Stopping Insulin Treatment in Middle-aged Diabetic Patients with High Postglucagon Plasma C-Peptide

ABSTRACT We studied the successfulness of stopping insulin treatment in middle-aged diabetic patients aged 45–64 with a high postglucagon C-peptide level and the effects of this change on glycaemic control, serum lipids and lipoproteins. Insulin treatment was successfully stopped in 15 of our 22 patients who satisfied the inclusion criteria for the study and were selected on the basis of a computer file including practically all diabetic patients treated with insulin in the Kuopio University Central Hospital region (population base 250000 inhabitants). Insulin therapy was restarted in seven patients during the first 3 months after discharge. During the following 9 months insulin therapy was restarted in another three patients so that after a 1-year follow-up period half of the diabetic patients whose insulin therapy was stopped had been switched back to insulin. Insulin therapy was seldom successfully stopped if the postglucagon C-peptide value was under the limit of 1.0 nmol/l. Glycaemic control did not change during the follow-up, although there was a significant weight loss in diabetic patients. No changes were observed in serum lipids or lipoproteins with the exception of LDL cholesterol, which showed a significant reduction during the 3-month follow-up. In conclusion, insulin therapy can often be successfully stopped in patients with postglucagon C-peptide over the limit of 1.0 nmol/l without worsening of glycaemic control and without unfavourable changes in serum lipid and lipoprotein levels.     

Perinatal Growth Retardation in Preterm Infants

Greisen, G. and Petersen, M. B. (Department of Neonatology, Rigshospitalet, Copenhagen, Denmark). Perinatal growth retardation in preterm infants. Acta Paediatr Scand Suppl 360: 43, 1989.
Perinatal and 4-year follow-up data were analysed for 137 children born after 26 to 35 weeks of gestation. All were free of severe prenatal or neonatal illness and of major handicaps. Infants who were light-for-gestation at birth were approximately 0.6 SDS smaller at 4 years than the appropriate-for-gestation infants as regards height, weight, and head circumference (p< 0.005). The McCarthy general cognitive score was reduced (p = 0.03). Motor scores, standardised for cognitive function, were also reduced (p = 0.02) indicating that motor—perhaps cerebellar—function is particularly vulnerable to perinatal growth retardation.     

Autonomic nervous function and its relationship to cardiac performance in middle-aged diabetic patients without clinically evident cardiovascular disease.

Autonomic nervous function was evaluated in 36 patients with insulin-dependent diabetes mellitus (IDDM), 39 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 48 control subjects, all without clinically evident cardiovascular disease. Valsalva ratio and heart rate variation during deep breathing were lower in both diabetic groups than in the control group. Autonomic nervous function score (ANFS) was more abnormal in patients with IDDM than in control subjects, but was not significantly increased in patients with NIDDM. There was a negative correlation between ANFS and left ventricular diastolic filling evaluated by echocardiography or peak heart rate during exercise in both diabetic groups. There were no correlations between ANFS and left ventricular systolic function at rest or during exercise in any of the groups. In conclusion, autonomic nervous function was abnormal in middle-aged diabetic patients, and it was associated with impaired left ventricular diastolic filling at rest and decreased heart rate response to exercise, but not with left ventricular systolic function.     

Influence of Age on Cardiovascular Effects of Increased Dietary Sodium and Angiotensin-converting Enzyme Inhibiton in Normotensive Wistar Rats

Recent studies have shown that increased intake of dietary sodium chloride produces blood pressure-independent increase in cardiac and renal mass even in young normotensive rats. With advancing age the harmful cardiovascular effects of increased dietary sodium are not so well known. In the present study the influence of advancing age on the cardiovascular effects of increased intake of sodium (control diet, 0.3% and high-sodium diet, 2.6% sodium in the chow) were examined in young and aged (3 and 18 months old, respectively, at the beginning of the experiment) male normotensive Wistar rats in a six-week study. Moreover, the potential role of renin-angiotensin system in ageing during normal and a high-sodium intake was studied using a pharmacological tool, angiotensin converting enzyme (ACE) inhibitor ramipril. Ageing did not significantly modify basal systolic blood pressure measured by the tail cuff method. A high intake of sodium chloride increased blood pressure significantly only in aged rats, while in young rats it increased renal weight. Left ventricular weight was not affected by high-sodium diet in either age group. The ACE inhibition during control diet lowered blood pressure and decreased left ventricular weight in young rats only and these effects were completely blocked by a high-sodium diet. The maximal vascular contraction force of mesenteric arterial rings to noradrenaline was decreased with ageing while endothelium-dependent and -independent relaxation responses were unaltered with ageing. The sensitivity to sodium nitroprusside was impaired by the high-sodium diet in young rats. In both age groups the urinary excretion of calcium was increased during the high-sodium diet. In conclusion, the increased intake of sodium produced different changes in cardiovascular function in normotensive rats depending on age. With advancing age, the sensitivity to sodium-induced increase in blood pressure was increased. In aged rats a high intake of dietary sodium elevated blood pressure, while in young rats it increased renal mass without increase in blood pressure. In both age groups sodium did not affect left ventricular hypertrophy. Both high-sodium intake and ageing attenuated or even abolished the cardiovascular effects of ACE inhibition.     

Comparison of effects of pentobarbital and ethanol on the neuronal activity in the posterior parietal association cortex

The problem of this study was whether the effects produced by alcohol in the posterior parietal association cortex are specific to this drug or shared by other centrally acting depressant drugs such as barbiturates. The effect of graded doses of pentobarbital on multineuronal impulse activity was recorded with transdural microelectrode technique in 30 expts. in Brodmann's area 7 of five stump-tailed monkeys (Macaca speciosa). The results were compared with those from 32 expts. performed with alcohol and published separately. The dosage of the two drugs was determined on the basis of the monkeys' sensori-motor coordination which was assessed with a rating scale of reaching accuracy for food rewards. There were several recording sites where the actions of the two drugs were similar at similar behavioural levels of intoxication. However, in the distribution of effects among various functional types of recording sites a significant difference was found between pentobarbital and alcohol. Alcohol commonly diminished cellular activity related to motor behaviour (reaching, grasping) and only rarely responses to somesthetic stimuli, whereas the effects of pentobarbital were the opposite being most common on somatosensory responses and least common on activity related to motor behaviour. Also responses to visual stimuli were more sensitive to pentobarbital than to alcohol. The actions of pentobarbital and alcohol on responses evoked by sensory stimulation differed significantly (P < 0.01). We conclude that significant differences exist in the mechanisms of action of alcohol and barbiturate on the associative systems of the brain.     

Myocardial infarct size and mortality in patients with non-insulin-dependent diabetes mellitus

Abstract. Objectives. To study the infarct size and mortality in patients with non-insulin-dependent diabetes mellitus (NIDDM) and in non-diabetic subjects with their first acute myocardial infarction. Design. Seven year follow-up study of large representative cohorts of patients with non-insulin-dependent diabetes mellitus and non-diabetic subjects (study 1) and the FINMONICA acute myocardial infarction register study in 1988-89 (study 2). Setting. Populations of the districts of the Kuopio University Hospital and Turku University Central Hospital (study 1). Populations of Kuopio and North Karelia provinces and Turku/Loimaa area (study 2). Subjects. Study 1: 1059 patients with non-insulin dependent diabetes mellitus and 1373 non-diabetic subjects aged 45–64 years at baseline; during the follow-up 166 patients with non-insulin-dependent diabetes mellitus (91 men and 75 women) and 30 non-diabetic subjects (25 men and five women) were hospitalized for their first acute myocardial infarction. Study 2: 1622 patients aged 25–64 years hospitalized for their first acute myocardial infarction; 144 patients (90 men and 54 women) had non-insulin-dependent diabetes mellitus and 1153 (890 men and 263 women) were non-diabetic. Main outcome measures. The infarct size was assessed on the basis of maximum levels of serum cardiac enzymes (studies 1 and 2) and QRS-score (study 1). Results. No differences were found in maximum levels of serum cardiac enzymes between diabetic and non-diabetic patients. Similarly QRS-score gave no suggestion of a difference in infarct size between diabetic and non-diabetic patients. In both studies mortality before hospital admission was similar in diabetic and non-diabetic patients, but mortality within 28 days from hospital admission was twice as high in diabetic patients as in non-diabetic patients. Cardiac failure was the main cause of death significantly more often in diabetic patients than in non-diabetic patients (study 2). Conclusions. Poorer prognosis of acute myocardial infarction in diabetic patients appears not to be explained by a larger infarct size but probably by adverse effects of the diabetic state itself on myocardial function.     

Threonine allele in codon 54 of the fatty acid binding protein 2 gene does not modify the fatty acid composition of serum lipids in obese subjects

Intestinal fatty acid binding protein (I-FABP) participates in the metabolism of fatty acids in the intestinal enterocytes. Threonine encoding allele in codon 54 of the I-FABP gene has been suggested as regulating the absorption of long-chain fatty acids. We examined the fatty acid composition of serum lipid fractions and the concentration of serum free fatty acids after an overnight fast in obese subjects, aged 24–56 years, on their habitual diet. The body mass index of the subjects ranged from 29.7 to 43.3 kg m⁻². Six subjects were homozygous for the Thr-54 allele of the I-FABP gene, 37 subjects were heterozygous for the Thr-54/Ala-54 allele and 24 subjects were homozygous for the Ala-54 allele. We did not find any consistent differences in the proportions of long-chain fatty acids in serum triglycerides, cholesterol esters or phospholipids, but the concentration of serum free fatty acids tended to be higher in subjects who were homozygous for the Thr-54 allele ( P  = 0.13, for trend). In conclusion, our findings suggest that a polymorphism at codon 54 of the I-FABP2 gene does not substantially modify the fatty acid composition of serum lipids in obese Finns.     

Blood flow in the lower limbs in the knee-chest position: Ultrasonographic study in unanaesthetised volunteers

The knee-chest position for lumbar spine surgery is favoured because decreased filling of the epidural veins is associated with reduced peroperative bleeding. However, the position may be unfavourable from a circulatory point of view. In the present study, non-invasive assessment of circulation in the lower limbs was performed in 21 unanaesthetised, healthy volunteers who were placed in the surgical knee-chest position. Measurements included blood flow velocity (colour Doppler ultrasonography), oscillotonometric arterial blood pressure from upper and lower limbs and pulse oximetry from a toe. There was a statistically significant reduction in the posterior tibial artery flow velocity, maximally 31.6%, when the subject was moved from the prone to the knee-chest position. An enlargement of the trunk-femoral angle at the hip did not improve arterial flow. In 10 of the 21 volunteers, no flow in the posterior tibial vein was detected in the knee-chest position. In spite of the deteriorated blood flow, pulse oximetry indicated sufficient capillary flow in the very periphery of the lower limb. The change from prone to knee-chest position resulted in an increase in arterial blood pressure of the upper limb; the increase in diastolic arterial pressure was statistically significant (p < 0.001). It is concluded that the surgical knee-chest position involves deterioration of both the arterial and venous flow of the lower limbs. This should be considered in patients undergoing surgery in this position and, in particular, in those at risk of developing cardiovascular complications.     

Changes in autonomic nervous function during the 4-year follow-up in middle-aged diabetic and nondiabetic subjects initially free of coronary heart disease

Objectives. To study the changes in autonomic nervous function during the 4-year follow-up period in diabetic patients and to investigate factors predicting autonomic nervous dysfunction Design. A 4-year follow-up study. Setting. At baseline the study subjects without known cardiovascular disease were recruited from a large group of diabetic and nondiabetic subjects selected randomly from a baseline population. Subjects. Middle-aged control subjects (n=44), patients with insulin-dependent diabetes mellitus (n=32) and patients with non-insulin-dependent diabetes mellitus (n=32) were studied at baseline and after the 4-year follow-up. Interventions. Autonomic nervous function tests and exercise test at baseline and after the 4-year follow-up. Results. At the baseline, heart rate variation during deep breathing was significantly lower in patients with insulin-dependent diabetes (13.0±1.2 beats min^?1; P<0.05) and in patients with non-insulin-dependent diabetes (12.9±1.5 beats min^?1; P<0.05) than in control subjects (16.6±1.1 beats min^?1). At baseline, autonomic nervous function score was significantly higher indicating disturbed autonomic nervous function in patients with insulin-dependent diabetes (1.74±0.19; P<0.01) than in control subjects (1.24±0.14), but the difference was not significant between control subjects and patients with non-insulin-dependent diabetes (1.47±0.12). During the follow-up, autonomic nervous function score increased in patients with noninsulin-dependent diabetes to 2.00±0.21 (P<0.001, as compared to baseline), but did not change in patients with insulin-dependent diabetes (1.77±0.18) or control subjects (1.22±0.12). In both diabetic groups, the deterioration of autonomic nervous function score during the 4-year follow-up was associated with poor glycaemic control at baseline. Clinical manifestation of coronary heart disease was found in three (7%) control subjects, 12 (37%; P<0.001) patients with insulin-dependent diabetes and 11 (34%; P<0.01) patients with non-insulin-dependent diabetes mellitus at follow-up examination. Autonomic nervous function was more abnormal in those insulin-dependent diabetic patients with coronary heart disease than those without. Conclusions. During the 4-year follow-up the impairment in autonomic nervous function occurred mainly in patients with noninsulin-dependent diabetes. Poor glycaemic control appears to be an important determinant of the progression of autonomic nervous dysfunction in diabetes.