Growth hormone and carbohydrate metabolism in myocardial infarct]

The indices of somatotropin were determined in myocardial infarction patients by means of immunological techniques, and those of blood sugar by the Hagedorn--Jensen technique. Single growth hormone determinations were conducted in 40 myocardial infarction patients, aged 45 to 80 years, with different periods from the onset of the disease. In 23 patients the somatotropin and blood sugar indices were studied dynamically on the 1st--3rd and 7th--10th days of the infarction. An equal number of patients was subjected on the 28th--30th day of the disease to determinations of growth hormones secretion in conjunction with the glucose-tolerance test (on an empty stomach, and 1 and 3 hours following the administration of 100 g of glucose). The conducted investigation demonstrates that single determinations of somatotropin fail to give grounds for conclusions as to its secretion due to the wide individual variations of this parameter. The dynamics of somatotropin content depends on the severity of the myocardial infarction in the given patient and does not correlate with the changes in the blood sugar level. Five types of somatotropin secretion were distinguished with the glucose-tolerance test. Patients with decreased tolerance of the carbohydrates tend to have a torpid and perverted types of somatotropin secretion.     

Content of immunoreactive insulin and catecholamines in blood plasma and disorders of carbohydrate metabolism in patients with myocardial infarct]

The blood plasma level of immunoreactive insulin was studied dynamically be means of radioimmunoassay and the blood sugar level by the orthotoluidine technique in 70 patients with large-focal myocardial. In 48 of them the plasma level of catecholamines was determined simultaneously by the fluorimetric technique. The control group of patients was composed of ischaemic heart disease cases without myocardial infarction. Patients with acute myocardial infarction appeared to have hypercatecholaminemia and insufficient insulin excretion: 65.4% of acute myocardial infarction patients having an absolute insulin insufficiency, and 34.6% -- a relative one. The most distinct hypercatecholaminemia and insulin secretion inhibition were observed in those with acute myocardial infarction and congestive heart failure. In patients with an absolute insulin insufficiency the plasma level of noradrenaline was considerably and statistically significantly higher, than in those with a relative insulin insufficiency. In patients with high hypercatecholaminemia the insulin secretion inhibition was noted more often and was more severe. In patients with acute myocardial infarction and an absolute insulin insufficiency complications, such as congestive heart failure and rhythm and conductivity disorders, were more frequent and lasting, than in those with a relative insulin insufficiency. During the acute period of myocardial infarction the disorders in the carbohydrate metabolism were observed in 82.2% of the cases, and were more distinct in those with an absolute insulin insufficiency. By the 20th--22nd postinfarction day the carbohydate metabolism disorders persisted in 35% of the myocardial infarction patients.     

冠心病介入治疗后血糖水平对临床疗效及预后的影响

目的 观察冠心病介入治疗后患者血糖水平对临床疗效以及预后的影响。方法 将来咸阳医院就诊的120例冠心病介入治疗患者,按患者血糖水平,将其分为3组:非糖尿病组〔空腹血糖（FPG）<7.0 mmol/L,n=30〕、糖尿病低血糖组（8.0 mmol/L>FPG≥7.0 mmol/L,n=50）和糖尿病高血糖组（FPG≥8.0 mmol/L,n=40）。记录临床资料以及分析生化指标〔血清总胆固醇(TC)、低密度脂蛋白胆固醇（LDL-C）、载脂蛋白水平、三酰甘油（TG）、纤维蛋白原（Fib）以及尿酸（UA）水平〕,并分析急性心肌梗死并发症的发生率。结果 糖尿病高血糖组TC、LDL-C、载脂蛋白、左室舒张末内径水平分别为（4.9±1.4）mmol/L、（3.3±0.9）mmol/L、（1.6±0.5）mmol/L和（55±7）mm,显著高于糖尿病低血糖组的（4.1±0.8）mmol/L、（2.7±0.5）mmol/L、（1.1±0.4）mmol/L、（51±8）mm (均P<0.05),糖尿病低血糖组相应指标水平显著高于非糖尿病组的（3.7±1.2）mmol/L、（2.2±0.6）mmol/L、（0.7±0.1）mmol/L和（44±7）mm(均P<0.05)。3组TG、Fib以及UA水平无统计学差异。非糖尿病组患者术后发生急性心肌梗死（AMI）、AMI并发恶性心律失常、AMI并发心衰以及病死率分别为:13%、10%、10%和3%;糖尿病低血糖组为:24%、26%、24%和8%。糖尿病高血糖组为30%、32%、30%和12%。与非糖尿病组比较,糖尿病低血糖组和糖尿病高血糖组相应指标水平均显著升高(均P<0.05),且糖尿病高血糖组指标水平较糖尿病低血糖组高(均P<0.05)。经过非条件Logistic回归分析后,血糖的OR值（95%CI）为4.6(0.8~21.7),P<0.05,结果显示血糖水平是独立的预测因素。结论 冠心病患者的血糖水平对于患者的临床疗效和预后有一定影响。     

Various mechanisms of disorders of carbohydrate metabolism in myocardial infarct]

A group of 112 patients with acute myocardial infarction was studied. Methods for determining the content of immunoreactive insulin, uric acid, triglycerides, and sugar in blood on a fasting stomach and under conditions of carbohydrate load in dynamics were used. The data obtained show that patients, mainly those with uncomplicated myocardial infarction, are marked by relative insulin insufficiency as well as by a high level of triglycerides and uric acid in the acute period of the disease. The causal relationship between hyperuricemia, hypertriglyceridemia, and carbohydrate metabolism disorders is discussed.     

Comparison of the nature of insulin secretion, determined by radioimmune and biological methods, normally and in diabetes mellitus]

The character of insulin secretion curves was studied under normal conditions and in diabetic patients during glucose tolerance test. Patients with diabetes mellitus were divided into the following groups: donors, patients with reduced glucose tolerance and with manifest diabetes. Insulin was determined in paralleled by 3 methods (biological ones and radioimmune one). An increase in immunoreactive insulin was seen in the group of patients with reduced glucose tolerance during the whole course of the test with a peak at the 30th minute and a simultaneous reduction and a sharp fall at the 60th minute of free insulin level. Apparently biologically less active forms of insulin and proinsulin are secreted which possess immunological properties and react well with antibodies to insulin.     

Impact of Diabetes on Postinfarction Heart Failure and Left Ventricular Remodeling

Diabetes mellitus, the metabolic syndrome, and the underlying insulin resistance are increasingly associated with diastolic dysfunction and reduced stress tolerance. The poor prognosis associated with heart failure in patients with diabetes after myocardial infarction is likely attributable to many factors, important among which is the metabolic impact from insulin resistance and hyperglycemia on the regulation of microvascular perfusion and energy generation in the cardiac myocyte. This review summarizes epidemiologic, pathophysiologic, diagnostic, and therapeutic data related to diabetes and heart failure in acute myocardial infarction and discusses novel perceptions and strategies that hold promise for the future and deserve further investigation.     

Oral modified insulin (HIM2) in patients with type 1 diabetes mellitus: results from a phase I/II clinical trial

An effective, orally administered insulin product would be of substantial benefit in the treatment of patients with diabetes mellitus. This phase I/II clinical trial was the first to investigate the safety and effectiveness of a single oral dose of a modified human insulin in controlling postprandial plasma glucose levels in patients with type 1 diabetes mellitus who were receiving basal continuous subcutaneous insulin infusion (CSII) therapy. Fourteen patients with type 1 diabetes mellitus were evaluated in an open-label, 2-center, dose-escalation, nonrandomized study of oral hexyl-insulin monoconjugate 2 (HIM2). After an overnight fast and prior to receiving a standardized meal (50% carbohydrates, 30% fat, 20% proteins; 650 calories), the patients received either no additional insulin (day 1), or 0.5 to 1.0 mg/kg of HIM2 (day 2). All patients received a basal insulin regimen by CSII throughout the study. Blood samples were collected for determination of glucose and insulin levels for 240 minutes post-dose. The postprandial glucose excursion versus time curves showed clear reductions in glucose values after both HIM2 doses (day 2) relative to no treatment (day 1), although the differences in the reductions were not statistically significant. When the data for both HIM2 doses were pooled, a statistically significant effect of HIM2 on glucose excursion (as measured by AUCex(30-240)) was observed. Mean +/- SD values for AUCex(30-240) were 501.35 +/- 124.1 mg. h/dL after no treatment and 375.81 +/- 215.5 mg. h/dL after HIM2 (Wilcoxon signed-rank test, P =.042). The results of this study suggest that oral HIM2, when added to a basal insulin regimen, was safe and may prove effective in controlling postprandial hyperglycemia in patients with type 1 diabetes mellitus. Further clinical investigation is necessary.     

Characteristics of hormonal regulation in patients with ischemic heart disease after the insulin test combined with physical load

Nine normal subjects and 6 coronary patients (aged 26 to 53 years) who had survived myocardial infarction more than 3 years before and showed no clinical signs of heart failure, obesity, hypertension and diabetes mellitus, while having normal glucose tolerance test values, were exposed to the insulin test in combination with physical stress in the presence of clinically manifest hypoglycemia. Plasma and erythrocyte glucose and immunoreactive insulin, and urinary excretion of catecholamines were measured. Coronary patients showed considerably increased erythrocyte immunoreactive insulin levels, recorded immediately upon discontinuation of exercise, while their sympathoadrenal hormonal activation was less significant, as compared to normal subjects. The combination of the insulin test and exercise in coronary patients with normal glucose tolerance values helps to detect disturbances of regulatory mechanisms at the erythrocyte level and can be used as an adjuvant method for the assessment of latent carbohydrate metabolic disorders.     

Postprandiale Blutglukoseverl?ufe in der (Insulinpumpen-)Therapie des Typ-1-Diabetes

In the treatment of diabetes mellitus type 1 prolonged postprandial hyperglycemia continues to appear after consumption of complex nutrient compositions. The extent and duration of the increase in glucose concentration does not seem to be only due to the supply of carbohydrates. The therapy of type 1 diabetes patients should therefore consider insulin cover for the fat and protein components of a meal as well as carbohydrates to optimize postprandial glucose values. Whether the presented concept for insulin cover of fat and protein in people with diabetes mellitus type 1 with multiple insulin injections is transferable and whether it can lead to improvement in postprandial glucose values even in people with other forms of diabetes needs further investigations.     

Accelerating impact of diabetes mellitus on mortality in the years following an acute myocardial infarction. TRACE Study Group. Trandolapril Cardiac Evaluation.

AIMS: The development of risk associated with diabetes mellitus during long-term follow-up after a myocardial infarction has not been studied in detail. We have studied time-related changes of risk of death during 10 years of follow-up in a cohort of patients not treated with thrombolytic therapy (the Glostrup cohort) and during 6 years in a cohort receiving such treatment in 40% of cases (the TRACE cohort). METHODS: A subgroup analysis of two cohorts: the Glostrup cohort, which consisted of consecutive cases of acute myocardial infarction who were admitted to one hospital between 1979 and 1983; the TRACE cohort which was comprised of patients with an acute myocardial infarction screened for entry into the Trandolapril Cardiac Evaluation study between May 1990 and June 1992. The Glostrup cohort consisted of 1954 patients and follow-up was for 10 years, The TRACE cohort consisted of 6676 patients and follow-up was for 6 years. Outcome measure was total death. RESULTS: A diagnosis of diabetes mellitus was present in 12% of the two study populations. In multivariate analysis, diabetes mellitus had an independent adverse effect on mortality which increased with time. In the Glostrup cohort risk ratio between day 0 and day 30 was 1.17 and increased to 2.51 (P=0.0002) 7-9 years after discharge from hospital. A similar increase in the risk ratio of diabetes mellitus on mortality was observed in the TRACE cohort (risk ratio for days 0-30 was 1.03, and for years 4-6 was 1.74 (P=0.0001). CONCLUSION: Diabetes mellitus has no independent influence on mortality immediately following an acute myocardial infarction, but has an important influence on long-term mortality which increases with time. The implication is that the effect of intervention against diabetes in patients with acute myocardial infarction and diabetes mellitus must be evaluated over a long course of time.     

alpha-Glucosidase inhibition improves postprandial hyperglycemia and decreases insulin requirements in insulin-dependent diabetes mellitus

In patients with diabetes mellitus, delayed increases in circulating insulin levels followed by prolonged hyperinsulinemia due to slow absorption of subcutaneously administered insulin hinders maintenance of euglycemia. To determine whether a delay in carbohydrate absorption would increase the effectiveness of subcutaneous insulin in controlling postprandial hyperglycemia in patients with insulin-dependent diabetes mellitus and whether it could allow insulin to be taken immediately prior to meals, the effects of an alpha-glucosidase inhibitor (Acarbose Boyer AG, Wuppertal, Germany) on postprandial plasma glucose profiles were determined in six subjects with insulin-dependent diabetes when a subcutaneous insulin infusion was started immediately or 30 minutes prior to meal ingestion. When 25% less insulin (9 v 12 units) was given along with Acarbose 30 minutes prior to meal ingestion, postprandial hyperglycemia decreased by 45% (areas under the curve, AUC, 8193 +/- 1960 v 14783 +/- 2260 mg/dL X min, P less than 0.02). When similar amounts of insulin (12 units) were given immediately prior to meal ingestion, postprandial hyperglycemia decreased 55% (AUC 6187 +/- 2240 v 13642 +/- 1579 mg/dL X min, P less than 0.001). These results indicate that delay in carbohydrate absorption improves the effectiveness of subcutaneous insulin in controlling postprandial hyperglycemia in patients with insulin-dependent diabetes mellitus and may permit satisfactory postprandial glycemic control when insulin is administered immediately prior to meal ingestion. Thus, an agent like Acarbose, which delays carbohydrate absorption, may be useful as an adjunct to insulin in the treatment of diabetes mellitus.     

Nateglinide may increase high-molecular weight adiponectin in type 2 diabetic patients with hypoadiponectinemia

We studied the effects of nateglinide on serum adiponectin in 26 patients with type 2 diabetes mellitus. The changes in serum insulin at 30min significantly correlated with those in serum high-molecular weight adiponectin. Nateglinide may ameliorate hypoadiponectinemia as well as postprandial hyperglycemia in patients with type 2 diabetes mellitus.     

老年糖尿病伴急性心肌梗死的特点及预后

目的：探讨糖尿病与非糖尿病急性心肌梗死（AMI）患住院期间病情,预后以及病死率的差异,方法：选择1994－1999年间住院糖尿病心肌梗死患18例（A组）,并与同期住院非糖尿病心肌梗死患92例（B组）作比较。结果：糖尿病AMI患心肌梗死症状严重,病死率高,病死率与心肌梗死前血糖水平有关,结论：糖尿病患急性心肌梗死发病率高,并发症多,病死率高,需积极控制血糖水平。     

Nateglinide may increase high-molecular weight adiponectin in type 2 diabetic patients with hypoadiponectinemia

We studied the effects of nateglinide on serum adiponectin in 26 patients with type 2 diabetes mellitus. The changes in serum insulin at 30 min significantly correlated with those in serum high-molecular weight adiponectin. Nateglinide may ameliorate hypoadiponectinemia as well as postprandial hyperglycemia in patients with type 2 diabetes mellitus.     

Diabetes and stress hyperglycemia associated with myocardial infarctions at an urban municipal hospital: prevalence and effect on mortality

Municipal hospitals in large cities provide care for patients from immigrant and mixed ethnic communities that are at high risk for diabetes. Both diabetes and stress hyperglycemia increase the risk of adverse outcome after myocardial infarctions, and the impact of stress hyperglycemia on the outcome of myocardial infarctions in this particular setting has not been previously studied. We therefore undertook a retrospective cohort study to determine the prevalence of diabetes and stress hyperglycemia in patients presenting to a university-affiliated Bronx municipal hospital with myocardial infarction, and the relationship of these conditions to the extent of coronary disease and mortality. We obtained data on 106 consecutive patients from July 1998 to April 1999 with a diagnosis-related group diagnosis of either myocardial infarction or acute coronary syndrome, in which myocardial infarction was confirmed by serum enzymes or characteristic electrocardiographic changes. Patients were followed until March 30, 2001. Measurements of clinical parameters and results of catheterization were obtained for all patients. Death rates were determined by laboratory database, direct patient contact, or data from National Death Index. Eighty percent of the cohort had either a diagnosis of diabetes (n = 45, 42% of cohort) or evidence of stress hyperglycemia (defined as serum glucose greater than 126 mg/dL at the time of admission without prior diagnosis of diabetes, n = 40, 38%). In-hospital mortality for patients with diabetes, stress hyperglycemia, or normal glucose was 20%, 15%, and 14%, respectively. Eighty-three percent of the cohort received beta blockers, and 61% of hospital survivors had catheterization. Left main or triple vessel disease was common in both patients with diabetes (52%) and patients with stress hyperglycemia (32%). Mortality at follow up (maximum follow up 3 years; mean follow up 19.6 months) was much higher in patients with either diabetes (42%) or stress hyperglycemia (52%) than normal subjects (24%). Kaplan-Meier analysis of the difference in mortality between patients with high glucose on admission and normal subjects was borderline significant (P = 0.06). Multivariate regression demonstrated that age (P = 0.020), increase in admission serum creatinine (P = 0.001), and reduction in either ejection fraction (P = 0.016) or admission systolic blood pressure (P = 0.005) were significant predictors of mortality. Glycemic status and sex were not independently associated with death after controlling for these other factors. These results show that the prevalence of both diabetes and stress hyperglycemia on presentation with myocardial infarction is strikingly high in this immigrant, mixed ethnic, urban population. Patients with diabetes and stress hyperglycemia had advanced disease on presentation and much higher mortality at 2 to 3 years than those with normal blood glucose. The mortality difference is the result of older age and more advanced disease rather than hyperglycemia per se.     

Dynamics of the level of insulin in blood in response to hydrocortisone loading in myocardial infarction

To elucidate the details of carbohydrate metabolism in the course of acute myocardial infarction, baseline blood insulin and glucose levels and changes thereof in response to acute hydrocortisone loading were investigated in patients with acute transmural and large-focal myocardial infarction that had developed in the presence of essential hypertension (patients with diabetes mellitus were excluded from the study). Basal hypoinsulinemia was discovered on Day 1 of myocardial infarction in these patients. On Days 3-5 of infarction, blood insulin concentration was increased significantly. The pattern of hydrocortisone-induced changes in glucose level suggests glucocorticoid involvement in "urgent" glucose mobilization. The state of and associations between the two hormonal systems throughout acute myocardial infarction are discussed on the basis of changes in insulin and glucose levels under hydrocortisone load.     

无糖尿病史急性心肌梗死患者入院早期动态血糖谱

对连续111例急性心肌梗死患者采用动态血糖监测方法观察早期血糖波动情况,根据血糖代谢紊乱程度依次分为血糖正常组(30例)、一过性血糖升高组(36例)和持续性血糖升高组(45例).与其他2组比较,持续性血糖升高组患者平均血糖、血糖水平标准差、最大血糖波动幅度、平均血糖波动幅度和日间血糖平均绝对差显著升高(均P<0.01),男性较少(P<0.05),陈旧性心梗、高血压更多(P<0.05),谷草转氨酶、肌酸磷酸激酶、肌酸磷酸激酶同工酶、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、HbA1C、C反应蛋白更高(均P<0.01).

Abstract：

One hundred and eleven patients with acute myocardial infarction and without known diabetes mellitus who underwent continuous glucose monitoring were divided into normoglycemia(n = 30),transient hyperglycemia(n = 36),and persistent hyperglycemia(n = 45)groups.Compared with other two groups,higher mean blood glucose,standard deviation of blood glucose,largest amplitude of glycemic excursions,mean amplitude of glycemic excursions,and absolute mean of daily differences were observed in the patients with persistent hyperglycemia group(all P<0.01),who were more likely to be female with the history of hypertension and old myocardial infarction(all P<0.05).It was shown that the levels of aspartate aminotransferase,creatine phosphokinase(CK),CK-MB,total cholesterol,triglyceride,low-density lipoprotein cholesterol,HbA1C,and C reactive protein levels were higher in these patients(P<0.01).     

Clinical Characteristics,Left and Right Ventricular Ejection Fraction,and Long-term Prognosis in Patients with Non-insulin-dependent Diabetes Surviving an Acute Myocardial Infarction

Patients with diabetes mellitus have a high morbidity and mortality from acute myocardial infarction, the reason for which is not fully understood. The relationship between congestive heart failure symptoms, left ventricular ejection fraction, and long-term mortality was examined in 578 hospital survivors of acute myocardial infarction, 47 of whom had Type 2 (non-insulin-dependent) diabetes mellitus. None of the patients were treated with insulin. The prevalence of congestive heart failure during hospitalization was similar in patients with and without diabetes, although mean diuretic dose was higher in the former patients. Left and right ventricular ejection fraction was measured with radionuclide ventriculography in the second week after acute myocardial infarction. At discharge from the coronary care unit, patients with and without diabetes had similar left ventricular ejection fraction (with diabetes: median 46% vs without diabetes: median 43%; p = 0.89). Median right ventricular ejection fraction (62 %) was within normal limits in both groups and did not differ statistically. Survival data were obtained for all patients. The 5-year mortality was increased in patients with diabetes compared with non-diabetic patients independent of left ventricular ejection fraction. Univariate analysis showed that the cumulative 5-year mortality rate was 53 % in the group with diabetes compared with 43% in the non-diabetic group (p = 0.007). Using multivariate regression analysis presence of diabetes was found to have a significant association with long-term mortality after myocardial infarction, that was independent of age, history of hypertension, congestive heart failure symptoms during hospitalization or of either left or right ventricular ejection fractions at discharge. We conclude that the excess mortality in patients with non-insulin-dependent diabetes mellitus is not explained by available risk markers after myocardial infarction. Even though left ventricular ejection fraction and serum creatinine did not differ significantly, the apparent higher dose of Frusemide in patients with than without non-insulin-dependent diabetes mellitus might indicate that heart failure, if present, is more severe in patients with than in those without diabetes. The importance of diastolic dysfunction in this context needs to be determined.     

Serum glucagon and insulin levels and their relationship to blood glucose values in patients with acute myocardial infarction and acute coronary insufficiency

Fasting serum glucagon, insulin and glucose levels were determined in 25 patients with acute myocardial infarction 1 day after their admission to the hospital and, in most instances, once again at a later date. Two control groups were used, one with coronary insufficiency but without myocardial infarction (10 patients) and the other without clinically recognizable coronary artery disease (12 patients). Serum glucagon levels were significantly higher in the patients with acute myocardial infarction on admission (121.6 ± 15.3 pg/ml) than in the other two groups and highest in patients with acute myocardial infarction and cardiogenic shock (239.3 ± 31 pg/ml, p < 0.001). Glucagon levels were elevated even in the three patients with cardiogenic shock who were not receiving catecholamines. Serum glucose values were also significantly higher in patients with acute myocardial infarction (155 ± 13.9 mg/100 ml), but serum insulin levels were not significantly different from those in patients with coronary insufficiency. These data suggest that the hyperglycemia of patients with acute myocardial infarction may be in part due to hyperglucagonemia.     

Alteration in risk factor accumulations of acute myocardial infarction during the last one decade: analysis of patients admitted in Coronary Care Unit

The present study was undertaken to determine accumulation of risk factors in acute myocardial infarction during two periods of 2002 and 1990-1991. We collected 173 and 153 patients with acute myocardial infarction in 2002 and 1990-1991, respectively, and analyzed the history of multiple risk factors, including diabetes mellitus, impaired glucose tolerance, hyperlipidemia, hypertension and obesity, and laboratory findings. The numbers and their percentages of all the risk factors increased in 2002 compared with 1990-1991. According to plasma glucose level, the patients who had type 2 diabetes mellitus, and impaired fasting glucose or impaired glucose tolerance had increased markedly from 41 to 65%. Multiple accumulation of risk factors had increased during the last one decade, and only one or no risk factor per se was not the case in the patients with acute myocardial infarction. Hyperlipidemia and hypertension became fairly controlled in the patients, but not hyperglycemia in type 2 diabetes mellitus in the period of 2002. These findings may indicate that increased multiple accumulation of risk factors accelerates the occurrence of acute myocardial infarction in 2002 as compared to 1990-1991.