Development Of Impaired Glucose Tolerance Research Articles

Association of Periodontal Condition With Impaired Glucose Tolerance: Results of a 15-Year Follow-Up Study.

The aim of this study was to investigate whether periodontal condition is associated with the development of impaired glucose tolerance (IGT). This study was based on a subpopulation of a cohort of persons born in 1935 and living in Oulu, Finland, on October 1, 1990. The participants were normoglycemic (no previously diagnosed diabetes mellitus and a 2-h oral glucose tolerance test [OGTT] blood glucose < 7.8 mmol/L) in the baseline examinations (1990-1992) and had fasting blood glucose < 7.0 mmol/L in the follow-up examinations (2007-2008) (n = 225). The outcome was IGT on follow-up, measured by a blood glucose level of ≥ 7.8 mmol/L after OGTT. The exposure was the periodontal condition at baseline categorized into four groups: 0, 1-6, ≥ 7 sites with deepened (≥ 4 mm) periodontal pockets, and edentulousness. A total of 23% of the participants developed IGT. The adjusted incidence rate ratios with 95% confidence intervals (CI) for dentate participants with 1-6 sites and ≥ 7 sites with deepened periodontal pockets, and edentate participants (reference category dentate participants without deepened periodontal pockets) were 1.5 (95% CI, 0.6-4.0), 1.8 (95% CI, 0.7-4.4), and 1.6 (95% CI, 0.6-4.0), respectively. Poor periodontal condition may predispose individuals to IGT; however, further studies on this matter are warranted.

Gut microbiota-based prediction for the transition from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) in a remote island cohort study

AimThe present cohort study explored whether specific gut microbiota (GM) profile would predict the development of impaired glucose tolerance (IGT) in individuals with normal glucose tolerance (NGT). MethodsA total of 114 study subjects with NGT in Kumejima island, Japan participated in the present study and underwent 75 g oral glucose tolerance tests at baseline and one year later. We compared the profile of GM at baseline between individuals who consistently maintained NGT (NRN, n = 108) and those who transitioned from NGT to IGT (NTI, n = 6). ResultsWithin-individual bacterial richness and evenness as well as inter-individual bacterial composition showed no significant differences between NRN and NTI. Of note, however, partial least squares discriminant analyses revealed distinct compositions of GM between groups, with no overlap in their 95 % confidence interval ellipses. Multi-factor analyses at the genus level demonstrated that the proportions of CF231, Corynebacterium, Succinivibrio, and Geobacillus were significantly elevated in NTI compared to NRN (p < 0.005, FDR < 0.1, respectively) after adjusting for age, sex, HbA1c level, and BMI. ConclusionsOur data suggest that increased proportion of specific GM is linked to the future deterioration of glucose tolerance, thereby serving as a promising predictive marker for type 2 diabetes mellitus.

Growth hormone treatment in children with Prader-Willi syndrome: safety and effectiveness data from the PATRO Children study.

Recombinant human growth hormone (rhGH, somatropin) therapy is approved in children with Prader-Willi syndrome (PWS). To report safety and effectiveness data for children with PWS treated with biosimilar rhGH (Omnitrope®, Sandoz) in the PAtients TReated with Omnitrope (PATRO) Children study. PATRO Children was a multicenter, non-interventional, postmarketing surveillance study. Children with PWS received Omnitrope according to standard clinical practice. Adverse events (AEs) were monitored for the duration of Omnitrope treatment. Effectiveness outcomes were also assessed, including height standard deviation (SD) scores (HSDS). As of July 2020 (study completion), 235 patients with PWS had been enrolled. At baseline, 95.7% (n = 225) of patients were prepubertal and 86.4% (n = 203) were rhGH treatment-naïve. At analysis, the median (range) treatment duration in the study was 56.8 (2.9-155.8) months. AEs were reported in 192 patients (81.7%) and were suspected as treatment-related in 39 patients (16.6%). Serious AEs (SAEs) were reported in 96 patients (40.9%) and were suspected as treatment-related in 22 patients (9.4%). The most frequent treatment-related SAEs were sleep apnea syndrome (n = 11; 4.7%), tonsillar hypertrophy (n = 4; 1.7%), and adenoidal hypertrophy (n = 4; 1.7%). Development of scoliosis was considered treatment-related in two patients; development of impaired glucose tolerance in one patient and type 2 diabetes mellitus in another patient were considered treatment-related. Effectiveness outcomes were primarily assessed in 153 patients who completed 3 years of treatment. Among the 151 prepubertal patients (135 treatment-naïve), mean (SD) change from baseline in HSDS after 3 years was +1.50 (1.07) across all patients and +1.57 (1.07) for treatment-naïve patients. These data suggest that biosimilar rhGH is well tolerated and effective in patients with PWS managed in real-life clinical practice. Patients with PWS should continue to be closely monitored for well-known safety issues (including respiratory, sleep, and glucose metabolism disorders, and scoliosis) during rhGH treatment.

The role of postprandial thermogenesis in the development of impaired glucose tolerance and type II diabetes.

Accounting for 5%-15% of total daily energy expenditure, postprandial thermogenesis (PPT) refers to an acute increase in resting metabolic rate (RMR) in the hours after eating. This is largely explained by the energy costs of processing the macronutrients of a meal. Most individuals spend the majority of the day in the postprandial state, thus over one's lifetime even minor differences in PPT may possess true clinical significance. In contrast to RMR, research indicates that PPT may be reduced in the development of both prediabetes and type II diabetes (T2D). The present analysis of existing literature has found that this impairment may be exaggerated in hyperinsulinemic-euglycemic clamp studies compared with food and beverage consumption studies. Nonetheless, it is estimated that daily PPT following carbohydrate consumption alone is approximately 150 kJ lower among individuals with T2D. This estimate fails to consider protein intake, which is notably more thermogenic than carbohydrate intake (20%-30% vs. 5%-8%, respectively). Putatively, dysglycemic individuals may lack the insulin sensitivity required to divert glucose toward storage-a more energy-taxing pathway. Accordingly, the majority of findings has associated an impaired PPT with a reduced "obligatory" energy output (i.e., the energy costs associated with nutrient processing). More recently, it has been reported that "facultative" thermogenesis [e.g., the energy costs associated with sympathetic nervous system (SNS) stimulation] may also contribute to any impairment in PPT among individuals with prediabetes and T2D. Further longitudinal research is required to truly ascertain whether meaningful changes in PPT manifest in the prediabetic state, before the development of T2D.

5613463 PREVALENCE OF HEMOCHROMATOSIS HFE GENE POLYMORPHISM AMONG EGYPTIAN βTHALASSEMIA PATIENTS AND ITS RELATION TO DEVELOPMENT OF DIABETES MELLITUS

Background: β-thalassemia constitutes a major health problem in Mediterranean countries. Impaired glucose tolerance and diabetes mellitus are observed complications in patients with thalassemia. However, the mechanisms leading to diabetes are still poorly understood.H63D gene polymorphism, is the second variant of hemochromatosis (HFE) gene, that causes hemochromatosis. Aims: We aimed to assess the frequency of diabetes mellitus in β -thalassemia patients and the frequency of H63D gene polymorphism as well as its relation to development prediabetes and diabetes mellitus in β -thalassemia patients. Methods: Case control study was conducted on 50 patients with β-thalassemia and 50 healthy control with matched age and sex. The age ranged from 6-18y. Study subjects were investigated with oral glucose tolerance test, fasting C-Peptide, fasting insulin, anti -gad and screened for frequency of H63D mutation of HFE gene using restriction fragment length polymorphism. Results: 32% of patients had normal glycemic state, 52% had impaired glucose tolerance and 16% were diabetic P<0.001. H63D mutation was more frequent in thalassemia patient. GG genotype was significantly higher in β- thalassemia patients versus healthy controls (68%vs24%) P<0.001. GG genotype was prevalent in 77%and 75% of prediabetes and diabetic thalassemia patients respectively, versus 50% in patients with normal glycemic state P<0.001. Conclusions: GG genotype of H63D mutation of hemochromatosis HFE gene was frequent in our β- thalassemia patients which may be considered as a genetic risk factor for development of impaired glucose tolerance and diabetes in patients with. β-thalassemia. Keywords: thalassemia; diabetes; HFE gene mutation

1330-P: Longitudinal Multiyear Prospective Study in 87 Diabetic Primates: Lack of Support for a Mechanistic Basis for the Disposition Index

Cross-sectional studies of individuals before, during, and after the development of overt type 2 diabetes (ADA definition) , as well as those in which 3 to 5 subgroups have been analyzed, typically have applied DM progression analyses using the parameters of the Disposition Index (DI) . In such correlation-based analyses, the inferences drawn do not reflect the relationships we and others have drawn from longitudinal analyses of the same data obtained within-subject across time during the development of diabetes. The problems with the DI and its interpretation have been a subject of concern for many years, but, nevertheless, its assumptions and interpretations have dominated the diabetes scientific literature. As recently noted by Arreola, et al 2022, the form of the relationship between two measures, insulin sensitivity as measured by the “gold standard” euglycemic hyperinsulinemic clamp and beta-cell responsiveness based on the intravenous glucose tolerance test induced Acute Insulin Response (AIR, 0 to min) is clearly nonlinear, and likely is not hyperbolic. In our longitudinal laboratory study of adult nonhuman primates, 87 developed overt type 2 diabetes[LS1] while under study. The laboratory provided standard monkey chow ad libitum to all individually caged Macaca mulatta rhesus monkeys throughout the study. We found that ß cell function was not a result of or associated with a decline in insulin sensitivity as measured by a euglycemic hyperinsulinemic clamp. Furthermore, hyperglycemia is clearly not the stimulus for nor cause of hypersecretion of insulin, the latter significantly preceding the development of impaired glucose tolerance followed by progression to overt DM. We conclude that the disposition index failed to predict the natural progression from normal to overt type 2 diabetes mellitus in this longitudinal data analysis, and its value is best considered only in the context of an epidemiological study using cross-sectional data. Disclosure L.Shiver: None. C.Bellido: None. A.Rosado: None. B.C.Hansen: None. Funding National Institutes of Health (NO1 AG3 1012)

Brown adipose tissue prevents glucose intolerance and cardiac remodeling in high-fat-fed mice after a mild myocardial infarction

BackgroundObesity increases the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes (T2D) after myocardial infarction (MI). Brown adipose tissue (BAT) is important to combat obesity and T2D, and increasing BAT mass by transplantation improves glucose metabolism and cardiac function. The objective of this study was to determine if BAT had a protective effect on glucose tolerance and cardiac function in high-fat diet (HFD) fed mice subjected to a mild MI.MethodsMale C57BL/6 mice were fed a HFD for eight weeks and then divided into Sham (Sham-operated) and +BAT (mice receiving 0.1 g BAT into their visceral cavity). Sixteen weeks post-transplantation, mice were further subdivided into ±MI (Sham; Sham-MI; +BAT; +BAT-MI) and maintained on a HFD. Cardiac (echocardiography) and metabolic function (glucose and insulin tolerance tests, body composition and exercise tolerance) were assessed throughout 22 weeks post-MI. Quantitative PCR (qPCR) was performed to determine the expression of genes related to metabolic function of perigonadal adipose tissue (pgWAT), subcutaneous white adipose tissue (scWAT), liver, heart, tibialis anterior skeletal muscle (TA); and BAT.Results+BAT prevented the increase in left ventricle mass (LVM) and exercise intolerance in response to MI. Similar to what is observed in humans, Sham-MI mice developed IGT post-MI, but this was negated in +BAT-MI mice. IGT was independent of changes in body composition. Genes involved in inflammation, insulin resistance, and metabolism were significantly altered in pgWAT, scWAT, and liver in Sham-MI mice compared to all other groups.ConclusionsBAT transplantation prevents IGT, the increase in LVM, and exercise intolerance following MI. MI alters the expression of several metabolic-related genes in WAT and liver in Sham-MI mice, suggesting that these tissues may contribute to the impaired metabolic response. Increasing BAT may be an important intervention to prevent the development of IGT or T2D and cardiac remodeling in obese patients post-MI.

Common Electrolyte and Metabolic Abnormalities Among Thyroid Patients.

The prevalence of thyroid diseases is high in the general population and causes serious abnormalities and disorders that can affect the quality of life. Many complications can result from poor or inappropriate management of the disease, leading to serious cardiovascular and metabolic complications. In the present review study, we aim to discuss the effect of thyroid diseases on metabolic and electrolyte abnormalities and the potential correlation with some common disorders. Evidence from previous studies has demonstrated that thyroid dysfunctions hugely affect the metabolism of glucose in the bodies of the affected patients, which can lead to the development of both type 1 and 2 diabetes mellitus (DM). Hyperthyroidism can lead to the development of impaired glucose tolerance and secondary diabetes mellitus. These include an increased glycogenolysis and gluconeogenesis process, increased intestinal absorption of glucose, and secondary ketogenesis and lipolysis, which will subsequently affect the functions of the insulin-secreting cells of the pancreas. Evidence showed that thyroid diseases are associated with the development of obesity and metabolic syndrome, and the management for these modalities should involve prior management of underlying thyroid diseases. Efforts should be made to adequately manage these cases with concomitant approaches to achieve the best clinical outcomes.

Hesperidin prevents hyperglycemia in diabetic rats by activating the insulin receptor pathway.

Diabetes, a disease with high prevalence in China, is a major risk factor of cardiovascular disease. Hesperidin is a flavanone glycoside with anti-hyperglycemic and anti-hyperlipidemic activities. Therefore, the present study aimed to investigate the potential preventive effect of hesperidin against type 2 diabetes mellitus (T2DM) using a rat model of alloxan and high fat diet (HFD)-induced insulin resistance. Male Sprague Dawley rats were orally administered with 100 mg/kg hesperidin or vehicle (sodium carboxy methyl cellulose) for 35 days. Insulin resistance was induced by feeding animals a HFD for 3 weeks (from day 7) and then with an alloxan injection on day 28. Results from the in vivo study demonstrated that hesperidin improved fasting serum glucose (from 19.8 to 10.6 mmol/l) without changing the fasting insulin level, suggesting that hesperidin prevented the development of insulin resistance and diabetes by improving insulin sensitivity. In the oral glucose tolerance test, the development of impaired glucose tolerance was also prevented by hesperidin treatment. Hesperidin was found to regulate glycolysis and gluconeogenesis by enhancing the activity of glucokinase, inducing the phosphorylation of insulin receptor (IR) and phosphoinositide-dependent kinase 1 (PDK1), while decreasing the activity of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the liver. In a cell-based assay, hesperidin increased glucose uptake in primary rat adipocytes. Collectively, the present study identified the potent preventive effect of hesperidin against HFD-induced insulin resistance by activating the IR/PDK1 pathway. The current results may provide a potential strategy lacking sides effects to improve metabolic health and reduce risks.

Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms

ObjectiveSleep loss has emerged as a risk factor for the development of impaired glucose tolerance. The mechanisms underpinning this observation are unknown; however, both mitochondrial dysfunction and circadian misalignment have been proposed. Because exercise improves glucose tolerance and mitochondrial function, and alters circadian rhythms, we investigated whether exercise may counteract the effects induced by inadequate sleep. MethodsTo minimize between-group differences of baseline characteristics, 24 healthy young males were allocated into one of the three experimental groups: a Normal Sleep (NS) group (8 h time in bed (TIB) per night, for five nights), a Sleep Restriction (SR) group (4 h TIB per night, for five nights), and a Sleep Restriction and Exercise group (SR+EX) (4 h TIB per night, for five nights and three high-intensity interval exercise (HIIE) sessions). Glucose tolerance, mitochondrial respiratory function, sarcoplasmic protein synthesis (SarcPS), and diurnal measures of peripheral skin temperature were assessed pre- and post-intervention. ResultsWe report that the SR group had reduced glucose tolerance post-intervention (mean change ± SD, P value, SR glucose AUC: 149 ± 115 A.U., P = 0.002), which was also associated with reductions in mitochondrial respiratory function (SR: -15.9 ± 12.4 pmol O2.s−1.mg−1, P = 0.001), a lower rate of SarcPS (FSR%/day SR: 1.11 ± 0.25%, P < 0.001), and reduced amplitude of diurnal rhythms. These effects were not observed when incorporating three sessions of HIIE during this period (SR+EX: glucose AUC 67 ± 57, P = 0.239, mitochondrial respiratory function: 0.6 ± 11.8 pmol O2.s−1.mg−1, P = 0.997, and SarcPS (FSR%/day): 1.77 ± 0.22%, P = 0.971). ConclusionsA five-night period of sleep restriction leads to reductions in mitochondrial respiratory function, SarcPS, and amplitude of skin temperature diurnal rhythms, with a concurrent reduction in glucose tolerance. We provide novel data demonstrating that these same detrimental effects are not observed when HIIE is performed during the period of sleep restriction. These data therefore provide evidence in support of the use of HIIE as an intervention to mitigate the detrimental physiological effects of sleep loss.

Prevention of the rise in plasma cholesterol and glucose levels by kaki-tannin and characterization of its bile acid binding capacity.

Bile acid-binding agents, such as cholestyramine and colesevelam, improve both cholesterol and glucose metabolism. Kaki-tannin, a polymerized condensed tannin derived from persimmon (Diospyros kaki), has been shown to have bile acid-binding capacity and a hypocholesterolemic effect. However, its effects on glucose metabolism have not been well studied, and the binding selectivity of kaki-tannin to bile acid molecules has not been reported. In vivo experiments using mice with high-fat diet-induced obesity showed that kaki-tannin intake (20 g kg-1 of the diet) increased fecal bile acid excretion by 2.3-fold and prevented a rise in plasma cholesterol levels and fasting plasma glucose levels. Kaki-tannin also suppressed the development of impaired glucose tolerance. To characterize the bile acid-binding capacity of kaki-tannin, we investigated its capacity to bind to eight types of bile acid and cholesterol in vitro. Kaki-tannin showed strong capacity to bind to lithocholic acid (85.5%), which has one hydroxy group. It also showed moderate capacity to bind to bile acids with two hydroxy groups (53.3%), followed by those with three hydroxy groups (39.0%), but kaki-tannin did not show binding capacity to cholesterol. These results suggest that the binding capacity of kaki-tannin to bile acids tends to decrease as the number of hydroxy groups increases. Interestingly, the binding capacity of kaki-tannin correlated with that of cholestyramine (correlation coefficient: r = 0.900). Our findings indicate that kaki-tannin binds preferentially to bile acids with fewer hydroxy groups and has beneficial effects on glucose metabolism as well as cholesterol metabolism. © 2020 Society of Chemical Industry.

Undernutrition in Pregnant Rats Induces Glucose Intolerance with Enhanced Expression of Inflammation-Related Genes in Peripheral Leukocytes of the Offspring.

Impaired glucose tolerance (IGT) induces chronic inflammation and subsequent development of complications triggered by arteriosclerosis. Moreover, undernutrition in pregnant rodents can induce IGT in their offspring. Here, we assessed whether undernutrition in pregnant rats would induce chronic inflammation in their offspring by measuring the expression levels of inflammation-related genes in peripheral blood leukocytes. Pregnant Wistar rats were divided into two groups: the control group received an American Institute of Nutrition Rodent diet (AIN-93G) ad libitum, and the undernutrition group had their diet restricted by 50% (w/w) compared with the control group from day 10 of pregnancy until birth of the offspring. Subsequently, mothers and pups were allowed to access the AIN-93G diet freely. At day 35 after birth, male pups were fasted for 4 h and subsequently orally administered with glucose solution (2 g/kg body weight). Blood glucose area under the curve (AUC) after glucose loading was significantly greater in the undernutrition group than the control group. The mRNA levels for inflammatory cytokines were increased by glucose loading especially in the undernutrition group. Expressions of genes encoding S100A9 and cell adhesion molecule CD11b were increased by glucose loading in the undernutrition group. Thus, undernutrition of pregnant rats during mid to late gestation induced the expression of inflammation-related genes in peripheral blood leukocytes of their offspring, with the development of IGT and impaired insulin secretion.

Diabetes development after distal pancreatectomy: results of a 10 year series

BackgroundLimited literature is available on the postoperative development of impaired glucose tolerance (IGT) and new-onset diabetes mellitus (NODM) following Distal Pancreatectomy (DP). We aimed to study the post-surgical clinical evolution of IGT/DM and its association with preoperative glycemic profiles of patients undergoing DP. MethodsPre- and postoperative glycemic laboratories were measured in patients undergoing DP by the senior author from 2007–2017. Multivariate risk factor analysis was performed to determine risk factors for new-onset IGT/DM after DP. Kaplan–Meier curves were constructed for development of NODM postoperatively. ResultsOf 216 included patients, n = 63, n = 68 and n = 85 were preoperatively diagnosed with no-diabetes (No-DM), pre-diabetes (Pre-DM), and diabetes (DM), respectively. At 2-year follow-up, n = 37, n = 80 and n = 99 were classified as No-DM, Pre-DM or DM, respectively. Pre-diabetics had a higher risk of developing postoperative dysglycemia (RR 2.230, 95% CI 1.732–2.870, p = 0.001). Preoperative OGTT>130, HbA1c >6.0, and chronic pancreatitis were risk factors for postoperative DM. Conclusion40% of patients undergoing DP were unaware of their dysglycemic status (pre-DM or DM) pre-operatively. At 2-year follow-up, 36% non-diabetic and 57% pre-diabetic patients had developed NODM. Appropriate pre-operative diabetic assessment is warranted for all patients undergoing pancreatic resections.

Development of Diabetes after Pancreaticoduodenectomy: Results of a 10-Year Series Using Prospective Endocrine Evaluation

Limited literature is available on the development of impaired glucose tolerance and diabetes mellitus after pancreaticoduodenectomy. The primary aim was to define the diabetic phenotype and correlate preoperative glycemic laboratory results to new-onset diabetes after pancreaticoduodenectomy. In this prospective study, perioperative fasting and postprandial (oral glucose tolerance test) plasma glucose, glycated hemoglobin, insulin, and c-peptide were measured in consecutive patients undergoing pancreaticoduodenectomy by the senior author from 2006 to 2017. American Diabetes Association definitions were used for glycemic classifications. Multivariate risk factor analysis was performed. Of 774 identified patients, 371 diabetics were excluded and 403 patients were included: 167 and 236 were preoperatively classified as nondiabetic and prediabetic, respectively. The incidence rates of diabetes at 120 months post pancreaticoduodenectomy were 9.0% (nondiabetics), 22.0% (prediabetics), and 16.6% (overall). Patients in whom diabetes developed demonstrated a 3-fold larger difference between oral glucose tolerance test and fasting glucose (Δ), and 2-fold larger Δinsulin and Δc-peptide values. Tiered multivariate analysis identified glycated hemoglobin >5.4% with a relative risk (RR) of 2.944 (p= 0.047) as an independent predictor of impaired glucose tolerance and diabetes mellitus. Analysis of patients stratified by preoperative classification identified fasting glucose >95 mg/dL (nondiabetics, RR 1.925; p= 0.002), and glycated hemoglobin ≥5.4% (prediabetics, RR 3.125; p= 0.040) as independent risk factors for diabetes. Compared with nondiabetics, prediabetics classified by any laboratory results demonstrated an RR of 2.471 (p=0.001) for diabetes developing postoperatively. There was no association between primary pathology, advancing age, or BMI and increased risk of diabetes development. Diabetes will develop after pancreaticoduodenectomy in approximately 16.6% of patients. A preoperative glycated hemoglobin >5.4% independently predicts new-onset diabetes. Pre- and postoperative endocrine analysis remains paramount for proper patient risk stratification.

Exercise As An Intervention To Mitigate Mitochondrial Dysfunction And Impaired Glucose Tolerance Induced By Sleep- loss

Sleep-loss is emerging as an important risk factor for the development of impaired glucose tolerance, insulin resistance (IR) and, subsequently, type 2 diabetes mellitus. While the mechanisms underlying these changes remain to be fully elucidated, in some instances their development may be associated with reduced mitochondrial function. This suggests sleep-loss may also impair mitochondrial function, but this has not been investigated. Given the possible relationship between mitochondrial function and IR, exercise could be used as a strategy to counteract the detrimental physiological changes induced by sleep-loss; however, this has not been demonstrated. PURPOSE: To investigate the effect of sleep-loss, with or without exercise, on skeletal muscle mitochondrial function and glucose tolerance. METHODS: Twenty healthy male participants were allocated into one of three experimental groups: a control group (CON, n=7) (8 h sleep opportunity for 5 nights), a sleep-restricted group (SR, n=7) (4 h sleep opportunity for 5 nights), and a sleep restricted and exercise group (SR+EX, n=6) (4 h sleep opportunity for 5 nights and 3 x high-intensity interval exercise (HIIE) sessions). The HIIE bouts consisted of 10 x 60-s intervals at 90% peak power, interspersed by 75 s of active recovery. Oral glucose tolerance tests (OGTT) and muscle biopsies were performed pre- and post-intervention. RESULTS: Mean sleep duration per night for CON, SR, and SR+EX was 448+25, 230+13 and 237+5 minutes, respectively. There was a significant reduction in mitochondrial respiratory function (O2 flux - pmol/s/mg tissue) from pre- to post-intervention in the SR group (80 + 16 vs 65 + 24, p<0.05), but this remained unchanged in the CON (70 + 5 vs 64 + 12, p>0.05) and SR+EX (78 + 20 vs 79 + 28, p>0.05) group. OGTT total area under the curve increased post intervention in the SR group (692 + 89 vs 832 + 57 units, p<0.05), but remained unchanged in the CON (741 + 202 vs 677 + 184, p>0.05) and SR+EX (645 + 51 vs 702 + 83, p>0.05) groups. CONCLUSION: Sleep-loss was associated with a reduction in mitochondrial respiratory function and a decrease in glucose tolerance. However, these changes were mitigated by performing HIIE, demonstrating exercise as a potent and cost-effective strategy to alleviate some of the negative metabolic effects of sleep loss.

CARDIOVASCULAR AND METABOLIC IMPAIRMENT IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA

Since the moment when the obstructive nature of sleep apnea was first revealed, many new in-formation on this disease have been obtained. Now obstructive sleep apnea (OSA) recognized as an independent predictor of the development of impaired glucose tolerance (insulin resistance, fasting hyperglycaemia), type 2 diabetes mellitus (DM2), resistant arterial hypertension, cardio- vascular death. The problem of identifying and treating patients with OSA is still actual. In real clinical practice, there is a need for an integrated approach to the diagnosis and therapy of comorbid OSA patients with metabolic impairment and cardiovascular diseases. The aim of this review is to assess the clinical and pathogenesis features of metabolic impaired, carbohydrate metabolism, basic metabolism, eating behavior, body weight fluctuations in patients with ob-structive sleep apnea syndrome. Methods. In our work, we used a retrospective analysis of pub-lished clinical research data of domestic and foreign authors over the past 20 years. The review included studies with adequate design from the standpoint of «good clinical practice» (GCP) and evidence-based medicine. The conclusion . According to modern interpretation, obstructive sleep apnea is considered as an independent disease that has its pathogenic mechanisms, clinical and functional manifestations. There are several main causes of the effect of OSA on the metabolic component and the work of the cardiovascular system. Among them, intermittent hypoxemia, endothelial dysfunction, fluctuations in intrathoracic pressure, increased activity of the sympathetic nervous system, disturbance of the structure of sleep are leading. OSA is considered as a disease capable of disabling patients of working age, dramatically changing the quality of life, leading to early mortality due to cardiovascular disasters. Timely detection of clinical symptoms of OSA and the strategy of early administration of CPAP therapy significantly improve the quality of treatment and prognosis of comorbid patients.

P6207ABCA1 gene polymorphism InsG319 prevents the development of impaired glucose tolerance in young and middle-aged women

P6207ABCA1 gene polymorphism InsG319 prevents the development of impaired glucose tolerance in young and middle-aged women

A novel botanical formula prevents diabetes by improving insulin resistance

BackgroundType 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease, and the prevalence has increased significantly in recent decades to epidemic proportions in China. Individually, fenugreek (Trigonella foenum graecum) seed, mulberry (Morus alba L.) leaf and American ginseng (Panax quinquefolius) root can improve glycemia in various animal models and humans with impaired glucose metabolism and T2DM. The aim of this study was to design an optimized botanical formula containing these herbal extracts as a nutritional strategy for the prevention of insulin resistance and T2DM.MethodsCell-free α-amylase and α-glucosidase enzyme assays were used to determine inhibitory potential of extracts. Glucose uptake was examined in differentiated human adipocytes using radiolabeled 2-deoxyglucose. Male Sprague Dawley rats were divided and glycemia balanced into 5 groups: two controls (naïve and model) and three doses of the botanical test formula containing standardized fenugreek seed, mulberry leaf and American ginseng extracts (42.33, 84.66 and 169.33 mg/kg BW). Insulin resistance and T2DM was induced by feeding animals a high fat diet and with an alloxan injection. Glucose tolerance was examined by measuring serum glucose levels following an oral glucose load.ResultsFenugreek seed and mulberry leaf dose dependently inhibited α-amylase (IC50 = 73.2 μg/mL) and α-glucosidase (IC50 = 111.8 ng/mL), respectively. All three botanical extracts improved insulin sensitivity and glucose uptake in human adipocytes, which lead to the design of an optimized botanical test formula. In a rat model of insulin resistance and T2DM, the optimized botanical test formula improved fasting serum glucose levels, fasting insulin resistance and the development of impaired glucose tolerance. The reduction in epididymal adipose tissue GLUT4 and PDK1 expression induced by high fat diet and alloxan was blunted by the botanical test formula.ConclusionsA novel botanical formula containing standardized extracts of mulberry leaf, fenugreek seed and American ginseng at a ratio of 1:1.3:3.4 prevented the development of insulin resistance, impaired glucose tolerance and T2DM. Given the rising need for effective non-drug targeting of insulin resistance and progression to T2DM, complementary and alternative nutritional strategies without intolerable side effects could have meaningful impact on metabolic health and diabetes risks.

Role of Vitamin D on glycemic control and oxidative stress in type 2 diabetes mellitus.

Background:Vitamin D deficiency may play a key role in the development of impaired glucose tolerance, type 2 diabetes mellitus (T2DM), and metabolic syndrome. Several studies have shown that Vitamin D has an antioxidant property. We aimed to investigate 25-hydroxy Vitamin D (25[OH]D) levels in patients with T2DM and in nondiabetic healthy controls and to ascertain the impact of 25(OH)D levels on glycemic control and oxidative stress in T2DM patients.Materials and Methods:Thirty male patients with T2DM and twenty age- and socioeconomic status-matched male healthy controls were included in the study. Fasting and postprandial blood sugar and glycated hemoglobin (HbA1c) were measured. Enzyme activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) was determined by spectrophotometric assay, and serum levels of 25(OH)D were measured using radioimmunoassay.Results:Serum Vitamin D levels were significantly lower in patients with T2DM than healthy controls (P = 0.015). There was a significantly lower GPx activity in patients with T2DM than controls (P = 0.048), but the difference in SOD activity did not reach statistical significance. There was a significant negative correlation between serum Vitamin D levels and HbA1c (P = 0.016), but no statistical correlation was shown between serum Vitamin D levels and GPx and SOD.Conclusion:We conclude that low level of Vitamin D might play a significant role in T2DM pathogenesis. Hence, Vitamin D supplementation may improve glycemic control and oxidative stress in T2DM.

Occurrence of Diabetes Mellitus in Obese Nondiabetic Patients, with Correlative Analysis of Visceral Fat, Fasting Insulin, and Insulin Resistance: A 3-year Follow-up Study (Mysore Visceral Adiposity in Diabetes Follow-up Study).

Objective:To assess the occurrence of diabetes in obese nondiabetic patients over a 3-year follow-up period with a correlative analysis of visceral fat (VF), fasting insulin levels, (FILs) and insulin resistance (IR).Material and Methods:Thirty-seven obese and nineteen nonobese nondiabetics of our previous study, Mysore Visceral Adiposity in Diabetes were followed for the next 3 years. Their blood pressure, body mass index, waist circumference (WC), fasting blood sugar (FBS), FIL, lipid profile and subcutaneous fat (SCF), and VF measurement by US method were repeated every 6 months for the next 3 years. The findings were analyzed with appropriate statistical methods.Results:Twenty-three obese and 18 nonobese nondiabetics completed the study. There were 17 dropouts. The changes in the physical and biochemical characteristics of the two groups before and after the study were not significant. SCF had no correlation with IR whereas VF correlated with FIL and IR. There were three diabetics in the obese group and two from the control group at the end of the study. There were 12 impaired glucose tolerance (IGT) in the test group and 2 in the control group. Those who developed diabetes had higher VF, WC, FBS, FIL, and IR. Those who showed IGT also had these at higher levels compared to others. There was no change in the VF at the end of the study.Conclusions:This follow-up study on South Indians has shown that VF is a significant risk factor for the development of IR. IR can develop without any increase in the volume of the VF, is the essential finding of this study. SCF has not shown any significant relationship with IR. We recommend FBS and FIL in all the obese nondiabetics to calculate IR, which has given much insight in the development of IGT and diabetes. Large multicentric, longitudinal studies are required to establish the cause of IR.