Mensud Hatunic

Impact of probiotics in women with gestational diabetes mellitus on metabolic health: a randomized controlled trial

OBJECTIVEnProbiotics are live microorganisms that may confer health benefits on the host. Recent trials of probiotic use among healthy pregnant women demonstrate potential for improved glycemic control. The aim of this study was to investigate the effects of a probiotic capsule intervention on maternal metabolic parameters and pregnancy outcome among women with gestational diabetes.nnnSTUDY DESIGNnThis double-blind placebo-controlled randomized trialxa0recruited pregnant women with a new diagnosis of gestational diabetes or impaired glucose tolerance following a 3-hour 100-g glucose tolerance test. Women were randomized to a daily probiotic (Lactobacillus salivarius UCC118) or placebo capsule from diagnosis until delivery. Fasting blood samples were collected at baseline and 4-6 weeks after capsule commencement for analysis of glucose, insulin, c-peptide, and lipids. The primary outcome was difference in fasting glucose postintervention, first analyzed on an intention-to-treat basis and followed by per-protocol analysis that excluded women commenced on pharmacological therapy (insulin or metformin). Secondary outcomes were changes in insulin, c-peptide, homeostasis model assessment and lipids, requirement for pharmacological therapy, and neonatal anthropometry.nnnRESULTSnOf 149 women recruited and randomized, there were noxa0differences between the probiotic and placebo groups in postintervention fasting glucose (4.65 ± 0.49 vs 4.65 ± 0.53 mmol/L; Pxa0= 373), requirement for pharmacological therapy (17% vs 14%; Pxa0= .643), or birthweight (3.57 ± 0.64 vs 3.60 ± 0.57 kg; Pxa0= .845). Among 100 women managed with diet and exercise alone, fastingxa0plasma glucose decreased significantly within both the probiotic (4.76 ± 0.45 to 4.57 ± 0.42 mmol/L; P < .001) and placebo (4.85 ± 0.58 to 4.58 ± 0.45 mmol/L; P < .001) groups, but the levels between groups did not differ (Pxa0= .316). The late gestation-related rise in totalxa0and low-density lipoprotein (LDL) cholesterol was attenuated in thexa0probiotic vs the placebo group (+0.27 ± 0.48 vsxa0+0.50 ± 0.52 mmol/L total cholesterol, Pxa0= .031;xa0+0.08 ± 0.51 vsxa0+0.31 ± 0.45 mmol/L LDL cholesterol, Pxa0= .011). No differences were notedxa0between groups in other metabolic parameters or pregnancy outcome.nnnCONCLUSIONnA probiotic capsule intervention among women with abnormal glucose tolerance had no impact on glycemic control. The observed attenuation of the normal pregnancy-induced rise in total and LDL cholesterol following probiotic treatment requires further investigation, particularly in this obstetric group at risk of future metabolic syndrome.

Modification and Validation of the Triglyceride-to–HDL Cholesterol Ratio as a Surrogate of Insulin Sensitivity in White Juveniles and Adults without Diabetes Mellitus: The Single Point Insulin Sensitivity Estimator (SPISE)

BACKGROUNDnThe triglyceride-to-HDL cholesterol (TG/HDL-C) ratio was introduced as a tool to estimate insulin resistance, because circulating lipid measurements are available in routine settings. Insulin, C-peptide, and free fatty acids are components of other insulin-sensitivity indices but their measurement is expensive. Easier and more affordable tools are of interest for both pediatric and adult patients.nnnMETHODSnStudy participants from the Relationship Between Insulin Sensitivity and Cardiovascular Disease [43.9 (8.3) years, n = 1260] as well as the Beta-Cell Function in Juvenile Diabetes and Obesity study cohorts [15 (1.9) years, n = 29] underwent oral-glucose-tolerance tests and euglycemic clamp tests for estimation of whole-body insulin sensitivity and calculation of insulin sensitivity indices. To refine the TG/HDL ratio, mathematical modeling was applied including body mass index (BMI), fasting TG, and HDL cholesterol and compared to the clamp-derived M-value as an estimate of insulin sensitivity. Each modeling result was scored by identifying insulin resistance and correlation coefficient. The Single Point Insulin Sensitivity Estimator (SPISE) was compared to traditional insulin sensitivity indices using area under the ROC curve (aROC) analysis and χ(2) test.nnnRESULTSnThe novel formula for SPISE was computed as follows: SPISE = 600 × HDL-C(0.185)/(TG(0.2) × BMI(1.338)), with fasting HDL-C (mg/dL), fasting TG concentrations (mg/dL), and BMI (kg/m(2)). A cutoff value of 6.61 corresponds to an M-value smaller than 4.7 mg · kg(-1) · min(-1) (aROC, M:0.797). SPISE showed a significantly better aROC than the TG/HDL-C ratio. SPISE aROC was comparable to the Matsuda ISI (insulin sensitivity index) and equal to the QUICKI (quantitative insulin sensitivity check index) and HOMA-IR (homeostasis model assessment-insulin resistance) when calculated with M-values.nnnCONCLUSIONSnThe SPISE seems well suited to surrogate whole-body insulin sensitivity from inexpensive fasting single-point blood draw and BMI in white adolescents and adults.

Maternal metabolic response to dietary treatment for impaired glucose tolerance and gestational diabetes mellitus

BackgroundDietary advice is a standard component of treatment for pregnant women with impaired glucose tolerance (IGT) and gestational diabetes (GDM), yet few studies report glycemic profiles in response to dietary therapies and the optimal dietary approach remains uncertain.AimTo assess changes in maternal glycemic profile and pregnancy outcomes among women with diet-controlled IGT and GDM.MethodsPregnant women who had one or more elevated values on a 3-h oral glucose tolerance test were enrolled. All participants received dietary advice and glucose monitoring as part of routine clinical care. Fasting and 1-h post-prandial blood samples, collected prior to initiation of clinical treatment and repeated 4–6xa0weeks later, were analyzed for glucose, insulin, and C-peptide. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Women who required pharmacological therapy for glucose control were excluded from analyses.ResultsParticipants (Nu2009=u200993) were of moderately older age (mean 33xa0years), with a high rate of overweight/obesity (mean body mass index (BMI) =u200928.65xa0kg/m2), and were diagnosed late in gestation (mean 29xa0weeks). Fasting (mean ± SD 4.82u2009±u20090.53 to 4.60u2009±u20090.42xa0mmol/l; pu2009<u20090.001) and post-prandial glucose (7.01u2009±u20091.19 to 6.47u2009±u20091.10; pu2009=u20090.004) decreased significantly following the intervention. Baseline HOMA-IR was elevated (3.12u2009±u20091.03) but did not significantly decrease (2.78u2009±u20091.52; pu2009=u20090.066). There were high rates of macrosomia (24.7%) and cesarean delivery (32.3%).ConclusionsAlthough improvements in blood glucose levels were observed among women with diet-controlled IGT and GDM, this was insufficient to significantly affect insulin resistance or perinatal outcome. Late diagnosis and treatment of IGT/GDM may have contributed to such outcomes.

Lixisenatide as add-on treatment among patients with different β-cell function levels as assessed by HOMA-β index

The effect of lixisenatide—a prandial once‐daily glucagon‐like peptide‐1 receptor agonist—on glycaemic control in patients with inadequately controlled type 2 diabetes mellitus (T2DM), stratified by baseline β‐cell function, was assessed.

Assessment of the effectiveness of group education on knowledge for women with newly diagnosed gestational diabetes

BackgroundGestational diabetes mellitus (GDM) is identified in pregnancy and resolves following delivery. It increases maternal and foetal morbidity and may increase risk of future type 2 diabetes. Women diagnosed with GDM need high-quality multidisciplinary education in order to apply necessary changes to their diet and lifestyle. There is a paucity of information on the effectiveness of group education for women with GDM.AimsThe aim of this study was to assess the effect of a multidisciplinary group intervention delivered by a specialist midwife and dietitian on women’s knowledge of GDM.MethodsAll women with a diagnosis of GDM were invited to attend a multidisciplinary group educational session on lifestyle and GDM management. Participants were invited to complete a questionnaire before and after the educational intervention; only individuals who completed both questionnaires were included. The questionnaire reviewed knowledge of suitable diet, implications of GDM diagnosis and management of GDM.ResultsA total of 716 women completed both questionnaires; mean age of the participants was 34xa0years. Just under half of women (46.9%, nxa0=xa0333) were primiparous. The majority of the women (62.5%, nxa0=xa0439) were Irish; 53.4% (nxa0=xa0382) had a family history of diabetes. There was a significant increase in median score for knowledge following the educational intervention (pre-intervention score 8 (−2–12); post-intervention score 12 (1–12); pxa0<xa00.001).ConclusionsThis study demonstrates the benefit of a multidisciplinary group educational session delivered by a specialized midwife and a dietitian on pregnant women’s knowledge and understanding of GDM.

Microvascular diabetes complications in a specialist young adult diabetes service

Background and aimsThe provision of medical care to young adults with type 1 diabetes mellitus is challenging. The aim of this study was to determine the rates of microvascular complications and their progression among patients with type 1 diabetes mellitus attending a specialist young adult diabetes service in Ireland.MethodsA retrospective review of 62 (male 56.5%) patients with type 1 diabetes mellitus attending the young adult diabetes service at our institution was undertaken. Data was recorded across two time points, clinic registration and at 5xa0years following initial contact.ResultsThe meanu2009±u2009SD age at first attendance was 17.4u2009±u20092.0xa0years. Meanu2009±u2009SD duration of diabetes was 6.3u2009±u20093.9xa0years with most patients treated using multiple daily insulin injections (75.8%). diabetic retinopathy rate at first attendance was 17.7% and after 5xa0years was 37.1% (pu2009=u20090.003). The majority of cases were background retinopathy. The prevalence of diabetic kidney disease was 6.4% and this remained unchanged at follow-up. Meanu2009±u2009SD HbA1c improved from 76.1u2009±u200922.4xa0mmol/mol (9.1u2009±u20094.2%) to 69.1u2009±u200914.9xa0mmol/mol (8.5u2009±u20093.5%), pu2009=u20090.044. Duration of diabetes was the only clinical variable associated with retinopathy risk at 5xa0years on multiple regression analysis (pu2009=u20090.037).ConclusionsDiabetic retinopathy is prevalent in young adults with type 1 diabetes attending specialist secondary care diabetes services. Duration of diabetes was the strongest determinant of retinopathy risk.

Pathophysiological Characteristics Underlying Different Glucose Response Curves: A Latent Class Trajectory Analysis From the Prospective EGIR-RISC Study

OBJECTIVE Glucose measurements during an oral glucose tolerance test (OGTT) are useful in predicting diabetes and its complications. However, knowledge of the pathophysiology underlying differences in glucose curve shapes is sparse. We examined the pathophysiological characteristics that create different glucose curve patterns and studied their stability and reproducibility over 3 years of follow-up. RESEARCH DESIGN AND METHODS We analyzed data from participants without diabetes from the observational cohort from the European Group for the Study of Insulin Resistance: Relationship between Insulin Sensitivity and Cardiovascular Disease study; participants had a five–time point OGTT at baseline (n = 1,443) and after 3 years (n = 1,045). Measures of insulin sensitivity and secretion were assessed at baseline with a euglycemic-hyperinsulinemic clamp and intravenous glucose tolerance test. Heterogeneous glucose response patterns during the OGTT were identified using latent class trajectory analysis at baseline and at follow-up. Transitions between classes were analyzed with multinomial logistic regression models. RESULTS We identified four different glucose response patterns, which differed with regard to insulin sensitivity and acute insulin response, obesity, and plasma levels of lipids and inflammatory markers. Some of these associations were confirmed prospectively. Time to glucose peak was driven mainly by insulin sensitivity, whereas glucose peak size was related to both insulin sensitivity and secretion. The glucose patterns identified at follow-up were similar to those at baseline, suggesting that the latent class method is robust. We integrated our classification model into an easy-to-use online application that facilitates the assessment of glucose curve patterns for other studies. CONCLUSIONS The latent class analysis approach is a pathophysiologically insightful way to classify individuals without diabetes based on their response to glucose during an OGTT.

The relationship between bone turnover and insulin sensitivity and secretion: Cross-sectional and prospective data from the RISC cohort study

Bone metabolism appears to influence insulin secretion and sensitivity, and insulin promotes bone formation in animals, but similar evidence in humans is limited. The objectives of this study are to explore if bone turnover markers were associated with insulin secretion and sensitivity and to determine if bone turnover markers predict changes in insulin secretion and sensitivity. The study population encompassed 576 non-diabetic adult men with normal glucose tolerance (NGT; n=503) or impaired glucose regulation (IGR; n=73). Baseline markers of bone resorption (CTX) and formation (P1NP) were determined in the fasting state and after a 2-h hyperinsulinaemic, euglycaemic clamp. An intravenous glucose tolerance test (IVGTT) and a 2-h oral glucose tolerance test (OGTT) were performed at baseline, and the OGTT was repeated after 3years. There were no differences in bone turnover marker levels between NGT and IGR. CTX and P1NP levels decreased by 8.0% (p<0.001) and 1.9% (p<0.01) between baseline and steady-state during the clamp. Fasting plasma glucose was inversely associated with CTX and P1NP both before and after adjustment for recruitment centre, age, BMI, smoking and physical activity. However, baseline bone turnover markers were neither associated with insulin sensitivity (assessed using hyperinsulinaemic euglycaemic clamp and OGTT) nor with insulin secretion capacity (based on IVGTT and OGTT) at baseline or at follow-up. Although inverse associations between fasting glucose and markers of bone turnover were identified, this study cannot support an association between insulin secretion and sensitivity in healthy, non-diabetic men.

The emotional journey of gestational diabetes

Gestational diabetes is an increasingly common diagnosis during pregnancy, and has a substantial effect on maternal and fetal morbidity as well as implications for future health. It is an unwelcome and often unexpected complication at an otherwise joyful time. We wished to study women’s attitudes towards a diagnosis of gestational diabetes. During a 6-week period (May–June, 2016), women with a diagnosis of gestational diabetes attending the National Maternity Hospital, Dublin, Ireland, were invited to participate. Women were invited if they were within one of three different timeframes: within 1 week of diagnosis, several weeks after diagnosis, or within 3 days after delivery. 95 women verbally consented to the study and were asked one question: “How do you feel about your diagnosis of gestational diabetes?” We transcribed their responses and did a thematic analysis of content. To visualise the results of our analysis, we developed an image using iStock, Wordle, and Tagxedo, which demonstrates the changing themes in the lived experience of a diagnosis of gestational diabetes (figure). As suggested by the image, women’s responses indicated that with time, support, and information, initial feelings of anxiety, annoyance, and guilt evolved into a view of gestational diabetes as a manageable complication. This image might indicate the important role of all support services—including multidisciplinary health-care teams, education, family, friends, and other women—in the care of women with gestational diabetes. Importantly, themes emerging from the image also suggest that at least some participants realised the implications of a diagnosis of gestational diabetes for their future health. As clinicians caring for patients with gestational diabetes, we tend to focus on insulin requirements and estimation of fetal weight, and might not appreciate the emotional impact of a diagnosis of gestational diabetes and how it can affect the care of our patients. Having an insight into women’s emotional reaction to a diagnosis of gestational diabetes can help all members of the clinical team to work with and care for women and their babies.

13. Lixisenatide as add-on treatment among patients with different beta-cell function levels as assessed by HOMA-beta index (1018-P)

SamenvattingThis study evaluated the effect of lixisenatide, a once-daily prandial glucagon-like peptide 1 receptor agonist, on glycemic control in patients with T2DM inadequately controlled by oral antidiabetics (OADs). Results were stratified by β-cell function, evaluated using the homeostasis model assessment (HOMA-β) index.