Urinary kallikrein excretion in non-insulin-dependent diabetes mellitus.

To investigate the status of urinary kallikrein excretion (UKE) in patients with non-insulin-dependent diabetes mellitus (NIDDM), we measured UKE in 31 NIDDM patients. They ranged in age from 40 to 70 years (mean, 54.3 +/- 7.8 years), comprising 18 males and 13 females. Their creatinine clearance (Ccr) was 91.6 +/- 5.5 mL/min, and the daily excretion rate of protein was 1.15 +/- 0.72 g/24 hours. Twenty-five normal persons, aged from 37 to 63 years (mean, 51.7 +/- 8.2 years), comprising 14 males and 11 females, were enrolled as controls. The NIDDM patients were further divided into two groups. Group A (n = 21) had regular blood sugar control, while Group B (n = 9) had poor blood sugar control. The autonomic nervous function was tested in 15 patients to study its relationship with UKE. UKE was measured by spectrophotometric assay of the kallikrein enzymatic product on the synthetic substrate S-2266. Autonomic function was evaluated by cardiovascular reflex tests. The results showed that UKE was elevated in Group B, but depressed in Group A (normal vs A vs B: 9.6 +/- 1.0 vs 4.8 +/- 0.9 vs 14.4 +/- 2.7 nkat/24 hours). The UKE/Ccr ratio was similarly elevated in Group B and reduced in Group A (normal vs A vs B: 0.1 +/- 0.01 vs 0.05 +/- 0.01 vs 0.18 +/- 0.04 nkat. mL/day.minute). There was no significant correlation between UKE or the UKE/Ccr ratio and the Valsalva ratio, the 30:15 ratio, or postural blood pressure change. These results suggest that NIDDM patients have abnormal urinary kallikrein excretion levels that are influenced by blood sugar control. The abnormal UKE/Ccr ratio suggests that intrarenal abnormality in the renal kallikrein-kinin system exists in NIDDM patients.     

Apolipoprotein levels in normolipidemic non-insulin-dependent diabetes mellitus.

The purpose of this study was to examine the change in apolipoprotein and lipoprotein levels in patients with normolipidemic untreated non-insulin-dependent diabetes mellitus (NIDDM). Fifteen untreated, non-obese male NIDDM patients without hyperlipidemia were chosen, and 15 healthy subjects, matched for age, sex, body weight, alcohol consumption and cigarette smoking served as the control group. We observed that the concentrations of plasma total cholesterol (TC), triacylglycerol (TG) and very low density lipoprotein cholesterol (VLDL-C) were identical in both NIDDM and control groups. The levels of low-density lipoprotein cholesterol (LDL-C) were slightly increased in the diabetic group, but the difference did not reach statistical significance in our study. High-density lipoprotein cholesterol (HDL-C) was lower in the NIDDM group than in the controls. Significantly increased TC/HDL-C and LDL-C/HDL-C ratios were found in NIDDM patients compared with controls. The apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II) levels were decreased in NIDDM patients, while the apolipoprotein B (apo B) level remained similar to that of the control subjects. The ratio of apo A-I/apo B was decreased significantly in the NIDDM group. Our results suggest that NIDDM patients are at higher risk of coronary heart disease, even if they remain normolipidemic.     

Contraception in women with diabetes mellitus

Contraception in women suffering of diabetes mellitus is an important question mainly due to it has been proven that pregnancy outcome both for the fetus and for the mother depends on glycemic control before conception right to delivery. That's made planning of future pregnancy mandatory for patients with diabetes mellitus. Patients are advised for contraception until optimization of metabolic control has been achieved or until complete and contemporary treatment of the diabetes complications has been fulfilled. Incorrect contraceptive method could extend metabolic disorders and to reinforce vascular complications of the diabetes. Choice of contraception depends on the aim: short lasting contraception aiming on future pregnancy planning or long lasting contraception aiming on family planning. In women with diabetes mellitus it is extremely important to take into consideration such factors as type of the diabetes, its lasting, degree of metabolic compensation, presence of diabetic complications, body-mass index of the patient, presence of risk factors for cardiovascular diseases and future pregnancy planning. In cases when pregnancy is planning it has been preferred local contraception, such as condoms, diaphragms. In cases of nullipara or in women with plenty of partners, condoms are method of choice. In women who gave birth intrauterine device is such a method. In women with diabetes mellitus type I (insulin dependent diabetes mellitus) it is possible to use hormonal contraception depending on patient's request or on medical indications only in cases when diabetes has less than 15 years duration and microangiopathic complications and other vascular risk factors lack. Combined hormonal contraceptive preparations have to contain less than 30 microg ethinylestradiol and gestagen of "third" or "fourth" generation. This contraception has to be prescribed together with insulin dosage correction and demands on strict metabolic control of the diabetes and body weight. When the combined preparations are contraindicated it could be suggested progestagenic oral hormonal contraception if gynecologic contraindications lack and if this not leads to menstrual disturbances. In women with diabetes mellitus type II (non insulin dependent diabetes mellitus) combined hormonal contraceptives has not to be used, because they could provoke clinical manifestation and deteriorate progress of the diabetes mellitus.     

Therapeutic effect of guar gum in patients with non-insulin-dependent diabetes mellitus.

Diets with a high-fiber content have been shown to produce some beneficial effects on metabolic factors in subjects with NIDDM. However, some controversies still exist. In this report, the long-term effect of guar gum (Guarina) on both glycemic and blood lipid profiles was assessed in a randomized, double-blind and cross-over study on 16 (seven male and nine female) subjects with NIDDM. Each subject received placebo (P) and Guarina (G) treatment for two eight-week periods separated by a four-week period to facilitate wash-out. Fasting plasma glucose levels showed significant improvement during G treatment but not during P treatment (151.7 +/- 7.9 vs 168.6 +/- 12.2 mg/dl, p less than 0.01 by paired Student's t test). Hemoglobin Alc levels decreased significantly during G treatment but not during P treatment (6.9 +/- 0.2 vs 7.2 +/- 0.8%, p less than 0.001). Fasting insulin concentrations also showed significant lowering during G treatment but not during P treatment (18.3 +/- 2.1 vs 23.1 +/- 2.9 U/ml, p less than 0.005). Other variables, including serum total cholesterol, triglyceride, HDLc, LDLc, sodium, potassium, chloride, magnesium and calcium levels showed no significant changes during G or P treatment. Ten out of the 16 patients (62.5%) suffered from side effects; these included abdominal cramps (one case), diarrhea (seven cases) and skin itching (one case). In conclusion, guar gum effectively lowers fasting plasma glucose and HbAlc levels in subjects with NIDDM. Hyperinsulinemia could also be ameliorated. The effectiveness and side effects of guar gum treatment should be cautiously evaluated in each NIDDM subject.     

Periconceptional care of women with diabetes mellitus

Pregestational diabetes is a common complication of pregnancy that can be associated with severe maternal and fetal morbidity. In addition, some women could have progression of diabetic complications secondary to pregnancy. Preconception care can significantly reduce pregnancy complications with a dramatic impact on the diabetic mother and her infant. For those women whose condition could be hastened by conception education, better understanding and an improved decision should be available to them and their families. Because unplanned pregnancy is common among diabetic women, they should be counseled early for the importance of preconception care in the progression of this disease.     

Etonogestrel implant in women with diabetes mellitus

Objectives To evaluate the effect of etonogestrel implant on the control of the carbohydrate and lipid metabolism and on the progression of vascular complications in diabetic women treated with insulin, and to assess the acceptability of this modality of contraception in these patients.

Methods Prospective-observational study of 23 women with insulin-treated diabetes. Clinical and metabolic evaluation was performed before and at 3, 6, 12, and 24 months after implant insertion. Changes from baseline were compared using the mixed effects models or Wilcoxon matched-pairs signed-rank tests.

Results There were no significant changes in BMI, in daily insulin requirement and in mean HbA1c. There was a significant reduction of total serum cholesterol (TC) at 6 and 12 months, of triglyceride levels at 6, 12 and 24 months, and of high-density lipoprotein cholesterol (HDL-C) at 6, 12 and 24 months. Neither the low-density lipoprotein (LDL) levels nor the HDL/TC ratio changed. Albuminuria decreased significantly at 12 and 24 months. No deterioration of the retina was observed over the study period. Amenorrhoea and infrequent bleeding were the most common menstrual bleeding patterns. One woman discontinued the method due to frequent bleeding.

Conclusion We found no evidence of impaired control of the carbohydrate and lipid metabolism or aggravation of vascular lesions during the two years an etonogestrel implant was used by diabetic women.     

Plasma prorenin and renin levels in non-insulin-dependent diabetes mellitus.

To investigate plasma renin and prorenin levels in non-insulin-dependent diabetes mellitus (NIDDM) and their relation with autonomic nervous function and renal impairment, we measured plasma renin and prorenin levels in 39 NIDDM patients. The patients included 21 males and 18 females, aged 56.3 +/- 6.2. Thirty-four normal age-matched subjects served as controls. Autonomic nervous function was evaluated in 23 patients by the performance of cardiovascular reflex tests. The plasma renin concentration was measured by angiotensin I generation after the addition of an exogenous substrate. Plasma prorenin was activated by trypsin. The results showed that the plasma renin concentration was similar between NIDDM patients and normal subjects, while plasma prorenin was higher in NIDDM patients. No correlation existed between the plasma renin or prorenin levels and autonomic nervous function. The patients with abnormally high levels of prorenin also had a similarly high plasma renin level but not a high creatinine clearance (Ccr) or daily proteinuria. The plasma renin level was correlated inversely with daily proteinuria but not with Ccr. These results suggest that the high plasma prorenin levels in some diabetic patients cannot be explained by renal impairment, poor prorenin conversion or autonomic dysfunction. The hyporeninemia in some patients may be related to microvascular involvement of the kidney.     

Predictive factors of developing diabetes mellitus in women with gestational diabetes

BACKGROUND: To investigate which factors during gestational diabetes pregnancies correlate with the risk of developing impaired glucose tolerance or diabetes 1 year postpartum and to compare this risk in women with gestational diabetes and women with a normal oral glucose tolerance test during pregnancy. METHODS: Of 315 women with gestational diabetes, defined as a 2-hr blood glucose value of at least 9.0 mmol/l at a 75-g oral glucose tolerance test, who delivered in Lund 1991-99, 229 (73%) performed a new test 1 year postpartum. We compared maternal and fetal factors during pregnancy with the test value at follow up. A control group of 153 women with a 2-hr test value below 7.8 mmol/l during pregnancy were invited to a new test 1 year postpartum and 60 (39%) accepted. RESULTS: At 1 year follow up, 31% of the women with gestational diabetes but only one of the 60 controls showed pathologic glucose tolerance and one had developed diabetes. The following factors in women with gestational diabetes were identified as predicting impaired glucose tolerance or diabetes at 1 year follow up: maternal age over 40 and--in a multiple regression analysis, independent of each other--a high 2-hr value at oral glucose tolerance test during pregnancy and insulin treatment during pregnancy. CONCLUSION: The risk of developing manifest diabetes after gestational diabetes may be high enough to justify a general screening or diagnostic procedure in all pregnant women to identify women with gestational diabetes and a postpartum follow up program for them. This study did not identify any particular factor during pregnancy with enough precision to predict a later progression to diabetes.     

Perinatal complications in women with gestational diabetes mellitus

BACKGROUND: The aim of the study was to examine the outcome of the pregnancy and neonatal period in 1) women with gestational diabetes mellitus and non-diabetic pregnant women, and 2) in women with early and late diagnosis of gestational diabetes mellitus. METHODS: Included were 327 women with gestational diabetes mellitus and 295 non-diabetic women, who were screened with a 75 g oral glucose tolerance test because of risk factors for gestational diabetes. Women with gestational diabetes mellitus were treated with low-caloric diet and insulin when appropriate, while women in the control group received routine antenatal care. RESULTS: Gestational age at delivery was significantly lower in the group with gestational diabetes mellitus, both when considering all deliveries (39.1+/-1.7 weeks versus 39.8+/-2.0 weeks, p<0.05) and only those with spontaneous onset of labor (38.8+/-2.0 weeks versus 40.0+/-1.6 weeks, p<0.05). The frequency of macrosomia was increased, although not statistically significant (8% vs. 2%, p=0.07), and the rate of admission to the neonatal ward was significantly increased (18% vs. 9%, p<0.05) in the group with gestational diabetes. Women with early diagnosis of gestational diabetes mellitus had a significantly increased need for insulin treatment during pregnancy (36% vs. 9% p<0.05) and a significantly higher occurrence of diabetes mellitus at follow-up from two months until three years postpartum. CONCLUSIONS: This study of women with gestational diabetes mellitus and non-diabetic pregnant women showed that gestational diabetes mellitus was associated with a significantly lower gestational age at delivery and an increased rate of admission to the neonatal ward. Women diagnosed with GDM before 20 weeks of gestation had an increased need for insulin treatment during pregnancy and a high risk of subsequent overt DM, compared with women diagnosed with GDM later in pregnancy.     

Sexual dysfunction in women with diabetes mellitus.

Sexual problems in men with diabetes mellitus are common and often result from diabetic complications. However, although diabetic complications are similar in both sexes, little attention has been given to the effects of diabetes on female sexuality and sexual function. It is reasonable to suggest that women with diabetes will experience sexual problems due to neuropathy, endocrine changes and vascular complications. However there is little research into the physical effects of diabetes on female sexual function. Reduced vaginal lubrication in women with diabetes has been reported yet this is rarely documented as a sexual problem. Previous studies in women with diabetes may also neglect the importance of the subjective qualities associated with female sexuality and sexual expression.     

Contraception in perimenopausal women with diabetes mellitus.

AIM: To assess the effect of combined oral contraceptives (COCs) and intrauterine devices (IUDs) on carbohydrate and lipid metabolism and hemostasis in perimenopausal diabetic women. METHODS: The open randomized study included a total of 113 diabetic women using COCs with different estrogen/progestogen profiles - ethinylestradiol (EE) 20 microg/desogestrel 150 microg, EE 30 microg/desogestrel 150 microg and EE 30 microg/gestodene 75 microg - and levonorgestrel-releasing or copper IUDs. Average daily insulin requirements, levels of glycosylated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, the state of coagulation hemostatis and fibrinolytic activity were determined at baseline and after 3, 6, 9 and 12 months of contraception. The control group was composed of 40 age-matched diabetic women who did not use any methods of contraception. RESULTS: Neither COCs nor IUDs influenced glycosylated hemoglobin and had little or no influence on the elevation in the requirements for insulin preparations. The majority of the preparations did not exert any unfavorable effect on the blood lipid profile. Taking COCs was accompanied by increased intravascular activation of blood platelets and to a lesser degree by alterations in parameters of hemostatic homeostasis. The use of IUDs had a neutral effect on blood coagulation and fibrinolysis systems. CONCLUSION: Comparing lipid levels and hemostatic variables as a function of glycosylated hemoglobin level, we conclude that diabetes control has greater influence on these parameters than the type and dose of steroids involved in the contraceptive devices.     

Outcome of fetuses in women with pregestational diabetes mellitus

OBJECTIVE: To investigate the effects of pregestational diabetes on pregnancy outcome. METHODS: Data of 126 women with pregestational diabetes prospectively collected and controlled in a single tertiary center. HbA(1C) levels at early pregnancy were registered. Adverse pregnancy outcome was defined as spontaneous abortion, congenital defect, stillbirth, or neonatal death. RESULTS: There were 10 spontaneous abortions (7.9%) and 17 fetuses with congenital anomalies (13.4%), including 8 major malformations (6.3%). Compared with pregnancies with a favorable outcome, a higher HbA(1C) concentration in early pregnancy was observed in pregnancies with adverse perinatal outcome [mean (SD): 6.3 (1.6) vs. 7.2 (1.7), P=0.001]. A positive correlation between increased maternal HbA(1C) levels and the rate of fetal malformations was observed, and the group of women with poor metabolic control (early maternal HbA(1c) concentration >7%) showed a 3 to 5-fold increase in the major malformation rate. Cardiovascular and genitourinary defects accounted for 58.8% of the anomalies, and the ultrasound examinations detected seven of them (41.2%). For major malformations, the detection rate was 50% (4/8). Perinatal mortality rate was 26 per thousand (3/116). There was almost 5-fold increase in the total pregnancy loss rate in the poor control group compared with the group with fair control [22.2% vs. 5.3%, OR (95% CI): 5.1 (1.4-17.1)]. Only 11.9% of mothers used a preconception care program. CONCLUSIONS: Pregestational diabetes mellitus is a significant risk factor for the developing fetus. Spontaneous abortions and congenital defects are more common when a poor metabolic control is present in early pregnancy. It is most important to improve access to preconception care programs for achieving a good metabolic control in early pregnancy. Ultrasound examinations have a low performance for detecting congenital defects in diabetic pregnancies.     

妊娠期糖尿病药物治疗新进展

随着经济和生活方式的改变,全球妊娠期糖尿病(gestational diabetes mellitus,GDM)的发病率呈上升趋势,越来越多的GDM患者需要接受孕期咨询和治疗,药物治疗是GDM综合治疗措施中的一个重要组成部分[1].妊娠期间可供临床使用的降糖药物有两大类:一类是胰岛素,另一类是口服降糖药.胰岛素是目前公认的、惟一能够在妊娠期使用的降糖药物,也是妊娠期首选的降糖药物.     

糖尿病合并妊娠时胰岛素的应用

目的研究糖尿病患者孕期胰岛素的应用特点. 方法回顾性分析1981年1月至2003年12月116例糖尿病合并妊娠妇女的治疗情况.116例患者中共有95例在孕期使用胰岛素治疗,其中妊娠36周以后开始治疗者3例;28周以前终止妊娠者7例;胰岛素剂量不详者2例;治疗过程中胎死宫内者1例,其余82例作为观察对象,研究其孕期胰岛素应用特点. 结果 82例孕妇中18例孕期行口服葡萄糖耐量试验,其各点血糖值明显异常,均已达到非孕期糖尿病诊断标准;孕期胰岛素用量随孕周增加而逐渐增加,孕32～36周达高峰,孕36周后略下降直至分娩;孕前未用胰岛素者胰岛素用量增加明显.使用动物胰岛素用量≥100 IU的孕妇的体重指数（BMI）明显高于胰岛素用量＜100 IU的孕妇（P=0.006）. 结论 （1）妊娠期胰岛素用量随孕周增加而变化.（2）动物胰岛素易产生胰岛素抵抗,建议孕期应用人胰岛素.     

Lower urinary tract dysfunctions in women with diabetes mellitus

PURPOSE OF REVIEW: This review discusses published data of the recent advances in understanding lower urinary tract dysfunctions in women with diabetes mellitus. RECENT FINDINGS: Many studies have shown a relationship between diabetes mellitus and lower urinary tract dysfunctions. Although the pathophysiology of these disorders is multifactorial, microvascular damage and neuropathy causing dysfunctions of smooth muscle, urothelium, and neuronal components in the lower urinary tract are the most likely etiologies. SUMMARY: Lower urinary tract dysfunctions are common in diabetes mellitus. Screening and effective management of these disorders should be promoted in an effort to decrease morbidity and improve quality of life.     

Twin pregnancy outcomes for women with gestational diabetes mellitus compared with glucose tolerant women

OBJECTIVE: To examine pregnancy outcomes for women with gestational diabetes mellitus (GDM) and a twin pregnancy compared with glucose tolerant women with a twin pregnancy. DESIGN: Comparison of selected pregnancy outcomes. SETTING: Wollongong, New South Wales, Australia. POPULATION: Women with GDM seen over a 10-year period by an endocrinologist, and women from a selected year of an obstetric database including Wollongong and Shellharbour Hospitals. METHODS: Examination of pregnancy outcome data from the two sources. MAIN OUTCOME MEASURES: Fetal birthweights and method of delivery. RESULTS: There were 28 GDM women with a twin pregnancy from 1229 consecutive referrals (2.3%) of women with GDM for medical management. For comparison there were 29 glucose tolerant women with twin pregnancies evaluable who had delivered over a 1-year period. For the women with GDM and a twin pregnancy there were no significant differences in demographics or outcomes except for a higher rate of elective Caesarean section. CONCLUSION: The higher rate of Caesarean section appeared to be related to the combination of a twin pregnancy and GDM rather than the twin pregnancy or the GDM independently.     

Effect of treatment of borderline hypertension on microalbuminuria in non-insulin-dependent diabetes mellitus.

The advantage of treatment for borderline hypertension has been a debate. We studied two of the commonly used antihypertensive drugs, i.e., trichlormethiazide (Fluitran 2 mg/tab) and enalapril (Renitec 5 mg/tab) on urinary albumin excretion in seven NIDDM subjects with borderline hypertension, who had never been treated with antihypertensive drugs before entry into this study. The observation period was 2 months, and the treatment period was 6 months. Trichlormethiazide (1 tab qd) or enalapril (1 tab qd) were randomly assigned for the first 3 months and then patients were switched to the other drug for the following 3 months. During the treatment period, blood pressure, body weight, blood chemistry including renal function tests, and urinary albumin excretion rate were regularly followed up every 1 to 3 months. The results showed that both of the regimens significantly lowered blood pressure and the urinary albumin excretion rate [12.72 (2.56-25.95) micrograms/min at baseline, to 5.11 (3.0-13.73) micrograms/min during trichlormethiazide treatment and 4.96 (1.38-11.14) micrograms/min during enalapril treatment, p less than 0.008]. However, no significant difference was noted between the two drugs. The magnitude of change in the urinary albumin excretion rate did not correlate with the changes in blood pressure. Renal function, glycemic control, and lipid profiles did not change significantly during the treatment period. In conclusion, both trichlormethiazide and enalapril are effective in lowering the urinary albumin excretion rate in NIDDM subjects with borderline hypertension.