Improve Blood Glucose Regulation Research Articles

Metabolic responses to albumin deficiency differ distinctly between partial and full ablation of albumin expression in mice

It had been observed that homozygous albumin knockout mice (Alb−/−) exhibit low plasma free fatty acid (FFA) concentration and improved blood glucose regulation. However, it was not yet known to what extent heterozygous albumin knockout (Alb+/−) mice would display a similar phenotype. Alb−/−, Alb+/−, and wild-type (WT) female mice were studied on a low-fat diet (LFD) or high-fat diet (HFD). On both diets, decreased plasma FFA concentration, and improved glucose tolerance test were observed in Alb−/−, but not in Alb+/−, compared to WT. Plasma adiponectin concentration showed greater elevation in Alb−/− than Alb+/−. Consistent with that, adiponectin gene expression was significantly higher in Alb−/− mice than in Alb+/− and WT mice. A dose-dependent response was observed for hepatic Acadl gene expression showing higher Acadl gene expression in Alb−/− mice than in Alb+/− and WT mice. In conclusion, although female Alb+/− mice exhibited some slight differences from WT mice (e.g., increased plasma adiponectin and hepatic Acadl gene expression), Alb+/− mice did not exhibit improved glucoregulation in comparison to WT mice, indicating that a minor suppression of albumin expression is not sufficient to improve glucoregulation. Furthermore, it is now clear that although the response of female mice to HFD might be unique from how males generally respond, still the complete albumin deficiency in Alb−/− mice and the associated FFA reduction is capable of improving glucoregulation in females on this diet. The present results have implications for the role of albumin and FFA in the regulation of metabolism.

Feasibility of Improving Glycemic Control via Heat Therapy in individuals at risk for Alzheimer’s Disease (FIGHT-AD): a pilot study

Impaired glycemic control increases the risk for type 2 diabetes and Alzheimer’s Disease (AD). Mechanisms such as impaired energy metabolism, cellular bioenergetic function, reduced intracellular protein homeostasis, and inflammation are all potential contributors to AD pathology. Heat therapy, via hot water immersion, has been shown to improve blood glucose regulation, insulin resistance, and inflammation. Given the potential contribution of these factors to brain health, heat therapy could offer immense clinical benefit to individuals at risk for AD. We performed a pilot study to test the feasibility of utilizing heat therapy in older individuals at risk for AD due to metabolic risk. The study intervention involved two pre-visits which included a cognitive function screen, sleep, diet, and physical activity questionnaires, as well as a glucose tolerance test and MRI scan. The intervention consisted of four weeks of heat therapy (3 visits/wk) for a total of 12 visits, followed by two post-intervention study visits identical to the pre-study visits. A total of 18 individuals (9 male, 9 female), average age 71.1 ± 3.9 y completed the intervention. Participants demonstrated metabolic risk based on average HbA1c values of 6.6 ± 0.67, Body Mass Index (BMI) of 29.1 ± 5.4, and 15 of the 18 participants were on hypertensive medications. Our cohort was highly diverse, with 33% underrepresented minority group representation. We had 96% participant adherence for the study (8 missed visits out of 216 total visits), and 1 study related Adverse Event (mild dizziness/nausea) that was mild. Overall, the research participants responded to a post-intervention survey saying they enjoyed participating in the study and it was not a burden on their schedules. In addition, we obtained preliminary data demonstrating a significant effect of the heat therapy intervention on body mass index, mean arterial pressure, and cerebral perfusion (p<0.05), and a trend for improved self-reported sleep quality (Pittsburgh Sleep Quality Index; p=0.06). Future studies of longer duration are needed to provide a comprehensive understanding of the impact of heat therapy on glucose homeostasis and brain health. NIH P30 AG035982 (KU ADRC), pilot funds to PCG. This is the full abstract presented at the American Physiology Summit 2024 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.

Association between weekend catch-up sleep and the risk of prediabetes and diabetes: A cross-sectional study using KNHANES

BackgroundThe objectives of this cross-sectional study were to explore the relationship between weekend catch-up sleep (WCUS) and the risk of prediabetes/diabetes and to assess how this risk varies based on WCUS duration, using a large population sample in South Korea. MethodsData were sourced from the 2021 Korea National Health and Nutrition Examination Survey, involving 2472 subjects aged 30 years and above, employed, and not using blood glucose-lowering medications. Prediabetes/diabetes risk was examined based on the presence of WCUS. Participants were categorized into four groups by WCUS duration (< 1, ≥ 1 and < 2, ≥ 2 and < 3, and ≥ 3 h) to evaluate the prediabetes/diabetes risk across varying WCUS durations. ResultsNo significant difference in prediabetes/diabetes risk was observed between the WCUS and non-WCUS groups. In subgroup analysis, a WCUS duration of 1 to 2 h was related to a lower odds ratio of prediabetes (aOR = 0.618, 95% CI = 0.382–0.999), while 3 h or more was associated with a higher odds ratio of diabetes (aOR = 3.098, 95% CI = 1.561–6.149). ConclusionsIn individuals who experience insufficient sleep during weekdays and manage to achieve the optimal average sleep duration of 1 to 2 h of WCUS, WCUS was associated with improved blood glucose regulation. However, compensating for excessive weekday sleep deprivation with WCUS of 3 h or more was associated with impaired blood glucose regulation.

Pax4 in Health and Diabetes

Paired box 4 (Pax4) is a key transcription factor involved in the embryonic development of the pancreatic islets of Langerhans. Consisting of a conserved paired box domain and a homeodomain, this transcription factor plays an essential role in early endocrine progenitor cells, where it is necessary for cell-fate commitment towards the insulin-secreting β cell lineage. Knockout of Pax4 in animal models leads to the absence of β cells, which is accompanied by a significant increase in glucagon-producing α cells, and typically results in lethality within days after birth. Mutations in Pax4 that cause an impaired Pax4 function are associated with diabetes pathogenesis in humans. In adulthood, Pax4 expression is limited to a distinct subset of β cells that possess the ability to proliferate in response to heightened metabolic needs. Upregulation of Pax4 expression is known to promote β cell survival and proliferation. Additionally, ectopic expression of Pax4 in pancreatic islet α cells or δ cells has been found to generate functional β-like cells that can improve blood glucose regulation in experimental diabetes models. Therefore, Pax4 represents a promising therapeutic target for the protection and regeneration of β cells in the treatment of diabetes. The purpose of this review is to provide a thorough and up-to-date overview of the role of Pax4 in pancreatic β cells and its potential as a therapeutic target for diabetes.

279-OR: Self-Efficacy, Diabetes Distress, Self-Care, and Blood Glucose: Within-Person Pathways in Adults with T1D

Introduction: Research links self-efficacy and diabetes distress to suboptimal diabetes self-care and blood glucose (BG) regulation. However, most studies rely on between-person comparisons that cannot rule out confounding by unmeasured variables or capture the dynamic interplay among these variables in real time. Pairing continuous glucose monitoring (CGM) with ecological momentary assessment, we sought to illuminate pathways of influence among these variables in a diverse sample of adults with T1D. Methods: Participants (N=127, 41±15 yrs, 53% women, 39% Latino, 35% White, 10% Black) wore blinded CGM for 10-14 days and completed smartphone surveys 5-6 times per day. Using dynamic structural equation modeling, we evaluated within-person pathways shown in Figure 1. Results: Hypothesized pathways were significant, as were indirect effects of:1) morning self-efficacy on that day’s mean BG via diabetes distress and self-care and2) diabetes distress on mean BG via self-care. Similar results were observed for time in range and SD of BG. Conclusion: Our findings provide novel evidence for a sequential pathway of influence of psychological, emotional, and behavioral variables on BG regulation, observed over time and within individuals. These results provide a roadmap for interventions that target self-efficacy, diabetes distress, and self-care to improve BG regulation among adults with T1D. Disclosure J.S.Gonzalez: Consultant; Virta Health Corp. H.Jin: None. L.T.Pham: None. A.Ali: None. P.Lee: None. V.F.Ruelas: n/a. R.Basile: None. E.Pyatak: Research Support; Abbott Diabetes. D.Spruijt-metz: None. S.Schneider: None. A.L.Peters: Advisory Panel; Abbott Diabetes, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Shouti, Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Other Relationship; Omada Health, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Leona M. and Harry B. Helmsley Charitable Trust, Stock/Shareholder; Teladoc Health. J.P.Crandall: Research Support; Abbott Diabetes. G.Crespo-ramos: None. H.Mendez-rodriguez: None. C.J.Hoogendoorn: None. S.Agarwal: Advisory Panel; Medtronic, Consultant; Beta Bionics, Inc. Funding National Institutes of Health (1R01DK121298-01; P30 DK111022)

Potential of karamunting (Rhodomyrtus tomentosa) fraction against kidney damage in diabetic rats

Summary Introduction: Karamunting (Rhodomyrtus tomentosa) is Indonesian native plant that contains high anti-oxidant compounds with the potential to suppress oxidative stress activity in cells. This study is the first research to specifically explore the role of the karamunting fraction in protecting kidney damage due to the formation of AGEs in the renal glomerulus in diabetes mellitus. Objective: This study aims to assess the impact of karamunting on blood glucose profile, HbA1c, insulin profile and kidney condition (AGEs expression, TNF-α and kidney histology) in diabetic rats. Methods: The karamunting extraction process was carried out by maceration with ethanol. Induction of diabetes mellitus was carried out using streptozotocin. Thirty male rats (Rattus norvegicus), Wistar strain weighing between 200–250 grams were the subject in this study. HbA1c, insulin, TNF-α, AGEs levels were evaluated in the kidney tissue. Histological assessment of the kidney was carried out. Results: Karamunting can improve blood glucose levels in diabetic rats. This improvement in blood glucose levels causes an improvement in the level of HbA1c. Administration of karamunting fraction can prevent AGEs deposition in renal tissue, which in turn will inhibits the inflammation and prevents further damage of kidneys. Conclusion: Karamunting fraction can improve blood glucose regulation so that it can prevent further damage and complications of kidney organs in diabetic rats.

The effects of blood glucose regulation and treatment regime on mean platelet volume in type 2 diabetic patients.

Mean platelet volume (MPV) is associated with cardiovascular morbidity and mortality in type 2 diabetic patients. However, the effects of blood glucose regulation and treatment regime on MPV has not been adequately studied in type 2 diabetic patients. Aims: We studied the effects of blood glucose regulation and treatment regimen on mean platelet volume in Type 2 diabetic patients. A total of 232 diabetic patients who were admitted to the hospital in short intervals of 3 months in the last 2 years were included in the study. When the second admission HbA1c was greater than the first admission HbA1c, they were classified as being in the deteriorated blood glucose regulation group, otherwise they were classified in the improved blood glucose regulation group. Also, the deteriorated and improved blood glucose regulation groups were classified based on therapy modalities as the sulfonylurea + metformin group and the insulin + metformin group. Paired t-test was used for comparison of the groups. Of the 232 patients, 98 (42.2%) were male and 134 (57.8%) were female. There were 126 (55.2%) patients using sulfonylurea + metformin, while 106 (44.8%) patients were using insulin + metformin. MPV levels were significantly increased in patients with deteriorating glucose regulation (p = 0.003). This increase in MPV was only seen in the oral hypoglycemic treatment group (p = 0.003). Our results suggested a close relationship between poor glycemic control and increased platelet activity in type 2 diabetic patients with oral antidiabetic therapy when compared to the insulin and metformin therapy modality.

Associations Between Characteristics of Web-Based Diabetes News and Readers' Sentiments: Observational Study in the Netherlands.

BackgroundAlthough experts agree that Web-based health information often contains exaggeration and misrepresentation of science, it is not yet known how this information affects the readers’ sentiments.ObjectiveThis study aimed to investigate whether specific aspects of Web-based diabetes research news are associated with positive or negative sentiments in readers.MethodsA retrospective observational study of the comments on diabetes research news posted on Facebook pages was conducted as a function of the innovations’ developmental phase, the intended treatment effect, and the use of strong language to intensify the news messages (superlatives). Data for the investigation were drawn from the diabetes research news posted between January 2014 and January 2018 on the two largest Dutch Facebook pages on diabetes and the corresponding reader comments. By manually coding these Facebook user comments, three binary outcome variables were created, reflecting the presence of a positive sentiment, the presence of a negative sentiment, and the presence of a statement expressing hopefulness.ResultsFacebook users made a total of 3710 comments on 173 diabetes research news posts that were eligible for further analysis. Facebook user comments on posts about diabetes prevention (odds ratio [OR] 0.55, 95% CI 0.37-0.84), improved blood glucose regulation (OR 0.68, 95% CI 0.56-0.84), and symptom relief (OR 0.31, 95% CI 0.21-0.44) were associated with less positive sentiments as compared with potential diabetes cures. Furthermore, comments on innovations supported by preclinical evidence in animals were associated with more positive sentiments (OR 1.46, 95% CI 1.07-1.99) and statements expressing hope (OR 1.47, 95% CI 1.01-2.14), when compared with innovations that have evidence from large human trials. This study found no evidence for the associations between language intensification of the news posts and the readers’ sentiments.ConclusionsOur finding that the attitudes toward diabetes research news on Facebook are most positive when clinical efficacy is not (or not yet) proven in large patient trials suggests that news authors and editors, as well as medical professionals, must exercise caution when acting as a conduit for diabetes research news.

A model for determining an effective in vivo dose of transplanted islets based on in vitro insulin secretion.

Allogeneic islet transplantation for the treatment of type 1 diabetes often requires multiple implant procedures, from as many as several human pancreas donors, to achieve lasting clinical benefit. Given the limited availability of human pancreases for islet isolation, porcine islets have long been considered a potential option for clinical use. Agarose-encapsulated porcine islets (macrobeads) permit long-term culture and thus a thorough evaluation of microbiological safety and daily insulin secretory capacity, prior to implantation. The goal of this study was the development of a method for determining an effective dose of encapsulated islets based on their measured in vitro insulin secretion in a preclinical model of type 1 diabetes. Spontaneously diabetic BioBreeding diabetes-prone rats were implanted with osmotic insulin pumps in combination with continuous glucose monitoring to establish the daily insulin dose required to achieve continuous euglycaemia in individual animals. Rats were then implanted with a 1×, 2× or 3× dose (defined as the ratio of macrobead in vitro insulin secretion per 24hours to the recipient animal's total daily insulin requirement) of porcine islet macrobeads, in the absence of immunosuppression. In vivo macrobead function was assessed by recipient non-fasted morning blood glucose values, continuous glucose monitoring and the presence of peritoneal porcine C-peptide. At the end of the study, the implanted macrobeads were removed and returned to in vitro culture for the evaluation of insulin secretion. Diabetic rats receiving a 2× macrobead implant exhibited significantly improved blood glucose regulation compared to that of rats receiving a 1× dose during a 30-day pilot study. In a 3-month follow-up study, 2× and 3× macrobead doses initially controlled blood glucose levels equally well, although several animals receiving a 3× dose maintained euglycaemia throughout the study, compared to none of the 2× animals. The presence of porcine C-peptide in rat peritoneal fluid 3months post-implant and the recurrence of hyperglycaemia following macrobead removal, along with the finding of persistent in vitro insulin secretion from retrieved macrobeads, confirmed long-term graft function. Increasing dosages of islet macrobeads transplanted into diabetic rats, based on multiples of in vitro insulin secretion matched to the recipient's exogenous insulin requirements, correlated with improved blood glucose regulation and increased duration of graft function. These results demonstrate the usefulness of a standardized model for the evaluation of the functional effectiveness of islets intended for transplantation, in this case using intraperitoneally implanted agarose macrobeads, in diabetic rats. The results suggest that some features of this islet-dosing methodology may be applicable, and indeed necessary, to clinical allogeneic and xenogeneic islet transplantation.

Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes.

The gut microbiota benefits humans via short-chain fatty acid (SCFA) production from carbohydrate fermentation, and deficiency in SCFA production is associated with type 2 diabetes mellitus (T2DM). We conducted a randomized clinical study of specifically designed isoenergetic diets, together with fecal shotgun metagenomics, to show that a select group of SCFA-producing strains was promoted by dietary fibers and that most other potential producers were either diminished or unchanged in patients with T2DM. When the fiber-promoted SCFA producers were present in greater diversity and abundance, participants had better improvement in hemoglobin A1c levels, partly via increased glucagon-like peptide-1 production. Promotion of these positive responders diminished producers of metabolically detrimental compounds such as indole and hydrogen sulfide. Targeted restoration of these SCFA producers may present a novel ecological approach for managing T2DM.

Daily supplementation of dietary protein improves the metabolic effects of GLP-1-based pharmacotherapy in lean and obese rats

Glucagon-like peptide-1 (GLP-1) is an incretin hormone released from intestinal L-cells in response to food entering into the gastrointestinal tract. GLP-1-based pharmaceuticals improve blood glucose regulation and reduce feeding. Specific macronutrients, when ingested, may trigger GLP-1 secretion and enhance the effects of systemic sitagliptin, a pharmacological inhibitor of DPP-IV (an enzyme that rapidly degrades GLP-1). In particular, macronutrient constituents found in dairy foods may act as potent secretagogues for GLP-1, and acute preclinical trials show that ingestion of dairy protein may represent a promising adjunct behavioral therapy in combination with sitagliptin. To test this hypothesis further, chow-maintained or high-fat diet (HFD)-induced obese rats received daily IP injections of sitagliptin (6mg/kg) or saline in combination with a twice-daily 8ml oral gavage of milk protein concentrate (MPC; 80/20% casein/whey; 0.5kcal/ml), soy protein (non-dairy control; 0.5kcal/ml) or 0.9% NaCl for two months. Food intake and body weight were recorded every 24–48h; blood glucose regulation was examined at baseline and at 3 and 6.5weeks via a 2h oral glucose tolerance test (OGTT; 25% glucose; 2g/kg). MPC and soy protein significantly suppressed cumulative caloric intake in HFD but not chow-maintained rats. AUC analyses for OGTT show suppression in glycemia by sitagliptin with MPC or soy in chow- and HFD-maintained rats, suggesting that chronic ingestion of dairy or soy proteins may augment endogenous GLP-1 signaling and the glycemic- and food intake-suppressive effects of DPP-IV inhibition.

Adaptations with Intermittent Exercise Training in Post- and Premenopausal Women.

The purposes of the present study was to examine the effect of intermittent exercise training on musculoskeletal and metabolic health in postmenopausal (PM) and premenopausal (PRM) women and, furthermore, to evaluate whether the adaptations can be maintained with a reduced training frequency. Eighteen PM (51 ± 1 yr, mean ± SEM) and 12 PRM (48 ± 1 yr) women participated in floorball training approximately two times per week for 12 wk. In a subgroup (n = 9) of PM women (PM40), exercise training was performed for an additional 40 wk with a reduced training frequency of approximately one training session per week. In PM, the body fat percentage decreased (P < 0.05) and the total lean leg mass increased (P < 0.05) during the 12-wk training period, with no changes in PRM. In both PM and PRM, lean body mass and maximal oxygen uptake (V˙O2max) were higher, and Yo-Yo intermittent endurance test 1 (YYIET-1) performance was better (P < 0.05) after the 12-wk training period. Procollagen type 1 amino-terminal propeptide was higher (P < 0.05) in PM, and total leg bone mineral density (BMD) was higher (P < 0.05) in both PM and PRM after the 12-wk training period. In PM40, total lean leg mass, V˙O2max, YYIET-1 performance, level of procollagen type 1 amino-terminal propeptide, and total leg BMD were maintained, whereas whole-body BMD and glycated hemoglobin (HbA1c) were reduced (P < 0.05) and the expression of muscle glucose transporter type 4 was higher (P < 0.05). Twelve weeks of intermittent exercise training increased BMD, intermittent exercise capacity, and V˙O2max in PM and PRM, with PM also having positive changes in body composition. Additional 40 wk of training with a reduced frequency was sufficient to preserve these physiological adaptations and also improve blood glucose regulation in PM.

Trichostatin A affects the secretion pathways of beta and intestinal endocrine cells

Histone deacetylase inhibitors (HDACi) were recently identified as having significant clinical potential in reversing β-cell functional inhibition caused by inflammation, a shared precursor of Type 1 and Type 2 diabetes. However, HDACi are highly complex and little is known of their direct effect on important cell secretion pathways for blood glucose regulation. The aims of the present study were to investigate the effect of HDACi on insulin secretion from β-cells, GLP-1 secretion from L-cells, and recombinant insulin secretion from engineered L-cells. The β-cell line βTC-tet, L-cell line GLUTag, or recombinant insulin-secreting L-cell lines were exposed to Trichostatin A for 24h. Effects on insulin or GLP-1 mRNA, intracellular protein content, processing efficiency, and secretion were measured by real-time PCR, ELISA, and radioimmunoassay. HDACi increased secretion per viable cell in a dose-dependent manner for all cell types. Effects on mRNA levels were variable, but enhanced intracellular polypeptide content and secretion were comparable among cell types. Enhanced recombinant insulin secretion was sustained for seven days in alginate microencapsulated L-cells. HDACi enhances β- and L-cell secretion fluxes in a way that could significantly improve blood glucose regulation in diabetes patients and holds potential as a novel method for enhancing insulin-secreting non-β or β-cell grafts.

Consumption of an egg‐based breakfast reduces hunger and increases postprandial energy metabolism in normal weight and overweight school‐aged children (381.4)

In the US, one in every three children ages 2‐19 is overweight or obese. Although multifactorial in nature, obesity is primarily attributed to a mismatch between energy intake and energy expenditure (EE). One factor that influences this balance is thermic effect of food (TEF). Diets higher in protein have been shown to increase TEF. Breakfast is a key component of a healthy diet and can positively impact children’s health. It has been suggested that skipping breakfast may lead to greater hunger later in the day, resulting in greater overeating. The objective of this study was to determine if an egg/protein (PRO)‐based breakfast (22% PRO, 48% carbohydrate (CHO), 30% fat) would enhance TE, improve glycemic control and reduce hunger in NW (n=14) and OW (n=11) school‐aged children compared to an isocaloric CHO‐based breakfast (5% PRO, 65% CHO, 30% fat). Twenty‐three children (8‐12 y) completed both the PRO and CHO breakfast trials. EE was determined via indirect calorimetry at 0, 30, 60, 120, and 240 min postprandial (PP). Blood glucose (BG) was collected at 0, 15, 30, 60, 120, and 240 min PP and levels of hunger were assessed using a visual analog scale at same interval. At 240 min, an ad libitum buffet lunch was provided. Results indicate no significant difference in PP BG values between groups. However, PRO significantly reduced PP hunger (p&lt;0.05) compared to CHO in NW and OW children. Consumption of PRO resulted in lower caloric intake at lunch (~100 kcal) compared to CHO. Relative to body weight, NW burn more calories per min compared to OW. NW have significantly higher TEF compared to OW (CHO p&lt;0.001, PRO p=0.001). There was a trend (p=0.068) for higher TEF (10%) with PRO compared to CHO in OW. These data suggest that consumption of a PRO‐based breakfast has the potential to modulate PP energy metabolism in OW children through increased TEF, improved BG regulation, and decreased hunger.Grant Funding Source: Supported by the American Egg Board/Egg Nutrition Center.

Intraduodenal milk protein concentrate augments the glycemic and food intake suppressive effects of DPP-IV inhibition

Glucagon-like peptide-1 (GLP-1) is an incretin hormone released from intestinal L-cells in response to food entering into the gastrointestinal tract. GLP-1-based pharmaceuticals improve blood glucose regulation and may hold promise for obesity treatment, as GLP-1 drugs reduce food intake and body weight in humans and animals. In an effort to improve GLP-1 pharmacotherapies, we focused our attention on macronutrients that, when present in the gastrointestinal tract, may enhance GLP-1 secretion and improve glycemic regulation and food intake suppression when combined with systemic administration of sitagliptin, a pharmacological inhibitor of DPP-IV (enzyme responsible for GLP-1 degradation). In particular, previous data suggest that specific macronutrient constituents found in dairy foods may act as potent secretagogues for GLP-1 and therefore may potentially serve as an adjunct dietary therapy in combination with sitagliptin. To directly test this hypothesis, rats received intraperitoneal injections of sitagliptin (6 mg/kg) or saline vehicle followed by intraduodenal infusions of either milk protein concentrate (MPC; 80/20% casein/whey; 4 kcal), soy protein (nondairy control infusate; 4 kcal), or 0.9% NaCl. Food intake was assessed 30 min postinfusion. In separate studies, regulation of blood glucose was examined via a 2-h oral glucose tolerance test (2 g/kg) following identical sitagliptin treatment and intraduodenal nutrient infusions. Collectively, results show that intraduodenal MPC, but not soy protein, significantly enhances both the food intake suppression and improved control of blood glucose produced by sitagliptin. These data support the hypothesis that dietary intake of dairy protein may be beneficial as an adjunct behavioral therapy to enhance the glycemic and food intake suppressive effects of GLP-1-based pharmacotherapies.

A habituating blood glucose control strategy for the critically ill

In the intensive care unit patients benefit from being fed and from having well controlled glucose levels. Insulin and glucose infusion serves as manipulated inputs to regulate blood glucose, while glucose infusion serves as a sole nutritional input. In this paper, a model predictive control strategy, based on simultaneously manipulating glucose and insulin infusion, is developed to improve blood glucose regulation in intensive care unit patients. In the short term, glucose infusion is used for tighter glucose control, particularly for disturbance rejection, while, in the long-term (24h period), glucose infusion is used to meet nutritional needs. The “habituating control” algorithm is proposed and tested against a model predictive control (MPC) strategy that only manipulates insulin. The simulation results indicate that the Habituating MPC strategy outperforms the single input–single output MPC by providing faster setpoint tracking and tighter glucose control for a patient population, and producing less glucose variability while rejecting disturbances in insulin infusion and insulin sensitivity.

Stable refraction and visual acuity in diabetic patients with variable glucose levels under routine care

To investigate how refraction and visual acuity may vary in patients with diabetes under routine care. Fifty-three eyes of 53 patients with various degrees of diabetic retinopathy were examined prospectively on four different occasions within a month. Refraction, best-corrected visual acuity (expressed as logMAR score) and blood glucose were measured on each occasion. Intraindividual variability was calculated as the range between the highest and lowest measurements. Associations between blood glucose levels and each of the other variables were tested by linear regression analysis for each patient. Refraction was completely stable in 43 patients and changed only slightly in 10, in whom the mean intraindividual variability of the spherical equivalent was 0.4 dioptres. Visual acuity test results were also highly reproducible. Mean intraindividual variability in visual acuity was 0.08 logMAR. Mean haemoglobin A1c (HbA1c) was 7.3 ± 1.5% but individual blood glucose levels ranged from 2.8 to > 22.2 mmol/l. Intraindividual variability ranged from 0.5 to 18.1 mmol/l, with a median of 6.0 mmol/l for the entire group. There were no associations between refraction or visual acuity and blood glucose levels or inter- or intraindividual glucose variations. Refraction and visual acuity test results were highly reproducible and stable in patients with reasonably well controlled diabetes but variable blood glucose levels under routine care.

Body-weight-support treadmill training improves blood glucose regulation in persons with incomplete spinal cord injury

The impact of a 6-mo body-weight-supported treadmill training program on glucose homeostasis and muscle metabolic characteristics was investigated. Nine individuals (31 +/- 3 yr, 8.1 +/- 2.5 yr postinjury; means +/- SE) with incomplete spinal cord injury trained three times weekly for a total of 6 mo. Training session duration and intensity (velocity) increased by 54 +/- 10% (P < 0.01) and 135 +/- 20%, respectively. Muscle biopsies and a modified glucose tolerance test (100 g glucose with [U-(13)C]glucose) were performed before (Pre) and after training (Post). Training resulted in a reduction in area under the curve of glucose x time (-15 +/- 4%) and insulin x time (-33 +/- 8%; both P < 0.05). Oxidation of exogenous (ingested) glucose increased as a result of training (Pre = 4.4 +/- 0.7 g/h, Post = 7.4 +/- 0.6 g/h; P < 0.05), as did oxidation of endogenous (liver) glucose (Pre = 3.8 +/- 0.3 g/h, Post = 5.2 +/- 0.3 g/h; P < 0.05). Training resulted in increased muscle glycogen (80 +/- 23%; P < 0.05) and GLUT-4 content and hexokinase II enzyme activity (126 +/- 34 and 49 +/- 4%, respectively, both P < 0.01). Resting muscle phosphocreatine content also increased after training (Pre = 62.1 +/- 4.3, Post = 78.7 +/- 3.8, both mmol/kg dry wt and P < 0.05). Six months of thrice-weekly body-weight-supported treadmill training in persons with an incomplete spinal cord injury improved blood glucose regulation by increasing oxidation and storage of an oral glucose load. Increases in the capacity for transport and phosphorylation glucose in skeletal muscle likely play a role in these adaptations.

Pharmacological Regulation of Blood Glucose Levels in Non—Insulin-Department Diabetes Mellitus

Non-insulin-dependent diabetes mellitus is a metabolic disease that is common and is characterized by insulin insufficiency and resistance. Measures such as body weight reduction and exercise improve the metabolic defects, but pharmacological therapy is the most frequently used and successful therapy. The sulphonylureas stimulate insulin secretion. Metformin and troglitazone increase disposal and decrease hepatic glucose output without causing hypoglycemia. Acarbose is a dietary aid that spreads the dietary carbohydrate challenge to endogenous insulin over time. These pharmacological agents, either alone or in combination, can improve blood glucose regulation in patients with non-insulin-dependent diabetes mellitus.

Oral antidiabetic drug use in the elderly.

Non-insulin-dependent diabetes mellitus (NIDDM) is a metabolic disease that is common in the elderly, and is characterised by insulin insufficiency and resistance. Measures such as bodyweight reduction and exercise improve the metabolic defects, but pharmacological therapy is the most frequently used and successful therapy. The sulphonylureas stimulate insulin secretion. Metformin and troglitazone increase glucose disposal and decrease hepatic glucose output without causing hypoglycaemia. Acarbose is a dietary aid that spreads the dietary carbohydrate challenge to endogenous insulin over time. These pharmacological agents, either alone or in combination, should improve blood glucose regulation in patients with NIDDM.