Hypoglycaemia in childhood diabetes. I. Clinical signs and hormonal counterregulation

Hypoglycaemia (blood glucose 1.3-2.5 mmol/l) was induced in twenty-eight diabetic children by reduction of their morning meal. Fatigue and pallor were the most common signs of hypoglycaemia. Compared to findings during normoglycaemia, plasma concentrations of adrenalin, noradrenalin and cortisol were significantly higher at glucose nadir. Plasma glucagon concentration at glucose nadir was correlated to the fasting C-peptide concentration and inversely to the duration of diabetes. Children who lacked C-peptide also lacked glucagon response to hypoglycaemia. The parents' opinion of the need to give carbohydrates corresponded to the blood glucose level. The presence of adrenergic signs correlated to the plasma adrenalin and the neuroglucopenic signs to blood glucose. The lowest glucose level correlated inversely to the concentration of free insulin. When facilities for glucose infusion are lacking, a rational step in treating the unconscious hypoglycaemic child seems to be the injection of glucagon, considering the blunted or absent glucagon secretion.     

Hypoglycaemia in Childhood Diabetes II.

ABSTRACT. Hypoglycaemia (blood glucose 1.3–2.5 mmol/1) was induced in thirty diabetic children by reduction of their morning meal. Glucagon, 10 or 20 μg/kg was then given by intramuscular or subcutaneous injection. Ten min later, all signs of hypoglycaemia had disappeared and blood glucose concentrations increased by 0.7–3.3 mmol/1. Glucagon plasma concentrations at glucose nadir were low, 23±8 pmol/l, rose to 300±42 ten min after the injection and reached peak values after another ten min. Later, a slow decrease was noted. No significant difference of blood glucose or plasma glucagon concentrations were found after subcutaneous or intramuscular injections of 20 μg/kg. After 10 μg/kg, slightly lower increase of blood glucose was seen, but the clinical effect was equally good. Nausea occurred in four children given 20 μg/kg. The rise of blood glucose did not correlate to the peak glucagon concentration obtained after the injection but showed significant correlations to the lowest glucose concentration and, inversely, to the concentration of free insulin in blood at glucose nadir. It is concluded that glucagon injections are effective in hypoglycaemia in insulin-treated diabetic children and that the injection of 10–20 μg/kg gives long-standing supraphysiological concentrations which make repeated injections unnecessary.     

Starting subcutaneous insulin doses in a paediatric population with newly diagnosed type 1 diabetes

BACKGROUND:

Starting subcutaneous insulin doses in children with newly diagnosed type 1 diabetes vary widely from 0.2 units/kg/day to 0.8 units/kg/day.

AIM:

To determine whether there are correlations between starting insulin dose and diabetes-related outcomes.

METHODS:

By reviewing the charts of children newly diagnosed with type 1 diabetes, the prevalence of hypoglycemia in the first 48 h was compared between those who received low (0.5 units/kg/day or less) and those who received high (greater than 0.5 units/kg/day) starting insulin doses.

RESULTS:

Forty-two children were initially prescribed a low dose of insulin, and 55 children were given a high dose. Approximately one-third of children (36.4%) younger than six years of age who received a high starting dose of insulin had mild hypoglycemia within 48 h of subcutaneous insulin initiation, compared with 16.0% of children six to 10 years of age and 5.3% of children older than 10 years of age.

CONCLUSIONS:

Hypoglycemia was not more frequent among children given high-insulin starting doses. However, children younger than six years of age remained at increased risk for hypoglycemia.     

Absorption of phenobarbital after the intramuscular administration of single doses in infants.

Blood concentrations of phenobarbital, following an intramuscular administration of a single large dose of approximately 10 mg/kg, were studied in 39 infants. A rapid rise was obtained with a mean concentration of 9.30 mug/ml at 30 minutes, 12.76 mug/ml at 90 minutes, and a mean peak concentration of 13.28 mug/ml, which was reached in most cases within 2 hours of injection or less. Cerebrospinal fluid values in 13 patients averaged half the blood phenobarbital concentrations.     

Prolonged use of continuous glucose monitors in children with type 1 diabetes on continuous subcutaneous insulin infusion or intensive multiple-daily injection therapy

Objective:  For continuous glucose sensors to improve the treatment of children with type 1 diabetes (T1D), they must be accurate, comfortable to wear, and easy to use. We conducted a pilot study of the FreeStyle Navigator™ Continuous Glucose Monitoring System (Abbott Diabetes Care) to examine the feasibility of daily use of a continuous glucose monitor (CGM) in an extended ambulatory setting.
Methods:  Following a 13-wk trial of daily Navigator use, 45 children with T1D [10.7 ± 3.7 yr, range 4.6–17.6, 24 using insulin pumps; continuous subcutaneous insulin infusion (CSII) and 21 using glargine-based multiple daily injections (MDI)] used the Navigator for an additional 13 wk.
Results:  Navigator use was initially slightly higher in the CSII users than in the MDI users but declined similarly in both groups by 22–26 wk. After 26 wk, 11 (46%) of 24 CSII users and 7 (33%) of 21 MDI users were using the CGM at least 5 d a week. No baseline demographic or clinical factors were predictive of the amount of sensor use at 26 wk. However, Navigator use during weeks 1–13 and scores on a CGM satisfaction survey at 13 wk were predictive of use in weeks 22–26.
Conclusions:  CGM was generally well-tolerated in children with T1D for more than 6 months, and early acceptance of CGM was predictive of extended use of the device. Although many subjects and parents found CGM valuable, the declining usage over time underscores the need to develop new technologies and strategies to increase acceptance, effectiveness, and long-term use of these devices in youth with T1D.     

Continuous subcutaneous insulin injection for self-care of young patients with insulin-dependent diabetes mellitus

Continuous subcutaneous insulin injection was used for the self-care of five patients aged 10–18 years with insulin-dependent diabetes mellitus. After an introduction to the concept and procedures for continuous subcutaneous injection, the patients soon became familiar with self-care using an insulin pump at home and at school. Three months later, the control of blood glucose improved with smaller doses of insulin in four cases and milder hypoglycemia was observed compared to when using multiple injections. Significantly decreased variations and lowered means of early morning blood glucose values were observed and seemed to explain the reason for better glycemic control. Buffered regular insulin continuously injected by pumps brought a more stable nocturnal blood glucose level compared to isophane insulin injected at bedtime, the absorption of which seemed to vary considerably. On the contrary, unbuffered regular insulin injected by pumps brought frequent nocturnal hypoglycemia, sudden worsening of glycemic control and skin infections and thus, was deemed inadequate for continuous subcutaneous injection.     

1型糖尿病患儿皮下连续输注胰岛素疗效观察

目的　观察胰岛素泵连续皮下输注胰岛素 (CSII)与皮下多次注射胰岛素 (MSII)治疗 1型糖尿病(T1DM)疗效。方法　利用CSII控制血糖为一组。MSII控制血糖分为两组 ,A组予MSII合用二甲双胍 ;B组单用MSII;并测定 3餐前后及凌晨 2∶0 0时血糖。结果　 3组血糖均可控制达标。CSII平均达标天数、胰岛素用量明显短于MSII组 ,A组达标天数也短于B组。结论　CSII控制血糖 ,达标时间短 ,血糖平稳下降 ,能够抑制黎明现象 ,低血糖及高血糖发生率低 ,适合T1DM治疗。     

Use of a subcutaneous injection port to improve glycemic control in children with type 1 diabetes

Objective:  To determine if use of an injection port, the Insuflon™, would help to improve glycemic control in youth with type 1 diabetes (TID) who were in suboptimal glycemic control (hemoglobin A1c, HbA1c >8.0%).
Study design:  A three-arm randomized protocol was used to study the effects of the Insuflon (a subcutaneous injection port) vs. an alarmable blood glucose meter vs. a control group on glycemic control in 66 youth with T1D. All participants used insulin glargine™ as their basal insulin and the NovoPen^® Junior with insulin aspart™ as their rapid-acting insulin. Participants were randomized into control, alarm, or Insuflon groups. HbA1c levels were the primary outcome with values at baseline, 3, and 6 months.
Results:  Initial parameters were similar in the three groups. HbA1c values were significantly lower for youth who used the Insuflon than for the control group at 3 and 6 months (p = 0.025). The HbA1c values (in %) for youth using the Insuflon decreased significantly from 9.4 at screening to 8.7 at 3 months (p < 0.001) and 8.5 at 6 months (p < 0.001). There were no significant reductions (p ≥ 0.05) in the HbA1c values within the other two groups.
Conclusion:  The Insuflon injection port helps some youth with T1D to improve glycemic control.     

Effect of diazoxide or glucagon on hepatic glucose production rate during extreme neonatal hypoglycaemia.

The relation between hepatic glucose production rate (HGPR) and plasma concentrations of insulin and glucagon was investigated in four term neonates who had severe hypoglycaemia. The hepatic glucose production rate was less than 20% of normal for fasting term neonates in all four babies and yet insulin concentrations were never greater than 12 microU/ml; two babies had very low glucagon concentrations (less than 60 ng/l). Two further neonates with similar histories also had plasma glucagon concentrations that were also extremely low (less than 20 ng/l). A single intravenous bolus of glucagon caused a rapid rise in hepatic glucose production rate towards the normal range, which was sustained for many hours after the bolus had been given. Diazoxide given to one baby suppressed previously ''normal'' insulin concentrations still further (4.2 to less than 1.6 microU/ml) and thereby restored the hepatic glucose production rate to normal. In view of the normal plasma insulin concentrations at a time when the hepatic glucose production rate was reduced, we feel that the absolute concentration of insulin may be less important than the insulin/glucagon molar ratio in the control of glucose homeostasis in this group of infants. The changing of this ratio by means of boluses of glucagon may be useful in preventing rebound hypoglycaemia, which so often occurs when dextrose infusions are reduced either accidentally or in an attempt to restart oral feeds.     

Asymptomatic diabetes in childhood and adolescence. A review.

An account is given of the present conception of asymptomatic (chemical) diabetes in the pediatric age group, which also has been named MODY (maturity-onset type of diabetes of young people). Long-term studies show that about 10% will eventually decompensate to overt diabetes. In contrast to classical juvenile-onset type of diabetes the inheritance of MODY seems to be autosomal dominant in many cases. Some authors have suggested that insulin resistance exists in non-obese patients with asymptomatic diabetes, but this view is not supported by observations of the author. Obese patients should reduce their body fat, but other therapeutic approaches are difficult to evaluate because of the normal fluctuation of the disease. There is no general agreement in the literature concerning the value of insulin treatment. The author supports the view that insulin treatment should be started in the late stages of chemical diabetes just before symptomatic disease emerges. In the long run this approach may ameliorate the condition due to the preservation of some beta-cell function for long periods. An unsettled question is whether early insulin treatment in asymptomatic diabetes will delay diabetic vascular complications.