Glycaemic variability and hypoglycaemia are associated with C-peptide levels in insulin-treated type 2 diabetes.

AIM: The aim of the study was to evaluate the association between C-peptide levels, glycaemic variability and hypoglycaemia in patients with insulin-treated type 2 diabetes (T2D). METHODS: A total of 98 patients with T2D treated with basal-bolus insulin were enrolled in a cross-sectional study. Glycaemic variability and hypoglycaemia were assessed from continuous glucose monitoring (CGM) data recorded over 6 days: Glycemic variability was assessed by calculating the mean coefficient of variation (CV), while hypoglycemia was defined as sensor glucose levels ≤ 3.9 mmol/L or < 3.0 mmol/L. Fasting C-peptide and fasting glucose were measured on day 1. RESULTS: Low levels of fasting C-peptide correlated with higher CV (r = -0.53, P < 0.0001). In a multivariate regression model with HbA1c, body mass index, diabetes duration and total daily insulin dose, only C-peptide was significantly associated with CV. Patients with ≥ 1 episode of hypoglycaemia had significantly lower median C-peptide levels than patients without hypoglycaemia (274 (136-620) pmol/L vs. 675 (445-1013) pmol/L, respectively; P = 0.0004). Also, 17 patients clinically diagnosed with T2D had detectable glutamic acid decarboxylase (GAD) antibodies (≥ 5 U/mL). These GAD-positive patients had significantly lower fasting C-peptide, higher CV and greater frequency of hypoglycaemia than GAD-negative patients. CONCLUSION: In patients with insulin-treated T2D, low levels of C-peptide are associated with greater glycaemic variability and higher risk of hypoglycaemia, suggesting that C-peptide levels should be taken into consideration when optimizing insulin treatment and assessing hypoglycaemia risk.

Fermi level and bands offsets determination in insulating (Ga,Mn)N/GaN structures.

The Fermi level position in (Ga,Mn)N has been determined from the period-analysis of GaN-related Franz-Keldysh oscillation obtained by contactless electroreflectance in a series of carefully prepared by molecular beam epitaxy GaN/Ga1-xMnxN/GaN(template) bilayers of various Mn concentration x. It is shown that the Fermi level in (Ga,Mn)N is strongly pinned in the middle of the band gap and the thickness of the depletion layer is negligibly small. For x > 0.1% the Fermi level is located about 1.25-1.55 eV above the valence band, that is very close to, but visibly below the Mn-related Mn2+/Mn3+ impurity band. The accumulated data allows us to estimate the Mn-related band offsets at the (Ga,Mn)N/GaN interface. It is found that most of the band gap change in (Ga,Mn)N takes place in the valence band on the absolute scale and amounts to -0.028 ± 0.008 eV/% Mn. The strong Fermi level pinning in the middle of the band gap, no carrier conductivity within the Mn-related impurity band, and a good homogeneity enable a novel functionality of (Ga,Mn)N as a semi-insulating buffer layers for applications in GaN-based heterostuctures.

Clinical, behavioural and social indicators for poor glycaemic control around the time of transfer to adult care: a longitudinal study of 126 young people with diabetes.

AIMS: To describe and compare changes in glycaemic control in young people with Type 1 diabetes over time between the last 2 years in paediatric care and the first 2 years in adult care and to identify risk factors for poor glycaemic control. METHODS: Our retrospective cohort study followed participants aged 14-22 years from 2 years before to 2 years after transfer from paediatric to adult care. Changes in glycaemic control were calculated using repeated measurements. We adjusted for gender, age at diabetes onset, age at transfer, duration of diabetes at transfer, gap (amount of time) between last paediatric and first adult visit, comorbidity, learning disability and/or mental health conditions and family structure. We examined associations between acute hospital admissions, low visit attendance rate, loss to follow-up and baseline HbA1c level. RESULTS: Among 126 participants, the mean HbA1c level was 80 mmol/mol (9.4%) pre-transfer but decreased by an average of 3 mmol/mol (0.3%) each year post-transfer (P = 0.005). Young people with a learning disability and/or a mental health condition had worse glycaemic control (P = 0.041) and the mean HbA1c of those with divorced parents was 14 mmol/mol (1.2%) higher (P = 0.014). Almost one-third of participants were admitted to the hospital for acute diabetes care. Low visit attendance rate, high baseline HbA1c level, learning disability and/or mental health conditions and divorced parents predicted acute hospital admissions. CONCLUSIONS: Glycaemic control improved significantly after transfer to adult care, but the mean HbA1c level remained high. Future interventions should focus on young people with divorced parents, those with a learning disability and/or mental health condition and those who do not attend clinical visits to improve HbA1c levels and thereby reduce hospitalization rates.

Effects of advanced carbohydrate counting guided by an automated bolus calculator in Type 1 diabetes mellitus (StenoABC): a 12-month, randomized clinical trial.

AIMS: To test whether concomitant use of an automated bolus calculator for people with Type 1 diabetes carrying out advanced carbohydrate counting would induce further improvements in metabolic control. METHODS: We conducted a 12-month, randomized, parallel-group, open-label, single-centre, investigator-initiated clinical study. We enrolled advanced carbohydrate counting-naïve adults with Type 1 diabetes and HbA1c levels 64-100 mmol/mol (8.0-11.3%), who were receiving multiple daily insulin injection therapy. In a 1:1-ratio, participants were randomized to receive training in either advanced carbohydrate counting using mental calculations (MC group) or advanced carbohydrate counting using an automated bolus calculator (ABC group) during a 3.5-h group training course. For 12 months after training, participants attended a specialized diabetes centre quarterly. The primary outcome was change in HbA1c from baseline to 12 months. RESULTS: Between August 2012 and September 2013, 168 participants (96 men and 72 women) were recruited and randomly assigned to the MC group (n = 84) and the ABC group (n = 84). Drop-out rates were 23.8 and 21.4%, respectively (P = 0.712); 130 participants completed the study. The baseline HbA1c was 75 ± 9 mmol/mol (9.0 ± 0.8%) in the MC group and 74 ± 8 mmol/mol (8.9 ± 0.7%) in the ABC group. At 12 months, change in HbA1c was significant within both groups: MC group: -2 mmol/mol (95% CI -4 to -1) or -0.2% (95% CI -0.4 to -0.1; P = 0.017) and ABC group: -5 mmol/mol (95% CI -6 to -3) or -0.5% (95% CI -0.6 to -0.3; P < 0.0001), but HbA1c reductions were significantly greater in the ABC group (P = 0.033). No episodes of severe hypoglycaemia were reported. CONCLUSIONS: People with Type 1 diabetes initiating advanced carbohydrate counting obtained significantly greater HbA1c reductions when guided by an automated bolus calculator (NCT02084498).

Potential positive impact of group-based diabetes dialogue meetings on diabetes distress and glucose control in people with type 1 diabetes.

OBJECTIVE: To evaluate the effect of group-based diabetes dialogue meetings (DDMs) on diabetes distress, perceived competence and glycaemic control. METHODS: Patients with type 1 diabetes (T1D) were invited to DDMs with peers and healthcare professionals. The impact of participation was evaluated by change in diabetes distress measured by Problem Areas in Diabetes (PAID), diabetes competence measured by Perceived Competence in Diabetes (PCD), change in HbA1c before and one year after the DDMs. RESULTS: 120 patients with T1D participated in at least one DDM: 75% female, mean age 50 years (range 21-76), mean diabetes duration 23 years (range 0-64); 39% of all participants had a baseline PAID score≥33, indicating high levels of distress. After one year, both PAID (from 30.4±16.6 to 27.4±17.1; n=81, p=0.03), and mean HbA1c (61.6±10.2 to 58.8±9.9; n=120, p<0.0001) had improved significantly. PCD showed no change. Meanwhile, the benefit from participating was rated high with a median of four out of five and the major gain being the possibility to share experiences with peers. CONCLUSION: Group-based DDMs were highly appreciated by participants and associated with significant improvements in diabetes distress and HbA1c. PRACTICE IMPLICATIONS: DDMs target a large group of patients using few staff resources.

Impact of continuous glucose monitoring on quality of life, treatment satisfaction, and use of medical care resources: analyses from the SWITCH study.

To investigate the impact of continuous glucose monitoring (CGM) on health-related quality of life (HRQOL), treatment satisfaction (TS) medical resource use, and indirect costs in the SWITCH study. SWITCH was a multicentre, randomized, crossover study. Patients with type 1 diabetes (n = 153) using continuous subcutaneous insulin infusion (CSII) were randomized to a 12 month sensor-On/Off or sensor-Off/On sequence (6 months each treatment), with a 4-month washout between periods. HRQOL in children and TS in adults were measured using validated questionnaires. Medical resource utilization data were collected. In adults, TS was significantly higher in the sensor-On arm, and there were significant improvements in ratings for treatment convenience and flexibility. There were no clinically significant differences in children's HRQOL or parents' proxy ratings. The incidence of severe hypoglycaemia, unscheduled visits, or diabetes-related hospitalizations did not differ significantly between the two arms. Adult patients made fewer telephone consultations during the sensor-On arm; children's caregivers made similar numbers of telephone consultations during both arms, and calls were on average only 3 min longer during the sensor-On arm. Regarding indirect costs, children with >70 % sensor usage missed fewer school days, compared with the sensor-Off arm (P = 0.0046) but there was no significant difference in the adults days of work off. The addition of CGM to CSII resulted in better metabolic control without imposing an additional burden on the patient or increased medical resource use, and offered the potential for cost offsets.

The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy: a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes. METHODS: Children and adults (n = 153) on CSII with HbA(1c) 7.5-9.5% (58.5-80.3 mmol/mol) were randomised to (CGM) a Sensor On or Sensor Off arm for 6 months. After 4 months' washout, participants crossed over to the other arm for 6 months. Paediatric and adult participants were separately electronically randomised through the case report form according to a predefined randomisation sequence in eight secondary and tertiary centres. The primary outcome was the difference in HbA(1c) levels between arms after 6 months. RESULTS: Seventy-seven participants were randomised to the On/Off sequence and 76 to the Off/On sequence; all were included in the primary analysis. The mean difference in HbA(1c) was -0.43% (-4.74 mmol/mol) in favour of the Sensor On arm (8.04% [64.34 mmol/mol] vs 8.47% [69.08 mmol/mol]; 95% CI -0.32%, -0.55% [-3.50, -6.01 mmol/mol]; p < 0.001). Following cessation of glucose sensing, HbA(1c) reverted to baseline levels. Less time was spent with sensor glucose <3.9 mmol/l during the Sensor On arm than in the Sensor Off arm (19 vs 31 min/day; p = 0.009). The mean number of daily boluses increased in the Sensor On arm (6.8 ± 2.5 vs 5.8 ± 1.9, p < 0.0001), together with the frequency of use of the temporary basal rate (0.75 ± 1.11 vs 0.26 ± 0.47, p < 0.0001) and manual insulin suspend (0.91 ± 1.25 vs 0.70 ± 0.75, p < 0.018) functions. Four vs two events of severe hypoglycaemia occurred in the Sensor On and Sensor Off arm, respectively (p = 0.40). CONCLUSIONS/INTERPRETATION: Continuous glucose monitoring was associated with decreased HbA(1c) levels and time spent in hypoglycaemia in individuals with type 1 diabetes using CSII. More frequent self-adjustments of insulin therapy may have contributed to these effects.

Can sharing experiences in groups reduce the burden of living with diabetes, regardless of glycaemic control?

AIMS: To test whether patients with Type 1 diabetes would join support groups and benefit by improving psychosocial functioning, regardless of their HbA1c levels. METHODS: A pre-post test with follow-up after 6 and 12 months was conducted as a concurrent mixed-method study. The convenience sample included patients with Type 1 diabetes aged ≥21 years, having been diagnosed ≥1 year earlier. Primary outcome was diabetes-related distress (using the Problem Areas in Diabetes scale). Secondary outcomes were psychological distress and depressive symptoms (Symptom Check List -90-R/Global Severity Index and depression subscale), well-being (World Health Organization 5) and HbA1c . RESULTS: Equal numbers of patients with HbA1c above and below 64 mmol/mol (8%) joined the support groups (n = 54). Focus group interviews revealed that major benefits were feeling less alone and being intuitively understood among peers. The patients perceived the support groups as a safe environment for sharing experiences. Problem Areas in Diabetes, Global Severity Index and depression subscale scores were significantly reduced post-intervention and maintained at 1-year follow-up. Well-being increased insignificantly. HbA1c was unchanged. CONCLUSIONS: Support groups are able to reduce diabetes-related and psychological distress 1 year after the intervention for patients with both good and poor glycaemic control displaying high levels of distress. Although patients with severely high levels of diabetes-related distress might need more extensive therapeutic interventions to further reduce their level of distress. Further, interventions that target specific self-management problems are needed for patients with poor glycaemic control to help them accomplish lower levels of HbA1c. Moreover, healthcare providers must be aware that patients with good glycaemic control might have an unacknowledged psychosocial burden of living with the illness.

Retinal function in relation to improved glycaemic control in type 1 diabetes.

AIMS/HYPOTHESIS: To study long-term changes in retinal function in response to sustained glycaemia reduction in participants with type 1 diabetes. METHODS: Prospective study using objective measures of retinal function in 17 participants with type 1 diabetes mellitus and minimal to moderate retinopathy who switched from conventional subcutaneous injection to continuous subcutaneous infusion of insulin (CSII). RESULTS: Glycated haemoglobin HbA(1c) gradually decreased from 9.1% at baseline before CSII to 7.4% after 1 year on CSII. Glycaemia was markedly reduced within 1 week after initiation of CSII and remained stable thereafter. Dark adaptation and retinal electroretinographic function at 1, 4 and 16 weeks after initiation of CSII were comparable with baseline values, whereas a significant improvement in rod photoreceptor dark adaptation and dark-adapted b-wave amplitudes were seen after 52 weeks (time to rod-cone break -25% [p < 0.0001], time to a standardised rod intercept -13% [p < 0.0001], dark-adapted rod b-wave full-field amplitude +15% [p = 0.0125], standard combined rod-cone b-wave amplitude +8% [p = 0.049]). No detectable change was observed in cone adaptation, electroretinographic cone function or retinopathy. CONCLUSIONS/INTERPRETATION: After initiation of CSII, the retinal visual pathway of the rods improved with a delay of more than 4 months, over a time scale comparable with the duration of the diabetic retinopathy early worsening response to sustained glycaemia reduction. This indicates that glycaemia has a long-term effect on the disposition of functional capacity in the retinal visual pathway of rod photoreceptors, the cells that appear to be driving the development of diabetic retinopathy.

Increased urinary orosomucoid excretion predicts preeclampsia in pregnant women with pregestational type 1 diabetes.

AIMS: We evaluated the urinary orosomucoid excretion (UOE) as a biomarker of preeclampsia and preterm delivery in pregnant women with type 1 diabetes. METHODS: Singleton pregnant women with pregestational type 1 diabetes were included provided one urine sample had been collected before 17 gestational weeks. Serum and urinary orosomucoid were analysed by immunoturbidimetry. Primary outcome measurements were development of preeclampsia (blood pressure>140/90mmHg and proteinuria) and preterm delivery before 37 weeks. RESULTS: In total 173 women were included. The UOE increased during pregnancy. Preeclampsia developed in 20 women and 65 women delivered preterm. Using logistic regression analysis we found that UOE>1.37mg/l (OR: 6.85 (95% CI: 1.97-23.88; p<0.003)), nulliparity (3.88 (1.10-13.72); p<0.04), systolic blood pressure>120mmHg (4.12 (1.35-12.59); p<0.02) and duration of diabetes>20 years (3.69 (1.18-11.52); p<0.03) independently predicted the development of preeclampsia. Independent predictors of preterm delivery were duration of diabetes and HbA1c>7%. The remaining covariates included in the regression models were BMI, serum creatinine, smoking and microalbuminuria. CONCLUSIONS: Increased UOE early in pregnancy predicted preeclampsia in women with pregestational type 1 diabetes independently of albuminuria and other known risk factors. No association to preterm delivery was found.

Local structure of uncapped and capped InGaN/GaN quantum dots.

The local structure around the indium atoms in uncapped and capped In(x)Ga(1-x)N quantum dots has been studied by In K-edge extended X-ray absorption fine structure (EXAFS) spectroscopy. The samples were grown by metal organic vapour phase epitaxy. The EXAFS was successfully applied to study the structural properties of buried quantum dots which are not optically active. The analysis revealed that capping the quantum dots with GaN does not affect the bond distances of the In-N and In-Ga, but makes the In-In distance shorter by 0.04 A.

Increased urinary orosomucoid excretion: a proposed marker for inflammation and endothelial dysfunction in patients with type 2 diabetes.

OBJECTIVE: In a previous study, urinary orosomucoid excretion rate (UOER) independently predicted cardiovascular mortality in patients with type 2 diabetes. The aim of the present study was to determine whether increased UOER is associated with cardiovascular risk factors such as inflammation, impaired left ventricular function and endothelial dysfunction in patients with type 2 diabetes. MATERIAL AND METHODS: We performed a cross-sectional study of 41 patients with type 2 diabetes (17 patients with normal UOER and 24 with increased UOER) with no history of cardiovascular disease and 21 healthy controls. Urinary orosomucoid was measured using a particle-enhanced immunoturbidimetric assay. Plasma interleukin-6 (IL-6), tissue plasminogen activator (tPA) and soluble intercellular adhesion molecule-1 (sICAM) were measured using ELISA. Endothelial function measured as vasodilatory capacity of the brachial artery and echocardiography were done in all participants. RESULTS: Patients with diabetes and increased UOER had subclinically increased serum orosomucoid (p<0.001), C-reactive protein (CRP) (p<0.001), IL-6 (p<0.001), tPA (p<0.003) and sICAM (p<0.003) compared with healthy controls. In patients with type 2 diabetes, UOER was independently associated with increasing values of IL-6 (1.43 (1.06-1.93)) and tPA (1.82 (1.20-2.77)). Measurements by echocardiography showed no signs of cardiac dysfunction. CONCLUSIONS: Asymptomatic patients with type 2 diabetes and increased UOER displayed signs of chronic low-grade inflammation and endothelial dysfunction. UOER was independently related to markers of proinflammation and endothelial dysfunction in patients with type 2 diabetes. The previously shown relation between increased UOER and cardiovascular mortality is proposed to be caused by chronic low-grade inflammation and early endothelial dysfunction.

Orosomucoid in urine is a powerful predictor of cardiovascular mortality in normoalbuminuric patients with type 2 diabetes at five years of follow-up.

AIMS/HYPOTHESIS: To study whether urinary orosomucoid excretion rate (UOER) predicts mortality in normoalbuminuric patients with diabetes at 5 years of follow-up, and to investigate the relationship between orosomucoid in serum and urine. METHODS: A cohort of 578 patients with diabetes (430 type 2, 148 type 1) was followed prospectively for an average of 5 years. UOER was measured in timed overnight urine samples. RESULTS: Eighty-two patients with type 2 diabetes and 17 patients with type 1 diabetes died. Among patients with type 2 diabetes, 251 (58%) had normoalbuminuria; increased UOER independently predicted cardiovascular mortality (OR 4.94, 95% CI 1.60-15.22; p<0.006) in those with normoalbuminuria and in the entire cohort of patients with type 2 diabetes (odds ratio 3.63, 95% CI 1.50-8.81; p<0.005). Patients with increased UOER had a higher all-cause mortality than those with normal UOER (log-rank test, p<0.001 for type 2 patients; p<0.04 for type 1 patients). In patients with type 1 diabetes, there were five cardiovascular deaths and no significant predictive value of UOER. Patients with increased UOER had a subclinical increase in serum orosomucoid. CONCLUSION/INTERPRETATION: Increased UOER was an independent, powerful predictor of cardiovascular mortality in normoalbuminuric patients with type 2 diabetes and in the entire cohort of patients with type 2 diabetes. There were indications of UOER as being a valuable marker in type 1 diabetes that showed differences in survival between patients with normal versus increased UOER. Serum orosomucoid was associated with UOER; UOER may be a marker of low-grade inflammation in patients with diabetes.

Pregnancy and progression of diabetic nephropathy.

AIMS/HYPOTHESIS: Pregnancy could damage kidney function in diabetic nephropathy. We investigated the long-term impact of pregnancy on the progression of diabetic nephropathy. METHODS: Our observational follow-up study included all women patients with Type I (insulin-dependent) diabetes mellitus who developed diabetic nephropathy between 1970 and 1989 at Steno Diabetes Center (n = 93). Follow-up lasted 16 years (range 3-28) from the onset of diabetic nephropathy until death or the year 2000. A total of 26 women became pregnant after the onset of diabetic nephropathy (group A). The remaining 67 served as control subjects (group B). All patients received aggressive antihypertensive treatment (blood pressure goal < 140/90 mmHg). RESULTS: The two groups were comparable at onset of diabetic nephropathy regarding blood pressure, albuminuria, s-cholesterol, smoking, retinopathy and s-creatinine (mean 79(SD 23) micromol/l). The slopes of 1/s-creatinine (1000.l.micromol(-1).year(-1)) during the whole observation period were -0.39(0.40) compared with -0.41(0.70) (group A vs B-NS). The slopes of 1/s-creatinine before and after pregnancy were similar. Decline in creatinine clearance (ml/min/yr) was 3.2 (3.4) compared with 3.2 (5.1) (group A vs B -NS). At the end of follow-up, 35 % (95 %-CI:17-53) of the pregnant women had died and 19 % (7-39) had reached end stage renal disease compared to 34 % (23-45) and 24 %(14-34) of the control subjects, respectively(NS). Group A and B had similar blood pressure levels during the whole observation period: 136(13)/83(7) vs 139 (14)/85(7) mmHg (NS). CONCLUSION/INTERPRETATION: Pregnancy has no adverse long-term impact on kidney function and survival in Type I diabetic patients with well-preserved kidney function (normal serum creatinine) suffering from diabetic nephropathy.

Orosomucoid in urine predicts cardiovascular and over-all mortality in patients with Type II diabetes.

AIMS/HYPOTHESIS: Urinary orosomucoid excretion rate is increased in a substantial proportion of patients with Type II (non-insulin-dependent) diabetes mellitus and normal urinary albumin excretion rate. The aim of this study was to determine whether increased urinary orosomucoid excretion rate is predictive of increased mortality in patients with Type II diabetes. METHODS: In a cohort study including 430 patients with Type II diabetes, baseline urinary samples were analysed for orosomucoid and albumin. Mean follow-up was 2.4 years. RESULTS: We found that 188 (44 %) patients had normal and 242 (56 %) patients had increased urinary orosomucoid excretion rates. During the study period 41 patients died; out of these 23 patients died of cardiovascular diseases. Odds ratio for all-cause mortality was 2.50 (95 % CI 1.00-6.22) and odds ratio for cardiovascular mortality was 9.81 (1.31-73.6) having increased urinary orosomucoid excretion rate at baseline (odds ratios adjusted for age, sex, duration of diabetes, cardiovascular diseases, weight, medication, HbA1 c, plasma creatinine and urinary albumin excretion rate). Urinary albumin excretion rate was an independent predictor of all-cause mortality when urinary orosomucoid excretion rate was not included in the analysis. Subgroup analysis revealed that 39 % of the patients with normal urinary albumin excretion rate (n = 251) had increased urinary orosomucoid excretion rates and that these patients had a higher cardiovascular mortality (p = 0.007) than patients with normal urinary albumin excretion rate and normal urinary orosomucoid excretion rates. CONCLUSION/INTERPRETATION: We found that urinary orosomucoid excretion rate predicted all-cause and cardiovascular mortality in patients with Type II diabetes independently from other risk factors.

Long-term beneficial effect of ACE inhibition on diabetic nephropathy in normotensive type 1 diabetic patients.

BACKGROUND: The purpose of this study was to assess whether long-term (8 years) inhibition of angiotensin-converting enzyme (ACE) protects kidney function in normotensive type 1 diabetic patients with diabetic nephropathy. METHODS: We performed an open randomized follow-up study of normotensive type 1 diabetics with nephropathy either treated (N = 15) or not (N = 17) with captopril twice per day (average 74, range 12.5 to 125 mg/day). The main outcome measures were arterial blood pressure, albuminuria, and glomerular filtration rate (GFR; 51Cr-EDTA plasma clearance, twice yearly). RESULTS: Arterial blood pressure (mm Hg) was kept constant in the captopril group, at baseline (mean, SEM), 128/78 (3/2) and during follow-up 129/77 (4/1) but increased significantly in the control group from 127/79 (2/1) to 137/84 (5/2) (P < 0.01). Furthermore, 8 out of the 17 control subjects required treatment with blood pressure-lowering drugs because they developed hypertension. The fractional albumin clearance (x10-5) remained unchanged in the captopril group: baseline [10.8 (1.25) geometric mean and antilog (SEM)] during the eight years [11.8 (1.47)], while a significant rise occurred in control patients: 13.3 (1.23) to 26.2 (1.42) (P < 0.05). Baseline GFR was nearly identical: 111 (6) and 115 (4) mL/min/1.73 m2 in the captopril and control group, respectively. The median (range) rate of decline in GFR (mL/min/year) was 1.7 (10.7 to -2.0) in the captopril group versus 2.8 (17.7 to -2.6) in the control group (P = NS). CONCLUSIONS: The beneficial effect of captopril in arresting the rise in systemic blood pressure and albuminuria is long lasting. A loss in GFR is minimal in most patients with diabetic nephropathy if normotension is sustained by prospective treatment with ACE inhibitors or restored by implementation of other antihypertensive medications with the development of hypertension.

Broadband sum frequency generation with two regenerative amplifiers: temporal overlap of femtosecond and picosecond light pulses.

Sum frequency generation (SFG) spectroscopy is a valuable tool for studying interfaces such that the boundary between two adjoining phases can be probed with minimal interference from the adjacent bulk material. More recently, broad-bandwidth sum frequency generation (BBSFG) techniques are being explored. This technique using IR broad-bandwidth fs pulses overlapped with narrow-bandwidth ps pulses to obtain BBSFG spectra is described. In the BBSFG system design presented here, the fs pulse and the ps pulse that are generated in separate regenerative amplifiers are overlapped temporally. This temporal overlap process is discussed. In addition, images of the sum frequency response demonstrate its viability. The new approach in experimental design described here for this emerging technology, BBSFG, has application for studying time-dependent processes at interfaces that inherently produce low SFG signal levels such as air-aqueous interfaces.

Broadband vibrational sum frequency generation spectroscopy of a liquid surface.

An important advance in surface science has been the evolution of sum frequency generation to the application of studying surface structure and chemistry of liquid surfaces at the molecular-level by probing the vibrational signatures of surface molecules. Recently, broad-bandwidth sum frequency generation (BBSFG) spectroscopy has become an important tool for investigating gas-solid interfaces. BBSFG spectroscopy allows, theoretically, a surface sum frequency spectrum to be acquired within one pulse of the laser. In this paper, the viability of BBSFG to study inherently small nonlinear response interfaces and the time-resolving capability of this surface-selective technology are demonstrated. Presented here are the first published accounts of spectra from a liquid surface utilizing the broad-bandwidth sum frequency technology with acquisition times as low as 500 milliseconds.

Impaired autoregulation of the glomerular filtration rate in patients with nondiabetic nephropathies.

BACKGROUND: The ability of the kidney to maintain constancy of the glomerular filtration rate (GFR) over a wide range of renal perfusion pressures is termed autoregulation. Defective autoregulation of GFR has been demonstrated in diabetic nephropathy. Whether this is also the case in patients with nondiabetic nephropathies is not known. METHODS: We investigated the effect of acute lowering of blood pressure (BP) on GFR in 16 (8 males and 8 females) albuminuric subjects suffering from different nondiabetic nephropathies and in 14 (7 males and 7 females) controls matched with respect to sex, age, BP, and baseline GFR. The subjects received in random order an intravenous injection of either clonidine (150 to 225 microg) or saline (0.154 mmol/liter) within two weeks. We measured GFR ([51Cr]-EDTA), albuminuria (enzyme-linked immunosorbent assay; ELISA), and BP (Takeda TM-2420). RESULTS: Clonidine induced similar reductions in mean arterial BP 17 (2) versus 19 (2) mm Hg [mean (SE)] in patients with nephropathy and in controls, respectively. GFR diminished in average from 89 (6) to 82 (5) ml/min/1.73 m2 (P < 0.05), and albuminuria declined from a geometric mean of 1218 (antilog SE 1.3) microg/min to 925 (1.3) in the patients with nondiabetic nephropathies (P < 0.05), whereas these variables remained unchanged in the control group. The mean difference between changes in GFR (95% confidence interval) between the nondiabetic macroalbuminuric and control subjects was 6.1 (-0.03 to 12.21) ml/min/1.73 m2 (P = 0.051). CONCLUSION: Our study suggests that albuminuric patients with nondiabetic nephropathies frequently suffer from impaired autoregulation of GFR.