measurements and fasting blood glucose in mice. To promote scientific rigor and improve reproducibility, bedding type should be included in published methods. NIH R01HL155618 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impact of Overnight Glucose on Next-Day Functioning in Adults With Type 1 Diabetes: An Exploratory Intensive Longitudinal Study.

While there is evidence that functioning, or ability to perform daily life activities, can be adversely influenced by type 1 diabetes, the impact of acute fluctuations in glucose levels on functioning is poorly understood. Using dynamic structural equation modeling, we examined whether overnight glucose (coefficient of variation[CV], percent time <70 mg/dL, percent time >250 mg/dL) predicted seven next-day functioning outcomes (mobile cognitive tasks, accelerometry-derived physical activity, self-reported activity participation) in adults with type 1 diabetes. We examined mediation, moderation, and whether short-term relationships were predictive of global patient-reported outcomes. Overall next-day functioning was significantly predicted from overnight CV (P = 0.017) and percent time >250 mg/dL (P = 0.037). Pairwise tests indicate that higher CV is associated with poorer sustained attention (P = 0.028) and lower engagement in demanding activities (P = 0.028), time <70 mg/dL is associated with poorer sustained attention (P = 0.007), and time >250 mg/dL is associated with more sedentary time (P = 0.024). The impact of CV on sustained attention is partially mediated by sleep fragmentation. Individual differences in the effect of overnight time <70 mg/dL on sustained attention predict global illness intrusiveness (P = 0.016) and diabetes-related quality of life (P = 0.036). Overnight glucose predicts problems with objective and self-reported next-day functioning and can adversely impact global patient-reported outcomes. These findings across diverse outcomes highlight the wide-ranging effects of glucose fluctuations on functioning in adults with type 1 diabetes.

Protein Ingestion in Reducing the Risk of Late-Onset Post-Exercise Hypoglycemia: A Pilot Study in Adolescents and Youth with Type 1 Diabetes.

Dietary protein causes dose-dependent hyperglycemia in individuals with type 1 diabetes (T1D). This study investigated the effect of consuming 50 g of protein on overnight blood glucose levels (BGLs) following late-afternoon moderate-intensity exercise. Six participants (3M:3F) with T1D, HbA1c 7.5 ± 0.8% (58.0 ± 8.7 mmol/mol) and aged 20.2 ± 3.1 years exercised for 45 min at 1600 h and consumed a protein drink or water alone at 2000 h, on two separate days. A basal insulin euglycemic clamp was employed to measure the mean glucose infusion rates (m-GIR) required to maintain euglycemia on both nights. The m-GIR on the protein and water nights during the hypoglycemia risk period and overnight were 0.27 ± 043 vs. 1.60 ± 0.66 mg/kg/min (p = 0.028, r = 0.63) and 0.51 ± 0.16 vs. 1.34 ± 0.71 mg/kg/min (p = 0.028, r = 0.63), respectively. Despite ceasing intravenous glucose infusion on the protein night, the BGLs peaked at 9.6 ± 1.6 mmol/L, with a hypoglycemia risk period mean of 7.8 ± 1.5 mmol/L compared to 5.9 ± 0.4 mmol/L (p = 0.028) on the water night. The mean plasma glucagon levels were 51.5 ± 14.1 and 27.2 ± 10.1 ng/L (p = 0.028) on the protein and water night, respectively. This suggests that an intake of protein is effective at reducing the post-exercise hypoglycemia risk, potentially via a glucagon-mediated stimulation of glucose production. However, 50 g of protein may be excessive for maintaining euglycemia.

A Pilot Study of the Effect of Evening Almond Butter Consumption on Overnight and Fasting Interstitial Glucose

Approximately 40% of patients with type 2 diabetes (T2D) experience an early-morning rise in fasting glucose that is not effectively treated by available oral hypoglycemic agents. This study aimed to determine the acute effect of consuming almond butter as an evening snack on fasting and overnight interstitial glucose, compared to a no-snack control, in people with T2D. Adults with T2D, not taking insulin, were recruited to participate in this two-week randomized, controlled, crossover pilot study. Participants received 2 tbsp of natural almond butter as an evening snack, or a no-snack control, for one week each. Glucose was measured by continuous glucose monitor (CGM). Analyses were performed using linear mixed effect modeling in R. Ten adults (60% female; age: 57 ± 5.6 years) completed the study. The intervention did not significantly influence fasting glucose [4–6 a.m.; β = 5.5, 95% CI = [−0.9, 12.0], p = 0.091; Marginal R2 = 0.001, Conditional R2 = 0.954] or overnight glucose (12–3 a.m.; β = 5.5, 95% CI = [−0.8, 11.8], p = 0.089; Marginal R2 = 0.001, Conditional R2 = 0.958). Significant variability in continuously measured glucose was observed. These findings will inform the design of a larger investigation.

Three short postmeal walks as an alternate therapy to continuous walking for women with gestational diabetes.

The purpose of this study was to determine whether postmeal walking (PMW, breaking up exercise into short bouts after meals) is an effective and feasible alternative to continuous walking for the management of gestational diabetes. Forty-one women with gestational diabetes were randomised between weeks 28-30 gestation to either standard care (30 minutes continuous exercise) or standard care with PMW (10 minutes of walking after breakfast, lunch, and dinner). Continuous glucose and activity monitors were worn to measure glycaemic control and adherence during 3 days of standard care (baseline) followed by 3 days of postmeal or continuous walking. A linear mixed model analysed the changes from baseline between postmeal and continuous walking, as an average of the 3-day periods. Thirty-two women (PMW n=17: control n=15, 33± 5 years, body mass index 25 ± 4kg·m-2) completed the trial. Postprandial and overnight glucose concentrations were similar between PMW and control; both interventions improved from baseline. There was no difference in adherence between groups; however, PMW completed more minutes of prescribed physical activity across baseline and intervention days compared to the continuous walking standard-care group. Preliminary findings from this proof-of-concept study suggest PMW could be a promising alternative to, and work interchangeably with, traditional advice to perform continuous moderate-intensity physical activity in women with gestational diabetes. Novelty: Three 10-minute postmeal walks may be comparable to 30 minutes continuous walking for glucose control in women with gestational diabetes. Accumulating activity in short bouts after meals is a feasible alternate to continuous exercise for women with gestational diabetes.

1325-P: Modulation of Overnight Free Fatty Acid and Glucose Concentrations and Their Effect on Postprandial Islet Function and Glucose Metabolism

Individuals with prediabetes can be classified by fasting and glucose tolerance status. Previously we observed that elevated fasting Free Fatty Acids (FFA) are associated with Impaired Glucose Tolerance (IGT) and decreased β-cell function (quantified as Disposition Index (DI)) . Impaired Fasting glucose (IFG) is associated with further decreases in DI. To examine how changes in fasting FFA and glucose alter islet function, we studied subjects with Normal Fasting Glucose (NFG) and Normal Glucose Tolerance (NGT) on 2 occasions. On one occasion, Intralipid and glucose were infused overnight to mimic conditions present in IFG / IGT. In addition, we studied 7 subjects with IFG / IGT on 2 occasions. On one occasion insulin was infused to lower overnight FFA and glucose concentrations to those observed in people with NFG / NGT. The 2 groups were matched for Body Mass Index (BMI: 32±3 vs. 31±2 kg/m2, NFG / NGT vs. IFG / IGT respectively, p = 0.87) . The following morning, a labeled mixed meal was used to measure postprandial glucose metabolism and β-cell function. Elevation of overnight fasting FFA and glucose in NFG / NGT did not alter peak or integrated glucose concentrations (2.0 ± 0.1 vs. 2.0 ± 0.1 Mol per 5 hrs, Saline vs. Intralipid / glucose, p = 0.55) . In people with IFG / IGT, insulin also did not alter peak and integrated glucose concentrations (2.5 ± 0.1 vs. 2.5 ± 0.2 Mol per 5 hrs, Saline vs. Insulin, p = 0.39) . Changing overnight concentrations of glucose and FFA did not alter postprandial concentrations of insulin and C-peptide in either group. While fasting Endogenous Glucose Production (EGP) differed between groups (14 ± 1 vs. 18 ± 1 μmol/kg/min, NFG / NGT vs. IFG / IGT, p &amp;lt; 0.01) , intervention did not change fasting and nadir EGP. Peak and integrated meal appearance and DI were also unchanged by intervention in either group. We conclude that acute, overnight changes in FFA and glucose concentrations do not alter islet function or glucose metabolism in prediabetes. Disclosure A.A.Welch: None. D.Schembri wismayer: None. A.M.Egan: None. R.A.Farahani: None. M.C.Laurenti: None. C.Cobelli: None. C.Dalla man: Research Support; Becton, Dickinson and Company, Sanofi-Aventis Deutschland GmbH. A.Vella: Advisory Panel; Crinetics Pharmaceuticals, Inc., Rezolute, Inc., vTv Therapeutics, Zealand Pharma A/S, Other Relationship; Novo Nordisk. Funding NIH DK 078646

762-P: Comparing Dual-Hormone and Single-Hormone Automated Insulin Delivery System on Nocturnal Glucose Management among Pediatric People Living with Type 1 Diabetes : A Pooled Analysis

Background: Only three studies have directly compared the efficacy of dual-hormone (DH) automated insulin delivery (AID) systems and single-hormone (SH) AID on overnight glucose management in pediatric people living with type 1 diabetes (PPWT1D) . Their conclusions differ. Pooling data could lead to stronger conclusions. Methods: Pooled data from 3 open-label, randomized, controlled, crossover studies on comparing DH-AID and SH-AID among PPWT1D (8-17 y/o) . The primary outcome was time in range% (TIR%) overnight (00:00-06:00) based on continuous glucose monitoring. Paired t-test was applied to compare the two groups. Results: Records from 50 PPWT1D [median (Q1-Q3) age: 14.0 years (11.8, 16.0) , mean ± SD HbA1c: 8.2 ± 0.8%] provided 246 nights of data (Table) . TIR% [ (median (IQR) ] for SH-AID and DH-AID was 91.3% (58.3, 100.0) and 94.4% (76.4, 100.0) , respectively (P=0.024) . DH-AID was superior to SH-AID in reducing time in hypo- (&amp;lt;3.9 mmol/L) and hyperglycemia (&amp;gt;13.9 mmol/L) but not glycemic variability. Conclusion: DH-AID has the potential to provide better overnight glucose management than SH-AID in PPWT1D. Disclosure Z.Wu: Other Relationship; Eli Lilly and Company. V.Messier: None. M.Lebbar: None. R.Rabasa-lhoret: Consultant; HLS Therapeutics Inc., Pfizer Inc., Other Relationship; Abbott Diabetes, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Janssen Pharmaceuticals, Inc., Medtronic, Merck &amp; Co., Inc., Novo Nordisk Canada Inc., Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Canadian Institutes of Health Research, Cystic Fibrosis Canada, Diabetes Canada, Fondation Francophone pour la Recherche en Diabète (FFRD) , JDRF, National Institutes of Health, Société Francophone du Diabète (SFD) , Speaker's Bureau; Canadian Medical &amp; Surgical Knowledge Translation Research Group (CMS) , CPD Network, Tandem Diabetes Care, Inc. Funding Diabetes Canada grant (OG-2-12-3868-RR,OG-2-13-42P, OG-3-14-4500-RR) and Fondation JA De Sève

Feasibility of Closed-Loop Insulin Delivery with a Pregnancy-Specific Zone Model Predictive Control Algorithm.

Objective: Evaluating the feasibility of closed-loop insulin delivery with a zone model predictive control (zone-MPC) algorithm designed for pregnancy complicated by type 1 diabetes (T1D). Research Design and Methods: Pregnant women with T1D from 14 to 32 weeks gestation already using continuous glucose monitor (CGM) augmented pump therapy were enrolled in a 2-day multicenter supervised outpatient study evaluating pregnancy-specific zone-MPC based closed-loop control (CLC) with the interoperable artificial pancreas system (iAPS) running on an unlocked smartphone. Meals and activities were unrestricted. The primary outcome was the CGM percentage of time between 63 and 140 mg/dL compared with participants' 1-week run-in period. Early (2-h) postprandial glucose control was also evaluated. Results: Eleven participants completed the study (age: 30.6 ± 4.1 years; gestational age: 20.7 ± 3.5 weeks; weight: 76.5 ± 15.3 kg; hemoglobin A1c: 5.6% ± 0.5% at enrollment). No serious adverse events occurred. Compared with the 1-week run-in, there was an increased percentage of time in 63-140 mg/dL during supervised CLC (CLC: 81.5%, run-in: 64%, P = 0.007) with less time >140 mg/dL (CLC: 16.5%, run-in: 30.8%, P = 0.029) and time <63 mg/dL (CLC: 2.0%, run-in:5.2%, P = 0.039). There was also less time <54 mg/dL (CLC: 0.7%, run-in:1.6%, P = 0.030) and >180 mg/dL (CLC: 4.9%, run-in: 13.1%, P = 0.032). Overnight glucose control was comparable, except for less time >250 mg/dL (CLC: 0%, run-in:3.9%, P = 0.030) and lower glucose standard deviation (CLC: 23.8 mg/dL, run-in:42.8 mg/dL, P = 0.007) during CLC. Conclusion: In this pilot study, use of the pregnancy-specific zone-MPC was feasible in pregnant women with T1D. Although the duration of our study was short and the number of participants was small, our findings add to the limited data available on the use of CLC systems during pregnancy (NCT04492566).

Continuous glucose monitoring to measure metabolic impact and recovery in sub-elite endurance athletes

Background and motivationAthletes experience substantial physiological impacts after exhaustive events, including post-exercise hyperglycemia. Objective measurement of athlete recovery is a major goal in sports training to optimize performance. Continuous glucose monitors (CGMs) provide frequent, minimally invasive blood glucose measurements to potentially observe the metabolic impact of a major endurance exercise event and subsequent recovery. MethodsTen sub-elite athletes were fitted with CGMs. Blood glucose levels (BGLs), exercise, and nutrition were monitored for 4–6 days. Athletes performed an endurance exercise test to exhaustion after 1–2 days of monitoring. Validated State and Substate pattern analyses quantified glycemic level and variability before and after the exercise test, including basal glucose levels and glycemic responses to carbohydrate intake. ResultsGlycemic variability and glycemic response to carbohydrate intake increased on the day of the test and returned to normal the next day. Overnight glucose levels remained elevated up to 3–4 days post-test. These results capture the metabolic impact of the test and subsequent recovery. Conclusions and significanceThe initial hyperglycemic period and lasting metabolic effects of an endurance test to exhaustion are quantifiable in commercially available CGM devices. The results encourage further investigation into using CGMs to monitor athletic recovery after intense exercise events.

Sleep quality and glycaemic variability in a real-life setting in adults with type 1 diabetes.

Suboptimal subjective sleep quality is very common in adults with type 1 diabetes. Reducing glycaemic variability is a key objective in this population. To date, no prior studies have examined the associations between objectively measured sleep quality and overnight glycaemic variability in adults with type 1 diabetes. We aimed to test the hypothesis that poor sleep quality would be associated with greater overnight glycaemic variability. Data were collected in the home setting from 20 adults (ten male and ten female participants) with type 1 diabetes who were current insulin pump users. Simultaneous assessments of objective sleep quality (Zmachine Insight+) and continuous glucose monitoring (CGM) were performed over multiple nights (up to 15 nights) in each participant. Due to the real-life nature of this study, the participants kept their usual CGM alerts for out-of-range glucose values. Sleep quality was categorised as 'good' or 'poor' using a composite of objective sleep features (i.e. sleep efficiency, wake after sleep onset and number of awakenings) based on the National Sleep Foundation's consensus criteria. Glycaemic variability was quantified using SD and CV of overnight glucose values based on overnight CGM profiles. A total of 170 nights were analysed. Overall, 86 (51%) nights were categorised as good sleep quality, and 84 (49%) nights were categorised as poor sleep quality. Using linear mixed-effects models, poor sleep quality was significantly associated with greater glycaemic variability as quantified by SD (coefficient: 0.39 [95% CI 0.10, 0.67], p = 0.009) and CV (coefficient: 4.35 [95% CI 0.8, 7.9], p = 0.02) of overnight glucose values, after accounting for age, sex, BMI and overnight insulin dose. There was large inter- and intra-individual variability in sleep and glycaemic characteristics. Both pooled and individual-level data revealed that the nights with poor sleep quality had larger SDs and CVs, and, conversely, the nights with good sleep quality had smaller SDs and CVs. No associations were found between sleep quality and time spent in the target glucose range, or above or below the target glucose range, where CGM alarms are most likely to occur. Objectively measured sleep quality is associated with overnight glycaemic variability in adults with type 1 diabetes. These findings highlight an important role of sleep quality in overnight glycaemic control in type 1 diabetes. They also provide a strong incentive to both patients and healthcare providers for considering sleep quality in personalised type 1 diabetes glycaemic management plans. Future studies should investigate the mechanisms linking sleep quality to glycaemic variability.

Influence of sodium valproate treatment on body mass and insulin resistance parameters in children with epilepsy

Introduction/Objective. One of the main side effects in patients undergoing valproic acid treatment is weight gain, which might be the reason for drug discontinuation, especially in adolescent girls, and it also has to be considered before introducing the drug. The main goal of our study is to investigate a possible influence of antiepileptic therapy with sodium valproate on weight and glucose homeostasis in pediatric patients with epilepsy. Methods. The investigation included 49 healthy children with recently diagnosed epilepsy. We measured height, weight, and serum 12-hour overnight fasting glucose and insulin level before initiation and after six- and 12-month valproic acid treatment periods. The body mass index and homeostasis model assessment indexes were calculated for each patient and correlated after the initiation of therapy and after six and 12 months of therapy. Results. We found that children significantly gained weight with statistical significance (p &lt; 0.01) even after six months of therapy with a significant glucose metabolism change and statistical difference in average serum glucose and insulin levels (p &lt; 0.05). Conclusion. Our results show that a 12-month treatment with valproic acid in children with epilepsy has a great impact on weight gain and glucose homeostasis and metabolism. We strongly recommend that all children with recently diagnosed epilepsy at the initiation of valproate therapy should be closely monitored on a six-month basis. Consultations with a nutritionist is advised especially in children with a preexisting body weight problem.

Predicting and Preventing Nocturnal Hypoglycemia in Type 1 Diabetes Using Big Data Analytics and Decision Theoretic Analysis.

Background: Despite new glucose sensing technologies, nocturnal hypoglycemia is still a problem for people with type 1 diabetes (T1D) as symptoms and sensor alarms may not be detected while sleeping. Accurately predicting nocturnal hypoglycemia before sleep may help minimize nighttime hypoglycemia. Methods: A support vector regression (SVR) model was trained to predict, before bedtime, the overnight minimum glucose and overnight nocturnal hypoglycemia for people with T1D. The algorithm was trained on continuous glucose measurements and insulin data collected from 124 people (22,804 valid nights of data) with T1D. The minimum glucose threshold for announcing nocturnal hypoglycemia risk was derived by applying a decision theoretic criterion to maximize expected net benefit. Accuracy was evaluated on a validation set from 10 people with T1D during a 4-week trial under free-living sensor-augmented insulin-pump therapy. The primary outcome measures were sensitivity and specificity of prediction, the correlation between predicted and actual minimum nocturnal glucose, and root-mean-square error. The impact of using the algorithm to prevent nocturnal hypoglycemia is shown in-silico. Results: The algorithm predicted 94.1% of nocturnal hypoglycemia events (<3.9 mmol/L, 95% confidence interval [CI], 71.3-99.9) with an area under the receiver operating characteristic curve of 0.86 (95% CI, 0.75-0.98). Correlation between actual and predicted minimum glucose was high (R = 0.71, P < 0.001). In-silico simulations showed that the algorithm could reduce nocturnal hypoglycemia by 77.0% (P = 0.006) without impacting time in target range (3.9-10 mmol/L). Conclusion: An SVR model trained on a big data set and optimized using decision theoretic criterion can accurately predict at bedtime if overnight nocturnal hypoglycemia will occur and may help reduce nocturnal hypoglycemia.

Diabetic Foot Ulceration in a Secondary Health Facility

Aims: To determine the prevalence, pattern and presentation of the diabetic foot ulcer.&#x0D; Background: A diabetic foot ulcer is a major complication in diabetes mellitus and probably the major component of diabetic foot. It occurs in 15% of all patients with diabetes and precedes 84% of all lower leg amputations.&#x0D; Poverty, low economic status and ignorance have resulted in this devastating disease. It may worsen in the next decade.&#x0D; There are multiple risk factors that predispose an individual to DM foot ulcer; they include age, gender(male), type of DM, glycaemic (HbA1c) or FBG level, duration of DM (&gt;10yrs) occupational status particular habits of self-foot care and infection.&#x0D; Patients and Methods: This consists of 69 diabetic patients; male and female included done between the months of January 2019 to March 2019.&#x0D; A demographic data questionnaire and social history were obtained. Overnight fasting serum glucose was obtained. Serum glucose was determined by enzymatic glucose oxidase method.&#x0D; Data obtained were subjected to Stata Version 11 Software to determine the graphical representation, mean, standard deviation of the analysis.&#x0D; Results: Thirty-Five 35 were male and 34 were female had type 2 diabetes. Forty-Three 43 patients had foot ulcer, 21 patients had gangrene and 5 had infection. The number of patients with peak glucose values 10 mmol/L and least glucose at 20-25 mmol/L. Those of duration 4-6 years were the most affected the age group most affected is between 40-59 yrs.&#x0D; Discussion and Conclusion: Risk factors for foot ulceration discovered among a host other factors identified in this study, were the infection, low socioeconomic status, improper footwear, poor glycaemic control, structural foot deformity and untreated gangrene.&#x0D; The role of poor glycaemic control in the genesis of diabetic complications cannot be overemphasized as the mean FPG was noted to be considerably higher in patients with foot ulceration As part of a comprehensive foot care programme, education on foot care should be directed at patients, family members and healthcare providers.&#x0D; Not less than 85% of all diabetic foot-related problems are preventable. This can be achieved through a combination of good care of foot, provided by an inter-professional diabetes care team, and appropriate education for people with diabetes.

Serum osteocalcin levels in saudi females with type 2 diabetes mellitus in Al Madinah Al Munawarah

Background: Osteocalcin (OC), a bone-derived protein hormone, regulates glucose and fat metabolism. In Saudi population, the relationship between serum OC levels and Type 2 diabetes mellitus (DM) is limited. The association of OC with cardiovascular disease (CVD) is also not clear. Objectives: We performed a case–control study to explore the relationship between OC and Type 2 DM and CVD among Saudi females in Almadinah. Materials and Methods: A case–control study was conducted between January 2017 and January 2019 for 50 female patients with Type 2 DM attending Prince Abdelaziz Ben Maged Ben Abdelaziz Diabetic Center in Almadinah enrolled as research subjects. Fifty Type 2 DM female patients, aged about 30–55 years, and 50 age-matched healthy female control subjects were enrolled in our study. After overnight fasting, total OC, glucose, glycated hemoglobin (HbA1c), and lipid profile were analyzed to determine association of OC with glucose intolerance and lipid profile. Data processing was performed using GraphPad Prism 7 (GraphPad Software, CA, USA). Results: There was a significant elevation in the frequency of low OC levels in Type 2 DM patients compared with controls (P < 0.001). Fasting serum glucose varied inversely with the OC tertials (P = 0.049). However, no statistically significant difference was noted in HbA1c or lipid levels with the OC tertials. The Atherogenic Index of Plasma (AIP = Log10 [TG/HDL]) was 36% among Type 2 DM patients, indicating higher cardiovascular risk, while 26% had intermediate risk, with increased frequency of low OC levels in patients with high and intermediate cardiovascular risk compared to low-risk patients group (P = 0.047). Conclusions: Low serum OC level was associated with impaired glucose metabolism and increased cardiovascular risk in Type 2 diabetes.

Antihyperglycemic effect of Novel combination of Ocimum sanctum, Trigonella foenum graecum and Curcuma longa by Oral Glucose Tolerance Test on Albino rats

The evaluation of antihyperglycemic effect of combination of Ocimum sanctum, Trigonella foenum graecum and Curcuma longa extracts was carried out by oral glucose tolerance test on albino rats. Methanol leaf extract of Ocimum sanctum, Curcuma longa rhizomes ethyl acetate extract, methanol seed extract of Trigonella foenum graecum were prepared and supplied by Sami labs, Bangalore. After Institutional animal ethical committee clearance Male albino rats (155-215g) were randomly assigned into 3 groups each consists of 6 animals i.e., Control (Normal saline) group, Standard (Vildagliptin 50mg/kg group) and combination of Ocimum sanctum (200mg/kg), Trigonella foenum graecum (2gm/kg) and Curcuma longa (200mg/kg) extracts group. After overnight fasting blood glucose level was done (−30minutes). Then control, standard and the extracts were administered by using rat oral feeding tube. 30 minutes later oral glucose load (dose 2.2gm/kg) was administered and sampling was done at 0, 15 and 45minutes interval and blood glucose estimation done by enzymatic assay. Combination of Ocimum sanctum+ Trigonella foenum graecum +Curcuma longa shows significant reduction in blood glucose (p= <0.05) a 15 and 45 minutes of OGTT when compared to control. Thus the combination of Ocimum sanctum, Trigonella foenum graecum and curcuma longa extracts shows significant antihyperglycemic effects. Further clinical studies are necessary to establish the therapeutic potential of these extracts in the treatment of type 2 diabetes mellitus.

Predicting Quality of Overnight Glycaemic Control in Type 1 Diabetes Using Binary Classifiers.

In type 1 diabetes management, maintaining nocturnal blood glucose within target range can be challenging. Although semi-automatic systems to modulate insulin pump delivery, such as low-glucose insulin suspension and the artificial pancreas, are starting to become a reality, their elevated cost and performance below user expectations is hindering their adoption. Hence, a decision support system that helps people with type 1 diabetes, on multiple daily injections or insulin pump therapy, to avoid undesirable overnight blood glucose fluctuations (hyper- or hypoglycaemic) is an attractive alternative. In this paper, we introduce a novel data-driven approach to predict the quality of overnight glycaemic control in people with type 1 diabetes by analyzing commonly gathered data during the day-time period (continuous glucose monitoring data, meal intake and insulin boluses). The proposed approach is able to predict whether overnight blood glucose concentrations are going to remain within or outside the target range, and therefore allows the user to take the appropriate preventive action (snack or change in basal insulin). For this purpose, a number of popular established machine learning algorithms for binary classification were evaluated and compared on a publicly available clinical dataset (i.e., OhioT1DM). Although there is no clearly superior classification algorithm, this study indicates that, by using commonly gathered data in type 1 diabetes management, it is possible to predict the quality of overnight glycaemic control with reasonable accuracy (AUC-ROC = 0.7).