Alterations in circulating lipidomic profile in patients with type 2 diabetes with or without non-alcoholic fatty liver disease.

Objective: Non-alcoholic fatty liver disease (NAFLD) and Type 2 diabetes mellitus (T2DM) often coexist and drive detrimental effects in a synergistic manner. This study was designed to understand the changes in circulating lipid and lipoprotein metabolism in patients with T2DM with or without NAFLD. Methods: Four hundred thirty-four T2DM patients aged 18-60 years were included in this study. Fatty liver was assessed by FibroScan. The comprehensive metabolic lipid profiling of serum samples was assessed by using high-throughput proton NMR metabolomics. Results: Our data revealed a significant association between steatosis and serum total lipids in VLDL and LDL lipoprotein subclasses, while total lipids in HDL subclasses were negatively associated. A significant positive association was found between steatosis and concentration of lipids, phospholipids, cholesterol, and triglycerides in VLDL and LDL subclasses, while HDL subclasses were negatively associated. Furthermore, a significant, association was observed between fibrosis and concentrations of lipids, phospholipids, cholesterol, and triglycerides in very small VLDL, large, and very large HDL subclasses. Subgroup analysis revealed a decrease in the concentrations of lipids, phospholipids, cholesterol, and other lipid biomolecules in patients using antilipemic medications. Conclusion: The metabolomics results provide evidence that patients with T2DM with higher steatosis grades have altered lipid metabolomics compared to patients without steatosis. Increased lipid, phospholipids, cholesterol, and triglycerides concentration of VLDL and LDL subclasses are associated with steatosis in patients with T2DM.

Higher carbohydrate intake in relation to non-alcoholic fatty liver disease in patients with type 2 diabetes.

Background: Non-alcoholic fatty liver disease (NAFLD) is an overlooked complication of type 2 diabetes (T2D). Current recommendations for the management of NAFLD are mainly focused on weight reduction, overlooking the role of macronutrient composition. Although dietary carbohydrates play a major role in intrahepatic fat synthesis, their association with the progression of liver steatosis has not been fully investigated in patients with T2D. Aim: To investigate the association between higher carbohydrate intake and the presence of liver steatosis in patients with T2D. Methods: This cross-sectional study included men and women aged 18-60 years diagnosed with T2D. Anthropometric measurements, hepatic steatosis assessment using the controlled attenuation parameter (CAP), blood samples, and dietary data were analyzed. Participants were divided into two groups: NAFLD and NAFLD-free. A two-sample t-test was used to evaluate the differences between the two groups. Stepwise multiple linear regression models adjusted for potential confounders were used to determine the association between CAP values and higher carbohydrate intake. Results: In total, 358 participants were included. NAFLD was present in 79.3% of the participants. Body mass index, waist circumference, ALT, HbA1c, and triglycerides showed direct, while HDL-Cholesterol revealed inverse associations with CAP values. No significant relationship was found between carbohydrate intake and steatosis in the total study sample; however, multiple linear regression analysis revealed a significant relationship between carbohydrate intake and CAP values in patients aged ≤50 years. Conclusion: In patients with T2D, higher carbohydrate intake was associated with liver steatosis in those aged 50 years and below. Further studies are required to confirm the causality between carbohydrate intake and liver steatosis.

Transient elastography for the prevalence of non-alcoholic fatty liver disease in patients with type 2 diabetes: Evidence from the CORDIAL cohort study.

Background: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the prevalence of NAFLD among Saudi patients with T2DM using transient elastography. Methods: A total of 490 patients with T2DM who attended diabetes and primary care clinics were recruited. Controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) were obtained via FibroScan to assess steatosis and fibrosis. Results: Of the examined 490 patients with T2DM, 396 (80.8%) had hepatic steatosis (CAP ≥248 dB/m): 326 (66.5%) had severe steatosis (CAP ≥280 dB/m), while 41 (8.4%) and 29 (5.9%) had mild (CAP ≥248 to <268 dB/m) and moderate steatosis (CAP ≥268 to <280 dB/m), respectively. Of the 396 patients with steatosis, only 35 (8.8%) had LSM ≥7.9 kPa, suggesting the presence of fibrosis, while 361 (91%) had LSM <7.9 kPa, indicating the absence of fibrosis. Increased body mass index (BMI), waist circumference, systolic blood pressure (SBP), and alanine aminotransferase (ALT) were positively associated with both steatosis and fibrosis. After adjusting for age and gender, data from logistic regression analysis demonstrated BMI, waist circumference, SBP, ALT, and high-density lipoprotein (HDL) as significant independent factors for steatosis, while SBP was the only significant predictor associated with fibrosis. Conclusions: Our results demonstrate an increase in prevalence of NAFLD in Saudi patients with T2DM, based on transient elastography and CAP score. The risk of NAFLD appears to be higher in T2DM patients with abdominal obesity, elevated SBP, and increased ALT levels, which supports the screening of these conditions in patients with T2DM.

Hypocalcemia in Pregnancy: A Clinical Review Update.

Though hypocalcemia in pregnancy is not often reported in the literature, it occurs in cases of hypoparathyroidism and in mothers with severe dietary inadequacy. Hypocalcemia during pregnancy can pose numerous problems to the mother and fetus. It is associated with hypertensive disorders and can increase the risk of numerous problems such as preeclampsia and fetal growth disorders. In this review, we summarize the challenges physicians face diagnosing and managing hypocalcemia during pregnancy. A multidisciplinary team including endocrinologists and obstetricians is warranted to ensure appropriate treatment and optimal outcomes.

Assessment of Ramadan Education and Knowledge Among Diabetic Patients.

BACKGROUND: During Ramadan, Muslims fast from dawn until dusk for one lunar month every year. Most of the Muslim patients with diabetes are unaware of the potential complications that can occur while fasting, such as hypoglycemia. The aim of this study is to assess the the patient education level and patients' overall awareness of any possible complications that could occur while fasting during Ramadan and to determine how these patients deal with these complications. METHODS: We conducted a cross-sectional study and surveyed diabetic patients about their diabetes-related knowledge over a period of 4 months from the outpatient clinic at the Obesity, Endocrine, and Metabolism Center at King Fahad Medical City. Patients were included if they were ≥16 years and if they had been receiving treatment for at least 1 year before the study, irrespective of the medications used; patients were also asked about the presence or absence of complications. RESULTS: This study included 477 patients (325 women and 152 men). Most patients (297; 62.3%) had type 2 diabetes. The patients' mean age was 39.72 ± 15.29 years, and the mean duration of diabetes was 10.80 ± 5.88 years. During the preceding Ramadan, 76% of patients reported fasting, whereas 58% said that they monitored their blood glucose levels once per day. Hypoglycemic episodes were reported in 60.3% of cases with type 2 diabetes and in 8.3% of cases with type 1 diabetes. Among those who had hypoglycemia, 2.8% of patients with type 1 diabetes and 17.8% with type 2 diabetes broke their fast. Finally, 54% of patients reported that their health care providers offered them instructions on diabetes management during Ramadan. CONCLUSIONS: Ramadan health education in diabetes can encourage, improve, and guide patients to change their lifestyles during Ramadan while minimizing the risk of acute complications.

Association of Glycosylated Hemoglobin Levels With Vitamin D Status.

BACKGROUND: The discovery of vitamin D is one of medicine's great achievements. Despite all the positive evidence emerging about the beneficial effect of vitamin D, we still find many are vitamin D deficient. The purposes of this study were to examine the association between serum 25-hydroxyvitamin D (25(OH)D) and glycosylated hemoglobin (HbA1c) levels, to test the hypothesis that lower 25(OH)D levels are associated with poorer glucose control in diabetes mellitus (DM) patients and to investigate the effect of vitamin D supplementation on HbA1c levels. METHODS: This was a prospective observational cohort study of all patients with type 1 and type 2 diabetes (above 12 years) who attended the outpatient clinics of a tertiary center in Riyadh. HbA1c and vitamin D levels were recorded prior to supplementation and after 9 months of supplementation with vitamin D. All patients were divided into four groups according to their vitamin D level and an association between 25(OH)D and HbA1c was tested. RESULTS: Results showed that 73.1% of the patients had 25(OH)D levels < 50 nmol/L. We observed lowering of HbA1c after vitamin D supplementation (from mean HbA1c of 10.55 to 7.70). We found HbA1c to be inversely related to serum vitamin D levels (r = -0.14 (P < 0.0000002) before supplementation and -0.16 (P < 0.000001) after supplementation with vitamin D). CONCLUSIONS: Advising patients with higher HbA1c to test their vitamin D level and correct any deficiency will result in better blood glucose control and benefit the patient's overall health.

Glycemic control and pregnancy outcomes in patients with diabetes in pregnancy: A retrospective study.

CONTEXT: Diabetes in pregnancy (DIP) is either pregestational or gestational. AIMS: To determine the relationship between glycemic control and pregnancy outcomes in a cohort of DIP patients. SETTINGS AND DESIGN: In this 12-month retrospective study, a total of 325 Saudi women with DIP who attended the outpatient clinics at a tertiary center Riyadh, Saudi Arabia, were included. SUBJECTS AND METHODS: The patients were divided into two groups, those with glycated hemoglobin (HbA1c) ≤6.5% (48 mmol/mol) and those with glycated hemoglobin (HbA1c) above 6.5%. The two groups were compared for differences in maternal and fetal outcomes. STATISTICAL ANALYSIS USED: Independent Student's t-test and analysis of variance were performed for comparison of continuous variables and Chi-square test for frequencies. Odds ratio and 95% confidence intervals were calculated using logistic regression. RESULTS: Patients with higher HbA1c were older (P = 0.0077), had significantly higher blood pressure, proteinuria (P < 0.0001), and were multiparous (P = 0.0269). They had significantly shorter gestational periods (P = 0.0002), more preterm labor (P < 0.0001), more perineal tears (P = 0.0406), more miscarriages (P < 0.0001), and more operative deliveries (P < 0.0001). Their babies were significantly of greater weight, had more Neonatal Intensive Care Unit (NICU) admissions, hypoglycemia, and macrosomia. CONCLUSIONS: Poor glycemic control during pregnancy is associated with adverse maternal and fetal outcomes (shortened gestational period, greater risk of miscarriage, increased likelihood of operative delivery, hypoglycemia, macrosomia, and increased NICU admission). Especially at risk are those with preexisting diabetes, who would benefit from earlier diabetes consultation and tighter glycemic control before conception.

Clinical and Biochemical Characteristics of Diabetes Ketoacidosis in a Tertiary Hospital in Riyadh.

Diabetes is the fifth leading cause of death worldwide. Diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes. The aim of this study is to investigate the clinical and biochemical characteristics of DKA among 400 patients admitted to hospital, most of whom had type 1 diabetes (n = 372; 93%). Vomiting (n = 319; 79.8%), nausea (n = 282; 70.5%), and abdominal pain (n = 303; 75.8%) were the presenting symptoms most commonly experienced by the patients. Tachycardia was the most common clinical sign noted in the patients on admission (n = 243; 61.8%). The predominant precipitating cause of DKA was noncompliance to an insulin regimen (n = 215; 54.2%). Recurrent DKA admissions in type 1 diabetes patients was higher than those with type 2 diabetes (n = 232 versus n = 9, respectively; P = 0.002). Recurrent DKA admissions in female patients were higher than in male patients (n = 167 versus n = 74, respectively; P = 0.002). Continued diabetic education (given to n = 384; 94%) and counseling on the importance of adhering to the recommended medical regime, addressing the social and cultural barriers that precipitate DKA, as well as the provision of timely medical attention may greatly reduce DKA episodes and their associated complications.

Treatment of retinitis pigmentosa due to MERTK mutations by ocular subretinal injection of adeno-associated virus gene vector: results of a phase I trial.

MERTK is an essential component of the signaling network that controls phagocytosis in retinal pigment epithelium (RPE), the loss of which results in photoreceptor degeneration. Previous proof-of-concept studies have demonstrated the efficacy of gene therapy using human MERTK (hMERTK) packaged into adeno-associated virus (AAV2) in treating RCS rats and mice with MERTK deficiency. The purpose of this study was to assess the safety of gene transfer via subretinal administration of rAAV2-VMD2-hMERTK in subjects with MERTK-associated retinitis pigmentosa (RP). After a preclinical phase confirming the safety of the study vector in monkeys, six patients (aged 14 to 54, mean 33.3 years) with MERTK-related RP and baseline visual acuity (VA) ranging from 20/50 to <20/6400 were entered in a phase I open-label, dose-escalation trial. One eye of each patient (the worse-seeing eye in five subjects) received a submacular injection of the viral vector, first at a dose of 150 µl (5.96 × 10(10)vg; 2 patients) and then 450 µl (17.88 × 10(10)vg; 4 patients). Patients were followed daily for 10 days at 30, 60, 90, 180, 270, 365, 540, and 730 days post-injection. Collected data included (1) full ophthalmologic examination including best-corrected VA, intraocular pressure, color fundus photographs, macular spectral domain optical coherence tomography and full-field stimulus threshold test (FST) in both the study and fellow eyes; (2) systemic safety data including CBC, liver and kidney function tests, coagulation profiles, urine analysis, AAV antibody titers, peripheral blood PCR and ASR measurement; and (3) listing of ophthalmological or systemic adverse effects. All patients completed the 2-year follow-up. Subretinal injection of rAAV2-VMD2-hMERTK was associated with acceptable ocular and systemic safety profiles based on 2-year follow-up. None of the patients developed complications that could be attributed to the gene vector with certainty. Postoperatively, one patient developed filamentary keratitis, and two patients developed progressive cataract. Of these two patients, one also developed transient subfoveal fluid after the injection as well as monocular oscillopsia. Two patients developed a rise in AAV antibodies, but neither patient was positive for rAAV vector genomes via PCR. Three patients also displayed measurable improved visual acuity in the treated eye following surgery, although the improvement was lost by 2 years in two of these patients. Gene therapy for MERTK-related RP using careful subretinal injection of rAAV2-VMD2-hMERTK is not associated with major side effects and may result in clinical improvement in a subset of patients.

Safety and effectiveness of biphasic insulin aspart 30 in people with type 2 diabetes switching from basal-bolus insulin regimens in the A1chieve study.

AIMS: Biphasic insulin aspart 30 allows fewer daily injections versus basal-bolus insulin regimens, which may improve adherence and treatment outcome. This sub-analysis of the observational A1chieve study assessed clinical safety and effectiveness of biphasic insulin aspart 30 in people with type 2 diabetes previously receiving basal-bolus insulin regimens. METHODS: A1chieve was an international, open-label, 24-week study in people with type 2 diabetes starting/switching to biphasic insulin aspart 30, insulin detemir or insulin aspart. This sub-analysis assessed patients switching from insulin glargine- or neutral protamine Hagedorn insulin-based basal-bolus insulin regimens to biphasic insulin aspart 30. RESULTS: 1024 patients were included. At 24 weeks, glycated haemoglobin and fasting plasma glucose were significantly reduced from baseline in both cohorts (all p<0.001). The proportion reporting any hypoglycaemia, major hypoglycaemia or nocturnal hypoglycaemia was significantly reduced after 24 weeks (all p<0.05). No serious adverse drug reactions were reported. Both cohorts had significantly improved health-related quality of life (HRQoL; p<0.001). CONCLUSIONS: 24 weeks after switching from basal-bolus insulin regimens to biphasic insulin aspart 30, glycaemic control and HRQoL were significantly improved, and hypoglycaemia was significantly reduced. This suggests that people with type 2 diabetes inadequately controlled on basal-bolus insulin regimens can consider biphasic insulin aspart 30.