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.

Targeting Mitochondria in Diabetes.

Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes.

Evaluation of Glycaemic Control, Glucose Variability and Hypoglycaemia on Long-Term Continuous Subcutaneous Infusion vs. Multiple Daily Injections: Observational Study in Pregnancies With Pre-Existing Type 1 Diabetes.

INTRODUCTION: We evaluated the effectiveness of long-term continuous subcutaneous insulin infusion (CSII) compared with multiple daily insulin (MDI) injections for glycaemic control and variability, hypoglycaemic episodes and maternal/neonatal outcomes in pregnant women with pre-existing type 1 diabetes (pT1D). METHODS: Our observational cohort study included 128 consecutive pregnant women with pT1D, who were treated from 1 January 2010 to 31 December 2017. Of 128 participants, 48 were on CSII and 80 were on MDI. Glycaemic control was determined by glycated haemoglobin (HbA1c) (captured in preconception and each trimester of pregnancy). Glucose variability (GV) was expressed as the coefficient of variation (CV) [calculated from self-monitoring of blood glucose (SMBG) values], and hypoglycaemia was defined as glucose values < 3.9 mmol/l. The data on maternal and neonatal outcomes were collected from obstetrical records. RESULTS: Duration of the treatment was 8.8 ± 5.3 years in the CSII and 12.6 ± 8.0 years in the MDI group. The CSII lowered HbA1c in preconception (7.1 ± 0.1 vs. 7.9 ± 0.2%, p = 0.03) and the first (6.9 ± 0.1 vs. 7.7 ± 0.2%, p = 0.02), second (6.6 ± 0.1 vs. 7.2 ± 0.1%, p = 0.003) and third (6.5 ± 0.1 vs. 6.8 ± 0.1%, p = 0.02) trimesters significantly better than MDI. Significantly lower CV was observed only for fasting glycaemia in the first trimester (17.1 vs 28.4%, p < 0.001) in favour of CSII. Moreover, the CSII group had significantly lower mean hypoglycaemic episodes/week/patient only during the first trimester (2.0 ± 1.7 vs 4.8 ± 1.5, p < 0.01). In early pregnancy, the majority of women on CSII had less hypoglycaemia than on MDI (0-3: 79.1 vs. 29.1%; 4-6: 18.8 vs. 65.8%; ≥ 7: 2.1 vs. 5.1%, p < 0.01, respectively). We found no difference in the incidence of adverse maternal/neonatal outcomes. CONCLUSIONS: Treatment with CSII resulted in a favourable reduction of HbA1c in the preconception period and each trimester in pregnancy. Moreover, long-term CSII treatment demonstrated more stable metabolic control with less GV of fasting glycaemia and fewer hypoglyacemic episodes only during early pregnancy.