Effect of Ramadan fasting on glycaemic parameters & body mass index in type II diabetic patients: A meta-analysis.

Background & objectives: There has been an ongoing debate about the impact of Ramadan fasting (RF) on the health of these individuals who fast during Ramadan. The aim of this meta-analysis was to evaluate the relationship between RF and glycaemic parameters in type 2 diabetes mellitus (T2DM) patients. Methods: Search terms were decided and databases such as MEDLINE EBSCO, Google Scholar and EMBASE were searched for eligible studies. Standardized mean differences and 95 per cent confidence intervals (CIs) of post-prandial plasma glucose (PPG), fasting plasma glucose (FPG), glycated haemoglobin (HbA1c) (%) and fructosamine levels were calculated for different treatment regimens. Results: Of the 40 studies, 19 were found eligible for inclusion in the meta-analysis. Based on pooled results, significant reductions in FPG were found in single oral antidiabetics (OAD) [standardized weighted mean difference (SMD)=0.47, 95% CI=(0.20-0.74)], multi-OAD [SMD=0.36, 95% CI=(0.11-0.61)] and multitreatment subgroups [SMD=0.65, 95% CI=(0.03-1.27)] and overall [SMD=0.48, 95% CI=(0.27-0.70)]. Furthermore, HbA1c(%) [SMD=0.26, 95% CI=(0.03-0.49)] and body mass index (BMI) [SMD=0.18, 95% CI=(0.04-0.31)] were significantly decreased in the multi-OAD group. Interpretation & conclusions: The meta-analysis showed that RF was not associated with any significant negative effects on PPG and fructosamine levels. However, BMI and FPG and HbA1c(%) were positively affected by RF.

Adolescent obesity and the role of the fat mass and obesity-associated gene polymorphism.

PURPOSE: The association between fat mass and obesity-associated (FTO) gene and obesity is unclear in both adults and adolescents. The aim of this study was to examine the role of the FTO gene variant rs9939609 as a candidate gene for obesity and the relationship between insulin resistance (IR), metabolic syndrome (MetS), estimated glomerular filtration rate (eGFR) and neutrophil-to-lymphocyte ratio (NLR). METHODS: Obese adolescents (n=100) and healthy controls (n=100) were included. Rs9939609 polymorphism in the FTO gene was genotyped by PCR-SNaPshot. RESULTS: The prevalence of insulin resistance (IR), metabolic syndrome (MetS) and hyperfiltration were 47%, 60% and 27%, respectively. There were no significant differences in genotype and allele frequencies between obese adolescents and controls; however, prevalence of MetS in female patients with A allele carriers was more frequent and prevalence of hyperfiltration was less frequent with T allele carriers (P.

Liraglutide-related cholelithiasis.

Liraglutide is a glucagon-like peptide-1 analog and recently started to be using as an incretin-based treatment for diabetes mellitus. Liraglutide causes some adverse affects including nausea, vomiting, acute nasopharyngitis and acute pancreatitis. However, development of liraglutide-dependent cholelithiasis has not been reported in the literature. A 75-year-old female patient had been diagnosed with type 2 diabetes mellitus for 10 years and she has been treated by liraglutide for 6 months. The patient was admitted to the emergency service due to sudden onset of abdominal pain. After laboratory and imaging studies, she was diagnosed with acute cholecystitis and cholelithiasis. And then patient's oral intake was stopped, intravenous fluid and ceftriaxone 2 g/day were started. Furthermore, liraglutide treatment discontinued and ursodeoxycholic acid (UDCA) was started to treat cholelithiasis. During follow-up, abdominal pain completely relieved. Hepatobiliary ultrasonography in sixth month follow-up showed entirely regression of cholelithiasis. Any liraglutide-related cholelithiasis case has not been reported in the literature previously. Therefore, our case is the first case. Especially, elderly diabetic patients who are started to liraglutide treatment should be monitored closely for the formation of cholelithiasis. UDCA treatment would be an alternative prior to surgical treatment for liraglutide-related cholelithiasis.

The significance of finerenone as a novel therapeutic option in diabetic kidney disease: a scoping review with emphasis on cardiorenal outcomes of the finerenone phase 3 trials.

This scoping review prepared by endocrinology and nephrology experts aimed to address the significance of finerenone, as a novel therapeutic option, in diabetic kidney disease (DKD), based on the biological prospect of cardiorenal benefit due to non-steroidal mineralocorticoid receptor antagonist (MRA) properties, and the recent evidence from the finerenone phase 3 program clinical trials. The importance of finerenone in slowing DKD progression was critically reviewed in relation to the role of MR overactivation in the pathogenesis of cardiorenal disease and unmet needs in the current practice patterns. The efficacy and safety outcomes of finerenone phase III study program including FIDELIO-DKD, FIGARO-DKD and FIDELITY were presented. Specifically, perspectives on inclusion of patients with preserved estimated glomerular filtration rate (eGFR) or high albuminuria, concomitant use of sodium-glucose co-transporter-2 inhibitor (SGLT2i) or glucagon-like peptide 1 receptor agonist (GLP-1 RA), baseline glycated hemoglobin (HbA1c) level and insulin treatment, clinically meaningful heart failure outcomes and treatment-induced hyperkalemia were addressed. Finerenone has emerged as a new therapeutic agent that slows DKD progression, reduces albuminuria and risk of cardiovascular complications, regardless of the baseline HbA1c levels and concomitant treatments (SGLT2i, GLP-1 RA, or insulin) and with a favorable benefit-risk profile. The evolving data on the benefit of SGLT2is and non-steroidal MRAs in slowing or reducing cardiorenal risk seem to provide the opportunity to use these pillars of therapy in the management of DKD, after a long-period of treatment scarcity in this field. Along with recognition of the albuminuria as a powerful marker to detect those patients at high risk of cardiorenal disease, these important developments would likely to impact standard-of-care options in the setting of DKD.

Mitochondrial uncoupling protein 2 (UCP2) gene polymorphisms are associated with childhood obesity and related metabolic disorders.

OBJECTIVE: This study aimed to investigate the possible role of uncoupling protein 2 (UCP2) gene polymorphisms in childhood obesity and related metabolic disorders. METHODS: Obese patients (n=100) and healthy controls (n=100) were analyzed for -866G>A and insertion/deletion (I/D) polymorphisms of the UCP2 gene by polymerase chain raction and/or restriction fragment length polymorphism. RESULTS: UCP2 I/D polymorphism showed an association with obesity. The insertion homozygous genotype (II) was higher in obese patients (p=0.0001), while the DD genotype was higher in controls (p=0.0034). Body mass index and relative weight were lower in patients carrying the A allele of the -866G>A polymorphism (p=0.021 and p=0.047, respectively). There was an association between insulin resistance and -866A allele carrier patients with consanguineous parents (p=0.005). CONCLUSION: Insertion homozygous genotype and the allele of I/D polymorphism were found to be risk factors for childhood obesity and related metabolic disorders. The -866A allele was associated with susceptibility to central adiposity, hypercholesterolemia, hypertriglyceridemia and insulin resistance.

The Relationship Between Dipeptidyl Peptidase-4 Inhibitor Usage and Asymptomatic Amylase Lipase Increment in Type 2 Diabetes Mellitus Patients.

OBJECTIVES: In different studies, it has been shown that the use of dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP-4 inh) does not increase the risk of pancreatitis or pancreatic cancer. Although the number of studies involving clinical pancreatitis clinics is sufficient, the number of studies involving clinical non-pancreatitis hyperamylasemia is rare. The aim of the study was to investigate the relationship between DPP-4 inh usage and amylase and lipase increment without clinical pancreatitis symptoms. MATERIALS AND METHODS: Eighty-seven patients who met the inclusion criteria were enrolled. The patients were divided into 3 groups according to their use of saxagliptin, sitagliptin, or vildagliptin. All patients included in the study were receiving metformin at a dose of 2 g/day. Fasting blood glucose, postprandial blood glucose, HbA1C, serum creatinine, ALT, amylase, and lipase results were recorded at the beginning of treatment and at the end of 3 months. RESULTS: There was an increase in all groups in terms of amylase and lipase values but there was no significant difference between the groups in terms of increase (p>0.05) There was no statistically significant increase in the saxagliptin and vildagliptin groups (p>0.05) when the baseline and 3-month values of lipase and amylase increase were examined. However, there was a statistically significant increase in amylase and lipase in the sitagliptin group (p<0.05). CONCLUSION: The use of DPP-4 inh can increase amylase and lipase levels without clinical findings of acute pancreatitis in the patient. DPP-4 inh should be used with caution in patients at risk for pancreatitis and pancreatic cancer. Patients using DPP-4 inh, especially sitagliptin, should be evaluated carefully for pancreatitis risk factors.

Association of melatonin receptor 1 B gene (rs10830963 and rs9192552) polymorphism with adolescent obesity and related comorbidities in Turkey.

Objective To examine the role of rs10830963 and rs8192552 polymorphisms in melatonin receptor 1 B (MTNR1B) gene on the development of obesity and related comorbidities among adolescents in South-Eastern Turkey. Methods The present study included 200 unrelated adolescents (100 obese, 100 normal weight). The rs8192552 and rs10830963 polymorphisms in the MTNR1B gene were genotyped using a PCR SNaPshot assay. Results No statistically significant association was observed between MTNR1B gene rs8192552/rs10830963 polymorphisms and adolescent obesity. In adolescents with an rs8192552 E allele, homeostasis model assessment for insulin resistance (IR) level was lower and IR was less common. In morbidly obese adolescents with an rs8192552 E allele, total cholesterol level was lower. In obese adolescents with metabolic syndrome, plasma fasting glucose level was higher in rs10830963G allele carriers. In obese girls, body weight was lower in those with a rs10830963 C allele, whereas in obese boys, body weight and waist circumference were higher in those with a rs10830963 C allele. Conclusions The MTNR1B gene was not confirmed as an obesity susceptibility gene in adolescents. However, an association between the MTNR1B gene and IR/hypercholesterolemia/metabolic syndrome was observed in obese adolescents. A sex-specific effect on obesity was also identified.

Expert Opinion: Patient Selection for Premixed Insulin Formulations in Diabetes Care.

Premixed insulins are an important tool for glycemic control in persons with diabetes. Equally important in diabetes care is the selection of the most appropriate insulin regimen for a particular individual at a specific time. Currently, the choice of insulin regimens for initiation or intensification of therapy is a subjective decision. In this article, we share insights, which will help in rational and objective selection of premixed formulations for initiation and intensification of insulin therapy. The glycemic status and its variations in a person help to identify the most appropriate insulin regimen and formulation for him or her. The evolution of objective glucometric indices has enabled better glycemic monitoring of individuals with diabetes. Management of diabetes has evolved from a 'glucocentric' approach to a 'patient-centered' approach; patient characteristics, needs, and preferences should be evaluated when considering premixed insulin for treatment of diabetes.Funding: Novo Nordisk, India.

Frequency of neonatal hypoglycemia in large for gestational age infants of non-diabetic mothers in a community maternity hospital.

Large for gestational age (LGA) infants are at increased risk for hypoglycemia. The aim of the study was to determine the frequency of neonatal hypoglycemia in LGA infants of non-diabetic mothers in a Community Maternity Hospital in Gaziantep, Turkey. Hospital records of 5229 infants of non-diabetic mothers were examined retrospectively. Newborns with birth weight more than 4000 g were defined as LGA. The control group consisted of 100 appropriate for gestational age (AGA) newborns. Capillary blood glucose was measured at the second hour of life. Glucose values lower than 40 mg/dL (2.2 mmol/L) were defined as hypoglycemia. Ninety-six (1.8%) of the 5229 infants were found to be LGA. The mean capillary glucose levels of the LGA newborns were significantly lower than those of the AGA newborns (54 mg/dL (3.0 mmol/L) vs. 95 mg/dL (5.2 mmol/L), p < 0.0001). Neonatal hypoglycemia was established in 16 of 96 LGA infants (16.7%). In the control group hypoglycemia was absent. The rate of hypoglycemia in LGA infants was significantly higher than the rate in the AGA infants (p = 0.0000). As hypoglycemia is not rare in LGA infants and can have serious consequences, blood glucose levels should be screened routinely in LGA infants.

Serum prolidase activity as a marker of osteoporosis in type 2 diabetes mellitus.

OBJECTIVES: Prolidase is a specific imidodipeptidase involved in collagen degradation. The increase in the enzyme activity is believed to be correlated with the increased intensity of collagen degradation This study aimed to evaluate serum prolidase activity and urinary deoxypyridinoline cross links in type 2 diabetic subjects with and without osteoporosis assessed by bone mineral density. DESIGN AND METHODS: Seventy-five patients (54 F/21 M) with type 2 DM and 43 age and gender matched healthy subjects (30 F/13 M) were recruited for this study. Serum prolidase activity was assessed with colorimetric determination. Urinary deoxypyridinoline (Dpy) was determined with electrochemiluminesence immunoassay. RESULTS: Serum prolidase activity was significantly lower in patients with type 2 DM than in the healthy controls (mean +/- SEM; 43.3 +/- 1.4 U/L and 53.3 +/- 2.2 U/L respectively, p: 0.000). Non osteoporotic diabetic patients had lower serum prolidase activity (median: 25th-75th percentiles; 39.5: 30.3-50.5 U/L) than osteoporotic diabetic patients (50.0: 41.8-56.3 U/L, p: 0.030) and healthy controls (52.0: 43.0-58.0 U/L, p: 0.004). Urinary Dpy excretion was not different between osteoporotic and nonosteoporotic diabetic patients. However it was lower in both diabetic groups than the healthy controls. We did not observe a statistically significant difference between the serum prolidase activity of dislipidemic/normolipidemic, hypertensive/normotensive, obese/nonobese, insulin/OAD treated, poorly/well-controlled patients and patients with/without diabetic nephropathy and retinopathy (p > 0.05). CONCLUSION: This study shows a significant decrease in serum prolidase activity in patients affected with type 2 DM, which may be interpreted as evidence of decreased bone resorption. Our data also suggest that serum prolidase activity may be a better marker of osteoporosis in diabetic state than Dpy.

Angiotensin-converting enzyme gene polymorphism and coronary heart disease in Turkish type 2 diabetic patients.

OBJECTIVE: It has been suggested that the insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) may be associated with atherosclerosis. The aim of the study was to examine the association between ACE gene polymorphism and coronary heart disease in Turkish type 2 diabetic patients. METHODS AND RESULTS: A total of 152 (97 female, 55 male) type 2 diabetic patients were included into the study. All patients underwent myocardial perfusion scintigraphic examination and forty-five of them with a perfusion defect underwent coronary angiography.Thirty-eight patients with a coronary stenosis of more than 50% on coronary angiography were considered as having coronary heart disease. The I/D polymorphism was determined by polymerase chain reaction. There was no statistically significant difference in genotypic and allelic frequencies of the ACE I/D polymorphism among patients with and without coronary heart disease (DD:ID:II (%), 32:58:11 and 39:44:17, respectively). CONCLUSIONS: ACE gene polymorphism is not a significant parameter to determine coronary heart disease in Turkish type 2 diabetic patients.

Hydatid cyst: a rare cause of ascites.

A 26 year old woman with ascites was admitted for further investigations. A diagnosis of hydatid cyst disease was suggested on the basis of a combination of abdominal ultrasonography, computerised tomography and latex agglutination tests. This diagnosis was confirmed following surgical intervention. Hydatid cyst disease is a rare cause of ascites and we review the etiology and clinical features of this condition.

Childhood obesity and the role of dopamine D2 receptor and cannabinoid receptor-1 gene polymorphisms.

AIMS: The dopaminergic and endocannabinoid systems are involved in regulation of feeding behavior. The aim of the study is to examine the possible relation between polymorphisms of the dopamine D2 receptor (DRD2) and cannabinoid receptor-1 (CNR1) genes and childhood obesity. METHODS: A hundred obese children and 100 healthy controls were analyzed for DRD2 Taq1A and Taq1B and CNR1 1359G/A polymorphisms. Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: There were no statistically significant differences in DRD2 Taq1A and DRD2 Taq1B genotypes or allelic frequencies between obese children and controls (p>0.05). In patients with Taq1B2 allele, morbid obesity was less frequent (p=0.010). The frequency of the A allele of CNR1 1359G/A polymorphism was significantly higher in obese children than in controls (21.0% vs. 13.0%, p=0.0166). The frequency of genotypes AG and GG of the CNR1 1359G/A SNP was different between obese children and control subjects (for AG: 34.0% vs. 22.0%, p=0.0294; for GG: 62.0% vs. 76.0%, p=0.0162, respectively). CONCLUSIONS: No significant difference was found between genotypes and alleles of DRD2 Taq1A and DRD2 Taq1B polymorphism in patients and controls, while the CNR1 receptor 1359G/A polymorphism and the presence of the A allele may be one risk factor for susceptibility to obesity.

Pseudolithiasis due to ceftriaxone treatment for meningitis in children: report of 8 cases.

Cholelithiasis rarely occurs in childhood. Ceftriaxone is a widely used antimicrobial agent in pediatrics due to the broad spectrum. Reversible biliary sludge and/or lithiasis, named as pseudolithiasis, have been reported in patients treated with ceftriaxone. We observed ceftriaxone-associated pseudolithiasis in 8 patients with meningitis. The aim of this study was to report the clinical characteristics of these patients and to evaluate the related factors for the development of ceftriaxone-associated pseudolithiasis in children. The study group consisted of 7 boys and 1 girl. All patients received ceftriaxone 100 mg/kg/day for meningitis. The ultrasonographic evaluation was performed on 5th-10th days after the initiation of the therapy. Biliary sludge was detected in one patient, and gallstone was detected in three patients, while biliary sludge with gallstone was detected in four patients. Six of the cases were diagnosed during summer time. Thus, high temperature may cause loss of fluid, leading to easier formation of sludge. Ceftriaxone treatment was discontinued after sonographic demonstration of pseudolithiasis. Gallbladder sonograms were found to be normal in all patients at the follow-up sonographic examinations performed after 30 days of the diagnosis without specific treatment. Clinicians should screen all pediatric patients living in areas with high temperature and receiving ceftriaxone treatment (over 100 mg/kg) by ultrasonography for biliary sludge or gallstone formation even if they are asymptomatic.