Serum thyrotropin is a better predictor of future thyroid dysfunction than thyroid autoantibody status in biochemically euthyroid patients with diabetes: implications for screening.

AIM: To ascertain the predictive values of thyroid autoantibodies and thyrotropin (TSH) levels for subsequent thyroid dysfunction in patients with diabetes. METHODS: Review of records of 467 patients who had attended diabetes clinics for a mean of 6.1 years. Baseline autoantibody and TSH results and thyroid status at annual review were determined. RESULTS: Thyroid disorders were known in 29 patients (6.2%), and newly identified in 32 (6.9%), at presentation. Of 406 patients with normal baseline thyroid status, 24 (5.9%) developed thyroid dysfunction during 6.1 years of mean follow-up. Higher baseline TSH concentration was associated with subsequent hypothyroidism; a threshold of 1.53 mU/L, approximately defining the top quartile, provided 75% sensitivity and specificity. Both TSH greater than 1.53 mU/L and positive autoantibody status predicted thyroid dysfunction, but only TSH was significant in multivariable analysis (odds ratio, 7.74, p < 0.001). No overt thyroid dysfunction developed in 293 patients with baseline TSH levels less than 1.53 mU/l. CONCLUSIONS: Baseline TSH level may be a better predictor of thyroid dysfunction than thyroid autoantibodies in people with diabetes. Patients with TSH levels below the top quartile have a risk of thyroid dysfunction similar to the general population. It may be appropriate to stop annual thyroid screening in this group, although confirmation is required.

The stepwise approach to the management of type 2 diabetes.

As the prevalence of type 2 diabetes continues to increase worldwide, there is an enhanced need for effective disease management. Type 2 diabetes is managed through a stepwise program of intensive therapy that consists of lifestyle modifications and sequential addition of oral antihyperglycemic agents and insulin as necessary. Successful implementation of this approach lessens the microvascular complications of the disease and promotes a lifestyle that may reduce macrovascular complications and comorbidities. Because of the progressive pancreatic beta-cell failure that causes hyperglycemia in type 2 diabetes, many people with type 2 diabetes will ultimately require insulin for disease management. Insulin may be used alone or in combination with oral agents to achieve glycemic control with a minimum of side effects. Although disease management regimens must be tailored to the needs of the individual with type 2 diabetes, the health care provider should always employ an aggressive, treat-to-target strategy to lower hyperglycemia and lessen diabetes-related risk factors.

Variability of office, 24-hour ambulatory, and self-monitored blood pressure measurements.

BACKGROUND: The diagnosis of hypertension is difficult when faced with several different blood pressure measurements in an individual. Using the average of several office measurements is recommended, although considerable uncertainty remains. Twenty-four-hour ambulatory monitoring is often considered the gold standard, but self-monitoring of blood pressure has been proposed as a superior method. AIM: Determination of within-individual variability of blood pressure measured in the office, by ambulatory monitoring, and by a week of self-monitoring. DESIGN OF STUDY: Retrospective analysis of a clinical trial of 163 subjects. METHOD: Within-patient variability of office and ambulatory blood pressure was determined from measurements at 0 and 6 weeks. Subjects had performed self-monitoring of blood pressure twice each morning and evening, for at least 6 weeks; variability was determined from the means of week 1 and week 6. RESULTS: The within-individual coefficients of variation (CVs) for systolic blood pressure were: office, 8.6%; ambulatory, 5.5%; self, 4.2%. Equivalent values for diastolic blood pressure were 8.6%, 4.9%, and 3.9%. CVs tended to be lower with longer self-monitoring duration, and higher with longer intervals between self-monitoring. CONCLUSION: Office blood pressure is impractical for precise assessment, as 10-13 measurements are required to give the accuracy required for rational titration of antihypertensive drugs. Twenty-four-hour ambulatory monitoring is better than a single office measurement, but considerable uncertainty remains around the estimate. A week of self-monitoring appears to be the most accurate method of measuring blood pressure, but remains imperfect. Further research may identify superior self-monitoring schedules. Given the inherent accuracy in blood pressure measurement, the importance of considering overall cardiovascular risk is emphasised.

Moderate hypoglycaemia after learning does not affect memory consolidation and brain activation during recognition in non-diabetic adults.

INTRODUCTION: Some aspects of memory performance are impaired during acute hypoglycaemia. The hippocampus is critical to formation of long-term memory, and may be particularly sensitive to hypoglycaemia. This study examined whether moderate hypoglycaemia occurring after learning would disrupt the consolidation process, and used functional magnetic resonance imaging (fMRI) to identify accompanying changes in brain activation. METHODS: Sixteen non-diabetic subjects each underwent two glucose clamp studies. During euglycaemia (4.5 mmol/L), subjects tried to memorize a series of words and a series of pictures of faces. Then, either hypoglycaemia (2.5 mmol/L) was induced for one hour, or euglycaemia was maintained. During subsequent uncontrolled euglycaemia, subjects' recognition of the word and face stimuli was tested, with simultaneous fMRI to measure brain activation during recognition. RESULTS: Face identification scores were 67.2% after euglycaemia and 66.9% after hypoglycaemia (p = 0.895). Word identification scores were 78.0 and 77.1% respectively (p = 0.701). Analysis of the fMRI identified two foci where activation was altered after hypoglycaemia compared with euglycaemia, but these were not in regions associated with memory, and were probably statistical artefacts. CONCLUSIONS: One hour of hypoglycaemia at 2.5 mmol/L induced 20-40 min after learning did not disrupt memory consolidation. fMRI did not show evidence of altered brain activation after hypoglycaemia. Consolidation may be relatively resistant to hypoglycaemia, or may have been complete before hypoglycaemia was induced. The study was powered to detect a large effect, and provides some reassurance that moderate hypoglycaemia does not cause major disruption of previously learned memories in people with insulin-treated diabetes.

Delayed recovery of cognitive function following hypoglycemia in adults with type 1 diabetes: effect of impaired awareness of hypoglycemia.

OBJECTIVE: Recovery times of cognitive functions were examined after exposure to hypoglycemia in people with diabetes with and without impaired hypoglycemia awareness. RESEARCH DESIGN AND METHODS: A total of 36 subjects with type 1 diabetes were studied (20 with normal hypoglycemia awareness [NHA] and 16 with impaired hypoglycemia awareness [IHA]). A hyperinsulinemic glucose clamp was used to lower blood glucose to 2.5 mmol/l (45 mg/dl) (hypoglycemia) for 1 h or to maintain blood glucose at 4.5 mmol/l (81 mg/dl) (euglycemia) on separate occasions. Cognitive tests were applied during each experimental condition and were repeated at 10- to 15-min intervals for 90 min after euglycemia had been restored. RESULTS: In the NHA group, performance was impaired on all cognitive tasks during hypoglycemia and remained impaired for up to 75 min on the choice reaction time (CRT) task (P = 0.03, eta(2) = 0.237). In the IHA group, performance did not deteriorate significantly during hypoglycemia. When all subjects were analyzed within the same general linear model, performance was impaired during hypoglycemia on all tasks. Significant impairment during recovery persisted for up to 40 min on the CRT task (P = 0.04, eta(2) = 0.125) with a significant glycemia-awareness interaction for CRT after one hour of hypoglycemia (P = 0.045, eta(2) = 0.124). Performance on the trail-making B task was impaired for up to 10 min after euglycemia was restored (P = 0.024, eta(2) = 0.158). CONCLUSIONS: Following hypoglycemia, the recovery time for different cognitive tasks varied considerably. In the IHA group, performance was not significantly impaired during hypoglycemia. The state of awareness of hypoglycemia may influence cognitive function during and after hypoglycemia.

Hypoglycaemia and cognitive function.

Acute hypoglycaemia impairs cerebral function, and available data indicate that cognitive performance becomes impaired at a blood glucose level of 2.6-3.0 mmol/l in healthy subjects. Methodological problems limit comparisons between studies, but in general complex tasks are more sensitive to hypoglycaemia than simple tasks, and some cognitive abilities are completely abolished. The onset of hypoglycaemic cognitive dysfunction is immediate, but recovery may be considerably delayed. There is persuasive evidence of adaptation to hypoglycaemia, partly due to increased brain glucose uptake capacity, although other mechanisms may exist. Patients who are exposed to chronic or recurrent hypoglycaemia become remarkably tolerant to the state, but this is insufficient to prevent severe hypoglycaemia with neuroglycopenic decompensation, probably because symptomatic and counterregulatory responses adapt even more. During experimental hypoglycaemia, administration of non-glucose cerebral fuels preserves cognitive function. However, little progress has been made as yet towards protecting cognitive function during hypoglycaemia in clinical practice. The chronic effects of recurrent hypoglycaemia remain contentious. There are numerous case reports of hypoglycaemic brain damage and of cognitive deterioration attributed to repeated severe hypoglycaemia. The major prospective studies, including the Diabetes Control and Complications Trial, did not report cognitive declines in intensively treated patients, but had unrepresentative study populations and may have been too short to detect such effects. Structural and functional brain changes are not only associated with recurrent severe hypoglycaemia, but also with hyperglycaemia and early disease onset and may in part be due to hyperglycaemic microvascular disease. Children may be more prone to acute metabolic insults, and there is evidence of developmental disadvantage associated with hypoglycaemic episodes.

The symptoms of hyperglycaemia in people with insulin-treated diabetes: classification using principal components analysis.

BACKGROUND AND AIMS: People with insulin-treated diabetes commonly experience symptoms of hyperglycaemia, but the nature of these symptoms and their origins are poorly understood. The aims of this study were (1) to identify and classify the symptoms of hyperglycaemia experienced by people with insulin-treated diabetes and (2) to identify patient characteristics associated with intensity of, and glycaemic threshold for, glycaemic symptoms. METHODS: Common hyperglycaemic symptoms were identified from preliminary interviews. Eighteen symptoms were used in a questionnaire. Four hundred participants estimated the intensities with which they experienced these symptoms during hyperglycaemia. Principal components analysis (PCA) was used to examine correlations between symptoms. Associations between symptom intensity, glycaemic threshold, and other characteristics were examined with multiple regression. RESULTS: In total, 361 participants (90.2%) reported experiencing hyperglycaemic symptoms. PCA suggested four symptom groupings: (1) feeling tense, irritability, restlessness, poor concentration (agitation) (2) thirst, dry mouth, need to urinate, not feeling right, sweet/funny taste, weakness (osmotic) (3) dizziness, blurred vision, light-headedness, weakness (neurological) (4) headache, nausea (malaise). Mean symptom intensity was associated with younger age. The median (range) estimated blood glucose threshold for symptom onset was 15 (8-30) mmol/L; there was a weak tendency for this threshold to be elevated in people who had impaired hypoglycaemia awareness. CONCLUSIONS: People with insulin-treated diabetes commonly reported symptoms associated with hyperglycaemia. PCA separated these into four groups. Osmotic symptoms appear to be specific to hyperglycaemia; symptoms in the other groups may suggest underlying physiological mechanisms, but are relatively non-specific. Symptoms are more intense in younger people and may be reported at lower blood glucose concentrations in people with normal awareness of hypoglycaemia.