Maintain Plasma Glucose Research Articles

Non-diabetic hypoglycemia

Glucose is the main substrate utilized by the brain, and therefore numerous counterregulatory mechanisms exist to maintain plasma glucose concentration. This makes it rare for hypoglycemia to develop in people who are not taking hypoglycemic drugs, such as insulin or sulfonylureas, for diabetes. The symptoms of hypoglycemia are nonspecific. The presence of Whipple’s triad is necessary for diagnosis. When symptoms occur spontaneously, the patient can be evaluated for hypoglycemia. If this is not possible, then a 72-hour fasting test or a mixed meal tolerance test can be performed to create conditions for symptoms to occur. Non-diabetic hypoglycemia is mainly divided into two main groups: insulin-mediated (hyperinsulinism) and insulin-independent. The main causes of hypoglycemia due to endogenous hyperinsulinism are insulinoma and islet cell hyperplasia (nesidioblastosis), post-bariatric surgery, and autoimmune hypoglycemia with the presence of anti-insulin antibodies. Other important causes of hypoglycemia include hypoglycemic drugs, non-islet cell tumors, hormonal deficiencies (primary adrenal insufficiency, anterior pituitary insufficiency), and critical illnesses (liver/kidney failure). In this article, we provide an overview of the pathogenesis and treatment of hypoglycemia.

Early programming effects of a hyperglucidic diet on carbohydrate and lipid metabolism in gibel carp (Carassius gibelio)

Previous nutritional studies have shown that intermediate metabolism in early fish development is highly plastic, and thus we hypothesized that there may be an early programming effect of a hyperglucidic diet on carbohydrate utilization in gibel carp. To test our hypothesis, gibel carp CAS Ⅴ (mean body weight: 0.10 g) were fed a high-carbohydrate/low protein (HC/LP) or low carbohydrate/high protein (LC/HP) diet for three weeks, and then were fed with normal feed for 12 weeks and a hyperglucidic diet for one week. We found that early HC/LP stimulus inhibited growth performance but altered the expression of glucose metabolism genes. After long-term feeding on the normal diet, the effects of early HC/LP stimulus were eliminated; these involved plasma metabolites, hepatic cholesterol, glycogen and triglyceride content, and glucose and lipid metabolism. However, the early HC stimulus group showed a better ability to maintain plasma glucose hemostasis when again given the HC diet. The capacity of carbohydrate and lipid metabolism in juvenile gibel carp was improved in the early HC diet group, as indicated by upregulated expression of genes related to glycolysis, lipid transport (gk, akt, srebp1, acc, fas, hsl, and acly) and downregulated expression of genes involved in gluconeogenesis (fbpase). Moreover, the early HC diet significantly upregulated AKT protein expression levels. The DNA methylation levels of akt in the HC/LP group were significantly lower than those in the LC/HP group. Overall, the study suggests that early HC stimulus in juvenile gibel carp can result in better carbohydrate utilization through DNA methylation of critical elements in the insulin signaling pathway.

Intestinal gluconeogenesis: metabolic benefits make sense in the light of evolution.

The intestine, like the liver and kidney, in various vertebrates and humans is able to carry out gluconeogenesis and release glucose into the blood. In the fed post-absorptive state, intestinal glucose is sensed by the gastrointestinal nervous system. The latter initiates a signal to the brain regions controlling energy homeostasis and stress-related behaviour. Intestinal gluconeogenesis (IGN) is activated by several complementary mechanisms, in particular nutritional situations (forexample, when food is enriched in protein or fermentable fibre and after gastric bypass surgery in obesity). In these situations, IGN has several metabolic and behavioural benefits. As IGN is activated by nutrients capable of fuelling systemic gluconeogenesis, IGN could be a signal to the brain that food previously ingested is suitable for maintaining plasma glucose for a while. This process might account for the benefits observed. Finally, in this Perspective, we discuss how the benefits of IGN in fasting and fed states could explain why IGN emerged and was maintained in vertebrates by natural selection.

Association between glucokinase regulator gene polymorphisms and serum uric acid levels in Taiwanese adolescents

The glucokinase regulator gene (GCKR) is located on chromosome 2p23. It plays a crucial role in maintaining plasma glucose homeostasis and metabolic traits. Recently, genome-wide association studies have revealed a positive association between hyperuricemia and GCKR variants in adults. This study investigated this genetic association in Taiwanese adolescents. Data were collected from our previous cross-sectional study (Taipei Children Heart Study). The frequencies of various genotypes (CC, CT, and TT) or alleles (C and T) of the GCKR intronic single-nucleotide polymorphism (SNP) rs780094 and the coding SNP rs1260326 (Pro446Leu, a common 1403C-T transition) were compared between a total of 968 Taiwanese adolescents (473 boys, 495 girls) with hyperuricemia or normal uric acid levels on the basis of gender differences. Logistic and linear regression analyses explored the role of GCKR in abnormal uric acid (UA) levels. Boys had higher UA levels than girls (6.68 ± 1.29 and 5.23 ± 0.95 mg/dl, respectively, p < 0.001). The analysis of both SNPs in girls revealed that the T allele was more likely to appear in patients with hyperuricemia than the C allele. After adjusting for confounders, the odds ratio (OR) for hyperuricemia incidence in the TT genotype was 1.75 (95% confidence interval [CI] 1.02–3.00), which was higher than that in the C allele carriers in rs1260326 in the girl population. Similarly, the TT genotypes had a higher risk of hyperuricemia, with an OR of 2.29 (95% CI 1.11–4.73) for rs1260326 and 2.28 (95% CI 1.09–4.75) for rs780094, than the CC genotype in girl adolescents. The T (Leu446) allele of GCKR rs1260326 polymorphism is associated with higher UA levels in Taiwanese adolescent girls.

Predictors of Poor Plasma Glucose Maintenance in Type II Diabetic People with Ophthalmic Complication: The Case of Dessie Hospitals in Ethiopia.

BackgroundDiabetes mellitus, the commonest metabolic disorder, leads to cardiovascular diseases, neurological problems, kidney injury, and visual disturbances. Such complications can be prevented by maintaining plasma glucose level in the normal range, including ophthalmic complications. Hence, this study intended to pinpoint predictors of poor plasma glucose maintenance in type II DM people with ophthalmic complication.MethodsWe conducted a cross-sectional survey using simple random sampling approach to recruit participants. An interviewer-based questionnaire was used and ophthalmic complication was determined by visual acuity test. We used statistical package for social sciences version 23 to analyze the data and descriptive statistics were calculated. Predictors were ascertained using multivariable logistic regression at p≤0.05. Besides, AOR with 95% CI was also estimated to show extent of association.ResultsThe prevalence of poor plasma glucose maintenance was 65.1% (56.6–73.6). Poor plasma maintenance was predicted by the absence of formal education (OR: 0.67; 0.20–2.23), DM history of family members (OR=4.29; 1.33–13.83), longer duration of diabetes (OR: 3.02; 1.09–8.63), insulin use (OR=10.05; 2.72–52.35), and less physical exercise (OR=2.91; 1.47–5.76).ConclusionStudy subjects with no education, DM history of family members, prolonged DM, insulin medication, and inadequate exercise had higher rate of poor plasma glucose maintenance. Health professionals should educate patients on the importance of self-adherence to plasma glucose monitoring, and encourage them to practice recommended physical activity.

The role of central corticotrophin-releasing factor receptor signalling in plasma glucose maintenance through ghrelin secretion in calorie-restricted mice.

Under severe calorie restriction (CR), the ghrelin-growth hormone axis in mice is involved in the maintenance of plasma glucose levels. Ghrelin, a stomach-derived acylated peptide, is up-regulated by the sympathetic nerve in the negative energy status. Central corticotrophin-releasing factor receptor (CRF-R) signalling stimulates the sympathetic tone. The present study aimed to examine the effect of central CRF-R signalling on the maintenance of plasma glucose concentrations in severe calorie-restricted mice with the involvement of ghrelin. Intracerebroventricular injections of urocorin-1 and urocorin-2, which are natural ligands for CRF-R1 and CRF-R2, elevated plasma ghrelin concentrations and ghrelin elevation with an i.c.v. injection of urocorin-1 was cancelled by atenolol (β1 adrenergic receptor antagonist) administration. We then established a mice model of 60% CR and found that the administration of [d-Lys3]-GHRP-6 (a ghrelin receptor antagonist) in mice under 60% CR reduced the plasma glucose concentration more compared to the vehicle mice. Similarly, the atenolol injection in mice under 60% CR significantly reduced the plasma glucose concentration, which was rescued by the co-administration of ghrelin. An i.c.v. injection of the alpha helical CRH, a non-selective corticotrophin-releasing factor receptor antagonist, in mice under 60% CR significantly reduced the plasma glucose concentration, although the co-administration of α-helical CRH with ghrelin maintained plasma glucose levels. These results suggest that central CRF-R signalling is involved in the maintenance of plasma glucose levels in mice under severe CR via the sympathetic-ghrelin pathway.

Effect of the Glycemic Index of Meals on Physical Exercise: A Case Report

Abstract Carbohydrate uptake before physical exercise allows to maintain plasma glucose concentration. Though, foods or beverages containing the same carbohydrate concentration do not produce the same glycemic and insulin responses which are related to their glycemic index (GI). Last, most studies of CHO loading have been conducted with male subjects, with the assumption that the results also apply to female athletes. Sixteen volunteer amateur athletes, eight men and eight women (age 39.1 ± 7.8 y; VO2max 55,7 ± 11,7 ml/kg/min), were selected and then divided into four groups of four people each one. The trial was divided into several days, one for each group. A carbohydrate source or a placebo (energy 86,5 ± 6,7 kcal; CHO 20,0 g; fat 0,3 ± 0,3 g; protein 0,8 ± 0,8 g) was assigned randomly to each athlete in the group: these supplements differed in the ability to increase blood glucose (banana: high-GI; dried apricots: low-GI; energy gel: mixture of CHO with different blood release), while the placebo was composed of water, sodium cyclamate, sodium saccharin and acesulfame potassium. Three blood samples were taken from each athlete from finger, by glucometer: one before supplementation, one half an hour later – at the start of the run – and one at the end of the exercise. Physical activity consisted of 40 minutes run at medium-high intensity, corresponding to 82% of maximum heart rate or 70% of VO2max. In order to improve the analysis of the results obtained from the detection of biological samples, a questionnaire was submitted to all participants to know their lifestyle and anthropometric and physiological data. Results highlighted a different glycemic response between men and women, suggesting the consumption of low-GI food rather than high-GI before physical exercise in order to keep plasma glucose levels constant.

Endocrinological aspects of managing patients after total duodenopancreatectomy

The presented review of literature reflects the endocrinological aspects of patient management after total duodenopancreatectomy without в -cell transplantation in the immediate and late postoperative period. Peculiarities of carbohydrate metabolism after total duodenopancreatectomy require other approaches and methods of correction. Mortality in specialized centers in the last decade is <3—5%. The largest number of life-threatening complications occurs in the early postoperative period and remains high (49% and higher) despite the observance of international treatment standards, starting from the intensive care unit. In the early postoperative period, imitation of insulin secretion from a healthy pancreas is of particular importance. The use of devices of the “closed loop” type after total pancreatectomy made it possible to identify the required dose of short-acting insulin (100-200 units per day intravenously) to maintain plasma glucose in the range 4.4—7.7 mmol/l, ensured patient safety, and reduced the number of surgical complications. Individually selected insulin therapy, enzyme replacement therapy and balanced nutrition in the long-term postoperative period provide patients who have undergone total duodenopancreatectomy an acceptable standard of living comparable to the quality of life of patients with type 1 and type 2 diabetes.

Delay in ATP-dependent calcium inflow may affect insulin secretion from pancreatic beta-cell

Any dysfunction in the secretion of insulin and/or in its use is critical in the development of type 2 diabetes. Calcium plays a very important role in the insulin secretion mechanism from beta-cell. In this paper, we studied the dynamic interaction of glucose-induced insulin secretion mechanism through glucose metabolism and ATP-dependent calcium influx. We proposed and analyzed a four dimensional system of nonlinear delay differential equations to give insights into different possible mechanisms for maintaining plasma glucose homeostasis through calcium-induced insulin secretion. The time duration between ATP formation and subsequent calcium influx through cell membrane has been found to be critical in maintaining insulin homeostasis. How variational effects of system parameters lead to various glycemic states are demonstrated. Possibility of new potential drug therapies is also discussed through parameter recalibration.

Sensing of blood glucose by the nervous system: why, where, how?

Maintaining plasma glucose concentration is a critical requirement for the body, making the detection of blood glucose by the nervous system essential. The reason generally given is that glucose is the main source of energy for living cells. In fact, other reasons make that glucose is so crucial. Glucose feeds two non-oxidative metabolic pathways, glycolysis and the pentose pathway, which allow the synthesis of molecules essential for cell survival and division, such as amino acids or nucleotides. The purpose of this review is to argue this statement and discuss the processes of glucose sensing by the central and peripheral nervous systems.

Glucose Homeostasis in Newborns: An Endocrinology Perspective.

Physiologic adaptations in the postnatal period, along with gradual establishment of enteral feeding, help maintain plasma glucose concentrations in the neonatal period. The definition of normal plasma glucose in the neonatal period has been a subject of debate because of a lack of evidence linking a set plasma or blood glucose concentration to clinical symptoms or predictors of short- and long-term outcomes. However, there is consensus that maintaining plasma glucose in the normal range for age is important to prevent immediate and long-term neurodevelopmental consequences of hypoglycemia or hyperglycemia. The specific management strategy for abnormal glucose levels in neonates depends on the underlying etiology, and interventions could include nutritional changes, medications, hormone therapy, or even surgery. Here, we will review the physiological processes that help maintain plasma glucose in newborns and discuss the approach to a newborn with disordered glucose homeostasis, with an emphasis on the endocrine basis of abnormal glucose homeostasis.

The role of glucose homeostasis on immune function in response to exercise: The impact of low or higher energetic conditions.

Immune cells are bioenergetically expensive during activation, which requires tightly regulated control of metabolic pathways. Both low and high glycemic conditions can modulate immune function. States of undernourishment depress the immune system, and in the same way, excessive intake of nutrients, such as an obesity state, compromise its functioning. Multicellular organisms depend on two mechanisms to survive: the regulation and ability to store energy to prevent starvation and the ability to fight against infection. Synergic interactions between metabolism and immunity affect many systems underpinning human health. In a chronic way, the breakdown of glycemic homeostasis in the body can influence cells of the immune system and consequently contribute to the onset of diseases such as type II diabetes, obesity, Alzheimer's, and fat and lean mass loss. On the contrary, exercise, recognized as a primary strategy to control hyperglycemic disorders, also induces a coordinated immune-neuro-endocrine response that acutely modulates cardiovascular, respiratory, and muscle functions and the immune response to exercise is widely dependent on the intensity and volume that may affect an immunodepressive state. These altered immune responses induced by exercise are modulated through the "stress hormones" adrenaline and cortisol, which are a threat to leukocyte metabolism. In this context, carbohydrates appear to have a positive acute response as a strategy to prevent depression of the immune system by maintaining plasma glucose concentrations to meet the energy demand from all systems involved during strenuous exercises. Therefore, herein, we discuss the mechanisms through which exercise may promotes changes on glycemic homeostasis in the metabolism and how it affects immune cell functions under higher or lower glucose conditions.

PO-296 Sex differences in the change of amino acid and cortisol concentration after marathon race

Objective As we all know, marathon exercise can induce dramatic changes in amino acid and hormone concentration in the plasma. However, little attention has been given to the role of sex in metabolic changes.&#x0D; Methods We compared the changing rates of amino acid and hormone after marathon running in male and female runners. Twenty-seven female (mean age: 41±15 years) and 66 male (mean age: 40±16 years) non-professional runners performed a marathon race. Amino acid and cortisol levels were assessed before and at 1h after race.&#x0D; Results At pre-race and post-race, cortisol concentrations in female runners were lower than in males. Cortisol increased in all subjects at post-race but the rising rate was substantially higher (P&lt;0.05) in females [median (range): 3.5 (21~ -0.25)] than in males [median (range): 2.09 (14.3~-0.43)]. Post-race, the glycogenic amino acid concentrations of Arg, Asn, Gly, Ile, Met, Ser and Thr were significantly decreased in females and males. But females have higher decreased rate (P&lt;0.02) [median (range):Arg -45% (12%~ -69%), Asn -42% (25%~ -72%), Gly -45% (5%~ -73%), Ile -35% (16%~ -64%), Met -28% (48%~ -62%), Ser -34% (17%~ -58%), Thr -33%(32%~ -52%)] than males [median (range):Arg -35% (65%~ -64%), Asn -29%(46% ~ -59%), Gly -33% (13%~ -64%), Ile -23% (37%~ -57%), Met -14% (92%~ -52%), Ser -23% ( 21%~ -56%), Thr -17% ( 84%~ -58%)]. This is because, during exercise, cortisol has the function of inducing gluconeogenesis to maintain plasma glucose supply.&#x0D; Conclusions There is significant sex differences in the change of cortisol and some glycogenic amino acid concentration before and after marathon race, which has potential value for training and nutrition supplement in marathon running.

The Role of Leptin in Maintaining Plasma Glucose During Starvation.

For 20 years it has been known that concentrations of leptin, a hormone produced by the white adipose tissue (WAT) largely in proportion to body fat, drops precipitously with starvation, particularly in lean humans and animals. The role of leptin to suppress the thyroid and reproductive axes during a prolonged fast has been well defined; however, the impact of leptin on metabolic regulation has been incompletely understood. However emerging evidence suggests that, in starvation, hypoleptinemia increases activity of the hypothalamic-pituitary-adrenal axis, promoting WAT lipolysis, increasing hepatic acetyl-CoA concentrations, and maintaining euglycemia. In addition, leptin may be largely responsible for mediating a shift from a reliance upon glucose metabolism (absorption and glycogenolysis) to fat metabolism (lipolysis increasing gluconeogenesis) which preserves substrates for the brain, heart, and other critical organs. In this way a leptin-mediated glucose-fatty acid cycle appears to maintain glycemia and permit survival in starvation.

Glucocorticoid Receptor and Adipocyte Biology.

Glucocorticoids are steroid hormones that play a key role in metabolic adaptations during stress, such as fasting and starvation, in order to maintain plasma glucose levels. Excess and chronic glucocorticoid exposure, however, causes metabolic syndrome including insulin resistance, dyslipidemia, and hyperglycemia. Studies in animal models of metabolic disorders frequently demonstrate that suppressing glucocorticoid signaling improves insulin sensitivity and metabolic profiles. Glucocorticoids convey their signals through an intracellular glucocorticoid receptor (GR), which is a transcriptional regulator. The adipocyte is one cell type that contributes to whole body metabolic homeostasis under the influence of GR. Glucocorticoids’ functions on adipose tissues are complex. Depending on various physiological or pathophysiological states as well as distinct fat depots, glucocorticoids can either increase or decrease lipid storage in adipose tissues. In rodents, glucocorticoids have been shown to reduce the thermogenic activity of brown adipocytes. However, in human acute glucocorticoid exposure, glucocorticoids act to promote thermogenesis. In this article, we will review the recent studies on the mechanisms underlying the complex metabolic functions of GR in adipocytes. These include studies of the metabolic outcomes of adipocyte specific GR knockout mice and identification of novel GR primary target genes that mediate glucocorticoid action in adipocytes.

Eighth Jesús Culebras Lecture. Critical Care, nutrition and hyperglycemia: a close relationship

Critically ill patients show a metabolic response to injury that affects carbohydrate metabolism, causing hyperglycemia and an increase in glycemic variability that makes the critically ill patient susceptible to infection, resulting in morbidity and mortality increase. Also, severe hypoglycemia was detected as a consequence of intensive insulin treatment that provokes deleterious effects in their clinical evolution, so a correct monitoring of plasma glucose would contribute to reduce morbidity and mortality. In critically ill patients, glucose metabolism is in allostasis stage as a consequence of metabolic stress, producing an increase in peripheral resistance to insulin that causes an imbalance with the pancreatic beta-cell function, increasing insulin secretion to maintain plasma glucose levels within normality ranges. Numerous studies have been published about treatments with insulin and glycemic variability, whereas there are very few about nutrometabolic treatment of hyperglycemia in critically ill patients. Of all of them we can conclude that it is always recommended to keep glucose levels under 180 mg/dl, and when possible, not over 150 mg/dl, establishing a lower range of 110-140 mg/dl. Moreover, tight glycemic control increases the risk of severe hypoglycemia (≤ 40 mg/dl) and its subsequent mortality, so we advise against it. Besides, glycemic variability has been independently associated with an increase of mortality in critically ill patients and, consequently, protocols should aim at avoiding it. Nutritional treatment with diabetes-specific diets not only improves hyperglycemic control and decreases insulin needs, but also decreases glycemic variability and could reduce the incidence of infectious complications. Therefore, they are recommended, at least during the first week of stay. Finally, diabetes seems to modulates the consequences of hyperglycemia in critically ill patients, so diabetic patients could benefit from a higher glycemic target than those without diabetes but with stress hyperglycemia.

Characterisation of Optimal Responses to Pulse Inputs in the Bergman Minimal Model

The Bergman minimal model is a dynamic model of plasma glucose concentration. It has two input variables - insulin delivery and carbohydrate intake. We investigate the behaviour of plasma glucose concentration predicted by the model given carbohydrate (CHO) inputs and commensurate insulin inputs. We observe that to maintain plasma glucose above a specified minimum concentration results in an unavoidable peak in plasma glucose. Additionally, we specify the timing and magnitude of a bolus pulse to minimise this unavoidable peak in plasma glucose concentration whilst attaining but not going below the desired minimum glucose concentration. Finally, we obtain necessary and sufficient conditions for the glucose concentration to be minimised.

PCK1 expression is correlated with the plasma glucose level in the duck.

Phosphoenolpyruvate carboxykinase 1 (soluble) (PCK1) is a key gene in gluconeogenesis and glyceroneogenesis. Although its functions have been extensively studied in mice, bats and humans, little is known in ducks. Here, PCK1 functions were studied using a duck domestication model and a 48-h fasting experiment. We found PCK1 expression significantly decreased in two breeds of domestic ducks (Jinyun Pockmark ducks and Cherry Valley ducks) as compared with wild ducks (Anas platyrhynchos). Simultaneously, plasma levels of glucose, triglycerides and free fatty acid in domestic ducks were lower than in wild ducks. When compared with fed ducks, the plasma triglyceride level was observed to be significantly decreased, while the glucose and free fatty acid levels remained constant in 48-h fasting ducks. The expression analysis of gluconeogenic genes revealed that fructose-1,6-bisphosphatase genes (FBP1 and FBP2) and the glucose-6-phosphatase gene (G6PC2) were not changed, whereas PCK1 was significantly upregulated. In addition, the reported regulators of PCK1, including forkhead box A2 (FOXA2) gene and orphan nuclear receptor NR4A family genes (NR4A1, NR4A2 and NR4A3), exhibited similar expression levels between 48-h fasting ducks and fed ducks, suggesting that PCK1 is not regulated by these genes in the duck under fasting conditions. In conclusion, PCK1 expression may affect plasma levels of glucose, triglycerides and free fatty acid during the duck domestication process. This work demonstrates for the first time in duck that PCK1 is a key gene in maintaining plasma glucose homeostasis during fasting and that the upregulated expression of PCK1 may be responsible for constant plasma free fatty acid level by the glyceroneogenesis process.

Bioenergetics and Type 2 Diabetes

Hyperglycemia of type 2 diabetes mellitus (T2DM) develops when pancreatic β-cells damaged by chronic exposure to elevated blood glucose and lipids (glucolipotoxicity) fail to synthesize and secrete sufficient quantities of insulin for maintaining plasma glucose level. Despite intensive studies in this field, the molecular mechanism by which fatty acids (FA) cause β-cell impairment is not well understood. It still remains unknown what are the lipid- or glucose-derived molecules directly responsible for the impairment of β-cell function? Our studies showed that in addition to impaired insulin secretion and loss of biphasicity, T2D islets exhibited altered cell bioenergetics as evidenced by decreased oxygen consumption rate as compared to those of the control islets. We also discovered that fuel overload (high level of FA and glucose leads to incomplete FA oxidation and results in accumulation of toxic long-chain 3-OH-fatty acids that could induce oxidative stress and disrupt mitochondrial function. Timedependent impairments of bioenergetics due to chronic exposure to elevated blood glucose and lipids would be the consequence leading to pancreatic β-cell failure.

Real-time estimation of plasma insulin concentration from continuous glucose monitor measurements

Continuous glucose monitors can measure interstitial glucose concentration in real time for closed-loop glucose control systems, known as artificial pancreas. These control systems use an insulin feedback to maintain plasma glucose concentration within a narrow and safe range, and thus to avoid health complications. As it is not possible to measure plasma insulin concentration in real time, insulin models have been used in literature to estimate them. Nevertheless, the significant inter- and intra-patient variability of insulin absorption jeopardizes the accuracy of these estimations. In order to reduce these limitations, our objective is to perform a real-time estimation of plasma insulin concentration from continuous glucose monitoring (CGM). Hovorka’s glucose–insulin model has been incorporated in an extended Kalman filter in which different selected time-variant model parameters have been considered as extended states. The observability of the original Hovorka’s model and of several extended models has been evaluated by their Lie derivatives. We have evaluated this methodology with an in-silico study with 100 patients with Type 1 diabetes during 25 h. Furthermore, it has been also validated using clinical data from 12 insulin pump patients with Type 1 diabetes who underwent four mixed meal studies. Real-time insulin estimations have been compared to plasma insulin measurements to assess performance showing the validity of the methodology here used in comparison with that formerly used for insulin models. Hence, real-time estimations for plasma insulin concentration based on subcutaneous glucose monitoring can be beneficial for increasing the efficiency of control algorithms for the artificial pancreas.