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The progression of diabetic nephropathy can be positively influenced by maintaining a low blood pressure level. This has been shown in studies with conventional antihypertensive treatment as well as with ACE inhibitors. Whether the latter group of drugs is more effective remains to be proven and was the aim of our study. In a prospective randomized study we compared the effects of ACE inhibition and beta-blockade on retarding progression of renal function in IDDM patients with an early stage of overt diabetic nephropathy. Twenty-nine patients were studied for 2 years, 15 were randomized for treatment with captopril and 14 for atenolol. Every 6 weeks blood pressure and urinary albumin and total protein excretion were measured. GFR was measured every 6 months as 51Cr-EDTA clearance. Baseline values for blood pressure, renal function and albuminuria were identical in the two groups. The effect of both drugs on blood pressure was not significantly different. In the captopril-treated patients MAP before and after 2 years was 110 +/- 3 (SEM) and 100 +/- 2 mm Hg, respectively and in the atenolol-treated patients 105 +/- 2 vs 101 +/- 2 mm Hg. Both drugs reduced albuminuria and total proteinuria to the same extent. With captopril albuminuria decreased from 1549 (989-2399) to 851 (537-1380) mg/24 h and proteinuria from 2.5 (1.6-3.8) to 1.2 (0.8-1.8) g/24 h. With atenolol albuminuria decreased from 933 (603-1445) to 676 (437-1047) mg/24 h and proteinuria from 1.5 (1.0-2.4) to 0.9 (0.6-1.5) g/24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Captopril and atenolol are equally effective in retarding progression of diabetic nephropathy. Results of a 2-year prospective, randomized study. 774 19

Pupillary test data of 103 normal and 119 diabetic subjects (47 IDDM, 72 NIDDM) were evaluated by factor analysis. From a total of nine pupillary parameters three factors were extracted in the analysis. Factor 1 represents maximal pupillary area, contraction velocity at 1 s, dilation velocity at 6 s and minimal pupillary area--static and simple dynamic parameters; factor 2 amplitude of pupillary unrest, area under the detrended curve of pupillary unrest and period of pupillary unrest--parameters of pupillary unrest; factor 3 fusion frequency of pupillary response following flicker stimuli and latency time of pupillary light reflex--second order dynamic parameters. Factor analysis was then applied to investigate diabetic patients with a high percentage of autonomic neuropathic participants (about 39% had pupillary and about 35% had cardiorespiratory function disorders), which revealed the same three factors as those identified in normal subjects. Furthermore, an age-related database of parameters of pupillary unrest is given. It demonstrates that normal subjects and diabetic patients did not differ in the period of pupillary unrest (normal vs diabetic (mean +/- SEM): 1550 +/- 29 vs 1536 +/- 27 ms; 2p > 0.5). The difference in amplitude (47.8 +/- 2.8 vs 41.0 +/- 2.6% percentile; 2p = 0.071) and area under the detrended curve of pupillary unrest (47.9 +/- 2.8 vs 40.8 +/- 2.6% percentile, 2p = 0.062) seems to show a trend but was not significant. In conclusion, factor analysis revealed three different pupillary test factors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Valid parameters for investigation of the pupillary light reflex in normal and diabetic subjects shown by factor analysis and partial correlation. 806 44

In cross-sectional studies of asymptomatic diabetic patients, multiple abnormalities in left ventricular (LV) function have been found. Long-term significance of these abnormalities is unknown because follow-up studies have not been previously performed. LV ejection fraction (EF) by radionuclide angiocardiography was examined in middle-aged control subjects (n = 44), in patients with insulin-dependent (IDDM) (n = 32) and non-insulin-dependent (NIDDM) (n = 32) diabetes mellitus at baseline and after 4-year follow-up. At baseline, all study subjects were free from cardiovascular disease. LVEF at rest did not differ between the groups at baseline. The decrease in LVEF at rest during follow-up was 1.1 +/- 1.1% (mean +/- SEM) in control subjects, 3.1 +/- 1.3% (p = NS, compared with control subjects) in patients with IDDM, and 7.2 +/- 1.4% (p < 0.01) in patients with NIDDM. At follow-up examination, abnormally low LVEF at rest (< 50%) was found in 7% of control subjects, 13% of patients with IDDM (p = NS), and in 31% of patients with NIDDM (p < 0.05). Compared with control subjects, the prevalence of an abnormal LVEF response to exercise (an increase by < 5%, or a decrease) was higher in diabetic groups at both examinations. This prevalence increased in control subjects from 10% at baseline to 26% at follow-up examination.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Left ventricular systolic function in middle-aged patients with diabetes mellitus. 820 39

Fifteen IDDM patients were evaluated for thyroid hormone abnormalities before and after control of diabetes mellitus/ketoacidosis. Blood sugar mean +/- SEM mg/dl on admission was 430 +/- 20.3 and after therapy fasting and post prandial blood sugar values were 120 +/- 14.5 and 150 +/- 20.2 respectively. GHb mean +/- SEM % on admission was 15.2 +/- 0.36. Serum T3 mean +/- SEM ng/dl of 0.36 +/- 0.04 was in hypothyroid range and rT3 mean +/- SEM ng/ml 0.40 +/- 0.6 was significantly raised (P < 0.001) before therapy. After metabolic control both T3 and rT3 became normal. T4 concentration mean +/- SEM meg/dl of 5.5 +/- 0.7 was well within normal range before therapy and rose to mean +/- SEM mcg/dl 8.8 +/- 0.5 after therapy (P < 0.01). TSH response to TRH was blunted in uncontrolled state. It is concluded that peripheral changes in T3, T4 and rT3 (low T3, high rT3 and low or normal T4) occurred in uncontrolled diabetic state during ketoacidosis. TSH response to TRH was blunted due to suppression of hypothalamic pituitary thyroid axis which takes more than a week for complete recovery.
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PMID:Thyroid hormones in diabetic ketoacidosis before and after therapy. 830 Apr 81

Pre-mixed insulin preparations are being used increasingly in the management of children with IDDM. Recently this form of insulin has been produced in a disposable insulin pen device. An open randomized 3-month crossover study was conducted to compare glycaemic control on a self-titrating insulin regimen with a pre-mixed (30:70) preparation, both given twice daily. The pre-mixed preparation was delivered by disposable pen. Forty children (age range 7-16 yr) entered the study. Mean +/- SEM glycosylated haemoglobin (HbA1 %) at the start of the study (13.1 +/- 0.6) compared with values at the end of the self-titrating (11.8 +/- 0.5) and pre-mixed periods (12.5 +/- 0.5), as well as blood glucose profiles taken at 3-weekly intervals, showed no significant change. Fourteen of the children were on insulin ratios other than 30:70 (range 10:90 to 50:50) and were unaffected by the switch (HbA1 at the start of the study 12.7 +/- 1; at the end of the self-titrating 11.5 +/- 0.8; and pre-mixed period 12.5 +/- 0.8). Twenty-one children continued on the pen for a further 12 months with no deterioration in control (HbA1 at the beginning and end of this period being 11.9 +/- 0.7 and 11.0 +/- 0.7, respectively). The children (95%) preferred the disposable pen and pre-mixed insulin regimen. Switching to pre-mixed insulin, while not improving, has no detrimental effect on glycaemic control.
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PMID:Pre-mixed insulin delivered by disposable pen in the management of children with diabetes. 830 95

To characterize its insulin-antagonistic effect, growth hormone (GH) was infused at variable rates (24, 12 or 6 mU kg-1 min-1) for 1 h in 7 IDDM patients. Saline infusion was used as control (C) and all patients participated in all studies. The effect of insulin was measured with the euglycaemic clamp technique for 6 h combined with d-(3-3H)-glucose to evaluate glucose turnover. The insulin levels during the clamps were similar in all studies (23 +/- 3 mU l-1). The infusions produced peak GH levels of (24 rate = 24) 157 +/- 11, (12 rate = 12) 76 +/- 7, and (6 rate = 6) 45 +/- 8 mU l-1 (mean +/- SEM). The insulin-antagonistic effect of GH on glucose uptake was seen after 2 h and was at a maximum 4 to 5 h after the start of the GH infusion (difference in glucose infusion rate between C and 24 was 1.7 +/- 0.4 mg kg-1 min-1, p < 0.01). The resistance was due to a less pronounced effect of insulin to both inhibit rate of appearance and to stimulate rate of disappearance. Infusion of GH at 12 mU kg-1 min-1 induced a less pronounced insulin resistance both with regards to maximal effect (glucose infusion rate C - GH 1.4 +/- 0.5 mg kg-1 min-1, p < 0.05) and duration (3 h). At 6 mU kg-1 min-1, a clear GH-induced insulin-antagonistic effect was only seen during the third hour of the clamp (glucose infusion rate C-GH 1.3 +/- 0.5 mg kg-1 min-1, p < 0.05). GH infusion impaired the effect of insulin to lower both the levels of free fatty acids (NEFA) and glycerol between 2 and 5 h after the start of the infusion (NEFA, C:110 +/- 29, 24:303 +/- 95, p < 0.05: glycerol, C:32 +/- 4, 24:50 +/- 7 mumol l-1, p < 0.05). The present study therefore demonstrates that the insulin-antagonistic effect of GH in IDDM is related to the plasma levels both with regard to duration and response. The results also indicate that GH impairs the effect of insulin on lipolysis in IDDM after physiological peaks.
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PMID:Characterization of the insulin-antagonistic effect of growth hormone in insulin-dependent diabetes mellitus. 858 32

Amylin has been reported to decrease glycogen storage in rodent skeletal muscles and produce insulin resistance in intact rats. To test the acute effect of a human amylin analog (AC137) on glucose metabolism in man, seven IDDM patients were infused in a randomized, double blind, cross-over study with AC137 (100 micrograms/h, n = 1; 50 micrograms/h, n = 6) or placebo for 330 min during a two-step euglycemic clamp (insulin infusion rates, 0.2 and 0.6 mU/kg.min; basal and hyperinsulinemic period, respectively) followed by a hyperinsulinemic hypoglycemic clamp (insulin infusion rate, 1.5 mU/kg.min; hypoglycemic period). During euglycemia, no differences were found in glucose disposal (step 1, 2.43 +/- 0.20 vs. 2.03 +/- 0.26; step 2, 4.28 +/- 0.54 vs. 4.11 +/- 0.45 mg/kg.min; AC137 vs. placebo, mean +/- SEM), arteriovenous substrate balances across the forearm, or hepatic glucose production. During hypoglycemia, glucose fluxes were also similar. However, lactate release from the forearm was more pronounced (P < 0.05) with the analog than with placebo (area under the curve, -11.2 +/- 4.6 vs. -1.4 +/- 2.2 mmol/min.L). Despite similar plasma glucose nadirs (2.7 +/- 0.0 vs. 2.6 +/- 0.1 mmol/L; AC137 vs. placebo), circulating cortisol and GH rose to significantly higher levels during hypoglycemia with the amylin analog (P < 0.05). In conclusion, acute administration of the amylin analog AC137 did not influence insulin-stimulated glucose metabolism during euglycemic conditions. During imposed hypoglycemia, lactate release from skeletal muscle was, however, enhanced, and the rise in cortisol and GH was augmented.
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PMID:Acute effects of the human amylin analog AC137 on basal and insulin-stimulated euglycemic and hypoglycemic fuel metabolism in patients with insulin-dependent diabetes mellitus. 877 80

Normolipidaemic insulin-dependent diabetic (IDDM) patients are characterized by an increase in the smaller VLDL particles, considered to be the most atherogenic. Since blood glucose control is one of the main regulators of lipid metabolism in diabetic patients, it could influence the shift in the distribution of VLDL subfractions towards smaller particles. To evaluate this possibility, VLDL subfractions, post-heparin lipoprotein lipase and hepatic lipase activities have been evaluated in male IDDM patients with either unsatisfactory blood glucose control (group 1, HbA1c > 8%, n = 18) or good blood glucose control (group 2, HbA1c < 8%, n = 16) and in 16 normoglycaemic individuals. The three groups were comparable for sex, age, body mass index, and plasma lipid levels. Three VLDL subfractions (large, Svedberg flotation unit (Sf) 175-400; intermediate, Sf 100-175; small, Sf 20-100) were separated by density gradient ultracentrifugation and analysed for cholesterol, triglyceride, and phospholipid levels. When compared to control subjects both groups of IDDM patients showed a clear shift in VLDL subfraction distribution with a significant increase in the proportion of small VLDL (group 1; 49 +/- 2%; p < 0.005; group 2: 51 +/- 3%, p < 0.01; control subjects 40 +/- 2%) (mean +/- SEM) in relation to total VLDL. By contrast, the absolute lipid concentration of small VLDL was higher only in group 1, compared to control subjects (35 +/- 4 vs 27 +/- 3 mg/dl, p = 0.05). Post-heparin hepatic lipase activity was significantly reduced in both IDDM groups (group 1: 254 +/- 19 mU/ml, p < 0.05; group 2: 202 +/- 19 mU/ml, p < 0.005; control subjects 317 +/- 31 mU/ml). In conclusion, normolipidaemic IDDM patients show an increase in the smallest VLDL, whatever their degree of blood glucose control. However, this abnormality may be clinically relevant only in patients with unsatisfactory blood glucose control, since absolute lipid concentration of these potentially atherogenic particles is only increased in this group.
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PMID:Very low density lipoprotein subfraction abnormalities in IDDM patients: any effect of blood glucose control? 878 15

Autonomic dysfunction in insulin-dependent diabetic (IDDM) patients has been associated with abnormalities of left ventricular function and an increased risk of sudden death. A group of 30 patients with IDDM and 30 age, sex and blood pressure matched control subjects underwent traditional tests of autonomic function. In addition, baroreceptor-cardiac reflex sensitivity (BRS) was assessed using time domain (sequence) analysis of systolic blood pressure and pulse interval data recorded non-invasively using the Finapres beat-to-beat blood pressure recording system. 'Up BRS' sequences-increases in systolic blood pressure associated with lengthening of R-R interval, and 'down BRS' sequences-decreases in systolic blood pressure associated with shortening of R-R interval were identified and BRS calculated from the regression of systolic blood pressure on R-R interval for all sequences. We also assessed heart rate variability using power spectral analysis and, after expressing components of the spectrum in normalised units, assessed sympathovagal balance from the ratio of low to high frequency powers. IDDM subjects underwent 2-D echocardiography to assess left ventricular mass index. Standard tests of autonomic function revealed no differences between IDDM patients and control subjects, but dramatic reductions in baroreceptor-cardiac reflex sensitivity were detected in IDDM patients. 'Up BRS' when supine was 11.2 +/- 1.5 ms/mmHg (mean +/- SEM) compared with 20.4 +/- 1.95 in control subjects (p < 0.003) and when standing was 4.1 +/- 1.9 vs 7.6 +/- 2.7 ms/mmHg (p < 0.001). Down BRS when supine was 11.5 +/- 1.2 vs 22 +/- 2.6 (p < 0.001) and standing was 4.4 +/- 1.9 vs 7.3 +/- 2.5 ms/mmHg (p < 0.003). There were significant relations between impairment of the baroreflex and duration of diabetes (p < 0.001) and poor glycaemic control (p < 0.001). From a fast Fourier transformation of supine heart rate data and using a band width of 0.05-0.15 Hz as low-frequency and 0.2-0.35 Hz as high frequency total spectral power of R-R interval variability was significantly reduced in the IDDM group for both low-frequency (473 +/- 62.8 vs 746.6 +/- 77.6 ms2 p = 0.002) and high frequency bands 125.2 +/- 12.9 vs 459.3 +/- 89.8 ms2 p < 0.0001. When the absolute powers were expressed in normalised units the ratio of low frequency to high frequency power (a measure of sympathovagal balance) was significantly increased in the IDDM group (2.9 +/- 0.53 vs 4.6 +/- 0.55, p < 0.002 supine: 3.8 +/- 0.49 vs 6.6 +/- 0.55, p < 0.001 standing). Thus, time domain analysis of baroreceptor-cardiac reflex sensitivity detects autonomic dysfunction more frequently in IDDM patients than conventional tests. Impaired BRS is associated with an increased left ventricular mass index and this abnormality may have a role in the increased incidence of sudden death seen in young IDDM patients.
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PMID:Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index. 893 9

Excessive production and deposition of extracellular matrix proteins are characteristic features of diabetic nephropathy. This study tests the hypothesis that cells from diabetic patients who develop nephropathy have a disturbance in collagen metabolism compared with cells from diabetic patients without complications. Kinetics of overall collagen metabolism and total protein synthesis were examined in serially passaged, subconfluent, quiescent skin fibroblasts cultured in either normal (5 mM) or high (25 mM) glucose concentrations from 14 insulin-dependent diabetic (IDDM) patients with nephropathy; 14 IDDM patients without nephropathy matched for age, diabetes duration, and body mass index; and 14 healthy subjects. Fibroblasts were incubated in the presence of 2 microCi/ml [3H]proline, and after labeling the incorporation of [3H]proline into total protein, collagen (collagenase-sensitive material), and noncollagen proteins (collagenase-resistant material) was determined at different time points. Collagen degradation was determined in pulse-chase experiments by following the residual collagen-bound radioactivity after incubation for 8 h with 10 microCi/ml [3H]proline. In high glucose concentrations (25 mM), overall collagen synthesis (measured as [3H]proline incorporation into extracellular and intracellular collagenase-sensitive material) was significantly greater in the patients with nephropathy (mean +/- SEM after a 24-h labeling period: 7189 +/- 671 dpm/10(6) cells) than in the patients without (4341 +/- 267 dpm/10(6) cells; P < 0.01) or healthy control subjects (3836 +/- 234 dpm/10(6) cells; P < 0.01). No significant differences were observed in noncollagen protein production or in collagen degradation rates among the three groups of subjects. In the presence of normal glucose concentrations (5 mM), collagen synthesis was lower in all groups studied, but the differences between IDDM patients with nephropathy and those without remained unaltered. These results suggest that long-term cultured fibroblasts derived from diabetic patients with nephropathy exhibit an abnormality in collagen metabolism. Cells from long-standing diabetic patients without nephropathy have normal collagen metabolism. The increased collagen synthesis is likely to be intrinsic to those diabetic patients susceptible to nephropathy and may play an important role in the sclerotic processes that occur in the kidneys, arteries, and heart.
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PMID:Enhanced collagen synthesis in cultured skin fibroblasts from insulin-dependent diabetic patients with nephropathy. 921 63


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