High Risk Of Severe Hypoglycemia Research Articles

The relationship between ACE genotype and risk of severe hypoglycaemia in a large population-based cohort of children and adolescents with type 1 diabetes

Genetic factors may account for familial clustering related to diabetes complications. Studies have shown a significant relationship between the presence of the deletion (D) allele of the gene encoding ACE and risk of severe hypoglycaemia. This large prospective cohort study assesses this relationship in a large sample of children and adolescents with type 1 diabetes. We studied 585 children and adolescents (mean age 11.9 +/- 4 years, 48.4% males). The frequency of severe hypoglycaemia (an event leading to loss of consciousness or seizure) was prospectively assessed over the 13-year period 1992-2004. Patients were seen with their parents every 3 months and data recorded at each visit. The ACE gene was detected using PCR. In our cohort of 585 children, 186 (31.8%) had at least one episode of severe hypoglycaemia, and of these 28.0% had the II genotype, 48.9% had the ID genotype and 23.1% had the DD genotype. This was in agreement with the Hardy-Weinberg proportion. A total of 477 severe hypoglycaemic episodes was recorded with a total of 3,404 person-years of follow-up, giving a total incidence of 14 per 100 patient-years. No significant increase in risk for DD genotype (incidence rate ratio = 0.97, 95% CI 0.61-1.55) relative to II genotype was observed. This large prospective study concludes that the presence of the D allele of the ACE gene does not predict a significantly higher risk of severe hypoglycaemia in type 1 diabetic children and adolescents.

Flexible Intensive Insulin Therapy in Adults With Type 1 Diabetes and High Risk for Severe Hypoglycemia and Diabetic Ketoacidosis

As we previously discussed, regression to the mean was an important bias of our study, since it was not controlled (1,2). A subgroup analysis may or may not contribute to this bias. Pennant et al. (3) performed statistical simulations of baseline results and found that a reduction from 6.1 to 4.7 (95% CI ±0.2) hypoglycemic events per patient per year may be due to regression to the mean. However, there would still remain a reduction from 4.7 to 1.4 hypoglycemic events per patient per year, which was of clinical importance in this high-risk population. The Diabetes Treatment and Teaching Program (DTTP) for type 1 diabetes has been extensively studied in …

Flexible Intensive Insulin Therapy in Adults With Type 1 Diabetes and High Risk for Severe Hypoglycemia and Diabetic Ketoacidosis

Diabetes treatment and teaching programs (DTTPs) for type 1 diabetes, which teach flexible intensive insulin therapy to enable dietary freedom, have proven to be safe and effective in routine care. This study evaluates DTTP outcomes in patients at high risk for severe hypoglycemia and severe ketoacidosis. There were 96 diabetes centers that participated between 1992 and 2004. A total of 9,583 routine-care patients with type 1 diabetes were examined before and 1 year after a DTTP. History of repeated severe hypoglycemia/severe ketoacidosis was an indication for DTTP participation. Before-after analyses were performed for subgroups of patients with three or more episodes of severe hypoglycemia or two or more episodes of severe ketoacidosis during the year before a DTTP. Main outcome measures were GHb, severe hypoglycemia, severe ketoacidosis, and hospitalization. A total of 341 participants had three or more episodes of severe hypoglycemia the year before a DTTP. Mean baseline GHb was 7.4 vs. 7.2% after the DTTP, incidence of severe hypoglycemia was 6.1 vs. 1.4 events x patient(-1) x year(-1), and hospitalization was 8.6 vs. 3.9 days x patient(-1) x year(-1). In mixed-effects models taking effects of centers and diabetes duration into account, mean difference was -0.3% (95% CI -0.5 to -0.1%; P = 0.0006) for GHb and -4.7 events x patient(-1) x year(-1) (-5.4 to -4; P < 0.0001) for severe hypoglycemia. A total of 95 patients had two or more episodes of severe ketoacidosis. GHb was 9.4% at baseline versus 8.7% after DTTP; incidence of severe ketoacidosis was 3.3 vs. 0.6 events x patient(-1) x year(-1), and hospitalization was 19.4 vs. 10.2 days x patient(-1) x year(-1). In linear models with diabetes duration as the fixed effect, the adjusted mean difference was -2.7 events x patient(-1) x year(-1) (95% CI -3.3 to -2.1; P < 0.0001) for severe ketoacidosis and -8.1 days (-12.9 to -3.2; P = 0.0014) for hospitalization. Patients at high risk for severe hypoglycemia or severe ketoacidosis may benefit from participation in a standard DTTP for intensive insulin therapy and dietary freedom.

Episodes of severe hypoglycemia in type 1 diabetes are preceded and followed within 48 hours by measurable disturbances in blood glucose.

This study quantifies blood glucose (BG) disturbances occurring before and after episodes of severe hypoglycemia (SH). For 6-8 months, 85 individuals with type 1 diabetes and a history of SH (age, 44+/-10 yr; 41 women and 44 men; duration of diabetes, 26+/-11 yr; hemoglobin A1c, 7.7+/-1.1%) used Lifescan One Touch BG meters for self-monitoring three to five times daily and recorded the date and time of SH episodes in diaries. For each subject, the timing of SH episodes was located in the temporal stream of SMBG readings recorded by the meter, and characteristics, including the Low BG index (LBGI), were computed in 24-h increments. In the 24-h period before the SH episode LBGI rose (P < 0.001), average BG was lower (P = 0.001), and BG variance increased (P = 0.001). In the 24 h after SH, LBGI and BGvariance remained elevated (P < 0.001), but average BG returned to baseline. These disturbances disappeared in 48 h. On the basis of LBGI we identified subjects at low, moderate, and high risk of SH, who reported, on the average, 1.7, 3.4, and 7.4 SH episodes (P < 0.005) during the study. In addition, we designed an algorithm that predicted 50% of all SH episodes that occurred in this subject group. We conclude that episodes of SH are preceded and followed by quantifiable BG disturbances, which could be used to devise warnings of imminent SH.

Perceived symptoms of hypoglycaemia in elderly type 2 diabetic patients treated with insulin.

Elderly insulin-treated diabetic patients have a high risk of severe hypoglycaemia, yet their hypoglycaemic symptom profile has attracted little research. In this study, the frequency and intensity of symptoms of hypoglycaemia were recorded using a validated questionnaire in 132 insulin-treated diabetic patients, aged 70 years or more. Principal components analysis (PCA) was used to discover the factorial structure of the symptoms. Lightheadedness and unsteadiness were prominent symptoms in the elderly patients. PCA suggested three separate groups of symptoms: (1) those related specifically to impairment of co-ordination and articulation; (2) more general neuroglycopenic symptoms, and (3) autonomic symptoms. The frequency and classification of hypoglycaemic symptoms in this elderly population is different from those seen in younger diabetic patients treated with insulin. Neurological symptoms of hypoglycaemia were more commonly reported and may be misinterpreted as features of cerebrovascular disease. Health professionals and carers involved in the treatment and education of diabetic patients should be aware of the age-specific differences in hypoglycaemic symptoms.

Diabetes Mellitus

Diabetes Mellitus

Hypoglycemia in the Diabetes Control and Complications Trial

A total of 1,441 patients with IDDM were randomly assigned to receive either intensive (n = 711) or conventional (n = 730) diabetes therapy in the Diabetes Control and Complications Trial (DCCT). The patients were followed for an average of 6.5 years. Subjects were instructed to report all episodes of suspected severe hypoglycemia to their health care team. In addition, at quarterly follow-up visits, each subject was asked about the occurrence of severe hypoglycemia. There were 3,788 episodes of severe hypoglycemia (requiring assistance); 1,027 of these episodes were associated with coma and/or seizure. A total of 65% percent of patients in the intensive group vs. 35% of patients in the conventional group had at least one episode of severe hypoglycemia by the study end; the overall rates of severe hypoglycemia were 61.2 per 100 patient-years vs. 18.7 per 100 patient-years in the intensive and conventional treatment groups, respectively, with a relative risk (RR) of 3.28. The relative risk for coma and/or seizure was 3.02 for intensive therapy. The increased risk with intensive treatment persisted over each of the 9 years of follow-up in the DCCT and over the calendar years 1984–1993 during which the study was conducted. When baseline patient characteristics were examined for effects on the risk of severe hypoglycemia, the relative risk of hypoglycemia for intensive versus conventional treatment was ≥2 for all subgroups. Several subgroups defined by baseline characteristics, including males, adolescents, and subjects with no residual C-peptide or with a prior history of hypoglycemia, had a particularly high risk of severe hypoglycemia in both treatment groups. Analyses of the cumulative incidence of successive episodes indicated that intensive treatment was also associated with an increased risk of multiple episodes within the same patient (e.g., 22% experienced five or more episodes of severe hypoglycemia within the first 5 years of follow-up vs. 4% in the conventional group). Within both treatment groups, patients who experienced severe hypoglycemia were at increased risk of subsequent episodes. Approximately 30% of patients in each group experienced a second episode within the 4 months following the first episode of severe hypoglycemia. Within each treatment group, the number of prior episodes of hypoglycemia was the strongest predictor of the risk of future episodes, followed closely by the current HbA1c value. After adjustment for the current quarterly HbA1c level, intensive treatment was still associated with a significantly increased risk of hypoglycemia, indicating that the increased risk with intensive treatment is not completely explained by differences in HbA1c values.

Hypoglycemia in the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group

A total of 1,441 patients with IDDM were randomly assigned to receive either intensive (n = 711) or conventional (n = 730) diabetes therapy in the Diabetes Control and Complications Trial (DCCT). The patients were followed for an average of 6.5 years. Subjects were instructed to report all episodes of suspected severe hypoglycemia to their health care team. In addition, at quarterly follow-up visits, each subject was asked about the occurrence of severe hypoglycemia. There were 3,788 episodes of severe hypoglycemia (requiring assistance); 1,027 of these episodes were associated with coma and/or seizure. A total of 65% percent of patients in the intensive group vs. 35% of patients in the conventional group had at least one episode of severe hypoglycemia by the study end; the overall rates of severe hypoglycemia were 61.2 per 100 patient-years vs. 18.7 per 100 patient-years in the intensive and conventional treatment groups, respectively, with a relative risk (RR) of 3.28. The relative risk for coma and/or seizure was 3.02 for intensive therapy. The increased risk with intensive treatment persisted over each of the 9 years of follow-up in the DCCT and over the calendar years 1984-1993 during which the study was conducted. When baseline patient characteristics were examined for effects on the risk of severe hypoglycemia, the relative risk of hypoglycemia for intensive versus conventional treatment was > or = 2 for all subgroups. Several subgroups defined by baseline characteristics, including males, adolescents, and subjects with no residual C-peptide or with a prior history of hypoglycemia, had a particularly high risk of severe hypoglycemia in both treatment groups. Analyses of the cumulative incidence of successive episodes indicated that intensive treatment was also associated with an increased risk of multiple episodes within the same patient (e.g., 22% experienced five or more episodes of severe hypoglycemia within the first 5 years of follow-up vs. 4% in the conventional group). Within both treatment groups, patients who experienced severe hypoglycemia were at increased risk of subsequent episodes. Approximately 30% of patients in each group experienced a second episode within the 4 months following the first episode of severe hypoglycemia. Within each treatment group, the number of prior episodes of hypoglycemia was the strongest predictor of the risk of future episodes, followed closely by the current HbA1c value. After adjustment for the current quarterly HbA1c level, intensive treatment was still associated with a significantly increased risk of hypoglycemia, indicating that the increased risk with intensive treatment is not completely explained by differences in HbA1c values.

Remission of severe hypoglycemic incidents in young diabetic children treated with subcutaneous infusion

Conventional insulin therapy for diabetes mellitus can be inadequate for controlling glycemia in young patients in whom the risk of hypoglycemia is particularly high. A retrospective study comparing all the children under 6 years of age treated in our department by continuous subcutaneous insulin infusion (group P, n = 10, mean age: 3.7 years) to 17 children with conventional insulin therapy (group C, mean age: 5.1 years) was conducted during a mean period of 2 years. Mean insulin doses, HbAlc, pre-prandial and daily glycemic levels, measured at 0, 3, 6, 12, 18 and 24 months, did not differ significantly between both groups. Mean HbAlc levels remained < or = 8% in the two groups. There was no episode of severe hypoglycemia in group P vs ten episodes in group C (P < 0.05); this benefit was confirmed in those six children belonging to group P who had previously followed a conventional therapy: 11 episodes during the conventional period vs 0 episode during the pump period (P < 0.05). Nine out of ten families were very satisfied with the treatment by pump mainly because of a more comfortable life style and a reduction of parents' anxiety due to disappearance of severe hypoglycemias. The insulin pump therapy had some limits: cutaneous complications and technical ones were responsible for two keto-acidosis episodes (0.1 episode per year-patient) and a higher frequency of hospitalizations. In group C, hospitalizations were caused by severe hypoglycemias and unbalanced glycemic control. Insulin pump therapy could be indicated in young diabetic children at high risk of severe hypoglycemia under conditions of a specialized medical and educational supervision and knowledge of the limits of such a treatment.

Severe Hypoglycemia in Type I Diabetic Patients With Impaired Kidney Function

To assess the frequency and possible risk indicators of severe hypoglycemia in insulin-dependent (type I) diabetic patients with impaired kidney function. Retrospective follow-up examination of case subjects and control subjects with mean follow-up periods of 2.9 and 1.3 yr, respectively. The setting was the diabetes center at the Düsseldorf University hospital. Subjects were consecutive type I diabetic patients. Case subjects consisted of 44 patients with initial serum creatinine levels of greater than or equal to 133 microM and pathological proteinuria. Control subjects consisted of 46 patients with normal serum creatinine levels matched for age, duration of diabetes, and hypertension; 57% of case subjects and 67% of control subjects were being treated with beta-blockers. Incidence of severe hypoglycemia (cases/patient-yr) was assessed through an interviewer-administered questionnaire. At comparable levels of HbA1c (7.9 +/- 1.8 vs. 7.6 +/- 1.1%), case subjects had a fivefold higher incidence of severe hypoglycemic episodes (1.28 vs. 0.25 cases/patient-yr, P less than 0.02) than control subjects. Within the group with impaired kidney function, patients with severe hypoglycemic episodes had lower HbA1c levels (7.4 +/- 1.6 vs. 8.7 +/- 2.0%, P less than 0.03) and a lower body mass index (22.0 +/- 3.4 vs. 24.4 +/- 3.8 kg/m2, P less than 0.04) than those without severe hypoglycemic episodes, whereas serum creatinine levels, body weight-related insulin dosage (U x kg-1 x day-1), prevalence of blindness, autonomic neuropathy, and treatment with beta-blockers were comparable. Type I diabetic patients with impaired kidney function are at an excessively high risk of severe hypoglycemia. In addition to low HbA1c levels, a low body mass index appears to be a risk indicator for this adverse effect of insulin therapy.

Incidence and management of severe hypoglycemia in 434 adults with insulin-dependent diabetes mellitus.

The risk of severe hypoglycemia associated with the particular therapeutic approach of two University hospitals was assessed in 96% of all patients with insulin-dependent diabetes mellitus (IDDM) who had been admitted during a period of almost 3 yr to the diabetic wards of two hospitals and who participated in a structured teaching and treatment program. During a mean follow-up period of 18 mo, 10% of the conventionally treated patients (N = 384; age 30 +/- 13 yr; duration of diabetes 12 +/- 9 yr) and 9% of the CSII-treated patients (N = 50, age 28 +/- 7 yr, duration of diabetes 13 +/- 7 yr, total follow-up period 1093 patient-mo) experienced at least one severe hypoglycemic episode per year, and a total of 123 severe hypoglycemic episodes occurred. In a subgroup of 169 conventionally treated patients, mean glycosylated hemoglobin values decreased from 10.5 +/- 1.9% before participation in the program to 9.2 +/- 2.0% (P less than 0.001) 18 +/- 4 mo thereafter. For the CSII-treated patients, glycosylated hemoglobin values were 9.7 +/- 1.9% before initiation of pump therapy and remained at the upper normal range from 3 mo thereafter throughout the study. There was no relationship between glycosylated hemoglobin levels and the occurrence of severe hypoglycemic episodes. Fifty-three severe hypoglycemic episodes were treated with glucagon injections by the patients' relatives (all but one effectively), 30 were managed by assisting physicians, and 44 led to hospitalization. Thus, successful attempts to improve glycosylated hemoglobin values in an unselected group of patients with IDDM were not associated with an unduly high risk of severe hypoglycemia when compared with the scarce data from the literature.