International Journal of Diabetes Mellitus

Diabetes epigenetics: Fact or fiction

Khalid Al-Rubeaan — 2010-07-08

Diabetes mellitus, especially type 2, is a disorder characterized by complex genetic components influenced by environmental perturbations. The field of epigenetics has emerged to bridge the gap between nature and nurture. It is defined as the development and maintenance of an organism orchestrated by a set of chemical reactions that switch parts of the genome on and off at strategic times and locations. Epigenetics is the study of these reactions, and the factors that influence them. In the beginning of this millennium, epigenetics is defined as the study of heritable changes in genome function that occur without a change in DNA sequence.

Neurocognitive differences between drivers with type 1 diabetes with and without a recent history of recurrent driving mishaps

2010-06-21

Abstract: Objective: A subset of drivers with type 1 diabetes mellitus (T1DM) may be at significant risk for hypoglycemia-related driving collisions and moving vehicle violations due to acute and chronic neurocognitive impairment. The present study compared drivers with T1DM with and without a recent history of multiple driving mishaps on a neurocognitive battery during euglycemia, progressive mild hypoglycemia, and recovery from hypoglycemia, to determine whether neurocognitive measures differentiate the two risk groups. We hypothesized that drivers with a history of multiple recent hypoglycemia-related driving mishaps would demonstrate greater psychomotor slowing, both during hypoglycemia and euglycemia.Study design: Participants were 42 adults with T1DM and were assigned to one of two groups: those reporting no driving mishaps in the last year (−History) and those reporting two or more (+History). Neurocognitive testing was conducted before and repeated during a hyper-insulinemic clamping procedure.Results: Not surprisingly, all drivers demonstrated a decrease in functioning across all neurocognitive tasks during hypoglycemia. However, in contrast to the common belief that neurocognitive functions return slowly and gradually following hypoglycemia, baseline neurocognitive functioning immediately recovered upon return of BG to euglycemia for all subjects. Between-group analyses revealed that subjects with a recent history of driving mishaps consistently demonstrated poorer performance on tasks measuring working memory.Conclusion: Working memory is a potential neurocognitive indicator that may help differentiate adults with T1DM with and without a history of driving mishaps, predict future risk for driving mishaps, and provide targeted intervention programs to address this critical public health issue.

Association between metabolic syndrome and risk of cardiovascular disease, using different criteria and stratified by sex

Somlak Chuengsamarn, Suthee Rattanamongkoulgul, Alfredo Villarroel — 2010-06-16

Abstract: Aim: The purpose of this study is to determine the association between the components used to define metabolic syndrome and cardiovascular risk using different criteria stratified by sex.Methods: A cross-sectional study with 608 subjects enrolled at the out-patients department of the Thai Internal Medicine Clinic was performed between October 2006 and September 2007. Included subjects had metabolic syndrome as defined by WHO, NCEP III, or IDF. The demographic and laboratory characteristic of the subjects including BMI, waist circumference, waist/hip ratio, fasting blood glucose, 2h postprandial blood glucose, triglyceride, HDL, blood pressure, and microalbuminuria, were measured and recorded by chart review. Cardiovascular risk was determined by pulse wave velocity. The sensitivity and specificity of the component of metabolic syndrome according to the three criteria were stratified by sex.Results: The HDL sensitivity was higher in females than in males. Among the different component of metabolic syndrome, blood pressure gave the strongest association with cardiovascular risk, with odds ratios of 13.6, 11.97, and 10.5 for the criteria of IDF, NCEP III, and WHO, respectively. Moreover, when analyzing by sex, the odds ratio for female subjects were about two times higher than that of males. The rest of the components in each of criteria exceptional HDL gave odds ratios of 2–4.Conclusions: The appropriate components to predict cardiovascular risks are: high blood pressure and cut off point of waist circumference in females, as defined by the IDF criterion, and high triglyceride in males, as defined by the IDF criterion.

Parameters of metabolic syndrome are markers of coronary heart disease – An observational study

Faria Afsana, Zafar Ahmed Latif, M. Maksumul Haq — 2010-06-14

Abstract: Aims: This study was undertaken to identify the parameters of metabolic syndrome which can predict cardiovascular and peripheral vascular disease.Subject: A total of 260 subjects were selected from Ibrahim Cardiac Hospital and Research Institute (ICHRI), who reported for coronary angiogram as per advice of a cardiologist.Method: Each subject undergoing angiogram was interviewed with a preset structured questionnaire. The study subjects were screened for PVD (peripheral vascular disease) by examining peripheral pulses and ankle brachial index measured. Subjects with absent pulse or non-recordable ankle brachial index was considered as ankle brachial index <0.9. Positive angiographic finding was defined by presence of mild to severe degree of coronary vascular narrowing of one or multiple of three coronary arteries.Result: Among the study subjects 64.6% had metabolic syndrome, 79.2% had positive and 20.8% had normal angiographic finding. Among the CAG positive subjects 38.8% had single vessel disease, 30.0% had double vessel disease and 31.08% had triple vessel disease. CAG positive subjects are mostly 40–60years of age, 78.6% male, 54.8% smoker, 62.1% had waist circumference above normal, and about 90% have dyslipidemia and dysglycemia (DM/IGT/IFG). In this study subjects 83.9% of diabetic and 69.7% of non-diabetic had positive angiographic finding. Among the CAG positive subjects 16.6% had low ABI (<0.9).Conclusions: This study reveals that hypertriglyceridemia, waist circumference and hypertension are significantly related with angiographic positivity. Peripheral vascular disease was not significantly higher among CAG positive subjects and no association was observed between metabolic syndrome and PVD.

Consideration of the validity of glycemic index using blood glucose and insulin levels and breath hydrogen excretion in healthy subjects

Tsuneyuki Oku, Mariko Nakamura, Sadako Nakamura — 2010-06-14

Abstract: Aim: Although glycemic index (GI) is very important in choosing appropriate foods for patients with diabetes mellitus, GI itself does not provide sufficient information for choosing adequate foods. The validity of GI is considered by measurement of blood glucose and insulin levels, and breath hydrogen excretion, testing several cultivars in the same type food.Methods: Twelve females, 23.8y participated in this within-subject, repeated-measures study. To clarify variations in GI in inter-cultivars of various foods, we examined four white rice and three potato cultivars and three noodle brands. Starchy-foods with a glucose equivalent of 50g were repeatedly and randomly given to each subject. Blood and end-expiration were collected at selected periods.Results: The significant difference of GI and insulinemic index (II) was not observed among the four white rice cultivars, though II of one cultivar were smaller than those of other three white rice cultivars. GI of three potato cultivars was relatively small, but the range of II was very large among three cultivars. Moreover, GI did not correspond to II among three noodle brands. AUC-3h-glucose and AUC-3h-insulin scores of white rice and noodle were significantly larger than those for 2h. The amount of breath hydrogen excretion showed a negative correlation to GI of tested foods.Conclusions: We should recognize that rare foods in which GI does not correspond to II exist in the cultivar of foods used for diet therapy of diabetes mellitus. We propose the addition of other information such as II and breath hydrogen excretion of selected foods.

Sustained gains from a diabetes prevention program and the role of telephone support

2010-06-01

Abstract: Background: An evaluation of the sustainability of lifestyle changes was undertaken for participants completing a 12month diabetes prevention program. This second part of the study also tested whether regular structured telephone calls could be effective in maintaining lifestyle changes.Methods: Originally, 237 participants completed a 12month group-based lifestyle intervention study. They were aged 40–75years, with a moderate to high risk of developing type 2 diabetes. Participants were then randomised to telephone support (n=107) or self-care only (n=98) for 18months, and re-assessed using anthropometric, clinical, psychological and general health measures.Results: A total of 164 participants (85 telephone support and 79 self-care only) completed the follow-up. Changes between 12 and 30months for the telephone support group were not significantly different from those found in the self-care only group. Beneficial lifestyle changes achieved by participants were generally sustained after the diabetes prevention program, with the exception of fasting plasma glucose and some psychological measures.Conclusions: Positive outcomes achieved at 12months were generally maintained after a further 18months. Telephone support did not appear to produce additional benefits.

Biological evaluation of (3β)-STIGMAST-5-EN-3-OL as potent anti-diabetic agent in regulating glucose transport using in vitro model

2010-02-01

Abstract: Aim: Insulin resistance is characterized by alterations in insulin signaling components thereby resulting in reduced glucose uptake. The mechanistic role of (3β)-stigmast-5-en-3-ol in augmenting glucose uptake to overcome insulin resistance is deciphered in this study.Main methods: L6 myotubes, rat skeletal muscle model have been used to check the effect of (3β)-stigmast-5-en-3-ol, a plant phytosterol isolated from the ethyl acetate extract of Adathoda vasica on glucose transport. The influence of (3β)-stigmast-5-en-3-ol on various cellular targets of insulin signaling cascade has been evaluated using inhibitors on glucose uptake as well as gene and protein expression to unravel the mechanistic action in triggering glucose uptake.Results: (3β)-stigmast-5-en-3-ol promoted glucose uptake in a dose dependent manner under insulin resistant condition. As assessed by inhibitor studies using Genistein (IRTK inhibitor) and Wortmannin (PI3K inhibitor), gene expression and protein expression studies using specific primers and antibodies, an activation of IR-β, IRS-1, PI3K, AKT/PKB, PKC by both the crude and (3β)-stigmast-5-en-3-ol were observed. This suggested that (3β)-stigmast-5-en-3-ol induced glucose uptake functions through the PI3K dependent pathway in L6 myotubes. Both, the crude and (3β)-stigmast-5-en-3-ol activates GLUT 4 transport (evident from increased mRNA levels and redistribution of GLUT4 from intracellular membrane to plasma membrane through translocation studies). Confocal microscopy revealed a substantial increase in redistribution of FITC tagged GLUT4 throughout the cells.Conclusion: Our results emphasize the insulin-like effect of (3β)-stigmast-5-en-3-ol in stimulating glucose transport in vitro and provide evidence in its beneficial role possessing antidiabetic property apart from its existing cholesterol lowering efficacy.

Safety and efficacy of switching to biphasic insulin aspart 30/70 (BIAsp 30) under the routine diabetic care in patients with type 2 diabetes: The IMPROVE™ observational study in the Gulf region

Saied Khader, Waleed AbdelFattah, Abdulqawi Almansari, Nabil K. Elnnagar — 2010-06-07

Abstract: The IMPROVE™ study was a 26-week, multinational, open-label, non-randomized study, carried out in 11 countries.Aim: To evaluate the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes under routine clinical practice.Study design: There were no prescribed procedures for this study except for the collection of data.Result: Data obtained at baseline and Week 26 in patients from the Gulf region is presented. From the Gulf region, 1613 patients (61% males) were enrolled with a mean age of 50.5years and a mean BMI of 30.4kg/m2. The majority of the patients (57.0%) were treated with OAD only, while 34.3% patients were previously treated with insulin ±OAD and 8.7% were treatment naive. After 26weeks of treatment, the mean HbA1c was reduced by 1.4% from 9.3% at baseline to 7.9% at Week 26. The mean FBG was reduced by 66.6mg/dL from 212.4mg/dL at baseline to 145.8mg/dL at Week 26. No major hypoglycaemic episodes were reported as SADRs during the study. The rate of major hypoglycaemic episodes was reduced from 0.13 episodes/patient year at baseline to 0.05 episodes/patient year at Week 26. A lower risk of minor hypoglycaemia was also observed. Body weight was reduced by 0.6kg from 85.4kg at baseline to 84.7kg at Week 26.Conclusion: BIAsp 30 improved glycaemic control without increasing the risk of hypoglycaemic episodes and weight gain after 26weeks’ treatment in patients with type 2 diabetes from the Gulf region.

T-cell protein tyrosine phosphatase: A role in inflammation and autoimmunity

Dimitry A. Chistiakov, Emma I. Chistiakova — 2010-06-16

Abstract: A cDNA of PTPN2 encoding for T-cell protein tyrosine phosphate (TC-PTP) was isolated and characterized as long as 20years ago. However, findings suggesting a potentially exciting role of this enzyme in general autoimmunity have only recently been obtained. Genome-wide association scans of the human genome revealed the involvement of PTPN2 in susceptibility to a several autoimmune disorders such as Crohn’s disease, type 1 diabetes, and Graves’ disease. Functional studies in immune cells revealed a key role of this enzyme in down-regulation of cytokine expression and inflammatory response, which provides an essential background to explaining the pathophysiological role of TC-PTP in autoimmunity. Thus, in addition to PTPN22, PTPN2 is likely to represent a second member of the broad family of non-receptor PTPs contributing to general autoimmunity.

Erythrocyte plasma membrane redox system in first degree relatives of type 2 diabetic patients

Syed Ibrahim Rizvi, Neeti Srivastava — 2010-06-14

Abstract: Diabetes mellitus (TDM) is strongly associated with oxidative stress. Human erythrocytes contain a plasma membrane redox system (PMRS) which transfers electrons from intracellular donors (NADH, ascorbate) to extracellular acceptors outside the cell. We show that the activity of erythrocyte PMRS and AFR reductase becomes elevated in first degree relatives of type 2 diabetics and in TDM subjects. The increase in PMRS and AFR reductase signifies compensatory mechanisms to mitigate increased oxidative stress. These findings show that an impaired redox balance may be a cause the disturbance of homeostasis in type 2 diabetic families, even before the development of the disease.

Medication adherence in low income elderly type-2 diabetes patients: A retrospective cohort study

I. Patel, J. Chang, R.A. Shenolikar, R. Balkrishnan — 2010-06-21

Abstract: The study objective was to determine the age associated medication adherence among low income type-2 diabetes patients enrolled in Medicaid. This was a retrospective cohort study consisting of patients aged 18–44years (n=681), 45–64years (n=2327) and 65+ years (n=161), respectively newly starting antidiabetic medication between July 2001 and June 2002. Medication adherence was measured as medication possession ratio using prescription refill patterns. Multiple regression analyzes showed that compared to age group 18–44years, age groups 65+ and 44–64years had significantly higher adherence rate by 13.4% and 12.5%, respectively. Better oral antidiabetic medication adherence was associated with increased age.

The kidneys as an emerging target for the treatment of diabetes mellitus: What we know, thought we knew and hope to gain

Mohamed H. Ahmed — 2010-06-07

Abstract: Glucose filtered by kidneys is reabsorbed into the proximal tubule through the sodium-coupled glucose co-transporter (SGLT2). This promotes urinary excretion of glucose and results in lowering of plasma glucose level. Administration of agents (e.g. dapagliflozin) that inhibits SGLT2 transporter have shown to be associated with improvement in hyperglycaemia without clinically persistent electrolytes disturbances or change in osmolarity. This may suggest that administration of dapagliflozin is effective and safe as treatment for hyperglycaemia. Ongoing clinical trials will reveal the potential benefit and safety of SGLT2 inhibitors as part of the therapy of type 2 diabetes.

Effects of Ramadan fasting on children with Type 1 diabetes

Ibrahim AlAlwan, Abdulhameed Al Banyan — 2010-06-10

Abstract: Some children with diabetes, despite their exemption, insist on fasting in Ramadan. We evaluated the safety of fasting among children with Type-1 diabetes.Methods: During Ramadan 2007, 20 children with Type-I diabetes were recruited and divided into two groups. Short term diabetes complications were recorded. Changes in weight, HbA1C and lipid profile before and after Ramadan were compared.Results: Fasting group (n=12, mean age 12.4years). Non-fasting group (n=8, mean age 10.5years) showed no significant difference in HbA1c (P=0.9), weight (P=0.96) or fasting lipid profiles.Conclusion: Supervised fasting with close observation may be safe with no short-term parameter changes.

Emphysematous pyelonephritis: A case report

Muhammad Ali, Nauman Bashir Barlas — 2010-06-14

Abstract: Emphysematous pyelonephritis is a severe, acute necrotizing renal parenchymal and perirenal infection with formation of gas. Emphysematous pyelonephritis predominantly affects females with uncontrolled diabetes and can occur in insulin-dependent as well as non-insulin dependant patients. CT scan is the modality of choice for the staging of the parenchymal gas and to rule out obstruction.We present a case of 83-year old female with uncontrolled diabetes mellitus who presented with dysurea and right flank pain in the emergency department. She was diagnosed as a case of emphysematous pyelonephritis. She was treated successfully in the urology department by antibiotics and percutaneous drainage.

Identification of genetic factors associated with Type 2 Diabetes in Saudis: The lessons from European studies

Stéphane Cauchi, Philippe Froguel — 2010-06-17

The Arab world is one of the largest geo cultural units in the world with a population exceeding 300 million and spanning more than 14,000,000 square kilometers, from the Atlantic Ocean in the west to the Arabian Sea in the east. The Arabs in general are genetically very diverse and united by history dating back to 3500 BC . In Saudi Arabia, both dramatic recent changes in lifestyle with subsequent obesity and metabolic syndrome, and possible specific genetic predisposition are probably responsible for Type 2 Diabetes (T2D) at epidemic levels. In the early eighties, T2D was not common in Saudi Arabia , and among the male Saudi population its prevalence was not different from other parts of the world . However, this seems to have changed in the last two decades since the prevalence of T2D in Saudis is now one of the highest in the world . Another particularity of Saudi Arabia is a rate of consanguinity as high as 57.7%, with first cousin marriage being 28.4% followed by distant relative marriage at 14.6% . Given this specific context, familial aggregation of T2D can yield an odds ratio of 6.2, suggesting an increased genetic susceptibility to the disease . The limited genetic diversity and reduced allelic heterogeneity observed in such isolated populations is well known to facilitate the discovery of loci contributing to both Mendelian and complex diseases. Genome-wide association studies (GWAS) in the Saudi population are therefore very promising in identifying novel genetic factors associated with T2D.

A case of unilateral adrenal hyperplasia

Asim Hassan, Tariq Javed Sheikh, Turki Jazi Al Harbi — 2010-06-28

A 55-year-old male, Saudi, diabetic and hypertensive patient was admitted with uncontrolled hypertension and hypokalemia. On clinical history patient revealed generalized weakness, polyurea and polydipsia. The patient had been suffering from hypertension [BP 160/110mm Hg] for the last 20 years, and diabetes mellitus for 1year.