Risk of recurrent severe hypoglycemia remains associated with a past history of severe hypoglycemia up to 4 years: Results from a large prospective contemporary pediatric cohort of the DPV initiative.

OBJECTIVES: In a contemporary cohort of youth with type 1 diabetes, we examined the interval between episodes of severe hypoglycemia (SH) as a risk factor for recurrent SH or hypoglycemic coma (HC). METHODS: This was a large longitudinal observational study. Using the DPV Diabetes Prospective follow-up data, we analyzed frequency and timing of recurrent SH (defined as requiring assistance from another person) and HC (loss of consciousness or seizures) in 14 177 youths with type 1 diabetes aged <20 years and at least 5 years of follow-up. RESULTS: Among 14 177 patients with type 1 diabetes, 72% (90%) had no, 14% (6.8%) had 1 and 14% (3.2%) >1 SH (HC). SH or HC in the last year of observation was highest with SH in the previous year (odds ratio [OR] 4.7 [CI 4.0-5.5]/4.6 [CI 3.6-6.0]), but remained elevated even 4 years after an episode (OR 2.0 [CI 1.6-2.7]/2.2 [CI 1.5-3.1]). The proportion of patients who experienced SH or HC during the last year of observation was highest with SH/HC recorded during the previous year (23% for SH and 13% for HC) and lowest in those with no event (4.6% for SH and 2% for HC) in the initial 4 years of observation. CONCLUSIONS: Even 4 years after an episode of SH/HC, risk for SH/HC remains higher compared to children who never experienced SH/HC. Clinicians should continue to regularly track hypoglycemia history at every visit, adjust diabetes education and therapy in order to avoid recurrences.

Hypoglycemia in type 1 diabetic pregnancy: role of preconception insulin aspart treatment in a randomized study.

OBJECTIVE A recent randomized trial compared prandial insulin aspart (IAsp) with human insulin in type 1 diabetic pregnancy. The aim of this exploratory analysis was to investigate the incidence of severe hypoglycemia during pregnancy and compare women enrolled preconception with women enrolled during early pregnancy. RESEARCH DESIGN AND METHODS IAsp administered immediately before each meal was compared with human insulin administered 30 min before each meal in 99 subjects (44 to IAsp and 55 to human insulin) randomly assigned preconception and in 223 subjects (113 for IAsp and 110 for human insulin) randomly assigned in early pregnancy (<10 weeks). NPH insulin was the basal insulin. Severe hypoglycemia (requiring third-party assistance) was recorded prospectively preconception (where possible), during pregnancy, and postpartum. Relative risk (RR) of severe hypoglycemia was evaluated with a gamma frailty model. RESULTS Of the patients, 23% experienced severe hypoglycemia during pregnancy with the peak incidence in early pregnancy. In the first half of pregnancy, the RR of severe hypoglycemia in women randomly assigned in early pregnancy/preconception was 1.70 (95% CI 0.91-3.18, P = 0.097); the RR in the second half of pregnancy was 1.35 (0.38-4.77, P = 0.640). In women randomly assigned preconception, severe hypoglycemia rates occurring before and during the first and second halves of pregnancy and postpartum for IAsp versus human insulin were 0.9 versus 2.4, 0.9 versus 2.4, 0.3 versus 1.2, and 0.2 versus 2.2 episodes per patient per year, respectively (NS). CONCLUSIONS These data suggest that initiation of insulin analog treatment preconception rather than during early pregnancy may result in a lower risk of severe hypoglycemia in women with type 1 diabetes.

Clinical characteristics of type 1 diabetic patients with and without severe hypoglycemia.

OBJECTIVE: To investigate the frequency of severe hypoglycemia (SH) and hypoglycemic coma and to identify clinical and behavioral risk indicators in a nonselected population of type 1 diabetic patients. RESEARCH DESIGN AND METHODS: This study involved a retrospective clinical survey of 195 consecutive patients using a questionnaire addressing the frequency of SH (i.e., help from others required) and hypoglycemic coma during the previous year, general characteristics, behavior, hypoglycemia awareness, and the Hypoglycemia Fear Survey Data regarding diabetes, treatment, long-term complications, comorbidity, and comedication were obtained from the patients' medical records. RESULTS: A total of 82% of subjects were receiving intensive insulin treatment, and mean +/- SD HbA(1c) was 7.8 +/- 1.2%. Mean duration of diabetes was 20 +/- 12 years. The occurrence of SH (including hypoglycemic coma) was 150 episodes/100 patient-years and affected 40.5% of the population. Hypoglycemic coma occurred in 19% of subjects (40 episodes/100 patient-years). SH without coma was independently related to nephropathy (odds ratio [OR] 4.8 [95% CI 1.5-15.1]), a threshold for hypoglycemic symptoms of <3 mmol/l (4.8 [1.8-12.0]), and a daily insulin dose 0.1 U/kg higher (1.3 [1.0-1.6]) (all ORs were adjusted for diabetes duration and use of comedication). Hypoglycemic coma was independently related to neuropathy (3.9 [1.5-10.4]), (nonselective) beta-blocking agents (14.9 [2.1-107.4]), and alcohol use (3.5 [1.3-9.1]) (all ORs were adjusted for diabetes duration). CONCLUSIONS: SH and hypoglycemic coma are common in a nonselected population with type 1 diabetes. The presence of long-term complications, a threshold for symptoms of <3 mmo/l, alcohol use, and (nonselective) beta-blockers were associated with SH during the previous year. If prospectively confirmed, these results may have consequences for clinical practice.

[Frequency and costs of hospital stays for hypoglycemia in France in 1995]. / Fréquence et coûts des séjours hospitaliers pour hypoglycémie en France en 1995.

OBJECTIVES: Diabetes is a highly prevalent chronic disease causing serious complications. Hypoglycemia is the most frequent, the most serious, and the most feared by patients and families. Hospitalization may be necessary and can be costly. The main objective of this study was to determine the number of cases of hypoglycemia cared for annually in France in an inpatient setting and to estimate the annual financial impact of hospitalizations. PATIENTS AND METHODS: The number of hypoglycemias seen annually by physician s in France and the frequencies of hospitalizations for hypoglycemia were determined from a literature search. Complementary data on costs were obtained from the national PMSI mission. Our sample included 817 hospital stays between 1994 and 1995. RESULTS: In 1992, physicians in France cared for 40,000 episodes of hypoglycemia. There were 10,800 hospitalizations. In 9 out of 10 cases, the hospital stay lasted several days and, despite hospitalization, 1.9% of the patients died. Mean total medical cost of a hospital stay for hypoglycemia was 14,000 FF ($2,100) (median 10,000 FF, range 1,200-120,000 FF). Mean length of stay was 6.6 days. DISCUSSION: Mean unit cost for hospital stays for hypoglycemia is high. Based on the 1993 SESI survey, the probable annual cost for the society for hospital care of patients with hypoglycemia was an estimated 108 to 151 million FF ($16-22 million) in 1995. This figure only takes into account the visible cost of caring for hypoglycemia patients. Ambulatory care was not taken into consideration. Education, for the patient and family, is fundamental for the prevention and treatment of hypoglycemia. CONCLUSION: It is important to have this estimation due to the absence of a medicoeconomic study on ambulatory and hospital care for hypoglycemia. Complementary studies should be conducted to estimate the total annual cost of hypoglycemia in France.

Trends in hospital admissions among children aged 0-19 years with type I diabetes in The Netherlands.

OBJECTIVE: To determine the number and duration of hospital admissions due to diabetes in children aged 0-19 years between 1980-1991. RESEARCH DESIGN AND METHODS: Secondary analysis of data collected by the SIG Health Care Information was based on the 9th revision of the International Classification of Diseases. The subjects were all children in The Netherlands, aged 0-19 years. The main outcome measures were number and duration of hospital admissions due to type I diabetes (ICD 9 code 250.0-250.9). RESULTS: The hospital admission rate due to diabetes decreased > 30%. This decrease was statistically significant in all age subgroups. The total number of days in hospital due to diabetes decreased dramatically: from 24,961 in 1980 to 11,305 in 1991. The average duration of hospital stay length due to diabetes decreased as well from 14.5 days in 1980 to 11.9 days in 1991. CONCLUSIONS: The hospital admission rate and the length of hospital stay for diabetes in children aged 0-19 years have decreased, in spite of an increasing incidence. The hospital admission rate may decrease still further if more children with newly diagnosed diabetes can be adequately managed by team management at home in the initial phase.

Regional cerebral hypoperfusion in long-term type 1 (insulin-dependent) diabetic patients: relation to hypoglycaemic events.

Regional distribution of cerebral blood flow was determined semi-quantitatively with 99Tcm-HMPAO brain SPET under basal conditions in Type 1 (insulin-dependent) diabetic patients of recent onset and longer disease duration, and related to metabolic control and history of hypoglycaemic events. Long-term diabetic patients showed significantly more alterations in regional cerebral blood flow than diabetics of recent onset and healthy controls. Regional hypoperfusion, predominantly localized in the fronto-temporal cortex, was almost exclusively observed in patients with long-term diabetes. The latter finding was related to lower HbA1c levels (i.e. better metabolic control) and to the frequency of impending hypoglycaemia, but not to age of the patient, duration of diabetes or to chronic diabetes complications. The incidence of hypoperfusion was comparable in patient groups with or without a medical history of hypoglycaemic coma. However, regions of hypoperfusion were larger in the patients who had experienced hypoglycaemic coma. It is concluded that regional cerebral hypoperfusion in long-term Type 1 (insulin-dependent) diabetics, as evidenced by HMPAO-SPET can be related to the frequency and degree of hypoglycaemic events and to tight metabolic control, which is however at the expense of an increased risk of recurrent hypoglycaemia.

Increasing incidence of hypoglycemic coma in children with IDDM.

OBJECTIVE: To examine the incidence of hypoglycemic coma in children with insulin-dependent diabetes mellitus (IDDM) over 8 yr from 1981 to 1988 and to investigate the importance of residual beta-cell function of HbA1 levels and other variables as risk factors for hypoglycemic coma. RESEARCH DESIGN AND METHODS: The study consisted of 155 children with IDDM aged less than 16 yr at study entry. Mean age at onset of diabetes was 7.9 yr (range 1.1-15.6 yr). We made a prospective assessment of hypoglycemic coma episodes, with a standardized questionnaire, over a total observation time of 816.6 person-yr. Three monthly clinical and laboratory examinations, which included determinations of C-peptide and HbA1 levels, were conducted. We compared children with hypoglycemic coma (cases) with children without hypoglycemic coma (controls) in a case-control analysis matched for diabetes duration. Yearly incidence of hypoglycemic coma, calculated as the number of subjects having an attack in 1 yr divided by the cumulative number of person-years for that year, was measured. Univariate and multivariate odds ratios were calculated from logistic regression. RESULTS: Over the first 4 yr, the average yearly incidence was 4.4/100 person-yr compared with 7.4/100 person-yr during the later 4 yr (P less than 0.0001). This tendency was accompanied by intensification of insulin treatment with an increase in the mean number of daily injections and a decrease in mean HbA1 levels. In the case-control analysis, absent residual beta-cell function was the most important risk factor for hypoglycemic coma (adjusted odds ratio 7.8, 95% confidence intervals 2.0-31.2), followed by near-normal HbA1 levels (adjusted odds ratio 4.5, 95% confidence intervals 1.9-10.5). CONCLUSIONS: In this group of children, improvement of glycemic control apparently led to an increase in the incidence of severe hypoglycemia. In children with recurrent hypoglycemic coma and undetectable C-peptide levels, it may be safer to aim for somewhat less tight glycemic control.

Hypoglycaemic episodes during intensified insulin treatment: increased frequency but no effect on cognitive function.

Ninety-seven patients with insulin dependent diabetes mellitus (IDDM) were randomized to intensified conventional treatment (ICT, n = 44) or regular treatment (RT, n = 53). The mean HbA1c level (+/- SEM) was reduced from 9.5 +/- 0.2% to 7.4 +/- 0.1% in the ICT group (P less than 0.001), and from 9.4 +/- 0.2% to 9.0 +/- 0.2% (P less than 0.01) in the RT group. The difference between the groups was significant (P less than 0.001). During a period of 3 years, 57% of the ICT patients (95% confidence interval 44-73%) and 23% of the RT patients (95% CI, 11-34%) (P less than 0.001) had at least one episode of serious hypoglycaemia, with the need for third-party assistance or resulting in coma. Eighteen of the 32 ICT patients who initially had adrenergic symptoms during hypoglycaemia changed to predominantly neuroglycopenic symptoms. This was the case with only 8 of 38 RT patients (P less than 0.01). The change in symptoms was related to the increased frequency of serious hypoglycaemia, but neither symptoms nor frequency of hypoglycaemia bor any relationship to insulin dose, body mass index, duration of diabetes or autonomic nerve function. The results of several neuropsychological tests did not differ between the groups at baseline, and did not change during the study. There were no signs of deteriorating cognitive function in the patients with serious hypoglycaemic episodes.

Outcome indicators for diabetes services--what do we have and what do we need?

Minimizing the need for hospital admissions for hyperglycaemic coma, hypoglycaemic coma and amputation of the lower limbs in patients with diabetes can be regarded as some of the legitimate objectives of a local diabetes service. Routinely collected data are available to calculate rates for such admissions for health service districts and for regions or their equivalents. East Anglian regional rates for admissions mentioning hyperglycaemic coma fell between 1981 and 1986 while rates for those mentioning hypoglycaemic coma rose. Amputation rates remained steady. Between-district variation for all rates was considerable and certain districts showed consistently high rates from year to year for hyperglycaemic coma with others having consistently high rates for amputations. Lack of standardization of case definition and uncertainty about the validity of routinely collected hospital admission data are the most important drawbacks of this approach. With careful interpretation, however, these data provide a possible source for the measurement of the effectiveness of local diabetes services.

Frequency of diabetic ketoacidosis and hypoglycemic coma during treatment with continuous subcutaneous insulin infusion. Audit of medical care.

The frequency of diabetic ketoacidosis and hypoglycemic coma in a large series of patients with insulin-dependent diabetes treated by long-term continuous subcutaneous insulin infusion was compared with the frequency of these events in a matched group of patients treated by conventional insulin injections at the same hospital over the same period of time. Ketoacidosis and hypoglycemic coma occurred no more frequently in continuous subcutaneous insulin infusion-treated patients. Therefore, intensified insulin therapy achieved by continuous subcutaneous insulin infusion does not appear to be associated with a greater risk of ketoacidosis or hypoglycemic coma than does conventional insulin therapy.

Acute complications associated with insulin infusion pump therapy. Report of experience with 161 patients.

We determined the frequency of acute complications associated with insulin pump therapy in 161 insulin-dependent patients followed up for a total of 2,978 patient-months. Diabetes control improved substantively with pump therapy, but 42% of the patients experienced one or more acute complications while using insulin pumps. Infected infusion sites, ketoacidosis, and hypoglycemic coma occurred once in every 27, 78, and 175 patient-months, respectively. More patients experienced ketoacidosis after the onset of pump therapy than in an equivalent interval immediately before the onset of pump therapy. Ketoacidosis also occurred in more patients using pump therapy than in a comparison group of 165 patients receiving conventional insulin injections surveyed during an equivalent period. The frequency of hypoglycemic coma was not significantly changed by pump therapy.