John A Duncan

Type b insulin resistance in a 15-year-old white youth

4. Bellur SN: Opsoclonus: Its clinical value. Neurology 25:502, 1975. 5. Pampiglione G, Maia M: Syndrome of rapid irregular movements of eyes and limbs in childhood. Br Med J 1:469, 1972. 6. Savino P J, Glasser JS: Opsoclonus pattern of regression in a child with neuroblastoma. Br J Ophthalmol 59:696, 1975. 7. Dyken P, Kolar O: Dancing eyes, dancing feet: Infantile polymyoclonia. Brain 91:305, 1968. 8. Ellenberger C, Campa JF, Netsky MG: Opsoclonus and parenchymatous degeneration of the cerebellum. Neurology 18:1041, 1968.

Continuous Basal Insulin Infusion: An Effective Means to Achieve Good Glycemic Control Without Premeal Boluses

In 11 insulin-dependent diabetic subjects, aged 12–32 yr, we evaluated the efficacy of dual, basal-rate pump delivery of insulin without preprandial boluses. Mean HbA1c fell from 11.6 ± 3.1% to 7.7 ± 1.8% at 30 days (P < 0.005), and remained at 7.1 ± 1.3% at the time of this evaluation (mean duration of therapy, 6.6 mo). These data suggest that dual-rate continuous basal insulin infusion is an effective means of achieving good diabetes control. Furthermore, it is simpler than the preprandial bolus approach currently used, which may make it suitable for more patients.

528 BREASTFEEDING: INFLUENCE ON SUBSEQUENT DEVELOPMENT OF INSULIN DEPENDENT DIABETES

The immunologic benefits of breastfeeding in infancy are well appreciated. Since trends in early infant feeding have changed over the past 25 years, we examined the frequency of insulin dependent diabetes (IDD) as a function of early infant feeding practice and duration of breastfeeding (BR) in 221 IDD patients and 240 of their non-diabetic siblings.There was no correlation of BR with age at diagnosis or incidence of IDD in a given sex. Since hereditary, immunologic and, presumably, environmental factors were similar for children within each family, we conclude that breastfeeding imparts no immunologic protection against later development of IDD.

NONKETOTIC HYPERGLYCINEMIA (NKH): PERHAPS NOT SO RARE

Since 1976 four unrelated patients have presented with NKH. Only one was of consanguineous parents. One presented by 8 hours of life, the others within 3 days. Findings included myotonic jerks, lethargy, hypotonia and respiratory failure. Diagnostic laboratory data are:Other organic acid and amino acid metabolites were normal. Sodium benzoate and protein restriction were used in all four patients. Other therapy included strychnine, pyridoxine, phenobarbital and dilantin. Two died before 8 months, one before 2 years, one survives at 6 years with severe psychomotor delay. In order to have diagnosed 4 cases in 7 years in our catchment area we estimate the frequency of NKH to be about 1 in 60,000 births.

1231 IDIOPATHIC HYPERCALCIURIA (IH): A POTENTIAL CAUSE OF RENAL DISEASE IN CHILDREN WITH INSULIN DEPENDENT DIABETES MELLITUS (IDDM)

Renal disease is a common complication of IDDM. The pathogenesis is believed to be microvascular and to increase with duration of IDDM. Hypercalciuria causes renal dysfunction and has been reported in children with IDDM. A group of children (157) with IDDM had urine and blood collected after a 10 hour fast. Thirty-seven age similar non-diabetic (ND) subjects were controls. Urine calcium (Ca), phosphate (PO4) and creatinine (Cr) were measured. The Ca/Cr and PO4/Cr ratios were calculated as an indicator of urinary excretion. IH (definition: Ca/Cr 2 SD>mean for ND) was found in 45 (29%) of the IDDM subjects (6% prevalence in ND children). PO4/Cr in IDDM (1.2±0.06) was greater than ND (0.72±0.08) p<0.002. Ca/Cr correlated with PO4/Cr in subjects with IDDM while no relationship was found in ND. Ca/Cr correlated both with coincident serum glucose (r=0.34, p<0.001) and glycosylated hemoglobin (r=0.25 p<0.001) but was not related to duration of diabetes or the current insulin dose. Both Ca/Cr and PO4/Cr correlated inversely with serum PO4 in IDDM; serum PO4 correlated directly with PO4/Cr but was not related to Ca/Cr in ND. PTH levels in ND and IDDM children were normal.Conclusion:1) a defect in tubular reabsorption of Ca and P exists in IDDM that is related to blood glucose concentration; 2) the ion product of Ca3(PO4)2 in the urine of (29%) IDDM children exceeds the solubility constant and is 3 times that of the ND children; 3) IH may be a cause, previously unrecognized, of some renal complications of IDDM.

IMPROVED METABOLIC CONTROL-A CAUSE OF DIABETIC NEUROPATHY

Two adolescents, both 17 years, began intensified therapy to improve glycemic control (HbA1c 17.0%, 9.0%). Physical examinations were normal. Baseline neurophysiologic studies (Biothesiometry and NCV) demonstrated mild sensory nerve dysfunction, not due to heavy metal toxicity or vitamin deficiency. Intensified conventional diabetes therapy improved their diabetes control. Hb A1c values were <8.5% at 8 weeks after beginning therapy. Four to six weeks after beginning therapy, each patient developed distal, symmetrical polyneuropathy characterized by pain and/or numbness of extremities. Despite improved metabolic control, repeat neurophysiologic studies were unchanged. A 15-year-old female presented with right facial paresis and pedal dysesthesias. Her glycemic control was similarly improved(Table). Six weeks later she reported severe leg pain and worsening of existing symptoms without neurophysiologic change. In all three patients, symptoms completely subsided in 3 to 4 months without improvement in neurophysiologic tests.Improved metabolic control may exacerbate silent or overt neuropathy in young diabetics. Resolution of symptoms in response to treatment protocols may not indicate improved nerve function.

HYPERCALCIURIA AND GROWTH FAILURE IN CHILDREN WITH DIABETES

Growth failure and hypercalciuria have been noted independently in children with insulin-dependent diabetes mellitus (IDDM). We evaluated growth and calcium metabolism in 175 IDDM children and 38 non-diabetic (ND) sibs of similar ages. Height was determined by 2 of the authors using a Stadiometer. Blood and urine were collected in the AM before food and insulin had been taken. Results: (mean ± SEM) urine calcium/creatinine (Ca/Cr) (ND=0.13±.01, IDDM=0.21±.01 p<.001), serum Ca (ND=9.7±.07 mg/dl, IDDM=9.6±.02 mg/dl p=NS), alkaline phosphatase (ND=105.8±7.0 IU, IDDM 284.9±7.5 IU p<.001) Vitamin D3 ND=20.0±1.8 ng/ml, IDDM=23.0±2.0 ng/ml p=NS), PTH (ND=140.3±7.9 pg/ml, IDDM=158.4±5.2 p=NS), Ht (ND=54±3.8 percentile, IDDM=43.7±2.3 percentile p<.05). Ca/Cr correlated with coincident serum glucose r=.28 p<.0002, HbA1c r=.24 p<.0004, but not with serum Ca, alkaline phosphatase, vitamin D or PTH. Ca/Cr correlated inversely with Ht percentile r=.20 p<.01. IDDM with Ca/Cr>ND range were shorter 37±3.2 percentile than ND 54±3.8 percentile p<.01. Hypercalciuria was associated with both poor glycemic control and growth failure in IDDM children. When coincident serum glucose, HbA1c and duration of IDDM are factored out of the analysis of variance the Ca/Cr continues to have a negative correlation to height percentile. Hypercalciuria appears to be an important factor in the growth failure associated with IDDM.

A NOVEL APPROACH TO METABOLIC STABILIZATION IN THE NEWLY-DIAGNOSED DIABETIC

Common practice for the management of the new patient with insulin dependent diabetes (IDD) is hospitalization for institution of insulin therapy, diet and daily home management instruction. Standard protocols include basal insulin doses of 0.5 u/kg/24 hrs. plus supplemental doses of regular insulin every 4-6 hrs. according to urine and blood glucose concentrations. After several days an insulin dose is calculated. We have successfully utilized a new insulin dose regimen in 52 IDD pts. All patients received 1.0 u/kg/24 hrs. of s.c. NPH U-100 insulin which was delivered as 0.5 u/kg BID. Except in 16 pts. hospitalized 6 days or fewer (11 for DKA) all pts. began this regimen as outpatients. Extensive nutritional and daily home management instructions were provided on an outpatient basis. Urine testing for glucose and acetone was performed TID. When all urinary tests were negative for 3 days, the insulin dose was lowered to 0.5 u/kg/24 hrs. administered in 0.25 u/kg BID. Pts. were reassessed at 1 wk,1 mo., 3 mos. and every 3 mos. thereafter. Insulin dosage was maintained at 0.5 u/kg until an increase in glucose and acetone spillage suggested total insulin dependence. An estimated 250 hospital days and

Hypercalciuria, hyperphosphaturia, and growth retardation in children with diabetes mellitus

98,000 were saved by using this regimen. A dosage decrease to 0.5 u/kg was experienced by 33 of 52 pts. Mean duration of 0.5 u/kg therapy was 7.2 mos.