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Metformin is an orally effective insulin-sensitizing drug widely prescribed for treating type 2 diabetes mellitus (T2DM). Metformin has been reported to alter lipid metabolism. However, the molecular mechanisms behind its impact on lipid metabolism remain partially explored and understood. In the current study, mass spectrometry-based lipid profiling was used to investigate the lipidomic changes in the serum of 26 healthy individuals after a single-dose intake of metformin. Samples were analyzed at five-time points: preadministration, before the maximum concentration of metformin (Cmax), Cmax, after Cmax, and 36 h post-administration. A total of 762 molecules were significantly altered between the five-time points. Based on a comparison between baseline level and Cmax, metformin significantly increased and decreased the level of 33 and 192 lipids, respectively (FDR ≤ 0.05 and fold change cutoff of 1.5). The altered lipids are mainly involved in arachidonic acid metabolism, steroid hormone biosynthesis, and glycerophospholipid metabolism. Furthermore, several lipids acted in an opposed or similar manner to metformin levels and included fatty acyls, sterol lipids, glycerolipids, and glycerophospholipids. The significantly altered lipid species pointed to fundamental lipid signaling pathways that could be linked to the pleiotropic effects of metformin in T2DM, insulin resistance, polycystic ovary syndrome, cancer, and cardiovascular diseases.

Khalid Siddiqui,1 Shaik Sarfaraz Nawaz,1 Assim A Alfadda,1– 3 Muhammad Mujammami1,2,4 1Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2Department of Medicine, College of Medicine, and King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 3Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 4University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Khalid Siddiqui, Strategic Center for Diabetes Research, College of Medicine, King Saud University, P.O. Box 245, Riyadh, 11411, Saudi Arabia, Tel +966 114724179 Ext.3106, Fax +966 114725682, Email ksiddiqui@ksu.edu.saBackground: Diabetic Nephropathy (DN) is one of the most typical causes of end-stage renal disease and thyroid hormone exerts effects on the kidney. There are few reports on the role of thyroid hormone in the progression of DN. We aimed to assess the relationship between thyroid hormone and DN.Methods: In this cross-sectional study, 400 patients with type 2 diabetes (T2D) (aged between 35 and 70 years) were divided into two groups T2D control and DN group according to albumin creatinine ratio (ACR). Clinical biochemistry parameters were measured using the Rx Daytona chemistry analyzer and thyroid hormone levels (TT4, TT3, TSH, FT4, and FT3) using the Evidence Biochip analyzer. To assess the relationship between thyroid hormone and DN, multiple logistic regression models were developed.Results: Serum FT4 and FT3 levels were significantly lower in DN compared to T2D controls (p< 0.05). Thyroid hormone levels tend to decrease with the progression of DN. In unadjusted and adjusted logistic regression models, FT3 levels were negatively associated with odds of having DN (OR=0.28, CI=0.128– 0.616, p=0.002).Conclusion: The free triiodothyronine level was negatively associated with the progression of DN. Further longitudinal studies are required to assess the cause of thyroid hormone differences.Keywords: diabetic nephropathy, type 2 diabetes, thyroid hormone

Saussurea costus (S. costus) belongs to family of Asteraceae and is one of the therapeutic plants extensively used as a traditional medicine in Saudi Arabia. Constituents of this plant have the potential to be developed as bioactive molecules. Among Arabs, the prevalence of thyroid disorders ranges from 6.18 % to 47.34% and hypothyroidism has been reported to be the most prevalent. Although there is no natural treatment that can directly replace thyroid hormones, their role as an alternate treatment or as an add-on to available thyroid treatment has been explored. Flavanoids and antioxidant properties of S. costus may be an important mechanism involved in supporting its medicinal use. Current data on the possible role of S. costus in thyroid disorders is lacking and the available evidence is inconclusive. This review deal with the current understanding of use and myth regarding the use of this medicinal plant in thyroid disease.

Nawaf A Alshammari,1,2,&ast; Abdulaziz A Alodhayani,3,&ast; Salini S Joy,4 Arthur Isnani,5 Muhammad Mujammami,1,4,6 Assim A Alfadda,4– 6 Khalid Siddiqui4 1University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 2King Salman Specialist Hospital, Diabetes and Endocrine Center, Hail Health Cluster, Hail, Hail Region, Saudi Arabia; 3Department of Family and Community Medicine College of Medicine, King Saud University, Riyadh, Saudi Arabia; 4Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 5Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 6Department of Medicine, College of Medicine, and King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia&ast;These authors contributed equally to this workCorrespondence: Khalid Siddiqui, Strategic Center for Diabetes Research, College of Medicine, King Saud University, P.O. Box 245, Riyadh, 11411, Saudi Arabia, Email ksiddiqui@ksu.edu.saBackground: Neuropathy is the most common microvascular complications among diabetic patients. Diabetic peripheral neuropathy (DPN) is the predominant variety which may associate with increased in mortality and morbidity among type 2 diabetes mellitus (T2DM).Objective: To assess the prevalence of diabetic peripheral neuropathy and its correlation with risk factors among T2DM.Methods: This was a cross-sectional retrospective study, data was collected from a previous cohort study conducted at the University Diabetes Center, King Saud University Medical City (KSUMC), King Saud University, Riyadh, Saudi Arabia. The data of T2DM patients were collected from case report form, included demographic data, history of chronic diabetes neuropathy, and laboratory reports. Statistical analysis includes Student`s t test, chi square test, and Pearson correlation and logistic regression were performed.Results: A total of 430 patients with T2DM data was collected and analyzed, and of them 54% were females, with the mean age of 55.88 years. The prevalence of diabetic neuropathy among study participants were 40.2%, and 73.3% of them having the subtype polyneuropathy. The mean BMI; p = 0.006, FBS; p < 0.001, HbA1c; p < 0.001, cholesterol p = 0.001, LDL; p < 0.001, and triglyceride; p < 0.001 levels were a significantly higher among participants with diabetic neuropathy than without neuropathy. The male gender (Risk Ratio: 1.294, 95% CI:1.090, 1.536) p = 0.003, fasting blood glucose (Risk Ratio: 1.157, 95% CI:1.051, 1.273) p = 0.003 Cholesterol (Risk Ratio: 1.588, 95% CI:1.174, 2.147) p = 0.003, triglyceride (Risk Ratio: 1.290, 95% CI:1.086, 1.538), p = 0.004, and LDL (Risk Ratio: 1.299, 95% CI:1.073, 1.574), p = 0.007) were found to be significant risk factors for DPN.Conclusion: DPN is highly prevalent among T2DM patients in Saudi Arabia. Poor glycemic control and hyperlipidemia were associated with significantly higher risk for DPN patients among T2DM.Keywords: diabetic peripheral neuropathy, hyperlipidemia, glycemic control, type 2 diabetes

Zobeida Eljaaly,1,2,&ast; Muhammad Mujammami,1– 3,&ast; Shaik Sarfaraz Nawaz,3 Mohamed Rafiullah,3 Khalid Siddiqui3 1University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 2Division of Endocrinology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 3Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia&ast;These authors contributed equally to this workCorrespondence: Khalid SiddiquiStrategic Center for Diabetes Research, College of Medicine, King Saud University, P.O. Box 245, Riyadh, 11411, Saudi ArabiaEmail ksiddiqui@ksu.edu.saObjective: Patients with diabetes are at higher risk of the negative consequences of hyperuricemia. The objective of this study was to investigate gender and age-specific differences in the uric acid levels and to evaluate the associated risk factors among patients with diabetes.Methods: A retrospective cross-sectional study was conducted at Strategic Center for Diabetes Research from September 2019 to January 2020, among adult type-2 diabetic patients. Serum uric acid (SUA) and several other metabolic and clinical parameters were examined. Multiple regression analysis was done to identify risk factors independently associated with hyperuricemia.Results: A total of 433 patients were included in the analysis. SUA level was higher in males than females (5.82± 1.65 mg/dL versus 5.29± 1.54 mg/dL, p < 0.001). The prevalence of hyperuricemia was higher in females than males (28.8% versus 20.5%, p = 0.049). There was no significant difference in uric acid levels or the prevalence of hyperuricemia by age groups in the total sample or gender-stratified samples. In multivariate analysis, hyperuricemia was associated with bigger hip circumference (odds ratios [OR] were 1.03, 95% CI = 1.01– 1.05), higher triglycerides (OR = 1.005, 95% CI = 1.002– 1.008), and higher serum creatinine (OR = 1.34, 95% CI = 1.21– 1.49). Hip circumference, total cholesterol, high-density lipoprotein, and serum creatinine were independent risk factors in males, while triglycerides and higher serum creatinine were independent risk factors among females.Conclusion: The present study demonstrates gender-specific differences in the uric acid levels and hyperuricemia prevalence. In males and females, hyperuricemia was associated with hip circumference, total cholesterol, high-density lipoprotein, triglycerides, and serum creatinine. Future large studies are needed to confirm our findings, especially in elderly females.Keywords: uric acid, hyperuricemia, gender, diabetes, risk factors, Saudi Arabia

Shaik Sarfaraz Nawaz,1,&ast; Khalid Siddiqui,1,&ast; Muhammad Mujammami,1– 3 Obeed Alotaibi,2 Saud Sulaiman Alanazi,1 Mohamed Rafiullah1 1Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 3Division of Endocrinology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia&ast;These authors contributed equally to this workCorrespondence: Khalid Siddiqui, Strategic Center for Diabetes Research, College of Medicine, King Saud University, P.o Box: 245, Riyadh, 11411, Saudi Arabia, Tel +966 114724179 Ext.3106, Fax +966 114725682, Email ksiddiqui@ksu.edu.saBackground: Osteopontin (OPN) is a 44-kDa multifunctional protein and has a diverse role in biomineralization, tissue remodeling, and chronic inflammation. However, its role in type 2 diabetes (T2D) patients with microvascular complications is not clear. Therefore, the present study aimed to investigate the role of OPN in T2D patients with microvascular complications.Methods: A total of 324 type 2 diabetes patients in the age group of 38– 66 years were included in this study; 249 T2D patients were diagnosed with microvascular complications. OPN was measured using an enzyme-linked immunosorbent assay kit. Clinical data, such as age, gender, diabetes duration, systolic blood pressure, diastolic blood pressure, were measured. Correlation between OPN levels with different clinical parameters was evaluated.Results: In patients with microvascular complications, OPN levels were significantly higher than those without microvascular complications (p < 0.05). Moreover, OPN levels were positively associated with systolic blood pressure (SBP), C-reactive protein, and albumin creatinine ratio (ACR). Multiple linear regression analysis showed that OPN levels were independently associated with C-reactive protein (p < 0.045).Conclusion: The findings in the present study showed that OPN level was more positively associated with C-reactive protein than that with glucose metabolism in patients with microvascular complications. Thus, OPN might serve as a marker in predicting vascular disease.Keywords: osteopontin, diabetes, microvascular complication, inflammation, C-reactive protein

Aishah Ekhzaimy,1 Shadin Alkatari,1 Mohamed AlMaatouq,1 Daad Alotaibi,1 Sarah Aljasser,1 Amal Aseeri,1 Anwar Jammah,1 Muhammad Mujammami,1– 3 Mona Fouda,1 Assim A Alfadda,1,2,4 Riad Sulaimani1 1Division of Endocrinology, Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Kingdom of Saudi Arabia; 2Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia; 3University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Kingdom of Saudi Arabia; 4Obesity Research Center, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi ArabiaCorrespondence: Aishah Ekhzaimy, Division of Endocrinology, Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Kingdom of Saudi Arabia, Email aishahekhzaimy@hotmail.comPurpose: Impact of ramadan fasting on healthy and women with diabetes is already known. However, there is a scarcity of data on impact of fasting on pregnant women with diabetes. Moreover, religious and medical recommendations advise pregnant women against fasting as it is unsafe. Despite being exempted, many pregnant Muslim women with diabetes still choose to fast during ramadan. This study investigated different glycemic marker as an indicator for diabetes control in fasting pregnant women.Patients and Methods: This is a prospective observational study. A total of 89 pregnant diabetes women were recruited. Blood glucose was self-monitored in all the pregnant women using glucose monitoring device at home. We measure the fructosamine, HbA1c levels before, during and after ramadan.Results: Pregnant women with type 1 diabetes were 14 (25%), type 2 diabetes were 21 (37.5%), and gestational diabetes were 21 (37.5%). The mean fructosamine level decreased during and after ramadan in gestation diabetes pregnant women compared to type 2 diabetes and type 1 diabetes pregnant women subjects (p = 0.009).Conclusion: The present study indicates that pregnant women with diabetes were able to fast during ramadan and there fructosamine level reduced during fasting. Utilization of fructosamine for short-term monitoring of glycemic control in addition to home glucose monitoring in pregnant women with diabetes will provide a good index of glycemic control.Recommendation: Religious and medical recommendations advise pregnant women against fasting as it is unsafe, and they are under high risk. However, if they insist to do fast, they must do under strict medical supervision and fructosamine can be used as a glycemic control marker.Keywords: ramadan fasting, gestational diabetes, type 2 diabetes, type 1 diabetes, pregnant women, fructosamine

Background Primary Empty Sella (PES) syndrome is an increasingly common disorder, mostly diagnosed as an incidental finding during brain imaging scans. We intended to review the clinical management and hormonal profile of patients with PES. Methods The study included ten-year retrospective analysis of registry containing PES cases in the period 2007 to 2017, from a single tertiary care center. The keyword ‘primary empty sella’ was used to retrieve patient details from the radiology unit. The clinical and biochemical profile of PES patients was analyzed. Case management of PES patients and their rate of referral to endocrinologists was explored. Results The registry had 765 cases with a male: female ratio of 1:3.8 suggesting female predominance by almost four times. Although not significant, the onset of disease was earlier for males [Mean ± standard deviation (SD) (46.7 years ±17.3 vs 48.8 years±14.1), p = 0.110]. Almost 79% of the cases were found as an incidental finding during Magnetic Resonance Imaging. Of the total PES cases, only 20% were referred to the endocrinologists and the rest were handled by general physicians. Only 1–2.5% of the cases were evaluated for gonadal, growth and adrenal hormones by the general physicians. The hormonal evaluation by the endocrinologists was also found to be sub-optimal. Headache and visual disturbances were the most common presenting complaints followed by menstrual abnormalities. Endocrine abnormalities like thyroid dysfunction, hyperprolactinemia, hypogonadism and hypocortisolism were highly prevalent among those assessed. Conclusion There is a gross under-evaluation of hormonal assessment and minimal case-referral to Endocrinologists. PES is associated with varying degrees of hormonal dysfunction, and hence early assessment and management is needed. Establishing a standard protocol for diagnosis and case management is essential with the involvement of a multidisciplinary team consisting of endocrinologists, neurologists, primary care phys icians and ophthalmologists.

Background Diabetes-related complications can be prevented by maintaining good glycemic control. Despite huge efforts to obtain acceptable glycemic control among diabetics, this has not yet been achieved. Thus, there is a need to discover all factors that might affect glycemic control. Here, our main aim was to assess the association between self-awareness of Hemoglobin A1c (HbA1c) among Saudi patients with type 2 diabetes and glycemic control, thereby identifying those factors that might affect the glycemic control. Methods The data for this study was collected using questionnaires through interviews among 600 patients with type 2 diabetes. The study was conducted in outpatient diabetes clinics in tertiary hospitals in Riyadh, Qassim and Jeddah, Saudi Arabia. The data collection was done during the period from March and April 2018. The subject’s self-awareness about the HbA1c test was assessed based on the combined score of four questions. The latest HbA1c result before the time of data collection was obtained from medical records. Frequencies and percentages were calculated for all categorical variables used in the analysis. Means and standard deviations were calculated for continuous variables. A p-value of less than 0.05 was considered statistically significant for all analyses. Results The mean age of the respondents was 54.7 years, and the mean duration of diabetes was 11.9 years. The prevalence of HbA1c self-awareness was approximately 40%. Overall, 63.9% accurately reported their Hemoglobin A1C Self-Knowledge (HbA1csk). The prevalence of good glycemic control (defined as HbA1c less than 7.0%) was 21.0%. Five of the participants’ characteristics were associated with better glycemic control: good HbA1c self-awareness (OR = 3.25, 95%CI: 1.15–9.24), duration of diabetes (negatively associated with glycemic control) (OR = 0.91, 95%CI: 0.87–0.95), discussed HbA1c target with the health care provider (OR = 2.42, 95%CI: 1.22–4.79), monthly income between 10,001 and 15,000 SR (OR = 2.28, 95%CI: 1.13–4.60), and number of follow up visit (OR = 0.77, 95%CI: 0.63–0.94). Conclusions We conclude that there is a positive association between HbA1c self-awareness and glycemic control. Glycemic control was good among those who were educated about the meaning of the test, their levels, and their target goal. Awareness among health care providers regarding the role of the patient’s education about their condition might help in providing the patient with optimal care. Further studies with different experimental designs are needed to study this association, which will contribute to the development of a structured educational program.

Background: High prevalence of undiagnosed cases of diabetes mellitus (DM) has increased over the last two decades, most patients with DM only become aware of their condition once they develop a complication. Limited data are available regarding the knowledge and awareness about DM and the associated risk factors, complications and management in Saudi society. Aim: This study aimed to assess knowledge of DM in general Saudi society and among Saudi healthcare workers. Results: Only 37.3% of the participants were aware of the current DM prevalence. Obesity was the most frequently identified risk factor for DM. Most comparisons indicated better awareness among health workers. Conclusion: A significant lack of knowledge about DM in Saudi society was identified. Social media and educational curriculum can improve knowledge and awareness of DM.

Summary Central diabetes insipidus (CDI) and several endocrine disorders previously classified as idiopathic are now considered to be of an autoimmune etiology. Dermatomyositis (DM), a rare autoimmune condition characterized by inflammatory myopathy and skin rashes, is also known to affect the gastrointestinal, pulmonary, and rarely the cardiac systems and the joints. The association of CDI and DM is extremely rare. After an extensive literature search and to the best of our knowledge this is the first reported case in literature, we report the case of a 36-year-old male with a history of CDI, who presented to the hospital’s endocrine outpatient clinic for evaluation of a 3-week history of progressive facial rash accompanied by weakness and aching of the muscles. Learning points: Accurate biochemical diagnosis should always be followed by etiological investigation. This clinical entity usually constitutes a therapeutic challenge, often requiring a multidisciplinary approach for optimal outcome. Dermatomyositis is an important differential diagnosis in patients presenting with proximal muscle weakness. Associated autoimmune conditions should be considered while evaluating patients with dermatomyositis. Dermatomyositis can relapse at any stage, even following a very long period of remission. Maintenance immunosuppressive therapy should be carefully considered in these patients.

Background: Type 1 diabetes is an autoimmune disorder with a high risk of celiac disease (CD). Aim: This study aimed to determine the celiac autoantibody status and the clinical characteristics among children with type 1 diabetes and autoantibody positivity for CD compared to those without serological evidence of CD. Materials and Methods: In this cross-sectional study, 240 children with type 1 diabetes underwent serological screening CD. Blood glucose, glycated hemoglobin (HbA1c), hemoglobin, calcium, phosphorous, Vitamin D, alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) were evaluated. The participants were screened for human anti-endomysial antibody and human anti-tissue transglutaminase antibody. Results: Of the 240 children with type 1 diabetes, 66 children were antibody positive for either anti-endomysial or anti-tissue transglutaminase or both autoantibodies for CD. There were 36 (54.5%) female and 30 (45.5%) male children with the mean age of 15.5±2.1 years. The mean duration of diabetes was 6.8±3.8 years. Only 35 (14.6%) children were found to have serological evidence of CD. Conclusion: CD is associated with type 1 diabetes. Serological screening for CD autoantibody should be performed routinely in children with type 1 diabetes. There is discrepancy in screening CD with antibodies, so a prospective follow-up of this cohort is needed for endoscopic evaluation and histopathological examination of intestinal biopsy to confirm CD in this population. Relevance for Patients: Anti-endomysial and anti-tissue transglutaminase autoantibodies should be included for screening CD among children with type 1 diabetes. Patients should undergo an endoscopy to confirm a diagnosis of CD.

Type-2 diabetes (T2D) is associated in observational studies with both higher bone mineral density (BMD) and higher fracture risk for given BMD. These relationships may however be confounded by factors such as body mass index (BMI). Here we used Mendelian randomization (MR) to obtain non-confounded estimates of the effect of T2D and glycemic traits on BMD. We identified genetic variants strongly associated with T2D risk (34,840 T2D cases and 114,981 controls) and fasting glucose (133,010 nondiabetic individuals), but not associated with BMI, and determined the effects of these variants on BMD (up to 83,894 individuals). Using these variants as instrumental variables, we found that a genetically-increased risk of T2D increased femoral neck BMD (+0.034 SD in BMD per unit increase in log-odds of T2D [95% CI, 0.001 to 0.067; p = 0.044]). Genetically-increased fasting glucose also increased femoral neck BMD (+0.13 SD in BMD per mmol/L increase in fasting glucose [95% CI, 0.01 to 0.25; p = 0.034]). Similar nonsignificant trends were observed for the effects of T2D and fasting glucose on lumbar spine BMD. Our results indicate that both genetically-increased T2D risk and genetically-increased fasting glucose have weak positive effects on BMD. © 2016 American Society for Bone and Mineral Research.

The coronavirus disease of 2019 (COVID-19) pandemic significantly affected different life aspects, including healthcare communities and academic institutes. We aimed to assess the level of stress and risk factors among medical students and interns during the COVID-19 pandemic in the setting of the middle east respiratory syndrome -CoV endemic area.A questionnaire-based cross-sectional study was conducted on a randomly selected sample of medical students and interns. The questionnaire was anonymously self-administered to indicate perceive hygienic practice change, importance of viral prevention domestic hygiene, perceive adequacy of received information, perceived agreement to facilitators to alleviate covid stress, self-reported stress level, and generalized anxiety disorder score.A total of 322 returned the questionnaire (69.7% response rate). Participants had good knowledge regarding severe acute respiratory syndrome -CoV2 in multiple aspects, with an average score of 13.8 out of 14. Two-thirds (62.4%) of the students experienced mild anxiety, (23.9%) had moderate anxiety, (6.8%) had clinically high anxiety level, and another (6.8%) had a clinically very high anxiety level. The stress level, as reported by the respondents (on a 1-10 scale), showed a correlation with the Generalized Anxiety Disorder scale. We observed an increased level of social avoidance and hygienic practice facilitated by availability of hand sanitizers. Majority of the students receive information regarding COVID-19 from reliable and official resourcesMost students reported mild to moderate levels of anxiety, and was associated with enhancement of their universal precaution measures. The availability of alcohol-based hand sanitizers and the off-campus study were great relievers. The importance of reliable pandemic resources in educating students during pandemics is emphasized. Furthermore, this study indicate the importance of students' support services to address mental health and students' wellbeing in the era of pandemics.

Type 1 diabetes mellitus (T1DM) is quite prevalent in the world, with a proportion of 1 in every 300 persons and steadily rising frequency of incidence of about 3% every year. More alarmingly, the incidence of T1DM among infants is also increasing, with children as young as 6 months succumbing to it, instead of that at a rather established vulnerable age of around seven and near puberty, when the hormones antagonize the action of insulin. These reports pose a unique challenge of developing efficient T1DM management system for the young children. The Kingdom of Saudi Arabia (KSA) is the largest country in the Middle East that occupies approximately four-fifths of the Arabian Peninsula supporting a population of more than 33.3 million people, of whom 26% are under the age of 14 years. As per the Diabetes Atlas (8th edition), 35,000 children and adolescents in Saudi Arabia suffer from T1DM, which makes Saudi Arabia rank the 8th in terms of numbers of TIDM patients and 4th country in the world in terms of the incidence rate (33.5 per 100,000 individuals) of TIDM. However, in comparison with that in the developed countries, the number of research interventions on the prevalence, incidence, and the sociodemographic aspects of T1DM is woefully inadequate. In this review we discuss different aspects of T1DM in Saudi Arabia drawing on the published literature currently available.

Type-2 diabetes (T2D) is associated in observational studies with both higher bone mineral density (BMD) and higher fracture risk for given BMD. These relationships may however be confounded by factors such as body mass index (BMI). Here we used Mendelian randomization (MR) to obtain non-confounded estimates of the effect of T2D and glycemic traits on BMD. We identified genetic variants strongly associated with T2D risk (34,840 T2D cases and 114,981 controls) and fasting glucose (133,010 nondiabetic individuals), but not associated with BMI, and determined the effects of these variants on BMD (up to 83,894 individuals). Using these variants as instrumental variables, we found that a genetically-increased risk of T2D increased femoral neck BMD (+0.034 SD in BMD per unit increase in log-odds of T2D [95% CI, 0.001 to 0.067; p = 0.044]). Genetically-increased fasting glucose also increased femoral neck BMD (+0.13 SD in BMD per mmol/L increase in fasting glucose [95% CI, 0.01 to 0.25; p = 0.034]). Similar nonsignificant trends were observed for the effects of T2D and fasting glucose on lumbar spine BMD. Our results indicate that both genetically-increased T2D risk and genetically-increased fasting glucose have weak positive effects on BMD. © 2016 American Society for Bone and Mineral Research.

In observational studies, type-2 diabetes (T2D) is associated with an increased risk of coronary heart disease (CHD), yet interventional trials have shown no clear effect of glucose-lowering on CHD. Confounding may have therefore influenced these observational estimates. Here we use Mendelian randomization to obtain unconfounded estimates of the influence of T2D and fasting glucose (FG) on CHD risk. Using multiple genetic variants associated with T2D and FG, we find that risk of T2D increases CHD risk (odds ratio (OR)=1.11 (1.05–1.17), per unit increase in odds of T2D, P=8.8 × 10−5; using data from 34,840/114,981 T2D cases/controls and 63,746/130,681 CHD cases/controls). FG in non-diabetic individuals tends to increase CHD risk (OR=1.15 (1.00–1.32), per mmol·per l, P=0.05; 133,010 non-diabetic individuals and 63,746/130,681 CHD cases/controls). These findings provide evidence supporting a causal relationship between T2D and CHD and suggest that long-term trials may be required to discern the effects of T2D therapies on CHD risk., In order to effectively design interventions, it is useful to understand the complex interplay between multiple syndromes. Here, Ahmad et al. use genome-wide association study data and Mendelian randomisation to examine the influence of Type 2 diabetes and fasting glucose levels on coronary heart disease.

AIM To determine the clinical and biological characteristics of double diabetes (DD) among young people in Saudi Arabia. METHODS This was a retrospective descriptive chart review study including 312 young newly diagnosed diabetic patients (aged 12-20 years), whom were admitted over a five year period (January 2009 to December 2013). Family history of diabetes mellitus (DM) (first degree), physical body mass index (BMI), acanthosis nigricans, history of auto-immune disease and laboratory information for glycosylated hemoglobin, basal C peptide level and diabetes autoantibody response (anti-GAD, anti-IA2 and anti-ICA) were collected from medical report. A mean follow-up of 3 years for these patients was performed. RESULTS Patients were categorized into 4 groups, based on the autoantibody response (Ab+ or Ab-) and C-peptide secretion (β+ for fasting level 0.4-2.1 ng/mL and β- if < 0.4 ng/mL). Group1 (type 1a): Ab+ β- (21%), group 2 (type 1b): Ab- β- (9%), group 3 (DD): Ab+ β+ (31%) and group 4 (classic type 2 DM): Ab- β+ (39%). The mean age of the DD patients in our study was 15.1 ± 6.4 years. A total of 41% of the study population presented with diabetic ketoacidosis and 61% of the study population presented with positive family history of DM. The mean BMI was 26.8 kg/m2 with 64% of overweight or obese patients. Ninety two percent of the patients were started on insulin at the time of diagnosis. During a mean follow-up of 3 years, only 32% of the patients with DD required insulin and 78% were on metformin alone or with insulin. CONCLUSION Our findings enable us to arrive at the conclusion that almost one-third of the young Saudi diabetic patients reveal atypical forms of DM (double diabetes) expressing features resulting from both T1D and T2D.