Relationship Between Blood Pressure and Urinary Albumin Excretion Rate in Young Danish Type 1 Diabetic Patients: Comparison to Non-diabetic Children

In 1989 a nation-wide investigation of blood pressure and urinary albumin excretion rate (AER) was carried out in 506 boys and 441 girls with Type 1 diabetes (approximately 80 % of total) treated at 22 paediatric departments. In addition a reference population from 1979 consisting of 663 healthy non-diabetic children (334 boys, 329 girls) served as a control group with respect to blood pressure and body mass index. Microalbuminuria was defined as AER of 20–150 μg min^-1 in at least two out of three timed overnight urine collections and was diagnosed in 30 adolescents (16 boys, 14 girls). Five patients (3 boys, 2 girls) had overt proteinuria (AER: > 150μg min^-1). Age-related percentile charts based on one blood pressure reading were provided for normoalbuminuric diabetic patients and the healthy control group. The study revealed an increase in arterial blood pressure during the period of the pubertal growth spurt for the diabetic and non-diabetic group. The changes were most pronounced for systolic blood pressure. No statistically significant difference was observed in systolic and diastolic blood pressure between normoalbuminuric diabetic children and healthy control children. However, diabetic females aged 15–18 years had significantly higher diastolic blood pressure (75 ± 1 mmHg, n = 139, mean ± SE) than healthy control females (72± 1 mmHg, n = 155, p ± 0.01), and significantly (p ± 0.001) higher body mass index (diabetic females: 22.3± 0.2 kg m^-2 vs healthy females: 20.9± 0.2 kg m^-2, mean± SE). Boys aged from 15 to 18 years with Type 1 diabetes had significantly higher systolic blood pressure (123± 1 mmHg, n = 164) than girls (117± 1 mmHg, n = 139, p± 0.0001), while girls aged from 15 to 18 years had significantly higher diastolic blood pressure (75± 1 mmHg, n = 139) than boys (72± 1 mmHg, n = 72, p ± 0.01). Among the 30 adolescents with persistent microalbuminuria, 18 (10 boys, 8 girls) had diastolic blood pressure above the upper quartile for normoalbuminuric patients, while 2 out of 5 with macroalbuminuria had diastolic blood pressure above this limit. By multiple logistic regression the only risk determinants for elevated urinary albumin levels were age and diastolic blood pressure. These findings suggest that elevated arterial blood pressure is related to the increased prevalance of microalbuminuria observed in adolescents with Type 1 diabetes.     

A Possible Relationship of Nocturnal Blood Pressure Variability with Coronary Artery Disease in Diabetic Nephropathy

Evidence suggests a relationship between short-term blood pressure (BP) variability and cardiovascular target-organ damage. Although a blunted nocturnal decrease in BP and reduced heart rate variability have been shown to be associated with cardiovascular morbidity in diabetic patients, little information is available on short-term BP variability. In this study, short-term BP variability was assessed in 36 subjects with type 2 diabetes and overt nephropathy who underwent ambulatory BP monitoring, and the factors that correlated with short-term BP variability were examined. The incidence of coronary artery disease (CAD) was significantly greater in the patients with increased 24-h systolic BP variability (67% versus 11%; p < 0.0005), while that of cerebrovascular disease was not significantly affected (61% versus 50%). Multiple stepwise regression analysis revealed that serum cholesterol (cholesterol) and plasma norepinephrine (p-NE) were significant and independent contributors to nighttime systolic BP variability (partial R² = 0.490, p < 0.001; partial R² = 0.470, p < 0.001) and demonstrated that body mass index and p-NE were primary determinants of nighttime diastolic BP variability (partial R² = 0.539, p < 0.0005; partial R² = 0.304, p < 0.05). Diabetic nephropathy patients with CAD had significantly increased daytime systolic (17.8 mmHg versus 13.1 mmHg, p < 0.0005), nighttime systolic (17.4 mmHg versus 10.5 mmHg, p < 0.0001), and nighttime diastolic (10.4 mmHg versus 7.2 mmHg, p < 0.05) BP variability. Furthermore, logistic regression analysis demonstrated that nighttime systolic BP variability was an independent risk factor for CAD (odds ratio 3.13 [95% CI 1.02–9.61]; p < 0.05). The increase in nighttime BP variability is associated with a proportional sympathetic activation in diabetic nephropathy. Elevated short-term BP variability combined with relative sympathetic prevalence during the night might represent an important risk factor for cardiovascular events in the diabetic population.     

Serum 7S domain of type IV collagen levels in essential hypertension and hypertensive type 2 diabetic patients

Metabolic alteration of Type IV collagen occurs in micro- or macrovascular basement membrane of diabetic patients. Hypertension, a risk factor for clinical progression of diabetic vascular disease, may influence this metabolic alteration. The object of this study was to evaluate the serum 7S domain of type IV collagen (7S-collagen) levels in patients with essential hypertension and in Type 2 diabetic patients with or without hypertension and to investigate the relationship between the type IV collagen metabolism and the arterial blood pressure. Serum 7S-collagen levels in 18 patients with essential hypertension were significantly higher than in 24 normal subjects (4.2 ± 0.5 vs 3.6 ± 0.4 ng ml⁻¹ p < 0.01). Serum 7S-collagen levels in 28 normotensive diabetic patients (4.2 ± 0.5 ng ml⁻¹) were significantly higher than in normal subjects (p < 0.01). The serum 7S-collagen levels were significantly higher in 22 diabetic patients with hypertension (4.8 ± 0.6 ng ml⁻¹) than in the other groups. There was a significant correlation between the serum 7S-collagen levels and the systolic blood pressure in cases with essential hypertension (r = 0.59, p < 0.001) and in all diabetic patients (r = 0.52, p < 0.001), suggesting that elevation of the systolic blood pressure may influence the type IV collagen metabolism of vascular basement membrane. We conclude that the metabolic alteration of basement membrane occurring in patients with diabetes mellitus may worsen in the presence of high systolic blood pressure. © 1997 by John Wiley & Sons, Ltd.     

Ambulatory Blood Pressure Variability Is Increased in Diabetic Hypertensives

The purpose of this study was to examine the possible difference in the 24-hr BP profile—including short-term BP variability, assessed as the standard deviation—between diabetic and non-diabetic hypertensives. We measured 24-hr ambulatory BP in 11 diabetic hypertensives (diabetic HT) and 10 non-diabetic hypertensives (non-diabetic HT) who were hospitalized for the educational program in our hospital and were under stable salt intake. Renal function and sleep apnea were also estimated. There were no significant differences in 24-hr systolic BP (141 mmHg vs. 135 mmHg, ns), daytime systolic BP (143 mmHg vs. 138 mmHg, ns), and nighttime systolic BP (135 mmHg vs. 130 mmHg, ns) between diabetic HT and non-diabetic HT. The values of 24‐hr HR (69.7 beats/min vs. 65.2 beats/min, ns) and 24-hr HR variability (9.9 beats/min vs. 10.1 beats/min, ns) were also similar between the groups. Interestingly, diabetic HT had a significantly greater 24-hr systolic and diastolic BP variability than non-diabetic HT (18.2 mmHg vs. 14.5 mmHg, p < 0.05; 11.5 mmHg vs. 9.6 mmHg, p < 0.05, respectively). The values for creatinine clearance, urinary protein excretion, and apnea-hypopnea index were similar between the groups. Bivariate linear regression analysis demonstrated that fasting blood glucose was the primary determinant of 24-hr diastolic BP variability (r = 0.661, p < 0.01). Multiple stepwise regression analysis revealed that fasting blood glucose was a significant and independent contributor to 24-hr systolic BP variability (r = 0.501, p < 0.05). Taken together, these results demonstrate that BP variability is increased in diabetic hypertensives. Furthermore, it is possible that an elevation of fasting blood glucose may contribute to the enhanced BP variability in hypertensives.     

Thrombomodulin Levels in Insulin-dependent Diabetic Patients with Microalbuminuria

Thrombomodulin (TM) plays an important role in the regulation of blood coagulation at the endothelial surface. TM is also present in plasma, where an increase of its level seems to reflect endothelial damage. Since microalbuminuria is associated with an increased atherothrombotic risk and is considered an expression of widespread vascular damage, we evaluated plasma thrombomodulin levels, blood pressure, and plasma lipid values in Type 1 diabetic patients with micro- and normoalbuminuria. Thrombomodulin was measured in 12 microalbuminuric (albumin excretion rate 20–200 μg min^?1 in 2 of 3 overnight urine collections) and in 12 normoalbuminuric (albumin excretion rate < 20 μg min^?1) Type 1 diabetic patients matched for age, sex, body mass index, smoking habits, diabetes duration, and glycated haemoglobin. Mean thrombomodulin was significantly higher in micro- than in normalbuminuric group (59.34 ± 3.58 vs 43.56 ± 3.52 ng ml^?1 p < 0.01). Systolic and diastolic blood pressure were significantly higher in micro- than in normoalbuminuric group (p < 0.05). There was a positive correlation between plasma thrombomodulin and albumin excretion rate (p = 0.013, r = 0.49), and between thrombomodulin and diastolic blood pressure (p = 0.023, r = 0.46) in diabetic patients as a whole but not in the individual groups. These findings suggest the presence of an endothelial injury in microalbuminuric patients.     

Structural cardiac changes in relation to 24-h ambulatory blood pressure levels in borderline hypertension

Abstract. Objectives. To investigate left ventricular hypertrophy (LVH) in relation to 24-h ambulatory blood pressure (24-ABPM) and insulin levels in borderline hypertension. Design. A case-control study. Subjects. Borderline hypertensive men (diastolic blood pressure (DBP) 85–94 mmHg, n = 69) and age-matched normotensive controls (DBP ≤ 80 mmHg. n = 69) from a population screening programme. Main outcome measures. Echocardiography (M-mode). insulin (RIA) and 24-APBM (Del Mar P-IV) levels. Results. The borderline group showed a significant increase in septal thickness (10.4±1.5 vs. 9.7±1.5 mm. P < 0.01), peak systolic wall stress (218±38 vs. 202±38 10³ dynes cm^?2, P < 0.05) and a decrease in LV ejection time (28.4±2.5 vs. 29.5±2.1s, P < 0.01). The septum vs. posterior wall thickness ratio was significantly higher in the borderline group (1.13±0.14 vs. 1.06±0.14, P < 0.01). Casual BP levels did not correlate with LVH indices, while 24-ABPM systolic levels correlated strongly with LVH indices in the borderline group (r = 0.22–0.52, P < 0.05) but not in the normotensive group. Insulin levels correlates strongly with LVH indices in the normotensive group (r = 0.34–0.47, P < 0.01) but not the borderline, group. Conclusions. Signs of asymmetric LVH and altered ventricular function are already detectable in borderline hypertension. The data also suggest that early structural cardiac changes are related to ambulatory blood pressure profile, but not to casual blood pressure or trophic factors such as insulin.     

The Influence of Hypertension on Microvascular Blood Flow and Resistance to Flow in the Skin of Patients with Type 2 (Non-insulin-dependent) Diabetes

Maximum microvascular blood flow and resistance to flow were determined in the skin of nine hypertensive and nine normotensive Type 2 (non-insulin-dependent) diabetic patients and nine control subjects to determine the influence of hypertension on these variables. Maximum blood flow was reduced in both the hypertensive (1.05 (0.70–1.42) V) and normotensive (1.04 (0.79–1.63) V) Type 2 diabetic patients when compared with control subjects (1.40 (1.26–2.13) V, p < 0.01 for hypertensive and p < 0.05 for normotensive patients, respectively); however, maximum blood flow was similar in both groups of diabetic patients (p = 0.82). In contrast, resistance to flow was significantly greater in the diabetic patients with hypertension (127.2 (87.5–181.3) mmHg V^?1 vs 84.7 (61.9–123.0) mmHg V^?1 normotensive diabetic patients, p < 0.02). In addition, R was greater in the normotensive Type 2 diabetic patients than in control subjects (70.7 (44.7–79.9) mmHg V^?1, p < 0.05). These results suggest that hypertension is associated with an additional rise in pre-capillary vascular resistance in Type 2 diabetes which, while protecting the microcirculation from the effects of increased arterial pressure, may further diminish protective hyperaemic responses.     

Increased vasopressor responsiveness to angiotensin II in Type 1 (insulin-dependent) diabetic patients without complications

Summary The blood pressure response to infused angiotensin II (0.3 to 3 ng · kg^–1 · min ^–1) was investigated in six normotensive patients with Type 1 (insulin-dependent) diabetes free of complications and in six healthy subjects matched for age, sex and weight. Basal blood pressures (111/68 and 114/72 mmHg) and basal plasma angiotensin II levels (18.0±5.2 and 14.1±2.4 pmol/l; mean + SD) were similar in the diabetic and control groups as were 24 h urinary excretions of sodium (157±88 and 154±84 mmol/24h). Equal increments in plasma angiotensin II were produced during the infusions in the two groups. Increases in both diastolic and systolic blood pressure were significantly greater in the diabetic patients throughout the infusion. Mean diastolic increments were: 6.7 versus 1.3 mmHg (0.3 ng dose), 11.0 versus 6.9 mmHg (1 ng dose) and 16.7 versus 12.3 mmHg (3 ng dose) (p<0.001). Corresponding figures for systolic pressure were: 8.7 versus 1.3mmHg, 10.3 versus 3.7mmHg and 15.3 versus 8.7mmHg (p<0.001). Vasopressor responsiveness to angiotensin II is thus increased in Type 1 diabetic patients without complications; it may, therefore, be a consequence of the diabetes rather than of the presence of microvascular disease or hypertension.     

The Relationship Between Plasminogen Activator Inhibitor-1 and Insulin Resistance in Newly Diagnosed Type 2 Diabetes Mellitus

It is not clear whether elevated levels of the fibrinolytic inhibitor, plasminogen activator inhibitor-1 (PAI-1) in Type 2 diabetes mellitus are the result of obesity or coexistent atherosclerosis. Therefore the relationship between PAI-1 and insulin resistance, determined by the homeostasis model assessment (HOMA) was investigated in a group of 26 insulin-resistant, normotensive newly diagnosed Type 2 diabetic patients with a low probability of atherosclerosis. Compared with a normal control group, closely matched for body mass index (BMI), fibrinolytic activity was depressed in the diabetic patients due to elevated levels of the inhibitor PAI-1, 17.6 (11.1–28) vs 8.4 (4.9–14.1) IU ml^?1, p < 0.001. PAI-1 was related to BMI, r = 0.59, p < 0.001 plasma insulin, r=0.66, p < 0.001; insulin resistance, r = 0.54, p< 0.005 and urinary albumin excretion, r=0.48, p < 0.01, but not HbA_1c or fasting glucose. PAI-1 was not related to blood pressure or plasma triglyceride levels. This study suggests that at the time of diagnosis of Type 2 diabetes mellitus, elevated PAI-1 levels are already linked to other risk factors for vascular disease including hyperinsulinaemia, insulin resistance, and urinary albumin excretion, and this is not the result of obesity or coexistent atherosclerosis.     

Long-term Effects of Captopril and Atenolol in Essential Hypertension

ABSTRACT Fifty patients with mild or moderate essential hypertension were randomized (double-blindly) to treatment with either captopril (n=26) or atenolol (n=24). Their mean supine diastolic blood pressure after placebo was 100–125 mmHg. The study included an initial dose finding phase (12 weeks) during which the dosages of captopril and atenolol were increased stepwise every second week in order to obtain normotension (supine diastolic blood pressure <95 mmHg). Hydrochlorothiazide was added when necessary. During the second phase of the study the patients were followed on active treatment for 2 years. After the initial 12 weeks of active treatment, recumbent and standing blood pressures had fallen significantly both in the captopril group (by 31/20 and 33/19 mmHg, p<0.001) and in the atenolol group (by 24/18 and 30/20 mmHg, p<0.01 (systolic), p<0.001 (diastolic)). The antihypertensive effect was maintained in both groups during long-term treatment. The antihypertensive effect of both agents was potentiated to the same extent by addition of hydrochlorothiazide. Side-effects were few and mild. It can be concluded that both captopril and atenolol are safe and effective antihypertensive drugs.     

Does impaired glucose tolerance predict hypertension?

Summary This study evaluates prospectively the relationship between impaired glucose tolerance (IGT) and blood pressure. From a population of 1376 men and women aged 40–59 years, all those with IGT (n=54) plus 133 age- weight- and sex-matched nor-moglycaemic control subjects were selected after excluding treated hypertensive patients. Blood pressure, fasting and postload blood glucose and plasma insulin were measured. At 11.5 years after the first visit 76% of the IGT patients and 80% of the control subjects were re-examined. At baseline blood pressure was significantly higher in IGT patients than in control subjects (systolic 135.5±2.3 vs 127.9±1.4mm Hg, p<0.001; and diastolic 88.0±1.5 vs 84.7±0.7 mmHg, p<0.05) independent of age, gender, weight, antihypertensive medication and insulin-aemia. Accordingly, hypertension was more frequent in subjects with IGT (odds ratio 2.1, 95% confidence, interval (CI) 0.9–4.9). Postload insulin was significantly associated with hypertension — both at univariate and multivariate analysis — in normoglycaemic subjects, but not in those with IGT. At follow-up systolic blood pressure increased in both groups; the increase was smaller in patients with IGT (6.0±2.4 vs 12.3±1.6 mmHg p<0.05). Likewise, the 11.5 years' cumulative incidence of hypertension was not significantly different in subjects with baseline IGT or normoglycaemia; if anything it was lower in the IGT group (odds ratio 0.36, 95% CI 0.1–1.2). In multivariate analysis incidence of hypertension was associated positively with baseline blood pressure (p<0.0003) and negatively with IGT status p<0.03), while no significant association was found with insulin. In conclusion, the findings of this study question IGT as a risk factor for hypertension. Furthermore, these data do not indicate a major role for hyperglycaemia and hyperinsulinaemia per se in the aetiology of hypertension and suggest that IGT and hypertension share one or more pathogenetic factor(s) (i.e., insulin resistance, hyperactivity of the sympathetic nervous system, etc.), which induce deterioration of blood pressure control first, and hyperglycaemia later.Abbreviations IGT Impaired glucose tolerance - CI confidence interval - BMI body mass index     

Effects of dietary sodium on blood pressure in IDDM patients with nephropathy

Summary The objectives of the study were to assess the effects of moderate sodium restriction on blood pressure in insulin-dependent diabetic (IDDM) patients with nephropathy and high normal or mildly hypertensive blood pressure (primary objective), and to document possible associated changes of exchangeable body sodium, body volumes, components of the renin-angiotensin-aldosterone system, atrial natriuretic peptide, and catecholamines (secondary objective). Sixteen patients with untreated systolic blood pressure 140 <160 mmHg and/or diastolic blood pressure 85 <100 mmHg were included in a double-blind, randomized, placebo-controlled trial. After a 4-week run-in period on their usual diet and a 2-week dietary training period to reduce sodium intake to about 90 mmol/day, eight patients received 100 mmol/day sodium supplement (group 2) and eight patients a matching placebo (group 1) for 4 weeks while continuing on the reduced-sodium diet. Patients were examined at weekly intervals. Main response variables were mean values of supine and sitting systolic and diastolic blood pressure as measured in the clinic and by the patients at home. The differences in blood pressure between the beginning and the end of the blinded 4-week study period were calculated and the differences in changes between the two patient groups were regarded as the main outcome parameters. During the blinded 4-week study period, average urinary sodium excretion was 92±33 (mean ± SD) mmol/day in group 1 and 199±52 mmol/day in group 2 (p=0.0002). The differences in blood pressure changes between the two patient groups were 3.9(–1.2 to 9) mmHg [mean (95% confidence intervals)] for systolic home blood pressure, 0.9(–3.7 to 5.5) mmHg for diastolic home blood pressure, 4.9(–3.3 to 13.1) mmHg for clinic systolic blood pressure and 5.3(1 to 9.7 mmHg, p=0.02) for clinic diastolic blood pressure. Combining all patients, there were relevant associations between changes of urinary sodium excretion and blood volume (Spearman correlation coefficient r=0.57), blood pressure and angiotensin II (diastolic: r=–0.7; systolic: r=–0.48), and exchangeable body sodium and renin activity (r=–0.5). In conclusion, in this study of IDDM patients with nephropathy and high normal or mildly hypertensive blood pressure, a difference in sodium intake of about 100 mmol/day for a period of 4 weeks led to a slight reduction of clinic diastolic blood pressure. Studies including larger numbers of patients with various stages of nephropathy and hypertension are needed to definitely clarify the effects of sodium restriction in IDDM.Abbreviations ACE Angiotensin converting enzyme - ANP atrial natriuretic peptide - CV coefficient of variation - GFR glomerular filtration rate - RPF renal plasma flow - PAH paraaminohippuric acid     

Effect of sodium intake on blood pressure and albuminuria in Type 2 diabetic patients: the role of insulin resistance

Aims/hypothesis This study was done to measure the effect of Na⁺ intake on blood pressure and albuminuria, in relation with insulin sensitivity and kidney haemodynamics, in Type 2 diabetic patients with and without microalbuminuria.Methods Type 2 diabetic patients, 20 with microalbuminuria, 21 without, spent two consecutive 7-day periods, one on a high (250 mmol), the other on a low-Na⁺ (20 mmol) diet. Body weight, 24-h blood pressure and albuminuria were measured at the end of each period. At the end of high-Na⁺ diet insulin sensitivity (euglycaemic insulin clamp; 2 mU·kg^–1·min^–1) and kidney haemodynamics were measured in nine patients from each group.Results Switching from low to high-Na⁺ diet resulted in an increase in blood pressure (7.4±4.7 mmHg; p<0.001), body weight (1.9±0.4 kg; p<0.05) and albuminuria [from 80 (31–183) µg/min to 101 (27–965) µg/min; p<0.01) in patients with microalbuminuria. No changes occurred in patients without microalbuminuria. Patients with microalbuminuria also had greater intraglomerular pressure (44±1 mmHg vs 36±1; p<0.001), calculated from glomerular filtration rate, renal plasma flow, plasma protein concentration and the relationship between pressure and natriuresis. In these patients insulin sensitivity was lower (5.16±49 vs 7.36±0.63 mg·kg^–1·min^–1; p=0.007). Urinary albumin excretion (r=0.40; p=0.009) and insulin sensitivity (r=–0.59; p=0.01) were correlated with intraglomerular pressure.Conclusion/interpretation High salt intake increases blood pressure and albuminuria in Type 2 diabetic patients with microalbuminuria. These responses are associated with insulin resistance and increased glomerular pressure. Insulin resistance could contribute to greater salt sensitivity, increased glomerular pressure and albuminuria.Abbreviations GFR Glomerular filtration rate - PGC intraglomerular pressure - AER albumin excretion rate     

Diurnal blood pressure variations in normoalbuminuric type 1 diabetic patients

Abstract. Objective. To test the hypothesis that normoal-buminuric type 1 diabetic patients segregate into groups with normal and elevated ambulatory blood pressure. To evaluate diurnal variation of blood pressure assessed by individual or fixed night-time periods. Design. Cross-sectional study. Setting. Tertiary referral centre. Subjects. Inclusion criteria for type 1 diabetic patients (n = 33): normal urinary albumin excretion (UAE age < 45 < 20 μg min^?1), diabetes duration ≤ 20 years, age 45 years. Healthy controls (n = 33) were matched for sex and age. Main outcome measure. Twenty-four hour, day-time, night-time and night/day ratio of ambulatory blood pressure. Results. Twenty-four-hour blood pressure in diabetic patients did not differ significantly from a normal distribution. The 24-h systolic blood pressure was higher in diabetic patients than in healthy controls (difference: 6 mmHg, 95% confidence interval (CI) from 1 to 10 mmHg, P < 0.05), while no significant differences were found for diastolic values. The 24-h systolic blood pressure in diabetic patients with UAE above the median value (5.8 μg min^?1) was higher than for those with lower UAE (difference: 7 mmHg, 95% CI from 0.5 to 13 mmHg, P < 0.05). The night/day ratio of diastolic blood pressure based on individual informations of the night period was (mean ± SD) 80 ± 6% in diabetic patients and 78 ± 8% in controls (difference: 2%, 95% CI from ?1 to 5%, not significant [NS]). This ratio increase significantly (P < 0.00001) to 90 ± 5% in diabetes and to 84 ± 7% in controls if a fixed night period from 22.30 hours to 06.30 hours was assumed. Conclusions. It was not possible to identify a well-separated group of normoalbuminuric type 1 diabetic patients with elevated ambulatory blood pressure. Values of UAE above the median in diabetic patients are associated with higher ambulatory blood pressure. Assessment of the night/day variation from fixed time-points should be abandoned because this leads to a serious underestimation of the nocturnal reduction in blood pressure.     

Insulin-like Growth Factor-I and IGF-I Receptors in Diabetic Patients with Neuropathy

Since a number of animal studies have shown that Insulin-like growth I (IGF-I) stimulates nerve regeneration, the aim of our study was to evaluate the possible relationship between IGF-I and IGF-I receptors in diabetic patients with peripheral neuropathy. One hundred and four patients with Type 2 diabetes (57 with peripheral neuropathy and 47 non-neuropathic) were studied. Controls were 17 non-diabetic persons. After an overnight fast, blood was taken for IGF-I, IGF-I receptors, glucose, HbA₁, C-peptide, and insulin. The neuropathy study group had significantly lower levels of IGF-I:144.5 ng mI^-1 (57.5–363.0, 95% confidence limits) compared to controls: 186.2 ng mI^-1 (93.3–371.5), p<0.01, and to diabetic patients without neuropathy: 173.7 ng mI^-1 (83.1–363.0), p<0.01. The study group also had a lower number of IGF-I receptors per red cell: 22.9 times 10³ (13.08–38.01) vs control subjects: 28.1 times 10³ (18.62–42.65), p<0.01, and non-neuropathic diabetic patients: 26.3 times 10³ (16.59–41.68), p<0.01. In diabetic subjects there was a positive correlation (r = 0.20, p<0.05) between IGF-I and HbA₁, while in the neuropathy group there was a negative correlation between the score for nerve dysfunction with the IGF-I (r = -0.39, p<0.01) and with IGF-I receptors (r = -0.34, p<0.01). We conclude that in diabetic patients with peripheral neuropathy there are abnormalities of IGF-I and IGF-I receptors which may contribute to impaired neuronal regeneration.     

Hypertension in Diabetes Study IV. Therapeutic requirements to maintain tight blood pressure control Hypertension in Diabetes Study Group*

Summary We report the efficacy of therapy over 5 years follow-up in 758 non-insulin-dependent diabetic patients in a prospective, randomised controlled study of therapy of mild hypertension. Patients were recruited who on antihypertensive therapy had systolic blood pressure over 150 mmHg or diastolic over 85 mmHg, or if not on therapy had systolic blood pressure over 160 mmHg or diastolic over 90 mmHg. Their mean blood pressure at entry to the study was 160/94 mmHg at a mean age of 57 years. They were allocated to tight control (aiming for systolic < 150/diastolic < 85 mmHg) or to less tight control (aiming for systolic < 180/ diastolic < 105 mmHg). The tight control group were allocated to primary therapy either with a beta blocker (atenolol) or with an antiotensin converting enzyme inhibitor (captopril), with addition of other agents as required. Over 5 years, the mean blood pressure in the tight control group was significantly lower (143/82 vs 154/88 mmHg, p < 0.001). No difference was seen between those allocated to atenolol or captopril. The proportion of patients requiring three or more antihypertensive therapies to maintain tight control in those allocated to atenolol or captopril increased from 16 and 15 %, respectively at 2 years to 25 and 26 %, respectively at 5 years, whereas in the less tight control group at 2 and 5 years only 5 and 7 %, respectively required three or more therapies. There was no difference in the incidence of side effects or hypoglycaemic episodes between those allocated to atenolol or captopril, but those allocated to atenolol increased their body weight by a mean of 2.3 kg compared with 0.5 kg in those allocated to captopril (p < 0.01). Allocation to atenolol was also associated with small increases in triglyceride, and decreases in LDL and HDL cholesterol, which are of uncertain clinical relevance. The study is continuing to determine whether the improved blood pressure control, which was obtained, will be beneficial in maintaining the health of patients by decreasing the incidence of major clinical complications, principally myocardial infarction and strokes, and microvascular complications, such as severe retinopathy requiring photocoagulation and deterioration of renal function. [Diabetologia (1996) 39: 1554–1561]     

Central role for sodium in the pathogenesis of blood pressure changes independent of angiotensin,aldosterone and catecholamines in Type 1 (insulin-dependent) diabetes mellitus

Summary We studied 73 Type 1 (insulin-dependent) diabetic patients, 18 to 50 years of age, with a diabetes duration of more than five years. Group 1: normal urinary albumin excretion below 30 mg per 24 h (n=19); group 2: microalbuminuria, 30–300 mg per 24 h (n=36); and group 3: diabetic nephropathy, above 300 mg per 24 h (n=18). Fifteen non-diabetic persons matched for sex and age served as control subjects. The sodium intake evaluated on the basis of 24-h urine sodium excretion was similar in patients and control subjects. Blood pressure in groups 1 and 2 and control subjects was below 160/95 mmHg. The blood pressure was increased in group 3 as compared with the other groups (systolic/diastolic 161±22/101±9 mmHg vs 131±13/84±10, mean±SD, p<0.0001). Exchangeable sodium was increased in patients (p<0.01) and correlated to the mean blood pressure (n=70, r=0.41, p<0.01). Extracellular volume was increased in patients (p<0.05), whereas plasma volume was normal. Supine serum angiotensin II was suppressed in the patients (p<0.001). A negative correlation was found between mean blood pressure and supine serum aldosterone (n=68, r=-0.24, p<0.05), and exchangeable sodium and aldosterone (n=66, r=-0.36, p<0.002) in all patients. The catecholamine levels were also suppressed or normal in the patients. These data suggest that sodium retention plays a major role and that the aldosterone, angiotensin II and catecholamine levels are suppressed during the blood pressure rise observed in the very early stages of diabetic renal disease.     

Cholesterol Rich apo B Containing Lipoproteins and Smoking are Independently Associated with Macrovascular Disease in Normotensive NIDDM Patients

A cross-sectional study of macrovascular disease (MVD) and associated metabolic and other risk factors was conducted in 87 normotensive NIDDM patients. MVD was assessed by Rose questionnaire, 12 lead resting ECG, duplex scanning of carotid and peripheral vessels, and ankle:brachial systolic blood pressure ratio. Fasting serum total cholesterol, total triglycerides, LDL cholesterol, HDL cholesterol, apolipoproteins AI and B, lipoprotein (a), HbA₁, plasma glucose, insulin, and C-peptide responses to a carbohydrate rich meal, body mass index (BMI), waist-hip ratio, urinary albumin excretion rate, blood pressure, smoking and family history were assessed as possible ‘risk factors’. Apolipoprotein:lipid ratios were calculated to estimate lipoprotein composition. Thirty-six patients had demonstrable MVD. The presence of MVD was associated with higher total triglycerides (p < 0.05), BMI (p < 0.05), systolic blood pressure (p < 0.01), a lower apo B:non HDL cholesterol ratio (p < 0.001), and smoking (p < 0.005) but no other measures. Multiple regression analysis revealed smoking and a low apo B:non HDL cholesterol to be independently associated with MVD. The low apo B:non HDL cholesterol suggests a high cholesterol content of apo B containing lipoproteins. This lipoprotein abnormality is not a feature of NIDDM, but when present in these patients may be particularly atherogenic.     

24-h ambulatory pulse wave velocity and central blood pressure in type 2 diabetes

BackgroundPulse wave analysis from a brachial cuff permits ambulatory measurements of pulse wave velocity (PWV) and central blood pressure parameters. The diurnal variation of PWV in type 2 diabetes is unknown.MethodsWe evaluated the Arteriograph24 which is a brachial cuff based equipment for estimating PWV and central blood pressure data without the use of a transfer function, in 22 type 2 diabetic patients, who had two 24 h measurements performed.ResultsThe mean number of valid day time and nighttime measurements were 29 (range 16–50) and 18 (11–25), respectively. 21 patients had at least one qualifying report. Nighttime PWV was significantly lower than during the day (9.1 vs. 9.7 ± 0.8 mm/s, p < 0.01). Systolic aortic blood pressure was 6 mmHg lower than brachial blood pressure in the day time (p < 0.01) and 4 mmHg lower during the night (p < 0.05). Each single measurement was standardized with the 24 h average as reference thus generating data from 1004 paired observations. The standardized PWV correlated with standardized values of heart rate (r = 0.24, p < 0.001) and systolic aorta blood pressure (r = 0.20, p < 0.001). A stepwise multiple regression model with standardized pulse wave velocity as dependent variable included standardized heart rate, systolic aorta blood pressure and a dummy variable for day/night status (R² = 0.091, p < 0.001).ConclusionThe Arteriograph24 is applicable for research purpose. PVW in type 2 diabetes is modestly reduced during the night. The intraindividual variation of heart rate contributed independently to the variation of PWV.     

The course of kidney function in Type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy

Summary We evaluated the impact of some putative progression promoters on kidney function in albuminuric Type 2 (non-insulin-dependent) diabetic patients with biopsyproven diabetic glomerulosclerosis. Twenty-six patients (1 female) with a mean age of 52 (standard error 2) years and a known mean duration of diabetes of 9 (1) years were followed-up prospectively for a mean of 5.2 (range 1.0–7.0) years. Twenty-one patients received antihypertensive treatment. During the observation period the glomerular filtration rate decreased from 83 (24–146) to 58 (2–145) ml·min⁻¹·1.73 m⁻² (mean (range)) (p<0.001). The mean rate of decline in glomerular filtration rate was 5.7 (−3.5 to 22.0) ml/min per year. Albuminuria increased from 1.2 (0.3–7.2) to 2.3 (0.4–8.0) g/24 h (geometric mean (range)) (p<0.001). Arterial blood pressure remained unchanged: 162/93 (SE 4/3) and 161/89 (4/2) mm Hg. Univariate analysis showed the rate of decline in glomerular filtration rate to correlate with systolic blood pressure (r=0.71,p<0.001), mean blood pressure (r=0.56,p<0.005), albuminuria (r=0.58,p<0.005) and the initial glomerular filtration rate (r=−0.49,p<0.02). The rate of decline in glomerular filtration rate did not correlate significantly with dietary protein intake, total cholesterol, high-density lipoprotein cholesterol or HbA_1c. Three patients died from uraemia and four patients died from cardiovascular disease. Two patients required renal replacement therapy at the end of the observation period. Our prospective observational study revealed that one-fifth of the patients developed end-stage renal failure during the 5-year observation period. The decline in glomerular filtration rate varied considerably between patients. Increase in arterial blood pressure to a hypertensive level is an early feature of diabetic nephropathy. Elevated systolic blood pressure accelerates the progression of diabetic nephropathy in Type 2 diabetic patients.