Quantitative approach to the histopathology of the biopsied right ventricular myocardium in patients with diabetes mellitus

For the purpose of studying the clinicopathology of the biopsied myocardium in patients with diabetes mellitus, the diameter of right ventricular myocardial cells and diffuse perimysial fibrosis of biopsied myocardium were measured quantitatively. Seven healthy controls and nine diabetic patients without hypertension or coronary arterial disease were subjected to this study. The degree of diabetic complications was mild to moderate. The diameter of myocardial cells was measured and the degree of diffuse perimysial fibrosis was assessed by the point-counting method using a square grid, in which the distance between the points was 10 micron. Over 2000 points which lay on the longitudinally cut myocardial cells and on the interstitial fibrosis stained by the Mallory-Azan method were measured. Percentage fibrosis was calculated according to the formula: percentage fibrosis = (points lying on the interstitial fibrosis)/[(points lying on the myocardial cell) + (points lying on the interstitial fibrosis)] X 100. The results were as follows. The mean diameter of right ventricular myocardial cells in patients with diabetes mellitus was significantly larger than that of controls (P less than 0.01). The percentage fibrosis of diabetic patients was significantly higher than that of controls (P less than 0.01). There was no significant correlation between the histopathological measurements and clinical features. It is concluded that hypertrophy of myocardial cells and interstitial fibrosis of the myocardium exist even in mild diabetes mellitus.     

Clinical and morphological features of human hypertensive-diabetic cardiomyopathy

The existence of a specific cardiomyopathy secondary to diabetes mellitus is controversial. During a 2-year period, we had the opportunity to examine nine diabetic patients at autopsy who had clinically severe congestive heart failure and minimal extramural coronary artery atherosclerosis. Unexpectedly, all nine patients were found to be hypertensive. Accordingly, we initiated a detailed study of the clinical and morphological features of this group, and compared the findings to age-matched autopsied subjects with either isolated hypertension, isolated diabetes mellitus, or no heart disease.The study of the hypertensive-diabetic hearts revealed severe interstitial fibrosis, focal or confluent scars, and extensive myocytolytic activity. Comparison with the diabetic, hypertensive, and normal groups showed statistically significant differences in regard to the degree of interstitial and focal scarring, and the presence of myocytolysis. Only the hypertensive group had minimal interstitial scarring. There were no statistical differences in the small vessel changes between the four groups, although subjectively the hypertensive and hypertensive-diabetic patients had more severe disease.It is concluded that the association of diabetes mellitus and hypertension in the absence of significant coronary artery atherosclerosis may lead to a severe cardiomyopathy. Although the etiology of myocardial failure in this syndrome is uncertain, the degree of myocardial fibrosis and the frequency of myocytolytic lesions possibly related to catecholamine hypersensitivity, are potential explanations. Several studies suggesting that hypertension has adverse consequences in diabetes, as well as an animal model of hypertensive-diabetic cardiomyopathy, support our conclusion that cardiomyopathy associated with diabetes mellitus is a specific entity which may be secondary to the combined effects of diabetes and hypertension on the myocardium.     

Diabetic cardiomyopathy

Diabetic cardiomyopathy is a myocardial disease caused by diabetes mellitus unrelated to vascular and valvular pathology or systemic arterial hypertension. Clinical and experimental studies have shown that diabetes mellitus causes myocardial hypertrophy, necrosis, and apoptosis, and increases interstitial tissue. The pathophysiology of diabetic cardiomyopathy is incompletely understood. It appears that metabolic perturbations such as hyperlipidemia, hyperinsulinemia, hyperglycemia, and changes in cardiac metabolism are involved in cellular consequences leading to increased oxidative stress, interstitial fibrosis, myocyte death, and altered intracellular ions transient and calcium homeostasis. Clinically, an early detection of asymptomatic diastolic dysfunction is possible. When patients develop signals and symptoms of heart failure, isolated diastolic dysfunction is usually detected. Systolic dysfunction is a late finding. Treatment of heart failure due to diabetic cardiomyopathy is not different from myocardiopathies of other etiologies and must follow the guidelines according to ventricular function, whether diastolic or diastolic and systolic impairment.     

Diabetische Kardiomyopathie

Diabetic cardiomyopathy is a myocardial disease caused by diabetes mellitus unrelated to vascular and valvular pathology or systemic arterial hypertension. Clinical and experimental studies have shown that diabetes mellitus causes myocardial hypertrophy, apoptosis and necrosis, and increases interstitial tissue. The pathophysiology of diabetic cardiomyopathy is incompletely understood and several mechanistical approaches are under debate. Metabolic impairments like hyperglycemia, hyperlipidemia, hyperinsulinemia, and alterations in the cardiac metabolism lead to structural and functional changes which show cellular effects leading to increased oxidative stress, interstitial fibrosis, myocyte death, and disturbances in ion transport and homeostasis. Diastolic dysfunction which consecutively results in systolic dysfunction with increased left ventricular volume and reduced ejection fraction is an early diagnostic parameter. Treatment of diabetic cardiomyopathy does not differ from myocardiopathies of other etiologies and therefore has to follow the appropriate guidelines. Early intervention to reverse metabolic toxicity is the most effective method of prevention.     

糖尿病人肝脏的超微结构研究

研究糖尿病（ＤＭ）人肝脏的超微结构变化。对２０例ＤＭ患者行肝穿活检，所取标本行光、电镜观察。光镜下见核内糖原空洞、脂肪变性及间质纤维化。电镜下见：核内糖原颗粒；胞浆糖原颗粒增多；粗面内质网（ＲＥＲ）脱粒；滑面内质网（ＳＥＲ）扩张；线粒体（Ｍｉ）肿胀，嵴紊乱，结构消失或电子密度增高，结构不清；脂肪变性；间质纤维化。ＤＭ肝超微结构改变中最具特征性的是核内糖原颗粒。     

Abnormal p38 mitogen-activated protein kinase signalling in human and experimental diabetic nephropathy

Aims/hypothesis Inflammation and fibrosis are pathological mechanisms that are partially regulated by cell signalling through the p38 mitogen-activated protein kinase (MAPK) pathway. Elements of the diabetic milieu such as high glucose and advanced glycation end-products induce activation of this pathway in renal cells. Therefore, we examined whether p38 MAPK signalling is associated with the development of human and experimental diabetic nephropathy.Methods Immunostaining identified phosphorylated (active) p38 MAPK in human biopsies with no abnormality (n=6) and with Type 2 diabetic nephropathy (n=12). Changes in kidney levels of phosphorylated p38 were assessed by immunostaining and western blotting in mice with streptozotocin-induced Type 1 diabetes that had been killed after 0.5, 2, 3, 4 and 8 months, and in Type 2 diabetic db/db mice at 2, 4, 6 and 8 months of age.Results Phosphorylated p38 was detected in some intrinsic cells in normal human kidney, including podocytes, cortical tubules and occasional interstitial cells. Greater numbers of these phosphorylated p38+ cells were observed in diabetic patients, and phosphorylated p38 was identified in accumulating interstitial macrophages and myofibroblasts. A similar pattern of p38 activation was observed in both mouse models of diabetes. In mice, kidney levels of phosphorylated p38 increased (2–6 fold) following the onset of Type 1 and Type 2 diabetes. In both mouse models, interstitial phosphorylated p38+ cells were associated with hyperglycaemia, increased HbA₁c levels and albuminuria. Further assessment of streptozotocin-induced diabetic nephropathy showed that interstitial phosphorylated p38+ cells correlated with interstitial fibrosis (myofibroblasts, collagen).Conclusions/interpretation Increased p38 MAPK signalling is a feature of human and experimental diabetic nephropathy. Time course studies in mouse models suggest that phosphorylation of p38 plays a pathological role, particularly in the development of interstitial fibrosis.Abbreviations ECL enhanced chemiluminescence - MAPK mitogen-activated protein kinase - p-p38 phosphorylated p38     

Non-invasive diagnostic imaging techniques as a window into the diabetic heart: a review of experimental and clinical data.

Epidemiological and clinical studies show a clear association of diabetes mellitus with congestive heart failure and cardiovascular events independent of blood pressure and ischemic heart disease. The definition of 'diabetic cardiomyopathy' as a clinical entity, however, relies on distinct myocellular and interstitial alterations found in the myocardium of patients with diabetes. The histological findings comprise myocellular hypertrophy, thickening of capillary basement membranes, interstitial fibrosis and rarification of mitochondria on the ultrastructural level. For clinical routine, early detection of diabetic cardiomyopathy seems crucial for identification of patients at cardiovascular risk since the prevalence of heart failure in individuals with diabetes is markedly increased. Recent technical developments in cardiac magnetic resonance imaging (MRI), echocardiography as well as nuclear scintigraphy have advanced the diagnostic applications for the detection of diabetic heart disease. This review aims to present distinct aspects of diabetic cardiomyopathy that were identified using non- invasive imaging techniques. Due to the wide availability and the low costs of echocardiography, it is the most frequently used imaging technique to detect left ventricular dysfunction in patients with diabetes. MRI on the other hand can provide assessment of myocardial structure with higher spatial resolution and allows objective assessment of left ventricular function. This makes MRI an attractive alternative for the detection of discrete alterations, particularly in patients with poor echogenic windows. Finally, nuclear scintigraphy can provide information on cardiac autonomic integrity and accurately detect defects in autonomic control, which are considered a major cardiovascular risk factor in patients with diabetes.     

Ultrastructural changes during myocardial hypertrophy and its regression: Long-term effects of nifedipine in adult spontaneously hypertensive rats

Summary Nifedipine (20mg/kg/day) was given to 15-week-old spontaneously hypertensive rats for 20 weeks (SHR-N,n=8). Comparison was done with sex-matched 15-week-old SHR (SHR-15,n=7), untreated 35-week-old SHR (SHR-C,n=10), 15-week-old normotensive Wistar-Kyoto rats (WKY-15,n=15), and 35-week-old WKY (WKY-15,n=5). Light and electron microscopic data on the subepicardial, middle, and subendocardial layers and papillary muscles of the left ventricle were compared among the five rat groups. In SHR-N, blood pressure was significantly reduced by nifedipine, but was higher than in WKY-35 (199±11 mmHg vs 121±13mmHg). The left ventricular weight/body weight ratio was much lower in SHR-N than in SHR-C, and was even below the baseline value in SHR-15. In addition, cardiac myocyte diameter was much smaller in each myocardial layer of SHR-N than in SHR-C, and was similar to the findings in SHR-15, but still larger than in WKY-35. The interstitial area ratio was markedly reduced in SHR-N and did not differ from that in SHR-15 or even WKY-15, while capillary density was significantly greater than in SHR-C and comparable to that in WKY-35. In SHR-C, large fibrotic foci were common, and many hypertrophic cardiac myocytes showed various degenerative changes including those of mitochondria and widening of the intermyofibrillar spaces. These changes were rarely seen in SHR-N. The intracellular volume ratio of myofibrils did not differ between SHR-N and WKY-35, but was significantly decreased in SHR-C, whereas that of mitochondria did not differ between SHR-N and SHR-C or WKY-35. These findings indicate that despite only a moderate suppression of hypertension, long-term nifedipine treatment caused regression of left ventricular hypertrophy, with cardiocyte hypertrophy, interstitial fibrosis, degenerative changes, and subcellular remodeling being reversed to the baseline levels in SHR-15. In addition, the capillary density was increased to that seen in WKY-35.     

Blood pressure changes in diabetes in urban Tanzania

Little is known of the natural history of blood pressure (BP) levels in diabetic patients from sub-Saharan Africa. BP levels were therefore recorded in such patients in Dar es Salaam, Tanzania, over 2, 5, and 7 years. Hypertension was found in 5% of insulin-treated diabetes mellitus (IDDM) and 29.2% of non-insulin-dependent diabetes mellitus (NIDDM) patients at presentation with diabetes. Hypertension developed in a further 2 IDDM (3.7%) and 27 NIDDM (15.6%) patients at 2 years, and in 3 IDDM (13.0%) and 9 NIDDM (9.8%) patients at 5 years. Seven NIDDM (18.4%) patients had developed hypertension by 7 years. In NIDDM patients with normal BP initially, the mean systolic BP rose from 131 to 141 mmHg (P<0.001) 2 years later (n=146); from 131 to 138 mmHg (P<0.001) for those followed for 5 years (n=82); and from 131 to 138 mmHg (P<0.05) for those followed for 7 years (n=31). The mean diastolic BP was 83 mmHg initially and 84 mmHg (NS) for those followed for 2 years (n=146). There was no observed rise in mean diastolic BP at 5 or 7 years of follow-up. In IDDM patients without hypertension, only the systolic BP rose significantly by 5 years, from 124 to 132 mmHg (P<0.001;n=20). These changes were independent of age, sex, body mass index, and proteinuria. We conclude that: (1) in black Tanzanians, as in other ethnic groups, it is likely that hypertension is significantly associated with diabetes; (2) rates of hypertension and BP levels continue to increase with time, particularly in NIDDM subjects; and (3) BP measurements should be a regular feature of diabetes care in the African diabetic population as in other populations.     

A comparison of the pathological spectrum of hypertensive, diabetic, and hypertensive-diabetic heart disease

The hearts obtained at autopsy of 67 patients with hypertension, diabetes mellitus, or both were examined microscopically and histochemically, and the amount of fibrosis was determined. Significant differences in heart weight, interstitial fibrosis, replacement fibrosis, and perivascular fibrosis were found among the groups. The mean heart weight of the hypertensive-diabetic patients was significantly greater than that of the hypertensive patients and the diabetic patients. The amount of microscopic fibrosis increased between the groups, the lowest in hypertensive hearts, midrange in diabetic hearts, and highest in hypertensive-diabetic hearts. Total fibrosis correlated with heart weight among diabetic and hypertensive-diabetic patients and was significantly greater among patients with congestive heart failure, most of whom had histories of both hypertension and diabetes. The microscopic grade of fibrosis correlated significantly (p less than 0.01) with a quantitative, histochemical determination of the amount of collagen per milligram of total noncollagenous protein in the heart tissue. Myocardial fibrosis may contribute to the diastolic dysfunction typical of hypertensive-diabetic cardiomyopathy, in which congestive heart failure is a common sequela. The importance of hypertension in the pathogenesis of severe diabetic heart disease is discussed.     

Effects of nifedipine and moxonidine on cardiac structure in spontaneously hypertensive rats. Stereological studies on myocytes, capillaries, arteries, and cardiac interstitium.

Light and electron microscopic stereological studies were performed on the myocardium of spontaneously hypertensive rats (SHR-SP) before and after treatment with nifedipine (27 mg/kg body weight/day) and the antisympathotonic agent moxonidine (8 mg/kg body weight/day). The treated groups were compared with nontreated SHR-SP and normotensive WKY (n = 10 in each group). At the beginning of therapy (when the male SHR-SP were 6 months old), blood pressure was increased and left ventricular hypertrophy had developed whereas pathologic changes of myocardial structure were not observed. After 3 months, the nontreated hypertensive rats showed cardiac fibrosis, activation and proliferation of interstitial cells, wall thickening of intramyocardial arteries, reduced capillarization as well as focal degeneration of myocytes at the ultrastructural level. Both treatments showed similar effects on blood pressure, degree of hypertrophy, and cardiac structure. Blood pressure as well as the degree of hypertrophy were significantly reduced. As far as myocardial fibrosis, capillarization, and regressive changes of myocytes are concerned a complete normalization was observed. Furthermore, nifedipine enhanced capillary supply beyond the normal level by induction of capillary neoformation. Microarteriopathy and activation of nonvascular interstitial cells (first step in development of interstitial myocardial fibrosis) were significantly suppressed by therapy, but the level of the normotensive control could not be maintained. Additional experiments with a low dose combination therapy of nifedipine and moxonidine that did not reduce blood pressure provided evidence that hypertension is an important determinant of the alterations of intramyocardial arteries, but not of cardiac interstitial fibrosis.     

Correlation between histopathological changes and mechanical dysfunction in diabetic rat hearts

Recent clinical and experimental studies have suggested that diabetic patients may develop myocardial dysfunction in the absence of coronary heart disease and hypertension. In this study, the correlation between histopathological changes and myocardial dysfunction was studied in experimental diabetic rat hearts. Male Wistar rats were made diabetic at 9 weeks of age with a single intravenous injection of streptozotocin 50 mg/kg. The diabetic rats were studied along with age-matched control and insulin-treated rats at 4, 8, 12 and 24 weeks after the induction of diabetes to investigate isolated papillary muscle contraction and the histopathological picture simultaneously. In the isometric contractions, resting and developed tensions were similar. Time to peak tension and time to 1/2 relaxation were prolonged and the peak rate of tension rise and tension fall was depressed. On histological examination of left ventricular walls, diameters of myocytes were similar at all disease durations. Interstitial fibrosis and disarrangement of myocytes after 12 weeks were slightly increased in the diabetic hearts. Mechanical parameters did not worsen in parallel with the duration of diabetes and histological changes, but correlated with the blood glucose level. These data suggest that short-term mechanical defects in the experimental diabetic rat heart result from the metabolic disorder itself, with histopathological changes occurring later.     

Early diastolic dysfunction of the left ventricle and its relation to histopathological findings in patients with diabetes mellitus

The relation of left ventricular diastolic function and the histopathological findings of the myocardium in patients with diabetes mellitus were observed using echocardiography and endomyocardial biopsy. The subjects consisted of six diabetic patients (mean age 49.3 years) and eight normal control subjects (mean age 44.8 years). Coronary angiography had no significant stenotic lesions in their coronary arteries. Their diabetic complications were mild to moderate in severity. Echoes from the left ventricular margin of the septum and from the posterior left ventricular wall were traced on a digitizing board; then the isovolumic relaxation period, rapid filling period, slow filling period and atrial contraction period were determined to calculate fractional shortening (FS), isovolumic relaxation time (IRT), and three filling volumes (RFV, SFV and ACV). The quotients of the left ventricular filling volume and stroke volume were also determined. Right ventricular endomyocardial biopsies were performed to determine the diameters of myocytes, the percentage of fibrosis and the eccentricity e, as a parameter of the degree of myocardial dysarrangement. The results were as follows: IRT was significantly longer and RFV/SV was significantly greater in patients with diabetes mellitus than those among the controls. Also the diameters of myocytes and the percentage of fibrosis were significantly greater, while the eccentricity e was less compared to that of the controls. There were no significant correlations, among IRT, RFV/SV, the diameters of myocytes, and eccentricity e, but the percentage of fibrosis significantly correlated with IRT and RFV/SV (r = 0.62, r = -0.63). IRT and RFV/SV were mainly responsible for the percentage of fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognosis after stroke in diabetic patients. A controlled prospective study

Summary Cohorts of diabetic (n=121) and non-diabetic (n=584) patients were prospectively followed for up to ten years after having suffered from a stroke. All but six of the diabetic patients had Type 2 (non-insulin-dependent) diabetes mellitus. The diabetic patients had more risk factors associated with stroke: heart failure (p<0.001) and angina pectoris (p<0.001), than the non-diabetic patients. Neither body mass index nor blood pressure levels differed between the groups at admission. Haematocrit levels were higher in the diabetic group (p<0.01). The diabetic patients were more commonly afflicted by cerebral embolism and to a lesser extent by transient ischaemic attacks than the nondiabetic patients. When calculated by log-rank tests, the diabetic group had an increased risk of death (p<0.001), recurrent stroke (p=0.001), and of myocardial infarction (p=0.001) after the initial stroke. Autopsy-verified causes of death between the groups did not differ significantly, although half of all deaths during the period one to six months after stroke were caused by pulmonary embolism in the diabetic group. Thus, diabetes increases the risk of death after a stroke, and it also increases among stroke survivors the risk of recurrent stroke and myocardial infarction.     

Diabetic glomerulosclerosis without glucose intolerance.

The pathophysiology of the microangiopathy of diabetes mellitus is poorly understood, and the relevance of carbohydrate intolerance remains uncertain. Four patients are presented with renal abnormalities suggestive of diffuse diabetic glomeruloscierosis. These patients have no evidence of carbohydrate intolerance by standard clinical technics. A familial incidence of diabetes mellitus and delayed insulin response to an oral glucose load support a classification of prediabetes or suspected diabetes mellitus for these patients. Early intercapillary nodule formation was seen in only two of the four patients. In the absence of this infrequent pathognomonic finding, an alternate approach to the diagnosis of diabetic glomerulosclerosis is suggested. Diffuse glomerular capillary basement membrane thickening, consistently present with diabetic glomerulosclerosis, is demonstrated by measurements utilizing the latex microsphere technic. The mean glomerular capillary basement membrane thickness of these patients was 4,403 A, compared with the control value of 3.098 A (P less than 0.001). Other pathologic findings suggestive of diabetic nephropathy include efferent arteriolosclerosis and linear immunofluorescence without electron dense deposits or inflammation. Skeletal muscle capillary basement membranes of all four patients also demonstrated significant thickening. The mean value for the patients was 1,510 A, as compared with a control value of 961 A (P less than 0.001). The importance of this muscle capillary basement membrane thickening to the diagnosis of diabetic microangiopathy is discussed. The pathologic alterations in the renal biopsy specimens and the demonstration of muscle capillary basement membrane thickening strongly suggest that diabetic glomerulosclerosis may occur in the absence of overt clinical carbohydrate intolerance.     

Examination of two genetic polymorphisms within the renin-angiotensin system: no evidence for an association with nephropathy in IDDM

Summary Premature cardiovascular disease is common in insulin-dependent diabetic (IDDM) patients who develop diabetic nephropathy. Genetic polymorphism within the renin-angiotensin system has been implicated in the aetiology of a number of cardiovascular disorders; these loci are therefore candidate genes for susceptibility to diabetic renal disease. We have examined the angiotensin converting enzyme insertion/deletion polymorphism and angiotensinogen methionine 235 threonine polymorphism in a large cohort of Caucasian patients with IDDM and diabetic nephropathy. Patients were classified as having nephropathy by the presence of persistent dipstick positive proteinuria (in the absence of other causes), retinopathy and hypertension (n=242). Three groups were examined for comparison: ethnically matched non-diabetic subjects (n=187); a geographically defined cohort of newly diagnosed diabetic patients (n=341); and IDDM patients with long duration of disease (>15 years) and no evidence of overt nephropathy (n=166). No significant difference was seen in distribution of angiotensin converting enzyme or angiotensinogen genotypes between IDDM patients with nephropathy and recently diagnosed diabetic subjects (p=0.282 and 0.584, respectively), nor the long-duration non-nephropathy diabetic subjects (p=0.701 and 0.190, respectively). We conclude that these genetic loci are unlikely to influence susceptibility to diabetic nephropathy in IDDM in the United Kingdom.Abbreviations IDDM Insulin-dependent diabetes mellitus - ACE angiotensin converting enzyme - PCR polymerase chain reaction - LDNN long duration-non-nephropathy group - I/D insertion/deletion - RAS renin-angiotension system     

Changes in diameter size and F-actin expression in the myocytes of patients with diabetes and streptozotocin-induced diabetes model rats

Diabetes mellitus may be an independent risk factor for disturbance of cardiac function, but the detailed mechanism remains unclear. In the present study, histological examinations were carried out on 25 hearts from diabetes model rats as well as myocardial biopsy materials from patients with diabetes (n = 25). The mean diameter of the cardiac myocytes in humans was 12.2 +/- 0.5 microns in the control group of patients without diabetes mellitus or hypertension (n = 6), 13.7 +/- 0.8 microns in the hypertension group (n = 3), 9.0 +/- 1.7 microns in the diabetes group (n = 8), and 11.9 +/- 2.0 microns in the diabetes with hypertension group (n = 8). The cardiac myocytes of diabetic patients appeared to be atrophic. Comparison of the size of myocytes in the control rats vs streptozotocin-induced diabetes model rats (n = 7, each) was 5.4 +/- 0.2 vs 5.2 +/- 0.3 microns at 2 weeks; 5.9 +/- 0.1 vs 4.9 +/- 0.9 microns at 12 weeks, and 5.7 +/- 0.1 vs 4.0 +/- 0.2 microns at 24 weeks, respectively, and gradually decreased in streptozotocin rats with aging. Immuno-histochemistry with phaloidin was used to assess F-actin in the cardiac myocytes. The relative cross-sectional area of F-actin in the cardiac myocytes of streptozotocin rats was compared to that in non-streptozotocin rat myocytes. F-actin fluorescence in streptozotocin rats was 89.9 +/- 3.9% at 2 weeks, 77.9 +/- 6.4% at 12 weeks, and 56.8 +/- 5.7% at 24 weeks, indicating a decrease in F-actin. These results suggest that the smaller myocytes observed in patients with diabetes and streptozotocin rats are related to the decrease in F-actin in myocytes.     

老年糖尿病患者微血管并发症的患病率及危险因素

目的 探讨老年糖尿病患者微血管并发症的患病率,并分析发生微血管病变的危险因素。方法 回顾性分析北京协和医院2020年1月至2022年12月收治的495例老年糖尿病患者的临床资料,收集患者基线资料和生化指标,统计糖尿病视网膜病变、糖尿病肾病、周围神经病变等微血管并发症的患病率。根据微血管并发症的类型将患者分为4组：糖尿病视网膜病变组(n=107)、糖尿病肾病组(n=81)、周围神经病变组(n=169)及非并发症组(n=138)。采用SPSS 22.0统计软件进行数据分析。根据数据类型,分别采用方差分析或χ²检验进行组间比较。采用多因素logistic回归分析糖尿病微血管病变发生的危险因素。结果 495例老年糖尿病患者中共357例发生微血管并发症,总患病率为72.12%,其中糖尿病视网膜病变占21.62%(107/495),糖尿病肾病占16.36%(81/495),周围神经病变占34.14%(169/495)。与非并发症组患者比较,糖尿病视网膜病变组患者糖尿病病程更长,收缩压(SBP)和糖化血红蛋白(HbA1c)水平更高,低密度脂蛋白胆固醇(LDL-C)水平较低;糖尿...     

Histologic and ultrastructural studies on the myocardium in spontaneously diabetic KK mice: A new animal model of cardiomyopathy

The hearts from spontaneously diabetic KK mice and control mice were examined by light and electron microscopy. Myocardial degeneration, myocardial fibrosis and calcium deposits in the myocardium were extensive in KK mice aged 8 weeks. In myocytes of newborn KK mice, an irregular arrangement of myofibrils and poorly formed Z bands were found. Ultrastructural changes in myocytes of KK mice aged 4 weeks consisted of destruction of mitochondria, degenerated myofibrils and abnormalities of Z bands. However, increased mucopolysaccharides in interstitium and thickened basement membranes of capillaries were not found in KK mice, in contrast to the previous reports of myocardial changes in diabetic C57BL/KsJ mice, alloxan-diabetic dogs and hypertensive-diabetic rats. These observations suggest that the cardiomyopathy found in KK mice is not secondary to diabetes mellitus but is caused by other factors.In conclusion, myocardial ultrastructural abnormalities are present in newborn KK mice. Thus, this animal can be used as a model of cardiomyopathy.     

Diabetic cardiomyopathy: ongoing controversies in 2012

Diabetic cardiomyopathy is a controversial clinical entity that in its initial state is usually characterized by left ventricular diastolic dysfunction in patients with diabetes mellitus that cannot be explained by coronary artery disease, hypertension, or any other known cardiac disease. It was reported in up to 52?C60% of well-controlled type-II diabetic subjects, but more recent studies, using standardized tissue Doppler criteria and more strict patient selection, revealed a much lower prevalence. The pathological substrate is myocardial damage, left ventricular hypertrophy, interstitial fibrosis, structural and functional changes of the small coronary vessels, metabolic disturbance, and autonomic cardiac neuropathy. Hyperglycemia causes myocardial necrosis and fibrosis, as well as the increase of myocardial free radicals and oxidants, which decrease nitric oxide levels, worsen the endothelial function, and induce myocardial inflammation. Insulin resistance with hyperinsulinemia and decreased insulin sensitivity may also contribute to the left ventricular hypertrophy. Clinical manifestations of diabetic cardiomyopathy may include dyspnea, arrhythmias, atypical chest pain, and dizziness. Currently, there is no specific treatment of diabetic cardiomyopathy that targets its pathophysiological substrate, but various therapeutic options are discussed that include improving diabetic control with both diet and drugs (metformin and thiazolidinediones), the use of ACE inhibitors, beta blockers, and calcium channel blockers. Daily physical activity and a reduction in body mass index may improve glucose homeostasis by reducing the glucose/insulin ratio and the increase of both insulin sensitivity and glucose oxidation by the skeletal and cardiac muscles.