Clinical benefits of switching to insulin degludec irrespective of previous basal insulin therapy in people with Type 1 or Type 2 diabetes: evidence from a European, multicentre, retrospective, non-interventional study (EU-TREAT).

AIMS: To investigate whether the benefits of switching to insulin degludec observed in the European retrospective chart review study EU-TREAT were dependent on the previous basal insulin used. METHODS: People with Type 1 or Type 2 diabetes were switched to insulin degludec from other basal insulins ≥6 months before data collection. Participants were stratified into three groups based on their previous basal insulin: insulin glargine 100 units/ml (Type 1: n=888; Type 2: n=259); insulin detemir (Type 1: n=726; Type 2: n=415); and neutral protamine Hagedorn (Type 1: n=53; Type 2: n=95). Their glycaemic control and hypoglycaemia incidence at 6 and 12 months post-switch vs pre-switch was then evaluated. RESULTS: Significant HbA1c reductions were achieved in all previous basal insulin groups for participants with Type 1 diabetes [insulin glargine 100 units/ml: -2.08 mmol/mol (-0.19%); insulin detemir: -2.40 mmol/mol (-0.22%)] and those with Type 2 diabetes [insulin glargine 100 units/ml: -5.90 mmol/mol (-0.54%); insulin detemir: -6.01 mmol/mol (-0.55%); neutral protamine Hagedorn: -2.73 mmol/mol (-0.25%)] at 6 months, except for the relatively small neutral protamine Hagedorn group in those with Type 1 diabetes [-1.75 mmol/mol (-0.16%)], where statistical significance was not reached. At 6 months in the Type 1 diabetes group, switching to insulin degludec from insulin glargine 100 units/ml resulted in significantly lower hypoglycaemia rates across all hypoglycaemia categories; for the insulin detemir group, this significance was also observed for severe and nocturnal non-severe hypoglycaemia, while the low number of people in the neutral protamine Hagedorn group resulted in nonsignificant reductions in hypoglycaemia rates. At 6 months in the people with Type 2 diabetes, switching to insulin degludec resulted in significantly lower rates of hypoglycaemia across all categories for all groups. Similar outcomes were observed at 12 months. CONCLUSIONS: Switching to insulin degludec from other basal insulins can improve glycaemic control and/or reduce hypoglycaemia risk in people with diabetes (although there was a nonsignificant reduction in HbA1c and hypoglycaemia rates for the neutral protamine Hagedorn group in Type 1 diabetes) under routine care.

Pulse pressure and systolic night-day ratio interact in prediction of macrovascular disease in patients with type 2 diabetes mellitus.

Patients with type 2 diabetes mellitus are at increased risk of cardiovascular disease (CVD). We examined the predictive ability of 24-hour ambulatory pulse pressure (24-h PP), ambulatory arterial stiffness index (AASI) and diurnal blood pressure (BP) parameters for fatal and non-fatal CVD in patients with type 2 diabetes mellitus. A total of 108 patients with type 2 diabetes mellitus (mean duration 6.6 years) were followed for 9.5 (0.5-14.5) years. At baseline, all patients underwent ambulatory BP monitoring. During follow-up, 45 patients had cardiovascular (CV) events (35 non-fatal and 10 fatal). In bivariate analysis, events during follow-up were predicted by 24-h PP (P<0.01), AASI, 24-h systolic BP and systolic and diastolic night-day BP ratio (P<0.05 for all). In Cox regression analysis adjusted for established risk markers, only 24-h PP and systolic night-day BP ratio predicted CV events, P<0.05 for both. A significant interaction between the two parameters was found, P<0.05; thus, the higher the systolic night-day ratio, the greater the increase in hazard ratio (HR) per mmHg increase in 24-h PP and vice versa. A combined 10 mmHg increase in 24-h PP and 10%-point increase in systolic night-day ratio from the 25th percentile increased the adjusted HR (95% confidence interval) for CV events with 1.29 (0.53; 3.12), whereas a similar increase from the 75th percentile increased the HR with 4.2 (1.54; 11,51). Our study showed that 24-h PP and systolic night-day ratio interact as predictors of CV events in type 2 diabetes patients, and should be considered in conjunction when evaluating the risk of CVD.

Ambulatory pulse pressure, decreased nocturnal blood pressure reduction and progression of nephropathy in type 2 diabetic patients.

AIMS/HYPOTHESIS: We followed type 2 diabetic patients over a long period to evaluate the predictive value of ambulatory pulse pressure (PP) and decreased nocturnal BP reduction (non-dipping) for nephropathy progression. METHODS: Type 2 diabetic patients (n = 112) were followed for an average of 9.5 (range 0.5-14.5) years. At baseline, all patients underwent 24 h ambulatory BP measurement. Urinary albumin excretion rate was evaluated by three urinary albumin:creatinine ratio measurements at baseline and follow-up. RESULTS: At baseline, patients who subsequently progressed to a more advanced nephropathy stage (n = 35) had reduced diastolic night/day BP variation and higher 24 h systolic BP and PP values; they also had more advanced nephropathy and were more likely to smoke than those with no progression of nephropathy (n = 77). In a Cox regression analysis, independent predictors of nephropathy progression were 24 h PP (p < 0.01), diastolic night:day BP ratio (p = 0.02) and smoking (p = 0.02). The adjusted hazards ratio (95% CI) for each mmHg increment in 24 h PP was 1.04 (1.01-1.07), whereas the adjusted hazards ratio (95% CI) for each 1% increase in diastolic night:day BP ratio was 1.06 (1.01-1.11). Only one of 33 patients (3.0%) with both a diastolic night:day BP ratio and a 24 h PP below the median progressed, whereas 17 of 32 patients (53.1%) with both a diastolic night:day BP ratio and a 24 h PP equal to or above the median progressed to a more advanced nephropathy stage (p < 0.001). CONCLUSIONS/INTERPRETATION: Ambulatory PP, impaired nocturnal BP decline and smoking are strong, independent predictors of nephropathy progression in type 2 diabetic patients.

Endothelial dysfunction, ambulatory pulse pressure and albuminuria are associated in Type 2 diabetic subjects.

AIM: Elevated pulse pressure (PP) is associated with microvascular complications in Type 2 diabetic patients. In non-diabetic subjects, elevated PP has been associated with endothelial dysfunction. The relation between endothelial dysfunction and PP in diabetic subjects has not previously been examined. We examined the relation between PP, markers of endothelial activation and albuminuria in Type 2 diabetic patients. METHODS: In 46 Type 2 diabetic patients and 19 non-diabetic subjects, we performed 24-h ambulatory blood pressure (AMBP) monitoring. Urinary albumin excretion rate was measured as three urinary albumin/creatinine ratios. Von Willebrand factor (vWF), fibrinogen, E-selectin and soluble intercellular adhesion molecule 1 (ICAM-1) were measured in plasma. RESULTS: Thirty-four patients had normoalbuminuria (group N) and 12 had micro- or macroalbuminuria (group A). PP levels increased in a stepwise manner from the control group (group C) to group N and group A; night PP 43 +/- 5, 48 +/- 10 and 59 +/- 12 mmHg (groups C, N and A, respectively, P < 0.001). Likewise, plasma levels of vWF, fibrinogen, E-selectin and ICAM-1 increased from group C to group A; e.g. ICAM-1 [median (interquartile range)] 191 (160-217), 213 (189-262) and 316 (260-417) ng/ml, groups C, N and A, respectively, P < 0.001). In diabetic patients, night PP and plasma levels of E-selectin and ICAM-1 correlated (r = 0.38, P < 0.01 and r = 0.37, P = 0.01, night PP with E-selectin and ICAM-1, respectively). CONCLUSION: Increased PP is associated with endothelial activation and albuminuria in Type 2 diabetic patients. Thus, endothelial dysfunction may represent a pathophysiological link between an elevated PP and microvascular complications in these subjects. Prospective studies are needed to further elucidate these associations.

Plasma concentrations of osteoprotegerin during normo- and hyperglycaemic clamping.

OBJECTIVE: Plasma levels of osteoprotegerin (OPG) are elevated in subjects with diabetes as well as in non-diabetic subjects with cardiovascular disease. In previous studies a positive correlation was found between plasma levels of OPG and markers of glycaemic control in diabetic subjects. The aim of the present study was to examine the effect of acute hyperglycaemia on plasma levels of OPG in non-diabetic subjects. MATERIAL AND METHODS: Nine healthy, lean, male subjects were examined in a randomized, blinded, cross-over study design during hyperglycaemic (plasma glucose = 15 mmol/L, study H) as well as during euglycaemic (plasma glucose = 5 mmol/L, study E) conditions. Blood samples were collected at baseline and at t=240 min. RESULTS: Plasma OPG decreased slightly during study H (1.26+/-0.39 versus 1.19+/-0.35 ng/mL, p<0.05), whereas the level did not change significantly during study E (1.40+/-0.46 ng/mL versus 1.57+/-0.50 ng/mL, NS). The decrease in plasma OPG during hyperglycaemia did not correlate with the change in plasma glucose but correlated significantly with changes in serum insulin (r=-0.70, p=0.038). CONCLUSIONS: Acute hyperglycaemia does not seem to increase plasma levels of OPG in non-diabetic subjects, whereas hyperinsulinaemia may suppress plasma levels of OPG. This finding indicates that the elevated plasma levels of OPG observed in diabetic subjects with poor metabolic control cannot be ascribed to hyperglycaemia per se.

Left ventricular dysfunction in hypertensive patients with Type 2 diabetes mellitus.

AIMS: To characterize left ventricular function in hypertensive patients with Type 2 diabetes and normal ejection fraction, and to relate these findings to pathogenic factors and clinical risk markers. METHODS: We examined 70 hypertensive patients with Type 2 diabetes mellitus with ejection fraction > 0.55 and fractional shortening > 0.25, all without any cardiac symptoms. Thirty-five non-diabetic subjects served as control subjects. Left ventricular longitudinal function was examined by tissue Doppler derived myocardial strain rate and peak systolic velocities. RESULTS: Hypertensive patients with diabetes had a significantly higher systolic strain rate (-1.1 +/- 0.3 s(-1) vs. -1.6 +/- 0.3 s(-1), P < 0.001) and lower systolic peak velocities (3.3 +/- 1.0 vs. 5.6 +/- 1.0 cm/s, P < 0.001) compared with control subjects. Myocardial systolic strain rate correlated significantly to left ventricular mass (r = 0.40, P < 0.01) and to both HbA1c (r = 0.43, P < 0.01), and fructosamine (r = 0.40, P < 0.01), but was not related to serum levels of carboxymethyllysine, albuminuria, blood pressure (dipping/non-dipping), or oral hypoglycaemic therapy. Patients with diastolic dysfunction had significantly higher levels of urine albumin [21.0 (5-2500) mg/l, vs. 9.5 (1-360), P < 0.01], heart rate (78 +/- 13 vs. 67 +/- 10 b.p.m., P < 0.005), and seated diastolic blood pressure (85 +/- 6 vs. 81 +/- 7 mmHg, P < 0.05) and non-dipping diastolic blood pressure was more frequent. CONCLUSIONS: Long axis left ventricular systolic function was significantly decreased in hypertensive patients with Type 2 diabetes mellitus, and is associated with hyperglycaemia and left ventricular hypertrophy. Diastolic dysfunction was closely related to increased diastolic blood pressure, non-dipping and increased urinary albumin excretion.

NT-proBNP in normoalbuminuric patients with Type 2 diabetes mellitus.

OBJECTIVE: To examine levels of NT-proBNP and its relation to hypertension, as well as diastolic function in normoalbuminuric patients with Type 2 diabetes. RESEARCH DESIGN AND METHODS: The study comprised 60 Type 2 diabetic patients without albuminuria. Thirty patients were normotensive and 30 had hypertension. Exclusion criteria were cardiac symptoms and an ejection fraction < 55%. Thirty age- and sex-matched normal subjects served as controls. Diastolic dysfunction was assessed with echocardiography, by means of mitral inflow and colour M-Mode flow propagation recordings. RESULTS: Overall NT-proBNP was significantly elevated in the Type 2 diabetes group, compared with the controls [54.5 pg/ml (5-162) vs. 32.7 pg/ml (5-74.3) P = 0.02]. NT-proBNP was significantly higher among hypertensive patients compared with both normotensive patients and controls but no difference was found between the normotensive patients and the controls [58.0 pg/ml (8.5-162), P < 0.05 vs. 50.8 pg/ml (5-131) P = 0.4]. Patients with concentric and eccentric hypertrophy had significantly higher NT-proBNP levels compared with the control group [81.0 pg/ml (5-147), P < 0.001 and 66.8 pg/ml (42-128), P < 0.001], whereas patients with left ventricular remodelling (enlarged relative wall diameter but normal left ventricular mass) were comparable with the control group [42.3 pg/ml (8.3-142) P = 0.55]. Patients with left atrial enlargement also had incremental NT-proBNP values. NT-proBNP was only moderately correlated to age (r = 0.33, P < 0.05) and left ventricular diastolic diameter (r = 0.41, P < 0.05), but unrelated to diastolic function. CONCLUSIONS: NT-proBNP is significantly increased in hypertensive, normoalbuminuric patients with Type 2 diabetes. These findings were related to left ventricular hypertrophy and increased left atrial and ventricular diameters.

Impact of essential hypertension and diabetes mellitus on left ventricular systolic and diastolic performance.

AIMS: To investigate left ventricular systolic and diastolic function in patients with essential hypertension and diabetes mellitus associated with hypertension by the myocardial performance index (MPI). METHODS AND RESULTS: The study included 45 patients with essential hypertension, 45 patients with diabetes mellitus and hypertension and 45 normal subjects, who underwent a complete two-dimensional and Doppler echocardiography including assessment of the isovolumetric Doppler time intervals for the estimation of the Doppler-derived MPI. The MPI was significantly higher in patients with essential hypertension and diabetes with hypertension, compared to controls (Essential hypertension=0.51+/-0.12; Diabetes=0.51+/-0.12 vs. controls 0.40+/-0.05, P=0.001). The isovolumetric contraction time was significantly prolonged in essential hypertension (56+/-26 msec vs. 40+/-17 msec, P<0.01 respectively) and among diabetes patients isovolumetric relaxation time was prolonged compared to normal subjects (100+/-20 ms vs. 87+/-16 ms, P<0.01, respectively). The index was not related to left ventricular mass, age or ejection fraction, but significantly correlated to E-wave deceleration time (rho=0.48, P<0.001). CONCLUSIONS: The MPI is increased, in both essential hypertensive patients and diabetes patients with associated hypertension, despite normal ejection fraction.

Effects of losartan on diabetic maculopathy in type 2 diabetic patients: a randomized, double-masked study.

OBJECTIVE: Diabetic maculopathy (DMa) is a leading cause of visual loss in the western world. Preliminary studies have suggested that angiotensin converting enzyme inhibitors might be effective in preventing the progression of diabetic retinopathy, but no studies have quantitatively assessed the effect of this treatment on macular oedema in patients with DMa. We evaluated the effect of treatment with the angiotensin II receptor antagonist losartan on macular oedema and hard exudates in patients with an advanced stage of DMa. DESIGN: Randomized, placebo-controlled, double-masked and parallel-group trial. SETTING: Academic medical centre. SUBJECTS: Twenty-four type 2 diabetic patients with DMa. INTERVENTION: Subjects were randomly assigned to a 4-month treatment with either losartan (50 mg o.d.) or placebo. MAIN OUTCOME MEASURES: (i) Degree of macular oedema as estimated by optical coherence tomography scanning of the retina; (ii) fundus photography and flourescein angiography; (iii) 24-h ambulatory blood pressure (BP); (iv) urinary albumin excretion (UAE); and (v) transcapillary escape rate of albumin (TERalb). RESULTS: Central retinal thickness increased from 244 +/- 16 to 256 +/- 31 microm in the losartan group, whilst there was no change in the placebo group (245 +/- 36 microm vs. 242 +/- 30 microm), P = 0.017. Day BP were lowered in the losartan group (from 144/83 +/- 17/10 to 138/78 +/- 20/11 mmHg) compared with the placebo group (140/81 +/- 14/5 to 139/82 +/- 13/9 mmHg), P = 0.27 for systolic and P = 0.009 for diastolic BP. Importantly, there were no changes in night BP in any of the groups. We found no changes in the number of hard exudates, semiquantitative retinopathy grade, visual acuity, UAE, or TERalb in any of the groups. CONCLUSIONS: Type 2 diabetic patients with maculopathy do not seem to benefit from short-term treatment with losartan (50 mg once daily) as far as retinal thickness is concerned, as this dose may increase retinal thickness in the central macular area. Long-term studies are required to assess the clinical implications of these findings.

Increased plasma concentrations of osteoprotegerin in type 2 diabetic patients with microvascular complications.

OBJECTIVE: Osteoprotegerin (OPG) is a newly identified inhibitor of bone resorption. Recent studies indicate that OPG also acts as an important regulatory molecule in the vasculature. Plasma levels of OPG seem to be elevated in subjects with diabetes as well as in non-diabetic subjects with cardiovascular disease. The aim of the present study was to examine the association between plasma OPG levels and microvascular complications and glycemic control in patients with type 2 diabetes. DESIGN AND METHODS: Four groups of 20 subjects in each, individually matched for age and gender, were included in the study: (i) subjects with normal glucose tolerance (NGT); (ii) subjects with impaired glucose tolerance (IGT); (iii) type 2 diabetic patients without retinopathy; and (iv) type 2 diabetic patients with diabetic maculopathy (DMa). Plasma concentration of OPG was measured in duplicate by a sandwich ELISA method. Furthermore, fundus photography, flourescein angiography, and measurements of urinary albumin excretion rate (RIA) were performed. RESULTS: Plasma OPG was significantly higher in diabetic (iii+iv) than in NGT (i) subjects (3.04+/-0.15 vs 2.54+/-0.16 ng/ml, P<0.05). Plasma OPG was significantly higher in the DMa (iv) group than in the NGT (i) group (3.25+/-0.23 vs 2.54+/-0.16 ng/ml, P=0.01). Moreover, plasma OPG was significantly higher (3.61+/-0.36 ng/ml) in the group of diabetic subjects with both microalbuminuria and DMa (n=7) than in the NGT (i) (2.54+/-0.16 ng/ml, P<0.01), IGT (ii) (2.82+/-0.21 ng/ml, P<0.05), and no retinopathy (iii) groups (2.83+/-0.20 ng/ml, P<0.05). CONCLUSIONS: We found increased levels of OPG in plasma from diabetic patients with microvascular complications. This finding indicates that OPG may be involved in the development of vascular dysfunction in diabetes [corrected].

E-selectin-inducing activity in plasma from type 2 diabetic patients with maculopathy.

Diabetic maculopathy (DMa) is a leading cause of visual loss in the western world. We examined whether plasma from type 2 diabetic patients with DMa contains factor(s) capable of inducing expression of the adhesion molecules E-selectin and VCAM-1 or cellular proliferation in cultured endothelial cells. Four gender-, age-, and duration (diabetes groups)-matched groups of 20 subjects each participated: 1) subjects with normal glucose tolerance (NGT), 2) subjects with impaired glucose tolerance (IGT), 3) type 2 diabetic patients without retinopathy, and 4) type 2 diabetic patients with DMa. Fasting plasma was added to in vitro-grown human umbilical vein endothelial cells for 6 h, after which E-selectin and VCAM-1 expression was measured. Proliferation was evaluated by thymidine incorporation. The individuals were characterized by measurement of 24-h ambulatory blood pressure, urinary albumin excretion rate, Hb A(1c), and blood lipids. Plasma from type 2 diabetic patients with DMa induced a significantly higher expression of E-selectin in endothelial cells than did plasma from subjects with NGT (259 +/- 23 x 10(3) vs. 198 +/- 19 x 10(3); arbitrary absorbance units; P < 0.05). There were no significant differences in plasma stimulatory effects on VCAM-1 expression or on thymidine incorporation between groups. These findings suggest that plasma from type 2 diabetic patients with DMa contains factor(s) capable of inducing the expression of E-selectin in endothelial cells. Enhanced expression of E-selectin may contribute to the development of DMa in type 2 diabetes.

Effects on heart rate variability of metoprolol supplementary to ongoing ACE-inhibitor treatment in Type I diabetic patients with abnormal albuminuria.

AIMS/HYPOTHESIS: Diabetic nephropathy is associated with a high risk of cardiac mortality including sudden death. This is presumably related to an imbalance between sympathetic and parasympathetic tone resulting in a decreased heart rate variability (HRV). In non-diabetic patients a decreased HRV is known to be a strong predictor of cardiovascular death. Studies in non-diabetic patients have shown that beta-blockers improve HRV parameters known to reflect parasympathetic function. The aim of our study was to investigate effects of additional beta-blocker treatment on: cardiac autonomic function, blood pressure, and urine albumin excretion in ACE-inhibitor treated Type I (insulin-dependent) diabetes mellitus patients with abnormal albuminuria. METHODS: We studied the effects of 6 weeks treatment with metoprolol (100 mg once daily, zero order kinetics formulation) in 20 patients participating in a randomised, placebo controlled, double blind, crossover trial. Patients were simultaneously monitored under ambulatory conditions with 24-h Holter-monitoring, 24-h ambulatory blood pressure recording, and 24-h fractionated urine collections. Heart rate variability was assessed by four different methods; ambulatory HRV analysis was carried out by spectral and time domain analysis, and on days of investigation short-term spectral analysis and bed-side tests were carried out. RESULTS: Metoprolol treatment improved in vagal tone assessed by short-term spectral analysis. The 24-h ambulatory HRV analysis showed improvement in some parameters reflecting vagal function. A minor decrease in daytime diastolic blood pressure was shown, no alterations in diurnal variation of blood pressure or urine albumin excretion were observed. CONCLUSION/INTERPRETATION: These preliminary findings indicate that beta-blocker treatment could improve autonomic function in Type I diabetic patients with abnormal albuminuria and an associated high risk of cardiovascular disease.

Increased QTc dispersion is related to blunted circadian blood pressure variation in normoalbuminuric type 1 diabetic patients.

A reduced nocturnal fall in blood pressure (BP) and increased QT dispersion both predict an increased risk of cardiovascular events in diabetic as well as nondiabetic subjects. The relationship between these two parameters remains unclear. The role of diabetic autonomic neuropathy in both QT dispersion and circadian BP variation has been proposed, but data have been conflicting. The aim of the present study was to describe associations between QT dispersion and circadian BP variation as well as autonomic function in type 1 diabetic patients. In 106 normoalbuminuric (urinary albumin excretion <20 microg/min) normotensive patients, we performed 24-h ambulatory BP (Spacelabs 90207) and short-term (three times in 5 min) power spectral analysis of RR interval oscillations, as well as cardiovascular reflex tests (deep breathing test, postural heart rate, and BP response). No patient had received (or had earlier received) antihypertensive or other medical treatment apart from insulin. In a resting 12-lead electrocardiogram, the QT interval was measured by the tangent method in all leads with well-defined T-waves. The measurement was made by one observer blinded to other data. The QT interval was corrected for heart rate using Bazett's formula. The QTc dispersion was defined as the difference between the maximum and the minimum QTc interval in any of the 12 leads. When comparing patients with QTc dispersion below and above the median (43 ms), the latter had significantly higher night BP (114/67 vs. 109/62 mmHg, P < 0.003/P < 0.001), whereas day BP was comparable (129/81 vs. 127/79 mmHg). Diurnal BP variation was blunted in the group with QTc dispersion >43 ms with significantly higher night/day ratio, both for systolic (88.8 vs. 86.2%, P < 0.01) and diastolic (83.1 vs. 79.5%, P < 0.01) BP. The association between QTc dispersion and diastolic night BP persisted after controlling for potential confounders such as sex, age, duration of diabetes, urinary albumin excretion, and HbA1c. Power spectral analysis suggested an altered sympathovagal balance in patients with QTc dispersion above the median (ratio of low-frequency/high-frequency power: 1.0 vs. 0.85, P < 0.01). In normoalbuminuric type 1 diabetic patients, increased QTc dispersion is associated with reduced nocturnal fall in BP and an altered sympathovagal balance. This coexistence may be operative in the ability of these parameters to predict cardiovascular events.

No deleterious effects of tight blood glucose control on 24-hour ambulatory blood pressure in normoalbuminuric insulin-dependent diabetes mellitus patients.

Intensive therapy aiming at near normalization of glucose levels effectively delays the onset and slows the progression of complications in insulin-dependent diabetes mellitus (IDDM) and is recommended in most patients. However, in a recent report, intensive insulin treatment was found to be associated with deleterious effects on nocturnal blood pressure (BP), the proposed mechanisms being subclinical nocturnal hypoglycemia or hyperinsulinemia. The aim of the present study was to evaluate the association between glycemic control, insulin dose, and 24-h ambulatory BP (AMBP) in a group of well-characterized IDDM patients. Twenty-four-h AMBP was measured in 123 normoalbuminuric [urinary albumin excretion (UAE) < 20 microg/min] IDDM patients using an oscillometric technique (SpaceLabs 90207) with readings at 20-min intervals. UAE was measured by RIA and expressed as geometric mean of three overnight collections made within 1 week. Tobacco use and level of physical activity was assessed by questionnaire. HbA1c was determined by high-pressure liquid chromatography (nondiabetic range, 4.4-6.4%), and patients were stratified into quartiles according to HbA1c levels. Mean HbA1c values in the four groups were 7.0% (n = 31), 8.0% (n = 31), 8.6% (n = 31), and 9.7% (n = 30). The groups were comparable regarding age, gender, diabetes duration, body mass index, UAE, smoking status, and physical activity. AMBP levels were almost identical in the HbA1c quartiles with night values of (increasing HbA1c order): 110/63, 112/66, 112/66, and 113/65 mm Hg (P = 0.69/P = 0.32). There was no association between tight glucose control and higher nocturnal BP or a more blunted circadian BP variation. On the contrary, a weak positive correlation between night to day ratios of mean arterial BP and HbA1c values was found (r = 0.26, P = 0.005), i.e. blunted circadian BP variation is most frequent in patients with high HbA1c values. Neither did we find doses of insulin to be associated with night BP (r = 0.04, P = 0.68). Tight blood glucose control is not associated with deleterious effects on 24-h AMBP in normoalbuminuric IDDM patients. Intensive therapy can be implemented without concerns of inducing high nocturnal BP and accelerating diabetic complications.

Follow-up study of individuals with high tetraplegia (C1-C4) 14 to 24 years postinjury.

OBJECTIVE: To determine the life circumstances and psychosocial status of individuals with respirator-assisted and respirator-independent high tetraplegia an average of 19 years after spinal cord injury. DESIGN: Survey data were analyzed separately for ventilator-assisted and ventilator-independent groups. SETTING: Three spinal cord injury rehabilitation centers in California, Colorado, and Texas. SUBJECTS: Eighty-two individuals with CI-C4 tetraplegia between 14 and 24 years postinjury who had received acute inpatient rehabilitation. MAIN OUTCOME MEASURES: Demographics, health care utilization patterns, activities of daily living (Katz Level of Free Time Activities Scale), self esteem (Rosenberg Self Esteem Scale), quality of life, and employment. RESULTS: Self esteem and quality of life were, reported as high. Most subjects had some form of health care insurance. More than 90% lived in private homes. Approximately one third of cases had at least a college degree, yet only one quarter reported being employed. One fifth of individuals were married. Almost half of ventilator-independent cases and one quarter of ventilator-assisted cases lived in households with income of less than $20,000 per year. Mean hospital days in the past year were 11 for the ventilator-independent group and 6 for the ventilator-assisted group. The latter group required more nursing level care, significantly more hours of care, and more paid attendants over the year. Ninety-five percent of individuals reported being "glad to be alive." CONCLUSIONS: Assistance in the areas of socialization, financial status, personal assistance services, transportation, and entry into competitive employment were defined as needed. Quality of life was higher than expected, considering the substantial physical limitations of the group. The sample was almost unanimously glad to be alive, including all ventilator-assisted individuals.