Effects of sodium glucose cotransporter-2 inhibitors on serum uric acid in type 2 diabetes mellitus: A systematic review with an indirect comparison meta-analysis

To describe the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). PubMed, EMBASE, and CENTRAL were searched for randomized controlled trials of SGLT2 inhibitors in patients with T2DM up to Aug 10, 2017, without language or date restrictions. Thirty-one studies totaling 13,650 patients were included. SGLT2 inhibitors significantly decreased SUA levels compared with placebo, canagliflozin WMD –37.02?μmol/L, 95% CI [–38.41, –35.63], dapagliflozin WMD –38.05?μmol/L, 95% CI [–44.47, –31.62], empagliflozin WMD –42.07?μmol/L, 95% CI [–46.27, –37.86]. The drug class effect of SUA reduction suggesting SGLT2 inhibitors might be beneficial for diabetic patients with hyperuricemia.     

Glucagon-like peptide analogues for type 2 diabetes mellitus: systematic review and meta-analysis

Background

Glucagon-like peptide (GLP-1) analogues are a new class of drugs used in the treatment of type 2 diabetes. They are given by injection, and regulate glucose levels by stimulating glucose-dependent insulin secretion and biosynthesis, suppressing glucagon secretion, and delaying gastric emptying and promoting satiety. This systematic review aims to provide evidence on the clinical effectiveness of the GLP-1 agonists in patients not achieving satisfactory glycaemic control with one or more oral glucose lowering drugs.

Methods

MEDLINE, EMBASE, the Cochrane Library and Web of Science were searched to find the relevant papers. We identified 28 randomised controlled trials comparing GLP-1 analogues with placebo, other glucose-lowering agents, or another GLP-1 analogue, in patients with type 2 diabetes with inadequate control on a single oral agent, or on dual therapy. Primary outcomes included HbA1c, weight change and adverse events.

Results

Studies were mostly of short duration, usually 26 weeks. All GLP-1 agonists reduced HbA1c by about 1% compared to placebo. Exenatide twice daily and insulin gave similar reductions in HbA1c, but exenatide 2 mg once weekly and liraglutide 1.8 mg daily reduced it by 0.20% and 0.30% respectively more than glargine. Liraglutide 1.2 mg daily reduced HbA1c by 0.34% more than sitagliptin 100 mg daily. Exenatide and liraglutide gave similar improvements in HbA1c to sulphonylureas. Exenatide 2 mg weekly and liraglutide 1.8 mg daily reduced HbA1c by more than exenatide 10 μg twice daily and sitagliptin 100 mg daily. Exenatide 2 mg weekly reduced HbA1c by 0.3% more than pioglitazone 45 mg daily. Exenatide and liraglutide resulted in greater weight loss (from 2.3 to 5.5 kg) than active comparators. This was not due simply to nausea. Hypoglycaemia was uncommon, except when combined with a sulphonylurea. The commonest adverse events with all GLP-1 agonists were initial nausea and vomiting. The GLP-1 agonists have some effect on beta-cell function, but this is not sustained after the drug is stopped.

Conclusions

GLP-1 agonists are effective in improving glycaemic control and promoting weight loss.     

The association between serum selenium and gestational diabetes mellitus: A systematic review and meta-analysis

BackgroundResults of the studies about association between serum selenium concentration and gestational hyperglycemia are inconsistent. Some studies have demonstrated that women with gestational diabetes mellitus (GDM) have lower Se concentrations while contrary results are reported in other studies.AimThe aim of this study is to compare the serum Se concentration in women with GDM and normoglycemic pregnant women via a systematic review and meta-analysis.MethodsA computerized literature search on four databases (PubMed, Cochrane register of control trials, Scopus and Google scholar) was performed from inception through August 2013. Necessary data were extracted and random effects model was used to conduct the meta-analysis.ResultsSix observational studies (containing 147 women with GDM and 360 normoglycemic pregnant women) were found, which had compared serum Se concentration in women suffering from GDM with normal pregnant ones. Our meta-analysis revealed that serum Se concentration was lower in women with GDM compared to normoglycemic pregnant women (Hedges = −1.34; 95% CI: −2.33 to −0.36; P < 0.01). Stratified meta-analysis demonstrated that concentration of Se in the sera of women with GDM was lower than normal pregnant women both in second and third trimesters, but the result was not significant in second trimester (second trimester: Hedges = −0.68; 95% CI: −1.60−0.25; P = 0.15, third trimester: Hedges = −2.81; 95% CI: −5.21 to −0.42; P < 0.05). It was also demonstrated that serum Se status was lower in pregnant women with impaired glucose tolerance (IGT) compared to normoglycemic pregnant women (Hedges = −0.85; 95% CI: −1.18 to −0.52).ConclusionThe available evidences suggest that serum Se concentration is significantly lower in pregnant women with gestational hyperglycemia compared to normal pregnant women.     

The effect of high-intensity breastfeeding on postpartum glucose tolerance in women with recent gestational diabetes

Background

Although breastfeeding is expected to reduce the incidence of diabetes in women with gestational diabetes, the effect has not been clearly confirmed. We examined whether or not high-intensity breastfeeding reduces the incidence of abnormal glucose tolerance and investigated the effect of high-intensity breastfeeding on insulin resistance during the first year postpartum in Japanese women with current gestational diabetes.

Methods

In this retrospective study, we included women with gestational diabetes who underwent postpartum 75 g oral glucose tolerance test during the first year (12-14 months) postpartum from 2009 to 2011 at a single tertiary perinatal care center in Japan. High-intensity breastfeeding was defined as the condition in which infants were fed by breastfeeding alone or 80% or more of the volume. We investigated the effect of high-intensity breastfeeding on the prevalence of postpartum abnormal glucose tolerance and the postpartum homeostasis model of assessment of insulin resistance (HOMA-IR), after controlling for confounders, including prepregnancy obesity and weight changes during pregnancy and postpartum.

Results

Among 88 women with gestational diabetes, 46 (52%) had abnormal glucose tolerance during the postpartum period. High-intensity breastfeeding women (n?=?70) were significantly less likely to have abnormal glucose tolerance than non-high-intensity breastfeeding women (n?=?18) (46% vs. 78%, p?=?0.015). High-intensity breastfeeding was also associated with a lower HOMA-IR at 12-14 months postpartum than non-high-intensity breastfeeding (1.41?±?1.02 vs. 2.28?±?1.05, p?=?0.035). Those associations remained significant after controlling for confounders. At least six months of high-intensity breastfeeding had a significant effect on lowering both the abnormal glucose tolerance prevalence and HOMA-IR compared with non-high-intensity breastfeeding.

Conclusions

In Japanese women with gestational diabetes, high-intensity breastfeeding ≥6 months had a protective effect against the development of abnormal glucose tolerance during the first year postpartum through improving insulin resistance, independent of obesity and postpartum weight change.

     

The role of serum fructosamine as a screening test for gestational diabetes mellitus

The serum fructosamine concentration indicates the degree of glycation of serum proteins, particularly albumin, and reflects an average blood glucose level over the previous 1-3 weeks. Serum fructosamine, glycated haemoglobin (HbA1c), total serum protein, serum albumin, fasting plasma glucose and oral glucose tolerance test (OGTT) have been measured in 127 healthy control subjects, 102 type 1 and 152 type 2 diabetes mellitus patients and 106 nondiabetic pregnant women. Fructosamine concentration of 2.24 +/- 0.16 and 3.21 +/- 0.41 mmol/l (mean +/- S.D.) has been found in control subjects and diabetics respectively (P less than 0.001). During the second trimester a significantly lower fructosamine level (1.92 +/- 0.21 mmol/l) has been found in pregnant women, most likely due to the low serum albumin concentration (31.35 +/- 3.97 g/l). None of them had a fructosamine level above the normal limit of 2.55 mmol/l. On the other hand, 12 pregnant women showed a disturbed OGTT with normal fructosamine. If the serum fructosamine concentration was adjusted for 40 g/l albumin, then a mean fructosamine of 2.16 +/- 0.24 mmol/l was found in patients with gestational diabetes. Our results show that serum fructosamine has a similar diagnostic value as HbA1c for non-pregnant adults, but neither can replace OGTT for the diagnosis of gestational diabetes.     

The prevalence and predictors of gestational diabetes mellitus in Hungary

There are conflicting results regarding the frequency of gestational diabetes (GDM) in Hungary. The aim of this study was to estimate the prevalence of GDM and to clarify the association between selected maternal characteristics and GDM risk. In a population-based screening program of GDM in Tolna County, Hungary, 75 g OGTTs were offered to all pregnant women between 24-28 weeks of gestation and evaluated according to WHO criteria in 2000 (WHO GDM). Women were also classified based on the IADPSG criteria (IADPSG GDM). Selected risk factors were recorded by district nurses. OGTT results were available for 1,835 (81.2%) pregnancies out of 2,261. Altogether 159 (8.7%) were diagnosed as WHO GDM and 304 (16.6%) as IADPSG GDM. Gestational diabetes was related to older age, higher BMI, and an increasing number of deliveries (all p<0.005). The risk of IADPSG GDM monotonously increased with age, -pre-pregnancy BMI and number of deliveries. The risk of WHO GDM increased linearly with age, however, women with the highest BMI (≥ 29.2 kg/m2) had decreased risk compared to women with a BMI of 26.1-29.1 kg/m2 (p<0.05). There was an inverse U-shaped association between GDM risk and number of deliveries with the highest risk observed in those with 3 deliveries (p quadratic term=0.008). We found a high prevalence of GDM in this Caucasian Hungarian population. Our results suggest that pre-pregnancy BMI and previous deliveries elevate the risk of WHO GDM only to a certain level, above which the risk decreases.     

Elemental contents in serum of pregnant women with gestational diabetes mellitus

Diabetes mellitus is characterized by hyperglycemia and is closely related to trace elements. Quite a few pregnant women suffer from impaired glucose tolerance (IGT) or gestational diabetes mellitus (GDM). Investigation of the changes of elemental contents in serum of the pregnant women with IGT and GDM is significant in the etiological research and cure of the diseases. In the present work, the elements Cu, Zn, Ca, Sr, Mg, P, Fe, and Al in the serum of pregnant women were determined. The elemental contents in different experimental groups were compared. Also, the correlation between elemental contents and gestational period was observed. The results showed that compared with normal pregnant women, the Cu contents in serum of pregnant women with GDM increased, but Zn contents had a decreasing trend. In addition, for all pregnant women, the Ca contents in serum had an obvious inverse correlation with gestational period.     

Changes of serum selenium in pregnant women with gestational diabetes mellitus

Gestational diabetes is one of the most common diseases in pregnancy. In the present work, the possible relationship between serum selenium concentration and gestational diabetes was investigated. Blood samples of 234 pregnant women were collected, including 98 subjects with impaired glucose tolerance (IGT), 46 subjects with gestational diabetes mellitus (GDM), and 90 normal pregnant women (NPW). An additional 17 samples of normal women of fertile age (NW) were collected for comparison. The hydride generation atomic fluorescence spectrometry was used for selenium determination. The mean serum selenium levels obtained for each group were 0.0741±0.0167 mg/L for NPW, 0.0631±0.0132 mg/L for IGT, 0.0635±0.0120 mg/L for GDM, and 0.108±0.0170 mg/L for NW. Serum selenium levels were significantly lower in pregnant woman with IGT (p<0.001) and GDM (p<0.001) than in NPW. Furthermore, an inverse correlation between the serum selenium concentration and the gestational period was also observed. Selenium supplementation during gestation for pregnant women, especially with IGT and GDM, should be considered.     

Screening of mitochondrial mutations in Saudi women diagnosed with gestational diabetes mellitus: A non-replicative case-control study

IntroductionAmong metabolic disorders, gestational diabetes mellitus (GDM) is specified as hyperglycemia caused by glucose or carbohydrate intolerance defects. GDM is distinguished by oxidative stress, and has been connected to mitochondrial dysfunction. Previous studies have documented the relation between A12026G, A8344G and A3243G mutations in ND4, tRNA^Leu(UUR), and tRNA^Lys genes in different modes of diabetes.AimThe purpose of this study was to investigate into the relationship between GDM women and common mitochondrial mutations including A12026, A8344G, and A3243G in Saudi women.MethodsIn this case-control study, we have opted 96 GDM and 102 non-GDM pregnant women and DNA was extracted using EDTA blood and based on specific primers, Polymerase Chain Reaction was followed and then Restriction Fragment Length Polymorphism (RFLP) analysis was performed. Restriction enzymes was cross-checked with Lambda DNA and 10% of the purified PCR products were performed the Sanger sequencing analysis to reconfirm the RFLP analysis of the studied results.ResultsNone of the heterozygous and homozygous mutations were not observed in our study. All the subjects were turned to be homozygous normal genotypes.ConclusionThis study confirms that A12026, A8344G, and A3243G mutations have no role in the Saudi women with GDM.     

Recent advances in molecular biomarkers for diabetes mellitus: a systematic review

Context: Diabetes is a growing global metabolic epidemic. Current research is focussing on exploring how the biological processes and clinical outcomes of diabetes are related and developing novel biomarkers to measure these relationships, as this can subsequently improve diagnostic, therapeutic and management capacity.

Objective: The objective of this study is to identify the most recent advances in molecular biomarkers of diabetes and directions that warrant further research.

Methods: Using a systematic search strategy, the MEDLINE, CINAHL and OVID MEDLINE databases were canvassed for articles that investigated molecular biomarkers for diabetes. Initial selections were made based on article title, whilst final inclusion was informed by a critical appraisal of the full text of each article.

Results: The systematic search returned 246 records, of which 113 were unique. Following screening, 29 records were included in the final review. Three main research strategies (the development of novel technologies, broad biomarker panels, and targeted approaches) identified a number of potential biomarkers for diabetes including miR-126, C-reactive protein, 2-aminoadipic acid and betatrophin.

Conclusion: The most promising research avenue identified is the detection and quantification of micro RNA. Further, the utilisation of functionalised electrodes as a means to detect biomarker compounds also warrants attention.     

Hypercalciuria in patients with diabetes mellitus type 1 and 2--studies of its pathogenesis using the oral calcium tolerance test

The study was aimed at the evaluation of changes in the urinary excretion of calcium in patients with diabetes of type I and II. The investigations were carried out in 34 patients with type I diabetes, 28 patients with type II diabetes and 30 control subjects having the normal glucose tolerance. The oral calcium tolerance test according to Pak was performed in all the patients and the controls. Besides normocalciuria, also hypercalciuria of renal origin, as well as hipercalciuria resulting from an elevated intestinal absorption of calcium have been found in diabetic patients. These disturbances occurred much more frequently in patients with type I diabetes, especially in those of age below 40.     

Pregnancy loss and neonatal death in women with type 1 or type 2 diabetes mellitus

Background: Diabetes mellitus (DM) is known to be a significant risk factor for pregnancy loss, either through still-birth or late intrauterine death or as the result of severe congenital malformation. Improved glycemic control and other advances in care substantially reduced the incidence of pregnancy loss in women with type 1 DM in most countries by the 1970s. However, because of a greater prevalence of obesity since the 1980s, the emergence of type 2 DM in pregnancy has become a significant problem. Although more pregnancies now occur in women with type 2 DM than in those with type 1 DM in many locations, relatively little information has been published about pregnancy loss in type 2 DM.Objectives: This article examines the prevalence and causes of pregnancy loss in type 1 and type 2 DM and identifies factors in addition to glycemic control that may influence pregnancy outcome.Methods: A MEDLINE search was conducted for recent literature on pregnancy loss in DM. Series reporting >200 pregnancies in type 1 DM and/or >100 pregnancies in type 2 DM were included.Results: Thirty-four studies were identified (15 in type 1 DM [1997-2007], 19 in type 2 DM [1986-2007]). In type 1 DM, major congenital anomalies now account for ~50% of pregnancy losses, and all-cause perinatal mortality remains higher than in the general population. Several studies have suggested that the perinatal mortality rate is higher in type 2 DM than in type 1 DM. Factors other than glycemic control probably explain this phenomenon: women with type 2 DM typically are older and more obese, and they come from disadvantaged communities—all risk factors for pregnancy loss, particularly late intrauterine death and chorioamnionitis. In some women, type 2 DM may be recognized for the first time during pregnancy; pregnancies in these women carry the same risks of pregnancy loss as those in women with established DM.Conclusions: Demographic changes in the prevalence of obesity suggest that the prevalence of type 2 DM in pregnancy will almost certainly increase. Although meticulous glycemic control is undoubtedly important in achieving good pregnancy outcomes, clinicians should be aware of the multiple risk factors faced by women with DM.     

Neonatal and obstetric outcomes in diet- and insulin-treated women with gestational diabetes mellitus: a retrospective study

Background

To evaluate the neonatal and obstetric outcomes of pregnancies complicated by gestational diabetes mellitus (GDM). Screening and treatment – diet-only versus additional insulin therapy – were based on the 2010 national Dutch guidelines.

Methods

Retrospective study of the electronic medical files of 820 singleton GDM pregnancies treated between January 2011 and September 2014 in a university and non-university hospital. Pregnancy outcomes were compared between regular care treatment regimens –diet-only versus additional insulin therapy- and pregnancy outcomes of the Northern region of the Netherlands served as a reference population.

Results

A total of 460 women (56 %) met glycaemic control on diet-only and 360 women (44 %) required additional insulin therapy. Between the groups, there were no differences in perinatal complications (mortality, birth trauma, hyperbilirubinaemia, hypoglycaemia), small for gestational age, large for gestational age (LGA), neonate weighing >4200 g, neonate weighing ≥4500 g, Apgar score <7 at 5 min, respiratory support, preterm delivery, and admission to the neonatology department. Neonates born in the insulin-group had a lower birth weight compared with the diet-group (3364 vs. 3467 g, p?=?0.005) and a lower gestational age at birth (p?=?0.001). However, birth weight was not different between the groups when expressed in percentiles, adjusted for gestational age, gender, parity, and ethnicity. The occurrence of preeclampsia and gestational hypertension was comparable between the groups. In the insulin-group, labour was more often induced and more planned caesarean sections were performed (p?=?0.001). Compared with the general obstetric population, the percentage of LGA neonates was higher in the GDM population (11.0 % vs.19.9 %, p?=?<0.001).

Conclusions

Neonatal and obstetric outcomes were comparable either with diet-only or additional insulin therapy. However, compared with the general obstetric population, the incidence of LGA neonates was significantly increased in this GDM cohort.

     

Association between shift work and risk of type 2 diabetes mellitus: a systematic review and dose-response meta-analysis of observational studies

ABSTRACT

To evaluate the association between shift work and risk of type 2 diabetes mellitus, we searched PubMed, EMBASE and Web of Science from their inception to June 8, 2019. Observational studies examining the relationship between shift work and type 2 diabetes were included. Subgroup analyses were conducted to explore whether specific characteristics would affect the relationship. A dose-response relationship was estimated by using generalized least squares trend regression. Finally, twelve cohort studies and nine cross-sectional studies were included (inter-rater agreement, k = 0.96). The result of meta-analysis indicated that shift work was associated with an increased risk of type 2 diabetes (relative risk = 1.10, 95% confidence interval = 1.05–1.14). Subgroup analyses demonstrated that female shift workers have increased risk of type 2 diabetes while male not observed, health care workers showed the highest risk compared with civil servants and manual workers, and night shift and rotating shift were associated with an increased risk of type 2 diabetes. Dose-response meta-analysis based on three cohorts among female workers indicated that there might be a positive association between duration of shift work and the risk of type 2 diabetes. In conclusion, shift work is positively associated with an increased risk of type 2 diabetes. Among female workers, with the years of exposure to shift work prolonged, the risk of type 2 diabetes might increase accordingly. In the future, more studies are needed to confirm the results of dose-response analysis.