Lipid modulation in insulin-dependent diabetes mellitus: effect on microvascular outcomes

Although hyperlipidemia is associated with the development of diabetes complications, the effect of lipid reduction on microvascular complications is unknown. We initiated a 2-year, randomized, double-blinded placebo-controlled pilot trial of simvastatin/diet vs. diet alone in Type 1 diabetic patients without overt nephropathy. Thirty-nine patients with LDL cholesterol 100-160 mg/dl, >10 year duration of diabetes and an albumin excretion rate (AER) <200 microg/min were recruited for study. The primary end-point was change in AER. Secondary end-points were change in ankle-brachial index, progression of retinopathy status, change in vibratory threshold, and development of new clinical neuropathy. Nineteen patients were treated with simvastatin and twenty with placebo. However, because of the lowering of drug initiation levels by the American Diabetes Association, the trial was terminated early with 2 subjects reaching 2 years, 17 reaching 18 months, 36 reaching 1 year, and all 6 months. Simvastatin significantly reduced total cholesterol (mean on treatment 173.4 vs. 191.4, P=.020) and LDL cholesterol (mean on treatment 105.0 vs. 127.7, P<.001). Simvastatin therapy was associated with a slower rise in AER compared to placebo, though the result was not statistically significant (median rate of change/month 0.004 vs. 0.029). There was a trend towards slower progression of neuropathy as measured by vibratory threshold (median change at 1 year 0.03 simvastatin vs. 0.94, P=.07). There was no difference in change in ankle-brachial index, clinical neuropathy status, or retinopathy status. In conclusion, treatment with simvastatin may have a beneficial effect on early nephropathy and diabetic neuropathy, justifying a fully powered trial. However, this would be difficult under current treatment guidelines.     

Long-term bone loss in insulin-dependent diabetic patients with microvascular complications

Insulin-dependent diabetic patients have an approximately 10% decreased bone mineral content (BMC) when they are studied a few years after clinical onset of diabetes. After that time, patients without diabetic microvascular complications have no, or only very little, further bone loss. The aim of the present study was to investigate if any substantial long-term bone loss occurs in diabetic patients with microvascular complications. We studied 19 insulin-dependent diabetic patients with neither physiologic nor pathologic conditions known to interfere with bone metabolism, other than diabetes. BMC was determined twice, with an interval of 11 years. At initial examination, no patient had diabetic microangiopathy, but at final examination 7 patients had developed diabetic microvascular complications while 12 patients had not. As compared with gender- and age-matched controls, both subgroups had significantly decreased BMC at the initial examination. During the study period, the patients with complications showed further bone loss, whereas the subgroup without complications had unchanged decreased BMC. At final examination, BMC was significantly lower in patients with microvascular complications than in patients without them. The biochemistry of bone metabolism showed a significantly increased fasting urinary excretion of calcium and hydroxyproline in patients with complications, but not in the group without complications, and there was a negative correlation between plasma BGP (osteocalcin) and hemoglobin A_1c for all patients. These findings indicate that, in addition to a decreased BMC (before or shortly after clinical onset of diabetes), patients who develop microvascular complications also develop ongoing bone loss. This loss may be caused by an increased bone resorption, but decreased bone formation during periods of poor diabetic control may be involved as well.     

Lipoprotein (a) and microvascular disease in type 1 (insulin-dependent) diabetes.

The influence of albuminuria and proliferative retinopathy on concentration of serum lipoprotein (a) was examined cross-sectionally in 90 Type 1 diabetic patients. Concentrations of lipoprotein (a) were less in those with normoalbuminuria (90 (8-882) (median (range] U l-1) than in those with micro- or macro-albuminuria (137 (19-1722) U l-1, p less than 0.05). The prevalence of patients whose lipoprotein (a) concentrations were greater than 200 U l-1 was also greater (45% vs 24%, p = 0.03) among patients with albuminuria, but no difference was found between the microalbuminuric and macroalbuminuric groups (53 and 41%, respectively), or between those with or without proliferative retinopathy. The present finding that lipoprotein (a) concentrations may be increased at an early stage of diabetic renal disease may in part account for the excess ischaemic heart disease associated with diabetic nephropathy.     

限蛋白质摄入对2型糖尿病早期肾病的影响

目的 评估限蛋白质摄入对２型糖尿病肾病在肾功能和营养状况方面的影响。方法 门诊６７例早期肾病病人,按就诊顺序分为限蛋白治疗组和正常蛋白组,试验期为１年。结果 两组病人体重指数、血常规及血液生化、血糖指标、血液肾功能治疗后无显著性差异。治疗组两组间血清白蛋白有显著性差异。实验组尿白蛋白排泄率明显下降。结论 限蛋白膳食可以显著减少２型糖尿病早期肾病病人尿白蛋白排泄率,从而改善营养状况,保护肾功能。     

The relationship of prorenin values to microvascular complications in patients with insulin-dependent diabetes mellitus

We have performed a cross-sectional analysis of the relationship between prorenin values and the microvascular complications of diabetes in a well controlled population of insulin-dependent diabetes mellitus (IDDM) subjects. One hundred and thirty-nine subjects (75 men, 64 women, age 44 +/- 17 years; duration of diabetes 19 +/- 15 years), formed the study group. Sixty-seven subjects (48.2%) had no complications, 55 (39.6%) had retinopathy alone, and 17 (12.2%) had retinopathy and albuminuria. Patients with no complications had lower prorenin values than those with microvascular complications (p < 0.001), whilst patients with both albuminuria and retinopathy had higher values than those with retinopathy alone (p < 0.05). Retinopathy was associated with duration of diabetes (p < 0.0001), diastolic blood pressure (p < 0.02) and albuminuria (p < 0.0001) while albuminuria was associated with prorenin (p < 0.02), serum triglyceride (p < 0.01) and retinopathy (p < 0.001). Patients with albuminuria were 5.5 times more likely to have raised prorenin values (>80 ng/mL/h) than those with normal albumin excretion [95% confidence interval (CI): 1.48-20.12] and those with retinopathy alone were 2.5 times as likely (95% CI: 1.19-5.15). Eighty patients with IDDM (40 males, 40 females; age: 47 +/- 17 years; duration of diabetes: 20 +/- 15 years), had retinal photography performed to determine the association between the severity of retinopathy and prorenin values. Retinopathy was more severe in patients with retinopathy and albuminuria than in those with retinopathy alone (p < 0.002). When the prorenin values of patients with more marked retinopathy (eye grade greater than 3) were compared, prorenin values of those with retinopathy and albuminuria were greater than those of patients with retinopathy alone [269 (139-1406) versus 91 (41-273) ng/mL/h: geometric mean (range); p < 0.05]. Furthermore, when patients without albuminuria were considered, there was no significant difference between the prorenin levels of patients with more severe retinopathy (eye grade >3) when compared to patients with lesser degrees of retinopathy [91 (41-273) versus 69 (23-375). In patients with microvascular complications, prorenin values were independently predicted by albuminuria (p < 0.0001) and diastolic blood pressure (p < 0.02) but not the severity of retinopathy. In conclusion, prorenin values are significantly associated with the presence of microvascular complications in patients with IDDM. The association with albuminuria may be stronger than the association with retinopathy.     

Hypotensive therapy reduces microvascular albumin leakage in insulin-dependent diabetic patients with nephropathy

The effect of hypotensive therapy on the transcapillary escape rate of albumin (TERalb) was studied in eight hypertensive insulin-dependent diabetic patients (mean age 29, range 19-42 years) with nephropathy and retinopathy. Transcapillary escape rate of albumin (initial disappearance of intravenously injected 125I-labelled human serum albumin), urinary albumin excretion rate (radial immunodiffusion), and glomerular filtrate rate (single bolus 51-Cr-EDTA technique) were measured. After hypotensive treatment (mean duration, 23 months, range 7-39 months) with combinations of metoprolol, hydralazine, and frusemide or thiazide diuretics, arterial blood pressure fell from 152/103 +/- 18/6 mmHg (mean +/- SD) to 133/81 +/- 12/10 mmHg (p less than 0.01), transcapillary escape rate of albumin from 10.2 +/- 1.8 to 8.1 +/- 1.8% of intravascular mass of albumin/h (p less than 0.01), albuminuria from 1803 (370-5066) micrograms/min to 940 (101-2676) micrograms/min (median and range, p less than 0.05), and glomerular filtration rate from 103 +/- 23 to 84 +/- 22 ml/min/1.73 m2 (p less than 0.01). Our study suggests that effective hypotensive treatment reduces the abnormally elevated albumin leakage characteristically found in insulin-dependent diabetic patients with clinical microangiopathy. This may be due to a reduction in the hydrostatic pressure in the microcirculation.     

角膜共焦显微镜检测在糖尿病微血管病变早期诊断及评估中的作用

糖尿病微血管病变的早期诊断及评估至关重要.角膜共焦显微镜(CCM)作为一项全新的临床检测方法,具有非侵入性、可重复性、快速性等特征,对于检测角膜神经纤维的结构、数量及部分功能有一定的作用,在糖尿病神经病变的早期诊断及治疗措施有效性的评估中有着重要的作用,同时,在糖尿病视网膜病变(DR)及糖尿病肾病(DN)中也有相关的应用价值.     

Frequency of insulin-dependent diabetes mellitus in Turkish adult-onset diabetic population

The frequency of insulin-dependent diabetes mellitus in the Turkish adult-onset diabetic population has not been assessed previously. In the present study, we retrospectively evaluated the medical records of 801 Turkish patients with adult-onset (30 years) diabetes to determine the frequency of cases diagnosed as insulin-dependent diabetes. Fifty-two (6.5%) patients met our criteria of adultonset insulin-dependent diabetes mellitus. At disease onset, 20 patients presented with ketoacidosis (38.5%), while 32 patients (61.5%) were non-ketotic. In the insulin-dependent diabetic group, islet cell antibodies were positive in 10 out of 16 (62.5%) patients studied. In contrast, none of the 16 patients had positive reactions with respect to insulin autoantibodies. Twelve out of 20 patients (60%) had glucagon-stimulated C-peptide levels above 0.6 nmol/l, suggesting a sufficient insulin secretory reserve. In view of these observations, we conclude that insulin-dependent diabetes mellitus is not rare among patients with adult-onset diabetes in the Turkish population. In a majority of cases, the disease onset is non-ketotic. Beta-cell function is relatively preserved, and insulin autoantibodies do not develop at diagnosis. In contrast, islet cell antibodies are frequently present at the onset of clinical insulin-dependent diabetes, possibly indicating continuing beta-cell destruction.     

Prevalence of diabetes among children of insulin-dependent diabetic mothers

Summary Eight diabetics were found among 464 children, mean age 11.2 years, of 311 unselected insulin-treated mothers. By a method of age correction the total diabetes prevalence among the children at the age of 25 years was calculated as 3.4%. Three children were non-insulin dependent and these patients and their mothers may belong to the autosomal dominant type of diabetes, so-called MODY. In two of the other five families the fathers also had insulin-dependent diabetes; in two more cases first or second degree paternal relatives were insulin-dependent diabetics. Thus the prevalence of insulin-dependent diabetes among the children of insulin dependent mothers married to non-diabetics is calculated as 1.5% at the age of 25 years.     

The effect of intravenous insulin infusion on kidney function in insulin-dependent diabetes mellitus

Summary Glomerular filtration rate, renal plasma flow, urinary excretion of -2-microglobulin and albumin, heart rate and blood pressure were studied in eight young male insulin-dependent diabetics. Measurements were performed before and during insulin infusion at 2 mU/kg/min. No patient had discernible insulin antibodies. Two studies were performed at random in each patient. In series A blood glucose concentration was allowed to decline, while in series B it was maintained at a constant level. Ten 20 min clearance periods were performed, four before and six during insulin infusion. Results are given as mean±SEM of values from the first four (control) and last four (test) clearance periods. Blood glucose declined in series A experiments from 10.8±0.8 mmol/l in the control period to 5.8±0.5 mmol/l during the test period, but remained constant during experiment B (9.8±1.1 and 9.5±1.1 mmol/l). Plasma insulin levels were comparable in the two series. Glomerular filtration rate fell from 141±7 ml/ min X 1.73m₂ to 132±7ml/min X 1.73m₂ (p< 0.01) in series A but did not change significantly during series B. Similarily renal plasma flow declined with declining glucose but remained constant when glucose was maintained at a constant level. In series A the magnitude of decrease in renal plasma flow was correlated with the magnitude of decrease in glomerular filtration rate (r=0.95, p< 0.001). -2-microglobulin excretion decreased significantly (p < 0.05) in both series (A: 89±17 to 60±13 ng/min, B: 117±46 to 62±17ng/min). Albumin excretion increased in five out of six patients with normal control values (not significant) in series A and in four out of six in series B. No significant changes in heart rate or blood pressure were observed. Thus insulin infusion reduced renal plasma flow and glomerular filtration rate, but this effect could be completely abolished by keeping blood glucose constant. This suggests that it is not the lack of insulin but the associated hyperglycaemia which contributes to the elevated renal plasma flow and glomerular filtration rate in insulin-dependent diabetics.     

Increased microvascular fluid permeability in young Type 1 (insulin-dependent) diabetic patients

Summary Microvascular fluid permeability was assessed by determination of the capillary filtration coefficient in the forearm of ten young Type 1 (insulin-dependent) diabetic patients with a short duration of diabetes, satisfactory glycaemic control and minimal evidence of micro angiopathy, and ten age- and sex-matched controlsubjects. A strain gauge plethysmographic method with a computer based logging and analysis system was used. This enabled differentiation between the volume filling and fluid filtration components of the response to venous pressure elevation. The median capillary filtration coefficient was found to be significantly higher in the young diabetic patients in comparison with control subjects (9.2×10^–3 ml · min^–1 · 100 g tissue^–1 mmHg^–1 vs 3.8×10^–3ml · min^–1 · 100 g tissue^–1 · mm Hg^–1, p<0.001). There were no significant correlations between capillary filtration coefficient and either plasma glucose concentration, haemoglobin A_1c or duration of diabetes. As there is no evidence from other studies to support an increase in capillary surface area in the forearms of young Type 1 diabetic patients, these results may reflect a primary change in microvascular fluid permeability.     

Severe microvascular disease in type II diabetes of early onset. A family study

Summary Both early onset and late onset type II diabetes were present in one family of nine siblings. The three early onset type II diabetic siblings showed severe microvascular complications: proliferative retinopathy, diabetic nephropathy, and peripheral neuropathy. Early onset type II diabetes was not associated with any particular HLA haplotype. Early onset type II diabetes could be considered a clinical and genetic disease entity different from MODY type diabetes.     

The association of diabetic microvascular and macrovascular disease with cutaneous circulation in patients with type 2 diabetes mellitus

Aims

To study the impact of diabetic neuropathy, both peripheral sensorimotor (DPN) and cardiac autonomic neuropathy (CAN), on transcutaneous oxygen tension (TcPO₂) in patients with type 2 diabetes mellitus (T2DM).

糖尿病合并高血压对微血管病变患病率的影响

目的　为了解糖尿病合并高血压对微血管病变患病率的影响。方法　对３２５ 例２ 型糖尿病合并与不合并高血压对糖尿病微血管病变患病率的影响进行了回顾性分析。结果　２ 型糖尿病合并高血压组糖尿病肾病（ Ｄ Ｎ） 、糖尿病视网膜病变（ Ｄ Ｒ） 、糖尿病周围神经病变（ Ｄ Ｐ Ｎ） 和糖尿病自主神经病变（ Ｄ Ａ Ｎ） 的患病率分别为６１ ．３２ ％ 、４９ ．０６ ％ 、４５ ．２８ ％ 和２４ ．５３ ％ ，均高于血压正常组（ 患病率分别为２７ ．８５ ％ 、２９ ．６８ ％ 、３２ ．４２ ％ 和１５ ．５３ ％ 。有关影响因素拟合 Ｌｏｇｉｓｔｉｃ 逐步回归方程分析，结果显示糖尿病病程是 Ｄ Ｎ、 Ｄ Ｒ、 Ｄ Ｐ Ｎ 和 Ｄ Ａ Ｎ 患病的共同影响因素。高血压是 Ｄ Ｎ、 Ｄ Ｐ Ｎ 患病的危险因素（ Ｏ Ｒ 值分别为２ ．５９ 、２ ．５５ ， Ｐ 值分别为＜ ０ ．０１ 、＜ ０ ．０５） 。结论　糖尿病合并高血压将增加糖尿病微血管病变的患病率。     

Short-term inhibition of prostaglandin synthesis has no effect on the elevated glomerular filtration rate of early insulin-dependent diabetes

Glomerular filtration rate and renal plasma flow (constant infusion technique using 125I-iothalamate and 131I-hippuran) were measured twice within a 1-week interval in nine young males with insulin-dependent diabetes of short duration (2-5 years). The study was performed in a randomized double-blind design, with the patients receiving either indomethacin (150 mg/day) or placebo for 3 days before the study. Measures of metabolic control did not change. No differences were found in glomerular filtration rate (144 +/- 9 versus 144 +/- 9 ml/min X 1.73 m2, mean +/- S.E.M.) or renal plasma flow (579 +/- 43 versus 560 +/- 52 ml/min X 1.73 m2), when measured during placebo or indomethacin treatment, respectively. It is concluded that the steady-state enhancement of glomerular filtration rate and renal plasma flow found in early insulin-dependent diabetes is not due to an excessive activity of the prostaglandin system.     

SUDOSCAN在糖尿病微血管并发症早期诊断及治疗评估中的作用

目前临床上对糖尿病微血管并发症采用的筛查和诊断方法很多,但诊断的敏感性和特异性差别较大,导致其无法得到早期诊断和及时治疗.SUDOSCAN作为一种新型糖尿病微血管并发症的检测技术,具有快速、简便、无创、定量、重复性好和准确性高的特点,其可通过测得的电化学传导率(ESC)计算出糖尿病微血管并发症的发生风险,对糖尿病微血管并发症早期诊断和治疗评估有重要作用.     

Neuroprotective effect of N-acetylcysteine in the development of diabetic encephalopathy in streptozotocin-induced diabetes

Diabetic encephalopathy is characterized by impaired cognitive functions that involve neuronal damage triggered by glucose driven oxidative stress. The objective of the present study was to determine whether N-acetylcysteine (NAC) supplementation ameliorates learning and memory deficits caused by hyperglycemia-induced oxidative stress in experimental diabetes. Male Wistar rats (200–250 g) were rendered diabetic by a single intraperitoneal injection of streptozotocin (50 mg/kg). Cognitive deficits were observed in diabetic animals assessed using elevated plus maze test after 8 weeks of induction of diabetes. Acetylcholinesterase activity, a marker of cholinergic function, was decreased by 15.6% in the cerebral cortex, 20.9% in cerebellum and 14.9% in brain stem of diabetic rats compared to control rats. There was an increase in lipid peroxidation in cerebral cortex (21.97%), cerebellum (20.4%) and brain stem (25.5%) of diabetic rats. This was accompanied by decrease in glutathione and total thiol content along with decrease in the activities of superoxide dismutase, catalase and glutathione reductase. However, glutathione peroxidase activity increased by 11.2%, 13.6% and 23.1% in cerebral cortex, cerebellum and brain stem respectively, while the activity of glutathione-s-transferase decreased only in cerebral cortex (21.7%). Supplementation with NAC (1.4 g/kg/day in drinking water) significantly attenuated cognitive deficits and oxidative stress in diabetic rats. Our results emphasize the involvement of increased oxidative stress in cognitive impairment in diabetic animals and point towards the potential beneficial role of NAC as an adjuvant therapy to conventional anti-hyperglycemic regimens for the prevention and treatment of diabetic encephalopathy.     

吸烟对早期糖尿病肾病静息能量消耗的影响

目的 观察吸烟对早期糖尿病肾病静息能量消耗(REE)的影响及与氧化应激和炎症反应之间的关系.方法 对31例吸烟和40例非吸烟的早期糖尿病肾病患者的一般情况、临床特征、REE、REE与去脂组织(FFM)的比值、氧化应激及炎症反应标志物进行比较分析.结果 吸烟组的REE/FFM比非吸烟组显著增高15.96%(P=0.001).相关分析提示,REE/FFM的增高与吸烟有关(t=0.395,P=0.001).氧化应激标志物丙二醛(MDA)、超氧化物歧化酶(SOD)和炎症反应标志物高敏C反应蛋白(hs-CRP)两组间差异有统计学意义(P＜0.05),脂联素、TNFα组间差异无统计学意义(P＞0.05),REE/FFM的增高与MDA、SOD、hs-CRP、脂联素、TNFα均不相关(P＞0.05).结论 吸烟可导致早期2型糖尿病肾病患者REE增加,引起氧化应激和炎症反应,但REE增高与氧化应激和炎症反应无关.