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Type 2 Diabetes Mellitus (type 2 + diabetes_mellitu)
Selected AbstractsPrevention of Type 2 diabetes mellitus.DIABETIC MEDICINE, Issue 5 2004A review of the evidence, its application in a UK setting Abstract Type 2 Diabetes mellitus (T2DM) is a complex metabolic, multifactorial disease, which affects the quality, quantity and style of life. People with T2DM have a life expectancy that can be shortened by as much as 15 years, with up to 75% dying of macrovascular complications. To reduce the impact of T2DM in the 21st century, we need an approach that not only optimally treats the person with established diabetes but also prevents diabetes from occurring in the first place. The best evidence for prevention of diabetes is for interventions that target individuals at highest risk. Targeting patients who have impaired glucose tolerance with lifestyle changes including physical activity and dietary factors has been shown to be effective in the Chinese, North American and Finnish populations. In order for such lifestyle interventions to be successful in other populations, they need to be culturally sensitive, individualized and sustained. Some pharmacological agents including metformin and acarbose have also been shown to be effective, although the profile of those who respond is different. There continues to be a need to develop and evaluate interventions that target communities and populations at risk in a UK setting. Diabet. Med. (2004) [source] Bariatric surgery vs. advanced practice medical management in the treatment of type 2 diabetes mellitus: rationale and design of the Surgical Therapy And Medications Potentially Eradicate Diabetes Efficiently trial (STAMPEDE)DIABETES OBESITY & METABOLISM, Issue 5 2010Sangeeta R. Kashyap Obesity and Type 2 diabetes mellitus (T2DM) are closely interrelated, and are two of the most common chronic, debilitating diseases worldwide. Surgical approaches to weight loss (bariatric surgery) result in marked improvement of T2DM, however randomized trials directly comparing the efficacy of surgical and medical approaches are lacking. The Surgical Therapy and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial was designed to evaluate the efficacy of two bariatric surgery procedures involving gastric restriction only (laparascopic sleeve gastrectomy) and gastric bypass (Roux-en-Y) to advanced medical therapy in patients with T2DM with modest obesity with BMI of 27,42 kg/m2. This single site, prospective, randomized controlled trial will enroll 150 subjects who will be followed. The primary end point will be the rate of biochemical resolution of T2DM at 1 year as measured by HbA1c < 6%. The safety and adverse event rates will also be compared between the three arms of the study. [source] Type 2 diabetes mellitus and obesity in sub-Saharan AfricaDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2010Vivian C. Tuei Abstract While communicable diseases such as human immunodeficiency virus/acquired immune deficiency syndrome, malaria, and tuberculosis have continued to pose greater threats to the public health system in sub-Saharan Africa (SSA), it is now apparent that non-communicable diseases such as diabetes mellitus are undoubtedly adding to the multiple burdens the peoples in this region suffer. Type 2 diabetes mellitus (T2DM) is the most common form of diabetes (90,95%), exhibiting an alarming prevalence among peoples of this region. Its main risk factors include obesity, rapid urbanization, physical inactivity, ageing, nutrition transitions, and socioeconomic changes. Patients in sub-Saharan Africa also show manifestations of ,-cell dysfunction and insulin resistance. However, because of strained economic resources and a poor health care system, most of the patients are diagnosed only after they have overt symptoms and complications. Microvascular complications are the most prevalent, but metabolic disorders and acute infections cause significant mortality. The high cost of treatment of T2DM and its comorbidities, the increasing prevalence of its risk factors, and the gaps in health care system necessitate that solutions be planned and implemented urgently. Aggressive actions and positive responses from well-informed governments appear to be needed for the conducive interplay of all forces required to curb the threat of T2DM in sub-Saharan Africa. Despite the varied ethnic and transitional factors and the limited population data on T2DM in sub-Saharan Africa, this review provides an extensive discussion of the literature on the epidemiology, risk factors, pathogenesis, complications, treatment, and care challenges of T2DM in this region. Copyright © 2010 John Wiley & Sons, Ltd. [source] Metformin action on AMP-activated protein kinase: a translational research approach to understanding a potential new therapeutic targetDIABETIC MEDICINE, Issue 10 2010J. G. Boyle Diabet. Med. 27, 1097,1106 (2010) Abstract Clinical studies in Type 2 diabetes mellitus have shown that the effects of metformin go beyond improving HbA1c and include reductions in cardiovascular endpoints. Metformin therapy has been widely used in the treatment of Type 2 diabetes for many years, yet the precise mode of action remains uncertain. It has recently been proposed that metformin-mediated stimulation of hepatic AMP-activated protein kinase (AMPK) underlies the hypoglycaemic effects of metformin. AMPK is a heterotrimeric enzyme that is expressed in many tissues and plays a central role in the regulation of energy homoeostasis. Furthermore, there is increasing evidence that AMPK is implicated in the pathophysiology of cardiovascular and metabolic diseases. The generation of more specific and potent activators of AMPK, however, could have additional metabolic and vascular benefits for patients with Type 2 diabetes. [source] Baseline serum 25-hydroxyvitamin D concentrations in the Tromsø Study 1994,95 and risk of developing type 2 diabetes mellitus during 11 years of follow-upDIABETIC MEDICINE, Issue 10 2010G. Grimnes Diabet. Med. 27, 1107,1115 (2010) Abstract Aims, We wanted to test the hypothesis that low serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with increased risk of developing Type 2 diabetes mellitus (DM) in a population-based cohort during 11 years of follow-up. Methods, The analyses included 4157 non-smokers and 1962 smokers from the Tromsø Study 1994,95 without diabetes at baseline. Subsequent Type 2 DM was defined using a hospital journal-based end-point registry, completed through the year 2005. Participants were allocated into quartiles of serum 25(OH)D within each month to account for seasonal variation, and serum 25(OH)D values both as a continuous variable and in quartiles were used in Cox regression models. The analyses were stratified by smoking. Adjustments were made for age, sex, body mass index (BMI), physical activity and, in non-smokers, former smoking. Results, Type 2 DM was registered in 183 non-smoking and 64 smoking participants. Using the fourth (highest) quartile of serum 25(OH)D as the reference, non-smoking participants in the third, second and first quartiles had age- and sex-adjusted hazard ratios (95% confidence intervals) of incident Type 2 DM of 1.00 (0.62,1.61), 1.50 (0.97,2.31) and 1.89 (1.25,2.88), respectively, whereas the corresponding values for smokers were 1.79 (0.77,4.19), 2.33 (1.02,5.35) and 2.68 (1.18,6.08). Adjustment for BMI attenuated the hazard ratios, and they were no longer significant. Conclusions, Baseline serum 25(OH)D was inversely associated with subsequent Type 2 DM in a population-based 11 year follow-up study, but not after adjustment for BMI. Randomized trials are needed to define the possible role of serum 25(OH)D status, and thereby the role of supplementation, in the prevention of Type 2 DM. [source] The prevalence of depressive symptoms in a white European and South Asian population with impaired glucose regulation and screen-detected Type 2 diabetes mellitus: a comparison of two screening toolsDIABETIC MEDICINE, Issue 8 2010N. Aujla Diabet. Med. 27, 896,905 (2010) Abstract Aims, To compare the identification of prevalent depressive symptoms by the World Health Organization-5 Wellbeing Index (WHO-5) and Centre for Epidemiological Studies Depression Scale (CES-D) for South Asian and white European people, male and female, attending a diabetes screening programme, and to explore the adequacy of the screening tools for this population. An additional aim was to further explore associations of depressive symptoms with impaired glucose regulation (IGR) and Type 2 diabetes mellitus (Type2 DM). Methods, Eight hundred and sixty-four white European (40,75 years old) and 290 South Asian people (25,75 years old) underwent an oral glucose tolerance test (OGTT), detailed history and anthropometric measurements and completed the WHO-5 and CES-D. Depressive symptoms were defined by a WHO-5 score , 13, and CES-D score , 16. Results, Unadjusted prevalence of depressive symptoms with the WHO-5, for people with Type2 DM was 42.3% (47.4% in white European; 28.6% in South Asian) and for IGR 30.7% (26% in white European; 45.8% in South Asian). With the CES-D, the prevalence in Type2 DM was 27.2% (25.4% in white European; 31.8% in South Asian) and for IGR 30.7% (27.8% in white European; 40.7% in South Asian). Statistically significant differences in the prevalence of depressive symptoms for sex or ethnicity were not identified. Odds ratios adjusted for age, sex and ethnicity showed no significant association of depression with Type2 DM or IGR, with either WHO-5 or CES-D. Agreement was moderate (, = 0.48, 95% confidence intervals 0.42,0.54), and reduced when identifying depressive symptoms in people with Type2 DM. For this group, a WHO-5 cut-point of , 10 was optimal. Conclusions, Depressive symptoms, identified by WHO-5 or CES-D, were not significantly more prevalent in people with Type2 DM or IGR. The WHO-5 and CES-D differed in their identification of depressive symptoms in people with Type2 DM, though discrepancies between sex and ethnicity were not identified. [source] Type 2 diabetes and cardiovascular disease in polycystic ovary syndrome: what are the risks and can they be reduced?DIABETIC MEDICINE, Issue 5 2010J. Tomlinson Diabet. Med. 27, 498,515 (2010) Abstract Polycystic ovary syndrome (PCOS) is a risk factor for Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), but these risks are poorly defined. This study aimed to evaluate the evidence for these risks and whether screening and risk reduction are feasible. Medline reviews and data quality analysis were used using standard tools. Results showed that (i) polycystic ovary syndrome is a risk factor forT2DM but the magnitude of risk is uncertain, (ii) fasting plasma glucose is an inadequate screening test forT2DM in this population and the oral glucose tolerance test is superior, (iii) the identification of women with PCOS for diabetes screening is constrained by current diagnostic criteria for PCOS; however, women with oligomenorrhoea and those with diagnosed PCOS and obesity or a family history of T2DM are at highest risk, (iv) risk factors for T2DM are improved by weight loss interventions and by metformin. However, no studies have determined whether T2DM incidence is reduced, (v) polycystic ovary syndrome is associated with cardiovascular disease (CVD) risk factors but data on CVD incidence are weak, (vi) risk factors for CVD are improved by the same interventions and statins and (vi) no studies have evaluated whether CVD incidence is reduced. While PCOS has important metabolic associations, and short-term interventions reduce risk factors for T2DM and CVD, data on prevalence and incidence of T2DM and particularly CVD are poor. There is a need for a clear definition of PCOS, for diabetes screening protocols and for long-term studies to determine whether risks can be reduced. [source] Role of glucotoxicity and lipotoxicity in the pathophysiology of Type 2 diabetes mellitus and emerging treatment strategiesDIABETIC MEDICINE, Issue 12 2009S. Del Prato Abstract Type 2 diabetes mellitus is a disease characterized by persistent and progressive deterioration of glucose tolerance. Both insulin resistance and impaired insulin secretion contribute to development of Type 2 diabetes. However, whilst insulin resistance is fully apparent in the pre-diabetic condition, impairment of insulin secretion worsens over the time, being paralleled by a progressive decline in both pancreatic B-cell function and B-cell mass. Intense research has identified a number of genetic variants that may predispose to impaired B-cell function, but such predisposition can be precipitated and worsened by toxic effects of hyperglycaemia (glucotoxicity) and elevated levels of free fatty acids (lipotoxicity). All these aspects of the pathogenesis of Type 2 diabetes are discussed in this review. Moreover, treatments that target reduction in glucotoxicity or lipotoxicity are outlined, including emerging strategies that target the role of glucagon-like peptide 1 and sodium glucose co-transporter 2. [source] Insulin resistance is not coupled with defective insulin secretion in primary hyperparathyroidismDIABETIC MEDICINE, Issue 10 2009F. Tassone Abstract Aims, An increased frequency of both impaired glucose tolerance and Type 2 diabetes mellitus (DM) has been reported in primary hyperparathyroidism (pHPT), thus we sought to investigate insulin sensitivity and insulin secretion in a large series of pHPT patients. Subjects and methods, One hundred and twenty-two consecutive pHPT patients without known DM were investigated [age (mean ± sd) 59.3 ± 13.6 years, body mass index (BMI) 25.7 ± 4.2 kg/m2; serum calcium 2.8 ± 0.25 mmol/l; PTH 203.2 ± 145.4 ng/l]. Sixty-one control subjects were matched, according to the degree of glucose tolerance, in a 2 : 1 patient:control ratio. Fasting- and oral glucose tolerance test-derived estimates of insulin sensitivity and secretion were determined by means of the quantitative insulin sensitivity check index (QUICKI) and the insulin sensitivity index (ISI) composite. Results, Both the QUICKI and ISI composite were lower in pHPT patients than control subjects (P < 0.03 and P < 0.05, respectively) after adjusting for age, systolic blood pressure and BMI. Conversely, all insulin secretion estimates were significantly increased in pHPT patients than in control subjects (P < 0.04 and P < 0.03, respectively) and after adjusting for age, systolic blood pressure and BMI. Log serum calcium levels were negatively associated with the QUICKI and log ISI composite (R = ,0.30, P = 0.001; R = ,0.23, P = 0.020, respectively) in pHPT patients. Serum calcium levels significantly and independently contributed to impaired insulin sensitivity in multivariate analysis (QUICKI as dependent variable: , = ,0.31, P = 0.004, R2 = 0.15; log ISI composite as dependent variable: , = ,0.29, P = 0.005, R2 = 0.16). Conclusions, Our study confirms a reduction in both basal and stimulated insulin sensitivity in primary hyperparathyroidism, in spite of increased insulin secretion. Moreover, our data show for the first time a significant relationship between hypercalcaemia and insulin sensitivity in this condition. [source] Plasma triglycerides and LDL cholesterol are related in a parabolic fashion in the general population and patients with Type 2 diabetes mellitus: long-term follow-up results from the Hoorn studyDIABETIC MEDICINE, Issue 9 2008M. C. G. J. Brouwers Abstract Aims Low-density lipoprotein cholesterol (LDL-C) levels are often fairly normal in Type 2 diabetes mellitus (DM). We anticipated that a parabolic relation between plasma triglycerides and LDL-C, as previously demonstrated in familial combined hyperlipidaemia (FCHL), might account for this phenomenon. Methods Our hypothesis was tested in 1343 subjects derived from the general population who were studied on two occasions 6 years apart (the Hoorn study). Three groups were constructed depending on plasma triglycerides: group A (individuals with both measurements below 1.5 mmol/l), group B (one measurement below and one above 1.5 mmol/l) and group C (both measurements above 1.5 mmol/l). Diabetes status was ascertained by an oral glucose tolerance test. Results In a mixed linear model, a significant, positive relation between triglycerides and LDL-C was observed for males in group A (,a = 0.5, P < 0.001) and group B (,b = 0.2, P < 0.001), whereas a significant negative relation was found for males in group C (,c = ,0.2, P = 0.003). The regression slopes did not differ between diabetic and non-diabetic subjects. Similar results were obtained for women, with the exception that the relation was not significantly negative in group C (,c = ,0.1, P = 0.4). Conclusion Plasma triglcyerides and LDL-C are related in a parabolic fashion, not only in FCHL, but also in the general population and Type 2 DM. These findings aid our interpretation of typical dyslipidaemia and the effects of treatment that are frequently observed in hypertriglyceridaemic states. [source] Leptin,a predictor of abnormal glucose tolerance and prognosis in patients with myocardial infarction and without previously known Type 2 diabetesDIABETIC MEDICINE, Issue 8 2008M. Wallander Abstract Aims High levels of leptin and low adiponectin are associated with Type 2 diabetes mellitus (T2DM) and cardiovascular (CV) disease. We studied the prognostic implications of leptin and adiponectin in patients with acute myocardial infarction (AMI) without previously known Type 2 DM. Methods One hundred and eighty-one patients were included. Based on an oral glucose tolerance test at hospital discharge (day 4,5), 168 (67% men) had normal or abnormal glucose tolerance (AGT), defined as impaired glucose tolerance or T2DM. Sex- and age-matched healthy persons served as control subjects (n = 185). The associations between fasting serum leptin and adiponectin (day 2) and newly discovered AGT and CV events (CV mortality, non-fatal stroke, reinfarction or severe heart failure) during a median follow-up of 34 months were investigated. Results Compared with control subjects, patients of both genders had significantly higher levels of leptin 2 days after an AMI. These levels were higher than those obtained at hospital discharge and 3 months later. Circulating levels of (ln) leptin 2 days after the AMI predicted AGT at discharge (odds ratio 2.03, P = 0.042). Ln leptin at day 2 was the only biochemical variable that significantly predicted CV events both on univariate [hazard ratio (HR) 1.60, P = 0.018] and on multivariate analysis (HR 1.75, P = 0.045). Adiponectin levels did not differ between patients and control subjects and did not relate to AGT or CV events. Conclusions Elevated circulating levels of leptin on the first morning after an AMI are associated with the presence of AGT at discharge and with a poorer long-term prognosis. [source] An increase in HbA1c after percutaneous coronary intervention raises the risk for restenosis in patients without Type 2 diabetes mellitusDIABETIC MEDICINE, Issue 2 2008H. Diedrichs Abstract Aims The influence of dynamic changes in glycated haemoglobin (HbA1c) on restenosis after elective percutaneous coronary intervention (PCI) in patients without diabetes has not been analysed. Therefore, the rate of restenosis was investigated after elective PCI in 101 consecutive patients without diabetes mellitus in relation to dynamic changes of HbA1c levels. Methods Follow-up angiography was performed in all patients 4,6 months after intervention. Results Multivariate analysis demonstrated that the change in HbA1c between first and second coronary angiography was the most powerful metabolic parameter for prediction of restenosis. The odds ratio for restenosis was 3.0 (95% CI 1.0,9.0) for any increase in HbA1c and 1.9 (95% CI 1.1,3.5) for an HbA1c increase of 0.2%. Conclusions Hence, chronic changes in the glucometabolic environment influence the incidence of restenosis after PCI in patients without diabetes. [source] Effect of long-term treatment with rosiglitazone on arterial elasticity and metabolic parameters in patients with Type 2 diabetes mellitus: a 2-year follow-up studyDIABETIC MEDICINE, Issue 11 2007M. Shargorodsky Abstract Aims, Thiazolidinediones may influence the atherogenic process by improving cardiovascular risk factors. The present study was designed to determine the long-term effect of rosiglitazone on arterial compliance and metabolic parameters in patients with Type 2 diabetes. Methods, In an open-label, prospective study, 65 diabetic patients received rosiglitazone orally (4,8 mg/day) for 6 months. After 6 months, the patients continued an open follow-up study and were divided into two groups: group 1 included patients continuing rosiglitazone for 2 years, group 2 included patients discontinuing rosiglitazone and receiving other oral glucose-lowering agents. Lipid profile, glycated haemoglobin (HbA1c), insulin, C-peptide, fibrinogen, high-sensitivity-CRP and homeostasis model assessment,insulin resistance were measured. Arterial elasticity was assessed using pulse wave contour analysis. Results, In patients treated with rosiglitazone for 2 years: the large artery elasticity index (LAEI) increased from 10.0 ± 4.6 to 13.9 ± 4.7 ml/mmHg × 100 after 2 years (P = 0.003). The small artery elasticity (SAEI) index increased significantly from 3.2 ± 1.2 to 5.1 ± 1.9 (P < 0.0001). In patients who discontinued rosiglitazone: LAEI did not change after 6 months, but decreased from 12.1 ± 5.4 to 8.9 ± 3.9 ml/mmHg × 10 (P < 0.0001) at the end of 2 years. SAEI increased during the first 6 months of treatment, from 3.9 ± 1.8 to 5.1 ± 1.5 ml/mmHg × 100 (P < 0.0001) and decreased after discontinuation of rosiglitazone (P = 0.042). Conclusions, Prolonged treatment with rosiglitazone improved arterial elasticity. However, significant deterioration in LAEI and SAEI was observed in patients who discontinued rosiglitazone. The beneficial vascular effect of rosiglitazone on arterial elasticity was independent of glycaemic control. [source] Interactive effect of retinopathy and macroalbuminuria on all-cause mortality, cardiovascular and renal end points in Chinese patients with Type 2 diabetes mellitusDIABETIC MEDICINE, Issue 7 2007P. C. Y. Tong Abstract Aims To examine the effect of albuminuria and retinopathy on the risk of cardiovascular and renal events, and all-cause mortality in patients with Type 2 diabetes. Methods A post-hoc analysis of 4416 Chinese patients without macrovascular complications at baseline (age 57.6 ± 13.3 years). Glomerular filtration rate (eGFR) was estimated by the abbreviated Modification of Diet in Renal Disease Study Group Formula, further adjusted for Chinese ethnicity. Clinical end points were all-cause mortality, cardiovascular events (heart failure or angina, myocardial infarction, lower limb amputation, re-vascularization procedures and stroke) and renal end points (reduction in eGFR by more than 50% or eGFR < 15 ml/min/1.73 m2 or death as a result of renal causes or need for dialysis). Results Compared with individuals without complications, subjects with retinopathy and macroalbuminuria had higher rates of cardiovascular events (14.1 vs. 2.4%), renal events (40.0 vs. 0.8%) and death (9.3 vs. 1.7%, P < 0.001). For composite event of death, cardiovascular and renal events, the presence of retinopathy, microalbuminuria alone, macroalbuminuria alone, retinopathy with microalbuminuria or retinopathy with macroalbuminuria increased the risk [hazard ratio (95% CI)] by 1.61 (1.05 to 2.47; P = 0.04), 1.93 (1.38 to 2.69; P < 0.001), 4.34 (3.02 to 6.22; P < 0.001), 2.59 [1.76 to 3.81; P < 0.001) and 6.83 (4.89 to 9.55; P < 0.001) fold, respectively. The relative excess risk as a result of interaction between retinopathy and macroalbuminuria was 15.31, implying biological interaction in the development of renal events. Conclusions In Chinese patients with Type 2 diabetes, retinopathy interacts with macroalbuminuria to increase the risk of composite cardio-renal events. [source] Near patient testing for glycated haemoglobin in people with Type 2 diabetes mellitus managed in primary care: acceptability and satisfactionDIABETIC MEDICINE, Issue 7 2007M. A. Stone Abstract Aims To assess the acceptability of and satisfaction with near patient testing for glycated haemoglobin in primary care in patients and health professionals. Methods A questionnaire survey and qualitative study were nested within a randomized controlled trial conducted in eight general practices in Leicester-shire, UK. Satisfaction with diabetes care was compared in the intervention group (near patient test) and in the control subjects (usual laboratory test), using the Diabetes Clinic Satisfaction Questionnaire. Semistructured interviews were conducted with a purposive sample of patients and healthcare professionals and analysed using thematic coding and framework charting. Results Questionnaire data for 344 patients were analysed and interviews were conducted with 15 patients and 11 health professionals. Interviews indicated that the near patient test was highly acceptable to patients and staff and confirmed that there may be potential benefits such as time saving, reduced anxiety and impact on patient management and job satisfaction. However, both the survey and the interviews identified high pre-existing levels of satisfaction with diabetes care in both intervention and control group patients and survey results failed to confirm increased patient satisfaction as a result of rapid testing. Limited patient understanding of glycated haemoglobin testing was noted. Conclusions We were unable to confirm actual rather than potential advantages of the near patient test. Widespread adoption in primary care cannot be recommended without further evidence of benefit. [source] How many cases of Type 2 diabetes mellitus are due to being overweight in middle age?DIABETIC MEDICINE, Issue 1 2007Evidence from the Midspan prospective cohort studies using mention of diabetes mellitus on hospital discharge or death records Abstract Aims To relate body mass index (BMI) in middle age to development of diabetes mellitus. Methods Participants were 6927 men and 8227 women from the Renfrew/Paisley general population study and 3993 men from the Collaborative occupational study. They were aged 45,64 years and did not have reported diabetes mellitus. Cases who developed diabetes mellitus, identified from acute hospital discharge data and from death certificates in the period from screening in 1970,1976 to 31 March 2004, were related to BMI at screening. Results Of Renfrew/Paisley study men 5.4%, 4.8% of women and 5% of Collaborative study men developed diabetes mellitus. Odds ratios for diabetes mellitus were higher in the overweight group (BMI 25 to < 30 kg/m2) than in the normal weight group (BMI 18.5 to < 25 kg/m2) and highest in the obese group (BMI , 30 kg/m2). Compared with the normal weight group, age-adjusted odds ratios for overweight and obese Renfrew/Paisley men were 2.73 [95% confidence interval (CI) 2.05, 3.64] and 7.26 (95% CI 5.26, 10.04), respectively. Further subdividing the normal, overweight and obese groups showed increasing odds ratios with increasing BMI, even at the higher normal level. Assuming a causal relation, around 60% of cases of diabetes could have been prevented if everyone had been of normal weight. Conclusions Overweight and obesity account for a major proportion of diabetes mellitus, as identified from hospital discharge and death records. With recent increases in the prevalence of overweight, the burden of disease related to diabetes mellitus is likely to increase markedly. Primordial prevention of obesity would be a major strategy for reducing the incidence of diabetes mellitus in populations. [source] Association analysis of genes in the renin-angiotensin system with subclinical cardiovascular disease in families with Type 2 diabetes mellitus: The Diabetes Heart StudyDIABETIC MEDICINE, Issue 3 2006K. P. Burdon Abstract Aims Cardiovascular disease (CVD) is a major complication of Type 2 diabetes mellitus. The renin-angiotensin system (RAS) and nitric oxide production are both important regulators of vascular function and blood pressure. Genes encoding proteins involved in these pathways are candidates for a contribution to CVD in diabetic patients. We have investigated variants of the angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AT1R) and endothelial nitric oxide synthase (NOS3) genes for association with subclinical measures of CVD in families with Type 2 diabetes mellitus (T2DM). Methods Atherosclerosis was measured by carotid intima-media thickness and calcification of the carotid and coronary arteries in 620 European Americans and 117 African Americans in the Diabetes Heart Study. Because of the role of these systems in blood pressure regulation, blood pressure was also investigated. Results Compelling evidence of association was not detected with any of the SNPs with any outcome measures after adjustments for covariates despite sufficient power to detect relatively small differences in traits for specific genotype combinations. Conclusions Genetic variation of the RAS and NOS3 genes do not appear to strongly influence subclinical cardiovascular disease or blood pressure in this diabetic population. [source] Incidence and outcome of asymptomatic bacteriuria in females with Type 2 diabetes mellitus over a 1-year follow-up period and association with risk factorsDIABETIC MEDICINE, Issue 11 2005A. Sotiropoulos No abstract is available for this article. [source] Glycaemic control in relation to xanthine oxidase and antioxidant indices in Malaysian Type 2 diabetes patientsDIABETIC MEDICINE, Issue 10 2005U. R. Kuppusamy Abstract Aims Increased oxidative stress and oxidative damage are present in Type 2 diabetes mellitus (DM). The aim of this study was to assess the oxidative stress levels in the three major ethnic groups in Malaysia and to study the association between glycaemic control and oxidant,antioxidant levels in these patients. Methods Oxidative indices and glycaemic control were assessed in 650 Type 2 DM patients and 280 healthy age-matched controls by known established methods. Results Type 2 DM patients had significantly lower levels of antioxidant enzymes and non-enzymatic antioxidant (FRAP) and increased levels of HbA1c, fasting blood glucose (FBG), malondialdehyde (MDA) and xanthine oxidase (XO) when compared with control subjects. Markers of oxidative stress were more apparent in Indian patients compared with Malay and Chinese patients. Correlation analysis of oxidant,antioxidant parameters as a function of HbA1c in each ethnic group revealed a strong association of HbA1c with oxidative indices. Conclusions The present study provides evidence for the possible contribution of XO to oxidative stress and the pathophysiology of diabetes. HbA1c remains an important marker of glycaemic control for the management of Type 2 DM, but other confounding factors that predispose or lead to oxidative stress should also be taken into consideration. [source] Pathophysiology of ketoacidosis in Type 2 diabetes mellitusDIABETIC MEDICINE, Issue 10 2005P. Linfoot Abstract Aims Despite an increasing number of reports of ketoacidosis in populations with Type 2 diabetes mellitus, the pathophysiology of the ketoacidosis in these patients is unclear. We therefore tested the roles of three possible mechanisms: elevated stress hormones, increased free fatty acids (FFA), and suppressed insulin secretion. Methods Forty-six patients who presented to the Emergency Department with decompensated diabetes (serum glucose > 22.2 mmol/l and/or ketoacid concentrations , 5 mmol/l), had blood sampled prior to insulin therapy. Three groups of subjects were studied: ketosis-prone Type 2 diabetes (KPDM2, n = 13) with ketoacidosis, non-ketosis-prone subjects with Type 2 diabetes (DM2, n = 15), and ketotic Type 1 diabetes (n = 18). Results All three groups had similar mean plasma glucose concentrations. The degree of ketoacidosis (plasma ketoacids, bicarbonate and anion gap) in Type 1 and 2 subjects was similar. Mean levels of counterregulatory hormones (glucagon, growth hormone, cortisol, epinephrine, norepinephrine), and FFA were not significantly different in DM2 and KPDM2 patients. In contrast, plasma C-peptide concentrations were approximately three-fold lower in KPDM2 vs. non-ketotic DM2 subjects (P = 0.0001). Type 1 ketotic subjects had significantly higher growth hormone (P = 0.024) and FFA (P < 0.002) and lower glucagon levels (P < 0.02) than DM2. Conclusions At the time of hospital presentation, the predominant mechanism for ketosis in KPDM2 is likely to be greater insulinopenia. [source] Association between MspI polymorphism of the APO AI gene and Type 2 diabetes mellitusDIABETIC MEDICINE, Issue 6 2005S. Morcillo Abstract Aims Genes of the Apo AI/CIII/AIV cluster on chromosome 11 have been related to plasma lipid patterns. The close relationship between carbohydrate metabolism and lipid metabolism warrants investigation of the association between this cluster and Type 2 diabetes mellitus. We therefore examined the possible association between polymorphisms of this cluster and Type 2 diabetes mellitus as part of a study of the prevalence of diabetes and the metabolic syndrome in southern Spain. Methods A total of 1224 persons were selected randomly from the town of Pizarra in the province of Malaga, southern Spain. The sample errors for the prevalence of Type 2 diabetes mellitus and the three polymorphisms studied were all , 4%. All subjects underwent phenotyping after an oral glucose tolerance test (75 g) (WHO 1998 criteria) and the XmnI and MspI polymorphisms of Apo AI and the SstI polymorphism of Apo CIII were genotyped. Results Those subjects with the mutated AA genotype of the MspI polymorphism (,75 G,A) of Apo AI had a greater risk of impaired glucose tolerance [odds ratio (OR) = 1.95, CI = 1.02,3.8, P = 0.05], Type 2 diabetes mellitus, both known (OR = 7.38, CI = 1.3,39.7, P = 0.02) and unknown (OR = 3.7, CI = 1.4,9.9, P = 0.009). This risk was independent of age, sex, obesity, triglyceride level, HDL cholesterol and pattern of insulin resistance. Conclusions Pending confirmation in prospective studies, the AA genotype of the MspI polymorphism of the Apo AI gene, within the Apo A-I/C-III/A-IV cluster, seems to be a risk factor for Type 2 diabetes mellitus. [source] Insulin treatment and cardiovascular disease; friend or foe?DIABETIC MEDICINE, Issue 2 2005A point of view Abstract Background Several observational studies have shown that higher insulin levels are associated with an increased risk of cardiovascular disease. If higher endogenous insulin levels are causally related to cardiovascular disease, one might expect an increased risk of cardiovascular disease in patients treated with insulin, as this results in high circulating insulin levels. Such risk elevation might counteract the benefits of tight glucose control. Our objective was to explore the relationship between insulin therapy and cardiovascular disease in Type 1 and Type 2 diabetes mellitus using information from available literature. Summary of comment Several experimental studies in animals and humans support the presence of a harmful effect of insulin on the vascular endothelium. In prospective follow-up studies increased insulin dosage was associated with increased risks of cardiovascular disease, although confounding by indication could not be excluded. Randomized controlled trials in diabetic patients, comparing conventional with intensive glucose-lowering treatment, although showing a reduction in microvascular disease, showed no significant difference in the incidence of cardiovascular disease. The results with respect to exposure to insulin are, however, difficult to interpret due to insufficient information on exposure to insulin levels as well as confounding by glycaemic control and body mass index. In addition, these studies were not designed to address the question whether higher insulin use relates to increased cardiovascular risk. Conclusion Published research provides conflicting evidence as to whether exposure to high levels of exogenous insulin in diabetes mellitus affects the risk of cardiovascular disease. The currently available studies have a number of serious methodological restraints that limit accurate interpretation and conclusions in this area. [source] Insulino-mimetic and anti-diabetic effects of vanadium compoundsDIABETIC MEDICINE, Issue 1 2005A. K. Srivastava Abstract Compounds of the trace element vanadium exert various insulin-like effects in in vitro and in vivo systems. These include their ability to improve glucose homeostasis and insulin resistance in animal models of Type 1 and Type 2 diabetes mellitus. In addition to animal studies, several reports have documented improvements in liver and muscle insulin sensitivity in a limited number of patients with Type 2 diabetes. These effects are, however, not as dramatic as those observed in animal experiments, probably because lower doses of vanadium were used and the duration of therapy was short in human studies as compared with animal work. The ability of these compounds to stimulate glucose uptake, glycogen and lipid synthesis in muscle, adipose and hepatic tissues and to inhibit gluconeogenesis, and the activities of the gluconeogenic enzymes: phosphoenol pyruvate carboxykinase and glucose-6-phosphatase in the liver and kidney as well as lipolysis in fat cells contributes as potential mechanisms to their anti-diabetic insulin-like effects. At the cellular level, vanadium activates several key elements of the insulin signal transduction pathway, such as the tyrosine phosphorylation of insulin receptor substrate-1, and extracellular signal-regulated kinase 1 and 2, phosphatidylinositol 3-kinase and protein kinase B activation. These pathways are believed to mediate the metabolic actions of insulin. Because protein tyrosine phosphatases (PTPases) are considered to be negative regulators of the insulin-signalling pathway, it is suggested that vanadium can enhance insulin signalling and action by virtue of its capacity to inhibit PTPase activity and increase tyrosine phosphorylation of substrate proteins. There are some concerns about the potential toxicity of available inorganic vanadium salts at higher doses and during long-term therapy. Therefore, new organo-vanadium compounds with higher potency and less toxicity need to be evaluated for their efficacy as potential treatment of human diabetes. [source] Interstitial glucose in skeletal muscle of diabetic patients during an oral glucose tolerance testDIABETIC MEDICINE, Issue 1 2005M. Frossard Abstract Aim The presence of a transcapillary arterial,interstitial gradient for glucose (AIGglu) in skeletal muscle may be interpreted as a consequence of intact cellular glucose uptake. We hypothesized that the AIGglu decreases in Type 2 diabetes mellitus as a consequence of insulin resistance, whereas it remains intact in Type 1 diabetes. Methods Glucose concentrations were measured in serum and interstitial space fluid of skeletal muscle during an oral glucose tolerance test (OGTT) in patients with Type 1 and Type 2 diabetes and in young and middle-aged healthy volunteers, using microdialysis. Results The area under the curve for glucose in serum (AUCSE) was higher than in interstitial space fluid of skeletal muscle (AUCMU) in healthy young (AUCSE = 1147 ± 332 vs. AUCMU = 633 ± 257 mM/min/ml; P = 0.006), healthy middle-aged volunteers (AUCSE = 1406 ± 186 vs. AUCMU = 1048 ± 229 mM/min/ml; P = 0.001) and in Type 1 diabetic patients (AUCSE = 2273 ± 486 vs. AUCMU = 1655 ± 178 mM/min/ml; P = 0.003). In contrast, in Type 2 diabetic patients AUCSE (2908 ± 1023 mM/min/ml) was not significantly different from AUCMU (2610 ± 722 mM/min/ml; P = NS). Conclusion The present data indicate that AIGglu is compromised in Type 2 diabetes in contrast to Type 1 diabetes where it appears to be normal. Because no changes in muscle blood flow were detected, insulin resistance appears to be the main cause for the observed decreased AIGglu in skeletal muscle in Type 2 diabetic patients. [source] Increasing prevalence of Type 2 diabetes mellitus in all ethnic groups in MauritiusDIABETIC MEDICINE, Issue 1 2005S. Söderberg Abstract Aims To describe the prevalence of different stages of glucose intolerance in a population from Mauritius followed over 11 years. Methods Population-based surveys were undertaken in the multiethnic nation of Mauritius in 1987, 1992 and 1998, with 5083, 6616, and 6291 participants, respectively. Questionnaires, anthropometric measurements, and a 2-h 75-g oral glucose tolerance test were included. Subjects aged between 25 and 75 years with classifiable data were identified; 4991, 6463 and 5392 from 1987, 1992 and 1998, respectively. Glucose tolerance was classified according to WHO 1999 criteria. Results The prevalence of Type 2 diabetes increased significantly during the period studied, from 12.8% in 1987, to 15.2% in 1992, and 17.9% in 1998. The increasing prevalence was seen in both men and women, and in all age groups. The prevalence of known diabetes (KDM) increased progressively, and more markedly than the increase in newly diagnosed diabetes (NDM). A diagnosis of impaired glucose tolerance (IGT) was more prevalent amongst women whereas impaired fasting glucose (IFG) was more common amongst men. The prevalences of IGT and IFG did not change markedly during the period. The prevalence of diabetes and IGT was similar for participants of Indian, Creole and Chinese background in each survey, and the increasing prevalence of diabetes was seen in all ethnic groups. Conclusion In this study, we report an increasing prevalence of diabetes over an 11-year period in Mauritius. This increase was seen in both sexes, and in all age and ethnic groups, and was mainly due to an increase in the numbers of those with known diabetes. [source] Statin use in Type 2 diabetes mellitus is associated with a delay in starting insulinDIABETIC MEDICINE, Issue 9 2004A. Yee Abstract Aims It has been suggested that HMG Co-A reductase inhibitors (,statins') may reduce the risk of developing Type 2 diabetes mellitus. This study was designed to evaluate whether use of statins would also delay progression to insulin therapy. Methods This was a retrospective cohort study using Saskatchewan Health databases to identify subjects newly started on oral antidiabetic agents from 1991 to 1996. Subjects < 30 years of age or with previous lipid-lowering drug use were excluded. Medications known to influence glycaemic control, co-morbidity, and demographic data were collected. Statin exposure was defined as at least 1 year of use. Primary outcome was starting insulin treatment. Multivariate Cox proportional hazards models were used to examine the association between statin use and starting insulin. Results The final cohort included 10 996 new users of oral antidiabetic agents, of which 484 (4.4%) used statins. Mean age was 64 years and 55% were male. Mean duration of follow-up was 5.1 years; 11.1% (n = 1221) eventually started insulin treatment. Statin users were no less likely than non-users to start insulin treatment eventually (11.6% vs. 11.1%, P = 0.74). After multivariate adjustment, however, statin use was associated with a 10-month delay before newly treated diabetic subjects needed to start insulin treatment (adjusted hazard ratio 0.74; 95% confidence interval 0.56, 0.97, P = 0.028). Conclusion The use of statins is associated with a delay in starting insulin treatment in patients with Type 2 diabetes initially treated with oral antidiabetic agents. Whether this relationship exists for patients at high risk of developing diabetes should be examined in a randomized trial. [source] HMG-CoA reductase inhibitors prevent bone loss in patients with Type 2 diabetes mellitusDIABETIC MEDICINE, Issue 9 2004A. Nakashima Abstract Aims It has been reported that 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors increase bone mineral density (BMD) in vivo. We investigated the effect of HMG-CoA reductase inhibitors on BMD in patients with Type 2 diabetes mellitus. Patients and methods We selected 122 patients with Type 2 diabetes, who were not taking active vitamin D preparations. Their mean age was 67.3 ± 9.2 years. They were divided into a control group (n = 63) without HMG-CoA reductase inhibitor therapy and an HMG-CoA group (n = 59) who were treated with these drugs. The BMD of the distal one-third of the radius was measured by dual-energy X-ray adsorptiometry at baseline and after 2 years. Results There were no significant differences between the control and HMG-CoA groups at baseline with respect to age, gender, body mass index, duration of diabetes, haemoglobin A1c, fasting plasma glucose, adjusted calcium, serum phosphorus, alkaline phosphatase, albumin excretion rate and radial BMD. However, there was a significantly smaller annual decrease of the radial BMD in the HMG-CoA group. Multiple regression analysis with a forward elimination procedure revealed a positive correlation of the radial BMD Z-score with body mass index, while there was a negative correlation with alkaline phosphatase and albumin excretion rate. In addition, the annual rate of change of the radial BMD showed a positive correlation with HMG-CoA reductase inhibitor therapy. Conclusions These findings suggest that HMG-CoA reductase inhibitors may prevent bone loss in patients with Type 2 diabetes. [source] Amelanotic malignant melanoma disguised as a diabetic foot ulcerDIABETIC MEDICINE, Issue 8 2004C. L. Gregson Abstract Background/case report A female patient with diet-controlled Type 2 diabetes mellitus, presented with disseminated malignancy. She had a 15-year history of a diabetic foot ulcer, which was subsequently found to be an amelanotic malignant melanoma. She had recently received immunosuppressive treatment for an episode of nephrotic syndrome secondary to focal segmental glomerulosclerosis. Conclusions This case raises two important points. Firstly, whether non-healing diabetic foot ulcers should be biopsied, and secondly, whether the spread of the malignant melanoma was precipitated by immunosuppressive treatment. [source] Prevention of Type 2 diabetes mellitus.DIABETIC MEDICINE, Issue 5 2004A review of the evidence, its application in a UK setting Abstract Type 2 Diabetes mellitus (T2DM) is a complex metabolic, multifactorial disease, which affects the quality, quantity and style of life. People with T2DM have a life expectancy that can be shortened by as much as 15 years, with up to 75% dying of macrovascular complications. To reduce the impact of T2DM in the 21st century, we need an approach that not only optimally treats the person with established diabetes but also prevents diabetes from occurring in the first place. The best evidence for prevention of diabetes is for interventions that target individuals at highest risk. Targeting patients who have impaired glucose tolerance with lifestyle changes including physical activity and dietary factors has been shown to be effective in the Chinese, North American and Finnish populations. In order for such lifestyle interventions to be successful in other populations, they need to be culturally sensitive, individualized and sustained. Some pharmacological agents including metformin and acarbose have also been shown to be effective, although the profile of those who respond is different. There continues to be a need to develop and evaluate interventions that target communities and populations at risk in a UK setting. Diabet. Med. (2004) [source] Type 2 diabetes mellitus: a disease of the innate immune system?DIABETIC MEDICINE, Issue 3 2004An update Abstract A few years ago a hypothesis was proposed suggesting that elements of the innate immune system, such as acute phase reactants, contribute to the development of Type 2 diabetes mellitus. Acute phase reactants such as C-reactive protein and sialic acid may thus predict risk of developing Type 2 diabetes mellitus, as well as being markers of diabetes microvascular and macrovascular complications. This article discusses these issues. [source] | |||||||||||||||||||||||||||||||