餐后血糖调节与糖尿病心血管疾病并发症

如何确定餐后高血糖水平及其与糖化血红蛋白(Hb)A1c的相关性,近年来研究结果不一致。虽然高血糖在糖尿病并发症发生、发展中的直接作用目前仍有争议,但众多流行病学研究已证实,与HbA1c相比,餐后血糖是一个更好的预测心血管疾病危险性的因素。其致病机制与氧化应激对血管内皮的毒性作用及其对总体血糖的贡献有关。目前的观点普遍认为,控制餐后血糖是预防与糖尿病相关的心血管疾病并发症的一项重要的策略。     

Control of post-prandial hyperglycemia--an essential part of good diabetes treatment and prevention of cardiovascular complications

AIM: This article reviews the relationship between the control of post-prandial hyperglycemia and diabetes-related complications. DATA SYNTHESIS: Hyperglycemia is a modifiable risk factor that has a deleterious effect on the development and progression of microvascular and macrovascular complications in patients with type 2 diabetes. The UK Prospective Diabetes Study revealed how reductions in hemoglobin A1c (HbA1c) correlate with a significant reduction in all-cause mortality and the incidence of myocardial infarction. The Diabetes Intervention Study showed that poor control of fasting glycemia does not increase the risk of myocardial infarction or mortality, whereas poor control of post-prandial glucose is associated with a high all-cause mortality rate. HbA1c is the standard measure for metabolic control and therapeutic efficacy, but does not reflect fluctuations in glycemic control. Plasma glucose concentrations in healthy subjects remain within a narrow range, which suggests that the fluctuations in glucose levels caused by inappropriate treatment may have negative consequences. These fluctuations have been associated with acute adverse effects (particularly excessive post-prandial hyperglycemia, pre-meal hypoglycemia and weight gain) that counteract the positive effect of lowering fasting plasma glucose and HbA1c. Post-prandial hyperglycemia and spikes also have deleterious effects on insulin secretion and sensitivity. Prandial oral antidiabetic agents such as alpha-glucosidase inhibitors (acarbose, miglitol) and rapidly acting insulin secretagogues (nateglinide, repaglinide) have recently been introduced to improve the control of post-prandial hyperglycemia. CONCLUSION: Near-normal post-prandial glycemic control is associated with lower rates of cardiovascular and all-cause mortality than excessive post-challenge hyperglycemia. In addition to the aggressive control of HbA1c and fasting plasma glucose, the strict normalisation of postprandial hyperglycemia is an essential part of good diabetes treatment. There is growing evidence from epidemiological and clinical studies that this also reduces the risk of cardiovascular complications.     

Clinicians can help their patients control postprandial hyperglycemia as a means of reducing cardiovascular risk

Cardiovascular disease is the leading cause of morbidity and mortality among patients with diabetes. Having diabetes is now recognized as conferring the same risk for cardiovascular disease as hyperlipidemia, hypertension, and smoking. HbA1c levels are the primary indicator of diabetes control and overall glycemic exposure. And recent research has pointed to postprandial hyperglycemia as conferring a greater risk of cardiovascular disease than elevated fasting plasma glucose levels. Unfortunately, clinicians sometimes forget that elevated HbA1c levels can arise from both fasting hyperglycemia and postprandial hyperglycemia. This is particularly important to remember when treating patients whose HbA1c levels may be higher than the desired target while fasting plasma glucose test results are within reference range. This article reviews the evidence supporting the view that postprandial hyperglycemia is a risk factor for cardiovascular disease and therefore should be controlled. Case studies are presented to aid clinicians in helping patients learn how to measure and control their postprandial glucose levels.     

Role of chronic and acute hyperglycemia in the development of diabetes complications

Chronic hyperglycemia, as assessed by hemoglobin A1c (HbA1c) levels, has been associated with the development of microvascular and macrovascular complications of diabetes. Several studies have shown that acute hyperglycemia can add to the effect of chronic hyperglycemia in inducing tissue damage. Acute hyperglycemia can activate the same metabolic and hemodynamic pathways as chronic hyperglycemia. In particular, it is associated with increased mitochondrial production of reactive oxidant species, which have been suggested as the link between hyperglycemia and the activation of downstream pathways, mediating tissue damage. Studies performed in subjects with diabetes have shown that there is a positive association between HbA1c and both fasting and postprandial glucose levels. However, it appears that the contribution of these two parameters to the total HbA1c concentrations varies according to the degree of metabolic control. Postprandial glucose excursions are predominant in patients with a good or mild glycemic control, whereas the contribution of fasting hyperglycemia is stronger as glycemic control worsens. Glucose variability, like the intra-day glucose fluctuations from peaks to nadirs, is another important parameter, which, mainly in subjects with type 2 diabetes, has emerged as an HbA1c-independent risk factor for the development of vascular complications. Based on the current knowledge on the association not only of HbA1c, but also of fasting and postprandial glucose, with diabetes complications, it is paramount that antidiabetes strategies are directed at improving all these components in order to reduce the burden associated with diabetes.     

Optimizing diabetes management through glucose profiling: a case-based approach

It is well documented that tight glucose control prevents the microvascular complications of diabetes, and many studies suggest that postprandial hyperglycemia may be associated with macrovascular complications. Maintaining target glucose values is challenging, as therapies are often not targeted to individual glucose excursion patterns. Postprandial SMBG values may be more tightly correlated to HbA1c than are fasting values. Studies of patients with pregnancies complicated by diabetes demonstrate that using SMBG around meals significantly improves glucose control and pregnancy outcomes. Adopting this model in type 2 diabetes may help achieve better glycemic control.     

Fasting but not postprandial (postmeal) glycemia predicts the risk of death in subjects with coronary artery disease

BACKGROUND: Chronic hyperglycemia plays a role in the pathogenesis of coronary artery disease (CAD); however, the cut-off level beyond which glycemia becomes detrimental is still controversial. Postprandial glycemia may be a stronger CAD risk factor than fasting glycemia in patients without documented heart disease. OBJECTIVES: To identify the contributions of fasting and postprandial glycemia to cardiovascular risk in patients with documented coronary artery disease. METHODS: The Coronary Artery Surgery Study (CASS) registry is a database of 24,958 patients with suspected or proven CAD who underwent cardiac catheterization between 1974 and 1979. Median long-term follow up was 14.7 years (interquartile range 9.8 to 16.2 years). Clinical outcomes were evaluated according to fasting glucose levels and 2 h postprandial (postmeal) plasma glucose (2hPG) levels. A total of 13,176 patients with baseline fasting glucose levels and 1691 patients with 2hPG levels were identified. RESULTS: Impaired fasting glycemia was associated with a 1.2-fold increase in both all-cause and cardiovascular mortality (adjusted hazard ratio 1.23; 95% CI 1.08 to 1.40 for cardiovascular mortality), while undiagnosed diabetes was associated with a 1.5-fold increased risk for the same end points. Postprandial hyperglycemia (2hPG of 7.8 mmol/L to 11.0 mmol/L following an average meal) was not associated with a significant risk of death after adjustment for traditional risk factors or in the presence of fasting glucose of less than 6.1 mmol/L. CONCLUSIONS: In CAD patients, impaired fasting glucose is associated with increased all-cause and cardiovascular mortality, whereas postprandial hyperglycemia following an average meal does not appear to be a risk factor.     

Optimal glycemic control in type 2 diabetes mellitus: fasting and postprandial glucose in context

Type 2 diabetes mellitus is the consequence of both insulin resistance and impaired insulin secretion. In the progression from normal glucose tolerance to diabetes, postprandial glucose (PPG) levels often rise before fasting plasma glucose (FPG) levels increase above 126 mg/dL (7.0 mmol/L). Numerous epidemiologic studies have shown that impaired glucose tolerance is associated with increased risk for macrovascular disease and that isolated postchallenge hyperglycemia is an independent factor for increased mortality. Reducing the risk for microvascular complications by improving glycosylated hemoglobin (HbA(1c)) levels is well documented. Emerging data now support the relationship between glycemic control and macrovascular disease. Epidemiologic studies documenting postprandial hyperglycemia and the risk for increased mortality suggest that lowering PPG levels might be beneficial. Optimizing both FPG and PPG is important in achieving normal/near-normal glucose levels. Many patients with type 2 diabetes have difficulty attaining the recommended HbA(1c) goal despite normal/near-normal FPG levels; thus, pharmacologic treatment targeting PPG levels may prove beneficial.     

Clinical significance,pathogenesis, and management of postprandial hyperglycemia

It is well established that strict glycemic control (hemoglobin A1c <7.0%) can prevent the microvascular complications of diabetes mellitus. Recent studies indicate that elevated plasma glucose concentrations are an independent and clinically significant risk factor for cardiovascular disease in nondiabetic and diabetic individuals. Thus, isolated postprandial hyperglycemia (2-hour postprandial glucose level >140 mg/dL [>7.8 mmol/L]) in the face of normal fasting plasma glucose (<110 mg/dL [<6.1 mmol/L]) and normal hemoglobin A1c (<6.1%) values is associated with a 2-fold increased risk of death from cardiovascular disease. These observations imply that more strict glycemic control is required to prevent macrovascular disease than microvascular disease. This review summarizes epidemiologic and experimental studies linking postprandial hyperglycemia to cardiovascular disease and therapeutic approaches available and in development to treat this disorder.     

Postprandial glycemia and cardiovascular disease in diabetes mellitus

This article reviews the role of fasting and postprandial glycemia to the overall glycemic control of patients with type 2 diabetes and glucose intolerance, as well as their causal relationship upon micro and macrovascular complications. Recent studies have suggested that a third component of the glucose triad, the postprandial glucose excursions, might have a role in the overall glycemic load and might also reflect glycemic control. Epidemiological and intervention studies are presented in the article, supporting the conclusion that postprandial hyperglycemia in impaired glucose tolerance and diabetic subjects is a more powerful marker of cardiovascular disease risk than fasting hyperglycemia, then the treatment directed at specifically lowering postprandial glucose is crucial, as underlined by the American Diabetes Association.     

Is the WHI relevant to HRT started in the perimenopause?

While it is well established that overall glycemic control reduces the complications of diabetes, the role of fasting glycemia versus postprandial glycemia in the pathophysiology of diabetes and its complications, and the relative importance of these parameters as specific targets of therapy, remain controversial. Evidence that postprandial glucose (PPG) plays an independent, modifiable role in cardiovascular disease is accumulating, largely from epidemiological studies. A large number of epidemiological studies show that high postprandial glucose is an independent risk factor for cardiovascular disease: indeed, a more powerful risk factor than fasting glucose or HbA_1c. Pathophysiological hypotheses that support these observations include the contribution of postprandial glucose to HbA_1c; postprandial glucose as a surrogate marker for other cardiovascular risk factors, serum lipids and triglycerides in particular; and direct toxicity of elevated glucose levels attributed to "spikes" in glucose concentration following caloric ingestion. Early interventional data suggest that therapy targeted at postprandial glucose can have a favorable impact on cardiovascular events. While more interventional studies clearly are needed, the growing weight of evidence supports a therapeutic approach more directed at excessive prandial glycemic excursions that are characteristic of both type 1 and 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.     

Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women: lessons from the San Luigi Gonzaga Diabetes Study

OBJECTIVE: The influence of postprandial blood glucose on diabetes complications is intensively debated. We aimed to evaluate the predictive role of both fasting and postprandial blood glucose on cardiovascular events in type 2 diabetes and the influence of gender. METHODS: In a population of 529 (284 men and 245 women) consecutive type 2 diabetic patients attending our diabetes clinic, we evaluated the relationships, corrected for cardiovascular risk factors and type of treatment, between cardiovascular events in a 5-yr follow-up and baseline values of hemoglobin A1c (HbA1c) and blood glucose measured: 1) after an overnight fast, 2) after breakfast, 3) after lunch, and 4) before dinner. Continuous variables were categorized into tertiles. RESULTS: We recorded cardiovascular events in 77 subjects: 54 of 284 men (19%) and 23 of 245 women (9.4%). Univariate analysis indicated that cardiovascular events were associated with increasing age, longer diabetes duration, and higher HbA1c and fibrinogen in men, and higher systolic blood pressure, albumin excretion rate, HbA1c, and all blood glucose values in women. Smoking was more frequent in subjects with events. When all blood glucose values and HbA1c were introduced simultaneously in the models, only blood glucose after lunch predicted cardiovascular events, with hazard ratio of the third tertile vs. the first and the second tertiles greater in women (5.54; confidence interval, 1.45-21.20) than in men (2.12; confidence interval, 1.04-4.32; P < 0.01). CONCLUSIONS: Postprandial, but not fasting, blood glucose is an independent risk factor for cardiovascular events in type 2 diabetes, with a stronger predictive power in women than in men, suggesting that more attention should be paid to postprandial hyperglycemia, particularly in women.     

Biosimulation Modeling for Diabetes: The Median Is Not the Only Message: A Clinician's Perspective on Mathematical Analysis of Glycemic Variability and Modeling in Diabetes Mellitus

Hemoglobin A1c (HbA1c), a long-term, integrated average of tissue exposure to hyperglycemia, is the best reflection of average glucose concentrations and the best proven predictor of microvascular complications of diabetes mellitus. However, HbA1c fails to capture glycemic variability and the risks associated with extremes of hypoglycemia and hyperglycemia.These risks are the primary barrier to achieving the level of average glucose control that will minimize both the microvascular and the long-term macrovascular complications of type 1 diabetes. High blood glucose levels largely due to prandial excursions produce oxidative and inflammatory stress with potential acceleration of preexisting atherosclerosis and increased cardiovascular risk. Moreover, some temporal aspects of glycemic variation, including the rates of rise and fall of glucose, are associated with adverse cognitive and mood symptoms in those with diabetes.Methods to quantify the risk of glycemic extremes, both high and low, and the variability including its temporal aspects are now more precise than ever. These important endpoints should be included for use in clinical trials as useful metrics and recognized by regulatory agencies, which has not been the case in the past. Precise evaluation of glycemic variability and its attendant risks are essential in the design of optimal therapies; for these reasons, inclusion of these metrics and the pulsatile hormone patterns in mathematical models may be essential. For the clinician, the incursion of mathematical models that simulate normal and pathophysiological mechanisms of glycemic control is a reality and should be also gradually incorporated into clinical practice.     

Chronic hyperglycemia but not glucose variability determines HbA1c levels in well-controlled patients with type 2 diabetes

To determine the relationships between HbA1c, characteristics of hyperglycemia and glycemic variability in well-controlled type 2 diabetes (HbA1c<7.0%), we studied 63 primary-care patients (36 men and 27 women), aged 34-75 years, with type 2 diabetes for 2-32 years using a continuous glucose monitoring system (CGMS) and standardized meal test (MMT). Duration of hyperglycemia (>8.0 mmol/l), standard deviation score (S.D.-score) and mean amplitude of glycemic excursions (MAGE) were analyzed from CGMS data and postprandial glucose during MMT (PPG(MMT)). Patients were hyperglycemic for 5.7h/day (median), experienced 4.1 hyperglycemic episodes/day, and 78% exceeded PPG levels of 8.0 mmol/l. HbA1c, though associated with the extent of hyperglycemia (r=0.40, p<0.001), failed to correlate with S.D.-score and MAGE. Multiple regression analysis demonstrated that HbA1c was predicted only by fasting glucose (R(2)=0.24, p<0.001) but neither by PPG(MMT), duration of hyperglycemia, S.D.-score nor MAGE. CGMS and meal test provide the tools for complete characterization of glycemia in type 2 diabetes. In well-controlled type 2 diabetes, HbA1c correlates with chronic hyperglycemia but not with glucose variability. Our data suggest that chronic sustained hyperglycemia and glucose fluctuations are two independent components of dysglycemia in diabetes.     

The glycemic index and cardiovascular disease risk

Postprandial hyperglycemia is increasingly recognized as an independent risk factor for cardiovascular disease. Glycemic “spikes” may adversely affect vascular structure and function via multiple mechanisms, including (acutely and/or chronically) oxidative stress, inflammation, low-density lipoprotein oxidation, protein glycation, and procoagulant activity. Postprandial glycemia can be reliably predicted by considering both the amount and type of carbohydrate. In particular, the glycemic index (GI), a measure of postprandial glycemic potency weight for weight of carbohydrate, has provided insights that knowledge of the sugar or starch content has not. In prospective observational studies, dietary GI and/or glycemic load independently predict cardiovascular disease, with relative risk ratios of 1.2 to 1.7 comparing highest and lowest quintiles. In randomized controlled trials in overweight subjects, diets based on low-GI carbohydrates have produced better cardiovascular-related outcomes than conventional low-fat diets. Taken together, the findings suggest that health professionals may be able to improve cardiovascular outcomes by recommending the judicious use of low-GI/glycemic load foods.     

Postprandial glycemic variations of pregnancy in diabetes

Postprandial blood glucose peaks are essential to consider in the high-risk situation featured by pregnancy in diabetic women, through several aspects. First, from a diagnostic point of view, post-stimulative situation offers the optimal sensitivity and specificity for a proper gestational diabetes screening. Next, when considering foetomaternal complications, third term postprandial hyperglycemia is highly predictive of child birth weight. Last, regarding metabolic monitoring, taking postprandial blood glucose into account leads to increasing insulin dosage, improving final term HbA1c and, finally, a lower average birth weight. However, it is mandatory for a proper management to avoid borderline glycemia, as blood glucose peaks are useful for fetal growth.     

Lower 1,5-anhydroglucitol is associated with adverse clinical events after percutaneous coronary intervention

Diabetes mellitus and impaired glucose tolerance are well-known risk factors for coronary artery disease (CAD) and adverse clinical events after percutaneous coronary intervention (PCI). Postprandial hyperglycemia is an important risk factor for CAD and serum 1,5-anhydroglucitol (1,5-AG) reflects postprandial hyperglycemia more robustly than hemoglobin (Hb)A1c. We aimed to clarify the relationship between serum 1,5-AG level and adverse clinical events after PCI. We enrolled 141 patients after PCI with follow-up coronary angiography. We evaluated associations between glycemic biomarkers including HbA1c and 1,5-AG and cardiovascular events during follow-up. Median serum 1,5-AG level was significantly lower in patients with any coronary revascularization and target lesion revascularization (TLR) [13.4 µg/ml (first quartile, third quartile 9.80, 18.3) vs. 18.7 (12.8, 24.2), p = 0.005; 13.4 µg/ml (10.2, 16.4) vs. 18.7 (12.9, 24.2), p = 0.001, respectively]. Multivariate logistic analysis showed lower 1,5-AG was independently associated with any coronary revascularization and TLR (odds ratio 0.93, 95 % confidence interval 0.86–0.99, p = 0.04; 0.90, 0.81–0.99, p = 0.044, respectively), whereas higher HbA1c was not. Postprandial hyperglycemia and lower 1,5-AG are important risk factors for adverse clinical events after PCI.     

Postprandial and basal glucose in type 2 diabetes: assessment and respective impacts

The independent contribution of postprandial glucose (PPG) excursions to the overall glucose exposure and its role in the development of both micro- and macrovascular complications of diabetes remain subject to continuing debate in type 2 diabetes. Discussion continues on whether postprandial hyperglycemia is the main contributor to the overall hyperglycemia in fairly well-controlled individuals, whereas basal hyperglycemia becomes the preponderant contributor in poorly controlled patients. The concern about the role of PPG as a risk factor for diabetes complications is related to the controversial data obtained in individuals with impaired glucose tolerance. It remains, however, that the total glucose exposure as reflected by hemoglobin A1c (HbA1c) levels is an undoubted major vascular risk factor. Excluding the contribution of PPG is nonsensical. In support of this position is the fact that the absolute impact of PPG on HbA1c, expressed as percentage levels of HbA1c, remains constant at 1% across the HbA1c continuum in non-insulin-treated type 2 diabetes patients. This key feature clearly depicts the absolute contribution of PPG in contrast to its relative contribution and better explains why PPG contributes to the excess of glycation with the basal hyperglycemia.     

Upper gastrointestinal function and glycemic control in diabetes mellitus

IntrodUctIon Diabetes and its long-term complications, which include cardiovascular, renal, neurologic, and ophthalmic dis- ease, represent a major cause of morbidity and mortality throughout the world[1]. The prevalence of both type 1 (insulin-dependant)…     

Can blood glucose self-monitoring improve treatment outcomes in type 2 diabetes?

BACKGROUND: Increased cardiovascular risk in diabetes cannot be attributed to the higher prevalence of classic risk factors. IMPORTANCE OF POSTPRANDIAL HYPERGLYCEMIA: Most of the cardiovascular risk factors have shown to be directly related to the degree of postprandial glycemia (PPG). PPG should be recognized as a marker for the increased risk of cardiovascular disease. ASSESSMENT OF TARGETS FOR GLYCEMIA CONTROL: Two important methods available-self-monitoring of blood glucose (SMBG) reveals immediate hour-to-hour blood glucose, while long-term glycemia is assessed by HbA1c. Reducing PPG and glycemia excursions is as important as lowering fasting plasma glucose and HbA1c levels. EFFECTIVENESS OF SMBG: SMBG plays a key role in diabetes care, and has proven to be effective for insulin treated type 2 diabetic patients. Debate continues on the effectiveness of SMBG in non-insulin treated type 2 diabetes. Whether non-insulin treated type 2 diabetic patients benefit from SMBG, a large-scale randomized controlled trial with the follow-up period to investigate long-term effects should be carried out. A general recommendation is that insulin treated patients perform SMBG at least three times per day. SMBG frequency for non-insulin users should be individualized to treatment regimen and level of control.