Sediment management in sustainable urban drainage system ponds.

Since removal and disposal of sustainable urban drainage system (SUDS) sediment can incur high maintenance costs, assessments of sediment volumes, quality and frequency of removal are required. Sediment depth and quality were surveyed annually from 1999-2003 in three ponds and one wetland in Dunfermline, Scotland, UK. Highest sediment accumulation occurred in Halbeath Pond, in the most developed watershed and with no surface water management train. From comparison of measured potentially toxic metal concentrations (Cd, Cr, Cu, Fe, Ni, Pb, Zn) with standards, the average sediment quality should not impair aquatic ecosystems. 72-84% of the metal flux into the SUDS was estimated to be associated with coarse sediment (> 500 microm diameter) suggesting that management of coarse sediment is particularly important at this site. The timing of sediment removal for these SUDS is expected to be determined by loss of storage volume, rather than by accumulation of contaminants. If sediment removal occurs when 25% of the SUDS storage volume has infilled, it would be required after 17 years in Halbeath Pond, but only after 98 years in Linburn Pond (which has upstream detention basins). From the quality measurements, sediment disposal should be acceptable on adjacent land within the boundaries of the SUDS studied.

Improved glycaemic control with insulin glargine plus insulin lispro: a multicentre, randomized, cross-over trial in people with Type 1 diabetes.

AIMS: To compare blood glucose control using insulin glargine + insulin lispro with that on NPH insulin + unmodified human insulin in adults with Type 1 diabetes managed with a multiple injection regimen. METHODS: In this 32-week, five-centre, two-way cross-over study, people with Type 1 diabetes (n = 56, baseline HbA1c 8.0 +/- 0.8%) were randomized to evening insulin glargine + mealtime insulin lispro or to NPH insulin (once- or twice-daily) + mealtime unmodified human insulin. Each 16-week period concluded with a 24-h inpatient plasma glucose profile. RESULTS: HbA1c was lower with glargine + lispro than with NPH + human insulin [7.5 vs. 8.0%, difference -0.5 (95% CI -0.7, -0.3) %, P < 0.001]. This was confirmed by an 8% lower 24-h plasma glucose area under the curve (AUC) (187 vs. 203 mmol l(-1) h(-1), P = 0.037), a 24% reduction in plasma glucose AUC > 7.0 mmol/l1 (47 vs. 62 mmol l(-1) h(-1), P = 0.017) and a 15% lower post-prandial plasma glucose AUC (75 vs. 88 mmol l(-1) h(-1), P = 0.002). There was no reduction in night-time plasma glucose AUC or increase in plasma glucose area < 3.5 mmol/l. Monthly rate of nocturnal hypoglycaemia was reduced by 44% with glargine + lispro (0.66 vs. 1.18 episodes/month, P < 0.001). CONCLUSIONS: Compared with NPH insulin + unmodified human insulin, the combination of insulin glargine with a rapid-acting insulin analogue as multiple-injection therapy for Type 1 diabetes improves overall glycaemic control as assessed by HbA1c and 24-h plasma glucose monitoring to a clinically significant degree, together with a reduction in nocturnal hypoglycaemia.

The biological variation of testosterone and sex hormone-binding globulin (SHBG) in polycystic ovarian syndrome: implications for SHBG as a surrogate marker of insulin resistance.

This study was designed to assess the biological variability of total testosterone and SHBG in polycystic ovarian syndrome (PCOS) and to determine the use of SHBG as a surrogate marker of insulin resistance in PCOS. Fasting blood samples were collected at 4-d intervals on 10 consecutive occasions from 12 PCOS patients and 11 age- and weight-matched controls. Duplicate samples were analyzed for SHBG, testosterone, and insulin in a single batch, and insulin resistance was calculated by the homeostasis model assessment method (HOMA-IR). The PCOS group had higher testosterone (mean +/- SD, 3.9 +/- 0.8 vs. 3.2 +/- 1.3 nmol/liter; P = 0.001), lower SHBG (28.6 +/- 17.1 vs. 57.6 +/- 30.2 nmol/liter; P = 0.001), and greater HOMA-IR (5.85 +/- 5.3 vs. 1.67 +/- 0.63 U; P = 0.001) than the controls. In contrast to HOMA-IR (1.09 vs. 0.48 U; P = 0.001), the intraindividual variation in SHBG was lower in the PCOS group (mean, 3.4 vs. 6.3 nmol/liter; P = 0.041). The index of individuality for SHBG and testosterone in PCOS was 0.49 and 0.69, respectively. This study shows that for patients with PCOS, SHBG is an integrated marker of insulin resistance that may be of use to identify insulin-resistant individuals for targeted treatment with insulin-sensitizing agents. However, SHBG and testosterone concentrations measured in isolation are inherently unsuitable for use as tests to detect hyperandrogenemia.

Survey of diabetic retinopathy screening services in England and Wales.

A postal survey of diabetologists was conducted regarding the provision of diabetic retinopathy screening services in England and Wales. About 2.5 million people had no existing or planned screening service. For the rest, the perceived percentage of patients with diabetes screened varied from less than 25% to more than 90%. Multiple modes of screening were used in most units. Lack of funding was identified as the major reason for non-provision of an adequate screening service. About 18% of the units had to use research or charitable funds for screening. Only 50% of the units using optometrists for screening had standard protocols for referral. The average wait before an ophthalmologist's opinion on sight threatening retinopathy detected by screening was unacceptably high in some units. We would suggest that establishment of identical screening protocols and provision of adequate funding on a national basis ought to be the priority if incidence of blindness from diabetic retinopathy is to be reduced according to the St Vincent Declaration.

The effects of acute hypoglycemia on relative cerebral blood flow distribution in patients with type I (insulin-dependent) diabetes and impaired hypoglycemia awareness.

To examine the hypothesis that in diabetic patients with impaired hypoglycemia awareness the relative regional distribution of cerebral blood flow (rCBF) would be abnormal in a specific area, namely the frontal lobes, rCBF was examined in 20 type I diabetic patients, of whom 10 had a normal awareness of hypoglycemia and 10 had a history of impaired hypoglycemia awareness. rCBF was determined sequentially using single photon emission computed tomography (SPECT) during (1) normoglycemia (arterialized blood glucose 4.5 mmol. L-1) and (2) hypoglycemia (blood glucose 2.5 mmol.L-1) induced by a hyperinsulinemic glucose clamp technique. Distribution of the isotope, 99mTc-Exametazime, was detected using a single-slice multi-detector head scanner. A split-dose technique was used, with 250 MBq being injected during steady-state normoglycemia and 250 MBq during subsequent hypoglycemia. rCBF was estimated in 30 regions of interest, derived from a standard neuroanatomical atlas on two parallel slices at 40 and 60 mm above the orbitomeatal line (OML). No between-group differences in the pattern of overall rCBF or changes in regional tracer uptake were demonstrated. In comparison to the rCBF during normoglycemia, both patient groups exhibited significant changes in the pattern of rCBF during hypoglycemia, with increments of rCBF to both superior frontal cortices and the right thalamus and reduced rCBF to the right posterior cingulate cortex and the right putamen. This pattern of relative redistribution of rCBF during hypoglycemia was preserved in patients who had impaired hypoglycemia awareness.

Structural equation modeling of symptoms, awareness and fear of hypoglycemia, and personality in patients with insulin-treated diabetes.

OBJECTIVE: To assess the possible influence of personality on self-reported awareness, symptoms, and fear of hypoglycemia and also to identify the relationship among these self-reported measures using formal structural equation modeling. RESEARCH DESIGN AND METHODS: A structured questionnaire, which included questions about sociodemographic details, awareness of the onset of hypoglycemia, and a list of symptoms of hypoglycemia, was completed by 305 consecutive insulin-treated diabetic patients attending the diabetic clinic at the Royal Infirmary of Edinburgh. They also completed the Hypoglycemia Fear Survey (HFS), and personality was assessed using the short form of the shortened Eysenck Personality Questionnaire-Revised (EPQ-R). Formal structural equation modeling was performed using the following variables: awareness, autonomic symptoms, neuroglycopenic symptoms, severe hypoglycemic episodes in the last year, worry and behavior (from the HFS), and extroversion and neuroticism (from the short EPQ-R). This allowed a model to be constructed that expressed the putative causal associations among the variables that could be tested statistically. RESULTS: Of the 302 patients who had experienced hypoglycemia, 111 (37%) reported reduced awareness, and these patients scored higher on the worry subscale of the HFS (reduced awareness: 41 +/- 12 vs. normal awareness: 34 +/- 12, P < 0.001). The patients with reduced awareness scored higher for neuroticism than did the patients with normal awareness (reduced awareness: 6.1 +/- 3.4 vs. normal awareness: 4.9 +/- 3.3, P < 0.01) and scored lower for extroversion (reduced awareness: 5.8 +/- 3.7 vs. normal awareness: 7.1 +/- 3.7, P < 0.01). In the structural equation modeling exercise, neuroticism was a significant putative determinant of many of the other variables. CONCLUSIONS: Personality was the major determinant of the variance that could be accounted for in this study and influenced self-reported symptoms, awareness, and fear of hypoglycemia. Personality factors may, therefore, influence self-reports from patients, particularly when soft measures, such as symptoms, are assessed and even when using validated clinical questionnaires. This finding stresses the importance of using additional evidence, such as reports from relatives, to substantiate reports from patients of loss of hypoglycemia awareness.

PASAT performance and the pattern of uptake of 99mTc-exametazime in brain estimated with single photon emission tomography.

The effect of the paced auditory serial addition test (PASAT) on the regional uptake of 99mTc-exametazime was determined by single photon emission computed tomography. Twenty insulin-treated diabetic outpatients were scanned at rest and during the performance of the PASAT task using split-dose injection of tracer. When resting and activation scans were compared there were significant decreases in tracer uptake in the right anterior cingulate and left posterior cingulate areas during PASAT activation. The findings are compared with previous studies which had implicated the anterior cingulate area in the mechanisms of attention in humans and other animals. The potentially confounding role of anxiety during attentional tasks is discussed.

Psychological and demographic correlates of glycaemic control in adult patients with type 1 diabetes.

The relationship between an objective measure of glycaemic control (glycated haemoglobin (HbA1)) and personality variables was examined in two separate groups of adult Type 1 (insulin-dependent) diabetic patients. Study 1 included 121 patients, all of whom also had subjective self-reporting of treatment compliance assessed, while the first 57 patients had individual differences in intelligence, major dimensions of personality and forgetfulness documented. Study 2 examined 303 patients, all of whom had their major dimensions of personality assessed using a shortened and updated version of the original personality questionnaire. Demographic indices (age, onset-age, duration of diabetes) were assessed in both groups. No significant correlation was found between HbA1 and self-report compliance suggesting that self-reporting may be invalid as a measure of glycaemic control. In study 1 personality and intelligence variables did not correlate significantly with HbA1 values. Older patients with shorter duration of diabetes had significantly better glycaemic control (p < 0.05). A significant correlation was observed between HbA1 concentration and onset-age of diabetes (p < 0.001); the patients who had developed diabetes later in life were achieving better control of their blood glucose. In the larger number of subjects in study 2 no significant correlations were evident between HbA1 and personality variables. It is concluded that the predictors of glycaemic control indexed by HbA1 may be distinct from predictors of self-report compliance and that the latter have limited or no value in providing an assessment of quality of glycaemic control. There is no evidence of an effect of personality on glycaemic control as measured by HbA1.

Regional cerebral blood flow in IDDM patients: effects of diabetes and of recurrent severe hypoglycaemia.

Chronic hyperglycaemia and recurrent severe hypoglycaemia have both been implicated as causing cerebral damage in patients with diabetes. Although cognitive dysfunction and intellectual impairment have been demonstrated in patients with recurrent severe hypoglycaemia, structural correlates have not been described, and it is not known whether specific functional changes occur in the brains of affected patients. Regional cerebral blood flow was estimated by SPECT with 99mTechnetium Exametazime in 20 patients with IDDM. Ten patients had never experienced severe hypoglycaemia and 10 had a history of recurrent severe hypoglycaemia. Patient results were compared with 20 age- and sex-matched healthy volunteers. We observed differences between the two patient groups and the control group. Tracer uptake was greater in diabetic patients in the superior pre-frontal cortex. This effect was particularly pronounced in the group who had a history of previous severe hypoglycaemia. Patients with a history of recurrent hypoglycaemia also had a relative reduction in tracer uptake to the calcarine cortex. This suggests an alteration in the pattern of baseline regional cerebral blood flow in diabetic patients with frontal excess and relative posterior reduction in cerebral blood flow.

Physiological, symptomatic and hormonal responses to acute hypoglycaemia in type 1 diabetic patients with autonomic neuropathy.

The effects of peripheral autonomic neuropathy on the symptomatic, physiological, and hormonal responses to acute insulin-induced hypoglycaemia were studied in two groups of patients with Type 1 diabetes, matched for age, duration of diabetes, and prevailing glycaemic control. A group of eight patients who gave a history of normal awareness of hypoglycaemia and had normal cardiovascular autonomic function tests were compared to a group of six patients who had symptoms of autonomic dysfunction and gross abnormalities of cardiovascular autonomic function tests. An additional two patients with autonomic neuropathy who also had hypoglycaemia unawareness were studied. Acute hypoglycaemia was induced by intravenous infusion of insulin (2.5 mU kg-1 min-1) and the onset of the acute autonomic reaction (R) was identified objectively by the sudden rise in heart rate and onset of sweating. Cognitive function and hypoglycaemia symptom scores were estimated serially, and plasma counterregulatory hormones were measured. Acute autonomic activation was observed to occur in all subjects in response to hypoglycaemia and commenced at similar venous plasma glucose concentrations in both groups (neuropathic patients: 1.6 +/- 0.2 mmol l-1 vs non-neuropathic patients 1.6 +/- 0.2 mmol l-1, p = 0.9,). In the neuropathic patients plasma adrenaline responses were significantly lower at all time points from time R until time R + 30 min (MANOVA for repeated measures, F = 19.4, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Partitioning the symptoms of hypoglycaemia using multi-sample confirmatory factor analysis.

The allocation of hypoglycaemic symptoms to autonomic or neuroglycopenic groups tends to occur on an a priori basis. In view of the practical need for clear symptom markers of hypoglycaemia more scientific approaches must be pursued. Substantial evidence is presented from two large scale studies we performed which support a three factor model of hypoglycaemic symptomatology, based on the statistical associations discovered among symptoms reported by diabetic patients. Study 1 involved 295 insulin-treated out-patients and found that 11 key hypoglycaemic symptoms segregated into three clear factors: autonomic (sweating, palpitation, shaking and hunger) neuroglycopenic (confusion, drowsiness, odd behaviour, speech difficulty and incoordination), and malaise (nausea and headache). The three factors were validated on a separate group of 303 insulin-treated diabetic out-patients. Confirmatory factor analyses showed that the three factor model was the optimal model for explaining symptom covariance in each group. A multi-sample confirmatory factor analysis tested the rigorous assumptions that the relative loadings of symptoms on factors across groups were equal, and that the residual variance for each symptom was identical across groups. These assumptions were successful, indicating that the three factor model was replicated in detail across these two large samples. It is suggested that the results indicate valid groupings of symptoms that may be used in future research and in clinical practice.

Changes in the anterior chamber of the eye during acute hypoglycaemia in humans.

1. The changes in the volume and depth of the anterior chamber of the eye during acute insulin-induced hypoglycaemia were examined in nine healthy non-diabetic subjects (aged 23-31 years). The dimensions of the anterior chamber of the eye were measured by a photogrammetric technique, with Polaroid photographs taken of the lower half of the mid-sagittal plane of the eye at an angle of 55 degrees at a magnification of x16. Photographs were taken before and at regular intervals after the induction of acute hypoglycaemia using an infusion of unmodified (soluble) insulin at 2.5 m-units min-1 kg-1. Plasma adrenaline was measured regularly throughout the study. 2. Plasma glucose fell from 4.5 +/- 0.2 mmol/l (mean +/- SEM) to a nadir of 1.0 +/- 0.1 mmol/l (P < 0.01), which coincided with the onset of the acute autonomic reaction. Plasma adrenaline rose from 0.3 +/- 0.1 nmol/l to a peak of 3.2 +/- 0.6 nmol/l (P < 0.01) at 15 min after the autonomic reaction. 3. The volume of the anterior chamber decreased by 8.2% from 284.7 +/- 21.5 microliters at baseline to 264.5 +/- 17.0 microliters (P < 0.01) at the onset of the autonomic reaction. No significant alteration in axial anterior chamber depth was evident, but peripheral anterior depth decreased from 2.25 +/- 0.20 mm at baseline to 2.07 +/- 0.14 mm (P < 0.05) at the onset of the autonomic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency and symptoms of hypoglycaemia experienced by patients with type 2 diabetes treated with insulin.

This study ascertained the prevalence of severe hypoglycaemia and loss of awareness of hypoglycaemia in patients with Type 2 diabetes treated with insulin. One hundred and four sequentially selected Type 2 diabetic patients were compared with 104 patients with Type 1 diabetes who were matched for duration of insulin therapy. The patients were interviewed using a standardized questionnaire. During treatment with insulin, 18 Type 2 patients had experienced fewer than two episodes of hypoglycaemia, while 86 had experienced two or more episodes; 80 (93%) reported normal awareness, six (7%) reported partial awareness, and none had absent awareness of hypoglycaemia. All 86 Type 1 diabetic patients matched to the 86 Type 2 patients had experienced multiple episodes of hypoglycaemia; 71 (83%) had normal awareness, 14 (16%) had partial awareness and one patient (1%) reported absent awareness of hypoglycaemia. The Type 1 patients who had altered awareness of hypoglycaemia had longer duration of diabetes and insulin therapy (normal awareness: 5 (1-17) years (median (range)) vs partial awareness: 9 (3-18) years, p < 0.01). Similarly, Type 2 patients with altered awareness had longer duration of diabetes (normal awareness: 11 (2-25) years vs partial awareness: 19 (8-24) years, p < 0.02) and had received insulin for longer (normal awareness: 3 (1-18) years vs partial awareness: 12 (6-17) years, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency and morbidity of severe hypoglycaemia in insulin-treated diabetic patients.

To estimate the frequency and morbidity of insulin-induced hypoglycaemia, a retrospective survey was undertaken of the frequency of severe hypoglycaemia in 600 randomly selected patients with insulin-treated diabetes who were attending a large diabetic outpatient clinic in a teaching hospital. The resulting morbidity (hypoglycaemia-related injuries, convulsions, and road traffic accidents) was ascertained in 302 patients. One hundred and seventy-five (29.2%) of the 600 patients reported a total of 964 episodes of severe hypoglycaemia in the preceding year, giving an overall frequency for the group of 1.60 episodes patient-1year-1. The frequency of severe hypoglycaemia which was documented in 544 Type 1 (ketosis prone) diabetic patients was double that observed in a subgroup of 56 Type 2 diabetic patients who were being treated with insulin (1.70 vs 0.73 episodes patient-1year-1). In the subset of 302 patients, those who had experienced severe hypoglycaemia had greater morbidity associated with an estimated rate of injury of 0.04 injuries person-1year-1. Twenty (6.6%) patients reported a total of 37 convulsions associated with hypoglycaemia, 5 of which had occurred in the preceding year (0.02 convulsions person-1year-1). Five patients reported road traffic accidents in the preceding year which had been caused by hypoglycaemia. The only reliable predictors of severe hypoglycaemia were a history of previous severe hypoglycaemia (p < 0.001), a history of hypoglycaemia-related injury (p < 0.001) or convulsion (p < 0.001), and the duration of insulin therapy (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Severe hypoglycemia and intelligence in adult patients with insulin-treated diabetes.

The IQ scores (WAIS-R) of 100 patients with insulin-treated diabetes (aged 25-52 yr) were compared with those of 100 healthy control subjects who were matched to the diabetic patients for sex, age, education, and social class. The diabetic group had lower WAIS-R performance and verbal IQ scores than the control group (P = 0.017 and P = 0.033, respectively) after controlling for premorbid IQ. The extent of the difference was modest, representing approximately 33% of an SD in IQ. When frequency of severe hypoglycemia was controlled for the difference in performance IQ between the diabetic patient group and the control group was abolished, whereas the difference between the groups in verbal IQ persisted. It is hypothesised that cumulative severe hypoglycemia might be the major factor in the slight performance IQ differences between diabetic patients and control subjects. The origin of the verbal IQ differences, although obscure, might be related to the social impact of the disorder.

Antinatriuretic action of insulin is preserved after angiotensin I converting enzyme inhibition in normal man.

To examine the potential role for intrarenal angiotensin II in mediating the antinatriuretic action of insulin, seven normal males were studied on three occasions, twice during euglycaemic hyperinsulinaemia (40 mU.m-2.min-1) after double-blind treatment for 1 week with placebo and the converting enzyme inhibitor perindopril, and on a time control day. Lithium carbonate 250 mg was given before each study as an indirect marker of tubular sodium handling. Renal haemodynamics did not change during hyperinsulinaemia. Insulin infusion reduced both the absolute and fractional urinary excretion rates of sodium (P < 0.001) and potassium (P < 0.001); these effects of insulin were not altered after converting enzyme inhibition. Lithium clearance did not change during insulin infusion on either day. The antinatriuretic effect of hyperinsulinaemia is mediated at a tubular site distal to the proximal tubule. The data does not support the hypothesis that intrarenal generation of angiotensin II plays a part in this action of insulin.

Pancreatic and pituitary hormonal responses to insulin-induced hypoglycaemia during muscarinic cholinergic blockade in man.

To investigate the role of muscarinic cholinergic mechanisms in mediating the pancreatic and pituitary hormonal responses to hypoglycaemia, six normal subjects were studied during acute insulin-induced hypoglycaemia under control conditions, and during blockade with intravenous atropine. During atropine blockade the response of pancreatic polypeptide was suppressed while the maximum response of plasma glucagon was significantly higher. The increment in plasma vasopressin was also increased significantly during cholinergic blockade. During blockade with atropine the responses of plasma prolactin was reduced, with a slight but significant reduction in the growth hormone response, and although a similar maximum response of plasma ACTH was achieved, this rise was delayed. These results implicate involvement of a cholinergic muscarinic inhibitory and stimulatory mechanisms in regulating the responses of pancreatic and pituitary hormones to hypoglycaemia.

Suppression of plasma intact parathyroid hormone levels during insulin-induced hypoglycemia in humans.

The adrenergic control of intact PTH secretion was investigated by measuring its plasma concentration during insulin-induced hypoglycemia in normal human subjects under control conditions (n = 12) and after alpha (n = 5)- or beta (n = 6)-adrenoceptor blockade. Blood samples were taken at baseline, at the time of the acute hypoglycemic reaction, and at regular intervals for 60 min thereafter. Plasma concentrations of intact PTH, catecholamines, total calcium, magnesium, albumin, phosphate, and glucose were measured in all subjects, and plasma ionized calcium was also assayed in three subjects during acute hypoglycemia without pharmacological blockade. At the time of the acute hypoglycemic reaction, the plasma concentration of intact PTH in the control subjects fell to 60.8% of baseline values and was accompanied by a small but significant increase in plasma total calcium. Intact PTH concentrations remained suppressed after the plasma calcium concentration had returned to normal. The two groups of subjects who were exposed to adrenoceptor blockade exhibited a reduced fall in plasma intact PTH and showed no significant increase in plasma total calcium. Therefore, insulin-induced acute hypoglycemia was associated with a fall in plasma intact PTH. Adrenoceptor blockade reduced, but did not abolish, the response, suggesting that other factors are involved.