International Journal of Diabetes Mellitus

Editorial Board

2009-04-01

Message from the Editor-in-Chief

Khalid Al-Rubeaan — 2009-04-01

The World Health Organization (WHO) has considered Diabetes Mellitus, especially type 2, a major healthcare problem faced by all the member states. It has been anticipated that more than 300 million individuals will be affected by this disease by the year 2025. The number of people with diabetes is increasing as a result of globalization, ageing, and obesity in addition to rapid universal population growth. Different international institutes like International Diabetes Federation (IDF) have sought to raise global awareness of this disease at governmental and public level. Diabetes Mellitus has also been in focus at the level of United Nations (UNO) with its recent resolution of adopting diabetes and recognizing the urgent need to pursue multilateral efforts to promote and improve human health and provide access to treatment and healthcare education.

Adding rosiglitazone to metformin in patients with type 2 diabetes: Effect on diabetes control and metabolic parameters

Hussein Raef, Abdulraof Al-Mahfouz, Abdullah Al-Khonaizan — 2009-04-01

Abstract: Aim: To evaluate the efficacy and tolerability, any changes in lipid parameters including free fatty acids and effect on weight and blood pressure, of adding Rosiglitazone to patients with type 2 DM who are not adequately controlled on maintenance dose of Metformin.Methods: Prospective study of 14 patients with type 2 DM who were maintained on Metformin alone (1.5–2.5g/day). Twelve patients met the inclusion criteria, and received 4mg of Rosiglitazone daily in addition to Metformin. Patients were followed for 24 weeks and seen for 6–7 visits. The dose of Rosiglitazone was increased after 8 weeks if FBG was still ⩾160mg/dl. Full biochemical evaluation was done and safety parameters were observed at base line, at intervals during the study and at the end of the study. All patients completed the study. T test was used for comparison.Results: Eight males and four females were studied. They had the following characteristics: Mean age was (52±6.9) years, weight was (78.2±10.1)kg BMI was (28±4)kg/m2, waist circumference was (97.5±6.5)cm, and duration of DM was (7.3±6) years. Four patients required an increase of Rosiglitazone dose to 8mg after 8 weeks.All patients showed improvement of HbA1c levels by the end of the study. When mean base line parameters were compared to those at the end of study: HbA1c level dropped from (8.9%±1.5) to (7.1%±1.1) (P: 0.00003) and FBG from (205±50.6) to (150±28)mg/dl (P: 0.002). Free Fatty Acids (FFA) dropped from (703±213) to (510±303.6) by 8 weeks and to (574±184.6) μeq/L by the end of the study, (P: 0.01 and 0.06, respectively). Improvement in HbA1c did not however correlate with the level of FFA drop. There was also significant increase in HDL level (1.15±0.14)–(1.27±0.2)mmol/L, (P: 0.02), and weight (78.2±10.1)–(80.1± 10.9)kg (P: 0.01). The changes in LDL (3.02±0.57)–(3.23±0.5)mmol/L, TG (2.16±1.1)–(2.2±1.33)mmol/L, waist circumference (97.5±6.5)–(99±8.1)cm, and BP (132.5±17)–(130.2±18.8)mm Hg (systolic), were not significant.When “Good Responders”, (HbA1c drop of >1.5%), (nine subjects) were compared to those with less than 1.5% drop (three subjects), there were no specific characteristics to define responders.Conclusion: Rosiglitazone, added to Metformin in type 2 DM patients, was effective and well tolerated. There was a significant decrease in FFA levels with treatment. The response to treatment, however could not be predicted from biochemical or clinical parameters. A larger study may be needed to define responder characteristics.

Thickness of the intima media as a new correlate for atherosclerosis risk factors in Indian type 2 diabetes patients

Syed Abdus Saboor Aftab — 2009-04-01

Abstract: Background and objectives: The evaluation of the Common Carotid Intima Media Thickness (CCIMT) assumes a special role in patients with diabetes mellitus because of being an indicator of the pan effect of atherosclerotic risk factors and an important predictor of catastrophic vascular events. Therefore, the present study was undertaken with the objective of correlating CCIMT with the numerous risk factors of atherosclerosis in diabetes patients.Subjects and methods: In the present study, 90 type 2 diabetic patients [67 males and 23 females, having assessed the CCIMT] with an age range from 32 to 78 years, with and without atherosclerotic events were recruited. Measurement of common carotid intima media thickness was measured on B-mode ultrasonography using high frequency linear transducer on a “GE LogiQ 700”.Results: The results showed that significant positive correlation and independent association of CCIMT turned out with the variables age and proteinuria. However, waist/hip ratio, duration of diabetes mellitus, systolic blood pressure, glycosylated hemoglobin, triglyceride, and total cholesterol/HDL cholesterol also had positive correlation with CCIMT, but they could not achieve the level of statistical significance. The patients who had higher CCIMT values and high odds ratios for atherosclerotic events had significantly higher durations of diabetes, hypertension and presence of dyslipidemia.Conclusion: This study has proven that age and proteinuria are the strongest correlates of CCIMT in type 2 diabetes mellitus. It is also suggested that further large size studies are needed to reconfirm similar results.

Mitochondrial tRNALeu(UUR) gene mutation and maternally inherited diabetes mellitus in Pakistani population

Abdul Khaliq Naveed, Maryam Wahid, Ayesha Naveed — 2009-04-01

Abstract: Background and objectives: Maternally Inherited Diabetes Mellitus and Deafness (MIDD) occurs due to the mutations in mitochondrial DNA (mtDNA). The most common heteroplasmic point mutation reported, is in the tRNALeu(UUR) gene, i.e., A3243G, accompanied with deafness. The objectives of the present study were to determine whether the cause of MIDD in selected Pakistani population, is also the mutation of A3243G in mitochondrial tRNALeu(UUR) gene or not, and is there any genotype–phenotype correlation for the MIDD in this population.Subjects and methods: The present study was conducted in the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, Pakistan, during the period November 2005 to November 2007. The patients and control subjects were randomly selected from the two cities; Rawalpindi and Multan (both rural and urban areas) and were divided into three groups. (1) Fifty patients with T2DM and maternal history with feature(s) of MIDD. (2) Fifty non-diabetic first-degree relatives of patients with T2DM. (3) Fifty non-diabetic controls with no maternal history of T2DM. The patients and control subjects were scanned for the detection of potential mutations in mitochondrial DNA tRNALeu(UUR) gene (np 3035–3456, 422 bp fragment).Results: On the basis of a polymerase chain reaction, electrophoresis and mtDNA sequencing along with insulin dependence, degree of deafness in patients and subjects, it is proved that there is no A-to-G mutation at np 3243 of mitochondrial leucine tRNA gene in any of the groups studied.Conclusion: It is concluded that in the Pakistani population, selected for the present study, the MIDD is not due to A3243G mutation in mitochondrial tRNALeu(UUR) gene.

Identification of loci conferring risk for premature CAD and heterozygous familial hyperlipidemia in the LDLR, APOB and PCSK9 genes

2009-04-01

Abstract: Background: Heterogeneous familial hypercholesterolemia (HFH) partly underlies polymorphic changes in the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB) and protein convertase subtilisin/kexin type 9 (PCSK9), exhibiting intra-ethnical variations in its clinical features.Methods: We employed the Affymetrix whole genome scan 250 sty1 array to characterize possible genomic linkage to heterozygous familial hypercholesterolemia (HFH) and sequencing techniques to identify related mutations in the above three genes in a Saudi family of 11 individuals harbouring clinical features of FH. The propositus had early onset of coronary artery disease (CAD) and very significantly elevated cholesterol (Chol) level of 10.1mmol/L and LDL-cholesterol (LDL-C) of 7.9mmol/L as well as low HDL-C level of 0.51mmol/L, while 4 siblings were affected with HFH.Results: Whole genome scan for the autosomal dominant model showed high homology for the affected individuals in several regions including chromosomes (chr) 1 and 2 which harbour PCSK9 and APOB, respectively. Subsequent sequencing of the coding regions of these two and LDLR identified 11 single nucleotide polymorphisms (SNPs) in the LDLR, 8 in the APOB and 6 in the PCSK9 genes. The propositus uniquely carried the homozygous mutant genotypes (haplotype) for all 11 LDLR SNPs, in direct contrast to the only normolipidemic sibling and a control who carried the homozygous wild type genotypes at these loci. Another set of 7 SNPs in the APOB also isolated with FH. Interestingly, all family members were heterozygous for all except the rs2228671 C>T of this gene, for which the mother shared the C/C genotype with the propositus, two other affected off-springs and a control, all of whom exhibited low HDL-C levels. A confirmation experiment involving 70 individuals harbouring low HDL-C revealed 74.3% of them as C/C carriers.Conclusions: Our study identified a haplotype in the LDLR as a marker for early onset of CAD, and rs2228671 C>T in the LDLR in association with a reduction in HDL-C concentrations in FH. The results also substantiate the notion of genetic heterogeneity in HFH, underlining the essence of recognizing ethnic-specific gene variability as a potential basis for appropriate management of FH.

Approach to dysglycemia: Do we need to treat impaired glucose tolerance and impaired fasting glucose?

Mousa A. Abujbara, Kamel M. Ajlouni — 2009-04-01

Abstract: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are not only a surrogate for the state of insulin resistance but are also associated with the microvascular and macrovascular complications traditionally linked to diabetes. They predict an increased risk for death and morbidity due to cardiovascular disease.There is growing evidence that early detection of this state of “pre-diabetes” enables us to limit these recognized complications and perhaps to halt the progression to diabetes. For all pre-diabetes patients’ life style modifications, emphasizing modest weight loss & moderate physical activity are strongly recommended. Pharmacological intervention may also be necessary. Many studies have shown several drugs, both antidiabetic and nonhypoglycemic agents to be useful. If pharmacological treatment is required, Metformin is considered the first choice because of its safety, tolerability, efficacy and low cost.

Nutritional challenges in the elderly with diabetes

Ali A. Rizvi — 2009-04-01

Abstract: Adults age 60 and older will comprise two-thirds of the diabetic population by the year 2025. Older patients with diabetes are more likely to have coexistent chronic conditions like hypertension, dyslipidemia, and cardiovascular disease that may impact their nutritional requirements. The issue of attainment and maintenance of an optimal body weight in elderly diabetic persons may not be as straightforward as in other age groups, and the risk-benefit ratio may be different as well. Although increased prevalence of overweight and obesity in the elderly contributes to insulin resistance and hyperglycemia, older inhabitants of long-term care facilities who suffer from diabetes tend to be underweight. Both may signify inadequate nutritional status and lead to increased morbidity and mortality. The attendant problems of appetite changes, palatability of food, dietary restrictions, loneliness, and depression may affect the type and quantity of food consumed by elderly persons. Structured screening tools may identify nutrition-related issues that warrant evidence-based interventions. Although glucose control and health concerns are important factors in diet modification in the older population, other considerations include quality of life and individual preferences. Customizing of nutritional guidelines to the needs of the older diabetic patient makes sense.

Genetics of type 2 diabetes in Arabs: What we know to date

Brian F. Meyer, Osama Alsmadi, Salma Wakil, Khalid Al-Rubeaan — 2009-04-01

Abstract: Type 2 diabetes (T2D) is among the most challenging health issues of the 21st century and is associated with an alarming rise in the incidence. The Arab population is no exception to this trend. The pathophysiological processes that lead to development of T2D are still unclear, however impairment in insulin secretion and/or action is clearly indicated. T2D is a complex disease with susceptibility being governed by the interaction of multiple genetic and environmental effects. Previous studies indicated that variants in genes encoding the pancreatic β-cell K+ATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) are associated with type 2 diabetes. The common Pro12Ala polymorphism in peroxisome proliferator-activated receptor-γ gene (PPAR-γ) was confirmed in several studies to be associated with type 2 diabetes as well. More recently, studies reported variants within a novel gene, TCF7L2, as a putative susceptibility gene for type 2 diabetes across many ethnic backgrounds around the world. However, studies to date in Arab cohorts remain limited.

Medical treatment of insulinomas: The role of diphenylhydantoin

Lara Al-Khoury Nabbout, Ibrahim S. Salti, Marie T. Merheb — 2009-04-01

Abstract: Surgical removal of the insulinoma continues to be the treatment of choice. Medical therapy should be considered in patients who cannot undergo surgery. We are reporting our experience with regard to the efficacy of Diphenylhydantoin (DPH) in controlling hypoglycemia and suppressing insulin release in patients with insulinomas. DPH was administered orally at a dose of 300–400mg/day to three patients with documented endogenous insulin excess. The first two patients received the drug temporarily during the preoperative period, with resolution of the hypoglycemic attacks, normalization of blood glucose, and reduction of insulin levels. Subsequent surgery confirmed the presence of insulin-secreting pancreatic tumor. Cure was achieved after excision of the tumor. The third patient represented a diagnostic and threrapeutic challenge. An insulin-secreting tumor located in the body of the pancreas was diagnosed in a patient with type 2 diabetes and end stage renal disease. The patient’s poor cardiac function contraindicated surgery. DPH resulted in an excellent sustained control of his blood sugar and a fall in insulin levels for several months. We believe that DPH is a potent inhibitor of insulin secretion and, thus, is suitable as a temporary therapeutic measure in the preoperative period of patients with insulinoma, as well as an alternative to surgery for those who are not surgical candidates.

Nerve conduction study and Fas mediated apoptosis of nerve cells in peripheral neuropathy in type 2 diabetes

Fawzia Al-Rouq — 2009-04-01

Abstract: Apoptosis may play a crucial role in the pathogenesis of late diabetic neuropathy. We determine the role of Fas mediated apoptosis in the aetiopathogenesis of diabetic neuropathy, by measurement of apoptosis markers, induction of apoptosis by Fas and/or serum and correlate the level of soluble Fas (marker of apoptosis) with the nerve conduction study. Furthermore, we elucidate the role of apoptosis inhibition in prevention of diabetic neuropathy by the Fas blocker (ZB4).There was significant increase in the sFas serum level in diabetics with neuropathy as compared to the controls and diabetic patients without neuropathy (p<0.005). All parameters of the motor median nerve conduction study showed significant correlation with the serum sFas levels, especially the nerve conduction velocity (r=−0.60, p<0.01). Cells treated with the serum of diabetic patients with neuropathy showed significantly higher percentages of early and late apoptosis (p<0.05) compared to the negative control. A 500ng/mL Fas blocker (ZB4), antagonistic anti-Fas antibody caused significantly lower levels of early and late apoptosis (p<0.025) compared to serum of diabetic patients with neuropathy treatment.In conclusion, Fas-mediated apoptosis of the neuronal cell line is responsible for the degradation of the neurons in patients with diabetic neuropathy and provides evidence for the involvement of the receptor pathway in Fas-mediated apoptosis of these cells. Thus, targeting and inhibiting Fas receptor offers an option for diabetic neuropathy therapy.

Entrapment of medial plantar nerve [tarsal tunnel syndrome] in type 2 diabetes mellitus: An electrophysiological study

2009-04-01

Abstract: Background: With increase in type 2 diabetes mellitus patients the complications of diabetes are being seen more frequently. Patients with diabetic neuropathy often present with distressing symptoms such as pain and burning sensation in the feet. Tarsal tunnel syndrome with electrophysiological changes may be a causative or contributing factor. The present study was designed to assess the presence and features of tarsal tunnel syndrome in diabetes mellitus patients.Method: In this study a group of 10 normal volunteers were selected who had no neurological complaints or foot trauma. Another group of 33 patients having longstanding diabetes mellitus with complaints of pain, burning sensation and paraesthesia in the feet were selected for electrophysiological tests and median plantar nerve was studied.Results: In the present study we observed that 15 (45%) of diabetic cases showed abnormal findings e.g., prolonged distal motor latency, decreased amplitude of M-response, low or absent sensory response suggesting tarsal tunnel syndrome.Conclusion: This study shows that the tarsal tunnel syndrome may be present in a significant number of diabetic patients with subjective neuropathic symptoms in the feet. The tarsal tunnel syndrome should be kept in mind during the diagnostic workup and management of diabetes mellitus.

Diabetes mellitus: Health and wealth threat

Sultan Ayoub Meo — 2009-04-01

Diabetes mellitus is a major and rapidly growing public health care problem. It is increasing in incidence, and brings with it long term complications. Presently, more than 200 million people have diabetes mellitus; by 2030, it is estimated that approximately 366 million will develop diabetes mellitus , and more than one third of diabetes victims are unaware that they have this disease. Over the last few decades, science and technology have dramatically revolutionized living standards, providing a luxurious life with remote control activities. Significant changes have been observed in the lifestyle of both the rural and urban population. Through this modernization and change, people are eating more, and engage in less physical activity; this contributes substantially to the development of diabetes mellitus, and indeed, is fuelling an epidemic. The ten countries estimated to have the highest number of people with diabetes by 2030 are India, China, USA, Indonesia, Pakistan, Brazil, Bangladesh, Japan, Philippines and Egypt . In spite of marvelous advancements in medicine, diabetes science and technology, diabetes mellitus remains an incurable, life-long disease. It involves multiple systems, with wide ranging and devastating complications, which may lead to severe disability, and is a prime cause of excess morbidity and mortality. Among the major complications of diabetes mellitus are retinopathy with potential loss of vision, nephropathy leading to renal failure, peripheral neuropathy with risk of foot ulcers, amputations, and charcot joints, autonomic neuropathy causing gastrointestinal, genitourinary, cardiovascular symptoms and sexual dysfunction. Patients with diabetes have an increased incidence of atherosclerotic cardiovascular, peripheral arterial and cerebrovascular disease.

Obesity, diabetes and longevity in the Gulf: Is there a Gulf Metabolic Syndrome?

Geoffrey W. Guy, Alistair V.W. Nunn, Louise E. Thomas, Jimmy D. Bell — 2009-04-01

“….we do not always bear in mind, that though food may be now superabundant, it is not so at all seasons of each recurring year”Charles Darwin (The Origin of Species) The above quote in the year of Darwin’s 200th birthday is highly poignant as modern humans inextricably move towards a lifestyle-induced pandemic, with rampant levels of obesity, type 2 diabetes mellitus (T2DM) and insulin resistance . Unfortunately, the Gulf appears to be leading the world, with T2DM rates reaching 35% in some populations .

A future hope for the treatment of diabetic retinopathy, manipulating hypoxia-inducible factor-1 alpha pathway

Ahmed M. Abu El-Asrar — 2009-04-01

The pathologic growth of new blood vessels is the common final pathway in proliferative diabetic retinopathy (PDR), and often leads to a catastrophic loss of vision due to vitreous hemorrhage and/or tractional retinal detachment. In diabetic retinopathy, hypoxia appears to be the primary stimulus to neovascularization by upregulating the production of angiogenic stimulators, and by reducing the production of angiogenic inhibitors, there by disturbing the balance between the positive and negative regulators of angiogenesis. Vascular endothelial growth factor (VEGF) and its cognate receptors are critical mediators of angiogenesis, mediating endothelial cell proliferation, migration, and tube formation . Recently, pigment epithelium-derived factor (PEDF) has been shown to be a highly effective inhibitor of angiogenesis as it specifically inhibits the migration of endothelial cells. It was also shown that PEDF contributes to most of the antiangiogenic activity in the vitreous . The elevated intraocular levels of the angiogenic VEGF and decreased intraocular levels of the antiangiogenic PEDF in patients with PDR have previously been demonstrated. The data support the concept that induction of angiogenesis in PDR requires not only elevation of angiogenic growth factors such as VEGF but also a decrease in angiogenesis inhibitors such as PEDF. In addition, strong evidence indicates that chronic, low-grade subclinical inflammation is implicated in the pathogenesis of diabetic retinopathy .

Lisfranc’s dislocation and fracture in the Charcot Foot

Nauman Bashir Barlas, Muhammad Ali, Sajjad Hussain — 2009-04-01

Abstract: Diabetic patients may present with Lisfranc’s Fracture Dislocation which may be confused with osteomyelitis. Rapid diagnosis and early intervention can prevent deformity. We suggest that the diagnosis of Charcot’s foot should be considered in any diabetic patient with unilateral swelling of lower extremity and/or foot.

Uveitis in diabetic woman

Fahad Shar Al Shehri — 2009-04-01

Abstract: A 42-year-old diabetic female complained of cough, mild dyspnea, malaise and weight loss. Red tender eye. Fundus with multiple white granuloma lesions. Fine crepitation was found in the right middle zone. Serum ACE level was high, and HbA1c was high. Chest X-ray revealed pulmonary infiltration in the right lower lobe, CT of the chest confirmed the same finding. A definitive diagnosis of sarcoidosis was made by histological study of the specimen by bronchial biopsy which revealed non-caseating granuloma.

Use of chitosan/polyamine biopolymers based cotton as a model system to prepare antimicrobial wound dressing

Moustafa M.G. Fouda, R. Wittke, D. Knittel, E. Schollmeyer — 2009-04-01

Abstract: The principle aim of this study is to explore and compare the effect of chitosan and linear polyvinyl amine, as biopolymer, on the antibacterial properties of the prepared dressing based cotton. The biopolymer molecules can be covalently fixed on to the cotton by using friendly anchor chemicals like butanetetracarboxylic acid. The treated cotton are characterised through monitoring the susceptibility of the amino groups created on the surface of the fabric. The bacteriostatic effect was evaluated against Escerichia coli (E. coli) DSMZ 498. The results obtained show a synergistic bacetriostatic effect of the treated cotton samples by using chitosan/polyvinyl amine finishing system. The produced dressing based cotton could be used as a model system to treat wounds, ulcers as well as diabetic ulcers, in addition some kind of burns.

International Journal of Diabetes Mellitus

Editorial Board

Contents

Message from the Editor-in-Chief

Adding rosiglitazone to metformin in patients with type 2 diabetes: Effect on diabetes control and metabolic parameters

Thickness of the intima media as a new correlate for atherosclerosis risk factors in Indian type 2 diabetes patients

Mitochondrial tRNALeu(UUR) gene mutation and maternally inherited diabetes mellitus in Pakistani population

Identification of loci conferring risk for premature CAD and heterozygous familial hyperlipidemia in the LDLR, APOB and PCSK9 genes

Approach to dysglycemia: Do we need to treat impaired glucose tolerance and impaired fasting glucose?

Nutritional challenges in the elderly with diabetes

Genetics of type 2 diabetes in Arabs: What we know to date

Medical treatment of insulinomas: The role of diphenylhydantoin

Nerve conduction study and Fas mediated apoptosis of nerve cells in peripheral neuropathy in type 2 diabetes

Entrapment of medial plantar nerve [tarsal tunnel syndrome] in type 2 diabetes mellitus: An electrophysiological study

Diabetes mellitus: Health and wealth threat

Obesity, diabetes and longevity in the Gulf: Is there a Gulf Metabolic Syndrome?

A future hope for the treatment of diabetic retinopathy, manipulating hypoxia-inducible factor-1 alpha pathway

Lisfranc’s dislocation and fracture in the Charcot Foot

Uveitis in diabetic woman

Use of chitosan/polyamine biopolymers based cotton as a model system to prepare antimicrobial wound dressing