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Gestational diabetes (GDM), defined as glucose intolerance during pregnancy, affects one in six pregnancies globally and significantly increases a woman's lifetime risk of type 2 diabetes mellitus (T2DM). Being a relatively young group, women with GDM are also at higher risk of developing diabetes related complications (e.g., cardiovascular disease, non-alcoholic fatty liver disease) later in life. Children of women with GDM are also likely to develop GDM and this perpetuates a cycle of diabetes, escalating our current pandemic of metabolic disease. The global prevalence of GDM has now risen by more than 30% over the last two decades, making it an emerging public health concern. Antepartum management of maternal glucose is unable to fully mitigate the associated lifetime cardiometabolic risk. Thus, efforts may need to focus on improving care for women with GDM during the postpartum period where prevention or therapeutic strategies could be implemented to attenuate progression of GDM to DM and its associated vascular complications. However, strategies to provide care for women in the postpartum period often showed disappointing results. This has led to a missed opportunity to halt the progression of impaired glucose tolerance/impaired fasting glucose to DM in women with GDM. In this review, we examined the challenges in the management of women with GDM after delivery and considered how each of these challenges are defined and could present as a gap in translating evidence to clinical care. We highlighted challenges related to postpartum surveillance, postpartum glucose testing strategies, postpartum risk factor modification, and problems encountered in engagement of patients/providers to implement interventions strategies in women with GDM after delivery. We reasoned that a multisystem approach is needed to address these challenges and to retard progression to DM and cardiovascular disease (CVD) in women with GDM pregnancies. This is very much needed to pave way for an improved, precise, culturally sensitive and wholistic care for women with GDM.

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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.

Asunto(s)

Glucemia , Ayuno , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Femenino , Glucemia/análisis , Glucemia/metabolismo , Persona de Mediana Edad , Ayuno/sangre , Anciano , Isquemia Miocárdica/mortalidad , Isquemia Miocárdica/sangre , Angiografía Coronaria , Vasos Coronarios/patología , Vasos Coronarios/metabolismo , Tasa de Filtración Glomerular , Diabetes Mellitus/mortalidad , Resistencia a la Insulina

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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.

Asunto(s)

Automonitorización de la Glucosa Sanguínea , Glucemia , Humanos , Masculino , Adulto , Glucemia/análisis , Automonitorización de la Glucosa Sanguínea/métodos , Automonitorización de la Glucosa Sanguínea/instrumentación , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Prueba de Tolerancia a la Glucosa/métodos , Adulto Joven , Voluntarios Sanos , Líquido Extracelular/química

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Background: We aimed to explore the still-debated association between smoking and hyperglycaemia in pregnancy (HIP). Methods: A multiethnic prospective study of 15,801 women who delivered at Jean Verdier University Hospital between 2012 and 2018. Of these, 13,943 (88.2%) were non-smokers, 624 (4.5%) former smokers, and 1234 (7.8%) current smokers. Universal HIP screening was proposed to the entire sample (IADPSG/WHO criteria). Results: A total of 13,958 women were screened for HIP. Uptake differed between non-smokers, former smokers, and current smokers (89.5%, 88.3%, and 75.7%, respectively, p < 0.0001). HIP prevalence in these groups was 19.9%, 15.4%, and 12.3%, respectively (p < 0.0001). After adjusting for age, body mass index, family history of diabetes, history of HIP, history of macrosomic baby, and ethnicity, current (odds ratio 0.790 [95% confidence interval 0.636-0.981], p < 0.05) but not former (1.017 [0.792-1.306]) smokers were less likely to have HIP than non-smokers. Furthermore, 1 h and 2 h oral plasma glucose test values were lower in current smokers than in non-smokers (p < 0.01). To exclude potential selection bias, we compared risk factors for HIP and HIP-related adverse pregnancy outcomes in current smokers according to HIP screening status. Compared with screened current smokers (n = 934), their unscreened counterparts (n = 300) were younger, less frequently employed, and more likely to be of non-European origin. Moreover, infant birthweight was lower in this group, and preterm deliveries and perinatal deaths were more likely (all p < 0.01). Conclusions: Smoking during pregnancy was independently associated with lower HIP prevalence. The low HIP screening rate in current smokers did not explain this finding.

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Background: Women who experience gestational diabetes mellitus (GDM) during their first pregnancy are at a high risk of developing GDM again in subsequent pregnancies. Even mothers with no previous history of GDM may develop the condition in a new pregnancy. Methods: In this retrospective cross-sectional observational study, 759 multiparous women tested for GDM in two successive pregnancies using the 75 g OGTT (IADPSG criteria) were enrolled. The OGTT was performed at 24-28 weeks' gestation or earlier if there was a history of GDM. Participants were categorized into four groups: women with normal glucose tolerance (NGT) in both pregnancies (n = 493), women with a first occurrence of GDM in their second pregnancy (n = 74), women with non-recurrent GDM in their second pregnancy (n = 92), and women with recurrent GDM in their second pregnancy (n = 100). Results: Intergroup comparisons revealed clinical predictors of GDM in the first pregnancy (family history of type 2 diabetes, PCOS, advanced maternal age, pregravid obesity) and in the second pregnancy (interpregnancy BMI gain), as well as predictors of recurrent GDM (pregravid obesity, PCOS). A positive correlation was observed between the OGTT glucose levels of consecutive pregnancies. Adjusted logistic regression indicated that a higher 1-h post-load glucose level (≥130 mg/dL) during the first pregnancy significantly increased the likelihood of new-onset GDM in the second pregnancy (OR: 2.496), whereas a higher 2-h post-load glucose level (≥153 mg/dL) at the first diagnostic OGTT increased the likelihood of recurrent GDM (OR: 2.214). Conclusions: Clinical risk factors and post-load glucose levels during the first gestational 75 g OGTT can help predict new-onset or recurrent GDM in multiparous women.

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Childhood obesity, with its metabolic complications, is a problem of public health. The International Diabetes Federation (IDF) has recommended glucose levels 1 h post oral glucose load (1h-PG) > 155-209 mg/dL as diagnostic for intermediate hyperglycemia (IH), while >209 mg/dL for type 2 diabetes (T2D). The aim of the study was to assess the occurrence of prediabetes, IH, and T2D in children and adolescents with simple obesity according to the criteria of American Diabetes Association (ADA) and of IDF, and the effect of COVID-19 pandemic on these disorders. Analysis included 263 children with simple obesity, screened either in prepandemic (PRE-113 cases) or post-pandemic period (POST-150 cases). All children underwent 2 h OGTT with measurements of glucose and insulin every 0.5 h, lipid profile, and other tests; indices if insulin resistance (IR): HOMA, QUICKI, Matsuda index, AUC (glu/ins) were calculated. The incidence of T2D, prediabetes, and IH was higher in POST with respect to PRE, with significant differences in the indices of IR, except for HOMA. Significant differences were observed in the assessed parameters of glucose metabolism among the groups with T2D, prediabetes, IH, and normal glucose tolerance (NGT), with some similarities between IH (based on 1h-PG) and prediabetes. Increased frequency of dysglycemia among children and adolescents with simple obesity is observed after COVID-19 pandemic. Metabolic profile of patients with IH at 1h-PG is "intermediate" between NGT and prediabetes.

Asunto(s)

Glucemia , COVID-19 , Diabetes Mellitus Tipo 2 , Prueba de Tolerancia a la Glucosa , Obesidad Infantil , Estado Prediabético , Humanos , COVID-19/epidemiología , COVID-19/sangre , COVID-19/complicaciones , Niño , Adolescente , Femenino , Masculino , Glucemia/metabolismo , Glucemia/análisis , Estado Prediabético/sangre , Estado Prediabético/epidemiología , Estado Prediabético/diagnóstico , Obesidad Infantil/complicaciones , Obesidad Infantil/sangre , Obesidad Infantil/epidemiología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , SARS-CoV-2 , Hiperglucemia/sangre , Hiperglucemia/epidemiología , Resistencia a la Insulina , Pandemias

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OBJECTIVE: We aimed to evaluate the heterogeneity of gestational diabetes mellitus (GDM) patients diagnosed with various screening criteria. METHODS: We stratified pregnant women using consecutive fasting plasma glucose (FPG) and 2-hour postprandial plasma glucose (2hPPG) intervals of 0.2 mmol/L. The incidence of abnormal neonatal birthweight and birth-related adverse outcomes was compared with that of pregnant women without GDM. RESULTS: The study included 39,988 pregnant women (18-45 years, mean [SD], 31.5 [4.7] years) in Ningbo, China. The means (SDs) of FPG and 2hPPG within 24-28 weeks of gestation were 4.5 (0.5) and 6.8 (1.3) mmol/L, respectively. A total of 3025 (7.6%) women had 5.1-6.9 mmol/L FPG and 4560 (11.4%) had 8.5-11.0 mmol/L 2hPPG. The incidence of GDM according to the two combination criteria was 17.3% (6908 cases). The relative risk (RR) for < 10th percentile birthweight (< 10th WT) was 0.82 (95% CI, 0.74-0.91, p < 0.001) by 5.1 mmol/L FPG criterion and 1.14 (95% CI, 1.06-1.23, p < 0.001) by 8.5 mmol/L 2hPPG criterion, while the RRs for > 90th percentile birthweight (> 90th WT) were 1.48 (95% CI, 1.35-1.63, p < 0.001) and 0.95 (95% CI, 0.86-1.04, p = 0.29) according to the corresponding criteria. The FPG criterion was more strongly associated with maternal hypertension than the 2hPPG criterion. Both criteria did not show a distinct association with other composite adverse outcomes. CONCLUSION: High FPG is significantly associated with high birth weight, whereas high 2hPPG is slightly associated with low birth weight. Our findings highlight the heterogeneity of patients with GDM diagnosed by different criteria.

Asunto(s)

Peso al Nacer , Glucemia , Diabetes Gestacional , Ayuno , Periodo Posprandial , Humanos , Femenino , Diabetes Gestacional/sangre , Diabetes Gestacional/epidemiología , Diabetes Gestacional/diagnóstico , Embarazo , Adulto , Ayuno/sangre , Glucemia/análisis , China/epidemiología , Adulto Joven , Adolescente , Resultado del Embarazo/epidemiología , Recién Nacido , Prueba de Tolerancia a la Glucosa , Persona de Mediana Edad , Incidencia

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AIMS: The gold standard clamp measurements for insulin sensitivity (cSI), ß-cell function (cBCF) and disposition index (cDI = cSI*cBCF), are not practical in large-scale studies. We sought to: 1) validate a mathematical model-derived DI from oral glucose tolerance tests (OGTT) with insulin (mDI) and without (mDI-woI) against cDI and oral disposition index (oDI) evaluate the ability of the novel indices to detect prediabetes and type 2 diabetes. METHODS: We carried out a secondary analysis of previously reported cross-sectional observational studies. The Insulin Sensitivity and Secretion mathematical model for glucose-insulin dynamics was applied to five-point and three-point OGTTs synchronized with hyperinsulinemic-euglycemic and hyperglycemic clamps from 130 youth with obesity (68 NGT, 33 IGT, 29 T2D). RESULTS: Model-derived DI correlated well with clamp DI (R = 0.76 (logged)). Between NGT and IGT, mDI and mDI-woI decreased more than oDI and cDI, (60 and 59% vs 29 and 27%), and by receiver operating characteristic (ROC) analysis were superior at detecting IGT than oDI and cDI (AUC 0.88, 0.87 vs 0.68, 0.65), as was mean glucose (AUC 0.87). CONCLUSIONS: mDI-woI is better than oDI or the labor-intensive cDI for detecting dysglycemia in obese youth. Bypassing insulin measurements with mDI-woI from the OGTT provides a cost-effective approach for large-scale epidemiological studies of dysglycemia in youth.

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OBJECTIVE: This study aimed to determine the likelihood of hyperglycemia postpartum in women with gestational diabetes mellitus (GDM) and to identify the predictors. METHODS: The retrospective cohort study involved 1 527 GDM patients who delivered at Peking University First Hospital from 1 January 2021, to 31 December 2021. According to the blood glucose level of postpartum oral glucose tolerance test (OGTT), women were divided into a normal glucose tolerance (NGT) group and a hyperglycemia group, and their characteristics and risk factors of hyperglycemia were compared. RESULTS: The prevalence of hyperglycemia was 33.9% (184/543) at 6-12 weeks postpartum. Compared with the NGT group, the fasting plasma glucose (FPG) of hyperglycemia group increased significantly during pregnancy and postpartum, the OGTT 1h postprandial glucose (PG) and 2hPG increased in the second trimester of pregnancy, the triglyceride (TG) increased in the first trimester of pregnancy and postpartum, the triglyceride glucose (TyG) index increased in the first trimester of pregnancy and postpartum, and the total cholesterol (TCHO) and low density lipoprotein cholesterol (LDL-C) decreased in the second trimester (p < 0.05). Fasting plasma glucose (FPG) in the first trimester [odds ratio (OR) = 3.583, p < 0.001], OGTT 2hPG in the second trimester (OR = 1.604, p < 0.001), the TyG index in the first trimester (OR = 1.863, p = 0.045) and FPG in third trimester (OR = 1.985, p = 0.024) were independent risk factors for postpartum hyperglycemia. CONCLUSIONS: Approximately one-third of women with GDM have hyperglycemia 6-12 weeks after delivery. FPG and the TyG index in the first trimester, OGTT 2hPG in the second trimester and FPG in third trimester are risk factors for postpartum hyperglycemia.

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Glucemia , Diabetes Gestacional , Prueba de Tolerancia a la Glucosa , Hiperglucemia , Periodo Posparto , Triglicéridos , Humanos , Femenino , Embarazo , Diabetes Gestacional/sangre , Diabetes Gestacional/diagnóstico , Adulto , Hiperglucemia/sangre , Hiperglucemia/diagnóstico , Hiperglucemia/epidemiología , Estudios Retrospectivos , Glucemia/análisis , Glucemia/metabolismo , Triglicéridos/sangre , Periodo Posparto/sangre , Ayuno/sangre , Factores de Riesgo , Valor Predictivo de las Pruebas

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Rationale & Objectives: Hyperglycemia is frequently observed early after transplantation and associated with development of post-transplant diabetes mellitus (PTDM). Here, we assessed continuous subcutaneous insulin infusion (CSII) targeting afternoon hyperglycemia. Study Design: Open-label randomized parallel 3-arm design. Settings & Participants: In total, 85 kidney transplant recipients without previous diabetes diagnosis were randomized to postoperative CSII therapy, basal insulin, or control. Interventions: Insulin was to be initiated at afternoon capillary blood glucose level of ≥140 mg/dL (7.8 mmol/L; CSII and basal insulin) or fasting plasma glucose level of ≥200 mg/dL (11.1 mmol/L; control). Outcomes: Hemoglobin A1c (HbA1c) levels at 3 months post-transplant (primary endpoint). PTDM assessed using oral glucose tolerance test at 12 and 24 months. Results: CSII therapy lasted until median day 18 and maximum day 88. The median HbA1c value at month 3 was 5.6% (38 mmol/mol) in the CSII group versus 5.7% (39 mmol/mol) in the control group (P = 0.70) and 5.4% (36 mmol/mol) in the basal insulin group (P = 0.02). At months 12 and 24, the odds for PTDM were similar compared with the control group (odds ratios [95% confidence intervals], 0.80 [0.18-3.49] and 0.71 [0.15-3.16], respectively) and the basal insulin group (0.96 [0.18-5.68] and 1.51 [0.24-12.84], respectively). Mild hypoglycemia events occurred in the CSII and the basal insulin groups. Limitations: This study is limited by outdated insulin pump technology, frequent discontinuations of CSII, a complex protocol, and concerns regarding reliability of HbA1c measurements. Conclusions: CSII therapy was not superior at reducing HbA1c levels at month 3 or PTDM prevalence at months 12 and 24 compared with the control or basal insulin group.

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Ras-related Rap1A GTPase is implicated in pancreas ß-cell insulin secretion and is stimulated by the cAMP sensor Epac2, a guanine exchange factor and activator of Rap1 GTPase. In this study, we examined the differential proteomic profiles of pancreata from C57BL/6 Rap1A-deficient (Null) and control wild-type (WT) mice with nanoLC-ESI-MS/MS to assess targets of Rap1A potentially involved in insulin regulation. We identified 77 overlapping identifier proteins in both groups, with 8 distinct identifier proteins in Null versus 56 distinct identifier proteins in WT mice pancreata. Functional enrichment analysis showed four of the eight Null unique proteins, ERO1-like protein ß (Ero1lß), triosephosphate isomerase (TP1), 14-3-3 protein γ, and kallikrein-1, were exclusively involved in insulin biogenesis, with roles in insulin metabolism. Specifically, the mRNA expression of Ero1lß and TP1 was significantly (p < 0.05) increased in Null versus WT pancreata. Rap1A deficiency significantly affected glucose tolerance during the first 15-30 min of glucose challenge but showed no impact on insulin sensitivity. Ex vivo glucose-stimulated insulin secretion (GSIS) studies on isolated Null islets showed significantly impaired GSIS. Furthermore, in GSIS-impaired islets, the cAMP-Epac2-Rap1A pathway was significantly compromised compared to the WT. Altogether, these studies underscore an essential role of Rap1A GTPase in pancreas physiological function.

Asunto(s)

Insulina , Ratones Endogámicos C57BL , Páncreas , Proteómica , Transducción de Señal , Proteínas de Unión al GTP rap1 , Animales , Proteínas de Unión al GTP rap1/metabolismo , Proteínas de Unión al GTP rap1/genética , Ratones , Proteómica/métodos , Insulina/metabolismo , Páncreas/metabolismo , Células Secretoras de Insulina/metabolismo , Ratones Noqueados , Factores de Intercambio de Guanina Nucleótido/metabolismo , Factores de Intercambio de Guanina Nucleótido/genética , Secreción de Insulina , Masculino , Glucosa/metabolismo

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AIM: To assess oxytocin's acute glucoregulatory impact in men with type 2 diabetes in the context of our previous findings that oxytocin improves ß-cell responsivity in healthy men. METHODS: In a double-blind, crossover comparison, intranasal oxytocin (24 IU) and placebo, respectively, were administered to 25 fasted men with non-insulin-treated type 2 diabetes (age ± standard error of the mean, 63.40 ± 1.36 years; body mass index, 27.77 ± 0.66 kg/m2; HbA1c, 6.86% ± 0.08%; Homeostatic Model Assessment of Insulin Resistance (HOMA-IR, 3.44 ± 0.39) 60 minutes before an oral glucose tolerance test (oGTT). Key outcomes were compared with previous results in men with normal weight or obesity. RESULTS: Oxytocin compared with placebo increased plasma oxytocin concentrations and reduced the heart rate, but did not alter glucose metabolism in the 3 hours after oGTT onset (area under the curve, glucose, 2240 ± 80.5 vs. 2190 ± 69.5 mmol/L × min; insulin, 45 663 ± 4538 vs. 44 343 ± 4269 pmol/L × min; C-peptide, 235 ± 5.1 vs. 231 ± 15.9 nmol/L × min). CONCLUSIONS: This outcome contrasts with the oxytocin-induced attenuation of early postprandial glucose excursions in normal-weight individuals, but is in line with the absence of respective effects in men with obesity. We conclude that insulin resistance in type 2 diabetes is associated with decreased sensitivity to the acute glucoregulatory effect of oxytocin in male individuals.

Asunto(s)

Glucemia , Estudios Cruzados , Diabetes Mellitus Tipo 2 , Prueba de Tolerancia a la Glucosa , Resistencia a la Insulina , Oxitocina , Humanos , Masculino , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Oxitocina/administración & dosificación , Oxitocina/sangre , Persona de Mediana Edad , Método Doble Ciego , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Insulina/sangre , Administración Intranasal , Intolerancia a la Glucosa/tratamiento farmacológico , Intolerancia a la Glucosa/sangre , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Hemoglobina Glucada/efectos de los fármacos

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The relationship of adipose tissue insulin resistance (AT-IR, a product of fasting insulin and free fatty acids) and homeostasis-model assessment-insulin resistance (HOMA-IR) to ß-cell function was studied cross-sectionally in the setting of subtle glucose dysregulation. Associations of AT-IR and HOMA-IR with fasting and post-glucose glycemia and ß-cell function inferred from serum insulin kinetics during a 75 g oral glucose tolerance test were studied in 168 young female Japanese students. ß-cell function was evaluated by disposition index calculated as a product of the insulinogenic index (IGI) and Matsuda index. AT-IR, not HOMA-IR, showed positive associations with post-glucose glycemia and area under the glucose response curve although both indices were associated with fasting glycemia. HOMA-IR, not AT-IR, was associated positively with log IGI whereas both indices were inversely associated with Matsuda index. AT-IR, not HOMA-IR, showed inverse associations with log disposition index. Associations of adipose tissue insulin resistance with ß-cell function (inverse) and glucose excursion in young Japanese women may suggest that lipotoxicity to pancreatic ß-cells for decades may be associated with ß cell dysfunction found in Japanese patients with type 2 diabetes. Positive association of HOMA-IR with insulinogenic index may be associated with compensatory increased insulin secretion.

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Tejido Adiposo , Resistencia a la Insulina , Células Secretoras de Insulina , Adulto , Femenino , Humanos , Adulto Joven , Tejido Adiposo/metabolismo , Glucemia/metabolismo , Estudios Transversales , Pueblos del Este de Asia , Ayuno/sangre , Prueba de Tolerancia a la Glucosa , Insulina/sangre , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Japón

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Preclinical work supports a role for the peripheral chemoreceptors in the progression of cardiovascular and metabolic pathologies. In the present study, we examined peripheral chemosensitivity in adults with type 2 diabetes (T2D) and the contribution of the peripheral chemoreceptors to resting cardiovascular and metabolic control. We hypothesized that: (1) adults with T2D exhibit exaggerated peripheral chemoreflex sensitivity; (2) the peripheral chemoreceptors contribute to cardiovascular dysfunction in T2D; and (3) attenuation of peripheral chemoreceptor activity improves glucose tolerance in T2D. Seventeen adults with diagnosed T2D [six males/11 females; aged 54 ± 11 years; glycated haemoglobin (HbA1c) 7.6 ± 1.5%] and 20 controls without T2D (9 males/11 females; aged 49 ± 13 years, HbA1c 5.2 ± 0.4%) participated in the study. The hypoxic ventilatory response (HVR) was assessed as an index of peripheral chemosensitivity. Resting heart rate, blood pressure and minute ventilation were measured when breathing normoxic followed by hyperoxic air (1.0 F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ) to acutely attenuate peripheral chemoreceptor activity. A subset of participants (n = 9 per group) completed two additional visits [normoxia (0.21 F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ), hyperoxia (1.0 F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ )] where glucose and insulin were measured for 2 h following an oral glucose challenge. HVR was augmented in adults with T2D (-0.84 ± 0.49 L min-1/%) vs. control (-0.48 ± 0.40 L min-1/%, P = 0.021). Attenuation of peripheral chemoreceptor activity decreased heart rate (P < 0.001), mean blood pressure (P = 0.009) and minute ventilation (P = 0.002); any effect of hyperoxia did not differ between groups. There was no effect of hyperoxia on the glucose (control, P = 0.864; T2D, P = 0.982), nor insulin (control, P = 0.763; T2D, P = 0.189) response to the oral glucose challenge. Peripheral chemoreflex sensitivity is elevated in adults with T2D; however, acute attenuation of peripheral chemoreflex activity with hyperoxia does not restore cardiometabolic function. KEY POINTS: Preclinical work supports a role for the peripheral chemoreceptors in the progression of cardiovascular and metabolic pathologies. In the present study, we examined peripheral chemosensitivity in adults with type 2 diabetes and the contribution of the peripheral chemoreceptors to resting cardiovascular control and glucose tolerance. We observed elevated peripheral chemoreflex sensitivity in adults with diabetes which was associated with glycaemic control (i.e. glycated haemoglobin). Notably, acute attenuation of peripheral chemoreflex activity with hyperoxia did not restore cardiometabolic function in the individuals studied.

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ISSUE ADDRESSED: The oral glucose tolerance test is the 'gold standard' for detecting gestational diabetes in Australian and International guidelines. Test completion in regional, rural and remote regions may be as low as 50%. We explored challenges and enablers for regional, rural and remote antenatal clinicians providing gestational diabetes screening to better understand low oral glucose tolerance test completion. METHODS: We conducted a qualitative descriptive study using semi-structured interviews. Participants eligible for the study were doctors or midwives providing antenatal care in regional, rural and remote Western Australia, between August 2019 and November 2020. Interviews were recorded digitally and transcribed into a Word document. We conducted a thematic analysis after initial categorisation and deduction of themes through workshops involving the research team. RESULTS: We found a diversity of viewpoints on oral glucose tolerance test reliability for detecting gestational diabetes. Themes that emerged were; good collaboration between antenatal clinicians is required for successful screening; screening occurs throughout pregnancy using various tests; clinicians make significant efforts to address barriers; clinicians prioritise therapeutic relationships. CONCLUSIONS: Effective universal screening for gestational diabetes in regional, rural and remote Western Australia is difficult and more complex in practice than guidelines imply. Detecting gestational diabetes requires creative solutions, early identification of at risk women and trust and collaboration between clinicians and women. SO WHAT?: Detection of gestational diabetes in regional, rural and remote Western Australia remains poorly completed. New strategies are required to adequately identify women at risk of adverse birth outcomes relating to hyperglycaemia in pregnancy.

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Neprilysin is a ubiquitous peptidase that can modulate glucose homeostasis by cleaving insulinotropic peptides. While global deletion of neprilysin protects mice against high-fat diet (HFD)-induced insulin secretory dysfunction, strategies to ablate neprilysin in a tissue-specific manner are favored to limit off-target effects. Since insulinotropic peptides are produced in the gut, we sought to determine whether gut-specific neprilysin deletion confers beneficial effects on insulin secretion similar to that of global neprilysin deletion in mice fed a HFD. Mice with conditional deletion of neprilysin in enterocytes (NEPGut-/-) were generated by crossing Vil-Cre and floxed neprilysin mice. Neprilysin activity was almost abolished throughout the gut in NEPGut-/- mice, and was similar in plasma, pancreas, and kidney in NEPGut-/- vs control mice. An oral glucose tolerance test was performed at baseline and following 14 weeks of HFD feeding, during which glucose tolerance and glucose-stimulated insulin secretion (GSIS) were assessed. Despite similar body weight gain at 14 weeks, NEPGut-/- displayed lower fasting plasma glucose levels, improved glucose tolerance, and increased GSIS compared to control mice. In conclusion, gut-specific neprilysin deletion recapitulates the enhanced GSIS seen with global neprilysin deletion in HFD-fed mice. Thus, strategies to inhibit neprilysin specifically in the gut may protect against fat-induced glucose intolerance and beta-cell dysfunction.

Asunto(s)

Dieta Alta en Grasa , Secreción de Insulina , Insulina , Neprilisina , Animales , Masculino , Ratones , Dieta Alta en Grasa/efectos adversos , Enterocitos/metabolismo , Eliminación de Gen , Prueba de Tolerancia a la Glucosa , Insulina/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Neprilisina/genética , Neprilisina/metabolismo

RESUMEN

Objective: To explore the effects of insulin resistance (IR) on embryo quality and pregnancy outcomes in women with or without polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Methods: A retrospective cohort study concerning patients with/without PCOS who received gonadotropin-releasing hormone (GnRH)-antagonist protocol for IVF/ICSI from January 2019 to July 2022 was conducted. All the patients included underwent oral glucose tolerance test plus the assessment of insulin release within 6 months before the controlled ovarian stimulation. The Matsuda Index was calculated to diagnose IR. Two populations (PCOS and non-PCOS) were included and each was divided into IR and non-IR groups and analyzed respectively. The primary outcome was the high-quality day 3 embryo rate. Results: A total of 895 patients were included (751 with PCOS and 144 without PCOS). For patients with PCOS, the IR group had a lower high-quality day 3 embryo rate (36.8% vs. 39.7%, p=0.005) and available day 3 embryo rate (67.2% vs. 70.6%, p<0.001). For patients without PCOS, there was no significant difference between the IR and non-IR groups in high-quality day 3 embryo rate (p=0.414) and available day 3 embryo rate (p=0.560). There was no significant difference in blastocyst outcomes and pregnancy outcomes for both populations. Conclusion: Based on the diagnosis by the Matsuda Index, IR may adversely affect the day 3 embryo quality in patients with PCOS but not pregnancy outcomes. In women without PCOS, IR alone seems to have less significant adverse effects on embryo quality than in patients with PCOS. Better-designed studies are still needed to compare the differences statistically between PCOS and non-PCOS populations.

Asunto(s)

Fertilización In Vitro , Prueba de Tolerancia a la Glucosa , Resistencia a la Insulina , Inducción de la Ovulación , Síndrome del Ovario Poliquístico , Resultado del Embarazo , Índice de Embarazo , Humanos , Síndrome del Ovario Poliquístico/complicaciones , Femenino , Embarazo , Estudios Retrospectivos , Adulto , Fertilización In Vitro/métodos , Inducción de la Ovulación/métodos , Inyecciones de Esperma Intracitoplasmáticas/métodos , Transferencia de Embrión/métodos , Infertilidad Femenina/terapia

RESUMEN

BACKGROUND: Dysregulation of bile acids (BAs), as important signalling molecules in regulating lipid and glucose metabolism, contributes to the development of non-alcoholic fatty liver disease (NAFLD). However, static BA profiles during fasting may obscure certain pathogenetic aspects. In this study, we investigate the dynamic alterations of BAs in response to an oral glucose tolerance test (OGTT) among children with NAFLD. METHODS: We recruited 230 subjects, including children with overweight/obesity, or complicated with NAFLD, and healthy controls. Serum BAs, 7-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) were quantified during OGTT. Clinical markers related to liver function, lipid metabolism and glucose metabolism were assessed at baseline or during OGTT. FINDINGS: Conjugated BAs increased while unconjugated ones decreased after glucose uptake. Most BAs were blunted in response to glucose in NAFLD (p > .05); only glycine and taurine-conjugated chenodeoxycholic acid (CDCA) and cholic acid (CA) were responsive (p < .05). Primary BAs were significantly increased while secondary BAs were decreased in NAFLD. C4 and FGF19 were significantly increased while their ratio FGF19/C4 ratio was decreased in NAFLD. The dynamic pattern of CDCA and taurine-conjugated hyocholic acid (THCA) species was closely correlated with glucose (correlation coefficient r = .175 and -.233, p < .05), insulin (r = .327 and -.236, p < .05) and c-peptide (r = .318 and -.238, p < .05). Among which, CDCA was positively associated with liver fat content in NAFLD (r = .438, p < .05). Additionally, glycochenodeoxycholic acid (GCDCA), CDCA and THCA were potential biomarkers to discriminate paediatric NAFLD from healthy controls and children with obesity. INTERPRETATION: This study provides novel insights into the dynamics of BAs during OGTT in paediatric NAFLD. The observed variations in CDCA and HCA species were associated with liver dysfunction, dyslipidaemia and dysglycaemia, highlighting their potential roles as promising diagnostic and therapeutic targets in NAFLD.

RESUMEN

CONTEXT: The pathophysiological mechanisms underlying the natural history of glucose intolerance and its fluctuations in subjects with cystic fibrosis (CF) are still unclear. OBJECTIVE: To investigate the relationship between longitudinal changes in glucose tolerance and concomitant changes in the main parameters of insulin secretion/metabolism/action determining glucose regulation in CF subjects. METHODS: Insulin sensitivity and glucose-stimulated insulin secretion (GSIS, a biomarker of beta cell functional mass), as estimated by the Oral Glucose Sensitivity Index (OGIS) and by a sophisticated mathematical model, respectively, and insulin clearance were assessed in 127 CF subjects, aged 10-25 years, who underwent two OGTT tests over at least 1-year follow-up period. Subjects were classified a posteriori as regressors (improved glucose tolerance), stable, or progressors (worsened glucose tolerance). The interplay between beta cell compensatory action and insulin sensitivity over time was analyzed by vector plots of insulin clearance adjusted GSIS (PCadj) versus OGIS. RESULTS: OGIS decreased in progressors and stable. Insulin clearance decreased in both regressors and progressors. GSIS (beta cell functional mass) improved in regressors and worsened in progressors, whereas it did not change in stable. Vector plot analysis confirmed that glucose regulation changed differently in each group. Multinomial logistic regression analysis showed that baseline glucose tolerance and GSIS changes were the only significant predictors of the changes in glucose tolerance (p<0.02, R2Nagelkerke=0.55), whereas age, gender, z-BMI, CF genotypes, and baseline PCadj were not. CONCLUSIONS: In CF subjects, changes in beta cell functional mass are associated with favorable or detrimental changes of glucose tolerance over time.