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PubMed2004

[How often does decreased consciousness of hypoglycaemia occur in children and adolescents with diabetes type 1 and what are its consequences?].

UNLABELLED: The inability of the patient to recognize the risk of hypoglycemia is a very frequent phenomenon, but it is also often an underestimated complication in diabetes treated with insulin. The results of DCCT trial revealed that intensification in insulin therapy increases three-fold the risk of severe hypoglycaemia. Feeling the state of hypoglycaemia is the basic defensive mechanism in patients with diabetes type 1, making possible to start the self treatment. The decreased consciousness of hypoglycaemia makes limitations to intensive insulin therapy, which main aim is to stop later complications. THE AIM OF THE STUDY was to answer the questions: 1. How often does lack of consciousness of hypoglycaemia occur in children and adolescents with diabetes type 1. 2. What are the possible factors influencing appearance of hypoglycaemia. 3. Is lack of hypoglycaemia consciousness of a risk factor for severe hypoglycaemia. MATERIAL AND METHODS: The study was carried out on 318 patients aged x=13.6 yrs (4-21), suffering from diabetes, mean 6.6 yrs (2-18). The study was retrospective taking into consideration the period from 1.01.1998 to 31.12.2002. RESULTS: In the analysis of the questionnaire assessing the occurrence of hypoglycaemia it was found that 82 patients (25.8%) have problems with feeling the state of hypoglycaemia. We analyzed the influence of time of lasting diabetes and we found that patients with a longer duration of the disease more frequently have problems with feeling hypoglycaemia, 57% patients with lack of hypoglycaemia consciousness have bad metabolic control of the disease. In the analyzed period, 64 incidences of severe hypoglycaemia in 48 patients (30 boys and 18 girls) were found. In patients with lack of consciousness of feeling hypoglycaemia the incidences of severe hypoglycaemia occurred ten times more frequently compared to patients who feel hypoglycaemia. Sleeping makes it impossible to perceive early symptoms of hypoglycaemia: in our patients 51 severe incidences (79.7%) occurred at 1.00-3.00 a.m., 6 (9.3%) occurred at daybreak and 7 (11%) in the evening. CONCLUSIONS: 1. In patients with diabetes type 1 the lack of hypoglycaemia consciousness occurs in about 25%. 2. The lack of hypoglycaemia consciousness is closely connected with time of diabetes duration and with recurrence of hypoglycaemia incidences. 3. Patients with lack of hypoglycaemia consciousness are at greater risk for severe hypoglycemia.

Adolescent↗
PubMed1997

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.

Adult↗
PubMed1994

Long-term recovery from unawareness, deficient counterregulation and lack of cognitive dysfunction during hypoglycaemia, following institution of rational, intensive insulin therapy in IDDM.

Hypoglycaemia unawareness, is a major risk factor for severe hypoglycaemia and a contraindication to the therapeutic goal of near-normoglycaemia in IDDM. We tested two hypotheses, first, that hypoglycaemia unawareness is reversible as long as hypoglycaemia is meticulously prevented by careful intensive insulin therapy in patients with short and long IDDM duration, and that such a result can be maintained long-term. Second, that intensive insulin therapy which strictly prevents hypoglycaemia, can maintain long-term near-normoglycaemia. We studied 21 IDDM patients with hypoglycaemia unawareness and frequent mild/severe hypoglycaemia episodes while on "conventional" insulin therapy, and 20 nondiabetic control subjects. Neuroendocrine and symptom responses, and deterioration in cognitive function were assessed in a stepped hypoglycaemia clamp before, and again after 2 weeks, 3 months and 1 year of either intensive insulin therapy which meticulously prevented hypoglycaemia (based on physiologic insulin replacement and continuous education, experimental group, EXP, n = 16), or maintenance of the original "conventional" therapy (control group, CON, n = 5). At entry to the study, all 21 IDDM-patients had subnormal neuroendocrine and symptom responses, and less deterioration of cognitive function during hypoglycaemia. After intensive insulin therapy in EXP, the frequency of hypoglycaemia decreased from 0.5 +/- 0.05 to 0.045 +/- 0.02 episodes/patient-day; HbA1c increased from 5.83 +/- 0.18 to 6.94 +/- 0.13% (range in non-diabetic subjects 3.8-5.5%) over a 1-year period; all counterregulatory hormone and symptom responses to hypoglycaemia improved between 2 weeks and 3 months with the exception of glucagon which improved at 1 year; and cognitive function deteriorated further as early as 2 weeks (p < 0.05). The improvement in responses was maintained at 1 year. The improvement in plasma adrenaline and symptom responses inversely correlated with IDDM duration. In contrast, in CON, neither frequency of hypoglycaemia, nor neuroendocrine responses to hypoglycaemia improved. Thus, meticulous prevention of hypoglycaemia by intensive insulin therapy reverses hypoglycaemia unawareness even in patients with long-term IDDM, and is compatible with long-term near-normoglycaemia. Because carefully conducted intensive insulin therapy reduces, not increases the frequency of moderate/severe hypoglycaemia, intensive insulin therapy should be extended to the majority of IDDM patients in whom it is desirable to prevent/delay the onset/progression of microvascular complications.

Adult↗
PubMed2004

Hypoglycaemia in elderly patients with diabetes mellitus: causes and strategies for prevention.

Achieving target glycaemic goals while avoiding hypoglycaemia is a major challenge in the management of elderly patients with diabetes mellitus. Repeated episodes of hypoglycaemia may cause extreme emotional distress in such patients, even when the episodes are relatively mild. Moreover, evidence is mounting that hypoglycaemia among elderly patients is a very real and costly health concern. The strongest predictors of severe hypoglycaemia in the elderly are advanced age, recent hospitalisation and polypharmacy. Education is the key to preventing recurrent or severe hypoglycaemia. As such, there should be close coordination of care between the patient, physician and all other healthcare providers in identifying the cause of hypoglycaemia in elderly patients, and appropriate steps should be taken to prevent further episodes. Prevention of hypoglycaemia has the potential to improve psychosocial aspects of elderly health, including enhanced quality of life, boosted confidence, improved compliance with antidiabetic regimens and avoidance of long-term complications. Since the elderly population represents a unique group, it is imperative to focus on the aetiologies that are exclusive to this group. Advanced age itself is a risk factor for hypoglycaemia, and elderly patients with comorbidities are at increased risk when they are hospitalised. Elderly patients with diabetes often have compromised renal function, which intereferes with drug elimination and thus predisposes them to prolonged life-threatening hypoglycaemia. In addition, patients on five or more prescription medications are prone to drug-associated hypoglycaemia. Although sulfonylurea-associated hypoglycaemia is common, drugs such as ACE inhibitors and nonselective beta-adrenoceptor antagonists can also predispose patients to hypoglycaemia. Greater attention should be paid to the avoidance of hypgolycaemia in nursing home residents. Recurrent hypoglycaemia in elderly patients is not only detrimental to achieving good glycaemic control, it is also a substantial economic burden. Once the causes of hypoglycaemia have been identified, it is crucial to formulate and institute a prevention plan. Firstly, global evaluation of the patient should be carried out to identify possible predisposing risk factors. Secondly, target glycaemic goals should be tailored to each patient. Thirdly, selection of antidiabetic agents should be judicious, then patients and family should be educated to recognise and treat hypoglycaemia. Finally, coordinated care should be provided to identify, treat and prevent hypoglycaemia.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Insulin therapy and hypoglycaemia: the size of the problem.

BACKGROUND AND METHODS: Hypoglycaemia is a fact of life for people with diabetes mellitus. Mild, asymptomatic episodes occur once or twice a week in insulin-treated diabetic subjects. Asymptomatic hypoglycaemia, including nocturnal hypoglycaemia, occurs in about 25% of diabetic subjects treated with insulin therapy. Mild hypoglycaemia, if recurrent, induces unawareness of hypoglycaemia and impairs glucose counterregulation, which in turn predisposes to severe hypoglycaemia. Even brief hypoglycaemia can cause profound dysfunction of the brain. Prolonged, severe hypoglycaemia can cause permanent neurological sequels. In addition, it is possible that hypoglycaemia may accelerate the vascular complications of diabetes by increasing platelet aggregation and/or fibrinogen formation. Finally, hypoglycaemia may be fatal. Hypoglycaemia induced by insulin as treatment of type 1 diabetes mellitus (T1 DM) is not the consequence of diabetes, but invariably of the non-physiological replacement of insulin. RESULTS: A number of studies have demonstrated that by moving from non-physiological to more physiological models of insulin therapy, most of the hypoglycaemia problems may be overcome, the percentage of glycated hemoglobin (A1c) decreased, and the quality of life improved. Interestingly, in T1 DM with hypoglycaemia unawareness, prevention of hypoglycaemia reverses not only unawareness but also improves glucose counterregulation, primarily the responses of adrenaline. CONCLUSIONS: In order to best prevent hypoglycaemia, insulin should preferably be given as continuous subcutaneous infusion via a minipump (the 'golden standard') or multiple daily insulin administrations with insulin analogues (basal insulin glargine, meal insulin rapid-acting insulin analogues) in T1 DM.

Awareness↗
PubMed2003

Hypoglycaemia in insulin-treated Type 2 diabetes: frequency, symptoms and impaired awareness.

AIMS: Hypoglycaemia is considered to be less common in people with insulin-treated Type 2 diabetes than in Type 1 diabetes. A retrospective survey was made of 215 people with insulin-treated Type 2 diabetes to quantify the frequency and nature of hypoglycaemia experienced. METHODS: The frequencies of mild (self-treated) and severe (required assistance) hypoglycaemia during the preceding year were estimated retrospectively. The usual symptoms of hypoglycaemia and state of awareness of hypoglycaemia were scored using validated questionnaires and any history suggestive of impaired hypoglycaemia awareness was documented. RESULTS: In this cohort, 157 (73%) had experienced hypoglycaemia since commencing insulin, the frequency of which increased with duration of diabetes and of insulin therapy and was inversely related to current HbA1c (all P < 0.05). During the preceding year, 32 individuals (15%) had experienced severe hypoglycaemia, with an estimated incidence for the entire group of 0.28 episodes/patient/year. Principal components analysis revealed two underlying symptom groups (autonomic and neuroglycopenic), similar to those reported previously by young adults with Type 1 diabetes, but the total symptom score declined with advancing age. Of the 157 with a history of hypoglycaemia, the 13 (8%) individuals who gave a history of impaired awareness of hypoglycaemia had experienced a ninefold higher incidence of severe hypoglycaemia than those with normal awareness, and reported experiencing mainly neuroglycopenic symptoms. CONCLUSIONS: While the overall frequencies of mild and severe hypoglycaemia were lower in insulin-treated Type 2 diabetes than have been reported previously in Type 1 diabetes, the risk of hypoglycaemia was greater with increasing duration of diabetes and of insulin therapy. Although impaired awareness of hypoglycaemia was uncommon, it was associated with a higher incidence of severe hypoglycaemia.

Adult↗
PubMed2002

Hypoglycaemia: the limiting factor in the glycaemic management of Type I and Type II diabetes.

Hypoglycaemia is the limiting factor in the glycaemic management of diabetes. Iatrogenic hypoglycaemia is typically the result of the interplay of insulin excess and compromised glucose counterregulation in Type I (insulin-dependent) diabetes mellitus. Insulin concentrations do not decrease and glucagon and epinephrine concentrations do not increase normally as glucose concentrations decrease. The concept of hypoglycaemia-associated autonomic failure (HAAF) in Type I diabetes posits that recent antecedent iatrogenic hypoglycaemia causes both defective glucose counterregulation (by reducing the epinephrine response in the setting of an absent glucagon response) and hypoglycaemia unawareness (by reducing the autonomic and the resulting neurogenic symptom responses). Perhaps the most compelling support for HAAF is the finding that as little as 2 to 3 weeks of scrupulous avoidance of hypoglycaemia reverses hypoglycaemia unawareness and improves the reduced epinephrine component of defective glucose counterregulation in most affected patients. The mediator and mechanism of HAAF are not known but are under active investigation. The glucagon response to hypoglycaemia is also reduced in patients approaching the insulin deficient end of the spectrum of Type II (non-insulin-dependent) diabetes mellitus, and glycaemic thresholds for autonomic (including epinephrine) and symptomatic responses to hypoglycaemia are shifted to lower plasma glucose concentrations after hypoglycaemia in Type II diabetes. Thus, patients with advanced Type II diabetes are also at risk for HAAF. While it is possible to minimise the risk of hypoglycaemia by reducing risks -- including a 2 to 3 week period of scrupulous avoidance of hypoglycaemia in patients with hypoglycaemia unawareness -- methods that provide glucose-regulated insulin replacement or secretion are needed to eliminate hypoglycaemia and maintain euglycaemia over a lifetime of diabetes.

Blood Glucose↗
PubMed1994

Physiological and symptomatic responses to postural change in non-diabetic subjects during hypoglycaemia.

1. Insulin-induced hypoglycaemia is characterized by an autonomic disturbance which produces some of the symptoms of hypoglycaemia. How an additional autonomic stress like postural change may alter physiological responses and symptoms of hypoglycaemia is not known. In 10 healthy male subjects (mean age 24 years) we observed physiological and symptomatic responses to postural change during acute (20 min) and prolonged (60 min) hyperinsulinaemic (60 m-units min-1 m-2) hypoglycaemia (2.5 mmol/l) and euglycaemia (4.5 mmol/l), and placebo control (saline). 2. In all studies standing increased plasma catecholamines (adrenaline, P < 0.001; noradrenaline, P < 0.0001), blood pressure (P < 0.0001) and heart rate (P < 0.0001). Catecholamine responses to standing were augmented by acute hypoglycaemia (adrenaline, P < 0.005; noradrenaline, P < 0.01), but less so by prolonged hypoglycaemia (adrenaline, P < 0.05; noradrenaline, P < 0.05). Supine heart rate was higher before standing during prolonged hypoglycaemia (P < 0.05), but did not increase as much on standing when compared with acute hypoglycaemia and prolonged euglycaemia. 3. During acute hypoglycaemia, autonomic symptoms increased on standing, but during prolonged hypoglycaemia, in the presence of generally higher symptom scores, standing had no effect. Autonomic symptoms, with the exception of hunger, tended to decrease with time (P < 0.05) during prolonged hypoglycaemia. 4. To conclude, posture does modify the catecholamine and symptomatic responses to hypoglycaemia, but this effect is dependent on the duration of hypoglycaemia. Hypoglycaemia and hyperinsulinaemia had little or no effect on the cardiovascular responses to changing posture.

Acute Disease↗
PubMedDate not supplied

Unawareness of hypoglycaemia in insulin-treated diabetic patients: prevalence and relationship to autonomic neuropathy.

Three-hundred and two insulin-treated diabetic patients were questioned about hypoglycaemia using a structured questionnaire interview. Two-hundred and twenty-six patients (75%) had normal symptomatic awareness, 48 (16%) had partial awareness, 21 (7%) had absent awareness of hypoglycaemia, and 7 (2%) denied ever experiencing hypoglycaemia. Patients with complete loss of awareness of hypoglycaemia had diabetes of longer duration; none had a HbA1 concentration within the non-diabetic range. Loss of awareness of hypoglycaemia was associated with an increased incidence of severe hypoglycaemia, 19 (91%) of the patients with absent awareness, and 33 (69%) with partial awareness of hypoglycaemia experiencing severe hypoglycaemia over 1 year compared with only 41 (18%) of patients with normal awareness of hypoglycaemia (p less than 0.001). Cardiovascular autonomic function tests were performed in 226 (75% of the whole group). Of the patients who had diabetes for more than 15 years, 54% (n = 39) with normal awareness of hypoglycaemia, compared with 59% (n = 10) with absent awareness of hypoglycaemia, had evidence of cardiovascular autonomic impairment (NS). Seven (41%) of the 17 patients with absent awareness of hypoglycaemia and diabetes of greater than 15 years duration had no evidence of autonomic dysfunction. Loss of hypoglycaemia awareness is a common problem in patients with insulin-treated diabetes of long duration, is associated with an increased incidence of severe hypoglycaemia, but is not invariably associated with abnormal cardiovascular autonomic function tests.

Adolescent↗
PubMed2006

The effects of acute hypoglycaemia on memory acquisition and recall and prospective memory in type 1 diabetes.

AIMS/HYPOTHESIS: Global memory performance is impaired during acute hypoglycaemia. This study assessed whether moderate hypoglycaemia disrupts learning and recall in isolation, and utilised a novel test of prospective memory which may better reflect the role of memory in daily life than conventional tests. SUBJECTS AND METHODS: Thirty-six subjects with type 1 diabetes participated, 20 with normal hypoglycaemia awareness (NHA) and 16 with impaired hypoglycaemia awareness (IHA). Each underwent a hypoglycaemic clamp with target blood glucose 2.5 mmol/l. Prior to hypoglycaemia, subjects attempted to memorise instructions for a prospective memory task, and recall was assessed during hypoglycaemia. Subjects then completed the learning and immediate recall stages of three conventional memory tasks (word recall, story recall, visual recall) during hypoglycaemia. Euglycaemia was restored and delayed memory for the conventional tasks was tested. The same procedures were completed in euglycaemic control studies (blood glucose 4.5 mmol/l). RESULTS: Hypoglycaemia impaired performance significantly on the prospective memory task (p = 0.004). Hypoglycaemia also significantly impaired both immediate and delayed recall for the word and story recall tasks (p < 0.01 in each case). There was no significant deterioration of performance on the visual memory task. The effect of hypoglycaemia did not differ significantly between subjects with NHA and IHA. CONCLUSIONS/INTERPRETATION: Impaired performance on the prospective memory task during hypoglycaemia demonstrates that recall is disrupted by hypoglycaemia. Impaired performance on the conventional memory tasks demonstrates that learning is also disrupted by hypoglycaemia. Results of the prospective memory task support the relevance of these findings to the everyday lives of people with diabetes.

Acute Disease↗
PubMed2000

Decrease of vigilance assessed by EEG-mapping in type I diabetic patients with history of recurrent severe hypoglycaemia.

In Type I diabetic patients with history of recurrent severe hypoglycaemia, a more rapid decrease in vigilance (slowing of brain function) during hypoglycaemia in comparison to patients without history of such events was found. Our aims were: (1) to study EEG parameters of vigilance in non-hypoglycaemic state in representative groups of Type I diabetic patients with and without previous recurrent severe hypoglycaemia; and (2) to compare them with non-diabetic controls. A vigilance-controlled EEG mapping (10-20 system, significance probability maps) was performed in a non-hypoglycaemic state (blood glucose 4.0-10.0 mmol/l) in a group of 13 Type I diabetic patients with a history of recurrent severe hypoglycaemia and compared to that of 14 Type I diabetic patients without history of severe hypoglycaemia, matched for HbA1c, age and gender, and to age- and gender-matched non-diabetic controls. When compared to non-diabetic controls, hypoglycaemia patients demonstrated a reduction in absolute power in beta band (13-35 Hz) and slowing of centroid frequencies of beta and total frequency bands (1.3-35 Hz) (up to P < 0.01), whereas patients without history of severe hypoglycaemia showed only a borderline reduction of absolute power in delta (1.3-3.5 Hz) band. Deceleration in hypoglycaemia patients versus those without recurrent hypoglycaemia was most remarkable (P < .01) in centroid frequency of total frequency band. Patients with history of recurrent severe hypoglycaemia demonstrated in non-hypoglycaemic state significantly reduced vigilance when compared to the group without hypoglycaemia history and to the controls, as well. Lower vigilance may be at least in part responsible for impaired hypoglycaemia perception in these patients, but, as it resembles EEG patterns seen in pathologic ageing, it might also represent a consequence of recurrent episodes of severe hypoglycaemia.

Adult↗
PubMed2006

Frequency and risk factors of severe hypoglycaemia in insulin-treated Type 2 diabetes: a cross-sectional survey.

AIMS: The reported risk of severe hypoglycaemia in insulin-treated Type 2 diabetes is highly variable and few studies have evaluated the influence of risk factors. We assessed the incidence and the influence of potential risk factors for severe hypoglycaemia in a questionnaire survey in subjects with insulin-treated Type 2 diabetes receiving currently recommended multifactorial intervention. METHODS: Consecutive patients with insulin-treated Type 2 diabetes (n = 401) completed a questionnaire about occurrence of hypoglycaemia in the past, hypoglycaemia awareness and socio-demographic factors. A zero-inflated negative binomial model was used to assess the influence of potential risk factors on the rate of severe hypoglycaemia. RESULTS: The overall incidence of severe hypoglycaemia in the preceding year was 0.44 episodes/person year. Sixty-six (16.5%) patients had experienced at least one event. The risk of any episode of severe hypoglycaemia positively correlated with impaired hypoglycaemia awareness, being married and long duration of diabetes. The risk of repeated episodes of severe hypoglycaemia positively correlated with the presence of peripheral neuropathy, while long duration of diabetes prior to insulin treatment and treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor antagonists (ARBs) were associated with reduced risk. C-peptide concentration and HbA1c were not associated with the risk of severe hypoglycaemia. CONCLUSIONS: In this cohort of insulin-treated Type 2 diabetic patients, the incidence of severe hypoglycaemia is higher than reported in most studies, corresponding to about one-third of that in Type 1 diabetes. Impaired hypoglycaemia awareness is the most important risk factor for severe hypoglycaemia.

Adult↗