Permeability and morphology of skeletal muscle capillaries in type 1 (insulin-dependent) diabetes mellitus

Summary Muscle blood flow and capillary diffusion capacity were determined in 21 Type 1 (insulin-dependent) diabetic patients and in 12 age-matched healthy subjects by measuring the simultaneous clearance of ¹³³xenon and ¹³¹iodide from hyperaemic anterior tibial muscle. Blood flow was significantly lower (mean ± SD: 46.7±14.1 versus 59.4±12.9 ml 100 g^-1 min^-1, p<0.02) and capillary diffusion capacity was significantly greater (mean ± SD: 8.0±2.1 versus 5.9±1.3 mol/min, p<0.005) in the diabetic patients than in the control subjects. Ultrastructural dimensions and density of capillaries in the gastrocnemius muscle of 11 diabetic patients and six control subjects were also studied. Diabetic and control capillaries did not differ in total capillary area. Compared with normal capillaries, the percentage area of basement membrane and the apparent basement membrane thickness were significantly greater (1.21±0.6 versus 0.78±0.2 , p<0.05) in diabetic capillaries, while there were no significant differences in luminal, endothelial and pericytial areas. There was no difference in capillary density between the two groups. No correlation was found between basement membrane thickness and capillary diffusion capacity in the diabetic patients. We conclude that the greater capillary diffusion capacity is due to increased permeability of diabetic capillaries, and that the basement membrane is probably not ratelimiting in the transcapillary transport of hydrophilic substances in diabetic subjects.     

The structural arteriolar changes in diabetes mellitus and essential hypertension: The relative contribution of ageing and high blood pressure

AIM: To evaluate the relative contribution of blood pressure, non-insulindependent diabetes mellitus and ageing on arteriolar structuralchanges in essential hypertension and diabetes mellitus. POPULATION AND METHODS: One hundred subjects, 25 with hypertension (A), 25 with hypertensionand diabetes (B), 25 with diabetes (C) and 25 healthy subjects(D). Blood pressure average values, obtained with non-invasivemonitoring, and minimal vascular resistance, calculated withstrain-gauge plethysmography, were statistically correlated.Multiple regression analysis was performed to assess the contributionof blood pressure and age. RESULTS: Minimal vascular resistance was higher in A, B and C than inD, and higher in B than in A and C. The coefficient of bloodpressure in the multiple regression analysis was significantfor all the parameters in A and B but not in C and D; that ofage was significant only in A and only for the average valuesof mean and diastolic blood pressure. CONCLUSION: Hypertension and diabetes show arteriolar structural changesof similar gravity. Age does play a role in hypertension buta smaller one than that played by blood pressure. In hypertensionand diabetes the lack of significance of the contribution ofage to the correlation between minimal vascular resistance andpressure could be ascribed to other neurohumoral factors. Thesefactors play a much more important role in diabetes, where neitherblood pressure nor age show any correlation with high vascularresistance.     

Reduced capillary hydraulic conductivity in skeletal muscle and skin in Type I diabetes: a possible cause for reduced transcapillary fluid absorption during hypovolaemia

Aims/hypothesis. Patients with Type I (insulin-dependent) diabetes mellitus have a reduced transcapillary fluid absorption from skeletal muscle and skin and thus defective plasma volume regulation during hypovolaemia. Our aim was to find whether a defective capillary filtration coefficient or impaired transcapillary driving force are aetiologic factors for this reduction. Methods. We investigated 11 diabetic patients (diabetes duration 6.9 ± 1.1 years, age 26 ± 1 years), without complications and 12 control subjects (26 ± 1 years). Their capillary filtration coefficient was measured in the upper arm using a volumetric technique at rest and during lower body negative pressure (LBNP). We calculated the driving force for transcapillary fluid transfer. Results. The increase in heart rate and the decrease in systolic blood pressure during lower body negative pressure were similar in diabetic and control subjects. The resting capillary filtration coefficient was decreased in the diabetic subjects, 0.033 ± 0.003 vs 0.051 ± 0.007 ml · 100 ml^–1· min^–1· mmHg^–1 (p < 0.05). During lower body negative pressure, the capillary filtration coefficient increased 35 % in both groups compared with resting capillary filtration coefficient and was still decreased in diabetes; 0.046 ± 0.004 compared with 0.069 ± 0.006 ml · 100ml^–1· min^–1· mmHg^–1 (p < 0.01). The established driving force during lower body negative pressure was 1.37 ± 0.11 vs 1.30 ± 0.15 mmHg (NS) in diabetic and control subjects, respectively. Conclusions/interpretation. Our study indicates that a reduced capillary filtration coefficient rather than defective regulation of transcapillary driving force, is the reason for the reduced transcapillary fluid absorption during hypovolaemic circulatory stress found in Type I diabetic patients. [Diabetologia (2000) 43: 1178–1184] Received: 28 January 2000 and in revised form: 8 May 2000     

Increased forearm blood flow in longstanding Type 1 diabetic patients without microvascular complications.

AIMS: According to the 'haemodynamic hypothesis', chronic hyperglycaemia induces an increase in tissue perfusion that predisposes to microangiopathy. We hypothesized that patients with longstanding diabetes mellitus (DM), who have not developed microvascular complications, would have normal tissue perfusion. METHODS: In six Type 1 diabetic patients (age 43.4 +/- 1.1 years; DM duration 25.3 +/- 2.6 years.; HbA(1c) 8.5 +/- 0.7%), who had no evidence of microvascular complications, and six age- and gender-matched healthy volunteers (Control) we measured haemodynamic parameters including forearm blood flow (FBF; plethysmography) and sympathetic tone, an important regulator of blood flow, by the combination of plasma sampling (catecholamine levels), microneurography and power spectral analysis of blood pressure and heart rate. RESULTS: FBF was increased in the diabetic compared with control subjects (4.8 +/- 1.2 vs. 2.2 +/- 0.3 ml/dl per min, P < 0.05) and forearm vascular resistance (FVR) was decreased (25 +/- 6 and 43 +/- 3 arbitrary units, P < 0.05). Heart rate was higher in diabetic subjects (77 +/- 10 vs. 57 +/- 2 beats/min, P < 0.05). All parameters of sympathetic tone were similar in diabetic and control subjects. CONCLUSIONS: In patients with Type 1 diabetes, without signs of microvascular complications and with diabetes duration of > 20 years, skeletal muscle blood flow was increased while sympathetic tone was normal. These results suggest that increased blood flow does not inevitably lead to microvascular complications and challenge the hypothesis that it has a causative role in the pathophysiology of complications.     

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.     

Comparison of vasodilator effects of substance P in human forearm vessels of normoalbuminuric Type 1 diabetic and non-diabetic subjects.

AIMS: To compare the vasodilatory responses to substance P in human forearm vessels in Type 1 normoalbuminuric diabetic and non-diabetic subjects. METHODS: Forearm blood flow (FBF) was measured using a plethysmography technique in 12 normoalbuminuric Type 1 diabetic subjects (six males, six females) (HbA(1c) 8.2 +/- 0.3% (mean +/- SEM)) and 12 non-diabetic healthy control subjects in response to the infusion of the vasodilators substance P (SP), acetylcholine (ACh) and nitroprusside. RESULTS: There was no significant difference in baseline FBF between the two groups (2.80 +/- 0.29 ml/min per 100 ml forearm tissue (diabetic group) vs. 2.85 +/- 0.37 ml/min per 100 ml (non-diabetic group), P = 0.45). Infusion of SP was associated with an incremental increase in FBF in the diabetic (0.6, 2 and 6 ng/min - 6.08 +/- 1.07, 7.82 +/- 1.08 and 9.48 +/- 1.14 ml/min per 100 ml, respectively) and the non-diabetic group (0.6, 2 and 6 ng/min - 5.41 +/- 0.80, 6.93 +/- 0.96 and 9.25 +/- 1.11 ml/min per 100 ml, respectively). Similarly, an incremental rise in FBF was observed during infusion of ACh (diabetic group: 7.5, 15 and 30 microg/min - 7.14 +/- 1.22, 8.91 +/- 1.40 and 11.67 +/- 1.93 ml/min per 100 ml, respectively; non-diabetic group: 7.5, 15 and 30 microg/min - 5.87 +/- 0.81, 7.49 +/- 0.96 and 10.74 +/- 1.29 ml/min per 100 ml, respectively). When FBF was expressed as percentage change from baseline, there was no significant difference in vasodilatory responses between the two groups for SP (0.6 ng/min, P = 0.21; 2 ng/min, P = 0.19; 6 ng/min, P = 0.19) or ACh (7.5 microg/min, P = 0.20; 15 microg/min, P = 0.20; 30 microg/min, P = 0.35). CONCLUSIONS: This study suggests that endothelium-dependent vasodilatory responses to SP (and ACh) are not impaired in Type 1 diabetic subjects with normal urinary albumin excretion.     

2型糖尿病患者肾小球滤过率与尿白蛋白的关系

目的探讨2型糖尿病患者慢性肾脏病(CKD)的患病率及肾小球滤过率与尿白蛋白排泄间的关系。方法收集自2008年1月至2009年12月在江苏省省级机关医院就诊的2型糖尿病患者资料,采用MDRD公式评估肾小球滤过率(eGFR),CKD定义为存在白蛋白尿或者eGFR60 ml/(min·1.73 m2)。白蛋白尿定义为尿白蛋白/肌酐比值(ACR)≥30 mg/g。采用多项式回归及曲线拟合分析eGFR与尿ACR之间的关系。结果研究纳入1521例2型糖尿病患者,平均年龄(63.9±12.0)岁,CKD及白蛋白尿的患病率分别为31.0%和28.9%。eGFR≥90、60~89、30~59、15~29 ml/(min·1.73 m2)患者白蛋白尿的患病率分别为19.9%、34.5%、65.6%和100%。在正常蛋白尿、微量白蛋白尿及大量白蛋白尿患者中,肾功能不全的比率分别为3.0%、9.3%和40.4%。多项式回归分析显示当患者尿ACR90 mg/g时,eGFR下降缓慢且稳定保持在90 ml/(min·1.73 m2)以上,而当尿ACR≥90 mg/g时,eGFR则迅速下降。结论 2型糖尿病患者CKD及白蛋白尿发生率高,对2型糖尿病人群进行CKD的筛查应该同时检测尿白蛋白与eGFR,为了延缓CKD的进展,应尽早对白蛋白尿进行干预治疗。     

Plasma disappearance of glycated and non-glycated albumin in Type 1 (insulin-dependent) diabetes mellitus: evidence for charge dependent alterations of the plasma to lymph pathway

Summary The fractional plasma escape rates of glycated and non-glycated albumin have earlier been measured in groups of Type 1 (insulin-dependent) diabetic patients and control subjects. The escape of non-glycated albumin was similar in control subjects and normoalbuminuric patients, but elevated in patients with micro or macroalbuminuria. In all groups the escape rate of glycated albumin was lower than that of non-glycated albumin. Glycation increases the anionic charge of albumin. To assay for charge-dependent alterations of transport a selectivity index (non-glycated albumin/glycated albumin transport ratio) was determined from the disappearance data. The index was high in control subjects (1.021±0.0057 (SEM)). This reflects a mean difference between the two escape rates of 2.1% per hour (for comparison the mean of the fractional escape rate of non-glycated albumin of the normal control subjects was 4.7% per hour). The index was numerically even higher in normoalbuminuric patients (1.031±0.0047 (SEM)), but reached significantly lower levels in patients with microalbuminuria (1.013±0.0030 (SEM), p<0.02). Patients with clinical nephropathy had very low levels indicating loss of selectivity (1.002±0.0068 (SEM), p<0.001). This pattern accords well with measurements of renal clearance selectivity indices, suggesting a general, progressive deterioration of anionic perivascular barrier components in diabetic microangiopathy. The structural target for these changes is likely to be the glycosaminoglycans of the glomerular basal membrane and the interstitial matrix.     

Studies on peripheral glucose metabolism using the experimental human forearm preparation

Summary Metabolic studies on the human forearm glucose uptake are described. The results of these investigations can be summarized as follows: the mean fasting forearm glucose uptake of normal subjects was found to be + 0.53/gmmol/min/100 ml of forearm (S.E. ± 0.20), of fasting insulin-dependent diabetics –0.32 mol/min/100 ml of forearm (S.E. ± 0.59) and of fasting insulin-independent diabetics of –0.50 mol/min/100 ml of forearm (S.E. ± 0.23). — Statistical analysis of these data show that in 3 insulin-dependent diabetic patients there is a significant correlation between arterial blood glucose and forearm glucose uptake pointing to a peripheral tissue threshold above which the glucose molecule moves from the intravascular space to the intracellular compartment. — No significant correlations were found between the deep venous blood glucose of the forearm and the forearm glucose uptake in the same patients. — The injection of 0.1 units glucagon-free insulin into the brachial artery increases the forearm glucose uptake without affecting the arterial blood glucose. Greater doses decrease the arterial blood glucose inhibiting the hepatic glucose output. — On the other hand in the insulin-dependent diabetics no peripheral insulin effect was shown with the same or higher insulin doses indicating that these patients may have a peripheral tissue resistance to the insulin action. — The mean average forearm phosphate uptake was estimated to be + 0.03 mol/min/100 ml of forearm (S.E. ± 0.04) in normals and. – 0.03,mol/min/100 ml of forearm (S.E. ± 0.13) in diabetics. Furthermore the statistical analysis of these data showed that there is a significant relationship (P < 0.05) between the forearm glucose uptake and the forearm phosphate uptake both in normals and in diabetics. This should mean that the phosphate molecule follows the glucose molecule moving from the extracellular space to the intracellular space according to the insulin effect. — Finally the mean fasting forearm potassium uptake was –0.93 /gmmol/min/100 ml of forearm (S.E. ± 0.45) in normals and –0.90 mol/min/100 ml of forearm (S.E. ± 2.7) in diabetics. No significant correlations were found between the forearm glucose uptake and the potassium glucose uptake in either normals or diabetic patients.

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Untersuchungen über den peripheren Glucosestoffwechsel am menschlichen Unterarm

Zusammenfassung Es werden Untersuchungen der Glucoseaufnahme am menschlichen Unterarm beschrieben. — Die Untersuchungsergebnisse können, wie folgt, zusammengefaßt werden: Die durchschnittliche Glucose Aufnahme am Unterarm im Nüchternzustand lag beim Normalen bei + 0.53 mol/min/100 ml Unterarm (S.E. ± 0.20), bei insulinabhängigen Diabetikern bei –0.32 mol/min/100 ml Unterarm (S.E. ± 0.59) und bei nicht insulinbedürftigen Diabetikern bei –0,50 mol/min/ 100 ml Unterarm (S.E. ± 0.23). — Die varianzanalytische Betrachtung dieser Ergebnisse zeigt für 3 insulinbedürftige, diabetische Patienten eine signifikante Korrelation zwischen arteriellem Blutzuckerspiegel und der Glucoseaufnahme am Unterarm und deutet damit auf das Vorliegen eines Schwellenwertes im peripheren Gewebe hin, bei dessen Überschreiten das Glucosemolekül aus dem intravaskulären Raum in den Intrazellulärraum eintritt. — Dieselben Patienten zeigten keine signifikante Korrelation zwischen dem Blutzuckerspiegel in den tiefen Venen und der Glucoseaufnahme des Unterarms. — Die Injektion von 0.1 E glucagonfreiem Insulin in die A. brachialis steigert die Glucose-Aufnahme am Unterarm, ohne den arteriellen Blutzuckerspiegel zu beeinflussen. Höhere Dosen senken den arteriellen Blutzuckerspiegel durch Hemmung der Glucoseausschüttung der Leber. -Bei den insulinbedürftigen Diabetikern fand sich jedoch mit den gleichen oder höheren Insulin-Dosen kein peripherer Insulin-Effekt, so daß die Annahme nahe liegt, daß bei diesen Patienten das periphere Gewebe eine Resistenz gegenüber der Insulin Wirkung aufweist. Die durchschnittliche Phosphat-Aufnahme am Unterarm lag schätzungsweise bei + 0.03 mol/min/100 ml Unterarm (S.E. ± 0.04) für die Normalpersonen und bei –0.03) mol/min/100 ml Unterarm (S.E. ± 0.13) für die Diabetiker. Die statistische Auswertung der Resultate ergab eine signifikante Abhängigkeit(p kleiner als 0.05) zwischen Glucose- und Phosphat-Aufnahme am Unterarm bei Normalpersonen und Diabetikern. Dies würde bedeuten, daß das Phosphat-Molekül dem Glucose-Molekül folgt, das unter der Insulin-Einwirkung aus dem Extrazellulärraum in den Intrazellulärraum übertritt. -Schließlich lag die Kalium-Aufnahme des Unterarms im Nüchternzustand für die Normalpersonen bei – 0.93,mol/ min/100 ml Unterarm (S.E. ± 0.45) und für die Diabetiker bei -0.90 mol/min/100 ml Unterarm (S.E. ± 2.7). Weder bei den Kontrollpersonen noch bei den Diabetikern ergab sich eine signifikante Korrelation zwischen Glucose- und Kalium-Aufnahme am Unterarm.

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Etudes sur le métabolisme périphérique du glucose à l'aide de la préparation expérimentale de l'avant-bras humain

Résumé Les auteurs décrivent des études métaboliques sur la captation du glucose par l'avant-bras humain. Les résultats de ces investigations peuvent être résumés comme suit : La captation moyenne de glucose par l'avantbras de sujets normaux à jeun, était de + 0.53 mol/min/ 100 ml d'avant-bras (S.E. ± 0.20), celle des diabétiques insulino-dépendants à jeun était de –0.32 mol/min/ 100 ml d'avant-bras (S.E. ± 0.59) et celle des diabétiques non-insulino-dépendants à jeun, était de –0.50 mol/ min/100 ml d'avant-bras (S.E. ± 0.23). — Les analyses statistiques de ces données montrent que chez 3 patients diabétiques insulino-dépendants, il y a une corrélation significative entre la glycémie artérielle et la captation de glucose par l'avant-bras, indiquant qu'il y a un seuil dans le tissu périphérique au-dessus duquel la molécule de glucose passe de l'espace intravasculaire dans le compartiment intracellulaire. — Chez les mêmes patients, on n'a trouvé aucune corrélation significative entre la glycémie de la veine profonde de l'avant-bras et la captation de glucose par l'avant-bras. — L'injection dans l'artère brachiale de 0.1 unité d'insuline sans glucagon augmente la captation de glucose par l'avant-bras sans modifier la glycémie artérielle. Des doses plus élevées diminuent la glycémie artériellle en inhibant la production de glucose hépatique. — D'autre part, chez les diabétiques insulinodépendants, il ne se produisait aucun effet périphérique de l'insuline, avec des doses d'insuline égales ou supérieures, ce qui indique que ces patients peuvent avoir une résistance des tissus périphériques à l'action de l'insuline. — La captation moyenne de phosphate par l'avant-bras a été estimée être de + 0.03mol/min/100ml d'avant-bras (S.E. ± 0.04) chez les sujets normaux, et de –0.03 mol/ min/100 ml d'avant-bras (S.E. ± 0.13) chez les diabétiques. En outre, l'analyse statistique de ces données a montré qu'il y a une relation significative (P< 0.05) entre la captation de glucose et la captation de phosphate par l'avant-bras, aussi bien chez les sujets normaux que chez les sujets diabétiques. Ceci signifierait que la molécule de phosphate suit la molécule de glucose passant de l'espace extracellulaire dans l'espace intracellulaire, sous l'effet de l'insuline. — Enfin, la captation moyenne de potassium par l'avant-bras était, à jeun, de -0.93 mol/min/100 ml d'avant-bras (S.E. ± 0.45) chez les sujets normaux, et de – 0.90 mol/min/100 ml d'avant bras (S.E. ± 2.7) chez les diabétiques. On n'a trouvé aucune corrélation significative entre la captation de glucose et celle de potassium par l'avant-bras, ni chez les sujets normaux, ni chez les diabétiques.

     

糖尿病患者血清生长激素与肌酐清除率

测定了１６例胰岛素依赖型糖尿病（ＩＤＤＭ）患者，１９例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者和２３例对照者的血清生长激素（ＧＨ）水平。在ＩＤＤＭ组，无论是肌酐清除率（Ｃｃｒ）正常或减低，其ＧＨ值均为２．５３±１．７３μｇ／Ｌ，均高于对照组的０．７１±０．５３μｇ／Ｌ（Ｐ＜０．０５），ＧＨ与Ｃｃｒ呈负相关（ｒ＝０．６３，Ｐ＜０．０１），ＮＩＤＤＭ组Ｃｃｒ＜５０ｍｌ／ｍｉｎ者ＧＨ值为１．８３±０．４７μｇ／Ｌ显著高于对照组（Ｐ＜０．０５）和Ｃｃｒ＞８０ｍｌ／ｍｉｎ组（ＧＨ０．８３±０．４９μｇ／Ｌ，Ｐ＜０．０５）。糖尿病（ＤＭ）伴微血管并发症者，ＧＨ值为２．９２±１．７０μｇ／Ｌ，高于无此并发症者ＧＨ１．２４±０．９７μｇ／Ｌ，（Ｐ＜０．０１），认为ＧＨ与ＤＭ微血管并发症有关。     

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妊娠糖尿病(GDM)的妇女产后发生2型糖尿病、高血压的危险增高。妊娠糖尿病易导致巨大儿,其次还会导致流产、早产、死胎的发生率增高等。高风险的妇女应在怀孕后即进行糖耐量试验,若未发现血糖的异常,则应在妊娠24～28周复查。经饮食控制后空腹血糖大于5.8 mmol/L或餐后2 h血糖大于6.7 mmol/L的患者需用药物治疗,治疗首选人胰岛素,其剂量和剂型应个体化。ADA指南推荐空腹时低于5.3 mmol/L,餐后1 h低于7.8 mmol/L,2 h低于6.7 mmol/L。     

2型糖尿病患者预估肾小球滤过率与血清胆红素的相关性

目的 研究2型糖尿病患者预估肾小球滤过率（eGFR）与血清总胆红素（TBIL）、直接胆红素（DBIL）、间接胆红素（IBIL）的相关性.方法 选取2011年11月至2012年9月于天津医科大学代谢病医院糖尿病肾病科住院治疗的2型糖尿病患者523例为研究对象,按eGFR分为肾小球高滤过组（133例）、肾功能正常组（194例）、肾功能轻度下降组（125例）、肾功能中重度下降组（71例）.比较各组TBIL、DBIL、IBIL水平,并行相关因素分析,多组计量资料间比较采用方差分析.结果 肾小球高滤过组各胆红素水平较肾功能正常组水平均明显下降[分别为TBIL：（10.9±4.0）比（12.5 ±4.5）μmol/L、DBIL：（3.8±1.6）比（4.4±1.7） μmol/L、IBIL：（7.1 ±2.8）比（8.0±3.1）μmol/L,均P＜0.05].肾功能中重度下降组TBIL、DBIL、IBIL水平较其他3组均明显下降（F=15.296、15.024、11.609,均P＜0.05）.在eGFR＜ 130 ml/min的人群中,eGFR的相关分析结果提示：eGFR与年龄、病程、总胆固醇、低密度脂蛋白胆固醇呈负相关（r=-0.307、-0.203、-0.149、-0.111,均P＜0.05）,与TBIL、DBIL、IBIL呈正相关（r=0.291、0.275、0.254,均P＜0.05）.结论 2型糖尿病患者血清胆红素水平与肾小球滤过率相关.     

Body position and blood pressure measurement in patients with diabetes mellitus

AIMS: World Health Organization (WHO) guidelines recommend that the blood pressure (BP) should be routinely measured in sitting or supine followed by standing position, providing that the arm of the patient is placed at the level of the right atrium in each position. The aim of our study was to test the influence of body and arm position on BP measurement in diabetic patients. METHODS: In 142 patients with diabetes mellitus the BP was measured using a semiautomatic oscillometric device (Bosomat-R): (i) after 5 min of rest sitting on a chair with one arm supported at the right atrial level and with the other arm placed on the arm support of the chair, (ii) after 5 min of rest lying on a bed with both arms placed on a bed, and (iii) after 30 s and after 2 min of standing with one arm (the same as in sitting position) supported at the right atrial level and with the other arm vertical, parallel to the body. RESULTS: Both systolic (SBP) and diastolic (DBP) blood pressures were significantly lower in sitting position with the arm at the right atrial level than in supine position (by 7.4 and 6.6 mmHg, respectively, P < 0.01). In sitting and standing positions, SBP and DBP were higher when the arm was placed either on the arm support of the chair or vertical, parallel to the body, than when the arm was supported at the level of the right atrium (by 6-10 mmHg, P < 0.001). Duration of standing did not influence the estimation of orthostatic hypotension. CONCLUSIONS: The data of this study indicate that the WHO recommendation with regard to the equivalence of sitting and supine BP readings is incorrect at least in diabetic patients, as the sitting BP is lower than the supine BP when the arm was positioned at the right atrial level. In addition, incorrect positioning of the arm in standing position results in an underestimation of prevalence of orthostatic hypotension. We conclude that during BP measurement the arm should be placed at the right atrial level regardless of the body position.     

Blood levels of alloxan in children with insulin-dependent diabetes mellitus

Alloxan is a well-known and universally used agent for evoking experimental diabetes through its toxic effect on the B cells of the Langerhans islets. In our study, blood levels of alloxan in children with insulin-dependent diabetes mellitus were investigated. The observations were made in 68 children aged 6–15 years and in a control group of 44 healthy children in the same age range. Alloxan levels were estimated spectrophotometrically. The mean level of alloxan in blood from children with insulin-dependent diabetes mellitus was 8.76±9.64 g/ml and in blood from healthy children was 1.53±1.10 g/ml. The difference was statistically significant (P<0.05). The metabolism of alloxan leads to the production of free superoxide radicals which, as is well known, injure cells and cause conditions conducive to the occurrence of diseases from autoimmunity. The results obtained suggest therefore that higher levels of alloxan in diabetic children are of significance in the onset of insulin-dependent diabetes mellitus.     

Glomerular size and structure in diabetes mellitus

Summary The present electron microscopic study shows that the kidney hyperfunction in early diabetes can be due to a significant morphological change: an increased glomerular filtration surface. Applying standard stereological methods, the area of the peripheral wall of the glomerular capillaries was measured in biopsy specimens obtained from 7 patients with early diabetes and 7 controls. — An 80 per cent enlargement of the capillary wall (the surface of the peripheral basement membrane) was found in the diabetics (2 p=0.0096). Also the total area of the interface between the tuft and the urinary space was increased by 70 per cent (2 p=0.029). Since the thickness of the peripheral basement membrane is known to be unchanged in patients with early diabetes the finding of an increased area of the membrane implies that an increased quantity of basement membrane material is present in these patients. The significance of this phenomenon for the understanding of the metabolism of the basement membrane is discussed, and a working hypothesis is advanced for the pathogenesis of the diabetic microangiopathy.     

Long-term glycaemic control directly correlates with glomerular filtration rate in early Type 1 diabetes mellitus before the onset of microalbuminuria

Hyperfiltration occurs early in diabetes mellitus and has been implicated in the development of microalbuminuria. Our aim was to re-examine the controversial relationship between glycaemic control and glomerular filtration (GFR) in normoalbuminuric, normotensive, non-obese patients with short duration Type 1 diabetes mellitus (DM). We studied 75 Type 1 DM patients, 35 male, aged 18–42 years, with a duration of diabetes of 4–8 years. GFR was determined by inulin clearance; hyperfiltration was defined as above 145 ml min⁻¹ 1.73 m⁻² (equivalent to 2 SD above mean for a control population). Analysis was by paired Student’s t-testing and linear regression. GFR correlated significantly with HbA_1c (r = 0.47, p < 0.0001) and fructosamine (r = 0.24, p = 0.035). Mean HbA_1c and fructosamine in the 13 patients with hyperfiltration was significantly higher than in the rest of the group (HbA_1c: 9.2 % (95 % C.I. 7.9–10.4 %) vs 7.6 % (7.2–7.9), p = 0.002; fructosamine: 479 μmol l⁻¹ (450–507) vs 410 μmol l⁻¹ (388–432), p = 0.009. This significant difference persisted even when the two highest values of HbA_1c or fructosamine were removed from analysis. Effective renal plasma flow, assessed by PAH clearance, also correlated in all patients with HbA_1c (r = 0.31, p = 0.039). We conclude that poor glycaemic control directly correlates with hyperfiltration and renal hyperperfusion in early Type 1 DM. Copyright © 1998 John Wiley & Sons, Ltd.     

Rapid gastric emptying of a liquid meal in long-term Type 2 diabetes mellitus

Both delayed and accelerated gastric emptying rate (GER) have been reported in patients with diabetes mellitus. Delayed GER has been attributed to autonomic neuropathy in established diabetes but rapid GER was demonstrated in early Type 2 diabetes. The aim of the study was to investigate rapid gastric emptying in a group of people with long-duration Type 2 diabetes. GER of a radiolabelled liquid meal was studied scintigraphically in 20 Type 2 patients with a mean (± SEM) duration of diabetes 13 (±1) years. The 50 % emptying time (t₅₀) for the liquid meal was shorter in diabetic patients (29.6 ± 2.1 min) than in controls (39.2 ± 1.9 min; p<0.0005). Accelerated emptying (t₅₀ value below the shortest t₅₀ of controls) was evidenced in 14/ 20 patients and delayed emptying (t₅₀ value exceeding the upper t₅₀ of controls) in none. Patients with accelerated GER were comparable for BMI, diabetes duration, HbA_1c and fasting glycaemia to those with normal GER. Rapid GER for liquids was found in the presence or absence of autonomic neuropathy. Seven of the patients with rapid emptying of the liquid meal were reassessed using a solid meal. Only one patient demonstrated rapid emptying of the solid meal, which was normal in 3 and delayed in 3 patients. In conclusion, accelerated GER can be found in long-term Type 2 diabetes but there is no concordance between GER of a liquid and a solid meal. Copyright © 1998 John Wiley & Sons, Ltd.     

Blood flow in the foot,polyneuropathy and foot ulceration in diabetes mellitus

Summary Comparable groups of diabetic patients asymptomatic of neuropathy (Group A), with chronic painful polyneuropathy (Group B) and painless polyneuropathy causing recurrent foot ulceration (Group C) were studied for differences in pedal blood flow, peripheral somatic and autonomic neuropathy and vascular calcification. Blood flow abnormalities detected by doppler waveform analysis, and consistent with reduced peripheral vascular resistance, were found in all three diabetic patient groups. The abnormalities were of similar severity in Group A and B but generally more marked in Group C. Tests of peripheral somatic nerve function became progressively more abnormal from Group A to Group C. Autonomic neuropathy was equally severe in Groups B and C, although mild abnormalities were recorded in diabetic patients asymptomatic of neuropathy. A similar pattern was seen for vascular calcification in the tarsal and metatarsal arteries: marked in both neuropathic groups (B and C) but mild in Group A. It was concluded that abnormal blood flow consistent with reduced peripheral vascular resistance is very common in the feet of diabetic patients whether or not they are symptomatic of neuropathy, and is most severe in those with chronic painless polyneuropathy and recurrent foot ulceration. No clear relationship was found between autonomic nerve dysfunction and the degree of abnormality of blood flow.     

Coronary flow reserve in patients with diabetes mellitus and prediabetes

Background: Abnormalities of coronary microcirculation have been reported in patients with diabetes mellitus (DM) even in the presence of normal coronary arteries. It is unknown when the microvascular effects on coronary arteries begin to appear in the DM disease course. Coronary flow reserve (CFR), determined by pharmacological stress transthoracic Doppler echocardiography, is a reliable indicator of coronary microvascular function. We sought to determine the coronary microvascular function of prediabetic patients compared to DM patients and normal population. Methods: Seventy‐four subjects with normal coronary arteries were enrolled. DM and prediabetes were diagnosed according to American Diabetes Association criteria. All subjects had Doppler recordings of the left anterior descending artery with adenosine infusion at a rate of 0.014 mg/kg per minute. Results: The demographical characteristics and laboratory findings of the three groups were similar (DM group: n = 25, mean age 62 ± 7 years, 19 females; prediabetic group: n = 25, mean age 64 ± 12 years, 21 females; control group: n = 24, mean age 63 ± 7 years, 15 females) except fasting glucose levels. CFR values of the three groups were significantly different (DM group: CFR = 1.75 ± 0.50; prediabetic group: CFR = 2.24 ± 0.43; control group: CFR = 2.38 ± 0.32, P < 0.001). CFR values of DM group were lower than those of prediabetic and control groups (DM vs. prediabetic: P < 0.001, DM vs. control: P < 0.001). However, CFR levels of prediabetic group were not different from those of the control group (P = 0.481). DM was an independent factor predictive of CFR < 2 (OR, 22.69; 95% CI, 6.47–79.51; P < 0.001). Conclusion: Coronary microvascular function seems to be normal in the prediabetic state, but dysfunction appears after DM becomes overt. (Echocardiography 2012;29:634‐640)     

The relationship of glycaemic control and triglycerides in patients with diabetes mellitus: a PreCIS Database Study

Aims:  A common therapeutic approach in patients with type 2 diabetes mellitus who have elevated triglycerides (TGs) is to treat the hyperglycaemia before specifically targeting high TG. The aims of the current study were (i) to determine whether there was a relationship between glycated haemoglobin (HgbA1c) and TG levels at the baseline visit and (ii) to analyse the relationship between ΔHgbA1c and ΔTG after treatment.
Methods:  Among 650 consecutive diabetic patients seen in the Cleveland Clinic Preventive Cardiology Department, 372 had both baseline and post-treatment HgbA1c and TG values. We analysed the relationship between baseline HgbA1c and TG as well as between the change in HgbA1c and the change in TG. For analysis, patients were divided into nine groups by tertiles of HgbA1c (≤6.6, 6.7–7.8 and >7.8%) and TG (≤1.75, 1.76–3.89 and >3.89 mmol/l) at baseline.
Results:  At baseline, there was a small correlation between HgbA1c and TG (r² = 0.051; p < 0.001). For the entire group, there was a significant correlation between ΔHgbA1c and ΔTG from baseline to follow-up (r² = 0.077; p < 0.001). Analyses by tertiles showed that ΔTG were only associated with changes in two groups: HgbA1c tertile 3 (>7.8%) and TG tertiles 2 (r² = 0.24; p < 0.0001) and 3 (r² = 0.187; p = 0.003). For every 1% change in the top tertile HgbA1c, there was a 9.3% change in TG (tertile 2) and a 9.8% change in TG (tertile 3).
Conclusions:  These observations suggest that for patients with diabetes mellitus and elevated TG, the effect of HgbA1c reduction has limited effects on TG reduction. Patients may benefit from TG-specific therapy initiated earlier rather than waiting to see effects of glycaemic control.