Follow-up of Children of Insulin-dependent and Gestational Diabetic Mothers: Neuropsychological Outcome

ABSTRACT. Ninety-four infants of 28 weeks gestation or more were born to 85 women, 64 type I and 21 gestational diabetics, between 1969–1972 at Sabbatsberg's Hospital, Stockholm. Perinatal mortality rate was 6.3%. The follow-up study was conducted when the children were approximately 5 years of age and included a physical and a neurological evaluation, IQ determination of mother and child, and an interview of mother by a psychologist. Fifty-three infants of insulin-dependent (IDM) and 20 infants of gestational diabetic mothers (IGDM) (83 %) participated, 3 families could not be traced and 12 were unwilling. The group lost to follow-up (13 IDM, 2 IGDM) had more perinatal complications induding congential malformations than the follow-up group. All children had normal physical and neurological development. IQ was normal, the majority were above 100, the average in IDM was 115 (range 89–144) and 112 in IGDM (range 95–133). No obvious relationship was found between maternal acetonuria during pregnancy, infant birthweight, blood glucose during first hours after birth or neonatal complications and IQ of the children. A correlation (r= 0.364, p<0.01) was found between maternal and child IQ. Mothers exhibiting emotional disorders (anxiety, depression) had significantly higher life stress scores based on 29 stress variables and reported more frequently about conduct and behavioural disorders in their children than mothers without emotional disturbances.     

具有特殊内分泌综合征的肾肿瘤(附3例报告)

作者报道了3例引起低血糖性昏迷、类癌综合征的肾肿瘤(1例肾被膜纤维瘤,1例成人肾母细胞瘤,1例肾类癌)。其中2例做了术前、术后血糖及胰岛素的测定。手术治疗后血糖恢复正常,3例内分泌症状均消失。提出肾脏起源于内胚层,有产生异位分泌的组织学基础,肾肿瘤亦是胰外诸多引起内分泌综合征肿瘤中的一种。     

Effects of severe hypoglycemia on the human brain neuropathological case reports

The neuropathological findings in two cases of irreversible hypoglycemic brain injury are described. A 26-year-old diabetic man injected insulin without adequate food intake and died after 2 months in coma. An 84-year-old nondiabetic man accidentally received 10 mg of glibenclamide and died after 3 months in relatively superficial coma.
In the first case, an extensive necrotizing injury with gliosis was present in the cerebral cortex with temporal preponderance, as well as in the amygdalae and hippocampus. Lesions were also present in the putamen and caudate nucleus whereas the globus pallidus and thalamus were less severely destroyed. The distribution of the lesions was therefore somewhat different from that commonly seen in hypoxic-ischemic brain injury, which, together with some previously published data, suggests some difference in the pathogenesis of hypoglycemic vs. hypoxic-ischemic brain injury.
In the second case only a slight loss of cortical neurons with secondary gliosis could be attributed to the hypoglycemic insult. This case demonstrates the danger of accidental intake of sulfonylurea preparations, which can cause an irreversible brain injury due to their prolonged hypoglycemic effect.     

The cerebral redox state in cats during severe insulin induced hypoglycemia

The cerebral metabolic state was studied in cats during insulin-induced hypoglycemia and the recovery after glucose infusion. Changes in the redox state of nicotinamide adenine dinucleotide (NAD) were monitored from the surface of the exposed cerebral cortex using microfluorometry. After insulin injection blood glucose fell from 6.85 μmol/ml to 0.45 μmol/ml at EEG isoelectricity and was accompanied by an oxidation of NADH⁺. Upon intravenous glucose infusion EEG activity rapidly returned and NAD became more reduced. The oxidation of NADH⁺ during severe hypoglycemia demonstrated that the in vivo redox state of mitochondria behave in a similar manner as isolated mitochondria when reducing equivalents become limiting to the respiratory chain.     

Megestrol acetate promotes euglycemia and appetite in a child with persistent hyperinsulinemic hypoglycemia of infancy

This report describes a successful treatment with megestrol acetate in a child with persistent hyperinsulinemic hypoglycemia of infancy (PHHI). An 8-y-old child with PHHI treated with octreotide had marked impairment of appetite sensation and feeding skills. Within 3 wk of starting megestrol acetate (8 mg/kg/d) to stimulate her appetite, she had a significant improvement. By 1 y postinitiation, she had acquired age-appropriate eating habits. The megestrol acetate caused hyperglycemia, necessitating the discontinuation of all other therapy for her hypoglycemia. Her height growth remained normal but she was found to have asymptomatic adrenal suppression. CONCLUSION: Megestrol acetate appeared to stimulate appetite and regulate glucose homeostasis in this child with PHHI. Additional studies will be required to document its efficacy and safety in other children with this disorder.     

Usefulness of measuring the gastric emptying time in a case of brittle diabetes

Gastric emptying time measurement by radionuclide study, although quite informative, is rarely remembered in clinical practice. We presented a patient with brittle diabetes who had multiple emergency admissions due to hypoglycemia under routinely prescribed insulin therapy. She had severe gastroparesis, which was determined by scintigraphic gastric emptying study (gastric half-emptying time = 260 min for a mixed meal). She had not presented to the emergency service for two years because of only a slight change the timing of her insulin administration time (after meal instead of before meal) in the light of gastric-emptying study.     

A case of severe diazoxide toxicity

Hyperinsulism is a rare cause of persistent hypoglycemia in the neonatal period. Therapy can be accomplished either surgically or pharmacologically. Diazoxide treatment remains the mainstay of medical therapy. Tolerance of diazoxide is usually excellent, but several adverse effects of this drug have been described. A case of severe diazoxide intoxication with fluid retention, congestive heart failure, and respiratory failure is reported. The patient was a 43-day-old infant, affected by persistent and severe hypoglycemia. After the diagnosis, hyperinsulinism was established he was treated with diazoxide (17 mg x kg(-1) daily) and octreotide (12 microg x kg(-1) daily). A few days later he presented with hepatomegaly, severe fluid retention, diffuse edema, congestive heart failure, and respiratory failure requiring mechanical ventilation. After introduction of ACE inhibitors he developed acute renal failure. The clinical condition worsened and he developed pulmonary hypertension requiring high-frequency oscillatory ventilation. Diazoxide was stopped on the 12th day in spite of poor control of blood sugar. During the next 5 days his hemodynamic status dramatically improved and he was weaned from catecholamines: he lost weight, had a negative fluid balance, and the edema disappeared, a normal diuresis resumed and renal function improved. Improvement of respiratory patterns and gas exchange made it possible to switch back to conventional ventilation and then to extubate the patient. Echocardiography demonstrated reduction of the PA pressure to normal and resolution of atrial enlargement. The patient was scheduled for elective subtotal pancreatectomy. Diagnosis and management of diazoxide intoxication are discussed.     

A characteristic reactive hypoglycemia induced by rapid change of eating behavior in anorexia nervosa: a case report

The relationship among reactive hypoglycemia, corresponding insulin metabolism, and eating behavior in anorexia nervosa (AN) has not been well documented. METHOD: A 22-year-old woman with AN was admitted to Kagoshima University Hospital. An oral glucose tolerance test was performed with additional sampling at 15 minutes on the seventh hospital day when her daily caloric intake rapidly increased, reaching 2,000kcal perday. RESULTS: An elevated level of insulin secretion (1,190pmol/L) was observed during the very early phase (15 minutes) after glucose load, whereas corresponding blood glucose elevations were not as high (1.2mmol/L). The patient experienced asymptomatic hypoglycemia (2.1mmol/L). CONCLUSIONS: Our findings suggested that a rapid increase of energy intake might cause reactive hypoglycemia with characteristic insulin metabolism, that is, an elevated level of insulin secretion during the very early phase.     

The Insulin Hypoglycemia Test: Hypoglycemic Criteria and Reproducibility

The insulin hypoglycemia test (IHT) is widely regarded as the "gold standard" for dynamic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. This study aimed to investigate the temporal relationship between a rapid decrease in plasma glucose and the corresponding rise in plasma adenocorticotropic hormone (ACTH), and to assess the reproducibility of hormone responses to hypoglycemia in normal humans. Ten normal subjects underwent IHTs, using an insulin dose of 0.15 U/kg. Of these, eight had a second IHT (IHT2) and three went on to a third test (IHT3). Plasma ACTH and cortisol were measured at 15-min intervals and, additionally, in four IHT2s and the three IHT3s, ACTH was measured at 2.5- or 5-min intervals. Mean glucose nadirs and mean ACTH and cortisol responses were not significantly different between IHT1, IHT2 and IHT3. Combined data from all 21 tests showed the magnitude of the cortisol responses, but not the ACTH responses, correlated significantly with the depth and duration of hypoglycemia. All subjects achieved glucose concentrations of of < or = 1.6 mmol/l before any detectable rise in ACTH occurred. In the seven tests performed with frequent sampling, an ACTH rise never preceded the glucose nadir, but occurred at the nadir, or up to 15 min after. On repeat testing, peak ACTH levels varied markedly within individuals, whereas peak cortisol levels were more reproducible (mean coefficient of variation 7%). In conclusion, hypoglycemia of < or = 1.6 mmol/l was sufficient to cause stimulation of the HPA axis in all 21 IHTs conducted in normal subjects. Nonetheless, our data cannot reveal whether higher glucose nadirs would stimulate increased HPA axis activity in all subjects. Overall, the cortisol response to hypoglycemia is more reproducible than the ACTH response but, in an individual subject, the difference in peak cortisol between two IHTs may exceed 100 nmol/l.     

Utilities and disutilities for type 2 diabetes treatment-related attributes

Introduction Although cost-utility analyses are frequently used to estimate treatment outcomes for type 2 diabetes, utilities are not available for key medication-related attributes. The purpose of this study was to identify the utility or disutility of diabetes medication-related attributes (weight change, gastrointestinal side effects, fear of hypoglycemia) that may influence patient preference. Methods Patients with type 2 diabetes in Scotland and England completed standard gamble (SG) interviews to assess utility of hypothetical health states and their own current health state. The EQ-5D, PGWB, and Appraisal of Diabetes Symptoms were administered. Construct validity and differences among health states were examined with correlations, t-tests, and ANOVAs. Results A total of 129 patients (51 Scotland; 78 England) completed interviews. Mean utility of diabetes without complications was 0.89. Greater body weight was associated with disutility, and lower body weight with added utility (e.g., 3% higher = −0.04; 3% lower = +0.02). Gastrointestinal side effects and fear of hypoglycemia were associated with significant disutility (p < 0.001). SG utility of current health (mean = 0.87) demonstrated construct validity through correlations with patient-reported outcome measures (r = 0.08–0.31). Discussion The vignette-based approach was feasible and useful for assessing added utility or disutility of medication-related attributes.