Influencing factors of glycemic control in singleton pregnancies complicated by gestational diabetes mellitus in western China: A retrospective study.

To investigate the factors influencing glycemic control in gestational diabetes mellitus (GDM) patients and their impacts on pregnancy outcomes, providing insights for GDM management. Pregnant women diagnosed with GDM at a tertiary hospital in western China in 2019. Participants were categorized based on varying levels of glycemic control during pregnancy. A retrospective analysis was conducted, utilizing univariate and multivariate regression analyses, to identify factors influencing glycemic control in GDM patients. Based on various approaches to manage glucose, subjects were categorized into A1 (diet and exercise guidance alone) and A2 (insulin usage) groups. Based on whether glucose levels met the glycemic target in women with GDM, subjects were further divided into satisfactory and unsatisfactory groups. A total of 2621 women meeting the inclusion criteria were enrolled in the study. Independent factors associated with GDM A2 included higher prepregnancy body mass index (odds ratio [OR] = 1.070, 95% confidence interval [CI]: 1.019-1.122, P = .006), a history of GDM (OR = 1.888, 95% CI: 1.052-3.389, P = .033), elevated fasting plasma glucose (FPG) in early pregnancy (OR = 1.828, 95% CI: 1.320-2.532, P < .001), elevated 1-hour postprandial glucose (1-h PG) (OR = 1.126, 95% CI: 1.0091.256, P = .034), and 2-h PG by oral glucose tolerance test (OGTT) (OR = 1.181, 95% CI: 1.046-1.333, P = .007). Higher FPG by OGTT was an independent risk factor for unsatisfactory glycemic control (OR = 1.590, 95% CI: 1.273-1.985, P < .001). Compared with the A1 group, the A2 group has longer hospitalization, higher rates of cesarean section, placenta previa, and neonatal pneumonia (P < .05). Compared with the satisfactory group, the unsatisfactory group has lower gestational age, lower rates of cesarean section and placenta previa, and higher rates of postpartum hemorrhage for mothers; lower length and weight, and higher rates of premature birth, jaundice, hypoglycemia, pneumonia, respiratory distress syndrome, anemia, hospitalization, and hospitalization for more than 15 days in both pediatric unit and neonatal intensive care unit for newborns (P < .05). Elevated prepregnancy body mass index, FPG in early pregnancy, 1-h and 2-h PG during OGTT, and with a history with GDM are independent factors influencing insulin utilization, while elevated 0-h PG is an independent influencing factor of unsatisfactory glycemic control. Poor glycemic control has negative impacts on both maternal and fetal outcomes under 2 classifications.

Maternal glucose homeostasis during pregnancy in women with overweight or obesity and offspring metabolic health.

Gestational diabetes mellitus (GDM) adversely affects offspring glucose homeostasis and risk of developing obesity. Here, we examined the association between glycemia in pregnant women with overweight or obesity without GDM and offspring metabolic health. Maternal fasting glucose concentrations and glucose 2-h after an oral glucose tolerance test (OGTT) were measured in 208 women with a pre-pregnancy body mass index (BMI) of 28-45 kg/m2 without GDM. Offspring outcomes were collected at birth, 3, and 5 years of age. Linear mixed models with time as fixed factor and subject ID as random effects were used for analysis. No associations were found between maternal fasting or 2-h glucose concentrations with offspring glucose and insulin concentrations from birth to 5 years of age. However, maternal fasting glucose in GW 28 and 36, and 2-h OGTT glucose in GW 28 were positively associated with C-peptide concentration at birth. Maternal fasting glucose concentrations in GW 28 and 36 were positively associated with weight-for-length, and maternal fasting glucose in GW 36 was associated with BMI z-score at birth. In summary, blood glucose in pregnant women with overweight or obesity is positively associated with offspring C-peptide concentration, weight-for-length, and BMI z-score at birth, even in the absence of GDM.

The impact of glycosylated hemoglobin and 75-g oral glucose tolerance test glucose levels on birthweight percentile.

OBJECTIVE: Our research objective was to validate and contribute further evidence to the studies regarding large for gestational age and birthweight percentile by examining oral glucose tolerance test and glycosylated hemoglobin levels in both healthy women and those with gestational diabetes mellitus. METHODS: This retrospective cohort study was conducted at a tertiary care hospital involving 106 women who delivered at gestational week 36 or later between February 2022 and February 2023. Maternal, obstetric, and neonatal data were collected from the participant's medical records. Large for gestational age and non-large for gestational age groups were compared. Correlation analysis was used to determine associations among oral glucose tolerance test, glycosylated hemoglobin levels, and the birthweight percentile. RESULTS: Mothers of neonates in the large for gestational age category had higher body mass indexes before pregnancy (p=0.002) and delivery (p=0.003), as well as a higher incidence of gestational diabetes mellitus (p=0.027). Mothers of male large for gestational age infants had higher fasting plasma glucose and glycosylated hemoglobin levels compared to male non-large for gestational age infants (p=0.007 and p=0.004, respectively). There was a weak positive correlation between fasting plasma glucose levels and birthweight percentile in the overall group (r=0.342, p<0.006). Further analysis by gender showed a weak positive correlation between birthweight percentile and fasting plasma glucose and glycosylated hemoglobin values in male newborns (r=0.393, p=0.004 and r=0.373, p=0.006, respectively). CONCLUSION: Our study has established a clear association between the birthweight percentile in male infants and the levels of glycosylated hemoglobin and fasting plasma glucose measured during oral glucose tolerance test. It is imperative to devise potential strategies aimed at achieving optimal glycosylated hemoglobin and fasting plasma glucose parameters to effectively reduce the frequency of large for gestational age in male infants.

Risk factors for cardiometabolic health in Ghana: Cardiometabolic Risks Study Protocol-APTI Project.

Introduction: Cardiometabolic diseases are rapidly becoming primary causes of death in developing countries, including Ghana. However, risk factors for these diseases, including obesity phenotype, and availability of cost-effective diagnostic criteria are poorly documented in an African-ancestry populations in their native locations. The extent to which the environment, occupation, geography, stress, and sleep habits contribute to the development of Cardiometabolic disorders should be examined. Purpose: The overall goal of this study is to determine the prevalence of undiagnosed diabetes, prediabetes, and associated cardiovascular risks using a multi-sampled oral glucose tolerance test. The study will also investigate the phenotype and ocular characteristics of diabetes and prediabetes subgroups, as well as determine if lifestyle changes over a one-year period will impact the progression of diabetes and prediabetes. Methods and analysis: The study employs a community-based quasi-experimental design, making use of pre- and post-intervention data, as well as a questionnaire survey of 1200 individuals residing in the Cape Coast metropolis to ascertain the prevalence and risk factors for undiagnosed diabetes and prediabetes. Physical activity, dietary habits, stress levels, sleep patterns, body image perception, and demographic characteristics will be assessed. Glucose dysregulation will be detected using oral glucose tolerance test, fasting plasma glucose, and glycated hemoglobin. Liver and kidney function will also be assessed. Diabetes and prediabetes will be classified using the American Diabetes Association criteria. Descriptive statistics, including percentages, will be used to determine the prevalence of undiagnosed diabetes and cardiovascular risks. Inferential statistics, including ANOVA, t-tests, chi-square tests, ROC curves, logistic regression, and linear mixed model regression will be used to analyze the phenotypic variations in the population, ocular characteristics, glycemic levels, sensitivity levels of diagnostic tests, etiological cause of diabetes in the population, and effects of lifestyle modifications, respectively. Additionally, t-tests will be used to assess changes in glucose regulation biomarkers after lifestyle modifications. Ethics and dissemination: Ethics approval was granted by the Institutional Review Board of the University of Cape Coast, Ghana (UCCIRB/EXT/2022/27). The findings will be disseminated in community workshops, online learning platforms, academic conferences and submitted to peer-reviewed journals for publication.

The Intake of Dietary Lipids Improves Glucose Tolerance via Modulating Gut Microbiota.

The composition of gut microbiota is determined not only by genetic factors but also by environmental factors, such as diet, exercise, and disease conditions. Among these factors, diet is crucial in changing the gut microbial composition. Dietary lipids composed of different fatty acids not only alter host metabolism but also have a significant impact on the composition of gut microbiota. However, the molecular mechanisms underlying the relationship between these host effects and their impact on gut microbiota remain unclear. Here, we demonstrated that intake of different dietary lipids improved glucose tolerance by modulating gut microbiota. The results of our analysis show that the taxa of bacteria that increase in number as a result of dietary lipid intake play an important role in glucose metabolism. Thus, we have identified a new mechanism underlying the function of dietary lipids in regulating glucose homeostasis. Our findings contribute to possible new methods to prevent and treat metabolic disorders by modifying the composition of gut microbiota.

Structured diabetes care routines in cardiac rehabilitation are associated with increased diabetes detection and improved treatment after myocardial infarction: a nationwide observational study.

BACKGROUND: Despite the detrimental impact of abnormal glucose metabolism on cardiovascular prognosis after myocardial infarction (MI), diabetes is both underdiagnosed and undertreated. We investigated associations between structured diabetes care routines in cardiac rehabilitation (CR) and detection and treatment of diabetes at one-year post-MI. METHODS: Center-level data was derived from the Perfect-CR survey, which evaluated work routines applied at Swedish CR centers (n = 76). Work routines involving diabetes care included: (1) routine assessment of fasting glucose and/or HbA1c, (2) routine use of oral glucose tolerance test (OGTT), (3) having regular case rounds with diabetologists, and (4) whether glucose-lowering medication was adjusted by CR physicians. Patient-level data was obtained from the national MI registry SWEDEHEART (n = 7601, 76% male, mean age 62.6 years) and included all post-MI patients irrespective of diabetes diagnosis. Using mixed-effects regression we estimated differences between patients exposed versus. not exposed to the four above-mentioned diabetes care routines. Outcomes were newly detected diabetes and the proportion of patients receiving oral glucose-lowering medication at one-year post-MI. RESULTS: Routine assessment of fasting glucose/HbA1c was performed at 63.2% (n = 48) of the centers, while 38.2% (n = 29) reported using OGTT for detecting glucose abnormalities. Glucose-lowering medication adjusted by CR physicians (n = 13, 17.1%) or regular case rounds with diabetologists (n = 7, 9.2%) were less frequently reported. In total, 4.0% of all patients (n = 304) were diagnosed with diabetes during follow-up and 17.9% (n = 1361) were on oral glucose-lowering treatment one-year post-MI. Routine use of OGTT was associated with a higher rate of newly detected diabetes at one-year (risk ratio [95% confidence interval]: 1.62 [1.26, 1.98], p = 0.0007). At one-year a higher proportion of patients were receiving oral glucose-lowering medication at centers using OGTT (1.22 [1.07, 1.37], p = 0.0046) and where such medication was adjusted by CR physicians (1.31 [1.06, 1.56], p = 0.0155). Compared to having none of the structured diabetes care routines, the more routines implemented the higher the rate of newly detected diabetes (from 0 routines: 2.7% to 4 routines: 6.3%; p for trend = 0.0014). CONCLUSIONS: Having structured routines for diabetes care implemented within CR can improve detection and treatment of diabetes post-MI. A cluster-randomized trial is warranted to ascertain causality.

Preserving insulin function in diabetes: a case report.

BACKGROUND: This case report explores the long-term dynamics of insulin secretion and glycemic control in two patients with diabetes mellitus type 2 over 20 years. The observations underscore the impact of lifestyle interventions, including weight loss and calorie restriction, on insulin secretion patterns and glucose levels during 75 g oral glucose tolerance tests. Additionally, the role of hemoglobin A1c fluctuations, influenced by various factors such as body weight, exercise, and pharmacological interventions, is investigated. CASE PRESENTATION: Case 1 involves a Japanese woman now in her late 70s who successfully maintained her hemoglobin A1c below 7% for over two decades through sustained weight loss and lifestyle changes. Despite a gradual decline in the homeostasis model assessment of ß cell function, the patient exhibited remarkable preservation of insulin secretion patterns over the 20-year follow-up. In case 2, a Japanese woman, now in her early 70s, experienced an improvement in hemoglobin A1c to 6.3% after a period of calorie limitation due to a wrist fracture in 2018. This incident seemed to trigger a temporary rescue of pancreatic ß cell function, emphasizing the dynamic nature of insulin secretion. Both cases highlight the potential for pancreatic ß cell rescue and underscore the persistence of insulin secretion over the 20-year follow-up. Additionally, we have briefly discussed three additional cases with follow-ups ranging from 10 to 17 years, demonstrating similar trends in glucose and insulin ratios. CONCLUSIONS: Long-term lifestyle interventions, such as weight loss and calorie restriction, can preserve pancreatic ß cell function and maintain glycemic control in type 2 diabetes patients over 20 years. Two patients showed stable or improved insulin secretion and favorable hemoglobin A1c levels, challenging the traditional view of irreversible ß cell decline. The findings highlight the importance of personalized, nonpharmacological approaches, suggesting that sustained lifestyle changes can significantly impact diabetes management and potentially rescue ß cell function.

Analytical Performance of the FreeStyle Libre 2 Glucose Sensor in Healthy Male Adults.

Continuous Glucose Monitoring (CGM) not only can be used for glycemic control in chronic diseases (e.g., diabetes), but is increasingly being utilized by individuals and athletes to monitor fluctuations in training and everyday life. However, it is not clear how accurately CGM reflects plasma glucose concentration in a healthy population in the absence of chronic diseases. In an oral glucose tolerance test (OGTT) with forty-four healthy male subjects (25.5 ± 4.5 years), the interstitial fluid glucose (ISFG) concentration obtained by a CGM sensor was compared against finger-prick capillary plasma glucose (CPG) concentration at fasting baseline (T0) and 30 (T30), 60 (T60), 90 (T90), and 120 (T120) min post OGTT to investigate differences in measurement accuracy. The overall mean absolute relative difference (MARD) was 12.9% (95%-CI: 11.8-14.0%). Approximately 100% of the ISFG values were within zones A and B in the Consensus Error Grid, indicating clinical accuracy. A paired t-test revealed statistically significant differences between CPG and ISFG at all time points (T0: 97.3 mg/dL vs. 89.7 mg/dL, T30: 159.9 mg/dL vs. 144.3 mg/dL, T60: 134.8 mg/dL vs. 126.2 mg/dL, T90: 113.7 mg/dL vs. 99.3 mg/dL, and T120: 91.8 mg/dL vs. 82.6 mg/dL; p < 0.001) with medium to large effect sizes (d = 0.57-1.02) and with ISFG systematically under-reporting the reference system CPG. CGM sensors provide a convenient and reliable method for monitoring blood glucose in the everyday lives of healthy adults. Nonetheless, their use in clinical settings wherein implications are drawn from CGM readings should be handled carefully.

Optimal fasting duration for mice as assessed by metabolic status.

In the study of obesity and diabetes, mice are widely used for experimental research, and fasting is a common procedure used to reset metabolism in mouse models. The fasting duration for experimental mice varies greatly in nutritional and metabolic studies, ranging from 2 to 48 h. This study aims to assess the optimal fasting duration for mice fed low- and high-fat diets over a short period of time. C57BL/6J mice were fed a low-fat diet (LFD) or high-fat diet (HFD) and fasted for 4, 6, 8, 10, 12, or 24 h. The effects of different conditions after fasting on the metabolic level of mice were explored, and the data were collected for analysis. Our data indicate that fasting has inconsistent effects on mice fed a low-fat or high-fat diet. To compare the metabolic differences between mice in different dietary levels and thereby secure better scientific data, mice should fast for 6 h in animal experiments. Fasting for 6 h is also recommended when comparing glucose tolerance with insulin tolerance.

Diabetes screening among women with polycystic ovary syndrome: a descriptive study of commercial claims, 2011-2019.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a hormonal disorder that affects 6-12% of United States women of reproductive age. Because women with PCOS are at an increased risk of developing type 2 diabetes, clinical practice guidelines from a number of organizations (e.g. American Diabetes Association, American College of Obstetricians and Gynecologists, US Preventive Services Task Force) recommend that individuals with PCOS are routinely screened for diabetes. Guidelines further indicate that an oral glucose tolerance test (OGTT) should be used for diabetes screening in women with PCOS as opposed to an A1C or fasting plasma glucose test. The purpose of this study is two-fold: 1) to estimate rates of diabetes screening among a nationwide sample of commercially insured women with PCOS and 2) to report the percentage of women screened using each test (OGTT, A1C, fasting plasma glucose) among those who were screened. METHODS: We used the MarketScan Commercial Claims database (2011-2019) to identify a sample of women aged 18-64 years with PCOS who were free from diabetes at baseline and had ≥ 5 years of continuous enrollment in their insurance plan. PCOS was ascertained using International Classification of Disease diagnosis codes (ICD-9: 256.4; ICD-10: E28.2). Diabetes screening was ascertained using Current Procedural Terminology (CPT) codes (A1C: 8303683037; Fasting blood sugar: 82947; OGTT: 82950). Diabetes screening rates were calculated for the overall study sample as well as across subgroups defined by age, overweight/obesity, hypertension, hypercholesterolemia, and vascular disease. RESULTS: In our sample of 191,110 commercially insured women with PCOS, 73.40% were screened at least once for diabetes during a five-year period. Among the women screened, 19.24% were screened using the Androgen Excess Society (AES)-recommended OGTT, 61.58% were screened using A1C, and 23.37% were screened using fasting blood sugar. CONCLUSIONS: In a sample of commercially insured individuals spanning the timeframe 2011-2019, nearly 75% of women with PCOS complied with the ACOG screening guidelines for diabetes. Although OGTT is recommended as the preferred screening tool for women with PCOS it was less commonly used than A1C and fasting blood sugar tests.

Glycemic status and effect on mortality: Multifactorial prevention programme for cardiovascular disease in Finnish primary care.

AIMS: To compare 13-year mortality rates in normoglycemic, prediabetic and diabetic subjects attending a community-based screening and intervention programme. METHODS: Population survey identified 2569 cardiovascular disease (CVD) white risk subjects aged 45-70 years and without manifested CVD or diabetes. Oral glucose tolerance test was performed, and multifactorial intervention was provided. Effect of glycemic status on mortality was estimated in models adjusted for age, gender, education years, smoking, body mass index, mean arterial pressure, total cholesterol, and physical activity. RESULTS: Of the subjects, 2055 (77 %) were normoglycemic, 380 (14 %) had prediabetes and 224 (9 %) diabetes. Compared to the normoglycemic group, the fully adjusted hazard ratios (HR) for all-cause mortality were 1.34 (95 % CI: 0.98-1.83) in the prediabetes group and 2.31 (95 % CI: 1.62-3.31) in the diabetes group. Standardized mortality rates were 0.63 (95 % CI: 0.54-0.73), 0.91 (95 % CI: 0.69-1.18), and 1.55 (95 % CI: 1.19-2.02) in the normoglycemic, prediabetes, and diabetes groups, respectively. The most common cause of death was cancer (42 % of all deaths), followed by CVD (28 %). CONCLUSIONS/INTERPRETATION: Screen-detected diabetes carries a substantial risk of death even after primary care intervention. The pattern of excess mortality has shifted towards cancer deaths.

Long-term Metabolic Dysfunction Programming in Female Mice by Serial Moderate Restriction of a High-fat High-sucrose Diet.

BACKGROUND: While intermittent fasting leads to weight loss and improved glucose metabolism, food insecurity, the insufficient access to food for a healthy life, is associated with obesity and adverse cardiometabolic health, especially in women. We aimed to characterize the effects of intermittently restricted feeding on energy balance and glucose tolerance in female mice. METHODS: Female C57BL/6J mice were fed a high-fat, high-sucrose diet and intermittently food restricted to 60% of control littermates' ad libitum intake, starting at weaning and until week 19. Restricted mice were subsequently allowed ad libitum access to the same diet. Body composition and energy balance were measured at weeks 18.5, 19, 30, and 40. At week 42, mice underwent an intraperitoneal glucose tolerance test and plasma appetitive hormones measurements after nutrient gavage. RESULTS: During the food restriction phase, restricted mice accrued lower weight and fat mass than controls despite periodic ad libitum food access. Reintroduction of continuous ad libitum food caused increased food intake during the light phase and increased body mass in restricted mice. Minor differences in body composition-adjusted energy expenditure between groups were observed at week 40. At week 42, glucose tolerance was impaired in restricted mice compared to controls, and trends toward lower levels of postprandial anorexigenic hormones glucagon-like peptide-1 and pancreatic polypeptide were observed. CONCLUSION: Our findings suggest that repeated intermittent food restriction leads to changes in eating behavior that predispose to glucose intolerance when food is freely available. Future studies are needed to elucidate the specific mechanisms underlying these changes.

Probing erythrocytes as sensitive and reliable sensors of metabolic disturbances in the crosstalk between childhood obesity and insulin resistance: findings from an observational study, in vivo challenge tests, and ex vivo incubation assays.

BACKGROUND: Although insulin resistance (IR) is among the most frequent and pathogenically relevant complications accompanying childhood obesity, its role in modulating and exacerbating obesity pathophysiology has not yet been completely clarified. METHODS: To get deeper insights into the interplay between childhood obesity and IR, we leveraged a comprehensive experimental design based on a combination of observational data, in vivo challenge tests (i.e., oral glucose tolerance test), and ex vivo assays (i.e., incubation of erythrocytes with insulin) using a population comprising children with obesity and IR, children with obesity without IR, and healthy controls, from whom plasma and erythrocyte samples were collected for subsequent metabolomics analysis. RESULTS: Children with concomitant IR showed exacerbated metabolic disturbances in the crosstalk between endogenous, microbial, and environmental determinants, including failures in energy homeostasis, amino acid metabolism, oxidative stress, synthesis of steroid hormones and bile acids, membrane lipid composition, as well as differences in exposome-related metabolites associated with diet, exposure to endocrine disruptors, and gut microbiota. Furthermore, challenge tests and ex vivo assays revealed a deleterious impact of IR on individuals' metabolic flexibility, as reflected in blunted capacity to regulate homeostasis in response to hyperinsulinemia, at both systemic and erythroid levels. CONCLUSIONS: Thus, we have demonstrated for the first time that metabolite alterations in erythrocytes represent reliable and sensitive biomarkers to disentangle the metabolic complexity of IR and childhood obesity. This study emphasizes the crucial need of addressing inter-individual variability factors, such as the presence of comorbidities, to obtain a more accurate understanding of obesity-related molecular mechanisms.

Higher fasting glucose is associated with poorer survival in non-diabetic subjects having ischemia with non-obstructive coronary arteries.

Subjects who have ischemia with non-obstructive coronary arteries (INOCA) experience angina pectoris with evidence of myocardial ischemia but without coronary stenosis. Few studies have investigated factors associated with its survival, especially insulin resistance. In this study, subjects with angina pectoris, without known diabetes mellites (DM), and with non-invasive tests showing myocardial ischemia were admitted for coronary angiography (CAG). Those whose CAG did not reveal stenosis and agreed to receive an oral glucose tolerance test (OGTT) 2 weeks after hospital discharge were enrolled for analysis. All-cause mortality was recorded, which served as the outcome of the study. A total of 587 subjects with INOCA, without known DM, and with OGTT data were analyzed. After OGTT and HbA1c tests, 86 subjects (14.7%) were newly diagnosed with DM and 59.8% had pre-DM. The median duration of follow-up was 7.03 years. Thirty-nine subjects died during the follow-up period. The incidence rate of mortality was 9.9 /1000 person-year. Those who died had a higher fasting glucose (101 ± 17 vs. 94 ± 13 mg/dl, p = 0.003) but a lower estimated glomerular filtration rate (eGFR) (54 ± 22 vs. 87 ± 30 ml/min, p < 0.001). In the Cox survival analysis, a higher fasting glucose (hazard ratio 1.053, p = 0.007) was associated with worse mortality for INOCA without DM (N = 501). On the contrary, a higher eGFR (hazard ratio 0.967, p = 0.012) was protective of better survival for non-diabetic INOCA (N = 501). In conclusion, for non-diabetic INOCA, higher fasting glucose was associated with worse mortality and higher eGFR was protective for better survival.

Mice lacking ASIC2 and ßENaC are protected from high-fat-diet-induced metabolic syndrome.

Introduction: Degenerin proteins, such as ßENaC and ASIC2, have been implicated in cardiovascular function. However, their role in metabolic syndrome have not been studied. To begin to assess this interaction, we evaluated the impact of a high fat diet (HFD) on mice lacking normal levels of ASIC2 (ASIC2-/-) and ßENaC (ßENaCm/m). Methods: Twenty-week-old male and female mice were placed on a 60% HFD for 12 weeks. Body weight was measured weekly, and body composition by non-invasive ECHO MRI and fasting blood glucose were measured at 0, 4, 8 and 12 weeks. A glucose tolerance test was administered after 12 weeks. Differences between ASIC2-/-/ßENaCm/m and WT groups were compared using independent t-tests or ANOVA where appropriate within each sex. Data are presented as mean ± SEM and ASIC2-/-/ßENaCm/m vs. WT. Results: At 20 weeks of age, ASIC2-/-/ßENaCm/m mice (n=9F/10M) weighed less and gained less weight than WT (n=12F/16M). Total body fat and lean body masses were reduced in female and male ASIC2-/-/ßENaCm/m mice. Total body fat and lean body masses as % control were identical at the end of 12 weeks. Fasting blood glucoses were lower in female and male ASIC2-/-/ßENaCm/m vs. WT mice after 12 weeks HFD. The area under the curve for the glucose tolerance test was reduced in female and tended (p=.079) to decrease in male ASIC2-/-/ßENaCm/m. Plasma leptin and insulin were reduced in female and male ASIC2-/-/ßENaCm/m vs. WT mice. Plasma insulin in female ASIC2-/-/ßENaCm/m mice remained unchanged throughout the HFD period. Liver and liver fat masses, as well as percent liver fat, were reduced in both female and male ASIC2-/-/ßENaCm/m mice after HFD. Plasma triglycerides, cholesterol, LDL- and HDL-cholesterols were markedly improved in male and/or female ASIC2-/-/ßENaCm/m following the HFD. Discussion: These novel findings suggest that loss of ASIC2 and ßENaC offer a significant protection against HFD-induced metabolic syndrome.

A comparative study of the relationship between time in range assessed by self-monitoring of blood glucose and continuous glucose monitoring with microalbuminuria outcome, HOMA-IR and HOMA-ß test.

AIMS: To compare the time in range (TIR) obtained from self-monitoring of blood glucose (SMBG) with that obtained from continuous glucose monitoring (CGM), and explore the relationship of TIR with microalbuminuria outcome, HOMA-IR and HOMA-ß test. METHODS: We recruited 400 patients with type 2 diabetes to carry out blood glucose monitoring by both SMBG and CGM for 3 consecutive days. TIR, TAR, TBR and other blood glucose variation indices were calculated respectively through the glucose data achieved from SMBG and CGM. The HOMA-IR and HOMA-ß test was evaluated by an oral glucose tolerance test. Urinary microalbumin-to-creatinine ratio completed in the laboratory. RESULTS: The median (25 %, 75 % quartile) of TIRCGM and TIRSMBG were 74.94(44.90, 88.04) and 70.83(46.88, 87.50) respectively, and there was no significant difference, p = 0.489; For every 1 % increase in TIRCGM, the risk of microalbuminuria decreased by 1.6 % (95%CI:0.973, 0.995, p = 0.006) and for every 1 % increase in TIRSMBG, the risk of microalbuminuria decreased by 1.3 % (95%CI:0.975, 0.999, p = 0.033). Stepwise multiple linear regression analysis showed an independent positive correlation between TIR (including TIRCGM and TIRSBMG) and LnDI30 and LnDI120 levels (p = 0.000). CONCLUSIONS: The TIR calculated by SMBG was highly consistent with that reported by CGM and was significantly associated with the risk of microalbuminuria and the HOMA-ß. Higher TIR quartiles were associated with lower incidence of microalbuminuria as well as higher lever of HOMA-ß. For patients with limited CGM application, SMBG-derived TIR may be an alternative to CGM-derived TIR, to assess blood glucose control.

Effect of dietary myo-inositol supplementation on the insulin resistance and the prevention of gestational diabetes mellitus: an open-label, randomized controlled trial.

PURPOSE: Myo-inositol (MI) is an insulin-sensitizing dietary supplement, enhancing the transfer of glucose into the cell. Gestational diabetes mellitus (GDM) is characterized by abnormal glucose tolerance, which is associated with elevated insulin resistance. The present study aimed to assess the effect of MI supplementation during pregnancy on the incidence of GDM. METHODS: We performed a single-center, open-label, randomized controlled trial. A cohort of 200 pregnant women at 11-13+6 weeks of gestation were randomly assigned in two groups: MI group (n = 100) and control group (n = 100). The MI group received MI and folic acid (4000 mg MI and 400 mcg folic acid daily), while the control group received folic acid alone (400 mcg folic acid daily) until 26-28 weeks of gestation, when the 75 g Oral Glucose Tolerance Test (OGTT) was performed for the diagnosis of GDM. Clinical and metabolic outcomes were assessed. RESULTS: The incidence of GDM was significantly higher in the MI group (14.9%) compared to the control group (28.5%) (P = 0.024). Women treated with MI had significantly lower OGTT glucose values, than those not treated with MI (P < 0.001). The insulin resistance as assessed by HOMA-IR was significantly lower in the MI group versus control (P = 0.045). Furthermore, MI group had significantly higher insulin sensitivity as measured by the Matsuda Index, compared to the control group (P = 0.037). CONCLUSION: MI supplementation seems to be an effective option to improve the glycemic control of pregnant women and prevent the onset of GDM. TRIAL REGISTRATION: ISRCTN registry: ISRCTN16142533. Registered 09 March 2017.

ß-cell function and long-term glycemic control in patients newly diagnosed with type 2 diabetes with moderate hyperglycemia after a 6-month course of basal insulin therapy.

AIMS: To evaluate whether treatment with insulin is advantageous compared with oral anti-diabetic drugs (OAD) for patients newly diagnosed with type 2 diabetes with moderate hyperglycemia. METHODS: Patients newly diagnosed with type 2 diabetes with moderate hyperglycemia were recruited and randomized to receive insulin, metformin or sitagliptin treatment. The oral glucose tolerance test (OGTT) was performed before treatment and 6 months thereafter. The primary outcome was the glycohemoglobin (HbA1c) level change. For the secondary efficacy analysis, the ß-cell function and insulin sensitivity were calculated from the OGTT, as was the proportion of subjects who reached the treatment target (HbA1c level < 7.0 % or < 6.5 %) at 6 months. RESULTS: We randomized 50 patients to the three groups and 32 patients who received the allocated treatment were analyzed. The change of HbA1c level in the insulin, metformin, and sitagliptin groups was - 2.06 ± 1.37 %, -0.43 ± 0.32 %, and - 1.62 ± 0.92 %, respectively. This change was smallest in the metformin group. There was no significant difference in the changes or final HbA1c levels between the insulin and sitagliptin groups. The treat-to-target (HbA1c level < 7.0 %) rates in the insulin, metformin and sitagliptin were 75 %, 50 % and 100 %, respectively. The treat-to-target rates were not significantly different among the three groups. The insulin secretion indices, including the Matsuda index and HOMA-IR, indicated that the groups did not differ after 6 months of therapy. CONCLUSION: A 6-month course of basal insulin therapy did not benefit patients newly diagnosed with diabetes with moderate hyperglycemia in terms of insulin sensitivity or insulin secretion.

Identifying metabotypes of insulin resistance severity in children with metabolic syndrome.

BACKGROUND: Insulin resistance is a frequent precursor of typical obesity and metabolic syndrome complications. However, accurate diagnosis remains elusive because of its pathophysiological complexity and heterogeneity. Herein, we have explored the utility of insulin secretion dynamics in response to an oral glucose tolerance test as a surrogate marker to identify distinct metabotypes of disease severity. METHODS: The study population consisted of children with obesity and insulin resistance, stratified according to the post-challenge insulin peak timing (i.e., early, middle, and late peak), from whom fasting and postprandial plasma and erythrocytes were collected for metabolomics analysis. RESULTS: Children with late insulin peak manifested worse cardiometabolic health (i.e., higher blood pressure, glycemia, and HOMA-IR scores) than early responders. These subjects also showed more pronounced changes in metabolites mirroring failures in energy homeostasis, oxidative stress, metabolism of cholesterol and phospholipids, and adherence to unhealthy dietary habits. Furthermore, delayed insulin peak was associated with impaired metabolic flexibility, as reflected in compromised capacity to regulate mitochondrial energy pathways and the antioxidant defense in response to glucose overload. CONCLUSIONS: Altogether, these findings suggest that insulin resistance could encompass several phenotypic subtypes characterized by graded disturbances in distinctive metabolic derangements occurring in childhood obesity, which serve as severity predictive markers.

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

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