Development of ALOHa-G Risk Score for Detecting Postpartum Dyslipidemia Among Normoglycemic Women with Previous Gestational Diabetes: Observational Cohort Study.

INTRODUCTION: Previous gestational diabetes (pGD) is associated with a high risk of postpartum dyslipidemia (pD). Our study was aimed at investigating the prevalence of pD and estimating the risk for pD based on metabolic pregnancy parameters in normoglycemic women with pGD. METHODS: 147 women with pGD and normoglycemia after delivery were divided into groups: A (n = 63) with pD and B (n = 84) with normal lipids, defined by the National Cholesterol Education Program's Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report (NCEP ATP III). We recorded age, body mass index (BMI) at conception, fasting glucose (FG), HbA1c, total cholesterol (TC), triglycerides (Tg), low-density lipoprotein (LDL-c), and high-density lipoprotein cholesterol (HDL-c) measured mid-pregnancy and 1-6 months after delivery. GD was diagnosed by 2 h oral glucose tolerance test (OGTT) between the 24th and the 28th week of gestation, which was repeated after delivery to confirm normoglycemia. RESULTS: 42.8% had pD (group A) while 57.2% had normal lipids (group B). Group A was older (36.8 ± 2.7) than B (33.0 ± 4.2 years, p < 0.001) and had a higher BMI (A 31.2 ± 6.4 vs. B 25.5 ± 2.4 kg/m2, p < 0.001). Simultaneously, HbA1c and FG were higher in group A (5.4 ± 0.3, 5.1 ± 0.4) than B (5.2 ± 0.0%, p = 0.001; 4.8 ± 0.0 mmol/L, p < 0.001). Also, group A had higher TC, LDL-c, and Tg [6.6 (6.1-6.9); 4.2 ± 0.4; 2.9 ± 0.8] compared to B [6.2 (5.4-6.9), p < 0.001; 3.4 ± 0.9, p = 0.001; 2.5 ± 0.6, p < 0.001], while the two groups had comparable HDL-c (A: 1.2 ± 0.3 vs. B: 1.2 ± 0.2 mmol/L, p = 0.998). Calculating the cutoff for age, BMI, HbA1c, FG, LDL-c, and Tg (> 35 years, 26.4 kg/m2, 5.2%, 4.8, 3.9 and 2.7 mmol/L, respectively), univariate regression analysis showed a difference for each (p < 0.001). Allocating 1 point to each predictor, we developed ALOHa G score, which showed high accuracy (AUC 0.931, p < 0.001) for risk of pD in normoglycemic women with pGD. According to the ALOHa-G score, more women in group A were at high risk (≥ 4) and medium risk (= 3) (61.9; 34.9) for pD than in group B (4.8; 14.3), with a lower percentage at low risk for PD (≤ 2) in group A than in group B (3.2 vs. 81.0%). CONCLUSION: Our results implied a remarkable occurrence of pD in normoglycemic women with pGD. Also, the ALOHa-G score was developed based on pregnancy metabolic predictors and could be used to identify normoglycemic women with pGD who are at high risk for pD.

Prevalence and Metabolic Predictors for Early Diagnosed Prediabetes in Women with Previous Gestational Diabetes: Observational Cohort Study.

INTRODUCTION: Women with previous gestational diabetes (pGD) are at higher risk of prediabetes (PD) after delivery. The aim of this study was to determine the prevalence of and predictors for PD among women with pGD. METHODS: The study included 186 women with pGD treated by lifestyle modification. After delivery, the women were divided into group A (n = 80) with PD and group B (n = 106) with normal glucose tolerance (NGT), defined by the results of the 2-h oral glucose tolerance test at 4-12 weeks after delivery. We recorded age, body mass index (BMI) at conception and after delivery, fasting glucose (FG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (Tg), low density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c) and the Tg/HDL-c ratio measured in the third trimester of pregnancy. RESULTS: Of the 186 women with pGD enrolled in the study, 43% showed prediabetes at 4-12 weeks after delivery, with 13.9% of these women showing impaired FG (IFG), 12.9% showing impaired glucose tolerance (IGT) and 16.2% with IFG/IGT. The groups differed in terms of age and BMI at conception and after delivery. In the third trimester of pregnancy, HbA1c was higher in women in group A than in those in group B (mean ± standard deviation: 5.6 ± 0.4 vs. 5.2 ± 0.3%; p < 0.001), while FG was comparable. Compared to women in group B, women in group A had higher TC (7.1 ± 0.8 vs. 6.6 ± 1.0 mmol/L), Tg (2.7 ± 0.9 vs. 2.1 ± 0.6 mmol/L) and LDL-c (4.7 ± 0.8 vs. 4.3 ± 1.0 mmol/L) (all p < 0.001), lower HDL-c (1.0 ± 0.2 vs. 1.4 ± 1.0; p < 0.001) and higher median Tg/HDL-c (5.4 [range 4.6-14.3] vs. 4.9 [range 1.1-11.5]; p < 0.001). Univariate analysis found an association between prediabetes and age, BMI at conception and after delivery, HbA1c, TC, LDL-c, HDL-c, Tg and Tg/HDL-c ratio. Of these variables, the multivariate analysis showed age (odds ratio [OR] 1.19; p < 0.001), HbA1c (OR 31.06; p < 0.001), Tg (OR 4.09; p < 0.001) and LDL-c (OR 2.00; p = 0.005) as predictors for prediabetes. CONCLUSION: High prevalence of early diagnosed PD in women with pGD was accompanied by advanced age and higher BMI at conception and after delivery. Moreover, age, HbA1c, Tg and LDL-c were predictors for PD.

A 26-Week Randomized Controlled Trial of Semaglutide Once Daily Versus Liraglutide and Placebo in Patients With Type 2 Diabetes Suboptimally Controlled on Diet and Exercise With or Without Metformin.

OBJECTIVE: To investigate the efficacy and safety of once-daily semaglutide in comparison with once-daily liraglutide and placebo in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This 26-week, multicenter, double-blind trial involved patients diagnosed with type 2 diabetes with HbA1c 7.0-10.0% (53-86 mmol/mol) and treated with diet and exercise with or without metformin. Patients were randomized 2:2:1 to once-daily semaglutide, liraglutide, or placebo in one of four volume-matched doses (semaglutide 0.05, 0.1, 0.2, or 0.3 mg and liraglutide 0.3, 0.6, 1.2, or 1.8 mg, with both compared within each volume-matched dose group). Primary end point was change in HbA1c from baseline to week 26. RESULTS: In total, 705 randomized patients were exposed to trial products. At week 26, a dose-dependent change in HbA1c was observed with semaglutide from -1.1% (0.05 mg) to -1.9% (0.3 mg) and with liraglutide from -0.5% (0.3 mg) to -1.3% (1.8 mg) (all P < 0.001 in favor of volume-matched semaglutide dose). Change with pooled placebo was -0.02% (P < 0.0001 vs. semaglutide). Gastrointestinal (GI) disorders were the most common adverse events (AEs) with semaglutide and liraglutide, occurring in 32.8-54.0% and 21.9-41.5% of patients, respectively. CONCLUSIONS: Once-daily semaglutide at doses up to 0.3 mg/day resulted in greater reductions in HbA1c compared with liraglutide or placebo but with a higher frequency of GI AEs.

Acute effects of ghrelin on insulin secretion and glucose disposal rate in gastrectomized patients.

CONTEXT: Plasma ghrelin concentration is diminished in gastrectomized patients. Acute ghrelin administration reduces insulin secretion, whereas insulin infusion has been shown to decrease ghrelin levels. Whether ghrelin has any effect on glucose utilization in humans is unknown. OBJECTIVE: Our objective was to reveal the effect of ghrelin on insulin-mediated glucose disposal in gastrectomized patients. STUDY AND SETTING: We conducted a double-blind, randomized, placebo-controlled, hospital-based study. PATIENTS: Seven men and three women who all had a previous total gastrectomy and truncal vagotomy entered and completed the study. INTERVENTION: Each individual received infusion of saline alone or saline with ghrelin (5.0 pmol/kg.min) during a 5-h hyperinsulinemic (80 mU/m(2).min) euglycemic clamp on 2 separate days. MAIN OUTCOME MEASURES: We assessed glucose disposal rate and concentrations of C-peptide, ghrelin, GH, IGF-I, IGF-binding protein (IGFBP)-3 and -1, cortisol, leptin, and adiponectin. RESULTS: Glucose disposal rate decreased during ghrelin infusion (control study 8.6 +/- 0.2 vs. 7.2 +/- 0.1 mg/kg.min P < 0.001). In experiments with saline infusion, levels of ghrelin (P < 0.001), C-peptide (P < 0.001), glucagon (P < 0.001), adiponectin (P = 0.005), cortisol (P = 0.012), IGF-I (P < 0.001), IGFBP-3 (P = 0.038), and IGFBP-1 (P = 0.001) fell in response to euglycemic hyperinsulinemia. GH concentration maintained at baseline, whereas leptin significantly rose (P < 0.001). In the ghrelin infusion study, the plateau level of ghrelin concentration (6963.6 +/- 212.9 pg/ml) was maintained from 90 min throughout the experiment. GH (P < 0.001) and cortisol (P = 0.04) concentrations rose, whereas C-peptide levels were more suppressed than in the control study (P < 0.001). Other hormones and IGFBPs changed similarly as in the study with saline infusion. CONCLUSION: It appears that ghrelin might be involved in the negative control of insulin secretion and glucose consumption in gastrectomized patients, at least after acute administration.