The role of exercise in type II diabetes mellitus

A number of studies have demonstrated a beneficial effect of regular physical activity on levels of HgbA₁C in patients with type II diabetes mellitus, largely due to an increase in insulin sensitivity. Benefits are related to short term improvements in insulin sensitivity following individual exercise bouts. Regular exercise can prevent or delay the onset of type II diabetes in high risk populations. The insulin resistant state is associated with a cluster of cardiovascular risk factors all of which improve with regular physical activity. Because of the high incidence of occult coronary disease, patients need a cardiovascular evaluation when initiating an exercise program. High intensity exercise may result in retinal hemorrhage and transient worsening of diabetic proteinuria. The most common complication is hypoglycemia. A combination of aerobic and light resistance exercise is appropriate. Patients should exercise a minimum of three times a week for 30–60 minutes at 50% to 75% of their Vo_2max.     

Cigarette smoking and diabetes

Smokers are insulin resistant, exhibit several aspects of the insulin resistance syndrome, and are at an increased risk for type 2 diabetes. Prospectively, the increased risk for diabetes in smoking men and women is around 50%. Many patients with type 1 and type 2 diabetes mellitus are at risk for micro- and macrovascular complications. Cigarette smoking increases this risk for diabetic nephropathy, retinopathy, and neuropathy, probably via its metabolic effects in combination with increased inflammation and endothelial dysfunction. This association is strongest in type 1 diabetic patients. The increased risk for macrovascular complications, coronary heart disease (CHD), stroke, and peripheral vascular disease, is most pronounced in type 2 diabetic patients. The development of type 2 diabetes is another possible consequence of cigarette smoking, besides the better-known increased risk for cardiovascular disease. In diabetes care, smoking cessation is of utmost importance to facilitate glycemic control and limit the development of diabetic complications.     

Type 2 diabetes mellitus and exercise impairment

Limitations in physical fitness, a consistent finding in individuals with both type I and type 2 diabetes mellitus, correlate strongly with cardiovascular and all-cause mortality. These limitations may significantly contribute to the persistent excess cardiovascular mortality affecting this group. Exercise impairments in VO2 peak and VO2 kinetics manifest early on in diabetes, even with good glycemic control and in the absence of clinically apparent complications. Subclinical cardiac dysfunction is often present but does not fully explain the observed defect in exercise capacity in persons with diabetes. In part, the cardiac limitations are secondary to decreased perfusion with exercise challenge. This is a reversible defect. Similarly, in the skeletal muscle, impairments in nutritive blood flow correlate with slowed (or inefficient) exercise kinetics and decreased exercise capacity. Several correlations highlight the likelihood of endothelial-specific impairments as mediators of exercise dysfunction in diabetes, including insulin resistance, endothelial dysfunction, decreased myocardial perfusion, slowed tissue hemoglobin oxygen saturation, and impairment in mitochondrial function. Both exercise training and therapies targeted at improving insulin sensitivity and endothelial function improve physical fitness in subjects with type 2 diabetes. Optimization of exercise functions in people with diabetes has implications for diabetes prevention and reductions in mortality risk. Understanding the molecular details of endothelial dysfunction in diabetes may provide specific therapeutic targets for the remediation of this defect. Rat models to test this hypothesis are under study.     

Long-term benefits of insulin therapy and glycemic control in overweight and obese adults with type 2 diabetes

ProblemObesity and type 2 diabetes have reached epidemic proportions in the United States. Obese patients are at especially high risk for the development of metabolic syndrome, a clustering of metabolic abnormalities associated with insulin resistance that usually precede the development of cardiovascular disease. Overweight or obesity, along with insulin resistance, is frequently present in people with type 2 diabetes.MethodsA literature search of the PubMed and MEDLINE databases, using the terms diabetes, obesity, metabolic syndrome, glycemic control, antidiabetic therapy, and insulin, was performed. Articles published between 1985 and 2006 that examined diabetes management in the obese population were selected and reviewed.ResultsThere is new evidence suggesting that tight glycemic control and earlier initiation of insulin therapy can improve outcomes in obese patients with type 2 diabetes, thereby reducing the risk for the development of both macrovascular and microvascular complications of the disease. Insulin also appears to exhibit anti-inflammatory effects, which may provide additional protection against the development of atherosclerosis. Despite the benefits of insulin therapy, many patients and physicians remain reluctant to start insulin due to concerns about weight gain.ConclusionNewer insulin formulations can effectively improve glycemic control without significant effects on patient weight and, therefore, may be particularly useful in patients who are overweight or obese. Implementation of comprehensive treatment regimens that emphasize dietary modification, physical activity, and exercise, and aggressive use of pharmacological agents to achieve tight glycemic control through physiological regimens offer the most promise for reducing long-term complications in obese patients with type 2 diabetes.     

Insulin resistance is a cardiovascular risk factor in humans

Diabetes is a common metabolic disorder associated to elevated cardiovascular morbidity and mortality that is not explained by hyperglycemia or traditional cardiovascular risk factors such as smoking or hypercholesterolemia. Intensive glycemic control with insulin that achieves near-normal glycemia does not reduce significantly macrovascular complications compared with conventional glycemic control. Cardiovascular disease continues to develop in patients with diabetes despite adequate glycemic control. In contrast, intensive control with metformin (leading to insulin resistance improvement) reduces diabetes complications, including cardiovascular events, suggesting that enhancement of insulin sensitivity rather than plasma glucose level has a major role improving diabetes outcomes. Accordingly, insulin resistance estimated by glucose tolerance tests is better predictor of future cardiovascular events than fasting glucose level in nondiabetic individuals. Insulin resistance precedes for decades the clinical onset of type 2 diabetes and deteriorates metabolic control of type 1 diabetes. Numerous investigations including cross-sectional and prospective studies, meta-analyses, and systematic reviews provide compelling evidence that insulin resistance by itself is a cardiovascular risk factor in a variety of population groups, including the general population and patients with diabetes. Several estimations of insulin resistance have been consistently associated with elevated rate of cardiovascular events independently of other cardiovascular risk factors and diabetes status. The clinical expression of insulin resistance (the metabolic syndrome or any of its components including obesity, hyperinsulinemia, hypertension, and dyslipemia) has been related to cardiovascular disease as well. An estimation conducted by the Archimedes model confirms that insulin resistance is the most important single cause of coronary artery disease.     

Bewegung als Therapie bei Diabetes mellitus Typ?2

The beneficial role of physical exercise on glycemic control in patients with type 2 diabetes mellitus has been confirmed by several controlled trials including both aerobic and resistance exercise protocols. Exercise has been shown to increase insulin sensitivity, lower blood sugar levels, reduce body fat and improve physical fitness. Grade A scientific evidence has been assigned to the effect of regular physical activity on glycemic control for both endurance and resistance exercise.The recommendations for endurance exercise are: aerobic physical activity of moderate intensity (40-60% of VO(2)max or 50-70% of maximum heart rate) for at least 150?min/week and/or at least 90?min/week of vigorous aerobic exercise (>?60% of VO(2)max or >?70% of maximum heart rate). The physical activity should be distributed over at least 3 days/week and with no more than 2 consecutive days without physical activity. The recommendations for resistance exercise are: resistance exercise should be performed at least 3 times a week, including all major muscle groups, progressing to 3 sets of 8-10 repetitions at a weight that cannot be lifted >?8-10 times.     

Thiazolidinedione therapy: the benefits of aggressive and early use in type 2 diabetes

Type 2 diabetes is now a global epidemic, with the number of people affected worldwide predicted to more than double to 300 million by the year 2025. While the importance of good glycemic control in countering the microvascular and macrovascular complications of diabetes is widely recognized, monotherapy with sulfonylureas or metformin achieves target blood glucose levels in only a minority of patients. Consequently, there is a pressing need for new treatment strategies that are more effective in providing sustained glycemic control and so reducing the burden of morbidity and mortality associated with diabetes and its complications. There is growing evidence of the benefits of early intervention with aggressive treatment strategies in improving glycemic control and reducing diabetic complications. To provide sustained control, such strategies need to address the combination of insulin resistance and beta-cell dysfunction that underlies most cases of type 2 diabetes. At the same time, treatment needs to address not only glycemic control but also the range of cardiovascular risk factors that are often found clustered together in patients with type 2 diabetes. This paper reviews the rationale and evidence for early combination therapy including a thiazolidinedione in improving glycemic control, and considers the potential for such aggressive therapy in reducing diabetic complications.     

Is There a Rationale for Insulin Therapy in Pre-Diabetic Individuals?

Type 2 diabetes mellitus is usually preceded by impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG), which are often referred to as pre-diabetes. Individuals with IGT demonstrate beta-cell dysfunction, insulin resistance, and increased hepatic glucose production; IGT and IFG are risk factors for both diabetes and cardiovascular disease. Type 2 diabetes is associated with micro- and macrovascular complications that lead to excessive mortality and morbidity and the risk of microvascular complications extends to people with pre-diabetes. Maintaining good glycemic control in type 2 diabetes can reduce the risk of developing chronic disease-associated complications. Most individuals who develop type 2 diabetes appear to pass through a stage of IFG or IGT; thus, early intervention (lifestyle and/or pharmacologic) in individuals with pre-diabetes may help prevent cardiovascular disease and the development of type 2 diabetes.The use of exogenous insulin treatment offers the potential to reduce the cardiovascular risk in individuals with type 2 diabetes or pre-diabetes through effective reductions in blood glucose and lipid levels, and in the associated tissue damage resulting from their chronic elevations. However, there are barriers associated with insulin initiation in both type 2 diabetes and pre-diabetes (e.g. hypoglycemia, weight gain, the possible unpredictable action of long-acting insulin, and the need for injections). Insulin glargine, with its flat time-action profile, near 24-hour duration of action, reduced risk of hypoglycemia, and improved glycemic control compared with insulin suspension isophane (neutral protamine hagedorn [NPH] insulin), may help to overcome some of these barriers.Initial results from a small study have indicated the feasibility of treating individuals with pre-diabetes to near-normoglycemia using a regimen of low-dose insulin glargine plus caloric restriction. This is being followed up in the ongoing ORIGIN (Outcomes Reduction with Initial Glargine INtervention) study, which will investigate whether treatment to near-normoglycemia with insulin glargine in individuals with IGT, IFG, or new-onset type 2 diabetes can reduce cardiovascular morbidity and mortality compared with conventional management of these conditions, and whether the rate of progression to type 2 diabetes can be similarly reduced.Further studies are needed to investigate the potential benefits of insulin therapy in individuals with pre-diabetes.     

Low-intensity exercise increases skeletal muscle protein expression of PPARdelta and UCP3 in type 2 diabetic patients

BACKGROUND: Physical exercise provides health benefits for people with type 2 diabetes mellitus, partly by enhancing skeletal muscle insulin action. We tested the hypothesis that changes in expression of key genes in skeletal muscles relate to exercise-induced improvements in type 2 diabetic patients. METHODS: We determined mRNA expression of 20 selected genes following a self-supervised program of walking (> 150 min per week) over a 4-month period. RESULTS: This level of physical activity improved clinical parameters in approximately half the participants, as determined by reduced hypertension and enhanced insulin sensitivity (defined by reduced plasma-insulin levels and improved homeostasis model assessment (HOMA)). Skeletal muscle mRNA expression of Cbl-associated protein (CAP), diacylglycerol kinase (DGK)delta, uncoupling protein (UCP) 3, nuclear respiratory factor (NRF)-1, and peroxisome proliferator-activated receptor (PPAR)delta tended to increase in type 2 diabetic patients with an improved clinical profile. Skeletal muscle protein expression of PPARdelta and UCP3 was increased significantly after physical exercise in patients with an improved clinical profile, but were unchanged in patients who did not show exercise-mediated improvements in clinical parameters. CONCLUSIONS: This study provides clinical evidence that improvements in insulin sensitivity can be achieved in type 2 diabetic patients after individually executed low-intensity exercise training. Moreover, the positive clinical response to exercise is correlated with changes in skeletal muscle proteins involved in the regulation of mitochondrial biogenesis and metabolism. These changes in skeletal muscle gene expression offer a possible molecular explanation for the improvements in clinical outcomes.     

Postprandial glucose regulation and diabetic complications

Atherosclerotic disease accounts for much of the increased mortality and morbidity associated with type 2 diabetes. Epidemiological studies support the potential of improved glycemic control to reduce cardiovascular complications. An association between glycosylated hemoglobin (HbA(1c)) level and the risk for cardiovascular complications has frequently been reported. Most epidemiological data implicate postprandial hyperglycemia in the development of cardiovascular disease, whereas the link between fasting glycemia and diabetic complications is inconclusive. Moreover, in many studies, postprandial glycemia is a better predictor of cardiovascular risk than HbA(1c) level. Postprandial glucose may have a direct toxic effect on the vascular endothelium, mediated by oxidative stress that is independent of other cardiovascular risk factors such as hyperlipidemia. Postprandial hyperglycemia also may exert its effects through its substantial contribution to total glycemic exposure. The present review examines the hypothesis that controlling postprandial glucose level is an important strategy in the prevention of cardiovascular complications associated with diabetes.     

Management of elderly diabetic patients in the subacute care setting

Type 2 diabetes is a commonly encountered condition in the subacute care setting. The results of the landmark UK prospective studies have confirmed that aggressive glycemic and blood pressure control delayed diabetes-related microvascular and macrovascular complications and significantly improved diabetic outcomes. Within the past few years, new drugs have been developed to address both aspects of the type 2 diabetes syndrome: insulin resistance and insulin secretory defect. C-peptide analysis may be useful to predict a successful response to therapy with insulin sensitizers or the need to initiate therapy with insulin or insulin stimulators. The issues regarding the general approach to elderly diabetics and the strategies of dealing with diabetic complications encountered in the subacute care program are discussed and updated. It is hoped that diabetic management can be improved and that suggested alternate therapies can be used in the subacute care facilities.     

Exercise training ameliorates the effects of rosiglitazone on traditional and novel cardiovascular risk factors in patients with type 2 diabetes mellitus

The aim of the study was to investigate the effects of rosiglitazone and/or exercise training on novel cardiovascular risk factors in patients with type 2 diabetes mellitus. One hundred overweight/obese type 2 diabetes mellitus patients, with inadequate glycemic control (hemoglobin A_1c >7%) despite combined treatment with gliclazide plus metformin, were randomized using a 2 × 2 factorial design to 4 equivalent (n = 25) groups, as follows: (1) CO: maintenance of habitual activities, (2) RSG: add-on therapy with rosiglitazone (8 mg/d), (3) EX: adjunctive exercise training, and (4) RSG + EX: supplementary administration of rosiglitazone (8 mg/d) plus exercise training. No participant had diabetic vascular complications or was receiving lipid-lowering therapy. Anthropometric parameters, cardiorespiratory capacity, glycemic and lipid profile, apolipoprotein (apo) A-I, apo B, interleukin (IL)-10, IL-18, insulin resistance, and blood pressure were measured before and after 12 months of intervention (P < .05). Both RSG and EX groups significantly reduced glycemic indexes, insulin resistance, blood pressure, and IL-18, whereas they significantly increased high-density lipoprotein, cardiorespiratory capacity, and IL-10, compared with CO group (P < .05). Besides this, exercise-treated patients conferred a remarkable down-regulation in the rest of lipid parameters (total cholesterol, low-density lipoprotein cholesterol, triglycerides, apo B) and body fat content (P < .05) in comparison with CO group. On the other hand, RSG group rather than CO group considerably increased apo A-I levels and body mass index (P < .05). Notably, the combined treatment group yielded pronounced beneficial changes in glycemic indexes, lipid profile, insulin resistance, blood pressure, IL-10, IL-18, apo A-I, and apo B (vs CO group, P < .05). Furthermore, the addition of exercise to rosiglitazone treatment counteracted the drug-related negative effects on body weight, low-density lipoprotein, and total cholesterol. Rosiglitazone plus exercise training elicited additive effects on body composition, glycemic control, and traditional and novel cardiovascular risk factors in type 2 diabetes mellitus patients, indicating complementary effects.     

口服降糖药物对2型糖尿病患者心血管结局的影响

改善血糖控制可减少糖尿病患者的心血管并发症,不同药物的作用机制不同,其对心血管结局的影响不同.此外,继2007年对罗格列酮潜在心血管风险的认识之后,陆续开展了大量的前瞻性、随机、对照研究,评估降糖药物对糖尿病患者的心血管系统的影响.传统药物中二甲双胍及噻唑烷二酮类药物对糖尿病患者的心血管系统具有保护作用,但必须警惕噻唑烷二酮类药物可增加心力衰竭的风险;第二代及第三代磺脲类促泌剂及非磺脲类促泌剂并不增加患者心血管事件的发生风险.新型药物中并没有看到二肽基肽酶4抑制剂对心血管系统具有有利或不良影响,是否增加心力衰竭风险目前结果并不统一.而胰高血糖糖素样肽-1受体激动剂及钠-葡萄糖协同转运蛋白2可减少糖尿病患者的心血管疾病风险并降低死亡率;但由于数据有限,仍需要更广泛的研究加以证实.     

Plasma ferritin and type 2 diabetes mellitus: a critical review.

Multiple factors appear to be involved in the pathogenesis of type 2 (non insulin dependent) diabetes mellitus (DM). One of these factors may be iron overload. This critical review summarizes the major studies on the link between type 2 DM, insulin resistance, glycemic control, diabetic complications and hyperferritinemia. Although some studies suggested that plasma ferritin concentration is positively correlated with insulin resistance and with the risk of acquiring type 2 DM, substantial iron overload is not a typical feature of DM. There is no correlation between plasma ferritin level and glycemic control or diabetic microangiopathic complications.     

Diabetes and exercise

This review describes (1) the metabolic and hormonal response to exercise in normal and diabetic man, and (2) the potential benefits of physical training in diabetes. Whereas in normal man plasma glucose varies little during exercise, the insulin-dependent diabetic subject may experience an increase in plasma glucose, a modest decrease or a marked decrease which can result in symptomatic hypoglycemia. Evidence is reviewed that the glycemic response depends on the ambient plasma concentration of insulin and that this may be influenced by an effect of exercise on the absorbtion of insulin from its site of injection. The response to exercise of noninsulin-dependent diabetic subjects and of diabetic subjects with autonomic neuropathy is also described. Physical training improves glucose tolerance in some noninsulin-dependent diabetic subjects and in insulin-dependent patients, it may diminish insulin requirements. It may also have a role in retarding the development of cardiovascular complications. Physical training is not totally innocuous, however, and in many patients with diabetes special precautions are required.     

Efficacy of a pedometer-based physical activity program on parameters of diabetes control in type 2 diabetes mellitus

The aim of the study was to determine whether a recommendation to walk 10000 steps per day would result in significant improvements in glycemic control, insulin sensitivity, and cardiovascular risk in patients with type 2 diabetes mellitus. The study was a 6-week randomized controlled trial that included 30 patients with type 2 diabetes mellitus. After 10 days of baseline activity, patients were randomized into 2 groups: control and active. The control group (n = 15) was instructed to continue with their baseline activity for 6 weeks. The active group (n = 15) was instructed to walk at least 10000 steps per day 5 or more days per week, for 6 weeks. Data relevant to glycemic control and other parameters of health were collected at study weeks 0 and 6. There were no differences in the baseline activity between groups (P = .36). Subjects in the active group significantly increased physical activity by 69% during the intervention phase of the study (P = .002), whereas there was no change in the physical activity of the control group (P > .05). High-density lipoprotein cholesterol and resting energy expenditure significantly increased in the active group (P < .05). Finally, plasminogen activator inhibitor 1 (PAI-1) activity was reduced by exercise relative to the control group (P = .03). There were no differences in any other study parameters during the 6-week study. In conclusion, short-term intervention with a pedometer increased physical activity and positively affected plasminogen activator inhibitor 1 activity in previously inactive patients with type 2 diabetes mellitus. The use of a pedometer may prove to be an effective tool for promoting healthy lifestyle changes that include daily physical activity and self-monitoring of therapeutic goals.     

Managing obesity and glycemic control in insulin-using patients: clinical relevance and practice recommendations

In a number of large-scale studies, intensive therapy regimens have improved glycemic control while reducing the microvascular complications of type 2 diabetes. However, insulin use has been associated with weight gain, thereby hampering patient compliance with intensive insulin therapy. As the prevalence of type 2 diabetes and obesity continues to increase worldwide, health care providers must incorporate the management of weight gain in therapeutic strategies that promote glycemic control. The central component in any such strategy is a tailored program of medical nutrition therapy (MNT), which includes a healthy diet, physical activity, and education. This article reviews several dietary options within a MNT program, including the uses of liquid meal replacements, low-glycemic index carbohydrates, and foods rich in monounsaturated fatty acids. It also provides several practice recommendations to encourage compliance in patients with type 2 diabetes who wish to manage their weight while receiving insulin therapy.     

Psychosocial aspects of diabetes with an emphasis on depression

Any chronic disease is associated with an increased prevalence of mood disorders and depression. Diabetes is unique in that it places the burdens of invasive blood glucose monitoring, regimentation of diet and exercise, and often multiple daily insulin injections into the hands of the individual. Therefore, it is not surprising that depression may be three times more prevalent in the diabetic population when compared with nondiabetic individuals. Depressed patients with diabetes have been shown to have poorer glycemic control and a higher incidence of microvascular and macrovascular complications. Treatment of the depression associated with diabetes with either pharmacologic therapy or behavioral intervention has been shown to result in improved glycemic control and quality of life. Specific side effects of commonly used antidepressant medications, which have particular bearing on the diabetic state, are discussed. Future research into the causal relationship of depression to the onset on diabetes, longitudinal studies looking at depression and the rate of occurrence of diabetic complications, and the impact of the early development of healthy coping mechanisms and the treatment of depression on the natural history of diabetes are needed.     

Treatment of diabetic dyslipoproteinemia.

Diabetes mellitus, specifically type 2, is often associated with disorders in lipid metabolism. Elevated levels of plasma free fatty acids play a pivotal role by contributing significantly to insulin resistance. In addition free fatty acids promote diabetic dyslipidemia through increasing VLDL synthesis in the liver, and by virtue of cholesterylester transfer protein, modifying LDL to increase small-dense LDL subfractions and to decrease HDL cholesterol. This atherogenic lipoprotein profile (elevated triglycerides, increased small-dense low-density lipoproteins, and decreased high-density lipoproteins), contributes to the development of atherosclerosis and increases the risk of experiencing cardiovascular events, the most common cause of death in type 2 diabetes. To decrease the risk of cardiovascular disease events in diabetics, dyslipidemia needs to be treated, as evidenced from epidemiology, from intervention trials, and from subgroup analyses of large intervention trials initiated to evaluate effects of lipid lowering treatment that also included patients with type 2 diabetes. Most measures used to counteract hyperglycemia, are also prone to ameliorate dyslipidemia: dietary intervention (medical nutrition) including omega-3 fatty acids as part of lifestyle changes that also comprise cessation of smoking, increases in physical activity and reduction in body weight. In addition insulin, biguanides, acarbose and glitazones applied for glycemic control also improve diabetic dyslipidemia. Additional pharmacological treatment of dyslipidemia if persisting after glycemic control relies on different drug classes. Fibrates effectively reduce free fatty acids, fasting and postprandial lipemia, shift the distribution of LDL particles towards less dense subfractions and increase HDL cholesterol, thus particularly addressing key components of diabetic dyslipidemia. For LDL cholesterol lowering statins are mainly used that decrease LDL cholesterol levels by competitive inhibition of the HMG-CoA reductase. As type 2 diabetes is found to be associated with a two- to fourfold increase in coronary heart disease risk and as the degree of glycemia is more related to microvascular complications, correcting dyslipidemia appears to be a major task in order to reduce macrovascular events in patients with type 2 diabetes.     

Diabetes in African Americans: Unique pathophysiologic features

Type 2 diabetes is an increasing public health problem among African Americans, especially children. Several features make type 2 diabetes among African Americans unique. First, African-American adults with type 2 diabetes, or Flatbush diabetes, present with diabetic ketoacidosis. Patients are insulin resistant with acute, severe defects in insulin secretion and no islet cell autoantibodies. Following treatment, some insulin secretory capacity is recovered and ketoacidosis generally does not recur. The second is remission in African Americans with type 2 diabetes. Recovery of glucose homeostasis, accompanied by recovery of β-cell function, follows intensive glycemic regulation. Finally, among African Americans with diabetes who are not obese, normal insulin sensitivity is not uncommon. Such individuals do not have the increased cardiovascular risk of insulin-resistant individuals. Differences in visceral, not subcutaneous, adipose tissue volume appear to determine insulin sensitivity. Understanding the unique physiologic and clinical features of African Americans is critical in designing appropriate treatment strategies.