Hemoglobin A1 Concentration Research Articles

Starting insulin treatment as an outpatient. Report of 100 consecutive patients followed up for at least one year.

Most textbooks advise that newly diagnosed insulin-dependent diabetics be admitted to the hospital. Nevertheless, if they are not acutely ill, we start insulin treatment on an outpatient basis. We report herein the logistics, efficacy, and safety of our system. Over two years, 115 newly diagnosed insulin-dependent diabetics were seen in our hospital. Fifteen (66% of them ketoacidotic) were admitted. The other 100 were treated as outpatients by a nurse specialist with a starting dosage of 6 to 10 units of intermediate-acting insulin twice daily. Hemoglobin A1 concentration at diagnosis was 15.2% +/- 2.7% (mean +/- SD); at six months, 10.9% +/- 2.9%; and at one year, 10.6% +/- 2.8%. Only three outpatient starters were hospitalized in the first year, one for hypoglycemia and two with respiratory tract infections. Our findings suggest that outpatient stabilization is both safe and cost-effective.

Starting Insulin Treatment as an Outpatient

Most textbooks advise that newly diagnosed insulin-dependent diabetics be admitted to the hospital. Nevertheless, if they are not acutely ill, we start insulin treatment on an outpatient basis. We report herein the logistics, efficacy, and safety of our system. Over two years, 115 newly diagnosed insulin-dependent diabetics were seen in our hospital. Fifteen (66% of them ketoacidotic) were admitted. The other 100 were treated as outpatients by a nurse specialist with a starting dosage of 6 to 10 units of intermediate-acting insulin twice daily. Hemoglobin A1 concentration at diagnosis was 15.2%±2.7% (mean±SD); at six months, 10.9%±2.9%; and at one year, 10.6%±2.8%. Only three outpatient starters were hospitalized in the first year, one for hypoglycemia and two with respiratory tract infections. Our findings suggest that outpatient stabilization is both safe and cost-effective. (<i>JAMA</i>1986;256:877-880)

Muscle capillary basement membrane width in patients with vacor-induced diabetes mellitus.

Muscle capillary basement membrane width is a sensitive marker for the presence of diabetic microangiopathy. Studies have indicated that genetic factors and alterations in glucose metabolism influence muscle capillary basement membrane width. To define the role of these factors we have measured muscle capillary basement membrane thickness in controls, insulin dependent diabetics, and individuals with diabetes secondary to the ingestion of Vacor, a rat poison, which results in hyperglycemia. Hemoglobin A1 concentrations were increased in both diabetic groups, but hemoglobin A1 levels and the duration of diabetes were similar in the two diabetic groups. The muscle capillary basement membrane width was increased to a similar extent in the insulin-dependent diabetics (control, 1,781 +/- 46 vs. IDD, 2,287 +/- 144 A, P less than 0.001) and in the Vacor diabetic group (2,320 +/- 149 A, P less than 0.001). In the insulin-dependent diabetic group, 63% of the patients had a muscle capillary basement membrane width greater than two standard deviations above the mean of the controls, while in the Vacor diabetic group this figure was 56%. Despite the relatively short duration of diabetes (6.2 +/- 0.3 yr), 44% of the Vacor diabetic patients had retinopathy and 28% had proteinuria. The present study provides strong evidence that even in the absence of genetic diabetes mellitus, hyperglycemia or some other abnormality related to insulin lack can cause microvascular changes.

Effect of tolrestat on red blood cell sorbitol levels in patients with diabetes

The effect of the aldose reductase inhibitor, tolrestat, on red blood cell (RBC) sorbitol levels was studied in 23 patients with diabetes after oral dosing with tolrestat, 25 or 100 mg b.i.d. The mean (+/- SE) RBC sorbitol levels (measured 12 hours after the preceding dose) after 3, 7, and 13 days of dosing decreased after both dose levels. After 25 mg tolrestat the RBC sorbitol levels fell from 25.1 +/- 4.0 to 20.0 +/- 5.7 nmol/gm hemoglobin (21%) and after 100 mg tolrestat the level fell from 26.7 +/- 3.7 to 11.4 +/- 1.7 nmol/gm hemoglobin (57%; P less than 0.001). This latter RBC sorbitol concentration is similar to levels in individuals without diabetes. At both dosage levels the maximum decrease in RBC sorbitol levels occurred after only 3 days of dosing. Tolrestat had no effect on plasma glucose or hemoglobin A1 concentrations. The overall mean plasma unbound drug concentration measured 12 hours after 100 mg tolrestat (11.7 +/- 3.0 ng/ml; 3.3 X 10(-8) mol/L) was similar to the median inhibitory level (3 X 10(-8) mol/L) of tolrestat for sorbitol accumulation in human RBCs incubated in a high-glucose medium. Our results demonstrate the systemic bioavailability of tolrestat and its aldose reductase inhibitory activity in erythrocytes of patients with diabetes.

What happens to defaulters from a diabetic clinic?

The annual rate at which patients defaulted from follow up at the Wolverhampton diabetic clinic between 1971 and 1981 was 4.1% overall and 3.5% in white patients. In 1982 a study was started to discover what happened to white patients, born after 1919, who defaulted from the hospital clinic. There were 162 defaulters, of whom 19 had died. Of the remaining 143 patients, 19 were attending another hospital diabetic clinic, 22 had moved out of the area, and 28 refused to participate in the study. Seventy four agreed to participate: 39 were treated with diet, 15 with oral hypoglycaemic agents, and 20 with insulin. They were matched for sex, age, treatment, and duration of diabetes with patients attending the clinic. Non-insulin dependent defaulters were significantly more overweight at diagnosis (40% v 25%; p less than 0.05) and remained more obese. They developed significantly higher diastolic blood pressure (94 v 86 mm Hg; p less than 0.02) and higher haemoglobin A1 (HbA1) concentrations (11.7% v 8.4%; p less than 0.01). They had significantly more neuropathy at reassessment (15 v 6 out of 54; p less than 0.05) and a greater incidence of new retinopathy (p less than 0.02), which correlated with their higher diastolic blood pressures (p less than 0.01) and HbA1 concentration (p less than 0.02). In defaulters who were treated with insulin only the prevalence of neuropathy was significantly different from that in controls (p less than 0.05). Defaulters received minimal medical supervision and suffered greater morbidity than regular attenders at the clinic.

Glycosylated haemoglobin as an alternative to the glucose tolerance test for the diagnosis of diabetes mellitus.

A comparison was made between the results of a standard 75 g oral glucose tolerance test and total haemoglobin A1 in 168 subjects referred by their general practitioners for the diagnosis of diabetes mellitus. The subjects were classified as having normal, impaired or diabetic glucose tolerance using WHO criteria. Of 108 subjects with normal glucose tolerance only three had haemoglobin A1 concentrations over 8%. Of 10 with impaired glucose tolerance two had haemoglobin A1 concentrations over 8%. Of 47 with diabetic responses, eight had haemoglobin A1 concentrations below 9%. There was a significant difference between the haemoglobin A1 concentration when fasting and that 2 hours after the glucose load in the subjects with a diabetic glucose tolerance response, but no significant difference between the two values in the other subjects.

Metabolic control in children and adolescents with insulin-dependent diabetes mellitus.

The metabolic control, assessed from the mean daily glucosuria, mean daily glucosuria index based on home tests, and mean haemoglobin A1 (HbA1) concentrations during 1980, and the influence of various factors on the control were analysed in 177 diabetic children and adolescents. The mean daily glucosuria was 21% of the carbohydrates in the subscribed diet, and the mean glucosuria index 55%. The mean HbA1 was 14.0%. Boys had better metabolic control than girls. Good motivation towards treatment was associated with better metabolic control. There was a negative correlation between metabolic control and both the age of the child and the duration of diabetes. Prepubertal children were better controlled than those in puberty. Adherence to the dietary regimen was related to better control, as was the patient's endogenous insulin secretion, measured by serum C-peptide concentration. There was also an association between the season and the metabolic control, the control being better in the spring than during the other seasons. On the basis of these results male sex, a good motivation towards treatment, residual beta-cell function and adherence to the prescribed diet favor good metabolic control, while a long duration of the disease, the presence of puberty and relatively high age in childhood are factors impairing the metabolic control.

Electrophoretically determined haemoglobin A1 concentrations during short-term changes in glucose concentration.

In our experience, electrophoresis on agar gel is a very satisfactory alternative to the more widely used chromatographic methods for the determination of haemoglobin A1 (HbA1). Like the chromatographic method, the electrophoretic method is unable to detect any difference between the labile intermediate form of HbA1, which changes rapidly with acute changes in blood glucose level, and the more stable end-product, which reflects long-term glucose levels. In vitro at 37 degrees C the electrophoretically determined HbA1 concentration increases with increasing glucose concentration and with time in both normal and diabetic erythrocytes, but decreases to the preincubation concentration during further incubation of the erythrocytes in a glucose-free medium at 37 degrees C. Similarly, if normal or diabetic erythrocytes are incubated with isotonic saline before the HbA1 assay, the labile fraction is eliminated. In diabetics, the decrease in HbA1 concentration correlates with both the blood glucose level and the preincubation HbA1 concentration. Thus for HbA1 to be an accurate indicator of long-term glucose control in diabetic patients saline incubation of the erythrocytes may be necessary before HbA1 assay by the electrophoretic method, otherwise the assay results will also reflect recent changes in the blood glucose level.

Remission phase, endogenous insulin secretion and metabolic control in diabetic children.

The occurrence and duration of clinical remission were analyzed in 173 diabetic children. One hundred and twelve (65%) children experienced a remission, which was complete in only five (3%) cases. Duration varied from one month to three years, the mean being 8.5 months. Boys showed a more frequent and longer remission phase (p less than 0.01) than girls. Children with a negative remission history were younger (p less than 0.05) at the onset of diabetes than children having remission periods. Duration of remission correlated positively with age at onset (rs = 0.19; p less than 0.01) and the non-fasting serum C-peptide concentration (rs = 0.31; p less than 0.001). There was a negative correlation between duration of remission and daily insulin dose (r = -0.23; p less than 0.005). We found no correlation between duration of remission and duration of diabetes or hemoglobin A1 (HbA1) concentrations beyond the remission period. Serum C-peptide concentrations correlated negatively with HbA1 levels (rs = -0.23; p less than 0.001) indicating that residual B-cell function favors good metabolic control. There was a negative correlation between HbA1 concentration and duration of diabetes (r= -0.30; p less than 0.001). Clinical remission of long duration is associated with persisting endogenous insulin secretion, and reduced daily insulin requirement, but its favorable effect on metabolic control beyond the remission period is questionable.

Glycosylated haemoglobin in chronic renal failure and after renal transplantation.

Haemoglobin A1 (HbA1) was determined by ion-exchange chromatography in 37 normoglycaemic patients with chronic renal failure (CRF) and 26 with successful renal transplants. Blood glucose concentrations in patients with CRF were similar to those in controls, and there was a significant correlation between fasting blood glucose concentration and HbA1 in these groups. HbA1 in patients with CRF was, however, significantly lower than that in control subjects. Concentrations of HbA1 in patients on haemodialysis, peritoneal dialysis, and those with steady state CRF prior to dialysis were not significantly different from each other. Whereas patients with successful renal transplants of greater than 3 months' duration had HbA1 concentrations indistinguishable from controls, HbA1 in patients with transplants of shorter duration were significantly lower. These observations are suggestive of a shortened erythrocyte survival in CRF per se. Furthermore, these results indicate: (a) the inadequacy of HbA1 in monitoring the quality of diabetic control in patients with CRF, and (b) the absence of a specific effect of dialysis on HbA1, and the restoration to normal HbA1 after successful renal transplantation.

Unsuspected Hypoglycaemia, Haemoglobin A&lt;sub&gt;1&lt;/sub&gt; and Diabetic Control

Control of diabetes in a group of 82 insulin-treated diabetics was assessed by in-patient 24-hour plasma glucose profiles and haemoglobin A1 (HbA1) estimation. Thirty-two of these patients (39 per cent) had hypoglycaemia (plasma glucose less than or equal to 2 mmol/l) which was rarely associated with symptoms. Twenty-seven (61 per cent) of 44 patients who took a series of out-patient pre-prandial capillary blood samples over a three-day period had hypoglycaemia. Conventional measurements of diabetic control including fasting plasma glucose and HbA1, were lower in patients with hypoglycaemia than in those without. Rebound hyperglycaemia following hypoglycaemia was not seen and its absence was not due to diabetic autonomic neuropathy. Cortisol/creatinine ratios in early morning urine samples were similar in patients with and without nocturnal hypoglycaemia, consistent with the absence or rebound hyperglycaemia. Diabetic retinopathy was less prevalent in patients with hypoglycaemia, possibly reflecting better long-term diabetic control in this group. HbA1 concentration reflects overall blood glucose control in diabetes but near-normal levels must be interpreted with caution since they may be associated with recurrent hypoglycaemia.

Metabolic Control in Diabetic Patients: Effect of Insulin-secretory Reserve (Measured by Plasma C-Peptide Levels) and Circulating Insulin Antibodies

We measured circulating hemoglobin A1 (HbA1) and fasting plasma C-peptide concentrations in 100 diabetic patients. Pancreatic insulin reserve showed a negative correlation with HbA1 concentrations in nonobese, insulin-treated patients but not in obese patients, whether they were treated with insulin, oral agent, or diet alone. Patients with fasting C-peptide concentrations above 0.1 pmol/ml had significantly better metabolic control than did those with lower values. Anti-insulin antibodies were measured in 37 patients. There was no correlation between metabolic control and the affinity constants or binding capacities of these antibodies.