Degree Of Glycemic Control Research Articles

Energy expenditure in children with type I diabetes: evidence for increased thermogenesis.

The aim of the study was to assess whether increased energy expenditure causes the negative energy balance (tissue catabolism) commonly seen in children with insulin dependent (type I) diabetes. Resting metabolic rate and thermogenesis induced by adrenaline were measured in five healthy children and 14 children with type I diabetes who were all free of clinical signs of late complications of diabetes mellitus but differed in their degree of glycaemic control (in eight glycated haemoglobin concentration was less than 10% and in the six others greater than or equal to 10%). When compared with the control subjects children with type I diabetes had normal resting metabolic rates but their urinary nitrogen excretion was significantly raised (11.5 (SD 5.4) mg/min in those with glycated haemoglobin concentration less than 10%, 11.6 (5.2) mg/min in those with concentration greater than or equal to 10% v 5.4 (3.0) mg/min in control subjects). During the infusion of adrenaline the diabetic children showed a threefold and sustained increase in thermogenesis and disproportionate increases in the work done by the heart, in lipid oxidation rate, and in plasma concentrations of glucose, free fatty acids, and ketone bodies. The increased thermogenic effect of adrenaline did not correlate with the degree of glycaemic control. Increased thermogenesis may explain the tissue wasting commonly seen in children with type I diabetes during intercurrent stress.

Appearance of multidisperse low density lipoprotein and altered lipoprotein composition in non-insulin-dependent diabetes with type IIa hyperlipoproteinemia

The purpose of the present study is to elucidate the characteristics of lipoprotein disorders in diabetes mellitus. By analytical ultracentrifugation, non-insulin-dependent diabetic patients (NIDDM) with type IIa hyperlipoproteinemia (HLP) showed significantly higher incidence of multidisperse low density lipoprotein (LDL) than non-diabetics with type IIa HLP. Furthermore, LDL multidispersity in diabetic subjects seemed to be directly related to neither triglyceride (TG) levels in very low density lipoprotein (VLDL) nor the degree of glycemic control. Diabetics with multidisperse LDL had a lipoprotein profile that was different from the subjects with paucidisperse LDL as follows: (1) enrichment in the cholesterol content of VLDL, (2) TG-rich LDL with small flotation coefficient, (3) low cholesterol levels in high density lipoprotein 2 along with enrichment in TG, and (4) high plasma concentrations of apoprotein B. Although the underlying mechanism behind the prevalence of multidisperse LDL in NIDDM with type IIa HLP remains unknown, it seems important that lipoprotein disorders in diabetics with multidisperse LDL were potentially atherogenic.

Upper gastrointestinal involvement in diabetes mellitus: study of esophagogastric function.

The aim of our study was to evaluate in 18 diabetic patients (11 with and 7 without evidence of autonomic neuropathy as revealed by common cardiovascular tests) alterations indicative of autonomic nervous involvement of the gastrointestinal tract, independently of the presence of suggestive symptoms. All patients, without evidence of obstructive or mucosal pathology of the upper gastrointestinal tract, underwent the following: 1) study of gastric emptying time of nonabsorbable radiopaque markers (90, 120, 150 and 210 min); 2) study of gastric acid secretion: basal (BAO) and peak (PAO) acid output after sham-feeding (PAOSF) and peak acid output after pentagastrin (PAOPENT).PAOSF/PAOPENT ratio is an index of vagal integrity; 3) esophageal manometry. Our data confirm that a delayed gastric emptying of undigestible solids is a frequent finding in diabetic subjects. This was highly significant (p less than 0.01) at 150 min after a standard meal, in patients with signs of autonomic neuropathy and was often associated with asymptomatic esophageal motor abnormalities. No correlation was found with index of vagal integrity, hormonal pattern and degree of glycemic control. Autonomic neuropathy cannot be considered the only explanation for gastric and esophageal abnormalities in decompensated diabetes.

Glycaemic control, smoking habits and diabetes duration affect the extrinsic fibrinolytic system in type I diabetic patients but microangiopathy does not.

The fibrinolytic system was studied in 43 type I diabetic patients with long duration of the disease, with or without evidence of microangiopathy, and in 26 control subjects. There were positive and independent correlations between tissue plasminogen activator (tPA) activity after venous occlusion and HbA1c, and between triglycerides and plasminogen activator inhibitor (PAI-1) and tPA antigen concentrations before and after venous occlusion. The tPA activities both at rest and after venous occlusion were higher in the patients. There were no differences with regard to sex, hypertension or nephropathy for the levels of fibrinolytic variables in these patients. Subjects with retinopathy did not differ from those without retinopathy. Diabetes duration showed a significant negative association with tPA activity in multivariate regression analysis. Tobacco-smoking diabetics, as compared to non-smoking, had an increased tPA antigen release at venous occlusion, but also higher PAI-1 levels and reduced specific activity of the tPA protein. When assessed with the new specific assays now available, the fibrinolytic parameters appear to be specific indicators of endothelial dysfunction related to smoking and to degree of glycaemic control in type I diabetic subjects.

Continuous ambulatory peritoneal dialysis (CAPD) in diabetic patients with end-stage renal failure in Hong Kong

The authors' experience in managing 17 diabetic patients among their first 100 consecutive patients treated with continuous ambulatory peritoneal dialysis (CAPD) was reviewed. The diabetics were significantly older than the non-diabetics, but their biochemistry was comparable to that of the non-diabetics. With three exchanges a day, the requirement for antihypertensives was high (60%). Exit-site infection occurred at a rate of one episode per 9.7 patient-months, and the frequency of peritonitis averaged one episode per 9.4 patient-months; the main culprit was Staphylococcus pyogenes. Rehabilitation was good because the patients had to finance their treatment. In spite of old age, 23% worked full-time. There was no progressive increase in serum cholesterol or triglycerides. Glycemic control was good and was comparable whether the patients were given insulin subcutaneously or intraperitoneally. There was a highly significant (p<0.001) positive correlation between fasting blood glucose levels and HbA 1 concentrations. Fasting blood glucose concentrations did not correlate with either serum cholesterol or triglyceride concentrations. Diabetic retinopathy progressed in five patients, to the point that their vision was severely impaired. There was no relationship between the degree of glycemic control and progression of diabetic retinopathy. Two patients died of cardiovascular causes, but there were no peritonitis-related deaths. Cummulative patient survival at 2 years was 86%, and the corresponding technique survival, 100%.

Hyperlipidaemia of diabetes

There is general agreement as to the effects of diabetes on the concentrations of certain plasma lipoprotein lipids. Subdivision of diabetic subjects into several clearly defined subgroups has revealed that the detailed patterns of lipoprotein and lipid changes are dependent upon several factors, perhaps the most important of which is the degree of glycaemic control. Several aspects remain controversial, the most outstanding being whether or not plasma LDL cholesterol levels are elevated. It is possible that this is the case in certain clearly defined subgroups but not in others. In assembling the results of recent research for this review, two important aspects have emerged which require clarification. The first is the question of whether or not insulin directly stimulates hepatic VLDL secretion. The possibility that insulin might regulate production of lipogenic substrate by the gut may have an important bearing on this problem. The exact means by which insulin co-ordinates the metabolic activities of these organs in such a way as to ensure plasma lipid balance is not yet known and further research in this area may help to resolve some outstanding problems associated with diabetic hyperlipidaemia. Second, changes in the relative lipid composition of certain lipoprotein fractions in diabetic subjects has provided indirect evidence that increased lipoprotein 'remnant' concentrations may contribute to the abnormalities observed in some groups of diabetic subjects. This interesting possibility has been supported by metabolic studies, mainly in experimental animals. If this proves to be correct, then it remains to be determined whether the remnants involved are of hepatic or intestinal origin and whether the metabolic defect is related to abnormal production, clearance, or both. Recent work on the effects of changes in the apoprotein and lipid content on the metabolism of other lipoproteins in diabetes may have a useful bearing on studies of this type. In this respect, the bulk of the evidence seems to suggest that these factors, rather than changes in lipoprotein receptor activity per se, are important in determining the clearance of atherogenic lipoproteins such as LDL in diabetes.

Errors in clinical assessment of glycemic control in patients with non-insulin-dependent diabetes mellitus.

Errors in the assessment of glycemic control by clinicians, using the conventional method, based on random blood glucose and clinical parameters other than HbA1, were assessed in 125 non-insulin-dependent diabetic (NIDDM) patients (Group B). The expected mean post-prandial plasma glucose concentrations (y) for these patients were obtained from their HbA1 values (x) using the regression equation y = 39.6 X x - 157.6. This equation was derived using the data from 35 NIDDM patients (Group A), in whom mean post-prandial plasma glucose concentrations (measured twice daily), correlated excellently (r = 0.82; n = 100; p less than 0.001) with mean HbA1 values (measured monthly) determined over a period of 3 months. A comparison of the observed and expected post-prandial plasma glucose concentrations in Group B indicated that only an overall 42% of the total (n = 455) observed values (as against 60% in Group A) fell within the 99% confidence limits of the expected mean value. Fifty-eight % of the observed plasma glucose values fell outside the expected range of which 36% were underestimates and 22% were overestimates. Thus, we concluded that even in patients with stable diabetes the physician's assessment of the overall degree of glycemic control should be based on both plasma glucose and HbA1 concentrations for optimizing therapeutic measures.

Insulin-like growth factor-I in type 2 (non-insulin-dependent) diabetics with myocardial infarction and without macroangiopathy

In order to evaluate whether insulin-like growth factor-I (IGF-I) is associated with the development of diabetic macroangiopathy, we measured its plasma concentration in type 2 diabetics with definite myocardial infarction (MI), in type 2 diabetics without macroangiopathy (MA), and in non-diabetic healthy controls. We also compared plasma IGF-I concentration in non-diabetics with definite MI to that in non-diabetics without MA. There was a large interindividual variation in plasma IGF-I concentration in all groups of subjects studied. The median values were as follows: 0.60 IU/ml in diabetics with MI, 0.59 IU/ml in diabetics without MA, 0.48 IU/ml in non-diabetics with MI and 0.76 IU/ml in non-diabetic healthy controls. The only statistically significant difference between the groups was that between non-diabetics with MI and non-diabetics without MA. In diabetics, irrespective of MA, no significant correlation existed between plasma IGF-I level and the degree of glycemic control, renal function or various risk factors for atherosclerosis. The results of this study suggest that the high prevalence of macroangiopathy in type 2 diabetics cannot be imputed to IGF-I.

Erythrocyte concentration of glycolytic phosphorylated intermediates and adenosine nucleotides in subjects with diabetes mellitus.

We determined erythrocyte concentration of phosphorylated glycolytic intermediates and adenosine nucleotides in 9 non-ketotic diabetics under different conditions of glycemic control. We showed a significant increase of G6P, F6P and FDP levels in the 9 diabetics with poor glycemic control, whereas other phosphorylated glycolytic intermediates were in the normal range. After achieving fair glycemic control G6P, F6P and FDP fell to normal value. G6P, F6P and FDP were well correlated with simultaneously determined plasma glucose. Another 5 diabetics with poor glycemic control were connected to Biostator in order to determine the time relationship between blood glucose and erythrocyte levels of G6P, F6P and FDP. We demonstrated a prompt decrease to the normal values of the phosphorylated glycolytic intermediates where blood glucose fell to normal 60-90 minutes after automatic insulin delivery. Finally, we determined RBC glycolytic intermediates in 5 subjects with normal OGTT and in 5 subjects with normal fasting plasma glucose but abnormal OGTT. In this group we observed a prompt and persistent increase of G6P, F6P and FDP levels over the three hours hyperglycemia phase which has been induced by glucose load. No significant increase was found in subjects with normal OGTT. Our results demonstrate that erythrocyte glycolytic metabolism in abnormal in diabetics, depending strictly on the degree of glycemic control.

Comparison of algorithms for the closed-loop control of blood glucose using the artificial beta cell.

Over the past 15 years, several algorithms have been proposed and used for closed-loop blood glucose regulation. Their intent is to artificially replace the normal responses of the pancreatic beta cell absent in insulin-dependent diabetes. All of these algorithms calculate insulin infusion rates on the basis of minute-by-minute measurements of whole blood glucose concentration and its calculated rate of rise or fall. In addition, various techniques are employed to compensate for measurement delay time and the presence of noise in the measured signals. The goal of these feedback systems is to normalize blood glucose in diabetes mellitus. Interestingly, some recently "optimized" versions provide only a near normalization of glycemia in patients with insulin-dependent diabetes, a degree ofglycemic control which is not significantly different from intensified conventional insulin therapy.

DEVELOPMENT OF MICROVASCULAR DISEASE IN CHILDREN WITH DIABETES

Flourescein angiography (FA) was performed on 80 children with diabetes one year after an initial evaluation with FA. The grading system: Stage 0 no microaneurysms (MA), Stage 1 10 MA, Stage 3>10 MA plus neovascularization. 2-3 DPG was measured as an indicator of vascular compromise and compared with FA. The levels in non-diabetics is 14.4 ± 1.0mM/gmHb, Stage 0 is 15.6 ± .2 and Stage 1-3 is 16.7 ± .5. The difference between controls and Stages 1-3 is significant at p<.02 and suggests that the abnormalities noted on FA indicate functional vascular abnormalities. The Stage was unchanged in 71/80, 9/71 remained Stage 0, 3 improved and 6 increased in severity. The percent of hemoglobin A1, (HbA1) and the concentration of sorbitol (S) in packed red blood cells (PRBC), indicators of glycemic control, were not significantly different in children with Stage 0 when compared to those with Stage 1,2 and 3. Three of 4 children with chemical diabetes (CD) had MA. A 12 yr. old child with diabetes of 3 mos. duration had Stage 3 retinopathy. The demonstration of MA early in the clinical course of diabetes (CD) plus the lack of apparent difference in the degree of glycemic control between those with progressive vascular abnormalities and those with none or stable retinopathy suggest that factors other than glycemic control are important in the prevention of the vascular complications of childhood diabetes.