Responsiveness of plasma aldosterone to angiotensin II in patients with diabetes mellitus

Aldosterone responsiveness to angiotensin II (A II) was evaluated in 65 diabetic patients with and without various diabetic complications versus 38 age-matched non-diabetic subjects. Plasma aldosterone (PA), together with plasma renin activity (PRA), was low and responded poorly to furosemide (80 mg, orally) plus upright posture (4 hours) stimulation in diabetic patients. When the PA response to stimulation relative to PRA response was estimated from the ratio of PA increase to PRA increase after stimulation (delta PA/delta PRA), the 38 non-diabetic subjects had ratios more than 3.0. Of the 65 diabetic patients, 48 had normal delta PA/delta PRA ratios (more than 3.0) and 17 had low delta PA/delta PRA ratios (less than 2.9). Graded A II infusions (1, 2, and 4 ng/kg/min each for 30 min) were performed under a low sodium intake (sodium, 120 mEq/day) in 25 of the 65 diabetic patients, whose delta PA/delta PRA ratios were normal in 15 and low in 10, and in 16 non-diabetic subjects. The PA responses to the graded A II infusions in the normal delta PA/delta PRA diabetic patients were similar to those in the non-diabetic subjects. However, the PA responses to the graded A II infusions in the low delta PA/delta PRA diabetic patients were significantly lower. It is concluded that, although the majority of diabetic patients have normal aldosterone responsiveness to A II, some diabetic patients have blunted aldosterone responsiveness to A II probably attributable to the abnormality of the adrenal cortex in addition to the impaired renin secretion.     

Motor vehicle driving among diabetics taking insulin and non-diabetics.

OBJECTIVE--To determine whether rates of road traffic accidents were higher in diabetics treated with insulin than in non-diabetic subjects. DESIGN--Controlled, five year retrospective survey. SETTING--Diabetic, dermatology, and gastroenterology outpatient clinics. PATIENTS--596 Diabetics treated with insulin (354 drivers) aged 18-65 attending two clinics and 476 non-diabetic outpatients (302 drivers). MAIN OUTCOME MEASURES--Rates of accidents in diabetic and non-diabetic subjects. RESULTS--A self completed questionnaire was used to record age, sex, driving state, and rates of accidents and convictions for motoring offences among diabetic and non-diabetic volunteers. For the diabetic volunteers further information was obtained on treatment, experience of hypoglycaemia, and declaration of disability to the Driving and Vehicle Licensing Centre and their insurance company. Accident rates were similar (81 (23%) diabetic and 76 (25%) non-diabetic drivers had had accidents in the previous five years). A total of 103 diabetic drivers had recognised hypoglycaemic symptoms while driving during the previous year. Only 12 reported that hypoglycaemia had ever caused an accident. Overall, 249 had declared their diabetes to an insurance company. Of these, 107 had been required to pay an increased premium, but there was no excess of accidents in this group. CONCLUSIONS--Diabetic drivers treated with insulin and attending clinics have no more accidents than non-diabetic subjects and may be penalised unfairly by insurance companies.     

Effect of insulin on von Willebrand factor release in normal and diabetic subjects: in vivo and in vitro studies.

The aim of this study was to evaluate the effect of insulin on the release of vWf in vivo during an oral glucose tolerance test (OGTT) performed in normal, glucose-intolerant and diabetic subjects and in vitro on human endothelial cells. Twenty-eight subjects exhibiting risk factors for diabetes underwent an OGTT: 11 subjects proved to be normal, 7 were glucose-intolerant and 10 diabetic. In each group, the vWf and PAI-1 plasmatic levels were measured at t = 0, 30 min and 180 min after the beginning of the test. Human endothelial cells from non-diabetic and diabetic subjects were incubated in the presence of human insulin at various concentrations (0.25, 2.5, 25 and 250 mUI/ml). After 1, 4, and 24 hours of incubation, the release of vWf and endothelin 1 was measured in the cell supernatant and the intracellular amount of vWf in the cell lysate. During the OGTT, the vWf levels in plasma were not affected despite a 4.5-, 6-, and 2.5-fold increase in insulin levels in normal, glucose-intolerant and diabetic subjects, respectively. Although raised in all three groups, PAI-1 plasmatic levels remained constant during the test. After 24 hours of exposure to insulin (0.25 mU/ml), the release of vWf by endothelial cells reached 35.94 +/- 23.08 % of the basal value for non-diabetic subjects, and 27.57 +/- 10.05 % for diabetic patients. Similar results were observed in non-stimulated cells. Insulin had no influence on intracellular vWf content, which remained comparable to control values. Regardless of its concentration, insulin failed to stimulate the release of vWf by endothelial cells of non-diabetic and diabetic subjects, while its ability to stimulate the release of endothelin 1 was preserved. In conclusion, hyperinsulinemia had no adverse effect on circulating vWf in normal or diabetic subjects. Neither release nor intracellular vWf content in non-diabetic or diabetic endothelial cells was influenced by insulin in vitro.     

Negative correlation between erythrocyte count and mean corpuscular volume or mean corpuscular haemoglobin in diabetic and non-diabetic subjects

Negative correlation was observed between erythrocyte count (RBC) and mean corpuscular volume (MCV) or mean corpuscular haemoglobin (MCH) in both sexes of diabetic and non-diabetic Libyans. The slopes of regression lines for MCV-RBC and MCH-RBC of diabetic patients were significantly lower (P less than 0.001) than those of their non-diabetic counterparts. Positive correlation was found between MCH and MCV. The slope of the regression line for MCH-MCV of diabetic patients was not significantly different from that of non-diabetic subjects.     

Differences in adiponectin protein expression: effect of fat depots and type 2 diabetic status.

Adiponectin is an adipocyte-derived hormone associated with insulin sensitivity and atherosclerotic risk. As central rather than gluteofemoral fat is known to increase the risk of type 2 diabetes and cardiovascular disease, we investigated the mRNA and protein expression of adiponectin in human adipose tissue depots. RNA was extracted from 46 human adipose tissue samples from non-diabetic subjects aged 44.33 +/- 12.4 with a BMI of 28.3 +/- 6.0 (mean +/- SD). The samples were as follows: 21 abdominal subcutaneous, 13 omentum, 6 thigh; samples were also taken from diabetic subjects aged 66.6 +/- 7.5 with BMI 28.9 +/- 3.17; samples were: 6 abdominal subcutaneous; 3 thigh. Quantitative PCR and Western analysis was used to determine adiponectin content. Protein content studies determined that when compared with non-diabetic abdominal subcutaneous adipose tissue (Abd Sc AT) (values expressed as percentage relative to Abd Sc AT -100 %). Adiponectin protein content was significantly lower in non-diabetic omental AT (25 +/- 1.6 %; p < 0.0001, n = 6) and in Abd Sc AT from diabetic subjects (36 +/- 1.5 %; p < 0.0001, n = 4). In contrast, gluteal fat maintained high adiponectin protein content from non-diabetic patients compared with diabetic patients. An increase in BMI was associated with lower adiponectin protein content in obese ND Abd Sc AT (25 +/- 0.4 %; p < 0.0001). These findings were in agreement with the mRNA expression data. In summary, this study indicates that adiponectin protein content in non-diabetic subjects remains high in abdominal subcutaneous fat, including gluteal fat, explaining the high serum adiponectin levels in these subjects. Omental fat, however, expresses little adiponectin. Furthermore, abdominal and gluteal subcutaneous fat appears to express significantly less adiponectin once diabetic status is reached. In conclusion, the adipose tissue depot-specific expression of adiponectin may influence the pattern of serum adiponectin concentrations and subsequent disease risk.     

Association of low birth weight with beta cell function in the adult first degree relatives of non-insulin dependent diabetic subjects.

OBJECTIVE--To examine the relation between birth weight and beta cell function in the first degree relatives of non-insulin dependent diabetic subjects. DESIGN--Cross sectional study of 101 adults of known birth weight from 47 families which had at least one member with non-insulin dependent diabetes. SUBJECTS--101 white adults aged mean 43 (SD 7) years. SETTING--Oxfordshire, England. MAIN OUTCOME MEASURES--Glucose tolerance was measured by continuous infusion glucose tolerance test. beta cell function and insulin sensitivity were calculated from the fasting plasma glucose and insulin concentrations with homeostasis model assessment. beta cell function was standardised to allow for the confounding effects of age and obesity. RESULTS--Twenty seven subjects had non-insulin dependent diabetes, 32 had impaired glucose tolerance, and 42 were normoglycaemic. Birth weight correlated with the beta cell function of the complete cohort (rs = 0.29, p = 0.005), the non-insulin dependent diabetic subjects (rs = 0.50, p = 0.023), and the non-diabetic subjects (rs = 0.29, p = 0.013). The non-insulin dependent diabetic (n = 27) and the non-diabetic (n = 74) subjects had similar mean (inter-quartile range) centile birth weight 50% (19%-91%), and 53% (30%-75%) respectively. Non-insulin dependent diabetic subjects had significantly lower beta function than the non-diabetic subjects: 69% (48%-83%) v 97% (86%-120%), p < 0.001. CONCLUSIONS--The cause of the association between low birth weight and reduced beta cell function in adult life is uncertain. Impaired beta cell function in non-insulin dependent diabetic subjects was not accounted for by low birth weight, and genetic or environmental factors are likely to be necessary for development of diabetes.     

Reduced insulin-mediated citrate synthase activity in cultured skeletal muscle cells from patients with type 2 diabetes: evidence for an intrinsic oxidative enzyme defect

In myotubes established from patients with type 2 diabetes (T2D), lipid oxidation and insulin-mediated glucose oxidation are reduced, whereas in myotubes from obese non-diabetic subjects, exposure to palmitate impairs insulin-mediated glucose oxidation. To determine the underlying mechanisms of these metabolic malfunctions, we studied mitochondrial respiration, uncoupled respiration and oxidative enzyme activities (citrate synthase (CS), 3-hydroxy-acyl-CoA-dehydrogenase activity (HAD)) before and after acute exposure to insulin and/or palmitate in myotubes established from healthy lean and obese subjects and T2D patients. Basal CS activity was lower (14%) in diabetic myotubes compared with myotubes from lean controls (P=0.03). Incubation with insulin (1 microM) for 4 h increased the CS activity (26-33%) in myotubes from both lean (P=0.02) and obese controls (P<0.001), but not from diabetic subjects. Co-incubation with palmitate (0.6 mM) for 4 h abolished the stimulatory effect of insulin on CS activity in non-diabetic myotubes. No differences were detected in mitochondrial respiration and HAD activity between myotubes from non-diabetic subjects and T2D patients, and none of these measures responded to high levels of insulin and/or palmitate. These results provide evidence for an intrinsic defect in CS activity, which may play a role in the pathogenesis of T2D. Moreover, the data suggest that insulin resistance at the CS level can be induced by exposure to high free fatty acid levels.     

Use of a biothesiometer to measure individual vibration thresholds and their variation in 519 non-diabetic subjects.

A series of 519 non-diabetic subjects had vibration thresholds at three points measured using a biothesiometer. Thresholds appeared to be log normally distributed and increased with age. Centile charts of this relation were derived from the data giving a range for normal thresholds. The biothesiometer provides a quick and reliable assessment of vibration thresholds, which when related to the centile charts gives an objective measure of the progress of diabetic peripheral neuropathy.     

Ala45Thr variation in neuroD1 gene is associated with early-onset type 2 diabetes with or without diabetic pedigree in Chinese

Objective: Based on onset-age stratified analysis may be useful to determine the association of NeuroD1-Ala45Thr variation with susceptibility to genetic heterogeneous type 2 diabetes mellitus (T2DM), we investigated the Ala45Thr variation in unrelated early-onset and late-onset T2DM with or without diabetic pedigree and unrelated non-diabetic control subjects in Chinese. Methods: 175 early-onset and 194 late-onset type 2 diabetic patients were further divided into two subgroups according to with or without diabetic pedigree respectively. This NeuroD1-Ala45Thr variation were screened by PCR-direct sequencing in above 369 type 2 diabetic patients and 87 unrelated non-diabetic control subjects. We then compared the distribution of the Ala45Thr variation among the groups, searching for the predictive trends. Results: Frequencies of the variant (AA + GA genotype) in early-onset T2DM are obviously elevated, especially among diabetic pedigree subjects when compared to non-diabetic controls (p= 0.003) and late-onset T2DM subjects (p = 0.014). However, no significant differences were observed between late-onset T2DM with or without diabetic pedigree and non-diabetic control subjects. Conclusions: Our results suggest that 1) the NeuroD1-Ala45Thr variation may itself have an important role in susceptibility to or be in disequilibrium with early-onset T2DM in Chinese; 2) the Ala45Thr may affect the onset pattern of T2DM, i.e., early-onset but not late-onset T2DM in Chinese; and 3) onset-age stratified analysis may be useful to determine the association of NeuroD1-Ala45Thr variation with susceptibility to genetic heterogeneous T2DM in Chinese.     

Metabolic abnormalities in first-degree relatives of type 2 diabetics

Diabetic relatives and obese subjects are at increased risk for development of diabetes mellitus, and therefore are classed as potential abnormality of glucose tolerance (POT-AGT). Disturbances of lipid and purine metabolisms have been reported in diabetic and obese non-diabetic subjects. In obese subjects above alterations are probably due to hyperinsulinemia. This study aimed at verifying whether similar metabolic abnormalities could be found in relatives of non-insulin dependent diabetic patients and whether they could be related to possible glucose intolerance. We have studied 10706 outpatients and 95 hospitalized subjects, aged between 20 and 50 years. We have selected 4 groups according to diabetic relationship and body mass index: A (normal weight subjects), B (obese subjects), C (normal weight NIDDM-relatives), D (overweight NIDDM-relatives). The NIDDM-relatives showed higher prevalence of hyperglycemia, as expected; furthermore the relatives with normal glucose tolerance had higher glucose area during OGTT. Serum levels of uric acid and insulin response to oral glucose were increased in all obese subjects, but abnormalities of lipid metabolism and fasting hyperinsulinemia were found only in obese NIDDM-relatives. These results suggest that family history of diabetes mellitus can be a risk for metabolic disturbance even in absence of glucose intolerance. Furthermore some metabolic disorders observed in obese subjects could be due to an associated and not sufficiently investigated family history of diabetes.     

Oral Lactobacillus species in type 2 diabetic patients living in southern Thailand

Although lactobacilli are part of normal oral, gastrointestinal and genitourinary flora, they are an uncommon cause of infections in human. Lactobacillus-associated infections have generally occurred in patients with serious underlying conditions e.g. diabetes and cancer that might favour certain microorganisms. The aim of this study was to characterize species and genotypes of lactobacilli isolated from diabetic patients and non-diabetic subjects. One hundred and five type 2 diabetic patients and 103 non-diabetic subjects were recruited in this study. A total of 170 isolates of Lactobacillus were identified using 16S rRNA gene PCR-RFLP and genotyping were performed using AP-PCR by ERIC primers. It was found that type 2 diabetic patients had a significantly higher prevalence (p = 0.008) and level of lactobacilli than non-diabetic controls (p = 0.030). The most frequently isolated Lactobacillus spp. were L. casei/paracasei and L. fermentum in both the diabetic and non-diabetic groups. Strains of L. casei/paracasei and L. fermentum from between and within individuals were genotyped, and the genotyping of Lactobacillus strains showed diversity between individuals. One up to three genotypes of these two species could be found in the same subject. Interestingly, fewer genotypes were found in the diabetic patients than in the non-diabetic subjects.     

Foot microcirculation and blood rheology in diabetes

Diabetes mellitus is associated with circulatory abnormalities. The blood flow in the skin of the dorsum of the foot and haemorheological variables were measured in 36 subjects. They were divided into three equal groups of diabetic patients: those with neuropathy, and both age and sex matched non-diabetic subjects; all were characterized by age, duration of diabetes and blood biochemistry. High and low shear rate blood viscosities were measured; aggregation was characterized using a Myrerene Aggregometer. The microcirculation in the skin of the dorsum of the foot was measured using a laser Doppler flowmeter. Measurements were made at room temperature with the subjects supine with the leg horizontal, and then with the lower leg vertical; the measurements were repeated at 42° C. Both diabetic groups had significantly increased low shear whole blood viscosity compared with normal subjects. The aggregation index was significantly greater in diabetic neuropaths than normal subjects. There were significant differences in the depth of vasomotor activity between the three groups, with the diabetic neuropaths commonly showing no motor activity at room temperature. The only significant correlations were between equilibrium laser Doppler values with the limb horizontal and both the low and high shear whole blood viscosities.     

Renal replacement treatment for diabetic patients in Newcastle upon Tyne and the Northern region, 1964-88.

OBJECTIVES--To review the experience of renal replacement treatment in diabetic patients treated in Newcastle upon Tyne and the Northern region from 1964 to 1988, and to compare the morbidity and mortality of diabetic patients treated with dialysis or transplantation with those of matched controls of non-diabetic patients. DESIGN--Retrospective study of clinical case notes. SETTING--Renal units of the Northern region, particularly that in Newcastle upon Tyne. PATIENTS--All 65 diabetic patients treated by renal replacement treatment in Newcastle upon Tyne from 1964 to 1987; 42 diabetic patients were matched with 42 non-diabetic patients according to age, sex, year of starting treatment, and type of treatment (dialysis or transplantation). MAIN OUTCOME MEASURES--Sex, age, renal biopsy findings, blood pressure, history of diabetic treatment, and plasma creatinine concentration at the start of renal replacement treatment. History of renal replacement treatments, suitability for transplantation, history of transplantation, cumulative survival, and cause of death during follow up. Survival of technique, cumulative survival of the first peritoneal catheter and history of peritonitis in patients treated with continuous ambulatory peritoneal dialysis; source of graft, histocompatibility antigens, duration of associated stay in hospital, and graft survival in patients receiving renal or pancreatic transplant. RESULTS--1259 Patients with chronic renal failure were accepted for renal replacement treatment in Newcastle upon Tyne, of whom 65 (5%) had diabetes. The first was accepted in 1974, and between 1974 and 1980 another 15 were treated (mean age 42 years; 4% of new patients). From 1981 to 1987, 49 diabetic patients (mean age 44; 9% of new patients) were treated. Fifty patients (77%) had insulin dependent diabetes and the remaining 15 (23%) non-insulin dependent diabetes. On average, the patients were aged 25 (range 5-57) when diabetes was first diagnosed and 44 (range 24-70) at the start of renal replacement treatment. The mean age at the start of treatment was 40 for patients with non-insulin dependent diabetes and 58 for patients with non-insulin dependent diabetes. Transplantation was performed in 33 of the diabetic patients, whose mean age was lower than that of those who did not receive a transplant (41 v 48 respectively, p less than 0.05). Comparison between the 42 diabetic patients and matched controls showed that the overall survival at five years was 46% and 77% respectively. The three year survival of the diabetic patients who did not receive a transplant was poor (41% v 79% respectively). Of patients transplanted, survival at five years was 73% in the diabetic patients and 90% in the controls. However, there was no significant difference in the five year graft survival (64% v 46% respectively). CONCLUSIONS--Diabetes adversely affects morbidity and mortality in patients having renal replacement treatment, but renal transplantation seems to be the best option for treating diabetic patients with end stage renal failure.     

Type 2 Diabetes Mellitus and Kidney Cancer Risk: A Retrospective Cohort Analysis of the National Health Insurance

Purpose

To evaluate the association between incidence of any kidney cancer and type 2 diabetes mellitus.

Methods

A random sample of 1,000,000 subjects covered by the National Health Insurance was recruited. A total of 998728 people (115655 diabetes and 883073 non-diabetes) without kidney cancer at recruitment were followed from 2003 to 2005. The cumulative incidence of kidney cancer from 2003 to 2005 in diabetic patients and non-diabetic people in all ages and in age <40, 40–64, 65–74 and ≥75 years were calculated in the diabetic patients and the non-diabetic people, respectively. Logistic regression was used to estimate the odds ratios comparing diabetic patients to non-diabetic people in the respective age groups. Multivariable-adjusted odds ratios for kidney cancer with regards to diabetes status and diabetes duration (as a continuous variable or categorized into subgroups of non-diabetes, diabetes duration <1 year, 1–2.9 years, 3–4.9 years and ≥5 years) were estimated after multivariable adjustment. The multivariable-adjusted odds ratios for all baseline variables were also estimated for diabetic patients and non-diabetic people, respectively.

Results

The 3-year cumulative incidence of kidney cancer in the diabetic patients and the non-diabetic people was 166.9 and 33.1 per 100,000 person-years, respectively. The incidence increased with regards to increasing age in both the diabetic patients and the non-diabetic people, but a higher risk of kidney cancer for the diabetic patients compared to the non-diabetic people was consistently observed in different age groups. After multivariable adjustment, the odds ratio for diabetic patients versus non-diabetic people was 1.7 (95% confidence interval: 1.3–2.1, P<0.01). While compared to the non-diabetic people, the odds ratio (95% confidence interval) for diabetes duration <1, 1–2.9 years, 3–4.9 years and ≥5 years was 1.5 (0.8–2.7), 1.6 (1.0–2.4), 1.6 (1.1–2.4) and 1.7 (1.3–2.3), respectively (P-trend <0.01). Analyses conducted in the diabetic patients and the non-diabetic people, respectively, consistently showed age, nephropathy and end-stage renal disease as significant risk factors of kidney cancer. Additionally, living in metropolitan Taipei region might also be associated with a higher risk of kidney cancer in the non-diabetic people, indicating a potential link between kidney cancer and some factors related to urbanization.

Conclusions

Patients with type 2 diabetes mellitus have a significantly higher risk of kidney cancer.     

Pioglitazone acutely influences glucose-sensitive insulin secretion in normal and diabetic human islets

We have studied acute effects of the PPARgamma agonist pioglitazone in vitro on human islets from both non-diabetic and type 2 diabetic subjects. In 5 mM glucose, pioglitazone caused a transient increase in insulin secretion in non-diabetic, but not diabetic, islets. Continuous presence of the drug suppressed insulin release in both non-diabetic and diabetic islets. In islets from non-diabetic subjects, both high glucose and tolbutamide-stimulated insulin secretion was inhibited by pioglitazone. When islets were continuously perifused with 5 mM glucose, short-term pretreatment with pioglitazone caused approximately 2-fold increase in insulin secretion after drug withdrawal. Pioglitazone pretreatment of diabetic islets restored their glucose sensitivity. Examination of cytosolic free Ca(2+) concentration ([Ca(2+)](i)) in non-diabetic islets revealed slight Ca(2+) transient by pioglitazone at 3 mM glucose with no significant changes at high glucose. Our data suggest that short-term pretreatment with pioglitazone primes both healthy and diabetic human islets for enhanced glucose-sensitive insulin secretion.     

Hyposensitivity of C-fiber Afferents at the Distal Extremities as an Indicator of Early Stages Diabetic Bladder Dysfunction in Type 2 Diabetic Women

Purpose

To investigate the relationship between distal symmetric peripheral neuropathy and early stages of autonomic bladder dysfunction in type 2 diabetic women.

Materials and Methods

A total of 137 diabetic women with minimal coexisting confounders of voiding dysfunction followed at a diabetes clinic were subject to the following evaluations: current perception threshold (CPT) tests on myelinated and unmyelinated nerves at the big toe for peroneal nerve and middle finger for median nerve, uroflowmetry, post-void residual urine volume, and overactive bladder (OAB) symptom score questionnaire. Patients presenting with voiding difficulty also underwent urodynamic studies and intravesical CPT tests.

Results

Based on the OAB symptom score and urodynamic studies, 19% of diabetic women had the OAB syndrome while 24.8% had unrecognized urodynamic bladder dysfunction (UBD). The OAB group had a significantly greater mean 5 Hz CPT test value at the big toe by comparison to those without OAB. When compared to diabetic women without UBD, those with UBD showed greater mean 5 Hz CPT test values at the middle finger and big toe. The diabetic women categorized as C-fiber hyposensitivity at the middle finger or big toe by using CPT test also had higher odds ratios of UBD. Among diabetic women with UBD, the 5 Hz CPT test values at the big toe and middle finger were significantly associated with intravesical 5 Hz CPT test values.

Conclusions

Using electrophysiological evidence, our study revealed that hyposensitivity of unmyelinated C fiber afferents at the distal extremities is an indicator of early stages diabetic bladder dysfunction in type 2 diabetic women. The C fiber dysfunction at the distal extremities seems concurrent with vesical C-fiber neuropathy and may be a sentinel for developing early diabetic bladder dysfunction among female patients.     

Usefulness of enhanced power Doppler imaging in monitoring acral microcirculation in type 2 diabetes mellitus and its complications

This study compared hemodynamic changes of acral arterioles (pulps and nail beds of fingers and toes) and the microcirculatory status of acra between patients with uncomplicated (n = 45) or complicated (n = 36) type 2 diabetic mellitus (type 2 DM) and healthy subjects (n = 40). Enhanced power Doppler imaging (e-Flow) was used to display the nail bed arterioles and distal branches of pulp arterioles (digitales palmares propriea and digitales plantares propriea) in the end knuckle of the right middle finger and right big toe. Arteriolar density (AD) was assessed by vascular pixel percentage. Compared to healthy subjects, in patients with DM the end diastolic velocity (EDV) of the nail bed arterioles of both finger and toe was diminished, while the vascular resistance index (RI) was increased. These changes became more prominent with a longer duration of the disease. Furthermore, both the peak systolic velocity (PSV) and AD were decreased in patients with DM. These hemodynamic changes were also evident in the pulp arterioles of fingers and toes, although they appeared at more advanced stages of the disease. Overall, the abnormal changes were more pronounced in patients with complications. In conclusion, hemodynamic changes (e.g. decrease in the number of acral arterioles) progress with a longer duration of the disease. The acral arteriolar damage is more pronounced in patients with a complicated type 2 DM.     

Waist-to-Hip Ratio,Dyslipidemia, Glycemic Levels,Blood Pressure and Depressive Symptoms among Diabetic and Non-Diabetic Chinese Women: A Cross-Sectional Study

Objectives

To explore the relationship between depressive symptoms and waist-to-hip ratio, dyslipidemia, glycemic levels or blood pressure among diabetic and non-diabetic Chinese women.

Methods

11,908 women aged ≥40 years were enrolled in this cross-sectional study, including 2,511 with type 2 diabetes and 9,397 without. Depressive symptoms (defined as having mild-to-severe depressive symptoms) were assessed by the Patient Health Questionnaire-9 (PHQ-9) diagnostic algorithm. The prevalence and the odds ratios (ORs) with 95% confidence intervals (CIs) for having depressive symptoms were estimated using logistic regression analysis.

Results

The age-adjusted prevalence of depressive symptoms was significantly higher in non-diabetic subjects with waist-to-hip ratio (WHR) ≥0.9 (8.6%, age-adjusted OR 1.51 [95% CI 1.17, 1.95]), total cholesterol (TC)>6.22 mmol/L (8.8%, 1.58 [1.16, 2.15]), and Hemoglobin A1c (HbA1c) ≥6.00 mmol/L (7.7%, 1.69 [1.34, 2.14]), while it was significantly lower in non-diabetic subjects with diastolic blood pressure (DBP) between 80 to 89 mmHg (6.2%, 0.78 [0.64, 0.95]). These relationships remained significant even after controlling for multiple factors (WHR ≥0.9: multivariable-adjusted OR 1.39 [95% CI 1.07, 1.80]; TC>6.22 mmol/L: 1.56 [1.14, 2.12]; HbA1c ≥6.00 mmol/L: 1.64 [1.30, 2.08]; DBP 80-89 mmHg: 0.78 [0.64, 0.95]). However, no significant trend between depressive symptoms and WHC, TC, HbA1c, DBP was observed in diabetic women, and no significant trend relationship between depressive symptoms and BMI, WC, TG, or SBP was observed in both non-diabetic and diabetic women. Moreover, the prevalence of depressive symptoms was significantly higher in previously-diagnosed diabetes, compared with non-diabetic subjects, while no significant differences were observed between newly-diagnosed diabetes and non-diabetic subjects.

Conclusion

The present study showed a relationship between WHR, TC, HbA1c, DBP and depressive symptoms among non-diabetic women, while no significant relationship between them was observed among diabetic women, even after controlling for multiple confounding factors.     

Outcome of renal replacement treatment in patients with diabetes mellitus.

OBJECTIVE--To compare the outcome of renal replacement treatment in patients with diabetes mellitus and in non-diabetic patients with end stage renal failure. DESIGN--Retrospective comparison of cases and matched controls. SETTING--Renal unit, Western Infirmary, Glasgow, providing both dialysis and renal transplantation. PATIENTS--82 Diabetic patients starting renal replacement treatment between 1979 and 1988, compared with 82 matched non-diabetic controls with renal failure and 39 different matched controls undergoing renal transplantation. MAIN OUTCOME MEASURES--Patient characteristics, history of smoking, prevalence of left ventricular hypertrophy and myocardial ischaemia at start of renal replacement treatment; survival of patients with renal replacement treatment and of patients and allografts with renal transplantation. RESULTS--The overall survival of the diabetic patients during the treatment was 83%, 59%, and 50% at one, three, and five years. Survival was significantly poorer in the diabetic patients than the controls (p less than 0.001). Particularly adverse features for outcome at the start of treatment were increasing age (p less than 0.01) and current cigarette smoking (relative risk (95% confidence interval) 2.28 (0.93 to 4.84), p less than 0.05). Deaths were mainly from cardiac and vascular causes. The incidence of peritonitis in patients on continuous ambulatory peritoneal dialysis was the same in diabetic patients and controls (49% in each group remained free of peritonitis after one year), and the survival of renal allografts was not significantly worse in diabetic patients (p less than 0.5). CONCLUSIONS--Renal replacement treatment may give good results in diabetic patients, although the outlook remains less favourable than for non-diabetic patients because of coexistent, progressive vascular disease, which is more severe in older patients.     

In vitro effect of gliclazide on DNA damage and repair in patients with type 2 diabetes mellitus (T2DM)

Type 2 diabetes mellitus is associated with elevated level of oxidative stress, which is one of the most important factors responsible for the development of chronic complications of this disease. Moreover, it was shown that diabetic patients had increased level of oxidative DNA damage and decreased effectiveness of DNA repair. These changes may be associated with increased risk of cancer in T2DM patients, since DNA damage and DNA repair play a pivotal role in malignant transformation. It was found that gliclazide, an oral hypoglycemic drug with antioxidant properties, diminished DNA damage induced by free radicals. Therefore, the aim of the present study was to evaluate the in vitro impact of gliclazide on: (i) endogenous basal and oxidative DNA damage, (ii) DNA damage induced by hydrogen peroxide and (iii) the efficacy of DNA repair of such damage. DNA damage and DNA repair in peripheral blood lymphocytes of 30 T2DM patients and 30 non-diabetic individuals were evaluated by alkaline single cell electrophoresis (comet) assay. The extent of oxidative DNA damage was assessed by DNA repair enzymes: endonuclease III and formamidopyrimidine-DNA glycosylase. The endogenous basal and oxidative DNA damages were higher in lymphocytes of T2DM patients compared to non-diabetic subjects and gliclazide decreased the level of such damage. The drug significantly decreased the level of DNA damage induced by hydrogen peroxide in both groups. Gliclazide increased the effectiveness of DNA repair in lymphocytes of T2DM patients (93.4% (with gliclazide) vs 79.9% (without gliclazide); P< or =0.001) and non-diabetic subjects (95.1% (with gliclazide) vs 90.5% (without gliclazide); P< or =0.001). These results suggest that gliclazide may protect against the oxidative stress-related chronic diabetes complications, including cancer, by decreasing the level of DNA damage induced by reactive oxygen species.