Diastolic Dysfunction in Patients with Non-insulin-dependent Diabetes Mellitus of Short Duration

To determine whether abnormal left ventricular diastolic function is present at an early stage of non-insulin-dependent diabetes mellitus (NIDDM), left ventricular diastolic filling was evaluated by pulsed doppler echocardiography in 16 normotensive patients with NIDDM of short duration (1.8 ± 1 years, mean ± SD) and no evidence of microangiopathy, and in 16 healthy volunteers comparable for age, body mass index, and sex distribution. All patients showed normal systolic function. The interventricular septum thickness, left atrial diameter, and left ventricular mass index were increased in the diabetic as compared with the control group (p < 0.01, p < 0.01, and p < 0.02, respectively). Isovolumic relaxation time and atrial peak filling velocity were greater in diabetic patients (p < 0.001, and p < 0.01, respectively), whereas early to atrial peak filling velocity ratio was significantly reduced (p < 0.05). This study demonstrates that an impairment of left ventricular diastolic function occurs early in the natural history of NIDDM, and that this abnormality is unlikely to be related to clinical evidence of microangiopathic complications.     

Non-insulin-dependent Diabetes Mellitus and Islet B-cell Mitochondrial Glycerophosphate Dehydrogenase Deficiency

A deficient activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase (m-GDH) in the pancreatic islet B-cell may represent a contributing factor in the pathogenesis of non-insulin-dependent (Type 2) diabetes. This enzyme controls circulation in the glycerol phosphate shuttle and, hence, plays a key role in the B-cell glucose-sensing device. An impaired activity of this enzyme in pancreatic islets was documented in several, but not all, animal models of inherited or acquired non-insulin-dependent diabetes. Enzymatic studies conducted in lymphocytes or islets from diabetic patients, as well as a search for possible mutations of the m-GDH gene, were recently undertaken to extend these observations to human subjects.     

实验性Ⅱ型糖尿病大鼠主动脉早期超微结构改变及影响因素

本实验测定了实验性Ⅱ型糖尿病大鼠血脂、血浆过氧化脂质及超氧化物歧化酶,观察了10周时大鼠主动脉超微结构的改变。结果表明:糖尿病组及单纯肥胖组大鼠均有主动脉内膜病变,前者较明显。与对照组大鼠比较,前二者过氧化脂质、甘油三脂及低密度脂蛋白胆固醇均增高,而高、低密度脂蛋白胆固醇比值下降,差异非常显著(p<0.01),糖尿病组大鼠超氧化物歧化酶下降而单纯肥胖组大鼠则升高。以上结果提示,实验性Ⅱ型糖尿病大鼠主动脉内膜有早期超微病理改变,这种病变与过氧化脂质升高及超氧化物歧化酶活性下降有关。与脂代谢紊乱也有一定的关系。     

实验性Ⅱ型糖尿病大鼠主动脉早期超微结构改变及影响因素

本实验测定了实验性Ⅱ型糖尿病大鼠血脂、血浆过氧化脂质及超氧化物歧化酶，观察了１０周时大鼠主动脉超微结构的改变。结果表明：糖尿病组及单纯肥胖组大鼠均有主动脉内膜病变，前者较明显。与对照组大鼠比较，前二者过氧化脂质、甘油三脂及低密度脂蛋白胆固醇均增高，而高、低密度脂蛋白胆固醇比值下降，差异非常显著（Ｐ＜０．０１），糖尿病组大鼠超氧化物歧化酶下降而单纯肥胖组大鼠则升高。以上结果提示，实验性Ⅱ型糖尿病大鼠主动脉内膜有早期超微病理改变，这种病变与过氧化脂质升高及超氧化物歧化酶活性下降有关。与脂代谢紊乱也有一定的关系。     

Cardiac autonomic function in fibrocalculous pancreatic diabetes

Cardiac autonomic function was evaluated in 23 patients with fibrocalculous pancreatic diabetes (FCPD). Though none of the patients had any symptoms referable to autonomic dysfunction, 5 had abnormal heart rate responses. The variability in the heart rate in response to deep breathing was the earliest abnormality found in our patients. Four of the 5 patients had clinical evidence of neuropathy while all 5 had retinopathy and overt nephropathy. We therefore conclude that the autonomic nervous system can be involved in patients with FCDP even as early as 2 years after the onset of the disease, and thus that evaluation of the autonomic nervous system should be part of the routine evaluation of all patients with FCPD.     

Autonomic Dysfunction and Silent Myocardial Ischaemia on Exercise Testing in Diabetes Mellitus

The incidence and mechanism of painless myocardial ischaemia on exercise testing in diabetic patients is not clear. Therefore, two studies were performed. Retrospectively, all exercise tests carried out in our hospital during the past 5 years were reviewed for silent ischaemia. Prospectively, diabetic patients with known or suspected coronary artery disease underwent autonomic function testing and a second exercise test. Of 1653 exercise tests reviewed, 247 were positive (ST depression > 0.1 mV). Of the 29 diabetic patients with positive tests 20 (69%) had painless ST depression, compared with 77 (35%) of the 218 non-diabetic patients (p < 0.001). The diabetic patients with painful and painless ST depression were comparable for age, sex, therapy, but the 20 with no pain on exercise testing had a longer duration of diabetes and a higher incidence of microvascular complications than the 9 with pain (70 vs 22%, p < 0.05). In the prospective study, 12 of 30 diabetic patients with positive exercise tests had pain in association with ST depression and 18 had no pain. Six patients had mild and 12 severe autonomic neuropathy on formal testing. Twelve had no autonomic dysfunction. Eleven (92%) of 12 patients with severe neuropathy had painless ST depression, compared with 7 (39%) of 18 without severe neuropathy (p < 0.01). Thus, silent myocardial ischaemia on exercise testing is common among patients with diabetes mellitus and is associated with severe autonomic dysfunction.     

Lipid Composition of Platelets in Patients with Non-insulin-dependent Diabetes Mellitus: Studies Before and After Treatment of Diabetes

The study was designed to investigate whether impaired composition of platelet lipids in untreated diabetic patients improved after diabetic treatment. Fourteen untreated patients with non-insulin-dependent diabetes mellitus (NIDDM) and 15 healthy control subjects were studied. In the diabetic patients, the ratio of free cholesterol to phospholipid (FC/PL) in platelets of 0.33 ± 0.02 (mean ± SEM) at pre-treatment, which was statistically (p < 0.05) higher than that of 0.26 ± 0.02 in control subjects, was significantly decreased to the value of 0.29 ± 0.02 (p < 0.01) after insulin therapy. Platelet FC level of 9.77 ± 0.77 μg 10^?8 cells pre-treatment was significantly (p < 0.01) reduced to the value of 7.72 ± 0.38 μg 10^?8 cells post-treatment. Platelet PL level showed no significant changes after the treatment. There was a significantly (p < 0.01) positive correlation between the decrease in FC/PL of platelets and that in haemoglobin A_1c (HbA_1c) after treatment for diabetes (rs = ?0.729). These results indicate that the impaired lipid composition in platelets can be improved after an adequate glycaemic control in patients with NIDDM.     

Prospective Assessment of Autonomic and Peripheral Nerve Function in Adolescents with Diabetes

Autonomic and peripheral nerve function were studied prospectively in 102 adolescents with Type 1 diabetes over a 5-year period. All adolescents were assessed three times; 54 were assessed four times. The median age at baseline was 14.5 (range 10.4–18.0) yr. The median diabetes duration at baseline was 6.8 (range 1.3–15.2) yr. Autonomic nerve function was assessed by measuring heart rate variation during deep breathing, valsalva manoeuvre, standing from a lying position (30/15 ratio), and the postural change in systolic blood pressure. Peripheral nerve function was assessed by determining the thermal threshold for heat and cold at the wrist and foot and the vibration threshold at the great toe and medial malleolus. At baseline, 29.5 % adolescents had at least one abnormal autonomic nerve test and 28.4 % had at least one abnormal peripheral nerve test. There was no significant increase in the number of abnormalities over the study period. Persisting abnormalities were present in only six individuals. Abnormalities were not related to age, diabetes duration or glycaemic control. In summary, a low rate of neurological abnormalities was found, suggesting that more than 3 years of follow-up is required to detect evolving neuropathy in this age group.     

糖尿病患者的胃电改变

观察具有及无上消化道症状的非胰岛素依赖型糖尿病（NIDDM）患者餐前及餐后2小时体表胃电图的变化。结果显示:①有症状组餐前、餐后胃电主频（Fp）均低于正常（P<0.01）,餐前、餐后Fp值无差异（P>0.05）。平均峰值幅值（Ap）正常。②无症状组餐前Fp值低于正常,餐后恢复至正常,餐前、餐后相比差异显著（P<0.05）,Ap值正常。③有症状组与无症状组间十二指肠球部的餐前及餐后即值异常率均存在差异（P<0.005）。④有症状组病程明显长于无症状组（P<0.05）。结论:NIDDM患者普遍存在胃电异常,主要表现为胃动过缓及胃一十二指肠球部运动不协调。及早发现无症状患者的胃动力异常,具有重要的临床意义。     

The Potential for Lifestyle Change to Influence the Progression of Impaired Glucose Tolerance to Non-insulin-dependent Diabetes Mellitus

Impaired glucose tolerance (IGT) is well recognized as a risk factor for the development of non-insulin-dependent diabetes mellitus (NIDDM). Detecting IGT offers a unique opportunity for targeting intervention to reduce the incidence of NIDDM. This article reviews current evidence for the efficacy of lifestyle intervention programmes involving people with IGT.     

Non-insulin-dependent Diabetes and 11-Year Mortality in Asian Indian and Melanesian Fijians

This study reports 11-year all-cause and cause-specific mortality rates according to baseline glucose tolerance for a population-based sample of adult Melanesian and Indian Fijians (n = 2638), first surveyed in 1980. Risk factors for all-cause and cardiovascular disease (CVD) mortality in subjects with non-insulin-dependent diabetes (NIDDM) are also described. The baseline survey included 75 g oral glucose tolerance tests, measurements of blood pressure, body mass index, and triceps skinfold, assays of plasma cholesterol and triglycerides, electrocardiograms, and details of smoking habits and physical activity. Mortality status was ascertained for 2546 subjects through surveillance of death certificates, medical records and interview of subjects (or relatives). Mortality rates were increased in diabetic men and women of both ethnic groups: relative risks compared to subjects without diabetes at baseline were 1.7 (CI:0.9–3.1) and 2.0 (1.1–3.7) in Melanesian and 4.2 (2.7–6.5), 3.2 (1.9–5.7) in Indian men and women, respectively. A large proportion of mortality among diabetic subjects was attributed to CVD (62 %, 66 % in Melanesian and 54 %, 58 % in Indian men and women, respectively). Mortality rates tended to be higher in Melanesians than Indians, except for diabetic men where Indians had higher total and cardiovascular disease rates. In contrast to non-diabetic Fijians, diabetic women of both ethnic groups lost their relative protection from coronary heart disease (CHD). Cox regressions for diabetic subjects showed age and fasting plasma glucose to be independent predictors of all-cause mortality in men, and age, body mass index (inversely) and systolic blood pressure in women, but lipid concentrations, and cigarette smoking were not related. After accounting for conventional CVD risk factors, diabetes conferred significantly increased risk of total, CVD, and CHD mortality. The mortality experience of Melanesian and Indian Fijians with NIDDM is similar to that documented in developed populations, with excess mortality due to cardiovascular causes.     

Serum Concentration of Cathodic Trypsin-Like Immunoreactivity and Pancreatic Isoamylase in Insulin-Dependent Diabetes Mellitus

ABSTRACT. The relationship between diabetes mellitus and the exocrine pancreatic function was evaluated in 29 patients with insulin-dependent diabetes mellitus by measuring cathodic trypsin-like immunoreactivity (TLI) and the enzymatic activity of pancreatic isoamylase in serum before and 90 min after breakfast and insulin. Thirty healthy subjects served as reference group. Median fasting serum concentrations in the diabetic subjects were significantly lower than in the reference subjects: for TLI 143 and 299 μg trypsin standard/I and for pancreatic isoamylase 43 and 101 U/I, respectively (p<0.001 for both). A positive correlation between TLI and pancreatic isoamylase was present in the diabetics (Sperman's rho=0.56, p<0.01). The serum concentrations of TLI and pancreatic isoamylase were not related to the duration of diabetes, daily insulin dose or glycemic control measured by blood glucose and total glycosylated hemoglobins. Cathodic TLI and pancreatic isoamylase in serum were not influenced by food and insulin.     

Outcome of Unstable Angina in Patients with Diabetes Mellitus

This prospective hospital-based, case–control study compares the outcome of unstable angina in non-insulin dependent diabetic patients and non-diabetic control subjects. One hundred and sixty-two diabetic patients and 162 non-diabetic control patients with unstable angina were entered into the study. The 3-month mortality was 8.6 % (95 % confidence interval, CI = 4.4–12.9 %) in diabetic patients and 2.5 % (CI = 0.1–4.9 %) in control patients (p = 0.014). The 1-year mortality was 16.7 % (CI = 10.9 %–22.4 %) in diabetic patients and 8.6 % (CI = 4.4 %–12.9 %) in non-diabetic patients (p = 0.029). Diabetic patients received beta-blockade and underwent coronary angiography and angioplasty less frequently than controls; the frequency of unstable angina, of acute myocardial infarction, and of coronary artery bypass grafting was similar in both groups at 1 year of follow-up. It is concluded that diabetic patients with unstable angina have a higher mortality than non-diabetic patients and that this difference is largely accounted for by early (first 3 months) mortality. © 1997 by John Wiley & Sons, Ltd.     

Gustatory Sweating in Diabetes Mellitus

Gustatory sweating has been only rarely reported in diabetes mellitus and is thought to be due to axonal regeneration within the autonomic nervous system. We investigated the relationship of gustatory sweating to other diabetic complications. 196 patients in four groups (diabetic nephropathy, diabetic neuropathy, diabetic controls, and non-diabetic renal failure) were questioned about gustatory sweating. Somatic and autonomic neuropathy were assessed by clinical signs, vibration perception threshold, and heart rate variability. Sixty-nine percent of patients with nephropathy and 36% of those with neuropathy reported gustatory sweating, whereas less than 5% reported it in the other two groups. Five subjects reported that gustatory sweating either disappeared or significantly improved immediately after renal transplantation. Analysis of the nephropathy and neuropathy groups separately showed a strong correlation between gustatory sweating and degree of neuropathy (p < 0.01). This study shows that gustatory sweating is much more common than previously believed and demonstrates that it is often very closely linked with diabetic nephropathy.     

Relationship between Pancreas Exocrine Insufficiency and Cardiac Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus

BackgroundThe exocrine function of the pancreas is controlled by the autonomic nervous system (ANS), and autonomic neuropathy is a common and serious complication of diabetes. There are many factors contributing to the development of autonomic neuropathy in diabetic patients. Cardiovascular tests have been developed to evaluate the function of the ANS. This study investigated the relationship between cardiovascular autonomic neuropathy (CAN) and pancreas exocrine insufficiency (PEI) in diabetic patients.Methods This study evaluated 110 individuals with type 2 diabetes mellitus (T2DM) and 40 healthy volunteers. Autonomous neuropathy tests were utilized to diagnose patients, and Ewing and Clarke’s criteria were employed to assess the severity of autonomous dysfunction. Stool samples were also collected from patients to measure fecal elastase-1 (FE-1). Results A 65.5% incidence of PEI was observed in DM patients. There was no significant correlation among the duration of disease, C-peptide, HbA1c, and PEI, respectively (P = .782, P = .521, P = .580). However, a significant difference between DM patients and controls in terms of cardiac dysautonomia (P = .001) was seen. Moreover, a statistically significant correlation between the degree of cardiac dysautonomia and FE-1 level was observed within the patient group (P =.001).Conclusion It is possible that the disruption of exocrine hormone secretion in the pancreas due to the impairment of enteropancreatic reflexes is secondary to diabetic autonomic neuropathy and resulting in PEI. This study also showed that autonomic neuropathy might develop and cause PEI in diabetic patients without known added confounding factors.     

Abnormal Digital Pressure Measurements in Diabetic Neuropathic Foot Ulceration

The diabetic neuropathic ulcer is typically slow to heal and recurrent. Macrovascular insufficiency is usually excluded as foot pulses are present and ankle:brachial pressure ratios are not decreased. These assessments cannot however exclude more distal vascular disease. Digital pressure measurements enable a reliable assessment of the distal peripheral vascular status to be made. The aim of this study was therefore to use toe pressures to assess the contribution of distal ischaemia in the pathogenesis of the neuropathic ulcer. Sixteen diabetic patients with recurrent neuropathic foot ulceration had their toe pressures compared to 10 neuropathic patients without a history of foot ulceration, 10 diabetic control subjects, and 11 normal subjects. Four non-diabetic patients with neuropathy and foot ulceration were also assessed. All subjects had ankle:brachial pressure indices ≧ 1. Toe pressure was assessed using laser Doppler flowmetry to record the return of skin blood flow. The toe:brachial pressure index (TBI) was then calculated. The diabetic patients with a history of recurrent neuropathic ulceration, had the lowest mean TBI, 0.63 ± 0.14 (SD), compared to the non-ulcerated diabetic neuropathy patients, the diabetic control subjects, and the normal subjects. 0.84 ± 0.11, 0.82 ± 0.1, and 0.81 ± 0.07, p < 0.01, respectively. Three of the four non-diabetic patients with neuropathic foot ulceration also had an abnormally low TBI. Reduced toe pressure measurements are thus found to be associated with neuropathic foot ulceration. The contribution of distal ischaemia in the pathogenesis of the diabetic neuropathic foot ulcer needs to be evaluated. One hundred and eight non-insulin-dependent diabetic patients who had been tested for autonomic dysfunction in 1984/85 were re-evaluated 5 years later. Autonomic function was assessed by means of four cardiovascular tests (heart rate variation during deep breathing and standing, and blood pressure variation after standing and sustained handgrip). Eighteen subjects were lost to follow-up; in the 90 patients who completed the study, both the deep breathing and the handgrip test significantly worsened (respectively from 13.7 ± 7.8 to 11.6 ± 6.3 beats min^?1 p < 0.01, and from 16.9 ± 8.2 to 12.7 ± 7.1 mmHg, p < 0.001), whereas both the 30:15 ratio and the variation of blood pressure on standing did not change. The impairment of a comprehensive evaluation score (from 2.5 ± 1.7 to 3.0 ± 1.5; p < 0.05) also confirmed the gradual deterioration of autonomic function over the study period.     

Familial Aggregation of Type 2 (Non-insulin-dependent) Diabetes Mellitus in South India; Absence of Excess Maternal Transmission

The family histories of 976 South Indian Type 2 diabetic patients were recorded in a questionnaire-based survey to establish whether the excess maternal transmission of Type 2 diabetes reported in low prevalence Europid populations was also evident in this medium prevalence population. In 450 families (46.1 %), no parental history of diabetes was reported. In 423 families with one parent diabetic, 222 fathers (52.5 %) and 201 (47.5 %) mothers were diabetic. In the remaining 103 (10.6 %) families, both parents were diabetic. In contrast to previous studies, we found no evidence for substantial maternal excess in the transmission of diabetes (325 diabetic fathers vs 304 mothers; p = 0.4; p = 0.07 when compared using life table methods). The age of diagnosis of diabetes in probands was lower than that of their diabetic parents (p < 0.001): furthermore increasing parental history of diabetes was associated with an earlier diagnosis of diabetes in probands (p < 0.001). These results emphasize the extensive familial aggregation of Type 2 diabetes in this population but fail to replicate the evidence for excess maternal transmission evident in lower prevalence Europid populations, suggesting ethnic differences in the extent of this phenomenon.     

Autonomic and Peripheral Nerve Function in Adolescents With and Without Diabetes

In this study reference ranges were established for autonomic and peripheral nerve tests in 122 non-diabetic adolescents. Regression analysis was used to evaluate the effect of age and gender on neurological function. Increasing age was associated with: less heart rate variability during deep breathing (p = 0.03), higher thermal threshold for cold at the wrist (p = 0.009), and higher vibration threshold at the toe (p = 0.001) and medial malleolus (p = 0.01). Male gender was associated with higher Valsalva ratio (p = 0.0004), higher thermal threshold for hot at the foot (p = 0.002), and higher vibration threshold at the malleolus (p = 0.03). The REFVAL programme was used to determine parametric or non-parametric reference limits: the 5% limits for autonomic and 95% limits for peripheral tests. One hundred and eighty-one adolescents with diabetes were studied under identical conditions and similar effects of age and gender were found. Twenty-eight percent of the group with diabetes had at least one abnormal autonomic test result out of four (expected 18.5%); 24% had at least one abnormal peripheral test result out of six (expected 26.5%). Glycaemic control was associated with autonomic (p = 0.04) but not peripheral abnormalities. Using multiple regression analysis and adjusting for age and gender, there was no effect of diabetes duration or glycaemic control on neurological function.