Dose Adjustment for Normal Eating (DAFNE) in routine clinical practice: who benefits?

AIMS: To explore the effectiveness of Dose Adjustment for Normal Eating in routine clinical practice in the UK. METHODS: Participants were 124 adults with Type 1 diabetes who had completed a Dose Adjustment for Normal Eating course. Data were collected before the course and again 1 year later on a variety of biological, psychological and social measures. RESULTS: There were a range of significant benefits consistent with Dose Adjustment for Normal Eating aims, including: better control among those with baseline HbA(1c) ≥ 81 mmol/mol (9.6%) (z = -2.8, P = 0.004); reduced number of participants reporting severe hypoglycaemia (χ² = 4.27, P = 0.039); total eradication of diabetic ketoacidosis (χ² = 4.17, P = 0.041) and lower diabetes-related distress (z = -4.5, P < 0.001). The most deprived of the clinic population were significantly under-represented (χ² = 17.8, P = 0.001) and the levels of clinical depression were unusually low. CONCLUSIONS: These results indicate that Dose Adjustment for Normal Eating delivered in routine clinical practice is associated with a range of benefits and that certain clinical and psychosocial characteristics are associated with better outcomes.

Severe hypoglycaemia during pregnancy in women with Type 1 diabetes is common and planning pregnancy does not decrease the risk.

AIMS: The aim of this study was to identify risk factors for severe hypoglycaemia (SH) in pregnancy in Type 1 diabetes, including associations with pregnancy planning and glycaemic control. METHODS: Clinical data including details of the pregnancy and its outcome, glycaemic control, frequency of SH and evidence of pregnancy planning were collected prospectively as part of a national audit of 160 pregnancies in women with Type 1 diabetes. RESULTS: An episode of SH was experienced by 29.4% of women at some point during the pregnancy, with the percentage of women experiencing SH decreasing from 21.9% in the first trimester to 18.1% in trimester 2 and 10.9% in trimester 3. Longer duration of diabetes was associated with increased frequency of SH during pregnancy (r = 0.191, P = 0.012). A greater fall in glycated haemoglobin (HbA(1c)) between pre-pregnancy and the first trimester was not associated with increased risk of SH in trimester 1. Planned pregnancies had better glycaemic control but higher risk of SH in trimester 1 (P = 0.047). Women with pre-pregnancy retinopathy and current smokers had an increased risk of SH in trimester 3 (P = 0.029, P = 0.033). CONCLUSIONS: SH is common during pregnancy and particularly in the first trimester. Planning pregnancy does not decrease the risk of SH. Improvements in glycaemic control at the start of pregnancy do not appear to increase the risk of SH. Education of women and their partners about the risks of SH and its management is essential when planning pregnancy.

Psychosocial factors and diabetes-related outcomes following diagnosis of Type 1 diabetes in adults: the Edinburgh Prospective Diabetes Study.

AIMS: To examine prospectively the relationships between psychosocial variables and diabetes-related outcomes in adults with newly diagnosed Type 1 diabetes. METHODS: A total of 84 adults (48 male) with a median (range) age of 30.8 (17-51) years with newly diagnosed Type 1 diabetes were recruited for the study. Shortly after initial diagnosis each participant's personality, cognitive ability, and recent psychiatric distress were assessed. At 4 months (n = 69) and at 12 months (n = 66) after diagnosis diabetes-related outcomes were measured, including each respondent's knowledge of diabetes, satisfaction with diabetes treatment and diabetes-related quality of life. Glycated haemoglobin (HbA1c) was recorded at each clinic attendance. RESULTS: Social class (Spearman's correlation r = -0.30 and -0.28, respectively, P < 0.05) and scores on the National Adult Reading Test (r = 0.38 and 0.36, respectively, P < 0.01) were consistently associated with knowledge of diabetes at 4 months and at 12 months after diagnosis. Hierarchical regression revealed that alcohol consumption recorded at diagnosis and knowledge of diabetes at 4 months were independent predictors of glycaemic control at 12 months (adjusted r2 = 0.16). Total scores on the Diabetes Treatment Satisfaction Questionnaire (DTSQ) at 12 months were significantly predicted by age at diagnosis (adjusted r2 = 0.08). High neuroticism at diagnosis was consistently associated with poorer self-reported diabetes quality of life at 4 months and at 12 months after diagnosis (rs between -0.30 and -0.39, P < 0.05). CONCLUSIONS: Long-standing psychosocial factors have a significant influence on self-reported outcomes during the 12 months following diagnosis of Type 1 diabetes but may not be reliable predictors of glycaemic control. Further follow-up is necessary to determine the longer-term predictors of objective (e.g. glycaemic control) and subjective (e.g. quality of life) indicators of coping in people with diabetes.

The effect of glycemic control in the pre-conception period and early pregnancy on birth weight in women with IDDM.

OBJECTIVE: To examine data from pregnancies in women with IDDM to assess the relative effects of mean glycosylated hemoglobin levels before conception, at booking, and during the 3 trimesters of pregnancy on birth weight. Good glycemic control during pregnancy in women with IDDM is important to minimize the risk of fetal malformation and macrosomia. Recent studies have suggested that glycemic control in the 1st trimester is more important than glycemic control during the 2nd or 3rd trimesters. RESEARCH DESIGN AND METHODS: The case records of 65 deliveries to women with IDDM were reviewed. Fifty-seven deliveries were included in the present study. Of the deliveries reviewed, 32 women were in their first pregnancy and 25 women were multiparous. Only viable pregnancies were included because the major outcome variable of interest was birth weight. Glycosylated hemoglobin was recorded for each time period. RESULTS: The median standardized birth weight was 1.1 SD higher than the nondiabetic mean. When pregnancies, in which the birth weight was greater than 1 SD above the nondiabetic mean, were compared with pregnancies, in which birth weight was less than 1 SD above the mean, significant differences were observed between the groups in HbA1 at 6-12 months pre-conception (10.0 +/- 2.3 vs. 8.6 +/- 1.4%, P = 0.02), at 0-6 months pre-conception (10.2 +/- 2.4 vs. 8.7 +/- 2.0%, P = 0.03), at booking (9.5 +/- 2.2 vs. 8.4 +/- 1.6%, P = 0.04), and at 0-12 weeks' gestation (9.5 +/- 2.2 vs. 8.0 +/- 1.3%, P = 0.04), but HbA1 later in pregnancy did not differ significantly between the groups. Correlational analysis of all 57 pregnancies revealed significant correlations between birth weight and HbA1 at 0-6 months pre-conception (r = 0.44, P = 0.002), at booking (r = 0.43, P = 0.001), at 0-12 weeks' gestation (r = 0.48, P = 0.001), at 12-24 weeks' gestation (r = 0.45, P = 0.001), and at 24 weeks to term (r = 0.34, P = 0.009). However, with stepwise regression analysis, only HbA1 at 0-12 weeks' gestation entered into the equation with a multiple r value of 0.48. CONCLUSIONS: Glycemic control in the immediate pre-conception period and early 1st trimester appears to have a greater influence on birth weight than does glycemic control during the later weeks of pregnancy.

Transient improvement in glycemic control. The impact of pregnancy in women with IDDM.

OBJECTIVE: Good glycemic control throughout pregnancy in patients with diabetes is of paramount importance but often appears to deteriorate in the postpartum period. The aim of this study was to ascertain the timing of the improvement in glycemic control associated with pregnancy in women with IDDM and to examine changes in glycemic control after delivery. RESEARCH DESIGN AND METHODS: Peripartum glycemic control was assessed in a retrospective study of 30 women with IDDM whose age was 28 +/- 6 years (means +/- SD) and whose diabetes duration was 14 +/- 6 years. RESULTS: Mean total HbA1 fell incrementally from a peak at 2-3 years preconception to a nadir between 24 weeks and term, only to return to preconception levels within a year after delivery. Of the 30 women, 15 (50%) attained an HbA1 in the nondiabetic range for pregnancy at some point during their pregnancy, and 7 (23%) women achieved this by 24 weeks gestation. Women with an HbA1 > 9% at booking had a significantly higher HbA1 at 0-6 and 6-12 months preconception, and throughout pregnancy their HbA1 was significantly higher. After delivery, attendance rates at routine diabetes review clinics were low, with 11% of women not attending for longer than 24 months. CONCLUSIONS: Nearly all women with IDDM can achieve near normoglycemia during pregnancy, irrespective of previous glycemic control, although those with high HbA1 levels at booking are less likely to achieve this. After delivery, glycemic control deteriorates. Efforts to improve glycemic control should be intensified in the preconception period and maintained after delivery. The poor postpartum attendance at diabetes clinics requires specific action.

A structural equation model for predictors of severe hypoglycaemia in patients with insulin-dependent diabetes mellitus.

There are several predictors of severe hypoglycaemia in patients with insulin-dependent diabetes mellitus (IDDM), many of which are correlated. To assess factors which may be predictive of severe hypoglycaemia, structural equation modelling was used to test specific hypotheses using prospective data. Sixty patients with insulin-dependent diabetes mellitus (IDDM) were studied prospectively for one year during which any episodes of severe hypoglycaemia, asymptomatic biochemical hypoglycaemia, and glycaemic control were documented. Half the patients reported hypoglycaemia unawareness and they were matched for HbA1 with the rest. Baseline measurements included symptomatic awareness of hypoglycaemia, fear of hypoglycaemia, previous history of hypoglycaemia, glycaemic control, and peripheral autonomic function. Formal structural equation modelling was performed on these variables and a model was constructed that expressed the putative causal associations among the variables. The frequency of severe hypoglycaemia (measured prospectively) correlated significantly with duration of diabetes, awareness of hypoglycaemia, patient's age, history of previous severe hypoglycaemia and autonomic function scores. HbA1 did not show significant correlation, possibly because of the narrow range in the subject population. In the structural equation modelling exercise, at least 18% of the variance of severe hypoglycaemia, measured prospectively, was accounted for by a history of severe hypoglycaemia, the state of awareness of hypoglycaemia, and the autonomic function score. Over 25% of the variance of 'worry' on the hypoglycaemia fear scale was accounted for by a history of previous severe hypoglycaemia. An assessment of multiple risk factors for hypoglycaemia may be of value in advising individual patients about their diabetes care.

Hypoglycaemia and non-cognitive aspects of psychological function in insulin-dependent (type 1) diabetes mellitus (IDDM).

Hypoglycaemia provokes unpleasant symptoms and sensations in patients with insulin-dependent (Type 1) diabetes mellitus (IDDM). There is much interest in, and information on, the cognitive effects of acute insulin-induced hypoglycaemia. However, the effects of hypoglycaemia on brain function extend to important, non-cognitive aspects of psychological functioning, which are reviewed here. Acute hypoglycaemia induces changes in mood which result in a transient state of 'tense tiredness', a decrease in happiness, an increase in tense arousal, and decreased energetic arousal. Appraisals of life problems are affected adversely. Frequent exposure to hypoglycaemia is associated with heightened fear of hypoglycaemia, which can be quantitated in individuals. Personality may also influence behavioural responses to hypoglycaemia and the ability of an individual to cope with diabetes. The adverse effects of hypoglycaemia on mood, behaviour, personality, social function and management of diabetes in individual patients may be profound and need to be identified and addressed appropriately.

Cortical blindness and cerebral infarction associated with severe hypoglycemia.

OBJECTIVE: To describe a case of cortical blindness and cerebral infarction associated with severe hypoglycemia. CONCLUSIONS: The possible pathogenesis of the neurological defects is discussed.

The effects of acute hypoglycemia on relative cerebral blood flow distribution in patients with type I (insulin-dependent) diabetes and impaired hypoglycemia awareness.

To examine the hypothesis that in diabetic patients with impaired hypoglycemia awareness the relative regional distribution of cerebral blood flow (rCBF) would be abnormal in a specific area, namely the frontal lobes, rCBF was examined in 20 type I diabetic patients, of whom 10 had a normal awareness of hypoglycemia and 10 had a history of impaired hypoglycemia awareness. rCBF was determined sequentially using single photon emission computed tomography (SPECT) during (1) normoglycemia (arterialized blood glucose 4.5 mmol. L-1) and (2) hypoglycemia (blood glucose 2.5 mmol.L-1) induced by a hyperinsulinemic glucose clamp technique. Distribution of the isotope, 99mTc-Exametazime, was detected using a single-slice multi-detector head scanner. A split-dose technique was used, with 250 MBq being injected during steady-state normoglycemia and 250 MBq during subsequent hypoglycemia. rCBF was estimated in 30 regions of interest, derived from a standard neuroanatomical atlas on two parallel slices at 40 and 60 mm above the orbitomeatal line (OML). No between-group differences in the pattern of overall rCBF or changes in regional tracer uptake were demonstrated. In comparison to the rCBF during normoglycemia, both patient groups exhibited significant changes in the pattern of rCBF during hypoglycemia, with increments of rCBF to both superior frontal cortices and the right thalamus and reduced rCBF to the right posterior cingulate cortex and the right putamen. This pattern of relative redistribution of rCBF during hypoglycemia was preserved in patients who had impaired hypoglycemia awareness.

A comparative study of responses to acute hypoglycaemia induced by human and porcine insulins in patients with Type 1 diabetes.

The effects of human and porcine insulins on the symptomatic, physiological, and counterregulatory hormonal responses to acute hypoglycaemia were compared in 40 patients with Type 1 diabetes, 20 of whom were newly diagnosed while 20 had been treated for between 5 and 20 years. In a double-blind, cross-over trial all patients were treated with human or porcine insulin, in random order, for two consecutive 3-month periods. At the end of each treatment period they were subjected to an acute episode of experimental hypoglycaemia induced by a continuous intravenous infusion (2.0 mU kg(-1)min(-1)) of the same insulin species. Haemodynamic, sweating, and tremor responses were measured during both studies, symptom scores were recorded and the arterialized plasma glucose thresholds for autonomic activation and the onset of subjective symptoms were identified. In all patients the glycaemic thresholds for the initiation of the autonomic physiological responses to hypoglycaemia and the onset of the symptomatic response were concurrent and did not differ with insulin species (plasma glucose 1.94 vs 1.96 mmol I(-1), human vs porcine studies). The onset, temporal pattern, nature, and magnitude of the physiological responses (sweating, heart rate, blood pressure, and tremor) during acute experimental hypoglycaemia were also identical with each insulin species. The magnitude and temporal pattern of the response of counterregulatory hormones (adrenaline, noradrenaline, glucagon, ACTH, and GH) to hypoglycaemia as induced by human and porcine insulins were indistinguishable, as were the total and individual scores of autonomic and neuroglycopenic symptoms. In conclusion, in patients who had newly diagnosed and intermediate duration (5-20 years) of diabetes, the symptomatic, physiological, and counterregulatory hormonal responses to acute insulin-induced hypoglycaemia did not differ between human and porcine insulins, and the plasma glucose thresholds at which the symptomatic and autonomic responses were initiated were identical with both insulin species. This study does not support the hypothesis that treatment with human insulin modifies the symptomatic, physiological, and counterregulatory hormonal responses to acute hypoglycaemia.

Hypoglycemia-induced cognitive dysfunction in diabetes mellitus: effect of hypoglycemia unawareness.

Hypoglycemia results in cognitive dysfunction. The aim of this study was to assess and compare the degree of cognitive dysfunction experienced by insulin-dependent diabetic patients (IDDM) with hypoglycemia unawareness with patients with normal awareness of hypoglycemia. Cognitive function was examined in 10 patients who had normal awareness of the onset of hypoglycemia and 10 patients who had a history of impaired awareness of hypoglycemia. A hyperinsulinemic glucose clamp was used to manipulate blood glucose concentrations. Cognitive function was assessed using Rapid Visual Information Processing (RVIP), Trial Making B (TMB), Paced Auditory Serial Addition Test (PASAT) and Digit Symbol Substitution Test (DSST). Multivariate analysis of variance demonstrated a significant effect of hypoglycemia on cognitive function (p < 0.01). A trend was observed towards an overall effect of awareness on performance (p = 0.08). There were trends in the effects of awareness on RVIP correct responses across time (p = 0.07) and the interaction of awareness by study by TMB (p = 0.08). During hypoglycemia subjects with impaired awareness were less cautious in their responses (RVIP misses p = 0.03) and on recovery from hypoglycemia, their cognitive function remained abnormal (TMB p = 0.04, RVIP correct responses p = 0.02, RVIP misses p = 0.04). Thus, IDDM patients with hypoglycemia unawareness exhibited more profound cognitive dysfunction during acute hypoglycemia which persisted for longer following blood glucose recovery.

Cognitive function during insulin-induced hypoglycemia in humans: short-term cerebral adaptation does not occur.

It has been suggested that cerebral adaptation may occur in response to short-term hypoglycemia. This was examined in the present study by measuring serial changes in cognitive function and symptoms after 60 min of continuous hypoglycemia. Hypoglycemia was induced with a hyperinsulinemic glucose clamp on two separate occasions in 24 non-diabetic human subjects. Cognitive function was assessed using the following cognitive test battery: Paced Auditory Serial Addition Test (PASAT), Rapid Visual Information Processing (RVIP), Trail-Making B (TMB), Digit Symbol Substitution Test (DSST) and Four Choice Reaction Time (CRT). In condition A the blood glucose was maintained at 4.5 mmol/l throughout. On two separate occasions (condition B and condition C) the blood glucose was stabilised at 4.5 mmol/l for 30 min, lowered to 2.5 mmol/l for 60 min and restored to 4.5 mmol/l for 30 min. In each condition the cognitive test battery was performed immediately after stabilisation of blood glucose at 4.5 mmol/l and the subsequent battery was repeated at different time intervals: condition A--after a further 40 min of euglycemia; condition B--after 5 min of hypoglycemia; condition C--after 40 min of hypoglycemia. Acute hypoglycemia induced a significant deterioration in cognitive function which was manifest in all tests except TMB (P < 0.05), but performance ability did not differ between conditions B and C. Symptom scores, assessed by a scaled questionnaire, increased significantly during hypoglycemia (P < 0.001) but no differences were detected between the scores at 30 min and 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Symptoms of hypoglycemia in children with IDDM.

OBJECTIVE: To examine the symptoms of hypoglycemia in children with insulin-dependent diabetes, from the perspective both of the child and of the child's parents, and to compare the symptom reporting of the diabetic children with that of adult diabetic patients. RESEARCH DESIGN AND METHODS: Interviews were conducted with 100 parents and 43 of their children. The frequency and intensity of symptoms of hypoglycemia were documented using a structured interview and classified into groups using Principal Components Analysis (PCA). RESULTS: Diabetic children and their parents showed close agreement concerning the relative frequency and the intensity of symptoms reported. PCA of the symptom reports showed that diabetic children and their parents identified the same distinct subgroups of hypoglycemia-related symptoms: behavioral disturbance and autonomic-neuroglycopenic subgroups. CONCLUSIONS: Hypoglycemic symptoms in children with diabetes clearly differ from those experienced by insulin-treated adults and, in particular, include behavioral changes as primary features of a low blood glucose. These observations have important implications for parental education on hypoglycemia.

Changes in mood during acute hypoglycemia in healthy participants.

Acute hypoglycemia provides a reproducible method of investigating the effect of biological changes induced during hypoglycemia on mood states. Hypoglycemia was induced twice using a hyperinsulinemic glucose clamp in 24 nondiabetic human participants; a euglycemic placebo control study was also performed. Serial changes in mood were assessed using the UWIST Mood Adjective Checklist before, during, and after 60 min of controlled hypoglycemia (2.5 mmol/l). Hypoglycemia induced a significant reduction in hedonic tone (p = .001), a significant increase in tense arousal (p < .0005), and a significant decline in energetic arousal (p = .01) in comparison with the euglycemia control study. Profound changes in mood were observed in nondiabetic participants during acute hypoglycemia, and a state called tense tiredness persisted for at least 30 min after restoration of euglycemia.

Frequency, severity and symptomatology of hypoglycaemia: a comparative trial of human and porcine insulins in type 1 diabetic patients.

A randomized, double-blind, cross-over trial was performed to compare the frequency, severity, and symptomatology of hypoglycaemia during treatment with porcine and human insulins. Forty patients with Type 1 diabetes (20 newly diagnosed and 20 with diabetes of 5-20 years duration) were treated with human and porcine insulins for consecutive 3-month periods, in random order. Episodes of hypoglycaemia were recorded prospectively with self-reporting of the presence and intensity of symptoms using a standardized scoring technique. Serial measurements of glycated haemoglobin and review of home blood glucose tests confirmed that similar glycaemic control was achieved with each insulin species. On comparison of the treatment periods with human and porcine insulins, no differences were demonstrated in the total frequency of symptomatic hypoglycaemia (3.10 vs 3.06 episodes patient-1 3-months-1; p = 0.94), the frequency of severe hypoglycaemia (0.1 vs 0.2 episodes patient-1 3-months-1; p = 0.44), the occurrence of asymptomatic biochemical hypoglycaemia (0.75 vs 0.68 episodes patient-1 3-months-1; p = 0.81), and the capillary blood glucose concentration at the onset of hypoglycaemic symptoms (2.6 +/- 0.2 vs 2.4 +/- 0.3 mmol l-1; p = 0.40), with all results being expressed for human vs porcine treatment periods, respectively. The symptoms of hypoglycaemia did not differ during the treatment periods with each insulin species. In conclusion, treatment with human insulin had no effect upon the symptomatic response to hypoglycaemia, did not increase the total frequency of hypoglycaemia, and did not emerge as a significant risk factor for severe hypoglycaemia in these patients.

Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia.

OBJECTIVE: To determine the frequency of hypoglycemia in patients with type I diabetes and impaired awareness of hypoglycemia by prospective assessment. RESEARCH DESIGN AND METHODS: A prospective study was undertaken for 12 months in 60 patients with type I diabetes: 29 had impaired awareness of hypoglycemia and 31 retained normal awareness of hypoglycemia. The two groups of patients were matched for age, age at onset of diabetes, duration of diabetes, and glycemic control. Episodes of severe hypoglycemia were recorded within 24 h of the event and verified where possible by witnesses. RESULTS: During the 12 months, 19 (66%) of the patients with impaired awareness had one or more episodes of severe hypoglycemia with an overall incidence of 2.8 episodes.patient-1.year-1. By comparison, 8 (26%) of the patients with normal awareness experienced severe hypoglycemia (P < 0.01) with an annual incidence of 0.5 episode.patient-1.year-1 (P < 0.001). Severe hypoglycemia occurred at different times of the day in the two groups: patients with impaired awareness experienced a greater proportion of episodes during the evening (P = 0.03), and patients with normal awareness experienced a greater proportion in the early morning (P = 0.05). An assessment of fear of hypoglycemia revealed that patients with impaired awareness of hypoglycemia worried more about hypoglycemia than did patients with normal awareness (P = 0.008), but did not modify their behavior accordingly. CONCLUSIONS: This prospective evaluation demonstrated that impaired awareness of hypoglycemia predisposes to a sixfold increase in the frequency of severe hypoglycemia, much of which occurred at home during waking hours.

Severe deterioration in cognitive function and personality in five patients with long-standing diabetes: a complication of diabetes or a consequence of treatment?

Changes in mood, personality, and social function were examined in a group of five Type 1 diabetic patients, aged 50 to 66 years, with duration of diabetes from 24 to 47 years. Information on medical history was obtained from their carers and hospital records. All patients had experienced multiple episodes of severe hypoglycaemia and had impaired awareness of hypoglycaemia. Cerebral dysfunction predated the development of minimal diabetic complications and had been apparent for between 1 and 17 years. The carers assessed the pre-morbid and present behaviour and personality of the patients using standard questionnaires. Significant deteriorations were demonstrated in cognitive (p = 0.04) and social functions (p = 0.04), compared with assessment of pre-morbid function. Patients had tended to become more neurotic (p = 0.08) and less extravert (p = 0.07). All of the patients and three of the carers recorded scores suggestive of psychiatric morbidity on the General Health Questionnaire. The patients had experienced loss of employment and the carers described a reduction in the patients' social interactions. Although the aetiology of their cerebral dysfunction can not be definitely ascertained this case series emphasizes the need for long-term prospective studies in patients with diabetes of long duration to assess the impact of the disorder on cognitive and social abilities particularly where there is evidence of cerebral dysfunction. The need for professional support for the carers of such patients should be recognized.