Capillaroscopy and diabetic microangiopathies

Using conjunctival capillaroscopy, the authors studied 40 diabetic patients during glycemic decompensation. The capillaroscopic test, after all metabolic control tests, was repeated 1 and 3 months later and demonstrated improved microcirculation in 10 patients, and proved that therapeutic control is possible during the progression of diabetic microangiopathy.     

Use of andekalin in treating diabetic microangiopathies

A combined study of the state of the blood kinin, coagulation and fibrinolytic systems and microcirculation in the peripheral microvessels of 19 patients with diabetic microangiopathies has shown a diverse nature of disorders of kininogenesis (the enhancement or weakening of the process) and corresponding to it hypo- and hypertonic stages of changes of microcirculation in the microvessels of the eyeball and I toe nail matrix. Activation of blood coagulation, Phase I, revealed both in weakened and enhanced kininogenesis, was more noticeable in the phase of hypokininemia. The administration of andekalin at a single dose of 0.6 units per 1 kg of body mass against a background of sugar reducing therapy in both types of disorders of the activity of the kinin system was accompanied by an insignificant increase in the activity of plasma callicrein but resulted in a marked increase in the initially lowered kinin destroying blood enzymes. The improvement of some indices of microcirculation was noted but in patients with microangiopathies against a background of the weakening of kininogenesis. The administration of andekalin with an enhanced process resulted in some cases in the deterioration of the condition and development of perivascular edema. Insufficient therapeutic efficacy of commonly used doses of andekalin was determined by the presence of andekalin agents in commercial samples and admixtures of a considerable amount of kininases of tissue origin. Proceeding from the earlier experiments and ongoing clinical trials it was proposed that andekalin should be administered to patients with suppressed activity of the blood kinin system only at doses which would not practically contain kininases and would correspond to 0.004-0.005 units per 1 kg of body mass a day.     

Television capillaroscopy in the diagnosis of diabetic microangiopathies

Great toe nail matrix capillaries were examined in 102 diabetes mellitus patients using the TM-I capillaroscope manufactured in the USSR. Changes of the capillaries and blood flow were revealed in 85.3% of the patients, of them 65.7% had aneurysmatic distention of the capillary walls. The expression and frequency of capillary pathology grew with age, period of disease and concomitant coronary heart disease, and arterial hypertension.     

Insulin resistance in offspring of type 2 diabetic patients

Diabetes mellitus is the disease with heterogeneous aetiology. Among the causes of hyperglycaemia the insulin resistance with it's genetical background is mentioned. The aim of the study was the assessment of insulin resistance in healthy offspring of type 2 diabetic patients as well as assessment whether the coexistence of nephropathy in parents has an impact on insulin resistance in offspring. 56 subjects with positive familial history of diabetes type 2 divided into 2 groups were admitted. Subgroup A1 30 subjects (mean age 33.0 +/- 8.5 years) consisted of those who had familial history of diabetes without nephropathy and subgroup A2 26 subjects (mean age 33.0 +/- 6.5 years) with familial history of diabetic nephropathy. Control group consisted of 30 healthy volunteers without familial history. Euglycemic hyperinsulinemic clamp test was performed in all subjects studied. Tissue glucose uptake (TGU) was significantly lower while fasting insulinemia In0 was significantly higher in A1 and A2 groups when compared to controls (respectively TGU 5.6 +/- 2.2, 6.3 +/- 2.5 and 9.5 +/- 2.2 mg/kg/min p < 0.005, In0 19.4 +/- 8.3, 20.8 +/- 8.9 and 11.4 +/- 6.0 p < 0.001). No differences in TGU and In0 when compared A1 vs. A2 group were found. In-depth analysis did not show any differences in relation on whether diabetes was inherited from father's or mother's side. It was also shown that BMI did not interfere on insulin resistance in patients with positive familial history of diabetes. We conclude that insulin resistance has the genetical background and that insulin resistance and nephropathy are inherited separately.     

Insulin resistance and metabolic parameters in type 2 diabetic patients

Background: The importance of insulin resistance in type 2 diabetes mellitus has been generally accepted. Only very few data about the degree of insulin resistance in a representative group of type 2 diabetic patients are available. The aim of this study was to ascertain the degree of insulin resistance and its relation to metabolic parameters in type 2 diabetic patients. Methods: We studied 96 type 2 diabetic patients. The inclusion criteria were type 2 diabetes according to WHO criteria and HbA(1c) between 6.8% and 10.5%. Insulin resistance was estimated in a euglycemic hyperinsulinemic clamp. Blood parameters like lipids, insulin, glucose, fatty acids, and leukocytes were also studied. Results: The insulin sensitivity of 71 of the type 2 diabetic patients was markedly lower than that of the controls. Twenty-five diabetic patients had an M(c) value within the range of the controls. The M(c) values, as a measure of insulin resistance, of the diabetic patients were between 0.3 and 5.2 mg/(kg min insulin), whereas the M(c) range of the controls was from 2.6 to 10.8 mg/(kg min insulin). Conclusions: Approximately 75% of the type 2 diabetic patients were insulin-resistant. Hence, type 2 diabetes mellitus was not equivalent to insulin resistance in every case.     

不同期糖尿病肾病的内皮功能障碍与胰岛素抵抗

目的探讨内皮功能障碍与胰岛素抵抗（IR）在糖尿病肾病（DN）不同时期患者的不同特点。方法2型糖尿病患者136例，按照蛋白尿及肾功能将DN分期：无白蛋白尿期40例，微量蛋白尿期36例，临床蛋白尿期30例，肾功能不全期30例，与正常人及糖尿病前期（糖调节异常）各30例作对比，观察血压（BP）、体重指数（BMI）、腰臀比（WHR）、空腹血糖（FPG）、空腹胰岛素（FINS）、空腹C肽（FCP）、糖化血红蛋白（HbAlc）、尿白蛋白排泄率（UAER）、血内皮素（SET—1）、尿内皮素（UET-1）、肌酐（Cr）、血脂与血液流变学，计算稳态模型IR指数（HOMA-IR）、稳态模型β细胞功能指数（HOMA-Is）、肌酐清除率（Cer）、平均动脉压（MAP）并进行对比分析。结果除肾功能不全期外，DN不同时期患者、糖尿病前期HOMA-IR、HOMA-Is、UAER、SET-1／UET-1、血脂与血液流变学均与正常人相比有显著性差异（P〈0．05或P〈0．01），HOMA-Is呈进行性下降，SET—1／UET-1、UAER与血液流变学呈进行性增高，SET-1／UET-1、UAER分别与FPG、HbAlc、MAP、HOMA-IR、HOMA-Is、血脂、血液流变学显著相关。结论DN各期均存在IR、胰岛功能减退与内皮功能障碍，DN基本的病机与高血糖、IR、胰岛功能减退及内皮功能障碍相互作用继发各种病理机制有关，高血脂、高血压、血液流变学的改变是DN的危险因素，肾功能不全期有特殊表现。     

Screening of subjects at high risk for diabetic microangiopathies

Chronic hyperglycemia is the single most important pathogenic factor in the diabetic triad: retinopathy, glomerulopathy and neuropathy. But at equal serum glucose balance, diabetics are not equally at risk of microangiopathy. Hence the importance of timely screening of patients who should be convinced to accept the constraints and risk of perfect serum glucose balance or to whom specific therapy independent from serum glucose balance could be proposed. But at present, there is no genetic or immunologic marker allowing for the individual identification of at risk patients. Attention is thus directed towards factors which may be directly involved in the pathogenesis of diabetic microangiopathy: --Special sensitivity of vascular collagen to protein glycosylation which could be reflected in the involvement of tendon and aponeurotic collagen, --platelet abnormalities of which the exacerbating role appears to be confirmed by the significant efficacy of aspirin in the treatment of nonproliferative retinopathy in insulin-independent diabetics, --rheological abnormalities which might essentially be secondary to chronic hyperglycemia, --hormonal abnormalities, in particular hypersecretion of growth hormone and/or somatomedin C, whose role has long been suspected and could be established by therapeutic trials with new somatostatin analogues. But the most recent advances concern the study of hemodynamic factors. Irreversible organic diabetic microangiopathy is thought to be preceded by a phase of reversible functional microangiopathy, characterized by increased capillary blood flow, vascular dilatation, hyperpermeability and altered regulation of flow. Thus, diabetic glomerulopathy with decreased glomerular filtration is preceded by a phase of renal "hyperfunctioning" and irreversible proteinuria is the outcome of a progressive increase in microalbuminuria, reversible at least while the levels are not too high.(ABSTRACT TRUNCATED AT 250 WORDS)     

Insulin resistance in Type 2 (non-insulin-dependent) diabetic patients with hypertriglyceridaemia

Summary Hypertriglyceridaemia, which is frequently seen in Type 2 (non-insulin-dependent) diabetes mellitus, is associated with insulin resistance. The connection between hypertriglyceridaemia and insulin resistance is not clear, but could be due to substrate competition between glucose and lipids. To address this question we measured glucose and lipid metabolism in 39 Type 2 diabetic patients with hypertriglyceridaemia, i. e. mean fasting serum triglyceride level equal to or above 2 mmol/l (age 59±1 years, BMI 27.4±0.5 kg/m², HbA_1c8.0±0.2%, serum triglycerides 3.2±0.2 mmol/l) and 41 Type 2 diabetic patients with normotriglyceridaemia, i. e. mean fasting serum triglyceride level below 2 mmol/l (age 58±1 years, BMI 27.0±0.7 kg/m², HbA_1c7.8±0.2 %, serum triglycerides 1.4±0.1 mmol/l). Insulin sensitivity was assessed using a 340 pmol·(m²)^–1· min^–1 euglycaemic insulin clamp. Substrate oxidation rates were measured with indirect calorimetry and hepatic glucose production was estimated using a primed (25 Ci)-constant (0.25 Ci/min) infusion of [3-³H]-glucose. Suppression of lipid oxidation by insulin was impaired in patients with hypertriglyceridaemia vs patients with normal triglyceride levels (3.5±0.2 vs 3.0±0.2mol·kg^–1· min^–1; p<0.05). Stimulation of glucose disposal by insulin was reduced in hypertriglyceridaemic vs normotriglyceridaemic patients (27.0±1.3 vs 31.9±1.6 mol·kg^–1·min^–1; p<0.05) primarily due to impaired glucose storage (9.8±1.0 vs 14.6±1.4mol·kg^–1·min^–1; p<0.01). In contrast, insulinstimulated glucose oxidation was similar in patients with hypertriglyceridaemia and in patients with normal triglyceride concentrations (16.9±0.8 vs 17.2±0.7mol·kg^–1·min^–1). Hepatic glucose production in the basal state and during the clamp did not differ between the two groups. We conclude therefore that oxidative substrate competition between glucose and lipids does not explain insulin resistance associated with hypertriglyceridaemia in Type 2 diabetes. The question remains whether the reduced nonoxidative glucose disposal observed in the patients with hypertriglyceridaemia is genetically determined or a consequence of increased lipid oxidation.     

Insulin resistance in PCOS

Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy affecting women of reproductive age, manifested with a variety of clinical signs, none of which is pathognomonic. The association of insulin resistance and reproductive abnormalities with clinical hyper-androgenism in a woman was first demonstrated by Achard and Thiers in the “diabetes of bearded woman.” The link of PCOS with insulin resistance was subsequently established by clinical studies characterizing the profound insulin resistance in obese and lean PCOS patients. Insulin resistance, hyperinsulinemia, and beta-cell dysfunction are very common in PCOS, but are not required for the diagnosis. The numerous in vivo and in vitro data supporting the central role of insulin resistance in the pathogenesis of PCOS found a broad clinical application in the management of the syndrome, where the regulation of cycle abnormalities and the facilitation of pregnancy in obese PCOS patients was assisted by co-administration of agents such as the well-known insulin sensitizers. The documentation of the presence of insulin resistance contributed substantially to unravel several metabolic components present in the syndrome. Today our knowledge about PCOS appers to have broader health implications and to have profoundly altered our view of the gravity of this condition.     

2型糖尿病患者胰岛素抵抗、血管内皮细胞功能与微量白蛋白尿

目的观察伴或不伴微量白蛋白尿的2型糖尿病(DM)患者胰岛素抵抗(IR)状态及内皮细胞功能,探讨2型DM大血管病变危险性增加的发病机制.方法伴微量白蛋白尿的2型DM组(DM-MA)、尿白蛋白正常的2型DM组(DM-NA)及正常对照组(NC)各12例.3组研究对象均采用正常血糖高胰岛素钳夹试验评价其外周组织葡萄糖利用率(GDR),采用彩色多普勒超声技术测定其内皮细胞依赖性血管舒张功能(EDV)以及非内皮细胞性血管舒张功能(EIV).结果 DM组GDR明显低于正常对照组,且DM-MA组GDR较DM-NA组更低[对照组(13.06±1.98)mg·kg-1·min-1,DM-MA和DM-NA组分别为(7.90±1.79)、(9.46±1.52) mg·kg-1·min-1,P＜0.05或P＜0.01].两组DM患者的EDV较正常对照组降低(均P＜0.05),且DM-MA组EDV受损程度重于DM-NA组(P＜0.05).3组间的EIV差异无显著性.DM组的血游离脂肪酸(FFA)水平明显高于正常对照组(P＜0.05),其中DM-MA组FFA水平最高.偏相关分析显示GDR与EDV呈显著正相关(r=0.47,P＜0.01,n=36).结论与尿白蛋白正常的2型DM患者相比,伴有微量白蛋白尿的2型DM患者具有更严重的IR,EDV明显受损和较高的血FFA水平.提示伴微量白蛋白尿的2型DM患者大血管病变危险性增高的机制可能与IR以及伴随的内皮细胞功能障碍有关.     

Insulin use in elderly diabetic patients

The prevalence of type 2 diabetes is increasing among older adults as is their diabetes-related mortality rate. Studies suggest that tighter glucose control reduces complications in elderly patients. However, too low a glycosylated hemoglobin (HbA_1c) value is associated with increased hypoglycemia. Moreover, the appropriateness of most clinical trial data and standards of care related to diabetes management in elderly patients is questionable given their heterogeneity. Having guidelines to safely achieve glycemic control in elderly patients is crucial. One of the biggest challenges in achieving tighter control is predicting when peak insulin action will occur. The clinician’s options have increased with new insulin analogs that physiologically match the insulin peaks of the normal glycemic state, enabling patients to achieve the tighter diabetes control in a potentially safer way. We discuss the function of insulin in managing diabetes and how the new insulin analogs modify that state. We offer some practical considerations for individualizing treatment for elderly patients with diabetes, including how to incorporate these agents into current regimens using several methods to help match carbohydrate intake with insulin requirements. Summarizing guidelines that focus on elderly patients hopefully will help reduce crises and complications in this growing segment of the population.