Type-2 Diabetes and Gene Therapy: The Promise of CRISPR Gene Therapy in type-2 Diabetes Mellitus

Gene therapy has entered a new era with the dawn of CRISPR/Cas9 technology which though were always available in nature but rediscovered to tame into a real-tlife genome editing tool. With the modernization upsurge and changes in ways the “homo sapiens” survived on this planet from hunger to current era of exuberance has led to multiple metabolic issues like type-2 diabetes. Notwithstanding the rapid emergence of medication to suppress the hyperglycemia and insulin resistance associated with this menace, need has definitely emerge to find more personalized and curative dimensions to therapeutics of type-2 diabetes mellitus. Gene therapy is one more addition to Type-2 Diabetes Mellitus (T2DM) therapy, where multiple options have emerged in the shape of microRNA, direct knocking out of cellular structures like proteins and enzymes and very recently the precision nucleases associated with CRISPR technologies. This mini-review attempt to summarize some of the recent examples of gene therapy with major focus on CRISPR/Cas technologies.

Hirsutism and Anthropometric Profiles Among Subjects with Polycystic Ovarian Morphology? A Cross-Sectional Analysis

Background Polycystic ovarian syndrome (PCOS) is increasingly being diagnosed and treated with sometimes variable lifestyle advice and pharmacological interventions. Obesity is considered as the sole culprit and variable definitions in clinics compound the understanding of pathogenic heterogeneity of this syndrome. We evaluated the differences between various simple to calculate anthropometric indices along with some anthropometric-biochemical equations in subjects with or without PCOS. Objective To compare traditional measures like waist to hip and height ratio (WHpR and WHtR), BMI, newer markers depicting central obesity like Abdominal Volume index(AVI), Body roundness index (BRI), A Body Shape index (ABSI), Conicity index (C-index) along with biochemical-anthropometric equations like lipid Accumulation Products (LAP), Visceral Adiposity Index (VAI) and Chinese Visceral Adiposity Index (CVAI) for diagnosing PCOS as per the Rotterdam criteria Design Cross-sectional analysis Place & Study Duration Naval hospital, Islamabad from Jan- 2018 to July- 2019 Subjects and Methods From our finally evaluated 333 female subjects we initially compared the differences for the presence of hirsutism as per modified Ferrimen Gallwey scores and biochemical hyperandrogenism by measuring free androgen index (Total testosterone/SHBG x 1000. We evaluated waist circumference, BMI, WHpR, WHtR,AVI, BRI, ABSI, C-index along with biochemical-anthropometric equations like LAP, VAI and CVAI for differences in subjects diagnosed to have PCOS by Rotterdam criteria or ultrasonography alone. Results Differences in hirsutism as defined by modified FG score between subjects defined to have PCOS or otherwise as per Rotterdam defined criteria were as [(PCOS=169, Mean=17.33 + 9.05) (No PCOS=164, Mean=8.21 + 5.74), p< 0.001] and ultrasound [(PCOS=87, Mean=16.95 + 9.57) (No PCOS=246, Mean=11.38 + 8.51), p< 0.001]. Similarly, the differences in FAI between subjects defined to have PCOS or otherwise as per Rotterdam criteria and ultrasound were as [(PCOS=169, Mean=6.41 + 4.88) (No PCOS=164, Mean=2.77 + 1.79), p< 0.001] and [(PCOS=87, Mean=5.75 + 5.01) (No PCOS=246, Mean=4.22 + 3.68), p= 0.011]. Anthropometric measures and anthropometric-mathematical equations were raised in non-PCOS subjects than PCOS subjects. Lean-PCOS demonstrated lower degree of hirsutism and biochemical hyperandrogenism in comparison to obese-PCOS. Conclusion Hirsutism and free androgen indices were raised in PCOS females. Anthropometric based measurements were not different in PCOS cases and non-PCOS females. Lean-PCOS demonstrated lower degree of hirsutism and biochemical hyperandrogenism in comparison to obese-PCOS.

Severe Vitamin D Deficiency in Saudi Patients with Type 2 Diabetes Mellitus

Introduction It has been demonstrated that vitamin D deficiency is associated with type 2 diabetes mellitus (T2DM). We conducted a cross sectional study to investigate the prevalence severe vitamin D deficiency in patients with T2DM. Method A cross-sectional single centre study was conducted in 4053 patients with T2DM. Patients with T2DM attended the Diabetes Centre at King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia between January 2018 and December 2018 were recruited. Results There were 4053 patients with T2DM, 1145 male and 2908 female (28 % vs.72% respectively). The mean age was 53.9 ±16.5 years. The mean and median 25-OHD concentrations were 57.8±30.5 and 51.9 respectively. Severe vitamin D deficiency (25-OHD<25 nmol/l) was found in 1916 (9.5%). Moreover, severe vitamin D deficiency was not statistically significant more prevalent among females than males with male to female ratio 1:2.3 (70% vs. 30% respectively, p=0.6). In addition, severe vitamin D deficient patients were statistically significant younger than non-vitamin D deficient (48.0±16.7 vs. 54.6±16.3 respectively, p<0.0001). Severe vitamin D deficient patients have statistically significant higher HbA1c than non-vitamin D deficient (8.3 ±2.3 vs. 7.6±1.9 respectively, p<0.0001). The mean 25-OHD was upward as age advanced with highest frequency of vitamin D deficiency was found in the age group ≥60 years (27%) with males statistically significant most frequent than females in the age group ≥60 years (39 s, 22 respectively, p=0.003). Regression analysis of odd ratio of risk factors for patients with severe vitamin D deficiency showed that age and HbA1c were statistically significant associated with vitamin D deficiency. Conclusions The prevalence of severe vitamin D deficiency in patients with T2DM is low and that more females with T2DM are affected with vitamin D deficiency than males.

Beneficial Effects of Fennel (Foeniculum Vulgare) in Treating Obesity in Rats

Obesity is associated with a number of serious medical complications, which are often referred to as the “insulin resistance syndrome”. The aim of the present study was performed to investigate the possible interaction between a conventional drug used for management of cholesterol and traditional herbal remedies on the obesity. This was carried through out: through estimation of blood test; Estimation of serum tests; Determination of oxidative stress biomarkers and the antioxidant enzymes activities in the liver were assayed; Histopathological examination of the liver and kidney of adult male albino rats were done. In the present study, the serum levels of the total protein and albumin in the obesity group (7.1± 0.2) and (4.78 ± 0.19); respectively were significantly (p ≤ 0.05) more than those of the control group (6.5±0.1) and (3.95± 0.1).The administration of (fennel group) revealed significant (P<0.05) decrease in the serum levels of the albumin and total protein (4.38± 0.1) and (6.65± 0.2); respectively as compared to the obesity group (4.78 ± 0.19) and (7.1± 0.2(. The total cholesterol of the group(5) (fennel and ator) after two weeks from a high fat diet than treatment with fennel and Ator through six weeks equal 142.86±5.9, 100.4±8.68, 93.29±5.99, 87.1±11.28, 80.4±21.55, 78.1±6.7 and 77.1±6.87; respectively. The present study showed a significant (P<0.05) increase in the activities of ALT, AST and ALP in the obesity group which recorded as (60.5±11.45), (57.25±6.3) and (845.0±49.47); respectively as compared to the control group (28.25±1.7), (38.5±3.87) and (537.0±41.5); respectively. The fennel group caused significant decrease in the activities of these enzymes (41.0± 2.9), (42.25+3.2) and (717.75+48.6); respectively compared to the obesity group. Ator group showed a significant decrease in the activities of these enzymes (40.0±2.16), (42.5±3.1) and (679.25±41.16); respectively compared as obesity group. The activity of AlT, AST and ALP in the fennel and ator group (32.75±2.5), (40.5±2.38) and (601.25±17.5); respectively were near to the control group.