Progression Of Impaired Glucose Tolerance Research Articles

4D-DIA-based proteomics analysis reveals the protective effects of Pidanjiangtang granules in IGT rat model

Ethnopharmacological relevanceThe Pidanjiangtang (PDJT) formula was founded on the "Pidan" theory from the "Nei Jing." PDJT is considered to eliminate the accumulation of pathological products, remove heat sources, and prevent damage to organs such as the liver and islets. It is widely used in clinical practice to treat impaired glucose tolerance (IGT). However, the bioactive ingredients and underlying mechanisms are still unclear and need further investigation. ObjectiveThis study aimed to determine the therapeutic effect of PDJT on IGT rats and explore the mechanism of PDJT intervention on IGT by four-dimensional independent data acquisition (4D-DIA) proteomics analysis. Materials and methodsThe IGT model was established by a high-fat diet combined with Streptozotocin (STZ) injection. The IGT rats were treated with low, medium, and high doses of PDJT orally for 42 days and compared with the Metformin positive control group. The therapeutic effects of PDJT on IGT rats were evaluated using the oral glucose tolerance test (OGTT), serum lipoprotein detection, insulin detection, liver histopathology, and hepatic steatosis assessment. 4D-DIA proteomics analysis was used to explore the differential proteins (DEPs) and potential pathways of PDJT. Finally, Western blotting and ELISA techniques were used to verify DEPs and major targets. ResultsPDJT can enhance glucose metabolism, restore islet β cell function, regulate lipoprotein metabolism, reduce hepatic steatosis, and consequently slow down the progression of IGT. In the proteomic analysis, a total of 355 DEPs were identified, and critical proteins were validated. The results indicated that the JAK2/STAT1 signaling pathway plays a pivotal role in the effects of PDJT. IκB-ζ may be a potential target for PDJT in regulating the inflammatory response of IGT. ConclusionPDJT is an effective formula for improving IGT, with its potential mechanism linked to the JAK2/STAT1/IκB-ζ signaling pathway. This study offers a novel approach to investigating the mechanisms of TCM formula through proteomics and offers new insight into exploring TCM treatment for IGT.

Network Meta-analysis of the Therapeutic Effects of Hypoglycemic Drugs and Intensive Lifestyle Modification on Impaired Glucose Tolerance

PurposeIn the Guidelines for the Prevention and Control of Type 2 Diabetes in China (2017 edition), intensive lifestyle interventions are recommended for preventing the progression of impaired glucose tolerance (IGT) to type 2 diabetes mellitus. Acarbose and metformin can also be considered if intensive lifestyle modification has been ineffective for 6 months. But the effects of intensive lifestyle modification and glucose-lowering drug interventions that work best in the population with IGT are unclear. This network meta-analysis assessed the effectiveness of intensive lifestyle modification, acarbose, and metformin in treating populations with IGT. MethodsWe systematically searched both Chinese- and English-language databases, including China Knowledge, the Cochrane Library, Embase, PubMed, VIP, and Wanfang, for articles published between database inception and September 2019. Randomized, controlled clinical trials in patients with IGT treated with acarbose, metformin, and intensive lifestyle modification were assessed for eligibility. The data from all included studies were evaluated by 2 reviewers independently in accordance with the Cochrane Handbook for Systematic Reviews of Intervention version 6.0. A network meta-analysis was performed by using R software version 3.6.1. FindingsThe data from 53 randomized controlled trials were included in the review, with a sample size of 21,208 patients. Compared with the control group, the use of acarbose, metformin, and/or intensive lifestyle modification was associated with reduced rates of progression to diabetes (relative risks [RRs] [95% credible intervals]: acarbose, 0.37 [0.29–0.47]; metformin, 0.39 [0.30–0.50]; intensive lifestyle modification, 0.61 [0.50–0.73]). The surface under the cumulative ranking (SUCRA) value of acarbose was 88.35%, supporting that acarbose was more effective in reducing the rate of progression to diabetes compared with controls. With acarbose, metformin, and intensive lifestyle modification, the rates of achieving a normal glucose level were increased by RR = 2.1, 1.7, and 1.2, respectively when compared with control group. The SUCRA value of acarbose was 99.69%, supporting the optimal effect of acarbose in achieving a normal blood glucose level. ImplicationsIn this meta-analysis in patients with IGT, compared with controls, acarbose and metformin were associated with decreased rates of progression to diabetes and increased rates of achieving a normal glucose level. Acarbose use was associated with an increased rate of achieving a normal glucose level, while intensive lifestyle modification was not.

Acetylation of Hsp90 reverses dexamethasone-mediated inhibition of insulin secretion

The deleterious effects of glucocorticoids on glucose homeostasis limit their clinical use. There is substantial evidence demonstrating that islet function impaired by long-term glucocorticoids exposure is a core defect in the progression of impaired glucose tolerance to diabetes. The activity of heat-shock protein (Hsp) 90 is required to maintain the hormone-binding activity and stability of glucocorticoid receptor (GR). In the present study, Hsp90 inhibition by 17-DMAG counteracted dexamethasone-mediated inhibition of glucose-stimulated insulin secretion in isolated rat islets as well as expressions of neuropeptide Y (NPY) and somatostatin receptor 3 (SSTR3), two negative regulators of insulin secretion. Like 17-DMAG, both the pan-histone deacetylase (HDAC) inhibitor TSA and HDAC6 inhibitor Tubacin exhibited a similar action in protecting islet function against dexamethasone-induced injury, along with the downregulation of NPY and SSTR3 expressions. The hyperacetylation of Hsp90 by TSA and Tubacin disrupted its binding ability to GR and blocked dexamethasone-elicited nuclear translocation of GR in INS-1 β-cell lines. In addition, Tubacin treatment triggered the GR protein degradation through the ubiquitin-proteasome pathway. These findings suggest that Hsp90 acetylation by inhibiting HDAC6 activity may be a potential strategy to prevent the development of steroid diabetes mellitus via alleviating glucocorticoid-impaired islet function.

2101-P: Adipose Tissue Insulin Resistance in Overweight and Lean Patients with Impaired Glucose Tolerance or Type 2 Diabetes

Background: When adipose tissue shows insulin resistance, insulin is unable to suppress lipolysis. Several Western studies have revealed a relationship between obesity and the antilipolytic effect of insulin. However, it is unclear whether a distinctly different degree of obesity between Westerner and Japanese could lead to a different outcome of the insulin antilipolytic effect. Thus, we investigated the impact of adipose tissue insulin resistance in Japanese patients with impaired glucose tolerance (IGT) and type 2 diabetes (T2D). Methods: Twenty Japanese patients with T2D and 20 participants without diabetes were recruited (January 2014 to March 2015). A 75-g oral glucose tolerance test (OGTT) was performed and plasma glucose, serum insulin, and free fatty acid (FFA) levels were measured during this test. Insulin resistance was estimated using the Matsuda index, HOMA-IR, and the adipocyte insulin resistance index (Adipo-IR). Glucose-stimulated insulin secretion was evaluated based on the insulinogenic index (II). The definition of overweight was BMI ≥ 25 kg/m2. Results: We included patients with IGT (n=19) and T2D (n=19). BMI in all patients was 26.0 ± 6.2 kg/m2. In T2D, HbA1c was higher and II was lower compared with those in IGT. No statistically significant difference in other parameters, such as BMI, FFA, insulin resistance, were observed between T2D and IGT. In overweight IGT, Adipo-IR was significantly higher (overweight IGT, 4.0 [2.0-9.4] vs, lean IGT, 1.0 [0.8-2.3], p<0.05), although there were no differences in the Matsuda index or HOMA-IR. However, there was no difference in Adipo-IR for overweight T2D (7.4 [2.6-10.9]) compared with lean T2D (1.9 [0.9-3.1], p=0.13). Conclusion: Overweight status in IGT, but not in T2D, could be related to worsening Adipo-IR. These findings suggest that encouraging weight loss to the ideal weight for IGT patients might reduce the risk of worsening adipose tissue insulin resistance, and progression of IGT to T2DM. Disclosure A. Miya: None. A. Nakamura: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Ono Pharmaceutical Co., Ltd. H. Kameda: None. K. Cho: None. H. Miyoshi: Research Support; Self; Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceutical Europe Co. Ltd., Mitsubishi Tanabe Pharma Corporation, MSD, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Europe Co. Ltd., Mitsubishi Tanabe Pharma Corporation, MSD, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. T. Atsumi: Research Support; Self; Astellas Pharma Inc., Bayer Yakuhin, Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; AbbVie Inc., Astellas Pharma Inc., Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Pfizer Inc., Takeda Pharmaceutical Company Limited, UCB, Inc.

The main mechanism associated with progression of glucose intolerance in older patients with cystic fibrosis is insulin resistance and not reduced insulin secretion capacity

BackgroundAging cystic fibrosis (CF) patients are at high risk of developing CF-related diabetes (CFRD). Decrease in insulin secretion over time is the main hypothesis to explain this increasing prevalence but mechanisms are still not well elucidated. The objective is to assess evolution of glucose tolerance and insulin secretion/sensitivity in aging CF patients. MethodsThis is a retro-prospective observational analysis in the older adult CF patients from the Montreal Cystic Fibrosis Cohort (n = 46; at least 35 years old at follow-up) and followed for at least 4 years. Baseline and follow-up (last visit to date) 2-h oral glucose tolerance test (OGTT with glucose and insulin measurements every 30 min) were performed. Pulmonary function test (FEV1) and anthropometric data were measured the same day. Insulin sensitivity was measured by the Stumvoll index. ResultsAfter a mean follow-up of 9.9 ± 2.6 years, mean age at follow-up was 43.5 ± 8.1 years old. An increase of body weight (+2.6 ± 6.5 kg, p = 0.01) and a decrease in pulmonary function (FEV1; 73.4 ± 21.2% to 64.5 ± 22.4%, p ≤ 0.001) were observed. Overall, insulin secretion is maintained at follow-up but all OGTT glucose values increased (for all values, p ≤ 0.028). At follow-up, 28.3% of patients had a normal glucose tolerance while 71.7% had abnormal glucose tolerance (AGT). AGT patients decreased their insulin sensitivity over time (p = 0.029) while it remained the same in NGT patients (p = 0.917). ConclusionIn older CF patients, the progression of impaired glucose tolerance is occurring with stable insulin secretion but reduced insulin sensitivity.

Type 2 Diabetes Mellitus in Children and Adolescents: An update

Childhood type 2 Diabetes Mellitus (DM) has increasingly been reported worldwide. It is commonly associated with childhood obesity.It may be presented with classical manifestation of DM such as polyuria, polydipsia, weight lossor acute complications like Diabetic ketoacidosis (DKA), Hyperglycemic Hyperosmolar State (HHS) or features of insulin resistance syndrome. Many a cases it may remain asymptomatic and hence undiagnosed.So,overweight children and adolescents who met screening criteria such as family history of type 2 DM, signs of insulin resistance, and high risk ethnics should undergo screening. Emphasis should be given on early diagnosis and optimum management plan to avoid grave consequences of it in early part of life. Diagnosis of type 2 Diabetes Mellitus in children should be done on the basis of standard diagnostic criteria such as American Diabetic Association (ADA) criteria. Both non-pharmacological and drug management are important equally. Multidisciplinary team approach including self-management plan is mandatory for obtaining optimal therapeutic goals of type 2 DM in children and adolescents. Lifestyle modification, dietary intervention, weight reduction, patient education, psychological support, and oral anti diabetic drugs and insulin therapy should be included in comprehensive diabetic management plan. Complications of type 2 DM should be minimized by all means with strict glycemic control and management of co-morbidity if any. Emphasis should also be given on prevention of type 2 DM by adopting a healthy lifestyle characterized by healthy eating behavior, regular physical activity and subsequent modest weight loss that can prevent the progression of impaired glucose tolerance to clinical diabetes mellitus.J Bangladesh Coll Phys Surg 2017; 35(1): 24-30

Prevention of type 2 diabetes mellitus by changes in diet among subjects with abnormal glucose metabolism: a randomized clinical trial

Previous studies demonstrated that changes in lifestyle slow the progression of impaired glucose tolerance to overt diabetes but few trials examined the effect of diet alone without weight loss on the prevention of diabetes. We investigated the efficacy of two types of diet with different macronutrients, on preventing or delaying the onset of type 2 diabetes in subjects with either impaired fasting glucose or impaired glucose tolerance. Three hundred and twenty-two subjects with prediabetes were randomly assigned to a high monounsaturated fat diet, normal fat diet, or control groups and followed for 2 years. For calculating the daily energy requirement in subjects with BMI ≥ 25 kg/m2, the weight was adjusted with the use of 110% of the ideal body weight with no attempt for losing body weight. There was no difference in body weight decrease among the three groups after 2 years. The cumulative incidence of diabetes was 9.3% (95% CI, 3.6–14%) in the high monounsaturated fat diet (HMD) group, 13.2% (95% CI, 6.4–19%) in the normal fat diet (NFD) group, and 18.3% (95% CI, 10–25%) in the control group. The cumulative incidence of diabetes was 57% lower in the HMD group than that in the control group (95% CI, 0.1–0.9%; P = 0.03). This value was not significant in the NFD group (RR, 0.60; 95% CI, 0.2–1.2%; P = 0.1). Type 2 diabetes can be prevented by a high-monounsaturated fat, low-carbohydrate diet and receiving energy based on the adjusted ideal body weight without a weight loss program. Trial registration number: NCT02250066

Methodological considerations when studying the skeletal response to glucose intolerance using the diet-induced obesity model.

The prevalence of obesity and type 2 diabetes mellitus (T2DM) continues to rise, and as a result, research aimed at understanding the molecular basis for the co-morbidities has become an area of much scientific interest. Among the more recently recognized chronic complications of T2DM is the increased risk of fracture, especially hip fracture, that has been reported independent of bone mineral density (BMD). A widely used animal model to study how the development and progression of impaired glucose tolerance affect the skeleton has been the diet-induce obesity (DIO) model. As the name implies, this model employs the use of a version of high-fat diets to induce obesity and the subsequent metabolic perturbations that occur with T2DM. Although the model offers a number of advantages, the literature reveals some inconsistent results. Upon further review, discrepancies in the choice of the experimental high-fat diets and the control diets have become a point of major concern. The variability between diets and study design has made it difficult to compare data and results across studies. Therefore, this review aims to provide guidelines that should be employed when designing studies using DIO models of T2DM.

Physical activity promotion in the primary care setting in pre- and type 2 diabetes - the Sophia step study, an RCT.

BackgroundPhysical activity prevents or delays progression of impaired glucose tolerance in high-risk individuals. Physical activity promotion should serve as a basis in diabetes care. It is necessary to develop and evaluate health-promoting methods that are feasible as well as cost-effective within diabetes care. The aim of Sophia Step Study is to evaluate the impact of a multi-component and a single component physical activity intervention aiming at improving HbA1c (primary outcome) and other metabolic and cardiovascular risk factors, physical activity levels and overall health in patients with pre- and type 2 diabetes.Methods/designSophia Step Study is a randomized controlled trial and participants are randomly assigned to either a multi-component intervention group (A), a pedometer group (B) or a control group (C). In total, 310 patients will be included and followed for 24 months. Group A participants are offered pedometers and a website to register steps, physical activity on prescription with yearly follow-ups, motivational interviewing (10 occasions) and group consultations (including walks, 12 occasions). Group B participants are offered pedometers and a website to register steps. Group C are offered usual care. The theoretical framework underpinning the interventions is the Health Belief Model, the Stages of Change Model, and the Social Cognitive Theory. Both the multi-component intervention (group A) and the pedometer intervention (group B) are using several techniques for behavior change such as self-monitoring, goal setting, feedback and relapse prevention.Measurements are made at week 0, 8, 12, 16, month 6, 9, 12, 18 and 24, including metabolic and cardiovascular biomarkers (HbA1c as primary health outcome), accelerometry and daily steps. Furthermore, questionnaires were used to evaluate dietary intake, physical activity, perceived ability to perform physical activity, perceived support for being active, quality of life, anxiety, depression, well-being, perceived treatment, perceived stress and diabetes self- efficacy.DiscussionThis study will show if a multi-component intervention using pedometers with group- and individual consultations is more effective than a single- component intervention using pedometers alone, in increasing physical activity and improving HbA1c, other metabolic and cardiovascular risk factors, physical activity levels and overall health in patients with pre- and type 2 diabetes.Trial registrationClinicalTrials.gov Identifier: NCT02374788. Registered 28 January 2015.

Pharmacological strategies for preventing type 2 diabetes in patients with impaired glucose tolerance

Type 2 diabetes is an increasingly prevalent disease in the United States, and is associated with microvascular and macrovascular complications. Prediabetes, which is defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), increases the risk of development of type 2 diabetes. Lifestyle improvements, including weight loss and increased physical activity are effective in reducing the conversion of IGT to type 2 diabetes by 58%. However, lifestyle interventions alone may be difficult to maintain. Oral pharmacological agents used to treat type 2 diabetes that improve insulin sensitivity, preserve beta cell function and delay carbohydrate metabolism have been shown to prevent the progression of IGT to type 2 diabetes. The risk reduction of diabetes using metformin, pioglitazone, acarbose, valsartan and orlistat in clinical studies has ranged from 14 to 72%. Therefore, persons with IGT tolerance may benefit from pharmacological therapy to prevent the development of type 2 diabetes.

Practical Diabetes Care. By David Levy. 3rd Edition Published by Wiley‐Blackwell, 2011 Paperback, price: ISBN: 978 1 4443 3385 5 Website: www.wiley.com

Each chapter has an attractive structure, beginning with a ‘key points’ box followed by a general introduction. Text for each clearly defined topic is kept to a minimum with clear, coloured headings and subheadings along with colour shading of boxes and tables. The references section to each chapter also contains suggestions for further reading and useful websites. The book tends to be more management rather than problem based, with coverage of all the recent major changes including new medications, clinical trials, and the move from DCCT-aligned HbA1c to IFCC measurement. There is discussion on the effects and lessons to be learnt from recent changes including withdrawn medications and the controversy over rosiglitazone. As a single author book, its main strength is that it is written by an experienced diabetes physician with a wealth of experience in managing patients and their problems on a day-to-day basis. This, however, is also its weakness as it misses out on the multidisciplinary team approach. The author by his own admission is not a dietitian but there is a brief personal viewpoint on the dietary management of type 2 diabetes. Although the DESMOND group education programme is mentioned it escapes an index entry. Parts of the book which are interesting or useful include trials to prevent progression of impaired glucose tolerance to diabetes, the limitations of screening, the timeline of new drugs in diabetes and the contrasting differences between diabetic ketoacidosis and hyperglycaemic hyperosmolar state. The information on the causes, classification and management of hypoglycaemia is useful, especially in the context of the current interest in this effect. In reading the book you are made aware of the prominence and influence of the ACCORD and ADVANCE trials on glycaemic, blood pressure and lipid control, as well as eye disease and neuropathy. This book has much to commend it for medical and nurse clinicians, although it may be less attractive for other members of the team or those interested in the process of care.

Reduced progression to type 2 diabetes from impaired glucose tolerance after a 2-day in-hospital diabetes educational program: the Joetsu Diabetes Prevention Trial.

OBJECTIVE—We assessed the effects of a 2-day in-hospital diabetes educational program in preventing or delaying progression of impaired glucose tolerance (IGT) to type 2 diabetes, including analysis of changes in serum lipids, body weight, and blood pressure after the program.RESEARCH DESIGN AND METHODS—A total of 426 subjects (51 ± 9 years, BMI 24.6 ± 3.9 kg/m2) with newly diagnosed IGT were randomly assigned to three groups, 143 as the short-term hospitalization with diabetes education and support (STH) group, 141 as the nonhospitalization but diabetes education and support (DES) group, and 142 as the neither hospitalization nor education (control) group.RESULTS—The average follow-up was 3.1 years. The incidence of diabetes was 8.0, 10.7, and 13.2 cases per 100 person-years for STH, DES, and control groups, respectively. The incidence of diabetes was 42% lower (95% CI 33–51%) in the STH group and 27% lower (15–37%) in the DES group than in the control group. The incidence of diabetes was 21% lower (10–31%) in the STH group than in the DES group.CONCLUSIONS—The 2-day in-hospital program with diabetes education and support every 3 months was more effective in preventing or delaying the progression from IGT to diabetes than only diabetes education and support every 3 months.

Orlistat in the prevention of diabetes in the obese patient.

There has been an increase in the concern about preventing type 2 diabetes mellitus (T2DM), a disease with great and increasing prevalence. The prevalence of obesity, physical inactivity, Western processed diet, important risk factors for the development of T2DM, are also rising. Free fatty acids are increased in obesity and reduce insulin clearance and increase hepatic glucose production. Implementation of a healthy lifestyle has been show to slow the progression of impaired glucose tolerance to T2DM. Orlistat is an inhibitor of lipase activity, with proved efficacy in body weight reduction and long-term management of obesity and more favorable effects on carbohydrate metabolism and it was prospectively shown in XENDOS study that orlistat promoted long-term weight loss and prevented T2DM onset in obese individuals with normal and impaired glucose tolerance at baseline over four years. This benefit could be associated to the weight loss itself, to the limited absorption of lipids and reduction of plasma free fatty acids, to increased production of incretins or to modulation of secretion of cytokines by adipocytes, all effects secondary to orlistat treatment. A proposed strategy is to identify subjects at highest risk to receive a drug intervention, using lifestyle interventions alone at the community level.

Prevention of Type 2 diabetes: fact or fiction?

The growing prevalence of Type 2 diabetes with its high morbidity and excess mortality is imposing a heavy burden on healthcare systems. Because of the magnitude of the problem, obviating diabetes has been a long-standing dream. In the last decade, a number of intervention strategies have been shown to be effective for the prevention of diabetes in high-risk populations with prediabetes. Seven studies have now confirmed that lifestyle modifications, including weight-reducing diets and exercise programs, are very effective in precluding or delaying Type 2 diabetes in high-risk populations with impaired glucose tolerance (IGT). Two major trials are the Diabetes Prevention Study (n = 522) from Finland and the Diabetes Prevention Program (n = 3234) from the US. Both studies have shown that intensive lifestyle intervention could reduce the progression of IGT to diabetes by 58%. Furthermore, four currently-available drugs have been established as being effective in preventing diabetes in subjects with prediabetes. The Diabetes Prevention Program revealed that metformin 850 mg b.i.d. reduced the risk of diabetes by 31%. The STOP-NIDDM (Study To Prevent Non-Insulin-Dependent Diabetes Mellitus) trial (n = 1429) showed that acarbose 100 mg t.i.d. with meals decreased the incidence of diabetes by 36% when the diagnosis was based on 2 oral glucose tolerance tests. The XENDOS (Xenical in the Prevention of Diabetes in Obese Subjects) study examined the use of orlistat, an antiobesity drug, as an adjunct to an intensive lifestyle modification program in obese non-diabetic subjects. Orlistat treatment resulted in a 37% decline in the development of diabetes. More recently, the DREAM (Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication) study (n = 5269) demonstrated that rosiglitazone at 8 mg once/day in subjects with prediabetes (IGT and/or impaired fasting glucose) was effective in reducing the risk of diabetes by 60%. It can be concluded that Type 2 diabetes can be prevented or delayed through lifestyle modifications and/or pharmacologic interventions. This is a fact.

Clinical aspects of physical exercise for diabetes/metabolic syndrome

Evidence-based medicine (EBM) has come to be regarded as essential in all fields of medical sciences and practical medicine. In the field of diabetes and exercise, among the epidemiological studies of physical exercise, recent mega-trials such as the Diabetes Prevention Program (DPP) in the U.S. have shown that lifestyle intervention programs involving diet and/or exercise reduce the progression of impaired glucose tolerance (IGT) to type 2 diabetes. In studies examining the endocrinological and metabolic effects of exercise, it has been demonstrated that physical exercise promotes the utilization of blood glucose and free fatty acids in muscles and lowers blood glucose levels in well-controlled diabetic patients. Long-term, mild, regular jogging increases the action of insulin in both carbohydrate and lipid metabolism without influencing body mass index or maximal oxygen uptake. A significant correlation has been observed between delta MCR (Δinsulin sensitivity) and the average number of steps performed in a day. Our recent data suggested that the improved effectiveness of insulin that occurs as a result of physical exercise is attributable, at least in part, to increases in GLUT4 protein, IRS1 and PI3-kinase protein in skeletal muscle. As a prescription for exercise, aerobic exercise of mild to moderate intensity, including walking and jogging, 10–30 min a day, 3–5 days a week, is recommended. Resistance training of mild intensity with the use of light dumbbells and stretch cords should be combined in elderly individuals who have decreased muscle strength. An active lifestyle is essential in the management of diabetes, which is one of typical lifestyle-related diseases.

Of Hopes and DREAMS: The Quest to Prevent Type 2 Diabetes

The old adage that “prevention is better than cure” holds particularly well for a chronic disease like type 2 diabetes, withitsepidemicscaleandmultiplecripplingcomplications. Clearly, any intervention that can halt this epidemic safely and effectively will have huge public health implications. Several clinical trials have therefore attempted to address the question of preventing diabetes. Among these, the Diabetes Prevention Program clearly demonstrated that intensive lifestyle change was effective not only in decreasing the progression of impaired glucose tolerance to diabetes, but was also associated with significant improvement in other cardiovascular risk factors (1). The Finnish Diabetes Prevention Study reported similar findings (2). One would think that therein lies the simple answer to diabetes prevention. Unfortunately,translationoftheseresultstothegeneralpublic has been difficult. Large, randomized trials have also assessed the potential of the medications metformin (Diabetes Prevention Program) and acarbose (STOP-NIDDM) to slow the progression to diabetes, and these have both demonstrated some benefit (1, 3). When one compares the results in the Diabetes Prevention Program, metformin was only abouthalfaseffectiveaswasintensivelifestylechange.Acarbose, although not compared head-to-head with intensive lifestyle,appearstobenobetterthanmetformin.Atthistime, neither of these drugs is currently approved for diabetes prevention. Whether they ever will be approved is another question. With the availability of other classes of agents with different mechanisms of action, many pharmaceutical companies and clinical trialists continue to investigate the effect of pharmacological therapy to prevent diabetes. The most recent large clinical trial to address the prevention of diabetes has been the Diabetes Reduction Assessment with Ramipril and Rosiglitazone (DREAM) trial (4, 5), for which there was a good rationale. First, post hoc analyses of a variety of studies have shown that blockade of the reninangiotensinsystemdecreasesincidentdiabetes.Inparticular, the HOPE study demonstrated a significant reduction in new-onset diabetes in people with increased cardiovascular risks (6). Second, rosiglitazone is a thiazolidinedione insulinsensitizer, and a previous drug in this class, which is no longer available, had been shown to prevent diabetes in a small single-center study in Hispanic women with a history of gestational diabetes (7); the same was suggested in a discontinued arm in the Diabetes Prevention Program (8). The DREAM trial was an international effort performed in 5269 individuals (59% women) of whom 44% had a history of hypertension, 44% were current or former smokers, and 36% had dyslipidemia. The results of the study were mixed (4, 5), which for the most part was not unexpected. The effect of ramipril (titrated to 15 mg/d) on glucose metabolism was small. Although the study demonstrated a modest glucoselowering effect, the drug did not slow the rate of development of diabetes. In contrast, rosiglitazone (titrated to 8 mg/d) very significantly reduced the development of diabetes by some 60% in this relatively healthy population with impaired fasting glucose or impaired glucose tolerance.

Prevalence and characteristics of impaired glucose metabolism in patients referred to comprehensive cardiac rehabilitation: the DANSUK study

Lifestyle and pharmacological interventions can delay the progression of impaired glucose tolerance (IGT) to type 2 diabetes (T2DM), and there is growing evidence that earlier detection of T2DM and intensified risk factor management may result in improved cardiovascular morbidity and mortality. We studied the prevalence of impaired glucose metabolism (T2DM, IGT and impaired fasting glucose; IFG) in patients referred to cardiac rehabilitation, and further studied whether we could identify groups in which an oral glucose tolerance test (OGTT) need not be performed. As part of a cardiac rehabilitation trial, 201 patients participated. Patients without a diagnosis of T2DM (N=159) underwent an OGTT 3 months after inclusion. Forty-two patients (21%) had known T2DM at enrolment. Based on the OGTT, 26 patients (13%) had unrecognized T2DM, 36 (18%) had IGT and 19 (9%) were diagnosed with isolated IFG according to the World Health Organization definition. Using fasting plasma glucose alone, 19% of the patients with unrecognized T2DM and two-thirds of patients with IGT would be misclassified. Using IFG as a means to detect IGT showed a sensitivity of only 33% and a positive predictive value of 39%. More than 60% of the patients (123/201) referred to cardiac rehabilitation had impaired glucose metabolism and 18% of the screened patients (29/159) would be misclassified if an OGTT was omitted. IFG and IGT did not identify the same patients or the same cardiovascular risk profile. An OGTT test should therefore be considered a constituent part of routine care management in cardiac rehabilitation settings.

Delaying the onset of type 2 diabetes mellitus in patients with prediabetes.

The frequency of type 2 diabetes mellitus is increasing at an alarming rate. Prediabetes, also referred to as impaired glucose tolerance (IGT) and/or impaired fasting glucose, is a major risk factor for development of type 2 diabetes mellitus. In addition, IGT has been associated with an increased risk of cardiovascular disease and mortality. Several studies have measured the effects of various interventions in patients with IGT on the development of type 2 diabetes mellitus. Intensive lifestyle modifications through alterations in diet and improvement in exercise have delayed the development of type 2 diabetes mellitus by 58% in patients with IGT. Therapy with metformin, troglitazone, or acarbose also has reduced the progression of IGT to diabetes mellitus by 31%, 49% and 25%, respectively. The mechanisms by which lifestyle interventions and drugs reduce the progression may be through alterations in insulin sensitivity. The American Diabetes Association recommends screening for prediabetes in patients who are 45 years or older and those with a body mass index of 25 kg/m2 or greater who have additional diabetes mellitus risk factors. Pharmacists can promote awareness, counsel patients on intervention strategies to delay the onset of diabetes mellitus, and screen high-risk patients.

Rare site for an intramuscular lipoma

Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393–403. 22 Bailey CJ. The diabetes prevention program: headline results. Br J Diabetes Vasc Dis 2001; 1: 62–64. 23 Harris MI. Impaired glucose tolerance—prevalence and conversion to NIDDM. Diabetic Med 1996; 13 (suppl): S9–S11. 24 Chen H-S, Shaw C-K, Tseng W-P, Chen H-I, Lee M-L. Prevalence of diabetes mellitus and impaired glucose tolerance in Aborigines and Chinese in eastern Taiwan. Diabetes Res Clin Practice 1997; 38: 199–205. 25 Chiasson J-L, Josse RG, Hunt JA, et al. The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus: a multicenter controlled clinical trial. Ann Intern Med 1994; 121: 928–35. 26 Heine RJ, Nijpels G, Mooy JM. New data on the rate of progression of impaired glucose tolerance to NIDDM and predicting factors. Diabetic Med 1996; 13 (suppl): S12–S14. ARTICLES

Promoting physical activity in people with type 2 diabetes

Extensive evidence demonstrates the benefits of physical activity in the management of type 2 diabetes. A recent meta-analysis of controlled clinical trials investigating the effect of exercise on glycaemic control concluded that exercise significantly reduced HbA1C values by 0.66%. This reduction is clinically significant and only slightly less than the difference between conventional and intensive glucose lowering therapy in the United Kingdom Prospective Diabetes Study (UKPDS),2 which significantly reduced the development of diabetic complications. Recent studies have shown that changes in lifestyle can delay the progression of impaired glucose tolerance to type 2 diabetes,3,4 lifestyle changes being significantly more effective than therapy with metformin. Furthermore some research suggests physical activity is more effective for improving glycaemic control during earlier stages of diabetes. These studies suggest the need for an early emphasis of physical activity promotion in the management of type 2 diabetes.