Models of hyperglycaemia in diabetes mellitus and its complications.
Diabetes mellitus is a metabolic disease marked by chronic high blood levels of glucose (also known as hyperglycaemia), which over time can cause damage to the blood vasculature, leading to devastating complications. The increase in global prevalence and the number of cases of type 2 diabetes mellitus continues unabated, prompting diabetes mellitus researchers to continue studying the aetiology of the disease in search of ways to improve therapeutic outcomes. Over the years, numerous in vivo and in vitro mammalian models have been developed to investigate the mechanisms underlying diabetes mellitus and its complications. The customary use or induction of high levels of glucose in vivo or in vitro to recapitulate chronic hyperglycaemia in diabetes mellitus is central to these models. However, there has never been a consensus as to how to standardize the re-creation of glucotoxicity conditions so that the pathophysiological effects in human diabetes mellitus can be accurately mimicked experimentally. In this Review, we critically discuss glucotoxicity (without lipotoxicity) in diabetes mellitus and analyse the various in vivo and in vitro models used to study the conditions created by high levels of glucose in diabetes mellitus. Efforts to standardize experimental induction or administration of high levels of glucose, and understanding the pros and cons of each model, could help harmonize findings that will benefit the diabetes mellitus research community.
- Research Article
- 10.22435/pgm.v28i1.1436
- Jan 1, 2005
- The Journal of Nutrition and Food Research
Background: The beta pancreas cell hypertrophy and hyperinsulinime occur in Obesity. If the compensation is not sufficient and with the addition of genetic and environment factors, diabetes mellitus are more likely to occur. The general parameter utilized to determine the condition of diabetes mellitus is blood glucose level, therefore the analysis of obesity risk to blood glucose level are performed. Objectives: To determine the relation of the risk of obesity level to the blood glucose level. Methods: The secondary data are analyzed based on SKRT 2004 and Susenas 2004 data. All the samples are female and male with the age among 25-65. Results: The people with obesity are 1.78 times more likely to have high blood glucose level than person with normal weight. The other variable is that the female have less risk of 0.72 times and 0.62 times to have borderline and high blood glucose level compared to male. The age groups of 36-45 and 46-65 have risk 1.28 times and 1.52 times respectively, to have high glucose level than the age group of 25-35. Another result shows that the people living in the city are 1.30 times more likely to have high blood glucose level than those living in countryside. Conclusions: The people with obesity are more risky to have high blood glucose level than people with normal weight. The other risk factors of borderline or high blood glucose level are men, living in city and above 36 years of age. Recommendations: The education about blood glucose level should be given priory to the risk groups which are; the people with obesity, male, living in city and more than 36 years of age. [Penel Gizi Makan 2005,28(1): 9-15] Keywords: overweight, obesity, blood glucose level
- Research Article
- 10.54350/jkr.v13i1.164
- Sep 23, 2023
- Jurnal Kesehatan Rajawali
Diabetes Mellitus (DM) is a disease caused by high blood glucose levels. High glucose levels in DM patients are thought to be at risk of bacteriuria infection which can cause UTI’s. High blood glucose levels result in glucosuria and neutrophil dysfunction which increases the risk of urinary tract infection. The purpose of this study was to determine the correlation between blood glucose levels and bacteriuria in patients with Diabetes Mellitus (DM) at Puskesmas I West Denpasar. Descriptive correlational research with a cross-sectional approach was conducted using purposive sampling. The study utilized the urine culture method with a total sample of 30 participants. The results revealed that 33% of respondents with uncontrolled glucose levels (>145 mg/dL) had positive bacteriuria results, while 57% of respondents with controlled glucose levels (≤145 mg/dL) had negative bacteriuria results. The Kendall Tau-b statistical test showed a significant correlation (p-value = 0.000, <0.05) between blood glucose levels and bacteriuria in Diabetes Mellitus sufferers at Puskesmas I West Denpasar. The correlation coefficient value is 0.809 (0.78-0.99) which states that there is a very strong correlation between blood glucose levels and bacteriuria. In conclusion, this study established a correlation between blood glucose levels and bacteriuria in Diabetes Mellitus (DM) sufferers at Puskesmas I West Denpasar.
- Research Article
7
- 10.1111/jgs.13870
- Jan 1, 2016
- Journal of the American Geriatrics Society
To investigate the association between random measured glucose levels in middle and old age and dementia-related death. Population-based cohort study. Norwegian Counties Study (middle-aged individuals; 35-49) and Cohort of Norway participants (older individuals; 65-80). Individuals without (n=74,630) and with (n=3,095) known diabetes mellitus (N=77,725); 67,865 without and 2,341 with diabetes mellitus were included in the complete case analyses (nonmissing for all included covariates), of whom 1,580 without and 131 with diabetes mellitus died from dementia-related causes. Dementia-related death was ascertained according to the Norwegian Cause of Death Registry. Cox regression was used to assess the relationship between random glucose levels (nonfasting) in individuals without and with diabetes mellitus and dementia-related death. Education, smoking, cardiovascular disease, body mass index, cholesterol, blood pressure, and physical activity were adjusted for. Individuals without diabetes mellitus at midlife with glucose levels between 6.5 and 11.0 mmol/L had a significantly greater risk of dementia-related death than those with levels less than 5.1 mmol/L (hazard ratio=1.32, 95% confidence interval=1.04-1.67) in a fully adjusted model. A dose-response relationship (P=.02) was observed. No significant association between high glucose levels in individuals aged 65 to 80 and dementia-related death was detected. High random glucose levels measured in middle-aged but not older age persons without known diabetes mellitus were associated with greater risk of dementia-related death up to four decades later.
- Research Article
1
- 10.1093/ehjci/ehaa946.1808
- Nov 1, 2020
- European Heart Journal
Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous clinically entity and represents 5% to 10% of all patients with myocardial infarction (MI). Besides type 2 diabetes mellitus (DM), which is a common comorbidity in patients hospitalized for an acute coronary syndrome, high glucose levels (HGL) at admission are frequently observed in this context. The risk of major adverse cardiovascular events following acute coronary syndrome is increased in people with DM and HGL. However, evidence regarding diabetes and high glucose level among MINOCA patients is lacking. Purpose To examine the incidence of major adverse cardiovascular events (MACEs) in diabetic and non-diabetic MINOCA patients as well as according to HGL at presentation. Methods Among 1995 patients with acute MI admitted to our coronary care unit from 2016 to 2018, we enrolled 186 consecutive MINOCA patients according to the current ESC diagnostic criteria. HGL at admission was defined as serum glucose level above 180 mg/dl. All-cause mortality and a composite end-point of all-cause mortality and myocardial re-infarction were compared. The median follow-up time was 19.6±12.9 months. Results Diabetic MINOCA patients were older (mean age 75.5±9.6 vs 66.5±14.7; p=0.002) and with higher prevalence of hypertension (p=0.016). Conversely, there were no significant differences in gender, BMI, dyslipidemia and atrial fibrillation. Similarly, no significant differences were observed regarding clinical and ECG presentation, echocardiographic features and laboratory tests. The rates of death (30.8% vs 8.3%; p=0.013) and MACEs (22.2% vs 6.8%; p=0.025) were significantly higher in MINOCA-DM patients; conversely, no significant differences were observed for re-MI (p=0.58). At multivariate regression model adjusted for age and sex, type 2 DM was not an independent predictor of all cause deaths (p=0.36) and MACE (p=0.24). Patients with admission HGL had similar baseline characteristics, cardiovascular risk factors, clinical presentations, echocardiographic features and troponin values as compared to patients with no-HGL. HGL at admission was associated with higher incidence of all-cause-death (p&lt;0.001) and MACE (p=0.003) during follow-up compared to patients with no HGL; conversely, no significant differences were observed in the incidence of re-MI (p=0.7). Multivariate analysis adjusted for age and sex demonstrated that HGL was an independent predictor of death (HR 6.25; CI 1.64–23.85; p=0.007) and MACEs (HR 6.17; CI 1.79–21.23, p=0.004). Conclusion In MINOCA patients, HGL was an independent risk factor for both MACEs and death while type 2 DM was not correlated with these hard endpoints. As a consequence, HGL could have a still unexplored pathophysiological role in MINOCA. Properly powered randomized trials are warranted. Funding Acknowledgement Type of funding source: None
- Research Article
- 10.56294/saludcyt20251034
- Jan 1, 2025
- Salud, Ciencia y Tecnología
Introduction: drowsiness is the tendency of a person to fall asleep when faced with any event and may be associated with high blood glucose levels. Objective: to know the state of sleepiness in people with type II diabetes mellitus in Mexico City and if it is a symptom of high glucose levels or lack of control of their diabetes mellitus.Methods: a descriptive cross-sectional study was carried out in adults with type II diabetes mellitus in Mexico City. The state of global sleepiness was measured using the Epworth Scale, valid in the Mexican population, which evaluates the probability of nodding off or staying asleep. asleep in everyday life situations, with a scale from 0 to 3. Regarding ethical aspects, the Declaration of Helsinki and the General Health Law were considered.Results: from April to July 2024, 93 people with type II diabetes mellitus were studied. The average age was 67 years, 76,3 % were female, 33,2 % were widowed and 32,3 % were married. 44,1 % of older adults with DM have excessive sleepiness. People with diabetes mellitus with a sleepiness scale greater than normal are people who have high glucose levels (>/131 mg/dl), with a PR=1.3 and a Fep=0.23Conclusions: excessive sleepiness can be a symptom of high blood glucose levels. Therefore, the nursing professional must carry out an intervention on sleep hygiene
- Research Article
28
- 10.1177/2048872620925265
- Sep 1, 2020
- European Heart Journal. Acute Cardiovascular Care
Cardiogenic shock is the leading cause of death in patients with acute myocardial infarction, with short-term mortality of approximately 50%. Whether diabetes mellitus and high blood glucose levels are associated with mortality in contemporary patients with acute myocardial infarction complicated by cardiogenic shock is inadequately described. To investigate if diabetes mellitus and high admission blood glucose were associated with 30-day mortality in a large, contemporary population with acute myocardial infarction complicated by cardiogenic shock. Patients with acute myocardial infarction complicated by cardiogenic shock admitted at two tertiary centres in Denmark from 2010 to 2017 were individually identified through patient charts, resulting in the inclusion of 1716 cardiogenic shock patients. Glucose level at admission to the intensive care unit was available in 1302 patients. There was no significant difference in 30-day mortality between diabetes mellitus types I and II (63% vs. 62%, NS). Thirty-day mortality was significantly higher in diabetes patients compared to non-diabetes patients (62% vs. 50%, P < 0.001). Increasing admission glucose was associated with increasing 30-day mortality in a dose-dependent manner in diabetes mellitus (4-8 mmol/L, 41%; 8-12 mmol/L, 49%; 12-16 mmol/L, 63%; >16 mmol/L, 67%; P = 0.028) and non-diabetes patients (4-8 mmol/L, 32%; 8-12 mmol/L, 43%; 12-16 mmol/L, 57%; >16 mmol/l; 68%; P < 0.001). Patients with acute myocardial infarction complicated by cardiogenic shock and concomitant diabetes mellitus type I or II had a significantly higher 30-day mortality in comparison to patients without diabetes mellitus, whereas no difference was found between diabetes mellitus types I and II. High glucose levels on admission to the intensive care unit were associated with increased 30-day mortality in diabetes mellitus and non-diabetes mellitus patients.
- Research Article
56
- 10.1016/j.matt.2021.08.011
- Oct 1, 2021
- Matter
Glucose-responsive oral insulin delivery platform for one treatment a day in diabetes
- Research Article
17
- 10.1074/jbc.m111.244111
- Jul 1, 2011
- Journal of Biological Chemistry
The SNF1/AMP-activated protein kinases are central energy regulators in eukaryotes. SNF1 of Saccharomyces cerevisiae is inhibited during growth on high levels of glucose and is activated in response to glucose depletion and other stresses. Activation entails phosphorylation of Thr(210) on the activation loop of the catalytic subunit Snf1 by Snf1-activating kinases. We have used mutational analysis to identify Snf1 residues that are important for regulation. Alteration of Tyr(106) in the αC helix or Leu(198) adjacent to the Asp-Phe-Gly motif on the activation loop relieved glucose inhibition of phosphorylation, resulting in phosphorylation of Thr(210) during growth on high levels of glucose. Substitution of Arg for Gly(53), at the N terminus of the kinase domain, increased activation on both high and low glucose. Alteration of the ubiquitin-associated domain revealed a modest autoinhibitory effect. Previous studies identified alterations of the Gal83 (β) and Snf4 (γ) subunits that relieve glucose inhibition, and we have here identified a distinct set of Gal83 residues that are required. Together, these results indicate that alterations at dispersed sites within each subunit of SNF1 cause phosphorylation of the kinase during growth on high levels of glucose. These findings suggest that the conformation of the SNF1 complex is crucial to maintenance of the inactive state during growth on high glucose and that the default state for SNF1 is one in which Thr(210) is phosphorylated and the kinase is active.
- Research Article
53
- 10.2147/bctt.s135665
- Jun 13, 2017
- Breast Cancer : Targets and Therapy
Hyperglycemia or diabetes mellitus (DM), which is characterized by high blood glucose levels, has been linked to an increased risk of cancer for years. However, the underlying molecular mechanisms of the pathophysiological link are not yet fully understood. In this study, we demonstrate that high glucose levels promote the proliferation of breast cancer cells by stimulating epidermal growth factor receptor (EGFR) activation and the Rho family GTPase Rac1 and Cdc42 mediate the corresponding signaling induced by high glucose levels. We further show that Cdc42 promotes EGFR phosphorylation by blocking EGFR degradation, which may be mediated by the Cbl proteins, whereas the Rac1-mediated EGFR phosphorylation is independent of EGFR degradation. Our findings elucidate a part of the underlying molecular mechanism of the link between high glucose levels and tumorigenesis in breast cancer and may provide new insights on the therapeutic strategy for cancer patients with diabetes or hyperglycemia.
- Research Article
25
- 10.2165/00023210-199809030-00006
- Jan 1, 1998
- CNS Drugs
Patients with type 1 (insulin-dependent) diabetes mellitus can experience both very low and very high blood glucose levels that may affect the CNS. Over time, high glucose levels (hyperglycaemia) may result in ketoacidosis, seizures, coma and death. Although a wide variation in response exists, acute hypoglycaemia (low blood sugar level) generally results in a decrease in the supply of glucose to the brain. Progressively lower glucose levels can result in confusion, inability to concentrate or cogitate, seizures, coma or death.
- Research Article
200
- 10.1210/me.2003-0283
- Mar 18, 2004
- Molecular Endocrinology
Hepatic glucose production by gluconeogenesis is the main source of glucose during fasting and contributes significantly to hyperglycemia in diabetes mellitus. Accordingly, glucose metabolism is tightly controlled by a variety of hormones including insulin, epinephrine, glucagon, and glucocorticoids (GCs) acting on various cell types. GC effects are mediated by the GC receptor (GR), a ligand-dependent transcription factor, which in the liver and kidney controls gluconeogenesis by induction of gluconeogenic enzymes. To specifically study the contribution of GC on liver carbohydrate metabolism, we generated mice with an inactivation of the GR gene exclusively in hepatocytes using the Cre/loxP technology. Half of the mutant mice die within the first 2 d after birth most likely due to hypoglycemia. Adult mice have normal blood sugar under basal conditions but show hypoglycemia after prolonged starvation due to reduced expression of genes involved in gluconeogenesis. We further demonstrate that absence of GR in hepatocytes limits the development of hyperglycemia in streptozotocin-induced diabetes mellitus probably due to impaired induction of gluconeogenesis. These findings show the essential role of GR function in liver glucose metabolism during fasting and in diabetic mice and indicate that liver-specific GC antagonists could be beneficial in control of diabetic hyperglycemia.
- Research Article
63
- 10.1002/cncr.24126
- Jan 20, 2009
- Cancer
Research suggests that glucose levels in cancer patients may be an important prognostic indicator. In ovarian tumors, increased expression of glucose transporter 1 (GLUT1), a transmembrane protein responsible for glucose uptake, is related to shorter survival time in ovarian cancer patients. This study tested the hypothesis that higher presurgical glucose levels predict shorter disease-specific survival time and time to recurrence in ovarian cancer patients. Nonfasting plasma glucose levels were determined for 74 patients with ovarian cancer at the time of their presurgical consultation and for 125 ovarian cancer patients in an independent validation set. Survival time and time to recurrence (disease-free interval [DFI]) were ascertained from medical records. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) for survival time and DFI in relation to glucose level, adjusting for body mass index (BMI), stage, grade, and cytoreduction as appropriate. Higher glucose levels were associated with shorter survival times in univariate analyses (HR, 1.88; P = .05). Multivariate analysis adjusting for stage showed that higher glucose levels were associated with shorter survival times (HR, 2.01; P = .04) and DFI (HR, 2.32; P = .05). In the validation set, higher glucose levels were associated with shorter survival times (HR, 2.01; P = .02) and DFI (HR, 2.48; P = .001) in univariate analysis, although glucose was not independent of the effect of cytoreduction when predicting survival time in this latter set. These findings contribute to mounting evidence that glucose levels have prognostic value in ovarian carcinoma.
- Research Article
18
- 10.1515/jpem.2002.15.1.59
- Jan 1, 2002
- Journal of pediatric endocrinology & metabolism : JPEM
The incidence of type 2 diabetes mellitus (DM) in children and adolescents has substantially increased over the past decade. The present study was conducted to evaluate the beta-cell response to intravenous glucagon (a non-glucose secretagogue) in children with type 2 DM. Twenty pediatric patients with type 2 DM were compared to 15 control subjects matched for body mass index and sexual maturation. The patients' ages ranged between 10 and 19 years. The duration of DM ranged from 1 to 5 years. Nine patients were on insulin treatment and 11 were on diet alone (3 patients) or metformin (8 patients). The criteria for type 2 DM were absent islet cell (IA-2) and glutamic acid decarboxylase (GAD65) antibodies and a fasting serum C-peptide level of > or = 0.23 nmol/l. Plasma glucose and serum C-peptide levels were determined in the fasting state and six minutes after an intravenous injection of 1 mg of glucagon. The fasting and stimulated plasma glucose levels and the fasting serum C-peptide levels (1.02 +/- 0.43 vs 0.79 +/- 0.26 nmol/l, p < 0.05) were higher in the patients with DM compared to weight-matched control subjects. While the absolute C-peptide responses to glucagon were not different between the two groups, the stimulated C-peptide to glucose ratios were significantly lower in the patients with DM compared to controls (0.039 +/- 0.026 vs 0.062 +/- 0.033, p < 0.05). Patients with DM treated with diet or oral therapy had significantly greater basal and stimulated C-peptide concentrations, incremental C-peptide, and C-peptide to glucose ratios than patients on insulin treatment. Both the fasting and the stimulated C-peptide levels were inversely correlated with the duration of DM (r = -0.53, p < 0.05). HbA1c at one year follow-up was inversely correlated with glucagon-stimulated C-peptide levels at the time of the study (r = -0.658, p < 0.01) and positively correlated with the duration of diabetes (r = 0.671, p = 0.002). The apparently normal serum C-peptide levels measured after glucagon challenge in these children with type 2 DM reflect their higher glucose levels. The lower stimulated C-peptide to glucose ratios in these children with type 2 DM compared to normal controls demonstrate their diminished beta-cell response to intravenous glucagon, a non-glucose secretagogue. Among the patients with DM, a higher glucagon-stimulated serum C-peptide response was associated with diet/metformin treatment, a shorter duration of DM and predicted improved glycemic control up to one year later. Thus, the fasting and glucagon-stimulated serum C-peptide levels provide an estimate of the potential insulin secretory capacity of the beta-cell and may predict glycemic control in pediatric type 2 DM.
- Research Article
2
- 10.22146/ijcn.18207
- Jan 1, 2012
- Jurnal Gizi Klinik Indonesia
Background: Hyperglycemia in diabetes mellitus increases the production of superoxide that cause oxidative stress and decrease the activity of superoxide dismutase (SOD). SOD enzyme reduces superoxide to hydrogen peroxide to lessen the reaction between superoxide and nitric oxide (NO). To reduce hyperglycemia in diabetes mellitus, diabetics are encouraged to consume diet with low glycemic index. Arrowroot chips is a product commonly used by the community as a snack. Arrowroot has low glycemic index (glycemic index = 14) so it can be used as an alternative snack for diabetics.Objective: The aim of this study is to determine the beneficial effects of arrowroot chips to help controlling the blood glucose level, SOD activity and NO concentration in type 2 diabetes. Method: This is a quasi-experimental research with a one group pre test - post test. Subjects were 14 patients with type 2 diabetes mellitus who regularly visited endocrine polyclinic of RSUP.Dr. Sardjito Yogyakarta. The inclusion criteria were: aged 35-60 years, had suffered from diabetes mellitus for at least one year and currently on insulin injection therapy. The subjects were given 20 grams/day arrowroot chips to be consumed as a snack for four weeks. The blood samples were drawn before and after treatment. Glucose level were analyzed by GOD-PAP method, SOD activity was determined by Ransod kits and NO concentration was analyzed by colorimetric Gies reagent system. Finally, data were analyzed by paired t-test and correlation regression test.Result: There was an increased glucose level from 124,43 ± 33,56 to 139,00 ± 67,96 mg/dl after treatment (p=0,551), SOD activity decreased from 77,09 + 19,33 to 43,99 + 17,45 unit/ml whole blood after treatment (p=0,000), decreased NO concentration from 1,28 + 1,32 to 1,15 + 0,577 µM after treatment (p=0,875), and a positive correlation between SOD activity and NO concentration (p=0,151; r=0,405; R2=0,164).Conclusion: Arrowroot chips consumption as a snack for 4 weeks was unable to help controlling the fasting plasma glucose level, SOD activity and NO concentration in type 2 diabetics.
- Research Article
136
- 10.2967/jnumed.109.074294
- Jun 16, 2010
- Journal of Nuclear Medicine
Diabetes mellitus (DM) is a common metabolic disorder. Hyperglycemia occurs in a significant proportion of patients with uncontrolled DM but can also be found in patients without diabetes. Although the relationship between (18)F-FDG uptake in malignant tumors and blood glucose levels has been previously addressed, it has not been investigated in cases of infection and inflammation, despite the high incidence of these entities in diabetic patients. The current study assessed whether hyperglycemia and DM affect the detectability rate of disease in (18)F-FDG PET/CT studies performed for patients with suspected infectious and inflammatory processes, as compared with a group of patients with malignant tumors. (18)F-FDG PET/CT studies of 123 consecutive patients investigated for suspected infection or inflammation and 320 patients evaluated for malignancy were retrospectively analyzed. The presence of DM and the level of glucose at the time of the study were recorded. Differences between the 2 study populations in false-negative (FN) rates in patients with and without hyperglycemia and DM were compared and analyzed for statistical significance. In the infection or inflammation group, 19 of 123 patients (15%) had serum glucose levels greater than 180 mg/dL and 43 of 123 (35%) had DM. There were no FN studies in patients with hyperglycemia and 4 FN studies in patients with normal glucose levels. There were 2 FN studies each in patients with and without DM. Neither glucose levels nor DM affects the detection rate of infection or inflammation with (18)F-FDG PET/CT. In the oncology group, 84 of 320 patients (26%) had serum glucose levels greater than 180 mg/dL and 183 of 320 (57%) had DM. There were 6 FN studies in cancer patients with hyperglycemia and 7 in patients with normal glucose levels. There were 8 FN studies in cancer patients with DM and 5 FN studies in patients without DM. Higher glucose levels but not DM affected the detection rate of malignancy with (18)F-FDG PET/CT. High glucose levels at the time of the study but not DM may reduce the sensitivity of (18)F-FDG PET/CT in the assessment of malignancy. No significant impact on the FN rate was found in patients with infection and inflammatory processes with either DM or hyperglycemia.
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