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1.
Lancet ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38909619

ABSTRACT

Gestational diabetes is the most common medical complication in pregnancy. Historically, gestational diabetes was considered a pregnancy complication involving treatment of rising glycaemia late in the second trimester. However, recent evidence challenges this view. Pre-pregnancy and pregnancy-specific factors influence gestational glycaemia, with open questions regarding roles of non-glycaemic factors in the aetiology and consequences of gestational diabetes. Varying patterns of insulin secretion and resistance in early and late pregnancy underlie a heterogeneity of gestational diabetes in the timing and pathophysiological subtypes with clinical implications: early gestational diabetes and insulin resistant gestational diabetes subtypes are associated with a higher risk of pregnancy complications. Metabolic perturbations of early gestational diabetes can affect early placental development, affecting maternal metabolism and fetal development. Fetal hyperinsulinaemia can affect the development of multiple fetal tissues, with short-term and long-term consequences. Pregnancy complications are prevented by managing glycaemia in early and late pregnancy in some, but not all women with gestational diabetes. A better understanding of the pathophysiology and heterogeneity of gestational diabetes will help to develop novel management approaches with focus on improved prevention of maternal and offspring short-term and long-term complications, from pre-conception, throughout pregnancy, and beyond.

2.
Curr Probl Cardiol ; 49(9): 102698, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38876163

ABSTRACT

BACKGROUND: . The long-term impact of gestational complications on cardiovascular outcomes in women remains a subject of debate. AIM: To assess the 5-year risk of cardiovascular events and all-cause mortality in women with gestational diabetes and hypertension. METHODS: Retrospective study utilising an health research network(TriNetX). The primary outcome was the composite risk of a cardiovascular event within 5 years with secondary outcomes being its components (all-cause death, acute heart failure, myocardial infarction, ischaemic stroke). Women were categorised into 8 different groups based on the ICD-codes for pregnancy related complications recorded 9 months before the delivery:1) gestational diabetes,2) gestational hypertension,3) gestational diabetes with gestational hypertension,4) gestational diabetes with gestational hypertension without pre-eclampsia or eclampsia,5) gestational diabetes with pre-eclampsia or eclampsia,6) gestational hypertension without pre-eclampsia or eclampsia,7) pre-eclampsia or eclampsia,and 8) no gestational complications. Cox-regression analyses were used to produce hazard ratios (HRs) and 95 % confidence intervals (CI) before and after propensity score matching (PSM). RESULTS: We identified, 24,402 women with gestational diabetes and gestational hypertension and 920,478 without gestational complications. After PSM, compared to women without pregnancy complications, women with gestational diabetes and gestational hypertension had a higher 5-year risk of composite outcome(HR 2.25,95 %CI 2.02-2.51), all-cause death(HR 1.64,95 %CI 1.31-2.06), acute heart failure(HR 2.06,95 %CI 1.69-2.52), myocardial infarction(HR 2.46,95 %CI 1.93-3.14), and ischemic stroke(HR 2.37,95 %CI 2.06-2.74). Women who experienced pre-eclampsia or eclampsia showed the highest risk of primary and secondary outcomes. CONCLUSIONS: Gestational complications are associated with worse long-term cardiovascular outcomes. There is a clear call to action required to improve the longitudinal management of gestational complications to improve women's long-term health.

3.
Peptides ; 176: 171186, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38490484

ABSTRACT

Circulating insulin levels are known to be increased in people with higher body mass index (BMI) due to effects of adiposity on insulin resistance, whilst gut hormones have a more complex relationship, with fasting peptideYY (PYY) reported to be inversely related to BMI. This study aimed to further explore fasting and post prandial pancreatic and gut hormone concentrations in plasma samples from obese and non-obese participants. Participants with healthy BMI (n=15), overweight BMI (n=29) and obesity (n=161) had samples taken fasting and 30 min post mixed liquid meal for analysis of glucagon-like peptide-1 (GLP-1), PYY, glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon. Data visualiation used linear discriminant analysis for dimensionality reduction, to visualise the data and assess scaling of each hormone. Fasting levels of insulin, GIP and PYY were shown to be key classifiers between the 3 groups on ANCOVA analysis, with an observation of increased GIP levels in overweight, but not obese participants. In non-obese subjects, fasting GIP, PYY and insulin correlated with BMI, whereas in subjects with obesity only the pancreatic hormones glucagon and insulin correlated with BMI. Concentrations of total GLP-1 in the fasting state correlated strongly with glucagon levels, highlighting potential assay cross-reactivities. The study, which included a relatively large number of subjects with severe obesity, supported previous evidence of BMI correlating negatively with fasting PYY and positively with fasting insulin. The observation of increased fasting GIP levels in overweight but not obese participants deserves further validation and mechanistic investigation.


Subject(s)
Body Mass Index , Fasting , Gastric Inhibitory Polypeptide , Glucagon-Like Peptide 1 , Insulin , Obesity , Peptide YY , Humans , Obesity/blood , Male , Female , Adult , Fasting/blood , Peptide YY/blood , Middle Aged , Glucagon-Like Peptide 1/blood , Gastric Inhibitory Polypeptide/blood , Insulin/blood , Postprandial Period , Glucagon/blood , Gastrointestinal Hormones/blood
4.
Nutrients ; 15(19)2023 Sep 25.
Article in English | MEDLINE | ID: mdl-37836424

ABSTRACT

BACKGROUND: Gestational diabetes is associated with increased risk of obesity, type 2 diabetes and cardiovascular disease. Effective nutritional strategies are needed to reduce BMI and improve long-term maternal cardiometabolic health, but the relative contribution of maternal eating behaviour, a potential barrier to dietary change, has not been explored. We compared eating behaviour in women with gestational diabetes with that of men and non-pregnant women with comparable risk factors, and tested associations between eating behaviour traits and BMI in women with gestational diabetes. We hypothesized that eating behaviour would be unfavourable in gestational diabetes and would be associated with BMI. METHODS: Participants (n = 417) including 53 men, 164 non-pregnant women and 200 women with gestational diabetes (singleton pregnancy; 29 weeks' gestation) were recruited into three prospective studies assessing weight loss interventions, with similar entry criteria. The three-factor eating questionnaire (TFEQ-R18) assessed uncontrolled eating, emotional eating and cognitive restraint at study enrolment. Associations between BMI at study enrolment and TFEQ-R18 (% maximum score) were assessed using linear regression. RESULTS: Women with gestational diabetes had significantly lower uncontrolled eating scores vs. men (53% vs. 65%; p < 0.001) and non-pregnant women (53% vs. 66%; p < 0.001), lower emotional eating scores vs. non-pregnant women (60% vs. 71%; p < 0.001) and higher cognitive restraint (p < 0.001 vs. men and non-pregnant women). In women with gestational diabetes, emotional eating scores were positively associated with BMI at study enrolment (beta coefficient 7.8 (95% CI 3.9 to 11.7), p < 0.001). CONCLUSIONS: Women with gestational diabetes have favourable eating behaviour compared with other population groups. Because BMI at study enrolment was associated with emotional eating, nutritional strategies which reduce emotional eating may provide new opportunities to improve long-term maternal health after gestational diabetes.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetes, Gestational , Pregnancy , Male , Humans , Adult , Female , Diabetes, Gestational/epidemiology , Diabetes Mellitus, Type 2/complications , Prospective Studies , Obesity/epidemiology , Feeding Behavior/psychology , Body Mass Index
5.
PLoS One ; 18(9): e0292094, 2023.
Article in English | MEDLINE | ID: mdl-37756288

ABSTRACT

BACKGROUND: Undiagnosed diabetes in pregnancy is associated with stillbirth and perinatal complications, but standard testing for gestational diabetes using the oral glucose tolerance test (OGTT) is impractical and exacerbates healthcare inequalities. There is an urgent need to improve the accuracy, acceptability and accessibility of glucose testing in pregnancy. We qualitatively assessed the feasibility and acceptability of two alternative home-based methods of glucose testing in pregnant women, using continuous glucose monitoring (CGM), with or without a home-based OGTT. METHODS: We recruited women with a singleton pregnancy at 28 weeks' gestation with ≥1 risk factor for gestational diabetes attending antenatal glucose testing. A Dexcom G6 CGM device was sited and women were asked to take a 75g OGTT solution (Rapilose) on day 4 after an overnight fast. Qualitative interviews were performed with 20 participants using video conferencing according to a semi-structured interview schedule and thematically analysed using NVIVO software. RESULTS: 92 women were recruited; 73 also underwent a home OGTT. Women had an average of 6.9 days of glucose monitoring and found the CGM painless, easy to use with few or no adverse events. During the qualitative study, the main themes identified were reassurance and convenience. All women interviewed would recommend CGM and a home OGTT for diagnosis of gestational diabetes. CONCLUSIONS: CGM with or without a home OGTT is feasible and acceptable to pregnant women for diagnosis of gestational diabetes and offered advantages of convenience and reassurance. Further work is needed to clarify diagnostic thresholds for gestational diabetes using CGM metrics.


Subject(s)
Diabetes, Gestational , Pregnancy , Female , Humans , Diabetes, Gestational/diagnosis , Blood Glucose Self-Monitoring , Feasibility Studies , Prospective Studies , Blood Glucose , Glucose
6.
Diabetologia ; 66(11): 2101-2116, 2023 11.
Article in English | MEDLINE | ID: mdl-37615689

ABSTRACT

AIMS/HYPOTHESIS: Type 1 diabetes in pregnancy is associated with suboptimal pregnancy outcomes, attributed to maternal hyperglycaemia and offspring hyperinsulinism (quantifiable by cord blood C-peptide). We assessed metabolomic patterns associated with risk factors (maternal hyperglycaemia, diet, BMI, weight gain) and perinatal complications (pre-eclampsia, large for gestational age [LGA], neonatal hypoglycaemia, hyperinsulinism) in the Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial (CONCEPTT). METHODS: A total of 174 CONCEPTT participants gave ≥1 non-fasting serum sample for the biorepository at 12 gestational weeks (147 women), 24 weeks (167 women) and 34 weeks (160 women) with cord blood from 93 infants. Results from untargeted metabolite analysis (ultrahigh performance LC-MS) are presented as adjusted logistic/linear regression of maternal and cord blood metabolites, risk factors and perinatal complications using a modified Bonferroni limit of significance for dependent variables. RESULTS: Maternal continuous glucose monitoring time-above-range (but not BMI or excessive gestational weight gain) was associated with increased triacylglycerols in maternal blood and increased carnitines in cord blood. LGA, adiposity, neonatal hypoglycaemia and offspring hyperinsulinism showed distinct metabolite profiles. LGA was associated with increased carnitines, steroid hormones and lipid metabolites, predominantly in the third trimester. However, neonatal hypoglycaemia and offspring hyperinsulinism were both associated with metabolite changes from the first trimester, featuring triacylglycerols or dietary phenols. Pre-eclampsia was associated with increased abundance of phosphatidylethanolamines, a membrane phospholipid, at 24 weeks. CONCLUSIONS/INTERPRETATION: Altered lipid metabolism is a key pathophysiological feature of type 1 diabetes pregnancy. New strategies for optimising maternal diet and insulin dosing from the first trimester are needed to improve pregnancy outcomes in type 1 diabetes.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetes, Gestational , Hyperglycemia , Hyperinsulinism , Hypoglycemia , Pre-Eclampsia , Female , Humans , Infant, Newborn , Pregnancy , Blood Glucose/metabolism , Blood Glucose Self-Monitoring , Diabetes Mellitus, Type 1/complications , Hyperglycemia/complications
8.
Acta Diabetol ; 60(12): 1635-1642, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37439859

ABSTRACT

AIMS: Incretin hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory peptide (GIP) cause increased insulin secretion in non-pregnant adults, but their role in pregnancy, where there are additional metabolically-active hormones from the placenta, is less clear. The aim of the present study was to assess if fasting and post-load incretin concentrations were predictive of pregnancy insulin and glucose concentrations. METHODS: Pregnant women (n = 394) with one or more risk factors for gestational diabetes were recruited at 28 weeks for a 75 g oral glucose tolerance test (OGTT). Glucose, insulin, GLP-1 and GIP were measured in the fasting state and 120 min after glucose ingestion. RESULTS: Fasting plasma GLP-1 concentrations were associated with plasma insulin (standardised ß' 0.393 (0.289-0.498), p = 1.3 × 10-12; n = 306), but not with glucose concentrations (p = 0.3). The association with insulin was still evident when adjusting for BMI (ß' 0.271 (0.180-0.362), p = 1.1 × 10-8; n = 297). Likewise, at 120 min the OGTT GLP-1 concentrations were associated with plasma insulin concentrations (ß' 0.216 (0.100-0.331), p = 2.7 × 10-4; n = 306) even after adjusting for BMI (ß' 0.178 (0.061-0.294), p = 2.9 × 10-3; n = 296), but not with glucose (p = 0.9). GIP concentrations were not associated with insulin or glucose concentrations at either time point (all p > 0.2). In pregnancy plasma GLP-1, but not GIP, concentrations appear to be predictive of circulating insulin concentrations, independently of associations with BMIs. CONCLUSIONS: These results suggest that the relationship between insulin and incretins is preserved in pregnancy, but that other factors, such as placental hormones or counter-regulatory hormones, may be more important determinants of glycaemia and gestational diabetes aetiology.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetes, Gestational , Adult , Female , Humans , Pregnancy , Insulin , Glucagon-Like Peptide 1 , Incretins , Blood Glucose , Placenta , Glucose , Gastric Inhibitory Polypeptide
9.
Diabetologia ; 66(11): 1961-1970, 2023 11.
Article in English | MEDLINE | ID: mdl-37442824

ABSTRACT

Diabetes in pregnancy affects 20 million women per year and is associated with increased risk of obesity in offspring, leading to insulin resistance and cardiometabolic disease. Despite the substantial public health ramifications, relatively little is known about the pathophysiological mechanisms underlying obesity in these high-risk children, which creates a barrier to successful intervention. While maternal glucose itself is undeniably a major stimulus upon intrauterine growth, the degree of offspring hyperinsulinism and disturbed lipid metabolism in mothers and offspring are also likely to be implicated in the disease process. The aim of this review is to summarise current understanding of the pathophysiology of childhood obesity after intrauterine exposure to maternal hyperglycaemia and to highlight possible opportunities for intervention. I present here a new unified hypothesis for the pathophysiology of childhood obesity in infants born to mothers with diabetes, which involves self-perpetuating twin cycles of pancreatic beta cell hyperfunction and altered lipid metabolism, both acutely and chronically upregulated by intrauterine exposure to maternal hyperglycaemia.


Subject(s)
Diabetes, Gestational , Hyperglycemia , Insulin Resistance , Pediatric Obesity , Prenatal Exposure Delayed Effects , Pregnancy , Infant , Humans , Child , Female , Pediatric Obesity/genetics , Diabetes, Gestational/genetics , Mothers , Insulin Resistance/genetics , Hyperglycemia/complications , Prenatal Exposure Delayed Effects/metabolism
10.
J Clin Endocrinol Metab ; 108(10): 2643-2652, 2023 09 18.
Article in English | MEDLINE | ID: mdl-36950879

ABSTRACT

AIMS: Precision medicine has revolutionized our understanding of type 1 diabetes and neonatal diabetes but has yet to improve insight into gestational diabetes mellitus (GDM), the most common obstetric complication and strongly linked to obesity. Here we explored if patterns of glycaemia (fasting, 1 hour, 2 hours) during the antenatal oral glucose tolerance test (OGTT), reflect distinct pathophysiological subtypes of GDM as defined by insulin secretion/sensitivity or lipid profiles. METHODS: 867 pregnant women with obesity (body mass index ≥ 30 kg/m2) from the UPBEAT trial (ISRCTN 89971375) were assessed for GDM at 28 weeks' gestation (75 g oral glucose tolerance test OGTT; World Health Organization criteria). Lipid profiling of the fasting plasma OGTT sample was undertaken using direct infusion mass spectrometry and analyzed by logistic/linear regression, with and without adjustment for confounders. Insulin secretion and sensitivity were characterized by homeostatic model assessment 2b and 2s, respectively. RESULTS: In women who developed GDM (n = 241), patterns of glycaemia were associated with distinct clinical and biochemical characteristics and changes to lipid abundance in the circulation. Severity of glucose derangement, rather than pattern of postload glycaemia, was most strongly related to insulin action and lipid abundance/profile. Unexpectedly, women with isolated postload hyperglycemia had comparable insulin secretion and sensitivity to euglycemic women, potentially indicative of a novel mechanistic pathway. CONCLUSIONS: Patterns of glycemia during the OGTT may contribute to a precision approach to GDM as assessed by differences in insulin resistance/secretion. Further research is indicated to determine if isolated postload hyperglycemia reflects a different mechanistic pathway for targeted management.


Subject(s)
Diabetes, Gestational , Hyperglycemia , Insulin Resistance , Infant, Newborn , Female , Pregnancy , Humans , Pregnant Women , Blood Glucose/analysis , Precision Medicine , Insulin/metabolism , Obesity/complications , Lipids
12.
Article in English | MEDLINE | ID: mdl-36242807

ABSTRACT

Routine immunoassays for insulin and C-peptide have the potential to cross-react with partially processed proinsulin products, although in healthy patients these are present at such low levels that the interference is insignificant. Elevated concentrations of proinsulin and des-31,32 proinsulin arising from pathological conditions, or injected insulin analogues, however can cause significant assay interferences, complicating interpretation. Clinical diagnosis and management therefore sometimes require methods that can distinguish true insulin and C-peptide from partially processed proinsulin or injected insulin analogues. In this scenario, the high specificity of mass spectrometric analysis offers potential benefit for patient care. A high throughput targeted LC-MS/MS method was developed as a fit for purpose investigation of insulin, insulin analogues, C-peptide and proinsulin processing intermediates in plasma samples from different patient groups. Using calibration standards and bovine insulin as an internal standard, absolute concentrations of insulin and C-peptide were quantified across a nominal human plasma postprandial range and correlated strongly with immunoassay-based measurements. The ability to distinguish between insulin, insulin analogues and proinsulin intermediates in a single extraction is an improvement over existing immunological based techniques, offering the advantage of exact identification of the species being measured. The method promises to aid in the detection of circulating peptides which have previously been overlooked but may interfere with standard insulin and C-peptide immunoassays.


Subject(s)
Insulin-Secreting Cells , Proinsulin , Humans , Cattle , Animals , C-Peptide , Chromatography, Liquid/methods , Tandem Mass Spectrometry , Insulin , Peptides
13.
Int J Mol Sci ; 23(19)2022 Oct 01.
Article in English | MEDLINE | ID: mdl-36232961

ABSTRACT

Male fertility, as manifest by the quantity and progressive motility of spermatozoa, is negatively impacted by obesity, dyslipidaemia and metabolic disease. However, the relative distribution of lipids in spermatozoa and the two compartments which supply lipids for spermatogenesis (seminal fluid and blood serum) has not been studied. We hypothesised that altered availability of lipids in blood serum and seminal fluid may affect the lipid composition and progressive motility of sperm. 60 men of age 35 years (median (range 20-45) and BMI 30.4 kg/m2 (24-36.5) under preliminary investigation for subfertility were recruited at an NHS clinic. Men provided samples of serum and semen, subject to strict acceptance criteria, for analysis of spermatozoa count and motility. Blood serum (n = 60), spermatozoa (n = 26) and seminal fluid (n = 60) were frozen for batch lipidomics analysis. Spermatozoa and seminal fluid had comparable lipid composition but showed marked differences with the serum lipidome. Spermatozoa demonstrated high abundance of ceramides, very-long-chain fatty acids (C20-22), and certain phospholipids (sphingomyelins, plasmalogens, phosphatidylethanolamines) with low abundance of phosphatidylcholines, cholesterol and triglycerides. Men with spermatozoa of low progressive motility had evidence of fewer concentration gradients for many lipid species between blood serum and spermatozoa compartments. Spermatozoa are abundant in multiple lipid species which are likely to contribute to key cellular functions. Lipid metabolism shows reduced regulation between compartments in men with spermatozoa with reduced progressive motility.


Subject(s)
Semen , Sperm Motility , Adult , Ceramides/metabolism , Cholesterol/metabolism , Fatty Acids/metabolism , Humans , Male , Middle Aged , Phosphatidylcholines/metabolism , Phosphatidylethanolamines/metabolism , Plasmalogens , Semen/metabolism , Sperm Count , Sperm Motility/physiology , Spermatozoa/metabolism , Sphingomyelins/metabolism , Triglycerides/metabolism , Young Adult
14.
J Clin Endocrinol Metab ; 107(7): e2825-e2832, 2022 06 16.
Article in English | MEDLINE | ID: mdl-35359001

ABSTRACT

CONTEXT: Gestational diabetes (GDM) affects 20 million women/year worldwide and is associated with childhood obesity. Infants of affected mothers have increased adiposity from birth, which leads to obesity in later life. However, it remains unknown whether the effect of GDM upon neonatal body composition is due to hyperglycemia alone or is mediated by other pathways. OBJECTIVE: To investigate plasma lipid profiles in obese women according to GDM diagnosis, infant birthweight percentiles, and adiposity. DESIGN: Prospective cohort from UPBEAT trial (ISRCTN 89971375). SETTING: Hospital and community. PATIENTS: 867 obese pregnant women recruited in early pregnancy, assessed at 28 weeks for GDM. Offspring anthropometry was assessed at birth. OUTCOME (PRESPECIFIED): Neonatal birth percentile and abdominal circumference. METHODS: Lipidomic profiling in the fasting plasma oral glucose tolerance test sample using direct infusion mass spectrometry. Analysis included logistic/linear regression, unadjusted and adjusted for maternal age, body mass index, parity, ethnicity, UPBEAT trial arm, and fetal sex. The limit of significance was P = 0.05 for offspring anthropometry and P = 0.002 for lipidomic data. RESULTS: GDM in obese women was associated with elevated plasma concentrations of specific diglycerides [DG(32:0)] and triglycerides [TG(48:0), (50:1), (50:2)] containing fatty acids (16:0), (16:1), (18:0), and (18:1), consistent with increased de novo lipogenesis. In the whole cohort, these species were associated with birthweight percentile and neonatal abdominal circumference. Effects upon infant abdominal circumference remained significant after adjustment for maternal glycemia. CONCLUSIONS: Increased de novo lipogenesis-related species in pregnant women with obesity and GDM are associated with measures of offspring adiposity and may be a target for improving lifelong health.


Subject(s)
Diabetes, Gestational , Pediatric Obesity , Adiposity , Birth Weight , Body Mass Index , Child , Female , Humans , Infant , Infant, Newborn , Lipid Metabolism , Pediatric Obesity/complications , Pregnancy , Prospective Studies
15.
PLoS One ; 17(1): e0262852, 2022.
Article in English | MEDLINE | ID: mdl-35061856

ABSTRACT

BACKGROUND: Women with a history of gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes mellitus (T2DM). They are therefore recommended to follow a healthy diet and be physically active in order to reduce that risk. However, achieving and maintaining these behaviours in the postpartum period is challenging. This study sought to explore women's views on suggested practical approaches to achieve and maintain a healthy diet and physical activity to reduce T2DM risk. METHODS: Semi-structured interviews with 20 participants in Cambridgeshire, UK were conducted at three to 48 months after GDM. The participants' current diet and physical activity, intentions for any changes, and views on potential interventions to help manage T2DM risk through these behaviours were discussed. Framework analysis was used to analyse the transcripts. The interview schedule, suggested interventions, and thematic framework were based on a recent systematic review. RESULTS: Most of the participants wanted to eat more healthily and be more active. A third of the participants considered that postpartum support for these behaviours would be transformative, a third thought it would be beneficial, and a third did not want additional support. The majority agreed that more information about the impact of diet and physical activity on diabetes risk, support to exercise with others, and advice about eating healthily, exercising with a busy schedule, monitoring progress and sustaining changes would facilitate a healthy diet and physical activity. Four other suggested interventions received mixed responses. It would be acceptable for this support to be delivered throughout pregnancy and postpartum through a range of formats. Clinicians were seen to have important roles in giving or signposting to support. CONCLUSIONS: Many women would appreciate more support to reduce their T2DM risk after GDM and believe that a variety of interventions to integrate changes into their daily lives would help them to sustain healthier lifestyles.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetes, Gestational , Diet, Healthy , Exercise , Health Knowledge, Attitudes, Practice , Postpartum Period , Pregnancy in Diabetics , Adult , Female , Humans , Pregnancy
18.
Ann Clin Biochem ; 59(1): 37-45, 2022 01.
Article in English | MEDLINE | ID: mdl-34260324

ABSTRACT

Despite recent advances in care, women with diabetes in pregnancy are still at increased risk of multiple pregnancy complications. Offspring exposed to hyperglycaemia in utero also experience long-term health sequelae, affecting neurocognitive and cardiometabolic status. Many of these adverse consequences can be prevented or ameliorated with good medical care, specifically to optimize glycaemic control. The accurate assessment of glycaemia in pregnancy is therefore vital to safeguard the health of mother and child. However, there is no consensus about the best method of monitoring glycaemic control in pregnancy. Short-term changes in insulin dosage and lifestyle, with altered appetite, insulin sensitivity and red cell turnover create difficulties in interpretation of standard laboratory measures such as HbA1c. The ideal marker would provide short-term feedback on daily or weekly glycaemic control, with additional capability to predict pregnancies at high risk of suboptimal outcomes. Several novel biochemical markers are available which allow assessment of dynamic changes in glycaemia over weeks rather than months. Continuous glucose monitoring devices have advanced in accuracy and provide new opportunities for robust assessment of glycaemia in pregnancy. Recent work from the continuous glucose monitoring in pregnant women with type 1 diabetes trial (CONCEPTT) has provided information about the ability of different markers of glycaemia to predict pregnancy outcomes.The aim of this review is to summarize the care for women with pre-existing diabetes in pregnancy and to highlight the important role of glycaemic monitoring in pregnancy.


Subject(s)
Blood Glucose Self-Monitoring , Diabetes Mellitus, Type 1 , Blood Glucose/metabolism , Blood Glucose Self-Monitoring/methods , Diabetes Mellitus, Type 1/complications , Female , Glycated Hemoglobin/metabolism , Humans , Pregnancy , Pregnancy Outcome
19.
J Proteome Res ; 20(9): 4507-4517, 2021 09 03.
Article in English | MEDLINE | ID: mdl-34423991

ABSTRACT

To characterize the impact of metabolic disease on the peptidome of human and mouse pancreatic islets, LC-MS was used to analyze extracts of human and mouse islets, purified mouse alpha, beta, and delta cells, supernatants from mouse islet incubations, and plasma from patients with type 2 diabetes. Islets were obtained from healthy and type 2 diabetic human donors, and mice on chow or high fat diet. All major islet hormones were detected in lysed islets as well as numerous peptides from vesicular proteins including granins and processing enzymes. Glucose-dependent insulinotropic peptide (GIP) was not detectable. High fat diet modestly increased islet content of proinsulin-derived peptides in mice. Human diabetic islets contained increased content of proglucagon-derived peptides at the expense of insulin, but no evident prohormone processing defects. Diabetic plasma, however, contained increased ratios of proinsulin and des-31,32-proinsulin to insulin. Active GLP-1 was detectable in human and mouse islets but 100-1000-fold less abundant than glucagon. LC-MS offers advantages over antibody-based approaches for identifying exact peptide sequences, and revealed a shift toward islet insulin production in high fat fed mice, and toward proglucagon production in type 2 diabetes, with no evidence of systematic defective prohormone processing.


Subject(s)
Diabetes Mellitus, Type 2 , Islets of Langerhans , Animals , Glucagon , Glucagon-Like Peptide 1 , Humans , Insulin , Mice , Obesity
20.
Diabet Med ; 38(10): e14650, 2021 10.
Article in English | MEDLINE | ID: mdl-34268798

ABSTRACT

AIMS: To explore the views of women with a history of gestational diabetes mellitus (GDM) on suggested practical approaches to support diabetes screening attendance after GDM, which is recommended but poorly attended. METHODS: We conducted semi-structured interviews with 20 participants in Cambridgeshire, UK who had been diagnosed with GDM and were 3-48 months postpartum. Interviews covered whether participants had been screened and why, plans for future screening and their views on potential interventions to facilitate attendance (at the first postpartum test and annual testing). Framework analysis was used to analyse the transcripts. The interview schedule, suggested interventions and thematic framework were based on a recent systematic review. RESULTS: Sixteen participants had undergone screening since pregnancy, explaining that they had an appointment arranged and wanted reassurance that they did not have diabetes. The participants who had not been tested were not aware that it was recommended. Only 13 had planned to attend subsequent tests at the start of the interview. Eight themes to support future attendance were discussed. The majority of the participants agreed that changing the processes for arranging tests, offering choice in test location and combining appointments would facilitate attendance. Child-friendly clinics, more opportunities to understand GDM and the role of postpartum testing, stopping self-testing and increasing their GP's awareness of their pregnancy received inconsistent feedback. The nature of the test used did not appear to influence attendance. CONCLUSIONS: The participants wanted to be screened for diabetes after GDM. We have identified interventions that could be relatively simply incorporated into routine practice to facilitate screening attendance, such as flexibility in the appointment location or time and sending invitations for tests.


Subject(s)
Appointments and Schedules , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/prevention & control , Diabetes, Gestational , Mass Screening/statistics & numerical data , Postpartum Period , Adolescent , Adult , Delivery of Health Care , Diabetes Mellitus, Type 2/etiology , Female , Humans , Interviews as Topic , Mass Screening/methods , Pregnancy , Qualitative Research , Young Adult
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